Brief Report: Pulmonary Function Tests: High Rate of False-Negative Results in the Early Detection and Screening of Scleroderma-Related Interstitial Lung Disease

Arthritis Rheumatol. 2015 Dec;67(12):3256-61. doi: 10.1002/art.39405.

Abstract

Objective: Validated methods for the screening and early diagnosis of systemic sclerosis (SSc; scleroderma)-related interstitial lung disease (ILD) are needed. The aim of this study was to evaluate the performance of pulmonary function tests (PFTs) compared with that of high-resolution computed tomography (HRCT) of the chest for the detection of SSc-related ILD in clinical practice, and to identify predictors of lung involvement that is functionally occult but significant on HRCT.

Methods: Prospectively enrolled patients with SSc were assessed according to the European League Against Rheumatism (EULAR)/EULAR Scleroderma Trial and Research standards. The assessment included PFTs and HRCT. The HRCT images were evaluated in a blinded manner by 2 experienced radiologists. The performance parameters of PFTs for the diagnosis of SSc-related ILD were calculated. Predictors of significant ILD as determined by HRCT in patients with normal forced vital capacity (FVC) values were identified through logistic regression.

Results: Among the 102 patients, 64 (63.0%) showed significant ILD on HRCT, while only 27 (26.0%) had an FVC <80% of predicted, and 54 (53.0%) had a decrease in the results of at least 1 PFT. Forty (62.5%) of 64 patients with significant ILD on HRCT had a normal FVC value, translating into a high false-negative rate. Notably, 5 of 40 patients with a normal FVC value had severe, functionally occult lung fibrosis; in 2 of these patients, the results of all of the PFTs were within normal limits. Patients with normal FVC values despite evidence of fibrosis on HRCT more frequently had anti-Scl-70 antibodies and diffuse SSc and less frequently had anticentromere antibodies (ACAs) compared with patients with both normal FVC values and normal HRCT results.

Conclusion: The derived evidence-based data reveal a high risk of missing significant SSc-related ILD when relying solely on PFTs. More comprehensive screening algorithms for early detection are warranted. In particular, additional imaging investigations for the early detection of SSc-related ILD should be considered in ACA-negative patients with normal FVC values.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Antinuclear
  • Cohort Studies
  • Diagnostic Errors*
  • Early Diagnosis
  • False Negative Reactions
  • Female
  • Humans
  • Logistic Models
  • Lung Diseases, Interstitial / diagnosis*
  • Lung Diseases, Interstitial / diagnostic imaging
  • Lung Diseases, Interstitial / etiology
  • Lung Diseases, Interstitial / immunology
  • Male
  • Middle Aged
  • Multidetector Computed Tomography
  • Prospective Studies
  • Pulmonary Diffusing Capacity
  • Pulmonary Fibrosis / diagnosis*
  • Pulmonary Fibrosis / diagnostic imaging
  • Pulmonary Fibrosis / etiology
  • Pulmonary Fibrosis / immunology
  • Respiratory Function Tests*
  • Scleroderma, Systemic / complications
  • Scleroderma, Systemic / diagnosis*
  • Scleroderma, Systemic / diagnostic imaging
  • Scleroderma, Systemic / immunology
  • Total Lung Capacity
  • Vital Capacity

Substances

  • Antibodies, Antinuclear
  • anticentromere antibody