In the present RCT, we compared the results of 8-week administration of 40 mg/day atorvastatin on asthma control and spirometric and serum parameters of patients with asthma. The results showed that asthmatic control score significantly improved in the intervention group, but did not change in placebo group, while neither spirometric parameters, nor the serum level of periostin and eosinophil counts were different between the groups. Serum lipid profile of the patients was also evaluated before and after the intervention in order to determine patients’ adherence to treatment, confirmed by the significant reduction in serum levels of total cholesterol, HDL, LDL, and triglyceride in the intervention group.
Atorvastatin is a cholesterol-lowering drug with anti-inflammatory effects and animal models have shown its efficacy on reduction of inflammatory cell infiltration and airway hyper-responsiveness [15, 16]. However, human studies have shown controversial results considering its efficacy in treatment of asthma. Some have reported better asthma control in patients with severe asthma using statins [23, 24], while other studies, like ours, have reported no significant difference [25–27]. In the study by Fahimi and colleagues, 17 adult patients with moderate to severe asthma received 10 mg/day atorvastatin or placebo for 4 weeks in a cross-over design study [25]. Similar to the results of the present study, they also reported no difference between spirometric parameters of the intervention or placebo group; however, there were some differences between the studies in the improvement of spirometric parameters by time in the intervention group, as they reported significant increase in the FVC (P = 0.01), while we detected significant reduction in TLC and RV in the intervention group, but not in FVC. These differences between the studies could be because of the different dose and duration of administered atorvastatin from our study. Alavi and others investigated the effects of 40 mg/day atorvastatin on patients with moderate to severe asthma compared with placebo, and reported changes in spirometric parameters in each of the groups without significant difference between the groups [26], which is consistent with the results of the present study. Similar to the methods of the present study, in a previous study on 62 patients, the researchers randomized patients with asthma to receive 40 mg/day atorvastatin or placebo for 8 weeks. The results showed elevated FEV1 and FVC in the placebo group after 8 weeks and elevated FEV1 in the intervention group after 8 weeks, without significant difference between the groups in spirometric parameters [27]. The dose/duration of administration of atorvastatin in this study was similar to ours and no significant difference in spirometric parameters between the groups was also consistent with the results of our study; however, they only evaluated FEV1 and FVC, while we reported complete spirometric results and showed significant changes in TLC and RV in the intervention group. Meanwhile, as TLC and RV were both lower in the intervention group of our study, it could not show any improvements in this group, which is consistent with the results of previous studies [25, 27].
In the present study, the results of ACT showed significant improvement in asthma control scores of the intervention group (from 17.95 ± 3.75 to 19.88 ± 3.28; P < 0.001), in addition to greater change in the scores in the intervention group compared with the placebo group (13.25 ± 2.96 vs. 5.19 ± 2.41, respectively; P = 0.038). These results confirm the beneficiary effect of the administered atorvastatin on clinical outcomes of the patients with asthma. In the study by Moini and colleagues, 62 patients with mild to moderate asthma were randomized to receive 40 mg/day atorvastatin or placebo for 8 weeks. The results showed significant reduction in asthma control scores both in intervention and placebo groups, while there was no difference between the groups in this regard [27]. They reported mean asthma control score of the placebo group increased from 15.27 ± 4.34 to 17.83 ± 4.47 (P < 0.001) and that of the intervention group from 16.78 ± 4.11 to 19.85 ± 3.20 (P < 0.001) [27]. Comparing the mean values of their study with our study shows that the baseline scores of their patients were lower than ours, while the mean asthma control score after 8 weeks in the intervention group of their study (19.85 ± 3.20) was close to that reported in our study (19.88 ± 3.28). Accordingly, these results confirm the significant effect of 8 weeks administration of 40 mg/day atorvastatin on asthma control, although this effect might not be the direct effect of the drug.
Atorvastatin has shown beneficiary effects on reducing the inflammatory markers such as tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and interleukins in other diseases, such as ischemic stroke [28], rheumatoid arthritis [29], and diabetes [30]. Accordingly, in the present study, we examined its efficacy on eosinophil count and periostin levels of patients’ sera, as these are considered as important inflammatory markers in asthma [12]. Nevertheless, the results of our study showed no significant changes in eosinophil count and periostin in the groups and no difference between the intervention and placebo group in this regard. The serum eosinophil count of the placebo group in the present study was 8.11 ± 4.63 at baseline and 8.06 ± 5.37 after 8 weeks, while in the intervention group, it was17.98 ± 9.9 at baseline and 8.3 ± 4.21 after the intervention; meanwhile, there was no significant change in either groups, or significant difference between the groups at baseline or after intervention. In the study by Moini and colleagues, eosinophil count significantly reduced in the placebo group (from 221.31 ± 134.01 to 204.62 ± 134.64) and in the intervention group (from 244.35 ± 154.4 to 179.14 ± 117.43; both P < 0.001), which is contrary to the results of the present study. But they also reported no significant difference between the groups, which is in line with the results of the present study. In the study by Hothersall and colleagues, patients’ outcomes were compared between the groups receiving 40 mg/day atorvastatin for 8 weeks and placebo in a cross-over design study with 6-week washout period and the results showed significant reduction in absolute sputum macrophage count in atorvastatin group, while morning peak expiratory flow was not different between the groups [17]. The results of studies could also depend on the main treatment of the studied patients, because of the possibility of drug interactions, as in the study by Hothersall and colleagues, inhaled corticosteroids were used as the background treatment.
As described above, the few studies addressing the efficacy of atorvastatin on asthma control and inflammatory markers in the patients with asthma have reported different results. The same discrepancy in the results of studies is observed regarding the effect of other statins, like simvastatin, on asthma control and reducing inflammation in such patients [31, 32]. However, a wide variety is observed among studies in terms of disease severity, parameters, and main treatments used to control asthma. These suggest that further studies are required to determine the exact efficacy of statins on asthma control. Current review studies indicated that atorvastatin reduced airway inflammation in patients with asthma, but could not improve lung function; however, the inflammatory markers studied vary among studies [20]. As studies that measured general inflammatory markers, like eosinophil count [27] and estimated sedimentation rate (ESR) [26], have declared the necessity to use more specific markers. In this study, we measured the change in serum levels of periostin on patients with asthma receiving atorvastatin for the first time, introduced as a novel biomarker in such patients [33]; but, the results of our study showed no significant difference between the groups in serum levels of periostin.
One of the limitations of the present study was that we did not examine the changes in airway tissue, endothelial, or cellular levels for a more accurate assessment of any change in patients’ airway hyper-responsiveness and inflammation, and only investigated clinical and serological parameters, while histopathological assessment of the patients could guide us better in this regard. Furthermore, follow-up period of the present study was short and the sample size was limited, although they were acceptable compared with similar studies.
As the intervention was on both sexes, young and middle age patients with varying degrees of body weights, this suggested that the results of the present study could be attributed to a wide range of asthmatic patients.