Exhaled breath condensate in chronic cough
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1 Academic Department of Medicine, Castle Hill Hospital, Cottingham, East Yorkshire HU16 5JQ, UK; a.h.morice@hull.ac.uk
Keywords: chronic cough; exhaled breath condensate; airway acidification
We read with interest the recent article by Niimi et al reporting low levels of exhaled breath condensate (EBC) pH in patients with chronic cough.1 We and others have described low EBC pH in association with airway inflammation in allergic asthma, cystic fibrosis, and chronic obstructive pulmonary disease.2–4 In these studies there is a relatively close association between inflammation and low pH which is shown by the further fall in pH during exacerbations.2 However, in non-asthmatic chronic cough, while there is a low grade inflammation present in some subjects, this is much less than would be required to invoke inflammation as the major cause of airway acidification.
It is unclear from the description of the assessment protocol how patients were allotted their individual diagnostic categories. A positive methacholine challenge test is not infrequently found in patients with reflux5 and, even in classical asthma, reflux is a common phenomenon.6 We suggest that there has been a significant underdiagnosis of reflux disease in this cohort because of the lack of a structured history, the non-uniform application of investigations, and the failure to perform full oesophageal assessment, particularly manometry. We have shown that, when oesophageal manometry is not performed, a significant number of patients with reflux cough will be missed.7 Proton pump inhibitors at conventional doses only temporarily increase the pH of gastric reflux and do not prevent reflux per se and, unsurprisingly, only improve symptoms in a proportion of patients with reflux cough. A failure of cough to improve with proton pump inhibitors does not therefore adequately rule out reflux cough.
The simplest explanation for the low airway pH observed by Niimi et al would be that a large proportion of the subjects had laryngopharyngeal reflux. This would also explain the otherwise surprising finding of similar EBC pH across the authors’ diagnostic categories.
References
Niimi A, Nguyen LT, Usmani O, et al. Reduced pH and chloride levels in exhaled breath condensate of patients with chronic cough. Thorax 2004;59:608–12.
Ojoo JC, Mulrennan S, Kastelik JA, et al. Exhaled breath condensate pH and exhaled nitric oxide in allergic asthma and in cystic fibrosis. Thorax 2005;60:22–6.
Kostikas K, Papatheodorou G, Ganas K, et al. pH in expired breath condensate of patients with inflammatory airway diseases. Am J Respir Crit Care Med 2002;165:1364–70.
Tate S, MacGregor G, Davis M, et al. Airways in cystic fibrosis are acidified: detection by exhaled breath condensate. Thorax 2002;57:926–9.
Bagnato GF, Gulli S, Giacobbe O, et al. Bronchial hyperresponsiveness in subjects with gastroesophageal reflux. Respiration 2000;67:507–9.
Vincent DAM, Leport J, et al. Gastro-oesophageal reflux prevalence and relationship with bronchial reactivity in asthma. Eur Respir J 1997;10:2255–9.
Kastelik JA, Redington AE, Aziz I, et al. Abnormal oesophageal motility in patients with chronic cough. Thorax 2003;58:699–702.
Authors’ reply
K F Chung2 and A Niimi2
2 Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK; f.chung@imperial.ac.uk
We thank Professor Morice and his colleagues for their interest in our paper. The main issue they raise concerns the possibility that we may have missed gastro-oesophageal disorders such as reflux and dysmotility in our cohort of patients with chronic cough. In our assessment protocol we state that we used oesophageal pH measurements in most patients (32 of 50), together with a trial of proton pump inhibitors. We are pleased to read from Professor Morice that proton pump inhibitors "only improve symptoms in a proportion of patients with reflux cough", when they reported previously a very excellent 82% therapeutic response in this group treated with "proton pump inhibitors, alginates and conventional advice regarding diet and posture".1 We agree entirely that proton pump inhibitors are not very efficacious in reflux cough. We have not performed oesophageal manometry and are aware of Professor Morice’s interesting observations. They also report that patients with abnormal oesophageal manometry respond to proton pump inhibition, and therefore we would have picked up such patients with a trial of proton pump inhibitor treatment. However, the direct link between oesophageal dysmotility and chronic cough still remains to be established.
We do not believe we have missed reflux as an associated cause of the cough and therefore do not agree with the explanation that the reduced exhaled breath condensate pH is a reflection of laryngopharyngeal reflux throughout the diagnostic categories. Rather, this is likely to be related to the chronic inflammatory and remodelling process that is present in the submucosa of chronic cough patients, associated with both asthma and non-asthmatic causes.2–4 We must emphasise that we are assuming that exhaled breath condensate is a reflection of the epithelial surface liquid, which needs to be confirmed.
References
Kastelik JA, Redington AE, Aziz I, et al. Abnormal oesophageal motility in patients with chronic cough. Thorax 2003;58:699–702.
Niimi A, Matsumoto H, Minakuchi M, et al. Airway remodelling in cough-variant asthma. Lancet 2000;356:564–5.
Boulet LP, Milot J, Boutet M, et al. Airway inflammation in non-asthmatic subjects with chronic cough. Am J Respir Crit Care Med 1994;149:482–9.
Niimi A, Cosio B, Oates T, et al. Airway inflammation and remodelling in non-asthmatic patients with chronic cough: comparison with asthmatics. Am J Respir Crit Care Med 2003;167:A353.(A Morice1, C F Everett1 a)
Keywords: chronic cough; exhaled breath condensate; airway acidification
We read with interest the recent article by Niimi et al reporting low levels of exhaled breath condensate (EBC) pH in patients with chronic cough.1 We and others have described low EBC pH in association with airway inflammation in allergic asthma, cystic fibrosis, and chronic obstructive pulmonary disease.2–4 In these studies there is a relatively close association between inflammation and low pH which is shown by the further fall in pH during exacerbations.2 However, in non-asthmatic chronic cough, while there is a low grade inflammation present in some subjects, this is much less than would be required to invoke inflammation as the major cause of airway acidification.
It is unclear from the description of the assessment protocol how patients were allotted their individual diagnostic categories. A positive methacholine challenge test is not infrequently found in patients with reflux5 and, even in classical asthma, reflux is a common phenomenon.6 We suggest that there has been a significant underdiagnosis of reflux disease in this cohort because of the lack of a structured history, the non-uniform application of investigations, and the failure to perform full oesophageal assessment, particularly manometry. We have shown that, when oesophageal manometry is not performed, a significant number of patients with reflux cough will be missed.7 Proton pump inhibitors at conventional doses only temporarily increase the pH of gastric reflux and do not prevent reflux per se and, unsurprisingly, only improve symptoms in a proportion of patients with reflux cough. A failure of cough to improve with proton pump inhibitors does not therefore adequately rule out reflux cough.
The simplest explanation for the low airway pH observed by Niimi et al would be that a large proportion of the subjects had laryngopharyngeal reflux. This would also explain the otherwise surprising finding of similar EBC pH across the authors’ diagnostic categories.
References
Niimi A, Nguyen LT, Usmani O, et al. Reduced pH and chloride levels in exhaled breath condensate of patients with chronic cough. Thorax 2004;59:608–12.
Ojoo JC, Mulrennan S, Kastelik JA, et al. Exhaled breath condensate pH and exhaled nitric oxide in allergic asthma and in cystic fibrosis. Thorax 2005;60:22–6.
Kostikas K, Papatheodorou G, Ganas K, et al. pH in expired breath condensate of patients with inflammatory airway diseases. Am J Respir Crit Care Med 2002;165:1364–70.
Tate S, MacGregor G, Davis M, et al. Airways in cystic fibrosis are acidified: detection by exhaled breath condensate. Thorax 2002;57:926–9.
Bagnato GF, Gulli S, Giacobbe O, et al. Bronchial hyperresponsiveness in subjects with gastroesophageal reflux. Respiration 2000;67:507–9.
Vincent DAM, Leport J, et al. Gastro-oesophageal reflux prevalence and relationship with bronchial reactivity in asthma. Eur Respir J 1997;10:2255–9.
Kastelik JA, Redington AE, Aziz I, et al. Abnormal oesophageal motility in patients with chronic cough. Thorax 2003;58:699–702.
Authors’ reply
K F Chung2 and A Niimi2
2 Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK; f.chung@imperial.ac.uk
We thank Professor Morice and his colleagues for their interest in our paper. The main issue they raise concerns the possibility that we may have missed gastro-oesophageal disorders such as reflux and dysmotility in our cohort of patients with chronic cough. In our assessment protocol we state that we used oesophageal pH measurements in most patients (32 of 50), together with a trial of proton pump inhibitors. We are pleased to read from Professor Morice that proton pump inhibitors "only improve symptoms in a proportion of patients with reflux cough", when they reported previously a very excellent 82% therapeutic response in this group treated with "proton pump inhibitors, alginates and conventional advice regarding diet and posture".1 We agree entirely that proton pump inhibitors are not very efficacious in reflux cough. We have not performed oesophageal manometry and are aware of Professor Morice’s interesting observations. They also report that patients with abnormal oesophageal manometry respond to proton pump inhibition, and therefore we would have picked up such patients with a trial of proton pump inhibitor treatment. However, the direct link between oesophageal dysmotility and chronic cough still remains to be established.
We do not believe we have missed reflux as an associated cause of the cough and therefore do not agree with the explanation that the reduced exhaled breath condensate pH is a reflection of laryngopharyngeal reflux throughout the diagnostic categories. Rather, this is likely to be related to the chronic inflammatory and remodelling process that is present in the submucosa of chronic cough patients, associated with both asthma and non-asthmatic causes.2–4 We must emphasise that we are assuming that exhaled breath condensate is a reflection of the epithelial surface liquid, which needs to be confirmed.
References
Kastelik JA, Redington AE, Aziz I, et al. Abnormal oesophageal motility in patients with chronic cough. Thorax 2003;58:699–702.
Niimi A, Matsumoto H, Minakuchi M, et al. Airway remodelling in cough-variant asthma. Lancet 2000;356:564–5.
Boulet LP, Milot J, Boutet M, et al. Airway inflammation in non-asthmatic subjects with chronic cough. Am J Respir Crit Care Med 1994;149:482–9.
Niimi A, Cosio B, Oates T, et al. Airway inflammation and remodelling in non-asthmatic patients with chronic cough: comparison with asthmatics. Am J Respir Crit Care Med 2003;167:A353.(A Morice1, C F Everett1 a)