Exercise limitation is common in chronic obstructive pulmonary disease (COPD). We determined the impact of pulmonary emphysema on the physiological response to exercise independent of contemporary measures of COPD severity. Smokers 40–79 years old with COPD underwent computed tomography, pulmonary function tesing, and symptom-limited incremental exercise testing. COPD severity was quantified according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) by spirometry (GOLD 1–4); and symptom burden and exacerbation risk (GOLD A-D). Emphysema severity was quantified as the percent lung volume <−950 Hounsfield units. Regression models adjusted for age, gender, body size, smoking status, airflow limitation, symptom burden and exacerbation risk. Among 67 COPD subjects (age 67 ± 8 years; 75% male; GOLD 1–4: 11%, 43%, 30%, 16%), median percent emphysema was 11%, and peak power output (PPO) was 61 ± 32 W. Higher percent emphysema independently predicted lower PPO (−24 W per 10% increment in emphysema; 95%CI −41 to −7 W). Throughout exercise, higher percent emphysema predicted 1) higher minute ventilation, ventilatory equivalent for CO2, and heart rate; and 2) lower oxy-hemoglobin saturation, and end-tidal PCO2. Independent of contemporary measures of COPD severity, the extent of pulmonary emphysema predicts lower exercise capacity, ventilatory inefficiency, impaired gas-exchange and increased heart rate response to exercise.

Background The nirmatrelvir/ritonavir has shown to reduce COVID-19 hospitalization and death before Omicron but updated real-world evidence studies are needed. This study aimed to assess whether nirmatrelvir/ritonavir reduces the risk of COVID-19-associated hospitalization among high-risk outpatients. Methods This was a retrospective cohort study of SARS-CoV-2-infected outpatients between March 15 and October 15, 2022, using data from the Québec clinico-administrative databases. Outpatients treated with nirmatrelvir/ritonavir were compared to infected ones not receiving nirmatrelvir/ritonavir using propensity-score matching. Relative risk of COVID-19-associated hospitalization occurring within 30 days following the index date was assessed using a Poisson regression. Results A total of 8,402 treated outpatients were matched to controls. Regardless of vaccination status, nirmatrelvir/ritonavir treatment was associated with a 69% reduced relative risk of hospitalization (RR: 0.31 [95%CI: 0.28; 0.36], NNT=13). The effect was more pronounced in outpatients with incomplete primary vaccination course (RR: 0.04 [95%CI: 0.03; 0.06], NNT=8), while no benefit was found in those with a complete primary vaccination course (RR: 0.93 [95%CI: 0.78; 1.08]). Subgroups analysis among high-risk outpatients with a primary vaccination course showed that nirmatrelvir/ritonavir treatment was associated with a significant decrease in relative risk of hospitalization in severely immunocompromised outpatients (RR: 0.66 [95%CI: 0.50; 0.89], NNT=16) and in high-risk outpatients aged 70 years and older (RR: 0.50 [95%CI: 0.34; 0.74], NNT=10) when the last dose of the vaccine was received at least six months ago. Conclusions Nirmatrelvir/ritonavir reduces the risk of COVID-19-associated hospitalization among incompletely vaccinated high-risk outpatients and among some subgroups of completely vaccinated high-risk outpatients.

AIMTo evaluate the safety and efficacy of inhaled milrinone in acute respiratory distress syndrome (ARDS).METHODSOpen-label prospective cross-over pilot study where fifteen adult patients with hypoxemic failure meeting standard ARDS criteria and monitored with a pulmonary artery catheter were recruited in an academic 24-bed medico-surgical intensive care unit. Random sequential administration of iNO (20 ppm) or nebulized epoprostenol (10 μg/mL) was done in all patients. Thereafter, inhaled milrinone (1 mg/mL) alone followed by inhaled milrinone in association with inhaled nitric oxide (iNO) was administered. A jet nebulization device synchronized with the mechanical ventilation was use to administrate the epoprostenol and the milrinone. Hemodynamic measurements and partial pressure of arterial oxygen (PaO2) were recorded before and after each inhaled therapy administration.RESULTSThe majority of ARDS were of pulmonary cause (n = 13) and pneumonia (n = 7) was the leading underlying initial disease. Other pulmonary causes of ARDS were: Post cardiopulmonary bypass (n = 2), smoke inhalation injury (n = 1), thoracic trauma and pulmonary contusions (n = 2) and aspiration (n = 1). Two patients had an extra pulmonary cause of ARDS: A polytrauma patient and an intra-abdominal abscess Inhaled nitric oxide, epoprostenol, inhaled milrinone and the combination of inhaled milrinone and iNO had no impact on systemic hemodynamics. No significant adverse events related to study medications were observed. The median increase of PaO2 from baseline was 8.8 mmHg [interquartile range (IQR) = 16.3], 6.0 mmHg (IQR = 18.4), 6 mmHg (IQR = 15.8) and 9.2 mmHg (IQR = 20.2) respectively with iNO, epoprostenol, inhaled milrinone, and iNO added to milrinone. Only iNO and the combination of inhaled milrinone and iNO had a statistically significant effect on PaO2.CONCLUSIONWhen comparing the effects of inhaled NO, milrinone and epoprostenol, only NO significantly improved oxygenation. Inhaled milrinone appeared safe but failed to improve oxygenation in ARDS.