Letters

Asthma and early childhood infectious disease

Infection is trigger rather than cause

Critical time for protective effect of large family on asthma may not be during first year of life

Infection is trigger rather than cause

EDITORThe study by Illi et al is suggestive of a protective role of early upper respiratory tract infections against the development of asthma later in life.¹ Concerning lower respiratory tract infections, a positive association with the development of asthma has been proposed. But as these infections were found to be significantly higher in children with a family history of atopy, Illi et al conclude that they rather represent manifestations of children already predisposed to asthma.

We analysed the preliminary results of a prospective study of infants with bronchiolitis during the first year of life. We enrolled all the 238 infants admitted to two major paediatric departments in Crete from January 1999 to April 2000. The infants were classified as positive or negative for respiratory syncytial virus from the results of a rapid test for respiratory syncytial virus antigen in nasopharyngeal secretions (Abbott Test Pack RSV rapid diagnostic kit). The outcome was evaluated on the basis of annual parental interview. Criteria for classification in the severe recurrent wheezing group included the need for asthma prophylaxis regimens or for admission because of respiratory distress. Among the 133 children who completed their first year of follow-up, the positive group (n=71) did not show any predisposition to develop severe recurrent wheezing. Remarkably, infants negative for respiratory syncytial virus (n=62) seemed to be more prone to severe recurrent wheezing than positive infants (² test, P=0.058; relative risk 1.51 (95% confidence interval 0.975 to 2.34)). Positive family history was significantly more frequent in the infants who developed severe wheezing than in those with mild or no wheezing episodes (² test, P<0.01).

The relation of respiratory syncytial virus infection in early life to the later development of asthma has not yet been defined. Both studies indicating respiratory syncytial virus as a risk factor predisposing to asthma through allergic sensitisation, and studies that implicate the virus as responsible for the development of asthma without increasing the risk for allergy have been published. ^{2 3} In our study respiratory syncytial virus infection seems unrelated to subsequent development of severe recurrent wheezing in the following year. In agreement with the findings of Illi et al, our findings indicate that severe wheezing in early life occurs more often in predisposed children, and infection is a trigger rather than a cause.

Vassiliki Angelakou, consultant in paediatrics. 
Maria Bitsori, specialist registrar in paediatrics. 
Emmanouil Galanakis, assistant professor of paediatrics. 
Department of Paediatrics, Venizelion and Pananion General Hospital of Heraklion, POB 44, Gr-71 001 Heraklion, Crete, Greece

Critical time for protective effect of large family on asthma may not be during first year of life

EDITORThe paper by Illi et al is in agreement with our prospective study in finding that a report of lower respiratory tract infections in the first year of life is associated with an increased risk of asthma at 7 years of age. ^{1 2} In our prospective study of 863 children followed up from birth to 7 years of age we also found that a history of a cold (upper respiratory tract infection) documented by home interview at one month was also associated with an increased risk of asthma at 7 years of age (adjusted relative risk 1.27 (95% confidence interval 1.05 to 1.53)).

Like the report of runny nose episodes by Illi et al, our outcome was determined by parental report. However, we examined the construct validity of our report on upper respiratory tract infection and found this infection to be positively associated with winter, resident density, maternal smoking, and bottle feeding, suggesting that this report was likely to reflect early upper respiratory tract infection. As Illi et al point out, events in early life have been postulated to be particularly relevant to the subsequent development of atopic disease. Thus our data are not consistent with the concept that viral infection at a critical period in very early life will protect against the subsequent development of asthma.

In the same study we found that the apparent protective effect of larger family size on asthma seemed to be operative at age 7 but not at 1 month and that children with no siblings were more likely to have asthma with an age of onset after 4 years but not earlier. This suggests that the critical time for the protective effect of a large household on asthma is not necessarily during the first year of life.

Anne-Louise Ponsonby, senior fellow. 
National Centre for Epidemiology and Population Health, Australian National University, Canberra ACT, Australia 0200

Andrew Kemp, head. 
Department Immunology, Royal Childrens Hospital, Parkville, Melbourne, Australia 3052