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.

Implementation of a Longitudinal Critical Care Fellowship Ultrasound Curriculum.

Background: The use of point-of-care ultrasound as a diagnostic and interventional tool is rapidly becoming standard of care in critical care medicine; a standardized training curriculum is needed to ensure provider proficiency. Objective: This study aimed to describe a longitudinal critical care ultrasound (CCUS) curriculum in a pulmonary critical care medicine (PCCM) fellowship training program. It evaluated the curriculum's impact on fellows' knowledge, skills, and self-reported confidence and retention of these attributes. Methods: We conducted a prospective observational study of a longitudinal CCUS training program within a single PCCM fellowship training program. Knowledge, skills, and confidence of 22 fellows were assessed at baseline; after initial training; and at 6, 12, and 18 months in five domains (ultrasound basics, vascular, lung/pleural, abdomen, and cardiac). We quantified changes in CCUS knowledge, confidence, and skills by fellowship class and assessed for longitudinal retention of these three attributes. The difference in scores between new first-year fellows undergoing formal training and second-year fellows with previous informal training was compared at matched time points. Results: After the initial formal training, there was a significant increase in knowledge, skills, and confidence scores, which were maintained or continued to increase up to 18 months. Fellows with 1 year of formal training also had a higher level of knowledge and skills than fellows with 1 year of informal training, although they had similar levels of self-reported confidence in their skills. Conclusion: A formal, longitudinal CCUS curriculum implemented in a PCCM fellowship program improves trainees' knowledge and skills in various ultrasound domains in addition to their confidence in using ultrasound for patient care. A longitudinal curriculum results in retention of all three attributes and appeared to be more effective than an informal training program based on teaching during rounds, but this needs to be replicated in a larger cohort.

Inspiratory Airway Resistance in Respiratory Failure Due to COVID-19.

To measure inspiratory airflow resistance in patients with acute respiratory distress syndrome (ARDS) due to COVID-19. DESIGN: Observational cohort of a convenience sample. SETTING: Three community ICUs. SUBJECTS: Fifty-five mechanically ventilated patients with COVID-19. INTERVENTIONS: Measurements of ventilatory mechanics during volume control ventilation. MEASUREMENTS: Flow-time and pressure-time scalars were used to measure inspiratory airways resistance. RESULTS: The median inspiratory airflow resistance was 12 cm H2O/L/s (interquartile range, 10-16). Inspiratory resistance was not significantly different among patients with asthma or chronic obstructive pulmonary disease compared with those without a history of obstructive airways disease (median 12.5 vs 12 cm H2O/L/s, respectively; p = 0.66). Survival to 90 days among patients with inspiratory resistance above 12 cm H2O/L/s was 68% compared with 60% for patients below 12 cm H2O/L/s (p = 0.58). Inspiratory resistance did not correlate with C-reactive protein, ferritin, Pao2/Fio2 ratio, or static compliance. CONCLUSIONS: Inspiratory airflow resistance was normal to slightly elevated among mechanically ventilated patients with ARDS due to COVID-19. Airways resistance was independent of a history of obstructive airways disease, did not correlate with biomarkers of disease severity, and did not predict mortality.

Cross sectional analysis of the effect of alcohol on pulmonary function in a cohort of men and women living with HIV.

People living with HIV (PLWH) are at increased risk for noncommunicable diseases such as lung disease in part due to opportunistic infections including pneumonia. HIV infection is associated with increased prevalence of impaired lung function and abnormal gas exchange. Alcohol use disorder (AUD) is exceedingly common in PLWH and is associated with higher risk of pneumonia in PLWH. Alcohol use may lead to lung damage through several mechanisms. Data on the long-term effect of AUD on pulmonary function in PLWH are sparse and conflicting. To evaluate this relationship, we conducted a cross-sectional analysis of adult PLWH in care in Louisiana. We hypothesized that chronic alcohol use would be associated with subsequent pulmonary dysfunction in a dose-dependent fashion. All participants performed standardized spirometry on study entry. In total, 350 participants with acceptable spirometry were included in this analysis. Thirty-one percent of participants were female. Women reported less lifetime alcohol use and less smoking; however, they reported more chronic respiratory symptoms. In adjusted models, total lifetime alcohol use was not associated with spirometry measures of pulmonary function. HIV-related variables (CD4 count and viral load) were also not associated with measures of pulmonary function. We then conducted sex-stratified analyses to eliminate residual confounding of sex and similarly found no association of total lifetime alcohol use and pulmonary function. We found no association of AUDIT score or early life alcohol use and pulmonary function. In latent class factor analysis, current heavy alcohol use was associated with lower measures of pulmonary function as compared to former heavy alcohol use. In summary, in this cohort of New Orleanian men and women living with HIV with robust measures of alcohol use, though total lifetime alcohol use and early life alcohol use were not associated with pulmonary function, current heavy alcohol use was associated with impaired pulmonary function.

Critically Ill Adults With Coronavirus Disease 2019 in New Orleans and Care With an Evidence-Based Protocol.

BACKGROUND: Characteristics of critically ill adults with coronavirus disease 2019 (COVID-19) in an academic safety net hospital and the effect of evidence-based practices in these patients are unknown. RESEARCH QUESTION: What are the outcomes of critically ill adults with COVID-19 admitted to a network of hospitals in New Orleans, Louisiana, and what is an evidence-based protocol for care associated with improved outcomes? STUDY DESIGN AND METHODS: In this multi-center, retrospective, observational cohort study of ICUs in four hospitals in New Orleans, Louisiana, we collected data on adults admitted to an ICU and tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between March 9, 2020 and April 14, 2020. The exposure of interest was admission to an ICU that implemented an evidence-based protocol for COVID-19 care. The primary outcome was ventilator-free days. RESULTS: The initial 147 patients admitted to any ICU and tested positive for SARS-CoV-2 constituted the cohort for this study. In the entire network, exposure to an evidence-based protocol was associated with more ventilator-free days (25 days; 0-28) compared with non-protocolized ICUs (0 days; 0-23, P = .005), including in adjusted analyses (P = .02). Twenty patients (37%) admitted to protocolized ICUs died compared with 51 (56%; P = .02) in non-protocolized ICUs. Among 82 patients admitted to the academic safety net hospital's ICUs, the median number of ventilator-free days was 22 (interquartile range, 0-27) and mortality rate was 39%. INTERPRETATION: Care of critically ill COVID-19 patients with an evidence-based protocol is associated with increased time alive and free of invasive mechanical ventilation. In-hospital survival occurred in most critically ill adults with COVID-19 admitted to an academic safety net hospital's ICUs despite a high rate of comorbidities.

Quartz Disrupts Iron Homeostasis in Alveolar Macrophages To Impact a Pro-Inflammatory Effect.

The biological response of bronchial epithelial cells to particles is associated with a sequestration of cell metal by the particle surface and a subsequent disruption in host iron homeostasis. The macrophage is the cell type resident in the respiratory tract that is most likely to make initial contact with inhaled particles. We tested the postulates that (1) silica, a prototypical particle, disrupts iron homeostasis in alveolar macrophages (AMs); and (2) the altered iron homeostasis results in both an oxidative stress and pro-inflammatory effects. Human AMs (1.0 × 106/mL) demonstrated an increased import of iron following particle exposure with nonheme iron concentrations of 0.57 ± 0.03, 1.72 ± 0.09, 0.88 ± 0.09, and 3.21 ± 0.11 ppm in cells exposed for 4 h to media, 500 µM ferric ammonium citrate (FAC), 100 µg/mL silica, and both silica and FAC, respectively. Intracellular ferritin concentrations and iron release were similarly increased after AM exposure to FAC and silica. Silica increased oxidant generation by AMs measured using both dichlorofluorescein diacetate fluorescence and reduction of nitroblue tetrazolium salt. Concentrations of interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor-α in macrophage supernatant increased following 100 µg/mL silica exposure for 24 h. Treatment of AMs with 500 µM FAC decreased both oxidant generation and cytokine release associated with silica exposure, supporting a dependence of these effects on sequestration of cell metal by the particle surface. We conclude that (1) silica exposure disrupts iron homeostasis resulting in increased import, accumulation, and release of the metal; and (2) the altered iron homeostasis following silica exposure impacts oxidant generation and pro-inflammatory effects.

Hilar asymmetry in endobronchial tuberculosis patients: An often-overlooked clue.

BACKGROUND: Endobronchial tuberculosis (EBTB) is a challenging diagnosis because of its varied clinical and radiological manifestations. Hilar asymmetry on chest radiograph (CXR) may be found in patient with EBTB but is often overlooked, which may lead to delayed diagnosis. CASE REPORT: We present five cases with EBTB. Clinicians failed to identify unilateral hilar abnormalities on CXR, and these patients were treated initially for pharyngitis, bronchitis, or pneumonia with no improvement. Subsequently, they visited the pulmonary clinic and bronchoscopy revealed endobronchial lesions and microbial/histopathological evidence of tuberculous infection consistent with EBTB. Anti-tuberculosis therapy resulted in complete clinical resolution in four of the five patients; one patient had persistent bronchial stenosis. CONCLUSION: Hilar asymmetry on CXR may occur with EBTB and may suggest this diagnosis in the appropriate clinical setting. Bronchoscopy has an important role in establishing the final diagnosis.

Using the emergency department to investigate smoking in young adults.

PURPOSE: Smoking in young adults identifies the population at risk for future tobacco-related disease. We investigated smoking in a young adult population and within high-risk groups using emergency department (ED) data in a metropolitan area. METHODS: Using the electronic health record, we performed a retrospective study of smoking in adults aged 18-30 years presenting to the ED. RESULTS: Smoking status was available for 55,777 subjects (90.9% of the total ED cohort); 60.8% were women, 55.0% were black, 35.3% were white, and 8.1% were Hispanic; 34.4% were uninsured. Most smokers used cigarettes (95.1%). Prevalence of current smoking was 21.7% for women and 42.5% for men. The electronic health record contains data about diagnosis and social history that can be used to investigate smoking status for high-risk populations. Smoking prevalence was highest for substance use disorder (58.0%), psychiatric illness (41.3%) and alcohol use (39.1%), and lowest for pregnancy (13.5%). In multivariable analyses, male gender, white race, lack of health insurance, alcohol use, and illicit drug use were independently associated with smoking. Smoking risk among alcohol and drug users varied by gender, race, and/or age. CONCLUSIONS: The ED provides access to a large, demographically diverse population, and supports investigation of smoking risk in young adults.

Low-voltage electricity-induced lung injury.

We report a case of bilateral pulmonary infiltrates and haemoptysis following low-voltage electricity exposure in an agricultural worker. A 58-year-old man standing in water reached for an electric watering machine and sustained an exposure to 220 V circuit for an uncertain duration. The electricity was turned off by another worker, and the patient was asymptomatic for the next 10 h until he developed haemoptysis. A chest radiograph demonstrated bilateral infiltrates, and chest computed tomography (CT) revealed ground-glass opacities with interstitial thickening. Evaluations, including electrocardiogram, serum troponin, N-terminal pro-B-type natriuretic peptide (NT-pro BNP), coagulation studies, and echocardiogram, found no abnormality. The patient was treated for suspected electricity-induced lung injury and bleeding with tranexamic acid and for rhabdomyolysis with volume resuscitation. He recovered with complete resolution of chest radiograph abnormalities by Day 7. This is the first reported case of bilateral lung oedema and/or injury after electricity exposure without cardiac arrest.

Comparative profiling of miRNA expression of lung adenocarcinoma cells in two-dimensional and three-dimensional cultures.

Three-dimensional organotypic culture using reconstituted basement membrane matrix (rBM 3-D) is an invaluable tool to characterize morphogenesis of epithelial cells and to elucidate the tumor-modulating actions of extracellular matrix. microRNAs (miRNA) are a novel class of tumor modulating genes. A substantial amount of investigation of miRNAs in cancer is carried out using monolayer 2-D culture on plastic substratum, which lacks a consideration of the matrix-mediated regulation of miRNAs. In the current study we compared the expression of miRNAs in rBM 3-D and 2-D cultures of two lung adenocarcinoma cell lines. Our findings revealed a profound difference in miRNA profiles between 2-D and rBM 3-D cultures of lung adenocarcinoma cells. The rBM 3-D culture-specific miRNA profile was highlighted with higher expression of the tumor suppressive miRNAs (i.e., miR-200 family) and lower expression of the oncogenic miRNAs (i.e., miR-17-92 cluster and miR-21) than that of 2-D culture. Moreover, the expression pattern of miR-17, miR-21, and miR-200a in rBM 3-D culture correlated with the expression of their targets and acinar morphogenesis, a differentiation behavior of lung epithelial cells in rBM 3-D culture. Over-expression of miR-21 suppressed its target PTEN and disrupted acinar morphogenesis. In summary, we provide the first miRNA profile of lung adenocarcinoma cells in rBM 3-D culture with respect to acinar morphogenesis. These results indicate that rBM 3-D culture is essential to a comprehensive understanding of the miRNA biology in lung epithelial cells pertinent to lung adenocarcinoma.

Pulmonary vasculitis: clinical presentation, differential diagnosis, and management.

This review focuses on vasculitides with prominent pulmonary manifestations and discusses key contributions from the recent literature. Pulmonary vasculitis should be considered when clinical findings include alveolar hemorrhage, nodular and cavitary lung disease, airway stenosis, pulmonary artery aneurysms, or pulmonary artery stenosis. The differential diagnostic considerations for common clinical presentations of vasculitis in the lung are important, and several recent additions are discussed. Treatment for established pulmonary vasculitis is effective and has decreased the morbidity and mortality associated with these diseases while introducing an increased risk of infectious complications. Advances in immunosuppressive therapy have improved treatment of refractory disease and are likely to change initial treatment strategies in the future.

Neutrophil-mediated lung permeability and host defense proteins.

Neutrophil recruitment to the alveolar space is associated with increased epithelial permeability. The present study investigated in mice whether neutrophil recruitment to the lung leads to accumulation of plasma-derived host defense proteins in the alveolar space and whether respiratory burst contributes to this increase in permeability. Albumin, complement C1q, and IgM were increased in bronchoalveolar lavage (BAL) fluid 6 h after intratracheal LPS challenge. Neutrophil depletion before LPS treatment completely prevented this increase in BAL fluid protein concentration. Respiratory burst was not detected in neutrophils isolated from BAL fluid, and BAL proteins were increased in mice deficient in a key subunit of the respiratory burst apparatus, gp91(phox), similar to wild-type mice. Neutrophil recruitment elicited by intratracheal instillation of the chemokines macrophage inflammatory protein-2 and keratinocyte-derived chemokine was also accompanied by accumulation of albumin, C1q, and IgM. During neutrophil recruitment to the alveolar space, epithelial permeability facilitates delivery of host defense proteins. The observed increase in epithelial permeability requires recruitment of neutrophils, but not activation of the respiratory burst, and occurs with chemokine-induced neutrophil migration independent of LPS exposure.

Coagulation in sepsis.

Activation of the coagulation cascade during invasive infection can result in purpura fulminans, with rapid progression of tissue ischemia, or may manifest as abnormal clotting indices alone. Although severe derangements in coagulation are associated with organ dysfunction and increased mortality, the contribution of coagulopathy to the pathophysiology of sepsis remains incompletely understood. Over the past decade, investigators have evaluated several therapeutic anticoagulant strategies in sepsis, and manipulation of the coagulation system has emerged as a key concept in the current management of this disease. Clinical observations during treatment of septic patients with the endogenous anticoagulant activated protein C have stimulated additional study of interactions between endothelial injury, coagulation, and inflammation. This review describes clotting abnormalities during sepsis and discusses the clinical experience with therapeutic strategies intended to oppose excessive coagulation.

Stable transgene expression in tumors and metastases after transduction with lentiviral vectors based on human immunodeficiency virus type 1.

The relatively low efficiency of target cell transduction and variations in the stability of transgene expression by retroviral vectors based on the Moloney murine leukemia virus (MoMLV) are major impediments to the use of such vectors in cancer gene therapy approaches. The present study was designed to investigate the stability and efficiency of transgene expression in human lung and breast cancer cell lines transduced with vectors based on human immunodeficiency virus type 1 (HIV-1) in vitro and in vivo in nude mouse models of metastasis. H460 lung carcinoma cells and MDA-MB-231 breast carcinoma cells were transduced with lentiviral vectors encoding enhanced green fluorescent protein (EGFP) and beta-galactosidase (beta-Gal), respectively. Transduced H460 cells were administered to nude mice by either intravenous or subcutaneous injection and MDA-MB-231 cells were implanted orthotopically into the mammary fat pad of such mice to induce primary tumor and metastatic lung tumor formation. High-level EGFP expression was maintained in transduced H460 cells in metastatic lung nodules for up to 6 weeks and transgene expression in vitro persisted for at least 23 days after retrieval of EGFP-positive H460 cells from the lungs of tumor-bearing mice and subsequent cultivation in vitro. Likewise, beta-Gal expression levels in metastatic MDA-MB-231 cells in lungs remained high for up to 11 weeks. Southern blot analyses carried out with DNA from lung nodules showed that proviral DNAs in H460 cells were maintained stably over many cell generations and during subsequent reimplantation in vivo. However, molecular analyses revealed variations in transgene copy numbers and expression levels among individual lung clones. These results demonstrate the usefulness of HIV-1-based lentiviral vectors for sustained and stable transgene expression in human lung and breast cancer cell lines in vitro and in vivo.

Success of lung transplantation without surveillance bronchoscopy.

BACKGROUND: No current evidence demonstrates improved survival or decreased rate of bronchiolitis obliterans syndrome (BOS) despite regularly scheduled fiberoptic bronchoscopy (FOB) with transbronchial biopsy and bronchoalveolar lavage (TBB/BAL) after lung transplantation. Reduced lung function detected with spirometry or oximetry in symptomatic and asymptomatic lung allograft recipients (LARs) may be a more appropriate indication for bronchoscopic sampling. HYPOTHESIS: Clinically indicated TBB/BAL without routine invasive surveillance sampling of the transplanted lung does not decrease survival or increase the rate of BOS in LARs. METHODS: We reviewed 91 consecutive LARs transplanted at Ochsner Clinic between January 1995 and December 1999. Clinical indications for FOB with TBB/BAL include 10% decline in forced expiratory volume in 1 second below baseline; 20% decrease in forced expiratory flow rate between 25% and 75% of the forced vital capacity; or unexplained respiratory symptoms, signs, or fever. Along with demographic and clinical data, 1-year and 3-year survival rates for these 91 LARs were compared with 5,430 LARs from the International Society for Heart and Lung Transplantation (ISHLT) Registry transplanted during the same 60-month period. Ten of the 91 patients did not survive to hospital discharge after transplantation. We divided the remaining 81 LARs into 2 subsets: Group A patients (n = 43) underwent zero to 1 TBB/BAL and Group B patients (n = 38) required more than 1 procedure. Demographic data, rejection, infection, and incidence of BOS were compared between groups. RESULTS: The 1-year and 3-year survival rates in the Ochsner LAR cohort were 85% and 73%, respectively, vs 72% and 57% in the ISHLT cohort p < 0.01. The relative risks of death in the Ochsner group at 1- and 3-years were 0.56 (0.35-0.91) and 0.66 (0.48-0.92), respectively, p < 0.05. The median (range) follow-up was 910 days (60-1,886) for Group A and 961 days (105-1,883) for Group B, p = not significant. We observed twice as many patients with cystic fibrosis and twice as many pneumonia episodes in Group B. The rate of acute rejection in each group was not statistically different. The cumulative incidence of BOS was increased in Group B at 1 year and at 3 years (5% and 56%) when compared with Group A (3% and 13%), p < 0.01. CONCLUSIONS: Based on the findings from this observational, single-institution study, clinically indicated TBB/BAL without routine surveillance sampling of the lung allograft is unlikely to pose greater risk than does regularly scheduled bronchoscopy after lung transplantation.