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Discussion
Our study did not reveal significant differences in pulmonary function tests measured as FEV1 at admission and discharge and PEF measured at specific intervals or length of hospital stay in patients hospitalized with acute asthma exacerbation that were given oral montelukast vs. placebo. The efficacy and tolerability profile of oral montelukast were comparable to placebo and no serious adverse effects were encountered.
The pathology of asthma triggers the arachnoid acid cascade leading to formation of leukotrienes via the 5-lipoxygenase pathway. The cysteinyl leukotrienes possess pro-inflammatory characteristics which can directly cause or potentiate airflow obstruction by increased mucosal secretion and bronchospasm. Leukotriene pathway modifiers, hence, are a subject of interest as a possible adjunct therapy in the acute management of asthma exacerbation. However, our results are in contrast to data recently published by Ramsay et al. They randomized 73 patients and found a significantly higher peak expiratory flows (PEFs) measured in the morning after admission in patients who received montelukast (p = 0.046, 95% CI of 1.15-113.6 L/min) as compared to patients who did not. A study by Silverman et al. evaluated the effects of another LTRA, zafirlukast. They randomized patients into three groups; oral zafirlukast at 20 mg and 160 mg vs. placebo. They looked at the time to relapse in the outpatient setting after discharge from the emergency department and found reduction in the absolute rate of relapse by 5.3% in patients treated with zafirlukast. They reported significant improvement in FEV1 and dyspnea in the ER only with 160 mg of zafirlukast. Other studies have also looked into effects of intravenous montelukast in managing acute asthma exacerbations. Camargo et al. randomized 201 patients to three groups with two receiving separate doses of montelukast (7 mg and 14 mg) and one group receiving placebo. They reported significantly higher FEV1 in patients receiving standard therapy with montelukast as compared to placebo at 10 minutes (p = 0.03), 20 minutes (p = 0.007) and two hours (p = 0.003). These results were validated in a more recent study in Japan which reported both IV monteleukast 7 mg and 14 mg to be effective as an adjunct therapy over 60 minutes; p < 0.05 and p < 0.001 respectively.
To the best of our knowledge, our study is the first one to report no added benefits of using montelukast in acute asthma exacerbation in hospitalized adult population. Other studies which report similar findings mostly correspond to the pediatric population. Nelson et al. and Morris et al. did not find any significant increase in FEV1 by using oral and intravenous montelukast respectively while Todi et al. reported similar proportion of children having Modified Pulmonary Index Score ≤ 9 in both the study and control groups.
A possible reason we failed to find significant improvement is that we looked at PEFs early in the course of hospitalization instead of FEV1 in comparison to the positive studies cited above. Another reason for failure of significant improvement might be the use of enteral route of administration. However, Dockhorn et al. conducted a study comparing the effectiveness of intravenous montelukast vs. oral montelukast vs. placebo in the setting of acute asthma. Though intravenous montelukast was quicker in onset of action with the mean percentage change in FEV1 higher at earlier time intervals (15 mins to 1 hour), this difference decreased over the time and was not significant (p > 0.05). Moreover, there was no difference in mean maximum percentage change in FEV1 from baseline between intravenous and oral montelukast (p = 0.071).
This study has several limitations. Firstly, our study sample is relatively small. Secondly, we excluded patients with respiratory failure requiring positive pressure ventilation, either noninvasive or invasive. Both these factors may have impacted on the strength of difference observed in the two groups. Another limitation is the lack of biological surrogate markers like cysteinyl leukotrienes levels which have been shown to be higher in states of acute asthma exacerbation. It is possible that these levels may have reduced in the patients but did not translate into clinical effectiveness yet. The use of Piko-1 pocket spirometer is another limitation in our study. A study from Switzerland revealed that the accuracy of Piko-1 spirometer is acceptable. However, it tended to underestimate FEV1 in the lower range in 20 volunteers. Lastly, this was a single center study and hence, cannot be generalized to the whole population.
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