BackgroundHuman 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.MethodsHu-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-α (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.ResultsThe 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-α 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-α stimulated hu-BEC was maximally decreased by 35 ± 24% (p < 0.01) with MXF (4 mg/l).ConclusionUsing ALI cultures of hu-BEC we observed differential effects of antibiotics on spontaneous and TNF-α induced cytokine release. Our data suggest that MXF and AZM, beyond bactericidal effects, may attenuate the inflammatory process mediated by hu-BEC.
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 ± 5.1 years, ex-smokers with 35.7 ± 21.2 pack years, BMI 22.3 ± 3.5 kg/m 2 , FEV 1 of 0.61 ± 0.2 L (21.1 ± 5.6% pred), pO 2 52.4 ± 8.4 mmHg, and BODE 6.9 ± 1.7. 68% had > 2 moderate or severe exacerbations annually. 16.1% (5/31) patients showed FEV 1 reversibility of > 12% and > 200 ml despite maximal therapy, 33% (15/45) had FENO ≥22.5 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 ≥150 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 (p < 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.
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