Treating silent reflux disease does not improve poorly controlled asthma
ABSTRACTMany patients with asthma also have gastroesophageal reflux disease (GERD), and GERD can cause symptoms that mimic those of poorly controlled asthma. Patients with poorly controlled asthma are often treated empirically for GERD, whether or not they have symptomatic reflux. However, a randomized, placebo-controlled trial funded by the American Lung Association and the National Institutes of Health found that treating silent GERD does not improve asthma control. These results warrant a reevaluation of current guidelines and clinical practice.
KEY POINTS
- Acid reflux is more prevalent in patients with asthma, and it often occurs without classic symptoms such as heartburn.
- Current guidelines, based on data from older studies with significant limitations, recommend considering treatment for reflux disease, even without the classic symptoms, in patients with uncontrolled asthma.
- The recent Study of Acid Reflux in Asthma found not only that treating silent acid reflux does not improve asthma control, but also that esophageal pH monitoring does not detect a subgroup of asthma patients who might respond to a proton pump inhibitor. These data suggest that we should reconsider clinical practice based on current guidelines.
SARA RESULTS: NO IMPROVEMENT IN ASTHMA WITH GERD TREATMENT
The SARA treatment and control groups had similar baseline characteristics, with similar asthma symptoms. Most of the patients were women: 72% of the placebo group and 64% of the esomeprazole group. Most had baseline spirometric results at the lower end of normal (the mean FEV1 was 76% ± 16 SD in the treatment group and 78% ± 15 in the placebo group) and had very poor asthma control, with an average Juniper Asthma Control Questionnaire score of 1.9 (> 1.5 is considered poor control).31 GERD was documented with esophageal pH monitoring in 40% of patients, showing that a significant number had silent GERD.
Episodes of poor asthma control occurred with similar frequency in the esomeprazole and placebo groups (2.5 vs 2.3 events per personyear, P = .66). Treatment made no difference in this end point regardless of the baseline results of pH monitoring. No treatment effect was noted in the individual components of the episodes of poor asthma control or in secondary outcomes, including pulmonary function, airway reactivity, asthma control, symptom scores, nocturnal awakening, or quality of life.
In addition, subgroup analysis failed to identify any group—including those with documented reflux on pH probe testing or those receiving a long-acting beta-agonist—who benefited from proton pump inhibitor therapy.
The investigators concluded that these data suggest treatment of silent GERD does not improve asthma control and thus that a reevaluation of current guidelines and clinical practice is warranted.2
ISSUES REMAIN
This large clinical trial, in which asthma and GERD were well defined and objectively measured, was robustly negative in terms of showing any benefit of treatment of silent GERD on asthma control. The study population was representative of those for whom such a treatment is recommended in the current NIH guidelines, which are based on data published prior to SARA.
However, while SARA was well designed and had clear results, it had some limitations, and some issues regarding GERD and asthma remain unanswered.
Is acid the only problem in GERD? SARA focused on acidic GERD. Aspiration of substances such as pancreatic enzymes, pepsin, and bile has also been shown to induce symptoms in asthma patients.2,32,35 In addition, distention of the esophagus and stimulation of neurogenically mediated reflexes can cause symptoms or neurogenic airway inflammation that is not mitigated by drugs that target acid reflux.32
Indirectly supporting this theory is evidence that surgical interventions such as fundoplication can improve asthma symptoms. 36 However, this evidence is only from small studies with significant limitations.
Is proximal GERD worse than distal GERD? SARA did not address whether proximal and distal reflux may affect asthma differently. The importance of proximal reflux in asthma has not been clearly established, but there is evidence that patients with proximal GERD have a higher incidence of nocturnal cough than patients who have only distal reflux. 37
Dimango et al38 recently reported additional data from SARA in which patients with poorly controlled asthma underwent both proximal and distal esophageal pH monitoring to see if proximal GERD was associated with poor asthma control: 304 patients underwent dual pH-probe assessment and 38% of them had proximal reflux. The authors found no difference between those with and without proximal GERD with regard to nocturnal awakenings, need to use a rescue inhaler, inhaled controller medication dose, lung function, or airway reactivity by methacholine challenge. However, they did find that those with proximal GERD had worse asthma quality-of-life scores, and worse health-related quality-of-life scores and were more likely to complain of cough.
Thus, it appears that proximal GERD may worsen quality of life in asthmatic patients but does not worsen asthma control.
SARA RESULTS: IMPLICATIONS FOR MANAGEMENT
The SARA results suggest that patients with poorly controlled asthma who are on adequate controller medications should not be treated empirically for silent GERD in the expectation that the asthma will improve. Rather, they suggest that the focus should be on other factors that can worsen asthma control, such as the ability to properly use an inhaler, the ability to afford medications, compliance with drug treatment, and adequate control of other significant comorbidities such as allergic bronchopulmonary aspergillosis, sinusitis, allergic rhinitis, vocal cord dysfunction, and occult heart disease. The most recent NIH guidelines also suggest considering referral to an asthma specialist if symptoms persist despite adequate controller therapy.
