The Study of Efficacy, Tolerability and Safety of Theophylline Given Along with Formoterol Plus Budesonide in COPD

Background: Chronic obstructive pulmonary disease (COPD) is a common disease causing significant socioeconomic burden. COPD patients, commonly smokers develop resistance to inhaled steroids attributed to deficiency of histone deacetylase 2 (HDAC2). The study of relationship between systemic inflammation and functional performance demonstrated that increased CRP level is inversely related to six minute walk distance (SMWD) and Forced Expired Volume in one second (FEV1). Theophylline restores HDAC2 activity thereby unlocking steroid resistance and potentiating inhaled corticosteroids (ICS) action culminating in reduced airway inflammation and mortality.

Aim: To study the effects of addition of Theophylline to the combination of Formoterol plus Budesonide on various objective and subjective parameters in moderate to severe COPD patients and to assess the safety profile of the combination. Setting and Study design: A single blinded, prospective, randomized, placebo controlled study at a tertiary care hospital in Jaipur, India.

Materials and methods: Fifty eight patients diagnosed with moderate to severe COPD were randomized into two groups. Group A patients received Formoterol 24μg plus budesonide 800μg daily in divided doses along with Theophylline while group B patients received Formoterol 24μg plus budesonide 800μg daily in divided doses along with placebo tablets. Both groups were followed up on 15th, 30th &60th day. During every visit all patients were assessed subjectively (symptom scoring) and objectively (spirometry, CRP, SMWT) and adverse effects if any were recorded. The obtained data subject to statistical analysis using"Graph pad Instat3" software.

Results: Statistically significant improvement with a decline in total symptom score (p < 0.0001) was found with respect to "Night symptoms"&"SOB on rising" in group A. Theophylline group showed significant improvement in SMWD and FEV1.Mean fall in CRP was greater in Group A (not statistically significant). No side effects requiring withdrawal of drug were noted with Theophylline.

Conclusion: Addition of Theophylline to Formoterol plus Budesonide reduces dyspnea, improves exercise performance and pulmonary functions in moderate to severe COPD. Further studies are required to explore if reduced dosage would have equal efficacy with better safety and tolerability profile.