Childhood wheeze phenotypes show less than expected growth in FEV1 across adolescence

Am J Respir Crit Care Med. 2014 Jun 1;189(11):1351-8. doi: 10.1164/rccm.201308-1487OC.


Rationale: Better characterization of childhood wheeze phenotypes using newer statistical methods provides a basis for addressing the heterogeneity of childhood asthma. Outcomes of these phenotypes beyond childhood are unknown.

Objectives: To determine if adolescent respiratory symptoms, lung function, and changes in lung function over adolescence differ by childhood wheeze phenotypes defined through latent class analysis.

Methods: A prospective birth cohort (Melbourne Atopy Cohort Study) followed 620 high allergy-risk children, recording respiratory symptoms and spirometry at 12 and 18 years. Regression analyses identified relationships between wheeze phenotypes (never/infrequent, early transient, early persistent, intermediate onset, and late onset) and lung function, change in lung function (12-18 yr), respiratory symptoms, and asthma. The baseline classification was never/infrequent wheeze.

Measurements and main results: Deficits in expected growth of lung function, measured by change in prebronchodilator FEV1 between 12 and 18 years, were found for early persistent (reduced 290 ml; 95% confidence interval [CI], 82-498), intermediate-onset (reduced 210 ml; 95% CI, 62-359), and late-onset wheeze (reduced 255 ml; 95% CI, 69-442). Intermediate-onset wheezers had persistent FEV1 deficit after bronchodilator at 18 years (reduced 198 ml; 46,350). Current asthma risk was increased for all phenotypes except early transient, which was also not associated with lung function deficits at 12 or 18 years.

Conclusions: Persistent wheeze phenotypes in childhood were associated with reduced growth in prebronchodilator FEV1 over adolescence. Intermediate-onset wheezers showed irreversible airflow limitation by 18 years. Conversely, early transient wheeze was a benign condition with no sequelae for respiratory health by age 18.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Asthma / complications
  • Asthma / diagnosis*
  • Asthma / epidemiology
  • Asthma / genetics
  • Asthma / physiopathology*
  • Australia / epidemiology
  • Child
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Forced Expiratory Volume*
  • Humans
  • Hypersensitivity / diagnosis
  • Male
  • Phenotype*
  • Prognosis
  • Prospective Studies
  • Respiratory Sounds / etiology*
  • Respiratory Sounds / physiopathology
  • Risk Factors
  • Spirometry
  • Surveys and Questionnaires
  • Time Factors