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Airway Hypersensitivity, Reflux, and Phonation Contribute to Chronic Cough.

ABSTRACT: Although chronic cough is common, its etiology is often elusive, making patient management a challenge. Gastroesophageal reflux and airway hypersensitivity can cause chronic cough. We explored the relationship between reflux, phonation, and cough in patients with idiopathic chronic cough.We performed a blinded, cross-sectional study of nonsmoking patients with chronic cough (duration, >8 weeks) refractory to reflux treatment referred to the Digestive Disease Center at Vanderbilt University. All underwent 24-hour acoustic recording concurrently and temporally synchronized with ambulatory pH-impedance monitoring. Cough, phonation, and pH-impedance events were recorded. We evaluated the temporal relationship between cough and phonation or reflux events using Poisson and logistic regression.Seventeen patients met the inclusion criteria (88% female; 100% white; median age, 63 years [interquartile age range, 52-66 years]; mean body mass index, 30.6 [interquartile range, 27.9-34.0]); there were 2048 analyzable coughing events. The probability of subsequent coughing increased with higher burdens of preceding cough, reflux, or phonation. Within the first 15 minutes after a cough event, the cough event itself was the main trigger of subsequent cough events. After this period, de novo coughing occurred with increases of 1.46-fold in association with reflux alone (95% confidence interval, 1.17-1.82; P < .001) and 1.71-fold in association with the combination of phonation and reflux events.Antecedent phonation and reflux increased the rate of cough events in patients with idiopathic chronic cough. Reflux events were more strongly associated with increased rate of coughing. Our findings support the concept that airway hypersensitivity is a cause of chronic cough, and that the vocal folds may be an effector in chronic cough ClinicalTrials.gov number: NCT01263626.

SUBMITTER: Francis DO

PROVIDER: S-EPMC4761487 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Airway Hypersensitivity, Reflux, and Phonation Contribute to Chronic Cough.

Francis David O DO Slaughter James C JC Ates Fehmi F Higginbotham Tina T Stevens Kristin L KL Garrett C Gaelyn CG Vaezi Michael F MF

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 20151019 3

<h4>Background & aims</h4>Although chronic cough is common, its etiology is often elusive, making patient management a challenge. Gastroesophageal reflux and airway hypersensitivity can cause chronic cough. We explored the relationship between reflux, phonation, and cough in patients with idiopathic chronic cough.<h4>Methods</h4>We performed a blinded, cross-sectional study of nonsmoking patients with chronic cough (duration, >8 weeks) refractory to reflux treatment referred to the Digestive Dis ...[more]

PMID: 26492842

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Project description:BackgroundThe differential sensitivity of cough to antitussive therapies implies the existence of heterogeneity in cough hypersensitivity, but how such heterogeneity is expressed across individual patients is poorly understood. We investigated the phenotypes of cough hypersensitivity by examining transient receptor potential ankyrin 1 (TRPA1)- and transient receptor potential vanilloid 1 (TRPV1)-mediated cough sensitivity in patients with chronic refractory cough.MethodsUsing a selective TRPA1 agonist, allyl isothiocyanate (AITC), we established an AITC cough challenge as a measure of TRPA1-mediated cough sensitivity. The AITC cough challenge and the widely used capsaicin (a selective TRPV1 agonist) cough challenge were performed with 250 patients with chronic refractory cough and 56 healthy subjects. The concentration of AITC or capsaicin solution causing at least two (C2) and five coughs (C5) was recorded. Cough sensitivity was expressed as the mean (95% confidence interval) of log C5, and cough hypersensitivity was defined as a log C5 value lower than that of healthy subjects.ResultsA distinct concentration-response effect of inhaled AITC was identified both in patients with chronic refractory cough and in healthy subjects. Cough sensitivity to AITC and capsaicin was significantly higher in patients than in healthy subjects (AITC: 2.42 [2.37-2.48] vs 2.72 [2.66-2.78] mM, p = 0.001; capsaicin: 1.87 [1.75-1.98] vs 2.53 [2.36-2.70] μM, p = 0.001) and was higher in females than in males for both healthy subjects and patients (all p < 0.05). Among the 234 patients who completed both challenges, 25 (10.7%) exhibited hypersensitivity to both AITC and capsaicin, 44 (18.8%) showed hypersensitivity to AITC only, 28 (11.9%) showed hypersensitivity to capsaicin only, and 137 (58.6%) exhibited hypersensitivity to neither. Those with TRPA1- and/or TRPV1-mediated hypersensitivity were predominantly female, while those without TRPA1- and TRPV1-mediated hypersensitivity were mainly male.ConclusionsFour phenotypes of cough hypersensitivity were identified by the activation of TRPV1 and TRPA1 channels, which supports the existence of heterogeneity in cough pathways and provides a new direction for personalized management of chronic refractory cough.Trial registrationClinicalTrials.gov NCT02591550 .

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Airway Hypersensitivity, Reflux, and Phonation Contribute to Chronic Cough.

Publications

Airway Hypersensitivity, Reflux, and Phonation Contribute to Chronic Cough.

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