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Prevalence and Prognostic Significance of Dendriform Pulmonary Ossification in the National Lung Screening Trial

Principal Investigator

Name
Kyung Hee Lee

Degrees
M.D., Ph.D.

Institution
University of Pittsburgh

Position Title
Associate Professor

Email
jil722@pitt.edu

About this CDAS Project

Study
NLST (Learn more about this study)

Project ID
NLST-1491

Initial CDAS Request Approval
Jan 26, 2026

Title
Prevalence and Prognostic Significance of Dendriform Pulmonary Ossification in the National Lung Screening Trial

Summary
Dendriform pulmonary ossification (DPO) is an uncommon form of diffuse pulmonary ossification characterized by branching, tree-like formations of mature bone within the lung parenchyma. DPO may occur idiopathically or secondary to chronic lung diseases and has been reported in association with interstitial lung disease (ILD), smoking, chronic obstructive pulmonary disease (COPD), and chronic aspiration. With the widespread adoption of thin-section chest CT, DPO is being increasingly recognized; however, its true prevalence and clinical relevance remain poorly defined.

Prior studies suggest that DPO occurs more frequently in idiopathic pulmonary fibrosis (IPF) than in other forms of ILD. In the absence of fibrotic ILD, DPO has been associated with aspiration, and it has been reported more commonly in male patients, smokers, and individuals with COPD. More recently, DPO has been proposed as a distinct radiologic phenotype within the spectrum of interstitial lung abnormalities (ILAs) (Japanese Journal of Radiology 2024;42:993–1002; J Thorac Dis 2025;17:3450–3455). Despite these observations, the prevalence of DPO as an ILA phenotype in lung cancer screening populations has not been evaluated. Moreover, although DPO has been described in association with fibrotic lung disease, its prognostic significance remains largely unknown.

The National Lung Screening Trial (NLST) provides a unique opportunity to address these knowledge gaps in a large, well-characterized cohort of high-risk individuals who underwent low-dose CT (LDCT) screening with longitudinal follow-up for lung cancer incidence and mortality. ILAs identified on LDCT have been associated with an increased incidence of lung cancer and worse clinical outcomes. Given emerging evidence linking DPO to ILAs and fibrotic lung disease, systematic evaluation of the prognostic significance of DPO in this population is warranted.

Accordingly, the aims of this study are to determine the prevalence of dendriform pulmonary ossification in the NLST cohort and investigate its association with clinical and prognostic outcomes, including lung cancer incidence and mortality.

Aims

Aim 1: Determine the prevalence of dendriform pulmonary ossification on baseline low-dose CT scans in the NLST cohort.
We will establish the prevalence of DPO in a large lung cancer screening population using baseline LDCT scans from the NLST. DPO will be identified as branching or linear ossified structures within the lung parenchyma that are distinct from nodular pulmonary calcifications or vascular calcification. Overall prevalence will be estimated with corresponding confidence intervals and stratified by age, sex, and other relevant demographic and clinical variables.

Aim 2: Evaluate the association between DPO and coexisting CT imaging features, including ILA, emphysema, fibrotic changes (traction bronchiectasis, honeycombing), hiatal hernia, and cardiovascular abnormalities.
We will characterize the imaging phenotype associated with DPO and examine its relationship with other thoracic abnormalities detected on LDCT. ILAs and their subtypes will be assessed using established Fleischner Society criteria, with particular attention to fibrotic features such as reticulation, traction bronchiectasis, and honeycombing. Emphysema severity will be assessed visually or quantitatively, as available. Additional CT features potentially relevant to DPO pathophysiology, including hiatal hernia as a surrogate marker of chronic aspiration and cardiovascular abnormalities such as coronary artery and aortic calcification, will also be evaluated.

Aim 3: Evaluate the longitudinal evolution of DPO and associated interstitial abnormalities on serial CT imaging.
Using available follow-up LDCT scans, we will assess temporal changes in the extent and distribution of DPO and coexisting interstitial abnormalities. We will examine whether DPO remains stable, progresses, or is associated with progression of fibrotic features over time. This aim will provide insight into the natural history of DPO and its relationship to progressive lung remodeling.

Aim 4: Determine the association between DPO and lung cancer risk.
We will evaluate whether the presence of DPO on baseline LDCT is independently associated with lung cancer risk.

Aim 5: Assess the prognostic significance of DPO for mortality outcomes.
We will examine the association between baseline DPO and all-cause mortality, lung cancer–specific mortality, and cardiovascular mortality using time-to-event analyses with Cox proportional hazards models. Models will adjust for demographic factors, emphysema, the extent of ILAs, cardiovascular CT findings, and other relevant covariates. This aim will determine whether DPO is a clinically meaningful imaging biomarker of prognosis.

Collaborators

Kyung Hee Lee University of Pittsburgh, University of Pittsburgh Medical Center
Onder Omer University of Pittsburgh, University of Pittsburgh Medical Center
Junwoo Kim University of Pittsburgh, University of Pittsburgh Medical Center
Zandifar, Afrooz University of Pittsburgh, University of Pittsburgh Medical Center