Sex differences in baseline risk factors for the incidence of asthma between early adolescence and young adulthood

Background: Several studies have shown sex differences in the prevalence of asthma and a relationship to age. The aim of the present study was to prospectively investigate the development of asthma, wheeze, rhinitis and allergic symptoms, between adolescence and adulthood. Furthermore, to determine if sex modifies the associations between baseline risk factors and incidence of asthma in early adulthood. Methods: In the study Screening Project Asthma in Schools(SPAIS), adolescents aged 12–15 years answered a standardised respiratory questionnaire (ISAAC) and underwent measurements of fractional exhaled nitric oxide (FeNO) and lung function (FEV1) at baseline. Two follow-ups with similar questionnaires were performed after four and 16 years, with 491 subjects participating in all three examinations. Results: The prevalence of asthma and wheeze were unchanged after four years, but had increased after 16 years. However, the increase was significant only for females. A more continuous increasein rhinitis and allergic symptoms showed no difference between the sexes. Sex interaction analysis showed that higher FeNO (p = 0.01) and family asthma (p = 0.02) increased the risk of incident asthma for males but not for females. Conclusions: An increased prevalence of respiratory symptoms was seen primarily between late adolescence and young adulthood, and was significant for females but not males. Allergic risk factors in early adolescence for incident asthma in early adulthood were confirmed in males but not in females. Awareness of these sex differences in the development of symptoms, and the associated risk factors, are important in clinical practice.

Demographic, lifestyle and comorbid risk factors for all-cause mortality in a Danish cohort of middle-aged adults with incident asthma

ObjectiveWe aimed to identify factors associated with all-cause mortality in adults with incident asthma.Design and settingCross-sectional cohort study, in the metropolitan areas of Copenhagen and Aarhus, Denmark.ParticipantsAdults aged 50–64 years enrolled in the Danish Diet, Cancer, and Health cohort were followed up from baseline (1993–1997) in the National Patients Registry for first-time admissions for asthma and vital status. We defined incident asthma as at least one first-time hospital admission with asthma as the primary registered diagnosis between baseline and end of follow-up (2013) in participants without previously known asthma. Among the cohort comprising 57 053 individuals, we identified 785 adults (aged 50—64) with incident asthma, of whom 76 died during follow-up.Primary and secondary outcome measuresBaseline reported socioeconomic and lifestyle traits, and comorbidities associated with all-cause mortality.ResultsSelf-reported leisure-time physical activity was associated with a substantial reduction in risk with an HR of 0.53 (95% CI 0.33 to 0.85). Being male, single and having a diagnosis of hypertension or diabetes were associated with an increased risk of all-cause mortality with an HR of 1.83 (95% CI 1.14 to 2.38), 2.16 (95% CI 2.06 to 4.40), 2.47 (95% CI 1.54 to 3.95) and of 2.42 (95% CI 0.96 to 6.11), respectively.ConclusionsThis long-term study of adults with hospital contacts for incident asthma revealed that self-reported leisure-time physical activity is associated with an approximately 50% reduction in all-cause mortality. In contrast, both hypertension and diabetes were associated with a higher risk of mortality.

Investigating Obesity-related Factors for Childhood Asthma

Background: We tested the hypothesis that multiple obesity-related risk factors (obesity, physical activity, cardiopulmonary physical fitness, sleep-disorder breathing (SDB), and sleep quality) are associated with childhood asthma using a Mendelian randomization (MR) design. Furthermore, we aim to investigate whether these risk factors were associated with incident asthma prospectively. Methods: In total, 7069 children aged 12 from the Taiwan Children Health Study were enrolled in the current study. Cross-sectional logistic regression, one-sample MR, summary-level MR sensitivity analyses, and prospective survival analyses were used to investigate each causal pathway. Results: In MR analysis, three of the five risk factors (obesity, SDB, and sleep quality) were associated with asthma, with the highest effect sizes per interquartile range (IQR) increase observed for sleep quality (odds ratio [OR] =1.42; 95% confidence interval [CI]: 1.06 to 1.92) and the lowest for obesity (OR = 1.08; 95% CI: 1.00–1.16). In the prospective survival analysis, obesity showed the highest risk of incident asthma per IQR increase (hazard ratio [HR] = 1.28; 95% CI: 1.05 to 1.56), followed by SDB (HR = 1.18; 95% CI: 1.08 to 1.29) and sleep quality (HR = 1.10; 95% CI: 1.03 to 1.17). Conclusion: The most plausible risk factors for asthma were obesity, SDB, and poor sleep quality. For the prevention of childhood asthma, relevant stakeholders should prioritize improving children’s sleep quality and preventing obesity comorbidities such as SDB.

The Association Between Proton Pump Inhibitors and Incident Asthma in Patients with Coronary Artery Disease: A Population-Based Cohort Study

Observational studies have found a significant association between acid-suppressive drug use and incident asthma. However, the association between proton pump inhibitors (PPIs) and incident asthma in patients with coronary artery disease (CAD) is unclear. Thus, this study assessed the association between PPI use and incident asthma in patients with CAD. We conducted a retrospective cohort study using the National Health Insurance Research Database in Taiwan from 2004 to 2013. Each patient who took PPIs was assigned to the PPI group, whereas 1:1 sex-, age-, and drug index date-matched randomly selected patients without PPI prescription were assigned to the non-PPI group. We analyzed the risk of incident asthma using Cox proportional hazard regression models, including sex, age, urbanization, low income, and comorbidities. Sensitivity and subgroup analyses were also conducted. A total of 8499 cases were identified as PPI‐treated patients, and 8,499 subjects were included in the control group of PPI non‐users. After adjusting for sex, age, urbanization, low income, and comorbidities, PPI user was associated with a 1.18-fold (HR: 1.18; 95% CI: 1.05–1.34) increase for incident asthma in patients with CAD. We concluded that PPI use increased the risk of incident asthma in patients with CAD. The risk of incident asthma should be considered when weighing the benefits and risks of PPI and aspirin treatment in patients with CAD in clinical practice.

Childhood food insecurity and incident asthma: A population-based cohort study of children in Ontario, Canada

Background Childhood food insecurity has been associated with prevalent asthma in cross-sectional studies. Little is known about the relationship between food insecurity and incident asthma. Methods We used administrative databases linked with the Canadian Community Health Survey, to conduct a retrospective cohort study of children <18 years in Ontario, Canada. Children without a previous diagnosis of asthma who had a household response to the Household Food Security Survey Module (HFSSM) were followed until March 31, 2018 for new asthma diagnoses using a validated administrative coding algorithm. We used multivariable Cox proportional hazard models to examine the association between food insecurity and incident asthma, and adjusted models sequentially for clinical and clinical/socioeconomic risk factors. As additional analyses, we examined associations by HFSSM respondent type, severity of food insecurity, and age of asthma diagnosis. Moreover, we assessed for interaction between food security and child’s sex, household smoking status, and maternal asthma on the risk of incident asthma. Results Among the 27,746 included children, 5.1% lived in food insecure households. Over a median of 8.34 years, the incidence of asthma was 7.33/1000 person-years (PY) among food insecure children and 5.91/1000 PY among food secure children (unadjusted hazard ratio [HR] 1.24, 95% CI 1.00 to 1.54, p = 0.051). In adjusted analyses associations were similar (HR 1.16, 95% CI 0.91 to 1.47, p = 0.24 adjusted for clinical risk factors, HR 1.24, 95% CI 0.97 to 1.60, p = 0.09 adjusted for clinical/socioeconomic factors). Associations did not qualitatively change by HFSSM respondent type, severity of food insecurity, and age of asthma diagnosis. There was no evidence of interaction in our models. Conclusions Food insecure children have numerous medical and social challenges. However, in this large population-based study, we did not observe that childhood food insecurity was associated with an increased risk of incident asthma when adjusted for important clinical and socioeconomic confounders.

Circulating MicroRNA: Incident Asthma Prediction and Vitamin D Effect Modification

Of children with recurrent wheezing in early childhood, approximately half go on to develop asthma. MicroRNAs have been described as excellent non-invasive biomarkers due to their prognostic utility. We hypothesized that circulating microRNAs can predict incident asthma and that that prediction might be modified by vitamin D. We selected 75 participants with recurrent wheezing at 3 years old from the Vitamin D Antenatal Asthma Reduction Trial (VDAART). Plasma samples were collected at age 3 and sequenced for small RNA-Seq. The read counts were normalized and filtered by depth and coverage. Logistic regression was employed to associate miRNAs at age 3 with asthma status at age 5. While the overall effect of miRNA on asthma occurrence was weak, we identified 38 miRNAs with a significant interaction effect with vitamin D and 32 miRNAs with a significant main effect in the high vitamin D treatment group in VDAART. We validated the VDAART results in Project Viva for both the main effect and interaction effect. Meta-analysis was performed on both cohorts to obtain the combined effect and a logistic regression model was used to predict incident asthma at age 7 in Project Viva. Of the 23 overlapped miRNAs in the stratified and interaction analysis above, 9 miRNAs were replicated in Project Viva with strong effect size and remained in the meta-analysis of the two populations. The target genes of the 9 miRNAs were enriched for asthma-related Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways. Using logistic regression, microRNA hsa-miR-574-5p had a good prognostic ability for incident asthma prognosis with an area under the receiver operating characteristic (AUROC) of 0.83. In conclusion, miRNAs appear to be good biomarkers of incident asthma, but only when vitamin D level is considered.

Dietary intake of vitamin A, lung function, and incident asthma in childhood

Longitudinal epidemiological data are scarce on the relation between dietary intake of vitamin A and respiratory outcomes in childhood. We investigated whether a higher intake of preformed vitamin A or provitamin β-carotene in mid-childhood is associated with higher lung function and with asthma risk in adolescence.In the Avon Longitudinal Study of Parents and Children, dietary intakes of preformed vitamin A and β-carotene equivalents were estimated by food frequency questionnaire at 7 years of age. Post- bronchodilator forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and forced expiratory flow at 25–75% of FVC (FEF25–75) were measured at 15.5 years and transformed to z scores. Incident asthma was defined by new cases of doctor-diagnosed asthma at age 11 or 14 years.In multivariable adjusted models, a higher intake of preformed vitamin A was associated with higher lung function and a lower risk of incident asthma: comparing top versus bottom quartiles of intake, regression coefficients (95% confidence intervals) for FEV1 and FEF25–75 were, respectively, 0.21 (0.05–0.38; P-trend 0.008) and 0.18 (0.03–0.32; P-trend 0.02); odds ratios (95% confidence intervals) for FEV1/FVC ratio below the lower limit of normal and incident asthma were, respectively, 0.49 (0.27–0.90, P-trend 0.04) and 0.68 (0.47, 0.99; P-trend 0.07). In contrast, there was no evidence for association with β-carotene. We also found some evidence for modification of the associations between preformed vitamin A intake and lung function by BCMO1, NCOR2 and CC16 gene polymorphisms.A higher intake of preformed vitamin A, but not β-carotene, in mid-childhood is associated with higher subsequent lung function and lower risk of fixed airflow limitation and incident asthma.