Comparison of Myocardial Blood Flow Quantification Models for Double ECG Gating Arterial Spin Labeling MRI: Reproducibility Assessment.

BACKGROUND: Arterial spin labeling (ASL) allows non-invasive quantification of myocardial blood flow (MBF). Double-ECG gating (DG) ASL is more robust to heart rate variability than single-ECG gating (SG), but its reproducibility requires further investigation. Moreover, the existence of multiple quantification models hinders its application. Frequency-offset-corrected-inversion (FOCI) pulses provide sharper edge profiles than hyperbolic-secant (HS), which could benefit myocardial ASL. PURPOSE: To assess the performance of MBF quantification models for DG compared to SG ASL, to evaluate their reproducibility and to compare the effects of HS and FOCI pulses. STUDY TYPE: Prospective. SUBJECTS: Sixteen subjects (27 ± 8 years). FIELD STRENGTH/SEQUENCE: 1.5 T/DG and SG flow-sensitive alternating inversion recovery ASL. ASSESSMENT: Three models for DG MBF quantification were compared using Monte Carlo simulations and in vivo experiments. Two models used a fitting approach (one using only a single label and control image pair per fit, the other using all available image pairs), while the third model used a T1 correction approach. Slice profile simulations were conducted for HS and FOCI pulses with varying B0 and B1. Temporal signal-to-noise ratio (tSNR) was computed for different acquisition/quantification strategies and inversion pulses. The number of images that minimized MBF error was investigated in the model with highest tSNR. Intra and intersession reproducibility were assessed in 10 subjects. STATISTICAL TESTS: Within-subject coefficient of variation, analysis of variance. P-value <0.05 was considered significant. RESULTS: MBF was not different across acquisition/quantification strategies (P = 0.27) nor pulses (P = 0.9). DG MBF quantification models exhibited significantly higher tSNR and superior reproducibility, particularly for the fitting model using multiple images (tSNR was 3.46 ± 2.18 in vivo and 3.32 ± 1.16 in simulations, respectively; wsCV = 16%). Reducing the number of ASL pairs to 13/15 did not increase MBF error (minimum = 0.22 mL/g/min). DATA CONCLUSION: Reproducibility of MBF was better for DG than SG acquisitions, especially when employing a fitting model. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Lung Cancer Screening in People With COPD: The Pamplona-IELCAP Experience.

INTRODUCTION: The Global Initiative for Obstructive Lung Disease (GOLD) recommends lung cancer screening for patients with Chronic Obstructive Pulmonary Disease (COPD), but data is lacking regarding results of screening in this high-risk population. The main goal of the present work is to explore if lung cancer screening with Low Dose Chest Tomography (LDCT) in people with COPD, allows lung cancer (LC) diagnosis in early stages with survival compatible with curative state. METHODS: This is a post hoc exploratory analysis. Pamplona International Early Lung Cancer Action Program (P-IELCAP) participants with a GOLD defined obstructive pattern (post bronchodilator FEV1/FVC<0.70) were selected for analysis. The characteristics of those who developed LC and their survival are described. A Cox proportional analysis explored the factors associated with LC diagnosis. RESULTS: Eight hundred and sixty-five patients (77% male, 93% in spirometric GOLD stage 1+2) were followed for 102±63 months. LC prevalence was 2.6% at baseline, with an annual LC diagnosis rate of 0.68%. Early-stage tumors predominated (74%) with a median survival (25-75th percentiles) of 139 (76-185) months. Cumulative tobacco exposure, FEV1%, and emphysema were the main predictors of an LC diagnosis. Eight (11%) patients with COPD had a second LC, most of them in early stage (92%), and 6 (8%) had recurrence. Median survival (25-75th percentiles) in these patients was 168 (108-191) months. CONCLUSIONS: Lung cancer screening of selected high-risk participants with COPD allowed the LC diagnosis in early stages with survival compatible with curative state.

Impact of Applying the Global Lung Initiative Criteria for Airway Obstruction in GOLD Defined COPD Cohorts: The BODE and CHAIN Experience.

INTRODUCTION: The Global Lung Function Initiative (GLI) has proposed new criteria for airflow limitation (AL) and recommends using these to interpret spirometry. The objective of this study was to explore the impact of the application of the AL GLI criteria in two well characterized GOLD-defined COPD cohorts. METHODS: COPD patients from the BODE (n=360) and the COPD History Assessment In SpaiN (CHAIN) cohorts (n=722) were enrolled and followed. Age, gender, pack-years history, BMI, dyspnea, lung function measurements, exercise capacity, BODE index, history of exacerbations and survival were recorded. CT-detected comorbidities were registered in the BODE cohort. The proportion of subjects without AL by GLI criteria was determined in each cohort. The clinical, CT-detected comorbidity, and overall survival of these patients were evaluated. RESULTS: In total, 18% of the BODE and 15% of the CHAIN cohort did not meet GLI AL criteria. In the BODE and CHAIN cohorts respectively, these patients had a high clinical burden (BODE≥3: 9% and 20%; mMRC≥2: 16% and 45%; exacerbations in the previous year: 31% and 9%; 6MWD<350m: 15% and 19%, respectively), and a similar prevalence of CT-diagnosed comorbidities compared with those with GLI AL. They also had a higher rate of long-term mortality - 33% and 22% respectively. CONCLUSIONS: An important proportion of patients from 2 GOLD-defined COPD cohorts did not meet GLI AL criteria at enrolment, although they had a significant burden of disease. Caution must be taken when applying the GLI AL criteria in clinical practice.

Safety, feasibility, and hemodynamic response of regadenoson for stress perfusion CMR.

Owing to its pharmacodynamics and posology, the use of regadenoson for stress cardiac magnetic resonance (CMR) has potential advantages over other vasodilators. We sought to evaluate the safety, hemodynamic response and diagnostic performance of regadenoson stress-CMR in routine clinical practice. All regadenoson stress-CMR examinations performed between May 2017 and July 2020 at our institution were retrospectively reviewed. A total of 698 studies were included for the final analysis. A conventional stress/rest protocol was performed using a 1.5T MRI scanner (Magnetom Aera, Siemens Healthineers, Erlangen, Germany). Adverse events, clinical symptoms, and hemodynamic response were assessed. Diagnostic accuracy of the test was evaluated in patients who underwent invasive coronary angiography. Nearly half of patients (48.5%) remained asymptomatic. Most common clinical symptoms included dyspnea (137, 19.6%), chest pain (116, 16.6%) and flushing (44, 6.3%). Two patients (0.28%) could not complete the examination due to severe hypotension or unbearable chest pain. Overall, an increase in heart rate (HR) response (36.2% [IQR: 22.5?50.9]) and a decrease in systolic and diastolic blood pressure (BP) (median systolic BP response of -5% [IQR: -11.5-0.6]; median diastolic BP response of -6.3 mmHg [IQR: -13.4-0]) was observed. Patients with symptoms induced by regadenoson showed higher HR response (40.3%, IQR: 26.4?56.1 vs. 32.4%, IQR: 19-45.6, p < 0.001), whereas a blunted HR response was observed in diabetic (29.6%, IQR: 18.4?42 p < 0.001), obese (31.7%, IQR: 20.7?46.2 p = 0.005) and patients aged 70 years or older (32.9%, IQR: 22.6?43.1 p < 0.001). Overall, regadenoson stress-CMR showed 95.65% (IQ 91.49?99.81) sensitivity, 54.84% (IQ 35.71?73.97) specificity, 86.99% (IQ 82.74?94.68) positive predictive value, and 77.27% (IQ 57.49?97.06) negative predictive value for detecting significant coronary stenosis as compared with invasive coronary angiography. Regadenoson is a well-tolerated vasodilator that can be safely employed for stress perfusion CMR, with high diagnostic performance.

Assessment of Splenic Switch-Off With Arterial Spin Labeling in Adenosine Perfusion Cardiac MRI.

BACKGROUND: In patients with suspected coronary artery disease (CAD), myocardial perfusion is assessed under rest and pharmacological stress to identify ischemia. Splenic switch-off, defined as the stress to rest splenic perfusion attenuation in response to adenosine, has been proposed as an indicator of stress adequacy. Its occurrence has been previously assessed in first-pass perfusion images, but the use of noncontrast techniques would be highly beneficial. PURPOSE: To explore the ability of pseudo-continuous arterial spin labeling (PCASL) to identify splenic switch-off in patients with suspected CAD. STUDY TYPE: Prospective. POPULATION: Five healthy volunteers (age 24.8 ± 3.8 years) and 32 patients (age 66.4 ± 8.2 years) with suspected CAD. FIELD STRENGTH/SEQUENCE: A 1.5-T/PCASL (spin-echo) and first-pass imaging (gradient-echo). ASSESSMENT: In healthy subjects, multi-delay PCASL data (500-2000 msec) were acquired to quantify splenic blood flow (SBF) and determine the adequate postlabeling delay (PLD) for single-delay acquisitions (PLD > arterial transit time). In patients, single-delay PCASL (1200 msec) and first-pass perfusion images were acquired under rest and adenosine conditions. PCASL data were used to compute SBF maps and SBF stress-to-rest ratios. Three observers classified patients into "switch-off" and "failed switch-off" groups by visually comparing rest-stress perfusion data acquired with PCASL and first-pass, independently. First-pass categories were used as reference to evaluate the accuracy of quantitative classification. STATISTICAL TESTS: Wilcoxon signed-rank, Pearson correlation, kappa, percentage agreement, Generalized Linear Mixed Model, Mann-Whitney, Pearson Chi-squared, receiver operating characteristic, area-under-the-curve (AUC) and confusion matrix. SIGNIFICANCE: P value < 0.05. RESULTS: A total of 27 patients (84.4%) experienced splenic switch-off according to first-pass categories. Comparison of PCASL-derived SBF maps during stress and rest allowed assessment of splenic switch-off, reflected in a reduction of SBF values during stress. SBF stress-to-rest ratios showed a 97% accuracy (sensitivity = 80%, specificity = 100%, AUC = 85.2%). DATA CONCLUSION: This study could demonstrate the feasibility of PCASL to identify splenic switch-off during adenosine perfusion MRI, both by qualitative and quantitative assessments. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: 2.

Cardiometabolic characterization in metabolic dysfunction-associated fatty liver disease.

Background: To better understand the patient's heterogeneity in fatty liver disease (FLD), metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed by international experts as a new nomenclature for nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the cardiovascular risk, assessed through coronary artery calcium (CAC) and epicardial adipose tissue (EAT), of patients without FLD and patients with FLD and its different subtypes. Methods: Cross sectional study of 370 patients. Patients with FLD were divided into 4 groups: FLD without metabolic dysfunction (non-MD FLD), MAFLD and the presence of overweight/obesity (MAFLD-OW), MAFLD and the presence of two metabolic abnormalities (MAFLD-MD) and MAFLD and the presence of T2D (MAFLD-T2D). MAFLD-OW included two subgroups: metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). The patients without FLD were divided into 2 groups: patients without FLD and without MD (non-FLD nor MD; reference group) and patients without FLD but with MD (non-FLD with MD). EAT and CAC (measured through the Agatston Score) were determined by computed tomography. Results: Compared with the reference group (non-FLD nor MD), regarding EAT, patients with MAFLD-T2D and MAFLD-MUHO had the highest risk for CVD (OR 15.87, 95% CI 4.26-59.12 and OR 17.60, 95% CI 6.71-46.20, respectively), patients with MAFLD-MHO were also at risk for CVD (OR 3.62, 95% CI 1.83-7.16), and patients with non-MD FLD did not have a significantly increased risk (OR 1.77; 95% CI 0.67-4.73). Regarding CAC, patients with MAFLD-T2D had an increased risk for CVD (OR 6.56, 95% CI 2.18-19.76). Patients with MAFLD-MUHO, MAFLD-MHO and non-MD FLD did not have a significantly increased risk compared with the reference group (OR 2.54, 95% CI 0.90-7.13; OR 1.84, 95% CI 0.67-5.00 and OR 2.11, 95% CI 0.46-9.74, respectively). Conclusion: MAFLD-T2D and MAFLD-OW phenotypes had a significant risk for CVD. MAFLD new criteria reinforced the importance of identifying metabolic phenotypes in populations as it may help to identify patients with higher CVD risk and offer a personalized therapeutic management in a primary prevention setting.

Transient elastography and serum markers of liver fibrosis associate with epicardial adipose tissue and coronary artery calcium in NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease morbimortality. However, it is not clear if NAFLD staging may help identify early or subclinical markers of cardiovascular disease. We aimed to evaluate the association of liver stiffness and serum markers of liver fibrosis with epicardial adipose tissue (EAT) and coronary artery calcium (CAC) in an observational cross-sectional study of 49 NAFLD patients that were seen at Clínica Universidad de Navarra (Spain) between 2009 and 2019. Liver elastography and non-invasive fibrosis markers were used to non-invasively measure fibrosis. EAT and CAC, measured through visual assessment, were determined by computed tomography. Liver stiffness showed a direct association with EAT (r = 0.283, p-value = 0.049) and CAC (r = 0.337, p-value = 0.018). NAFLD fibrosis score was associated with EAT (r = 0.329, p-value = 0.021) and CAC (r = 0.387, p-value = 0.006). The association of liver stiffness with CAC remained significant after adjusting for metabolic syndrome features (including carbohydrate intolerance/diabetes, hypertension, dyslipidaemia, visceral adipose tissue, and obesity). The evaluation of NAFLD severity through liver elastography or non-invasive liver fibrosis biomarkers may contribute to guide risk factor modification to reduce cardiovascular risk in asymptomatic patients. Inversely, subclinical cardiovascular disease assessment, through Visual Scale for CAC scoring, may be a simple and effective measure for patients with potential liver fibrosis, independently of the existence of other cardiovascular risk factors.

Chest CT-assessed comorbidities and all-cause mortality risk in COPD patients in the BODE cohort.

BACKGROUND AND OBJECTIVE: The availability of chest computed tomography (CT) imaging can help diagnose comorbidities associated with chronic obstructive pulmonary disease (COPD). Their systematic identification and relationship with all-cause mortality have not been explored. Furthermore, whether their CT-detected prevalence differs from clinical diagnosis is unknown. METHODS: The prevalence of 10 CT-assessed comorbidities was retrospectively determined at baseline in 379 patients (71% men) with mild to severe COPD attending pulmonary clinics. Anthropometrics, smoking history, dyspnoea, lung function, exercise capacity, BODE (BMI, Obstruction, Dyspnoea and Exercise capacity) index and exacerbations rate were recorded. The prevalence of CT-determined comorbidities was compared with that recorded clinically. Over a median of 78 months of observation, the independent association with all-cause mortality was analysed. A 'CT-comorbidome' graphically expressed the strength of their association with mortality risk. RESULTS: Coronary artery calcification, emphysema and bronchiectasis were the most prevalent comorbidities (79.8%, 62.7% and 33.9%, respectively). All were underdiagnosed before CT. Coronary artery calcium (hazard ratio [HR] 2.09; 95% CI 1.03-4.26, p = 0.042), bronchiectasis (HR 2.12; 95% CI 1.05-4.26, p = 0.036) and low psoas muscle density (HR 2.61; 95% CI 1.23-5.57, p = 0.010) were independently associated with all-cause mortality and helped define the 'CT-comorbidome'. CONCLUSION: This study of COPD patients shows that systematic detection of 10 CT-diagnosed comorbidities, most of which were not detected clinically, provides information of potential use to patients and clinicians caring for them.

Psoas Muscle Density Evaluated by Chest CT and Long-Term Mortality in COPD Patients.

RATIONALE: Poor muscle quality in COPD patients relates to exercise intolerance and mortality. Muscle quality can be estimated on computed tomography (CT) by estimating psoas density (PsD). We tested the hypothesis that PsD is lower in COPD patients than in controls and relates to all-cause mortality. METHODS: At baseline, PsD was measured using axial low-dose chest CT images in 220 COPD patients, 80% men, who were 65±8 years old with mild to severe airflow limitation and in a control group of 58 subjects matched by age, sex, body mass index (BMI) and body surface area (BSA). COPD patients were prospectively followed for 76.5 (48-119) months. Anthropometrics, smoking history, BMI, dyspnoea, lung function, exercise capacity, BODE index and exacerbations history were recorded. Cox proportional risk analysis determined the factors more strongly associated with long-term mortality. RESULTS: PsD was lower in COPD patients than in controls (40.5 vs 42.5, p=0.045). During the follow-up, 54 (24.5%) deaths occurred in the COPD group. PsD as well as age, sex, pack-year history, FEV1%, 6MWD, mMRC, BODE index, were independently associated with mortality. Multivariate analysis showed that age (HR 1.06; 95% CI 1.02-1.12, p=0.006) and CT-assessed PsD (HR 0.97; 95%CI 0.94-0.99, p=0.023) were the variables independently associated with all-cause mortality. CONCLUSIONS: In COPD patients with mild to severe airflow limitation, chest CT-assessed psoas muscle density was lower than in matched controls and independently associated with long-term mortality. Muscle quality using the easy to evaluate psoas muscle density from chest CT may provide clinicians with important prognostic information in COPD.

Clinical and Prognostic Impact of Low Diffusing Capacity for Carbon Monoxide Values in Patients With Global Initiative for Obstructive Lung Disease I COPD.

BACKGROUND: The Global Initiative for Obstructive Lung Disease (GOLD) does not promote diffusing capacity for carbon monoxide (Dlco) values in the evaluation of COPD. In GOLD spirometric stage I COPD patients, the clinical and prognostic impact of a low Dlco has not been explored. RESEARCH QUESTION: Could a Dlco threshold help define an increased risk of death and a different clinical presentation in these patients? STUDY DESIGN AND METHODS: GOLD stage I COPD patients (n = 360) were enrolled and followed over 109 ± 50 months. Age, sex, pack-years' history, BMI, dyspnea, lung function measurements, exercise capacity, BODE index, and history of exacerbations were recorded. A cutoff value for Dlco was identified for all-cause mortality and the clinical and physiological characteristics of patients above and below the threshold compared. Cox regression analysis explored the predictive power of that cutoff value for all-cause mortality. RESULTS: A Dlco cutoff value of <60% predicted was associated with all-cause mortality (Dlco ≥ 60%: 9% vs Dlco < 60%: 23%, P = .01). At a same FEV1% predicted and Charlson score, patients with Dlco < 60% had lower BMI, more dyspnea, lower inspiratory capacity (IC)/total lung capacity (TLC) ratio, lower 6-min walk distance (6MWD), and higher BODE. Cox multiple regression analysis confirmed that after adjusting for age, sex, pack-years history, smoking status, and BMI, a Dlco < 60% is associated with all-cause mortality (hazard ratio [HR], 95% CI = 3.37, 1.35-8.39; P = .009) INTERPRETATION: In GOLD I COPD patients, a Dlco < 60% predicted is associated with increased risk of death and worse clinical presentation. What the cause(s) of this association are and whether they can be treated need to be determined.

The joint use of 99mTc-MAA-SPECT/CT and cone-beam CT optimizes radioembolization planning.

PURPOSE: To determine which imaging method used during radioembolization (RE) work-up: contrast-enhanced computed tomography (CECT), 99mTc-MAA-SPECT/CT or cone beam-CT (CBCT), more accurately predicts the final target volume (TgV) as well as the influence that each modality has in the dosimetric calculation. METHODS: TgVs from 99mTc-MAA-SPECT/CT, CECT and CBCT were consecutively obtained in 24 patients treated with RE and compared with 90Y PET/CT TgV. Using the TgVs estimated by each imaging modality and a fictitious activity of 1 GBq, the corresponding absorbed doses by tumor and non-tumoral parenchyma were calculated for each patient. The absorbed doses for each modality were compared with the ones obtained using 90Y PET/CT TgV. RESULTS: 99mTc-MAA-SPECT/CT predicted 90Y PET/CT TgV better than CBCT or CECT, even for selective or superselective administrations. Likewise, 99mTc-MAA-SPECT/CT showed dosimetric values more similar to those obtained with 90Y PET/CT. Nevertheless, CBCT provided essential information for RE planning, such as ensuring the total coverage of the tumor and, in cases with more than one feeding artery, splitting the activity according to the volume of tumor perfused by each artery. CONCLUSION: The joint use of 99mTc-MAA-SPECT/CT and CBCT optimizes dosimetric planning for RE procedures, enabling a more accurate personalized approach.

Long-Term Prognostic Value of Coronary CTA in Orthotopic Heart Transplant Recipients.

OBJECTIVE. This study aimed to evaluate the long-term prognostic value of coronary CTA (CCTA) in heart transplant recipients. MATERIALS AND METHODS. The records of 114 patients who had undergone a heart transplant (mean age, 61.7 ± 11.1 [SD] years; 83.3% men) and who underwent CCTA for the surveillance of coronary allograft vasculopathy (CAV) from June 2007 to December 2017 were retrospectively evaluated for the occurrence of major adverse cardiovascular events (MACEs) (cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, coronary revascularization, cardiac arrhythmias, stroke, and retransplant). Patients were classified according to the presence of nonobstructive CAV (lumen reduction < 50%) or obstructive disease (lumen reduction ≥ 50%) and using a coronary segment involvement score (SIS). Differences in MACE rate between groups were compared. RESULTS. Obstructive CAV was observed in 12 heart transplant recipients (10.5%). During a mean follow-up of 67.5 ± 41.4 months the overall rates of MACE were 50% and 14.7% in patients with obstructive and nonobstructive CAV, respectively (p < .05), resulting in an odds ratio for MACE of 6 (95% CI, 1.7-21.2). Comparison of event-free survival showed a hazard ratio (HR) of 5 (95% CI, 1.95-13; p =. 004) for patients with obstructive disease. The presence of four or more stenotic coronary segments (SIS ≥ 4) was associated with a higher rate of events (HR, 3.46; 95% CI, 1.46-8.23). CONCLUSION. In patients who have undergone a heart transplant, CCTA offers a significant long-term prognostic impact on the prediction of MACEs.

A proof-of-concept study of the in-vivo validation of a computational fluid dynamics model of personalized radioembolization.

Radioembolization (RE) with yttrium-90 (90Y) microspheres, a transcatheter intraarterial therapy for patients with liver cancer, can be modeled computationally. The purpose of this work was to correlate the results obtained with this methodology using in vivo data, so that this computational tool could be used for the optimization of the RE procedure. The hepatic artery three-dimensional (3D) hemodynamics and microsphere distribution during RE were modeled for six 90Y-loaded microsphere infusions in three patients with hepatocellular carcinoma using a commercially available computational fluid dynamics (CFD) software package. The model was built based on in vivo data acquired during the pretreatment stage. The results of the simulations were compared with the in vivo distribution assessed by 90Y PET/CT. Specifically, the microsphere distribution predicted was compared with the actual 90Y activity per liver segment with a commercially available 3D-voxel dosimetry software (PLANET Dose, DOSIsoft). The average difference between the CFD-based and the PET/CT-based activity distribution was 2.36 percentage points for Patient 1, 3.51 percentage points for Patient 2 and 2.02 percentage points for Patient 3. These results suggest that CFD simulations may help to predict 90Y-microsphere distribution after RE and could be used to optimize the RE procedure on a patient-specific basis.

Nocturnal Hypoxemia and CT Determined Pulmonary Artery Enlargement in Smokers.

BACKGROUND: Pulmonary artery enlargement (PAE) detected using chest computed tomography (CT) is associated with poor outcomes in chronic obstructive pulmonary disease (COPD). It is unknown whether nocturnal hypoxemia occurring in smokers, with or without COPD, obstructive sleep apnoea (OSA) or their overlap, may be associated with PAE assessed by chest CT. METHODS: We analysed data from two prospective cohort studies that enrolled 284 smokers in lung cancer screening programs and completing baseline home sleep studies and chest CT scans. Main pulmonary artery diameter (PAD) and the ratio of the PAD to that of the aorta (PA:Ao ratio) were measured. PAE was defined as a PAD ≥ 29 mm in men and ≥27 mm in women or as a PA:Ao ratio > 0.9. We evaluated the association of PAE with baseline characteristics using multivariate logistic models. RESULTS: PAE prevalence was 27% as defined by PAD measurements and 11.6% by the PA:Ao ratio. A body mass index ≥ 30 kg/m2 (OR 2.01; 95%CI 1.06-3.78), lower % predicted of forced expiratory volume in one second (FEV1) (OR 1.03; 95%CI 1.02-1.05) and higher % of sleep time with O2 saturation < 90% (T90) (OR 1.02; 95%CI 1.00-1.03), were associated with PAE as determined by PAD. However, only T90 remained significantly associated with PAE as defined by the PA:Ao ratio (OR 1.02; 95%CI 1.01-1.03). In the subset group without OSA, only T90 remains associated with PAE, whether defined by PAD measurement (OR 1.02; 95%CI 1.01-1.03) or PA:Ao ratio (OR 1.04; 95%CI 1.01-1.07). CONCLUSIONS: In smokers with or without COPD, nocturnal hypoxemia was associated with PAE independently of OSA coexistence.