Clinical, imaging, and blood biomarkers to assess 1-year progression risk in fibrotic interstitial lung diseases-Development and validation of the honeycombing, traction bronchiectasis, and monocyte (HTM)-score

Guangyu Shao; Patricia Hawle; Kaveh Akbari; Andreas Horner; Rainer Hintenberger; Bernhard Kaiser; Bernd Lamprecht; David Lang

doi:10.3389/fmed.2022.1043720

Clinical, imaging, and blood biomarkers to assess 1-year progression risk in fibrotic interstitial lung diseases-Development and validation of the honeycombing, traction bronchiectasis, and monocyte (HTM)-score

Front Med (Lausanne). 2022 Nov 16:9:1043720. doi: 10.3389/fmed.2022.1043720. eCollection 2022.

Authors

Guangyu Shao^{1

2}, Patricia Hawle², Kaveh Akbari^{2

3}, Andreas Horner^{1

2}, Rainer Hintenberger^{2

4}, Bernhard Kaiser¹, Bernd Lamprecht^{1

2}, David Lang^{1

2}

Affiliations

¹ Department of Internal Medicine 4 - Pneumology, Kepler University Hospital, Linz, Austria.
² Medical Faculty, Johannes Kepler University Linz, Linz, Austria.
³ Central Radiology Institute, Kepler University Hospital, Linz, Austria.
⁴ Department of Internal Medicine 2, Kepler University Hospital, Linz, Austria.

Abstract

Introduction: Progression of fibrotic interstitial lung disease (ILD) leads to irreversible loss of lung function and increased mortality. Based on an institutional ILD registry, we aimed to evaluate biomarkers derived from baseline patient characteristics, computed tomography (CT), and peripheral blood for prognosis of disease progression in fibrotic ILD patients.

Methods: Of 209 subsequent ILD-board patients enregistered, 142 had complete follow-up information and were classified fibrotic ILD as defined by presence of reticulation or honeycombing using a standardized semi-quantitative CT evaluation, adding up typical ILD findings in 0-6 defined lung fields. Progression at 1 year was defined as relative loss of ≥10% in forced vital capacity, of ≥15% in diffusion capacity for carbon monoxide, death, or lung transplant. Two-thirds of the patients were randomly assigned to a derivation cohort evaluated for the impact of age, sex, baseline lung function, CT finding scores, and blood biomarkers on disease progression. Significant variables were included into a regression model, its results were used to derive a progression-risk score which was then applied to the validation cohort.

Results: In the derivation cohort, age, monocyte count ≥0.65 G/L, honeycombing and traction bronchiectasis extent had significant impact. Multivariate analyses revealed the variables monocyte count ≥0.65 G/L (1 point) and combined honeycombing or traction bronchiectasis score [0 vs. 1-4 (1 point) vs. 5-6 lung fields (2 points)] as significant, so these were used for score development. In the derivation cohort, resulting scores of 0, 1, 2, and 3 accounted for 1-year progression rates of 20, 25, 46.9, and 88.9%, respectively. Similarly, in the validation cohort, progression at 1 year occurred in 0, 23.8, 53.9, and 62.5%, respectively. A score ≥2 showed 70.6% sensitivity and 67.9% specificity, receiver operating characteristic analysis for the scoring model had an area under the curve of 71.7%.

Conclusion: The extent of honeycombing and traction bronchiectasis, as well as elevated blood monocyte count predicted progression within 1 year in fibrotic ILD patients.

Keywords: autoimmune disease; diffusion capacity (DL); forced vital capacity (FVC); honeycombing; idiopathic pulmonary fibrosis; lung fibrosis; monocyte count; traction bronchiectasis.