Richmond Ronald Gomes1* and Fazle Rabbi2
1Department of Medicine, Ad-Din Women’s Medical College Hospital, Bangladesh 2Department of Respiratory Medicine, Square Hospitals Limited, BangladeshFulltext PDF
Background: Idiopathic pulmonary fibrosis is a chronic progressive disease with poor prognosis. Some recent studies revealed that N-acetylcysteine slowed the deterioration in IPF. This trial tried to find out whether addition of N-acetylcysteine to prednisolone is superior to prednisolone monotherapy in Idiopathic Pulmonary Fibrosis (IPF). Materials and Methods: We conducted this single blind, randomized, placebo controlled trial in the National Institute of Diseases of the Chest and Hospital (NIDCH), Mohakhali, Dhaka, Bangladesh over a period of one year from January 2018 to December 2018 to assess effectiveness of high dose oral N-acetylcysteine (600 mg three times daily) added to standard therapy with prednisolone (start with 40 mg and tapered 2.5 mg after each 10 days) alone. Drug trial was conducted for a period of 12 weeks. Total 65 patients had been clinically diagnosed as Idiopathic pulmonary fibrosis confirmed by high resolution computed tomography of the chest and excluding other known causes of interstitial lung disease. Group-I patients (Nn=35) got N-acetylcysteine (600 mg three times daily for 12 weeks) with prednisolone (start with 40 mg and tapered 2.5 mg after each 10 days). Group- II patients (Np=30) got placebo (three times daily for 12 weeks) with prednisolone (start with 40 mg and tapered 2.5 mg after each 10 days). Within this period, total 12 patients (18%); 5 patients (14%) from group-I and 7 patients (23%) from group-II were dropped out, so ultimately 30 patients in group-I and 23 patients in group-II came for final follow-up. Pulmonary function tests with spirometry and carbon monoxide diffusing capacity (DLCO) was performed in each case at the beginning and at the end of study, after 12 weeks. The primary end points were changes between baseline and week 12 in vital capacity (in liter and % of predicted value) and single breath carbon monoxide diffusing capacity (DLCO) (in ml/min/kPa and % of predicted value) between two groups to assess the N-acetylcysteine efficacy. Results: A total number of 65 patients with IPF were randomly enrolled and assigned to treatment. Among them 35 patients were treated with N-acetylcysteine and prednisolone (Group-I) and the remaining 30 patients were treated with placebo and prednisolone (Group-II). Ultimately 30 patients (85.71%) in group-I and 23 patients (76.67%) in group-II came for final follow-up. The mean (± SD) difference of MRC dyspnea index at base line and follow-up during 12th week was found 0.067 ± 0.365 and -0.652 ± 0.647 in group-I & group-II respectively, which was statistically significant (p<0.05). Thus current study revealed a significant deterioration of dyspnoea in placebo group in relation to N-acetylcysteine group. Absolute mean difference at 12th week at 95% CI between two group was -0.571 (-0.989 to -0.153). The mean (± SD) difference of forced vital capacity in liter and in percentage at base line and follow-up during 12th week was found -0.05 ± 0.14, 0.22 ± 0.34 and -0.78 ± 5.59, 8.36 ± 11.19 in group-I and group-II respectively, which was statistically significant in both cases (p<0.05). The absolute mean difference at 12th week with 95% CI was -0.27 (-0.40 to -0.13) and -9.14 (-13.85 to -4.43) respectively which signified less deterioration of forced vital capacity (L and %) with N-acetylcysteine in the current study. The mean (± SD) difference of carbon monoxide diffusing capacity in ml/min/kPa and in percentage at base line and follow-up during 12th week was found -1.41 ± 2.11, 2.22 ± 2.24 and 6.14 ± 11.51, 7.55 ± 10.18 respectively in group-I and group-II, which was statistically significant (p<0.05) in both cases. Thus the absolute mean difference at 12th week with 95% CI was -3.62 (-4.83 to -2.42) and -13.69 (-19.79 to -7.59) respectively which signified less deterioration of carbon monoxide diffusing capacity in ml/min/kPa and in percentage with N-acetylcysteine in our current study. Mortality during the study was 3% among patients taking acetylcysteine and 10% among those taking placebo (P=). There were no significant differences in the type or severity of adverse events between patients taking N-acetylcysteine and those taking placebo, except for a significantly lower rate of fever (P=0.014), respiratory tract infection (P=0.001) in the group taking N-acetylcysteine (P=0.03). Conclusion: Therapy with N-acetylcysteine at a dose of 600 mg three times daily, added to prednisolone in patients with Idiopathic pulmonary fibrosis preserves vital capacity and DLCO and patients experienced better symptomatic improvement than prednisolone monotherapy.
Gomes RR, Rabbi F. Comparison of Prednisolone Monotherapy vs. Combined Prednisolone and N-Acetylcystiene Dual Therapy to Treat Idiopathic Pulmonary Fibrosis. J Respir Med Lung Dis. 2020; 5(2): 1055.