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Gastroesophageal Reflux Disease and Asthma

1995; Elsevier BV; Volume: 108; Issue: 5 Linguagem: Inglês

10.1378/chest.108.5.1186

1931-3543

Donald O. Castell, Peter F. Schnatz,

Tracheal and airway disorders

A relationship between gastroesophageal (GE) function and asthmatic symptoms has been suggested for over a century since William Osier first made the following observations in the first edition of his classic text on internal medicine: “Severe paroxysms may be induced by overloading the stomach,” and “Asthmatic patients learn to take the heavy meals in the early part of the day.”1Osier W Bronchial asthma.in: The principles and practice of medicine. Appleton, New York1892: 497-501Google Scholar One cannot be certain whether Osier recognized the potential for GE reflux to induce asthmatic symptoms, but he was clearly aware of the relationship of heavy meals which have the potential to induce reflux as precipitating bronchospastic attacks. It was more than half a century later when Kennedy2Kennedy JH ‘Silent’ gastroesophageal reflux: an important but little known cause of pulmonary complications.Dis Chest. 1962; 42: 42-45Abstract Full Text Full Text PDF Google Scholar first suggested that occult GE reflux might play a role in the production of pulmonary symptoms, including bronchospastic conditions. Over the past 30 years, numerous publications have called attention to the relationship between various manifestations of GE reflux and respiratory symptoms with the most commonly considered mechanism being that of pulmonary aspiration of refluxed gastric contents producing acid-induced injury and infection: the “reflux theory.”In a series of experiments, Mansfield and Stein3Mansfield LE Stein MR Gastroesophageal reflux and asthma: a possible reflex mechanism.Ann Allergy. 1978; 41: 224-226PubMed Google Scholar showed that intraesophageal acid instillation could increase pulmonary flow resistance in asthmatic patients and that antacid therapy would reverse the respiratory changes. In addition, these investigators also induced esophagitis in dogs and demonstrated a fall in respiratory function after intraesophageal acid infusion. Interestingly, this response did not occur in dogs after bilateral cervical vagotomy.4Mansfield LE Hameister HH Spaulding HS et al.The role of the vagus nerve in airway narrowing caused by intraesophageal hydrochloric acid provocation and esophageal distention.Ann Allergy. 1981; 47: 431-434PubMed Google Scholar The observations by Mansfield and Stein3Mansfield LE Stein MR Gastroesophageal reflux and asthma: a possible reflex mechanism.Ann Allergy. 1978; 41: 224-226PubMed Google Scholar generated the hypothesis that stimulation of esophageal mucosal receptors might trigger a vagally-mediated bronchoconstriction: the “reflex theory.”The asthmatic patient having no documented allergic component and with primarily nocturnal symptoms should raise a serious consideration of possible reflux-induced bronchoconstriction. Reflux in the recumbent position is more likely to remain in the esophagus due to less effective acid clearance and has the potential to flow into the proximal esophagus. In this issue of CHEST (see page 1220), Harding and colleagues have compared the results of intraesophageal acid instillation in a recumbent position in patients with asthma and GE reflux compared with patients with GE reflux only. They were able to demonstrate a decrease in peak expiratory flow and an increase in specific airway resistance in the former group but not in the latter. Because they showed a poor association of these airway responses with evidence of proximal esophageal flow of the acid, they have concluded that their data strongly support the “reflex” theory rather than the “reflux” microaspiration theory.Further evidence for a lesser importance of microaspiration in production of pulmonary symptoms secondary to GE reflux was shown in a study by Gastal et al5Gastal OL Castell JA Castell DO Frequency and site of gastroesophageal reflux in patients with chest symptoms: studies using proximal and distal pH monitoring.Chest. 1994; 106: 1793-1796Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar from patients evaluated in our laboratory. In this study, we compared the presence of both abnormal proximal and distal esophageal acid in 27 asthmatics, 28 patients with chronic cough, 37 patients with noncardiac chest pain, and 27 healthy control subjects. Although abnormal distal esophageal GE reflux was prevalent in both the asthmatic (44%) and cough patients (50%), abnormal proximal acid exposure was actually significantly more prevalent in patients with unexplained chest pain secondary to reflux who did not have pulmonary symptoms. These results supported the major importance of the reflex mechanism for GE reflux and pulmonary symptoms and suggested a lesser role for reflux microaspiration.However, as with many interesting theories in medicine, it would appear that the bottom line has yet to be written. Subsequent studies from our laboratory have revealed that the finding of abnormal proximal esophageal acid exposure in the patient with asthma or cough can have prognostic importance.6Schnatz PF Castell JA Bracy NA et al.Pulmonary symptoms (PS) associated with GERD: use of ambulatory pH monitoring for diagnosis and to direct therapy [abstract].Am J Gastroenterol. 1994; 89: 1626Google Scholar When evaluating the effect of antireflux therapy on pulmonary symptoms, we have recently found that those patients showing abnormal proximal acid exposure on ambulatory pH monitoring had the highest positive response rate. These data suggest that reflux microaspiration may still play a role in some patients and that ambulatory pH monitoring seeking evidence of proximal acid exposure is a valuable clue as to which patients should have aggressive antireflux therapy.Does GE reflux play a role in the production of bronchospasm and associated wheezing or coughing? There is no question that this is true in many patients. Is the major mechanism by which this occurs merely distal esophageal acid exposure causing a reflex bronchoconstriction or need one always invoke high reflux and microaspiration as the cause? From our perspective, it would appear that this question has not been completely answered. A relationship between gastroesophageal (GE) function and asthmatic symptoms has been suggested for over a century since William Osier first made the following observations in the first edition of his classic text on internal medicine: “Severe paroxysms may be induced by overloading the stomach,” and “Asthmatic patients learn to take the heavy meals in the early part of the day.”1Osier W Bronchial asthma.in: The principles and practice of medicine. Appleton, New York1892: 497-501Google Scholar One cannot be certain whether Osier recognized the potential for GE reflux to induce asthmatic symptoms, but he was clearly aware of the relationship of heavy meals which have the potential to induce reflux as precipitating bronchospastic attacks. It was more than half a century later when Kennedy2Kennedy JH ‘Silent’ gastroesophageal reflux: an important but little known cause of pulmonary complications.Dis Chest. 1962; 42: 42-45Abstract Full Text Full Text PDF Google Scholar first suggested that occult GE reflux might play a role in the production of pulmonary symptoms, including bronchospastic conditions. Over the past 30 years, numerous publications have called attention to the relationship between various manifestations of GE reflux and respiratory symptoms with the most commonly considered mechanism being that of pulmonary aspiration of refluxed gastric contents producing acid-induced injury and infection: the “reflux theory.” In a series of experiments, Mansfield and Stein3Mansfield LE Stein MR Gastroesophageal reflux and asthma: a possible reflex mechanism.Ann Allergy. 1978; 41: 224-226PubMed Google Scholar showed that intraesophageal acid instillation could increase pulmonary flow resistance in asthmatic patients and that antacid therapy would reverse the respiratory changes. In addition, these investigators also induced esophagitis in dogs and demonstrated a fall in respiratory function after intraesophageal acid infusion. Interestingly, this response did not occur in dogs after bilateral cervical vagotomy.4Mansfield LE Hameister HH Spaulding HS et al.The role of the vagus nerve in airway narrowing caused by intraesophageal hydrochloric acid provocation and esophageal distention.Ann Allergy. 1981; 47: 431-434PubMed Google Scholar The observations by Mansfield and Stein3Mansfield LE Stein MR Gastroesophageal reflux and asthma: a possible reflex mechanism.Ann Allergy. 1978; 41: 224-226PubMed Google Scholar generated the hypothesis that stimulation of esophageal mucosal receptors might trigger a vagally-mediated bronchoconstriction: the “reflex theory.” The asthmatic patient having no documented allergic component and with primarily nocturnal symptoms should raise a serious consideration of possible reflux-induced bronchoconstriction. Reflux in the recumbent position is more likely to remain in the esophagus due to less effective acid clearance and has the potential to flow into the proximal esophagus. In this issue of CHEST (see page 1220), Harding and colleagues have compared the results of intraesophageal acid instillation in a recumbent position in patients with asthma and GE reflux compared with patients with GE reflux only. They were able to demonstrate a decrease in peak expiratory flow and an increase in specific airway resistance in the former group but not in the latter. Because they showed a poor association of these airway responses with evidence of proximal esophageal flow of the acid, they have concluded that their data strongly support the “reflex” theory rather than the “reflux” microaspiration theory. Further evidence for a lesser importance of microaspiration in production of pulmonary symptoms secondary to GE reflux was shown in a study by Gastal et al5Gastal OL Castell JA Castell DO Frequency and site of gastroesophageal reflux in patients with chest symptoms: studies using proximal and distal pH monitoring.Chest. 1994; 106: 1793-1796Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar from patients evaluated in our laboratory. In this study, we compared the presence of both abnormal proximal and distal esophageal acid in 27 asthmatics, 28 patients with chronic cough, 37 patients with noncardiac chest pain, and 27 healthy control subjects. Although abnormal distal esophageal GE reflux was prevalent in both the asthmatic (44%) and cough patients (50%), abnormal proximal acid exposure was actually significantly more prevalent in patients with unexplained chest pain secondary to reflux who did not have pulmonary symptoms. These results supported the major importance of the reflex mechanism for GE reflux and pulmonary symptoms and suggested a lesser role for reflux microaspiration. However, as with many interesting theories in medicine, it would appear that the bottom line has yet to be written. Subsequent studies from our laboratory have revealed that the finding of abnormal proximal esophageal acid exposure in the patient with asthma or cough can have prognostic importance.6Schnatz PF Castell JA Bracy NA et al.Pulmonary symptoms (PS) associated with GERD: use of ambulatory pH monitoring for diagnosis and to direct therapy [abstract].Am J Gastroenterol. 1994; 89: 1626Google Scholar When evaluating the effect of antireflux therapy on pulmonary symptoms, we have recently found that those patients showing abnormal proximal acid exposure on ambulatory pH monitoring had the highest positive response rate. These data suggest that reflux microaspiration may still play a role in some patients and that ambulatory pH monitoring seeking evidence of proximal acid exposure is a valuable clue as to which patients should have aggressive antireflux therapy. Does GE reflux play a role in the production of bronchospasm and associated wheezing or coughing? There is no question that this is true in many patients. Is the major mechanism by which this occurs merely distal esophageal acid exposure causing a reflex bronchoconstriction or need one always invoke high reflux and microaspiration as the cause? From our perspective, it would appear that this question has not been completely answered.