Karwoski, Ronald

A usual interstitial pneumonia (UIP) imaging pattern can be seen in both idiopathic pulmonary fibrosis (IPF) and connective tissue disease-related interstitial lung disease (CTD-ILD). The purpose of this multicenter study was to assess whether quantitative imaging data differ between IPF and CTD-ILD in the setting of UIP. Patients evaluated at two medical centers with CTD-ILD or IPF and a UIP pattern on CT or pathology served as derivation and validation cohorts. Chest CT data were quantitatively analyzed including total volumes of honeycombing, reticulation, ground-glass opacity, normal lung, and vessel related structures (VRS). VRS was compared with forced vital capacity percent predicted (FVC%) and percent predicted diffusing capacity of the lungs for carbon monoxide (DLCO%). There were 296 subjects in total, with 40 CTD-ILD and 85 IPF subjects in the derivation cohort, and 62 CTD-ILD and 109 IPF subjects in the validation cohort. VRS was greater in IPF across the cohorts on univariate (p < 0.001) and multivariable (p < 0.001–0.047) analyses. VRS was inversely correlated with DLCO% in both cohorts on univariate (p < 0.001) and in the derivation cohort on multivariable analysis (p = 0.003) but not FVC%. Total volume of normal lung was associated with DLCO% (p < 0.001) and FVC% (p < 0.001–0.009) on multivariable analysis in both cohorts. VRS appears to have promise in differentiating CTD-ILD from IPF. The underlying pathophysiological relationship between VRS and ILD is complex and is likely not explained solely by lung fibrosis.

Purpose: Optimal strategies to detect early interstitial lung disease (ILD) are unknown. ILD is frequently subpleural in distribution and affects lung elasticity. Lung ultrasound surface wave elastography (LUSWE) is a noninvasive method of quantifying superficial lung tissue elastic properties. In LUWSE a handheld device applied at the intercostal space vibrates the chest at a set frequency, and the lung surface wave velocity is measured by an ultrasound probe 5 mm away in the same intercostal space. We explored LUWSE’s ability to detect ILD and correlated LUSWE velocity with physiological, quantitative, and visual radiologic features of subjects with known ILD and of healthy controls. Materials and Methods: Seventy-seven subjects with ILD, mostly caused by connective tissue disease, and 19 healthy controls were recruited. LUSWE was performed on all subjects in 3 intercostal lung regions bilaterally. Comparison of LUSWE velocities pulmonary function testing, visual assessment, and quantitative analysis of recent computed tomographic imaging with Computer-Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER) software. Results: Sonographic velocities were higher in all lung regions for cases, with the greatest difference in the lateral lower lung. Median velocity in m/s was 5.84 versus 4.11 and 5.96 versus 4.27 (P<0.00001) for cases versus controls, left and right lateral lower lung zones, respectively. LUSWE velocity correlated negatively with vital capacity and positively with radiologist and CALIPER-detected interstitial abnormalities. Conclusions: LUSWE is a safe and noninvasive technique that shows high sensitivity to detect ILD and correlated with clinical, physiological, radiologic, and quantitative assessments of ILD. Prospective study in detecting ILD is indicated.

Abstract Rationale Quantitative computed tomographic (CT) measures of baseline disease severity might identify patients with idiopathic pulmonary fibrosis (IPF) with an increased mortality risk. We evaluated whether quantitative CT variables could act as a cohort enrichment tool in future IPF drug trials. Objectives To determine whether computer-derived CT measures, specifically measures of pulmonary vessel–related structures (VRSs), can better predict functional decline and survival in IPF and reduce requisite sample sizes in drug trial populations. Methods Patients with IPF undergoing volumetric noncontrast CT imaging at the Royal Brompton Hospital, London, and St. Antonius Hospital, Utrecht, were examined to identify pulmonary function measures (including FVC) and visual and computer-derived (CALIPER [Computer-Aided Lung Informatics for Pathology Evaluation and Rating] software) CT features predictive of mortality and FVC decline. The discovery cohort comprised 247 consecutive patients, with validation of results conducted in a separate cohort of 284 patients, all fulfilling drug trial entry criteria. Measurements and Main Results In the discovery and validation cohorts, CALIPER-derived features, particularly VRS scores, were among the strongest predictors of survival and FVC decline. CALIPER results were accentuated in patients with less extensive disease, outperforming pulmonary function measures. When used as a cohort enrichment tool, a CALIPER VRS score greater than 4.4% of the lung was able to reduce the requisite sample size of an IPF drug trial by 26%. Conclusions Our study has validated a new quantitative CT measure in patients with IPF fulfilling drug trial entry criteria—the VRS score—that outperformed current gold standard measures of outcome. When used for cohort enrichment in an IPF drug trial setting, VRS threshold scores can reduce a required IPF drug trial population size by 25%, thereby limiting prohibitive trial costs. Importantly, VRS scores identify patients in whom antifibrotic medication prolongs life and reduces FVC decline.

ABSTRACT Background and objective This study evaluated whether patients with combined pulmonary fibrosis and emphysema (CPFE) have an increased likelihood of pulmonary hypertension (PHT) when compared with idiopathic pulmonary fibrosis (IPF) patients without emphysema. Methods Two consecutive IPF populations having undergone transthoracic echocardiography were examined ( n = 223 and n = 162). Emphysema and interstitial lung disease (ILD) extent were quantified visually; ILD extent was also quantified by a software tool, CALIPER. Echocardiographic criteria categorized PHT risk. Results The prevalence of an increased PHT likelihood was 29% and 31% in each CPFE cohort. Survival at 12 months was 60% across both CPFE cohorts with no significantly worsened outcome identified when compared with IPF patients without emphysema. Using logistic regression models in both cohorts, total computed tomography (CT) disease extent (ILD and emphysema) predicted the likelihood of PHT. After adjustment for total disease extent, CPFE had no stronger association with PHT likelihood than IPF patients without emphysema. Conclusion Our findings indicate that the reported association between CPFE and PHT is explained by the summed baseline CT extents of ILD and emphysema. Once baseline severity is taken into account, CPFE is not selectively associated with a malignant microvascular phenotype, when compared with IPF patients without emphysema.

ABSTRACTBackground and objectiveTo determine whether computer‐based quantification (CALIPER software) is superior to visual computed tomography (CT) scoring in the identification of CT patterns indicative of restrictive and obstructive functional indices in hypersensitivity pneumonitis (HP).MethodsA total of 135 consecutive HP patients had CT parenchymal patterns evaluated quantitatively by both visual scoring and CALIPER. Results were evaluated against: forced vital capacity (FVC), total lung capacity (TLC), diffusing capacity for carbon monoxide (DLCO) and a composite physiological index (CPI) to identify which CT scoring method better correlated with functional indices.ResultsCALIPER‐derived scores of total interstitial lung disease extent correlated more strongly than visual scores: FVC (CALIPER R = 0.73, visual R = 0.51); DLCO (CALIPER R = 0.61, visual R = 0.48); and CPI (CALIPER R = 0·70, visual R = 0·55). The CT variable that correlated most strongly with restrictive functional indices was CALIPER pulmonary vessel volume (PVV): FVC R = 0.75, DLCO R = 0.68 and CPI R = 0.76.Ground‐glass opacity quantified by CALIPER alone demonstrated strong associations with restrictive functional indices: CALIPER FVC R = 0.65; DLCO R = 0.59; CPI R = 0.64; and visual = not significant. Decreased attenuation lung quantified by CALIPER was a better morphological measure of obstructive lung disease than equivalent visual scores as judged by relationships with TLC (CALIPER R = 0.63 and visual R = 0.12). All results were maintained on multivariate analysis.ConclusionCALIPER improved on visual scoring in HP as judged by restrictive and obstructive functional correlations. Decreased attenuation regions of the lung quantified by CALIPER demonstrated better linkages to obstructive lung physiology than visually quantified CT scores. A novel CALIPER variable, the PVV, demonstrated the strongest linkages with restrictive functional indices and could represent a new automated index of disease severity in HP.