Association of hypoglossal nerve stimulator response with machine learning identified negative effort dependence patterns.

BACKGROUND: Hypoglossal nerve stimulator (HGNS) is a therapeutic option for moderate to severe obstructive sleep apnea (OSA). Improved patient selection criteria are needed to target those most likely to benefit. We hypothesized that the pattern of negative effort dependence (NED) on inspiratory flow limited waveforms recorded during sleep, which has been correlated with the site of upper airway collapse, would contribute to the prediction of HGNS outcome. We developed a machine learning (ML) algorithm to identify NED patterns in pre-treatment sleep studies. We hypothesized that the predominant NED pattern would differ between HGNS responders and non-responders. METHODS: An ML algorithm to identify NED patterns on the inspiratory portion of the nasal pressure waveform was derived from 5 development set polysomnograms. The algorithm was applied to pre-treatment sleep studies of subjects who underwent HGNS implantation to determine the percentage of each NED pattern. HGNS response was defined by STAR trial criteria for success (apnea-hypopnea index (AHI) reduced by > 50% and < 20/h) as well as by a change in AHI and oxygenation metrics. The predominant NED pattern in HGNS responders and non-responders was determined. Other variables including demographics and oxygenation metrics were also assessed between responders and non-responders. RESULTS: Of 45 subjects, 4 were excluded due to technically inadequate polysomnograms. In the remaining 41 subjects, ML accurately distinguished three NED patterns (minimal, non-discontinuous, and discontinuous). The percentage of NED minimal breaths was significantly greater in responders compared with non-responders (p = 0.01) when the response was defined based on STAR trial criteria, change in AHI, and oxygenation metrics. CONCLUSION: ML can accurately identify NED patterns in pre-treatment sleep studies. There was a statistically significant difference in the predominant NED pattern between HGNS responders and non-responders with a greater NED minimal pattern in responders. Prospective studies incorporating NED patterns into predictive modeling of factors determining HGNS outcomes are needed.

Impact of Timing of Tocilizumab Use in Hospitalized Patients With SARS-CoV-2 Infection.

BACKGROUND: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) continues to be a global challenge due to the lack of definitive treatment strategies. We sought to determine the efficacy of early administration of anti-interleukin 6 therapy in reducing hospital mortality and progression to mechanical ventilation. METHODS: This was a retrospective chart review of 11,512 patients infected with SARS-CoV-2 who were admitted to a New York health system from March to May 2020. Tocilizumab was administered to subjects at the nasal cannula level of oxygen support to maintain an oxygen saturation of >88%. The Charlson comorbidity index was used as an objective assessment of the burden of comorbidities to predict 10-year mortality. The primary outcome of interest was hospital mortality. Secondary outcomes were progression to mechanical ventilation; the prevalence of venous thromboembolism and renal failure; and the change in C-reactive protein, D-dimer, and ferritin levels after tocilizumab administration. Propensity score matching by using a 1:2 protocol was used to match the tocilizumab and non-tocilizumab groups to minimize selection bias. The groups were matched on baseline demographic characteristics, including age, sex, and body mass index; Charlson comorbidity index score; laboratory markers, including ferritin, D-dimer, lactate dehydrogenase, and C-reactive protein values; and the maximum oxygen requirement at the time of tocilizumab administration. Mortality outcomes were evaluated based on the level of oxygen requirement and the day of hospitalization at the time of tocilizumab administration. RESULTS: The overall hospital mortality was significantly reduced in the tocilizumab group when tocilizumab was administered at the nasal cannula level (10.4% vs 22.0%; P = .002). In subjects who received tocilizumab at the nasal cannula level, the progression to mechanical ventilation was reduced versus subjects who were initially on higher levels of oxygen support (6.3% vs 18.7%; P < .001). There was no improvement in mortality when tocilizumab was given at the time of requiring non-rebreather, high-flow nasal cannula, noninvasive ventilator, or invasive ventilator. CONCLUSIONS: Early use of anti-interleukin 6 therapy may be associated with improved hospital mortality and reduction in progression to more severe coronavirus disease 2019.

Usefulness of the HACOR score in predicting success of CPAP in COVID-19-related hypoxemia.

INTRODUCTION: In COVID-19 associated hypoxemic acute respiratory failure (ARF) without mandatory indication for urgent endotracheal intubation, a trial of CPAP may be considered. We aimed to evaluate HACOR (heart rate, acidosis, consciousness, oxygenation, respiratory rate) score performance in these patients as predictor of CPAP failure. METHODS: Prospective observational multicentric study (three centers in different countries), including adult patients with SARS-CoV-2 pneumonia admitted to a respiratory intermediate care unit, presenting PaO2/FiO2 < 300 and PaCO2 < 45 mmHg, who received CPAP. One hour after starting CPAP, HACOR was calculated. RESULTS: We enrolled 128 patients, mean age 61,7 years. Mean HACOR at 1 h after starting CPAP was 3,27 ± 3,84 and mean PaO2/FiO2 was 203,30 ± 92,21 mmHg; 35 patients (27,3 %) presented CPAP failure: 29 underwent oro-tracheal intubation and 6 died due to COVID-19 (all having a do-not-intubate order). HACOR accuracy for predicting CPAP failure was 82,03 %, while PaO2/FiO2 accuracy was 81,25 %. CONCLUSION: Although HACOR score had a good diagnostic performance in predicting CPAP failure in COVID-19-related ARF, PaO2/FiO2 has also shown to be a good predictor of failure.

Central Sleep Apnea.

Central sleep apnea (CSA) is characterized by intermittent repetitive cessation and/or decreased breathing without effort caused by an abnormal ventilatory drive. Although less prevalent than obstructive sleep apnea, it is frequently encountered. CSA can be primary (idiopathic) or secondary in association with Cheyne-Stokes respiration, drug-induced, medical conditions such as chronic renal failure, or high-altitude periodic breathing. Risk factors have been proposed, including gender, age, heart failure, opioid use, stroke, and other chronic medical conditions. This article discusses the prevalence of CSA in the general population and within each of these at-risk populations, and clinical presentation, diagnostic methods, and treatment.

Association Between Inhaled Corticosteroids and Tracheobronchomalacia.

OBJECTIVE: The aim of this study was to assess any association between use of inhaled corticosteroids (ICS) and tracheobronchomalacia (TBM). METHODS: This study was a retrospective analysis of patients with asthma and COPD, with and without TBM. Patients were diagnosed with TBM on the basis of CT imaging, flexible bronchoscopy, or both. Patients were deemed to be on ICS if they had been receiving treatment for at least 3 months. Simple logistic regression models were used to assess the association between TBM status and each proposed factor. A multivariable logistic regression model was used to assess the association between TBM and steroid dose. RESULTS: A total of 463 patients with COPD (n = 153) and asthma (n = 310) were studied. In multivariate analysis, the odds of TBM were 3.5 times higher in patients on high-dose steroids compared with patients not on steroids (OR, 3.5; 95% CI, 1.4-8.5; P = .007). Age (P < .0001), presence of gastroesophageal reflux disease (P < .0001), use of long-acting muscarinic antagonists (P < .0001), and type of pulmonary disease (P = .002) were also associated with TBM. In patients using ICS, the odds of having TBM were 2.9 times greater in patients on high-dose inhaled steroids compared with those on low-dose inhaled steroids (OR, 2.9; 95% CI, 1.2-7.1; P = .02). Age (P = .003), presence of gastroesophageal reflux disease (P = .002), use of long-acting muscarinic antagonists (P = .004), type of ICS (P = .04), and number of months on ICS (P < .0001) were all associated with TBM. CONCLUSIONS: There was a significant association between ICS use in higher doses for a longer duration of time with TBM. Prospective randomized controlled trials are needed to show causality of this observed association.

A 44-Year-Old Man With Dyspnea and a Pulmonary Artery Filling Defect.

CASE PRESENTATION: A 44-year-old man with a history of coronary artery disease, type 2 diabetes mellitus, and OSA reported progressively worsening dyspnea on exertion over a 6-week period. Outpatient CT angiogram revealed a pulmonary artery filling defect. He was sent to the ED where he was started on a heparin drip for unprovoked pulmonary embolism (PE). Echocardiogram revealed normal cardiac function without evidence of right heart strain. Lower extremity ultrasound was negative for DVT. He improved symptomatically, and no risk factors for PE were identified. He was discharged on apixaban. Five weeks later, the patient returned to the ED with hemoptysis. He reported compliance with anticoagulation and improvement of his dyspnea on exertion. History remained negative for recent travel, trauma, surgery, clotting disorders, thromboembolic disease, and alcohol or drug use. He had a 60 pack-year cigarette smoking history and quit 3 months prior.

Pulmonary Arterial Hypertension and Therapeutic Interventions.

Pulmonary hypertension is an uncommon disease that carries a significant morbidity and mortality. Pulmonary arterial hypertension is a subtype of pulmonary hypertension that describes a group of disease entities that lead to an elevation in precapillary pulmonary artery pressure. Despite advances in the diagnosis and treatment of pulmonary arterial hypertension, it remains a difficult disease to recognize and manage. In this review article, we will discuss the definition and diagnosis of pulmonary arterial hypertension. Additionally, we will discuss the ever-expanding management options, their mechanisms and strategies, including combination therapy and the most recent advances and future directions.