Materiały źródłowe

• #1

  https://grantome.com/grant/NIH/F30-ES024622-02

  10-25% of adult asthma is occupation-induced, a subtype caused by exposure to environmental irritants in the workplace. […] Recently, a genome-wide association study (GWAS) identified single nucleotide polymorphisms (SNPs) in ?-T-catenin (?-T-cat) that correlated with the incidence and severity of toluene diisocyanate (TDI) occupational asthma. […] We suspect ?-T-cat dysfunction may contribute to asthma through a cardiac cell defect that leads to increased airway edema. […] Together, these findings suggest that cardiac cell junction dysfunction may underlie occupational asthma. This is a novel mechanism and contributor to the pathogenesis of asthma, which has long been considered primarily a disease mediated by inflammation. […] The pathogenesis of occupational asthma has been linked to mutations in the cardiac cell adhesion protein ?-T-cat.

• #2 Asthma (include occupational asthma): Pathogenesis and Epidemiology – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/pulmonary-medicine/asthma-include-occupational-asthma-pathogenesis-and-epidemiology/

  Occupational asthma is defined as asthma triggered by allergens isolated to the work place environment. Once a patient is sensitized to the trigger, very low dose exposures can trigger symptoms, which are often accompanied by allergic rhinitis and conjunctivitis. […] Occupational asthma is an under diagnosed and undertreated clinical entity. About 16% of all adult-onset asthma is attributed to occupational asthma, and it should be considered in all cases of adult-onset asthma. […] The pathophysiology of asthma is characterized by: bronchoconstriction, airway edema, airway hyperresponsiveness, and lastly airway remodeling. […] Airway inflammation is thought to be a major underlying cause of asthma. However, details of the inflammatory process are a source of considerable controversy. […] Chronic inflammation also promotes bronchial hyper-responsiveness, which is the hallmark of asthma.

• #3 British Thoracic Society Clinical Statement on occupational asthma | Thorax

  https://thorax.bmj.com/content/77/5/433

  Healthcare professionals should be aware that occupational exposures account for around one in six cases of asthma in adults of working age. […] Over 400 causes of Occupational Asthma (OA) have been described; these are categorised as high-molecular weight (HMW) or low-molecular weight (LMW) respiratory sensitisers. […] Although individual susceptibility plays a key role, the main risk factor for the development of OA is the level of allergen exposure in the workplace. […] OA caused by repeated exposure to HMW proteins is an IgE-associated response, involving T-helper cells. This immune mechanism is also known to be relevant to a small number of LMW causes (eg, acid anhydrides and platinum salts), but for the majority, the immune pathways responsible for sensitisation remain to be determined.

• #4 Pathogenesis and Disease Mechanisms of Occupational Asthma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4683932/

  A generally accepted definition proposed in an authoritative text, Asthma in the Workplace, has defined OA as variable airflow limitation and/or airway hyperresponsiveness due to exposure to a specific causal agent present in a particular work environment and not to stimuli encountered outside the workplace. […] OA can be further subclassified into two different types: OA appearing after an asymptomatic latent period (during which immune sensitization is thought to develop), including (a) IgE-associated OA typically triggered by high molecular weight (HMW) protein antigens, and (b) IgE-independent OA typically triggered by low molecular weight (LMW) chemicals (isocyanates, red cedar dust). […] Nearly all asthmatics with active symptoms exhibit airway hyperresponsiveness (AHR), an exaggerated response to bronchoconstrictor stimuli, which can be assessed by pharmacologic testing (e.g., methacholine inhalation challenge) or non pharmacologic means (e.g., exercise challenge).

• #5 Occupational asthma: Pathogenesis – UpToDate

  https://www.uptodate.com/contents/occupational-asthma-pathogenesis

  Occupational asthma is a type of work-related asthma that is caused by immunologic (identified or presumed) and nonimmunologic stimuli present in the workplace. […] The pathogenesis and pathology of occupational asthma will be reviewed here. […] Two main types of occupational asthma have been recognized: Immunologically-mediated. This type includes immunoglobulin E (IgE) and non-IgE-mediated responses following chronic exposure and respiratory sensitization to high or low molecular weight agents. […] Nonimmunologic, irritant-mediated, also called irritant-induced asthma. This type includes reactive airways dysfunction syndrome (RADS) caused by a single high-level exposure to an irritant, irritant-induced asthma caused by multiple high-level exposures to an irritant, and possibly asthma caused by chronic lower level of exposure, although the latter is controversial.

• #6 Diagnosis of Occupational Asthma – Quirce S, Sastre J (Updated 2020)

  https://www.worldallergy.org/component/content/article/diagnosis-of-occupational-asthma-quirce-s-sastre-j-updated-2020?catid=16&Itemid=101

  The frequency of OA, however, varies among types of industries, and it is dependent on physiochemical properties of the inhaled agent, level and duration of exposure, host factors and industrial hygiene practices. About 400 agents encountered in the workplace have been reported to induce OA in susceptible individuals. These agents can be divided into three major categories based on their pathogenesis: high-molecular weight (HMW) agents, low-molecular weight (LMW) agents and irritants. The type of exposure to these agents very often determines the type of asthma. […] OA is defined as a disease characterized by variable airflow limitation and/or airway hyperresponsiveness due to causes and conditions attributable to a particular environment and not to stimuli encountered outside the workplace.

• #7 British Thoracic Society Clinical Statement on occupational asthma | Thorax

  https://thorax.bmj.com/content/77/5/433

  Healthcare professionals should be aware that occupational exposures account for around one in six cases of asthma in adults of working age. […] Over 400 causes of Occupational Asthma (OA) have been described; these are categorised as high-molecular weight (HMW) or low-molecular weight (LMW) respiratory sensitisers. […] Although individual susceptibility plays a key role, the main risk factor for the development of OA is the level of allergen exposure in the workplace. […] OA caused by repeated exposure to HMW proteins is an IgE-associated response, involving T-helper cells. This immune mechanism is also known to be relevant to a small number of LMW causes (eg, acid anhydrides and platinum salts), but for the majority, the immune pathways responsible for sensitisation remain to be determined.

• #8 Diagnosis of Occupational Asthma – Quirce S, Sastre J (Updated 2020)

  https://www.worldallergy.org/component/content/article/diagnosis-of-occupational-asthma-quirce-s-sastre-j-updated-2020?catid=16&Itemid=101

  The frequency of OA, however, varies among types of industries, and it is dependent on physiochemical properties of the inhaled agent, level and duration of exposure, host factors and industrial hygiene practices. About 400 agents encountered in the workplace have been reported to induce OA in susceptible individuals. These agents can be divided into three major categories based on their pathogenesis: high-molecular weight (HMW) agents, low-molecular weight (LMW) agents and irritants. The type of exposure to these agents very often determines the type of asthma. […] OA is defined as a disease characterized by variable airflow limitation and/or airway hyperresponsiveness due to causes and conditions attributable to a particular environment and not to stimuli encountered outside the workplace.

• #9 A compendium of causative agents of occupational asthma | Journal of Occupational Medicine and Toxicology | Full Text

  https://occup-med.biomedcentral.com/articles/10.1186/1745-6673-8-15

  The objective is to provide an evidence-based compendium of allergenic and irritant agents that are known to cause occupational asthma in order to improve diagnostics and disease management. […] Occupational asthma involves IgE-mediated asthma after a latency period, irritant asthma with or without a latency period, including reactive airways dysfunction syndrome (RADS), resulting from high exposure, and asthma due to specific occupational agents with unknown pathomechanisms that may also show a latency period. […] Previous reports and reviews have accumulated narrative and experimental evidence for about 300 causative agents, which are often divided into high or low molecular weight groups. High molecular weight agents typically induce asthma through an IgE-mediated mechanism while the pathomechanism of low molecular weight agents is mostly airway irritation or unknown.

• #10 Work-Related Asthma | Respiratory Therapy

  https://respiratory-therapy.com/disorders-diseases/chronic-pulmonary-disorders/asthma/work-related-asthma/

  Well over 400 substances have been identified in the workplace that can cause occupational asthma. The majority of these are antigens; a list with descriptions is maintained on the Internet. Antigens causing OA are typically categorized as high or low molecular weight (MW) compounds, although the two groups cannot be distinguished on clinical grounds. Generally, high molecular weight compounds are mostly proteins from animals and plants; low molecular weight compounds include numerous chemicals. […] Note that OA can occur in clean environments, such as in the pharmaceutical industry, where workers may develop sensitization after repeated exposures to low molecular weight antibiotics. […] Distinguishing between immunologic and irritant OA usually requires identifying the offending agent(s). Clinically, this distinction is not nearly as important as is removing the patient from the source and providing proper treatment.

• #11 British Thoracic Society Clinical Statement on occupational asthma | Thorax

  https://thorax.bmj.com/content/77/5/433

  Healthcare professionals should be aware that occupational exposures account for around one in six cases of asthma in adults of working age. […] Over 400 causes of Occupational Asthma (OA) have been described; these are categorised as high-molecular weight (HMW) or low-molecular weight (LMW) respiratory sensitisers. […] Although individual susceptibility plays a key role, the main risk factor for the development of OA is the level of allergen exposure in the workplace. […] OA caused by repeated exposure to HMW proteins is an IgE-associated response, involving T-helper cells. This immune mechanism is also known to be relevant to a small number of LMW causes (eg, acid anhydrides and platinum salts), but for the majority, the immune pathways responsible for sensitisation remain to be determined.

• #12 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  Occupational asthma (OA) represents one of the major public health problems due to its high prevalence, important social and economic burden. The aim of this review is to summarize current data about clinical phenotypes, biomarkers, diagnosis and management of OA, a subtype of work-related asthma. Most studies have identified two phenotypes of OA. One is sensitizer-induced asthma, occurring after a latency period and caused by hypersensitivity to high- or low-molecular weight agents. The other is irritant-induced asthma, which can occur after one or more exposures to high concentrations of irritants without latency period. More than 400 agents causing OA have been identified and its list is growing fast. The best diagnostic approach for OA is a combination of clinical history and objective tests. An important tool is a specific inhalation challenge. Additional tests include assessments of bronchial hyperresponsiveness to methacholine/histamine in patients without airflow limitations, monitoring peak expiratory flow at- and off-work, sputum eosinophil count, exhaled nitric oxide measurement, skin prick tests with occupational allergens and serum specific IgE. Treatment of OA implies avoidance of exposure, pharmacotherapy and education. OA is a heterogeneous disease. Mechanisms of its different phenotypes, their diagnosis, role of new biomarkers and treatment require further investigation.

• #13 Occupational asthma: Pathogenesis – UpToDate

  https://www.uptodate.com/contents/occupational-asthma-pathogenesis

  Occupational asthma is a type of work-related asthma that is caused by immunologic (identified or presumed) and nonimmunologic stimuli present in the workplace. […] The pathogenesis and pathology of occupational asthma will be reviewed here. […] Two main types of occupational asthma have been recognized: Immunologically-mediated. This type includes immunoglobulin E (IgE) and non-IgE-mediated responses following chronic exposure and respiratory sensitization to high or low molecular weight agents. […] Nonimmunologic, irritant-mediated, also called irritant-induced asthma. This type includes reactive airways dysfunction syndrome (RADS) caused by a single high-level exposure to an irritant, irritant-induced asthma caused by multiple high-level exposures to an irritant, and possibly asthma caused by chronic lower level of exposure, although the latter is controversial.

• #14 Work-Related Asthma | Respiratory Therapy

  https://respiratory-therapy.com/disorders-diseases/chronic-pulmonary-disorders/asthma/work-related-asthma/

  Immunologically mediated. An immunologic mechanism inhaled antigen eliciting antibody reaction has been identified or is thought to play a role. Characteristic of this type of OA is a latency period; symptoms do not occur immediately, but often days or longer after the initial sensitization. […] Immunologic OA is reversible airway obstruction due to an allergic mechanism. There is a reaction between the offending substance (an antigen) and an antibody produced by the body’s immune system; the resultant antigen-antibody reaction triggers a release of chemicals that cause bronchial inflammation, airway narrowing, and asthma symptoms. This mechanism is far more common than irritant-induced, accounting for more than 85% of cases of OA. […] Characteristic of immunologic OA is a latency period (from days to years) between first contact with the allergen and development of asthma; this is because the worker must first become sensitized to the allergen and build up an immune response before there is clinical asthma.

• #15 Pathogenesis and Disease Mechanisms of Occupational Asthma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4683932/

  A generally accepted definition proposed in an authoritative text, Asthma in the Workplace, has defined OA as variable airflow limitation and/or airway hyperresponsiveness due to exposure to a specific causal agent present in a particular work environment and not to stimuli encountered outside the workplace. […] OA can be further subclassified into two different types: OA appearing after an asymptomatic latent period (during which immune sensitization is thought to develop), including (a) IgE-associated OA typically triggered by high molecular weight (HMW) protein antigens, and (b) IgE-independent OA typically triggered by low molecular weight (LMW) chemicals (isocyanates, red cedar dust). […] Nearly all asthmatics with active symptoms exhibit airway hyperresponsiveness (AHR), an exaggerated response to bronchoconstrictor stimuli, which can be assessed by pharmacologic testing (e.g., methacholine inhalation challenge) or non pharmacologic means (e.g., exercise challenge).

• #16 Occupational Asthma

  https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/allergy/occupational-asthma/

  Like childhood asthma, OA is the result of interactions between multiple environmental and genetic factors. Some of the known environmental factors include the route, duration, and intensity of exposure, and the substance (or agent) to which the subject is exposed. Using the definition given above, OA can be divided into immunologic causes (associated with a latency period) and nonimmunologic causes. Agents associated with an immunologic cause can be further divided into HMW agents, usually allergens such as proteins from laboratory animals, flour, or plants, or LMW agents, usually chemicals such as isocyanates, biocides, or drugs. […] HMW agents can induce an immunoglobulin E (IgE) response in susceptible individuals and can cause asthma by an IgE-mediated mechanism, similar to that seen in a patient with atopic asthma. The bridging of IgE molecules by antigen leads to mast-cell degranulation and the initiation of an inflammatory cascade that results in airway inflammation and airway hyperresponsiveness. It is therefore not surprising that patients with atopic asthma or patients with a family history of atopy are at increased risk for developing OA from exposure to HMW agents. Smoking is also a risk factor for sensitization.

• #17 Pathogenesis and Disease Mechanisms of Occupational Asthma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4683932/

  A generally accepted definition proposed in an authoritative text, Asthma in the Workplace, has defined OA as variable airflow limitation and/or airway hyperresponsiveness due to exposure to a specific causal agent present in a particular work environment and not to stimuli encountered outside the workplace. […] OA can be further subclassified into two different types: OA appearing after an asymptomatic latent period (during which immune sensitization is thought to develop), including (a) IgE-associated OA typically triggered by high molecular weight (HMW) protein antigens, and (b) IgE-independent OA typically triggered by low molecular weight (LMW) chemicals (isocyanates, red cedar dust). […] Nearly all asthmatics with active symptoms exhibit airway hyperresponsiveness (AHR), an exaggerated response to bronchoconstrictor stimuli, which can be assessed by pharmacologic testing (e.g., methacholine inhalation challenge) or non pharmacologic means (e.g., exercise challenge).

• #18

  https://www.hsa.ie/eng/workplace_health/occupational_asthma_and_dermatitis/occupational_asthma_frequently_asked_questions/

  Occupational asthma is caused as a direct result of workplace exposure. There are 2 forms of occupational asthma: […] Irritant Induced Occupational Asthma usually develops after a single, very high exposure to an irritant chemical. It is a direct burn effect on the airways and is not related to the immune system. […] Allergic Occupational Asthma is caused by sensitisation or becoming allergic to a specific chemical agent in the workplace over a period of time. This is the mechanism for the vast majority (90%) of cases of occupational asthma. The sensitisation process does not occur after one exposure but develops over time (i.e., latency period). […] If exposure to the causative agent ceases completely, the condition will nearly always improve. […] Health surveillance is used to detect the early onset or symptoms of asthma. It is deemed to be secondary prevention, (by detecting adverse effects early rather than total prevention) and not as effective as the primary prevention measures outlined above. […] The evaluation of a potential case of occupational asthma is usually best done by a specialist occupational physician or a specialist respiratory physician with an interest in occupational asthma or ideally both.

• #19 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  The most common form of OA is SI-OA, which represents >90% of cases. OA incidence varies between countries and industries. Efforts to identify risk factors to develop OA have been done. The level of exposure to a sensitizing agent is the most recognized environmental risk factor for OA but evidences suggest that occupational exposure to vapors, dust, gas and fumes increases prevalence of asthma. Previous data showed that cigarette smoking increases IgE sensitization to HMW and LMW agents, so smoking could also play a role in the development of OA. Several host factors have been associated with OA. Atopy is a strong risk factor for OA due to HMW agents. Despite the fact that atopy is associated with a high risk for OA in bakers/pastry-makers and hairdressers, the atopic status seems to not precipitate the occurrence of respiratory symptoms in these specific populations. Other evidence suggests that genetic factors including HLA class II polymorphisms contribute to individual susceptibility for OA induced by LMW agents. Despite that currently the utility of these factors in practice to determine the ability of a worker to do a job with a risk of sensitization is limited, the identification of workers at risk according to their individual characteristics and worker’s education about the workplaces with high levels of occupational allergens/irritants represent very important steps in the prevention of OA.

• #20 Diagnosis of Occupational Asthma – Quirce S, Sastre J (Updated 2020)

  https://www.worldallergy.org/component/content/article/diagnosis-of-occupational-asthma-quirce-s-sastre-j-updated-2020?catid=16&Itemid=101

  Allergic, induced by sensitizers, which appears after a latency period necessary for the worker to acquire sensitization to the causal agent. It encompasses OA caused by most high (HMW) and some low-molecular-weight (LMW) agents for which an IgE-mediated mechanism has proven, and OA induced by some specific LMW agents in which the allergic mechanisms responsible have not yet been fully characterized. […] Irritant-induced OA (IIOA) (or non-immunologic/non-allergic OA) is a form of OA characterized by the development of asthma (or the reactivation of quiescent asthma) caused by exposure to irritant substances at the workplace that are capable of inducing an inflammatory reaction of the airways and non-specific bronchial hyperresponsiveness (NSBH) through non-sensitizing mechanisms. […] The diagnosis of irritant-induced OA depends entirely on the clinical and occupational/environmental history, along with documentation of decreases in airway caliber and objective evidence of nonspecific bronchial hyperresponsiveness.

• #21 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  The prevalence of II-OA is estimated at 5–10% of cases of OA. According to current guidelines three clinical phenotypes of II-OA are described: (i) definite IIA (RADS or “acute-onset II-OA”) characterized by the rapid onset of asthma within a few hours after a single exposure to very high levels of irritant substances; (ii) probable IIA (“sub-acute II-OA”) defined as insidious asthma developed in workers with multiple symptomatic moderate-high-level exposures to irritants; and (iii) possible IIA (“chronic II-OA”) described as asthma occurring with a delayed-onset after chronic exposure to low-moderate levels of irritants. The diagnostic criteria for RADS include the occurrence of asthma symptoms within minutes to hours following a single identifiable high level exposure to an irritant, the absence of preexisting asthma symptomatology, the exclusion of other pulmonary disorders that can explain the symptoms, and the evidence of BHR or reversible airflow obstruction on spirometry.

• #22 Work-Related Asthma | AAFP

  https://www.aafp.org/pubs/afp/issues/2001/1201/p1839.html

  Work-related asthma accounts for at least 10 percent of all cases of adult asthma. Work-related asthma includes work aggravation of preexisting asthma and new-onset asthma induced by occupational exposure. Occupational exposure to very high concentrations of an irritant substance can produce reactive airway dysfunction syndrome, while exposure to allergenic substances can result in allergic occupational asthma. An important step in the diagnosis of work-related asthma is recognition by the physician of the work relatedness of the illness. […] Occupational asthma develops as a direct result of workplace exposure. Two forms of occupational asthma are recognized: reactive airway dysfunction syndrome and allergic occupational asthma. […] Reactive airway dysfunction syndrome (also known as irritant-induced asthma), usually develops after a single, very high exposure to an irritant chemical. These causal agents include ammonia, chlorine gas, and hydrochloric acid.

• #23 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  The prevalence of II-OA is estimated at 5–10% of cases of OA. According to current guidelines three clinical phenotypes of II-OA are described: (i) definite IIA (RADS or “acute-onset II-OA”) characterized by the rapid onset of asthma within a few hours after a single exposure to very high levels of irritant substances; (ii) probable IIA (“sub-acute II-OA”) defined as insidious asthma developed in workers with multiple symptomatic moderate-high-level exposures to irritants; and (iii) possible IIA (“chronic II-OA”) described as asthma occurring with a delayed-onset after chronic exposure to low-moderate levels of irritants. The diagnostic criteria for RADS include the occurrence of asthma symptoms within minutes to hours following a single identifiable high level exposure to an irritant, the absence of preexisting asthma symptomatology, the exclusion of other pulmonary disorders that can explain the symptoms, and the evidence of BHR or reversible airflow obstruction on spirometry.

• #24 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  The prevalence of II-OA is estimated at 5–10% of cases of OA. According to current guidelines three clinical phenotypes of II-OA are described: (i) definite IIA (RADS or “acute-onset II-OA”) characterized by the rapid onset of asthma within a few hours after a single exposure to very high levels of irritant substances; (ii) probable IIA (“sub-acute II-OA”) defined as insidious asthma developed in workers with multiple symptomatic moderate-high-level exposures to irritants; and (iii) possible IIA (“chronic II-OA”) described as asthma occurring with a delayed-onset after chronic exposure to low-moderate levels of irritants. The diagnostic criteria for RADS include the occurrence of asthma symptoms within minutes to hours following a single identifiable high level exposure to an irritant, the absence of preexisting asthma symptomatology, the exclusion of other pulmonary disorders that can explain the symptoms, and the evidence of BHR or reversible airflow obstruction on spirometry.

• #25 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  The prevalence of II-OA is estimated at 5–10% of cases of OA. According to current guidelines three clinical phenotypes of II-OA are described: (i) definite IIA (RADS or “acute-onset II-OA”) characterized by the rapid onset of asthma within a few hours after a single exposure to very high levels of irritant substances; (ii) probable IIA (“sub-acute II-OA”) defined as insidious asthma developed in workers with multiple symptomatic moderate-high-level exposures to irritants; and (iii) possible IIA (“chronic II-OA”) described as asthma occurring with a delayed-onset after chronic exposure to low-moderate levels of irritants. The diagnostic criteria for RADS include the occurrence of asthma symptoms within minutes to hours following a single identifiable high level exposure to an irritant, the absence of preexisting asthma symptomatology, the exclusion of other pulmonary disorders that can explain the symptoms, and the evidence of BHR or reversible airflow obstruction on spirometry.

• #26 British Thoracic Society Clinical Statement on occupational asthma | Thorax

  https://thorax.bmj.com/content/77/5/433

  Healthcare professionals should be aware that occupational exposures account for around one in six cases of asthma in adults of working age. […] Over 400 causes of Occupational Asthma (OA) have been described; these are categorised as high-molecular weight (HMW) or low-molecular weight (LMW) respiratory sensitisers. […] Although individual susceptibility plays a key role, the main risk factor for the development of OA is the level of allergen exposure in the workplace. […] OA caused by repeated exposure to HMW proteins is an IgE-associated response, involving T-helper cells. This immune mechanism is also known to be relevant to a small number of LMW causes (eg, acid anhydrides and platinum salts), but for the majority, the immune pathways responsible for sensitisation remain to be determined.

• #27 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  Most of HMW and a limited number of LMW agents induce asthma through immunoglobulin E (IgE)-dependent mechanism, while the immunologic pathways involved into the sensitization to LMW agents are poorly understood. HMW agents act as complete antigens and induce the production of specific IgE antibodies, whereas LMW agents act as haptens and bind proteins to form functional antigens. After IgE-cross-linking by the antigen, mast cells release histamine, prostaglandins and cysteinyl-leukotriens. After antigen presentation by dendritic cells, T-lymphocytes differentiate into several subtypes of effector cells. Antigen-activated CD4+ cells can differentiate into Th1-cells which produce interferon-γ and interleukin-2 involved in classical macrophage activation and T lymphocytes differentiation, respectively Th2-cells which release interleukin-4, -5, and -13, activate B-cells, promote IgE-synthesis, recruitment of mast cells, and eosinophilia. Evidence suggests that several LMW agents, such as diisocyanates, can induce innate immune responses by up-regulation/activation of the immune pattern-recognition receptor of monocytes, increasing expression of chemokines that regulate monocyte/macrophage trafficking and the release of important proinflammatory cytokines such as interleukin-1 or interleukin-15. Innate natural killer cells stimulated by interleukin-15 could also release interleukin-13. Even than all the mechanisms involved are not identified, this data suggests a complex collaboration between innate and adaptive immunes systems in the SI-OA pathogenesis.

• #28 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  Most of HMW and a limited number of LMW agents induce asthma through immunoglobulin E (IgE)-dependent mechanism, while the immunologic pathways involved into the sensitization to LMW agents are poorly understood. HMW agents act as complete antigens and induce the production of specific IgE antibodies, whereas LMW agents act as haptens and bind proteins to form functional antigens. After IgE-cross-linking by the antigen, mast cells release histamine, prostaglandins and cysteinyl-leukotriens. After antigen presentation by dendritic cells, T-lymphocytes differentiate into several subtypes of effector cells. Antigen-activated CD4+ cells can differentiate into Th1-cells which produce interferon-γ and interleukin-2 involved in classical macrophage activation and T lymphocytes differentiation, respectively Th2-cells which release interleukin-4, -5, and -13, activate B-cells, promote IgE-synthesis, recruitment of mast cells, and eosinophilia. Evidence suggests that several LMW agents, such as diisocyanates, can induce innate immune responses by up-regulation/activation of the immune pattern-recognition receptor of monocytes, increasing expression of chemokines that regulate monocyte/macrophage trafficking and the release of important proinflammatory cytokines such as interleukin-1 or interleukin-15. Innate natural killer cells stimulated by interleukin-15 could also release interleukin-13. Even than all the mechanisms involved are not identified, this data suggests a complex collaboration between innate and adaptive immunes systems in the SI-OA pathogenesis.

• #29 Pathogenesis and Disease Mechanisms of Occupational Asthma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4683932/

  Although pre-existing airway hyperresponsiveness does not consistently predict development of OA caused by a sensitizer, a link between AHR and active symptoms of OA is firmly established. […] Chronic irreversible airflow obstruction observed in some workers with OA is believed to be associated with airway remodeling. Changes reflecting airway remodeling include loss of ciliated epithelial cells, increased mucus secretion by goblet cells, basement membrane thickening due to subepithelial fibrosis with fibroblast and myelofibroblast activation, and hypertrophy of airway smooth muscle cells. […] Specific IgE mediated sensitization to a workplace antigen accounts for 90% of cases of OA. […] In type I IgE-mediated hypersensitivity reactions, IgE antibodies bind to and cross-link mast cell receptors, leading to degranulation and release of mediators that elicit asthmatic reactions in susceptible individuals.

• #30 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  Most of HMW and a limited number of LMW agents induce asthma through immunoglobulin E (IgE)-dependent mechanism, while the immunologic pathways involved into the sensitization to LMW agents are poorly understood. HMW agents act as complete antigens and induce the production of specific IgE antibodies, whereas LMW agents act as haptens and bind proteins to form functional antigens. After IgE-cross-linking by the antigen, mast cells release histamine, prostaglandins and cysteinyl-leukotriens. After antigen presentation by dendritic cells, T-lymphocytes differentiate into several subtypes of effector cells. Antigen-activated CD4+ cells can differentiate into Th1-cells which produce interferon-γ and interleukin-2 involved in classical macrophage activation and T lymphocytes differentiation, respectively Th2-cells which release interleukin-4, -5, and -13, activate B-cells, promote IgE-synthesis, recruitment of mast cells, and eosinophilia. Evidence suggests that several LMW agents, such as diisocyanates, can induce innate immune responses by up-regulation/activation of the immune pattern-recognition receptor of monocytes, increasing expression of chemokines that regulate monocyte/macrophage trafficking and the release of important proinflammatory cytokines such as interleukin-1 or interleukin-15. Innate natural killer cells stimulated by interleukin-15 could also release interleukin-13. Even than all the mechanisms involved are not identified, this data suggests a complex collaboration between innate and adaptive immunes systems in the SI-OA pathogenesis.

• #31 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  Most of HMW and a limited number of LMW agents induce asthma through immunoglobulin E (IgE)-dependent mechanism, while the immunologic pathways involved into the sensitization to LMW agents are poorly understood. HMW agents act as complete antigens and induce the production of specific IgE antibodies, whereas LMW agents act as haptens and bind proteins to form functional antigens. After IgE-cross-linking by the antigen, mast cells release histamine, prostaglandins and cysteinyl-leukotriens. After antigen presentation by dendritic cells, T-lymphocytes differentiate into several subtypes of effector cells. Antigen-activated CD4+ cells can differentiate into Th1-cells which produce interferon-γ and interleukin-2 involved in classical macrophage activation and T lymphocytes differentiation, respectively Th2-cells which release interleukin-4, -5, and -13, activate B-cells, promote IgE-synthesis, recruitment of mast cells, and eosinophilia. Evidence suggests that several LMW agents, such as diisocyanates, can induce innate immune responses by up-regulation/activation of the immune pattern-recognition receptor of monocytes, increasing expression of chemokines that regulate monocyte/macrophage trafficking and the release of important proinflammatory cytokines such as interleukin-1 or interleukin-15. Innate natural killer cells stimulated by interleukin-15 could also release interleukin-13. Even than all the mechanisms involved are not identified, this data suggests a complex collaboration between innate and adaptive immunes systems in the SI-OA pathogenesis.

• #32 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  Most of HMW and a limited number of LMW agents induce asthma through immunoglobulin E (IgE)-dependent mechanism, while the immunologic pathways involved into the sensitization to LMW agents are poorly understood. HMW agents act as complete antigens and induce the production of specific IgE antibodies, whereas LMW agents act as haptens and bind proteins to form functional antigens. After IgE-cross-linking by the antigen, mast cells release histamine, prostaglandins and cysteinyl-leukotriens. After antigen presentation by dendritic cells, T-lymphocytes differentiate into several subtypes of effector cells. Antigen-activated CD4+ cells can differentiate into Th1-cells which produce interferon-γ and interleukin-2 involved in classical macrophage activation and T lymphocytes differentiation, respectively Th2-cells which release interleukin-4, -5, and -13, activate B-cells, promote IgE-synthesis, recruitment of mast cells, and eosinophilia. Evidence suggests that several LMW agents, such as diisocyanates, can induce innate immune responses by up-regulation/activation of the immune pattern-recognition receptor of monocytes, increasing expression of chemokines that regulate monocyte/macrophage trafficking and the release of important proinflammatory cytokines such as interleukin-1 or interleukin-15. Innate natural killer cells stimulated by interleukin-15 could also release interleukin-13. Even than all the mechanisms involved are not identified, this data suggests a complex collaboration between innate and adaptive immunes systems in the SI-OA pathogenesis.

• #33 Occupational Asthma

  https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/allergy/occupational-asthma/

  Like childhood asthma, OA is the result of interactions between multiple environmental and genetic factors. Some of the known environmental factors include the route, duration, and intensity of exposure, and the substance (or agent) to which the subject is exposed. Using the definition given above, OA can be divided into immunologic causes (associated with a latency period) and nonimmunologic causes. Agents associated with an immunologic cause can be further divided into HMW agents, usually allergens such as proteins from laboratory animals, flour, or plants, or LMW agents, usually chemicals such as isocyanates, biocides, or drugs. […] HMW agents can induce an immunoglobulin E (IgE) response in susceptible individuals and can cause asthma by an IgE-mediated mechanism, similar to that seen in a patient with atopic asthma. The bridging of IgE molecules by antigen leads to mast-cell degranulation and the initiation of an inflammatory cascade that results in airway inflammation and airway hyperresponsiveness. It is therefore not surprising that patients with atopic asthma or patients with a family history of atopy are at increased risk for developing OA from exposure to HMW agents. Smoking is also a risk factor for sensitization.

• #34 Occupational Asthma

  https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/allergy/occupational-asthma/

  Like childhood asthma, OA is the result of interactions between multiple environmental and genetic factors. Some of the known environmental factors include the route, duration, and intensity of exposure, and the substance (or agent) to which the subject is exposed. Using the definition given above, OA can be divided into immunologic causes (associated with a latency period) and nonimmunologic causes. Agents associated with an immunologic cause can be further divided into HMW agents, usually allergens such as proteins from laboratory animals, flour, or plants, or LMW agents, usually chemicals such as isocyanates, biocides, or drugs. […] HMW agents can induce an immunoglobulin E (IgE) response in susceptible individuals and can cause asthma by an IgE-mediated mechanism, similar to that seen in a patient with atopic asthma. The bridging of IgE molecules by antigen leads to mast-cell degranulation and the initiation of an inflammatory cascade that results in airway inflammation and airway hyperresponsiveness. It is therefore not surprising that patients with atopic asthma or patients with a family history of atopy are at increased risk for developing OA from exposure to HMW agents. Smoking is also a risk factor for sensitization.

• #35 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  The most common form of OA is SI-OA, which represents >90% of cases. OA incidence varies between countries and industries. Efforts to identify risk factors to develop OA have been done. The level of exposure to a sensitizing agent is the most recognized environmental risk factor for OA but evidences suggest that occupational exposure to vapors, dust, gas and fumes increases prevalence of asthma. Previous data showed that cigarette smoking increases IgE sensitization to HMW and LMW agents, so smoking could also play a role in the development of OA. Several host factors have been associated with OA. Atopy is a strong risk factor for OA due to HMW agents. Despite the fact that atopy is associated with a high risk for OA in bakers/pastry-makers and hairdressers, the atopic status seems to not precipitate the occurrence of respiratory symptoms in these specific populations. Other evidence suggests that genetic factors including HLA class II polymorphisms contribute to individual susceptibility for OA induced by LMW agents. Despite that currently the utility of these factors in practice to determine the ability of a worker to do a job with a risk of sensitization is limited, the identification of workers at risk according to their individual characteristics and worker’s education about the workplaces with high levels of occupational allergens/irritants represent very important steps in the prevention of OA.

• #36 Occupational Asthma

  https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/allergy/occupational-asthma/

  The pathogenic mechanisms of LMW agents are less well understood; however, there appear to be several mechanisms, both immunologic and nonimmunologic, that can lead to OA. LMW agents probably act as haptens, combining with human proteins in the respiratory tract to become complete immunogens. Atopy and smoking are not risk factors for OA caused by LMW agents as they are for OA caused by HMW agents. Some of the better-studied agents include isocyanates and plicatic acid. Isocyanates are found in paints and are involved in the manufacture of plastics, rubber, and foam, whereas plicatic acid is the causative agent in asthma caused by western red cedar. Specific IgE for isocyanates or plicatic acid is found in only a small percentage of patients with documented disease. However, the detection of specific IgE may be a marker of exposure and not of disease.

• #37 Occupational Asthma (OA)

  https://haz-map.com/OA.htm

  Immunologic asthma develops after a variable period of time during which „sensitization” to an agent present in the workplace takes place. Irritant-induced asthma occurs without a latency period after an intense exposure to an irritating dust, mist, vapor, or fume. The pathophysiologic mechanism underlying irritant-induced asthma is not well understood, and it is not known why the asthmatic response persists in certain individuals. […] An IgE- or IgG-dependent mechanism has not been consistently seen with low-molecular-weight agents (isocyanates, for example). These agents can cause sensitization through a hapten-mediated effect. The role of lymphocytes or other immunologic mechanisms remain unclear.

• #38 Occupational Asthma

  https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/allergy/occupational-asthma/

  The pathogenic mechanisms of LMW agents are less well understood; however, there appear to be several mechanisms, both immunologic and nonimmunologic, that can lead to OA. LMW agents probably act as haptens, combining with human proteins in the respiratory tract to become complete immunogens. Atopy and smoking are not risk factors for OA caused by LMW agents as they are for OA caused by HMW agents. Some of the better-studied agents include isocyanates and plicatic acid. Isocyanates are found in paints and are involved in the manufacture of plastics, rubber, and foam, whereas plicatic acid is the causative agent in asthma caused by western red cedar. Specific IgE for isocyanates or plicatic acid is found in only a small percentage of patients with documented disease. However, the detection of specific IgE may be a marker of exposure and not of disease.

• #39 Occupational asthma in industry | Allergologia et Immunopathologia

  https://www.elsevier.es/en-revista-revista-generica-105-articulo-occupational-asthma-in-industry-13094029

  Occupational asthma remains a minority diagnosis among occupational diseases in general. […] Two groups of asthma are considered, depending on the pathogenic mechanism involved in the development of professional asthma: Inmunologic asthma […] In this form of the disease there is a latency period between occupational exposure and the appearance of asthma. […] Non-Inmunologic asthma […] No latency period is observed in this form of the disease, which is represented by reactive airways dysfunction syndrome (RADS) or, more globally, by irritant-induced asthma. […] The pathogenesis of professional asthma caused by these salts is little known. […] Because of their small size, metal ions are incomplete antigens that must bind to endogenous peptides to become truly antigenic. […] It has been shown that T lymphocyte clones specifically targeted to metal ions recognize haptens in the context of MHC II molecules. […] Concomitant sensitization to different metals is a contrasted clinical observation.

• #40 Pathogenesis and Disease Mechanisms of Occupational Asthma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4683932/

  The main feature of chronic OA caused by the prototypic LMW chemical sensitizer, toluene diisocyanate (TDI), is airway inflammation. […] It is noteworthy that despite the fact that specific IgE is detectable in only a minority of cases of diisocyanate-induced asthma (DA), the histopathologic findings are indistinguishable from those observed in subjects with allergic asthma. […] Alternative mechanisms have been invoked to explain chemically induced OA. Cell mediated immunity or delayed-type hypersensitivity has been postulated as a possible mechanism for isocyanate asthma; however, scientific evidence for this hypothesis is lacking. […] Non adaptive immune responses could play a role in chemically induced OA. Isocyanates may have intrinsic effects resulting in production of pro-inflammatory cytokines.

• #41 Occupational Asthma

  https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/allergy/occupational-asthma/

  The pathogenic mechanisms of LMW agents are less well understood; however, there appear to be several mechanisms, both immunologic and nonimmunologic, that can lead to OA. LMW agents probably act as haptens, combining with human proteins in the respiratory tract to become complete immunogens. Atopy and smoking are not risk factors for OA caused by LMW agents as they are for OA caused by HMW agents. Some of the better-studied agents include isocyanates and plicatic acid. Isocyanates are found in paints and are involved in the manufacture of plastics, rubber, and foam, whereas plicatic acid is the causative agent in asthma caused by western red cedar. Specific IgE for isocyanates or plicatic acid is found in only a small percentage of patients with documented disease. However, the detection of specific IgE may be a marker of exposure and not of disease.

• #42 Occupational Asthma

  https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/allergy/occupational-asthma/

  Activated T cells also play an important role in the pathogenesis and in the inflammation of OA as they do in other forms of asthma. Bronchial biopsies of patients with isocyanate- or red cedar-induced OA show many activated T cells. […] Other mechanisms by which LMW agents cause OA include direct pharmacologic actions of these agents. Isocyanates can block beta 2-adrenergic receptors, and high concentrations of plicatic acid can activate complement. Moreover, isocyanates and other agents can stimulate sensory nerves, leading to the release of substance P and other neuropeptides. They can also inhibit the neutral endopeptidases that normally inactivate these substances. This affects a variety of cells in the airways, resulting in cough, smooth muscle contraction, and mucus production. […] The mechanisms of IrIA or RADS are also poorly understood. IrIA is a nonimmunologically induced asthma that occurs without a latency period. It typically occurs after a brief, high-intensity inhalation exposure followed by the acute onset of persistent respiratory symptoms and ongoing airway hyperresponsiveness. It is postulated that extensive denudation of the airway epithelium occurs, resulting in airway inflammation due to the loss of epithelium-derived relaxing factors, exposure of nerve endings leading to neurogenic inflammation, and nonspecific activation of mast cells with release of inflammatory mediators and cytokines.

• #43 Occupational Asthma

  https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/allergy/occupational-asthma/

  Activated T cells also play an important role in the pathogenesis and in the inflammation of OA as they do in other forms of asthma. Bronchial biopsies of patients with isocyanate- or red cedar-induced OA show many activated T cells. […] Other mechanisms by which LMW agents cause OA include direct pharmacologic actions of these agents. Isocyanates can block beta 2-adrenergic receptors, and high concentrations of plicatic acid can activate complement. Moreover, isocyanates and other agents can stimulate sensory nerves, leading to the release of substance P and other neuropeptides. They can also inhibit the neutral endopeptidases that normally inactivate these substances. This affects a variety of cells in the airways, resulting in cough, smooth muscle contraction, and mucus production. […] The mechanisms of IrIA or RADS are also poorly understood. IrIA is a nonimmunologically induced asthma that occurs without a latency period. It typically occurs after a brief, high-intensity inhalation exposure followed by the acute onset of persistent respiratory symptoms and ongoing airway hyperresponsiveness. It is postulated that extensive denudation of the airway epithelium occurs, resulting in airway inflammation due to the loss of epithelium-derived relaxing factors, exposure of nerve endings leading to neurogenic inflammation, and nonspecific activation of mast cells with release of inflammatory mediators and cytokines.

• #44 Pathogenesis and Disease Mechanisms of Occupational Asthma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4683932/

  The main feature of chronic OA caused by the prototypic LMW chemical sensitizer, toluene diisocyanate (TDI), is airway inflammation. […] It is noteworthy that despite the fact that specific IgE is detectable in only a minority of cases of diisocyanate-induced asthma (DA), the histopathologic findings are indistinguishable from those observed in subjects with allergic asthma. […] Alternative mechanisms have been invoked to explain chemically induced OA. Cell mediated immunity or delayed-type hypersensitivity has been postulated as a possible mechanism for isocyanate asthma; however, scientific evidence for this hypothesis is lacking. […] Non adaptive immune responses could play a role in chemically induced OA. Isocyanates may have intrinsic effects resulting in production of pro-inflammatory cytokines.

• #45 Occupational Asthma

  https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/allergy/occupational-asthma/

  Activated T cells also play an important role in the pathogenesis and in the inflammation of OA as they do in other forms of asthma. Bronchial biopsies of patients with isocyanate- or red cedar-induced OA show many activated T cells. […] Other mechanisms by which LMW agents cause OA include direct pharmacologic actions of these agents. Isocyanates can block beta 2-adrenergic receptors, and high concentrations of plicatic acid can activate complement. Moreover, isocyanates and other agents can stimulate sensory nerves, leading to the release of substance P and other neuropeptides. They can also inhibit the neutral endopeptidases that normally inactivate these substances. This affects a variety of cells in the airways, resulting in cough, smooth muscle contraction, and mucus production. […] The mechanisms of IrIA or RADS are also poorly understood. IrIA is a nonimmunologically induced asthma that occurs without a latency period. It typically occurs after a brief, high-intensity inhalation exposure followed by the acute onset of persistent respiratory symptoms and ongoing airway hyperresponsiveness. It is postulated that extensive denudation of the airway epithelium occurs, resulting in airway inflammation due to the loss of epithelium-derived relaxing factors, exposure of nerve endings leading to neurogenic inflammation, and nonspecific activation of mast cells with release of inflammatory mediators and cytokines.

• #46 Occupational Asthma

  https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/allergy/occupational-asthma/

  Activated T cells also play an important role in the pathogenesis and in the inflammation of OA as they do in other forms of asthma. Bronchial biopsies of patients with isocyanate- or red cedar-induced OA show many activated T cells. […] Other mechanisms by which LMW agents cause OA include direct pharmacologic actions of these agents. Isocyanates can block beta 2-adrenergic receptors, and high concentrations of plicatic acid can activate complement. Moreover, isocyanates and other agents can stimulate sensory nerves, leading to the release of substance P and other neuropeptides. They can also inhibit the neutral endopeptidases that normally inactivate these substances. This affects a variety of cells in the airways, resulting in cough, smooth muscle contraction, and mucus production. […] The mechanisms of IrIA or RADS are also poorly understood. IrIA is a nonimmunologically induced asthma that occurs without a latency period. It typically occurs after a brief, high-intensity inhalation exposure followed by the acute onset of persistent respiratory symptoms and ongoing airway hyperresponsiveness. It is postulated that extensive denudation of the airway epithelium occurs, resulting in airway inflammation due to the loss of epithelium-derived relaxing factors, exposure of nerve endings leading to neurogenic inflammation, and nonspecific activation of mast cells with release of inflammatory mediators and cytokines.

• #47 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  Most of HMW and a limited number of LMW agents induce asthma through immunoglobulin E (IgE)-dependent mechanism, while the immunologic pathways involved into the sensitization to LMW agents are poorly understood. HMW agents act as complete antigens and induce the production of specific IgE antibodies, whereas LMW agents act as haptens and bind proteins to form functional antigens. After IgE-cross-linking by the antigen, mast cells release histamine, prostaglandins and cysteinyl-leukotriens. After antigen presentation by dendritic cells, T-lymphocytes differentiate into several subtypes of effector cells. Antigen-activated CD4+ cells can differentiate into Th1-cells which produce interferon-γ and interleukin-2 involved in classical macrophage activation and T lymphocytes differentiation, respectively Th2-cells which release interleukin-4, -5, and -13, activate B-cells, promote IgE-synthesis, recruitment of mast cells, and eosinophilia. Evidence suggests that several LMW agents, such as diisocyanates, can induce innate immune responses by up-regulation/activation of the immune pattern-recognition receptor of monocytes, increasing expression of chemokines that regulate monocyte/macrophage trafficking and the release of important proinflammatory cytokines such as interleukin-1 or interleukin-15. Innate natural killer cells stimulated by interleukin-15 could also release interleukin-13. Even than all the mechanisms involved are not identified, this data suggests a complex collaboration between innate and adaptive immunes systems in the SI-OA pathogenesis.

• #48 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  Mechanisms of II-OA are poorly understood. Inhalation of irritants can induce bronchial epithelial damage, resulting in proinflammatory responses, neurogenic inflammation due to exposed nerve endings, increased lung permeability, and remodeling of the airway epithelium. Oxidative stress is one of the mechanisms causing the epithelial damage. Inhalation of irritants induces the release of reactive oxygen species and alarmins. Secreted by stimulated epithelial cells, leukocytes and necrotic cells, alarmins promote the activation of innate immune cells and recruitment/activation of antigen-presenting cells involved in tissue repair and host defense through Toll-like receptors. Chemical irritants could also directly activate sensory nerves by stimulating transient receptor potential (TRP) channels followed by the release of neuropeptides triggering neurogenic inflammation with plasma protein extravasation, vasodilatation, bronchoconstriction, and increased mucus secretion.

• #49 Occupational Asthma

  https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/allergy/occupational-asthma/

  Activated T cells also play an important role in the pathogenesis and in the inflammation of OA as they do in other forms of asthma. Bronchial biopsies of patients with isocyanate- or red cedar-induced OA show many activated T cells. […] Other mechanisms by which LMW agents cause OA include direct pharmacologic actions of these agents. Isocyanates can block beta 2-adrenergic receptors, and high concentrations of plicatic acid can activate complement. Moreover, isocyanates and other agents can stimulate sensory nerves, leading to the release of substance P and other neuropeptides. They can also inhibit the neutral endopeptidases that normally inactivate these substances. This affects a variety of cells in the airways, resulting in cough, smooth muscle contraction, and mucus production. […] The mechanisms of IrIA or RADS are also poorly understood. IrIA is a nonimmunologically induced asthma that occurs without a latency period. It typically occurs after a brief, high-intensity inhalation exposure followed by the acute onset of persistent respiratory symptoms and ongoing airway hyperresponsiveness. It is postulated that extensive denudation of the airway epithelium occurs, resulting in airway inflammation due to the loss of epithelium-derived relaxing factors, exposure of nerve endings leading to neurogenic inflammation, and nonspecific activation of mast cells with release of inflammatory mediators and cytokines.

• #50 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  Mechanisms of II-OA are poorly understood. Inhalation of irritants can induce bronchial epithelial damage, resulting in proinflammatory responses, neurogenic inflammation due to exposed nerve endings, increased lung permeability, and remodeling of the airway epithelium. Oxidative stress is one of the mechanisms causing the epithelial damage. Inhalation of irritants induces the release of reactive oxygen species and alarmins. Secreted by stimulated epithelial cells, leukocytes and necrotic cells, alarmins promote the activation of innate immune cells and recruitment/activation of antigen-presenting cells involved in tissue repair and host defense through Toll-like receptors. Chemical irritants could also directly activate sensory nerves by stimulating transient receptor potential (TRP) channels followed by the release of neuropeptides triggering neurogenic inflammation with plasma protein extravasation, vasodilatation, bronchoconstriction, and increased mucus secretion.

• #51 Occupational Asthma

  https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/allergy/occupational-asthma/

  Activated T cells also play an important role in the pathogenesis and in the inflammation of OA as they do in other forms of asthma. Bronchial biopsies of patients with isocyanate- or red cedar-induced OA show many activated T cells. […] Other mechanisms by which LMW agents cause OA include direct pharmacologic actions of these agents. Isocyanates can block beta 2-adrenergic receptors, and high concentrations of plicatic acid can activate complement. Moreover, isocyanates and other agents can stimulate sensory nerves, leading to the release of substance P and other neuropeptides. They can also inhibit the neutral endopeptidases that normally inactivate these substances. This affects a variety of cells in the airways, resulting in cough, smooth muscle contraction, and mucus production. […] The mechanisms of IrIA or RADS are also poorly understood. IrIA is a nonimmunologically induced asthma that occurs without a latency period. It typically occurs after a brief, high-intensity inhalation exposure followed by the acute onset of persistent respiratory symptoms and ongoing airway hyperresponsiveness. It is postulated that extensive denudation of the airway epithelium occurs, resulting in airway inflammation due to the loss of epithelium-derived relaxing factors, exposure of nerve endings leading to neurogenic inflammation, and nonspecific activation of mast cells with release of inflammatory mediators and cytokines.

• #52 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  Mechanisms of II-OA are poorly understood. Inhalation of irritants can induce bronchial epithelial damage, resulting in proinflammatory responses, neurogenic inflammation due to exposed nerve endings, increased lung permeability, and remodeling of the airway epithelium. Oxidative stress is one of the mechanisms causing the epithelial damage. Inhalation of irritants induces the release of reactive oxygen species and alarmins. Secreted by stimulated epithelial cells, leukocytes and necrotic cells, alarmins promote the activation of innate immune cells and recruitment/activation of antigen-presenting cells involved in tissue repair and host defense through Toll-like receptors. Chemical irritants could also directly activate sensory nerves by stimulating transient receptor potential (TRP) channels followed by the release of neuropeptides triggering neurogenic inflammation with plasma protein extravasation, vasodilatation, bronchoconstriction, and increased mucus secretion.

• #53 Occupational Asthma

  https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/allergy/occupational-asthma/

  Activated T cells also play an important role in the pathogenesis and in the inflammation of OA as they do in other forms of asthma. Bronchial biopsies of patients with isocyanate- or red cedar-induced OA show many activated T cells. […] Other mechanisms by which LMW agents cause OA include direct pharmacologic actions of these agents. Isocyanates can block beta 2-adrenergic receptors, and high concentrations of plicatic acid can activate complement. Moreover, isocyanates and other agents can stimulate sensory nerves, leading to the release of substance P and other neuropeptides. They can also inhibit the neutral endopeptidases that normally inactivate these substances. This affects a variety of cells in the airways, resulting in cough, smooth muscle contraction, and mucus production. […] The mechanisms of IrIA or RADS are also poorly understood. IrIA is a nonimmunologically induced asthma that occurs without a latency period. It typically occurs after a brief, high-intensity inhalation exposure followed by the acute onset of persistent respiratory symptoms and ongoing airway hyperresponsiveness. It is postulated that extensive denudation of the airway epithelium occurs, resulting in airway inflammation due to the loss of epithelium-derived relaxing factors, exposure of nerve endings leading to neurogenic inflammation, and nonspecific activation of mast cells with release of inflammatory mediators and cytokines.

• #54 Occupational Asthma

  https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/allergy/occupational-asthma/

  Activated T cells also play an important role in the pathogenesis and in the inflammation of OA as they do in other forms of asthma. Bronchial biopsies of patients with isocyanate- or red cedar-induced OA show many activated T cells. […] Other mechanisms by which LMW agents cause OA include direct pharmacologic actions of these agents. Isocyanates can block beta 2-adrenergic receptors, and high concentrations of plicatic acid can activate complement. Moreover, isocyanates and other agents can stimulate sensory nerves, leading to the release of substance P and other neuropeptides. They can also inhibit the neutral endopeptidases that normally inactivate these substances. This affects a variety of cells in the airways, resulting in cough, smooth muscle contraction, and mucus production. […] The mechanisms of IrIA or RADS are also poorly understood. IrIA is a nonimmunologically induced asthma that occurs without a latency period. It typically occurs after a brief, high-intensity inhalation exposure followed by the acute onset of persistent respiratory symptoms and ongoing airway hyperresponsiveness. It is postulated that extensive denudation of the airway epithelium occurs, resulting in airway inflammation due to the loss of epithelium-derived relaxing factors, exposure of nerve endings leading to neurogenic inflammation, and nonspecific activation of mast cells with release of inflammatory mediators and cytokines.

• #55 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  Mechanisms of II-OA are poorly understood. Inhalation of irritants can induce bronchial epithelial damage, resulting in proinflammatory responses, neurogenic inflammation due to exposed nerve endings, increased lung permeability, and remodeling of the airway epithelium. Oxidative stress is one of the mechanisms causing the epithelial damage. Inhalation of irritants induces the release of reactive oxygen species and alarmins. Secreted by stimulated epithelial cells, leukocytes and necrotic cells, alarmins promote the activation of innate immune cells and recruitment/activation of antigen-presenting cells involved in tissue repair and host defense through Toll-like receptors. Chemical irritants could also directly activate sensory nerves by stimulating transient receptor potential (TRP) channels followed by the release of neuropeptides triggering neurogenic inflammation with plasma protein extravasation, vasodilatation, bronchoconstriction, and increased mucus secretion.

• #56 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  Mechanisms of II-OA are poorly understood. Inhalation of irritants can induce bronchial epithelial damage, resulting in proinflammatory responses, neurogenic inflammation due to exposed nerve endings, increased lung permeability, and remodeling of the airway epithelium. Oxidative stress is one of the mechanisms causing the epithelial damage. Inhalation of irritants induces the release of reactive oxygen species and alarmins. Secreted by stimulated epithelial cells, leukocytes and necrotic cells, alarmins promote the activation of innate immune cells and recruitment/activation of antigen-presenting cells involved in tissue repair and host defense through Toll-like receptors. Chemical irritants could also directly activate sensory nerves by stimulating transient receptor potential (TRP) channels followed by the release of neuropeptides triggering neurogenic inflammation with plasma protein extravasation, vasodilatation, bronchoconstriction, and increased mucus secretion.

• #57 Pathogenesis and Disease Mechanisms of Occupational Asthma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4683932/

  The main feature of chronic OA caused by the prototypic LMW chemical sensitizer, toluene diisocyanate (TDI), is airway inflammation. […] It is noteworthy that despite the fact that specific IgE is detectable in only a minority of cases of diisocyanate-induced asthma (DA), the histopathologic findings are indistinguishable from those observed in subjects with allergic asthma. […] Alternative mechanisms have been invoked to explain chemically induced OA. Cell mediated immunity or delayed-type hypersensitivity has been postulated as a possible mechanism for isocyanate asthma; however, scientific evidence for this hypothesis is lacking. […] Non adaptive immune responses could play a role in chemically induced OA. Isocyanates may have intrinsic effects resulting in production of pro-inflammatory cytokines.

• #58 Asthma (include occupational asthma): Pathogenesis and Epidemiology – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/pulmonary-medicine/asthma-include-occupational-asthma-pathogenesis-and-epidemiology/

  Occupational asthma is defined as asthma triggered by allergens isolated to the work place environment. Once a patient is sensitized to the trigger, very low dose exposures can trigger symptoms, which are often accompanied by allergic rhinitis and conjunctivitis. […] Occupational asthma is an under diagnosed and undertreated clinical entity. About 16% of all adult-onset asthma is attributed to occupational asthma, and it should be considered in all cases of adult-onset asthma. […] The pathophysiology of asthma is characterized by: bronchoconstriction, airway edema, airway hyperresponsiveness, and lastly airway remodeling. […] Airway inflammation is thought to be a major underlying cause of asthma. However, details of the inflammatory process are a source of considerable controversy. […] Chronic inflammation also promotes bronchial hyper-responsiveness, which is the hallmark of asthma.

• #59 Asthma: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/296301-overview

  Pathogenesis of asthma. Antigen presentation by the dendritic cell with the lymphocyte and cytokine response leading to airway inflammation and asthma symptoms. […] The pathophysiology of asthma is complex and involves airway inflammation, intermittent airflow obstruction, and bronchial hyperresponsiveness. The mechanism of inflammation in asthma may be acute, subacute, or chronic, and the presence of airway edema and mucus secretion also contributes to airflow obstruction and bronchial reactivity. Varying degrees of mononuclear cell and eosinophil infiltration, mucus hypersecretion, desquamation of the epithelium, smooth muscle hyperplasia, and airway remodeling are present. […] The presence of airway hyperresponsiveness or bronchial hyperreactivity in asthma is an exaggerated response to numerous exogenous and endogenous stimuli. The mechanisms involved include direct stimulation of airway smooth muscle and indirect stimulation by pharmacologically active substances from mediator-secreting cells such as mast cells or nonmyelinated sensory neurons. The degree of airway hyperresponsiveness generally correlates with the clinical severity of asthma.

• #60 Asthma: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/296301-overview

  Pathogenesis of asthma. Antigen presentation by the dendritic cell with the lymphocyte and cytokine response leading to airway inflammation and asthma symptoms. […] The pathophysiology of asthma is complex and involves airway inflammation, intermittent airflow obstruction, and bronchial hyperresponsiveness. The mechanism of inflammation in asthma may be acute, subacute, or chronic, and the presence of airway edema and mucus secretion also contributes to airflow obstruction and bronchial reactivity. Varying degrees of mononuclear cell and eosinophil infiltration, mucus hypersecretion, desquamation of the epithelium, smooth muscle hyperplasia, and airway remodeling are present. […] The presence of airway hyperresponsiveness or bronchial hyperreactivity in asthma is an exaggerated response to numerous exogenous and endogenous stimuli. The mechanisms involved include direct stimulation of airway smooth muscle and indirect stimulation by pharmacologically active substances from mediator-secreting cells such as mast cells or nonmyelinated sensory neurons. The degree of airway hyperresponsiveness generally correlates with the clinical severity of asthma.

• #61 Asthma: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/296301-overview

  Pathogenesis of asthma. Antigen presentation by the dendritic cell with the lymphocyte and cytokine response leading to airway inflammation and asthma symptoms. […] The pathophysiology of asthma is complex and involves airway inflammation, intermittent airflow obstruction, and bronchial hyperresponsiveness. The mechanism of inflammation in asthma may be acute, subacute, or chronic, and the presence of airway edema and mucus secretion also contributes to airflow obstruction and bronchial reactivity. Varying degrees of mononuclear cell and eosinophil infiltration, mucus hypersecretion, desquamation of the epithelium, smooth muscle hyperplasia, and airway remodeling are present. […] The presence of airway hyperresponsiveness or bronchial hyperreactivity in asthma is an exaggerated response to numerous exogenous and endogenous stimuli. The mechanisms involved include direct stimulation of airway smooth muscle and indirect stimulation by pharmacologically active substances from mediator-secreting cells such as mast cells or nonmyelinated sensory neurons. The degree of airway hyperresponsiveness generally correlates with the clinical severity of asthma.

• #62 Asthma: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/296301-overview

  Pathogenesis of asthma. Antigen presentation by the dendritic cell with the lymphocyte and cytokine response leading to airway inflammation and asthma symptoms. […] The pathophysiology of asthma is complex and involves airway inflammation, intermittent airflow obstruction, and bronchial hyperresponsiveness. The mechanism of inflammation in asthma may be acute, subacute, or chronic, and the presence of airway edema and mucus secretion also contributes to airflow obstruction and bronchial reactivity. Varying degrees of mononuclear cell and eosinophil infiltration, mucus hypersecretion, desquamation of the epithelium, smooth muscle hyperplasia, and airway remodeling are present. […] The presence of airway hyperresponsiveness or bronchial hyperreactivity in asthma is an exaggerated response to numerous exogenous and endogenous stimuli. The mechanisms involved include direct stimulation of airway smooth muscle and indirect stimulation by pharmacologically active substances from mediator-secreting cells such as mast cells or nonmyelinated sensory neurons. The degree of airway hyperresponsiveness generally correlates with the clinical severity of asthma.

• #63 Asthma: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/296301-overview

  Pathogenesis of asthma. Antigen presentation by the dendritic cell with the lymphocyte and cytokine response leading to airway inflammation and asthma symptoms. […] The pathophysiology of asthma is complex and involves airway inflammation, intermittent airflow obstruction, and bronchial hyperresponsiveness. The mechanism of inflammation in asthma may be acute, subacute, or chronic, and the presence of airway edema and mucus secretion also contributes to airflow obstruction and bronchial reactivity. Varying degrees of mononuclear cell and eosinophil infiltration, mucus hypersecretion, desquamation of the epithelium, smooth muscle hyperplasia, and airway remodeling are present. […] The presence of airway hyperresponsiveness or bronchial hyperreactivity in asthma is an exaggerated response to numerous exogenous and endogenous stimuli. The mechanisms involved include direct stimulation of airway smooth muscle and indirect stimulation by pharmacologically active substances from mediator-secreting cells such as mast cells or nonmyelinated sensory neurons. The degree of airway hyperresponsiveness generally correlates with the clinical severity of asthma.

• #64 Diagnosis of Occupational Asthma – Quirce S, Sastre J (Updated 2020)

  https://www.worldallergy.org/component/content/article/diagnosis-of-occupational-asthma-quirce-s-sastre-j-updated-2020?catid=16&Itemid=101

  Exposure to allergens or chemical sensitizers in the workplace often induces eosinophilic inflammation in sensitized subjects, although in some cases neutrophilia has been reported. Although bronchial hyperresponsiveness may provide indirect evidence of airway inflammation, this functional parameter and noninvasive markers of airway inflammation are non-overlapping dimensions. Moreover, some patients may develop eosinophilic bronchitis without asthma, which is a condition presenting with chronic cough and characterized by sputum eosinophilia like asthma, but unlike asthma the patients have no evidence of variable airflow obstruction and bronchial hyperresponsiveness. Thus, the investigation of OA should be complemented with the assessment of the inflammatory component, such as induced sputum parameters. […] Specific inhalation challenges are the „gold standard” in the diagnosis of OA. These tests are indicated in studying new causes of OA and in determining the precise etiologic agent, as well as for research on mechanisms of OA.

• #65 Asthma (include occupational asthma): Pathogenesis and Epidemiology – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/pulmonary-medicine/asthma-include-occupational-asthma-pathogenesis-and-epidemiology/

  Eosinophils are characteristically associated with both allergic disease and asthma. […] Neutrophils appear to play an important role in asthma pathogenesis for some subtypes of the disease. […] Macrophages are important regulatory cells of the innate immune response. […] Mast cells are key mediators of allergic disease and of allergy-associated asthma phenotypes. […] Asthma is considered an atopic disease in about half of all cases, which results in so-called Th2 skewing, a CD4+ profile that favors Th2 over Th1 expression. […] Airway inflammation is believed to underlie bronchial hyper-responsiveness. […] Airways remodeling is a complex process and the driving force behind airway remodeling in asthma remains unclear. […] Regardless of the cause, thickening of the airways combined with increased smooth muscle contraction leads to airway narrowing and obstruction of airflow.

• #66 Asthma (include occupational asthma): Pathogenesis and Epidemiology – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/pulmonary-medicine/asthma-include-occupational-asthma-pathogenesis-and-epidemiology/

  Eosinophils are characteristically associated with both allergic disease and asthma. […] Neutrophils appear to play an important role in asthma pathogenesis for some subtypes of the disease. […] Macrophages are important regulatory cells of the innate immune response. […] Mast cells are key mediators of allergic disease and of allergy-associated asthma phenotypes. […] Asthma is considered an atopic disease in about half of all cases, which results in so-called Th2 skewing, a CD4+ profile that favors Th2 over Th1 expression. […] Airway inflammation is believed to underlie bronchial hyper-responsiveness. […] Airways remodeling is a complex process and the driving force behind airway remodeling in asthma remains unclear. […] Regardless of the cause, thickening of the airways combined with increased smooth muscle contraction leads to airway narrowing and obstruction of airflow.

• #67 Asthma (include occupational asthma): Pathogenesis and Epidemiology – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/pulmonary-medicine/asthma-include-occupational-asthma-pathogenesis-and-epidemiology/

  Eosinophils are characteristically associated with both allergic disease and asthma. […] Neutrophils appear to play an important role in asthma pathogenesis for some subtypes of the disease. […] Macrophages are important regulatory cells of the innate immune response. […] Mast cells are key mediators of allergic disease and of allergy-associated asthma phenotypes. […] Asthma is considered an atopic disease in about half of all cases, which results in so-called Th2 skewing, a CD4+ profile that favors Th2 over Th1 expression. […] Airway inflammation is believed to underlie bronchial hyper-responsiveness. […] Airways remodeling is a complex process and the driving force behind airway remodeling in asthma remains unclear. […] Regardless of the cause, thickening of the airways combined with increased smooth muscle contraction leads to airway narrowing and obstruction of airflow.

• #68 Asthma (include occupational asthma): Pathogenesis and Epidemiology – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/pulmonary-medicine/asthma-include-occupational-asthma-pathogenesis-and-epidemiology/

  Eosinophils are characteristically associated with both allergic disease and asthma. […] Neutrophils appear to play an important role in asthma pathogenesis for some subtypes of the disease. […] Macrophages are important regulatory cells of the innate immune response. […] Mast cells are key mediators of allergic disease and of allergy-associated asthma phenotypes. […] Asthma is considered an atopic disease in about half of all cases, which results in so-called Th2 skewing, a CD4+ profile that favors Th2 over Th1 expression. […] Airway inflammation is believed to underlie bronchial hyper-responsiveness. […] Airways remodeling is a complex process and the driving force behind airway remodeling in asthma remains unclear. […] Regardless of the cause, thickening of the airways combined with increased smooth muscle contraction leads to airway narrowing and obstruction of airflow.

• #69 Asthma (include occupational asthma): Pathogenesis and Epidemiology – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/pulmonary-medicine/asthma-include-occupational-asthma-pathogenesis-and-epidemiology/

  Eosinophils are characteristically associated with both allergic disease and asthma. […] Neutrophils appear to play an important role in asthma pathogenesis for some subtypes of the disease. […] Macrophages are important regulatory cells of the innate immune response. […] Mast cells are key mediators of allergic disease and of allergy-associated asthma phenotypes. […] Asthma is considered an atopic disease in about half of all cases, which results in so-called Th2 skewing, a CD4+ profile that favors Th2 over Th1 expression. […] Airway inflammation is believed to underlie bronchial hyper-responsiveness. […] Airways remodeling is a complex process and the driving force behind airway remodeling in asthma remains unclear. […] Regardless of the cause, thickening of the airways combined with increased smooth muscle contraction leads to airway narrowing and obstruction of airflow.

• #70 Pathogenesis and Disease Mechanisms of Occupational Asthma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4683932/

  A generally accepted definition proposed in an authoritative text, Asthma in the Workplace, has defined OA as variable airflow limitation and/or airway hyperresponsiveness due to exposure to a specific causal agent present in a particular work environment and not to stimuli encountered outside the workplace. […] OA can be further subclassified into two different types: OA appearing after an asymptomatic latent period (during which immune sensitization is thought to develop), including (a) IgE-associated OA typically triggered by high molecular weight (HMW) protein antigens, and (b) IgE-independent OA typically triggered by low molecular weight (LMW) chemicals (isocyanates, red cedar dust). […] Nearly all asthmatics with active symptoms exhibit airway hyperresponsiveness (AHR), an exaggerated response to bronchoconstrictor stimuli, which can be assessed by pharmacologic testing (e.g., methacholine inhalation challenge) or non pharmacologic means (e.g., exercise challenge).

• #71 Asthma: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/296301-overview

  Pathogenesis of asthma. Antigen presentation by the dendritic cell with the lymphocyte and cytokine response leading to airway inflammation and asthma symptoms. […] The pathophysiology of asthma is complex and involves airway inflammation, intermittent airflow obstruction, and bronchial hyperresponsiveness. The mechanism of inflammation in asthma may be acute, subacute, or chronic, and the presence of airway edema and mucus secretion also contributes to airflow obstruction and bronchial reactivity. Varying degrees of mononuclear cell and eosinophil infiltration, mucus hypersecretion, desquamation of the epithelium, smooth muscle hyperplasia, and airway remodeling are present. […] The presence of airway hyperresponsiveness or bronchial hyperreactivity in asthma is an exaggerated response to numerous exogenous and endogenous stimuli. The mechanisms involved include direct stimulation of airway smooth muscle and indirect stimulation by pharmacologically active substances from mediator-secreting cells such as mast cells or nonmyelinated sensory neurons. The degree of airway hyperresponsiveness generally correlates with the clinical severity of asthma.

• #72 Asthma: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/296301-overview

  Pathogenesis of asthma. Antigen presentation by the dendritic cell with the lymphocyte and cytokine response leading to airway inflammation and asthma symptoms. […] The pathophysiology of asthma is complex and involves airway inflammation, intermittent airflow obstruction, and bronchial hyperresponsiveness. The mechanism of inflammation in asthma may be acute, subacute, or chronic, and the presence of airway edema and mucus secretion also contributes to airflow obstruction and bronchial reactivity. Varying degrees of mononuclear cell and eosinophil infiltration, mucus hypersecretion, desquamation of the epithelium, smooth muscle hyperplasia, and airway remodeling are present. […] The presence of airway hyperresponsiveness or bronchial hyperreactivity in asthma is an exaggerated response to numerous exogenous and endogenous stimuli. The mechanisms involved include direct stimulation of airway smooth muscle and indirect stimulation by pharmacologically active substances from mediator-secreting cells such as mast cells or nonmyelinated sensory neurons. The degree of airway hyperresponsiveness generally correlates with the clinical severity of asthma.

• #73 Asthma: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/296301-overview

  Pathogenesis of asthma. Antigen presentation by the dendritic cell with the lymphocyte and cytokine response leading to airway inflammation and asthma symptoms. […] The pathophysiology of asthma is complex and involves airway inflammation, intermittent airflow obstruction, and bronchial hyperresponsiveness. The mechanism of inflammation in asthma may be acute, subacute, or chronic, and the presence of airway edema and mucus secretion also contributes to airflow obstruction and bronchial reactivity. Varying degrees of mononuclear cell and eosinophil infiltration, mucus hypersecretion, desquamation of the epithelium, smooth muscle hyperplasia, and airway remodeling are present. […] The presence of airway hyperresponsiveness or bronchial hyperreactivity in asthma is an exaggerated response to numerous exogenous and endogenous stimuli. The mechanisms involved include direct stimulation of airway smooth muscle and indirect stimulation by pharmacologically active substances from mediator-secreting cells such as mast cells or nonmyelinated sensory neurons. The degree of airway hyperresponsiveness generally correlates with the clinical severity of asthma.

• #74 Pathogenesis and Disease Mechanisms of Occupational Asthma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4683932/

  Although the respiratory tract has been the focus of most studies on occupational asthma, evidence is accumulating that the skin may also play an important role in pathogenesis, as an exposure route for initiating immune sensitization. […] While the immune system clearly plays an important role in occupational asthma, it has been suggested that this response is a secondary phenomenon, rather than the underlying cause of disease. […] It is theorized that the primary defect in asthma may relate to impaired barrier function of the epithelium, which allows greater access of environmental allergens, microorganisms, and toxicants, which in turn trigger allergic-type inflammation. […] The airway epithelium constitutes the interface between the internal milieu of the lung and the external environment.

• #75 Pathogenesis and Disease Mechanisms of Occupational Asthma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4683932/

  Although the respiratory tract has been the focus of most studies on occupational asthma, evidence is accumulating that the skin may also play an important role in pathogenesis, as an exposure route for initiating immune sensitization. […] While the immune system clearly plays an important role in occupational asthma, it has been suggested that this response is a secondary phenomenon, rather than the underlying cause of disease. […] It is theorized that the primary defect in asthma may relate to impaired barrier function of the epithelium, which allows greater access of environmental allergens, microorganisms, and toxicants, which in turn trigger allergic-type inflammation. […] The airway epithelium constitutes the interface between the internal milieu of the lung and the external environment.

• #76 Pathogenesis and Disease Mechanisms of Occupational Asthma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4683932/

  It has been postulated that when epithelial injury and repair becomes a chronic cycle, the structure of the airway wall may become remodeled, further increasing the opportunity for tissue penetration by allergens/toxins/viruses. […] Many of the compounds that cause occupational asthma are cytotoxic at relatively low doses, including the low molecular weight chemicals, isocyanates, acid anhydrides, acrylates and certain metals. […] A number of different studies provide evidence of increased oxidative stress during asthma, both locally within the airways, as well as systemically. […] Thiols, especially glutathione, play a major role in protecting the airway against oxidant damage. […] The airway wall is entwined with fibers from neurons, some of which penetrate the basement membrane, reaching into the epithelial cell layer, where they sense external signals via specific receptors, and secrete factors capable of eliciting inflammation and bronchoconstriction.

• #77 Pathogenesis and Disease Mechanisms of Occupational Asthma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4683932/

  It has been postulated that when epithelial injury and repair becomes a chronic cycle, the structure of the airway wall may become remodeled, further increasing the opportunity for tissue penetration by allergens/toxins/viruses. […] Many of the compounds that cause occupational asthma are cytotoxic at relatively low doses, including the low molecular weight chemicals, isocyanates, acid anhydrides, acrylates and certain metals. […] A number of different studies provide evidence of increased oxidative stress during asthma, both locally within the airways, as well as systemically. […] Thiols, especially glutathione, play a major role in protecting the airway against oxidant damage. […] The airway wall is entwined with fibers from neurons, some of which penetrate the basement membrane, reaching into the epithelial cell layer, where they sense external signals via specific receptors, and secrete factors capable of eliciting inflammation and bronchoconstriction.

• #78 Pathogenesis and Disease Mechanisms of Occupational Asthma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4683932/

  It has been postulated that when epithelial injury and repair becomes a chronic cycle, the structure of the airway wall may become remodeled, further increasing the opportunity for tissue penetration by allergens/toxins/viruses. […] Many of the compounds that cause occupational asthma are cytotoxic at relatively low doses, including the low molecular weight chemicals, isocyanates, acid anhydrides, acrylates and certain metals. […] A number of different studies provide evidence of increased oxidative stress during asthma, both locally within the airways, as well as systemically. […] Thiols, especially glutathione, play a major role in protecting the airway against oxidant damage. […] The airway wall is entwined with fibers from neurons, some of which penetrate the basement membrane, reaching into the epithelial cell layer, where they sense external signals via specific receptors, and secrete factors capable of eliciting inflammation and bronchoconstriction.

• #79 Pathogenesis and Disease Mechanisms of Occupational Asthma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4683932/

  It has been postulated that when epithelial injury and repair becomes a chronic cycle, the structure of the airway wall may become remodeled, further increasing the opportunity for tissue penetration by allergens/toxins/viruses. […] Many of the compounds that cause occupational asthma are cytotoxic at relatively low doses, including the low molecular weight chemicals, isocyanates, acid anhydrides, acrylates and certain metals. […] A number of different studies provide evidence of increased oxidative stress during asthma, both locally within the airways, as well as systemically. […] Thiols, especially glutathione, play a major role in protecting the airway against oxidant damage. […] The airway wall is entwined with fibers from neurons, some of which penetrate the basement membrane, reaching into the epithelial cell layer, where they sense external signals via specific receptors, and secrete factors capable of eliciting inflammation and bronchoconstriction.

• #80 Pathogenesis and Disease Mechanisms of Occupational Asthma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4683932/

  It has been postulated that when epithelial injury and repair becomes a chronic cycle, the structure of the airway wall may become remodeled, further increasing the opportunity for tissue penetration by allergens/toxins/viruses. […] Many of the compounds that cause occupational asthma are cytotoxic at relatively low doses, including the low molecular weight chemicals, isocyanates, acid anhydrides, acrylates and certain metals. […] A number of different studies provide evidence of increased oxidative stress during asthma, both locally within the airways, as well as systemically. […] Thiols, especially glutathione, play a major role in protecting the airway against oxidant damage. […] The airway wall is entwined with fibers from neurons, some of which penetrate the basement membrane, reaching into the epithelial cell layer, where they sense external signals via specific receptors, and secrete factors capable of eliciting inflammation and bronchoconstriction.

• #81 Pathogenesis and Disease Mechanisms of Occupational Asthma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4683932/

  Although the respiratory tract has been the focus of most studies on occupational asthma, evidence is accumulating that the skin may also play an important role in pathogenesis, as an exposure route for initiating immune sensitization. […] While the immune system clearly plays an important role in occupational asthma, it has been suggested that this response is a secondary phenomenon, rather than the underlying cause of disease. […] It is theorized that the primary defect in asthma may relate to impaired barrier function of the epithelium, which allows greater access of environmental allergens, microorganisms, and toxicants, which in turn trigger allergic-type inflammation. […] The airway epithelium constitutes the interface between the internal milieu of the lung and the external environment.

• #82 Diagnosis of Occupational Asthma – Quirce S, Sastre J (Updated 2020)

  https://www.worldallergy.org/component/content/article/diagnosis-of-occupational-asthma-quirce-s-sastre-j-updated-2020?catid=16&Itemid=101

  Occupational allergy refers to those disorders or conditions that are caused by exposure to allergenic substances in the work environment. The allergic diseases that may be contracted as a consequence of exposure to sensitizing agents in the workplace are rhinitis, conjunctivitis, asthma, hypersensitivity pneumonitis and skin diseases, such as contact urticaria and contact dermatitis. Different immunologic mechanisms may underlie these disorders. Occupational rhinitis and occupational asthma (OA) are usually due to an allergic response to high or low molecular weight agents, either through the interaction with specific IgE antibodies or by other immune mechanisms. These allergic events lead to chronic and acute airway inflammation. Less commonly, OA can result from high level irritant exposures at work. OA is included into a wider term call work-related asthma.

• #83 Pathogenesis and Disease Mechanisms of Occupational Asthma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4683932/

  OA syndromes, like non-occupational asthma, are likely polygenic disorders. […] Specific genes that contribute to OA has been challenging because study populations are relatively smaller than those needed for genetic association studies. […] The clinical management of patients with OA depends on an understanding of the multifactorial pathogenetic mechanisms that can contribute to this disease.

• #84 Pathogenesis and Disease Mechanisms of Occupational Asthma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4683932/

  OA syndromes, like non-occupational asthma, are likely polygenic disorders. […] Specific genes that contribute to OA has been challenging because study populations are relatively smaller than those needed for genetic association studies. […] The clinical management of patients with OA depends on an understanding of the multifactorial pathogenetic mechanisms that can contribute to this disease.

• #85 British Thoracic Society Clinical Statement on occupational asthma | Thorax

  https://thorax.bmj.com/content/77/5/433

  Whatever the underlying mechanism, OA due to allergic sensitisation requires a period of repeated allergen exposure, the duration of time between first exposure and symptom onset being referred to as the latent period. […] The most important risk factor for the development of OA (and the preceding allergic sensitisation) is the level of exposure to the cause. […] In addition, individual susceptibility plays an important role, as only a proportion of similarly exposed workers become sensitised, and only some of these will ever develop OA.

• #86 Occupational Asthma

  https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/allergy/occupational-asthma/

  Like childhood asthma, OA is the result of interactions between multiple environmental and genetic factors. Some of the known environmental factors include the route, duration, and intensity of exposure, and the substance (or agent) to which the subject is exposed. Using the definition given above, OA can be divided into immunologic causes (associated with a latency period) and nonimmunologic causes. Agents associated with an immunologic cause can be further divided into HMW agents, usually allergens such as proteins from laboratory animals, flour, or plants, or LMW agents, usually chemicals such as isocyanates, biocides, or drugs. […] HMW agents can induce an immunoglobulin E (IgE) response in susceptible individuals and can cause asthma by an IgE-mediated mechanism, similar to that seen in a patient with atopic asthma. The bridging of IgE molecules by antigen leads to mast-cell degranulation and the initiation of an inflammatory cascade that results in airway inflammation and airway hyperresponsiveness. It is therefore not surprising that patients with atopic asthma or patients with a family history of atopy are at increased risk for developing OA from exposure to HMW agents. Smoking is also a risk factor for sensitization.

• #87 Occupational Asthma

  https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/allergy/occupational-asthma/

  The pathogenic mechanisms of LMW agents are less well understood; however, there appear to be several mechanisms, both immunologic and nonimmunologic, that can lead to OA. LMW agents probably act as haptens, combining with human proteins in the respiratory tract to become complete immunogens. Atopy and smoking are not risk factors for OA caused by LMW agents as they are for OA caused by HMW agents. Some of the better-studied agents include isocyanates and plicatic acid. Isocyanates are found in paints and are involved in the manufacture of plastics, rubber, and foam, whereas plicatic acid is the causative agent in asthma caused by western red cedar. Specific IgE for isocyanates or plicatic acid is found in only a small percentage of patients with documented disease. However, the detection of specific IgE may be a marker of exposure and not of disease.

• #88 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  The most common form of OA is SI-OA, which represents >90% of cases. OA incidence varies between countries and industries. Efforts to identify risk factors to develop OA have been done. The level of exposure to a sensitizing agent is the most recognized environmental risk factor for OA but evidences suggest that occupational exposure to vapors, dust, gas and fumes increases prevalence of asthma. Previous data showed that cigarette smoking increases IgE sensitization to HMW and LMW agents, so smoking could also play a role in the development of OA. Several host factors have been associated with OA. Atopy is a strong risk factor for OA due to HMW agents. Despite the fact that atopy is associated with a high risk for OA in bakers/pastry-makers and hairdressers, the atopic status seems to not precipitate the occurrence of respiratory symptoms in these specific populations. Other evidence suggests that genetic factors including HLA class II polymorphisms contribute to individual susceptibility for OA induced by LMW agents. Despite that currently the utility of these factors in practice to determine the ability of a worker to do a job with a risk of sensitization is limited, the identification of workers at risk according to their individual characteristics and worker’s education about the workplaces with high levels of occupational allergens/irritants represent very important steps in the prevention of OA.

• #89 Occupational Asthma

  https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/allergy/occupational-asthma/

  Like childhood asthma, OA is the result of interactions between multiple environmental and genetic factors. Some of the known environmental factors include the route, duration, and intensity of exposure, and the substance (or agent) to which the subject is exposed. Using the definition given above, OA can be divided into immunologic causes (associated with a latency period) and nonimmunologic causes. Agents associated with an immunologic cause can be further divided into HMW agents, usually allergens such as proteins from laboratory animals, flour, or plants, or LMW agents, usually chemicals such as isocyanates, biocides, or drugs. […] HMW agents can induce an immunoglobulin E (IgE) response in susceptible individuals and can cause asthma by an IgE-mediated mechanism, similar to that seen in a patient with atopic asthma. The bridging of IgE molecules by antigen leads to mast-cell degranulation and the initiation of an inflammatory cascade that results in airway inflammation and airway hyperresponsiveness. It is therefore not surprising that patients with atopic asthma or patients with a family history of atopy are at increased risk for developing OA from exposure to HMW agents. Smoking is also a risk factor for sensitization.

• #90 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  The most common form of OA is SI-OA, which represents >90% of cases. OA incidence varies between countries and industries. Efforts to identify risk factors to develop OA have been done. The level of exposure to a sensitizing agent is the most recognized environmental risk factor for OA but evidences suggest that occupational exposure to vapors, dust, gas and fumes increases prevalence of asthma. Previous data showed that cigarette smoking increases IgE sensitization to HMW and LMW agents, so smoking could also play a role in the development of OA. Several host factors have been associated with OA. Atopy is a strong risk factor for OA due to HMW agents. Despite the fact that atopy is associated with a high risk for OA in bakers/pastry-makers and hairdressers, the atopic status seems to not precipitate the occurrence of respiratory symptoms in these specific populations. Other evidence suggests that genetic factors including HLA class II polymorphisms contribute to individual susceptibility for OA induced by LMW agents. Despite that currently the utility of these factors in practice to determine the ability of a worker to do a job with a risk of sensitization is limited, the identification of workers at risk according to their individual characteristics and worker’s education about the workplaces with high levels of occupational allergens/irritants represent very important steps in the prevention of OA.

• #91 Work-Related Asthma | AAFP

  https://www.aafp.org/pubs/afp/issues/2001/1201/p1839.html

  The capacity for irritant substances to cause reactive airway dysfunction syndrome depends on their corrosive properties, reactivity, and water solubility. The chemical structure of an agent may be the determining factor in its potential to sensitize. […] The determinants for individual susceptibility are largely unknown. A number of studies have identified an association between several human leukocyte antigen class II molecules and the risk of developing allergic occupational asthma following exposure to LMW substances.

• #92

  https://grantome.com/grant/NIH/F30-ES024622-02

  10-25% of adult asthma is occupation-induced, a subtype caused by exposure to environmental irritants in the workplace. […] Recently, a genome-wide association study (GWAS) identified single nucleotide polymorphisms (SNPs) in ?-T-catenin (?-T-cat) that correlated with the incidence and severity of toluene diisocyanate (TDI) occupational asthma. […] We suspect ?-T-cat dysfunction may contribute to asthma through a cardiac cell defect that leads to increased airway edema. […] Together, these findings suggest that cardiac cell junction dysfunction may underlie occupational asthma. This is a novel mechanism and contributor to the pathogenesis of asthma, which has long been considered primarily a disease mediated by inflammation. […] The pathogenesis of occupational asthma has been linked to mutations in the cardiac cell adhesion protein ?-T-cat.

• #93

  https://grantome.com/grant/NIH/F30-ES024622-02

  10-25% of adult asthma is occupation-induced, a subtype caused by exposure to environmental irritants in the workplace. […] Recently, a genome-wide association study (GWAS) identified single nucleotide polymorphisms (SNPs) in ?-T-catenin (?-T-cat) that correlated with the incidence and severity of toluene diisocyanate (TDI) occupational asthma. […] We suspect ?-T-cat dysfunction may contribute to asthma through a cardiac cell defect that leads to increased airway edema. […] Together, these findings suggest that cardiac cell junction dysfunction may underlie occupational asthma. This is a novel mechanism and contributor to the pathogenesis of asthma, which has long been considered primarily a disease mediated by inflammation. […] The pathogenesis of occupational asthma has been linked to mutations in the cardiac cell adhesion protein ?-T-cat.

• #94 Pathogenesis and Disease Mechanisms of Occupational Asthma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4683932/

  Although pre-existing airway hyperresponsiveness does not consistently predict development of OA caused by a sensitizer, a link between AHR and active symptoms of OA is firmly established. […] Chronic irreversible airflow obstruction observed in some workers with OA is believed to be associated with airway remodeling. Changes reflecting airway remodeling include loss of ciliated epithelial cells, increased mucus secretion by goblet cells, basement membrane thickening due to subepithelial fibrosis with fibroblast and myelofibroblast activation, and hypertrophy of airway smooth muscle cells. […] Specific IgE mediated sensitization to a workplace antigen accounts for 90% of cases of OA. […] In type I IgE-mediated hypersensitivity reactions, IgE antibodies bind to and cross-link mast cell receptors, leading to degranulation and release of mediators that elicit asthmatic reactions in susceptible individuals.

• #95 Pathogenesis and Disease Mechanisms of Occupational Asthma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4683932/

  Although pre-existing airway hyperresponsiveness does not consistently predict development of OA caused by a sensitizer, a link between AHR and active symptoms of OA is firmly established. […] Chronic irreversible airflow obstruction observed in some workers with OA is believed to be associated with airway remodeling. Changes reflecting airway remodeling include loss of ciliated epithelial cells, increased mucus secretion by goblet cells, basement membrane thickening due to subepithelial fibrosis with fibroblast and myelofibroblast activation, and hypertrophy of airway smooth muscle cells. […] Specific IgE mediated sensitization to a workplace antigen accounts for 90% of cases of OA. […] In type I IgE-mediated hypersensitivity reactions, IgE antibodies bind to and cross-link mast cell receptors, leading to degranulation and release of mediators that elicit asthmatic reactions in susceptible individuals.

• #96 Pathogenesis and Disease Mechanisms of Occupational Asthma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4683932/

  Although pre-existing airway hyperresponsiveness does not consistently predict development of OA caused by a sensitizer, a link between AHR and active symptoms of OA is firmly established. […] Chronic irreversible airflow obstruction observed in some workers with OA is believed to be associated with airway remodeling. Changes reflecting airway remodeling include loss of ciliated epithelial cells, increased mucus secretion by goblet cells, basement membrane thickening due to subepithelial fibrosis with fibroblast and myelofibroblast activation, and hypertrophy of airway smooth muscle cells. […] Specific IgE mediated sensitization to a workplace antigen accounts for 90% of cases of OA. […] In type I IgE-mediated hypersensitivity reactions, IgE antibodies bind to and cross-link mast cell receptors, leading to degranulation and release of mediators that elicit asthmatic reactions in susceptible individuals.

• #97 Pathogenesis and Disease Mechanisms of Occupational Asthma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4683932/

  Although pre-existing airway hyperresponsiveness does not consistently predict development of OA caused by a sensitizer, a link between AHR and active symptoms of OA is firmly established. […] Chronic irreversible airflow obstruction observed in some workers with OA is believed to be associated with airway remodeling. Changes reflecting airway remodeling include loss of ciliated epithelial cells, increased mucus secretion by goblet cells, basement membrane thickening due to subepithelial fibrosis with fibroblast and myelofibroblast activation, and hypertrophy of airway smooth muscle cells. […] Specific IgE mediated sensitization to a workplace antigen accounts for 90% of cases of OA. […] In type I IgE-mediated hypersensitivity reactions, IgE antibodies bind to and cross-link mast cell receptors, leading to degranulation and release of mediators that elicit asthmatic reactions in susceptible individuals.

• #98 Pathogenesis and Disease Mechanisms of Occupational Asthma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4683932/

  Although pre-existing airway hyperresponsiveness does not consistently predict development of OA caused by a sensitizer, a link between AHR and active symptoms of OA is firmly established. […] Chronic irreversible airflow obstruction observed in some workers with OA is believed to be associated with airway remodeling. Changes reflecting airway remodeling include loss of ciliated epithelial cells, increased mucus secretion by goblet cells, basement membrane thickening due to subepithelial fibrosis with fibroblast and myelofibroblast activation, and hypertrophy of airway smooth muscle cells. […] Specific IgE mediated sensitization to a workplace antigen accounts for 90% of cases of OA. […] In type I IgE-mediated hypersensitivity reactions, IgE antibodies bind to and cross-link mast cell receptors, leading to degranulation and release of mediators that elicit asthmatic reactions in susceptible individuals.

• #99 Asthma (include occupational asthma): Pathogenesis and Epidemiology – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/pulmonary-medicine/asthma-include-occupational-asthma-pathogenesis-and-epidemiology/

  Eosinophils are characteristically associated with both allergic disease and asthma. […] Neutrophils appear to play an important role in asthma pathogenesis for some subtypes of the disease. […] Macrophages are important regulatory cells of the innate immune response. […] Mast cells are key mediators of allergic disease and of allergy-associated asthma phenotypes. […] Asthma is considered an atopic disease in about half of all cases, which results in so-called Th2 skewing, a CD4+ profile that favors Th2 over Th1 expression. […] Airway inflammation is believed to underlie bronchial hyper-responsiveness. […] Airways remodeling is a complex process and the driving force behind airway remodeling in asthma remains unclear. […] Regardless of the cause, thickening of the airways combined with increased smooth muscle contraction leads to airway narrowing and obstruction of airflow.

• #100 Asthma (include occupational asthma): Pathogenesis and Epidemiology – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/pulmonary-medicine/asthma-include-occupational-asthma-pathogenesis-and-epidemiology/

  Eosinophils are characteristically associated with both allergic disease and asthma. […] Neutrophils appear to play an important role in asthma pathogenesis for some subtypes of the disease. […] Macrophages are important regulatory cells of the innate immune response. […] Mast cells are key mediators of allergic disease and of allergy-associated asthma phenotypes. […] Asthma is considered an atopic disease in about half of all cases, which results in so-called Th2 skewing, a CD4+ profile that favors Th2 over Th1 expression. […] Airway inflammation is believed to underlie bronchial hyper-responsiveness. […] Airways remodeling is a complex process and the driving force behind airway remodeling in asthma remains unclear. […] Regardless of the cause, thickening of the airways combined with increased smooth muscle contraction leads to airway narrowing and obstruction of airflow.

• #101 Asthma: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/296301-overview

  Chronic inflammation of the airways is associated with increased bronchial hyperresponsiveness, which leads to bronchospasm and typical symptoms of wheezing, shortness of breath, and coughing after exposure to allergens, environmental irritants, viruses, cold air, or exercise. In some patients with chronic asthma, airflow limitation may be only partially reversible because of airway remodeling (hypertrophy and hyperplasia of smooth muscle, angiogenesis, and subepithelial fibrosis) that occurs with chronic untreated disease. […] Airflow obstruction can be caused by a variety of changes, including acute bronchoconstriction, airway edema, chronic mucous plug formation, and airway remodeling. Acute bronchoconstriction is the consequence of immunoglobulin E-dependent mediator release upon exposure to aeroallergens and is the primary component of the early asthmatic response. Airway edema occurs 6-24 hours following an allergen challenge and is referred to as the late asthmatic response. Chronic mucous plug formation consists of an exudate of serum proteins and cell debris that may take weeks to resolve. Airway remodeling is associated with structural changes due to long-standing inflammation and may profoundly affect the extent of reversibility of airway obstruction.

• #102 Asthma: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/296301-overview

  Chronic inflammation of the airways is associated with increased bronchial hyperresponsiveness, which leads to bronchospasm and typical symptoms of wheezing, shortness of breath, and coughing after exposure to allergens, environmental irritants, viruses, cold air, or exercise. In some patients with chronic asthma, airflow limitation may be only partially reversible because of airway remodeling (hypertrophy and hyperplasia of smooth muscle, angiogenesis, and subepithelial fibrosis) that occurs with chronic untreated disease. […] Airflow obstruction can be caused by a variety of changes, including acute bronchoconstriction, airway edema, chronic mucous plug formation, and airway remodeling. Acute bronchoconstriction is the consequence of immunoglobulin E-dependent mediator release upon exposure to aeroallergens and is the primary component of the early asthmatic response. Airway edema occurs 6-24 hours following an allergen challenge and is referred to as the late asthmatic response. Chronic mucous plug formation consists of an exudate of serum proteins and cell debris that may take weeks to resolve. Airway remodeling is associated with structural changes due to long-standing inflammation and may profoundly affect the extent of reversibility of airway obstruction.

• #103 Pathogenesis and Disease Mechanisms of Occupational Asthma

  https://stacks.cdc.gov/view/cdc/36914

  Occupational asthma (OA) is one of the most common forms of work-related lung disease in all industrialized nations. […] The clinical management of patients with OA depends on an understanding of the multifactorial pathogenetic mechanisms that can contribute to this disease. […] This article discusses the various immunologic and nonimmunologic mechanisms and genetic susceptibility factors that drive the inflammatory processes of OA.

• #104 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  The best diagnostic approach for OA is to combine a detailed clinical history with objective diagnostic tests. The latter include evidence for work-related changes in the airways—peak expiratory flow (PEF), non-specific BHR, sputum eosinophil count, FeNO and/or evidence for specific sensitization—SPT, sIgE, SIC, and basophil activation test. In the differential diagnosis, it is important to consider other conditions that can mimic asthma symptoms following exposure to irritants in the workplace. […] SIC is considered to be the gold standard for confirmation of OA. It mimics the workplace exposure in a controlled environment. SIC should be conducted in hospital-based specialised centers, by trained personnel and closely supervised by physicians with expertise in the field and able to manage acute asthmatic or anaphylactic reactions.

• #105 Occupational asthma in industry | Allergologia et Immunopathologia

  https://www.elsevier.es/en-revista-revista-generica-105-articulo-occupational-asthma-in-industry-13094029

  Occupational or professional asthma is defined as adult asthma, i.e., an inflammatory respiratory disease characterized by the presence of variable airflow limitation or bronchial hyperreactivity secondary to conditions and causes associated with a given occupational or working environment not with stimuli found outside the workplace. […] Depending on the physiopathological mechanism involved, a distinction is made between immune asthma (with or without IgE mediation) and non-immune asthma. […] Guided compilation of the case history and measurement of nonspecific bronchial hyperreactivity and bronchial inflammation are currently essential in the diagnostic approach to occupational asthma. […] Whenever possible, allergists should establish the cause-effect relationship in occupational asthma, as required by the medical-legal and social implications of the disease.

• #106 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  The best diagnostic approach for OA is to combine a detailed clinical history with objective diagnostic tests. The latter include evidence for work-related changes in the airways—peak expiratory flow (PEF), non-specific BHR, sputum eosinophil count, FeNO and/or evidence for specific sensitization—SPT, sIgE, SIC, and basophil activation test. In the differential diagnosis, it is important to consider other conditions that can mimic asthma symptoms following exposure to irritants in the workplace. […] SIC is considered to be the gold standard for confirmation of OA. It mimics the workplace exposure in a controlled environment. SIC should be conducted in hospital-based specialised centers, by trained personnel and closely supervised by physicians with expertise in the field and able to manage acute asthmatic or anaphylactic reactions.

• #107 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  The best diagnostic approach for OA is to combine a detailed clinical history with objective diagnostic tests. The latter include evidence for work-related changes in the airways—peak expiratory flow (PEF), non-specific BHR, sputum eosinophil count, FeNO and/or evidence for specific sensitization—SPT, sIgE, SIC, and basophil activation test. In the differential diagnosis, it is important to consider other conditions that can mimic asthma symptoms following exposure to irritants in the workplace. […] SIC is considered to be the gold standard for confirmation of OA. It mimics the workplace exposure in a controlled environment. SIC should be conducted in hospital-based specialised centers, by trained personnel and closely supervised by physicians with expertise in the field and able to manage acute asthmatic or anaphylactic reactions.

• #108 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  The best diagnostic approach for OA is to combine a detailed clinical history with objective diagnostic tests. The latter include evidence for work-related changes in the airways—peak expiratory flow (PEF), non-specific BHR, sputum eosinophil count, FeNO and/or evidence for specific sensitization—SPT, sIgE, SIC, and basophil activation test. In the differential diagnosis, it is important to consider other conditions that can mimic asthma symptoms following exposure to irritants in the workplace. […] SIC is considered to be the gold standard for confirmation of OA. It mimics the workplace exposure in a controlled environment. SIC should be conducted in hospital-based specialised centers, by trained personnel and closely supervised by physicians with expertise in the field and able to manage acute asthmatic or anaphylactic reactions.

• #109 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  The best diagnostic approach for OA is to combine a detailed clinical history with objective diagnostic tests. The latter include evidence for work-related changes in the airways—peak expiratory flow (PEF), non-specific BHR, sputum eosinophil count, FeNO and/or evidence for specific sensitization—SPT, sIgE, SIC, and basophil activation test. In the differential diagnosis, it is important to consider other conditions that can mimic asthma symptoms following exposure to irritants in the workplace. […] SIC is considered to be the gold standard for confirmation of OA. It mimics the workplace exposure in a controlled environment. SIC should be conducted in hospital-based specialised centers, by trained personnel and closely supervised by physicians with expertise in the field and able to manage acute asthmatic or anaphylactic reactions.

• #110 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  The best diagnostic approach for OA is to combine a detailed clinical history with objective diagnostic tests. The latter include evidence for work-related changes in the airways—peak expiratory flow (PEF), non-specific BHR, sputum eosinophil count, FeNO and/or evidence for specific sensitization—SPT, sIgE, SIC, and basophil activation test. In the differential diagnosis, it is important to consider other conditions that can mimic asthma symptoms following exposure to irritants in the workplace. […] SIC is considered to be the gold standard for confirmation of OA. It mimics the workplace exposure in a controlled environment. SIC should be conducted in hospital-based specialised centers, by trained personnel and closely supervised by physicians with expertise in the field and able to manage acute asthmatic or anaphylactic reactions.

• #111 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  The best diagnostic approach for OA is to combine a detailed clinical history with objective diagnostic tests. The latter include evidence for work-related changes in the airways—peak expiratory flow (PEF), non-specific BHR, sputum eosinophil count, FeNO and/or evidence for specific sensitization—SPT, sIgE, SIC, and basophil activation test. In the differential diagnosis, it is important to consider other conditions that can mimic asthma symptoms following exposure to irritants in the workplace. […] SIC is considered to be the gold standard for confirmation of OA. It mimics the workplace exposure in a controlled environment. SIC should be conducted in hospital-based specialised centers, by trained personnel and closely supervised by physicians with expertise in the field and able to manage acute asthmatic or anaphylactic reactions.

• #112 Diagnosis of Occupational Asthma – Quirce S, Sastre J (Updated 2020)

  https://www.worldallergy.org/component/content/article/diagnosis-of-occupational-asthma-quirce-s-sastre-j-updated-2020?catid=16&Itemid=101

  Exposure to allergens or chemical sensitizers in the workplace often induces eosinophilic inflammation in sensitized subjects, although in some cases neutrophilia has been reported. Although bronchial hyperresponsiveness may provide indirect evidence of airway inflammation, this functional parameter and noninvasive markers of airway inflammation are non-overlapping dimensions. Moreover, some patients may develop eosinophilic bronchitis without asthma, which is a condition presenting with chronic cough and characterized by sputum eosinophilia like asthma, but unlike asthma the patients have no evidence of variable airflow obstruction and bronchial hyperresponsiveness. Thus, the investigation of OA should be complemented with the assessment of the inflammatory component, such as induced sputum parameters. […] Specific inhalation challenges are the „gold standard” in the diagnosis of OA. These tests are indicated in studying new causes of OA and in determining the precise etiologic agent, as well as for research on mechanisms of OA.

• #113 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  The best diagnostic approach for OA is to combine a detailed clinical history with objective diagnostic tests. The latter include evidence for work-related changes in the airways—peak expiratory flow (PEF), non-specific BHR, sputum eosinophil count, FeNO and/or evidence for specific sensitization—SPT, sIgE, SIC, and basophil activation test. In the differential diagnosis, it is important to consider other conditions that can mimic asthma symptoms following exposure to irritants in the workplace. […] SIC is considered to be the gold standard for confirmation of OA. It mimics the workplace exposure in a controlled environment. SIC should be conducted in hospital-based specialised centers, by trained personnel and closely supervised by physicians with expertise in the field and able to manage acute asthmatic or anaphylactic reactions.

• #114 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  Occupational asthma (OA) represents one of the major public health problems due to its high prevalence, important social and economic burden. The aim of this review is to summarize current data about clinical phenotypes, biomarkers, diagnosis and management of OA, a subtype of work-related asthma. Most studies have identified two phenotypes of OA. One is sensitizer-induced asthma, occurring after a latency period and caused by hypersensitivity to high- or low-molecular weight agents. The other is irritant-induced asthma, which can occur after one or more exposures to high concentrations of irritants without latency period. More than 400 agents causing OA have been identified and its list is growing fast. The best diagnostic approach for OA is a combination of clinical history and objective tests. An important tool is a specific inhalation challenge. Additional tests include assessments of bronchial hyperresponsiveness to methacholine/histamine in patients without airflow limitations, monitoring peak expiratory flow at- and off-work, sputum eosinophil count, exhaled nitric oxide measurement, skin prick tests with occupational allergens and serum specific IgE. Treatment of OA implies avoidance of exposure, pharmacotherapy and education. OA is a heterogeneous disease. Mechanisms of its different phenotypes, their diagnosis, role of new biomarkers and treatment require further investigation.

• #115 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  Once a sensitizer-induced OA is confirmed, early removal of the workers from exposure is associated with a better prognosis and outcomes. Complete avoidance is more effective than partial mitigation. Primary, secondary and tertiary prevention are mandatory in the management of sensitizer-induced OA. Patients with irritant-induced OA may continue to work if their respiratory symptoms are controlled with appropriate treatment. The pharmacologic therapy relies on a stepwise approach, with the goal of obtaining and maintaining asthma control.

• #116 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  Once a sensitizer-induced OA is confirmed, early removal of the workers from exposure is associated with a better prognosis and outcomes. Complete avoidance is more effective than partial mitigation. Primary, secondary and tertiary prevention are mandatory in the management of sensitizer-induced OA. Patients with irritant-induced OA may continue to work if their respiratory symptoms are controlled with appropriate treatment. The pharmacologic therapy relies on a stepwise approach, with the goal of obtaining and maintaining asthma control.

• #117 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  Once a sensitizer-induced OA is confirmed, early removal of the workers from exposure is associated with a better prognosis and outcomes. Complete avoidance is more effective than partial mitigation. Primary, secondary and tertiary prevention are mandatory in the management of sensitizer-induced OA. Patients with irritant-induced OA may continue to work if their respiratory symptoms are controlled with appropriate treatment. The pharmacologic therapy relies on a stepwise approach, with the goal of obtaining and maintaining asthma control.

• #118 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  Once a sensitizer-induced OA is confirmed, early removal of the workers from exposure is associated with a better prognosis and outcomes. Complete avoidance is more effective than partial mitigation. Primary, secondary and tertiary prevention are mandatory in the management of sensitizer-induced OA. Patients with irritant-induced OA may continue to work if their respiratory symptoms are controlled with appropriate treatment. The pharmacologic therapy relies on a stepwise approach, with the goal of obtaining and maintaining asthma control.

• #119 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  Occupational asthma (OA) represents one of the major public health problems due to its high prevalence, important social and economic burden. The aim of this review is to summarize current data about clinical phenotypes, biomarkers, diagnosis and management of OA, a subtype of work-related asthma. Most studies have identified two phenotypes of OA. One is sensitizer-induced asthma, occurring after a latency period and caused by hypersensitivity to high- or low-molecular weight agents. The other is irritant-induced asthma, which can occur after one or more exposures to high concentrations of irritants without latency period. More than 400 agents causing OA have been identified and its list is growing fast. The best diagnostic approach for OA is a combination of clinical history and objective tests. An important tool is a specific inhalation challenge. Additional tests include assessments of bronchial hyperresponsiveness to methacholine/histamine in patients without airflow limitations, monitoring peak expiratory flow at- and off-work, sputum eosinophil count, exhaled nitric oxide measurement, skin prick tests with occupational allergens and serum specific IgE. Treatment of OA implies avoidance of exposure, pharmacotherapy and education. OA is a heterogeneous disease. Mechanisms of its different phenotypes, their diagnosis, role of new biomarkers and treatment require further investigation.

• #120 Pathogenesis and Disease Mechanisms of Occupational Asthma

  https://stacks.cdc.gov/view/cdc/36914

  Occupational asthma (OA) is one of the most common forms of work-related lung disease in all industrialized nations. […] The clinical management of patients with OA depends on an understanding of the multifactorial pathogenetic mechanisms that can contribute to this disease. […] This article discusses the various immunologic and nonimmunologic mechanisms and genetic susceptibility factors that drive the inflammatory processes of OA.

• #121 Animal Models of Occupational Asthma: Tools for Understanding Disease

  https://www.taylorfrancis.com/chapters/edit/10.3109/9780849374531-9/animal-models-occupational-asthma-tools-understanding-disease-pathogenesis-victor-johnson-michael-luster

  Occupational asthma is the most frequently reported occupational respiratory disease in industrialized nations, and numerous low-molecular-weight chemicals and high-molecular-weight proteins encountered in the workplace are known or suspected causative agents. Classical and novel animal models are being used to investigate exposure determinants, epitope identity, and the role played by the immune system in occupational asthma in order to recapitulate disease phenotype and further current understanding of its pathogenesis. […] Important aspects of exposure determinants that can be addressed and controlled using animal models include (i) relevant routes of exposure including respiratory and/or skin, (ii) exposure dose, (iii) exposure duration and frequency, and (iv) determination of relevant epitopes. In addition, well-defined genetics of animal models present unique opportunities for detailed investigations into pathogenic mechanisms through the use of transgenic models and antibody neutralization strategies. The data generated through the use of animal models is instrumental for risk assessment used to refine workplace exposure limits. […] It is likely that key molecular and cellular events will be identified through the use of these models, potentially leading to new treatment modalities that may be specific for these classes of asthmogen and will aid in establishing more protective workplace exposure limits.

• #122 Animal Models of Occupational Asthma: Tools for Understanding Disease

  https://www.taylorfrancis.com/chapters/edit/10.3109/9780849374531-9/animal-models-occupational-asthma-tools-understanding-disease-pathogenesis-victor-johnson-michael-luster

  Occupational asthma is the most frequently reported occupational respiratory disease in industrialized nations, and numerous low-molecular-weight chemicals and high-molecular-weight proteins encountered in the workplace are known or suspected causative agents. Classical and novel animal models are being used to investigate exposure determinants, epitope identity, and the role played by the immune system in occupational asthma in order to recapitulate disease phenotype and further current understanding of its pathogenesis. […] Important aspects of exposure determinants that can be addressed and controlled using animal models include (i) relevant routes of exposure including respiratory and/or skin, (ii) exposure dose, (iii) exposure duration and frequency, and (iv) determination of relevant epitopes. In addition, well-defined genetics of animal models present unique opportunities for detailed investigations into pathogenic mechanisms through the use of transgenic models and antibody neutralization strategies. The data generated through the use of animal models is instrumental for risk assessment used to refine workplace exposure limits. […] It is likely that key molecular and cellular events will be identified through the use of these models, potentially leading to new treatment modalities that may be specific for these classes of asthmogen and will aid in establishing more protective workplace exposure limits.

• #123 Animal Models of Occupational Asthma: Tools for Understanding Disease

  https://www.taylorfrancis.com/chapters/edit/10.3109/9780849374531-9/animal-models-occupational-asthma-tools-understanding-disease-pathogenesis-victor-johnson-michael-luster

  Occupational asthma is the most frequently reported occupational respiratory disease in industrialized nations, and numerous low-molecular-weight chemicals and high-molecular-weight proteins encountered in the workplace are known or suspected causative agents. Classical and novel animal models are being used to investigate exposure determinants, epitope identity, and the role played by the immune system in occupational asthma in order to recapitulate disease phenotype and further current understanding of its pathogenesis. […] Important aspects of exposure determinants that can be addressed and controlled using animal models include (i) relevant routes of exposure including respiratory and/or skin, (ii) exposure dose, (iii) exposure duration and frequency, and (iv) determination of relevant epitopes. In addition, well-defined genetics of animal models present unique opportunities for detailed investigations into pathogenic mechanisms through the use of transgenic models and antibody neutralization strategies. The data generated through the use of animal models is instrumental for risk assessment used to refine workplace exposure limits. […] It is likely that key molecular and cellular events will be identified through the use of these models, potentially leading to new treatment modalities that may be specific for these classes of asthmogen and will aid in establishing more protective workplace exposure limits.

• #124 Animal Models of Occupational Asthma: Tools for Understanding Disease

  https://www.taylorfrancis.com/chapters/edit/10.3109/9780849374531-9/animal-models-occupational-asthma-tools-understanding-disease-pathogenesis-victor-johnson-michael-luster

  Occupational asthma is the most frequently reported occupational respiratory disease in industrialized nations, and numerous low-molecular-weight chemicals and high-molecular-weight proteins encountered in the workplace are known or suspected causative agents. Classical and novel animal models are being used to investigate exposure determinants, epitope identity, and the role played by the immune system in occupational asthma in order to recapitulate disease phenotype and further current understanding of its pathogenesis. […] Important aspects of exposure determinants that can be addressed and controlled using animal models include (i) relevant routes of exposure including respiratory and/or skin, (ii) exposure dose, (iii) exposure duration and frequency, and (iv) determination of relevant epitopes. In addition, well-defined genetics of animal models present unique opportunities for detailed investigations into pathogenic mechanisms through the use of transgenic models and antibody neutralization strategies. The data generated through the use of animal models is instrumental for risk assessment used to refine workplace exposure limits. […] It is likely that key molecular and cellular events will be identified through the use of these models, potentially leading to new treatment modalities that may be specific for these classes of asthmogen and will aid in establishing more protective workplace exposure limits.

• #125 Animal Models of Occupational Asthma: Tools for Understanding Disease

  https://www.taylorfrancis.com/chapters/edit/10.3109/9780849374531-9/animal-models-occupational-asthma-tools-understanding-disease-pathogenesis-victor-johnson-michael-luster

  Occupational asthma is the most frequently reported occupational respiratory disease in industrialized nations, and numerous low-molecular-weight chemicals and high-molecular-weight proteins encountered in the workplace are known or suspected causative agents. Classical and novel animal models are being used to investigate exposure determinants, epitope identity, and the role played by the immune system in occupational asthma in order to recapitulate disease phenotype and further current understanding of its pathogenesis. […] Important aspects of exposure determinants that can be addressed and controlled using animal models include (i) relevant routes of exposure including respiratory and/or skin, (ii) exposure dose, (iii) exposure duration and frequency, and (iv) determination of relevant epitopes. In addition, well-defined genetics of animal models present unique opportunities for detailed investigations into pathogenic mechanisms through the use of transgenic models and antibody neutralization strategies. The data generated through the use of animal models is instrumental for risk assessment used to refine workplace exposure limits. […] It is likely that key molecular and cellular events will be identified through the use of these models, potentially leading to new treatment modalities that may be specific for these classes of asthmogen and will aid in establishing more protective workplace exposure limits.

• #126 Animal Models of Occupational Asthma: Tools for Understanding Disease

  https://www.taylorfrancis.com/chapters/edit/10.3109/9780849374531-9/animal-models-occupational-asthma-tools-understanding-disease-pathogenesis-victor-johnson-michael-luster

  Occupational asthma is the most frequently reported occupational respiratory disease in industrialized nations, and numerous low-molecular-weight chemicals and high-molecular-weight proteins encountered in the workplace are known or suspected causative agents. Classical and novel animal models are being used to investigate exposure determinants, epitope identity, and the role played by the immune system in occupational asthma in order to recapitulate disease phenotype and further current understanding of its pathogenesis. […] Important aspects of exposure determinants that can be addressed and controlled using animal models include (i) relevant routes of exposure including respiratory and/or skin, (ii) exposure dose, (iii) exposure duration and frequency, and (iv) determination of relevant epitopes. In addition, well-defined genetics of animal models present unique opportunities for detailed investigations into pathogenic mechanisms through the use of transgenic models and antibody neutralization strategies. The data generated through the use of animal models is instrumental for risk assessment used to refine workplace exposure limits. […] It is likely that key molecular and cellular events will be identified through the use of these models, potentially leading to new treatment modalities that may be specific for these classes of asthmogen and will aid in establishing more protective workplace exposure limits.

• #127 Animal Models of Occupational Asthma: Tools for Understanding Disease

  https://www.taylorfrancis.com/chapters/edit/10.3109/9780849374531-9/animal-models-occupational-asthma-tools-understanding-disease-pathogenesis-victor-johnson-michael-luster

  Occupational asthma is the most frequently reported occupational respiratory disease in industrialized nations, and numerous low-molecular-weight chemicals and high-molecular-weight proteins encountered in the workplace are known or suspected causative agents. Classical and novel animal models are being used to investigate exposure determinants, epitope identity, and the role played by the immune system in occupational asthma in order to recapitulate disease phenotype and further current understanding of its pathogenesis. […] Important aspects of exposure determinants that can be addressed and controlled using animal models include (i) relevant routes of exposure including respiratory and/or skin, (ii) exposure dose, (iii) exposure duration and frequency, and (iv) determination of relevant epitopes. In addition, well-defined genetics of animal models present unique opportunities for detailed investigations into pathogenic mechanisms through the use of transgenic models and antibody neutralization strategies. The data generated through the use of animal models is instrumental for risk assessment used to refine workplace exposure limits. […] It is likely that key molecular and cellular events will be identified through the use of these models, potentially leading to new treatment modalities that may be specific for these classes of asthmogen and will aid in establishing more protective workplace exposure limits.

• #128 Progress in Occupational Asthma

  https://www.mdpi.com/1660-4601/17/12/4553

  Occupational asthma (OA) represents one of the major public health problems due to its high prevalence, important social and economic burden. The aim of this review is to summarize current data about clinical phenotypes, biomarkers, diagnosis and management of OA, a subtype of work-related asthma. Most studies have identified two phenotypes of OA. One is sensitizer-induced asthma, occurring after a latency period and caused by hypersensitivity to high- or low-molecular weight agents. The other is irritant-induced asthma, which can occur after one or more exposures to high concentrations of irritants without latency period. More than 400 agents causing OA have been identified and its list is growing fast. The best diagnostic approach for OA is a combination of clinical history and objective tests. An important tool is a specific inhalation challenge. Additional tests include assessments of bronchial hyperresponsiveness to methacholine/histamine in patients without airflow limitations, monitoring peak expiratory flow at- and off-work, sputum eosinophil count, exhaled nitric oxide measurement, skin prick tests with occupational allergens and serum specific IgE. Treatment of OA implies avoidance of exposure, pharmacotherapy and education. OA is a heterogeneous disease. Mechanisms of its different phenotypes, their diagnosis, role of new biomarkers and treatment require further investigation.

• #129 A compendium of causative agents of occupational asthma | Journal of Occupational Medicine and Toxicology | Full Text

  https://occup-med.biomedcentral.com/articles/10.1186/1745-6673-8-15

  The evidence levels for causing occupational asthma of many of the listed agents or worksites are moderate to low since only about a quarter of the identified studies were analytical, primarily because randomised controlled trials are not considered ethical when studying the exposure effects of harmful agents. Therefore, high quality studies are largely absent and the few available studies are frequently small in number of workers studied. […] It is evident that more work is needed to consolidate the gaps, such as the study of potential asthma-inducing agents which have not or only rarely been investigated so far.

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