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#GarjoDyspnee #Medecine #Pneumologie
In contrast, increased voluntary motor drive to respiratory muscles, which originates in the cerebral cortex (95, 96), predominantly evokes a perception of respiratory effort (58, 61), which, in healthy volunteers, is not as unpleasant as air hunger (97).
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conveyed to the cerebral cortex as corollary discharge (e.g., 47, 93, 94). When this is not matched by an adequate ventilatory response, individuals perceive air hunger/unsatisfied inspiration. <span>In contrast, increased voluntary motor drive to respiratory muscles, which originates in the cerebral cortex (95, 96), predominantly evokes a perception of respiratory effort (58, 61), which, in healthy volunteers, is not as unpleasant as air hunger (97). Mechanoreceptors in the lungs, airways, and chest wall provide afferent information about achieved pulmonary ventilation and can inhibit (relieve) air hunger/unsatisfied inspiration (98




#GarjoDyspnee #Medecine #Pneumologie
Mechanoreceptors in the lungs, airways, and chest wall provide afferent information about achieved pulmonary ventilation and can inhibit (relieve) air hunger/unsatisfied inspiration (98103)
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scles, which originates in the cerebral cortex (95, 96), predominantly evokes a perception of respiratory effort (58, 61), which, in healthy volunteers, is not as unpleasant as air hunger (97). <span>Mechanoreceptors in the lungs, airways, and chest wall provide afferent information about achieved pulmonary ventilation and can inhibit (relieve) air hunger/unsatisfied inspiration (98–103). In animal models of emphysema, pulmonary stretch receptor discharge is decreased (104). Pulmonary stretch receptor activation alone provides potent relief (100), independent of vagal i




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Unsatisfied inspiration or air hunger is not specific to any particular disease or stimulus
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However, these studies were performed before it was discovered that transplanted lungs are re-innervated quickly, and thus may have overestimated the contribution of chest wall receptors (112). <span>Unsatisfied inspiration or air hunger is not specific to any particular disease or stimulus. It has been reported in quadriplegic patients in response to increased partial pressure of carbon dioxide (Pco2) (47), decreased tidal volume (100), or methacholine challenge (66), as




#GarjoDyspnee #Medecine #Pneumologie
A consistent finding across experimental exercise and clinical studies is that patients with a variety of conditions (or normal subjects with chest wall corseting) report greater difficulty and discomfort during inspiration compared with expiration (inspiratory difficulty)
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idiopathic hyperventilation are significantly more likely than healthy control subjects to report perceptions of air hunger when recalling perceptions of breathing at the end of exercise (113). <span>A consistent finding across experimental exercise and clinical studies is that patients with a variety of conditions (or normal subjects with chest wall corseting) report greater difficulty and discomfort during inspiration compared with expiration (inspiratory difficulty) (31, 32, 36, 52, 70, 79, 83, 85, 113, 114). Naïve experimental subjects exposed to a variety of similar stimuli have chosen descriptors listed in Table 3 (37, 58, 83, 115). Although rel




#GarjoDyspnee #Medecine #Pneumologie
This suggests that, in susceptible individuals, air hunger may occur even in the absence of reduced ventilatory capacity. Factors such as excessive ventilatory drive or impaired perception of achieved ventilation may play a role. There also may be a role for increased sensitivity to CO2 (which may, in turn, have a component of genetic predisposition) or excessive response to cerebral alkalosis or hypoxia due to hyperventilation-induced hypocapnia (118, 124)
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eneral population (121–123), but similar clustering of descriptors has been reported in patients with idiopathic hyperventilation (113) who do not have cardiopulmonary or neuromuscular disease. <span>This suggests that, in susceptible individuals, air hunger may occur even in the absence of reduced ventilatory capacity. Factors such as excessive ventilatory drive or impaired perception of achieved ventilation may play a role. There also may be a role for increased sensitivity to CO2 (which may, in turn, have a component of genetic predisposition) or excessive response to cerebral alkalosis or hypoxia due to hyperventilation-induced hypocapnia (118, 124). Whatever term is used to characterize this cluster of related descriptors, it is not merely the awareness that breathing has increased, as that is not necessarily uncomfortable (93). R




#GarjoDyspnee #Medecine #Pneumologie
A core pattern has emerged: dyspnea activates cortico-limbic structures (134143) that also subserve interoceptive awareness of homeostatic threats such as thirst and hunger (144148) or pain (134, 137140, 149152)
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contributes as much to the image as the test condition. Nonetheless, some important conclusions can be drawn from several studies that have produced similar results using different approaches. <span>A core pattern has emerged: dyspnea activates cortico-limbic structures (134–143) that also subserve interoceptive awareness of homeostatic threats such as thirst and hunger (144–148) or pain (134, 137–140, 149–152). Recent reviews provide a comprehensive analysis of both the power and limitations of these techniques (141, 153). Using PET imaging of the forebrain, Banzett and coworkers (134) report




#GarjoDyspnee #Medecine #Pneumologie
There is good evidence that opioid drugs reduce dyspnea (see E valuation and T reatment ). Laboratory studies in healthy subjects show that opioids reduce the discomfort of air hunger (166) but not the discomfort of work or effort (167).
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ngside this symptom. Over the long run, results of neuroimaging studies may contribute to developing more effective therapeutic strategies for the dyspneic patient. Opioid Modulation of Dyspnea <span>There is good evidence that opioid drugs reduce dyspnea (see Evaluation and Treatment). Laboratory studies in healthy subjects show that opioids reduce the discomfort of air hunger (166) but not the discomfort of work or effort (167). Opioids likely act both by depressing spontaneous respiratory drive (thus reducing corollary discharge), and by modulating cortical activity, as they do in pain. Decreased insular activ




#GarjoDyspnee #Medecine #Pneumologie
Opioids likely act both by depressing spontaneous respiratory drive (thus reducing corollary discharge), and by modulating cortical activity, as they do in pain
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reduce dyspnea (see Evaluation and Treatment). Laboratory studies in healthy subjects show that opioids reduce the discomfort of air hunger (166) but not the discomfort of work or effort (167). <span>Opioids likely act both by depressing spontaneous respiratory drive (thus reducing corollary discharge), and by modulating cortical activity, as they do in pain. Decreased insular activation in response to breath-holding has been observed after opiate administration (162), and it is possible that further imaging experiments will ascertain the s




#GarjoDyspnee #Medecine #Pneumologie
In addition to laboratory, radiographic, and clinical studies, the words or phrases patients use to describe the quality of the breathing discomfort ( Table 3 ) may provide insight into the underlying pathophysiological mechanisms (27, 2932, 36).
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these are receptors that are postulated to lie in muscles and that are stimulated by changes in the metabolic milieu of the tissue that result when oxygen delivery does not meet oxygen demand. <span>In addition to laboratory, radiographic, and clinical studies, the words or phrases patients use to describe the quality of the breathing discomfort (Table 3) may provide insight into the underlying pathophysiological mechanisms (27, 29–32, 36). Chest tightness may be relatively specific for dyspnea due to bronchoconstriction (30, 67, 68, 74, 132). Sensations of “air hunger” and “inability to get a deep breath,” which probably




#GarjoDyspnee #Medecine #Pneumologie
Chest tightness may be relatively specific for dyspnea due to bronchoconstriction ( 30, 67, 68, 74, 132). Sensations of “air hunger” and “inability to get a deep breath,” which probably represent the combined effects of increased drive to breathe and limited tidal volume, are commonly seen in association with dynamic hyperinflation (31, 86) and other conditions characterized by restrictive mechanics (e.g., heart failure or pulmonary fibrosis). Sensations of effort, suffocation, and rapid breathing have been found to characterize CO2-induced panic attacks in patients diagnosed with panic disorder (119), but are nonspecific (200)
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l studies, the words or phrases patients use to describe the quality of the breathing discomfort (Table 3) may provide insight into the underlying pathophysiological mechanisms (27, 29–32, 36). <span>Chest tightness may be relatively specific for dyspnea due to bronchoconstriction (30, 67, 68, 74, 132). Sensations of “air hunger” and “inability to get a deep breath,” which probably represent the combined effects of increased drive to breathe and limited tidal volume, are commonly seen in association with dynamic hyperinflation (31, 86) and other conditions characterized by restrictive mechanics (e.g., heart failure or pulmonary fibrosis). Sensations of effort, suffocation, and rapid breathing have been found to characterize CO2-induced panic attacks in patients diagnosed with panic disorder (119), but are nonspecific (200). There also may be linguistic and cultural differences in how patients characterize their symptoms (201–203), especially symptoms of affective distress (201), and some patients have dif




#GarjoDyspnee #Medecine #Pneumologie
Although supplemental oxygen improves mortality in chronically hypoxemic patients with COPD, there are conflicting data about its ability to relieve breathlessness (220224)
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r se (as opposed to approval for treatment of diseases in which dyspnea may be a prominent symptom), and even when evidence of efficacy exists, the magnitude of the benefit is variable. Oxygen. <span>Although supplemental oxygen improves mortality in chronically hypoxemic patients with COPD, there are conflicting data about its ability to relieve breathlessness (220–224). A beneficial effect of oxygen could be related to changes in chemoreceptor stimulation, the resulting changes in breathing pattern (225, 226), and/or stimulation of receptors related t




#GarjoDyspnee #Medecine #Pneumologie
Oxygen therapy may be useful for patients with advanced heart or lung disease, in particular those who are hypoxemic at rest or with minimal activity (204, 212, 213, 224, 230)
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of receptors related to gas flow through the upper airway (227, 228). Thus, symptomatic benefit may not be confined to patients who meet Medicare guidelines for supplemental oxygen (225, 229). <span>Oxygen therapy may be useful for patients with advanced heart or lung disease, in particular those who are hypoxemic at rest or with minimal activity (204, 212, 213, 224, 230). Heliox. As a result of their decreased density, helium-containing gas mixtures reduce the resistance to airflow, which in turn may decrease the work of breathing, reduce the severity o




#GarjoToux
The receptors are placed throughout the bronchial tree and, although in a lesser extent, also in other areas: ear, paranasal sinuses, pleura, diaphragm, pericardium and esophagus
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Cough, a vital reflex. Mechanisms, determinants and measurements
tions (1). Cough may be a voluntary act or a spontaneous reflex arc and in this case involves receptors, an afferent pathway, a center processing information, an efferent pathway and effectors. <span>The receptors are placed throughout the bronchial tree and, although in a lesser extent, also in other areas: ear, paranasal sinuses, pleura, diaphragm, pericardium and esophagus. From receptors the afferent impulses are channeled through the vagus nerve in the medulla oblongata, where they are processed. Then, efferent impulses are conveyed by motor nerves and




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Schematically, we may distinguish four different phases of cough, as a vital reflex arc, the first of which is a part in the afferent pathway while the last three in the efferent one (2)
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Cough, a vital reflex. Mechanisms, determinants and measurements
he vagus nerve in the medulla oblongata, where they are processed. Then, efferent impulses are conveyed by motor nerves and reach the effectors, which are the respiratory and laryngeal muscles. <span>Schematically, we may distinguish four different phases of cough, as a vital reflex arc, the first of which is a part in the afferent pathway while the last three in the efferent one (2): Receptorial phase: there is the stimulation of cough receptors that are activated and, accordingly, send an impulse to the center through the vagus nerve; Inspiratory phase: that consi




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Since the result of the cough reflex arc is the production of an airflow, the determinant factor of cough efficacy is the operational volume of the lung (3), which in turn relies on the strength and coordination of respiratory and laryngeal muscles as well as on lung mechanics
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Cough, a vital reflex. Mechanisms, determinants and measurements
e determinants of the cough efficacy and the clinical conditions affecting cough efficacy as well as the cough’s efficacy measurements in clinical setting. Go to: Determinants of cough efficacy <span>Since the result of the cough reflex arc is the production of an airflow, the determinant factor of cough efficacy is the operational volume of the lung (3), which in turn relies on the strength and coordination of respiratory and laryngeal muscles as well as on lung mechanics. The weakness and/or the incoordination of the respiratory and/or laryngeal muscles may significantly decrease the driving pressure applied to the alveoli and to the bronchial airways.




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The decrease of operational volume of the lung can be the consequence not only of a weakness of respiratory muscles, but also of the expiratory flow limitation and lung hyperinflation
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Cough, a vital reflex. Mechanisms, determinants and measurements
ase Myasthenia Myasthenia gravis Lambert-Eaton syndrome Muscular dystrophies Duchenne dystrophy Myotonic dystrophy Toxic myopathies Alcoholic myopathy Steroid myopathy Open in a separate window <span>The decrease of operational volume of the lung can be the consequence not only of a weakness of respiratory muscles, but also of the expiratory flow limitation and lung hyperinflation. These pathophysiological features may occur in some obstructive airway diseases, such as chronic obstructive pulmonary disease (COPD), cystic fibrosis, bronchiectasis, tracheomalacia a




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CPF evaluation is clinically relevant and it can be considered an overall parameter of cough efficacy (7)
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Cough, a vital reflex. Mechanisms, determinants and measurements
r mechanical insufflation-exsufflation (4). CEV can be measured together with CPF assessment. In healthy individuals, CEV values are usually greater than 1 L with an average value of 2.4 L (6). <span>CPF evaluation is clinically relevant and it can be considered an overall parameter of cough efficacy (7). Neuromuscular patients with values of CPF less than 270 L/minute are at risk of retention of bronchial secretions and respiratory failure in case of bronchial infection (8). Interestin




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The measurement of cough efficacy should be a routine assessment in patients suffering from progressive neurological disorders with lung involvement and in patients who are at high risk of an ineffective cough
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Cough, a vital reflex. Mechanisms, determinants and measurements
with acute stroke, higher values of CPF are associated with a low risk of secondary aspiration pneumonia. Up to now, no data has been published on the clinical relevance of the CEV measurement. <span>The measurement of cough efficacy should be a routine assessment in patients suffering from progressive neurological disorders with lung involvement and in patients who are at high risk of an ineffective cough. In these patients, a non-invasive evaluation of respiratory muscles function is required and usually consists in some volitional tests. These tests include the vital capacity (CV) meas




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Moreover, in case of a documented impairment of respiratory muscle function, an arterial blood-gas analysis may be requested to ascertain whether a hypoxemic-hypercapnic respiratory failure due to a ventilatory pump impairment may occur
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Cough, a vital reflex. Mechanisms, determinants and measurements
difficulties to perform MEP manoeuvre (13). Non-volitional and invasive tests may be required in non-cooperative patients or in patients providing non-univocal results at volitional tests (4). <span>Moreover, in case of a documented impairment of respiratory muscle function, an arterial blood-gas analysis may be requested to ascertain whether a hypoxemic-hypercapnic respiratory failure due to a ventilatory pump impairment may occur. Patients with a decreased operational volume of the lung due to an obstructive ventilatory defect and lung hyperinflation show a reduced forced expiratory volume at 1st second (FEV1)/C




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Moreover, in patients with COPD the use of bronchodilators, such as beta2-agonists or muscarinic antagonists, can significantly reduce the exacerbation rate and this effect might be linked to an improvement in operational volume of the lung and, accordingly, to a more effective cough
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Cough, a vital reflex. Mechanisms, determinants and measurements
operational volume of the lung are now available. Notably, in bulbar and in non-bulbar ALS patients, mechanical insufflation-exsufflation can significantly increase air flow during cough (14). <span>Moreover, in patients with COPD the use of bronchodilators, such as beta2-agonists or muscarinic antagonists, can significantly reduce the exacerbation rate and this effect might be linked to an improvement in operational volume of the lung and, accordingly, to a more effective cough. Go to: References 1. Bouros D, Siafakas N, Green M. second edition. New York: Marcel Dekker Inc; 1995. Cough. Physiological and Pathophysiological Considerations. In: C. Roussos (Ed).




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Under normal conditions cough serves an important protective role in the airways and lungs, but in some conditions it may become excessive and nonproductive, and is troublesome and potentially harmful to the airway mucosa
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Anatomy and neuro-pathophysiology of the cough reflex arc
erials occurring as a consequence of aspiration or inhalation of particulate matter, pathogens, accumulated secretions, postnasal drip, inflammation, and mediators associated with inflammation. <span>Under normal conditions cough serves an important protective role in the airways and lungs, but in some conditions it may become excessive and nonproductive, and is troublesome and potentially harmful to the airway mucosa. These contrasting consequences of coughing can be attributed to the parallel afferent pathways regulating this important defensive reflex of the airways. Each cough occurs through the




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In addition, more airway receptors are in the external auditory canals, eardrums, paranasal sinuses, pharynx, diaphragm, pleura, pericardium, and stomach. These are probably mechanical receptors only, which can be stimulated by triggers such as touch or displacement
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Anatomy and neuro-pathophysiology of the cough reflex arc
anical and chemical stimuli. Chemical receptors sensitive to acid, heat, and capsaicin-like compounds trigger the cough reflex via activation of the type 1 vanilloid (capsaicin) receptor [3-5]. <span>In addition, more airway receptors are in the external auditory canals, eardrums, paranasal sinuses, pharynx, diaphragm, pleura, pericardium, and stomach. These are probably mechanical receptors only, which can be stimulated by triggers such as touch or displacement. 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




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These attributes can be used to identify at least three broad classes of airway afferent nerves:

1. Rapidly Adapting Receptors (RAR)

2. Slowly Adapting Stretch Receptors (SARs)

3. C-Fibers

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Anatomy and neuro-pathophysiology of the cough reflex arc
ensitivity, adaptation to sustained lung inflation, neurochemistry, origin, myelination, conduction velocity (A-fiber, > 3 m/s; C-fiber, < 2 m/s), and sites of termination in the airways. <span>These attributes can be used to identify at least three broad classes of airway afferent nerves: 1. Rapidly Adapting Receptors (RAR) 2. Slowly Adapting Stretch Receptors (SARs) 3. C-Fibers Rapidly adapting receptors (RAR) Functional studies of RARs suggest that they terminate within or beneath the epithelium of both intrapulmonary and extrapulmonary airways, but primarily




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RARs are activated by stimuli that evoke bronchospasm or obstruction resulting from mucus secretion or edema. Substances such as histamine, capsaicin, substance P, and bradykinin activate RARs in a way that can be markedly inhibited or abolished by preventing the local end-organ effects that these stimuli produce (e.g. bronchospasm and mucus secretion)
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Anatomy and neuro-pathophysiology of the cough reflex arc
ughout the respiratory cycle, are activated by the dynamic mechanical forces accompanying lung inflation and deflation, and become more active as the rate and volume of lung inflation increase. <span>RARs are activated by stimuli that evoke bronchospasm or obstruction resulting from mucus secretion or edema. Substances such as histamine, capsaicin, substance P, and bradykinin activate RARs in a way that can be markedly inhibited or abolished by preventing the local end-organ effects that these stimuli produce (e.g. bronchospasm and mucus secretion). RAR activation initiates reflex bronchospasm and mucus secretion through parasympathetic pathways. RARs can also respond to stimuli that evoke cough and fulfill many criteria for media




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RAR activation initiates reflex bronchospasm and mucus secretion through parasympathetic pathways
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Anatomy and neuro-pathophysiology of the cough reflex arc
, and bradykinin activate RARs in a way that can be markedly inhibited or abolished by preventing the local end-organ effects that these stimuli produce (e.g. bronchospasm and mucus secretion). <span>RAR activation initiates reflex bronchospasm and mucus secretion through parasympathetic pathways. RARs can also respond to stimuli that evoke cough and fulfill many criteria for mediating cough. Further evidence for their role in coughing comes from studies of vagal cooling, which




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RARs may act synergistically with other afferent nerve subtypes to induce coughing
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Anatomy and neuro-pathophysiology of the cough reflex arc
le in coughing comes from studies of vagal cooling, which blocks cough at temperatures that selectively abolish activity in myelinated fibers (including RARs) while preserving C-fiber activity. <span>RARs may act synergistically with other afferent nerve subtypes to induce coughing. Slowly adapting stretch receptors (SARs) SARs are highly sensitive to the mechanical forces that are put on the lung during breathing. SAR activity increases during inspiration and pea




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SARs are highly sensitive to the mechanical forces that are put on the lung during breathing. SAR activity increases during inspiration and peaks just prior to the initiation of expiration [13]
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Anatomy and neuro-pathophysiology of the cough reflex arc
yelinated fibers (including RARs) while preserving C-fiber activity. RARs may act synergistically with other afferent nerve subtypes to induce coughing. Slowly adapting stretch receptors (SARs) <span>SARs are highly sensitive to the mechanical forces that are put on the lung during breathing. SAR activity increases during inspiration and peaks just prior to the initiation of expiration [13]. SARs are thus thought to be the afferent fibers involved in the Hering-Breuer reflex, which terminates inspiration and initiates expiration when the lungs are adequately inflated. SARs




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SARs are thus thought to be the afferent fibers involved in the Hering-Breuer reflex, which terminates inspiration and initiates expiration when the lungs are adequately inflated
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Anatomy and neuro-pathophysiology of the cough reflex arc
ARs are highly sensitive to the mechanical forces that are put on the lung during breathing. SAR activity increases during inspiration and peaks just prior to the initiation of expiration [13]. <span>SARs are thus thought to be the afferent fibers involved in the Hering-Breuer reflex, which terminates inspiration and initiates expiration when the lungs are adequately inflated. SARs can be differentiated from RARs in some species based on action potential conduction velocity, and in most species by their lack of adaptation to sustained lung inflations. SARs m




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SAR activation results in the central inhibition of respiration and the inhibition of the cholinergic drive to the airways, leading to decreased phrenic nerve activity and decreased airway smooth muscle tone (due to a withdrawal of cholinergic nerve activity) [ 14]
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Anatomy and neuro-pathophysiology of the cough reflex arc
be differentially distributed throughout the airways: they appear to terminate primarily in the intrapulmonary airways. SARs also differ from RARs with respect to the reflexes they precipitate. <span>SAR activation results in the central inhibition of respiration and the inhibition of the cholinergic drive to the airways, leading to decreased phrenic nerve activity and decreased airway smooth muscle tone (due to a withdrawal of cholinergic nerve activity) [14]. The sensory terminals of SARs assume a complex and varying position within the airway wall: most of these SARs are found in the peripheral airways (associated with alveoli or bronchiol




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SARs may facilitate coughing by a central cough network via activation of brainstem second-order neurons of the SAR reflex pathway.
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Anatomy and neuro-pathophysiology of the cough reflex arc
rway wall: most of these SARs are found in the peripheral airways (associated with alveoli or bronchioles). Occasionally, SAR dendritic arbors are associated with the bronchiolar smooth muscle. <span>SARs may facilitate coughing by a central cough network via activation of brainstem second-order neurons of the SAR reflex pathway. C-fibers The majority of afferent nerves innervating the airways and lungs are unmyelinated C-fibers. They are similar in many ways to the unmyelinated somatic sensory nerves innervatin




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The majority of afferent nerves innervating the airways and lungs are unmyelinated C-fibers
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Anatomy and neuro-pathophysiology of the cough reflex arc
s are associated with the bronchiolar smooth muscle. SARs may facilitate coughing by a central cough network via activation of brainstem second-order neurons of the SAR reflex pathway. C-fibers <span>The majority of afferent nerves innervating the airways and lungs are unmyelinated C-fibers. They are similar in many ways to the unmyelinated somatic sensory nerves innervating the skin, skeletal muscle, joints, and bones that respond to noxious chemical and mechanical stimul




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In addition to their conduction velocity (< 2 m/s), airway vagal afferent C-fibers are distinguished from RARs and SARs by their relative insensitivity to mechanical stimulation and lung inflation. C-fibers are further distinguished from RARs by the observation that they are directly activated by bradykinin and capsaicin, not indirectly through effects on smooth muscle or the airway vasculature
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Anatomy and neuro-pathophysiology of the cough reflex arc
ar in many ways to the unmyelinated somatic sensory nerves innervating the skin, skeletal muscle, joints, and bones that respond to noxious chemical and mechanical stimuli (called nociceptors). <span>In addition to their conduction velocity (< 2 m/s), airway vagal afferent C-fibers are distinguished from RARs and SARs by their relative insensitivity to mechanical stimulation and lung inflation. C-fibers are further distinguished from RARs by the observation that they are directly activated by bradykinin and capsaicin, not indirectly through effects on smooth muscle or the airway vasculature. Moreover, prostaglandin E2, adrenaline, and adenosine, which by bronchodilating the airways might inhibit RAR activation by bradykinin and capsaicin, actually sensitize C-fibers to cap




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Reflex responses evoked by C-fiber activation include increased airway parasympathetic nerve activity, and the chemoreflex, characterized by apnea (followed by rapid shallow breathing), bradycardia, and hypotension
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Anatomy and neuro-pathophysiology of the cough reflex arc
are generally quiescent throughout the respiratory cycle but are activated by chemical stimuli such as capsaicin, bradykinin, citric acid, hypertonic saline solution, and sulfur dioxide (SO2). <span>Reflex responses evoked by C-fiber activation include increased airway parasympathetic nerve activity, and the chemoreflex, characterized by apnea (followed by rapid shallow breathing), bradycardia, and hypotension. Stimulants of C-fibers such as capsaicin, bradykinin, SO2, and citric acid evoke cough in conscious animals and in humans, and capsaicin desensitization abolishes citric acid-induced c




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Sex-related differences in cough reflex sensitivity explain the observation that women are more likely than men to develop chronic cough [18-20]
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Anatomy and neuro-pathophysiology of the cough reflex arc
C-fibers such as capsaicin, bradykinin, SO2, and citric acid evoke cough in conscious animals and in humans, and capsaicin desensitization abolishes citric acid-induced coughing in guinea pigs. <span>Sex-related differences in cough reflex sensitivity explain the observation that women are more likely than men to develop chronic cough [18-20]. The mechanical events of a cough can be divided into three phases [21]: 1. Inspiratory phase: Inhalation, which generates the volume necessary for an effective cough. 2. Compression ph




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The specific pattern of the cough depends on the site and type of stimulation. Mechanical laryngeal stimulation results in immediate expiratory stimulation (sometimes termed the expiratory reflex), probably to protect the airway from aspiration; stimulation distal to the larynx causes a more prominent inspiratory phase, presumably to generate the airflow necessary to remove the stimulus.
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Anatomy and neuro-pathophysiology of the cough reflex arc
s, resulting in high expiratory airflow and the coughing sound. Large airway compression occurs. The high flows dislodge mucus from the airways and allow removal from the tracheobronchial tree. <span>The specific pattern of the cough depends on the site and type of stimulation. Mechanical laryngeal stimulation results in immediate expiratory stimulation (sometimes termed the expiratory reflex), probably to protect the airway from aspiration; stimulation distal to the larynx causes a more prominent inspiratory phase, presumably to generate the airflow necessary to remove the stimulus. During vigorous coughing, intrathoracic pressures may reach 300 mm Hg and expiratory velocities approach 800 kilometers per hour [22]. While these pressures and velocities are responsib




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Cough-induced rib fractures are another painful and potentially serious complication of chronic cough. Fractures often involve multiple ribs, particularly ribs five through seven. Women with decreased bone density are at the greatest risk of this complication; however, fractures can occur in patients with normal bone density as well [24]
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Anatomy and neuro-pathophysiology of the cough reflex arc
many of the complications of cough, including exhaustion, self-consciousness, insomnia, headache, dizziness, musculoskeletal pain, hoarseness, excessive perspiration, urinary incontinence [23]. <span>Cough-induced rib fractures are another painful and potentially serious complication of chronic cough. Fractures often involve multiple ribs, particularly ribs five through seven. Women with decreased bone density are at the greatest risk of this complication; however, fractures can occur in patients with normal bone density as well [24]. 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 [




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During vigorous coughing, intrathoracic pressures may reach 300 mm Hg and expiratory velocities approach 800 kilometers per hour [22]
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Anatomy and neuro-pathophysiology of the cough reflex arc
probably to protect the airway from aspiration; stimulation distal to the larynx causes a more prominent inspiratory phase, presumably to generate the airflow necessary to remove the stimulus. <span>During vigorous coughing, intrathoracic pressures may reach 300 mm Hg and expiratory velocities approach 800 kilometers per hour [22]. While these pressures and velocities are responsible for the beneficial effects of cough on mucus clearance, they are also responsible for many of the complications of cough, including




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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 [25]. 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 [26]
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Anatomy and neuro-pathophysiology of the cough reflex arc
cularly ribs five through seven. Women with decreased bone density are at the greatest risk of this complication; however, fractures can occur in patients with normal bone density as well [24]. <span>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 [25]. 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 [26]. 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)




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Another rare cause of chronic cough is Holmes-Adie syndrome due to autonomic dysfunction affecting the vagus nerve [36] patients present anisocoria, abnormal deep tendon reflexes, and patchy areas of hyperhidrosis or anhidrosis
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Anatomy and neuro-pathophysiology of the cough reflex arc
usual cause of chronic dry cough [33]. The etiology of the ‘ear-cough’ (or oto-respiratory) reflex is related to stimulation of the auricular branch of the vagus nerve (Arnold's nerve) [34,35]. <span>Another rare cause of chronic cough is Holmes-Adie syndrome due to autonomic dysfunction affecting the vagus nerve [36] patients present anisocoria, abnormal deep tendon reflexes, and patchy areas of hyperhidrosis or anhidrosis. In adults, habit (also known as ‘psychogenic’) cough may rarely be the cause of a chronic cough that remains troublesome despite a thorough evaluation, including ruling out tic disorde




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Irritation of the external auditory canal by impacted foreign bodies or cerumen is another unusual cause of chronic dry cough [33]. The etiology of the ‘ear-cough’ (or oto-respiratory) reflex is related to stimulation of the auricular branch of the vagus nerve (Arnold's nerve) [34,35]
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Anatomy and neuro-pathophysiology of the cough reflex arc
viduals [32]. Following tonsillectomy, these patients had decreased cough sensitivity and significantly improved symptom control. At this moment, these observations need further investigations. <span>Irritation of the external auditory canal by impacted foreign bodies or cerumen is another unusual cause of chronic dry cough [33]. The etiology of the ‘ear-cough’ (or oto-respiratory) reflex is related to stimulation of the auricular branch of the vagus nerve (Arnold's nerve) [34,35]. Another rare cause of chronic cough is Holmes-Adie syndrome due to autonomic dysfunction affecting the vagus nerve [36] patients present anisocoria, abnormal deep tendon reflexes, and




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Differences among several sites from which cough stimuli can originate may result in variations in the sounds and patterns of coughing
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Anatomy and neuro-pathophysiology of the cough reflex arc
osis. In adults, habit (also known as ‘psychogenic’) cough may rarely be the cause of a chronic cough that remains troublesome despite a thorough evaluation, including ruling out tic disorders. <span>Differences among several sites from which cough stimuli can originate may result in variations in the sounds and patterns of coughing. Laryngeal stimulation produces a choking type of cough without a preceding inspiration. Inadequate mucociliary clearance mechanisms (as in bronchiectasis or cystic fibrosis) may produc




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Laryngeal stimulation produces a choking type of cough without a preceding inspiration
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Anatomy and neuro-pathophysiology of the cough reflex arc
thorough evaluation, including ruling out tic disorders. Differences among several sites from which cough stimuli can originate may result in variations in the sounds and patterns of coughing. <span>Laryngeal stimulation produces a choking type of cough without a preceding inspiration. Inadequate mucociliary clearance mechanisms (as in bronchiectasis or cystic fibrosis) may produce a pattern of coughing with less violent acceleration of air and a sequence of interrup




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Inadequate mucociliary clearance mechanisms (as in bronchiectasis or cystic fibrosis) may produce a pattern of coughing with less violent acceleration of air and a sequence of interrupted expirations without any intervening inspiration
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Anatomy and neuro-pathophysiology of the cough reflex arc
s from which cough stimuli can originate may result in variations in the sounds and patterns of coughing. Laryngeal stimulation produces a choking type of cough without a preceding inspiration. <span>Inadequate mucociliary clearance mechanisms (as in bronchiectasis or cystic fibrosis) may produce a pattern of coughing with less violent acceleration of air and a sequence of interrupted expirations without any intervening inspiration. Awareness of cough varies considerably: it can be distressing when it appears suddenly, especially if associated with discomfort due to chest pain, dyspnea, or copious secretions, whil




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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
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Anatomy and neuro-pathophysiology of the cough reflex arc
st pain, dyspnea, or copious secretions, while a cough that develops over decades (e.g. in a smoker with chronic bronchitis) may be hardly noticeable or may be considered normal by the patient. <span>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. Many disorders can impair the ability to cough effectively, which may result in persistent cough. The elderly, newborns, lung transplant recipients, and patients with paralysis or neur




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The vagus is the most important afferent nerve, although the glossopharyngeal and trigeminal nerves may operate, depending on the receptors involved
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Cough and Sputum Production - Clinical Methods - NCBI Bookshelf
demonstrated or suspected in other sites, including the pharynx, peripheral airways, and other intra- or extrathoracic sites such as pleura, ear canals, tympanic membrane, and even the stomach. <span>The vagus is the most important afferent nerve, although the glossopharyngeal and trigeminal nerves may operate, depending on the receptors involved. A medullary cough center has been postulated with no proof of its precise anatomic location. This "center" is under the influence of the higher voluntary nerve centers, which may initi




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The combination of a high airflow and airway narrowing results in the expulsion of an airstream with a linear velocity sometimes nearing the speed of sound.
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Cough and Sputum Production - Clinical Methods - NCBI Bookshelf
ngs once the glottis is open. In addition, the pressure difference between the outside and the inside of the intrathoracic airways during phase 4 causes their dynamic compression and narrowing. <span>The combination of a high airflow and airway narrowing results in the expulsion of an airstream with a linear velocity sometimes nearing the speed of sound. The blast of air thus produced is capable of expelling the secretions with a great force. The site and the extent of the dynamic compression are determined by the lung volumes. With lar




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With large lung volumes, only the trachea and large bronchi are compressed; with smaller lung volumes, more distal airways are also narrowed
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Cough and Sputum Production - Clinical Methods - NCBI Bookshelf
speed of sound. The blast of air thus produced is capable of expelling the secretions with a great force. The site and the extent of the dynamic compression are determined by the lung volumes. <span>With large lung volumes, only the trachea and large bronchi are compressed; with smaller lung volumes, more distal airways are also narrowed. With each successive cough without an intervening inspiration, as seen in patients with chronic bronchitis, lung volumes become smaller, and the cough becomes effective also in removin




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Variation in sounds of coughing is due to several factors, including the nature and quantity of secretions, anatomic differences and pathologic change of the larynx and other air passages, and the force of the cough
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Cough and Sputum Production - Clinical Methods - NCBI Bookshelf
e cycle repeats itself. The characteristic explosive sound of coughing results from the vibrations of the vocal cords, mucosal folds above and below the glottis, and the accumulated secretions. <span>Variation in sounds of coughing is due to several factors, including the nature and quantity of secretions, anatomic differences and pathologic change of the larynx and other air passages, and the force of the cough. Vibrations of coughing also help in dislodging secretions from the airway walls. The small amounts of tracheobronchial secretions normally produced are very effectively handled by the




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With an adequate function of the mucociliary escalator, the cough has no additional benefit in removing the amount of secretions formed under normal conditions. In pathologic states, however, when the mucociliary function is ineffective or insufficient because of the quantity or alteration of the physical properties of secretions, the cough becomes essential for airway clearance
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Cough and Sputum Production - Clinical Methods - NCBI Bookshelf
ts formation and its clearance maintains a thin protective layer of mucus for trapping and removing the impurities of the inspired air while preventing the excessive accumulation of secretions. <span>With an adequate function of the mucociliary escalator, the cough has no additional benefit in removing the amount of secretions formed under normal conditions. In pathologic states, however, when the mucociliary function is ineffective or insufficient because of the quantity or alteration of the physical properties of secretions, the cough becomes essential for airway clearance. Although coughing is most effective when the excessive secretions are accumulated in the large, centrally located airways, it also plays an important role in clearing the peripheral ai




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Mucous sputum is clear or translucent and viscous, containing only small numbers of microscopic elements. Purulent sputum is off-white, yellow or green, and opaque. It indicates the presence of large numbers of white blood cells, especially neutrophilic granulocytes. In asthmatics, the sputum may look purulent from the eosinophilic cells. Red coloration, uniform or streaky, is usually due to its mixture with blood. Carbon particles discolor the sputum gray (as in cigarette smokers) or black (as in coal miners or with smoke inhalation)
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Cough and Sputum Production - Clinical Methods - NCBI Bookshelf
ic tissues or cells, aspirated vomitus, or other foreign particles. Gross appearance and other physical characteristics of the sputum are the result of its content of these and other materials. <span>Mucous sputum is clear or translucent and viscous, containing only small numbers of microscopic elements. Purulent sputum is off-white, yellow or green, and opaque. It indicates the presence of large numbers of white blood cells, especially neutrophilic granulocytes. In asthmatics, the sputum may look purulent from the eosinophilic cells. Red coloration, uniform or streaky, is usually due to its mixture with blood. Carbon particles discolor the sputum gray (as in cigarette smokers) or black (as in coal miners or with smoke inhalation). Go to: Clinical Significance As a cardinal manifestation of respiratory diseases, coughing is one of the most common symptoms encountered in clinical medicine. Being a physiologic refl




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Pathologic conditions causing the cough are usually the ones that irritate the airways, increase their irritability, result in their deformation, or increase the tracheobronchial secretions
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may be a voluntary act or may result from nervous habit. Although the clinical significance of coughing in many instances is trivial, it may be an indication of a serious intrathoracic disease. <span>Pathologic conditions causing the cough are usually the ones that irritate the airways, increase their irritability, result in their deformation, or increase the tracheobronchial secretions. These factors may operate singly or in various combinations. Sputum production with coughing occurs when the respiratory tract secretions are beyond the ability of the mucociliary mech




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Sputum production with coughing occurs when the respiratory tract secretions are beyond the ability of the mucociliary mechanism to deal with them
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Cough and Sputum Production - Clinical Methods - NCBI Bookshelf
es that irritate the airways, increase their irritability, result in their deformation, or increase the tracheobronchial secretions. These factors may operate singly or in various combinations. <span>Sputum production with coughing occurs when the respiratory tract secretions are beyond the ability of the mucociliary mechanism to deal with them. The most common cause of the acute cough of clinical significance is viral tracheobronchitis. The cough in this transient and self-limited condition is, at the beginning, nonproductive




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Inflammation of the respiratory tract mucosa, from infectious or noninfectious causes, results in hyper-reactivity of the cough receptors. This results from the alteration of the surface epithelium, making them more sensitive to the cough-producing effect of commonly occurring mild irritants such as cold air, respiratory pollutants, deep or fast respiration, and excessive use of the larynx. At times, the mechanical irritation of coughing itself brings about more coughing
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Cough and Sputum Production - Clinical Methods - NCBI Bookshelf
gh in this transient and self-limited condition is, at the beginning, nonproductive and quite annoying; later it becomes productive of mucous or mucopurulent sputum before it begins to subside. <span>Inflammation of the respiratory tract mucosa, from infectious or noninfectious causes, results in hyper-reactivity of the cough receptors. This results from the alteration of the surface epithelium, making them more sensitive to the cough-producing effect of commonly occurring mild irritants such as cold air, respiratory pollutants, deep or fast respiration, and excessive use of the larynx. At times, the mechanical irritation of coughing itself brings about more coughing. Inflammation, in addition, increases the secretions. In acute viral respiratory tract infection, post-nasal drip may be another cause for triggering the cough. Other infectious, as wel




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As chronic bronchitis and lung cancer are very uncommon among nonsmokers, a chronic persistent cough has a different significance in this population. Airway hyperreactivity, the hallmark of bronchial asthma, is a rather common condition in which the cough may be the predominant or even the sole manifestation
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ncer has become most feared among the people with a chronic cough. The cough in lung cancer may develop de novo when there is no underlying chronic bronchitis and may be its only manifestation. <span>As chronic bronchitis and lung cancer are very uncommon among nonsmokers, a chronic persistent cough has a different significance in this population. Airway hyperreactivity, the hallmark of bronchial asthma, is a rather common condition in which the cough may be the predominant or even the sole manifestation. Patients with hyperreactive airways, without other manifestations of asthma, may have a chronic cough for as long as several years until the condition is suspected, accurately diagnose




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Left-sided heart failure not only results in a cough with acute pulmonary edema but also may be a cause of a chronic nocturnal cough. Recurrent aspiration is another condition in which the cough characteristically occurs in a supine position. Foreign-body aspiration should always be considered in the differential diagnosis of the chronic cough. After the initial coughing or choking episode at the time of its aspiration, the cough may restart and continue long after the incident
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Cough and Sputum Production - Clinical Methods - NCBI Bookshelf
o clear the throat are very suggestive of this disorder. The chronic cough may be a manifestation of many other pathologic conditions involving the intra- and extrathoracic organs (Table 38.1). <span>Left-sided heart failure not only results in a cough with acute pulmonary edema but also may be a cause of a chronic nocturnal cough. Recurrent aspiration is another condition in which the cough characteristically occurs in a supine position. Foreign-body aspiration should always be considered in the differential diagnosis of the chronic cough. After the initial coughing or choking episode at the time of its aspiration, the cough may restart and continue long after the incident. Other, less common intraluminal or compressing lesions of the tracheobronchial tree, chronic inflammatory or fibrosing lung diseases, and extrapulmonary lesions may have cough as their




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Chronic expectoration of large amounts of purulent and foul-smelling sputum is strongly suggestive of bronchiectasis. Sudden production of such a sputum in a febrile patient indicates a lung abscess. Rust-colored purulent sputum in pneumococcal pneumonia, currant jelly and sticky sputum in klebsiella pneumonia, and blood-tinged foamy sputum in pulmonary edema are other examples in which the diagnosis of the underlying disease is strongly suggested
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of a dry, annoying, and often incessant cough, which disappears only after the discontinuation of these agents. Characteristics of expectorated sputum often suggest the diagnosis of its cause. <span>Chronic expectoration of large amounts of purulent and foul-smelling sputum is strongly suggestive of bronchiectasis. Sudden production of such a sputum in a febrile patient indicates a lung abscess. Rust-colored purulent sputum in pneumococcal pneumonia, currant jelly and sticky sputum in klebsiella pneumonia, and blood-tinged foamy sputum in pulmonary edema are other examples in which the diagnosis of the underlying disease is strongly suggested. A cough with the expectoration of blood (hemoptysis) is discussed in Chapter 39. Go to: References Coulter DM, Edwards IR. Cough associated with captopril and enalapril. Br Med J. 1987




Myth seeks to answer perplexing questions but does so in such a way as to create and preserve a kind of civic coherence. The mythology of a people is the basis on which they recognize themselves as a people and have a coherent relationship, not only to each other but with their own past. To some extent, philosophy is disruptive in this regard. The enterprise is not an essentially civic one. It does not begin with a settled position on political and moral matters, then seek ways to enshrine the settled view. Rather, the mission is a broadly epistemological one. The search, as we shall discover, is the search for truth.
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The questions that mythology must set out to answer are not unlike the questions that philosophy sets out to answer. We can identify three overarching issues that consume much of the subject matter of philosophy: the problem of knowledge, the problem of conduct, and the problem of governance.
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