There are several shortcomings of previously published similar intervention studies done in adults: (1) there are personal bias and differences in the assessment of severity and treatment strategy of asthma by different treating physicians, so the quality and quantity of medication used by different physicians may not be comparable; (2) the efficacy of anti-GER therapy has not been defined and the degree of acid suppression required for response, and that achieved by the treatment rendered, has not been defined; (3) the optimal duration of the intervention to produce discernable asthma response has not been determined; (4) appropriate control groups have not been included; (5) the potential order and carry-over effects have not been eliminated in blind cross-over trials; (6) the severity of asthma, an important variable, has not been controlled as an inclusion criteria, since patients with different severities may respond differently; and (7) multiple risk factors for asthma have not been controlled. In our study, we tried to control for the different confounding variables that could affect the results as well as including only those patients who had no obvious risk factors for asthma. As part of the entry criteria, we preselected patients with a similar severity of disease as well as the lack of risk factors such as atopy, family history, and smoking. All patients had a long follow-up history, so their present treatment for asthma was stable and had evolved over an extended period of time that was at least 2 years. All patients were treated by the same physician using a standard pre-established protocol, thus eliminating physician-to-physician differences in diagnosis and treatment. The diagnostic methodology and criteria for GER were uniform. The same physician treated all patients for GER in a uniform manner. Patients served as their own controls, eliminating the individual and patient-to-patient differences in severity and risk factors. A sufficiently long time was used for follow-up, thus minimizing the effects of month-to-month variations in the disease activity. Our follow-up of 12 months was much longer than the 1- to 3-month follow-up used in the adult studies.8–10
Further, we allowed an initial 6-month period just for the anti-GER treatment to take effect. Based on some studies, it seems that a discernable improvement in asthma outcomes should not be expected in a short time.8
Accordingly, we believed that data collected during the initial 6 months may not show the full impact of anti-GER treatment on asthma, as well as merely reflect the variation in disease status seen from month to month. For ethical reasons, we did not include a placebo group. We did not have a crossover design; therefore, there was no order or carry-over effect. We included a group of patients (group D) who had a comparable asthma severity but did not have GER and were not treated for GER. This group served as a good control to show that the variation in the asthma medication used was not significant in 6-month periods over the course of 18 months, and that the significant differences observed in groups A and B pre-GER treatment and post-GER treatment were far greater than in group D and were true differences. Despite the above-mentioned strengths, some shortcomings of our study also need to be mentioned. Though uniform anti-GER therapy was provided, the efficacy was presumed and not proven. The lack of response to anti-GER treatment could have been due to lack of adequate acid suppression. Further, though all patients were treated for asthma along a standard protocol and by the same physician, the physician was indeed aware of the anti-GER treatment. This could have influenced him to be more attentive to smaller changes in the severity of asthma during anti-GER treatment phase as compared to before anti-GER treatment was instituted. This bias could have led to a lesser or greater use of asthma medications following anti-GER treatment. However, this bias would have been uniform for all the patients and less likely to affect the overall trend. Nevertheless, the fact that a majority of patients did not require either inhaled corticosteroids or short-acting bronchodilators following 6 months of anti-GER treatment is in itself a significant finding. Furthermore, following 6 months of anti-GER medical or surgical treatment, none of the patients required the use of leukotriene antagonists or long-acting bronchodilators. None of these patients had ever been off any asthma medication for a continuous 3-month period prior to anti-GER treatment. It is needless to mention that inhaled corticosteroids and long-acting bronchodilators are regarded as the maintenance medications for patients with persistent moderate asthma. Alleviation of the need for the use of these maintenance medications is yet another indicator of significant improvement in the status of the patients’ asthma.