Long-term clinical course and outcomes of immunoglobulin G4-related lung disease

Abstract

Background: Immunoglobulin G4-related lung disease (IgG4-RLD) is the pulmonary manifestation of a systemic fibroinflammatory disease characterized by lymphoplasmacytic infiltration with an abundance of IgG4-positive plasma cells. Long-term clinical course and outcomes of IgG4-RLD remain unclear. We aimed to identify clinical characteristics, treatment outcomes, and longitudinal pulmonary function changes in patients with IgG4-RLD according to the radiologic classification.

Methods: Chest computed tomography findings of 37 subjects were classified into five subtypes: solid nodular, bronchovascular, alveolar interstitial, round ground glass opacity, and alveolar consolidative. Radiologic treatment outcomes and longitudinal pulmonary function changes were compared among the different radiologic subtypes.

Results: The mean age of the subjects was 55.6 years, and 78.4% were male. Among the five radiologic subtypes, alveolar consolidative and solid nodular type were most common, accounting for approximately 29.7% each of the total cases. Prednisone with or without azathioprine was administered to 31 patients (median treatment duration 14 months). In the treated patients, serial images showed complete response or partial response in 77.4%. However, relapse was documented in 25.0% of those who showed complete or partial response. In patients whose longitudinal lung function data were available (n = 20), the lung function was found to be stable during follow-up. Alveolar consolidative type showed the highest complete response rate, whereas alveolar interstitial type showed the lowest response rate, either complete or partial.

Conclusions: Most patients showed a favorable outcome with regards to radiologic improvement and maintenance of pulmonary function; however, the response differed according to the radiologic subtype.

Keywords: Chest computed tomography; Immunoglobulin G4-related disease; Lung function; Treatment outcome.

Fig. 1

Radiologic subtypes of IgG4-RLD. a Alveolar consolidative type, distinguished by airspace filling opacities obscuring vasculature in a segmental or lobar distribution; b Solid nodular type, characterized by a lung nodule or mass; c Bronchovascular type, characterized by a thickening of bronchovascular bundle and interlobular septa; d Alveolar interstitial type, showing reticulation, diffuse GGO, and honeycombing; e Round ground glass opacity type, showing multiple round-shaped GGO lesions

Fig. 2

Clinical course of the patients with IgG4-RLD. ^aMean initial prednisone dose was 37.8 mg/day (48.5 mg and 27.0 mg for prednisone alone and azathioprine combination groups, respectively). ^bFor patients with relapse, mean initial prednisone dose was 34.1 mg/day (35.0 mg and 33.8 mg for prednisone alone and azathioprine combination groups, respectively). IgG4-RLD immunoglobulin G4-related lung disease, PD prednisone, AZA azathioprine, CR complete response, PR partial response, SD stable disease, F/U follow up

Fig. 3

Longitudinal pulmonary function changes in patients who were treated for IgG4-RLD. A linear mixed model was used to calculate the estimated mean changes in lung function parameters. TLC total lung capacity, FVC forced vital capacity, FEV₁ forced expiratory volume at 1 s, DL_CO diffusing capacity of the lung for carbon monoxide