Affiliations: Hartford, CT
Dr. Cloutier is Professor of Pediatrics, University of Connecticut Health Center, and Director, Asthma Center and Easy Breathing, Connecticut Children’s Medical Center.
Correspondence to: Michelle M. Cloutier, MD, Professor of Pediatrics, Connecticut Children’s Medical Center, 282 Washington St, Hartford, CT 06106; e-mail: firstname.lastname@example.org
In this issue of CHEST (see page 791), Le Bourgeois and colleagues from Hôpital Necker- Enfants Malades in Paris, France describe the BAL cell profiles of 83 young children aged 4 to 32 months with wheezing. These children were identified retrospectively from a bronchoscopy database. All children had had recurrent wheezing associated with at least monthly oral corticosteroid therapy and had poorly responded to inhaled corticosteroid therapy. BAL was performed at least 15 days after an acute exacerbation and at least 15 days after a short course of oral steroids. Viral cultures were obtained in two thirds of the wheezing children, and bacterial cultures were obtained in one third of the wheezing children. Positive viral culture findings were found in 9 of the infants, and positive microbiologic culture findings were found in 18 of the infants; thus, 41% of the children tested had either a positive viral or a positive microbiologic culture finding (assuming no overlap). Seventeen children with nonwheezing pulmonary diseases were used as control subjects. Compared to these control children, the authors found an increased cell count and an increased percentage and absolute neutrophil count in infants with wheezing regardless of the presence of bacteria and/or viruses. The authors also found a low number and percentage of eosinophils, with no difference between children with wheezing and control subjects.
In adults, BAL studies have improved the understanding of the pathophysiology of asthma. In general, adults with asthma have increased total cells, increased lymphocytes, and increased eosinophils, all believed to contribute to the airway inflammation characteristic of this disease. In children, and especially in young children (< 2 years old) with wheezing, only a small number of studies have been performed. While there is little reason to suspect that older children with asthma will have BAL cell profiles different from those in adults, there is significant reason to suspect that these cell profiles may be different in young children with wheezing. The pathology and especially the prognosis of wheezing in young children have not been well characterized. Approximately one half of the children with wheezing in infancy and young childhood will no longer be wheezing at 6 years of age.1 The study by Le Bourgeois et al thus represents the single largest study of BAL cell profiles in very young children with wheezing.
Similar to other, smaller BAL studies in children with wheezing, Le Bourgeois et al found increased numbers of cells and increased neutrophils in BAL samples. This finding has now been confirmed in at least three other BAL studies in young children with wheezing.2–4 And despite the limitations of this study, it suggests that neutrophil-induced inflammation is important in the early stages of wheezing in infants. While it is possible that this neutrophil influx is due to unrecognized infection (and 41% of the children in this study had either a positive viral or microbiologic culture finding), the authors report no relationship between the degree of neutrophilia and the present of a positive microbiologic or virologic culture finding.
BAL eosinophilia is a common finding in adults with asthma. Eosinophilia and elevated IgE levels in cord blood have also been found in infants who subsequently have asthma develop. The results of the BAL eosinophilia are thus surprising. BAL specimens, however, contain those cells that have “escaped” from the lung, and caution must be used in interpreting the results of the BAL in terms of processes occurring in the lung parenchyma. In addition, there is some apparent disagreement on the presence of increased eosinophils in BAL specimens between the three reports in young children. On further inspection, however, the differences in eosinophils in BAL specimens in wheezing children compared to children without wheezing appear to be small and, thus, eosinophilic influx does not appear to be as important as neutrophils in the inflammatory response in the airways of these children. The children were also slightly older in the study by Marguet et al,2 suggesting that eosinophil influx could occur later in the development of asthma. Finally, all of these children had received multiple courses of oral steroids and at least one course of inhaled corticosteroids, which could have affected the eosinophil counts in the lung.
There are significant limitations to this study, and the results must be viewed with caution. The most significant limitation is the retrospective nature of the study. Thus, there were not clear-cut entry criteria, and the children undergoing bronchoscopy have different clinical symptoms, past history, and previous therapy. They represent a diverse group of etiologies for wheezing; because only those with unsuccessful therapy underwent bronchoscopy, they may not be representative of wheezing illnesses in young children. Nevertheless, the results of Le Bourgeois et al are similar to those reported in a smaller, prospective study4 of young children of similar age with prolonged wheezing.
There are few large studies of BAL profiles in children with respiratory diseases. In part, this is because most pediatric pulmonologists are very conservative in whom they perform bronchoscopy. Universal standards for BAL for children have not been developed, and despite technological advances, suction channels in pediatric bronchoscopes are small and frequently plug with contamination by upper airway secretions. Some of the bacteriologic data are therefore difficult to interpret. Most specialists and institutional review boards are hard-pressed to approve bronchoscopic examination in otherwise well, young children, which limits the control group for all of these studies. The control group in this study consisted of children with nonwheezing respiratory disorders. It is difficult to say that these children are “true” control subjects.
This study raises an important point and asks a number of important questions. Clearly, airway inflammation is present in very young children with wheezing, particularly those who fail to respond to oral and inhaled corticosteroids. Similar to adults, the inflammation is characterized by an increase in total number of cells. In contrast to adults, however, younger children with wheezing have fewer eosinophils and more neutrophils. Whether this is due to differences in the pathologic processes responsible for wheezing in young children, to differences in the stage of developing asthma, or to the previous exposure to corticosteroids is not known. Longitudinal studies of young children with prospective follow- up are needed to identify the inflammatory processes that predispose to the development of chronic asthma. Thus, this study by Le Bourgeois and colleagues is a place to start.
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