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Peripheral neural regulation of the laryngopharynx involves a complex sequence the laryngopharyngeal sensitivity receptors, triggering conscious or reflexive perception through the peripheral course of the vagus nerve. Laryngopharyngeal sensitivity receptors include the nociceptor bronchopulmonary C-fibers, mechanoreceptor (Widdicombe) cough receptors, transient receptor/ion channel potential vanilloid (TRPV), rapidly and slowly adapting receptors (RAR and SAR, respectively).The latter involves nuances of the right and left recurrent laryngeal nerves, in addition to the superior laryngeal nerves. Proposed mechanisms of laryngopharyngeal hypersensitivity include 1) chronic vagal neuropathy, 2) virally induced neural injury (antigen exposure or viral inflammation induces neuropeptide production by mechanosensitive neurons), 3) acidification of sensory nerves during repeated reflux events, and 4) pepsin-induced proliferation of laryngeal epithelium. The challenges in diagnosing these scenarios are discussed.

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 CHEST's 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.

We updated the 2006 ACCP clinical practice guidelines for management of reflux-cough syndrome.Two 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?We found no high-quality studies pertinent to either question. From available randomized controlled trials (RCTs) addressing question #1, we concluded that (1) there was a 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% to 100% of 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.The 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.