Childhood asthma — all that wheezes is not inflammation

Most of us as children will have picked up a telescope or a pair of binoculars the wrong way round to look at an object of interest, which then appeared miniaturized rather than enlarged. The understanding of wheeze in early childhood has been retarded by a very similar approach. The use of fibreoptic bronchoscopy, bronchial biopsy and bronchoalveolar lavage (BAL) has elegantly delineated the T-cell driven, eosinophil-mediated airway inflammation that is the fundamental feature of adult asthma, both atopic and non-atopic [1-4]. These studies have laid the scientific foundation of the early use of anti-inflammatory therapy in asthma [5]. The downside to these studies has been the assumption that wheezy infants are miniaturized adults, and need to be treated in the same way, with early and aggressive use of inhaled steroids. This despite a wealth of evidence that this approach is not useful [6], and may possibly even be dangerous. If any sense is to be made of wheeze in young children, it must be approached not from adulthood downwards, but from before birth, prospectively. The first practical consideration in approaching the wheezing child is to ensure that an alternative diagnosis is not being overlooked. Wheeze literally from the day of birth is never due to any form of asthma, and should prompt a search for structural airway malformations, cysts, vascular ring or primary ciliary dyskinesia. Sudden onset wheeze suggests an endobronchial foreign body. Chronic rhinitis and postnasal drip may cause wheeze, and in particular cough. Associated chronic, especially daily, sputum production or moist cough suggests cystic fibrosis, which is frequently diagnosed late [7], or another pulmonary or systemic problem of host defence. Oesophageal related cause of wheeze include gastro-oesophageal reflux, inco-ordinate swallowing in those with neurological disease, H-type fistula or laryngeai cleft. An interesting (and increasingly large) group is infants wheezing after pre-term birth and neonatal ventilation. In most cases, a detailed history and physical examination, possibly combined with a chest radiograph, will have excluded these and other diagnostic possibilities for all practical purposes. The clinician is left with a ragbag diagnosis of 'baby asthma', and the family want to know about treatment and prognosis (Is it asthma. Doctor? '). How best can the family be advised on the basis of current knowledge? It is very clear that events even before birth can profoundly influence long-term lung health. The factors which may be important include parental smoking during pregnancy and maternal atopic status. Young et al. studied 63 babies using the squeeze technique to measure forced expiratory flow at functional residual capacity at age between 2 and 12 weeks [8]. They performed histamine challenges, and showed reduced PC40 to histamine in infants whose parents were smokers or atopic or both, compared with a control group of babies. More recently, LeSoeuf's group used a non-invasive index of lung function to study 461 babies in the first two days of life, prior to discharge from hospital [9]. They showed altered lung function in the infants of smoking and atopic mothers. The interpretation of these data are controversial, but it is clear that airway development can be adversely affected before birth. The likeliest explanation is that the distal airway generations have developed with reduced calibre in the second half of pregnancy, and thus the child is vulnerable to symptomatic airflow obstruction and wheezing with even minimal amounts of (say) mucosal swelling. Prenatal allergic sensitization to maternal ingested and even aeroallergens may have a role in the later development of atopic asthma [10]. We have learned much about the postnatal natural history of wheeze from the large prospective studies in Tucson, Boston and Perth [11-13]. These groups have shown that infants who wheeze with viral infections have had abnormal lung function, determined prospectively, before their first episode of wheeze. At one extreme, babies with pure viral associated wheeze have symptoms dating from the first year of life solely during viral colds, and are totally well between colds. This group of babies do not have bronchial hyperreactivity and have neither a personal nor a family history of atopy [6]. Many of these babies will grow out of their symptoms, with the possibility that they will be more vulnerable to chronic obstructive airways disease in later life. At the other extreme, babies with atopic eczema or a strong family history of atopic disorders wheeze between colds, with many of the familiar triggers such as cold air and pet and dust exposure. Even in this group, 50% will become asymptomatic by the early school years [14]. A further group of virus associated, non-atopic wheezers, start to manifest at about age two to three years [15]. It would be idle to assume that the pathophysiology of wheeze is the same in these different groups. Allergy is also important in the immediate postnatal period. It is clear that the early months represent a window of particular vulnerability to allergic sensitisation to house dust mite [16] and birch pollen [17]. Intensive intervention may reduce the prevalence of allergic disease [18]. However, wheezing before age 2 did not seem to be related to allergic sensitisation in the main [6,16,19].