A total of 18 studies have been included in this research. Of these, only three studies demonstrated that statins could enhance the lung function in asthmatics, whilst 15 studies failed to support this. There was a tendency that statins were associated with reduced airway inflammation, suggesting that statins may be used as a supplement for anti-inflammatory treatment of asthma at present. The effects of statins were inconsistent in different studies with respect to the symptoms, quality of life, asthma hospitalization/ED visits and maintenance medications. Further large placebo-controlled studies are needed in well-defined subsets of asthmatics patients treated or not treated with corticosteroids before a consensus can be reached.
The clinical status of participants may affect the clinical effectiveness of statins, such as the severity of asthma, age of participants, smoking status and obesity. Feschenko et al. selected 31 severe asthma as the subjects and found that atorvastatin significantly improved clinical and functional outcomes , which indicated statins might be effective in severe asthma. However, the results of other included studies, in which the participants were mostly mild to moderate asthmatics did not show a beneficial effect of statins. Further studies on severe asthmatics are needed to confirm this.
A retrospective study found that increasing age was independently associated with an increased risk of hospitalization for asthma patients . This may be due to poor asthma control and medication compliance in elderly patients [32–34] and this may explain the effects of statins.
In addition, some results have shown that ex-smokers and current smokers have a lower decline in FEV1 and FVC when taking statins [35, 36]. Furthermore, Braganza et al. showed that in smokers with mild to moderate asthma, short term treatment with statins could improve asthma quality of life . Cigarette smoking in asthma is associated with a reduced sensitivity to ICS , so statins may act as an effective therapy for asthma patients who have reduced sensitivity to ICS. Finally, studies have demonstrated that obesity was associated with poor asthma control [37, 38] and poor response to ICS treatment . Statins are lipid-lowering agents and may be used to relieve the symptoms of obesity-related asthma.
Our analysis of the clinical data reported to date indicates marked differences in study design. Statins inhibit contraction and migration of human airway smooth muscle cells . It was estimated that smooth muscle cells of the mouse aorta divide with a half-life in the range of 300  to 800  days, and this half-life is much longer than the duration of treatment of most clinical studies (4 or 8 weeks). Therefore, if these results are translated to man, the therapeutic effects of statins in asthma may only become apparent after long-term treatment. Long-term studies should be designed to investigate the long- term effects of statins.
There is evidence that the therapeutic effects of individual statins are different. For example, simvastatin and lovastatin are more effective against human smooth muscle cells than atrovastatin in vitro . Furthermore, cerivastatin has the greatest potency in reducing NF-κB-mediated inflammation . Lipophilic statins such as atorvastatin and simvastatin have much greater effects on inflammatory responses in human monocytes in vitro and mice leukocytes in vivo than hydrophilic pravastatin . Thus, new clinical trials should compare the efficacy of different statins since these may have different effects. Animal experiments have confirmed the effective dosage of statins used in animal asthma models, the high-dose being 40mg/kg for simvastatin [11, 46] in comparison with 4mg/kg for lovastatin . The maximum recommended dosage of atorvastatin is 80mg/day in man. However, the dosage of statins was below 40mg/day in all eligible studies. In addition, the effect of the small sample size in most of the reported studies must not be ignored.
There are certain limitations of our study. We used a loose selection criteria; for example, abstracts and studies with comparison against baseline only were also selected, because there have not been many studies in this area. In addition, we were unable to conduct a meta-analysis due to limited information, and therefore we could not provide statistically significant evidence to confirm the effectiveness of statins.
In conclusion, statins may reduce airway inflammation in asthmatics, although there is not sufficient evidence to make a conclusion that statins can improve lung function. A sub-population of asthmatics, including smokers and obese individuals who respond poorly to ICS may respond preferentially to statins. The immunomodulating property of statins may shed new light on their promising use in the treatment of asthma. Large sample and multicenter clinical trials in selected specific subpopulations will be needed to investigate the full potential effects of statins in asthma treatment.