Impact of long-term doxycycline on lung function & exacerbations: A real-world open, prospective pilot observation on chronic obstructive pulmonary disease

Background & objectives: Upregulation of matrix metalloproteinases (MMPs) is related to the pathogenesis of chronic obstructive pulmonary disease (COPD). We aimed at assessing the tolerability and impact of long-term use of MMP inhibitor doxycycline in COPD. Methods: A cohort of COPD patients was randomized to continue a uniform COPD treatment with or without add-on long-term oral doxycycline. The lung exacerbations (spirometry), adverse events and health status (COPD Assessment Test score) were noted at 3, 6, 9 and 12 months of therapy. Measurement of the serum MMP-2, and 9 and high-sensitive C-reactive protein (hs-CRP) levels was done at the start of the study and at three months, whenever possible. Results: There were 27, 19, 13 and 10 patients with add-on doxycycline group and 22, 19, 11 and 7 patients with COPD treatment alone at 3, 6, 9 and 12 months of treatment respectively. The improvement was obvious and mostly (at 6 and 12 months) significant (P >0.05) for lung function parameters [forced expiratory volume in one second (FEV1), FEV1/forced vital capacity (FVC) and forced expiratory flow at 25-75% of FVC (FEF25-75)] and universal for health status at all measurements, with an overall 26.69 per cent reduction in exacerbations. The analysis with the lung function changes in the available population with protocol violation also supported the same trend. The concomitant reduction in serum MMP-9 (P =0.01), MMP-2 (P =0.01) and hs-CRP (P =0.0001) levels (n=21) at three months was also significant. The adverse reactions with add-on doxycycline appeared acceptable. Interpretation & conclusions: Long-term doxycycline appears well tolerated and seems to improve lung function, health status and exacerbations in COPD. The claim needs further scientific validations.