Materiały źródłowe

• #1 Cough – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK493221/

  Coughing is a largely uncontrolled, protective reflex mechanism responsible for mucociliary clearance of the airway and excess secretions within the airway. This reflex is characterized by the closing of the glottis apparatus with subsequent increases in the intrathoracic pressure, which often exceeds 300 mm Hg. This is followed by the forceful expulsion of the airway contents through the glottis into the pharyngeal space and out of the body. Given the forceful nature of this process, with a velocity of exhalation exceeding 500 mph in some cases, mucous secretions are loosened from the wall of the airway and expelled. […] The reflex of coughing is initiated by a chemical irritation at peripheral nerve receptors within the trachea, main carina, branching points of large airways, and distal smaller airways. They are also present in the pharynx. Laryngeal and tracheobronchial receptors respond to mechanical and chemical stimuli. Chemical receptors are sensitive to acid, heat, and capsaicin-like compounds via activation of the type-1 capsaicin receptor. Additionally, there are multiple neural sensory receptors located within the external auditory canals, eardrums, paranasal sinuses, pharynx, diaphragm, pleura, pericardium, and stomach, which are all capable of stimulating the coughing reflex.

• #2 Chronic Cough: Practice Essentials, Mechanism of Cough, Causes of Chronic Cough

  https://emedicine.medscape.com/article/1048560-overview

  Cough is a protective reflex serving a normal physiologic function of clearing excessive secretions and debris from the pulmonary tract. […] The cough reflex has 3 components: an afferent sensory limb, a central processing center, and an efferent limb. […] The trigeminal, glossopharyngeal, and vagus nerves supply the afferent pathways for cough receptors; the vagus, through its pharyngeal, superior laryngeal, and pulmonary branches, supplies the large majority of these receptors. […] Receptors are located throughout the airway from the pharynx to the terminal bronchioles, with the greatest concentration located in the larynx, carina, and the bifurcation of larger bronchi. […] Three types of receptors are predominant: Rapidly adapting receptors (RARs) that respond to mechanical stimuli, cigarette smoke, ammonia, acidic and alkaline solutions, hypotonic and hypertonic saline, pulmonary congestion, atelectasis, and bronchoconstriction; Slowly adapting receptors (SARs); Nociceptors on C-fibers that respond to chemical stimuli as well as inflammatory and immunological mediators such as histamine, bradykinin, prostaglandins, substance P, capsaicin, and acidic pH.

• #3 Cough – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK493221/

  The mechanism of action for coughing can be subdivided into three overarching phases: the inspiration phase, the compression phase, and the expiratory phase. During the inspiration phase, inhalation occurs, generating an increase in volume within the pulmonary system. This volume is necessary for generating enough air movement to be productive. The compression phase is marked by the closure of the larynx combined with the contraction of muscles of exhalation, including the intercostals, diaphragm, and abdominals leading to a net increase in intrathoracic pressure without any air movement occurring. The expiration phase is marked by the rapid opening of the glottis resulting in rapid, high-volume expiratory airflow. This rapid airflow causes vibrations within the larynx and pharynx, inducing the characteristic sounds of a cough. Throughout this process, airway compression occurs, resulting in a net decrease in intrathoracic volume. After exhalation, rebound inhalation may occur, depending on the duration of a coughing episode as well as the volume of airflow movement, in compensation for developed hypoxia or reflexive inhalation.

• #4 How Coughing Works and Remedies for It

  https://www.verywellhealth.com/coughing-facts-1298408

  The cough reflex consists of two components: a sensory component, in which your central nervous system (CNS) senses something that shouldn’t be in your airways, and a motor component, in which your muscles expand and contract to remove it. […] Your CNS, airways, and muscles work together to form a cough through the following process: […] Sensory nerves in the tissues lining your trachea (windpipe), larynx (voice box), bronchi, and carina are instantly activated when a foreign invader touches their lining. […] The vagus nerve signals the medulla located in the brainstem to initiate the cough reflex. […] As the air clears your trachea, the irritant attached to the lining of your airway is cleared with it. […] People with weakened respiratory muscles may be unable to cough. This can be an effect of several health conditions, including stroke, Parkinson’s disease, and multiple sclerosis.

• #5 Cough reflex – Wikipedia

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

  The cough reflex occurs when stimulation of cough receptors in the respiratory tract by dust or other foreign particles produces a cough, which causes rapidly moving air which usually remove the foreign material before it reaches the lungs. This typically clears particles from the bronchi and trachea, the tubes that feed air to lung tissue from the nose and mouth. […] The cough receptors or rapidly adapting irritant receptors are located mainly on the posterior wall of the trachea, larynx, and at the carina of trachea, the point where the trachea branches into the main bronchi. […] The mechanism of a cough is as follows: […] The bronchi and non-cartilaginous portions of the trachea collapse to form slits through which the air is forced, which clears out any irritants attached to the respiratory lining. […] This reflex may also be impaired by damage to the internal branch of the superior laryngeal nerve which relays the afferent branch of the reflex arc.

• #6 Mechanism of cough and sneeze reflex | PPT

  https://www.slideshare.net/nacool99/mechanism-of-cough-and-sneeze-reflex

  Cough is a protective reflex triggered by irritants in the lungs and respiratory tract, while sneeze protects the nasal mucosa from irritants. […] Cough receptors are in the trachea and bronchi, while sneeze receptors are in the nose. […] Cough is an expulsive reflex that protects the lungs and respiratory passages from foreign bodies. […] The mechanism of cough reflex involves about 2.5L of air being inspired, with the epiglottis closing and vocal cords shutting tightly to entrap the air within the lung. […] Abdominal muscles contract forcefully, pushing against the diaphragm, and internal intercostal muscles also contract forcefully, causing pressure in the lungs to rise to 100mmHg or more. […] Markedly positive intrathoracic pressure causes narrowing of the trachea. […] Vocal cords and epiglottis suddenly open widely, and air is expelled at velocities ranging from 75 to 100 miles/hr.

• #7

  https://www.meddean.luc.edu/lumen/meded/elective/pulmonary/cough/cough.htm

  Cough is an important normal protective reflex activity which can become a major sign and symptom of lung disease and a significant clinical problem for a large number of patients. […] The normal mechanism occurs with an inhalation of gas above FRC followed by closure of the glottis and an increase in intrapleural pressure to 100 cm H2O. About 0.2 seconds after glottis closure, it reflexively opens with resulting turbulent expiratory flow. […] The cough reflex has 5 components: 1) cough receptors, 2) afferent nerves, 3) a poorly defined cough center, 4) efferent nerves, 5) effector muscles. Key to cough particularly in pathology is the cough receptors. In summary, cough receptors are throughout all the airways and upper G.I. tract. as well as the pericardium and diaphragm. […] Reflex begins with deep inspiration, followed by glottic closure, diaphragmatic relaxation, and thoracic and abdominal expiratory muscle contraction. Posterior wall of airway invaginates and causes shearing of mucus. […] Positive pleural pressure generated up to 100-300 mm Hg; peak flows of 12 L/sec. […] Alteration of surface epithelium of major airways exposes irritant receptors which become sensitized and cause cough.

• #8 Anatomy and neuro-pathophysiology of the cough reflex arc

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3415124/

  Coughing is an important defensive reflex that occurs through the stimulation of a complex reflex arc. […] Each cough occurs through the stimulation of a complex reflex arc. This is initiated by the irritation of cough receptors which are found in the trachea, main carina, branching points of large airways, and more distal smaller airways; also, they are present in the pharynx. […] Impulses from stimulated cough receptors traverse an afferent pathway via the vagus nerve to a cough center in the medulla, which itself may be under some control by higher cortical centers. The cough center generates an efferent signal that travels down the vagus, phrenic, and spinal motor nerves to expiratory musculature to produce the cough. […] Therefore, the cough reflex arc is constituted by: 1. Afferent pathway: Sensory nerve fibers (branches of the vagus nerve) located in the ciliated epithelium of the upper airways (pulmonary, auricular, pharyngeal, superior laryngeal, gastric) and cardiac and esophageal branches from the diaphragm.

• #9 Chronic Cough: Practice Essentials, Mechanism of Cough, Causes of Chronic Cough

  https://emedicine.medscape.com/article/1048560-overview

  Cough is a protective reflex serving a normal physiologic function of clearing excessive secretions and debris from the pulmonary tract. […] The cough reflex has 3 components: an afferent sensory limb, a central processing center, and an efferent limb. […] The trigeminal, glossopharyngeal, and vagus nerves supply the afferent pathways for cough receptors; the vagus, through its pharyngeal, superior laryngeal, and pulmonary branches, supplies the large majority of these receptors. […] Receptors are located throughout the airway from the pharynx to the terminal bronchioles, with the greatest concentration located in the larynx, carina, and the bifurcation of larger bronchi. […] Three types of receptors are predominant: Rapidly adapting receptors (RARs) that respond to mechanical stimuli, cigarette smoke, ammonia, acidic and alkaline solutions, hypotonic and hypertonic saline, pulmonary congestion, atelectasis, and bronchoconstriction; Slowly adapting receptors (SARs); Nociceptors on C-fibers that respond to chemical stimuli as well as inflammatory and immunological mediators such as histamine, bradykinin, prostaglandins, substance P, capsaicin, and acidic pH.

• #10 Cough – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK493221/

  Coughing is a largely uncontrolled, protective reflex mechanism responsible for mucociliary clearance of the airway and excess secretions within the airway. This reflex is characterized by the closing of the glottis apparatus with subsequent increases in the intrathoracic pressure, which often exceeds 300 mm Hg. This is followed by the forceful expulsion of the airway contents through the glottis into the pharyngeal space and out of the body. Given the forceful nature of this process, with a velocity of exhalation exceeding 500 mph in some cases, mucous secretions are loosened from the wall of the airway and expelled. […] The reflex of coughing is initiated by a chemical irritation at peripheral nerve receptors within the trachea, main carina, branching points of large airways, and distal smaller airways. They are also present in the pharynx. Laryngeal and tracheobronchial receptors respond to mechanical and chemical stimuli. Chemical receptors are sensitive to acid, heat, and capsaicin-like compounds via activation of the type-1 capsaicin receptor. Additionally, there are multiple neural sensory receptors located within the external auditory canals, eardrums, paranasal sinuses, pharynx, diaphragm, pleura, pericardium, and stomach, which are all capable of stimulating the coughing reflex.

• #11 Chronic Cough: Practice Essentials, Mechanism of Cough, Causes of Chronic Cough

  https://emedicine.medscape.com/article/1048560-overview

  Cough is a protective reflex serving a normal physiologic function of clearing excessive secretions and debris from the pulmonary tract. […] The cough reflex has 3 components: an afferent sensory limb, a central processing center, and an efferent limb. […] The trigeminal, glossopharyngeal, and vagus nerves supply the afferent pathways for cough receptors; the vagus, through its pharyngeal, superior laryngeal, and pulmonary branches, supplies the large majority of these receptors. […] Receptors are located throughout the airway from the pharynx to the terminal bronchioles, with the greatest concentration located in the larynx, carina, and the bifurcation of larger bronchi. […] Three types of receptors are predominant: Rapidly adapting receptors (RARs) that respond to mechanical stimuli, cigarette smoke, ammonia, acidic and alkaline solutions, hypotonic and hypertonic saline, pulmonary congestion, atelectasis, and bronchoconstriction; Slowly adapting receptors (SARs); Nociceptors on C-fibers that respond to chemical stimuli as well as inflammatory and immunological mediators such as histamine, bradykinin, prostaglandins, substance P, capsaicin, and acidic pH.

• #12 Chronic Cough: Practice Essentials, Mechanism of Cough, Causes of Chronic Cough

  https://emedicine.medscape.com/article/1048560-overview

  Cough is a protective reflex serving a normal physiologic function of clearing excessive secretions and debris from the pulmonary tract. […] The cough reflex has 3 components: an afferent sensory limb, a central processing center, and an efferent limb. […] The trigeminal, glossopharyngeal, and vagus nerves supply the afferent pathways for cough receptors; the vagus, through its pharyngeal, superior laryngeal, and pulmonary branches, supplies the large majority of these receptors. […] Receptors are located throughout the airway from the pharynx to the terminal bronchioles, with the greatest concentration located in the larynx, carina, and the bifurcation of larger bronchi. […] Three types of receptors are predominant: Rapidly adapting receptors (RARs) that respond to mechanical stimuli, cigarette smoke, ammonia, acidic and alkaline solutions, hypotonic and hypertonic saline, pulmonary congestion, atelectasis, and bronchoconstriction; Slowly adapting receptors (SARs); Nociceptors on C-fibers that respond to chemical stimuli as well as inflammatory and immunological mediators such as histamine, bradykinin, prostaglandins, substance P, capsaicin, and acidic pH.

• #13 Cough (Proceedings)

  https://www.dvm360.com/view/cough-proceedings

  The first step in creation of a cough is stimulation of the cough receptors. Cough receptors are made up of sensory nerves. […] At least three different receptors are involved in stimulation of a cough response. These three cough receptors are 1) the rapidly adapting stretch receptors, 2) the pulmonary C-fibers and 3) the bronchial C-fibers. […] The cough pathway may be stimulated by mechanical and/or chemical factors. Endogenous triggers to cough include the presence of airway secretions and airway inflammation. Exogenous agents include smoke or aspirated foreign materials such as food or water. […] Certain diseases can magnify the response to a specific agent, resulting in increased cough, such as with Bordetella infection. […] Direct stimulation of the larynx will result in the „expiratory reflex”; which is a cough without prior inspiration. Stimulation of receptors from distal airways typically results in an inspiratory phase prior to the cough.

• #14 How Coughing Works and Remedies for It

  https://www.verywellhealth.com/coughing-facts-1298408

  The cough reflex consists of two components: a sensory component, in which your central nervous system (CNS) senses something that shouldn’t be in your airways, and a motor component, in which your muscles expand and contract to remove it. […] Your CNS, airways, and muscles work together to form a cough through the following process: […] Sensory nerves in the tissues lining your trachea (windpipe), larynx (voice box), bronchi, and carina are instantly activated when a foreign invader touches their lining. […] The vagus nerve signals the medulla located in the brainstem to initiate the cough reflex. […] As the air clears your trachea, the irritant attached to the lining of your airway is cleared with it. […] People with weakened respiratory muscles may be unable to cough. This can be an effect of several health conditions, including stroke, Parkinson’s disease, and multiple sclerosis.

• #15 Anatomy and neuro-pathophysiology of the cough reflex arc

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3415124/

  Coughing is an important defensive reflex that occurs through the stimulation of a complex reflex arc. […] Each cough occurs through the stimulation of a complex reflex arc. This is initiated by the irritation of cough receptors which are found in the trachea, main carina, branching points of large airways, and more distal smaller airways; also, they are present in the pharynx. […] Impulses from stimulated cough receptors traverse an afferent pathway via the vagus nerve to a cough center in the medulla, which itself may be under some control by higher cortical centers. The cough center generates an efferent signal that travels down the vagus, phrenic, and spinal motor nerves to expiratory musculature to produce the cough. […] Therefore, the cough reflex arc is constituted by: 1. Afferent pathway: Sensory nerve fibers (branches of the vagus nerve) located in the ciliated epithelium of the upper airways (pulmonary, auricular, pharyngeal, superior laryngeal, gastric) and cardiac and esophageal branches from the diaphragm.

• #16 Anatomy and neuro-pathophysiology of the cough reflex arc | Multidisciplinary Respiratory Medicine | Full Text

  https://mrmjournal.biomedcentral.com/articles/10.1186/2049-6958-7-5

  Coughing is an important defensive reflex that occurs through the stimulation of a complex reflex arc. […] Each cough occurs through the stimulation of a complex reflex arc. This is initiated by the irritation of cough receptors which are found in the trachea, main carina, branching points of large airways, and more distal smaller airways; also, they are present in the pharynx. […] Impulses from stimulated cough receptors traverse an afferent pathway via the vagus nerve to a cough center in the medulla, which itself may be under some control by higher cortical centers. The cough center generates an efferent signal that travels down the vagus, phrenic, and spinal motor nerves to expiratory musculature to produce the cough. […] The terminations of the vagal afferents are found in abundance in the airway mucosa and in the airway wall from the upper airways to the terminal bronchioles and lung parenchyma.

• #17 Cough Reflex TeachMePhysiology

  https://teachmephysiology.com/respiratory-system/regulation/cough-reflex/

  The cough reflex is an important defence mechanism which clears the airways of irritants by forcefully expelling air from the respiratory tract. […] The cough reflex arc is initiated by irritation of cough receptors, for example, mechanoreceptors or chemoreceptors. […] Sensory information travels to the nucleus tractus solitarius (NTS) of the medulla. The vagus nerve then synapses with motor neurones, delivering information to effector muscles which triggers the cough reflex to occur. […] Various respiratory muscles contract to allow initiation of the cough reflex. […] Irritation of cough receptors causes the vocal cords to open more widely, allowing more air to enter the lungs. […] The epiglottis and vocal cords close, trapping the air within the lungs. […] The internal intercostal muscles and abdominal muscles contract to depress the thoracic cavity.

• #18 Anatomy and neuro-pathophysiology of the cough reflex arc

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3415124/

  Coughing is an important defensive reflex that occurs through the stimulation of a complex reflex arc. […] Each cough occurs through the stimulation of a complex reflex arc. This is initiated by the irritation of cough receptors which are found in the trachea, main carina, branching points of large airways, and more distal smaller airways; also, they are present in the pharynx. […] Impulses from stimulated cough receptors traverse an afferent pathway via the vagus nerve to a cough center in the medulla, which itself may be under some control by higher cortical centers. The cough center generates an efferent signal that travels down the vagus, phrenic, and spinal motor nerves to expiratory musculature to produce the cough. […] Therefore, the cough reflex arc is constituted by: 1. Afferent pathway: Sensory nerve fibers (branches of the vagus nerve) located in the ciliated epithelium of the upper airways (pulmonary, auricular, pharyngeal, superior laryngeal, gastric) and cardiac and esophageal branches from the diaphragm.

• #19 Chronic Cough: Practice Essentials, Mechanism of Cough, Causes of Chronic Cough

  https://emedicine.medscape.com/article/1048560-overview

  Afferent impulses are transmitted to the cough center of the brain, located in the nucleus tractus solitarius of the medulla of the brainstem, which is connected to the central respiratory generator. […] This cough reflex has been shown to have neuroplasticity such that a hypersensitive response is elicited over time due to the cough itself inducing chronic irritation and inflammation and tissue remodeling. […] Both peripheral (increase in sensitivity of cough receptors) and central (changes in central processing in the brainstem) sensitization can account for an exaggerated cough response that is common in patients and further contributes to the maintenance of chronic cough. […] Recently, the term chronic cough hypersensitivity syndrome has been proposed as the new way to label chronic cough owing to the fact that the underlying abnormality leading to chronic coughing is an abnormally sensitive cough reflex.

• #20 Peripheral and central mechanisms of cough hypersensitivity – Singh – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/43624/html

  Chronic cough is a difficult to treat symptom of many respiratory and some non-respiratory diseases, indicating that varied pathologies can underpin the development of chronic cough. […] A strong argument has emerged that changes in the excitability and/or normal regulation of the peripheral and central neural circuits responsible for cough are instrumental in establishing cough hypersensitivity and for causing excessive cough in disease. […] Chronic cough is now widely considered a syndrome (cough hypersensitivity syndrome) characterised by troublesome coughing to low level stimuli, consistent with an upregulation of activity in the neural circuits that ordinarily regulate coughing. […] Neural hypersensitivity is argued to reflect the clinical observation that cough can be more easily triggered by tussive stimuli (hypertussivity) as well as by stimuli that would be considered innocuous in healthy people such as talking, laughing or eating (allotussivity).

• #21 Peripheral and central mechanisms of cough hypersensitivity – Singh – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/43624/html

  Chronic cough is a difficult to treat symptom of many respiratory and some non-respiratory diseases, indicating that varied pathologies can underpin the development of chronic cough. […] A strong argument has emerged that changes in the excitability and/or normal regulation of the peripheral and central neural circuits responsible for cough are instrumental in establishing cough hypersensitivity and for causing excessive cough in disease. […] Chronic cough is now widely considered a syndrome (cough hypersensitivity syndrome) characterised by troublesome coughing to low level stimuli, consistent with an upregulation of activity in the neural circuits that ordinarily regulate coughing. […] Neural hypersensitivity is argued to reflect the clinical observation that cough can be more easily triggered by tussive stimuli (hypertussivity) as well as by stimuli that would be considered innocuous in healthy people such as talking, laughing or eating (allotussivity).

• #22

  https://link.springer.com/article/10.1007/s40136-019-00239-9

  The term Cough Hypersensitivity Syndrome was first proposed by a European Respiratory Society Task Force and is defined as a clinical syndrome characterised by troublesome coughing triggered by low levels of thermal, mechanical or chemical exposure. […] Although the causes of chronic cough vary, cough reflex hypersensitivity is likely to be a shared clinical and mechanistic characteristic. Therefore, while CHS may be present in a wide variety of conditions, common mechanisms likely underpin its development, offering great potential for the development of effective therapies. […] The recognition that chronic cough is characterised by hypersensitivity of the peripheral and central neural pathways involved in cough has expanded the range of potential therapeutic targets currently under evaluation.

• #23 Peripheral and central mechanisms of cough hypersensitivity – Singh – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/43624/html

  Chronic cough is a difficult to treat symptom of many respiratory and some non-respiratory diseases, indicating that varied pathologies can underpin the development of chronic cough. […] A strong argument has emerged that changes in the excitability and/or normal regulation of the peripheral and central neural circuits responsible for cough are instrumental in establishing cough hypersensitivity and for causing excessive cough in disease. […] Chronic cough is now widely considered a syndrome (cough hypersensitivity syndrome) characterised by troublesome coughing to low level stimuli, consistent with an upregulation of activity in the neural circuits that ordinarily regulate coughing. […] Neural hypersensitivity is argued to reflect the clinical observation that cough can be more easily triggered by tussive stimuli (hypertussivity) as well as by stimuli that would be considered innocuous in healthy people such as talking, laughing or eating (allotussivity).

• #24

  https://link.springer.com/article/10.1007/s40136-019-00239-9

  The term Cough Hypersensitivity Syndrome was first proposed by a European Respiratory Society Task Force and is defined as a clinical syndrome characterised by troublesome coughing triggered by low levels of thermal, mechanical or chemical exposure. […] Although the causes of chronic cough vary, cough reflex hypersensitivity is likely to be a shared clinical and mechanistic characteristic. Therefore, while CHS may be present in a wide variety of conditions, common mechanisms likely underpin its development, offering great potential for the development of effective therapies. […] The recognition that chronic cough is characterised by hypersensitivity of the peripheral and central neural pathways involved in cough has expanded the range of potential therapeutic targets currently under evaluation.

• #25 Cough Hypersensitivity Syndrome | AAO-HNS Bulletin

  https://bulletin.entnet.org/clinical-patient-care/article/22892267/cough-hypersensitivity-syndrome

  Cough hypersensitivity syndrome (CHS) represents a significant clinical concern characterized by a troublesome cough in response to low-level stimuli that would not typically provoke such a response in healthy individuals. […] The pathogenesis of CHS is not fully understood but is believed to involve neural dysregulation at both the peripheral and central levels of the cough reflex pathway. Sensitization of the cough reflex is thought to result from neuroplastic changes within the airway innervation, leading to an exaggerated cough response. […] This sensitization can be triggered by various factors, including viral infections, exposure to environmental irritants, gastroesophageal reflux disease (GERD), and postnasal drip, suggesting a multifactorial etiology. […] Recent research has focused on identifying new therapeutic targets for CHS, including transient receptor potential channel antagonists, P2X3 antagonists, and others that play a crucial role in cough reflex sensitivity. […] Understanding the underlying pathophysiology, recognizing the clinical manifestations, and employing a comprehensive management strategy are crucial to improving patient outcomes.

• #26 Peripheral and central mechanisms of cough hypersensitivity – Singh – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/43624/html

  This argues that changes in cough neural activity can occur at multiple locations within the neural circuits that ordinarily regulate coughing. […] The description of the neural networks and processes governing airway sensory processing and cough above provides a framework to help understand how cough can become sensitised or upregulated in disease. […] The clinical phenotype of patients with cough hypersensitivity is increased cough frequency and enhanced cough sensitivity, which suggests that changes in two fundamental neural processes may be at play. […] Enhanced central nervous system (CNS) processing may involve neuroinflammatory mechanisms that activate glial cells, the primary cells regulating inflammatory states in the brain. […] This includes the activation of microglia and astrocytes which release mediators capable of sensitising CNS neurons and evoking molecular and structural plasticity in neurons.

• #27 Chronic Cough: Practice Essentials, Mechanism of Cough, Causes of Chronic Cough

  https://emedicine.medscape.com/article/1048560-overview

  Afferent impulses are transmitted to the cough center of the brain, located in the nucleus tractus solitarius of the medulla of the brainstem, which is connected to the central respiratory generator. […] This cough reflex has been shown to have neuroplasticity such that a hypersensitive response is elicited over time due to the cough itself inducing chronic irritation and inflammation and tissue remodeling. […] Both peripheral (increase in sensitivity of cough receptors) and central (changes in central processing in the brainstem) sensitization can account for an exaggerated cough response that is common in patients and further contributes to the maintenance of chronic cough. […] Recently, the term chronic cough hypersensitivity syndrome has been proposed as the new way to label chronic cough owing to the fact that the underlying abnormality leading to chronic coughing is an abnormally sensitive cough reflex.

• #28 Peripheral and central mechanisms of cough hypersensitivity – Singh – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/43624/html

  This argues that changes in cough neural activity can occur at multiple locations within the neural circuits that ordinarily regulate coughing. […] The description of the neural networks and processes governing airway sensory processing and cough above provides a framework to help understand how cough can become sensitised or upregulated in disease. […] The clinical phenotype of patients with cough hypersensitivity is increased cough frequency and enhanced cough sensitivity, which suggests that changes in two fundamental neural processes may be at play. […] Enhanced central nervous system (CNS) processing may involve neuroinflammatory mechanisms that activate glial cells, the primary cells regulating inflammatory states in the brain. […] This includes the activation of microglia and astrocytes which release mediators capable of sensitising CNS neurons and evoking molecular and structural plasticity in neurons.

• #29

  https://link.springer.com/article/10.1007/s40136-019-00239-9

  The mechanisms underpinning the development of CHS may be akin to those described in pain where disordered peripheral and central neurophysiology are thought to be responsible for a variety of chronic pain syndromes. Chronic cough patients appear to have altered brain activity with evidence of both central sensitisation and dysfunctional inhibitory control.

• #30 Chronic Cough: Practice Essentials, Mechanism of Cough, Causes of Chronic Cough

  https://emedicine.medscape.com/article/1048560-overview

  Indeed, evidence suggests that members of the transient receptor potential (TRP) ion channel family, specifically the vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) channels, are receptors that mediate cough. […] Patients with chronic cough hypersensitivity syndrome have a negative workup and lack of response to common treatments and are characterized by having a sensation of a tickle or itch in the throat, as well as being sensitive to triggers such as cold air, eating, and odors.

• #31

  https://journals.lww.com/lungindia/fulltext/2015/32010/chronic_dry_cough__diagnostic_and_management.11.aspx

  Cough is an important natural defense mechanism of the respiratory tract. […] Chronic cough, in more severe cases, can also cause rib fractures, pneumothorax, pneumomediastinum (PM), and subcutaneous emphysema. […] This review will discuss the mechanism and etiology of the cough, along with recent advances in the field of cough, highlighting some of the diagnostic and management challenges. […] Stimulation of the peripheral sensory nerves is the first step that drives resultant cough. […] The transmission mechanism in these neurons is controlled by transient receptor potential cation channels, especially the transient receptor potential vanilloid 1 and ankyrin 1 (TRPV1 and TRPA1). […] The vagally-mediated esophageal-tracheobronchial cough reflex is the major mechanism responsible for GERD-associated cough.

• #32

  https://journals.lww.com/lungindia/fulltext/2015/32010/chronic_dry_cough__diagnostic_and_management.11.aspx

  Cough is an important natural defense mechanism of the respiratory tract. […] Chronic cough, in more severe cases, can also cause rib fractures, pneumothorax, pneumomediastinum (PM), and subcutaneous emphysema. […] This review will discuss the mechanism and etiology of the cough, along with recent advances in the field of cough, highlighting some of the diagnostic and management challenges. […] Stimulation of the peripheral sensory nerves is the first step that drives resultant cough. […] The transmission mechanism in these neurons is controlled by transient receptor potential cation channels, especially the transient receptor potential vanilloid 1 and ankyrin 1 (TRPV1 and TRPA1). […] The vagally-mediated esophageal-tracheobronchial cough reflex is the major mechanism responsible for GERD-associated cough.

• #33 How does rhinovirus cause the common cold cough? | BMJ Open Respiratory Research

  https://bmjopenrespres.bmj.com/content/3/1/e000118

  Cough is clearly a neuronal reflex, so the hypothesis that neuronal modulation underlies the pathogenesis of viral cough is the most convincing. However, at present, there is no single comprehensive mechanism which explains cough induced by HRV or indeed any other respiratory pathogen. Theories include a cooperative role of pulmonary oxidative stress in vagal sensory nerves between TRPV1, TRPA1 and P2X receptors.

• #34 Cough Hypersensitivity Syndrome | AAO-HNS Bulletin

  https://bulletin.entnet.org/clinical-patient-care/article/22892267/cough-hypersensitivity-syndrome

  Cough hypersensitivity syndrome (CHS) represents a significant clinical concern characterized by a troublesome cough in response to low-level stimuli that would not typically provoke such a response in healthy individuals. […] The pathogenesis of CHS is not fully understood but is believed to involve neural dysregulation at both the peripheral and central levels of the cough reflex pathway. Sensitization of the cough reflex is thought to result from neuroplastic changes within the airway innervation, leading to an exaggerated cough response. […] This sensitization can be triggered by various factors, including viral infections, exposure to environmental irritants, gastroesophageal reflux disease (GERD), and postnasal drip, suggesting a multifactorial etiology. […] Recent research has focused on identifying new therapeutic targets for CHS, including transient receptor potential channel antagonists, P2X3 antagonists, and others that play a crucial role in cough reflex sensitivity. […] Understanding the underlying pathophysiology, recognizing the clinical manifestations, and employing a comprehensive management strategy are crucial to improving patient outcomes.

• #35 Anatomy and neuro-pathophysiology of the cough reflex arc

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3415124/

  A nonproductive cough is a well-recognized complication of treatment with angiotensin converting enzyme (ACE) inhibitors, occurring in up to 15% of patients treated with these agents. Although the pathogenesis of the cough is not known with certainty, it has commonly been hypothesized that accumulation of bradykinin, which is normally degraded in part by ACE, may stimulate afferent C-fibers in the airway. […] The important observation that cough does not appear to occur with increased frequency in patients treated with angiotensin II receptor antagonists (which do not increase kinin levels) is consistent with the kinin hypothesis. […] Since cough is an important defensive reflex, required to maintain the health of the lungs, people who do not cough effectively are at risk of atelectasis, recurrent pneumonia, and chronic airways disease from aspiration and retention of secretions.

• #36 Anatomy and neuro-pathophysiology of the cough reflex arc | Multidisciplinary Respiratory Medicine | Full Text

  https://mrmjournal.biomedcentral.com/articles/10.1186/2049-6958-7-5

  Cough-induced rib fractures are another painful and potentially serious complication of chronic cough. […] A nonproductive cough is a well-recognized complication of treatment with angiotensin converting enzyme (ACE) inhibitors, occurring in up to 15% of patients treated with these agents. […] The important observation that cough does not appear to occur with increased frequency in patients treated with angiotensin II receptor antagonists (which do not increase kinin levels) is consistent with the kinin hypothesis. […] Since cough is an important defensive reflex, required to maintain the health of the lungs, people who do not cough effectively are at risk of atelectasis, recurrent pneumonia, and chronic airways disease from aspiration and retention of secretions.

• #37 Anatomy and neuro-pathophysiology of the cough reflex arc

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3415124/

  A nonproductive cough is a well-recognized complication of treatment with angiotensin converting enzyme (ACE) inhibitors, occurring in up to 15% of patients treated with these agents. Although the pathogenesis of the cough is not known with certainty, it has commonly been hypothesized that accumulation of bradykinin, which is normally degraded in part by ACE, may stimulate afferent C-fibers in the airway. […] The important observation that cough does not appear to occur with increased frequency in patients treated with angiotensin II receptor antagonists (which do not increase kinin levels) is consistent with the kinin hypothesis. […] Since cough is an important defensive reflex, required to maintain the health of the lungs, people who do not cough effectively are at risk of atelectasis, recurrent pneumonia, and chronic airways disease from aspiration and retention of secretions.

• #38 Anatomy and neuro-pathophysiology of the cough reflex arc | Multidisciplinary Respiratory Medicine | Full Text

  https://mrmjournal.biomedcentral.com/articles/10.1186/2049-6958-7-5

  Cough-induced rib fractures are another painful and potentially serious complication of chronic cough. […] A nonproductive cough is a well-recognized complication of treatment with angiotensin converting enzyme (ACE) inhibitors, occurring in up to 15% of patients treated with these agents. […] The important observation that cough does not appear to occur with increased frequency in patients treated with angiotensin II receptor antagonists (which do not increase kinin levels) is consistent with the kinin hypothesis. […] Since cough is an important defensive reflex, required to maintain the health of the lungs, people who do not cough effectively are at risk of atelectasis, recurrent pneumonia, and chronic airways disease from aspiration and retention of secretions.

• #39 Cough Reflex TeachMePhysiology

  https://teachmephysiology.com/respiratory-system/regulation/cough-reflex/

  ACE inhibitors prevent the inactivation of bradykinin, and cause it to accumulate in the respiratory tract. Bradykinin can cause chemical irritation of the C-fibres of the respiratory tract through the release of proinflammatory peptides (e.g. substance P) and histamine, which results in hyperstimulation of the cough reflex.

• #40 Drug-induced chronic cough and the possible mechanism of action – Ding – Annals of Palliative Medicine

  https://apm.amegroups.org/article/view/50825/html

  Chronic cough is defined as a cough lasting for 8 weeks with a normal chest radiograph. […] Drug-induced chronic cough, a rare cause of chronic cough, refers to a chronic cough caused by certain drugs. […] An important step in the diagnosis and treatment of chronic cough is to determine the history of the patient with regard to any drugs that can induce chronic cough. […] This article reviews the relevant drugs that may cause cough and their possible mechanisms of action. […] The mechanism of ACEI-inducing cough mainly includes the following aspects. […] The cough induced by lisinopril was reversed by bradykinin B2 and NK1 receptor antagonists. […] These results indicated that bradykinin/substance P might be involved in ACEI-associated cough through the upregulation of vagal nerve excitability.

• #41 Recurrent Cough Syncope Due to Pertussis in Adults: Report of Three Cases and Review of the Literature | Kogan | Journal of Medical Cases

  https://www.journalmc.org/index.php/JMC/article/view/2537/1888

  Cough syncope, also called tussive syncope, is a well-recognized syndrome for about 70 years, in which loss of consciousness usually occurs immediately after a violent cough or prolonged bouts of violent coughing, lasting for seconds with rapid restoration of full consciousness. Its precise pathophysiologic mechanism is not fully understood and remains a matter of debate. […] The precise pathophysiologic mechanism of cough syncope is not fully understood, and remains a matter of debate. Several mechanisms have been proposed in this regard. With continuous coughing, intra-thoracic pressure increases resulting in decrease in venous return, ventricular filling, cardiac output, and blood pressure. […] Other suggested mechanisms indicates that the increased intra-thoracic pressure during coughing is transmitted to the cerebrospinal fluid, causing an acute pressure increase in the skull, compromising cerebral perfusion and resulting in syncope.

• #42 Recurrent Cough Syncope Due to Pertussis in Adults: Report of Three Cases and Review of the Literature | Kogan | Journal of Medical Cases

  https://www.journalmc.org/index.php/JMC/article/view/2537/1888

  Cough syncope, also called tussive syncope, is a well-recognized syndrome for about 70 years, in which loss of consciousness usually occurs immediately after a violent cough or prolonged bouts of violent coughing, lasting for seconds with rapid restoration of full consciousness. Its precise pathophysiologic mechanism is not fully understood and remains a matter of debate. […] The precise pathophysiologic mechanism of cough syncope is not fully understood, and remains a matter of debate. Several mechanisms have been proposed in this regard. With continuous coughing, intra-thoracic pressure increases resulting in decrease in venous return, ventricular filling, cardiac output, and blood pressure. […] Other suggested mechanisms indicates that the increased intra-thoracic pressure during coughing is transmitted to the cerebrospinal fluid, causing an acute pressure increase in the skull, compromising cerebral perfusion and resulting in syncope.

• #43 Cough syncope | MedLink Neurology

  https://www.medlink.com/articles/cough-syncope

  Several pathophysiologic processes may cause or contribute to cough-related syncope: Valsalva-induced decreased cardiac output. Cough acts like a strong Valsalva maneuver, increasing intrathoracic pressures by up to 300 mm Hg, which causes decreased venous return to the atria with resultant decreased stroke volume, decreased blood pressure, and decreased cerebral perfusion. […] Increased intracranial pressure. Cough-induced increased intrathoracic pressure is transmitted to the cerebrospinal fluid with resultant sudden increased intracranial pressure that may act like a cerebral concussion or may force blood out of the closed cranial vault and cause decreased cerebral blood flow or even transient cerebral circulatory arrest. […] Cardiac arrhythmias. Cough may produce vagally mediated cardiac arrhythmias, including sinus arrest and atrioventricular conduction block.

• #44 Cough syncope | MedLink Neurology

  https://www.medlink.com/articles/cough-syncope

  Stimulation of hypersensitive carotid sinus. Cough may stimulate a hypersensitive carotid sinus and cause reflex hypotension or vagally mediated, high-grade, atrioventricular block and syncope. […] Cough-triggered neural reflex-mediated hypotension-bradycardia. Many patients with cough syncope exhibit prolonged hypotension in response to cough or Valsalva maneuver, and in at least some cases, this appears to be mediated via a neural reflex mechanism. […] Laryngospasm. Patients with severe gastroesophageal reflux disease can develop severe laryngospasm and syncope, particularly in association with a recent or concurrent respiratory infection that contributes to protracted cough and an increased amount of refluxate. […] Tracheal compression. A single case of cough syncope and tracheal compression due to a retrosternal goiter has been reported, but the case was confounded by a concomitant pulmonary embolus from a deep vein thrombosis.

• #45 Cough syncope | MedLink Neurology

  https://www.medlink.com/articles/cough-syncope

  Augmentation of left ventricular outflow obstruction. Cough may dynamically augment left ventricular outflow obstruction in patients with idiopathic hypertrophic subaortic stenosis, partly due to reflex sympathetic stimulation. […] Impaired left ventricular diastolic filling. Cough may augment impaired diastolic filling and produce a marked decrease in cardiac output in patients with constrictive pericarditis. […] Impaction of a brainstem herniation. Cough or sneezing may cause impaction of a brainstem herniation in the foramen magnum in patients with a Chiari malformation with resulting compression of efferent sympathetic and parasympathetic cardiovascular pathways in the brainstem, dysfunction of the midbrain reticular activating system, craniospinal pressure dissociation, transient increased intracranial pressure, and vertebrobasilar compression with brainstem ischemia.

• #46 Cough syncope | MedLink Neurology

  https://www.medlink.com/articles/cough-syncope

  Decreased cerebral blood flow. Cough may further impair cerebral circulation in patients with already compromised cerebral blood flow because of extracranial or intracranial arterial stenosis or occlusion. […] Internal jugular vein valve insufficiency. Cough syncope can result from transient increases in intracranial pressure and consequent reduction in cerebral blood flow due to abnormally high internal jugular vein pressures transmitted from the thoracic cavity because of incompetent internal jugular vein valves. […] Seizure. Rarely, cough and its associated changes in cerebral blood flow or other pathophysiologic processes may actually trigger a seizure with resultant loss of consciousness followed by a postictal state.

• #47 A Review on Cough in Asthma Published by Professor Lai Kefang with Other International Experts-Progress In Scientific Research-Home-State Key Laboratory of Respiratory Disease

  http://www.sklrd.cn/en/show.php?id=958

  Two thirds of adult patients with cough-variant asthma (CVA) are dry cough cases. […] Based on cough symptoms, asthma can be classified into CVA, cough-predominant asthma (CPA) and typical asthma or wheezing-predominant asthma (WPA). […] Due to the similarities between CVA and CPA in pathogenesis, clinical manifestations and treatment, the authors propose that CVA and CPA are collectively referred to as asthmatic cough or cough associated with asthma. […] Previous studies have found cough hypersensitivity in adult patients with stable asthma, and increased capsaicin cough response was associated with more severe asthma in patients with non-atopic asthma, which is possibly due to altered sensory nerve excitability and activity of the upper-airway laryngeal vagal sensory nerve fibres driven by the inflammatory pathology of asthma.

• #48 A Review on Cough in Asthma Published by Professor Lai Kefang with Other International Experts-Progress In Scientific Research-Home-State Key Laboratory of Respiratory Disease

  http://www.sklrd.cn/en/show.php?id=958

  Two thirds of adult patients with cough-variant asthma (CVA) are dry cough cases. […] Based on cough symptoms, asthma can be classified into CVA, cough-predominant asthma (CPA) and typical asthma or wheezing-predominant asthma (WPA). […] Due to the similarities between CVA and CPA in pathogenesis, clinical manifestations and treatment, the authors propose that CVA and CPA are collectively referred to as asthmatic cough or cough associated with asthma. […] Previous studies have found cough hypersensitivity in adult patients with stable asthma, and increased capsaicin cough response was associated with more severe asthma in patients with non-atopic asthma, which is possibly due to altered sensory nerve excitability and activity of the upper-airway laryngeal vagal sensory nerve fibres driven by the inflammatory pathology of asthma.

• #49 A Review on Cough in Asthma Published by Professor Lai Kefang with Other International Experts-Progress In Scientific Research-Home-State Key Laboratory of Respiratory Disease

  http://www.sklrd.cn/en/show.php?id=958

  Two thirds of adult patients with cough-variant asthma (CVA) are dry cough cases. […] Based on cough symptoms, asthma can be classified into CVA, cough-predominant asthma (CPA) and typical asthma or wheezing-predominant asthma (WPA). […] Due to the similarities between CVA and CPA in pathogenesis, clinical manifestations and treatment, the authors propose that CVA and CPA are collectively referred to as asthmatic cough or cough associated with asthma. […] Previous studies have found cough hypersensitivity in adult patients with stable asthma, and increased capsaicin cough response was associated with more severe asthma in patients with non-atopic asthma, which is possibly due to altered sensory nerve excitability and activity of the upper-airway laryngeal vagal sensory nerve fibres driven by the inflammatory pathology of asthma.

• #50 A Review on Cough in Asthma Published by Professor Lai Kefang with Other International Experts-Progress In Scientific Research-Home-State Key Laboratory of Respiratory Disease

  http://www.sklrd.cn/en/show.php?id=958

  Smooth muscle constriction induced by asthma mediators, such as histamine and cysteinyl leukotrienes may be an important mechanism of asthmatic cough. […] Cough and capsaicin cough sensitivity can be improved with anti-IL-5 antibody in patients with severe eosinophilic asthma, suggesting that eosinophilic inflammation may underlie the chronic cough and cough hypersensitivity of corticosteroid-resistant cough in asthma. […] Asthmatic cough in adults is heterogeneous, involving multiple different pathophysiological mechanisms. […] For asthmatic cough patients with bronchoconstriction and type 2 inflammation, inhaled corticosteroids and long-acting -adrenoceptor agonists are effective in relieving cough. […] For cough patients with cough hypersensitivity, to identify and manage cough triggers and comorbid diseases associated with persistent cough and, second, to control cough hypersensitivity.

• #51 How does rhinovirus cause the common cold cough? | BMJ Open Respiratory Research

  https://bmjopenrespres.bmj.com/content/3/1/e000118

  Cough is a protective reflex to prevent aspiration and can be triggered by a multitude of stimuli. The commonest form of cough is caused by upper respiratory tract infection and has no benefit to the host. […] Unfortunately, the mechanism of infectious cough brought on by pathogenic viruses, such as human rhinovirus, during colds, remains elusive despite the extensive work that has been undertaken. For socioeconomic reasons, it is imperative we identify the mechanism of cough. There are several theories which have been proposed as the causative mechanism of cough in rhinovirus infection, encompassing a range of different processes. Those of which hold most promise are physical disruption of the epithelial lining, excess mucus production and an inflammatory response to rhinovirus infection which may be excessive. And finally, neuronal modulation, the most convincing hypothesis, is thought to potentiate cough long after the original stimulus has been cleared.

• #52 How does rhinovirus cause the common cold cough? | BMJ Open Respiratory Research

  https://bmjopenrespres.bmj.com/content/3/1/e000118

  Cough is a protective reflex to prevent aspiration and can be triggered by a multitude of stimuli. The commonest form of cough is caused by upper respiratory tract infection and has no benefit to the host. […] Unfortunately, the mechanism of infectious cough brought on by pathogenic viruses, such as human rhinovirus, during colds, remains elusive despite the extensive work that has been undertaken. For socioeconomic reasons, it is imperative we identify the mechanism of cough. There are several theories which have been proposed as the causative mechanism of cough in rhinovirus infection, encompassing a range of different processes. Those of which hold most promise are physical disruption of the epithelial lining, excess mucus production and an inflammatory response to rhinovirus infection which may be excessive. And finally, neuronal modulation, the most convincing hypothesis, is thought to potentiate cough long after the original stimulus has been cleared.

• #53 How does rhinovirus cause the common cold cough? | BMJ Open Respiratory Research

  https://bmjopenrespres.bmj.com/content/3/1/e000118

  HRV infection results in the production a broad profile of inflammatory mediators in the host. The primary inflammatory cytokines reported in HRV infection are interferon (IFN), interleukin (IL) 1, IL-6, IL-8, tumour necrosis factor (TNF), granulocyte-macrophage colony-stimulating factor and RANTES. The infection leads to massive upregulation, and, consequently, it is often described as a cytokine disease. […] By comparison with other respiratory viruses such as influenza, HRV is renowned for its minimal cytopathic effects. It has been suggested that influenza has a higher incidence of cough than that seen with HRV infections. Thus, physical disruption of airway integrity may be a factor in a heightened cough response. […] Excessive mucus production and secretion is common in URTI, initiating symptoms such as a cough and sneezing, and thus facilitating transmission of infection. HRV, in particular, upregulates the transcription of various mucin genes including MUC5AC.

• #54 How does rhinovirus cause the common cold cough? | BMJ Open Respiratory Research

  https://bmjopenrespres.bmj.com/content/3/1/e000118

  Cough is clearly a neuronal reflex, so the hypothesis that neuronal modulation underlies the pathogenesis of viral cough is the most convincing. However, at present, there is no single comprehensive mechanism which explains cough induced by HRV or indeed any other respiratory pathogen. Theories include a cooperative role of pulmonary oxidative stress in vagal sensory nerves between TRPV1, TRPA1 and P2X receptors.

• #55 15.3E: Whooping Cough – Biology LibreTexts

  https://bio.libretexts.org/Bookshelves/Microbiology/Microbiology_(Boundless)/15%3A_Diseases/15.03%3A_Bacterial_Diseases_of_the_Respiratory_System/15.3E%3A_Whooping_Cough

  Pertussis is caused by the bacteria, Bordetella pertussis, a gram-negative, aerobic coccobacillus capsulate of the genus Bordetella. Bordetella pertussis infects its host by colonizing lung epithelial cells. The bacterium contains a surface protein, filamentous haemagglutinin adhesin, which binds to the sulfatides found on the cilia of epithelial cells. Once anchored, the bacterium produces tracheal cytotoxin, which stops the cilia from beating. This prevents the cilia from clearing debris from an organism s lungs, and the body responds by sending the host into a coughing fit. These coughs expel some bacteria into the air, which are free to infect other hosts. […] B. pertussis has the ability to inhibit the function of a hosts immune system, through virulence factors. Its virulence factors include pertussis toxin, filamentous hmagglutinin, pertactin, fimbria, and tracheal cytotoxin. The pertussis toxin, or PTx, inhibits G protein coupling that regulates an adenylate cyclase-mediated conversion of ATP to cyclic AMP. The end result is that phagocytes convert too much ATP to cyclic AMP, which can cause disturbances in cellular signaling mechanisms. This prevents phagocytes from correctly responding to an infection. PTx, formerly known as lymphocytosis -promoting factor, causes a decrease in the entry of lymphocytes into lymph nodes. This can lead to a condition known as lymphocytosis, which is a large increase in the number of lymphocytes in an organisms blood. […] Whooping cough is caused by the bacteria Bordetella pertussis, which infects the respiratory system. Bordetella pertussis produces a number of virulence factors, notably Ptx, which inhibits the ability of phagocytes to respond to infections. This helps Bordetella pertussis spread throughout a host.

• #56 15.3E: Whooping Cough – Biology LibreTexts

  https://bio.libretexts.org/Bookshelves/Microbiology/Microbiology_(Boundless)/15%3A_Diseases/15.03%3A_Bacterial_Diseases_of_the_Respiratory_System/15.3E%3A_Whooping_Cough

  Pertussis is caused by the bacteria, Bordetella pertussis, a gram-negative, aerobic coccobacillus capsulate of the genus Bordetella. Bordetella pertussis infects its host by colonizing lung epithelial cells. The bacterium contains a surface protein, filamentous haemagglutinin adhesin, which binds to the sulfatides found on the cilia of epithelial cells. Once anchored, the bacterium produces tracheal cytotoxin, which stops the cilia from beating. This prevents the cilia from clearing debris from an organism s lungs, and the body responds by sending the host into a coughing fit. These coughs expel some bacteria into the air, which are free to infect other hosts. […] B. pertussis has the ability to inhibit the function of a hosts immune system, through virulence factors. Its virulence factors include pertussis toxin, filamentous hmagglutinin, pertactin, fimbria, and tracheal cytotoxin. The pertussis toxin, or PTx, inhibits G protein coupling that regulates an adenylate cyclase-mediated conversion of ATP to cyclic AMP. The end result is that phagocytes convert too much ATP to cyclic AMP, which can cause disturbances in cellular signaling mechanisms. This prevents phagocytes from correctly responding to an infection. PTx, formerly known as lymphocytosis -promoting factor, causes a decrease in the entry of lymphocytes into lymph nodes. This can lead to a condition known as lymphocytosis, which is a large increase in the number of lymphocytes in an organisms blood. […] Whooping cough is caused by the bacteria Bordetella pertussis, which infects the respiratory system. Bordetella pertussis produces a number of virulence factors, notably Ptx, which inhibits the ability of phagocytes to respond to infections. This helps Bordetella pertussis spread throughout a host.

• #57 Anatomy and neuro-pathophysiology of the cough reflex arc

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3415124/

  Coughing is an important defensive reflex that occurs through the stimulation of a complex reflex arc. […] Each cough occurs through the stimulation of a complex reflex arc. This is initiated by the irritation of cough receptors which are found in the trachea, main carina, branching points of large airways, and more distal smaller airways; also, they are present in the pharynx. […] Impulses from stimulated cough receptors traverse an afferent pathway via the vagus nerve to a cough center in the medulla, which itself may be under some control by higher cortical centers. The cough center generates an efferent signal that travels down the vagus, phrenic, and spinal motor nerves to expiratory musculature to produce the cough. […] Therefore, the cough reflex arc is constituted by: 1. Afferent pathway: Sensory nerve fibers (branches of the vagus nerve) located in the ciliated epithelium of the upper airways (pulmonary, auricular, pharyngeal, superior laryngeal, gastric) and cardiac and esophageal branches from the diaphragm.

• #58 Anatomy and neuro-pathophysiology of the cough reflex arc | Multidisciplinary Respiratory Medicine | Full Text

  https://mrmjournal.biomedcentral.com/articles/10.1186/2049-6958-7-5

  Coughing is an important defensive reflex that occurs through the stimulation of a complex reflex arc. […] Each cough occurs through the stimulation of a complex reflex arc. This is initiated by the irritation of cough receptors which are found in the trachea, main carina, branching points of large airways, and more distal smaller airways; also, they are present in the pharynx. […] Impulses from stimulated cough receptors traverse an afferent pathway via the vagus nerve to a cough center in the medulla, which itself may be under some control by higher cortical centers. The cough center generates an efferent signal that travels down the vagus, phrenic, and spinal motor nerves to expiratory musculature to produce the cough. […] The terminations of the vagal afferents are found in abundance in the airway mucosa and in the airway wall from the upper airways to the terminal bronchioles and lung parenchyma.

• #59 Mechanism of cough | PPT

  https://www.slideshare.net/slideshow/mechanism-of-cough/14039175

  Coughing is a normal protective mechanism that acts to clear secretions and foreign materials from the tracheobronchial tree. […] The coughing mechanism involves inspiration of air, followed by forced contraction of abdominal and intercostal muscles to increase lung pressure and expel air rapidly through the vocal cords to shear and remove mucus or foreign materials from the airways. […] Cough is an explosive expiration that provides a normal protective mechanism for clearing the tracheobronchial tree of secretions and foreign material. […] Coughing may be initiated either voluntarily or reflexively. […] As a defensive reflex it has both afferent and efferent pathways. […] The afferent limb includes receptors within the sensory distribution of the trigeminal, glossopharyngeal, superior laryngeal, and vagus nerves. The efferent limb includes the recurrent laryngeal nerve and the spinal nerves.

• #60 Cough management: a practical approach | Cough | Full Text

  https://coughjournal.biomedcentral.com/articles/10.1186/1745-9974-7-7

  Cough is an important defensive reflex that enhances the clearance of secretions and particles from the airways and protects the lower airways from the aspiration of foreign materials. […] The present review provides a summary of the most clinically relevant anti-tussive drugs in addition to their potential mechanism of action. […] The potential benefits of treating cough early could be in preventing the vicious cycle of cough perpetuating cough. […] The acute phase of the cough could be caused by a respiratory virus or by an episode of gastroesophageal reflux disease (GERD) through direct stimulation of cough receptors. The inducing agent may also be involved in the process of sensitization that may contribute to a more persistent cough. […] The most common causes of chronic cough are UACS due to a variety of rhinosinus conditions, asthma, and GERD. Each of these diagnoses may be present alone or in combination and may be clinically silent apart from the cough itself.

• #61 Anatomy and neuro-pathophysiology of the cough reflex arc

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3415124/

  A nonproductive cough is a well-recognized complication of treatment with angiotensin converting enzyme (ACE) inhibitors, occurring in up to 15% of patients treated with these agents. Although the pathogenesis of the cough is not known with certainty, it has commonly been hypothesized that accumulation of bradykinin, which is normally degraded in part by ACE, may stimulate afferent C-fibers in the airway. […] The important observation that cough does not appear to occur with increased frequency in patients treated with angiotensin II receptor antagonists (which do not increase kinin levels) is consistent with the kinin hypothesis. […] Since cough is an important defensive reflex, required to maintain the health of the lungs, people who do not cough effectively are at risk of atelectasis, recurrent pneumonia, and chronic airways disease from aspiration and retention of secretions.

• #62 Anatomy and neuro-pathophysiology of the cough reflex arc | Multidisciplinary Respiratory Medicine | Full Text

  https://mrmjournal.biomedcentral.com/articles/10.1186/2049-6958-7-5

  Cough-induced rib fractures are another painful and potentially serious complication of chronic cough. […] A nonproductive cough is a well-recognized complication of treatment with angiotensin converting enzyme (ACE) inhibitors, occurring in up to 15% of patients treated with these agents. […] The important observation that cough does not appear to occur with increased frequency in patients treated with angiotensin II receptor antagonists (which do not increase kinin levels) is consistent with the kinin hypothesis. […] Since cough is an important defensive reflex, required to maintain the health of the lungs, people who do not cough effectively are at risk of atelectasis, recurrent pneumonia, and chronic airways disease from aspiration and retention of secretions.

• #63 Cough Techniques For Tracheostomy | Tracheostomy Education

  https://tracheostomyeducation.com/cough-techniques/

  Patients with tracheostomy and mechanical ventilation have an impaired cough mechanism. Coughing is an important defense mechanism to remove irritants, pollutants, bacteria or any foreign objects (food, liquids, secretions) that have entered the airway. […] A normal cough is initiated by the irritation of cough receptors which are found in the trachea, main carina, branching points of large airways, more distal smaller airways and are also present in the pharynx. […] Individuals with tracheostomy will typically, at some point, have an impaired cough reflex. This may be due to the underlying medical condition. […] Individuals with tracheostomy, particularly with an inflated cuff, are unable to generate the pressure for an effective cough. […] The goal of airway clearance is to reduce airway obstruction, improve mucociliary clearance, improve ventilation and optimize gas exchange.

• #64 Cough Techniques For Tracheostomy | Tracheostomy Education

  https://tracheostomyeducation.com/cough-techniques/

  Patients with tracheostomy and mechanical ventilation have an impaired cough mechanism. Coughing is an important defense mechanism to remove irritants, pollutants, bacteria or any foreign objects (food, liquids, secretions) that have entered the airway. […] A normal cough is initiated by the irritation of cough receptors which are found in the trachea, main carina, branching points of large airways, more distal smaller airways and are also present in the pharynx. […] Individuals with tracheostomy will typically, at some point, have an impaired cough reflex. This may be due to the underlying medical condition. […] Individuals with tracheostomy, particularly with an inflated cuff, are unable to generate the pressure for an effective cough. […] The goal of airway clearance is to reduce airway obstruction, improve mucociliary clearance, improve ventilation and optimize gas exchange.

• #65 Cough as a neurological sign: What a clinician should know

  https://www.wjgnet.com/2220-3141/full/v11/i3/115.htm

  The ability to voluntarily produce and suppress a cough is an example of the cortical control of the cough. Reduced strength of the voluntary cough may increase the risk of aspiration and other pulmonary consequences due to inadequate clearing of the aspirated material from the airway, as seen in patients with brainstem or cerebral stroke associated with an abnormal laryngeal cough reflex.

• #66 Cough hypersensitivity and chronic cough | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-022-00370-w

  Chronic cough is globally prevalent across all age groups. […] Most patients with chronic cough have cough hypersensitivity, which is characterized by increased neural responsivity to a range of stimuli that affect the airways and lungs, and other tissues innervated by common nerve supplies. […] Understanding of the mechanisms that contribute to cough hypersensitivity and excessive coughing in different patient populations and across the lifespan is advancing and has contributed to the development of new therapies for chronic cough in adults. […] Owing to differences in the pathology, the organs involved and individual patient factors, treatment of chronic cough is progressing towards a personalized approach, and, in the future, novel ways to endotype patients with cough may prove valuable in management.

• #67

  https://link.springer.com/article/10.1007/s40136-019-00239-9

  Chronic cough, defined in adults as one lasting longer than 8 weeks, is among the commonest clinical problems encountered by doctors both in general practice and in hospital. […] The underlying principle recommended in these guidelines is first to consider common respiratory diseases associated with obvious chest radiology and lung function abnormalities and then systematically evaluate the patient for other common causes such as asthma, reflux disease and upper airway disorders. […] Central to this has been the notion that cough develops as a result of inflammation causing damage to the nerve cells (neuroinflammation) that conduct the cough signal from the lungs to the brain resulting in the clinical state now termed, cough hypersensitivity syndrome (CHS). Understanding the mechanisms responsible for this nerve damage (neuropathy) will be key to developing better treatments.

• #68 Cough hypersensitivity and chronic cough | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-022-00370-w

  Chronic cough is globally prevalent across all age groups. […] Most patients with chronic cough have cough hypersensitivity, which is characterized by increased neural responsivity to a range of stimuli that affect the airways and lungs, and other tissues innervated by common nerve supplies. […] Understanding of the mechanisms that contribute to cough hypersensitivity and excessive coughing in different patient populations and across the lifespan is advancing and has contributed to the development of new therapies for chronic cough in adults. […] Owing to differences in the pathology, the organs involved and individual patient factors, treatment of chronic cough is progressing towards a personalized approach, and, in the future, novel ways to endotype patients with cough may prove valuable in management.

• #69

  https://link.springer.com/article/10.1007/s40136-019-00239-9

  The term Cough Hypersensitivity Syndrome was first proposed by a European Respiratory Society Task Force and is defined as a clinical syndrome characterised by troublesome coughing triggered by low levels of thermal, mechanical or chemical exposure. […] Although the causes of chronic cough vary, cough reflex hypersensitivity is likely to be a shared clinical and mechanistic characteristic. Therefore, while CHS may be present in a wide variety of conditions, common mechanisms likely underpin its development, offering great potential for the development of effective therapies. […] The recognition that chronic cough is characterised by hypersensitivity of the peripheral and central neural pathways involved in cough has expanded the range of potential therapeutic targets currently under evaluation.

• #70 Cough hypersensitivity and chronic cough | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-022-00370-w

  Chronic cough is globally prevalent across all age groups. […] Most patients with chronic cough have cough hypersensitivity, which is characterized by increased neural responsivity to a range of stimuli that affect the airways and lungs, and other tissues innervated by common nerve supplies. […] Understanding of the mechanisms that contribute to cough hypersensitivity and excessive coughing in different patient populations and across the lifespan is advancing and has contributed to the development of new therapies for chronic cough in adults. […] Owing to differences in the pathology, the organs involved and individual patient factors, treatment of chronic cough is progressing towards a personalized approach, and, in the future, novel ways to endotype patients with cough may prove valuable in management.

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