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• W2000643503 abstract "The article by Ekstrom and Tibbling published in this issue of Chest (p 995) showed in eight patients with bronchial asthma that intraesophageal perfusion of 0.1 NHCl did not trigger symptoms and/or signs of bronchoconstriction. One could challenge the validity of this observation based on the absence of a double-blind study design. That is, while the patients were having heartburn, the authors listened for rhonchi and prolonged expiration as well as asked the patients to report any occurrence of respiratory distress. Despite this opportunity for bias, the credibility of their study remains intact. First, intraesophageal acid did not provoke an episode of bronchial asthma that would override the authors’ potential bias to demonstrate the lack of provocation. Second, the acid did not provoke symptoms of respiratory distress in the patients while they were having heartburn—a symptom that some had previously associated with their attacks of asthma. We conclude from this study that intraesophageal acid does not trigger symptoms and/or signs of bronchoconstriction. In their article the authors cite data from other studies that support this observation. Our confidence in the validity of the observation that acid failed to trigger symptoms and/or signs of bronchoconstriction is further strengthened by the intellectual honesty of the authors in reporting subclinical laboratory data that would not necessarily support their subjective observation. For instance, they found that the degree of airway sensitivity as determined by the histamine challenge test and measured by changes in the FEV1 significantly correlated in a direct manner with the propensity for acid to provoke changes in the FEV1. This correlation raises the following question: How can intraesophageal acid fail to trigger symptoms and/or signs of bronchoconstriction, yet in the same eight patients be associated with a subclinical but statistically significant, direct correlation in bronchial reactivity (FEV1) with that measured by the histamine challenge test? An explanation for this paradox may reside in the time segment that the authors studied their patients, ie, day as opposed to nighttime. It is known that patients with bronchial asthma and gastroesophageal reflux can either become worse or experience adverse pathophysiology at night.1Barnes P Fitz Gerald G Brown M Dollery C Nocturnal asthma and changes in circulating epinephrine, histamine, and cortisol..N Engl J Med. 1980; 303: 263-267Crossref PubMed Scopus (314) Google Scholar, 2DeMeester TR Johnson LF Guy GJ Toscano MS Skinner DB Pattern of gastroesophageal reflux in health and disease..Ann Surg. 1976; 184: 459-470Crossref PubMed Scopus (648) Google Scholar, 3Johnson LF DeMeester TR Haggitt RC Esophageal epithelial response to gastroesophageal reflux, a quantitative study..Am J Dig Dis. 1978; 23: 498-509Crossref PubMed Scopus (162) Google Scholar Thus, it is conceivable that daytime provided a less than ideal segment of the circadian cycle during which to ask the question whether intraesophageal acid triggers clinically relevant bronchial asthma. If this hypothesis is true, one would expect to find evidence that physiologic events and/or pathophysiology of the two disorders could interrelate at night to adversely affect each other. That evidence exists. For instance, during REM sleep there are rapid changes in autonomic nervous system activity that affect airway smooth muscle tone4Sullivan CE Zamel N Kozar LF Murphy E Phillipson EA Regulation of airway smooth muscle tone in sleeping dogs..Am Rev Respir Dis. 1979; 119: 87-99Google Scholar and might provoke bronchospasm if potentiated by the effect of acid on the esophagobronchial reflex. This possible potentiation is relevant, especially since increased bronchial responsiveness to histamine and methacholine have been demonstrated more than 1 h after esophageal acid stimulation.5Wilson NM Charette L Thomson A Silverman M Gastroesophageal reflux and childhood asthma: the acid test..Thorax. 1985; 40: 592-597Crossref PubMed Scopus (57) Google Scholar, 6Herve P Denjean A Jian R Simonneau G Duroux P Intraesophageal perfusion of acid increases the bronchomotor response to methacholine and to isocapnic hyperventilation in asthmatic subjects..Am Rev Respir Dis. 1986; 134: 986-989Crossref PubMed Scopus (173) Google Scholar Alternatively, the effect of sleep on the pathophysiology of gastroesophageal reflux could adversely affect bronchial reactivity by the esophagobronchial reflex. For instance, both recumbency7Johnson LF DeMeester TR Evaluation of elevation of the head of the bed, bethanechol, and antacid foam tablets on gastroesophageal reflux..Dig Dis Sci. 1981; 26: 673-680Crossref PubMed Scopus (142) Google Scholar and sleep8Orr WC Robinson MG Johnson LF Acid clearing during sleep in patients with esophagitis and controls..Dig Dis Sci. 1981; 26: 423-427Crossref PubMed Scopus (148) Google Scholar, 9Orr WC Johnson LF Robinson MG The effect of sleep on swallowing, esophageal peristalsis, acid sensitivity and clearance time..Gastroenterology. 1984; 86: 814-819PubMed Google Scholar can prolong the esophageal acid clearance time, increasing the acid mucosal contact time. This prolonged contact could further stimulate the esophagobronchial reflex, especially since proteolytic enzymes such as pepsin in the acid refluxate can cause a “leaky” mucosal barrier that would facilitate [H]+ ion back-diffusion.10Lillemoe KD Johnson LF Harmon JW Role of the components of the gastroduodenal contents in experimental acid esophagitis..Surgery. 1982; 92: 276-284PubMed Google Scholar That nocturnal acid gastroesopageal reflux may trigger asthmatic attacks is a relevant clinical concern, especially since intraesophageal acid perfusion at night in asthmatic children with an acid-sensitive esophagus causes symptoms and signs of bronchoconstriction.11Davis RS Larsen GL Grunstein MM Respiratory response to intraesophageal acid infusion in asthmatic children during sleep..J Allergy Clin Immunol. 1983; 72: 393-398Abstract Full Text PDF PubMed Scopus (110) Google Scholar Hence, the segment of the circadian cycle during which the authors perfused the acid, ie, day rather than the nighttime may explain why acid failed to trigger symptoms and/or signs of bronchoconstriction, yet still subclinically correlated directly with bronchial hyperreactivity as determined by the histamine challenge test. A two-step procedure similar to that used by the authors seems in order to depict those patients whose asthma may be triggered by gastroesophageal reflux. First, one would want to demonstrate the presence of acid gastroesophageal reflux, especially that which occurs at night and has a long clearance time. This reflux pattern not only represents a risk factor for esophagitis2,3,12 as well as symptoms and signs of pulmonary aspiration,13Pellegrini CA DeMeester TR Johnson LF Skinner DB Gastroesophageal reflux and pulmonary aspiration: incidence, functional abnormality and results of surgical therapy..Surgery. 1979; 86: 110-119PubMed Google Scholar, 14Chernow B Johnson LF Janowitz W Castell DO Pulmonary aspiration as a consequence of gastroesophageal reflux– diagnostic approach..Dig Dis Sci. 1979; 24: 839-844Crossref PubMed Scopus (105) Google Scholar but also provides the prolonged acid mucosal contact that may stimulate the esophagobronchial reflex to increase bronchial reactivity. Second, following pH monitoring one could demonstrate the presence or absence of acid-induced symptoms and/or signs of bronchoconstriction. This demonstration can be accomplished by using a combination of intraesophageal acid perfusion and pulmonary function test(s) that determine increased bronchial reactivity. In conclusion, while Ekstrom and Tibbling showed in eight awake asthmatic patients that intraesophageal acid failed to trigger clinically apparent bronchospasm, other aspects of their data did not preclude an important association between these two factors. It is conceivable that processes during the sleep period could modulate the effect of acid gastroesophageal reflux on increased bronchial reactivity." @default.
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• W2000643503 title "Does Intraesophageal Acid Trigger Bronchial Asthma?" @default.
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