Description of the condition
Wheeze is an abnormal, usually high-pitched whistling sound made during breathing, especially during expiration. This sound is produced as the air passes through narrowed airways and is caused by vibration of the airway wall at a site of flow limitation. It is, thus, a marker of narrowing at some point in the airway, as a result of infection, inflammation or other causes of obstruction (e.g. foreign body inhalation). Generalised wheezing in infants and toddlers may be precipitated by various infectious or allergenic agents: commonly viruses, less commonly house dust mite or foods.
Asthma is a chronic condition characterised by the triad of symptoms: wheeze, cough and breathlessness. It is associated with hyper-responsiveness of the airways due to inflammation. At least half of the children who wheeze in infancy grow out of this tendency; however, some go on to develop chronic asthma (von Mutius 2001; Frank 2008; Turner 2008) and the risk of such progression is increased by a family or personal history of atopy.
The exact causes of recurrent wheezing and airway hyper-responsiveness are poorly understood, but they may develop as a response to allergen exposure in susceptible individuals. Infants may be exposed to allergens through their diet in the initial few months of life. In particular, there is some evidence that early exposure to cow's milk, which contains powerful allergens such as beta-lactoglobulin and casein (Taylor 1986; Savilahti 1992) may be associated with the development of allergies in infants (Foucard 1985).
Description of the intervention
In children with a family history of atopy, maternal allergen exposure can be reduced during pregnancy, lactation or both (Zeiger 1989), by periods of exclusive breast feeding (Gruskay 1982; Saarinen 1995; Oddy 1999; Saarinen 2000), and avoidance of potential allergens including food and environmental antigens (Custovic 2001). Exposure to milk protein allergens may be avoided by substituting cow's milk with other hypoallergenic formulae in the infant's diet in the early months of life ( Vandenplas 1992).These 'hypoallergenic' formulae include:
soya-based formulae, which are also somewhat allergenic and may present some cross-reactivity with cow's milk proteins; and
extensively or partially hydrolysed formulae, in which the protein source (cow's milk – casein or whey) has been enzymatically hydrolysed and heat-denatured, resulting in smaller molecules with reduced allergenic potential (Pahud 1985; Mäkinen-Kiljunen 1993; Ragno 1993).
How the intervention might work
Substituting cow's milk with hypoallergenic formulae in the infant's diet might reduce the risk of sensitisation occurring via the infant's immature gut, and thus reduce the risk of atopic and other allergic diseases developing.
Why it is important to do this review
There is sufficient evidence of other benefits of breast feeding that all mothers should be advised to breast feed (Howie 1990; Wilson 1998), and this is not suitable for assessment by randomised controlled trials. However, there will always be some women who are unable, or choose not to breast feed. The choice of formula feed becomes particularly important for these mothers, particularly in infants at high-risk of atopy owing to a family history.
A number of methodological issues complicate the evaluation of the available evidence; many studies have a cohort design and are therefore subject to sampling, and other types of, bias (Kramer 1988).
Two reviews have studied avoidance of cow's milk in infants. Baumgartner 1998 studied the effect of cow's milk avoidance on the development of atopic symptoms (not asthma or wheeze). A Cochrane review that studied the effect of cow's milk avoidance along with a range of other potentially active co-interventions in infants has been withdrawn because it is out of date (Ducharme 2007) and due to concerns over the reliability of one of the included studies. Subsequently, a further large randomised study on this topic has been published. It is therefore appropriate and timely to carry out a new review to study the effect of one specific intervention (cow's milk avoidance in infancy) on the development of wheeze and asthma in children with family history of atopy, and this protocol forms a basis for this endeavour.