The challenge of managing wheezing in infants.

Around the world, thousands of times a day, an infant 6 to 8 months old with a runny nose, a cough, and wheezing arrives in a pediatrician’s office or an outpatient clinic. In Western countries about one in three children has at least one episode of wheezing before his or her third birthday.1 Even with all these wheezy children, we still do not know the answers to a number of basic questions. What is the cause and type of the wheezing illness in an individual child? What does it portend for the future of this child? How should it be treated? A first episode of wheezing is usually triggered by a viral infection. If respiratory distress occurs along with this episode, the condition is labeled bronchiolitis. The diagnosis is even firmer if there is also evidence of infection with respiratory syncytial virus (RSV). In many children, a first episode is followed by more symptoms. Based on the occurrence of symptoms, two general patterns of wheezing can be distinguished: episodic and unremitting wheeze (Fig. 1). Episodic wheezing is defined as wheezing in discrete episodes of 2 to 4 weeks in duration, with the child being well in between episodes.2 The trigger is usually a viral infection. In unremitting wheezing, the child has distinct episodes of wheezing but between these severe episodes also has intermittent symptoms, such as coughing or wheezing at night or in response to exercise, crying, laughter, mist, or cold air. Viral infections are also the most common causes of these severe episodes, but they may persist in the presence of other triggers, such as passive smoking, allergen exposure, or air pollution. Consequently, this wheezing phenotype has also been termed multitrigger wheezing.2 The wheezing phenotypes can sometimes be hard to distinguish and can change as children grow older: episodic wheezing may give way to unremitting wheezing and vice versa, depending on environmental exposures and stages of development.3 Episodic wheezing is usually not associated with atopy and rarely progresses to asthma. In contrast, unremitting wheezing in children of preschool age is often associated with atopic sensitization as early as the first year of life. These children often have allergies to foods such as hen’s eggs and cow’s milk. Many of these children have atopic dermatitis or sensitization to indoor allergens, with subsequent development of impaired lung function.1 By the time they are in school, we call their disease asthma. It is the progression from episodic to unremitting and atopic wheezing that allows such classification — not the clinical presentation at the first episode. If it were only that simple. Unremitting wheezing may also occur after the development of RSVinduced bronchiolitis and has also been associated with early and repetitive rhinovirus infections.4 Environmental exposures affecting airway growth, such as prenatal exposure to tobacco smoke and environmental air pollution, are associated with decreased postnatal lung function5,6 and with unremitting preschool wheezing. Chronic lung disease of infancy after premature birth, a separate entity that involves considerable developmental disturbance of the lung, becomes manifest with episodic or unremitting wheezing in the preschool years.7 This etiologic heterogeneity makes it difficult to interpret therapeutic trials involving preschool children. If children with wheezing are enrolled in a study, it is likely that they represent a spectrum of wheezing phenotypes. For example, if children with a first episode of wheezing are studFigure 1 (facing page). Management of Preschool Wheezing Disorders.