Elucidating the risk factors for chronic obstructive pulmonary disease: an umbrella review of meta-analyses.

Chronic obstructive pulmonary disease (COPD) is commonly attributed to smoking, and other potential risk factors are ignored. We aimed to critically appraise the epidemiological credibility of the risk factors for COPD that have been examined in published meta-analyses. We performed a systematic search to capture systematic reviews and meta-analyses of observational studies on environmental factors and biomarkers for risk of COPD. We applied a set of standardised methodological criteria based on the level of statistical significance, sample size, between-study heterogeneity and statistical biases. Our search yielded 11 eligible papers, including 18 meta-analyses on environmental factors or biomarkers for COPD risk, and eight eligible papers with systematic reviews only. Eleven associations achieved statistical significance at P < 0.001 and six associations at P < 1 × 10-6. Thirteen associations presented an I²  50%, while six associations had evidence of small-study effects and/or excess significance bias. History of tuberculosis or rheumatoid arthritis, exposure to biomass fuels, tobacco smoking and second hand smoking were supported by high epidemiological credibility for an increased risk of COPD. Furthermore, highly suggestive evidence was found for increased levels of serum C-reactive protein, and serum fibrinogen in COPD patients compared with healthy controls. To summarise, our approach suggests that, while a proportion of COPD patients are non-smokers, only a narrow range of risk factors not related to smoking have been studied for an association with COPD. There is also a need to decipher possible protective factors in COPD pathogenesis given that more than a half of ever-smokers do not develop COPD.

Risk factors and peripheral biomarkers for schizophrenia spectrum disorders: an umbrella review of meta-analyses.

OBJECTIVE: This study aimed to systematically appraise the meta-analyses of observational studies on risk factors and peripheral biomarkers for schizophrenia spectrum disorders. METHODS: We conducted an umbrella review to capture all meta-analyses and Mendelian randomization studies that examined associations between non-genetic risk factors and schizophrenia spectrum disorders. For each eligible meta-analysis, we estimated the summary effect size estimate, its 95% confidence and prediction intervals and the I2 metric. Additionally, evidence for small-study effects and excess significance bias was assessed. RESULTS: Overall, we found 41 eligible papers including 98 associations. Sixty-two associations had a nominally significant (P-value <0.05) effect. Seventy-two of the associations exhibited large or very large between-study heterogeneity, while 13 associations had evidence for small-study effects. Excess significance bias was found in 18 associations. Only five factors (childhood adversities, cannabis use, history of obstetric complications, stressful events during adulthood, and serum folate level) showed robust evidence. CONCLUSION: Despite identifying 98 associations, there is only robust evidence to suggest that cannabis use, exposure to stressful events during childhood and adulthood, history of obstetric complications, and low serum folate level confer a higher risk for developing schizophrenia spectrum disorders. The evidence on peripheral biomarkers for schizophrenia spectrum disorders remains limited.