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Impact of long-term doxycycline on lung function & exacerbations: A real-world open, prospective pilot observation on chronic obstructive pulmonary disease
Indian Journal of Medical Research ( IF 4.2 ) Pub Date : 2021-04-01 , DOI: 10.4103/ijmr.ijmr_1254_18 Parthasarathi Bhattacharyya 1 , Brajesh Singh 2 , Surita Sarkar 3 , Soumen Kumar Das 1 , Bodhisattwa Chakraborty 1 , Dipanjan Saha 1 , Kumar Chakraborty 4 , Indranil Saha 5 , Koel Chaudhury 6
Indian Journal of Medical Research ( IF 4.2 ) Pub Date : 2021-04-01 , DOI: 10.4103/ijmr.ijmr_1254_18 Parthasarathi Bhattacharyya 1 , Brajesh Singh 2 , Surita Sarkar 3 , Soumen Kumar Das 1 , Bodhisattwa Chakraborty 1 , Dipanjan Saha 1 , Kumar Chakraborty 4 , Indranil Saha 5 , Koel Chaudhury 6
Affiliation
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.
中文翻译：
长期多西环素对肺功能和恶化的影响：对慢性阻塞性肺疾病的真实世界开放、前瞻性试点观察
背景与目的：基质金属蛋白酶 (MMPs) 的上调与慢性阻塞性肺病 (COPD) 的发病机制有关。我们旨在评估长期使用 MMP 抑制剂强力霉素治疗 COPD 的耐受性和影响。
方法：一组慢性阻塞性肺病患者被随机分配继续统一的慢性阻塞性肺病治疗，加或不加长期口服多西环素。在治疗的第 3、6、9 和 12 个月时记录了肺恶化（肺量计）、不良事件和健康状况（COPD 评估测试评分）。尽可能在研究开始时和三个月时测量血清 MMP-2、9 和高敏 C 反应蛋白 (hs-CRP) 水平。
结果：治疗3、6、9、12个月时，加用强力霉素组27、19、13、10例，单纯COPD治疗22、19、11、7例。肺功能参数 [1 秒用力呼气量 (FEV 1 )、FEV 1 /用力肺活量 (FVC) 和25 -75% 的 FVC (FEF 25-75 )] 并且在所有测量中普遍适用于健康状况，总体上减少了 26.69% 的恶化。对违反协议的可用人群中肺功能变化的分析也支持相同的趋势。血清 MMP-9 随之降低（P= 0.01)、MMP-2 ( P = 0.01) 和 hs-CRP ( P = 0.0001) 水平 (n=21) 在三个月时也显着。加用强力霉素的不良反应似乎是可以接受的。
解释和结论：长期多西环素似乎耐受性良好，似乎可以改善 COPD 的肺功能、健康状况和恶化。该说法需要进一步的科学验证。
更新日期：2021-04-01
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.
中文翻译：
长期多西环素对肺功能和恶化的影响：对慢性阻塞性肺疾病的真实世界开放、前瞻性试点观察
背景与目的：基质金属蛋白酶 (MMPs) 的上调与慢性阻塞性肺病 (COPD) 的发病机制有关。我们旨在评估长期使用 MMP 抑制剂强力霉素治疗 COPD 的耐受性和影响。
方法：一组慢性阻塞性肺病患者被随机分配继续统一的慢性阻塞性肺病治疗，加或不加长期口服多西环素。在治疗的第 3、6、9 和 12 个月时记录了肺恶化（肺量计）、不良事件和健康状况（COPD 评估测试评分）。尽可能在研究开始时和三个月时测量血清 MMP-2、9 和高敏 C 反应蛋白 (hs-CRP) 水平。
结果：治疗3、6、9、12个月时，加用强力霉素组27、19、13、10例，单纯COPD治疗22、19、11、7例。肺功能参数 [1 秒用力呼气量 (FEV 1 )、FEV 1 /用力肺活量 (FVC) 和25 -75% 的 FVC (FEF 25-75 )] 并且在所有测量中普遍适用于健康状况，总体上减少了 26.69% 的恶化。对违反协议的可用人群中肺功能变化的分析也支持相同的趋势。血清 MMP-9 随之降低（P= 0.01)、MMP-2 ( P = 0.01) 和 hs-CRP ( P = 0.0001) 水平 (n=21) 在三个月时也显着。加用强力霉素的不良反应似乎是可以接受的。
解释和结论：长期多西环素似乎耐受性良好，似乎可以改善 COPD 的肺功能、健康状况和恶化。该说法需要进一步的科学验证。
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