Airway Hypersensitivity, Reflux, and Phonation Contribute to Chronic Cough

Abstract

Background & aims: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Cough; GERD; Hypersensitivity; Phonation; Reflux.

Figure 1

A) Acoustic cough detection device composed of acoustic sensors, ambient microphone, and recorder device. B) Close up view of phonopneumography sensors and relative diameter compared to quarter. C) Illustration of chest wall and neck positioning of acoustic cough sensors.

Figure 2

Percent of 2-minute intervals that cough occurred in conjunction with phonation (P), pH-Impedance (I) event or both (+ presence; − absence)

Figure 3

Median and distribution of objectively measured Symptom Associated Probability (SAP) and Symptom Index (SI) for Cough in relation to preceding pH-Impedance event (I) and phonation (P) events

Figure 4

a) Burden of 1-minute intervals in which cough, phonation, or reflux events occurred in 60 minutes before cough event or no cough event; b) probability of cough event based on burden of cough, reflux or phonation in preceding 60 minutes

Figure 5

Cough rate and time since last cough based on whether it was preceded by phonation (P) and/or pH-impedance (I) events