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

Publication date: Available online 14 January 2019

Source: The Journal of Allergy and Clinical Immunology: In Practice

Author(s): W. Gerald Teague, Monica G. Lawrence, Debbie-Ann T. Shirley, Andrea S. Garrod, Stephen V. Early, Jackie B. Payne, Julia A. Wisniewski, Peter W. Heymann, James J. Daniero, John W. Steinke, Deborah K. Froh, Thomas J. Braciale, Michael Ellwood, Drew Harris, Larry Borish

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.

Results

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

Conclusions

In children with severe, therapy-resistant asthma, BAL granulocyte patterns and infectious species are associated with novel phenotypic features which 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.

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