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| LETTER TO EDITOR |
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| Year : 2020 | Volume
: 8
| Issue : 1 | Page : 37-38 |
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Doxycycline orally on long term is well tolerated and may be beneficial in DPLD
Parthasarathi Bhattacharyya, Mintu Paul
Institute of Pulmocare and Research, Kolkata, West Bengal, India
| Date of Submission | 20-Nov-2019 |
| Date of Acceptance | 28-Nov-2019 |
| Date of Web Publication | 11-Feb-2020 |
Correspondence Address:
Dr. Parthasarathi Bhattacharyya
Institute of Pulmocare and Research, DG-8, Action area-1, New Town, Kolkata 700 156, West Bengal
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/jacp.jacp_44_19
How to cite this article:
Bhattacharyya P, Paul M. Doxycycline orally on long term is well tolerated and may be beneficial in DPLD. J Assoc Chest Physicians 2020;8:37-8 |
Sir,
Diffuse parenchymal lung disease (DPLD) is a global problem with varied etiologies.[1] It can largely be divided into IPF and non IPF as per the prognostic outlook is concerned. The treatment of DPLD has been evolving with introduction of new agents[2],[3]; yet the armamentarium is inadequate to ensure universally favourable outcome especially for IPF, the predominant fibrotic variety of DPLD.
The dysregulated fibrogenesis that remains the target of treatment of DPLD at large can be modulated through inhibition of matrix metalloproteinase MMPs[4], we have seen in real-world clinical experience that a non-specificMMP inhibitors, doxycycline, carries potential to treat DPLD.[5],[6],[7]
We have collected our small real-world experience of use of doxycycline in an ethically approved protocol with informed consent on 154 patients so far. The agent has been given alone or in combination with other drugs and the outcome in terms of change in forced vital capacity (FVC) is noted with the adverse effects of the agent been used. The DPLD population selected was heterogeneous clinico-radiologically. Etiologically, the patients remained not clearly defined in most of the circumstances as the evaluation contained no surgical biopsy, limited use of bronchoscopy, and serology. No patient was included in acute state or with history exacerbation in the preceding 3 months. The patients with any uncontrolled or severe systemic disease or having any other concomitant pulmonary disease were also excluded. Simultaneously, the suspected cases of sarcoidosis and advanced cases of DPLD (FVC < 40 % of predicted) were not included in the protocol.
The investigator was given the freedom to choose the treatment considering the disease status, the HRCT revealed pattern, and the real-world situations including financial and other logistic status relating to the patients. HRCT plates played an important role in decision making as the investigator tended to prescribe oral steroid or azathioprine with doxycycline in predominantly inflammatory pattern (haze and mosaic appearance with some occasional reticulations suggesting hypersensitivity pneumonitis, connective tissue disease-related DPLD). On the other hand, the predominant fibrotic pattern honeycombing and sharp reticulations suggesting (UIP/fibrotic NSIP) were offered pirfenidone with doxycycline. Early or mixed cases with relatively preserved FVC were put on doxycycline alone or doxycycline with NAC (n-acetyl cysteine).
The universal prescription of doxycycline (doxycycline hyclate) was in a dose of 100 mg twice or once daily for body weight over or under 50 kilograms respectively. The prescribed dose of azathioprine was 1.5 to 2 mg per kilogram of body weight, and that of NAC and pirfenidone were 600 mg and 400 mg thrice daily respectively.
Out of 154 patients included in the protocol there were 10 surviving dropouts (without any history of intolerance to doxycycline) and 14 deaths over the span of the study period (from 2009 to 2015). We could finally come up with the follow up of 144 patients at the time of calculations having at least one PFT following the initiate on of treatment; the details of them are elaborated in [Table 1]. | Table 1 Details of lung function changes on treatment with doxycycline ± other agents
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It appears obvious that the patients who received doxycycline or doxycycline plus n-acetyl cysteine had the best initial lung function signifying that the milder cases were possibly included here. The result signifies that doxycycline is a very well tolerated agent in DPLD patients and incidentally the decline rate of FVC in all the subgroups are essentially low and the annual percent of decline of FVC appears as the lowest in patents receiving doxycycline plus steroid (0.17 %) and is highest in the fibrotic group receiving pirfenidone (5.36%). This observation is suggestive of doxycycline working possibly better on the pre-fibrotic inflammatory state in combination with corticosteroid.
Since the observation is not randomized and there is no parallel (control) group to compare, the strength and impact of the observation are compromised. However, despite the other weaknesses, including the small number of recruits in each group, absence of confirmation of etiology, lack of use of other assessment tools etc., it appears that doxycycline carries prospect in treating different categories of DPLD alone or possibly better in combination with other drugs. Thorough research therefore indicated to explore the prospect of clinical use of doxycycline in DPLD.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | |  |
| 1. | King TE Jr., Clinical Advances in the Diagnosis and Therapy of the Interstitial Lung Diseases. Am J Respir Crit Care Med 2005;172:268-79.  |
| 2. | Noble PW, Albera C, Bradford WZ, Costabel U, du Bois Roland M, Fagan EA et al. Pirfenidone for idiopathic pulmonary fibrosis: analysis of pooled data from three multinational phase 3 trials. Eur Respir J 2016;47:27-30 [DOI: 10.1183/13993003.01669-2015] |
| 3. | Richeldi L, du Bois RM, Raghu G et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med 2014;370:2071-82. |
| 4. | Craig VJ, Zhang Li, Hagood JS, Owen CA. Matrix metalloproteinases as therapeutic targets for idiopathic pulmonary fibrosis. J Respir Cell Mol Biol 2015;53:585-600. |
| 5. | Mishra A, Bhattacharyya P, Paul S, Paul R, Swarnarkar S. An alternative therapy for Idiopathic Pulmonary Fibrosis by Doxycycline through matrix metallo proteinase inhibition. Lung India 2011;28:174-9. [ PUBMED] [Full text] |
| 6. | Bhattacharyya P. Lessons from the interstitial lung disease-India registry: A proposed practical scheme of classification of diffuse parenchymal lung diseases in the Indian subcontinent. Lung India 2018;35:428-30. [ PUBMED] [Full text] |
| 7. | Bhattacharyya P, Nag S, Ghosh D, Roy Chowdhury S, Bardhan S, Mukherjee A. treatment of probable idiopathic pulmonary fibrosis with long term doxycycline, a matrix metalloproteinase inhibitor. Indian J Chest Dis Allied Sci 2007;49:180. |
[Table 1]
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