Lung imaging patterns in connective tissue disease-associated interstitial lung disease impact prognosis and immunosuppression response

Abstract

Objectives: Interstitial lung disease (ILD) in CTDs has highly variable morphology. We aimed to identify imaging features and their impact on ILD progression, mortality, and immunosuppression response.

Methods: Patients with CTD-ILD had high-resolution chest CT (HRCT) reviewed by expert radiologists blinded to clinical data for overall imaging pattern [usual interstitial pneumonia (UIP); non-specific interstitial pneumonia (NSIP); organizing pneumonia (OP); fibrotic hypersensitivity pneumonitis (fHP); and other]. Transplant-free survival and change in percent-predicted forced vital capacity (FVC) were compared using Cox and linear mixed-effects models adjusted for age, sex, smoking, and baseline FVC. FVC decline after immunosuppression was compared with pre-treatment.

Results: Among 645 CTD-ILD patients, the most frequent CTDs were SSc (n = 215), RA (n = 127), and inflammatory myopathies (n = 100). NSIP was the most common pattern (54%), followed by UIP (20%), fHP (9%), and OP (5%). Compared with the case for patients with UIP, FVC decline was slower in patients with NSIP (by 1.1%/year, 95% CI 0.2, 1.9) or OP (by 3.5%/year, 95% CI 2.0, 4.9), and mortality was lower in patients with NSIP [hazard ratio (HR) 0.65, 95% CI 0.45, 0.93] or OP (HR 0.18, 95% CI 0.05, 0.57), but higher in fHP (HR 1.58, 95% CI 1.01, 2.40). The extent of fibrosis also predicted FVC decline and mortality. After immunosuppression, FVC decline was slower compared with pre-treatment in NSIP (by 2.1%/year, 95% CI 1.4, 2.8), with no change for UIP or fHP.

Conclusion: Multiple radiologic patterns are possible in CTD-ILD, including a fHP pattern. NSIP and OP were associated with better outcomes and response to immunosuppression, while fHP had worse survival compared with UIP.

Keywords: connective tissue disease; interstitial lung disease; prognosis; radiologic patterns.

Figure 1.

Radiologist-defined imaging patterns (a) and individual features (b) present in CTD-ILD. n: number of patients with each CTD diagnosis; fHP: fibrotic hypersensitivity pneumonitis; GGO: ground-glass opacities; IIM: idiopathic inflammatory myositis; LIP: lymphoid interstitial pneumonia; MCTD: mixed CTD; NSIP: non-specific interstitial pneumonia; OP: organizing pneumonia; UCTD: undifferentiated CTD; UIP: usual interstitial pneumonia

Figure 2.

Linear mixed-model of FVC decline in all CTD-ILD. Multivariable analyses adjusted for age, sex, smoking pack years, and baseline FVC. CTD-ILD: CTD-associated interstitial lung disease; FVC: forced vital capacity; FVC%: percent-predicted forced vital capacity; UIP: usual interstitial pneumonia; NSIP: non-specific interstitial pneumonia; OP: organizing pneumonia; fHP: fibrotic hypersensitivity pneumonitis

Figure 3.

Mortality in CTD-ILD stratified by imaging pattern. Adjusted HR, hazard ratio adjusted for age, sex, smoking pack years, and baseline FVC using Cox regression analyses. CTD-ILD: CTD-associated interstitial lung disease; FVC: forced vital capacity; UIP: usual interstitial pneumonia; NSIP: non-specific interstitial pneumonia; OP: organizing pneumonia; fHP: fibrotic hypersensitivity pneumonitis

Figure 4.

FVC decline before and after immunosuppression in CTD-ILD. There were too few patients with relevant treatment data to perform a similar analysis for patients with a CT pattern of fHP. CTD-ILD: CTD-associated interstitial lung disease; UIP: usual interstitial pneumonia; NSIP: non-specific interstitial pneumonia; Tx: treatment, P adj, P value for multivariable analyses adjusted for age, sex, smoking pack years, and baseline FVC