Gastroesophageal reflux and bronchial asthma are frequently encountered comorbidities that maintain an ambivalent relationship, generating a vicious circle where gastroesophageal reflux increases asthmatic symptoms or precipitates bronchial asthma and asthma can trigger or worsen gastroesophageal reflux disease. Gastroesophageal reflux disease (GERD) afflicts approximately 20% of adults in the United States on a weekly basis and 40% on a monthly basis, and is also a trigger for asthma. The prevalence of GERD is higher in asthmatics compared to control groups, with 77% of asthma patients having reflux symptoms and 82% of asthmatics having abnormal esophageal acid contact times on 24-hour esophageal pH testing. Pathogenetic mechanisms of these interrelation are imperfectly understood, despite intense concerns of specialists in both areas. There have been incriminated: eso-bronchial constrictor vagal mediated reflexes, bronchial hyperreactivity, neurogenic inflammation induced by hydrochloric acid penetration in the oesofagus, airways hydrochloric acid microaspiration with asthmatic trigger effects, increased bronchial resistance or increased immune response to antigens. Bronchial obstruction and some antiasthmatic medication can decrease lower esophageal sphincter pressure and thus triggering or aggravating gastroesophageal reflux. The diagnosis of the gastroesophageal reflux in asthmatics involves a careful clinical exam, digestive functional test (up to 24 hours monitoring esophageal pH) and esogastroscopy. Gastroesophageal reflux treatment in asthmatic patients claims elimination of both disease risk factors, diet, proton-pump inhibitors.
Gastroesophageal reflux (GER) is a potential trigger of asthma. Approximately 77% of asthmatics report heartburn. GER is a risk factor for asthma-related hospitalization and oral steroid burst use. Asthmatics may be predisposed to GER development because of a high prevalence of hiatal hernia and autonomic dysregulation and an increased pressure gradient between the abdominal cavity and the thorax, over-riding the lower esophageal sphincter pressure barrier. Asthma medications may potentiate GER.
An association between gastroesophageal reflux (GER) and lung diseases has for some time been known to exist. As early as 1967, Urschel and Paulson1 reported that of 636 patients scheduled for an operative treatment for GER, 60% also had symptoms related to pulmonary disease. Since then, many studies23 have shown a high prevalence ofGER among patients with asthma. In a recent report,4 even asthmatics without reflux symptoms had a high prevalence (62%) of abnormal results for 24-h esophageal tests. The simultaneous occurrence of GER and asthma suggests a causal relationship. The aspiration of gastric contents or a vagally mediated bronchoconstriction has been suggested as an explanatory mechanism. Medical antireflux therapy and antireflux surgery, however, have only minimal effect or no effect on lung function, although asthma symptoms improve.
The majority of studies in this field have concentrated on highly selected populations at secondary or tertiary referral hospitals. There are few epidemiologic studies of the general population, and little is known about a possible association between respiratory symptoms and GER in an unselected random population. Between 1990 and 1993, an epidemiologic investigation into the prevalence of asthma and allergy, the European Community Respiratory Health Survey (ECRHS), was conducted in different centers throughout the world.
The association between asthma and gastroesophageal reflux (GER) has been further delineated with recent clinical investigations. The prevalence of GER development in asthmatics is higher than in control populations. Furthermore, asthmatics with GER have a higher risk of asthma hospitalization. Asthma medications may be one of the promoting factors for GER development in asthmatics. Inhaled albuterol decreases lower esophageal sphincter (LES) pressure and esophageal contraction amplitude. Oral prednisone results in increased esophageal acid contact times. Respiratory symptoms also correlate with esophageal acid events. The role of neurogenic inflammation in asthma-induced bronchoconstriction is also being further developed. Therapy of GER may improve asthma outcomes in selected asthmatics. Currently, there are no double-blind, placebo-controlled, multicenter trials reporting asthma outcomes with antireflux therapy.
Potential mechanisms of esophageal acid-induced bronchoconstriction include a vagally mediated reflex, local axonal reflexes, heightened bronchial reactivity, and microaspiration, all resulting in neurogenic inflammation. Anti-reflux therapy improves asthma symptoms in approximately 70% of asthmatics with GER. A 3-month empiric trial of twice-daily proton pump inhibitor given 30 to 60 minutes before breakfast and dinner can identify asthmatics who have GER as a trigger of their asthma.
Esophageal acid elicits respiratory responses including decreases in airflow, oxygen saturation, and increases in respiratory resistance, minute ventilation, and respiratory rate. Mechanisms of esophageal acid-induced bronchoconstriction include a vagally-mediated reflex, heightened bronchial reactivity, and microaspiration. Esophageal acid also produces airway neurogenic inflammatory responses with the release of substance P, tachykinins, nitric oxide, and other cytokines. Predisposing factors to GERD development in asthmatics include autonomic dysregulation, an increased pressure gradient between the thorax and the abdomen, a high prevalence of hiatal hernia, and altered crural diaphragm function. Theophylline may also potentiate GERD. Therapy of GERD improves asthma outcome. In combined studies examining 326 medically treated asthma patients, asthma symptoms improved in 69% of patients. Surgical therapy trials in 417 asthma patients show asthma symptoms improved in 79%. Management strategies for GERD in asthmatics with reflux symptoms include utilizing an empiric trial of a proton pump inhibitor for three months while measuring asthma outcomes. Since GERD may be clinically ”silent” in asthma patients, consider 24-hour esophageal pH testing in severe asthma patients who do not have GERD symptoms. Future research will develop the association between asthma and GERD.
Nocturnal asthma and nocturnal gastroesophageal reflux.
Gastroesophageal reflux (GER) is common in those with asthma, with 77% of asthmatics complaining of heartburn, with 41% experiencing reflux-associated respiratory symptoms. Likewise, 24% of those with asthma that is difficult to control have “clinically silent” GER. There are no studies examining nocturnal reflux symptoms in asthmatics. Esophageal dysmotility is also common, and abnormal esophageal acid contact times on 24h esophageal pH tests were found in 82% of asthmatics examined consecutively. Most asthmatics with GER also have abnormal esophageal acid contact times while in the supine position, reflecting sleep time. Endoscopic evidence of esophagitis was found in 43% of asthmatics.
Bronchial asthma is a complex disease involving various cyclic environmental and chronobiologic factors. In patients with asthma, nocturnal gastroesophageal reflux (GER) has been associated with triggering and worsening bronchoconstriction. There are data to suggest that the prevalence of GER is higher in patients with asthma than in the general population and that GER is directly associated with asthma severity. However, the role of GER in asthma remains controversial; some studies suggest that reflux does not mediate nocturnal asthma symptoms. This article reports the results from a study conducted in 7 adult patients affected by nocturnal asthma and moderate to severe GER disease. The relation between GER and asthma was tested by continuously and simultaneously monitoring respiratory resistances and esophageal pH. The study demonstrated a significant correlation between lower respiratory resistances and spontaneous GER. More specifically, both long (more than 5 minutes’ duration) and short (5 minutes’ or less duration) GER episodes elicited bronchoconstriction in patients with asthma who had moderate to severe GER disease. The severity and duration of bronchoconstriction were related to the duration of GER.
Gastroesophageal reflux (GER) is a potential trigger of asthma. GER symptoms are more prevalent in asthma patients compared with control populations, with a prevalence of approximately 75%. GER symptoms are associated with respiratory symptoms and inhaler use. GER may also occur without esophageal symptoms. Abnormal esophageal acid contact times are also more prevalent in patients with asthma compared with control populations, with a prevalence of 80%. Pathophysiologic mechanisms of esophageal acid-induced bronchoconstriction include a vagally mediated reflex, heightened bronchial reactivity, and microaspiration. Esophageal acid may increase minute ventilation without evidence of bronchoconstriction. Esophageal acid is associated with the release of substance P in the bronchial mucosa, resulting in airway edema. Medical antireflux therapy with proton pump inhibitors results in asthma symptom improvement in approximately 70% of patients, similar to surgical results. Predictors of asthma response include the presence of regurgitation, proximal acid reflux, esophagitis healing with therapy, reflux-associated respiratory symptoms, or nocturnal asthma. Management of GER in adult patients with asthma should include a 3-month trial of high-dose proton pump inhibitor while monitoring asthma outcome. GER should be considered as a potential asthma trigger in all patients.
Gastroesophageal reflux (GERD) may trigger asthma. Approximately 77% of asthmatic people experience reflux symptoms, although GERD may be clinically silent in some. Esophagitis is found in 43% of asthmatic people, and 82% have abnormal esophageal acid contact times on esophageal pH testing. Clearly, GERD is prevalent in asthmatic people. Pathophysiologic mechanisms of acid-induced bronchoconstriction include a vagally mediated reflex and microaspiration. Whether these airway responses are clinically significant is the subject of some debate. Interestingly, peak expiratory flow rates and specific airway resistance alterations persist despite esophageal acid clearance. Preliminary evidence shows that substance P, an inflammatory mediator that causes airway edema, is released with esophageal acid. Although therapeutic studies are limited by their small population sizes and study design, up to 70% of asthmatic people have asthma improvement with antireflux therapy. Possible predictors of asthma response include patients with symptomatic esophageal regurgitation; abnormal proximal esophageal acid exposure; and, in surgical studies, those with normal esophageal motility and asthma response with medical therapy. Future research will further define the association between asthma and gastroesophageal reflux.
The medical literature has been deluged with articles on the relation between gastroesophageal reflux (GER) and asthma. In an effort to piece together the complex puzzle, investigators from all disciplines have gathered their patients with wheezing and heartburn and studied the epidemiology, the possible cause or effect mechanisms and the therapeutic response to GER treatment. Indeed, since humans first began to hunker down and work together to discuss interesting observations, the world has begun to breathe easier. Epidemiological evidence for a GER/asthma association suggests that about three-fourths of asthmatics, independent of the use of bronchodilators, have acid GER, increased frequency of reflux episodes, or heartburn; and 40% have reflux esophagitis. Physiological studies suggest that 2 separate mechanisms are involved in the GER/asthma relationship a vagally mediated pathway and microaspiration. In any given patient, however, there is no acceptable diagnostic method available to confirm the presence or absence of GER-induced asthma. Clinical trials, using antireflux medical therapy and antireflux surgery have begun to provide some clues about GER-related pulmonary symptoms. The trials of medical therapy using acid suppressing drugs (e.g. histamine-2 receptor antagonists) have ranged from no benefit to modest improvement of only nocturnal asthma symptoms. Studies with proton-pump inhibitors are underway. In uncontrolled surgical studies, antireflux surgery has resulted in partial or complete remission of asthma symptoms in a large proportion of patients. Despite the uncontrolled nature of these studies, many patients have had dramatic subjective improvement in pulmonary symptoms. It appears for now that clinical trials are the only available means to assess whether medical or surgical treatment of GER in patients with both GER and asthma improves the symptoms of asthma and decreases the need for pulmonary medications.
Two mechanisms of bronchoconstriction induced by esophageal acid have been proposed: a vagally mediated reflex, by which esophageal acid in the distal esophagus causes reflex bronchoconstriction, and microaspiration. Although there is conflicting evidence, distal esophageal acid causes a decrease in peak expiratory flow rates, an increase in respiratory resistance, and an increase in minute ventilation. If microaspiration is present, there is further augmentation of this airway response. Although only a few studies have been performed in those with nocturnal asthma with GER, one study in a pediatric population showed that esophageal acid infusions caused more airway responses at 04:00 than at 24:00. Also, asthmatic children with nocturnal asthma symptoms have a higher reflux score, with a positive correlation between reflux score and nighttime-associated wheezing. Despite these findings in children, a study performed in sleeping adults with nocturnal asthma noted no alterations in airflow resistance with esophageal acid, concluding that GER contributed little to the nocturnal worsening of asthma.
There are also gastroesophageal circadian issues that may influence GER in asthmatics. Gastric acid secretion peaks at approximately 21:00, and gastric emptying is delayed when a meal is given at 20:00 versus 08:00. Esophageal acid clearance is delayed significantly during sleep, and acid clearance occurs during arousals. Upper esophageal sphincter (UES) pressure also decreases with sleep onset, which may predispose to microaspiration. Further research is needed to clarify what role nocturnal reflux has on nocturnal asthma and airway inflammation and whether circadian rhythm factors alter airway responses to esophageal acid.
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