Sears MR, Greene JM, Willan AR. N Engl J Med. 2003;349:1414–1422
Purpose of the Study.
To describe risk factors that may predict the severity and duration of childhood asthma in adult life.
A complete birth cohort of 1390 children born between April 1972 and March 1973 in Dunedin, New Zealand, was studied. Of those children, 1037 (91%) were present for the follow-up assessment at 3 years.
The children were examined every 2 years from 3 to 15 years of age and then at 18, 21, and 26 years. Respiratory questionnaire assessment and pulmonary function testing were performed at ages 9, 11, 13, 15, 18, 21, and 26 years and methacholine challenge testing was performed at all except the 18- and 26-year visits, when bronchodilator responses were studied. Allergic diathesis was measured with immunoglobulin E assays at 11 years, skin tests at 13 years, and both at 21 years.
A total of 613 patients (59%) provided data at every assessment. Seventy-three percent reported ≥1 episode of wheezing, whereas 51% reported >1 episode of wheezing. At age 26 years, 27% of the cohort was currently wheezing, with 15% experiencing persistent symptoms and 12% relapsing after a symptom-free period. The predictors of persistent wheezing included severity of house dust mite sensitivity, increased bronchial hyperreactivity, smoking at 21 years of age, and earlier age of symptom onset. Pulmonary function test results were consistently lower for patients with persistent wheezing and those who experienced relapses. The degree of pulmonary function abnormality was measured as the forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio. Among male patients with persistent wheezing, those who experienced relapses began with a FEV1/FVC ratio of 82% at 9 years of age, which decreased to ∼75% by 26 years of age. Similar but less profound abnormalities were seen in the female cohort. Patients with no wheeze ever, intermittent wheezing, or transient wheezing maintained FEV1/FVC ratios at or just below 85% through the study.
More than 5% of children who wheezed experienced persistence of symptoms into adulthood. The abnormalities in pulmonary function among patients with persistent wheezing and relapse of wheezing occurred early in life (<9 years of age) and persisted throughout life. Patients with transient wheezing or resolved wheezing did not experience progressive loss of lung function.
These data confirm that early airway damage attributable to infection, allergen exposure, or both may lead to abnormalities in pulmonary function that persist throughout life. The chance to intervene in asthma may well occur before our patients are able to tell us that they have any difficulty breathing.