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

Carregando...
Imagem de Miniatura
Citações na Scopus
3
Tipo de produção
article
Data de publicação
2022
Título da Revista
ISSN da Revista
Título do Volume
Editora
BMC
Citação
RESPIRATORY RESEARCH, v.23, n.1, article ID 335, 12p, 2022
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
BackgroundStudies 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. ObjectiveWe 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. MethodsInflammatory 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. ResultsEndobronchial 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 IL1 beta, IL2, IL5, IL7, IL10, IL12, IL17, GCSF, MCP-1, INF-delta, and TNF alpha in sputum supernatant. The ASM chymase + mast cell density correlated positively with quality-of-life score (pAQLQ) and ACT. ConclusionEosinophils 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.
Palavras-chave
Severe asthma, Children, Inflammatory cells profile, Sputum, Endobronchial biopsy, CD8+T cell
Referências
  1. Alonso AM, 2017, FRONT PEDIATR, V5, DOI 10.3389/fped.2017.00154
  2. Andersson CK, 2017, J ALLERGY CLIN IMMUN, V139, P1819, DOI 10.1016/j.jaci.2016.09.022
  3. Bossley CJ, 2012, J ALLERGY CLIN IMMUN, V129, P974, DOI 10.1016/j.jaci.2012.01.059
  4. Chatkin José Miguel, 2006, J. bras. pneumol., V32, P277, DOI 10.1590/S1806-37132006000400004
  5. Chung KF, 2016, J INTERN MED, V279, P192, DOI 10.1111/joim.12382
  6. Chung KF, 2014, EUR RESPIR J, V43, P343, DOI 10.1183/09031936.00202013
  7. Ciepiela O, 2015, RESP PHYSIOL NEUROBI, V209, P13, DOI 10.1016/j.resp.2014.12.004
  8. Cook J, 2017, J ASTHMA ALLERGY, V10, P123, DOI 10.2147/JAA.S129159
  9. Davis KU, 2021, INFLAMMATION, V44, P450, DOI 10.1007/s10753-020-01362-2
  10. Picinin IFD, 2010, J BRAS PNEUMOL, V36, P372, DOI 10.1590/S1806-37132010000300016
  11. Dweik RA, 2011, AM J RESP CRIT CARE, V184, P602, DOI 10.1164/rccm.9120-11ST
  12. Eller MCN, 2018, PEDIATR PULM, V53, P1208, DOI 10.1002/ppul.24075
  13. Roxo JPF, 2010, J BRAS PNEUMOL, V36, P159, DOI 10.1590/S1806-37132010000200002
  14. Ferreira DS, 2018, ALLERGY, V73, P635, DOI 10.1111/all.13323
  15. Fleming L, 2019, FRONT PEDIATR, V7, DOI 10.3389/fped.2019.00389
  16. Global initiative for asthma (GINA), US
  17. dos Santos ABG, 2013, ANN ANAT, V195, P596, DOI 10.1016/j.aanat.2013.05.003
  18. Januska MN, 2020, PEDIATR PULM, V55, P795, DOI 10.1002/ppul.24569
  19. Juniper EF, 1999, CHEST, V115, P1265, DOI 10.1378/chest.115.5.1265
  20. Lex C, 2005, PEDIATR PULM, V39, P318, DOI 10.1002/ppul.20159
  21. Louis R, 2009, SWISS MED WKLY, V139, P274, DOI smw-12365
  22. Mthembu N., 2021, FRONT ALLERGY, V2
  23. Palomino Addy L. M., 2005, J. Pediatr. (Rio J.), V81, P216, DOI 10.1590/S0021-75572005000400008
  24. Pineros YSS, 2019, ALLERGY, V74, P1898, DOI 10.1111/all.13802
  25. Pizzichini E, 1996, AM J RESP CRIT CARE, V154, P308, DOI 10.1164/ajrccm.154.2.8756799
  26. Poritz MA, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0026047
  27. Quanjer PH, 2012, EUR RESPIR J, V40, P1324, DOI 10.1183/09031936.00080312
  28. Sole Dirceu, 2017, Asthma Res Pract, V3, P4, DOI 10.1186/s40733-017-0032-3
  29. STOCKS J, 1995, EUR RESPIR J, V8, P492, DOI 10.1183/09031936.95.08030492
  30. Stocks J, 2001, EUR RESPIR J, V17, P302, DOI 10.1183/09031936.01.17203020
  31. Woolhouse IS, 2002, THORAX, V57, P667, DOI 10.1136/thorax.57.8.667