Materiały źródłowe

• #1 Bronchiectasis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430810/

  Bronchiectasis is a chronic lung disease characterized by persistent and lifelong widening of the bronchial airways and weakening of the function mucociliary transport mechanism owing to repeated infection contributing to bacterial invasion and mucus pooling throughout the bronchial tree. […] The three most important mechanisms that contribute to the pathogenesis of bronchiectasis are recurrent infections, airway obstruction, and peribronchial fibrosis. […] Neutrophils dominate airway inflammation in bronchiectasis, driven by high concentrations of neutrophil chemoattractants such as interleukin-8 (CXCL-8), and leukotriene B4. Airway bacterial colonization occurs because of impaired mucociliary clearance and because of the failure of neutrophil opsonophagocytic killing. Other mechanisms of immune dysfunction include the inability to clear apoptotic cells and invasion of T-cells, with recent reports leading to Th17 cells playing a significant role. Histologic changes in bronchiectasis include cartilage destruction and fibrosis, mucosal and mucous gland hyperplasia, inflammatory cell infiltration, and increased mucous and exudate.

• #2 Bronchiectasis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/296961-overview

  The result is abnormal bronchial dilatation with bronchial wall destruction and transmural inflammation. The most important functional finding of altered airway anatomy is severely impaired clearance of secretions from the bronchial tree. […] Impaired clearance of secretions causes colonization and infection with pathogenic organisms, contributing to the purulent expectoration commonly observed in patients with bronchiectasis. The result is further bronchial damage and a vicious cycle of bronchial damage, bronchial dilation, impaired clearance of secretions, recurrent infection, and more bronchial damage. […] Coles vicious cycle has been central to understanding the pathophysiology of bronchiectasis since 1986. […] However, it was renamed as the vicious vortex model due to the high interconnection between its components where each component depends on all of the others and each of these factors may help perpetuate the other three and contribute to progressive lung damage.

• #3

  https://www.rethinkbronchiectasis.com/bronchiectasis-pathophysiology/

  Bronchiectasis has been characterized in scientific literature as a vicious cycle or vortex consisting of 4 primary drivers. […] Each primary driver can lead to the worsening of the others and contribute to progressive lung damage and damaging exacerbations. […] There is an impairment of its normal mucociliary clearance function, and when that is abnormal, it becomes a ripe place for opportunistic bacteria to set up shop. […] With that growth of bacteria then comes an influx of inflammation. […] The inflammation, although its necessary to combat the bacteria, unfortunately is also injurious to the normal tissues. […] Each of these processes are interconnected, and one often begets the other. […] The bacterial infection doesn’t just cause direct injury, but it incites inflammation, and the white blood cells release products, such as serine proteases, that will cause more inflammation and damage.

• #4 Radiology – Bronchiectasis

  https://bronchiectasis.com.au/bronchiectasis/diagnosis-2/radiology

  Bronchiectasis is defined as irreversible dilatation of a portion of the bronchial tree. The three most important mechanisms that contribute to the pathogenesis of bronchiectasis are infection, airway obstruction and peribronchial fibrosis. […] HRCT continues to be the gold standard for establishing the diagnosis, the anatomic extent and severity of bronchiectasis.

• #5

  https://www.rethinkbronchiectasis.com/bronchiectasis-pathophysiology/

  When we talk about the vicious vortex, when you have inflammation, it’s important to try to treat that because if inflammation is not well controlled, it can lead to further bronchiectasis and furthering lung destruction and kind of perpetuates that vortex into worsening lung function overall. […] Bronchiectasis pathophysiology has been described in literature as a „vicious cycle” or „vicious vortex,” consisting of 4 interconnected components: abnormal mucus production and mucociliary clearance, where thick mucus becomes trapped in the airways, which renders the airway more susceptible to chronic infections. […] The inflammatory response is complex. It is primarily neutrophilic, but also involves a network of cytokines and other inflammatory cells, including macrophages, eosinophils, and lymphocytes.

• #6 Bronchiectasis Exacerbations: Are We Doing Everything We Can? – European Medical Journal

  https://www.emjreviews.com/respiratory/symposium/bronchiectasis-exacerbations-are-we-doing-everything-we-can-j160124/

  At the European Respiratory Society (ERS) Congress 2024, two experts in bronchiectasis, Pieter Goeminne, Department of Respiratory Diseases, Vitaz Saint-Nicholas Hospitals, Belgium, and Michal Shteinberg, Pulmonology Institute and CF Center Carmel Medical Center; Israel Institute of Technology; and The B. Rappaport Faculty of Medicine, Haifa, Israel, discussed bronchiectasis pathogenesis and exacerbations, along with unmet needs regarding diagnosis and treatment. […] Development of bronchiectasis involves the intersection of four pathogenic components: chronic infections, airway ciliary dysfunction, chronic inflammation (mostly neutrophilic), and structural lung damage, commonly known as the vicious vortex. […] In particular, bronchiectasis development, progression, and exacerbation also involve upregulated and dysregulated neutrophil function.

• #7 Bronchiectasis – Wikipedia

  https://en.wikipedia.org/wiki/Bronchiectasis

  Bronchiectasis may result from a number of infectious and acquired causes, including measles, pneumonia, tuberculosis, immune system problems, as well as the genetic disorder cystic fibrosis. […] The mechanism of disease is breakdown of the airways due to an excessive inflammatory response. […] Involved airways (bronchi) become enlarged and thus less able to clear secretions. […] These secretions increase the amount of bacteria in the lungs, resulting in airway blockage and further breakdown of the airways. […] The development of bronchiectasis requires two factors: an initial injury to the lung (such as from infection, auto-immune destruction of lung tissue, or other destruction of lung tissue (as seen in gastroesophageal reflux disease or aspiration syndromes)) which leads to impaired mucociliary clearance, obstruction, or a defect in host defense.

• #8 Bronchiectasis – Pulmonary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pulmonary-disorders/bronchiectasis-and-atelectasis/bronchiectasis

  Bronchiectasis represents a common end-point of several disorders predisposing to chronic airway inflammation. The most widely accepted model describes a „vicious cycle” that results in airway damage and dilation. An initial insult to the airways (eg, infectious, autoimmune, toxic inhalations, etc) leads to airway inflammation and epithelial damage. This initial damage and the resulting inflammatory response create structural changes in the airways that impair mucociliary clearance and promote bacterial colonization and infection. This process perpetuates, ultimately resulting in irreversible airway damage if the cycle continues untreated. […] The role of neutrophilic inflammation in the development of bronchiectasis is increasingly recognized. Inflammation of small and medium-sized airways from a causative disorder releases inflammatory mediators such as proteases (specifically, elastase) from intraluminal neutrophils. The inflammatory mediators destroy elastin, cartilage, and muscle in larger airways, resulting in irreversible bronchodilation. Neutrophil extracellular traps (NETs), a web of DNA ejected from neutrophils that are studded with neutrophil granule enzymes and proteins, are a key mechanism underlying chronic and self-perpetuating airway inflammation.

• #9 Bronchiectasis – Wikipedia

  https://en.wikipedia.org/wiki/Bronchiectasis

  This triggers a host immune response from neutrophils (elastases), reactive oxygen species, and inflammatory cytokines that results in progressive destruction of normal lung architecture. […] Disordered neutrophil function is believed to play a role in the pathogenesis of bronchiectasis. […] The initial lung injury in bronchiectasis leads to an impaired mucociliary clearance of the lung airways, which leads to mucous stasis. […] This mucous stasis leads to bacterial colonization in bronchiectasis which leads to neutrophil activation. […] The distorted, damaged lung airways thus have impaired mucociliary clearance; leading to mucous stasis and bacterial colonization leading to further neutrophil activation and thus fueling a self-perpetuating „vicious cycle” of inflammation in bronchiectasis. […] This „vicious cycle” theory is the generally accepted explanation for the pathogenesis of bronchiectasis.

• #10

  https://journals.lww.com/aotm/fulltext/2006/01010/pathogenesis,_etiology_and_treatment_of.10.aspx

  Bronchiectasis is a chronic lung disease, defined pathologically as irreversible dilatation of the bronchi. […] The common feature among all the conditions that lead to bronchiectasis, is that they either lead to alteration in the pulmonary defense mechanisms, or are associated with inflammation. […] The end result, is that the individual becomes susceptible to bacterial colonization and infection. Regardless of the initiating event, any damage to the airways that results in loss of the mucociliary transport, renders the airways susceptible to microbial colonization. Infection leads to inflammatory response and progressive lung damage. […] Neutrophils are thought to play a central role in the pathogenesis of tissue damage that occurs in bronchiectasis. […] The progressive nature of bronchiectasis is thought to result from a continuous vicious circle of inflammation and tissue damage.

• #11

  https://www.rethinkbronchiectasis.com/bronchiectasis-pathophysiology/

  Neutrophilic inflammation plays an important role in the development and progression of bronchiectasis. […] However, in bronchiectasis, chronic infection and changes in the airway environment can lead to neutrophil dysregulation. […] This unresolved inflammatory process contributes to tissue damage, impaired mucociliary clearance, impaired bacterial phagocytosis, and killing resulting in airway damage. […] Targeting the underlying neutrophilic inflammation associated with bronchiectasis continues to be an unmet need, and a comprehensive treatment approach is desirable. […] Therefore, a comprehensive multimodal treatment approach that addresses all 4 interrelated components of bronchiectasis may help to reduce the frequency of exacerbations in bronchiectasis patients and improve their quality of life.

• #12 The pathophysiology of bronchiectasis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2793069/

  The dominant cell types involved in the inflammatory process in bronchiectasis are neutrophils, lymphocytes, and macrophages. Neutrophils are the most prominent cell type in the bronchial lumen and release mediators, particularly proteases/elastase which cause bronchial dilation (ie, bronchiectasis). […] The inflammation appears to arise as a combination of immune deficiency and persistent infection. As proposed by Cole this inflammatory process is progressive and results in a cycle of worsening pulmonary damage. […] Bronchiectasis is a heterogeneous condition and there are a large number of etiologic factors have been described. Because of the long-term nature of the disease it is often hard to be clear about the exact role of such factors in the pathogenesis.

• #13

  https://www.rethinkbronchiectasis.com/bronchiectasis-pathophysiology/

  Neutrophils normally serve as the first line of defense against a range of pathogenic infections, but during bronchiectasis, changes in the airway environment cause neutrophils to become dysregulated, which leads to longer survival and release of excessive neutrophil serine proteases, including neutrophil elastase. […] The overactivity of neutrophil elastase contributes to chronic inflammation, concomitant tissue damage, and an increased risk of future exacerbations.

• #14 Bronchiectasis Exacerbations: Are We Doing Everything We Can? – European Medical Journal

  https://www.emjreviews.com/respiratory/symposium/bronchiectasis-exacerbations-are-we-doing-everything-we-can-j160124/

  The primary protease involved in tissue damage and remodelling in bronchiectasis is neutrophil elastase. […] The pathogenesis of lung damage associated with neutrophil elastase release includes activation of pro-inflammatory cytokines and pathways; impaired immune cell function; goblet cell metaplasia and increased airway mucin expression and dehydration; impaired ciliary motility; and epithelial cell apoptosis and impaired proliferation. […] Neutrophil elastase activity is associated with increased exacerbation risk as well as with disease severity, as evidenced by clinical and radiological extent of bronchiectasis, sputum volume, and lung function decline (both occurrence and rate). […] Current thinking points to the existence of a number of endotypes of bronchiectasis exacerbations based on neutrophil and eosinophil expression and bacterial species. […] These are exciting findings regarding bronchiectasis, explained Goeminne, as we are now realising how important inflammation really is.

• #15 Clinical Pathology Glossary: Bronchiectasis | ditki medical & biological sciences

  https://ditki.com/course/pathology/glossary/pathophysiologic-disorder/bronchiectasis

  Bronchiectasis refers to a disease of elastic, muscular, and cartilaginous tissue destruction with resultant dilation fibrosis in the setting of chronic airway infection and inflammation. […] It is a chronic, heterogeneous disorder caused by repeated bouts of infection and inflammation that cause permanent dilation of the medium and medium-large airways. […] Impaired mucociliary clearance and retention of airway secretions creates an environment vulnerable to chronic infection. […] Chronic infection results in chronic inflammation with neutrophilic and T-cell infiltration. These inflammatory cells release cytokines that cause tissue destruction and airway remodeling. […] Neutrophil elastase (NE) is a key inflammatory protease released by neutrophils cited in tissue destruction in multiple chronic inflammatory pulmonary diseases, including bronchiectasis.

• #16 Thieme E-Journals – Seminars in Respiratory and Critical Care Medicine / Full Text

  https://www.thieme-connect.com/products/ejournals/html/10.1055/s-0041-1730891

  The contribution of chronic inflammation, infection, and mucus obstruction leads to progressive structural lung damage. […] Chronic inflammation is a key component of bronchiectasis pathophysiology. Patients have extensive infiltration of the airways by inflammatory cells, particularly in severe disease. […] Neutrophils are among the first immune cells to be recruited in response to an infection but are also regarded as a key component in the pathophysiology of bronchiectasis. […] The main stimulant of neutrophil migration into the airway is believed to be bacterial colonization. […] Once recruited to the site of infection, neutrophils deploy several host defense mechanisms including phagocytosis, degranulation, production of reactive oxygen species, proinflammatory cytokine production, and neutrophil extracellular trap (NET) formation.

• #17 Bronchiectasis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/296961-overview

  Bronchiectasis is an abnormal dilation of the proximal and medium-sized bronchi (2 mm in diameter) caused by weakening or destruction of the muscular and elastic components of the bronchial walls. Affected areas may show a variety of changes, including transmural inflammation, edema, scarring, and ulceration, among other findings. Distal lung parenchyma may also be damaged secondary to persistent microbial infection and frequent postobstructive pneumonia. Bronchiectasis can be congenital but is most often acquired. […] Acquired forms occur in adults and older children and require an infectious insult, impairment of drainage, airway obstruction, and/or a defect in host defense. The tissue is also damaged in part by the host response of neutrophilic proteases, inflammatory cytokines, nitric oxide, and oxygen radicals. This results in damage to the muscular and elastic components of the bronchial wall. Additionally, peribronchial alveolar tissue may be damaged, resulting in diffuse peribronchial fibrosis.

• #18 The pathophysiology of bronchiectasis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2793069/

  Bronchiectasis is defined by permanent and abnormal widening of the bronchi. This process occurs in the context of chronic airway infection and inflammation. Studies have demonstrated that the small airways in bronchiectasis are obstructed from an inflammatory infiltrate in the wall. […] The bronchial wall is typically thickened by an inflammatory infiltrate of lymphocytes and macrophages which may form lymphoid follicles. […] The current view is that the two factors required for the development of this condition are persistent infection and a defect in host defense. […] The inflammatory process commenced in the small airway. This small airway inflammation caused the release of mediators such as proteases which damaged the large airways causing loss of elastin and other components such as muscle and cartilage which resulted in bronchial dilation.

• #19 Pathology of BRONCHIECTASIS – Pathology Made Simple

  https://ilovepathology.com/pathology-of-bronchiectasis/

  It is one of the obstructive airway disorder,defined as permanent dilation of bronchi and bronchioles due to destruction of smooth muscle and elastic tissue by chronic necrotising infections. […] The major conditions associated with bronchiectasis are OBSTRUCTION INFECTION. […] Dilated airways with acute and chronic inflammatory cells within their walls Lining epithelium shows ulceration and desquamation Squamous metaplasia and pseudostratification may be seen Necrosis of lung tissue with abscess formation Chronic cases may show fibrosis.

• #20 Bronchiectasis – Pulmonary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pulmonary-disorders/bronchiectasis-and-atelectasis/bronchiectasis

  With disease progression, inflammation spreads beyond the airways, causing fibrosis of the surrounding lung parenchyma. What inflames the small airways depends on the etiology of bronchiectasis. Common contributors include impaired airway clearance (due to the production of thick, viscous mucus in CF, lack of ciliary motility in primary ciliary dyskinesia [PCD], or damage to the cilia and/or airways secondary to infection or injury) and impaired host defenses; these factors predispose patients to chronic infection and inflammation. […] As ongoing inflammation changes airway anatomy, pathogenic bacteria (sometimes including mycobacteria), colonize the airways. Common organisms include: Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, Nontuberculous mycobacteria, Moraxella catarrhalis, Streptococcus pneumoniae. […] Colonization with P. aeruginosa tends to indicate severe disease and predicts worse outcomes, including increased risk of exacerbations, hospitalization, poor quality of life, rapid decline in lung function, and death.

• #21 Pathophysiology – Bronchiectasis

  https://bronchiectasis.com.au/bronchiectasis/bronchiectasis/pathophysiology

  This loss of mucociliary transport renders the airways susceptible to microbial colonization. Neutrophils are also believed to promote this process by allowing bacterial adherence to the lung epithelium. In response to this colonisation, a cycle of an intense chronic inflammatory response is triggered. This encourages further release of inflammatory mediators, which facilitate neutrophil migration to the bronchial lumen and mucosa. Neutrophils play a central role in the tissue damage in bronchiectasis, by releasing mediators (including inflammatory cytokines, elastases and matrix metalloproteinases) which destroy the bronchial elastin and other supporting lung structure, leading to permanent dilatation of the bronchi. […] Airway walls become thickened with normal mucosal and muscular layers substituted by oedema, ulceration or fibrosis. In proximal airways, the structural cartilage may be diminished, provoking a reduction in supportive structure. These changes in airway structure further contribute to pooling of mucus, and the self-perpetuating cycle of infection and inflammation, which promotes progressive airway damage and recurrent infections.

• #22 Frontiers | Lung microbiome: new insights into bronchiectasis’ outcome

  https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2024.1405399/full

  Understanding the pathogenesis of bronchiectasis and possible therapeutic strategies for its clinical management can be based on a culture-based assessment of the local microbial pathogens and the features of the immune responses linked with it. […] The most common pathogens found in culture-based studies to be associated with bronchiectasis are Pseudomonas aeruginosa, Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus. […] A poor prognostic sign is the occurrence of fungal infections such as Candida, Penicillium, Cryptococcus, Clavispora, and Scedosporium, particularly when allergic bronchopulmonary aspergillosis (ABPA) develops. […] The microbiome in bronchiectasis is significantly less explored than in other lung illnesses such as cystic fibrosis and chronic obstructive pulmonary disease; much of the evidence comes from the BLESS project.

• #23 Emerging Concepts in Bronchiectasis: Diagnosis, Pathophysiology, and Relevance in Lung Disease – European Medical Journal

  https://www.emjreviews.com/respiratory/symposium/emerging-concepts-in-bronchiectasis-diagnosis-pathophysiology-and-relevance-in-lung-disease-j160124/

  Because the pathogenesis is more complex than was previously thought, Polverino stressed the need for a more personalised approach to treatment. […] In most cases of bronchiectasis, the disease is driven by neutrophilic inflammation, and a Phase II trial of an inhibitor of dipeptidyl peptidase 1, an enzyme that activates neutrophil proteases, resulted in fewer exacerbations and less sputum neutrophil elastase. […] In addition to local inflammation, chronic respiratory disease can be associated with varying levels of systemic inflammation. […] The presence of bacteria in the lungs is associated with inflammation in a dose-response relationship; higher bacterial loads are associated with a higher intensity of inflammation and more frequent exacerbations. […] Understanding disease phenotypes in bronchiectasis is important because treatment strategies are based on the patients symptoms and risk factors.

• #24 Pathophysiology – Bronchiectasis

  https://bronchiectasis.com.au/bronchiectasis/bronchiectasis/pathophysiology

  The severity of airway obstruction and rate of decline in lung function may be influenced by the colonizing microorganisms. Individuals who show signs of colonization with Pseudomonas aeruginosa have had more extensive disease on HRCT, greater airflow obstruction and a faster rate of decline in airflow obstruction. Haemophilus influenzae is also known to induce detrimental effects on lung function.

• #25 Bronchiectasis Pathogenesis and clinical findings | Calgary Guide

  https://calgaryguide.ucalgary.ca/bronchiectasis-pathogenesis-and-clinical-findings/bronchiectasis-pathogenesis-and-clinical-findings/

  Bronchiectasis: Pathogenesis and clinical findings Acquired immunodeficiency Lymphoma, HIV, transplant Autoimmune Lupus, inflammatory bowel disease, rheumatoid arthritis Congenital/Genetic Cystic fibrosis, A1AT deficiency, Marfan, immunoglobulin deficiency, Kartagener syndrome, Young syndrome Endobronchial obstruction Neoplasm, foreign body, lymph node compression Other Inhalation exposure (smoke, ammonia), MAC complex infection, COPD, allergic bronchopulmonary aspergillosis, chronic infections Irreversibly dilated bronchi Chronic bronchial infection and inflammation 1 Easily collapsible airways I Bronchiectasis (persistent and progressive damage to lungs) Chronic cough (mucopurulent) Defect in immunity and/or mucus clearance Persistent bacteria in airway (commonly Pseudomonas/Staph aureus) Inflammatory response Rhinosinusitis

• #26 Bronchiectasis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/296961-overview

  These components are: (1) lung dysfunction with airway epithelial and ciliary dysfunction, and mucus hypersecretion (2) chronic airway infections that induce further airway damage and mucus hypersecretion (3) chronic airway inflammation, primarily neutrophilic, resulting in permanent airway injury and dilation (4) impaired mucociliary clearance perpetuating the chronic infection, inflammation, and airway epithelial cell and ciliary dysfunction. […] Transmural inflammation causes damage to the airways, which become susceptible to chronic colonization by certain microorganisms resulting in further injury and in less resistance to infection. […] Airway inflammation in bronchiectatic airways is characterized by tissue neutrophilia, a mononuclear cell infiltrate composed mainly of CD4+ T cells and CD68+ macrophages, and increased IL-8 expression.

• #27

  https://journals.lww.com/aotm/fulltext/2006/01010/pathogenesis,_etiology_and_treatment_of.10.aspx

  Although all patients with bronchiectasis have impaired mucociliary clearance and excess sputum production, not all patients are persistently colonized with bacteria. […] In addition to promoting tissue damage, there is a strong evidence that neutrophil elastase promotes bacterial colonization. […] A number of inflammatory mediators are involved in the recruitment and activation of neutrophils, in patients with bronchiectasis. […] The combination of these inflammatory mediators, acts synergistically to induce airway inflammation. Airway hyper-responsiveness is frequently seen in patients with bronchiectasis. […] As mentioned above, airway obstruction and bronchial hyper-responsiveness play role in the pathogenesis of bronchiectasis and treatment modalities that reduce airway hyper-rectivity has a significant role in the management of patients with bronchiectasis.

• #28 Frontiers | Lung microbiome: new insights into bronchiectasis’ outcome

  https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2024.1405399/full

  The present treatments for bronchiectasis, which is defined by pathological dilatation of the airways, are confined to symptom relief and minimizing exacerbations. […] The interplay of chronic infection, inflammation, and compromised mucociliary clearance, which results in structural alterations and the emergence of new infection, is most likely responsible for the progression of bronchiectasis. […] The gradual progression of the disease may be attributed to the interplay among chronic infection, inflammation, and impaired mucociliary clearance, all of which contribute to structural alterations and the emergence of new infections. […] The vicious cycle hypothesis, initially presented by Cole, postulates that trigger factors linked to genetic susceptibility and host defense deficiencies determine a self-reinforcing cycle of inflammation, infection, and impaired mucociliary clearance, culminating in a progressive dilatation and destruction of the bronchial wall.

• #29 Bronchiectasis Exacerbations: Are We Doing Everything We Can? – European Medical Journal

  https://www.emjreviews.com/respiratory/symposium/bronchiectasis-exacerbations-are-we-doing-everything-we-can-j160124/

  As shown in Figure 1, four pathogenic components intersect to drive bronchiectasis development, persistence, and exacerbations. […] This opens the airways up to increased epithelial cell damage, infection, and inflammation. […] The model of bronchiectasis has moved from being seen as a vicious cycle to being recognised as a vicious vortex. […] Neutrophils usually contribute to acute infection control in a number of ways, including phagocytosis of pathogens, release of granule-resident cytotoxic and microbicidal molecules, extrudation of neutrophil extracellular traps, and generation of reactive oxygen and nitric oxide species. […] A key feature of bronchiectasis is persistent overabundant neutrophil infiltration into the airways that helps drive the viscous vortex through inflammation and promotion of bacterial colonisation.

• #30 Insmed Announces Positive Topline Results from Landmark ASPEN Study of Brensocatib in Patients with Bronchiectasis – May 28, 2024

  https://investor.insmed.com/2024-05-28-Insmed-Announces-Positive-Topline-Results-from-Landmark-ASPEN-Study-of-Brensocatib-in-Patients-with-Bronchiectasis

  Bronchiectasis is a serious, chronic lung disease in which the bronchi become permanently dilated due to a cycle of infection, inflammation, and lung tissue damage. […] Brensocatib is a small molecule, oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP1) being developed by Insmed for the treatment of patients with bronchiectasis, CRSsNP, and other neutrophil-mediated diseases. DPP1 is an enzyme responsible for activating neutrophil serine proteases (NSPs), such as neutrophil elastase, in neutrophils when they are formed in the bone marrow. Neutrophils are the most common type of white blood cell and play an essential role in pathogen destruction and inflammatory mediation. In chronic inflammatory lung diseases, neutrophils accumulate in the airways and result in excessive active NSPs that cause lung destruction and inflammation. Brensocatib may decrease the damaging effects of inflammatory diseases such as bronchiectasis by inhibiting DPP1 and its activation of NSPs. […] Results from ASPEN validate DPP1 inhibition as new mechanism of action with potential to address range of neutrophil-mediated diseases.

• #31 Thieme E-Journals – Seminars in Respiratory and Critical Care Medicine / Full Text

  https://www.thieme-connect.com/products/ejournals/html/10.1055/s-0041-1730891

  NET formation was a key component of bronchiectasis pathophysiology. […] A central role for neutrophil serine proteases and NETs in the pathophysiology of bronchiectasis is suggested by the recent demonstration of prolonged time to next exacerbation and reduced frequency of exacerbations in patients treated with two doses of a novel dipeptidyl peptidase-1 (DPP1/cathepsin-C) inhibitor compared with placebo in 256 patients with bronchiectasis.

• #32 Brensocatib Slows Lung Function Decline in Bronchiectasis | Respiratory Therapy

  https://respiratory-therapy.com/products-treatment/pharmaceuticals/clinical-trials/drug-candidate-slows-lung-function-decline-bronchiectasis-patients/

  Insmeds brensocatib demonstrates a reduction in exacerbations and lung function decline measures compared to placebo in a 52-week phase 3 trial for non-cystic fibrosis bronchiectasis. […] The ASPEN findings are critically important given that there is no approved treatment for bronchiectasis and there remains an urgent need for a therapy that can both reduce pulmonary exacerbations and lessen the burden of this disease. […] Bronchiectasis is a progressive disease that causes patients to lose lung function over time. Therefore, I am particularly encouraged by the data which showed that the 25 mg dose of brensocatib may slow the rate of decline of FEV1 (forced expiratory volume over one second) and FVC (forced vital capacity), which represent clinically meaningful parameters of lung function that physicians consider important outcome measures.

• #33 Bronchiectasis | Open Respiratory Archives

  https://www.elsevier.es/en-revista-open-respiratory-archives-11-avance-resumen-bronchiectasis-S2659663624000420

  The formation of NETs is a crucial part of the body’s defense mechanism to eliminate pathogenic microorganisms. However, excessive NET production can lead to tissue damage and persistent airway inflammation. NETs release a large amount of enzymes, including NE, which contributes to tissue degranulation, impaired bacterial clearance, and increased mucus production. […] Eosinophilic inflammation represents a significant treatable trait characteristic in both asthma and COPD. Its presence and intensity correlate with a poorer disease prognosis, manifesting a higher frequency and severity of exacerbations. […] The airway microbiome plays a pivotal role in the initiation, progression, and exacerbations of respiratory diseases. The vicious cycle or vicious vortex models propose a self-sustaining cycle involving infection, inflammation, impairment of mucociliary clearance, and persistent bacterial colonization, leading to the development of bronchiectasis.

• #34 Frontiers | Lung microbiome: new insights into bronchiectasis’ outcome

  https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2024.1405399/full

  Existing data show lung bacterial communities dominated by Haemophillus, Pseudomonas, and Streptococcus, with significant interindividual variability and intraindividual stability. […] Frequent exacerbations and more severe disease have been shown to be associated with Pseudomonas and Haemophilus dominating microbiomes.

• #35 Pathophysiology of Chronic Bronchial Infection in Bronchiectasis | Archivos de Bronconeumología

  https://www.archbronconeumol.org/en-pathophysiology-chronic-bronchial-infection-in-articulo-S0300289622005257

  Bronchiectasis is a complex and heterogeneous disease. Its pathophysiology is poorly understood, but chronic bronchial infection plays an important role in its natural history, and is associated with poor quality of life, more exacerbations and increased mortality. […] A dysregulated inflammatory response results in lung damage, abnormal and irreversible dilatation of the bronchi and recurrent respiratory infections. Bronchial infection plays a key role in the natural history of bronchiectasis. Infective agents such as bacteria, non-tuberculous mycobacteria (NTM), viruses and fungi, have all been proposed to contribute to the pathogenesis by promoting airway damage, increasing bronchial and systemic inflammation and evading host immune responses. […] Understanding the molecular mechanisms leading to development of airway inflammation and bacterial persistence in bronchiectasis are essential to find new treatments and to improve the management for this disease.

• #36 Bronchiectasis | Open Respiratory Archives

  https://www.elsevier.es/en-revista-open-respiratory-archives-11-avance-resumen-bronchiectasis-S2659663624000420

  Instead of targeting individual pathogens, antibiotics appear to exert a more significant impact on microbial interaction networks. This phenomenon could be explained by the influence of antibiotics on the interactome, affecting susceptible microbes that, in turn, modulate the virulence of the targeted, resistant pathogen.

• #37 Research on the Mechanism Affecting Progression of Bronchiectasis | Clinical Research Trial Listing

  https://www.centerwatch.com/clinical-trials/listings/NCT05731427/research-on-the-mechanism-affecting-progression-of-bronchiectasis

  Bronchiectasis is a chronic inflammatory respiratory disease defined as the irreversible dilatation of one or more bronchi and is associated with chronic and frequently purulent expectoration, multiple exacerbations and progressive dyspnea. […] Previous studies showed that there are significant relationship between the airway microbiome and the severity of the disease. […] A large number of studies have reported that long-term treatment of low-dose macrolides such as azithromycin or clarithromycin has anti-inflammatory and immunomodulatory effects, which can improve the clinical symptoms and disease progression of various chronic airway diseases, such as diffuse panbronchiolitis, chronic obstructive pulmonary disease, bronchiectasis. […] but the specific mechanism is unknown. This study is based on omics methods (Microbiology and Metabolomics) to deeply explore the composition of airway and gut microbiota in patients with bronchiectasis, the factors affecting the colonization of Pseudomonas aeruginosa and the mechanism of macrolides in the treatment of bronchiectasis. […] Through the above methods, investigators further understand the mechanism affecting progression of bronchiectasis and some factors that lead to the colonization of Pseudomonas aeruginosa, as well as mechanisms of macrolides in the treatment of bronchiectasis.

• #38 Bronchiectasis | Open Respiratory Archives

  https://www.elsevier.es/en-revista-open-respiratory-archives-11-avance-resumen-bronchiectasis-S2659663624000420

  Non-cystic fibrosis bronchiectasis, a condition that remains relatively underrecognized, has garnered increasing research focus in recent years. This scientific interest has catalyzed advancements in diagnostic methodologies, enabling comprehensive clinical and molecular profiling. Such progress facilitates the development of personalized treatment strategies, marking a significant step toward precision medicine for these patients. […] The precision medicine paradigm calls for refined characterization of bronchiectasis patients by analyzing their inflammatory and molecular profiles. Research into the underlying mechanisms of inflammation and the evaluation of biomarkers such as neutrophil elastase, mucins, and antimicrobial peptides have led to the identification of distinct patient endotypes. These endotypes present variable clinical outcomes, necessitating tailored therapeutic interventions.

• #39 Bronchiectasis | Open Respiratory Archives

  https://www.elsevier.es/en-revista-open-respiratory-archives-11-avance-resumen-bronchiectasis-S2659663624000420

  A deeper understanding of the microbiome’s influence on the pathogenesis and progression of bronchiectasis has inspired a holistic approach, which considers the multibiome as an interconnected microbial network rather than treating pathogens as solitary entities. […] The vicious cycle hypothesis of bronchiectasis. CXCL-8: interleukin-8; IL-1: interleukin-1; IL-17: interleukin 17; LTB4: leukotriene B4; MMP: matrix metalloproteinase; NE: neutrophil elastase; NET: neutrophil extracellular traps; ROS: reactive oxygen species; TNF-: tumor necrosis factor. […] Neutrophilic inflammation plays a key role in the pathophysiology and progression of bronchiectasis. The dysregulated inflammatory response results in lung damage, abnormal and irreversible dilatation of the bronchi, and recurrent respiratory infections.

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