Pulmonary vascular dysfunction without pulmonary hypertension: A distinct phenotype in idiopathic pulmonary fibrosis.

Pulmonary vascular dysfunction in the absence of pulmonary hypertension (PH) has been observed in patients with idiopathic pulmonary fibrosis (IPF). We describe the prevalence and etiology of elevated pulmonary vascular resistance (PVR) without PH among patients with IPF. Hemodynamic, echocardiographic, and functional respiratory imaging (FRI) data was compared between patients with IPF without PH with normal (<3 wood units) and elevated PVR (≥3 wood units). Mortality between these two groups were compared to patients with IPF and PH. Of 205 patients with IPF, there were 146 patients without PH, of whom 114 (78.1%) had a normal PVR and 32 (21.9%) who had a high PVR. Functional testing and hemodynamics were similar in the two groups, except for the cardiac index which was significantly lower in patients with a high PVR (2.3 vs. 2.6 L/min/m2; p = 0.004). Echocardiographic comparison demonstrated a higher tricuspid regurgitant velocity in those with a high PVR (3.4 vs 3.0 m/s; p = 0.046). FRI revealed proportionately fewer large vessels as a proportion of the vasculature in the patients without PH and elevated PVRs. Among patients without PH, PVR was associated with increased mortality. In conclusion, patients with IPF without PH but a high PVR appear to be a distinct phenotype with a prognosis between those with and without PH, likely reflecting the continuum of vascular dysfunction. The basis for this unique hemodynamic profile could not be definitively discerned although FRI suggested an aberrant anatomical vascular response.

Quantitative CT measures of pulmonary vascular volume distribution in pulmonary hypertension associated with COPD: Association with clinical characteristics and outcomes.

To determine whether quantitative computed tomography (qCT)-derived metrics of pulmonary vascular volume distribution could distinguish chronic obstructive pulmonary disease (COPD) subjects with associated pulmonary hypertension (PH) from those without and to characterize associations of these measurements with clinical and physiological characteristics and outcomes. We collected retrospective CT, pulmonary hemodynamic, clinical, and outcomes data from subjects with COPD and right-heart catheterization-confirmed PH (PH-COPD) and control subjects with COPD but without PH. We measured the volumes of pulmonary vessels < 5 and >10 mm2 in cross-sectional area as a percentage of total pulmonary vascular volume (qCT-derived volume of pulmonary vessels < 5 mm2 in cross-sectional area as a volume fraction of total pulmonary blood volume [BV5%] and qCT-derived volume of pulmonary vessels > 10 mm2 in cross-sectional area [BV10] as a volume fraction of total pulmonary blood volume [BV10%], respectively) using Functional Respiratory Imaging (FRI), an automated qCT platform, and compared them between PH and control arms and between subjects with mild-moderate PH and those with severe disease. Correlations of hemodynamics with pulmonary function and associations with survival were tested. Forty-five PH-COPD and 42 control subjects were studied. BV5% was lower in PH subjects (32.2% vs. 37.7%, p = 0.003), and BV10% was higher (50.2% vs. 43.5, p = 0.001). Subjects with severe PH did not differ from those with mild-moderate PH in qCT. Pulmonary vascular volumes were not associated with pulmonary function. BV10 was associated with mean pulmonary artery pressure (r = 0.3, p = 0.05). Associations with survival were observed for BV5% (hazard ratio 0.63, p = 0.02) and BV10% (hazard ratio 1.43, p = 0.03) in the PH-COPD arm, but not for controls. qCT-derived measures of pulmonary vascular volume may have diagnostic and prognostic significance in PH-COPD and should be investigated further as screening and risk stratification tools.

CT-derived measurements of pulmonary blood volume in small vessels and the need for supplemental oxygen in COVID-19 patients.

Throughout the COVID-19 pandemic, a portion of those affected have evolved toward acute hypoxic respiratory failure. Initially, this was hypothesized to result from acute lung injury leading to acute respiratory distress syndrome (ARDS). In previous research, a novel quantitative CT post-processing technique was described to quantify the volume of blood contained within pulmonary blood vessels of a given size. We hypothesized that patients with lower BV5 blood flow would have higher supplemental oxygen needs and less favorable arterial blood gas profiles. From the initial data analysis, 111 hospitalized COVID-19 patients were retrospectively selected based on the availability of CT scans of the lungs with a slice thickness of 1.5 mm or less, as well as PCR-confirmed SARS-CoV2 infection. Three-dimensional (3-D) reconstructions of the lungs and pulmonary vasculature were created. Further analysis was performed on 50 patients. Patients were divided into groups based on their need for oxygen at the time of CT scan acquisition. Eighteen out of 50 patients needed >2 L/min supplemental oxygen and this group demonstrated a significantly lower median percentage of total blood flow in the BV5 vessels compared with the 32 patients who needed <2 L/min supplemental oxygen (41.61% vs. 46.89%, P = 0.023). Both groups had significantly less blood as a proportion in BV5 vessels compared with healthy volunteers. These data are consistent with the hypothesis that reduced blood volume within small (BV5) pulmonary vessels is associated with higher needs for supplemental oxygen and more severe gas exchange anomalies in COVID-19 infections.NEW & NOTEWORTHY This research provides, by using new imaging analysis on CT imaging, an insight into the pathophysiology of patients with COVID-19 infection. By visualizing and quantifying the blood in small vessels in the lung, we can link these results to the clinical need for oxygen in patients with COVID-19 infection.

Pulmonary thromboembolic events in COVID-19-A systematic literature review.

Pulmonary thromboembolic events have been linked to coronavirus disease 2019 (COVID-19), but their incidence and long-term sequelae remain unclear. We performed a systematic literature review to investigate the incidence of pulmonary embolism (PE), microthrombi, thrombosis in situ (thromboinflammatory disease), and chronic thromboembolic pulmonary hypertension (CTEPH) during and after COVID-19. PubMed and the World Health Organization Global Research Database were searched on May 7, 2021. Hospital cohort and database studies reporting data for ≥1000 patients and autopsy studies reporting data for ≥20 patients were included. Results were summarized descriptively. We screened 1438 records and included 41 references (32 hospital/database studies and 9 autopsy studies). The hospital/database studies reported the incidence of PE but not CTEPH, microthrombi, or thromboinflammatory disease. PE incidence varied widely (0%-1.1% of outpatients, 0.9%-8.2% of hospitalized patients, and 1.8%-18.9% of patients in intensive care). One study reported PE events occurring within 45 days after hospital discharge (incidence in discharged patients: 0.2%). Segmental arteries were generally the most common location for PE. In autopsy studies, PE, thromboinflammatory disease, and microthrombi were reported in 6%-23%, 43%-100%, and 45%-84% of deceased patients, respectively. Overall, the included studies mostly focused on PE during the acute phase of COVID-19. The results demonstrate the challenges of identifying and characterizing vascular abnormalities using current protocols (e.g., visual computed tomography reads). Further research is needed to detect subtle pulmonary vascular abnormalities, distinguish thromboinflammatory disease from PE, optimize treatment, and assess the incidence of long-term sequelae after COVID-19.

Expiratory CT scanning in COVID-19 patients: can we add useful data?

OBJECTIVE: To evaluate small airway disease in COVID-19 patients using the prevalence of air trapping (AT) and correlating it with clinical outcomes. The relationship between CT-based opacities in small blood vessels and ventilation in patients with SARS-CoV-2 pneumonia was also assessed. METHODS: We retrospectively included 53 patients with positive RT-PCR results for SARS-CoV-2 between March and April of 2020. All subjects underwent HRCT scanning, including inspiratory and expiratory acquisitions. Subjects were divided into two groups based on visual identification of AT. Small blood vessel volumes were estimated by means of cross-sectional areas < 5 mm2 (BV5) derived from automated segmentation algorithms. Mixed-effect models were obtained to represent the BV5 as a function of CT-based lobar opacities and lobar ventilation. RESULTS: Of the 53 participants, AT was identified in 23 (43.4%). The presence of AT was associated with increased SpO2 at admission (OR = 1.25; 95% CI, 1.07-1.45; p = 0.004) and reduced D-dimer levels (OR = 0.99; 95% CI, 0.99-0.99; p = 0.039). Patients with AT were less likely to be hospitalized (OR = 0.27; 95% CI, 0.08-0.89; p = 0.032). There was a significant but weak inverse correlation between BV5 and CT-based lobar opacities (R2 = 0.19; p = 0.03), as well as a nonsignificant and weak direct correlation between BV5 and lobar ventilation (R2 = 0.08; p = 0.54). CONCLUSIONS: AT is a common finding in patients with COVID-19 that undergo expiratory CT scanning. The presence of AT may correlate with higher SpO2 at admission, lower D-dimer levels, and fewer hospitalizations when compared with absence of AT. Also, the volume of small pulmonary vessels may negatively correlate with CT opacities but not with lobar ventilation.

Expiratory CT scanning in COVID-19 patients: can we add useful data? / TC expiratória em pacientes com COVID-19: podemos adicionar dados úteis?

ABSTRACT Objective: To evaluate small airway disease in COVID-19 patients using the prevalence of air trapping (AT) and correlating it with clinical outcomes. The relationship between CT-based opacities in small blood vessels and ventilation in patients with SARS-CoV-2 pneumonia was also assessed. Methods: We retrospectively included 53 patients with positive RT-PCR results for SARS-CoV-2 between March and April of 2020. All subjects underwent HRCT scanning, including inspiratory and expiratory acquisitions. Subjects were divided into two groups based on visual identification of AT. Small blood vessel volumes were estimated by means of cross-sectional areas < 5 mm2 (BV5) derived from automated segmentation algorithms. Mixed-effect models were obtained to represent the BV5 as a function of CT-based lobar opacities and lobar ventilation. Results: Of the 53 participants, AT was identified in 23 (43.4%). The presence of AT was associated with increased SpO2 at admission (OR = 1.25; 95% CI, 1.07-1.45; p = 0.004) and reduced D-dimer levels (OR = 0.99; 95% CI, 0.99-0.99; p = 0.039). Patients with AT were less likely to be hospitalized (OR = 0.27; 95% CI, 0.08-0.89; p = 0.032). There was a significant but weak inverse correlation between BV5 and CT-based lobar opacities (R2 = 0.19; p = 0.03), as well as a nonsignificant and weak direct correlation between BV5 and lobar ventilation (R2 = 0.08; p = 0.54). Conclusions: AT is a common finding in patients with COVID-19 that undergo expiratory CT scanning. The presence of AT may correlate with higher SpO2 at admission, lower D-dimer levels, and fewer hospitalizations when compared with absence of AT. Also, the volume of small pulmonary vessels may negatively correlate with CT opacities but not with lobar ventilation.

RESUMO Objetivo: Avaliar a doença das pequenas vias aéreas em pacientes com COVID-19 por meio da prevalência de aprisionamento aéreo (AA) e sua correlação com desfechos clínicos. Também foi avaliada a relação entre opacidades tomográficas nos pequenos vasos sanguíneos e ventilação em pacientes com pneumonia por SARS-CoV-2. Métodos: Foram incluídos, retrospectivamente, 53 pacientes com teste de RT-PCR positivo para SARS-CoV-2 entre março e abril de 2020. Todos os indivíduos foram submetidos à TCAR, incluindo aquisições inspiratórias e expiratórias. Os indivíduos foram divididos em dois grupos com base na identificação visual de AA. Os volumes dos pequenos vasos sanguíneos foram estimados por meio de seções transversais < 5 mm2 (VS5) derivadas de algoritmos automatizados de segmentação. Modelos de efeito misto foram obtidos para representar o VS5 em função das opacidades lobares tomográficas e da ventilação lobar. Resultados: Identificou-se AA em 23 (43,4%) dos 53 participantes. A presença de AA apresentou associação com SpO2 elevada na admissão (OR = 1,25; IC95%: 1,07-1,45; p = 0,004) e níveis reduzidos de dímero D (OR = 0,99; IC95%: 0,99-0,99; p = 0,039). Pacientes com AA apresentaram menor probabilidade de hospitalização (OR = 0,27; IC95%: 0,08-0,89; p = 0,032). Houve correlação inversa significativa, mas fraca, entre VS5 e opacidades lobares tomográficas (R2 = 0,19; p = 0,03) e correlação direta não significativa e fraca entre VS5 e ventilação lobar (R2 = 0,08; p = 0,54). Conclusões: AA é um achado comum em pacientes com COVID-19 submetidos à TC expiratória. A presença de AA pode apresentar correlação com SpO2 elevada na admissão, níveis reduzidos de dímero D e menor probabilidade de hospitalização. Além disso, o volume dos pequenos vasos pulmonares pode apresentar correlação negativa com opacidades tomográficas, mas não com ventilação lobar.

Association of abnormal pulmonary vasculature on CT scan for COVID-19 infection with decreased diffusion capacity in follow up: A retrospective cohort study.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is a respiratory viral illness causing pneumonia and systemic disease. Abnormalities in pulmonary function tests (PFT) after COVID-19 infection have been described. The determinants of these abnormalities are unclear. We hypothesized that inflammatory biomarkers and CT scan parameters at the time of infection would be associated with abnormal gas transfer at short term follow-up. METHODS: We retrospectively studied subjects who were hospitalized for COVID-19 pneumonia and discharged. Serum inflammatory biomarkers, CT scan and clinical characteristics were assessed. CT images were evaluated by Functional Respiratory Imaging with automated tissue segmentation algorithms of the lungs and pulmonary vasculature. Volumes of the pulmonary vessels that were ≤5mm (BV5), 5-10mm (BV5_10), and ≥10mm (BV10) in cross sectional area were analyzed. Also the amount of opacification on CT (ground glass opacities). PFT were performed 2-3 months after discharge. The diffusion capacity of carbon monoxide (DLCO) was obtained. We divided subjects into those with a DLCO <80% predicted (Low DLCO) and those with a DLCO ≥80% predicted (Normal DLCO). RESULTS: 38 subjects were included in our cohort. 31 out of 38 (81.6%) subjects had a DLCO<80% predicted. The groups were similar in terms of demographics, body mass index, comorbidities, and smoking status. Hemoglobin, inflammatory biomarkers, spirometry and lung volumes were similar between groups. CT opacification and BV5 were not different between groups, but both Low and Normal DLCO groups had lower BV5 measures compared to healthy controls. BV5_10 and BV10 measures were higher in the Low DLCO group compared to the normal DLCO group. Both BV5_10 and BV10 in the Low DLCO group were greater compared to healthy controls. BV5_10 was independently associated with DLCO<80% in multivariable logistic regression (OR 1.29, 95% CI 1.01, 1.64). BV10 negatively correlated with DLCO% predicted (r = -0.343, p = 0.035). CONCLUSIONS: Abnormalities in pulmonary vascular volumes at the time of hospitalization are independently associated with a low DLCO at follow-up. There was no relationship between inflammatory biomarkers during hospitalization and DLCO. Pulmonary vascular abnormalities during hospitalization for COVID-19 may serve as a biomarker for abnormal gas transfer after COVID-19 pneumonia.

Altered pulmonary blood volume distribution as a biomarker for predicting outcomes in COVID-19 disease.

INTRODUCTION: Evidence suggests that vascular inflammation and thrombosis may be important drivers of poor clinical outcomes in patients with COVID-19. We hypothesised that a significant decrease in the percentage of blood volume in vessels with a cross-sectional area between 1.25 and 5 mm2 relative to the total pulmonary blood volume (BV5%) on chest computed tomography (CT) in COVID-19 patients is predictive of adverse clinical outcomes. METHODS: We performed a retrospective analysis of chest CT scans from 10 hospitals across two US states in 313 COVID-19-positive and 195 COVID-19-negative patients seeking acute medical care. RESULTS: BV5% was predictive of outcomes in COVID-19 patients in a multivariate model, with a BV5% threshold below 25% associated with OR 5.58 for mortality, OR 3.20 for intubation and OR 2.54 for the composite of mortality or intubation. A model using age and BV5% had an area under the receiver operating characteristic curve of 0.85 to predict the composite of mortality or intubation in COVID-19 patients. BV5% was not predictive of clinical outcomes in patients without COVID-19. CONCLUSIONS: The data suggest BV5% as a novel biomarker for predicting adverse outcomes in patients with COVID-19 seeking acute medical care.

Interstitial lung disease in systemic sclerosis quantification of disease classification and progression with high-resolution computed tomography: An observational study.

Introduction: Systemic sclerosis-associated interstitial lung disease accounts for up to 20% of mortality in these patients and has a highly variable prognosis. Functional respiratory imaging, a quantitative computed tomography imaging technique which allows mapping of regional information, can provide a detailed view of lung structures. It thereby shows potential to better characterize this disease. Purpose: To evaluate the use of functional respiratory imaging quantitative computed tomography in systemic sclerosis-associated interstitial lung disease staging, as well as the relationship between short-term changes in pulmonary function tests and functional respiratory imaging quantitative computed tomography with respect to disease severity. Materials and methods: An observational cohort of 35 patients with systemic sclerosis was retrospectively studied by comparing serial pulmonary function tests and in- and expiratory high-resolution computed tomography over 1.5-year interval. After classification into moderate to severe lung disease and limited lung disease (using a hybrid method integrating quantitative computed tomography and pulmonary function tests), post hoc analysis was performed using mixed-effects models and estimated marginal means in terms of functional respiratory imaging parameters. Results: At follow-up, relative mean forced vital capacity percentage change was not significantly different in the limited (6.37%; N = 13; p = 0.053) and moderate to severe disease (-3.54%; N = 16; p = 0.102) groups, respectively. Specific airway resistance decreased from baseline for both groups. (Least square mean changes -25.11% predicted (p = 0.006) and -14.02% predicted (p = 0.001) for limited and moderate to severe diseases.) In contrast to limited disease from baseline, specific airway radius increased in moderate to severe disease by 8.57% predicted (p = 0.011) with decline of lower lobe volumes of 2.97% predicted (p = 0.031). Conclusion: Functional respiratory imaging is able to differentiate moderate to severe disease versus limited disease and to detect disease progression in systemic sclerosis.

Assessment of Small Pulmonary Blood Vessels in COVID-19 Patients Using HRCT.

RATIONALE AND OBJECTIVES: Mounting evidence supports the role of pulmonary hemodynamic alternations in the pathogenesis of COVID-19. Previous studies have demonstrated that changes in pulmonary blood volumes measured on computed tomography (CT) are associated with histopathological markers of pulmonary vascular pruning, suggesting that quantitative CT analysis may eventually be useful in the assessment pulmonary vascular dysfunction more broadly. MATERIALS AND METHODS: Building upon previous work, automated quantitative CT measures of small blood vessel volume and pulmonary vascular density were developed. Scans from 103 COVID-19 patients and 107 healthy volunteers were analyzed and their results compared, with comparisons made both on lobar and global levels. RESULTS: Compared to healthy volunteers, COVID-19 patients showed significant reduction in BV5 (pulmonary blood volume contained in blood vessels of <5 mm2) expressed as BV5/(total pulmonary blood volume; p < 0.0001), and significant increases in BV5-10 and BV 10 (pulmonary blood volumes contained in vessels between 5 and 10 mm2 and above 10 mm2, respectively, p < 0.0001). These changes were consistent across lobes. CONCLUSION: COVID-19 patients display striking anomalies in the distribution of blood volume within the pulmonary vascular tree, consistent with increased pulmonary vasculature resistance in the pulmonary vessels below the resolution of CT.