Mortality surrogates in combined pulmonary fibrosis and emphysema.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) with coexistent emphysema, termed combined pulmonary fibrosis and emphysema (CPFE) may associate with reduced forced vital capacity (FVC) declines compared to non-CPFE IPF patients. We examined associations between mortality and functional measures of disease progression in two IPF cohorts. METHODS: Visual emphysema presence (>0% emphysema) scored on computed tomography identified CPFE patients (CPFE/non-CPFE: derivation cohort n=317/n=183, replication cohort n=358/n=152), who were subgrouped using 10% or 15% visual emphysema thresholds, and an unsupervised machine-learning model considering emphysema and interstitial lung disease extents. Baseline characteristics, 1-year relative FVC and diffusing capacity of the lung for carbon monoxide (D LCO) decline (linear mixed-effects models), and their associations with mortality (multivariable Cox regression models) were compared across non-CPFE and CPFE subgroups. RESULTS: In both IPF cohorts, CPFE patients with ≥10% emphysema had a greater smoking history and lower baseline D LCO compared to CPFE patients with <10% emphysema. Using multivariable Cox regression analyses in patients with ≥10% emphysema, 1-year D LCO decline showed stronger mortality associations than 1-year FVC decline. Results were maintained in patients suitable for therapeutic IPF trials and in subjects subgrouped by ≥15% emphysema and using unsupervised machine learning. Importantly, the unsupervised machine-learning approach identified CPFE patients in whom FVC decline did not associate strongly with mortality. In non-CPFE IPF patients, 1-year FVC declines ≥5% and ≥10% showed strong mortality associations. CONCLUSION: When assessing disease progression in IPF, D LCO decline should be considered in patients with ≥10% emphysema and a ≥5% 1-year relative FVC decline threshold considered in non-CPFE IPF patients.

Quantitative texture-based analysis of pulmonary parenchymal features on chest CT: comparison with densitometric indices and short-term effect of changes in smoking habit.

PURPOSE: To investigate the correlations between densitometric and Computer Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER)-derived indices of pulmonary emphysema and their change in the short-term period for groups of patients with different smoking habits. METHOD: This retrospective study included 284 subjects from the ITALUNG trial (198 men and 86 women; mean±sd age 60±4 years) who underwent low-dose chest computed tomography at baseline and 2-year follow-up. Subjects were divided into four groups (persistent smokers, restarters, quitters and former smokers) according to their smoking habit at baseline and follow-up. Densitometric and texture analyses were performed, using CALIPER software. A correlation analysis was conducted between CALIPER-derived low-attenuation areas (LAAs) and densitometric indices, including the 15th percentile of the whole-lung attenuation histogram (Perc15) and the relative areas with density ≤-950 HU (RA950). Densitometric indices and LAAs were evaluated at baseline and variation assessed longitudinally with comparisons between groups with different smoking habit. Further analysis of parenchymal changes per pulmonary zone was performed. RESULTS: LAAs were strongly correlated with Perc15 (rs=0.81; p<0.001) and RA950 (rs=0.905; p<0.001). At baseline, the group of smokers showed higher Perc15, lower RA950, lower LAAs (particularly mild sub-class of LAAs) than the group of ex-smokers (p<0.001). At 2-year follow-up, densitometric indices and LAAs increased in persistent smokers, former smokers and quitters (p<0.05). The progression was larger and statistically more significant in quitters (p<0.001). CONCLUSION: CALIPER texture analysis provides an objective measure comparable to traditional density/histogram features to assess the lung parenchymal changes in relation to different smoking habits.

Automated Computed Tomography analysis in the assessment of Idiopathic Pulmonary Fibrosis severity and progression.

PURPOSE: To investigate the role of a quantitative analysis software (CALIPER) in identifying HRCT thresholds predicting IPF patients' survival and lung function decline and its role in detecting changes of HRCT abnormalities related to treatment and their correlation with Forced Vital Capacity (FVC). METHODS: This retrospective study included 105 patients with a multidisciplinary diagnosis of IPF for whom one HRCT at baseline and concomitant FVC were available. HRCTs were evaluated with CALIPER and the correlation between FVC and radiological features were assessed. Radiological thresholds for survival prediction and functional decline were calculated for all patients. Fifty-nine patients with at least 2 serial HRCTs were classified into two groups based on treatment. For patients for whom a FVC within 3 months of the HRCT was available (n = 44), the correlation of radiological and clinical progression was evaluated. RESULTS: The correlation between FVC and CALIPER-derived features at baseline was significant and strong. A baseline CALIPER-derived interstitial lung disease (ILD%) extent higher than 20 % and pulmonary vascular related structures (PVRS%) score greater than 5 % defined a worse prognosis. A significant progression of CALIPER-derived features in all patients was found with a faster increase in untreated patients. ILD% and PVRS% changes during follow-up demonstrated strong correlations with FVC changes. CONCLUSIONS: CALIPER quantification of fibrosis and vascular involvement could distinguish disease progression in treated versus untreated patients and predict the survival. The changes in CALIPER-derived variables over time were significantly correlated to changes in FVC.