Mesenchymal stromal cell therapy for acute respiratory distress syndrome due to coronavirus disease 2019.

BACKGROUND AIMS: The acute respiratory distress syndrome (ARDS) resulting from coronavirus disease 2019 (COVID-19) is associated with a massive release of inflammatory cytokines and high mortality. Mesenchymal stromal cells (MSCs) have anti-inflammatory properties and have shown activity in treating acute lung injury. Here the authors report a case series of 11 patients with COVID-19-associated ARDS (CARDS) requiring mechanical ventilation who were treated with remestemcel-L, an allogeneic MSC product, under individual patient emergency investigational new drug applications. METHODS: Patients were eligible if they were mechanically ventilated for less than 72 h prior to the first infusion. Patients with pre-existing lung disease requiring supplemental oxygen or severe liver or kidney injury were excluded. Each patient received two infusions of remestemcel-L at a dose of 2 million cells/kg per infusion given 48-120 h apart. RESULTS: Remestemcel-L infusions were well tolerated in all 11 patients. At the end of the 28-day follow-up period, 10 (91%, 95% confidence interval [CI], 59-100%) patients were extubated, nine (82%, 95% CI, 48-97%) patients remained liberated from mechanical ventilation and were discharged from the intensive care unit and two (18%, 95 CI%, 2-52%) patients died. The median time to extubation was 10 days. Eight (73%, 95% CI, 34-100%) patients were discharged from the hospital. C-reactive protein levels significantly declined within 5 days of MSC infusion. CONCLUSIONS: The authors demonstrate in this case series that remestemcel-L infusions to treat moderate to severe CARDS were safe and well tolerated and resulted in improved clinical outcomes.

Recent Advances in the Management of Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease is a chronic, irreversible obstructive lung disease that results from exposure to noxious stimuli. Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) usually result from viral or bacterial respiratory infections, but may also result from exposure to environmental pollution. AECOPD are associated with functional decline, increased risk of subsequent exacerbations, and death. Despite the poor prognosis of AECOPD, patients are empowered through self-management programs in their battle against this lethal disease. Morbidity and mortality of chronic obstructive pulmonary disease hospitalizations are reduced by implementing standardized treatment modalities outlined in this article throughout the hospitalization and beyond.

Comparative Effectiveness of Robotic-Assisted Surgery for Resectable Lung Cancer in Older Patients.

BACKGROUND: Robotic-assisted surgery (RAS) is a novel surgical approach increasingly used for patients with non-small cell lung cancer (NSCLC). However, data comparing the effectiveness and costs of RAS vs open thoracotomy and video-assisted thoracoscopic surgery (VATS) for NSCLC are limited. METHODS: Patients > 65 years old with stage I to IIIA NSCLC treated with RAS, VATS, or open thoracotomy were identified from the Surveillance, Epidemiology, and End Results-Medicare database and matched according to age, sex, stage, and extent of resection. Propensity score methods were used to compare adjusted rates of postoperative complications, adequate lymph node staging, survival, and treatment-related costs. RESULTS: In this matched study cohort of 2,766 patients with resected NSCLC, RAS was associated with lower complication rates (OR, 0.57; 95% CI, 0.42-0.79) compared with open thoracotomy, and similar complication rates (OR, 1.02; 95% CI, 0.76-1.37) compared with VATS. Patients undergoing RAS were as likely to have adequate lymph node sampling as those undergoing open thoracotomy (OR, 1.28; 95% CI, 0.94-1.74) or VATS (OR, 0.88; 95% CI, 0.66-1.18). There was no significant difference in overall survival after RAS vs open thoracotomy (hazard ratio, 0.81; 95% CI, 0.63-1.04) or VATS (hazard ratio, 0.91; 95% CI, 0.70-1.18). Costs were similar for RAS ($54,702) vs open thoracotomy ($57,104; P = .08), and higher compared with VATS ($48,729; P = .02). CONCLUSIONS: RAS led to improved operative outcomes compared with open thoracotomy but may not offer an advantage over VATS. The comparative effectiveness of RAS should be further evaluated prior to widespread adoption.

Outcomes of Older Patients with Pulmonary Fibrosis and Non-Small Cell Lung Cancer.

Rationale: Characteristics and outcomes of lung cancer in patients with idiopathic pulmonary fibrosis (IPF) in the United States remain understudied.Objectives: To determine the tumor characteristics and survival of patients with IPF with non-small cell lung cancer (NSCLC) using U.S. population-based data.Methods: We selected Medicare beneficiaries from the Surveillance, Epidemiology, and End Results registry with histologically confirmed NSCLC diagnosed between 2007 and 2011. IPF was identified using two validated claims-based algorithms. We compared tumor characteristics and used logistic and Cox regression to compare rates of stage-appropriate therapy and of overall and lung cancer-specific survival in those with IPF and without IPF.Results: A total of 54,453 patients with NSCLC were included. Those with IPF were more likely to be diagnosed at an earlier stage (P < 0.01) and to have squamous histology (46% vs. 35%; P < 0.01) and lower-lobe tumors (38% vs. 28%; P < 0.01) than those without IPF. Patients with IPF and stages I-II disease had odds of receiving stage-appropriate therapy similar to patients without IPF who had stages I-II disease (odds ratio [OR], 1.13; 95% confidence interval [CI], 0.89-1.43); however, those with advanced disease were less likely to be treated (OR, 0.82; 95% CI, 0.68-0.99). Overall and lung cancer-specific survival were worse in patients with IPF (respectively, hazard ratio [HR], 1.35; 95% CI, 1.26-1.45; and HR, 1.21; 95% CI, 1.10-1.32).Conclusions: NSCLC has a unique presentation in patients with IPF and is associated with poorer prognosis. Further research is needed to identify optimal treatment strategies in this population.

Obesity Trends among Asthma Patients in the United States: A Population-based Study.

BACKGROUND: Obesity is strongly associated with worse asthma control and poorer quality of life. The current obesity epidemic has reached historically high levels, with an estimated prevalence rate of 37% in the general United States (US) population. However, less is known about trends in the prevalence of obesity among individuals with asthma or which sociodemographic groups are at higher risk for increased weight. METHODS: The study was conducted with data from the Behavioral Risk Factor Surveillance System (BRFSS) study, a nationally representative probability-based sample of the US population. We included participants ≥18 years of age who were interviewed between 1999 and 2016. Using stratified weighting, we estimated the annual prevalence of participants with, and without a diagnosis of asthma, classified according to their body mass index (BMI), into: normal weight (18.5-25 kg/m2), overweight (25-30 kg/m2), or obese (>30 kg/m2). We calculated the annual odds of obesity among participants with vs. without asthma to assess if trends among individuals with asthma followed those of the general US population. Nominal regression analysis assessed the association between age, sex, race/ethnicity, and income with prevalence of obesity among participants with asthma. RESULTS: Among the 543,574 BRSFF participants with asthma, the prevalence of overweight and obesity changed from 34.3% and 24.7% in 1999 to 28.8% and 41.1% in 2016, respectively. The odds ratio (OR) of obesity in patients with asthma compared to the general population without asthma, increased during the same period from 1.39 (95% confidence interval [CI]: 1.36-1.36) in 1999 to 1.75 (95% CI: 1.75-1.76) in 2016. Adjusted analysis showed that older (OR: 2.32, 95% CI: 2.32-2.33), Black (OR: 1.61, 95% CI: 1.61-1.61) and Hispanic (OR: 1.29, 95%. CI: 1.28-1.29) participants with asthma had higher rates of obesity. CONCLUSIONS: There has been a substantial increase in the prevalence of obesity among individuals with asthma in the last two decades, beyond what could be explained by general population trends. These results suggest that obesity is an increasing determinant of asthma morbidity and should be particularly targeted in minorities with asthma.

Interstitial Lung Abnormalities and Lung Cancer Risk in the National Lung Screening Trial.

BACKGROUND: Some interstitial lung diseases are associated with lung cancer. However, it is unclear whether asymptomatic interstitial lung abnormalities convey an independent risk. OBJECTIVES: The goal of this study was to assess whether interstitial lung abnormalities are associated with an increased risk of lung cancer. METHODS: Data from all participants in the National Lung Cancer Trial were analyzed, except for subjects with preexisting interstitial lung disease or prevalent lung cancers. The primary analysis included those who underwent low-dose CT imaging; those undergoing chest radiography were included in a confirmatory analysis. Participants with evidence of reticular/reticulonodular opacities, honeycombing, fibrosis, or scarring were classified as having interstitial lung abnormalities. Lung cancer incidence and mortality in participants with and without interstitial lung abnormalities were compared by using Poisson and Cox regression, respectively. RESULTS: Of the 25,041 participants undergoing low-dose CT imaging included in the primary analysis, 20.2% had interstitial lung abnormalities. Participants with interstitial lung abnormalities had a higher incidence of lung cancer (incidence rate ratio, 1.61; 95% CI, 1.30-1.99). Interstitial lung abnormalities were associated with higher lung cancer incidence on adjusted analyses (incidence rate ratio, 1.33; 95% CI, 1.07-1.65). Lung cancer-specific mortality was also greater in participants with interstitial lung abnormalities. Similar findings were obtained in the analysis of participants undergoing chest radiography. CONCLUSIONS: Asymptomatic interstitial lung abnormalities are an independent risk factor for lung cancer that can be incorporated into risk score models.