Investigating the important factors influencing long-term doxycycline responsiveness in COPD

<bold>Background:</bold> The claimed significant improvement of spirometric lung function parameters by long-term add-on doxycycline may not be homogeneous and universal in COPD patients. <bold>Aim:</bold> To understand the differences between the responders and non-responders to add-on doxycycline in COPD. <bold>Methods:</bold> COPD patients receiving add-on doxycycline treatment for 6 months were selected from an ethically approved long-term doxycycline clinical trial. Based on their lung function changes at 6 months of the add-on therapy patients were divided into responsive and non-responsive groups and their clinical parameters and spirometric variables were compared statistically. <bold>Results:</bold> We collected 84 patients receiving doxycycline add-on to standard therapy of which 63.09% (n=53) and 36.90% (n=31) were found to be responsive and non-responsive respectively. The responders had shown significant improvement in predicted values of FEV₁% (p<0.0001), FVC% (p<0.0001), FEV₁/FVC (p<0.05) and FEF_25-75% (p<0.05) while the non-responders had significant worsening of same parameters. The mean BMI of the non-responders was significantly low (p<0.05) with more frequent exacerbations and more shortness of breath. They also had a higher frequency of smoking (39.62% vs. 45.16%), occupational exposure to noxious agents (47.17% vs. 51.61%), and history of allergy (18.87% vs. 38.71%). The partial least square discriminant analysis highlighted the distinguishing factors between the two groups were BMI, history of allergy history, occupational exposure to noxious agents, and frequent exacerbations. <bold>Conclusion:</bold> Doxycycline-responsive and non-responsive COPD patients might belong to distinct phenotypes with specific discriminatory factors.