In the late 1960s, most forms of childhood wheezing were labeled as asthma (1). Consequently, subjects with asthma or wheezy bronchitis were considered together in the British 1958 cohort, a longitudinal study of all subjects born during a specific week in the United Kingdom (2, 3). Later, Sporik demonstrated, in high-risk infants, that early exposure to mite allergens was critical in the development of atopic asthma (4), but the risk for asthma at school age was not greater in the children who wheezed in the first 2 years of life, suggesting that wheezing disorders of infancy and atopic childhood asthma are two independent disorders. This was confirmed in the German birth cohort, where exposure to high levels of mites in the first years of life was associated with more severe asthma in atopic children at school age and puberty, whereas 90% of children wheezing in the first years of life but not developing atopy lost their symptoms at school age (5). Furthermore, the Tucson cohort demonstrated that infant wheeze and atopy are causally unrelated and that the prevalence of different wheezing phenotypes (transient vs. persistent) is already established by the age of 6 years (6). For this reason, although the cohort described by Marossy and colleagues in this issue of the Journal (pp. 355–359) (7) does not distinguish between the different phenotypes, the fact that patients have been evaluated taking into consideration the threshold of 6 years for wheezing onset and relapse provides important information on long-term prognosis in relation to classical asthma phenotypes (6). Subjects who were wheezing only before the age of 7 represent transient wheezers, and those always wheezing represent true asthmatics.

Three major messages come out from this cohort. First, childhood pneumonia was associated with reduced ventilatory parameters in 35-year-old subjects (3), suggesting that this condition may determine a reduction in the maximal attained lung function. However, in the same subjects, no further pulmonary decline was reported 10 years later (7). These results, together with the previous observation that the age at which a child had pneumonia did not affect pulmonary function in adults (3), and that reduced lung function at birth is a predisposing factor for pneumonia itself before the age of 3 years (8), are strongly suggestive of premorbid low lung function as a predisposing factor for infective lung disease. The alveolar phase of human lung development extends postnatally; therefore, earlier lung injury should be associated with a greater loss of lung function.

Second, young adults who continued to wheeze since childhood had, at age 35 years, baseline spirometry that was worse than in healthy subjects (2), but thereafter no difference was observed between the two groups in the rate of FEV₁ decline. Improved care of wheezing subjects seems to be the most obvious explanation for this slowing down of the negative trend. In fact, in a 10-year follow-up of adults with asthma, treatment with inhaled corticosteroids (ICS) was associated with a lesser decline in FEV₁ compared with non-ICS regimens (9). The first British guidelines on asthma management were published in 1990. Since then, a marked increase in the ratio of ICS to β₂-agonists prescribed to patients with asthma was observed (10). It seems reasonable to speculate that patients enrolled in a long-term study may have benefited the most.

Third, children who manifested symptoms of asthma or wheezy bronchitis limited to the age of 6 years, showed at the age 35 years a slightly lower FEV₁ than healthy peers (2), whereas at the age of 45 years, this group demonstrated the steepest functional decline (7). These transient wheezers, who typically do not become atopic, present from birth the lowest lung function and maintain this characteristic through adolescence according to the Tucson cohort (6), and throughout life according to the British one. It has been previously suggested that in these patients, classically considered to have wheezy bronchitis, there might be the seeds of chronic pulmonary disease (1) and epidemiologic data continue to support this hypothesis.

What can be done? All efforts should be made to prevent intrauterine insults that may perturb lung development. Because a major risk factor for abnormal lung function at birth is maternal smoking during pregnancy, and because the earlier a woman starts smoking, the more likely it is that she will continue to smoke during pregnancy (11), the central responsibility of pediatricians in smoking prevention is evident. Most smokers acquire the habit in their teens; therefore, physicians caring for children have a special opportunity to reduce active smoking in this population. A number of other factors that influence lung growth during fetal life should be carefully controlled by obstetricians and potential risk prevented (12). Such factors include the following: maternal undernutrition (particularly vitamin A); maternal hypertension, which may cause placental hypoxia; oligohydramnios, which complicates about 10% of pregnancies and can be corrected by transabdominal amnioinfusion (to maintain a correct amniontic fluid volume essential for normal lung growth); and glucocorticoid use, which should be carefully monitored. Antenatal glucocorticoids, routinely used to enhance fetal lung maturation in women at high risk of preterm delivery, have not reduced the incidence of bronchopulmonary dysplasia (BDP). Even if this can be attributed to the increased survival of very preterm infants, who are most at risk of BDP, we cannot exclude that this might be related to decreased alveolar septation induced by these drugs.

Similar concerns about using corticosteroids are raised in the treatment of wheezing children. This precaution has to be taken into consideration because alveolar multiplication might not yet be completed and also because this treatment does not seem able to prevent early loss of lung function (13). Therefore, in wheezing that occurs in early life, pharmacologic interventions should be combined with strategies aimed at preventing lung function decline and ameliorating lung growth. In this regard, stringent environmental control measures during pregnancy and early life did not prevent sensitization to indoor allergens but were associated with better lung function in high-risk children at the age of 3 years (14). Furthermore, regular consumption of fresh fruit appears to have a positive effect (15). Of course, a reduction in indoor and outdoor pollutants should also be beneficial (16), but this matter does not concern only obstetricians and pediatricians.

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