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Introduction: Acute exacerbations of COPD (AE-COPD) are a leading cause of health service utilisation and are associated with morbidity and mortality. Identifying the prodrome of AE-COPD by monitoring symptoms and physiological parameters (telemonitoring) has proven disappointing and false alerts limit clinical utility. We report objective monitoring of cough counts around AE-COPD and the performance of a novel alert system identifying meaningful change in cough frequency. Methods: This prospective longitudinal study of cough monitoring included chronic obstructive pulmonary disease (COPD) patients experienced in telemonitoring that had two or more AE-COPD in the past year. Participants underwent cough monitoring and completed a daily questionnaire for 90 days. The automated system identified deteriorating trends in cough and this was compared with alerts generated by an established telemonitoring questionnaire. Results: 28 patients [median age 66 (range 46–86), mean FEV-1% predicted 36% (SD 18%)] completed the study and had a total of 58 exacerbations (43 moderate and 15 severe). Alerts based on cough monitoring were generated mean 3.4 days before 45% of AE-COPD with one false alert every 100 days. In contrast, questionnaire-based alerts occurred in the prodrome of 88% of AE-COPD with one false alert every 10 days. Conclusion: An alert system based on cough frequency alone predicted 45% AE-COPD; the low false alert rate with cough monitoring suggests it is a practical and clinically relevant tool. In contrast, the utility of questionnaire-based symptom monitoring is limited by frequent false alerts. [ABSTRACT FROM AUTHOR]

Background: Cough is predictive of exacerbations of chronic obstructive pulmonary disease (COPD). Little is known about cough reflex sensitivity during exacerbation of COPD and whether it is associated with exacerbation frequency. This pilot study aimed to investigate cough reflex sensitivity during and following recovery from exacerbation of COPD, and its association with the frequency of future exacerbations. In addition, the repeatability of cough reflex sensitivity in stable COPD was investigated. Methods: Twenty participants hospitalised with exacerbation of COPD underwent inhaled capsaicin challenge during exacerbation and after 6 weeks of recovery. The frequency of future exacerbations was monitored for 12 months. The repeatability of cough reflex sensitivity was assessed in separate participants with stable COPD, who underwent 2 capsaicin challenge tests, 6 weeks apart. Results: Cough reflex sensitivity was heightened during exacerbation of COPD. Geometric mean (SD) capsaicin concentration thresholds to elicit 5 coughs (C5) during exacerbation and after 6 weeks of recovery were 1.76 (3.73) vs. 8.09 (6.25) μmol L−1, respectively (p < 0.001). The change in C5 from exacerbation to 6-week recovery was associated with the frequency of future exacerbations (ρ = − 0.687, p = 0.003). C5 was highly repeatable over 6 weeks in stable COPD, and intraclass correlation coefficient was 0.85. Conclusion: Cough reflex sensitivity is heightened during exacerbation of COPD and reduces after recovery. The persistence of cough reflex hypersensitivity at recovery was associated with the frequency of future exacerbations. [ABSTRACT FROM AUTHOR]

Respiratory virus infections leads to coughing, sneezing, and increases in reflex parasympathetic bronchoconstriction and secretions. These responses to viral infection are exclusively or largely secondary to changes in the function of the nervous system. For many with underlying airway pathologies such as asthma and COPD, this neuroplasticity can lead to disease exacerbations and hospitalization. Relatively little is understood about the cellular and molecular mechanisms that underlie the changes in neuronal control of the respiratory tract during viral infection, but the evidence supports the idea that changes occur in the physiology of both the sensory and autonomic innervation. Virus infection can lead to acute increases in the activity of sensory nerves as well as to genetic changes causing alterations in sensory nerve phenotype. In addition, respiratory viral infections are associated with changes in the control of neurotransmitter release from cholinergic nerve endings terminating at the level of the airway smooth muscle. [ABSTRACT FROM AUTHOR]

Chronic cough is increasingly being recognized as a process that has multiple initiating and perpetuating triggers. Obstructive sleep apnea has recently emerged as a possible disease that can lead to chronic cough. This review details the available clinical evidence that links these two disparate diseases and explores mechanistic bases of their relationship. [ABSTRACT FROM AUTHOR]

The pathophysiology of cough variant asthma is poorly understood. In particular, the mechanisms that cause different symptoms in typical asthma (in which wheeze predominates) compared with cough variant asthma (in which cough predominates) have not been determined. Traditional explanations include higher wheezing thresholds, differences in cough sensitivity, and/or differences in small airway function. Recent studies using high-dose methacholine challenge testing suggest that altered small-airway function plays a role. Preservation or loss of the bronchoprotective effect of a deep inspiration may be a fundamental pathophysiologic difference between asthma, cough variant asthma, methacholine-induced cough with normal sensitivity, and eosinophilic bronchitis. [ABSTRACT FROM AUTHOR]

Upper-airway cough syndrome often coexists with other diseases that elicit chronic cough. However, the concomitant conditions are not always relevant to chronic cough, which complicates the cause diagnosis of chronic cough. The objective of this study was to explore the diagnosis and clinical implication of upper-airway cough syndrome with latent eosinophilic bronchitis. Eleven patients with upper-airway cough syndrome and latent eosinophilic bronchitis were retrospectively analyzed for their clinical manifestations, changes of eosinophilia in induced sputum, and cough threshold with capsaicin defined as capsaicin concentration that elicits two or more coughs (C2) and five or more coughs (C5) between pretreatment and post-treatment. All patients reported a history of allergic rhinitis, showed persistent dry cough or small amounts of viscid sputum with a time course of 2–60 months (median = 7 months), and presented with symptoms and signs of rhinitis, normal lung function, and airway responsiveness. Initial eosinophil percentage in induced sputum was 3.5–8.0%. Cough disappeared after 2–5 (3 ± 1) weeks of only oral antihistamine. With successful treatment, cough threshold C2 increased from 1.73 ± 1.45 to 4.43 ± 4.50 μmol/L ( t = 2.64, P = 0.025) and C5 increased from 2.79 ± 2.16 to 10.10 ± 8.22 μmol/L ( t = 3.10, P = 0.011). However, there was no significant change of eosinophil percentage in induced sputum (4.8 ± 1.5% vs. 4.4 ± 1.4%, t = 0.84, P = 0.427). Upper-airway cough syndrome with latent eosinophilic bronchitis is a unique condition. The recognition of the entity may avoid unnecessary use of corticosteroids. [ABSTRACT FROM AUTHOR]

Cough reflex sensitivity has not been studied extensively in patients with chronic obstructive pulmonary disease (COPD). The aim of the study was to evaluate cough reflex sensitivity to capsaicin in current and former smokers with COPD and examine its association with potentially protussive mediators. Fifteen active smokers and 18 ex-smokers with moderate to severe COPD, 14 healthy active smokers, and 13 healthy never smokers were enrolled. Capsaicin aerosol was administered in order of ascending concentration until the concentrations inducing two or more coughs (C2) and five or more coughs (C5) were attained. The concentrations of leukotriene E4 (LTE4), leukotriene B4 (LTB4), and interleukin-8 (IL-8) in bronchoalveolar lavage (BAL) fluid were analyzed by ELISA. Cough reflex sensitivity in COPD smokers [mean log C2 = 1.20 ± 0.23 (SEM) μM; log C5 = 1.85 ± 0.21 μM] did not differ from that in COPD ex-smokers (log C2 = 1.15 ± 0.14 μM; log C5 = 2.10 ± 0.19 μM; p > 0.05). Mean C2 and C5 in both COPD groups were significantly lower than in healthy active smokers, but higher compared with the healthy never-smokers. BAL fluid concentrations of LTE4 and LTB4 were similar in all groups. IL-8 concentrations did not differ between COPD smokers, COPD ex-smokers, and healthy active smokers, but were significantly higher in all three groups compared with healthy never smokers. Cough reflex sensitivity to capsaicin does not differ between smokers and ex-smokers with COPD. [ABSTRACT FROM AUTHOR]

Chronic cough is a common symptom but only a fraction of patients seek medical attention. Addressing the causes of chronic cough may lead to control of cough; however, this approach is not always successful since there is a certain degree of failure even when the cause(s) of cough are adequately treated; in idiopathic cough, there is no cause to treat. Persistent cough may be associated with deterioration of quality of life, and treatment with cough suppressants is indicated. Currently available cough suppressants include the centrally acting opioids such as morphine, codeine, and dextromethorphan. Peripherally acting antitussives include moguisteine and levodropropizine. Early studies report success in reducing cough in patients with chronic bronchitis or COPD; however, a carefully conducted study showed no effect of codeine on cough of COPD. Success with these cough suppressants can be achieved at high doses that are associated with side effects. Slow-release morphine has been reported to be useful in controlling intractable cough with good tolerance to constipation and drowsiness. There have been case reports of the success of centrally acting drugs such as amitryptiline, paroxetine, gabapentin, and carbamezepine in chronic cough. New opioids such as nociceptin or antagonists of TRPV1 may turn out to be more effective. Efficacy of cough suppressants must be tested in double-blind randomised trials using validated measures of cough in patients with chronic cough not responding to specific treatments. Patients with chronic cough are in desperate need of effective antitussives that can be used either on demand or on a long-term basis. [ABSTRACT FROM AUTHOR]

Erdosteine is a multifactorial drug currently used in COPD for its rheologic activity on bronchial secretions and its positive effects on bacterial adhesiveness. Erdosteine produces an active metabolite (Met 1) which was shown to produce antioxidant effects during the respiratory burst of human PMNs, due to the presence of an SH group. The substantial antitussive effects of erdosteine were first documented in clinical trials even though mucolytic agents are regarded as not consistently effective in ameliorating cough in patients with bronchitis, although they may be of benefit to this population in other ways. Actually, a mucolytic drug could exert antitussive effects if it also affects mucus consistency and enhances ciliary function. In the last decade, data from several studies on animal models pointed to the possible antitussive and anti-inflammatory properties of erdosteine and an indirect anti-inflammatory mechanism of action was suggested. Recently, data from some controlled versus placebo studies documented the antioxidant properties of erdosteine in humans and in current smokers with COPD. The mechanism of action was described as related to erdosteine's ability to inhibit some inflammatory mediators and some pro-inflammatory cytokines that are specifically involved in oxidative stress. As oxidative stress is also presumed to impair β-adrenoceptor function and contribute to airway obstruction, specific controlled studies recently investigated the effect of antioxidant intervention on short-term airway response to salbutamol in nonreversible COPD, according to a double-blind design versus placebo and NAC. Only erdosteine consistently restored a significant short-term reversibility in COPD subjects, previously unresponsive to β adrenergics. This peculiar activity of erdosteine (to our knowledge never previously assessed) proved related to the ROS scavenging activity (which actually proved equal to that of N), and its significant inhibiting effect on lipoperoxidation (8-isoprostane) proved discriminant between treatments, with antioxidant and anti-inflammatory effects the main determinants of the erdosteine multifactorial properties. In addition, antitussive effects may be regarded as related to its anti-inflammatory properties via the improvement of mucociliary clearance and the reduction of chemokines from epithelial cells. Finally, a sort of 'sensitization' of 2-adrenoceptors can also be speculated due to the same mechanisms of action; if confirmed by further controlled studies, this particular property would suggest a novel therapeutic role of erdosteine in COPD. [ABSTRACT FROM AUTHOR]

It is important to make a differential diagnosis of cough variant asthma in patients with chronic cough. To examine whether or not peak expiratory How rate (PEFR) is useful for the differential diagnosis of cough variant asthma in such patients, diurnal variation rates of PEFR were calculated in 23 patients who presented with dry cough lasting four or more weeks and who showed no abnormalities on chest radiographs. None of the patients had wheezes, and pulmonary function testing at the time of visit to the hospital revealed no abnormalities. During the control period, the mean diurnal variation rate of PEFR in 23 patients was 16.3 ± 7.9%. Six, nine and eight patients had PEFR diurnal variations rates of <10% (Group 1). 10-19% (Group 2), and ≥ 20% (Group 3). respeetively. At week 3 of treatment with bronchodilators, only Group 3 showed a significant decrease in PHFR diurnal variation rate from 25.7% to 10.1%. The cough score decreased significantly in Group 3 only. These patients had enhanced bronchial hyperresponsiveness and showed eosinophils in induced sputum, leading to the diagnosis of cough variant asthma (CVA). After making the diagnosis of CVA, an inhaled corticosteroid or a Th2 cytokine production inhibitor suplatast tosilate was administered to patients; consequently, they showed no recurrence of cough. PEFR monitoring allowed the detection of morning dip and was suggested to be potentially useful for the differential diagnosis of cough variant asthma in patients with chronic cough. [ABSTRACT FROM AUTHOR]