The rationale, design, and methods of a trial to evaluate the efficacy and safety of oxygen therapy in patients with intermediate-risk acute pulmonary embolism.

BACKGROUND: In patients with intermediate-risk pulmonary embolism (PE), reversal of hypoxic vasoconstriction could constitute a target for treatment that protects the right ventricular (RV) function until endogenous fibrinolysis occurs. The Air vs oxygen for Intermediate-Risk pulmonary embolism (AIR) trial aims to assess the effect of oxygen therapy in patients with intermediate-risk acute PE who do not have hypoxemia at baseline. METHODS AND ANALYSES: AIR is a prospective, multicenter, randomized, open-label, parallel-group, proof-of-concept trial. A total of 90 patients hospitalized with intermediate-risk PE and an oxygen saturation of 90% or higher at baseline will be randomized in a 1:1 fashion to receive supplemental oxygen or ambient air. The primary outcome is a RV/LV diameter ratio equal or less than 1.0 on echocardiography measured 48 hours after the start of treatment. Secondary efficacy outcomes are the numerical change in the ratio of the RV to the LV diameter measured 48 hours and 7 days after the start of treatment, with respect to the baseline ratio measured at randomization. Clinical adverse events will be also collected. RESULTS: Enrollment started in July 2019 and is expected to proceed until 2022. Median age of the first 50 patients was 74 years (interquartile range, 61-81), and 50% were female. CONCLUSIONS: This multicenter trial will provide information about the value of supplemental oxygen in patients with intermediate-risk acute PE who do not have hypoxemia at baseline. The results will contribute to research that may assist patients with intermediate-risk PE in the future.

Predictive factors over time of health-related quality of life in COPD patients.

BACKGROUND: Health-related quality of life (HRQoL) should be seen as a tool that provides an overall view of the general clinical condition of a COPD patient. The aims of this study were to identify variables associated with HRQoL and whether they continue to have an influence in the medium term, during follow-up. METHODS: Overall, 543 patients with COPD were included in this prospective observational longitudinal study. At all four visits during a 5-year follow-up, the patients completed the Saint George's Respiratory Questionnaire (SGRQ), pulmonary function tests, the 6-min walk test (6MWT), and a physical activity (PA) questionnaire, among others measurements. Data on hospitalization for COPD exacerbations and comorbidities were retrieved from the personal electronic clinical record of each patient at every visit. RESULTS: The best fit to the data of the cohort was obtained with a beta-binomial distribution. The following variables were related over time to SGRQ components: age, inhaled medication, smoking habit, forced expiratory volume in one second, handgrip strength, 6MWT distance, body mass index, residual volume, diffusing capacity of the lung for carbon monoxide, PA (depending on level, 13 to 35% better HRQoL, in activity and impacts components), and hospitalizations (5 to 45% poorer HRQoL, depending on the component). CONCLUSIONS: Among COPD patients, HRQoL was associated with the same variables throughout the study period (5-year follow-up), and the variables with the strongest influence were PA and hospitalizations.

Influence of physical activity on the prognosis of COPD patients: the HADO.2 score - health, activity, dyspnoea and obstruction.

Objective: The aim of this study was to create a prognostic instrument for COPD with a multidimensional perspective that includes physical activity (PA). The score also included health status, dyspnoea and forced expiratory volume in 1 s (HADO.2 score). Methods: A prospective, observational, non-intervention study was carried out. Patients were recruited from the six outpatient clinics of the respiratory service of a single university hospital. The component variables of the HADO.2 score and BODE index were studied, and PA was measured using an accelerometer. The outcomes for the HADO.2 score were mortality and hospitalisations during follow-up and an exploration of the correlation with health-related quality of life at the moment of inclusion in the study. Results: 401 patients were included in the study and followed up for three years. The HADO.2 score showed good predictive capacity for mortality: C-index 0.79 (0.72-0.85). The C-index for hospitalisations was 0.72 (0.66-0.77) and the predictive ability for quality of life, as measured by R2, was 0.63 and 0.53 respectively for the Saint George's Respiratory Questionnaire and COPD Assessment Test. Conclusions: There was no statistically significant difference between the mortality predictive capacity of the HADO.2 score and the BODE index. Adding PA to the original BODE index significantly improved the predictive capacity of the index. The HADO.2 score, which includes PA as a key variable, showed good predictive capacity for mortality and hospitalisations. There were no differences in the predictive capacity of the HADO.2 score and the BODE index.

Oxygen Therapy in Patients With Intermediate-Risk Acute Pulmonary Embolism: A Randomized Trial.

BACKGROUND: The effect of supplemental oxygen therapy in patients with intermediate-risk pulmonary embolism (PE) who do not have hypoxemia at baseline is uncertain. RESEARCH QUESTION: Does supplemental oxygen improve echocardiographic parameters in nonhypoxemic patients with intermediate-risk PE? STUDY DESIGN AND METHODS: This pilot trial randomly assigned nonhypoxemic patients with stable PE and echocardiographic right ventricle (RV) enlargement to receive anticoagulation plus supplemental oxygen for the first 48 h vs anticoagulation alone. The primary outcome was normal echocardiographic RV size 48 h after randomization. Secondary efficacy outcomes were the numerical change in the RV to left ventricle (LV) diameter ratio measured 48 h and 7 days after randomization with respect to the baseline ratio measured at inclusion. RESULTS: The study was stopped prematurely because of the COVID-19 pandemic after recruiting 70 patients (mean ± SD age, 67.3 ± 16.1 years; 36 female [51.4%]) with primary outcome data. Forty-eight h after randomization, normalization of the RV size occurred in 14 of the 33 patients (42.4%) assigned to oxygen and in eight of the 37 patients (21.6%) assigned to ambient air (P = .08). In the oxygen group, the mean RV to LV ratio was reduced from 1.28 ± 0.28 at baseline to 1.01 ± 0.16 at 48 h (P < .001); in the ambient air group, mean RV to LV ratios were 1.21 ± 0.18 at baseline and 1.08 ± 0.19 at 48 h (P < .01). At 90 days, one major bleeding event and one death (both in the ambient air group) had occurred. INTERPRETATION: In analyses limited by a small number of enrollees, compared with ambient air, supplemental oxygen did not significantly increase the proportion of patients with nonhypoxemic intermediate-risk PE whose RV to LV ratio normalized after 48 h of treatment. This pilot trial showed improvement in some ancillary efficacy outcomes and provides support for a definitive clinical outcomes trial. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04003116; URL: www. CLINICALTRIALS: gov.

Change in physical activity related to admission for exacerbation in COPD patients.

INTRODUCTION: The aim of this study was to determine the impact of hospitalizations on levels of physical activity (PA) and whether other factors were associated with subsequent changes in PA. METHODS: Prospective observational cohort study with a nested case-control study, with follow-up 60 days from the index hospital admission. Nine hospitals participated in the study. Patients were recruited consecutively. Several variables and questionnaires of the clinical baseline status of the patients were recorded including: the COPD Assessment Test (CAT), the Hospital Anxiety-Depression scale (HADS), comorbidities and the Yale Physical Activity Survey. Patients' data related to admission and up to two months after discharge were also recorded. RESULTS: 883 patients were studied: 79.7% male; FEV1 48%; Charlson index 2; 28.7% active smokers. The baseline PA level for the total sample was 23 points. A statistically significant difference in PA was found between patients readmitted up to 2 months after the index admission and those not readmitted (17vs. 27, p < 0.0001). Multivariable linear regression analysis identified the following as predictors of the decrease of PA from baseline (index admission) up to 2 months follow-up: admission for COPD exacerbation in the two months prior to the index admission; readmission up to 2 months after the index admission; baseline HAD depressive symptoms, worse CAT score, and patient-reported "need for help". CONCLUSIONS: In a cohort of admitted COPD patients, we identified a strong relationship between hospitalization for exacerbation and PA. In addition, some other potentially modifiable factors were found associated with the change in PA level after an admission.

Physical activity and sedentary behaviour in patients admitted with COPD: Associated factors.

AIM: To establish amongst a cohort of patients admitted with Chronic Obstructive Pulmonary Disease which factors were associated with their level of Physical Activity and Sedentary Behavior prior to the admission event. METHODS: Prospective observational cohort study. Nine Spanish hospitals participated. Patients were recruited consecutively. Variables relating to the patients' clinical baseline status were recorded, including the COPD Assessment test, the HADS anxiety-depression test, comorbidities and the Yale Physical Activity Survey. Data relating to admission and up to two months after discharge were also recorded. RESULTS: 1638 COPD patients were studied, with a mean age of 72.39 (SD 10.33), 76.56 % male, FEV1 49.41 % (SD19.19), Charlson index 2. The level of PA at baseline was 30.79 points (SD 22.43). Multivariable linear regression analysis identified the following as being associated with low PA: older age, obesity, higher level of hemoglobin, lower score of Barthel index, which means disability, health related quality of life (EuroQoL-5d and CAT) and dyspnea. Variables associated with sedentary behavior were: older age, presence of obstructive apnea syndrome, higher disability, presence of depressive symptoms and dyspnea. CONCLUSIONS: In a cohort of hospitalized COPD patients, we have found several variables, some of them modifiable, associated with physical activity/inactivity and sedentary behavior.

Changes in health-related quality of life as a marker in the prognosis in COPD patients.

Chronic obstructive pulmonary disease (COPD) is understood as a complex, heterogeneous and multisystem airway obstructive disease. The association of deterioration in health-related quality of life (HRQoL) with mortality and hospitalisation for COPD exacerbation has been explored in general terms. The specific objectives of this study were to determine whether a change in HRQoL is related, over time, to mortality and hospitalisation. Overall, 543 patients were recruited through Galdakao Hospital's five outpatient respiratory clinics. Patients were assessed at baseline, and the end of the first and second year, and were followed up for 3 years. At each assessment, measurements were made of several variables, including HRQoL using the St George's Respiratory Questionnaire (SGRQ). The cohort had moderate obstruction (forced expiratory volume in 1 s 55% of the predicted value). SGRQ total, symptoms, activity and impact scores at baseline were 39.2, 44.5, 48.7 and 32.0, respectively. Every 4-point increase in the SGRQ was associated with an increase in the likelihood of death: "symptoms" domain odds ratio 1.04 (95% CI 1.00-1.08); "activity" domain OR 1.12 (95% CI 1.08-1.17) and "impacts" domain OR 1.11 (95% CI 1.06-1.15). The rate of hospitalisations per year was 5% (95% CI 3-8%) to 7% (95% CI 5-10%) higher for each 4-point increase in the separate domains of the SGRQ. Deterioration in HRQoL by 4 points in SGRQ domain scores over 1 year was associated with an increased likelihood of death and hospitalisation.