Gestational Exposure to Sidestream (Secondhand) Cigarette Smoke Promotes Transgenerational Epigenetic Transmission of Exacerbated Allergic Asthma and Bronchopulmonary Dysplasia.

Embryonic development is highly sensitive to xenobiotic toxicity and in utero exposure to environmental toxins affects physiological responses of the progeny. In the United States, the prevalence of allergic asthma (AA) is inexplicably rising and in utero exposure to cigarette smoke increases the risk of AA and bronchopulmonary dysplasia (BPD) in children and animal models. We reported that gestational exposure to sidestream cigarette smoke (SS), or secondhand smoke, promoted nicotinic acetylcholine receptor-dependent exacerbation of AA and BPD in mice. Recently, perinatal nicotine injections in rats were reported to induce peroxisome proliferator-activated receptor γ-dependent transgenerational transmission of asthma. Herein, we show that first generation and second generation progeny from gestationally SS-exposed mice exhibit exacerbated AA and BPD that is not dependent on the decrease in peroxisome proliferator-activated receptor γ levels. Lungs from these mice show strong eosinophilic infiltration, excessive Th2 polarization, marked airway hyperresponsiveness, alveolar simplification, decreased lung compliance, and decreased lung angiogenesis. At the molecular level, these changes are associated with increased RUNX3 expression, alveolar cell apoptosis, and the antiangiogenic factor GAX, and decreased expression of HIF-1α and proangiogenic factors NF-κB and VEGFR2 in the 7-d first generation and second generation lungs. Moreover, the lungs from these mice exhibit lower levels of microRNA (miR)-130a and increased levels of miR-16 and miR-221. These miRs regulate HIF-1α-regulated apoptotic, angiogenic, and immune pathways. Thus the intergenerational effects of gestational SS involve epigenetic regulation of HIF-1α through specific miRs contributing to increased incidence of AA and BPD in the progenies.

A novel cytokine profile associated with cancer metastasis to mediastinal and hilar lymph nodes identified using fine needle aspiration biopsy - A pilot study.

Cancer metastasis to the lymph nodes is indicative of a poor prognosis. An endobronchial ultrasound-guided fine needle aspiration (EBUS-FNA) biopsy is increasingly being used to sample paratracheal lymph nodes for simultaneous cancer diagnosis and staging. In this prospective, single-center study, we collected dedicated EBUS-FNA biopsies from 27 patients with enlarged paratracheal and hilar lymph nodes. Cytokines were assayed using Bio-Plex Pro human cancer biomarker panels (34 cytokines), in a Bio-Rad 200 suspension array system. A mean cytokine value was taken from each subject with more than 1 lymph node station EBUS-FNA biopsies. Malignant and benign histologic diagnoses were established in 16 and 12 patients, respectively. An initial analysis using the Kruskal-Wallis test with Sidak correction for multiple comparisons, showed significant elevation of sVEGFR-1, IL-6, VEGF-A, Angiopoeintin-2, uPA, sHER-2/neu and PLGF in malignant lymph node samples compared to benign samples. The univariate logistic regression analyses revealed that 6 cytokines were significant predictors and 1 cytokine (PLGF) was marginally significant for discrimination between benign and malignant samples. The prediction power of these cytokines as biomarkers were very high according to the area under the ROC curve. Multiple logistic regression for subsets of the seven cytokine combined; provided an almost complete discrimination between benign and malignant samples (AUC=0.989). For screening and diagnostic purposes, we presented the optimal discrimination cut-off for each cytokine: sVEGFR-1 (2124.5pg/mL), IL-6 (40.2pg/mL), VEGF-A (1060.1pg/mL), Angiopoeintin-2 (913.7pg/mL), uPA (248.1pg/mL), sHER-2/neu (5010pg/mL) and PLGF (93.4pg/mL). For the very first time, a novel cytokine profile associated with cancer metastasis to the paratracheal lymph nodes were reported.

Patient Perspectives on Low-Dose Computed Tomography for Lung Cancer Screening, New Mexico, 2014.

INTRODUCTION: National guidelines call for annual lung cancer screening for high-risk smokers using low-dose computed tomography (LDCT). The objective of our study was to characterize patient knowledge and attitudes about lung cancer screening, smoking cessation, and shared decision making by patient and health care provider. METHODS: We conducted semistructured qualitative interviews with patients with histories of heavy smoking who received care at a Federally Qualified Health Center (FQHC Clinic) and at a comprehensive cancer center-affiliated chest clinic (Chest Clinic) in Albuquerque, New Mexico. The interviews, conducted from February through September 2014, focused on perceptions about health screening, knowledge and attitudes about LDCT screening, and preferences regarding decision aids. We used a systematic iterative analytic process to identify preliminary and emergent themes and to create a coding structure. RESULTS: We reached thematic saturation after 22 interviews (10 at the FQHC Clinic, 12 at the Chest Clinic). Most patients were unaware of LDCT screening for lung cancer but were receptive to the test. Some smokers said they would consider quitting smoking if their screening result were positive. Concerns regarding screening were cost, radiation exposure, and transportation issues. To support decision making, most patients said they preferred one-on-one discussions with a provider. They also valued decision support tools (print materials, videos), but raised concerns about readability and Internet access. CONCLUSION: Implementing lung cancer screening in sociodemographically diverse populations poses significant challenges. The value of tobacco cessation counseling cannot be overemphasized. Effective interventions for shared decision making to undergo lung cancer screening will need the active engagement of health care providers and will require the use of accessible decision aids designed for people with low health literacy.

Attitudes and Beliefs of Primary Care Providers in New Mexico About Lung Cancer Screening Using Low-Dose Computed Tomography.

INTRODUCTION: On the basis of results from the National Lung Screening Trial (NLST), national guidelines now recommend using low-dose computed tomography (LDCT) to screen high-risk smokers for lung cancer. Our study objective was to characterize the knowledge, attitudes, and beliefs of primary care providers about implementing LDCT screening. METHODS: We conducted semistructured interviews with primary care providers practicing in New Mexico clinics for underserved minority populations. The interviews, conducted from February through September 2014, focused on providers' tobacco cessation efforts, lung cancer screening practices, perceptions of NLST and screening guidelines, and attitudes about informed decision making for cancer screening. Investigators iteratively reviewed transcripts to create a coding structure. RESULTS: We reached thematic saturation after interviewing 10 providers practicing in 6 urban and 4 rural settings; 8 practiced at federally qualified health centers. All 10 providers promoted smoking cessation, some screened with chest x-rays, and none screened with LDCT. Not all were aware of NLST results or current guideline recommendations. Providers viewed study results skeptically, particularly the 95% false-positive rate, the need to screen 320 patients to prevent 1 lung cancer death, and the small proportion of minority participants. Providers were uncertain whether New Mexico had the necessary infrastructure to support high-quality screening, and worried about access barriers and financial burdens for rural, underinsured populations. Providers noted the complexity of discussing benefits and harms of screening and surveillance with their patient population. CONCLUSION: Providers have several concerns about the feasibility and appropriateness of implementing LDCT screening. Effective lung cancer screening programs will need to educate providers and patients to support informed decision making and to ensure that high-quality screening can be efficiently delivered in community practice.

Prognostic Values of Serum Ferritin and D-Dimer Trajectory in Patients with COVID-19.

Cytokine storm syndrome in patients with COVID-19 is mediated by pro-inflammatory cytokines resulting in acute lung injury and multiorgan failure. Elevation in serum ferritin and D-dimer is observed in COVID-19 patients. To determine prognostic values of optimal serum cutoff with trajectory plots for both serum ferritin and D-dimer in COVID-19 patients with invasive ventilator dependence and in-hospital mortality. We used retrospective longitudinal data from the Cerner COVID-19 de-identified cohort. COVID-19 infected patients with valid repeated values of serum ferritin and D-dimer during hospitalization were used in mixed-effects logistic-regression models. Among 52,411 patients, 28.5% (14,958) had valid serum ferritin and 28.6% (15,005) D-dimer laboratory results. Optimal cutoffs of ferritin (714 ng/mL) and D-dimer (2.1 mg/L) revealed AUCs ≥ 0.99 for in-hospital mortality. Optimal cutoffs for ferritin (502 ng/mL) and D-dimer (2.0 mg/L) revealed AUCs ≥ 0.99 for invasive ventilator dependence. Optimal cutoffs for in-house mortality, among females, were lower in serum ferritin (433 ng/mL) and D-dimer (1.9 mg/L) compared to males (740 ng/mL and 2.5 mg/L, respectively). Optimal cutoffs for invasive ventilator dependence, among females, were lower in ferritin (270 ng/mL) and D-dimer (1.3 mg/L) compared to males (860 ng/mL and 2.3 mg/L, respectively). Optimal prognostic cutoffs for serum ferritin and D-dimer require considering the entire trajectory of laboratory values during the disease course. Females have an overall lower optimal cutoff for both serum ferritin and D-dimer. The presented research allows health professionals to predict clinical outcomes and appropriate allocation of resources during the COVID-19 pandemic, especially early recognition of COVID-19 patients needing higher levels of care.

Opioid use disorder and health service utilization among COVID-19 patients in the US: A nationwide cohort from the Cerner Real-World Data.

BACKGROUND: Both opioid use and COVID-19 affect respiratory and pulmonary health, potentially putting individuals with opioid use disorders (OUD) at risk for complications from COVID-19. We examine the relationship between OUD and subsequent hospitalization, length of stay, risk for invasive ventilator dependence (IVD), and COVID-19 mortality. METHODS: Multivariable logistic and exponential regression models using electronic health records data from the Cerner COVID-19 De-Identified Data Cohort from January through June 2020. FINDINGS: Out of 52,312 patients with COVID-19, 1.9% (n=1,013) had an OUD. COVID-19 patients with an OUD had higher odds of hospitalization (aOR=3.44, 95% CI=2.81-4.21), maximum length of stay ( e ß ^ =1.16, 95% CI=1.09-1.22), and odds of IVD (aOR=1.26, 95% CI=1.06-1.49) than patients without an OUD, but did not differ with respect to COVID-19 mortality. However, OUD patients under age 45 exhibited greater COVID-19 mortality (aOR=3.23, 95% CI=1.59-6.56) compared to patients under age 45 without an OUD. OUD patients using opioid agonist treatment (OAT) exhibited higher odds of hospitalization (aOR=5.14, 95% CI=2.75-10.60) and higher maximum length of stay ( e ß ^ =1.22, 95% CI=1.01-1.48) than patients without OUDs; however, risk for IVD and COVID-19 mortality did not differ. OUD patients using naltrexone had higher odds of hospitalization (aOR=32.19, 95% CI=4.29-4,119.83), higher maximum length of stay ( e ß ^ =1.59, 95% CI=1.06-2.38), and higher odds of IVD (aOR=3.15, 95% CI=1.04-9.51) than patients without OUDs, but mortality did not differ. OUD patients who did not use treatment medication had higher odds of hospitalization (aOR=4.05, 95% CI=3.32-4.98), higher maximum length of stay ( e ß ^ =1.14, 95% CI=1.08-1.21), and higher odds of IVD (aOR=1.25, 95% CI=1.04-1.50) and COVID-19 mortality (aOR=1.31, 95% CI=1.07-1.61) than patients without OUDs. INTERPRETATION: This study suggests people with OUD and COVID-19 often require higher levels of care, and OUD patients who are younger or not using medication treatment for OUDs are particularly vulnerable to death due to COVID-19.

Racial disparities in COVID-19 outcomes exist despite comparable Elixhauser comorbidity indices between Blacks, Hispanics, Native Americans, and Whites.

Factors contributing to racial inequities in outcomes from coronavirus disease 2019 (COVID-19) remain poorly understood. We compared by race the risk of 4 COVID-19 health outcomes--maximum length of hospital stay (LOS), invasive ventilation, hospitalization exceeding 24 h, and death--stratified by Elixhauser comorbidity index (ECI) ranking. Outcomes and ECI scores were constructed from retrospective data obtained from the Cerner COVID-19 De-Identified Data cohort. We hypothesized that racial disparities in COVID-19 outcomes would exist despite comparable ECI scores among non-Hispanic (NH) Blacks, Hispanics, American Indians/Alaska Natives (AI/ANs), and NH Whites. Compared with NH Whites, NH Blacks had longer hospital LOS, higher rates of ventilator dependence, and a higher mortality rate; AI/ANs, higher odds of hospitalization for ECI = 0 but lower for ECI ≥ 5, longer LOS for ECI = 0, a higher risk of death across all ECI categories except ECI ≥ 5, and higher odds of ventilator dependence; Hispanics, a lower risk of death across all ECI categories except ECI = 0, lower odds of hospitalization, shorter LOS for ECI ≥ 5, and higher odds of ventilator dependence for ECI = 0 but lower for ECI = 1-4. Our findings contest arguments that higher comorbidity levels explain elevated COVID-19 death rates among NH Blacks and AI/ANs compared with Hispanics and NH Whites.

Radial Probe Ultrasound-Guided Cryobiopsy.

Fluoroscopy-guided transbronchial forceps biopsy has a low diagnostic yield in patients with radiographic suspicion of interstitial lung disease. Cryobiopsy has a higher diagnostic yield likely due to preserved lung architecture and larger biopsies; however, there is an increased risk of major airway bleeding and pneumothorax. Simultaneous use of endobronchial balloon blocker allows for containment of bleeding after cryobiopsy to the affected lobe. In the current article we describe use of radial ultrasound in identification of a target lung parenchyma without a major blood vessel adjacent to distal bronchi. After fluoroscopic marking of the selected airway a 3 second cryobiopsy was performed after localization of cryoprobe. Simultaneous use of radial ultrasound and fluoroscopy can possibly decrease bleeding complication associated with cryobiopsy in patients with suspected interstitial lung disease.

Endobronchial-Guided Vascularized Tissue Flaps for a Bronchopleural Fistula.

The management of bronchopleural fistulas can be challenging. The initial treatment is usually conservative, but operative intervention with transposition of vascularized pedicled flaps may be required in refractory cases. We present the case of a 67-year-old man with stage IIIa squamous cell carcinoma of the lung who underwent a lower and middle bilobectomy after receiving neoadjuvant chemoradiation. His postoperative course was complicated by empyema and a bronchopleural fistula. Because of difficulty accessing the fistula, endobronchial-guided vascularized tissue flaps were successfully used to close the fistula.

Cuerpo extraño endobronquial que imitaba una neoplasia maligna pulmonar con tomografía por emisión de positrones positiva / Endobronchial foreign body mimicking a positron emission tomography-positive lung malignancy

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Bronchoscopic view of pulmonary blastomycosis.

Blastomycosis is a chronic fungal infection often diagnosed in the south-central and midwestern United States. Lungs are primarily involved, with lymphatic or hematogenous spread to other organs. Bronchoscopy is considered when the noninvasive tests fail to establish the diagnosis. We describe bronchoscopic finding of blastomycosis involving the upper and lower respiratory tract. Inhaled steroids may have suppressed cellular immunity, allowing fungus to grow in the submucosa with histology significant for extensive eosinophilic infiltration. To our knowledge, such a detailed pictorial description of pulmonary blastomycosis with a cobblestone appearance of the tracheobronchial mucosa has not been reported in the past.