Cough reflex is a vital protective mechanism against aspiration, but when dysregulated, it can become hypersensitive. In fact, chronic cough is a significant medical problem with a high degree of morbidity. Recently, a unifying paradigm of cough hypersensitivity syndrome has been proposed. It represents a clinical entity in which chronic cough is a major presenting problem, regardless of the underlying condition. Although it remains a theoretical construct, emerging evidence suggests that aberrant neurophysiology is the common etiology of this syndrome. Recent success in randomized clinical trials using a P2X3 receptor antagonist is the first major advance in the therapeutics of cough in the past 30 years; it at last provides a strategy for treating intractable cough as well as an invaluable tool for dissecting the mechanism underpinning cough hypersensitivity. Additionally, several cough measurement tools have been validated for use and will help assess the clinical relevance of cough in various underlying conditions. Along with this paradigm shift, our understanding of cough mechanisms has improved during the past decades, allowing us to continue to take more steps forward in the future.
Cough* ; Hypersensitivity* ; Neurophysiology ; Receptors, Purinergic P2X3 ; Reflex

No abstract available.
Macrophages*

No abstract available.
Cough ; Humans

Chronic cough is a common reason for patients to seek medication attention. Over the last few decades, we have experienced significant clinical success by applying the paradigm of 'evaluating and treating the causes for chronic cough'. However, we still ask ourselves 'what underlies chronic cough. Indeed in a considerable proportion of patients cough is idiopathic, or unexplained despite vigorous evaluation. Commonly associated conditions such as rhinitis, eosinophilic bronchitis, asthma, or gastroesophageal acidic reflux may not be fundamental to cough, and thus may be triggers rather than causes. The cardinal feature of chronic cough is persistent upregulation the cough reflex, which may be driven by complex interactions between biologic, neurologic, immunologic, genetic, comorbid, and environmental factors. We suggest the new paradigm 'cough hypersensitivity syndrome' should finally bring us further advances in understanding and management of chronic cough.
Asthma ; Bronchitis ; Cough ; Eosinophils ; Humans ; Hypersensitivity ; Reflex ; Respiratory Hypersensitivity ; Rhinitis ; Up-Regulation

PURPOSE: Inhaled corticosteroids (ICSs) are often considered an empirical therapy in the management of patients with cough. However, ICS responsiveness is difficult to interpret in daily clinical practice, as the improvements may include placebo effects or self-remission. We aimed to evaluate ICS and placebo treatment effects in adult patients with cough. METHODS: Electronic databases were searched for studies published until June 2018, without language restriction. Randomized controlled trials reporting the effects of ICSs compared with placebo in adult patients with cough were included. Random effects meta-analyses were conducted to estimate the treatment effects. Therapeutic gain was calculated by subtracting the percentage change from baseline in the cough score in the ICS treatment group from that in the placebo treatment group. RESULTS: A total of 9 studies were identified and 8 studies measuring cough severity outcomes were included for meta-analyses. Therapeutic gain from ICSs ranged from −5.0% to +94.6% across the studies included; however, it did not exceed +22%, except for an outlier reporting very high therapeutic gains (+45.6% to +94.6%, depending on outcomes). Overall ICS treatment effects in cough severity outcomes were small-to-moderate (standardized mean difference [SMD], −0.38; 95% confidence interval [CI], −0.54, −0.23), which were comparable between subacute and chronic coughs. However, pooled placebo treatment effects were very large in subacute cough (SMD, −2.58; 95% CI, −3.03, −2.1), and modest but significant in chronic cough (SMD, −0.46; 95% CI, −0.72, −0.21). CONCLUSIONS: Overall therapeutic gain from ICSs is small-to-moderate. However, placebo treatment effects of ICS are large in subacute cough, and modest but still significant in chronic cough. These findings indicate the need for careful interpretation of ICS responsiveness in the management of cough patients in the clinic, and also for rigorous patient selection to identify ICS-responders.
Adrenal Cortex Hormones ; Adult ; Cough ; Humans ; Overall ; Patient Selection ; Placebo Effect ; Steroids

PURPOSE: Recent evidence suggests a global burden of chronic cough in general populations. However, the definitions vary greatly among epidemiological studies, and none have been validated for clinical relevance. We aimed to examine previous epidemiological definitions in detail and explore the operational characteristics. METHODS: A systematic review was conducted for epidemiological surveys that reported the prevalence of chronic cough in general adult populations during the years 1980 to 2013. A literature search was performed on Pubmed and Embase without language restriction. Epidemiological definitions for chronic cough were classified according to their components, such as cutoff duration. Meta-analyses were performed for the male-to-female ratio of chronic cough prevalence to explore operational characteristics of epidemiological definitions. RESULTS: A total of 70 studies were included in the systematic review. The most common epidemiological definition was identified as 'cough > or =3 months' duration without specification of phlegm (n=50); however, it conflicted with the cutoff duration in current clinical guidelines (cough > or =8 weeks). Meta-analyses were performed for the male-to-female ratio of chronic cough among 28 studies that reported sex-specific prevalence using the most common definition. The pooled male-to-female odds ratio was 1.26 (95% confidence interval 0.92-1.73) with significant heterogeneity (I2=96%, P<0.001), which was in contrast to clinical observations of female predominance from specialist clinics. Subgroup analyses did not reverse the ratio or reduce the heterogeneity. CONCLUSIONS: This study identified major issues in defining chronic cough in future epidemiological studies. The conflict between epidemiological and clinical diagnostic criteria needs to be resolved. The unexpected difference in the gender predominance between the community and clinics warrants further studies. Clinical validation of the existing definition is required.
Adult ; Cough* ; Epidemiologic Studies ; Epidemiology ; Female ; Humans ; Odds Ratio ; Population Characteristics ; Prevalence ; Specialization