Lung Lavage Granulocyte Patterns and Clinical Phenotypes in Children with Severe, Therapy-Resistant Asthma

Abstract

Background: Children with severe asthma have frequent exacerbations despite guidelines-based treatment with high-dose corticosteroids. The importance of refractory lung inflammation and infectious species as factors contributing to poorly-controlled asthma in children are poorly understood.Objective: To identify prevalent granulocyte patterns and potential pathogens as targets for revised treatment, 126 children with severe asthma underwent clinically-indicated bronchoscopy.Methods: Diagnostic tests included BAL for cell count and differential, bacterial and viral studies, spirometry, and measurements of blood eosinophils, total IgE, and allergen-specific IgE. Outcomes were compared among 4 BAL granulocyte patterns.

Hypersensitivity Reactions: An Everyday Occurrence in Pediatric Allergy Clinics

“…It is probable this pediatric nonallergic phenotype is several distinct phenotypes, but studies are limited, although starting to emerge, but usually limited to ''refractory/chronic'' patients (Table 12). 40 This recent report of lavage data in therapyresistant children suggest there are several less typical pediatric phenotypes and also provides a summary of existing reports of phenotypic differentiation that has been published. 40 Data in adults often characterize less or (non-) Type 2 asthma.…”

Bronchoscopy in severe childhood asthma: Irresponsible or irreplaceable?

“…Ullman et al were the first to prospectively and rigorously analyze surrogate markers of airway inflammation in children with severe asthma, concluding that “peripheral blood counts are not reliable in characterizing airway inflammation in severely asthmatic children exposed to high dose steroid therapy, therefore bronchoscopy with BAL should be considered.” More recently, Ribeiro et al demonstrated similar discordance between blood and BAL eosinophils, also highlighting the possibility that the analysis of BAL eosinophils may help to identify patients who might be candidates for anti‐IL‐5 therapy despite having blood values outside the recommended parameters for treatment. Similarly, Teague et al concluded that “in 32% of children evaluated, BAL revealed corticosteroid‐refractory eosinophilic infiltration amenable to anti‐T H 2 biological therapies.” While data from these studies are insufficient to routinely inform treatment changes at present, ongoing investigations may identify a larger role in the assessment of lower airway inflammation in clinical care. Indeed, recent reports suggest that analysis of inflammatory patterns in bronchial biopsies may be useful in predicting future lung function …”

“…Those groups who have chosen to employ the procedure typically reserve it for the minority of patients who fail standard therapy. For example, Teague et al recently reported their experience over a 9‐year period. Of approximately 2800 children referred to their asthma center for management, 311 underwent bronchoscopy after failing guideline‐based treatment; 185 were found to have an alternate diagnosis causing persistent symptoms, while 126 retained the primary diagnosis of asthma.…”

“…Of approximately 2800 children referred to their asthma center for management, 311 underwent bronchoscopy after failing guideline‐based treatment; 185 were found to have an alternate diagnosis causing persistent symptoms, while 126 retained the primary diagnosis of asthma. Although this and other studies have documented the safety of bronchoscopy in childhood asthma, studies demonstrating clinical efficacy are still lacking . In this section, we briefly discuss specific conditions for which we believe bronchoscopy may have immediate, or at the very least expectant, applications.…”

“…The methods described by Good et al 21 were not widely adopted by other clinicians at the time, in part, because some of the phenotypes lacking. [31][32][33] In this section, we briefly discuss specific conditions for which we believe bronchoscopy may have immediate, or at the very least expectant, applications. In a similar manner, we and others have long proposed that subacute fungal infection may contribute to severe asthma, although proof of such infection has remained elusive.…”