BACKGROUND:Existing computed tomography (CT) vascular pruning measures rely on volumes, such as the proportion of blood volume in vessels with cross-sectional area (CSA) ≤5 mm2 or CSA ≤10 mm2/total blood vessel volume (BV5/TBV or BV10/TBV, respectively), but may underestimate vascular pruning due to blood redistribution to larger vessels in individuals with milder COPD. We aim to develop a novel CT vessel measure, the total vessel count (TVC), quantify small and combined small/intermediate vessel count percentages, and compare these measures with BV5/TBV and BV10/TBV in terms of associations with lung function and its decline. As a secondary aim, associations with exercise capacity and COPD symptoms will be investigated. METHODS:CanCOLD (Canadian Cohort Obstructive Lung Disease) participants underwent CT imaging. BV5/TBV and BV10/TBV were generated using vessel segmentation. TVC and small (CSA ≤5 mm2, VC≤5/TVC) and combined small/intermediate (CSA ≤10 mm2, VC≤10/TVC) vessel count percentages were calculated. Fully adjusted regression models assessed associations with forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (D LCO), accelerated FEV1 decline over 3 years, peak oxygen uptake (V̇ O2 peak), 6-min walk distance (6MWD) and Medical Research Council (MRC) dyspnoea scale. RESULTS:1254 CanCOLD participants were investigated. TVC, VC≤5/TVC and VC≤10/TVC were associated with FEV1/FVC (p<0.05), D LCO (p<0.05) and FEV1 decline (p<0.05); VC≤10/TVC was associated with V̇ O2 peak (p<0.05), and both VC≤5/TVC and VC≤10/TVC were associated with MRC (p<0.05). BV5/TBV and BV10/TBV were only associated with 6MWD (p<0.05) and MRC (p<0.05). CONCLUSION:Pulmonary vessel count percent, a measure of vasculature narrowing/loss, is associated with lung function and its decline, reduced exercise capacity, and increased symptoms in COPD.

Purpose To develop a deep learning model for segmenting pectoralis muscle volume (PMV) at CT and evaluate the reproducibility, group differences, and associations of pectoralis muscle area (PMA) and PMV with chronic obstructive pulmonary disease (COPD)-related outcomes. Materials and Methods This study was a secondary analysis of the prospective Canadian Cohort Obstructive Lung Disease study (CanCOLD, data collected from November 2009 to July 2015). Randomly sampled CT scans from CanCOLD were used for model training, validation, and internal testing (n = 96, 16, and 32, respectively) and an external dataset for external testing (n = 32). A U-Net model was trained for PMV segmentation, and performance was assessed using the Dice similarity coefficient (DSC). PMA and PMV values were extracted from paired inspiration and expiration scans to assess segmentation reproducibility. Differences between individuals with or without COPD and associations with forced expiratory volume in 1 second (FEV1), diffusing capacity of the lungs for carbon monoxide (Dlco), and peak oxygen uptake during exercise (VO2) were reported. Results Individuals included those with (n = 634; mean age, 67.3 years ± 10.1 [SD]; 394 male participants) and without (n = 601; mean age, 65.8 years ± 9.6; 327 male participants) COPD. The model yielded DSCs of 0.94 ± 0.04, 0.93 ± 0.03, and 0.92 ± 0.04 in the training and validation, internal testing, and external testing datasets, respectively. Contrary to PMV (bias, 0.1 cm3; P = .77), PMA showed bias between inspiration and expiration (bias, -2.7 cm2; P < .001). Both PMA and PMV were reduced in patients with COPD (P < .05), but PMV was more strongly associated with FEV1 (adjusted R2 [Radj2], 0.609/0.598), Dlco (Radj2, 0.645/0.627), and VO2 (Radj2, 0.680/0.666). Conclusion An accurate and generalizable CT-based deep learning model for pectoralis muscle segmentation was developed. Compared with PMA, PMV showed better reproducibility and stronger associations with COPD outcomes. Keywords: CT, Thorax, Lung, Volume Analysis, Chronic Obstructive Pulmonary Disease, Segmentation ClinicalTrials.gov identifier no. NCT00920348 © RSNA, 2026 Supplemental material is available for this article.

Higher pulmonary microvascular function may contribute to higher rest and exercise diffusing capacity (DLCO), pulmonary capillary blood volume (VC) and membrane diffusing capacity (DM) in trained individuals. We hypothesized that pulmonary vasodilatation with sildenafil would increase resting and exercise DLCO, VC and DM in untrained (UT) individuals, whereas trained (T) individuals would have a smaller response. This double-blind randomized crossover trial recruited n = 24 healthy participants (nine females) into UT and T groups (n = 12 each) based on V ̇ O 2 peak $\dot{V}{{{\mathrm{O}}}_{2{\mathrm{peak}}}}$ (mean ± SD V ̇ O 2 peak $\dot{V}{{{\mathrm{O}}}_{2{\mathrm{peak}}}}$ = 37.5 ± 3.8 and 65.3 ± 6.7 mL.kg-1 .min-1, respectively). Rest and exercise DLCO (cycle ergometry; 60 W, 30%, 60% and 90% of V ̇ O 2 peak $\dot{V}{{{\mathrm{O}}}_{2{\mathrm{peak}}}}$ ) was measured following oral sildenafil (50 mg) or placebo (block randomized) and evaluated using one-way ANOVA and linear mixed effects modelling. At rest, right ventricular systolic pressure was reduced with sildenafil across groups (mean ∆ = -2.1 mmHg; P = 0.01), indicating effective pulmonary vasodilatation. No group, drug or drug by group interaction effect was detected in resting DLCO, VC or DM (all Pgroup > 0.058). T had higher exercise DLCO during all workloads (all Pgroup < 0.031) and higher VC in relative workloads (Pgroup = 0.006). Sildenafil did not impact exercise DLCO, VC or DM at any workload (all Pdrug > 0.395), with no significant drug by group interaction (all Pinteraction > 0.086). As sildenafil did not impact rest or exercise DLCO, VC or DM in either group, there was no evidence that improved nitric oxide-mediated pulmonary vasodilatory function would explain the greater DLCO observed in trained individuals. KEY POINTS: Higher pulmonary vascular function may explain why trained individuals have higher pulmonary diffusing capacity for carbon monoxide (DLCO) compared to untrained individuals. This double-blind randomized crossover trial investigated whether pulmonary vasodilatation with sildenafil would elucidate changes in resting and exercise DLCO within trained and untrained groups. Trained individuals had higher DLCO, but sildenafil did not elicit alterations in DLCO in either group. Our findings suggest that improved nitric oxide-mediated pulmonary vasodilatation is not likely the primary mechanism responsible for the greater DLCO observed in trained individuals. Future work should investigate which mechanism(s) are responsible for the higher DLCO in trained individuals.

BACKGROUND:Patients with advanced COPD have pulmonary vascular dysfunction and destruction; thus, it is unclear whether they are responsive to selective pulmonary vasodilators. RESEARCH QUESTION:What is the effect of inhaled nitric oxide (iNO) on exercise capacity in patients without hypoxemia with mild-to-severe COPD without pulmonary hypertension, and are there structural and/or functional predictors of response? STUDY DESIGN AND METHODS:Sixty-one patients with mild-to-severe COPD (mean FEV1, 65% ± 18% predicted) were recruited to this randomized, placebo-controlled, double-anonymized, crossover trial. Assessments included pulmonary function, echocardiography, and quantitative CT scan. Small vessel volume fraction, defined as the vascular volume of blood vessels with a cross-sectional area < 5 mm2 (BV5) divided by total vascular volume (TVV), was used as an index of small vessel perfusion or pulmonary vascular pruning. Participants received iNO or placebo (randomized) during 2 separate incremental exercise tests to determine exercise capacity (peak rate of oxygen consumption [Vo2peak]). RESULTS:The mean effect of iNO on Vo2peak was 0.36 mL/kg/min (95% CI, -0.18 to 0.89) in an unadjusted linear mixed effects model. In prespecified analyses, there was evidence of iNO effect modification by BV5/TVV, whereby higher BV5/TVV was associated with greater iNO-induced improvement in Vo2peak (adjusted mean change, 0.14 mL/kg/min; 95% CI, 0.02-0.26 per 1% increment in BV5/TVV), independent of severity of airflow obstruction, pulmonary diffusing capacity, emphysema, or total lung capacity. iNO-induced increases in Vo2peak were associated with improved ventilatory efficiency and reduced dyspnea (both P < .05). INTERPRETATION:Our results show that despite a null mean effect of iNO on Vo2peak in unadjusted analysis, a significant drug-induced improvement in Vo2peak was observed in patients with higher BV5/TVV. Improvements in Vo2peak with iNO were associated with improved ventilatory efficiency and reduced dyspnea. Our findings suggest a potential COPD pulmonary vascular endotype responsive to inhaled pulmonary vasodilators, characterized by greater small vessel perfusion or less vascular pruning, that is independent of severity of airflow obstruction, diffusing capacity, emphysema, or lung size. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov; No.: NCT03679312; URL: www. CLINICALTRIALS:gov.

Following pulmonary embolism (PE), up to a third of patients develop persistent activity-related dyspnea without evidence of pulmonary hypertension at rest. In such individuals, dyspnea appears to be associated with relatively high inspiratory neural drive (IND, assessed via diaphragm electromyography) during exercise. Excessive IND is multifactorial, but the effects of regional pulmonary capillary hypoperfusion and increased physiological dead space may be contributory. We aimed to determine the effect of iNO on IND, perceived dyspnea intensity, and exercise endurance in patients post-PE. We undertook a randomized, double-blind, placebo-controlled crossover study where 14 symptomatic individuals post-PE completed constant work rate cycle exercise tests while breathing iNO (40 ppm) or placebo, on separate days. Detailed measurements of expired gas, respiratory neuromechanics, and perceived dyspnea were acquired at rest and throughout exercise. iNO administration, compared with placebo, was associated with reduced isotime IND and breathing effort (esophageal pressure-time product of inspiratory muscles) by 9 ± 8 and 19 ± 35%, respectively (both P < 0.01), increased exercise endurance time by 27 ± 12% (P < 0.001), and reduced isotime dyspnea ratings by 1 ± 1 Borg units (P = 0.011). The reduction in IND was related to reduced dyspnea (r = 0.59, P < 0.018), which in turn, correlated with increased exercise endurance time (r = -0.60, P < 0.024). At standardized exercise times, iNO was associated with small reductions in ventilatory requirements for CO2 and heart rate, and increased oxygen pulse, vs. placebo (all P < 0.05). This study demonstrated that excessive IND contributed to troublesome dyspnea and exercise intolerance in individuals post-PE and that these could be partially mitigated by selective pulmonary vasodilation.NEW & NOTEWORTHY The current study confirmed that excessive inspiratory neural drive contributed to troublesome dyspnea and exercise intolerance in individuals with a history of pulmonary embolism and that these could be partially mitigated by acute selective pulmonary vasodilation via inhaled nitric oxide. This study increased our understanding of the complex mechanisms of exertional dyspnea in individuals post-PE with persistent abnormal physiological responses during CPET.

BACKGROUND:The prevalence of e-cigarette use is increasing, and young adults who report e-cigarette use and no history of tobacco smoking report greater respiratory symptoms. Traditional evaluation of resting pulmonary function may fail to detect subclinical abnormalities. RESEARCH QUESTION:To what extent do otherwise healthy, young adults who report regular e-cigarette use and no tobacco smoking history exhibit altered cardiopulmonary function during exercise and blunted recruitment of pulmonary diffusing capacity for carbon monoxide (Dlco)? STUDY DESIGN AND METHODS:Twenty participants with chronic e-cigarette exposure (mean age, 23 ± 4 years) with no tobacco smoking history and 20 age-, height-, and sex-matched control participants underwent a pulmonary function test and cardiopulmonary exercise test. Key outcomes included exercise capacity (V˙O2peak), ventilatory efficiency (minute ventilation/CO2 output nadir), exertional dyspnea, and operating lung volumes during exercise. A secondary aim investigated recruitment of resting Dlco and its components, measured as the change from the seated to supine posture. Adjusted linear regression models were used to evaluate the effect of group on key outcome variables at rest and during exercise. RESULTS:Both groups presented with normal pulmonary function (all, Pgroup > .05). Individuals who use e-cigarettes exhibited a lower V˙O2peak (Pgroup = .017), elevated minute ventilation/carbon dioxide output nadir (Pgroup = .037), and greater exertional dyspnea (Pgroup < .001, Pgroup∗workload < .001), whereas operating lung volumes did not differ from control participants (all, P > .05). Individuals who use e-cigarettes also displayed a blunted Dlco recruitment to a postural change (Pgroup∗posture = .036). Between-group differences in dyspnea and Dlco recruitment were independent of V˙O2peak. INTERPRETATION:In this study, otherwise healthy young adults who report regular e-cigarette use exhibited evidence of abnormal cardiopulmonary responses to exercise and blunted Dlco recruitment. These findings suggest early cardiopulmonary impairment and pulmonary vascular dysfunction in young adults with chronic e-cigarette exposure.

RATIONALE:Chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are characterized by exaggerated carotid chemoreceptor (CC) sensitivity and exercise intolerance. We tested the hypothesis that participants with elevated CC sensitivity would have the greatest improvement in exercise tolerance with CC inhibition, secondary to increased vascular conductance, and lower ventilatory requirements, dyspnea and leg discomfort. METHODS:Data from healthy controls, and patients with CHF or COPD were included in this secondary analysis of results from 2 randomized placebo-controlled double-blind crossover trials. Assessments included pulmonary function, incremental cardiopulmonary exercise test, and basal CC sensitivity assessment. High CC sensitivity was defined as either a stepwise hypoxic ventilatory response (HVR) or transient HVR greater than one SD above the mean in healthy controls. Participants received 2 μg/kg/min dopamine or placebo infusions (randomized) during 2 separate constant work-rate exercise tests to examine exercise endurance time (EET) and cardiopulmonary responses. RESULTS:Among 33 adults, 17 were categorized to normal HVR (11 controls/3 COPD/3 CHF), and 16 to high HVR (1 control/7 COPD/8 CHF). Participants with high HVR experienced significant dopamine-induced improvements in EET (pinteraction = 0.011), and reduced leg discomfort at the 4-min isotime (pinteraction = 0.024). Those with improved vascular conductance and leg discomfort had the greatest improvements in EET (p = 0.042 and p = 0.021, respectively). CONCLUSIONS:CC inhibition with dopamine in participants with high HVR was associated with improvement in EET. These findings suggest that high HVR is related to exercise limitation, and that improvement in EET is associated with a CC-mediated increase in vascular conductance and leg discomfort.

INTRODUCTION:Physiological outcomes, like pulmonary diffusing capacity, can be impacted by non-modifiable ( e.g. , biological sex) and modifiable ( e.g. , cardiorespiratory fitness) factors. The quantification of potential combined, interactive effects of these factors remains unreported in the literature. PURPOSE:This study aimed to examine the independent and combined associations of sex and cardiorespiratory fitness ( V̇ O 2peak ) with pulmonary diffusing capacity (DL CO ) and its determinants (capillary blood volume, V C ; and membrane diffusing capacity, D M ) at rest and during exercise, while controlling for lung size. METHODS:This retrospective study utilized general linear regression and linear mixed effects modeling to evaluate DL CO (adjusted for hemoglobin) and its determinants at rest and during exercise in n = 113 participants (57 female). RESULTS:Sex, V̇ O 2peak , and alveolar volume (V A ) all showed significant bivariate associations with diffusing capacity of the lung for carbon monoxide (DL CO ) when tested separately (all P < 0.001). In our final model, after accounting for V A , only sex remained significantly associated with resting DL CO ( P = 0.047), whereas V̇ O 2peak was associated with resting V C ( P = 0.009). No significant interaction effects were detected for resting data. After accounting for V A , exercise DL CO was significantly associated with sex but not V̇ O 2peak ( P < 0.001). A significant sex* V̇ O 2peak *intensity interaction was detected in exercise DL CO whereby individuals with higher V̇ O 2peak have greater exercise DL CO , and trained males have a greater DL CO compared with trained females ( Pinteraction < 0.001; males, P < 0.001; females, P < 0.001). Exercise V C was not associated with V̇ O 2peak or sex after accounting for V A , but a significant sex* V̇ O 2peak *intensity interaction effect on exercise V C was detected ( Pinteraction = 0.009; males, P = 0.039; females, P = 0.298). CONCLUSIONS:By examining the independent and combined associations of sex and V̇ O 2peak with DL CO and its determinants, our findings identified that the DL CO response to exercise is modified by the combined effects of sex and fitness.

Existing computed tomography (CT) vascular pruning measures rely on volumes, such as the proportion of blood volume in vessels with cross-sectional area (CSA)<5 mm 2 or <10 mm 2 /total blood volume (BV5/TBV, BV10/TBV, respectively), but may underestimate vascular pruning due to blood redistribution to larger vessels in individuals with milder chronic obstructive pulmonary disease (COPD). We aim to develop a novel CT vessel measure, the total vessel count (TVC), quantify small and combined small/intermediate vessel count percentages, and compare these measures with BV5/TBV and BV10/TBV in terms of associations with lung function and its decline. As a secondary aim, associations with exercise capacity and COPD symptoms will be investigated. CanCOLD participants underwent CT imaging. BV5/TBV and BV10/TBV were generated using vessel segmentation. TVC, and small (CSA<5 mm 2 , VC ≤5 /TVC) and combined small/intermediate (CSA<10 mm 2 , VC ≤10 /TVC) vessel count percentages were calculated. Fully adjusted regression models assessed associations with forced expiratory volume in 1 s (FEV 1 ), FEV 1 /forced vital capacity (FEV 1 /FVC), carbon monoxide diffusing capacity (DL CO ), accelerated FEV 1 decline over 3-years, maximal oxygen consumption (VO 2peak ), 6-minute walk distance (6MWD) and Medical Research Council (MRC). 1254 CanCOLD participants were investigated. TVC, VC ≤5 /TVC and VC ≤10 /TVC were associated with FEV 1 /FVC (p<0.05), DL CO (p<0.05) and FEV 1 decline (p<0.05); VC ≤10 /TVC was associated with VO 2peak (p<0.05) and both VC ≤5 /TVC and VC ≤10 /TVC were associated with MRC (p<0.05). BV5/TBV and BV10/TBV were only associated with 6MWD (p<0.05) and MRC (p<0.05). Pulmonary vessel count percent, a measure of vasculature narrowing/loss, is associated with lung function and its decline, reduced exercise capacity and increased symptoms in COPD.

The elevation of pulmonary artery pressure (PAP) with hypoxia may impair peak cardiac output ([Formula: see text]) and therefore V̇o 2max . Our novel findings show that despite reducing resting RVSP in acute moderate ([Formula: see text] = 89 mmHg) and severe hypoxia ([Formula: see text] = 79 mmHg) with inspired nitric oxide, peak [Formula: see text], and V̇o 2max were unaffected.

Endurance-trained athletes exhibit a greater diffusing capacity for carbon monoxide (DLCO) at rest and during exercise as compared with untrained individuals; however, the mechanism(s) are unclear. The supine position translocates blood centrally and can be used to investigate DLCO responses independent of metabolic rate. We hypothesized that endurance-trained individuals would have a greater DLCO response to postural change at rest as compared with untrained and that the supine position would elicit a greater DLCO response as compared with the upright position during exercise in both groups. Fourteen endurance-trained (Trained) individuals (V̇o2peak: 61.1 ± 4.4 mL·kg-1·min-1) and 14 untrained individuals (V̇o2peak: 37.4 ± 3.0 mL·kg-1·min-1) completed DLCO maneuvers at rest and during exercise in the upright and supine position. At rest, there was a significant group-by-position interaction (P = 0.02) effect on DLCO with post hoc analysis determining DLCO increased from upright to supine position in Trained (P < 0.01), but not untrained (P = 0.58). There was no effect of position on exercising DLCO (P = 0.16) regardless of group; however, pulmonary capillary blood volume (VC) was increased with supine exercise (P = 0.03). There was an apparent plateau in DLCO and VC in the Trained group near-maximal exercise as Trained failed to increase DLCO (P = 0.25) and Vc (P = 0.46) up to near-maximal exercise. Trained individuals demonstrate greater DLCO recruitment with postural change at rest suggesting a greater ability to recruit/distend the pulmonary microvasculature. However, the supine position did not augment DLCO as compared with upright position in Trained individuals near-maximal exercise, suggesting a plateau may be reached at maximal exercise.NEW & NOTEWORTHY We demonstrate that the supine position increases resting DLCO significantly more in endurance-trained individuals as compared with untrained individuals. Furthermore, the supine position increases pulmonary capillary blood volume, but not diffusing capacity during exercise. Lastly, there was an apparent plateau in DLCO and VC in the Trained group suggesting the pulmonary microvasculature may reach a morphological limit.

Contrary to our traditional understanding, the pulmonary vasculature may adapt to endurance training. Improved pulmonary vasodilation may be the principal mediator for trained individuals who exhibit greater diffusing capacity (DLCO), capillary blood volume (VC; representing recruitment and distension) and membrane diffusing capacity (DM; representing recruitment) at rest and during exercise as compared to untrained. Potential functional differences may be investigated using pulmonary vasodilators ( e.g., oral sildenafil). The purpose of this study was to examine the effects of sildenafil on DLCO, VC, and DM, in trained and untrained participants. We hypothesized that sildenafil would increase rest and exercise DLCO, VC, and DM, with a lesser relative response in trained due to improved baseline pulmonary vascular function. In this randomized, double-blind, placebo-controlled cross-over design (NCT: 04985929), DLCO was measured at rest (supine and seated) and during cycle ergometry (60 Watts, 30%, 60%, and 90% of V̇O2peak). DLCO was conducted using the modified Roughton-Forster multiple FiO2 breath-hold technique over 6 visits, where participants were given either oral placebo or sildenafil (50 mg, single dose, 30 min wash-in). To date, 18 participants (6 female) (56% target sample size) have been recruited into two groups: trained (T) and untrained (UT) (Mean V̇O2peak = 66.6 ± 7.2 mL.kg−1.min−1 and 37.8 ± 3.2 mL.kg−1.min−1, respectively). Estimated PASP was reduced between placebo and sildenafil across all participants at rest (mean Δ = -2.7 mmHg; p<0.01), indicating effective pulmonary vasodilation. Under placebo, T had higher DLCO at rest (supine), 30%, 60%, and 90% of V̇O2peak (p<0.05), consistent with previous literature. There was no effect of sildenafil on DLCO, VC, or DM (all p>0.200) or drug by workload interactions (all p>0.189) in either group. These preliminary results suggest that pharmacological augmentation of the nitric oxide vasodilatory pathway does not increase DLCO regardless of training status. We speculate that this pathway may not be the primary driver responsible for the elevated DLCO observed in endurance trained participants. Natural Sciences and Engineering Research Council of Canada. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

BACKGROUND:Although it is generally accepted that aerobic exercise training does not change lung structure or function, some work suggests that greater pulmonary vascular structure and function are associated with higher exercise capacity (peak rate of oxygen consumption [V˙o2peak]). RESEARCH QUESTION:Is there a cross-sectional association between the pulmonary vasculature and V˙o2peak? We hypothesized that those with higher CT blood vessel volumes and pulmonary diffusing capacity for carbon monoxide (Dlco) would have higher V˙o2peak, independent of airflow limitation. STUDY DESIGN AND METHODS:Participants from the Canadian Cohort Obstructive Lung Disease (CanCOLD) study were categorized as follows: participants with normal spirometry who had never smoked (n = 263), participants with normal spirometry who had ever smoked (n = 407), and COPD: individuals with spirometric airflow obstruction (n = 334). Total vessel volume (TVV), volume for vessels < 5 mm2 in cross-sectional area (BV5), and volume for vessels between 5 and 10 mm2 in cross-sectional area (BV5-10) were generated from CT scans and used as indices of pulmonary vascular structure. Dlco was used as an index of pulmonary microvascular function. V˙o2peak was evaluated via incremental cardiopulmonary exercise testing. RESULTS:General linear regression models revealed that even after controlling for FEV1, emphysema severity, and body morphology, Dlco, TVV, BV5, and BV5-10, were independently associated with V˙o2peak. Interaction effects were observed between COPD and TVV, BV5, and BV5-10, indicating a weaker association between pulmonary vascular volumes and V˙o2peak in COPD. INTERPRETATION:Our results suggest that pulmonary vascular structure and Dlco are independently associated with V˙o2peak, regardless of severity of airflow limitation and emphysema, suggesting that these associations are not limited to COPD.

Background: Accumulating evidence indicates that pulmonary vascular insults, particularly at the level of the endothelium, may contribute to the pathogenesis of COPD. Further, the mechanism(s) underpinning pulmonary vascular remodeling/dysfunction in COPD may also contribute to systemic vascular dysfunction. Indeed, brachial artery flow-mediated dilation (FMD; an assessment of systemic vascular endothelial function) is inversely associated with emphysema among patients with COPD. However, it remains unclear whether systemic vascular function is related to pulmonary vascular structure in COPD. Thus, we aimed to evaluate the relationships between FMD and computed tomography (CT)-derived emphysema and pulmonary vascular structure in patients with mild-to-severe COPD. We hypothesized that FMD would be inversely related with CT-derived emphysema severity, and positively related with pulmonary vascular structure. Methods: 36 individuals with COPD (16 females, age: 69±6 years, FEV1: 62±19 %predicted) completed three experimental days: Day 1: Enrollment and full pulmonary function test. Day 2: Chest CT scan to quantify emphysema severity (LAA-950), total vessel volume (TVV), and the volume of vessels with a cross sectional area of <5mm2 (BV5) and between 5-10mm2 (BV5-10). Day 3: Brachial artery FMD (5-minute forearm occlusion followed by 3-minute reactive hyperemia). FMD was allometrically scaled and corrected for the prevailing shear stimulus (shear rate area under the curve). Results: FMD was not correlated with LAA-950, (r2=0.09; P=0.09); however, positive relationships were observed between FMD and TVV normalized to total lung volume (r2=0.24; P<0.01), as well as BV5-10 (r2=0.34; P<0.01). FMD was not correlated to BV5 (r2=0.09, P=0.10). Conclusion: Collectively, these preliminary data indicate that, among patients with COPD, impaired pulmonary vascular structure is associated with attenuated systemic vascular function; suggesting an interplay between the pulmonary and systemic vasculature in the pathogenesis of COPD. Supported by the Canadian Institutes for Health Research, the Canadian Respiratory Research Network, and the “Fondation Baxter et Alma Ricard”. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Background: People with chronic obstructive pulmonary disease (COPD) have reduced pulmonary diffusing capacity for carbon monoxide (DLCO) compared to healthy controls, likely due to lower pulmonary capillary blood volume (Vc) or membrane diffusing capacity (Dm). Previous work has shown reduced pulmonary vascular volumes measured by computed tomography (CT) in COPD compared to controls. The purpose of this study was to explore the potential associations between CT measured pulmonary vascular structure with DLCO, Vc and Dm. We hypothesized that those with greater pulmonary vascular volumes would show higher DLCO, Vc and Dm. Methods: Day 1: Enrollment and pulmonary function test. Day 2: Chest CT scan to quantify emphysema severity, total vessel volume (TVV), volume of vessels with a cross-sectional area <5mm2 (BV5), and between 5-10mm2 (BV5-10). Day 3: Multiple fraction of inspired O2 DLCO technique to determine Vc and Dm. Potential associations were evaluated by Pearson correlation. Results: To date, 35 people with COPD (18 females, mean FEV1 65±16% predicted; 69±7 years) have been recruited. DLCO adjusted for alveolar volume was correlated with TVV (r= 0.55, p<0.001), BV5 (r=0.47, p=0.006) and BV5-10 (r=0.48, p=0.004). Exploratory analyses revealed that among CT variables, Dm was associated with BV5-10 (r=0.46, p=0.006) and TVV (r=0.37, p=0.03), while Vc was not associated with any CT pulmonary vascular measurements. Conclusions: Our results suggest that DLCO and Dm are related to CT-measured pulmonary vascular volumes in COPD; supporting an association between pulmonary vascular function and structure.

Background Computed tomography (CT)-derived pectoralis muscle area (PMA) measurements are prognostic in people with or at-risk of COPD, but fully automated PMA extraction has yet to be developed. Our objective was to develop and validate a PMA extraction pipeline that can automatically: 1) identify the aortic arch slice; and 2) perform pectoralis segmentation at that slice. Methods CT images from the Canadian Cohort of Obstructive Lung Disease (CanCOLD) study were used for pipeline development. Aorta atlases were used to automatically identify the slice containing the aortic arch by group-based registration. A deep learning model was trained to segment the PMA. The pipeline was evaluated in comparison to manual segmentation. An external dataset was used to evaluate generalisability. Model performance was assessed using the Dice–Sorensen coefficient (DSC) and PMA error. Results In total 90 participants were used for training (age 67.0±9.9 years; forced expiratory volume in 1 s (FEV1) 93±21% predicted; FEV1/forced vital capacity (FVC) 0.69±0.10; 47 men), and 32 for external testing (age 68.6±7.4 years; FEV1 65±17% predicted; FEV1/FVC 0.50±0.09; 16 men). Compared with manual segmentation, the deep learning model achieved a DSC of 0.94±0.02, 0.94±0.01 and 0.90±0.04 on the true aortic arch slice in the train, validation and external test sets, respectively. Automated aortic arch slice detection obtained distance errors of 1.2±1.3 mm and 1.6±1.5 mm on the train and test data, respectively. Fully automated PMA measurements were not different from manual segmentation (p>0.05). PMA measurements were different between people with and without COPD (p=0.01) and correlated with FEV1 % predicted (p<0.05). Conclusion A fully automated CT PMA extraction pipeline was developed and validated for use in research and clinical practice.