Journal Article

Bronchial eosinophils, neutrophils, and CD8 + T cells influence asthma control and lung function in schoolchildren and adolescents with severe treatment-resistant asthma

Faria, Caroline Silvério, de Brito, Jôse Mára, Rodrigues, Joaquim Carlos, Mauad, Thais, Antonangelo, Leila, de Souza Xavier Costa, Natália, Eller, Miriam Cardoso Neves, Pierantozzi Vergani, Karina, Saraiva-Romanholo, Beatriz Mangueira

2022

Overview

Background Studies in adult severe treatment-resistant asthma (STRA) have demonstrated heterogeneous pathophysiology. Studies in the pediatric age group are still scarce, and few include bronchial tissue analysis. Objective We investigated 6–18-year-old patients diagnosed with STRA in Sao Paulo, Brazil, by characterizing the different lung compartments and their correlations with asthma control and lung function. Methods Inflammatory profiles of 13 patients with a confirmed diagnosis of STRA were analyzed using blood, induced sputum, bronchoalveolar lavage, viral and bacterial screens and endobronchial biopsy. Inflammatory cells, cytokines, and basement membrane thickening were tested for correlations with the asthma control test (ACT) and spirometry and plethysmography parameters. Results Endobronchial biopsy specimens from 11 patients were viable for analysis. All biopsies showed eosinophilic infiltration. Submucosal (SM) eosinophils and neutrophils were correlated with worse lung function (pre-BD FEV1), and SM neutrophils were correlated with fixed obstruction (post-BD FEV1). Intraepithelial (IE) neutrophils were positively correlated with lung function (pre-BD sGaw). CD8 + T cells had the highest density in the IE and SM layers and were positively correlated with ACT and negatively correlated with the cytokines IL1β, IL2, IL5, IL7, IL10, IL12, IL17, GCSF, MCP-1, INF-δ, and TNFα in sputum supernatant. The ASM chymase + mast cell density correlated positively with quality-of-life score (pAQLQ) and ACT. Conclusion Eosinophils and SM neutrophils correlated with worse lung function, while IE neutrophils correlated with better lung function. Most importantly, CD8 + T cells were abundant in bronchial biopsies of STRA patients and showed protective associations, as did chymase + mast cells.

• Publisher: BioMed Central,BioMed Central Ltd,Nature Publishing Group,BMC
• Subject: Adolescent / Adult / Asthma / Asthma in children / Basement membranes / Biopsy / Brazil - epidemiology / Bronchoscopy / Bronchus / Care and treatment / CD8 + T cell / CD8 antigen / Cell density / Child / Children / Children & youth / Chymase / Correlation / Cytokines / Density / Endobronchial biopsy / Eosinophils / Eosinophils - pathology / General anesthesia / Granulocytes / Health aspects / Humans / Inflammation / Inflammatory cells profile / Interleukin 10 / Interleukin 12 / Interleukin 17 / Laboratories / Lavage / Leukocytes (eosinophilic) / Leukocytes (neutrophilic) / Lung / Lungs / Lymphocytes / Lymphocytes T / Mast cells / Medicine / Medicine & Public Health / Monocyte chemoattractant protein 1 / Neutrophils / Neutrophils - pathology / Nitric oxide / Patient outcomes / Patients / Pediatrics / Plethysmography / Pneumology/Respiratory System / Quality of life / Respiratory function / Severe asthma / Spirometry / Sputum / Steroids / Streptococcus infections / T cells / T-Lymphocytes - pathology / Teenagers / Thickening / Tissue analysis / Treatment resistance / Tumor necrosis factor-TNF / Tumor necrosis factor-α / Viruses