Effect of doxycyline in chronic obstructive pulmonary disease - An exploratory study.

PURPOSE: Various mechanisms, including oxidative stress, inflammation, and protease-antiprotease imbalance are proposed for the progressive decline in lung function in chronic obstructive pulmonary disease (COPD). Doxycycline, a broad spectrum tetracycline antibiotic, is reported to have non-antimicrobial matrix metalloproteinases (MMP) inhibitory action in various inflammatory conditions. The effect of doxycycline in COPD is hereby assessed in the present randomized prospective study. PATIENTS AND METHODS: The first group of COPD patients (n = 30; mild (n = 3), moderate (n = 6), severe (n = 7), very severe (n = 14) as per GOLD II & III criteria was prescribed the standard therapy, a combination of (i) short acting anti-muscarinic agent (SAMA) + short acting ß2 agonist (SABA) inhaled and (ii) corticosteroid inhaled (ICS) + long acting ß2 agonist (LABA) (iii) ICS + LABA + LAMA. Whereas doxycycline (100 mg), was used daily once or twice as per Body Mass Index (BMI), as an add-on to existing standard therapy for the second group of patients (n = 30; mild (n = 2), moderate (n = 7), severe (n = 8), very severe (n = 13). All recruited patients were followed-up after 3 months of treatment. Lung function index FEV1(%) predicted, FEV1/FVC (%), quality of life status including COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ) were assessed. Routine blood cell count also was performed. RESULTS: Biochemical analysis included estimation of oxidative stress markers, inflammatory cytokines and proteases in plasma of both the groups. Reduction in oxidative stress is evidenced by a significant decrease in Lipid hydro peroxides (LPO), total oxidative stress (TOS) and increase in glutathione peroxidase (GSH-PX), reduced glutathione (GSH) and total anti-oxidant capacity (TAO) nitrite and nitrate (NOx) along with peroxynitrate following 3 months of add-on doxycycline treatment. Reduced levels of cytokines such as interleukin IL-6, TNF-α, IL-8 were also observed. Multivariate analysis identified TNF-α major effective discriminant among pre and post doxycycline treated COPD patients. The expression of TNF-α was inversely correlated with FEV1/FVC (%) changes. The levels of MMP-2 and MMP-9/tissue inhibitors of metalloproteinases (TIMP)-1 ratio (MMP-9/ TIMP-1), also decreased significantly and the decline could be associated with TOS. A significant increase in bilirubin and reduced glutathione (GSH) level was noticed in standard therapy group. CONCLUSION: These data suggest that the improvement in lung function and quality of life in COPD patients may probably be attributed to the antioxidant, anti-inflammatory and anti-MMP activity of doxycycline. The potential therapeutic role of long-term doxycycline, in addition to its traditional antibiotic effect, definitely warrants further attention.

The impact on health status in short- and long-terms of a novel and non-orthodox real-world COPD rehabilitation effort in rural India: an appraisal.

BACKGROUND: Rehabilitation has been an integral part of management of COPD. Since the implementation of the standard rehabilitation protocol is hardly possible in the rural developing world, aiming to make a feasible alternate effort may be worthwhile. METHODS: COPD patients diagnosed through spirometry were first stabilized with 6 weeks of uniform pharmacotherapy. Subsequently, they were subjected to a curriculum-based intensive single-session intervention with education, bronchial hygiene, and exercise training. The latter involved whole body exercise, pursed lip breathing, and diaphragmatic exercise. The participants continued to practice the exercises under real-world encouragement and supervision from trained volunteers. The impact was appraised in terms of change in health status through COPD assessment test (CAT) score measurements at stabilization, and after 6 weeks and 1 year of the intensive training and education. RESULTS: At stabilization, 70 out of 96 selected COPD subjects (73%) turned up (with mean age 62±9 years and mean FEV1 as 1.16±0.39 L) showing improvement as per CAT score (p=0.0001) from pharmacotherapy. After practicing the imparted education and training for 6 weeks, all these 70 participants had further significant improvement in the health status (n=70, p=0.00001). This improvement, been reinforced and supervised, continued to last even at 1 year (n=54, p=0.0001). CONCLUSION: The self-managed practice of a single-session education and training under real-world supervision can bring forth significant long-term improvement in the health status of COPD sufferers. Such simple and feasible intervention may substitute formal COPD rehabilitation programs in resource constraint situations.