Sildenafil Versus Placebo for Early Pulmonary Vascular Disease in Scleroderma (SEPVADIS): protocol for a randomized controlled trial.

BACKGROUND: Pulmonary hypertension (PH) is a leading cause of death in patients with systemic sclerosis (SSc). An important component of SSc patient management is early detection and treatment of PH. Recently the threshold for the diagnosis of PH has been lowered to a mean pulmonary artery pressure (mPAP) threshold of > 20 mmHg on right heart catheterization (RHC). However, it is unknown if PH-specific therapy is beneficial in SSc patients with mildly elevated pressure (SSc-MEP, mPAP 21-24 mmHg). METHODS: The SEPVADIS trial is a randomized, double-blind, placebo-controlled phase 2 trial of sildenafil in SSc-MEP patients with a target enrollment of 30 patients from two academic sites in the United States. The primary outcome is change in six-minute walk distance after 16 weeks of treatment. Secondary endpoints include change in pulmonary arterial compliance by RHC and right ventricular function by cardiac magnetic resonance imaging at 16 weeks. Echocardiography, serum N-terminal probrain natriuretic peptide, and health-related quality of life is being measured at 16 and 52 weeks. DISCUSSION: The SEPVADIS trial will be the first randomized study of sildenafil in SSc-MEP patients. The results of this trial will be used to inform a phase 3 study to investigate the efficacy of treating patients with mild elevations in mPAP. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04797286.

Discordance Between Invasive and NonInvasive Oxygen Saturation in Critically Ill COVID-19 Patients.

OBJECTIVES: To investigate discordance in oxy-hemoglobin saturation measured both by pulse oximetry (SpO2) and arterial blood gas (ABG, SaO2) among critically ill coronavirus disease 2019 (COVID-19(+)) patients compared to COVID-19(-) patients. METHODS: Paired SpO2 and SaO2 readings were collected retrospectively from consecutive adult admissions to four critical care units in the United States between March and May 2020. The primary outcome was the rate of discordance (|SaO2-SpO2|>4%) in COVID-19(+) versus COVID-19(-) patients. The odds each cohort could have been incorrectly categorized as having a PaO2/FiO2 above or below 150 by their SpO2: Fractional inhaled oxygen ratio (pulse oximetry-derived oxyhemoglobin saturation:fraction of inspired oxygen ratio [SF]) was examined. A multivariate regression analysis assessed confounding by clinical differences between cohorts including pH, body temperature, renal replacement therapy at time of blood draw, and self-identified race. RESULTS: There were 263 patients (173 COVID-19(+)) included. The rate of saturation discordance between SaO2 and SpO2 in COVID-19(+) patients was higher than in COVID-19(-) patients (27.9% vs 16.7%, odds ratio [OR] 1.94, 95% confidence interval [CI]: 1.11 to 2.27). The average difference between SaO2 and SpO2 for COVID-19(+) patients was -1.24% (limits of agreement, -13.6 to 11.1) versus -0.11 [-10.3 to 10.1] for COVID-19(-) patients. COVID-19(+) patients had higher odds (OR: 2.61, 95% CI: 1.14-5.98) of having an SF that misclassified that patient as having a PaO2:FiO2 ratio above or below 150. There was not an association between discordance and the confounders of pH, body temperature, or renal replacement therapy at time of blood draw. After controlling for self-identified race, the association between COVID-19 status and discordance was lost. CONCLUSIONS: Pulse oximetry was discordant with ABG more often in critically ill COVID-19(+) than COVID-19(-) patients. However, these findings appear to be driven by racial differences between cohorts.

Pulmonary artery compliance in different forms of pulmonary hypertension.

OBJECTIVE: Pulmonary artery compliance (PAC), estimated as stroke volume (SV) divided by pulmonary artery pulse pressure (PP), may be a predictor of survival in pulmonary arterial hypertension (PAH). Resistance-compliance (RC) time, the product of PAC and pulmonary vascular resistance, is reported to be a physiological constant. We investigated if differences in PAC and RC time exist between pulmonary hypertension (PH) subgroups and examined whether PAC is an independent predictor of transplant-free survival in PAH. METHODS: This was a retrospective analysis of adult PAH (n=532) and chronic thromboembolic PH (CTEPH, n=84) patients enrolled in the US Pulmonary Hypertension Association Registry from 2015 to 2019. PAC and RC time were compared between PH subgroups (connective tissue disease-PAH (CTD-PAH), idiopathic/heritable-PAH (i/h-PAH), drug/toxin-PAH (d/t-PAH)). Cox proportional hazards models were constructed for transplant-free survival, adjusting for REVEAL 2.0 risk score. RESULTS: There were no differences in estimated PAC between PAH subgroups, nor between PAH and CTEPH. RC time was shorter in CTEPH compared with PAH (median 0.55 (IQR 0.45-0.64) vs 0.62 (0.52-0.73) s, p<0.0001). RC time was shortest in CTD-PAH when compared with i/h-PAH and d/t-PAH ((0.59±0.18) vs (0.65±0.20) vs (0.73±0.25) s, p=0.0001). PAC was associated with transplant-free survival (HR 0.72, 95% CI 0.55 to 0.94, p=0.02) but was not an independent predictor of outcome after adjustment for REVEAL 2.0 score. CONCLUSION: PAC was similar between PH groups and was not an independent predictor of transplant-free survival in PAH. RC time was different between PH subgroups, challenging RC time constancy. TRIAL REGISTRATION NUMBER: NCT04071327.

ATS Core Curriculum 2020. Adult Pulmonary Medicine.

The American Thoracic Society Core Curriculum updates clinicians annually in adult and pediatric pulmonary disease, medical critical care, and sleep medicine in a 3- to 4-year recurring cycle of topics. The topics of the 2020 Pulmonary Core Curriculum include pulmonary vascular disease (submassive pulmonary embolism, chronic thromboembolic pulmonary hypertension, and pulmonary hypertension) and pulmonary infections (community-acquired pneumonia, pulmonary nontuberculous mycobacteria, opportunistic infections in immunocompromised hosts, and coronavirus disease [COVID-19]).

Omalizumab versus Mepolizumab as add-on therapy in asthma patients not well controlled on at least an inhaled corticosteroid: A network meta-analysis.

OBJECTIVE: The purpose of this study is to examine the comparative efficacy of Omalizumab (OMA) and Mepolizumab (Mepo) in the treatment of severe asthma by performing a network meta-analysis. METHOD: Data Sources: A systematic review of the literature was performed through four databases from their inception to February 2016. STUDY SELECTIONS: Randomized control trials and cohort studies were considered if they addressed the individual efficacy of OMA and Mepo in the treatment of asthma that was not well controlled on inhaled corticosteroids (ICSs) with or without other agents. RESULTS: OMA was significantly better than Mepo in improving the Asthma Quality of Life Questionnaire with a mean difference of 0.38 and a confidence interval of (0.21-0.55), p < 0.0001, without reaching the minimal clinically important difference of 0.5. No significant difference was seen in Asthma Control Questionnaire, forced expiratory volume in second 1 (FEV1), and Peak Expiratory Flow Rate (PEFR) improvement from baseline. Both medications were successful in reducing the calculated annualized rates of asthma exacerbations (AEs) vs placebo by approximately 50%. The heterogeneity score for the different comparisons were elevated except for the PEFR. CONCLUSION: When compared indirectly via a network meta-analysis, the efficacy of OMA and Mepo was similar in the treatment of asthma that was not well controlled on at least high-dose ICS. The high heterogeneity observed and the different selection criteria for the use of the two drugs do not permit us to make any definitive recommendations for the preferential use of OMA vs Mepo in the patient populations studied. However, the current data do not suggest any major differences in efficacy.

Improving OSA screening and diagnosis in patients with hypertension in an academic safety net primary care clinic: quality improvement project.

Obstructive sleep apnoea (OSA) is more prevalent in patients with hypertension (HTN), and associated morbidities include stroke, heart failure and premature death. In the Internal Medicine Clinic (IMC), over 70% of the patients had a diagnosis of HTN and obesity. We identified a lack of OSA screening in patients with HTN. The aim of this quality improvement (QI) was to increase OSA diagnosis to 5% from the baseline rate of less than 1% in patients with HTN between the ages of 18 and 75 years over 6 months at IMC. We used the Plan-Do-Study-Act (PDSA) method. The QI team performed root cause analysis to identify materials/methods, provider and patient-related barriers. PDSA cycle included: (1) integration of customised workflow of loud Snoring, Tiredness, Observed apnea, high blood Pressure (STOP)-Body mass index (BMI), Age, Neck circumference, and Gender (BANG) OSA screening tool in the electronic health record (EHR); (2) physician education of OSA and EHR workflow; and (3) completion of STOP survey by patients, which was facilitated by nursing staff. The outcome measure was the percentage of OSA diagnosis in patients with HTN. The process measures included the percentage of patients with HTN screened for OSA and the increase in sleep study referrals in hypertensive patients with STOP-BANG score of ≥3. Increase in patient wait time and cost of sleep study were the balance measures. Data analysis was performed using weekly statistical process control chart. The average increase in OSA screening rate using the STOP-BANG tool was 3.88%. The significant variation seen in relation to PDSA cycles was not sustainable. 32% of patients scored ≥3 on the STOP-BANG tool, and 10.4% had a confirmed diagnosis of OSA. STOP-BANG tool integration in the EHR and a team approach did not result in a sustainable increase in OSA screening. OSA diagnosis was increased to 3.3% in IMC patient population within the 6-month period. The team identified multiple barriers to screening and diagnosis of OSA in the IMC.

Endobronchial Ultrasound Bronchoscope Damage.

Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration is an effective, safe, and cost-effective diagnostic bronchoscopy technique for the work-up of mediastinal lymphadenopathy. Concern has been raised, however, about the high cost of convex-probe EBUS bronchoscope repairs. The damage is usually due to breakage of the insertion tube (the flexible part that is advanced into the airways), moisture invasion and damages to the working channel, image guide bundle, or umbilical cord. Understanding the root cause of EBUS scope damage is important for its prevention. We describe 2 unusual cases of EBUS scope damage. In the first case, the distal black rubber covering of the EBUS scope insertion tube was damaged due to friction with the edge of an endotracheal tube and in the second case, the EBUS scope insertion tube was angulating laterally instead of vertically during the flexion maneuver, probably due to scope manipulation while wedged tightly in a segmental bronchus.