Efficacy of treatment with corticosteroids for fibrotic hypersensitivity pneumonitis: a propensity score-matched cohort analysis

Abstract

Background: Fibrotic hypersensitivity pneumonitis (HP) is a chronic interstitial lung disease caused by allergic responses to repeated exposures to a causative antigen. Therapeutic evidence of the use of corticosteroids to treat fibrotic HP remains lacking, although corticosteroids are recognized as a major treatment option. The purpose of this study was to evaluate the efficacy of corticosteroid treatment in patients with fibrotic HP in a propensity score-matched cohort.

Methods: A retrospective review of the medical records from 2005 to 2019 in a single center was conducted, and 144 patients with fibrotic HP were identified. Semiquantitative scores for lung abnormalities on HRCT were evaluated. Patients who received (PDN group) and did not receive (non-PDN group) corticosteroid treatment were matched using a propensity score method. Survival rates, serial changes in pulmonary function and annual changes in HRCT scores were compared in the matched cohort.

Results: In the matched analysis, 30 individuals in the PDN group were matched with 30 individuals in the non-PDN group, the majority of whom had ILD without extensive fibrosis. The survival rate was significantly better in the PDN group (P = 0.032 for the stratified Cox proportional hazards model; HR, 0.250). The absolute changes in FVC at 6, 12, and 24 months from baseline were significantly better in the PDN group. Fewer patients in the PDN group experienced annual deterioration, as reflected in the HRCT score, due to ground-glass attenuation, consolidation, reticulation, traction bronchiectasis and honeycombing.

Conclusion: We demonstrated that corticosteroids improved survival and slowed fibrotic progression in a matched cohort, the majority of whom had ILD without extensive fibrosis. Fibrotic HP with less severe fibrosis may benefit from corticosteroid treatment. We propose that the early initiation of corticosteroids should be considered for fibrotic HP when worsening fibrosis is observed.

Keywords: Corticosteroid; Fibrotic hypersensitivity pneumonitis; Propensity score matching.

Fig. 1

Patient recruitment flow diagram detailing the inclusion and exclusion of patients and the reasons for exclusion. The bold lines represent the patient groups included in further analysis. HP hypersensitivity pneumonitis; ILD interstitial lung disease; PDN prednisolone

Fig. 2

Kaplan–Meier curves for survival in the entire cohort and the matched cohort. Solid and dotted lines represent the PDN group and the non-PDN group, respectively. a In the entire cohort, the survival rate was significantly worse in the PDN group, with P = 0.040 (hazard ratio [HR], 1.878; 95% confidence interval [CI], 1.029–3.426). The median survival periods were 37 months (95% CI 26–55 months) and NR, respectively. b In the matched cohort, the survival rate was better in the PDN group, with P = 0.032 (HR, 0.250; 95% CI, 0.071–0.886). The median survival durations were NR and 60 months, respectively. CI confidence interval; HR hazard ratio; NR not reached; PDN prednisolone; SD standard deviation

Fig. 3

Absolute changes in %FVC from baseline in the entire cohort and the matched cohort. Between-group differences in the absolute changes in %FVC from baseline (Δ%FVC) described as the mean (SD) at the 6-, 12-, and 24-month follow-ups were compared. Solid and dotted lines represent the PDN group and the non-PDN group, respectively. a In the entire cohort, the Δ%FVC in the PDN group was significantly different from that in the non-PDN group at 6 months (4.0% [8.8] vs − 3.2% [3.8], P < 0.001), 12 months (2.9% [10.0] vs − 5.5% [6.5], P < 0.001), and 24 months (0.8% [11.8] vs − 10.3% [9.8], P < 0.001). P-values were obtained with the Mann–Whitney U test. b In the matched cohort, the Δ%FVC in the PDN group was significantly different from that in the non-PDN group at 6 months (6.6% [8.2] vs − 3.2% [3.6], P < 0.001), 12 months (5.0% [9.7] vs − 4.9% [5.6], P < 0.001), and 24 months (0.9% [13.4] vs − 9.4% [8.6], P = 0.001). P-values were obtained with the Wilcoxon signed-rank test. A *** indicates a P-value < 0.001, a ** indicates a P-value < 0.01. FVC forced vital capacity; PDN prednisolone; SD standard deviation

Fig. 4

Trends in the 1-year change in total scores from baseline for each HRCT finding. The total scores for GGA and consolidation appeared to improve, with slow progression in reticulation, traction bronchiectasis, and honeycombing in the PDN group. The whiskers at the bottom and top represent the 25th and 75th percentiles, respectively. The middle horizontal lines are the median. GGA ground glass attenuation; PDN prednisolone

Fig. 5

Representative matched pairs of patients. A, B A 63-year-old male with fibrotic bird-related hypersensitivity pneumonitis was treated with prednisolone from baseline until the end of the follow-up period at 60 months. At baseline, the patient’s %FVC was 57.9%, his annual %FVC decline before treatment was 26.1%, and his BAL lymphocyte count was 29%. At the 1-year follow-up, the change in %FVC from baseline was + 15.9%. A reduction in the extent of GGA with minimal fibrotic progression was observed on HRCT after one year. The total scores for the HRCT findings (baseline to the 1-year follow-up) were as follows: GGA (22 to 14), consolidation (2 to 0), reticulation (12 to 13), traction bronchiectasis (6 to 8), honeycombing (13 to 14), and mosaic attenuation (2 to 0). C, D A 66-year-old male with fibrotic bird-related hypersensitivity pneumonitis did not undergo treatment with corticosteroids and died at 17 months. At baseline, his %FVC was 46.6%, and his annual FVC decline until the date of diagnosis was 4.7%. At the 1-year follow-up, the change in %FVC from baseline was − 12.3%. Severe fibrotic progression was observed on HRCT. The total scores for the HRCT findings were as follows: GGA (11 to 18), consolidation (5 to 6), reticulation (16 to 19), traction bronchiectasis (10 to 15), honeycombing (14 to 19), and mosaic attenuation (0 to 0). BAL bronchoalveolar lavage; %FVC percent forced vital capacity; GGA ground glass attenuation; HP hypersensitivity pneumonitis; HRCT high-resolution computed tomography