Cross-sectional distribution of asthma severity in subjects with data available at both surveys.

*<p><b><i>comparison of men and women in EC1 by GINA (p = 0.04) is weak.</i></b></p

Distribution of asthma severity at EC2 in subjects without current asthma at EC1 (ECI-0) and in subjects with asthma, according to asthma severity at EC-1.

<p>Distribution of asthma severity at EC2 in subjects without current asthma at EC1 (ECI-0) and in subjects with asthma, according to asthma severity at EC-1.</p

Study design.

<p>Study design.</p

Characteristics of subjects who provided respiratory data in the two assessments as compared with those not followed-up at the second survey by gender.

<p>Characteristics of subjects who provided respiratory data in the two assessments as compared with those not followed-up at the second survey by gender.</p

An Interleukin 13 Polymorphism Is Associated with Symptom Severity in Adult Subjects with Ever Asthma

<div><p>Different genes are associated with categorical classifications of asthma severity. However, continuous outcomes should be used to catch the heterogeneity of asthma phenotypes and to increase the power in association studies. Accordingly, the aim of this study was to evaluate the association between single nucleotide polymorphisms (SNPs) in candidate gene regions and continuous measures of asthma severity, in adult patients from the general population. In the Gene Environment Interactions in Respiratory Diseases (GEIRD) study (<a href="http://www.geird.org/" target="_blank">www.geird.org</a>), 326 subjects (aged 20–64) with ever asthma were identified from the general population in Verona (Italy) between 2007 and 2010. A panel of 236 SNPs tagging 51 candidate gene regions (including one or more genes) was analysed. A symptom and treatment score (STS) and pre-bronchodilator FEV₁% predicted were used as continuous measures of asthma severity. The association of each SNP with STS and FEV₁% predicted was tested by fitting quasi-gamma and linear regression models, respectively, with gender, body mass index and smoking habits as potential confounders. The Simes multiple-test procedure was used for controlling the false discovery rate (FDR). SNP rs848 in the IL13 gene region (IL5/RAD50/IL13/IL4) was associated with STS (TG/GG <i>vs</i> TT genotype: uncorrected p-value = 0.00006, FDR-corrected p-value = 0.04), whereas rs20541 in the same gene region, in linkage disequilibrium with rs848 (r² = 0.94) in our sample, did not reach the statistical significance after adjusting for multiple testing (TC/CC <i>vs</i> TT: uncorrected p-value = 0.0003, FDR-corrected p-value = 0.09). Polymorphisms in other gene regions showed a non-significant moderate association with STS (IL12B, TNS1) or lung function (SERPINE2, GATA3, IL5, NPNT, FAM13A) only. After adjusting for multiple testing and potential confounders, SNP rs848 in the IL13 gene region is significantly associated with a continuous measure of symptom severity in adult subjects with ever asthma.</p></div

Age-specific rates of asthma in Italy by period of asthma onset and birth cohort:

<p><b>A)</b> Age-specific rates by year of onset: age at onset on x axis, with rates corresponding to same period connected by lines; <b>B)</b> Age-specific rates by birth cohort: age at onset on x axis, with rates corresponding to same cohorts connected by lines; <b>C)</b> Period-specific rates by age: year of onset on x axis, with rates corresponding to same age groups connected by lines; <b>D)</b> Cohort-specific rates by age: year of birth on x axis, with rates corresponding to same age groups connected by lines.</p

Person-years, number of subjects reporting ever having had asthma, and the crude incidence (95%CI) of asthma by sex, age at onset, birth cohort, and period, type of study and presence of hay fever.

<p>Person-years, number of subjects reporting ever having had asthma, and the crude incidence (95%CI) of asthma by sex, age at onset, birth cohort, and period, type of study and presence of hay fever.</p

A-C. Estimated effects from the APC model for asthma incidence rates.

<p>Fig 2A represents the age-specific incidence rates, referred to the reference period 1975; Fig 2B represents the merged period and drift effects (rate ratios): the linear increasing trend is given by the drift, while deviations from linearity (curvature) are determined by the period effect; Fig 2C represents the birth cohort effect. The arrow in B indicates the calendar period when the incidence of asthma has begun to level off. The respective regions surrounding the lines provide the 95% confidence intervals.</p

Incidence rate ratios (RR, with 95%CI) of asthma by age in men vs. women.

<p>Incidence rate ratios (RR, with 95%CI) of asthma by age in men vs. women.</p

Number of subjects with asthma and asthma remissions, crude incidence and risk ratios (RR) of asthma remission adjusted by sex, presence of hay fever, age at onset, birth cohort, and time since onset.

<p>CI: confidence interval</p><p>Number of subjects with asthma and asthma remissions, crude incidence and risk ratios (RR) of asthma remission adjusted by sex, presence of hay fever, age at onset, birth cohort, and time since onset.</p