Wheezing in early childhood : predictive factors for asthma in the 11-year follow-up

Wheezing in infants when they have a lower respiratory tract infection is not uncommon. However, some of these wheezing infants, specifically those requiring hospitalization, are at high risk of later asthma. Identifying at-risk infants would be helpful for monitoring and focusing treatment on the right subjects. In 1992-1993, 100 infants aged 1-23 months were hospitalized for wheezing associated with respiratory tract infection. The baseline data, blood specimens and nasopharyngeal aspirates (NPAs) were collected on entry to the study. As an acute intervention, the clinical responses to racemic adrenaline and salbutamol were evaluated. The asthma and allergy status of the children have been clinically evaluated at the median ages of 4.0 and 7.2 years. In 2004, on average 11 years after the hospitalization for wheezing, 81/100 children attended the clinical follow-up in teenage years, i.e median age of 12.3 years (range 10.9-13.7). Symptoms suggestive of asthma and allergy were recorded and studies on allergy, baseline lung function and bronchial hyper-reactivity (BHR) were performed. Teenage asthma was present in 40 % (32/81) of the children, and 25 % (20/81) of the children had asthma at all three visits and were considered to have persistent childhood asthma (PCA). Most of the children with teenage asthma (90%) or PCA (95%) were sensitized to at least one allergen. Early factors predicting both teenage asthma and PCA were atopic dermatitis (adjusted odds ratios, aORs 3.5 and 4.5, respectively) and the presence of serum specific immunoglobulin E (sIgE) to inhalant allergens (aORs 11.3 and 13.1, respectively) and to wheat (aORs 20.2 and 9.7). Respiratory syncytial virus (RSV) aetiology of early wheezing was associated with a restrictive pattern of lung function, and early atopy and maternal smoking during pregnancy were associated with BHR. Though minor evidence was found that the children with later PCA may respond better to bronchodilators than those children with no PCA, the overall clinical responses to bronchodilators did not differ between these groups. Early exposures to cats and dogs were not associated with the prevalence of teenage asthma or PCA or atopic sensitization in infancy or at teenage. Neutrophil derived serum myeloperoxidase was not associated with later asthma. Children with teenage asthma and children with PCA had higher blood eosinophil (B-EOS) count at the time of wheezing in infancy than their counterparts who did not develop teenage asthma (median 0.41x10 cells/L vs. 0.17x10, p=0.027) or PCA (0.53x10 vs. 0.20x10, p= 0.006). The level of eosinophil cationic protein (ECP) in NPA (NPA-ECP), but not in serum (SECP), was higher in children with PCA than in children with no PCA (926 ng/g vs. 347 ng/g, p=0.013). At least one eosinophilic marker measured in infancy, was elevated (B-EOS ≥0.45 x 10 cells/L or NPA-ECP ≥815.0 ng/g or S-ECP ≥20.0μg/L) in 61% of the children with teenage asthma and in 75% of the children with PCA. In addition, elevated NPA-ECP predicted PCA independently of the presence of early atopic dermatitis (aOR 4.09). In conclusion, a quarter of children hospitalized for wheezing in infancy will suffer from persistent asthma during childhood, and as many as 40 % will have asthma in teenage years. The features known to be related to chronic bronchial asthma, such as eosinophilic inflammation, atopic dermatitis and sensitization to inhalant allergens, are present already in some wheezing infants and in these children, their presence is predictive of later asthma. National Library of Medicine Classification: QW 120, WF 102, WF 141, WF 150, WF 553 Medical Subject Headings: Adolescent; Asthma; Bronchial Hyperreactivity; Bronchiolitis; Bronchodilator Agents; Child; Child, Preschool; Finland; Follow-Up Studies; Hospitalization; Hypersensitivity; Infant; Infant, Newborn; Lung/physiology; Respiratory Function Tests; Respiratory Sounds; Risk Factors; Spirometry Hyvärinen, Mari. Varhaislapsuuden hengenahdistus – Astman riskitekijät 11 vuoden seurannassa. Kuopion yliopiston julkaisuja D. Lääketiede 464. 2009. 128 s. ISBN 978-951-27-1364-6 ISBN 978-951-27-1381-3 (PDF) ISSN 1235-0303