Vida Diagnostics (United States)

<bold>Introduction:</bold> Patients with advanced COPD and pulmonary emphysema undergo endoscopic valve implantation to improve symptoms and quality of life. As a side effect, some patients report an increase in mucus production due to the implantation of foreign material. Mucus scoring on chest computed tomography (CT) is an objective method of quantifying mucus load. <bold>Aim:</bold> The prospective, single-center MMCOPD study aims to characterize the microbiome, metabolome, mucus load, symptoms (COPD assessment test, CAT) and exacerbation history of COPD patients before and after bronchoscopic interventions. Chest CT scan-based mucus scoring was performed to assess mucus load before and after endoscopic valve implantation, separately for each lung segment. <bold>Results:</bold> 50 patients (emphysema index 34 ± 10%) were analyzed with a mean total mucus score of 5.4 ± 4.9 plugs. 2.9% of all segments were unscorable due to highly diseased regions or motion artifact. 58% of all patients had ≥3 mucus plugs in total. Mucus plugs were more prevalent in lower lobes (highest score in segment LB10) than in upper lobes. For 42 patients with a follow up CT scan, mucus score decreased significantly from 5.5 ± 3.6 to 3.6 ± 4.4 plugs (p=0.002). After exclusion of all unscorable segments the results were still significant. The first two questions on cough and sputum in the CAT score did not change significantly. <bold>Conclusion:</bold> Mucus load is high in patients with pulmonary emphysema. Unexpectedly and fortunately, the mucus score on the chest CT scan decreased after endoscopic valve implantation. This finding needs further evaluation and interpretation.

"Residual Volume versus FRC Computed Tomography Assessment of Functional Small Airway Disease in Smokers with and without Chronic Obstructive Pulmonary Disease ." American Journal of Respiratory and Critical Care Medicine, 207(11), pp. 1536–1539

Introduction: The in vivo relationship between small pulmonary vessels (SPV) and pulmonary hypertension (PH) and its association with pulmonary function and prognosis in PH is not fully understood. Hypothesis: The morphological change in SPV volumes (SPVV) can be quantitatively estimated from CT pulmonary angiography (CTPA) in different subtypes of PH and is associated with pulmonary function metrics and prognosis in PH. Methods: : In this retrospective single center study performed from January 2008 to February 2018, quantitative CTPA analysis of total SPVV (TSPVV) (0.4-2mm vessel diameter) was performed using VIDA Diagnostics software (LungPrintTM, VIDA Diagnostics, Inc., Coralville, IA, USA). Results: 1823 patients (mean (SD) age 69 (13) years, 65% females) were analysed. 1593 patients with PH (mPAP = 43 (13) mmHg) were compared to 230 patient controls (mPAP=20 (3) mmHg). Mean small vessel volumes at a diameter below 2 mm were lower in PAH and PH associated with left heart disease compared to controls (-4.3 (-8 to -0.1) ml for 1.6 mm vessels, p=.03 and -6.8 (-11 to -2) ml, p&lt;.001, respectively). In patients with PH, the most significant positive correlation was noted with FVC%predicted (r=0.30-0.40, all p&lt;.001). Median survival for TSPVV≤1.2mm greater than 50 ml was longer than TSPVV≤1.2mm less than or equal 50 ml (85 versus 71 months, 95% C.I 73-97, p=.02, respectively). Median survival for TSPVV&gt;1.2mm greater than 135 ml was longer than TSPVV&gt;1.2mm less than or equal 135 ml (88 versus 72 months, 95% C.I 73-98, p=.02, respectively). TSPVV≤1.2mm greater than 50 ml (HR 0.851, p=.02) and TSPVV&gt;1.2mm greater than 135 ml (HR 0.839, p=.02) were significant predictors of mortality on univariate analysis. TSPVV≤1.2mm greater than 50 ml (HR 0.785, p=.04) was independent predictor of mortality on multivariate analysis in addition to age, Male gender, mRAP, PVR and SvO2. Conclusions: The morphological change in small vessels can be successfully quantified from CTPA in different subtypes of PH and is associated with pulmonary function metrics and prognosis in PH.

BackgroundMucus plugs are associated with airway inflammation and obstruction in patients with asthma. The impact of treatment on mucus plugs has not been investigated in randomized controlled trials (RCTs) of severe asthma.ObjectiveTo assess mucus plugging in the lungs of patients with uncontrolled, moderate-to-severe asthma pre- and post-treatment with tezepelumab, a human monoclonal antibody that blocks thymic stromal lymphopoietin.MethodsCASCADE (NCT03688074) was an exploratory, double-blind, placebo-controlled study. Patients (18–75 years old) were randomized 1:1 to tezepelumab 210 mg or placebo subcutaneously every 4 weeks for at least 28 weeks. Mucus plugging was scored at baseline and end of treatment in 18 lung segments using standardized computed tomography imaging.ResultsMucus plugging scores were reduced in patients receiving tezepelumab (n = 37) versus placebo (n = 45) (nominal p = 0.0007; figure 1). At baseline, mucus score correlated positively with inflammatory markers (blood eosinophils, eosinophil-derived neurotoxin, fractional exhaled nitric oxide, IL-5 and IL-13) and negatively with lung function (FEV1 and FEF25–75%). Reduction in mucus score with tezepelumab was correlated with improvements in these lung function parameters. S46 Figure 1Change in mucus plugging scores from baseline to EOT in patients receiving (A) tezepelumab 210 mg Q4W and (B) placeboConclusionTezepelumab is the first biologic shown to reduce mucus plugging in patients with moderate-to-severe, uncontrolled asthma in an RCT.Please refer to page A209 for declarations of interest related to this abstract.

BackgroundPulmonary hypertension (PH) in patients with chronic lung disease (CLD) predicts reduced functional status, clinical worsening and increased mortality, with patients with severe PH-CLD (≥35 mmHg) having a significantly worse prognosis than mild to moderate PH-CLD (21–34 mmHg). The aim of this cross-sectional study was to assess the association between computed tomography (CT)-derived quantitative pulmonary vessel volume, PH severity and disease aetiology in CLD.MethodsTreatment-naïve patients with CLD who underwent CT pulmonary angiography, lung function testing and right heart catheterisation were identified from the ASPIRE registry between October 2012 and July 2018. Quantitative assessments of total pulmonary vessel and small pulmonary vessel volume were performed.Results90 patients had PH-CLD including 44 associated with COPD/emphysema and 46 with interstitial lung disease (ILD). Patients with severe PH-CLD (n=40) had lower small pulmonary vessel volume compared to patients with mild to moderate PH-CLD (n=50). Patients with PH-ILD had significantly reduced small pulmonary blood vessel volume, compared to PH-COPD/emphysema. Higher mortality was identified in patients with lower small pulmonary vessel volume.ConclusionPatients with severe PH-CLD, regardless of aetiology, have lower small pulmonary vessel volume compared to patients with mild–moderate PH-CLD, and this is associated with a higher mortality. Whether pulmonary vessel changes quantified by CT are a marker of remodelling of the distal pulmonary vasculature requires further study.

Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation, caused by emphysema and small airways disease (SAD). Computed tomography (CT) coupled with image analysis enables the quantification of these abnormalities; however, the optimum method for doing so has not been determined.Objectives: This study aims to compare two CT quantitative analysis techniques, disease probability measure (DPM) and parametric response mapping (PRM), and assess their relationship with specific physiological measures of SAD.Methods: Subjects with mild to moderate COPD, never smokers, and healthy ex-smokers were recruited. Each had airway oscillometry and multiple-breath nitrogen washout, measuring peripheral airway resistance, peripheral airway reactance, and acinar airway inhomogeneity. Subjects also had an inspiratory and expiratory chest CT, with DPM and PRM analysis performed by coregistering images and classifying each voxel as normal, emphysema, or nonemphysematous gas trapping related to SAD.Results: Thirty-eight subjects with COPD, 18 never smokers, and 23 healthy ex-smokers were recruited. There were strong associations between DPM and PRM analysis when measuring gas trapping (ρ = 0.87; P < 0.001) and emphysema (ρ = 0.99; P < 0.001). DPM assigned significantly more voxels as emphysema and gas trapped than PRM (P < 0.001). Both techniques showed significantly greater emphysema and gas trapping in subjects with COPD than in never smokers and ex-smokers (P < 0.001). All CT measures had significant associations with peripheral airway resistance and reactance, with disease probability measure of nonemphysematous gas trapping related to SAD having the strongest independent association with peripheral airway resistance (β = 0.42; P = 0.001) and peripheral airway reactance (β = 0.41; P = 0.001). Emphysema measures had the strongest associations with acinar airway inhomogeneity (β = 0.35-0.38).Conclusions: These results provide further validation for the use of DPM/PRM analysis in COPD by demonstrating significant relationships with specific physiological measures of SAD.

<b>Rationale:</b> Pulmonary hypertension is a common complication in patients with severe chronic obstructive pulmonary disease (COPD). Our objective was to determine if quantitative MDCT (multi-detector computed tomography) assessment of airways, emphysema and peripheral pulmonary vascular predict pulmonary hypertension in patients with COPD. <b>Methods:</b> Patients with severe COPD who underwent pulmonary function measurements, MDCT and right heart catheterization (RHC) were enrolled in this retrospective analysis. Quantitative CT measurements, generated by VIDA Diagnostics Inc. (LungPrintTM, VIDA Diagnostics, Inc, Coralville, IA, USA), include: low attenuation areas of the lung below -950HU (LAA950), mean segmental airway wall thickness (WT), small vessel volume relative to the overall pulmonary vasculature (SVPVV) and functional small airway disease (fSAD). <b>Results:</b> In this interim analysis, 15 patients with advanced COPD (mean FEV1=0.7±0.2L, 30.7±8.6% predicted; mean RV=5.7±1.3L, 256.5±56.7% predicted) and mean pulmonary arterial pressure (mPAP) of 30.9±10.5mmHg were evaluated. In 4 out of the 15 patients, RHC revealed mPAP of &gt; 35mmHg. mPAP was significantly correlated with SVPVV (r=-0.70, p=0.004), but not with LAA950 (r=-0.05, p=0.86), WT (r=-0.31, p=0.26) or fSAD (r=-0.57, p=0.09). <b>Conclusions:</b> In COPD patients, CT measurements that reflect the small pulmonary vessels may predict pulmonary hypertension.