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. 2019 Jul-Aug;7(6):1803-1812.e10.
doi: 10.1016/j.jaip.2018.12.027. Epub 2019 Jan 14.

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

W Gerald Teague  1 , Monica G Lawrence  2 , Debbie-Ann T Shirley  3 , Andrea S Garrod  3 , Stephen V Early  4 , Jackie B Payne  3 , Julia A Wisniewski  3 , Peter W Heymann  3 , James J Daniero  4 , John W Steinke  2 , Deborah K Froh  3 , Thomas J Braciale  5 , Michael Ellwood  6 , Drew Harris  7 , Larry Borish  8
Affiliations

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

W Gerald Teague et al. J Allergy Clin Immunol Pract. 2019 Jul-Aug.

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 is 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 bronchoalveolar lavage (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.

Results: Pauci-granulocytic BAL was the most prevalent granulocyte category (52%), and children with pauci-granulocytic BAL had less postbronchodilator airflow limitation, less blood eosinophilia, and less detection of BAL enterovirus compared with children with mixed granulocytic BAL. Children with isolated neutrophilia BAL were differentiated by less blood eosinophilia than those with mixed granulocytic BAL, but greater prevalence of potential bacterial pathogens compared with those with pauci-granulocytic BAL. Children with isolated eosinophilia BAL had features similar to those with mixed granulocytic BAL. Children with mixed granulocytic BAL took more maintenance prednisone, and had greater blood eosinophilia and allergen sensitization compared with those with pauci-granulocytic BAL.

Conclusions: In children with severe, therapy-resistant asthma, BAL granulocyte patterns and infectious species are associated with novel phenotypic features that can inform pathway-specific revisions in treatment. In 32% of children evaluated, BAL revealed corticosteroid-refractory eosinophilic infiltration amenable to anti-TH2 biological therapies, and in 12%, a treatable bacterial pathogen.

Keywords: Asthma phenotypes; Bronchoalveolar lavage; Severe asthma.

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Figures

Figure 1.
Figure 1.
Consort plot and schematic of the geographic source and clinical assessment, treatment, characterization procedures, and indications for diagnostic bronchoscopy in the study sample.
Figure 2.
Figure 2.
Prevalent BAL granulocyte patterns and corresponding clinical features
See this image and copyright information in PMC

Comment in

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