Kefang Lai

A worldwide survey of chronic cough: a manifestation of enhanced somatosensory response

Reports from individual centres suggest a preponderance of females with chronic cough. Females also have heightened cough reflex sensitivity. Here we have reviewed the age and sex of unselected referrals to 11 cough clinics. To investigate the cause of any observed sex dimorphism, functional magnetic resonance imaging of putative cough centres was analysed in normal volunteers. The demographic profile of consecutive patients presenting with chronic cough was evaluated. Cough challenge with capsaicin was undertaken in normal volunteers to construct a concentration-response curve. Subsequent functional magnetic resonance imaging during repeated inhalation of sub-tussive concentrations of capsaicin observed areas of activation within the brain and differences in the sexes identified. Of the 10 032 patients presenting with chronic cough, two-thirds (6591) were female (mean age 55 years). The patient profile was largely uniform across centres. The most common age for presentation was 60–69 years. The maximum tolerable dose of inhaled capsaicin was lower in females; however, a significantly greater activation of the somatosensory cortex was observed. Patients presenting with chronic cough from diverse racial and geographic backgrounds have a strikingly homogeneous demographic profile, suggesting a distinct clinical entity. The preponderance of females may be explained by sex-related differences in the central processing of cough sensation. Chronic cough in specialist clinics have homogenous demographic profiles, suggesting single clinical entity http://ow.ly/zrNAa

Chronic Cough Due to Gastroesophageal Reflux in Adults : CHEST Guideline and Expert Panel Report

BACKGROUNDnWe updated the 2006 ACCP clinical practice guidelines for management of reflux-cough syndrome.nnnMETHODSnTwo population, intervention, comparison, outcome (PICO) questions were addressed by systematic review: (1) Can therapy for gastroesophageal reflux improve or eliminate cough in adults with chronic and persistently troublesome cough? and (2) Are there minimal clinical criteria to guide practice in determining that chronic cough is likely to respond to therapy for gastroesophageal reflux?nnnRESULTSnWe found no high-quality studies pertinent to either question. From available randomized controlled trials (RCTs) addressing question #1, we concluded that (1) there wasxa0a strong placebo effect for cough improvement; (2) studies including diet modification and weight loss had better cough outcomes; (3) although lifestyle modifications and weight reduction may be beneficial in suspected reflux-cough syndrome, proton pump inhibitors (PPIs) demonstrated no benefit when used in isolation; and (4) because of potential carryover effect, crossover studies using PPIs should be avoided. For question #2, we concluded from the available observational trials that (1) an algorithmic approach to management resolved chronic cough in 82%xa0to 100%xa0of instances; (2) cough variant asthma and upper airway cough syndrome (UACS) (previously referred to as postnasal drip syndrome) from rhinosinus conditions were the most commonly reported causes; and (3) the reported prevalence of reflux-cough syndrome varied widely.nnnCONCLUSIONSnThe panelists (1) endorsed the use of a diagnostic/therapeutic algorithm addressing causes of common cough, including symptomatic reflux; (2) advised that although lifestyle modifications and weight reduction may be beneficial in suspected reflux-cough syndrome, PPIs demonstrated no benefit when used in isolation; and (3) suggested that physiological testing be reserved for refractory patients being considered for antireflux surgery or for those in whom there is strong clinical suspicion warranting diagnostic testing.

Adult and paediatric cough guidelines: Ready for an overhaul?

Cough is one of the most common reasons that patients seek medical attention. Cough guidelines from numerous countries and societies are available to assist the clinician to investigate and manage patients with cough. We review some of the recent progress in the field of cough that may lead to revision of these guidelines. In adults with chronic cough, new causes such as obstructive sleep apnoea have been identified. A new terminology, cough hypersensitivity syndrome (CHS), has been proposed for patients with chronic cough, which emphasises cough reflex hypersensitivity as a key feature. New therapeutic options are now available, particularly for patients with refractory or idiopathic chronic cough, which include gabapentin, speech pathology management and morphine. There has been great progress in the assessment of cough with the development of validated quality of life questionnaires and cough frequency monitoring tools. In children, common aetiologies differ from adults and those managed according to guidelines have better outcomes compared to usual care. New diagnostic entities such asxa0protracted bacterial bronchitis have been described. Paediatric-specific cough assessment tools such as the Parent/Child Quality of Life Questionnaire will help improve the assessment of patients. Further research is necessary to improve the evidence base for future clinical guideline recommendations. Guidelines in future should also aim to reach a wider audience that includes primary care physicians, non-specialists and patients.

Cough in the Athlete: CHEST Guideline and Expert Panel Report

Background: Cough is a common symptom experienced by athletes, particularly after exercise. We performed a systematic review to assess the following in this population: (1) the main causes of acute and recurrent cough, either exercise‐induced or not, (2) how cough is assessed, and (3) how cough is treated in this population. From the systematic review, suggestions for management were developed. Methods: This review was performed according to the CHEST methodological guidelines and Grading of Recommendations Assessment, Development and Evaluation framework until April 2015. To be included, studies had to meet the following criteria: participants had to be athletes and adults and adolescents aged ≥ 12 years and had to complain of cough, regardless of its duration or relationship to exercise. The Expert Cough Panel based their suggestions on the data extracted from the review and final grading by consensus according to a Delphi process. Results: Only 60 reports fulfilled the inclusion criteria, and the results of our analysis revealed only low‐quality evidence on the causes of cough and how to assess and treat cough specifically in athletes. Although there was no formal evaluation of causes of cough in the athletic population, the most common causes reported were asthma, exercise‐induced bronchoconstriction, respiratory tract infection (RTI), upper airway cough syndrome (UACS) (mostly from rhinitis), and environmental exposures. Cough was also reported to be related to exercise‐induced vocal cord dysfunction among a variety of less common causes. Although gastroesophageal reflux disease (GERD) is frequent in athletes, we found no publication on cough and GERD in this population. Assessment of the causes of cough was performed mainly with bronchoprovocation tests and suspected disease‐specific investigations. The evidence to guide treatment of cough in the athlete was weak or nonexistent, depending on the cause. As data on cough in athletes were hidden in a set of other data (respiratory symptoms), evidence tables were difficult to produce and were done only for cough treatment in athletes. Conclusions: The causes of cough in the athlete appear to differ slightly from those in the general population. It is often associated with environmental exposures related to the sport training environment and occurs predominantly following intense exercise. Clinical history and specific investigations should allow identification of the cause of cough as well as targeting of the treatment. Until management studies have been performed in the athlete, current guidelines that exist for the general population should be applied for the evaluation and treatment of cough in the athlete, taking into account specific training context and anti‐doping regulations.

Symptomatic Treatment of Cough Among Adult Patients With Lung Cancer: CHEST Guideline and Expert Panel Report

Background Cough among patients with lung cancer is a common but often undertreated symptom. We used a 2015 Cochrane systematic review, among other sources of evidence, to update the recommendations and suggestions of the American College of Chest Physicians (CHEST) 2006 guideline on this topic. Methods The CHEST methodologic guidelines and the Grading of Recommendations, Assessment, Development, and Evaluation framework were used. The Expert Cough Panel based their recommendations on data from the Cochrane systematic review on the topic, uncontrolled studies, case studies, and the clinical context. Final grading was reached by consensus according to the Delphi method. Results The Cochrane systematic review identified 17 trials of primarily low‐quality evidence. Such evidence was related to both nonpharmacologic (cough suppression) and pharmacologic (demulcents, opioids, peripherally acting antitussives, or local anesthetics) treatments, as well as endobronchial brachytherapy. Conclusions Compared with the 2006 CHEST Cough Guideline, the current recommendations and suggestions are more specific and follow a step‐up approach to the management of cough among patients with lung cancer, acknowledging the low‐quality evidence in the field and the urgent need to develop more effective, evidence‐based interventions through high‐quality research.

Occupational and Environmental Contributions to Chronic Cough in Adults: Chest Expert Panel Report

BACKGROUNDnIn response to occupational and environmental exposures, cough can be an isolated symptom reflecting exposure to an irritant with little physiological consequence, or it can be a manifestation of more significant disease. This document reviews occupational and environmental contributions to chronic cough in adults, focusing on aspects not previously covered in the 2006 ACCP Cough Guideline or our more recent systematic review, and suggests an approach to investigation of these factors when suspected.nnnMETHODSnMEDLINE and TOXLINE literature searches were supplemented by articles identified by the cough panel occupational and environmental subgroup members, to identify occupational and environmental aspects of chronic cough not previously covered in the 2006 ACCP Cough Guideline. Based on the literature reviews and the Delphi methodology, the cough panel occupational and environmental subgroup developed guideline suggestions that were approved after review and voting by the full cough panel.nnnRESULTSnThe literature review identified relevant articles regarding: mechanisms; allergic environmental causes; chronic cough and the recreational and involuntary inhalation of tobacco and marijuana smoke; nonallergic environmental triggers; laryngeal syndromes; and occupational diseases and exposures. Consensus-based statements were developed for the approach to diagnosis due to a lack of strong evidence from published literature.nnnCONCLUSIONSnDespite increased understanding of cough related to occupational and environmental triggers, there remains a gap between the recommended assessment of occupational and environmental causes of cough and the reported systematic assessment of these factors. There is a need for further documentation of occupational and environmental causes of cough in the future.

Classification of Cough As a Symptom in Adults and Management Algorithms: CHEST Guideline and Expert Panel Report

Background We performed systematic reviews using the population, intervention, comparison, outcome (PICO) format to answer the following key clinical question: Are the CHEST 2006 classifications of acute, subacute and chronic cough and associated management algorithms in adults that were based on durations of cough useful? Methods We used the CHEST Expert Cough Panel’s protocol for the systematic reviews and the American College of Chest Physicians (CHEST) methodological guidelines and Grading of Recommendations Assessment, Development, and Evaluation framework. Data from the systematic reviews in conjunction with patient values and preferences and the clinical context were used to form recommendations or suggestions. Delphi methodology was used to obtain the final grading. Results With respect to acute cough (< 3 weeks), only three studies met our criteria for quality assessment, and all had a high risk of bias. As predicted by the 2006 CHEST Cough Guidelines, the most common causes were respiratory infections, most likely of viral cause, followed by exacerbations of underlying diseases such as asthma and COPD and pneumonia. The subjects resided on three continents: North America, Europe, and Asia. With respect to subacute cough (duration, 3‐8 weeks), only two studies met our criteria for quality assessment, and both had a high risk of bias. As predicted by the 2006 guidelines, the most common causes were postinfectious cough and exacerbation of underlying diseases such as asthma, COPD, and upper airway cough syndrome (UACS). The subjects resided in countries in Asia. With respect to chronic cough (> 8 weeks), 11 studies met our criteria for quality assessment, and all had a high risk of bias. As predicted by the 2006 guidelines, the most common causes were UACS from rhinosinus conditions, asthma, gastroesophageal reflux disease, nonasthmatic eosinophilic bronchitis, combinations of these four conditions, and, less commonly, a variety of miscellaneous conditions and atopic cough in Asian countries. The subjects resided on four continents: North America, South America, Europe, and Asia. Conclusions Although the quality of evidence was low, the published literature since 2006 suggests that CHESTs 2006 Cough Guidelines and management algorithms for acute, subacute, and chronic cough in adults appeared useful in diagnosing and treating patients with cough around the globe. These same algorithms have been updated to reflect the advances in cough management as of 2017.

Cough in Ambulatory Immunocompromised Adults: CHEST Expert Panel Report

BACKGROUND: Cough is a common symptom prompting patients to seek medical care. Like patients in the general population, patients with compromised immune systems also seek care for cough. However, it is unclear whether the causes of cough in immunocompromised patients who are deemed unlikely to have a life‐threating condition and a normal or unchanged chest radiograph are similar to those in persons with cough and normal immune systems. METHODS: We conducted a systematic review to answer the question: What are the most common causes of cough in ambulatory immunodeficient adults with normal chest radiographs? Studies of patients ≥ 18 years of age with immune deficiency, cough of any duration, and normal or unchanged chest radiographs were included and assessed for relevance and quality. Based on the systematic review, suggestions were developed and voted on using the American College of Chest Physicians (CHEST) methodology framework. RESULTS: The results of the systematic review revealed no high‐quality evidence to guide the clinician in determining the likely causes of cough specifically in immunocompromised ambulatory patients with normal chest radiographs. CONCLUSIONS: Based on a systematic review, we found no evidence to assess whether or not the proper initial evaluation of cough in immunocompromised patients is different from that in immunocompetent persons. A consensus of the panel suggested that the initial diagnostic algorithm should be similar to that for immunocompetent persons but that the context of the type and severity of the immune defect, geographic location, and social determinants be considered. The major modifications to the 2006 CHEST Cough Guidelines are the suggestions that TB should be part of the initial evaluation of patients with cough and HIV infection who reside in regions with a high prevalence of TB, regardless of the radiographic findings, and that specific causes and immune defects be considered in all patients in whom the initial evaluation is unrevealing.

Pharmacologic and Nonpharmacologic Treatment for Acute Cough Associated With the Common Cold: CHEST Expert Panel Report

BACKGROUND: Acute cough associated with the common cold (CACC) causes significant impairment in quality of life. Effective treatment approaches are needed for CACC. We conducted a systematic review on the management of CACC to update the recommendations and suggestions of the CHEST 2006 guideline on this topic. METHODS: This systematic review of randomized controlled trials (RCTs) asked the question: Is there evidence of clinically relevant treatment effects for pharmacologic or nonpharmacologic therapies in reducing the duration/severity of acute CACC? Studies of adults and pediatric patients with CACC were included and assessed for relevance and quality. Based on the systematic review, guideline suggestions were developed and voted on using the American College of Chest Physicians organization methodology. RESULTS: Six systematic reviews and four primary studies identified from updated literature searches for each of the reviews or from hand searching were included and reported data on 6,496 participants with CACC who received one or more of a variety of interventions. The studies used an assortment of descriptors and assessments to identify CACC. CONCLUSIONS: The evidence supporting the management of CACC is overall of low quality. This document provides treatment suggestions based on the best currently available evidence and identifies gaps in our knowledge and areas for future research.

Cough Due to TB and Other Chronic Infections: CHEST Guideline and Expert Panel Report

Background Cough is common in pulmonary TB and other chronic respiratory infections. Identifying features that predict whether pulmonary TB is the cause would help target appropriate individuals for rapid and cost‐effective screening, potentially limiting disease progression and preventing transmission to others. Methods A systematic literature search for individual studies to answer eight key questions (KQs) was conducted according to established Chest Organization methods by using the following databases: MEDLINE via PubMed, Embase, Scopus, and the Cochrane Database of Systematic Reviews from January 1, 1984, to April 2014. Searches for KQ 1 and KQ 3 were updated in February 2016. An updated KQ 2 search was undertaken in March 2017. Results Even where TB prevalence is greatest, most individuals with cough do not have pulmonary TB. There was no evidence that 1, 3, or 4 weeks’ duration were better predictors than cough lasting ≥ 2 weeks to screen for pulmonary TB. In people living with HIV (PLWHIV), screening for fever, night sweats, hemoptysis, and/or weight loss in addition to cough (any World Health Organization [WHO]‐endorsed symptom) increases the diagnostic sensitivity for TB. Although the diagnostic accuracy of symptom‐based screening remains low, the negative predictive value of the WHO‐endorsed symptom screen in PLWHIV may help to risk‐stratify individuals who are not close TB contacts and who do not require further testing for pulmonary TB in resource‐limited settings. However, pregnant PLWHIV are more likely to be asymptomatic, and the WHO‐endorsed symptom screen is not sensitive enough to be reliable. Combined with passive case finding (PCF), active case finding (ACF) identifies pulmonary TB cases earlier and possibly when less advanced. Whether outcomes are improved or transmission is reduced is unclear. Screening asymptomatic patients is cost‐effective only in populations with a very high TB prevalence. The Xpert MTB/RIF assay on sputum is more cost‐effective than clinical diagnosis. To our knowledge, no published comparative studies addressed whether the rate of cough resolution is a reliable determinant of the response to treatment or whether the rate of cough resolution was faster in the absence of cavitary lung disease. All studies on cough prevalence in Mycobacterium avium complex (MAC) lung disease, other nontuberculous mycobacterial infections, fungal lung disease, and paragonimiasis were of poor quality and were excluded from the evidence review. Conclusions On the basis of relatively few studies of fair to good quality, we conclude that most individuals at high risk and household contacts with cough ≥ 2 weeks do not have pulmonary TB, but we suggest screening them regardless of cough duration. In PLWHIV, the addition of the other WHO‐endorsed symptoms increases the diagnostic sensitivity of cough. Earlier screening of patients with cough will help diagnose pulmonary TB sooner but will increase the cost of screening. The addition of ACF to PCF will increase the number of pulmonary TB cases identified. Screening asymptomatic individuals is cost‐effective only in groups with a very high TB prevalence. Data are insufficient to determine whether cough resolution is delayed in individuals with cavitary lung disease or in those for whom treatment fails because of drug resistance, poor adherence, and/or drug malabsorption compared with results in other individuals with pulmonary TB. Cough is common in patients with lung infections due to MAC, other nontuberculous mycobacteria, fungal diseases, and paragonimiasis.