We read with great interest the article by Sifrim and colleagues (Gut 2005;54:449–54) addressing the issue of the importance of weakly acidic reflux (as measured by 24 hour ambulatory pressure and pH impedance monitoring) in patients with chronic cough. The presence of asthma, postnasal drip, or use of angiotensin converting enzyme inhibitors was ruled out so that an association with gastro‐oesophageal reflux was probable. They found that only 15% of cough bursts were preceded by reflux episodes, which in 4% of cases were weakly acidic and therefore not detectable by conventional automated analysis of oesophageal pH tracings. Although the temporal relationship between acid or weakly acidic reflux and cough was highly significant, it could not be demonstrated in most episodes. In this respect their findings are in agreement with a previous study by Laukka and colleagues,1 who also used manometry for a more accurate timing of cough. Taken together, the results of the two studies suggest that the pathogenetic mechanisms usually proposed as a link between reflux and cough (micro/macroaspiration of refluxate into the airways and vagally mediated cough reflex) may be involved, at best, in a minority of cough episodes.
A different explanation has therefore to be formulated, not requiring a strict temporal relationship between reflux and cough. We suggest that such an explanation is represented by a low cough threshold induced by repeated reflux.
We have previously demonstrated that patients with reflux oesophagitis present a tussive response to minute amounts of inhaled capsaicin.2 In our series, the temporal relationship between irritant inhalation and cough bursts was so reproducible and immediate that a casual association with a single reflux was unlikely. Rather, our finding strongly suggests the presence of a reduction in cough threshold, related to the cumulated effect of repeated oesophageal acid exposures. These lead to nociceptor sensitisation, which has been reported to be reversible by proton pump inhibitor treatment.3 In fact, in our series of oesophagitis patients, only five days of omeprazole treatment produced a striking improvement in tussive reactivity, so that a dose of capsaicin 15‐fold higher was required to elicit cough.4 Once this acid driven mechanism is activated, a variety of otherwise subliminal stimuli (smoke, pollution, etc) can cause cough.
For this reason, the temporal association of reflux with cough does not appear to be a reliable criterion to diagnose reflux associated cough, even using state of the art methodology. Future studies will clarify whether variations in cough threshold after proton pump inhibitor therapy has a role in identifying among patients with cough those in whom the symptom is due to reflux.5
Footnotes
Conflict of interest: None declared.
References
- 1.Laukka M A, Cameron A J, Schei A J. Gastroesophageal reflux and chronic cough: which comes first? J Clin Gastroenterol 199419100–104. [DOI] [PubMed] [Google Scholar]
- 2.Ferrari M, Olivieri M, Sembenini C.et al Tussive effect of capsaicin in patients with gastroesophageal reflux without cough. Am J Respir Crit Care Med 1995151557–561. [DOI] [PubMed] [Google Scholar]
- 3.Fass R, Nalibof B, Higa L.et al Differential effect of long‐term esophageal acid exposure on mechanosensitivity and chemosensitivity in humans. Gastroenterology 19981151363–1373. [DOI] [PubMed] [Google Scholar]
- 4.Benini L, Ferrari M, Sembenini C.et al Cough threshold in reflux oesophagitis: influence of acid and of laryngeal and oesophageal damage. Gut 200046762–767. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Benini L, Ferrari M, Tacchella N.et al Short term omeprazole treatment reduces the tussive response to capsaicin but not bronchial reactivity to methacholine in asthmatic patients. Gastroenterology 2005128(Suppl 2)A91. [DOI] [PubMed] [Google Scholar]