Outcome of asthma and wheezing in the first 6 years of life: follow-up through adolescence

Abstract

Rationale: The effect of early life wheezing on respiratory function and continued symptoms through adolescence has not been fully described. Using data from a population-based birth cohort in Tucson, Arizona, we previously described four phenotypes based on the occurrence of wheezing lower respiratory illnesses before age 3 yr and active wheeze at age 6 yr: never wheezers (n = 425), transient early wheezers (n = 164), persistent wheezers (n = 113), and late-onset wheezers (n = 124).

Objective: We sought to determine the prognosis for these phenotypes, with reference to lung function and symptoms, through adolescence.

Methods: Current wheeze was assessed by questionnaire, lung function was measured by conventional spirometry, and atopy was determined by skin prick tests.

Results: The prevalence of atopy and wheeze by age 16 yr was similar for never and transient wheezers and for persistent and late-onset wheezers. Both transient early, and persistent wheezers had significantly lower FEF(25-75) (-259 ml/s, p < 0.001, and -260 ml/s, p = 0.001, respectively), FEV1 (-75 ml, p = 0.02, and -87 ml, p = 0.03, respectively), and FEV1:FVC ratio (-1.9%, p = 0.002, and -2.5%, p = 0.001, respectively) through age 16 yr compared with never wheezers. Late-onset wheezers had levels of lung function similar to those of never wheezers through age 16 yr. There was no significant change in lung function among subjects with any of the four phenotypes, relative to their peers, from age 6 to 16 yr.

Conclusion: Patterns of wheezing prevalence and levels of lung function are established by age 6 yr and do not appear to change significantly by age 16 yr in children who start having asthma-like symptoms during the preschool years.

Figure 1.

Study flow chart. Definitions of the preschool wheeze phenotypes were previously published (5) and are defined as follows: no wheeze from birth to age 6 yr (never wheeze), wheezing lower respiratory illness (LRI) before age 3 yr only (transient early wheeze), wheeze at age 6 yr only (late-onset wheeze), and wheezing LRI before age 3 yr and wheeze at age 6 yr (persistent wheeze). FEF_25–75 = forced expiratory flow between 25 and 75% of the FVC; V̇maxFRC = maximal expired flow at functional residual capacity.

Figure 2.

Prevalence of infrequent and frequent wheeze at ages 8, 11, 13, and 16 yr for the preschool wheeze phenotypes. The preschool wheeze phenotypes were defined as follows: no wheeze from birth to age 6 yr (never wheeze, NW), wheezing LRI before age 3 yr only (transient early wheeze, TEW), wheeze at age 6 yr only (late-onset wheeze, LOW), and wheezing LRI before age 3 yr and wheeze at age 6 yr (persistent wheeze, PW). Group sample sizes at each age are listed below the acronyms.

Figure 3.

Cross-sectional z scores of height-adjusted maximal expiratory flows at ages 2.4 mo and 6, 11, and 16 yr for the preschool wheeze phenotypes. The preschool wheeze phenotypes were defined as follows: no wheeze from birth to age 6 yr (never wheeze), wheezing LRI before age 3 yr only (transient early wheeze), wheeze at age 6 yr only (late-onset wheeze), and wheezing LRI before age 3 yr and wheeze at age 6 yr (persistent wheeze). One-way analysis of variance with Bonferroni's multiple comparison test was used to assess differences between groups. Sample sizes for each of the preschool wheeze phenotypes (never wheeze, transient early wheeze, late-onset wheeze, and persistent wheeze) were as follows: at 2.4 mo, n = 67, 21, 21, and 16; at age 6 yr, n = 260, 104, 81, and 81; at age 11 yr, n = 266, 113, 84, and 78; and at age 16 yr, n = 206, 91, 69, and 56, respectively. *p < 0.001 compared with never wheeze; ^†p = 0.03 compared with never wheeze; ^‡p = 0.002 compared with never wheeze; ^δp = 0.02 compared with never wheeze.