Cough Hypersensitivity Syndrome: Why Its Use Is Inappropriate in Children.

In children and adults, chronic cough is a common symptom presenting to health professionals worldwide. It is internationally accepted that children with chronic cough should be managed with pediatric specific management guidelines. The newly proposed clinical entity of 'cough hypersensitivity syndrome' has gained significant attention in adult literature. Given the significant differences between childhood and adult chronic cough, including in respiratory physiology and anatomy, and cough sensitivity, we address the suitability of the use of cough hypersensitivity syndrome in children. We explore these differences between childhood and adult chronic cough, explain what cough hypersensitivity is and highlight why the term cough hypersensitivity syndrome should not be used in children.

Yardstick for managing cough, part 2: In children.

Nationwide statistics in the United States and Australia reveal that cough of undifferentiated duration is the most common complaint for which patients of all ages seek medical care in the ambulatory setting. Management of chronic cough is one of the most common reasons for new patient visits to respiratory specialists. Because symptomatic cough is such a common problem and so much has been learned about how to diagnose and treat cough of all durations but especially chronic cough, this 2-part yardstick has been written to review in a practical way the evidence-based guidelines most of which have been developed from high-quality systematic reviews on how best to manage cough of all durations in adults, adolescents, and children. Chronic cough in children is often benign and self-limiting. Using established and validated protocols and specific pointers (clues in history, findings on examination) can aid the clinician in identifying causes when present and improve outcomes. In this manuscript, part 2 of the 2-part series, we provide evidence-based, expert opinion recommendations on the management of chronic cough in the pediatric patient (<14 years of age).

Yardstick for managing cough, part 1: In adults and adolescent patients older than 14 years of age.

Nationwide statistics in the United States and Australia reveal that cough of undifferentiated duration is the most common complaint for which patients of all ages seek medical care in the ambulatory setting. Management of chronic cough is one of the most common reasons for new patient visits to pulmonologists. Because symptomatic cough is such a common problem and so much has been learned about how to diagnose and treat cough of all durations but especially chronic cough, this 2-part yardstick has been written to review in a practical way the latest evidence-based guidelines most of which have been developed from recent high quality systematic reviews on how best to manage cough of all durations in adults, adolescents, and children. In this manuscript, part 1 of the 2-part series, we provide evidence-based, and expert opinion recommendations on the management of chronic cough in adult and adolescent patients (>14 years of age).

Managing Chronic Cough Associated with Idiopathic Pulmonary Fibrosis - Will Nalbuphine Fill an Unmet Need?

In this issue of NEJM Evidence, Maher et al.1 report the results of a randomized, controlled, 22-day treatment crossover trial comparing the antitussive effect of extended-release nalbuphine, an opioid agonist-antagonist, with placebo in a cohort of patients with definite or probable idiopathic pulmonary fibrosis (IPF). In this small, short-term trial of 38 evaluable patients, the active drug was associated with a 75.1% reduction in daytime objective cough frequency (the primary outcome) compared with a 22.6% reduction in placebo-treated patients, yielding a substantial and statistically significant 52.5 percentage point placebo-adjusted change from baseline.

Assessing cough symptom severity in refractory or unexplained chronic cough: findings from patient focus groups and an international expert panel.

Background: Cough symptom severity represents an important subjective end-point to assess the impact of therapies for patients with refractory or unexplained chronic cough (RCC/UCC). As existing instruments assessing the severity of cough are neither widely available nor tested for measurement properties, we aim to develop a new patient-reported outcome measure addressing cough severity. Objective: The aim of this study was to establish items and domains that would inform development of a new cough severity instrument. Methods: Three focus groups involving 16 adult patients with RCC/UCC provided data that we analysed using directed content analysis. Discussions led to consensus among an international panel of 15 experts on candidate items and domains to assess cough severity. Results: The patient focus group provided 48 unique items arranged under broad domains of urge-to-cough sensations and cough symptom. Feedback from expert panel members confirmed the appropriateness of items and domains, and provided an additional subdomain related to cough triggers. The final conceptual framework comprised 51 items in the following domains: urge-to-cough sensations (subdomains: frequency and intensity) and cough symptom (subdomains: triggers, control, frequency, fit/bout duration, intensity, quality and associated features/sequelae). Conclusions: Consensus findings from patients and international experts established domains of urge-to-cough and cough symptom with associated subdomains and relevant items. The results support item generation and content validity for a novel patient-reported outcome measure for use in health research and clinical practice.

Global Physiology and Pathophysiology of Cough: Part 2. Demographic and Clinical Considerations: CHEST Expert Panel Report.

BACKGROUND: Cough characteristics vary between patients, and this can impact clinical diagnosis and care. The purpose of part two of this state-of-the-art review is to update the American College of Chest Physicians (CHEST) 2006 guideline on global physiology and pathophysiology of cough. STUDY DESIGN AND METHODS: A review of the literature was conducted using PubMed and MEDLINE databases from 1951 to 2019 using prespecified search terms. RESULTS: We describe the demographics of typical patients with cough in the clinical setting, including how cough characteristics change across age. We summarize the effect of common clinical conditions impacting cough mechanics and the physical properties of mucus on airway clearance. INTERPRETATION: This is the second of a two-part update to the 2006 CHEST cough guideline; it complements part one on basic phenomenology of cough by providing an extended clinical picture of cough along with the factors that alter cough mechanics and efficiency in patients. A greater understanding of the physiology and pathophysiology of cough will improve clinical management.

Global Physiology and Pathophysiology of Cough: Part 1: Cough Phenomenology - CHEST Guideline and Expert Panel Report.

The purpose of this state-of-the-art review is to update the American College of Chest Physicians 2006 guideline on global physiology and pathophysiology of cough. A review of the literature was conducted using PubMed and MEDLINE databases from 1951 to 2019 and using prespecified search terms. We describe the basic phenomenology of cough patterns, behaviors, and morphological features. We update the understanding of mechanical and physiological characteristics of cough, adding a contemporary view of the types of cough and their associated behaviors and sensations. New information about acoustic characteristics is presented, and recent insights into cough triggers and the patient cough hypersensitivity phenotype are explored. Lastly, because the clinical assessment of patients largely focuses on the duration rather than morphological features of cough, we review the morphological features of cough that can be measured in the clinic. This is the first of a two-part update to the American College of Chest Physicians 2006 cough guideline; it provides a more global consideration of cough phenomenology, beyond simply the mechanical aspects of a cough. A greater understanding of the typical features of cough, and their variations, may allow a more informed interpretation of cough measurements and the clinical relevance for patients.

Life-Threatening and Non-Life-Threatening Complications Associated With Coughing: A Scoping Review.

BACKGROUND: This is an update of the section on complications that are associated with coughing in the 2006 CHEST cough guidelines that addresses two aims: (1) to systematically identify and thematically categorize the diverse complications of cough by providing a guide for future studies and (2) to identify gaps in the literature for future research. RESEARCH QUESTION: What are the potential complications that are associated with the act of coughing that have been reported in infants, children, adolescents, and adults? STUDY DESIGN AND METHODS: A scoping review was performed with the use of PubMed and SCOPUS databases that were searched from their beginning until September 6, 2019. RESULTS: Two hundred forty-seven publications met our inclusion criteria. To these, we added 38 articles from the 2006 complications paper that were not identified in the literature search plus the paper itself for a final total of 286 publications that formed the basis of this review. Since 2006, three new categories of complications have been reported: ear, nose and throat; disease transmission; and laboratory testing. Multiple additional complications that fall outside of these three categories have also been identified and included in the following categories: cardiovascular, constitutional symptoms, dermatologic, GI, genitourinary, musculoskeletal, neurologic, ophthalmologic, psychosocial/quality of life, and respiratory. Not previously highlighted is that some of the complications led to serious morbidity that included death, especially in patients with comorbid conditions, and potentially resulted in harm to others when cough resulted in a motor vehicle accident. INTERPRETATION: Our work identified a large number of cough complications that we thematically categorized primarily by organ system so that future studies of each system or each complication can be conducted. The gap in the literature that future studies should address is to identify the frequency of the complications and the strength of their association with cough. Only then will one be able to describe the findings in a manner that allows specific recommendations for avoiding these complications. In the meantime, patients with cough should be evaluated and treated according to evidence-based guidelines to mitigate or prevent the myriad of potential complications that are associated with coughing.

Vaping-Associated Respiratory Distress Syndrome: Case Classification and Clinical Guidance.

Exposure to vaping is associated with a growing list of respiratory syndromes including an acute progressive form with life-threatening hypoxemic respiratory failure and pathologic changes of lung injury termed vaping-associated respiratory distress syndrome. DATA SOURCES: Center from Disease Control, Departments of Public Health, MEDLINE (via PubMed), and the Cochrane Library. STUDY SELECTION DATA EXTRACTION AND DATA SYNTHESIS: Cases, series, and public health reports of cases that met the Centers for Disease Control and Prevention case definition of vaping-associated respiratory disease were extracted by an author with perfect verification by a second. Cases were classified on the basis of toxin exposure, symptoms, oxygen saturation, progression to respiratory failure, and pathologic features, and a clinically actionable system of classification was based on expert opinion. CONCLUSIONS: The reported spectrum of vaping-associated respiratory diseases allows clinical classification of cases into groups with distinct evaluation, management, and recommendations for prevention and follow-up. Clinical stratification also identifies a small proportion of vaping-exposed patients who are at risk for progression to hypoxemic respiratory failure and an acute respiratory distress syndrome-like illness.

Managing Chronic Cough as a Symptom in Children and Management Algorithms: CHEST Guideline and Expert Panel Report.

BACKGROUND: Cough is one of the most common presenting symptoms to general practitioners. The objective of this article is to collate the pediatric components of the CHEST chronic cough guidelines that have recently updated the 2006 guidelines to assist general and specialist medical practitioners in the evaluation and management of children who present with chronic cough. METHODS: We reviewed all current CHEST Expert Cough Panel's statements and extracted recommendations and suggestions relating to children aged ≤ 14 years with chronic cough (> 4 weeks duration). Additionally, we undertook systematic reviews to update other sections we considered relevant and important. RESULTS: The eight recent CHEST guidelines relevant to children, based on systematic reviews, reported some high-quality evidence in the management of chronic cough in children (eg, use of algorithms and management of wet/productive cough using appropriate antibiotics). However, much evidence is still inadequate, particularly in the management of non-specific cough in the community. CONCLUSIONS: The recommendations and suggestions related to the management of chronic cough in the pediatric age group have been based upon high-quality systematic reviews and are summarized in this article. Compared to the 2006 Cough Guidelines, there is now high-quality evidence for some aspects of the management of chronic cough in children. However, further studies particularly in primary health care are required.

Acute Cough Due to Acute Bronchitis in Immunocompetent Adult Outpatients: CHEST Expert Panel Report.

BACKGROUND: Evidence for the diagnosis and management of cough due to acute bronchitis in immunocompetent adult outpatients was reviewed as an update to the 2006 "Chronic Cough Due to Acute Bronchitis: American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines." METHODS: Acute bronchitis was defined as an acute lower respiratory tract infection manifested predominantly by cough with or without sputum production, lasting no more than 3 weeks with no clinical or any recent radiographic evidence to suggest an alternative explanation. Two clinical population, intervention, comparison, outcome questions were addressed by systematic review in July 2017: (1) the role of investigations beyond the clinical assessment of patients presenting with suspected acute bronchitis, and (2) the efficacy and safety of prescribing medication for cough in acute bronchitis. An updated search was undertaken in May 2018. RESULTS: No eligible studies relevant to the first question were identified. For the second question, only one relevant study met eligibility criteria. This study found no difference in number of days with cough between patients treated with an antibiotic or an oral nonsteroidal antiinflammatory agent compared with placebo. Clinical suggestions and research recommendations were made based on the consensus opinion of the CHEST Expert Cough Panel. CONCLUSIONS: The panelists suggested that no routine investigations be ordered and no routine medications be prescribed in immunocompetent adult outpatients first presenting with cough due to suspected acute bronchitis, until such investigations and treatments have been shown to be safe and effective at making cough less severe or resolve sooner. If the cough due to suspected acute bronchitis persists or worsens, a reassessment and consideration of targeted investigations should be considered.

Chronic Cough Due to Stable Chronic Bronchitis: CHEST Expert Panel Report.

BACKGROUND: Chronic cough due to chronic bronchitis (CB) causes significant impairment in quality of life, and effective treatment strategies are needed. We conducted a systematic review on the management of chronic cough due to CB to update the recommendations and suggestions of the American College of Chest Physicians (CHEST) 2006 guideline on this topic. METHODS: This systematic review asked three questions: (1) What are the clinical features of the history that suggest a patient's cough-phlegm syndrome is due to CB? (2) Can treatment of stable CB improve or eliminate chronic cough? (3) Can therapy that targets chronic cough due to CB prevent or reduce the occurrence of acute CB exacerbations? Studies of adult patients with CB were included and assessed for relevance and quality. Based on the systematic review, guideline suggestions were developed and voted on by using the CHEST organization methodology. RESULTS: The search strategy used an assortment of descriptors and assessments to identify studies of chronic cough due to CB. CONCLUSIONS: The evidence supporting the management of chronic cough due to CB is limited overall and of low quality. This article provides guidance on treatment by presenting suggestions based on the best currently available evidence and identifies gaps in our knowledge and areas for future research.

Managing Chronic Cough Due to Asthma and NAEB in Adults and Adolescents: CHEST Guideline and Expert Panel Report.

BACKGROUND: Asthma and non-asthmatic eosinophilic bronchitis (NAEB) are among the commonest causes of chronic cough in adults. We sought to determine the role of non-invasive measurements of airway inflammation, including induced sputum and fractional exhaled nitric oxide, in the evaluation of cough associated with asthma, and what the best treatment is for cough due to asthma or NAEB. METHODS: We undertook three systematic reviews of randomized controlled trials and observational trials of adults and adolescents > 12 years of age with a chronic cough due to asthma or NAEB. Eligible studies were identified in MEDLINE, CENTRAL, and SCOPUS and assessed for relevance and quality. Guidelines were developed and voted upon using CHEST guideline methodology. RESULTS: Of the citations reviewed, 3/1,175, 53/656, and 6/134 were identified as being eligible for inclusion in the three systematic reviews, respectively. In contrast to established guidelines for asthma therapies in general and the inclusion in some guidelines for a role of biomarkers of airway inflammation to guide treatment in severe disease, the evidence of specific benefit related to the use of non-invasive biomarkers in patients with chronic cough due to asthma was weak. The best therapeutic option for cough in asthma or NAEB is inhaled corticosteroids followed by leukotriene receptor antagonism. CONCLUSIONS: This guideline offers recommendations on the role of non-invasive measurements of airway inflammation and treatment for cough due to asthma or NAEB based on the available literature, and identifies gaps in knowledge and areas for future research.