Airway pathology in severe asthma is related to airflow obstruction but not symptom control

被引:56
作者
Ferreira, D. S. [1 ]
Carvalho-Pinto, R. M. [2 ]
Gregorio, M. G. [2 ]
Annoni, R. [1 ]
Teles, A. M. [1 ]
Buttignol, M. [1 ]
Araujo-Paulino, B. B. [1 ]
Katayama, E. H. [3 ]
Oliveira, B. L. [3 ]
Del Frari, H. S. [3 ]
Cukier, A. [2 ]
Dolhnikoff, M. [1 ]
Stelmach, R. [2 ]
Rabe, K. F. [4 ,5 ]
Mauad, T. [1 ]
机构
[1] Univ Sao Paulo, Dept Pathol, Sch Med, Sao Paulo, Brazil
[2] Univ Sao Paulo, Heart Inst InCor, Div Pulm, Sch Med, Sao Paulo, Brazil
[3] Univ Sao Paulo, Sch Med, Sao Paulo, Brazil
[4] LungenClin Grosshansdorf, Grosshansdorf, Germany
[5] German Ctr Lung Res DZL, Airway Res Ctr North, Heidelberg, Germany
基金
巴西圣保罗研究基金会;
关键词
airway smooth muscle; biopsy; bronchi; extracellular matrix proteins; SMOOTH-MUSCLE-CELLS; CLINICAL CHARACTERISTICS; PULMONARY-DISEASE; RESEARCH-PROGRAM; LUNG-FUNCTION; MAST-CELLS; TGF-BETA; INFLAMMATION; PHENOTYPE; PERIOSTIN;
D O I
10.1111/all.13323
中图分类号
R392 [医学免疫学];
学科分类号
100108 [医学免疫学];
摘要
BackgroundPatients with asthma present structural and inflammatory alterations that are believed to play a role in disease severity. However, airway remodeling and inflammation have not been extensively investigated in relation to both symptom control and airflow obstruction in severe asthmatics. We aimed to investigate several inflammatory and structural pathological features in bronchial biopsies of severe asthmatics that could be related to symptom control and airflow obstruction after standardized treatment. MethodsFifty severe asthmatics received prednisone 40 mg/d for 2 weeks and maintenance therapy with budesonide/formoterol 400/12 g twice daily + budesonide/formoterol 200/6 g as needed for 12 weeks. Endobronchial biopsies were performed at the end of 12 weeks. We performed extensive immunopathological analyses of airway tissue inflammation and remodeling features in patients stratified by asthma symptom control and by airflow obstruction. ResultsAirway tissue inflammation and remodeling were not associated with symptom control. Asthmatics with persistent airflow obstruction had greater airway smooth muscle (Asm) area with decreased periostin and transforming growth factor beta-positive cells within Asm bundles, in addition to lower numbers of chymase-positive mast cells in the submucosa compared to patients with nonpersistent obstruction. ConclusionsSymptom control in severe asthmatics was not associated with airway tissue inflammation and remodeling, although persistent airflow obstruction in these patients was associated with bronchial inflammation and airway structural changes.
引用
收藏
页码:635 / 643
页数:9
相关论文
共 41 条
[1]
TH17-associated cytokines (IL-17A and IL-17F) in severe asthma [J].
Al-Ramli, Wisam ;
Prefontaine, David ;
Chouiali, Fazila ;
Martin, James G. ;
Olivenstein, Ron ;
Lamiere, Catherine ;
Hamid, Qutayba .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2009, 123 (05) :1185-1187
[2]
Human lung mast cells modulate the functions of airway smooth muscle cells in asthma [J].
Alkhouri, H. ;
Hollins, F. ;
Moir, L. M. ;
Brightling, C. E. ;
Armour, C. L. ;
Hughes, J. M. .
ALLERGY, 2011, 66 (09) :1231-1241
[3]
Alterations in Lung Mast Cell Populations in Patients with Chronic Obstructive Pulmonary Disease [J].
Andersson, Cecilia K. ;
Mori, Michiko ;
Bjermer, Leif ;
Lofdahl, Claes-Goran ;
Erjefalt, Jonas S. .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2010, 181 (03) :206-217
[4]
[Anonymous], 2015, GLOB STRAT ASTHM MAN
[5]
Can severe asthmatic patients achieve asthma control? A systematic approach in patients with difficult to control asthma followed in a specialized clinic [J].
Athanazio, Rodrigo ;
Carvalho-Pinto, Regina ;
Arrabal Fernandes, Frederico Leon ;
Rached, Samia ;
Rabe, Klaus ;
Cukier, Alberto ;
Stelmach, Rafael .
BMC PULMONARY MEDICINE, 2016, 16
[6]
Airway Remodeling Measured by Multidetector CT Is Increased in Severe Asthma and Correlates With Pathology [J].
Aysola, Ravi S. ;
Hoffman, Eric A. ;
Gierada, David ;
Wenzel, Sally ;
Cook-Granroth, Janice ;
Tarsi, Jaime ;
Zheng, Jie ;
Schechtman, Kenneth B. ;
Ramkumar, Thiruvamoor P. ;
Cochran, Rebecca ;
Xueping, E. ;
Christie, Chandrika ;
Newell, John ;
Fain, Sean ;
Altes, Talissa A. ;
Castro, Mario .
CHEST, 2008, 134 (06) :1183-1191
[7]
Relationship of small airway chymase-positive mast cells and lung function in severe asthma [J].
Balzar, S ;
Chu, HW ;
Strand, M ;
Wenzel, S .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2005, 171 (05) :431-439
[8]
Mast Cell Phenotype, Location, and Activation in Severe Asthma Data from the Severe Asthma Research Program [J].
Balzar, Silvana ;
Fajt, Merritt L. ;
Comhair, Suzy A. A. ;
Erzurum, Serpil C. ;
Bleecker, Eugene ;
Busse, William W. ;
Castro, Mario ;
Gaston, Benjamin ;
Israel, Elliot ;
Schwartz, Lawrence B. ;
Curran-Everett, Douglas ;
Moore, Charity G. ;
Wenzel, Sally E. .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2011, 183 (03) :299-309
[9]
Airway structural alterations selectively associated with severe asthma [J].
Benayoun, L ;
Druilhe, A ;
Dombret, MC ;
Aubier, M ;
Pretolani, M .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2003, 167 (10) :1360-1368
[10]
Sputum periostin in patients with different severe asthma phenotypes [J].
Bobolea, I. ;
Barranco, P. ;
Del Pozo, V. ;
Romero, D. ;
Sanz, V. ;
Lopez-Carrasco, V. ;
Canabal, J. ;
Villasante, C. ;
Quirce, S. .
ALLERGY, 2015, 70 (05) :540-546