Performance of Forced Vital Capacity and Lung Diffusion Cutpoints for Associated Radiographic Interstitial Lung Disease in Systemic Sclerosis

Abstract

Objective Forced vital capacity (FVC) and carbon monoxide diffusion (DLCO) are used for systemic sclerosis-associated interstitial lung disease (SSc-ILD) screening. The study purpose was to determine the sensitivity, specificity, and negative predictive value (NPV) (proportion of true negative screening tests) of FVC and DLCO thresholds for SSc-ILD on chest high-resolution computed tomography (HRCT) scans. Methods Patients fulfilling American College of Rheumatology 2013 SSc criteria with a chest HRCT scan and pulmonary function tests (PFT) were studied. A thoracic radiologist quantified radiographic ILD. Optimal FVC and DLCO % predicted thresholds for ILD were identified using receiver operating characteristic curves. The FVC and DLCO combinations with greatest sensitivity and specificity were also determined. Sub-analysis was performed in patients with positive Scl-70 autoantibodies. Results 265 patients were studied. Of 188 (71%) with radiographic ILD, 59 out of 188 (31%) had “normal” FVC (≥80% predicted), and 65 out of 151 (43%) had “normal” DLCO (≥60% predicted). FVC <80% (sensitivity 0.69, specificity 0.74), and DLCO <62% (sensitivity 0.60, specificity 0.70) were optimal thresholds for radiographic SSc-ILD. All FVC and DLCO threshold combinations evaluated had NPV <0.70. The NPV for radiographic ILD for FVC <80% was lower in patients with positive Scl-70 autoantibody (NPV=0.05) compared to negative Scl-70 autoantibody (NPV=0.57). Conclusions Radiographic ILD is prevalent in SSc despite “normal” PFTs. No % predicted FVC or DLCO threshold combinations yielded high NPV for SSc-ILD screening. “Normal” FVC and DLCO in SSc patients, especially those with positive Scl-70 autoantibodies, should not obviate consideration of HRCT for ILD evaluation.

Performance Characteristics of Pulmonary Function Tests for the Detection of Interstitial Lung Disease in Adults With Early Diffuse Cutaneous Systemic Sclerosis

“…Although pulmonary function tests (PFTs) are frequently used by rheumatologists as a screening test for ILD in their patients with SSc, studies have shown that they lack sensitivity for the detection of ILD in a general population of patients with SSc (4,7). For example, in a cross‐sectional study of 102 patients with SSc (41% with diffuse cutaneous SSc [dcSSc]) with a median disease duration of 6 years (interquartile range [IQR] 3–12.5 years), a forced vital capacity (FVC) <80% predicted had a sensitivity of only 37.5% for the detection of ILD on HRCT imaging (4).…”

Rituximab and antimetabolite treatment of granulomatous and lymphocytic interstitial lung disease in common variable immunodeficiency

“…These results are consistent with an increasing body of literature indicating that PFTs are less sensitive than HRCT in detecting the presence of or assessing the severity of interstitial lung disease in CVID or collagen vascular diseases. [27][28][29] Combination immunosuppressive therapy induced long-lived remissions in the majority of patients. Excluding 2 patients who died and 1 who had a lung transplant, 9 of 36 patients (25%) had a relapse of GLILD when not undergoing immunosuppressive therapy.…”

Regulator combinations identify systemic sclerosis patients with more severe disease

“…For the Assassi et al data set (14), which was used as the training data set, patients were classified as having ILD when the percentage FVC predicted was less than 70%. For the Hinchcliff et al data set (5), which was used as validation cohort, ILD was defined as the presence of radiographic findings consistent with ILD in the opinion of an expert thoracic radiologist (5,51). The Cheadle et al data set (38), also used as a validation cohort, defined ILD according to pulmonary function tests and chest high-resolution computed tomography.…”