BACKGROUND: Patients 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. METHODS: Fifty severe asthmatics received prednisone 40 mg/d for 2 weeks and maintenance therapy with budesonide/formoterol 400/12 mug twice daily + budesonide/formoterol 200/6 mug 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. RESULTS: Airway 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. CONCLUSIONS: Symptom 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.
- Ferreira, D. S.
- Carvalho-Pinto, R. M.
- Gregorio, M. G.
- Annoni, R.
- Teles, A. M.
- Buttignol, M.
- Araujo-Paulino, B. B.
- Katayama, E. H.
- Oliveira, B. L.
- Del Frari, H. S.
- Cukier, A.
- Dolhnikoff, M.
- Stelmach, R.
- Rabe, K. F.
- Mauad, T.
Keywords
- Adult
- Airway Obstruction/etiology/pathology
- Airway Remodeling/drug effects/physiology
- Anti-Asthmatic Agents/*therapeutic use
- Asthma/complications/*drug therapy/*pathology
- Bronchi/*pathology
- Budesonide, Formoterol Fumarate Drug Combination/therapeutic use
- Female
- Humans
- Inflammation/pathology
- Male
- Middle Aged
- Prednisone/therapeutic use
- *airway smooth muscle
- *biopsy
- *bronchi
- *extracellular matrix proteins