An increased asthma risk continued until young adulthood after early-childhood hospitalisation for wheezing.

AIM: The aim of this cohort study was to evaluate doctor-diagnosed and self-reported asthma in young adults after early-childhood hospitalisation for wheezing. METHODS: In this prospective-controlled follow-up, questionnaires were sent to 95 subjects aged 24-28 years, who had been hospitalised for their first episodes of wheezing under 24 months of age. Fifty-eight cases and 100 controls returned the questionnaires. RESULTS: The risk of doctor-diagnosed asthma was 2.14-fold (95% confidence interval 0.61-7.41), and the risk of self-reported asthma 2.39-fold (1.14-4.99) in cases compared to controls. The increased risk of self-reported asthma remained as statistically significant in analyses adjusted for current smoking, overweight and allergic rhinitis. Study subjects presented with wheezing symptoms, use of bronchodilators and inhaled corticosteroids, and with seasonal symptoms presumptive for allergic rhinitis during the last 12 months, more often than controls. The identification of a respiratory syncytial virus or rhinovirus during hospitalisation in early childhood was not anymore associated with asthma risk in adulthood. As expected, previous asthma during early childhood was a strong risk factor for asthma in young adulthood. CONCLUSION: In this controlled questionnaire study, early-childhood hospitalisation for lower respiratory infection with wheezing was an independently significant risk factor of asthma in young adults.

Long-term health-related quality-of-life data in subjects with a history of wheezing in early childhood.

Background: Wheezing in early childhood has implications for respiratory morbidity in later life. Objectives: We evaluated respiratory health-related quality of life (HRQoL) in young adults ages 17-20 years with a history of early childhood wheezing. Methods: Between 1992 and 1993, 100 children ages < 24 months were treated in the hospital for a lower respiratory tract infection with wheezing, and we followed up this cohort. In 2010, 49 of the patients (cases) and 60 population-based controls attended a clinical follow-up. St. George's Respiratory Questionnaire (SGRQ) was used to evaluate respiratory HRQoL, expressed as symptom, activity, impact, and total scores. Results: The median (interquartile range) SGRQ symptom scores were higher (13.7 [3.8-29.1]) in the 49 subjects (cases) with early childhood wheezing compared with the 60 population controls (7.8 [0.0-18.3]; p = 0.019). However, there were no between-group differences in total scores or in other SGRQ domains. Current asthma was a major risk factor for reduced HRQoL. In univariate analyses, the median symptom scores were 20.2 in those with asthma and 7.8 in those without asthma (p < 0.001), and, in multivariate analyses, the odds ratio (OR) was 8.7 for high total scores (95% confidence intervals, 2.1-36.6). Other factors associated with reduced HRQoL were current allergy (OR 4.4 for symptom scores), overweight (OR 3.3 for activity scores), tobacco smoking (OR 4.3 for symptom scores), and female sex (OR 3.2 for impact score). Furthermore, we performed post hoc analyses by excluding those with asthma and those who smoked, and found no significant differences on SGRQ scores between the subjects (cases) and the controls. Conclusion: Hospitalization for wheezing in early childhood mainly had indirect effects on HRQoL by increasing the risk of asthma.

NKG2D gene variation and susceptibility to viral bronchiolitis in childhood.

BACKGROUND: Genetic factors associated with bronchiolitis are inadequately characterized. We therefore inspected a selected subpopulation of our previous genome-wide association study (GWAS) of bronchiolitis for overlap with known quantitative trait loci (QTLs) to identify susceptibility loci that potentially affect mRNA and protein levels. METHODS: GWAS included a Finnish-Swedish case-control population (n = 187), matched for age and site. We integrated GWAS variants (p < 10-4) with QTL data. We subsequently verified allele-specific expression of identified QTLs by flow cytometry. Association of the resulting candidate loci with bronchiolitis was tested in three additional cohorts from Finland and Denmark (n = 1201). RESULTS: Bronchiolitis-susceptibility variant rs10772271 resided within QTLs previously associated with NKG2D (NK group 2, member D) mRNA and protein levels. Flow cytometric analysis confirmed the association with protein level in NK cells. The GWAS susceptibility allele (A) of rs10772271 (odds ratio [OR] = 2.34) corresponded with decreased NKG2D expression. The allele was nominally associated with bronchiolitis in one Finnish replicate (OR = 1.50), and the other showed directional consistency (OR = 1.43). No association was detected in Danish population CONCLUSIONS: The bronchiolitis GWAS susceptibility allele was linked to decreased NKG2D expression in the QTL data and in our expression analysis. We propose that reduced NKG2D expression predisposes infants to severe bronchiolitis.

No association between overweight and asthma or allergy in adolescence after wheezing in infancy.

AIMS: The aim of the study was to evaluate the association between weight status and asthma, allergy and respiratory symptoms in adolescents with bronchiolitis in infancy. SUBJECTS AND METHODS: At age 15-18 years, a questionnaire was sent to 96 study subjects hospitalized for wheezing at age <24 months and followed up subsequently. Sixty-seven (70%) of them answered. Weight and height data for body mass index (BMI) calculation were available in 60 (63%) cases. Asthma, allergy, respiratory symptoms and the use of asthma medication were compared between overweight or obese and normal weight groups constructed by age- and sex-specific BMI standard deviation scores (BMI-SDS). Population controls matched for sex, and birth month and place, were recruited for this study phase at age 15-18 years. RESULTS: Eleven (18.3%) study subjects were overweight (BMI-SDS >0.78 in males and >1.16 in females) and only 3 (5.0%) were obese (BMI-SDS >1.70 in males and >2.10 in females) at 16.5 (median) years of age. Overweight or obesity had no significant association with doctor-diagnosed or self-reported asthma, allergy or the use of inhaled corticosteroids. The negative results were confirmed by adjusted analyses. CONCLUSION: Weight status had no association with asthma or allergy in adolescence after wheezing in infancy.

Viral wheezing in early childhood as a risk factor for asthma in young adulthood: A prospective long-term cohort study.

Background and Aims: There is an increased risk of asthma after viral wheezing episodes in early childhood, but unfortunately, prospective longitudinal data until adulthood are mostly lacking. The aim of this cohort study was to evaluate the risk of asthma in young adulthood after hospitalization for viral wheezing episodes in early childhood. Methods: The original cohort comprised 100 individuals aged <24 months who were hospitalized for viral wheezing episodes in 1992-1993. After the index episode, data on a diagnosis of asthma 1 year later and at median ages of 4.0, 7.2, and 12.3 years were recorded in follow-up visits. Forty-nine individuals attended the latest follow-up visit at the age of 17-20 years. Current asthma was diagnosed based on symptoms at the time of the last follow-up, use of inhaled corticosteroids and peak expiratory flow monitoring. Results: A total of 26 (53%) of the 49 cohort individuals had asthma at a mean age of 18.8 years. In multivariate analyses, a diagnosis of asthma 1 year after index hospitalization and at ages 4.0, 7.2, and 12.3 years were significant risk factors for current asthma (adjusted odds ratios [aORs] of 7.13, 8.86, 8.05, and 21.16, respectively). Atopic dermatitis in infancy (aOR: 4.20) and eosinophilia on admission (5.18) were also significant predictive factors for asthma. Conclusion: Over half (26/49) of the participants who had been hospitalized for viral wheezing episodes in early childhood had asthma in young adulthood. An asthma diagnosis at any age during childhood, as well as eosinophilia in early childhood, were independent significant predictive factors for asthma.

Genome-Wide Association Study of Polymorphisms Predisposing to Bronchiolitis.

Bronchiolitis is a major cause of hospitalization among infants. Severe bronchiolitis is associated with later asthma, suggesting a common genetic predisposition. Genetic background of bronchiolitis is not well characterized. To identify polymorphisms associated with bronchiolitis, we conducted a genome-wide association study (GWAS) in which 5,300,000 single nucleotide polymorphisms (SNPs) were tested for association in a Finnish-Swedish population of 217 children hospitalized for bronchiolitis and 778 controls. The most promising SNPs (n = 77) were genotyped in a Dutch replication population of 416 cases and 432 controls. Finally, we used a set of 202 Finnish bronchiolitis cases to further investigate candidate SNPs. We did not detect genome-wide significant associations, but several suggestive association signals (p < 10-5) were observed in the GWAS. In the replication population, three SNPs were nominally associated (p < 0.05). Of them, rs269094 was an expression quantitative trait locus (eQTL) for KCND3, previously shown to be associated with occupational asthma. In the additional set of Finnish cases, the association for another SNP (rs9591920) within a noncoding RNA locus was further strengthened. Our results provide a first genome-wide examination of the genetics underlying bronchiolitis. These preliminary findings require further validation in a larger sample size.

Adolescent asthma after rhinovirus and respiratory syncytial virus bronchiolitis.

BACKGROUND AND AIMS: Asthma risk is increased after bronchiolitis in infancy. Recent studies have suggested that the risk may be dependent on the causative virus. The aim of the study was to evaluate the asthma risk in adolescence in subjects hospitalized for rhinovirus or respiratory syncytial virus (RSV) bronchiolitis in infancy. SUBJECTS AND METHODS: At the median age of 16.5 years, a questionnaire was sent to 96 study subjects hospitalized for bronchiolitis at <24 months of age and since then prospectively followed-up. Sixty-seven (70%) returned the fulfilled questionnaire. RSV and rhinovirus etiology of bronchiolitis had been studied in serum and respiratory samples obtained on admission in infancy. The occurrence of asthma was compared between former bronchiolitis patients and population controls recruited for this study in adolescence. RESULTS: Doctor-diagnosed asthma was present in 30% of former bronchiolitis patients and in 5% of controls (OR 7.9, 95% CI 3.3-19.3). The respective figures for self-reported asthma were 64% and 11% (OR 14.7, 95% CI 7.2-30.0). Self-reported asthma was more common in the former rhinovirus than RSV patients (83.3% vs. 47.6%, P = 0.023, mixed infections included; 81.3% vs. 50%, P = 0.067, mixed infections excluded). CONCLUSIONS: Patients hospitalized for RSV and rhinovirus bronchiolitis at <24 months of age had an increased asthma risk at 15-18 years of age compared with population controls. Within the former bronchiolitis group, the risk of self-reported asthma was higher after non-RSV versus RSV and after rhinovirus versus non-rhinovirus bronchiolitis.

Respiratory morbidity in adulthood after respiratory syncytial virus hospitalization in infancy.

A prospective >25-year follow-up study evaluated the outcome of patients hospitalized for respiratory syncytial virus (RSV) infection at <24 months of age. Questionnaires were sent to 51 study subjects and to population controls. Self-reported asthma was present in 30% of the former RSV patients, compared with 3.8% of controls. In adjusted analyses, RSV hospitalization was an independent risk factor of adulthood asthma.