1.
Calcium channel blockers for lung function improvement in asthma: A systematic review and meta-analysis.
Chiu, KY, Li, JG, Lin, Y
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2017;(6):518-523.e3
Abstract
BACKGROUND For decades, calcium channel blockers (CCBs) have been believed to play a role in asthma treatment. However, the clinical efficacy of CCBs for lung function improvement in patients with asthma has not been qualitatively evaluated. OBJECTIVE To assess the effect of CCBs vs placebo on lung function test results in adults with asthma. METHODS Various databases were systematically searched to identify all randomized clinical trials with adults with asthma. We aimed to assess the influence of CCBs on forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), peak expiratory flow rate (PEFR), and provocative concentration of bronchoconstrictive agents causing a 20% decrease in FEV1 (PC20) compared with a placebo. All effect estimates were pooled by the generic inverse variance method with random-effects meta-analysis. Subgroup analysis, sensitivity analysis, and heterogeneity investigation were performed. RESULTS Thirty eligible articles with 301 patients were included in this meta-analysis. Our results revealed that in a standard exercise test CCBs could produce a mean maximal percentage decrease in FEV1 of 11.56% (95% confidence interval, 8.97%-14.16%; P < .001) and an increase in postdose FEV1 by 80 mL (95% confidence interval, 0.02-0.15 mL; P = .01). However, there was no statistical significance for CCBs in postdose FVC, PEFR, or PC20 of histamine and methacholine. CONCLUSION CCBs may be beneficial for lung function improvement in asthma, especially in exercise-induced asthma. However, there is a lack of evidence for CCBs protecting asthma patients from chemical irritation.
2.
Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function.
Hancock, DB, Soler Artigas, M, Gharib, SA, Henry, A, Manichaikul, A, Ramasamy, A, Loth, DW, Imboden, M, Koch, B, McArdle, WL, et al
PLoS genetics. 2012;(12):e1003098
Abstract
Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV(1)), and its ratio to forced vital capacity (FEV(1)/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV(1) and FEV(1)/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P(JMA = )5.00×10(-11)), HLA-DQB1 and HLA-DQA2 (smallest P(JMA = )4.35×10(-9)), and KCNJ2 and SOX9 (smallest P(JMA = )1.28×10(-8)) were associated with FEV(1)/FVC or FEV(1) in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.