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.