Gastroesophageal reflux disease - GERD - Acid Reflux Disease - Gastroenterology

Study Objectives: 1. To assess the prevalence of specific factors considered causative or contributive to asthma in a population of patients seen in a specialized asthma clinic, and to determine whether any of these factors were associated with more severe disease; and 2. To assess the utilization of inhaled steroids by asthma severity in this population and compare it with published guidelines of the National Heart, Lung, and Blood Institute (NHLBI).
Design, Setting, and Patient Population: We conducted a retrospective chart review of new patients seen in a specialized asthma treatment center over a 2.5-year period and recorded the prevalence of 14 causative or contributive factors, the severity of asthma, and the intensity of treatment with inhaled corticosteroids in each patient. Patients were grouped as mild asthma vs moderate/severe asthma and compared by chi² analysis and stepwise logistic regression to determine whether certain factors were associated with more severe asthma.
Measurements and Results: The average number of factors recorded was 2.9 ± 1.8 in the mild group (± SD) and 3.5 ± 1.6 in the moderate/severe asthma group. This difference was statistically significant (P = .014). Increasing age, male gender, symptomatic gastroesophageal reflux disease (GERD), and chronic sinusitis were independently associated with more severe asthma. Suboptimal use of inhaled corticosteroids was more common in patients with mild persistent asthma, but suboptimal dosing of inhaled corticosteroids was equally common in mild and moderate/severe asthma. No relationship was found between allergen sensitization combined with exposure to cats, dogs, dust mite, or molds and more severe asthma.
Conclusions: This study confirms earlier studies showing that symptomatic GERD and chronic sinusitis are important comorbid conditions in patients with asthma, both being associated with greater asthma severity. This study further shows that the doses of inhaled corticosteroids used for treatment of asthma fall short of NHLBI guidelines in the majority of patients regardless of asthma severity.

The Role of Proton Pump Inhibitors in the Management of Gastroesophageal Reflux Disease-Related Asthma and Chronic Cough

Kiljander TO
Am J Med. 2003;115(suppl 3A):65S-71S

Gastroesophageal reflux disease (GERD) occurs in at least one third of patients with asthma and is recognized as a potential trigger for asthma symptoms. The results of studies conducted in patients with both asthma and GERD, in which proton pump inhibitor (PPI) therapy is used to evaluate its effect on asthma outcome, are inconsistent, and many of these studies suffer from different design flaws. However, it does appear that PPI treatment may improve nocturnal asthma symptoms in patients who also have GERD. Moreover, both daytime asthmatic symptoms and pulmonary function seem to improve in some patients with PPI treatment. There is evidence that more severe GERD might predict a more favorable asthma outcome with PPI therapy. For effective management of GERD-related asthma, PPIs should be used at a dose double that of the standard dose for a minimum of 2 to 3 months. Although GERD is also known to be an important cause of chronic cough, there have been only 2 placebo-controlled trials investigating the efficacy of PPI on GERD-related chronic cough. Results of both of these trials suggest that PPI treatment relieves GERD-related chronic cough. As with GERD-related asthma, it would seem reasonable to use a double-standard dose of a PPI for a minimum of 2 to 3 months in the management of GERD-related chronic cough. However, larger, adequately planned studies are needed to confirm the role of PPIs in the management of GERD-related asthma and chronic cough.

Possible Mechanisms of Influence of Esophageal Acid on Airway Hyperresponsiveness

Stein MR
Am J Med. 2003;115(suppl 3A):55S-59S

Airway hyperresponsiveness is among the defining phenomena in asthma. In this article, 3 mechanisms are reviewed to explain how gastroesophageal reflux (GER) may influence airway hyperresponsiveness. First, microaspiration may cause not only direct tissue injury, but may also trigger vagal reflexes. Second, acid infusion of the esophagus in a dog model and in humans has been shown to result in vagally mediated reflexes leading to bronchoconstriction. These reflexes have been studied using immunohistochemical techniques. Third, neuroinflammatory reflexes have been found to play a role in airway responses through the release of tachykinins, including substance P and neurokinin A. Combined, these 3 mechanisms may lead to an increase in vagal efferent impulses that can cause or augment airway hyperresponsiveness. Studies indicate that there is an increase in airway responsiveness in asthma patients who have documented GER. Further, based on the reported number of reflux episodes occurring during 24-hour pH monitoring, airway hyperresponsiveness to methacholine challenge tends to increase as GER worsens.

Reflex Mechanisms in Gastroesophageal Reflux Disease and Asthma

Canning BJ, Mazzone SB
Am J Med. 2003;115(suppl 3A):45S-48S

This article presents a brief description of the reflex mechanisms responsible for cough and bronchospasm, and identifies several potential mechanisms by which gastroesophageal reflux (GER) may precipitate these reflexes. Airway and esophageal reflexes related to various mechanoreceptors and chemoreceptors have been elucidated, primarily in animal studies. Central nervous system (CNS) reflex pathways as well as local axon reflexes may each contribute to the pathogenesis of both asthma and GER disease (GERD). When activated, airway nociceptors precipitate defensive reflexes such as cough, bronchospasm, and mucus secretion. Nociceptors innervating both the airways and the esophagus respond to similar stimuli with defensive manuevers. The pathways of some esophageal and airway sensory nerves terminate in the same regions of the CNS. It appears possible that synergistic interactions between esophageal nociceptors and airway sensory nerves may precipitate the asthma-like symptoms associated with GERD.

Recent Clinical Investigations Examining the Association of Asthma and Gastroesophageal Reflux

Harding SM
Am J Med. 2003;115(suppl 3A):39S-44S

For more than a decade, investigations have examined the association between asthma and gastroesophageal reflux (GER), and have demonstrated that the presence of esophageal acid events is associated with respiratory symptoms. The most current research shows that GER is prevalent in patients with asthma, that esophageal acid may alter bronchial hyperresponsiveness, and that medical or surgical GER therapy may improve asthma outcome in selected asthma patients. Further research will build on our current knowledge base and, hopefully, enable us to better identify those patients with asthma who will most benefit from reflux therapy.

Asthmatics With Gastroesophageal Reflux: Long-term Results of a Randomized Trial of Medical and Surgical Antireflux Therapies

Sontag SJ, O'Connell S, Khandelwal S, et al
Am J Gastroenterol. 2003;98:987-999

Objective: In short-term studies, asthma symptoms and pulmonary function have been reported to improve during and after medical treatment or surgical correction of gastroesophageal reflux (GER). In this study, we aimed to determine whether prolonged treatment of GER altered the long-term natural history of asthma in asthmatics with GER.
Methods: A total of 62 patients with both GER and asthma entered a randomized study of antireflux treatments for at least 2 years: 24 controls (antacids as needed); 22 medical (ranitidine 150 mg tid); and 16 surgical (Nissen fundoplication). Asthma was defined as a previous diagnosis of asthma with discrete attacks of wheezing and 20% reversibility in airway disease. GER was defined as an abnormal ambulatory 24-hour esophageal pH test and macroscopic or microscopic evidence of GER disease. Overall clinical status, asthma symptom scores, and pulmonary medication requirements were recorded monthly. Peak expiratory flow rates were recorded up to 7 times per day for 1 week of each month throughout the years. Pulmonary function, esophageal manometry, and endoscopy with biopsy were repeated yearly.
Results: The 62 patients were followed for up to 19.1 years. In the surgical group, but not in the medical or control groups, there was an immediate and sustained reduction in acute nocturnal exacerbations of wheezing, coughing, and dyspnea. By the end of 2 years, improvement, marked improvement, or cure in the overall asthma status occurred in 74.9% of the surgical group, 9.1% of the medical group, and 4.2% of the control group, whereas the overall status worsened in 47.8% of the control group, 36.4% of the medical group, and 12.5% of the surgical group (P < .001, surgical vs medical and control). The mean asthma symptom score of the surgical group improved 43%, compared with less than 10% in the medical and control groups (P = .0009). As determined by changes in peak expiratory flow rates, there was no statistically significant difference in pulmonary function during the 2-year period or during regularly scheduled follow-up. There was no difference in medication requirements among the groups. There was no difference between the groups in overall survival.
Conclusion: In patients with both GER and asthma, antireflux surgery (but not medical therapy with ranitidine 150 mg tid) has minimal effect on pulmonary function, pulmonary medication requirements, or survival, but significantly improves asthma symptoms and overall clinical status.

Gastroesophageal Reflux Treatment for Asthma in Adults and Children

Gibson PG, Henry RL, Coughlan JL
Cochrane Database Syst Rev. 2003;(2):CD001496

Background: Asthma and gastroesophageal reflux are both common medical conditions and often co-exist. Studies have shown conflicting results concerning the effects of lower esophageal acidification as a trigger of asthma. Furthermore, asthma might precipitate gastroesophageal reflux. Thus a temporal association between the two does not establish that gastroesophageal reflux triggers asthma. Randomized trials of a number of treatments for gastroesophageal reflux in asthma have been conducted to determine whether treatment of reflux improves asthma.
Objectives: The objective of this review was to evaluate the effectiveness of treatments for gastroesophageal reflux in terms of their benefit on asthma.
Search Strategy: The Cochrane Airways Group trials register, review articles, and reference lists of articles were searched.
Selection Criteria: Randomized controlled trials of treatment for esophageal reflux in adults and children with a diagnosis of both asthma and gastroesophageal reflux.
Data Collection and Analysis: Trial quality and data extraction were carried out by two independent reviewers. Authors were contacted for confirmation or more data.
Main Results: Twelve trials met the inclusion criteria. Interventions included proton pump inhibitors (n = 6), histamine antagonists (n = 5), surgery (n = 1), and conservative management (n = 1). Treatment duration ranged from 1 week to 6 months. A temporal association between asthma and gastroesophageal reflux was investigated in 4 trials and found to be present in a proportion of participants in these trials. Anti-reflux treatment did not consistently improve lung function, asthma symptoms, nocturnal asthma, or the use of asthma medications.
Reviewer's Conclusions: In asthmatic subjects with gastroesophageal reflux, (but who were not recruited specifically on the basis of reflux-associated respiratory symptoms), there was no overall improvement in asthma following treatment for gastroesophageal reflux. Subgroups of patients may gain benefit, but it appears difficult to predict responders.

A Proton-Pump Inhibitor, Rabeprazole, Improves Ventilatory Function in Patients With Asthma Associated With Gastroesophageal Reflux

Tsugeno H, Mizuno M, Fujiki S, et al
Scand J Gastroenterol. 2003;38:456-461

Background: Treatment of gastroesophageal reflux (GER) with proton-pump inhibitors (PPI) improves symptoms of asthma in some patients. However, the effects of a PPI on ventilatory function are still controversial. In this study, we measured ventilatory function in asthma patients treated with a PPI in order to identify those in whom a therapeutic effect on asthma can be expected from the acid suppression.
Methods: From a cohort of 114 consecutive patients with bronchial asthma, 53 patients agreed to participate in the study and were treated with rabeprazole 20 mg daily for 8 weeks during an asymptomatic, stable period with no exacerbations of their asthma. Of the 53 patients, 22 were diagnosed as GER on the basis of the QUEST questionnaire and endoscopic examination. The patients were monitored for improvement in ventilatory function.
Results: Four patients dropped out because of adverse drug reactions. All the patients with GER noted an improvement in reflux symptoms with PPI treatment. An improvement of more than 20% in peak expiratory flow (PEF) was observed in 8 of 21 GER patients but in none of the non-GER patients. Factors predictive of improvement in PEF with rabeprazole therapy were the QUEST score (odds ratio: 1.47, 95% CI: 1.06-2.04, P = .022) and steroid-dependency of asthma (odds ratio: 0.01, 95% CI: 0.001-0.31, P = .008).
Conclusions: Treatment with rabeprazole is expected to ameliorate asthma in non-steroid-dependent patients who have symptomatic GER defined by the QUEST score.

Effects of Antireflux Treatment on Bronchial Hyper-responsiveness and Lung Function in Asthmatic Patients With Gastroesophageal Reflux Disease

Jiang SP, Liang RY, Zeng ZY, Liu QL, Liang YK, Li JG
World J Gastroenterol. 2003;9:1123-1125

Aim: To investigate the effects of antireflux treatment on bronchial hyper-responsiveness and lung function in asthmatic patients with gastroesophageal reflux disease (GERD).
Methods: Thirty asthmatic patients with GERD were randomly divided into 2 groups (group A and group B). Patients in group A (n = 15) only received asthma medication including inhaled salbutamol 200 mcg 4 times a day and budesonide 400 mcg twice a day for 6 weeks. Patients in Group B (n = 15) received the same medication as group A, and also antireflux therapy including oral omeprazole 20 mg once a day and domperidone 10 mg three times a day for 6 weeks. Pulmonary function tests and histamine bronchoprovocation test were performed before and after the study.
Results: There was no significant difference in the baseline values of pulmonary function and histamine PC(20-FEV₁) between the 2 groups. At the end of the study, the mean values for VC, VC%, FVC, FVC%, FEV₁, FEV₁%, PEF, PEF%, PC(20-FEV₁) were all significantly improved in group B, compared with group A.
Conclusion: Antireflux therapy may improve pulmonary function and inhibit bronchial hyper-responsiveness in asthmatic patients with GERD.

Abstracts: Gastroesophageal Reflux in Asthma

Causative and Contributive Factors to Asthma Severity and Patterns of Medication Use in Patients Seeking Specialized Asthma Care