RESUMO
BACKGROUND: Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma. METHODS: Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow-up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti-IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV1) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV1 increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day. RESULTS: 5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics. Biologic initiators had worse baseline impairment than non-initiators, despite having similar biomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54% FEV1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and 39%, respectively, were super-responses. Responses/super-responses were more frequent in biologic initiators than in non-initiators; nevertheless, ~40-50% of initiators did not meet response criteria. CONCLUSIONS: Most patients with severe asthma are ineligible for RCTs of biologic therapies. Biologics are initiated in patients who have worse baseline impairments than non-initiators despite similar biomarker levels. Although biologic initiators exhibited clinical responses and super-responses in all outcome domains, 40-50% did not meet the response criteria.
RESUMO
BACKGROUND: Systemic manifestations and comorbidities are characteristics of chronic obstructive pulmonary disease (COPD) and are probably due to systemic inflammation. The histone methyltransferase SUV39H1 controls the Th1/Th2 balance. We previously reported that reduced SUV39H1 expression contributed to abnormal inflammation in COPD. Here, we aimed to determine whether impaired SUV39H1 expression in COPD patients associated with neutrophilic/eosinophilic inflammation responses and comorbidities. METHODS: A total of 213 COPD patients and 13 healthy controls were recruited from the Shuang Ho Hospital, Taipei Medical University. SUV39H1 levels in peripheral blood mononuclear cells (PBMCs) from 13 healthy and 30 COPD participants were measured by immunoblotting. We classified the patients into two groups based on low (fold change, FC < 0.5) and high SUV39H1 expression (FC ≥ 0.5) compared to normal controls. Clinical outcomes including neutrophil or eosinophil counts associated with SUV39H1-related inflammation were evaluated by Chi square analyses or Mann-Whitney U test. The correlations between the percentage of neutrophils and number of COPD comorbidities or Charlson Comorbidity Index (CCI) scores were performed by Spearman's rank analysis. RESULTS: Low SUV39H1 expression group had high neutrophil counts relative to high SUV39H1expression group. In the COPD cohort, the high comorbidity group (≥ 2 comorbidities) had higher counts of whole white blood cell (WBC) and neutrophil, and lower proportion of eosinophil and eosinophil/neutrophil, as compared with low comorbidity group (0 and 1 comorbidities). The quantity of neutrophils was associated with COPD comorbidities (Spearman's r = 0.388, p < 0.001), but not with CCI scores. We also found that the high comorbidity group had more exacerbations per year compared with low comorbidity group (1.5 vs. 0.9 average exacerbations, p = 0.005). However, there were no significant differences between groups with these non-frequent (0-1 exacerbation) and frequent exacerbations per year (> 1 exacerbation) in numbers of WBC and proportion of neutrophils, eosinophils or eosinophil/neutrophil. Finally, patients with high comorbidities had lower SUV39H1 levels in their PBMCs than did those with low comorbidities. CONCLUSION: Blood neutrophil counts are associated with comorbidities in COPD patients. Impaired SUV39H1 expression in PBMCs from COPD patients are correlated with neutrophilic inflammation and comorbidities.
