Long-term use of doxycycline can improve chronic asthma and possibly remodeling: the result of a pilot observation

Abstract

Parthasarathi Bhattacharyya, Rantu Paul, Partha Bhattacharjee, Arko Ghosh, Ratna Dey, Malabika Ghosh, Madan SharmaInstitute of Pulmocare and Research, CB 16, Salt Lake, Sector 1, Kolkata-700064, IndiaAbstract: Progressive loss of lung function and reversibility characterize chronic asthma. The conventional therapy is targeted to control the disease without targeting the loss of lung function or reversibility. In a prospective real-world observation of long-term use of add-on doxycycline as a matrix-metalloproteinase inhibitor, we documented significant improvement in lung function with possible reversal of remodeling.Background: Chronic asthma shows progressive decline in lung function with reduction or even loss of reversibility secondary to remodeling. A set of endopeptidase enzymes known as matrix metalloproteinases are intimately related to the pathogenesis of asthma and remodeling. The inhibition of matrix metalloproteinases is recognized as a prospective way of treating asthma and its corresponding structural remodeling.Methods: In a randomized, prospective, real-world study, we have observed the change in lung function (spirometry) with an add-on of long-term doxycycline to standard asthma therapy as per the Global Initiative for Asthma guidelines in a small asthmatic population. The change in terms of forced expiratory volume (FEV1), forced vital capacity (FVC), percent of FEV1 (FEV1%), and forced expiratory flow (FEF25–75) were noted following variable duration of doxycycline therapy.Results: There has been a global improvement in all the parameters in all the six patients suggesting improvement in obstruction, and reduction in air trapping following a treatment of add-on doxycycline for a mean duration of 162.83 ± 83.07 days. Of the changes seen, the post bronchodilator FEV1, the FVC, and the FEF25–75 showed significant improvements with the P-value set at 0.004, 0.054, and 0.031, respectively. There was also evidence of the reversal of remodeling from the improvement in the FEV1/FVC ratio. Moreover there was a greater than expected improvement of pre-bronchodilator FEV1 after treatment that far surpassed the initial post-bronchodialator FEV1 value. Even after such a change, there were presences of some reversibility suggesting room for further improvement.Conclusion: The results suggest significant improvements in the obstructive parameters used to evaluate asthma, with possible reversal of remodeling evident in chronic asthmatics when treated with doxycycline in addition to standard therapies. This observation needs further scientific validation.Keywords: chronic asthma, doxycycline, FEV1, FEV1/FVC, matrix metalliproteinase