A systematic review of asthma case definitions in 67 birth cohort studies.

BACKGROUND: Birth cohort studies are a valuable source of information about potential risk factors for childhood asthma. To better understand similarities and variations in findings between birth cohort studies, the methodologies used to measure asthma require consideration. OBJECTIVE: To review and appraise the definitions of "asthma" used in birth cohort studies. METHODS: A literature search, conducted in December 2017 in the MEDLINE database and birth cohort repositories, identified 1721 citations published since 1990. Information extracted included: study name, year of publication, sample size, sample age, prevalence of asthma (%), study region, source of information about asthma, measured outcome, and asthma case definition. A meta-analysis evaluated whether asthma prevalence in cohorts from Europe and North America varied by the studies' definition of asthma and by their data sources. RESULTS: The final review included 67 birth cohorts, of which 48 (72%) were from Europe, 14 (21%) from North America, 3 (5%) from Oceania, 1 (1%) from Asia and 1 (1%) from South America. We identified three measured outcomes: "asthma ever", "current asthma", and "asthma" without further specification. Definitions of "asthma ever" were primarily based upon an affirmative parental response to the question whether the child had ever been diagnosed with asthma by a physician. The most frequently used definition of "current asthma" was "asthma ever" and either asthma symptoms or asthma medications in the last 12 months. This definition of "current asthma" was used in 16 cohorts. There was no statistically significant difference in the pooled asthma prevalence in European and North American cohorts that used questionnaire alone versus other data sources to classify asthma. CONCLUSION: There is substantial heterogeneity in childhood asthma definitions in birth cohort studies. Standardisation of asthma case definitions will improve the comparability and utility of future cohort studies and enable meta-analyses.

Association of the CD14 C159T and the Toll-like receptor 4 Asp299Gly polymorphisms with various phenotypes of asthma in adults from Crimea.

Background: This study assessed gene polymorphisms of the CD14 receptor (C-159T) and Toll-like receptor 4 (Asp299Gly) in a patient population in Crimea, Ukraine, stratified by clinical (early versus late onset; frequent versus occasional relapses; fixed versus reversible obstruction) and immunologic (atopic versus nonatopic; eosinophilic; neutrophilic or paucigranulocytic inflammation) subtype. Methods: Two polymorphisms, CD14 C-159T and TLR4 Asp299Gly, were assessed in 331 patients with asthma. The control group included 285 volunteers who were nonatopic. The single nucleotide polymorphisms were studied by using polymerase chain reaction with electrophoretic detection. Results: There were increased odds of asthma development in patients with the Asp299Gly TLR4 mutation compared with the general population underdominant odds ratio (OR) 1.52 [95% confidence interval (CI), 1.00-2.32] and overdominant (OR 1.55 [95% CI, 1.01-2.38]) models after adjustment for gender and age. In addition, mutations in this gene decreased the odds of nonatopic asthma in underdominant (OR 0.26 [95% CI, 0.07-0.93]; p = 0.027), overdominant (OR 0.27 [95% CI, 0.07-0.96]; p = 0.033), and log-additive models (OR 0.26 [95% CI, 0.07-0.93]; p = 0.026) compared with the atopic subgroup after adjustment for gender, age, number of exacerbations, and type of airway inflammation. Allele frequencies for CD14 and TLR4 polymorphisms did not show statistical differences between the patients with asthma and the control subjects. Conclusion: CD14 C-159T polymorphisms were not associated with asthma in the adult population in Crimea. TLR4 Asp299Gly polymorphisms were associated with asthma and with decreased odds of nonatopic asthma compared with atopic asthma in the adult population in Crimea.