Blood Eosinophils in Chinese COPD Participants and Response to Treatment with Combination Low-Dose Theophylline and Prednisone: A Post-Hoc Analysis of the TASCS Trial

Abstract

Background and Objectives:The burden of chronic obstructive pulmonary disease (COPD) disproportionately affects patients in low to middle-income countries. Although the Theophylline and Steroids in COPD Study (TASCS) showed no clinical benefit from administering low-dose theophylline and prednisone in COPD patients compared to placebo, it was hypothesized that those with elevated blood eosinophil counts would receive clinical benefit from the intervention. Methods: This was a post-hoc analysis of the TASCS dataset -a double-blinded, placebo-controlled trial conducted in patients with moderate-severe COPD in China. Participants were allocated 1:1:1 to low-dose oral theophylline (100mg bd) and prednisone (5mg qd; PrT), theophylline (100mg bd) and prednisone-matched placebo (TP), or double-matched placebo (DP) groups and followed-up for 48 weeks. A baseline count of ≥300 eosinophils/µL blood was categorized as elevated/eosinophilic, and the primary outcome was the annualized moderate-severe exacerbation rate. Results: Of 1487 participants eligible for analysis, 325 (22%) were eosinophilic. These participants were predominantly male (82%), had a mean (SD) age of 64 (±8) years and a predicted forced expiratory volume in 1s (FEV 1 ) of 43% (±16). The annualized moderate-severe exacerbation rate was significantly higher in the PrT group compared to the pooled results of the TP and DP groups (incidence rate ratio = 1.6; ([95% CI 1.06-1.76]) p = 0.016). Changes in spirometry values and reported disease impact scores (St. George's Respiratory Questionnaire and COPD Assessment Test) at week 48 were not significantly different between groups. Conclusion: Combination low-dose theophylline and prednisone was associated with a significant increase in the annual moderatesevere exacerbation rate in participants with a blood eosinophil count ≥300 cells/µL compared to placebo.

Effects of combination treatment with theophylline sustained release tablets and thymalfasin on pulmonary function, immunity, and inflammation in elderly patients with chronic obstructive pulmonary disease and respiratory failure

“…The study group showed an incidence of adverse events of 14.75 %, which was slightly but not significantly higher than the 13.11 % rate of adverse events in the control group. Consistent with similar local and international studies, our results showed that combination treatment with theophylline sustained-release tablets and thymalfasin was effective in the treatment of COPD with respiratory failure [14,15]. It has been reported that sICAM-1, PGE2, and hs-CRP are clinically serum inflammatory factors [16,17].…”