Background/Purpose: We previously reported that there was patterns of coexistence of pulmonary lesions and airway disease (AD) were common abnormities of patients with pulmonary involvement. However, it remains unknown through what pathways various pulmonary lesions develop.@The purpose of this study was to determine the sequential development of pulmonary lesions in RA. For this purpose, we examined the pattern of newly emerging pulmonary lesions and relationship between pre-existing and new lesions.

Methods: A retrospective cohort study. Subjects were consecutive 208 RA patients who started bDMARDs in our department and received HRCT scan before and during the therapy. Based on HR-CT, pulmonary abnormalities were classified 20 lesions such as ground-glass opacity (GGO), reticular pattern, and bronchiolitis. We recorded their existence and changes during the therapy. Cluster analysis was conducted according to new lesions by Ward method. A checkerboard analysis of pre-existing and new lesions was conducted.

Results: Subjects were 208 RA patients, M/F; 64/144, mean age; 59.2 years old, disease duration; 7.9 years. bDMARDs used for the longest period were TNF inhibitors in 79.8% of the subjects. Pulmonary abnormalities were found in 146 (70.2%) of RA patients (ILD 81,(38.9%); nodular lesions 45,(21.6%); and AD 115,(55.3%)) at the entry. During the observation period (3.26}2.61 years), new pulmonary lesions were found in 31.3% of patients and the incidence was 10.0/100-person year. New lesions were frequently occurred in patients with pre-existing pulmonary lesions. Cluster analysis of new lesions showed 7 clusters; Cluster 1:nodular lesions developed mainly patients with AD and reticular pattern, Cluster 2;curved linear opacities with/ without reticular pattern which occurs in patients without pre-existing diseases or bronchiolitis with nodules, Cluster3; bronchiectasis developed in patients with bronchiolitis, Cluster 4; consolidation developed in patients with pre-existing pulmonary diseases, particularly AD, Cluster 5; bronchiolitis occurred in patients with bronchiectasis, Cluster 6; no new pulmonary lesions and Cluster 7; GGO developed in patients with AD and fibrotic ILD. Similarly, a checkerboard analysis of pre-existing and new lesions revealed followings (Fig.1); 1) in patients without pre-existing lesions, bronchiolitis or curved linear opacities occurred, 2) patients with bronchiolitis developed bronchiectasis, 3) reticular pattern occurred in patients with AD (bronchiolitis/ bronchiectasis), and 4) patients with AD with reticular pattern developed GGO and/or consolidation.

Conclusion: Pulmonary lesions were developed in several patterns, not at random. Pre-existing pulmonary lesion induced new pulmonary lesions. Airway diseases, particularly bronchiolitis, might be an important lesion that induce ILD (and nodular lesions).