Nosing out the future asthmatic?
Authors: A. Bush
Journal: Allergy (2000)

“Is it asthma, doctor?” must be among the commonest questions asked by anxious parents of a wheezy child, and the paediatrician dealing with this problem must sigh for a simple answer to a superficially simple quest-ion. According to the simple (and excellent) definition of the Paediatric Consensus Group ( 1), asthma is “wheeze and/or cough in a setting where asthma is likely, and other, rarer, conditions have been excluded”. Therefore, if the child truly is wheezing (and this may be difficult to determine even in English, but much more so in languages with no word for “wheeze” [ 2]), then, by definition, the child has asthma – of a sort. However, it is abundantly clear that the word “asthma” covers a number of phenotypes (Crimi et al. [ 3], Table 1), and that refining my opening question would lead to the supplementary question, “Does my child have the sort of asthma that means his airways are inflamed, and that if he is not treated aggressively, his airways will undergo structural remodelling and later develop fixed airflow obstruction?” The difficulty is that we simply do not know how to answer that question. At one end of the spectrum of the wheezing pheno-types ( 4) are the virus-associated wheezers; they have neither a personal nor a significant family history of atopic disease, and wheeze only with viral colds. There is compelling evidence that the basis of their symptoms lies in prenatal events affecting baseline airway calibre. This evidence includes the detection of airway obstruction soon after birth in infants of mothers who smoked in pregnancy, or were atopic, or, interestingly but inexplicably, had hypertension of pregnancy ( 5-7); the detection of airflow obstruction prior to the first wheezy episode ( 8-10); the absence of an association between bronchial hyperreactivity and wheeze ( 11, 12); the poor response of viral associated symptoms to inhaled corticosteroids ( 13); the lack of airway eosinophilia on blind lavage studies ( 14); and the excellent prognosis for long-term lung function, whatever treatment is given ( 15). At the other extreme is the infant who has atopic dermatitis and perhaps multiple food allergies, with wheezing with viral colds, but also wheezing triggered by dust, furry pets, and other triggers. Even in this group, half will remit by the early school years ( 16). The vast majority of wheezers fall neatly between these extremes, and this makes advising parents and planning treatment sensibly very difficult. Defining the wheezing phenotype is of great practical therapeutic importance. Up to 50% of children wheeze before the age of 6 years. Evidence from a randomized controlled trial in adults ( 17) and observational data in children ( 18) suggest that delay in initiating inhaled corticosteroids may prejudice ultimate lung function. On the other hand, overtreatment with even low-dose inhaled steroids may cause growth failure ( 19), and, according to animal studies, possible reduction in alveolarization in the developing lung ( 20). The obvious way to resolve these difficulties is to find a way of measuring airway inflammation in these small infants. Studies using serum levels of markers such as eosinophil cationic protein have either been unpromising or lacked follow-up for a sufficient length of time to allow a balanced judgement of their importance ( 21, 22). Unfortunately, sputum induction is not feasible in infants, and there are only limited data on the use of nitric oxide in this age group ( 23). Since it is not unreasonable to assume that there is no sudden change at the level of the vocal cords, and the nose is contigu-ous with the bronchial tree, changes in the nose may reflect the lower airway and increase diagnostic pre-cision. A number of groups have used nasal lavage, biopsy, aspirates, brushing, and swabs ( 24-32), and in this issue of Allergy Frischer et al. ( 33) report a nasal lavage study which attempted prospectively to identify infants at risk of developing respiratory symptoms in the first year of life. They are to be congratulated on the large number of infants studied, and their prospective design. However, their study, although admirable, needs to be interpreted with caution at this time. Firstly, the nose is not the bronchus; it is designed to filter out especially particulate materials that are undesirable in the lower airway, and ensure that the variable atmospheric air is warmed and humidified before it reaches the bronchial tree. Although nasal and bronchial biopsy may be similar, at least one study showed important quantitative differences between the two sites in normal and asthmatic adults ( 34). During exercise, the responses of lower airway and nose are different, at least physiologically ( 35). Thus, caution is always warranted before assuming that the bronchus is but the nose in miniature. However, in one respect, nasal studies are easier to interpret than bronchoalveolar lavage, in that indicators such as inulin can be added to nasal lavage fluid to correct for the effects of dilution ( 25, 26); in this context, it is a pity that Frischer et al. ( 33) did not do this. It is also surprising that they did not look at lavage eosinophil counts, as well as eosinophil products. Secondly, it is not clear that sufficient care had been taken to distinguish the different patterns of wheeze described above. One would expect an eosinophilic lavage possibly to predict atopic wheeze, but not virus-associated, noneosinophilic wheeze, and failure to separate the two is likely to reduce the power of any study. Finally, the results of this study will become relevant only in several years' time, when it is clear whether or not there is a correlation between early eosinophilic lavage and atopic asthma in mid-childhood. It is not possible at an early stage to determine the prognosis of even atopic wheezers, half of whom may outgrow their symptoms by the early school years (16). For their data to be useful, Frischer et al. will have to show that their test predicts the onset of wheeze that persists that early treatment is beneficial in preventing wheeze or secondary consequences such as airway remodelling. This will take time. Nevertheless, it is clear that Frischer et al. have commenced a study which must be continued long term, and has the potential to give us very interesting and important information. At follow-up, it will be particularly important to define carefully the various wheezing phenotypes by clinical descriptions, and measurements of bronchial hyperreactivity and, if possible, noninvasive markers of airway inflammation such as induced sputum and exhaled nitric oxide ( 36). It is obvious that questions about long-term prognosis (the most important ones, and the most difficult to answer) can be answered only by a long-term study, which, by definition, takes a long time; and the lack of the passage of time is what weakens this report. Nonetheless, this preliminary report should whet our appetite for more.