Identification of acid reflux cough using serial assays of exhaled breath condensate pH

Abstract

BackgroundChronic cough is a common problem, frequently caused or exacerbated by acid reflux. Diagnosis of acid reflux cough is haphazard currently, often relying on long therapeutic trials of expensive medications. We tested the hypothesis that the most relevant mechanistic component of acid reflux in chronic cough is when it rises to the level of the airway where acid can potentially be aspirated. We further wished to determine if multi-sample exhaled breath condensate (EBC) pH profiles can identify chronic cough patients likely to respond to proton pump inhibitor therapy.Methods59 subjects were recruited for this study. Initially we examined EBC pH (gas-standardized with Argon) in the setting of 15 experimental pharyngeal acid challenges to determine duration of EBC acidification. Subsequently, we enrolled 22 healthy subjects to determine a normal multi-sample exhaled breath condensate pH profile over 1–3 days. We additionally obtained multi-sample EBC pH profiles in 22 patients with chronic cough. These samples were timed to occur after coughing episodes. Exhaled breath condensate pH was measured after gas standardization.ResultsWe found that exhaled breath condensate pH is substantially reduced for approximately 15 minutes after pharyngeal acid load. Healthy subjects rarely have any low EBC pH values (defined as < 7.4 based on a normative reference range from 404 healthy subjects). Patients with chronic cough who subsequently responded well to proton pump inhibition (n = 8) invariably had one or more cough episodes associated with EBC acidification. No patient who had normal EBC pH with each of their cough episodes reported a clinically relevant response to proton-pump inhibition.ConclusionPatients whose cough responds to proton pump inhibition have transient exhaled breath condensate acidification with coughing episodes, supporting the role of airway acidification in reflux-triggered cough. Multi-sample EBC pH profiles, involving samples collected immediately subsequent to a coughing episode, may be useful appropriately to direct therapy to those patients with cough who have relevant acid reflux.

Changes in Exhaled Nitric Oxide and Breath pH during Fluticasone Wean in Asthma

“…However, additional studies will be required. There was a good deal of intersubject variability among subjects who had an exacerbation, likely reflecting the heterogeneity of determinants of asthma exacerbation reflected in airway pH, ranging from response to viral infection to gastroesophageal reflux [11,17,28]. The principle difference with previous studies of pH in asthma exacerbations is that previous studies, in cross-section only, looked at exacerbations severe enough to require emergency department visits and/or hospitalization [10].…”

“…Careful review did not reveal any distinguishing characteristics of these patients. Sustained acidopnea unrelated to asthma exacerbation has been observed in active tuberculosis [27], human rhinovirus infection [25], and chronic bronchitis and cystic fibrosis [12,27], suggesting that chronic airway infection could explain persistently low EBC pH; it may also be associated with gastroesophageal reflux [17]. We do not have evidence for a sustained airway infection or reflux in these 2 subjects.…”

“…Condensate pH stability was measured in this setting and shown to be stable and highly repeatable (coefficient of variation <5%, for both asthmatic and normal subjects) in several studies [10,15,17]. …”

Exhaled Breath Condensates as a Source for Biomarkers for Characterization of Inflammatory Lung Diseases

“…Similarly, EBC pH levels have been reported to be lower in patients with COPD compared to age and gender matched controls and correlate with disease severity, as expressed by GOLD stages, especially in ex-smokers [27]. EBC pH may have potential role in diagnosis of upper respiratory symptoms like chronic cough due to underlying acid reflux [28]. A system for continuous monitoring of EBC pH in intubated patients on mechanical ventilation has also been developed to monitor lung health in critically ill patients [24,29].…”

“…NO and related molecules are non-specific markers of oxidative stress and may be useful in monitoring various pro-inflammatory pathologies of lower airways. Asthma [16,17] COPD [14] Smokers [13] Bronchiestasis [18] ARDS [19] pH Non-specific marker of Oxidative stress pH meter after gas standardization [24] Asthma [26], COPD [27], cough related to GERD [28] Acute lung injury (ALI) and ARDS [29] Nitric oxide related biomarkers Nitrates Non-specific marker of Oxidative stress Fluorimetry [32] Elevated in smokers with COPD [32] S-Nitroso-thiols Non-specific marker of Oxidative stress Spectophotometry [34] Asthma Cystic Fibrosis Asthma, COPD and cystic fibrosis [34] 3-Nitroso-tyrosine liquid chromatography-tandem mass spectrometry [35], EIA [36] Asthma [35] …”