Bronchial eosinophils, neutrophils, and CD8 + T cells influence asthma control and lung function in schoolchildren and adolescents with severe treatment-resistant asthma
Abstract 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 P...
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Respiratory Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12931-022-02259-4 |
| _version_ | 1811188221902585856 |
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| author | Miriam Cardoso Neves Eller Karina Pierantozzi Vergani Beatriz Mangueira Saraiva-Romanholo Natália de Souza Xavier Costa Jôse Mára de Brito Leila Antonangelo Caroline Silvério Faria Joaquim Carlos Rodrigues Thais Mauad |
| author_facet | Miriam Cardoso Neves Eller Karina Pierantozzi Vergani Beatriz Mangueira Saraiva-Romanholo Natália de Souza Xavier Costa Jôse Mára de Brito Leila Antonangelo Caroline Silvério Faria Joaquim Carlos Rodrigues Thais Mauad |
| author_sort | Miriam Cardoso Neves Eller |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-11T14:15:59Z |
| format | Article |
| id | doaj.art-8991f0e7c5434013bb8c5844390060f3 |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-04-11T14:15:59Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-8991f0e7c5434013bb8c5844390060f32022-12-22T04:19:25ZengBMCRespiratory Research1465-993X2022-12-0123111210.1186/s12931-022-02259-4Bronchial eosinophils, neutrophils, and CD8 + T cells influence asthma control and lung function in schoolchildren and adolescents with severe treatment-resistant asthmaMiriam Cardoso Neves Eller0Karina Pierantozzi Vergani1Beatriz Mangueira Saraiva-Romanholo2Natália de Souza Xavier Costa3Jôse Mára de Brito4Leila Antonangelo5Caroline Silvério Faria6Joaquim Carlos Rodrigues7Thais Mauad8Unidade de Pneumologia Pediátrica, Instituto da Criança, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São PauloUnidade de Pneumologia Pediátrica, Instituto da Criança, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São PauloUniversidade da Cidade de São Paulo (UNICID)Departamento de Patologia, Faculdade de Medicina, Universidade de São PauloDepartamento de Patologia, Faculdade de Medicina, Universidade de São PauloDivisao de Patologia Clinica, Departamento de Patologia, Faculdade de Medicina, Hospital das Clinicas HCFMUSP, Universidade de São PauloLaboratorio de Investigacao Clinica (LIM03), Faculdade de Medicina, Universidade de São PauloUnidade de Pneumologia Pediátrica, Instituto da Criança, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São PauloDepartamento de Patologia, Faculdade de Medicina, Universidade de São PauloAbstract 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.https://doi.org/10.1186/s12931-022-02259-4Severe asthmaChildrenInflammatory cells profileSputumEndobronchial biopsyCD8 + T cell |
| spellingShingle | Miriam Cardoso Neves Eller Karina Pierantozzi Vergani Beatriz Mangueira Saraiva-Romanholo Natália de Souza Xavier Costa Jôse Mára de Brito Leila Antonangelo Caroline Silvério Faria Joaquim Carlos Rodrigues Thais Mauad Bronchial eosinophils, neutrophils, and CD8 + T cells influence asthma control and lung function in schoolchildren and adolescents with severe treatment-resistant asthma Respiratory Research Severe asthma Children Inflammatory cells profile Sputum Endobronchial biopsy CD8 + T cell |
| title | Bronchial eosinophils, neutrophils, and CD8 + T cells influence asthma control and lung function in schoolchildren and adolescents with severe treatment-resistant asthma |
| title_full | Bronchial eosinophils, neutrophils, and CD8 + T cells influence asthma control and lung function in schoolchildren and adolescents with severe treatment-resistant asthma |
| title_fullStr | Bronchial eosinophils, neutrophils, and CD8 + T cells influence asthma control and lung function in schoolchildren and adolescents with severe treatment-resistant asthma |
| title_full_unstemmed | Bronchial eosinophils, neutrophils, and CD8 + T cells influence asthma control and lung function in schoolchildren and adolescents with severe treatment-resistant asthma |
| title_short | Bronchial eosinophils, neutrophils, and CD8 + T cells influence asthma control and lung function in schoolchildren and adolescents with severe treatment-resistant asthma |
| title_sort | bronchial eosinophils neutrophils and cd8 t cells influence asthma control and lung function in schoolchildren and adolescents with severe treatment resistant asthma |
| topic | Severe asthma Children Inflammatory cells profile Sputum Endobronchial biopsy CD8 + T cell |
| url | https://doi.org/10.1186/s12931-022-02259-4 |
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