Chronic Persistent Cough and Clearance of Esophageal Acid

doi:10.1378/chest.102.6.1668

Chest

Volume 102, Issue 6, December 1992, Pages 1668-1671

https://doi.org/10.1378/chest.102.6.1668 Get rights and content

Unexplained chronic persistent cough has been shown to be associated with increased episodes of otherwise asymptomatic gastroesophageal reflux; however, normal subjects without cough also exhibit some reflux. We postulate that the prompt clearance of refluxed acid from the esophagus may play an important role in the prevention of cough, and we sought to determine if patients with chronic cough have impaired clearance. Thirty patients with unexplained chronic cough underwent 24-h ambulatory esophageal pH monitoring. Compared to 12 matched control subjects, patients experienced significantly more episodes (all values expressed as median [range]) of reflux per 24 h (88.3 [5.0 to 338.0] vs 5.7 [0 to 13.0]; p<0.0001) and had impaired clearance of esophageal acid as measured by the duration of individual reflux episodes (3.0 [0.1 to 20.5] min per reflux vs 0.7 [0 to 2.5] min per reflux; p<0.01). We conclude that patients with chronic persistent cough have impaired clearance of esophageal acid.

Section snippets

Materials And Methods

Patients were entered into our study if they had chronic cough (greater than 2-mo duration) which was unexplained after a standard diagnostic evaluation. This has been previously described in detail¹ and consists of a full history and physical examination, chest x-ray film, full pulmonary function testing (including spirometry, lung volumes, and transfer factor for carbon monoxide), home peak expiratory flow rate monitoring for at least three weeks, and histamine inhalation testing performed as

Results

Thirty patients with unexplained chronic cough were identified. The mean (±SE) age was 45.7 (±2.9) years, and there were equal numbers of male and female patients. The mean duration of cough was 14.1 (±9.6) months. The BMI pulmonary function for the group overall was in the normal range (Table 1). Twenty-three patients were lifelong nonsmokers, with the remaining being ex-smokers who had ceased smoking over ten years prior to this study and prior to the onset of cough. Twenty patients have

Discussion

In chronic persistent cough unexplained after an extensive diagnostic evaluation, otherwise asymptomatic gastroesophageal reflux is a possible etiologic factor.1, 7 We postulate that a neuronally mediated esophageal-tracheobronchial reflex may be the mechanism by which reflux of gastric acid leads to cough; and we realize that cough may in turn lead to reflux episodes via increasing transdiaphragmatic pressure or by causing the failure of suppression of transient lower esophageal sphincter

Acknowledgments

We thank Dr. Christopher Clarke, Dr. Allan Glanville, Dr. Christine Jenkins, and Dr. Jonathan Rutland for allowing us to study their patients.

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There are more references available in the full text version of this article.

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The paucity of proximal reflux events and airway complications is proposed to be due to the presence of protective mechanisms that have been well characterized in the esophagus. Some of these include mechanisms resulting in esophageal acid clearance,25 secondary peristalsis,26 and esophagoglottal reflexes.23 In contrast, the protective role of the UES during coughing has not been systematically studied.
Vagal reflex initiated by esophageal stimulation and microaspiration can cause chronic cough in patients with gastroesophageal reflux disease (GERD). By raising intraabdominal pressure, cough can, in turn, predispose to GERD. The role of the upper esophageal sphincter (UES) in preventing esophagopharyngeal reflux during coughing is not well known. The aim of this study was to evaluate the UES response during coughing.
We studied 20 healthy young (10 women; age, 27 ± 5 years) and 15 healthy elderly (nine women; age, 73 ± 4 years) subjects. Hard and soft cough-induced pressure changes in the UES, distal esophagus, lower esophageal sphincter, and stomach were determined simultaneously using high-resolution manometry and concurrent acoustic cough recordings.
Resting UES pressure was significantly higher in the young compared with the elderly subjects (42 ± 14 mm Hg vs 24 ± 9 mm Hg; P < .001). Cough induced a UES contractile response in all subjects. Despite lower UES resting pressures in the elderly subjects, the maximum UES pressure during cough was similar between the young and the elderly subjects (hard cough, 230 ± 107 mm Hg vs 278 ± 125 mm Hg, respectively; soft cough, 156 ± 85 mm Hg vs 164 ± 119 mm Hg, respectively; P not significant for both). The UES pressure increase over baseline during cough was significantly higher than that in the esophagus, lower esophageal sphincter, and stomach for both groups (P < .001).
Cough induces a rise in UES pressure, and this response is preserved in elderly people. A cough-induced rise in UES pressure is significantly higher than that in the esophagus and stomach, thereby providing a barrier against retrograde entry of gastric contents into the pharynx.
The role of pH monitoring in extraesophageal gastroesophageal reflux disease
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Les manifestations respiratoires associées au reflux gastro-œsophagien sont fréquentes et variées, qu'il s'agisse de toux chronique, d'asthme, de bronchites, de pneumopathies segmentaires ou non ; elles peuvent concerner aussi les voies aériennes supérieures (laryngites, sinusites, otites, stridor). Le problème essentiel est de savoir quel est le rôle exact du reflux gastro-œsophagien dans la pathologie respiratoire observée : le reflux est-il la cause unique ou tout au moins primordiale, le reflux est-il secondaire ou aucun lien n'existe-t-il entre les deux pathologies ? Dans cette démarche, la pHmétrie de longue durée est l'examen de référence, mais il faut s'aider également d'arguments cliniques et d'un bilan pneumologique, afin d'éliminer les autres causes de pathologie respiratoire. Lorsque le reflux paraît en cause dans la pathologie respiratoire, un traitement médical est entrepris comportant un prokinétique et un antisécrétoire. Ce traitement est généralement efficace et les indications de la chirurgie sont exceptionnelles chez l'enfant.
Gastroesophageal reflux (GER)-associated respiratory disorders are frequent and varied: chronic cough, asthma, bronchitis, pneumonia, laryngitis, sinusitis, otitis, stridor. A cause/ effect relationship between GER and respiratory disorders has never been demonstrated and identifying the exact role of GER in respiratory pathology remains difficult. The "gold standard" for the diagnosis is the 24-hour continuous esophageal pH monitoring, but clinical data and pulmonary check-up should be considered for the elimination of other respiratory diseases. Following GER diagnosis, medical therapy including prokinetic and antisecretory agents is recommended since the efficacy of these drugs has been shown; indications for surgery are rare in children.
Extraesophageal Manifestations of GERD
2003, American Journal of the Medical Sciences
The association between gastroesophageal reflux disease (GERD) and extraesophageal disease is often referred to as extraesophageal reflux (EER). This article reviews EER, discussing epidemiology, pathogenesis, diagnosis, and treatment with a focus on the most studied and convincing EER disorders—asthma, cough, and laryngitis. Although EER comprises a heterogeneous group of disorders, some general characterizations can be made, as follows. First, although GERD's association with extraesophageal diseases is well-established, definitive evidence of causation has been more elusive, rendering epidemiological data scarce. Secondly, regarding the pathogenesis of EER, 2 basic models have been proposed: direct injury to extraesophageal tissue by acid and pepsin exposure or injury mediated through an esophageal reflex mechanism. Third, because heartburn and regurgitation are often absent in patients with EER, GERD may not be suspected. Even when GERD is suspected, the diagnosis may be difficult to confirm. Although endoscopy and barium esophagram remain important tools for detecting esophageal complications, they may fail to establish the presence of GERD. Even when GERD is diagnosed by endoscopy or barium esophagram, causation between GERD and extraesophageal symptoms cannot be determined. Esophageal pH is the most sensitive tool for detecting GERD, and it plays an important role in EER. However, even pH testing cannot establish GERD's causative relationship to extraesophageal symptoms. In this regard, effective treatment of GERD resulting in significant improvement or remission of the extraesophageal symptoms provides the best evidence for GERD's pathogenic role. Finally, EER generally requires more prolonged and aggressive antisecretory therapy than typical GERD requires.

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Supported in part by a Commonwealth Department of Veterans Affairs research grant.

Manuscript received January 6; revision accepted April 29

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Chest

Clinical InvestigationsChronic Persistent Cough and Clearance of Esophageal Acid

Section snippets

Materials And Methods

Results

Discussion

Acknowledgments

Chest

Chronic persistent cough and gastro-esophageal reflux

Thorax

Relationship between asthma and gastro-esophageal reflux

Thorax

Mechanisms for the association of gastro-esophageal reflux and bronchospam

Am Rev Respir Dis

Gastro-esophageal reflux: a possible reflex mechanism

Ann Allergy

Clinical Investigations
Chronic Persistent Cough and Clearance of Esophageal Acid