ABSTRACT
AIM: Biological therapies developed for severe asthma may have a role in COPD patients with asthma features. METHOD: We carried out a prospective, consecutive, cross-sectional analysis of 80 patients with severe COPD GOLD IV/D. RESULTS: We studied 80 patients (48.8% female), aged 57.6⯱â¯5.1 years, ex-smokers with 35.7⯱â¯21.2 pack years, BMI 22.3⯱â¯3.5â¯kg/m2, FEV1 of 0.61⯱â¯0.2â¯L (21.1⯱â¯5.6% pred), pO2 52.4⯱â¯8.4â¯mmHg, and BODE 6.9⯱â¯1.7. 68% had >2 moderate or severe exacerbations annually. 16.1% (5/31) patients showed FEV1 reversibility of >12% and >200â¯ml despite maximal therapy, 33% (15/45) had FENO ≥22.5â¯ppb, 33% (24/73) had serum IgE ≥100 I.E./ml and there was positive allergen sensitization in 51.5% (35/68). Blood eosinophilia of ≥150â¯cells/µl was seen in 47% (35/74). Induced sputum showed eosinophilia of ≥2% in 56% (14/24) with respiratory pathogens in 63.8% (30/47). We identified 12 (15%) patients with asthma-COPD overlap. Of these, 10 (83.3%) had frequent exacerbations and these patients had significantly more severe exacerbations requiring NIV or ICU than those without asthma features (pâ¯<â¯0.005). CONCLUSION: We detected asthma features in a substantial subset of stable patients with severe COPD. Asthma features were associated with more severe exacerbation despite optimal COPD therapy, representing potential candidates for targeted therapy with anti- IgE or anti-IL5.
Subject(s)
Asthma/drug therapy , Asthma/etiology , Pulmonary Disease, Chronic Obstructive/complications , Aged , Allergens/immunology , Antibodies, Monoclonal/therapeutic use , Asthma/immunology , Asthma/physiopathology , Cross-Sectional Studies , Disease Progression , Forced Expiratory Volume , Humans , Immunoglobulin E/immunology , Interleukin-5/immunology , Middle Aged , Molecular Targeted Therapy , Prospective Studies , Pulmonary Disease, Chronic Obstructive/physiopathology , Severity of Illness IndexABSTRACT
BACKGROUND: Human Bronchial epithelial cells (hu-BEC) have been claimed to play a significant role in the pathogenesis of chronic inflammatory airway diseases like COPD. In this context IL-8 and GM-CSF have been shown to be key cytokines. Some antibiotics which are routinely used to treat lower respiratory tract infections have been shown to exert additional immunomodulatory or anti-inflammatory effects. We investigated whether these effects can also be detected in hu-BEC. METHODS: Hu-BEC obtained from patients undergoing lung resections were transferred to air-liquid-interface (ALI) culture. These cultures were incubated with cefuroxime (CXM, 10-62.5 mg/l), azithromycin (AZM, 0.1-1.5 mg/l), levofloxacin (LVX, 1-8 mg/l) and moxifloxacin (MXF, 1-16 mg/l). The spontaneous and TNF-alpha (10 ng/ml) induced expression and release of IL-8 and GM-CSF were measured using PCR and ELISA in the absence or presence of these antibiotics. RESULTS: The spontaneous IL-8 and GM-CSF release was significantly reduced with MXF (8 mg/l) by 37 +/- 20% and 45 +/- 31%, respectively (both p < 0.01). IL-8 release in TNF-alpha stimulated hu-BEC decreased by 16 +/- 8% (p < 0.05) with AZM (1.5 mg/l). With MXF a concentration dependent decrease of IL-8 release was noted up to 39 +/- 7% (p < 0.05). GM-CSF release from TNF-alpha stimulated hu-BEC was maximally decreased by 35 +/- 24% (p < 0.01) with MXF (4 mg/l). CONCLUSION: Using ALI cultures of hu-BEC we observed differential effects of antibiotics on spontaneous and TNF-alpha induced cytokine release. Our data suggest that MXF and AZM, beyond bactericidal effects, may attenuate the inflammatory process mediated by hu-BEC.
