J Clin Med. 2021;10(17):jcm10173812.

The Extent and Diverse Trajectories of Longitudinal Changes in Rheumatoid Arthritis Interstitial Lung Diseases Using Quantitative HRCT Scores.

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제1저자 이정석, Grace-Hyun J Kim · 교신저자 이은영

PMID 34501260 PMC8432030 DOI 10.3390/jcm10173812 IF 3.3 류마티스내과

소속 (6)

Clinic Pappalardo Center, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea.
GENOME INSIGHT Inc., Daejeon 34051, Korea.
Department of Radiology, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Department of Internal Medicine, Division of Rheumatology, Seoul National University Bundang Hospital, Seongnam-si 13620, Korea.
Department of Internal Medicine, Division of Rheumatology, College of Medicine, Seoul National University, Seoul 03080, Korea.

Abstract

We aimed to validate quantitative high-resolution computed tomography (HRCT) imaging analyses of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients, and to delineate a broad spectrum of annual longitudinal changes of ILD severity in the RA-ILD cohorts. Retrospective cohort 1 (n = 26) had matched PFT results and prospective cohort 2 (n = 34) were followed for over two years with baseline serum specimen. Automated quantitative analysis of HRCT was expressed as the extent of ground-glass opacity, lung fibrosis, honeycombing, and their summation-the total extent of quantitative ILD (QILD). Higher QILD score was associated with lower pulmonary function especially for DLCO% (ρ = -0.433, p = 0.027). Higher serum level of Krebs von den Lungen 6 were significantly associated with high QILD scores (ρ = 0.400, p = 0.026). Regarding QILD score changes in whole lung, even a single point increase was significantly associated with interval progression detected by the radiologist. Four distinct patterns (improvement, worsening, convex-like, and concave-like) during the 24 months were described by QILD scores. Prolonged disease duration of ILD at baseline was significantly associated with worsening of QILD scores. QILD has the potential to reliably evaluate the dynamic severity changes in patients with RA-ILD.

Keywords

interstitial lung diseasequantitative scorerheumatoid arthritis

Figures

**Figure 1** Quantitative correlation among QILD scores, computed total lung capacity, and the pulmonary function in the whole lung of RA-ILD patients at baseline (cohort 1). (A) FVC% (B) DLCO%. DLCO%, diffusing capacity of carbon monoxide % predicted; FVC%, forced vital capacity % predicted; ILD, interstitial lung disease; QILD, quantitative ILD score; RA, rheumatoid arthritis.

**Figure 2** Quantitative correlation between QILD scores and serum concentration of KL-6 in the RA-ILD patients at baseline (cohort 2, n = 31). (A) QILD, (B) QGG, (C) QLF, (D) QHC. QGG, quantitative ground glass score; QLF, quantitative lung fibrosis score; QHC, quantitative honeycombing score.

**Figure 3** Two distinct patterns of association between QILD score and serum KL-6 level were presented by representative cases having similar serum KL-6 levels (cohort 2). (A) HRCT scans of 3 cases with bronchiectasis; QLF 6.7 ± 0.9, QILD 32.1 ± 3.6, TLC 2.9 ± 0.5 L, and KL-6 337.9 ± 41.2 U/mL. (B) HRCT scans of 3 cases without bronchiectasis; QLF 1.5 ± 0.8, QILD 8.9 ± 4.5, TLC 3.6 ± 0.6 L, and KL-6 359.9 ± 8.2 U/mL. Mean ± standard deviation; Upper row: transverse view; Lower row: coronal view; QLF = sum of red and blue dot, QGG = yellow dot.

**Figure 4** Changing patterns of QILD scores in whole lung (left panels) and lobe of maximal involvement (right panels). (A) Cohort 1 (n = 26). (B) Cohort 2 (n = 34). Red dashed line: +3; Blue dashed line: −3.

**Figure 5** Four distinct patterns of change in 3 longitudinally obtained QILD scores (cohort 2, n = 24). (A) Whole lung QILD scores were depicted as four patterns of change: Improving (n = 4), worsening (n = 6), convex-like dynamic change (n = 4), and concave-like dynamic change (n = 10). (B) Velocity of QILD score change per year between visits 1 and 2 and visits 2 and 3.

**Figure 6** Four cases representing dynamic change of the severity of RA-ILD during 2 years (cohort 2). QILD scores were calculated for each patient who had 3 HRCT scans with 1 year interval without obvious acute exacerbation: (A) Improved case (Patient 9), (B) Worsened (Patient 5), (C) Convex (Patient 12), and (D) Concaved changed (Patient 3). Upper row: transverse view; Lower row: coronal view; QLF = sum of red and blue dot, QGG = yellow dot. Four distinct patterns of change in 3 longitudinally-obtained QILD scores (cohort 2, n = 24). (A) Whole lung QILD sc.

그림 출처: PubMed Central 공개 논문 (PMC8432030)

Conflict of interest statement

Lee J.S. is a board member of GENOME INSIGHT Inc.

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