Quantitative imaging approaches compute features within images' regions of interest. Segmentation is rarely completely automatic, requiring time-consuming editing by experts. We propose a new paradigm, called "digital biopsy," that allows for the collection of intensity- and texture-based features from these regions at least 1 order of magnitude faster than the current manual or semiautomated methods. A radiologist reviewed automated segmentations of lung nodules from 100 preoperative volume computed tomography scans of patients with non-small cell lung cancer, and manually adjusted the nodule boundaries in each section, to be used as a reference standard, requiring up to 45 minutes per nodule. We also asked a different expert to generate a digital biopsy for each patient using a paintbrush tool to paint a contiguous region of each tumor over multiple cross-sections, a procedure that required an average of <3 minutes per nodule. We simulated additional digital biopsies using morphological procedures. Finally, we compared the features extracted from these digital biopsies with our reference standard using intraclass correlation coefficient (ICC) to characterize robustness. Comparing the reference standard segmentations to our digital biopsies, we found that 84/94 features had an ICC >0.7; comparing erosions and dilations, using a sphere of 1.5-mm radius, of our digital biopsies to the reference standard segmentations resulted in 41/94 and 53/94 features, respectively, with ICCs >0.7. We conclude that many intensity- and texture-based features remain consistent between the reference standard and our method while substantially reducing the amount of operator time required.

Background

Interstitial lung abnormality (ILA) is found in 5-10% of the general population and is associated with increased mortality risk. Risk factors for ILA, including advanced age and smoking history also increase the risk for aortic stenosis (AS). Transcatheter aortic valve replacement (TAVR) has become an increasingly utilized intervention for patients with severe AS, and requires a high-resolution computed tomography (HRCT) of the chest to assess aortic valve dimensions.

Objectives

To determine the prevalence and clinical significance of ILA on HRCT performed in patients referred for TAVR.

Methods

Consecutive pre-TAVR HRCTs performed over a 5-year period were reviewed. ILA was defined as bilateral, nondependent reticular opacities. All-cause mortality among TAVR recipients was compared between ILA cases and non-ILA controls matched 2:1 by age and gender using Cox proportional hazards regression and the Kaplan Meier estimator.

Results

Of 623 HRCTs screened, ILA was detected in 92 (14.7%), including 62 patients that underwent TAVR. Among ILA cases, 17 (27.4%) had a typical or probable usual interstitial pneumonia pattern, suggesting a diagnosis of idiopathic pulmonary fibrosis. Survival was worse in ILA cases compared to non-ILA controls (p = 0.008) and ILA was an independent predictor of mortality after multivariable adjustment (HR 3.29, 95% CI 1.34-8.08; p = 0.009).

Conclusions

ILA is a common finding among patients with severe AS and is associated with increased mortality in those undergoing TAVR. Further research is needed to elucidate the biology underpinning this observation and determine whether ILA evaluation and risk stratification modulates this mortality risk.

Background

Diagnostic delays are common in patients with interstitial lung disease (ILD). A substantial percentage of patients experience a diagnostic delay in the primary care setting, but the factors underpinning this observation remain unclear. In this multi-center investigation, we assessed ILD reporting on diagnostic test interpretation and its association with subsequent pulmonology referral by a primary care physician (PCP).

Methods

A retrospective cohort analysis of patients referred to the ILD programs at UC-Davis and University of Chicago by a PCP within each institution was performed. Computed tomography (CT) of the chest and abdomen and pulmonary function test (PFT) were reviewed to identify the date ILD features were first present and determine the time from diagnostic test to pulmonology referral. The association between ILD reporting on diagnostic test interpretation and pulmonology referral was assessed, as was the association between years of diagnostic delay and changes in fibrotic features on longitudinal chest CT.

Results

One hundred and forty-six patients were included in the final analysis. Prior to pulmonology referral, 66% (n = 97) of patients underwent chest CT, 15% (n = 21) underwent PFT and 15% (n = 21) underwent abdominal CT. ILD features were reported on 84, 62 and 33% of chest CT, PFT and abdominal CT interpretations, respectively. ILD reporting was associated with shorter time to pulmonology referral when undergoing chest CT (1.3 vs 15.1 months, respectively; p = 0.02), but not PFT or abdominal CT. ILD reporting was associated with increased likelihood of pulmonology referral within 6 months of diagnostic test when undergoing chest CT (rate ratio 2.17, 95% CI 1.03-4.56; p = 0.04), but not PFT or abdominal CT. Each year of diagnostic delay was associated with a 1.8% increase in percent fibrosis on chest CT. Patients with documented dyspnea had shorter time to chest CT acquisition and pulmonology referral than patients with documented cough and lung crackles.

Conclusions

Determinants of ILD diagnostic delays in the primary care setting include underreporting of ILD features on diagnostic testing and prolonged time to pulmonology referral even when ILD is reported. Interventions to modulate these factors may reduce ILD diagnostic delays in the primary care setting.

Background

Interstitial lung abnormalities (ILA) may represent undiagnosed early-stage or subclinical interstitial lung disease (ILD). ILA are often observed incidentally in patients who subsequently develop clinically overt ILD. There is limited information on consensus definitions for, and the appropriate evaluation of, ILA. Early recognition of patients with ILD remains challenging, yet critically important. Expert consensus could inform early recognition and referral.

Research question

Can consensus-based expert recommendations be identified to guide clinicians in the recognition, referral, and follow-up of patients with or at risk of developing early ILDs?

Study design and methods

Pulmonologists and radiologists with expertise in ILD participated in two iterative rounds of surveys. The surveys aimed to establish consensus regarding ILA reporting, identification of patients with ILA, and identification of populations that might benefit from screening for ILD. Recommended referral criteria and follow-up processes were also addressed. Threshold for consensus was defined a priori as ≥ 75% agreement or disagreement.

Results

Fifty-five experts were invited and 44 participated; consensus was reached on 39 of 85 questions. The following clinically important statements achieved consensus: honeycombing and traction bronchiectasis or bronchiolectasis indicate potentially progressive ILD; honeycombing detected during lung cancer screening should be reported as potentially significant (eg, with the Lung CT Screening Reporting and Data System "S-modifier" [Lung-RADS; which indicates clinically significant or potentially significant noncancer findings]), recommending referral to a pulmonologist in the radiology report; high-resolution CT imaging and full pulmonary function tests should be ordered if nondependent subpleural reticulation, traction bronchiectasis, honeycombing, centrilobular ground-glass nodules, or patchy ground-glass opacity are observed on CT imaging; patients with honeycombing or traction bronchiectasis should be referred to a pulmonologist irrespective of diffusion capacity values; and patients with systemic sclerosis should be screened with pulmonary function tests for early-stage ILD.

Interpretation

Guidance was established for identifying clinically relevant ILA, subsequent referral, and follow-up. These results lay the foundation for developing practical guidance on managing patients with ILA.