Evaluation of the role of Matrix metalloproteinases (MMPs) in Idiopathic Pulmonary Fibrosis (IPF) and assessment of clinicoradiological effect of Matrix metalloproteinases inhibition with Doxycycline.

Idiopathic pulmonary fibrosis is a problem of progressive fibrosis of the lung parenchyma without any apparent etiology leading to significant morbidity and premature mortality. The present treatment is limited to the use of corticosteroid and immunosuppressive agents with variable outcome and poor survival expectancy as 30 to 50% at 5 years after the diagnosis. In the process of fibrogenesis, there is a potential role of a class of enzyme called matrix metalloproteinases (MMPs). An imbalance of the MMPs and their tissue inhibitor (TIMPs) can lead to release of growth factors for fibroblast proliferation. Thus MMPs may play an important role in the pathogenesis of IPF and inhibition of MMPs could be a therapeutic target for the disease. The authors have experienced such therapeutic improvement in cases of IPF with doxycycline, an agent known for its MMPs inhibitory property with its use being accepted as MMPs inhibitor for periodontal disease by the FDA, xml:namespace prefix = st1 ns = "urn:schemas-microsoft-com:office:smarttags" /USA. The drug, doxycycline, has been well in use for a prolonged period of time in many conditions without problem of tolerance or toxicity.  It is a drug easily available in the market as an antibiotic for over three decades and has got certain established long term use too.xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /

The proposed project is to evaluate the role of MMPs in clinicoradiologically diagnosed IPF as per ATS-ERS guideline and also to assess the use of doxycycline in MMPs inhibition in the disease. The entire work can be simply and effectively done by way of observing the changes in different MMPs and TIMPs levels in BAL (broncho alveolar lavage) fluid of IPF patients before and following administration of doxycycline simultaneous to objective documentation of favourable effects on clinical, radiological and physiological status of the patients.