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.

A WeChat-based smoking cessation intervention for Chinese smokers: a feasibility study.

WeChat is the largest social media platform in China, yet few WeChat-based smoking cessation interventions have been investigated to date. The objective of this study was to develop and test the feasibility of a WeChat-based smoking cessation intervention for smokers in China. Participants were recruited using WeChat and were then randomized into one of three groups: the Standard Group, the Enhanced Group, and the wait-list Control Group. Feasibility indicators including program reach, recruitment rate, recruitment efficiency, cost per person, attrition rate, intervention message exposure, group discussion utilization rate, intervention message engagement, satisfaction, and the likelihood of recommending to others were measured with assessed. Analyses included Chi-square and Fisher exact test, as well as analysis of variance test. A responsive participant is defined as a participant that responded to a certain assessment. A total of 1,132 individuals connected with ("friended") our project on WeChat between July 1 and August 5, 2019. Of these, 403 were eligible to participate, consented, and completed the baseline assessment. As a result, 136, 135, and 132 smokers were randomly assigned to the Standard Group, the Enhanced Group, and the Control Group, respectively. The total program recruitment rate was 35.6% and the attrition rate was 46.4%. The program cost was $0.85 per person. All responsive participants read at least one message during the intervention and engaged with intervention messages 56.8% of the time. Most responsive participants reported being very or somewhat satisfied, highly or somewhat engaged, and were willing to recommend our program to others. This study demonstrated the feasibility of a smoking cessation interventions using WeChat. The program could be expanded to deliver smoking cessation interventions to a large population of smokers.

A WeChat-based smoking cessation intervention for Chinese smokers: A pilot study.

Background: China is the largest tobacco producer and has the highest number of tobacco consumers in the world. Extensive research has demonstrated the utility of social media for smoking cessation. WeChat is the most commonly used social media platform in China, but has not yet been utilized for smoking cessation interventions. The objectives of this study are (1) to evaluate the efficacy of a WeChat-based smoking cessation intervention; and (2) to examine a possible additive effect of integrating oral health and smoking-related information into a tailored, Transtheoretical Model (TTM) guided smoking cessation intervention. Methods: Eligible adults were recruited through WeChat from July 1 to August 6, 2019, to participate in a 3-arm, single-blinded, randomized controlled trial. We enrolled and randomized 403 participants into three groups: the Standard Group, Enhanced Group, or a Waitlist-Control Group. Participants in the Standard Group received 20 smoking cessation-related messages for 2 weeks; participants in the Enhanced Group received this same protocol plus 6 oral health-related messages over an additional week. Participants in the Control Group received smoking cessation-related messages, after the post-intervention assessment. The primary outcome was TTM Stage of Change, and the secondary outcomes were 7-day Point Prevalence Abstinence (PPA), 24-h PPA, daily cigarette use, and nicotine dependence at 4 weeks follow-up post intervention, comparing intervention groups with the control group. The overall program attrition rate was 46%. Paired t-tests, McNemar tests, and linear and logistic regression were used to examine differences in smoking cessation outcomes within and between groups. Results: Participants in the Enhanced Group (ß = -1.28, 95%CI: -2.13, -0.44) and the Standard Group (ß = -1.13, 95%CI: -1.95, -0.30) reported larger changes in nicotine dependence scores, compared to participants in the Waitlist Group. No statistically significant differences were found between the Enhanced Group and the Standard Group. Discussion: This WeChat-based intervention was effective for smoking cessation overall. The addition of oral health information did not significantly improve the intervention.

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.

Extended Duration Treatment of Tobacco Dependence: A Systematic Review and Meta-Analysis.

Rationale: The American Thoracic Society (ATS) developed a clinical practice guideline on initiating pharmacologic treatment in tobacco-dependent adults. Controller pharmacotherapies treat tobacco dependence effectively when taken as prescribed, but relapse after pharmacologic discontinuation is common. Objectives: To evaluate the effectiveness and safety of initiating controller for an extended (>12 wk) versus a standard duration (6-12 wk) in tobacco-dependent adults. Methods: We systematically searched PubMed, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials from database inception to December 2021 to identify randomized controlled trials comparing extended versus standard duration of controllers for tobacco-dependent adults. We conducted meta-analyses using the Mantel-Haenszel method with random effects model. Outcomes of interest include point-prevalent abstinence at 1-year follow-up or longer, relapse, adverse events, quality of life, and withdrawal symptoms. Subgroup analyses were conducted according to types of treatment and duration of extended therapy when feasible. We assessed the certainty of the estimate following the grading of recommendations, assessment, development and evaluation methodology. Results: We included 13 randomized controlled trials including 8,695 participants that directly compared extended- (>12 wk) versus standard-duration controller therapy with varenicline, bupropion, or nicotine replacement therapy. Compared with standard-duration controller therapy, extended-duration controller therapy probably increased abstinence at 1-year follow-up, measured as 7-day point-prevalence abstinence (relative risk, 1.18; 95% confidence interval [CI], 1.05-1.33; moderate certainty). Extended-duration controller therapy probably reduced relapse compared with standard-duration controller therapy, assessed at 12-18 months after initiation of therapy (hazard ratio, 0.43; 95% CI, 0.29-0.64; moderate certainty). Moderate certainty evidence also suggested that extended-duration controller therapy probably did not increase risk of serious adverse events (relative risk, 1.37; 95% CI, 0.79-2.36). Conclusions: This systematic review supported the recommendation for extended-duration therapy with controllers. Further studies on optimal extended duration are warranted.

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.

Implementation of a WeChat-Based Smoking Cessation Program for Chinese Smokers.

Introduction: Although smoking prevalence has recently declined, the smoking prevalence in China remains high. Extensive research has demonstrated ways that social media can assist in quitting smoking. WeChat is the most commonly used social media platform in China but has not been used for smoking cessation. A process evaluation of a novel WeChat-based smoking cessation intervention was conducted to measure its efficacy of content delivery, participant satisfaction, engagement, and likelihood of recommendation to others. Methods: A three-week, three-arm, single-blind randomized control trial was established. WeChat was used to recruit 403 participants and to deliver intervention messages and process evaluation surveys to them. Recruitment advertisements were posted on an official WeChat account and were forwarded to WeChat Moments. Intervention messages were delivered once a day during weekdays, using the WeChat broadcasting messages function, with two messages being sent each time. Process evaluation surveys were organized using Wenjuanwang and were delivered via WeChat. Process assessments were conducted every Friday to assess intervention message receipt, satisfaction level, engagement level, and recommendation to others. The receipt of intervention messages was measured by a self-reported question indicating which messages were read each week. Satisfaction was measured by a five-item Likert scale survey. Engagement was measured by a one-item Likert scale survey. Recommendation to others was measured by one self-reported question. Results: Participants read an average of 4.76 (out of 10), 5.80 (out of 10), and 4.25 (out of 6) messages at week 1, week 2, and week 3, respectively. The second messages were less likely to be read compared to the first messages (52.3% vs. 61.6%, respectively). Moreover, within each single week, the number of participants who read the intervention messages gradually decreases over time. Picture-based intervention messages tended to be less likely to be read than video-based intervention messages. Total program satisfaction scores ranged between 5 and 25, and the overall scores for satisfaction for each week were 21.55, 22.27, and 22.76, respectively. No significant differences were found in all the satisfaction indicators between groups. More than 60% of participants reported being either highly engaged or somewhat engaged each week. In addition, most participants (93.0% at week 1, 95.8% at week 2, and 96.2% at week 3) reported that they were willing to recommend our program to others. Discussion: A WeChat-based smoking cessation intervention for Chinese smokers was implemented and evaluated. For future studies, one should consider sending messages of a higher importance as the first message of a given day. Smokers had a higher rate of reading intervention messages at the beginning part of each week, during which, relatively important messages should be prioritized. One might also consider alternating the topics and formats of the messages for a better engagement of the users in future studies.

Urban and Rural Disparities in a WeChat-Based Smoking Cessation Intervention among Chinese Smokers.

INTRODUCTION: Tobacco use, which is directly responsible for 10% of total deaths per year globally, remains consistently high, with approximately 20% of the population reporting regular consumption globally. Moreover, health disparities regarding tobacco consumption and smoking cessation are growing between rural and urban populations worldwide. Social media interventions for tobacco cessation may effectively reach both groups. The objective of this study was to evaluate the efficacy of a WeChat-delivered smoking cessation intervention among rural and urban Chinese smokers, and to assess moderating variables that may contribute to differential intervention efficacy. METHODS: WeChat was used to recruit smokers into this intervention study between 1 July and 5 August 2019. Participants were randomized to one of three intervention schedules: participants in the Standard Group and the Enhanced Group received 20 smoking-related messages over 2 weeks, whereas participants in the Enhanced Group received an extra 6 oral health-related messages for one week. Participants in the control group received 20 smoking-related messages after the post-intervention assessment. Participants completed questionnaires at baseline and at 4 weeks follow-up. Our primary outcome was smoking cessation stage of change and secondary outcome was 24-h point prevalence abstinence (PPA). Urban and rural areas were based on self-reported living areas. Chi-squared test, Fisher's exact test, ANOVA test, linear regression, and logistic regression were used for analysis. RESULTS: Overall, 403 participants completed the intervention (233 rural, 107 suburban, 63 urban). Compared to urban participants, rural participants were more likely to have progressed to a later stage of change (ß = 0.40, 95% CI: 0.13, 0.67) and to report higher 24-h PPA rates at follow-up (aOR = 3.23, 95% CI: 1.36, 7.68). After stratification by living area, the intervention effects in stage of change and 24-h PPA rate at follow-up were only found in the urban subgroup. DISCUSSION: Smokers who lived in rural areas reported better smoking cessation outcomes compared with urban smokers; however, the efficacy of a WeChat-based smoking cessation intervention was only found for participants living in an urban area. WeChat based smoking cessation interventions should be used to promote smoking cessation in urban, suburban, and rural areas.

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.

Initiating Pharmacologic Treatment in Tobacco-Dependent Adults. An Official American Thoracic Society Clinical Practice Guideline.

Background: Current tobacco treatment guidelines have established the efficacy of available interventions, but they do not provide detailed guidance for common implementation questions frequently faced in the clinic. An evidence-based guideline was created that addresses several pharmacotherapy-initiation questions that routinely confront treatment teams.Methods: Individuals with diverse expertise related to smoking cessation were empaneled to prioritize questions and outcomes important to clinicians. An evidence-synthesis team conducted systematic reviews, which informed recommendations to answer the questions. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to rate the certainty in the estimated effects and the strength of recommendations.Results: The guideline panel formulated five strong recommendations and two conditional recommendations regarding pharmacotherapy choices. Strong recommendations include using varenicline rather than a nicotine patch, using varenicline rather than bupropion, using varenicline rather than a nicotine patch in adults with a comorbid psychiatric condition, initiating varenicline in adults even if they are unready to quit, and using controller therapy for an extended treatment duration greater than 12 weeks. Conditional recommendations include combining a nicotine patch with varenicline rather than using varenicline alone and using varenicline rather than electronic cigarettes.Conclusions: Seven recommendations are provided, which represent simple practice changes that are likely to increase the effectiveness of tobacco-dependence pharmacotherapy.

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.

Small cell lung cancer: time to diagnosis and treatment.

OBJECTIVES: Small cell lung cancer (SCLC) is the most rapidly progressive form of lung cancer, and delays in treatment may increase the tumor burden. We determined the time from abnormal radiograph to diagnosis and treatment for patients with SCLC and investigated the effect of emergent presentation, stage, radiographic findings, and race on these measures and survival. METHODS: Retrospective analysis of clinical data for 45 consecutive evaluable patients at a single institution diagnosed as having SCLC. RESULTS: Median time from first abnormal radiograph to tissue diagnosis was 10 days and time from first abnormal radiograph to initiation of treatment was 35 days. Emergency department presentation led to earlier diagnosis compared with the clinic (3 vs 21 days), with a trend toward earlier treatment (15 vs 39 days; P = 0.057). No significant effect of radiographic findings, disease stage, or race was observed from time to diagnosis or treatment. Forty-three patients (96%) died, with a median survival time from initial abnormal radiograph to death of 375 days. Survival was longer for patients with limited stage disease (619 vs 230 days), but it was not significantly affected by emergent presentation, radiographic findings, or race. Consistent with the aggressive behavior of SCLC, 10 patients (22%) had a normal radiograph within 6 months prediagnosis, and 7 of these had extensive disease. CONCLUSIONS: The median time from abnormal radiograph to initiation of treatment for SCLC in our single-center study overlapped with the expected doubling time for this malignancy and likely allowed a preventable increase in tumor burden.

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.