Introduction:
Asthma continues to be a leading chronic childhood illness in the US. The prevalence among children less than 18 years of age remains at 7.5%1. Approximately 30 % of wheezy infants and toddlers continue to wheeze at the age of six2. Wheezing in young children includes a heterogeneous group of patients, and whether an infant or a young child is expected to develop asthma remains a challenging clinical question.
In an effort to understand the natural history of asthma, several epidemiological studies have developed different classifications of wheezing phenotypes3,4,5. Using data from the Tucson Children’s Respiratory Study 3, the Asthma Predictive Index6,7 (API) was developed in 2000 to predict the future development of asthma in young preschool children with frequent wheeze. Since then, the API has been well validated and internationally supported in clinical practice as well as in pediatric asthma research8,9. Few studies, however, have been carried out looking at airway inflammation in early childhood, to elucidate the underlying pathophysiology and correlate those findings with what is known about wheezing phenotypes and outcomes10-14.
Based on the current knowledge of the role of airway inflammation in wheezing, anti-inflammatory therapy, specifically inhaled corticosteroids (ICS), remain the first line therapy for persistent asthma in all age groups, including preschool children. ICS are recommended by the National Asthma Education and Prevention Program (NAEPP)15 for daily use in children at high risk for asthma (positive API), and by the Global Initiative of Asthma (GINA) guidelines in its most updated document for all preschool children with recurrent wheezing16. ICS have proven efficacy in controlling inflammation, reducing asthma symptoms and reducing the frequency of exacerbations in this age group. However, they do not modify the long term outcome17. In the case of persistence of symptoms while receiving ICS, a thorough workup is strongly recommended to exclude other causes of wheezing18. This includes flexible bronchoscopy to examine airway anatomy and dynamics and obtain a bronchoalveolar lavage (BAL) for cytology and culture. Utilizing BAL cytology is one of the methodologies that has contributed to understanding the underlying inflammatory processes responsible for asthma and perhaps the structural remodeling that is sometimes seen. In recent years, the role of protracted bacterial bronchitis (PBB) and airway infection in recurrent wheeze has become clearer 19-21. PBB is recently recognized by the European Respiratory Society as one of the most common causes of chronic wet cough in children with or without wheezing in the absence of other underlying causes. It is often misdiagnosed as or found to exacerbate existing asthma leading to increased usage of ICS. It usually responds to treatment with antibiotics of 2-4 weeks duration21.
We undertook this retrospective analysis to clarify the underlying causes of recurrent wheeze in infants and pre-school aged children unresponsive to low to moderate dose ICS treatment and to determine whether the two API (positive and negative) groups differed in their BAL inflammatory profiles. We specifically wished to ascertain whether the risk of PBB differed between these two groups. We hypothesized that eosinophilic inflammation would predominate in the airways of children with positive API compared to neutrophilic inflammation for children with negative API.