Characterization of wheezing phenotypes in the first 10 years of life.

ABSTRACT

BACKGROUND: Childhood wheezing illnesses are characterized into different phenotypes. However, severity of the disease associated with these phenotypes has not been extensively studied. OBJECTIVES: To determine characteristics of childhood wheezing phenotypes in the first decade of life using health outcomes plus measurements of atopy, lung function and bronchial hyper-responsiveness. METHODS: A whole population birth cohort (n = 1456) was prospectively studied to examine the natural history of childhood wheezing. Children were seen at 1, 2, 4 and 10 years for questionnaire completion and prospectively collected data used to define wheezing phenotypes. Assessment was made of adverse health outcomes plus spirometry, bronchial hyper-responsiveness, serum IgE measurement at 10 years and skin test sensitization at both 4 and 10 years for wheezing phenotypes. RESULTS: Phenotypic analysis identified that 37% early life wheezers (symptom onset by age 4 years) still wheezed at 10 years. These persistent wheezers showed significantly more physician-diagnosed asthma in early life (P < 0.005 at 2 years) than early transient wheezers (wheezing transiently with onset by age 4 years). Overall they experienced greater multiple hospital admissions (P = 0.024), specialist referral (P = 0.009) and use of inhaled (P < 0.001) and oral steroids (P < 0.001) than early transient wheezers. They also demonstrated enhanced bronchial hyper-responsiveness compared with early transient wheezers (P < 0.001). However, both groups of early life wheezers showed impairment of baseline lung function at 10 years in comparison with non-wheezers FEV1 (P < 0.029) and FEV1/FVC ratio (P < 0.001) with persistent wheeze and PEF (P = 0.036) with early transient wheeze. Late-onset wheezers (onset from 5 years onwards) had similar BHR to persistent wheezers but maintained normal lung function at age 10 and had lower cumulative prevalence of adverse health outcomes than persistent wheezers. CONCLUSIONS: Persistent wheezing with early childhood onset is associated with substantial morbidity in the first decade of life in association with high levels of atopy, bronchial hyper-responsiveness and impaired lung function at 10 years of age. Late-onset wheezing in the first decade of life could harbour potential for similarly significant disease subsequently.