Chronic cough: new insights and future prospects

Chronic cough is defined in adults as a cough that lasts for ≥8 weeks. When it proves intractable to standard-of-care treatment, it can be referred to as refractory chronic cough (RCC). Chronic cough is now understood to be a condition of neural dysregulation. Chronic cough and RCC result in a serious, often unrecognized, disease burden, which forms the focus of the current review.The estimated global prevalence of chronic cough is 2-18%. Patients with chronic cough and RCC report many physical and psychological effects, which impair their quality of life. Chronic cough also has a significant economic burden for the patient and healthcare systems. RCC diagnosis and treatment are often delayed for many years as potential treatable triggers must be excluded first and a stepwise empirical therapeutic regimen is recommended.Evidence supporting most currently recommended treatments is limited. Many treatments do not address the underlying pathology, are used off-label, have limited efficacy and produce significant side-effects. There is therefore a significant unmet need for alternative therapies for RCC that target the underlying disease mechanisms. Early clinical data suggest that antagonists of the purinergic P2X3 receptor, an important mediator of RCC, are promising, though more evidence is needed

Summary of papers presented at the 2012 seventh international cough symposium

Twenty six papers were presented as posters in the Seventh International Symposium on Cough; 12 papers were presented in the Basic Science of Cough session, and 14 papers presented in the Clinical Science of Cough session. These papers explored a wide spectrum of cough-related areas including pathophysiological mechanisms, treatment and detection of cough, and symptom assessment and perception, and were grouped into several general themes for facilitate the discussion. Studies presented in these posters have provided new information that should improve our knowledge on the basic physiology and pharmacology of cough, and the peripheral and central neural mechanisms involved in the generation of the cough motor pattern. In addition, in the clinical science section, studies reporting potential new anti-tussive agents and further characterisation of cough symptoms and perception have provided a base for the fruitful strategies for the development of novel anti-tussive therapies and cough management

Effect of viral upper respiratory tract infection on the urge-to-cough sensation

SummaryBackgroundRecently, interest has emerged in the sensation of irritation that precedes the motor act of coughing; this phenomenon has been termed the urge-to-cough (UTC). Although one previous study has demonstrated a transient enhancement of cough reflex sensitivity during acute upper respiratory tract infection (URI), the effect of URI on UTC has not previously been investigated.MethodsEmploying standard cough challenge methodology, we measured cough reflex sensitivity in 24 otherwise healthy adult nonsmokers during URI and again after recovery (4–8 weeks later) by determining C2 and C5, the concentrations of capsaicin inducing 2 or more and 5 or more coughs, respectively. In addition, we determined the capsaicin concentration at which the UTC sensation first occurred, without an associated motor cough, and termed it Cu. Furthermore, we determined the difference between concentrations of capsaicin inducing the first motor event of cough (C1) and Cu, and have termed it CΔ.ResultsDuring URI, cough reflex sensitivity as measured by C1 (p = 0.033) and C5 (p = 0.001), as well as the urge-to-cough threshold, Cu (p = 0.046), were significantly enhanced compared to the post-recovery state. The degree of change in cough reflex sensitivity (C5) was significantly greater than that of the urge-to-cough threshold, Cu (p = 0.044).ConclusionOur results demonstrate that the UTC sensation is transiently enhanced during URI. We also confirm the results of the lone previous study that demonstrated transient enhancement of cough reflex sensitivity during URI. The UTC threshold may represent an additional relevant end point to measure in future studies evaluating potential antitussive agents

An observational study on cough in children: epidemiology, impact on quality of sleep and treatment outcome

Background Cough is one of the most frequent symptoms in children and is the most common symptom for which children visit a health care provider. Methods This is an observational study on acute cough associated with upper respiratory tract infection (URTI) in children. The study evaluates the epidemiology and impact of cough on quality of sleep and children\u27s activities, and the outcome of cough with antitussive treatments in pediatric routine clinical practice. Study assessments were performed through a pediatric cough questionnaire (PCQ), developed by the Italian Society of Cough Study. A total of 433 children visited by family care pediatricians for acute cough due to a URTI were enrolled in this study, with mean age of 6.1 years (SD 3.6). Cough type, duration, severity and frequency, cough impact on sleep disturbances of children and parents and on school and sport activities were assessed at baseline. In a subset of 241 children who were either treated with antitussive drugs (levodropropizine n = 101, central antitussives n = 60) or received no treatment (n = 80), the outcome of cough after 6 days was analyzed in terms of resolution, improvement, no change, or worsening. Descriptive analysis, χ2 test, and multivariate analysis with stepwise logistic regression were performed. Results Cough disturbed sleep in 88% of children and 72% of parents. In children treated with cough suppressants, the duration, type, intensity, and frequency cough were similar at baseline in the two groups respectively treated with levodropropizine and central antitussives (cloperastine and codeine). Both levodropropizine and central drugs reduced cough intensity and frequency. However, percentage of cough resolution was higher with levodropropizine than with central antitussives (47% vs. 28% respectively, p = 0.0012). Conclusions Acute cough disturbs sleep in most children and their parents. Both levodropropizine and central antitussives reduced cough intensity, with levodropropizine producing a higher cough resolution rate

Acute cough: a diagnostic and therapeutic challenge

Abstract Background Acute cough is one of the most common complaints prompting patient visits to healthcare professionals. Despite the broad repercussions of acute cough on patient quality of life, school and work productivity, and public health resources, research on this condition is minimal, as are the available treatment options. Many patients use over-the-counter medicines, which are often ineffective for symptom relief. Some therapies may achieve antitussive activity, but at the expense of unpleasant or intolerable side effects. Unmet needs When considering the treatments currently available for the management of acute cough, the multiple limitations of such treatments are quite apparent. Most of these treatments lack clinically proven efficacy and reliability to support their use. This reinforces the need for the generation of quality scientific data from well-performed clinical trials. Hopefully, the result will be the development of safer, more effective and more reliable therapeutic options in the management of acute cough. Cough assessment and management Acute cough can be due to a variety of causes, and it is worthwhile to consider these pathogenic factors in some detail. It is also important to be familiar with the effects that acute cough has on patients' quality of life, work productivity, and the healthcare system; proper awareness of these effects may contribute to better understanding of the social impact of cough. In reference to the available treatments for the management of acute cough, adequate knowledge of the type of over-the-counter and prescription products in the market, as well as their mode of action and advantages/disadvantages, may provide expanded pharmacotherapeutic opportunities and facilitate better clinical decisions. However, due to the drawbacks of current treatment options, ideas for future cough management and newer products need to be considered and tested. Conclusion In view of the socio-economic impact of acute cough and the limitations of available treatments, a renewed interest in the management of acute cough needs to be encouraged. The current strategies for acute cough management need to be reassessed, with a focus on developing new, reliable products and formulations with proven efficacy and safety

Identifying and Characterizing a Chronic Cough Cohort Through Electronic Health Records

Background Chronic cough (CC) of 8 weeks or more affects about 10% of adults and may lead to expensive treatments and reduced quality of life. Incomplete diagnostic coding complicates identifying CC in electronic health records (EHRs). Natural language processing (NLP) of EHR text could improve detection. Research Question Can NLP be used to identify cough in EHRs, and to characterize adults and encounters with CC? Study Design and Methods A Midwestern EHR system identified patients aged 18 to 85 years during 2005 to 2015. NLP was used to evaluate text notes, except prescriptions and instructions, for mentions of cough. Two physicians and a biostatistician reviewed 12 sets of 50 encounters each, with iterative refinements, until the positive predictive value for cough encounters exceeded 90%. NLP, International Classification of Diseases, 10th revision, or medication was used to identify cough. Three encounters spanning 56 to 120 days defined CC. Descriptive statistics summarized patients and encounters, including referrals. Results Optimizing NLP required identifying and eliminating cough denials, instructions, and historical references. Of 235,457 cough encounters, 23% had a relevant diagnostic code or medication. Applying chronicity to cough encounters identified 23,371 patients (61% women) with CC. NLP alone identified 74% of these patients; diagnoses or medications alone identified 15%. The positive predictive value of NLP in the reviewed sample was 97%. Referrals for cough occurred for 3.0% of patients; pulmonary medicine was most common initially (64% of referrals). Limitations Some patients with diagnosis codes for cough, encounters at intervals greater than 4 months, or multiple acute cough episodes may have been misclassified. Interpretation NLP successfully identified a large cohort with CC. Most patients were identified through NLP alone, rather than diagnoses or medications. NLP improved detection of patients nearly sevenfold, addressing the gap in ability to identify and characterize CC disease burden. Nearly all cases appeared to be managed in primary care. Identifying these patients is important for characterizing treatment and unmet needs

A causal relationship between cough and gastroesophageal reflux disease (GERD) has been established: A Pro/Con debate

Along with upper airway cough syndrome (formerly, postnasal drip syndrome) and eosinophilic airway inflammation (asthma, non-asthmatic eosinophilic bronchitis), gastroesophageal reflux disease (GERD) is generally considered among the most common etiologies of chronic cough. Indeed, cough management guidelines published by numerous respiratory societies worldwide recommend evaluation and treatment of GERD as an integral component of the diagnostic/therapeutic algorithm for the management of chronic cough. However, a significant number of patients with chronic cough presumed due to GERD do not report improvement despite aggressive acid-suppressive therapy. Some of these refractory cases may be due to the recently appreciated entity of non-acid or weakly acidic reflux. Further contributing to the controversy are recent studies demonstrating that patients with chronic cough do not have excessive reflux events relative to healthy volunteers. Although a temporal relationship between cough and reflux events has been suggested by studies utilizing impedance-pH monitoring of reflux events and objective cough recording, consensus is lacking in terms of whether this temporal relationship proves a causal link between reflux and cough. The 4(th) American Cough Conference, held in New York in June, 2013, provided an ideal forum for the debate of this issue between two internationally recognized experts in the field of reflux and chronic cough