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. CONCLUSION: 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.

Elevated Exhaled Nitric Oxide in Adolescents Is Associated With Incident Allergic Symptoms: A Prospective Cohort Study.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is a marker of type-2 inflammation in the airways. Elevated FeNO may precede the development of allergic disease. The aim of the present study was to investigate the association between elevated FeNO and the development of allergic symptoms. METHODS: A total of 959 adolescents from the general population and their parents completed a standardized questionnaire. Lung function and FeNO were assessed at baseline. Four years later, 921 of these individuals (96%) completed the same version of the baseline questionnaire. RESULTS: Adolescents with self-reported incident allergic symptoms to cat (n=50) or dog (n=33) had higher baseline FeNO (P<.001) than those without allergic symptoms to cat and dog at both time points (n=776 and n=838, respectively). Adolescents with incident allergic symptoms to pollen did not have elevated baseline FeNO. The adjusted odds ratio (aOR [95%CI]) for incident allergic symptoms to cat was 4.2 (2.2-8.0) times higher if FeNO was >75th percentile (vs <75th percentile) at baseline. This was consistent after exclusion of individuals with reported asthma, wheeze, or rhinitis at baseline (8.6 [3.0-24.1]). CONCLUSION: Elevated FeNO in adolescents was associated with an increased risk of developing allergic symptoms to cat and dog allergens, but not to pollen allergens, after 4 years.

Increased exhaled nitric oxide predicts new-onset rhinitis and persistent rhinitis in adolescents without allergic symptoms.

BACKGROUND: The fraction of nitric oxide in exhaled air (FE(NO)) is increased in rhinitis and asthma. We have previously suggested that elevated FE(NO) levels in the absence of asthma symptoms may be a sign of 'early asthma'. In the present study, we hypothesize that elevated exhaled NO levels may also precede rhinitis symptoms. OBJECTIVE: To investigate in a cohort of adolescents whether or not increased exhaled NO levels at the age of 13-14 years predicted new-onset or persistent rhinitis within a 4-year period. METHODS: A total of 959 randomly selected adolescents (13-14 years) completed a questionnaire on respiratory symptoms at baseline and follow-up, 4 years later. Exhaled NO was measured at baseline. After exclusion of subjects with asthma diagnosis or asthma symptoms at baseline, 657 participants were eligible for the present study. RESULTS: Higher FE(NO) levels at baseline were associated with increased risk for new-onset (P = 0.009) and persistent rhinitis (P = 0.03) within a 4-year period. The risk of new-onset rhinitis was 2.32 (1.23, 4.37) [OR (95% CI)] times higher if FE(NO) > 90th percentile of the group without rhinitis at baseline. This increased risk for new-onset rhinitis was significant [2.49 (1.24, 5.01)] after excluding subjects with allergic symptoms. The risk of persistent rhinitis was 5.11 (1.34, 19.57) times higher if FE(NO) > 90th percentile of the group without rhinitis at baseline. CONCLUSION: Elevated exhaled nitric oxide levels predicted incident and persistent rhinitis in this population-based study of adolescents. Moreover, these findings were consistent after excluding subjects with allergic symptoms. Thus, it appears that elevation of exhaled NO precedes airway symptoms and predicts development of rhinitis in subjects without allergic symptoms or family history of allergic disease.

Exhaled nitric oxide in a population-based study of asthma and allergy in schoolchildren.

Exhaled nitric oxide (NO) reflects inflammation in the lower airways and is well adapted for use in children. The aims of this study were to investigate the distribution of the fraction of expired NO (FENO) in school children and to compare FENO and spirometry in relation to the International Study of Asthma and Allergies in Childhood questionnaire. The study was performed in 959 randomly selected 13-14-year-old school children in Uppsala, Sweden. Exhaled NO was measured at an inhalation rate of 0.1 l/s (FENO0.1) and a spirometric test was performed and data from these measurements were related to questionnaire data. Exhaled NO was measured according to American Thoracic Society recommendations, except the use of a mouth wash and an exhalation flow rate of 0.1 l/s. The distribution of the mean FENO0.1 values was skewed, with a preponderance of very low levels and a widespread tail of values ranging up to 102 parts per billion (ppb). Boys exhibited significantly higher mean FENO0.1 values than girls, 5.2 (4.7-5.7) vs 4.4 (4.0-4.8) ppb (geometric mean and 95% CI), P <0.01). Children who reported wheezing in the last year had higher FENO0.1 values than children that had not, 8.5 (7.1-10.2) vs 4.3 (4.0-4.6) ppb, P <0.001). The same association was found to most symptoms indicating hay fever and eczema. In contrast to this, only weak or inconsistent associations were found between asthma and spirometric indices. Exhaled NO levels were found to be independently related to male gender, wheeze and rhinoconjuctivitis but not to current eczema. In conclusion, exhaled NO was closely associated with reported asthma and allergy symptoms whereas spirometric indices such as percent predicted forced expiratory volume in 1 s were not. As most asthma cases in a population are mild, the findings suggest that exhaled NO is a sensitive marker of asthma and allergy.