American Lung Association Research Articles

Longitudinal Characterization of Circulating Neutrophils Uncovers Distinct Phenotypes Associated with Disease Severity in Hospitalized COVID-19 Patients

Multiple studies have identified an association between neutrophils and COVID-19 disease severity; however, the mechanistic basis of this association remains incompletely understood. Here we collected 781 longitudinal blood samples from 306 hospitalized COVID-19 + patients, 78 COVID-19 - acute respiratory distress syndrome patients, and 8 healthy controls, and performed bulk RNA-sequencing of enriched neutrophils, plasma proteomics, cfDNA measurements and high throughput antibody profiling assays to investigate the relationship between neutrophil states and disease severity or death. We identified dynamic switches between six distinct neutrophil subtypes using non-negative matrix factorization (NMF) clustering. At days 3 and 7 post-hospitalization, patients with severe disease had an enrichment of a granulocytic myeloid derived suppressor cell-like state gene expression signature, while non-severe patients with resolved disease were enriched for a progenitor-like immature neutrophil state signature. Severe disease was associated with gene sets related to neutrophil degranulation, neutrophil extracellular trap (NET) signatures, distinct metabolic signatures, and enhanced neutrophil activation and generation of reactive oxygen species (ROS). We found that the majority of patients had a transient interferon-stimulated gene signature upon presentation to the emergency department (ED) defined here as Day 0, regardless of disease severity, which persisted only in patients who subsequently died. Humoral responses were identified as potential drivers of neutrophil effector functions, as enhanced antibody-dependent neutrophil phagocytosis and reduced NETosis was associated with elevated SARS-CoV-2-specific IgG1-to-IgA1 ratios in plasma of severe patients who survived. In vitro experiments confirmed that while patient-derived IgG antibodies mostly drove neutrophil phagocytosis and ROS production in healthy donor neutrophils, patient-derived IgA antibodies induced a predominant NETosis response. Overall, our study demonstrates neutrophil dysregulation in severe COVID-19 and a potential role for IgA-dominant responses in driving neutrophil effector functions in severe disease and mortality.Funding:We acknowledge support from the Ragon Institute of MGH, MIT and Harvard, the Massachusetts Consortium on Pathogen Readiness (MassCPR), the NIH (3R37AI080289-11S1, R01AI146785, U19AI42790-01, U19AI135995-02, U19AI42790-01, 1U01CA260476 – 01, CIVIC75N93019C00052, T32 GM007592), the American Lung Association, and the MGH Executive Committee on Research. A.-C.V. acknowledges funding support from the COVID-19 Clinical Trials Pilot grant from the Executive Committee on Research at MGH, a COVID-19 Chan Zuckerberg Initiative grant (2020-216954), and funds from the Manton Foundation and the Klarman Family Foundation.Declaration of Interests: M.S.F receives funding from Bristol-Myers Squibb. G.A. is a founder of Seromyx Systems Inc. N.H. holds equity in Biontech and holds equity in and advises Danger Bio. Ethics Approval Statement: The study was approved by the Mass General Brigham Institutional Review Board under protocol 2017P001681, with an approval for a waiver of informed consent in compliance with the 45CFR 46, 2018 Common rule.

Editorial introductions

Editorial introductions

Losartan Effects on Emphysema Progression Randomized Clinical Trial: Rationale, Design, Recruitment, and Retention.

The Losartan Effects on Emphysema Progression (LEEP) trial was designed to test the hypothesis that losartan slows progression of emphysema in chronic obstructive pulmonary disease (COPD) patients (NCT00720226). It was conducted by the Pulmonary Trials Cooperative consortium, in collaboration with the American Lung Association Airways Clinical Research Centers network. We describe the design of the trial and challenges for recruitment and follow-up of participants. LEEP is a placebo-controlled, parallel randomized trial, allocation ratio of 1:1, with a planned sample size of 220. Primary eligibility criteria were mild emphysema based on high-resolution computed tomography (HRCT) scans with 5% to 35% voxels <-950 Hounsfield units (HU), airway obstruction based on spirometry, and not taking an angiotensin receptor blocker or angiotensin converting enzyme (ACE) inhibitor. Participants received either losartan or placebo for 48 weeks. A total of 2779 individuals were screened to enroll 220 eligible participants at 26 clinical sites, all located in the continental United States. Recruitment took 45% longer than planned (32 months versus 22 months), with an average accrual rate of 6.7 participants per month. Recruitment challenges included identification of eligible participants who were not already taking or who did not have an established clinical indication for an angiotensin receptor blocker or ACE inhibitor drug and recalls of contaminated lots of losartan by the Food and Drug Administration. A number of recruitment initiatives were launched in response. Recruitment was completed in February 2020, just prior to a nationwide shutdown of research activities due to the coronavirus disease 2019 (COVID-19) pandemic.

Automatic discovery of clinically interpretable imaging biomarkers for Mycobacterium tuberculosis supersusceptibility using deep learning.

BackgroundIdentifying which individuals will develop tuberculosis (TB) remains an unresolved problem due to few animal models and computational approaches that effectively address its heterogeneity. To meet these shortcomings, we show that Diversity Outbred (DO) mice reflect human-like genetic diversity and develop human-like lung granulomas when infected with Mycobacterium tuberculosis (M.tb) .MethodsFollowing M.tb infection, a “supersusceptible” phenotype develops in approximately one-third of DO mice characterized by rapid morbidity and mortality within 8 weeks. These supersusceptible DO mice develop lung granulomas patterns akin to humans. This led us to utilize deep learning to identify supersusceptibility from hematoxylin & eosin (H&E) lung tissue sections utilizing only clinical outcomes (supersusceptible or not-supersusceptible) as labels.FindingsThe proposed machine learning model diagnosed supersusceptibility with high accuracy (91.50 ± 4.68%) compared to two expert pathologists using H&E stained lung sections (94.95% and 94.58%). Two non-experts used the imaging biomarker to diagnose supersusceptibility with high accuracy (88.25% and 87.95%) and agreement (96.00%). A board-certified veterinary pathologist (GB) examined the imaging biomarker and determined the model was making diagnostic decisions using a form of granuloma necrosis (karyorrhectic and pyknotic nuclear debris). This was corroborated by one other board-certified veterinary pathologist. Finally, the imaging biomarker was quantified, providing a novel means to convert visual patterns within granulomas to data suitable for statistical analyses.ImplicationsOverall, our results have translatable implication to improve our understanding of TB and also to the broader field of computational pathology in which clinical outcomes alone can drive automatic identification of interpretable imaging biomarkers, knowledge discovery, and validation of existing clinical biomarkers.FundingNational Institutes of Health and American Lung Association.

Novel investigation of perovskite membrane based electrochemical nitric oxide control phenomenon

The combustion of hydrocarbon fuels within the automotive industry results in harmful and reactive incomplete combustion byproducts. Specifically, nitric oxide emissions (NO) lead to increased smog, acid rain, climate change, and respiratory inflammation within the population [Nitrogen Dioxide | American Lung Association]. Current methods for treating combustion exhaust include the catalytic converter in conjunction with nitrogen oxide traps. However, there is no active, continuous reduction method that does not require restrictions on the combustion environment (Hirata in Catal Surv Asia 18:128–133, 2014). Here, a small voltage potential oscillation across a newly designed electro-chemical catalytic membrane significantly reduces NO emissions. A ceramic membrane consisting of two dissimilar metal electrodes, sandwiching a dielectric layer, is able to achieve an NO reduction in excess of 2X that of a platinum group metal (PGM) three way catalytic converter. An analysis of the exhaust effluent from the membranes indicates N2O as a precursor to N2 and O2 formation, without the introduction of ammonia (NH3), during the reaction of NO indicating a divergence from current literature. Our results demonstrate how an oscillatory electric potential on a catalytic surface may alter anticipated reaction chemistry and interaction between the catalytic surface and fluid flow.

A CURIOUS CASE OF GRANULOMATOUS INFLAMMATION OF THE LUNG

SESSION TITLE: Medical Student/Resident Tobacco Cessation and Prevention Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Young patients may have a multitude of causes for incidental lung lesions. Granulomatous lung lesions are frequently associated with infections, less common causes such as toxin mediated and vasculitis should be ruled out. We present the case of a patient who presented with granulomatous nodules due to water pipe smoking (WPS). CASE PRESENTATION: 21 year-old female presented with chest pain and dyspnea. She reported a 3-year history of tobacco use in the form of WPS and a remote history of vaping. Chest x-ray revealed a right middle lobe infiltrate concerning for pneumonia which was treated with antibiotics. CT chest further characterized the lesion as a 4 cm mass with additional clusters of irregular sub-centimetre nodules with subcarinal and mediastinal lymphadenopathy (Fig 1). Bronchoscopy showed large endobronchial lesions and histology showed necrotizing granulomas with negative stains and cultures for fungal or tuberculosis or evidence of malignancy. lymph node biopsy tissue samples demonstrated necrotizing granulomas. The patient was subsequently discharged from the hospital for outpatient management with a brief course of corticosteroids and was lost to follow up thereafter. DISCUSSION: Our patient who presented with an incidental lung lesion on her radiographs was found to have granulomatous lung nodules on histology. Workup remained negative for common causes such as Fungal infections, Tuberculosis or malignancy and she was eventually presumed to have WPS induced granulomatous lung disease given her prolonged and recent exposure. WPS as a trend has been silently picking up among certain young adult populations in the West with some studies indicating usage rates as high as 46.4% among college students. Contents in water pipe smoke such as ultrafine particulate matter (PM), carcinogenic particles and heavy metals have been implicated in a host of lung pathologies ranging from emphysema to infections and even lung cancers. Granulomatous inflammation however remains an infrequent complication and the mechanism underlying this pathology has yet to be elucidated. Such a finding has only been reported once before by Dyal et al who described the case of a young female with bilateral granulomatous secondary to WPS who was treated successfully with steroids, suggesting a component of underlying inflammation. CONCLUSIONS: Detailed and updated review could help strengthen evidence for the truly disastrous effects of WPS on long term health of our young adults, and potentially support litigation for the ban on sale and use of these products, as was accomplished recently in case of E-cigarettes or vaping. Reference #1: American Lung Association. Hookah smoking: a growing threat to public health [accessed 2016 Apr 9] Reference #2: Shafagoj Y.A., Mohammad F.I. Levels of maximum endexpiratory carbon-monoxide and certain cardio vascular parameters following hubble-bubble smoking. Saudi. Med. J. 2002;23:953958 Reference #3: Dyal H, Singhvi A, Patel R, et al. 2014. A case of Eosinophilic pneumonia following recent onset of hookah smoking. Chest 146:406A DISCLOSURES: No relevant relationships by Sanjay Dogra, source=Web Response No relevant relationships by Sandeep Kumar, source=Web Response No relevant relationships by Shaiva Meka, source=Web Response No relevant relationships by Syed Mustafa, source=Web Response No relevant relationships by Ehsun Naeem, source=Web Response

Local complement activation is associated with primary graft dysfunction after lung transplantation.

BACKGROUNDThe complement system plays a key role in host defense but is activated by ischemia/reperfusion injury (IRI). Primary graft dysfunction (PGD) is a form of acute lung injury occurring predominantly due to IRI, which worsens survival after lung transplantation (LTx). Local complement activation is associated with acute lung injury, but whether it is more reflective of allograft injury compared with systemic activation remains unclear. We proposed that local complement activation would help identify those who develop PGD after LTx. We also aimed to identify which complement activation pathways are associated with PGD.METHODSWe performed a multicenter cohort study at the University of Pennsylvania and Washington University School of Medicine. Bronchoalveolar lavage (BAL) and plasma specimens were obtained from recipients within 24 hours after LTx. PGD was scored based on the consensus definition. Complement activation products and components of each arm of the complement cascade were measured using ELISA.RESULTSIn both cohorts, sC4d and sC5b-9 levels were increased in BAL of subjects with PGD compared with those without PGD. Subjects with PGD also had higher C1q, C2, C4, and C4b, compared with subjects without PGD, suggesting classical and lectin pathway involvement. Ba levels were higher in subjects with PGD, suggesting alternative pathway activation. Among lectin pathway–specific components, MBL and FCN-3 had a moderate-to-strong correlation with the terminal complement complex in the BAL but not in the plasma.CONCLUSIONComplement activation fragments are detected in the BAL within 24 hours after LTx. Components of all 3 pathways are locally increased in subjects with PGD. Our findings create a precedent for investigating complement-targeted therapeutics to mitigate PGD.FUNDINGThis research was supported by the NIH, American Lung Association, Children’s Discovery Institute, Robert Wood Johnson Foundation, Cystic Fibrosis Foundation, Barnes-Jewish Hospital Foundation, Danish Heart Foundation, Danish Research Foundation of Independent Research, Svend Andersen Research Foundation, and Novo Nordisk Research Foundation.

COVID-19 After Effects: Concerns for Singers

COVID-19 After Effects: Concerns for Singers

A View from the Frontline: Palliative and Ethical Considerations of the COVID-19 Pandemic.

A View from the Frontline: Palliative and Ethical Considerations of the COVID-19 Pandemic.

Breathe Well, Live Well: Implementing an Adult Asthma Self-Management Education Program.

Asthma remains a significant health problem in the United States. Adults with poorly controlled asthma can affect their community in a number of ways, from lost productivity in the workplace to health care costs to premature death. Asthma self-management education helps individuals achieve better control of their asthma and is critical for the overall health and well-being of individuals with asthma. While there are numerous programs and initiatives targeting children with asthma, there is a lack of comparable focus on the needs of adults with asthma. The American Lung Association developed Breathe Well, Live Well, an adult asthma self-management education program, and launched it nationwide in 2007. The program for adults has a flexible delivery format for community-based implementation. This article describes the development, dissemination, and transformation of the program. Each stage of implementation showed positive changes in asthma self-management practices that contribute to better asthma control, and one local implementation additionally showed decreased reports of missed work and unscheduled health care visits among participants. The findings from the three evaluations support the use of Breathe Well, Live Well for broad community-based implementation to improve asthma self-management efficacy and behaviors.

Caring for Miners During the Coronavirus Disease-2019 (COVID-19) Pandemic.

Caring for Miners During the Coronavirus Disease-2019 (COVID-19) Pandemic.

Screening of flour mill workers for respiratory morbidities: a cross-sectional study in rural Bangalore

Background: Flour mill workers are highly exposed to organic wheat flour dust with a large diversity of antigenic/allergic component leading to respiratory morbidity and skin allergies. This work environment may affect workers health and safety if the effects are unchecked periodically.Methods: A cross-sectional study was conducted among 194 workers of 4 flour mills in Bangalore Rural district. Prior permission (factory) and informed consent *(workers) were obtained. Pre-structured interview-schedule was administered. Peak expiratory flow rate (PEFR) readings were measured by using wrights flow meter and best of 3 readings recorded. Respiratory morbidity was assessed on PEFR classification - based on American lung association (ALA) colour coding - red, yellow and green zones. Respiratory morbidity was compared with years of experience, type of work, smoking habits and usage of appropriate PPEs. Data was analyzed using Epi-info 08.Results: Among 194 workers studied, 188 were males, 6 were females. They were in the age group of 15-50 years. 143 (73.7%) were engaged in work with direct dust exposure. 84 (43%) were working for more than 3 years, 50 (25%) between 1-3 years and 60 (30%) for less than a year. 7.2% regularly smoked. According to ALA classification, PEFRs of 71 (36%) of the workers were classified into RED, 91 (46%) to yellow and 32 (16%) to green zones respectively. Usage of PPEs was only among 126 (64%).Conclusions: Respiratory morbidity among flour mill workers was high. Adequate use of PPEs was low. Half of the workers fell into yellow zone that had a potential to fall into red zone if external factors were not considered.

Regulation of Airway Progenitor Homeostasis and Cell Composition by Tight Junction Protein Claudin‐18

RationaleClaudin‐18 (Cldn18) is comprised of two isoforms, Cldn 18.1 and Cldn18.2. The lung‐specific isoform, Cldn18.1, regulates distal lung epithelial progenitor cell homeostasis. Its role in airway epithelium has not been elucidated, although Cldn18 expression is decreased in lungs of patients with chronic airway diseases (e.g., asthma and chronic obstructive pulmonary disease (COPD)). The airway epithelium is comprised of three progenitor populations, basal cells (BC), pulmonary neuroendocrine cells (PNEC) and club cells, and two non‐progenitor cell populations, namely goblet and ciliated cells. Club cells are secretory cells that are susceptible to naphthalene (NAP) injury. Club cell depletion occurs by day 3 post‐NAP, with spreading of ciliated cells to cover the denuded epithelial surface, and full reconstitution of the airway epithelium by day 14–21. Here we investigated the role of Cldn18.1 in airway epithelium using a previously developed global Cldn18 knockout (KO) mouse model.MethodsWild‐type (WT) and Cldn18 KO mice were injected intraperitoneally with NAP (225–275 mg/kg, corn oil as control). Lungs were harvested at baseline and 3‐days (maximal injury), 7‐days (beginning of regeneration) and 21‐days (full regeneration) post‐NAP, inflated with 4% paraformaldehyde and fixed overnight prior to embedding and sectioning. Hematoxylin and eosin, Periodic Acid‐Schiff (PAS) and immunofluorescence staining were performed.ResultsIn WT mice, Cldn18.1 was expressed in a small subset of airway ciliated cells. Cldn18 KO mice showed increased numbers of pulmonary neuroendocrine cells and neuroendocrine bodies, as well as ectopic localization of club cells and localization of keratin 5‐positive cells within the distal parenchyma. At day 3 post‐NAP in WT mice, Cldn18.1 was transiently expressed in all the ciliated cells covering the denuded epithelium, returning to being expressed in only a subset of cells by day 7. Cldn18 KO mice subjected to injury unexpectedly developed marked goblet cell hyperplasia at day 14–21 post‐NAP, with cells expressing markers for both club (CC‐10) and goblet (MUC5AC) cells.ConclusionsOur findings demonstrate an unexpected role for Cldn18.1 in regulating airway progenitor homeostasis and cell composition, implicating Cldn18.1 in regulation of downstream signaling pathways that inhibit goblet cell differentiation. A transient increase in the number of Cldn18.1‐positive ciliated cells in WT mice in the initial stages post‐injury suggests paracrine regulation of these inhibitory effects. Modulation of Cldn18 expression may be beneficial in the treatment of airway diseases characterized by goblet cell metaplasia.Support or Funding InformationFunding: American Lung Association, Hastings Foundation, NIH

Biotech Plays Critical Role in Protecting Against Coronavirus Outbreak

Industrial BiotechnologyVol. 16, No. 2 EditorialFree AccessBiotech Plays Critical Role in Protecting Against Coronavirus OutbreakStephanie BatchelorStephanie BatchelorVice President of the Industrial and Environmental Section, Biotechnology Innovation Organization, Washington, DC, USA and Consulting Editor, Industrial BiotechnologySearch for more papers by this authorPublished Online:17 Apr 2020https://doi.org/10.1089/ind.2020.29207.sbaAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail First and foremost, I hope readers of the Industrial Biotechnology are safe and doing everything they can to protect themselves from the coronavirus disease 2019 (COVID-19) outbreak. At the Biotechnology Innovation Organization (BIO), we have heard and seen many requests from medical research centers, biopharmaceutical companies, testing developers and testing sites for various supplies.In this challenging and unprecedented time, we want to ensure critical research and development programs can continue. For this reason, BIO has launched a Coronavirus Hub (hub.bio.org), connecting companies that have extra capacity and resources with those that need them. The hub allows users to post requests in real time for urgently needed items and announce the availability of supplies and capacity.As a biotech community, we have the responsibility to rise to this global call for action. I echo BIO's CEO and President Jim Greenwood when saying, “The coronavirus is no match for science, but we must finish the job.”Unfortunately, as the global community works to contain the COVID-19 outbreak, other challenges like climate change continue to grip the planet. In fact, the health impacts from low air quality only increase the risk of infections from viruses such as the novel COVID-19.As we know, transportation continues to be the leading cause of greenhouse gas emissions in the United States—thanks in large part to the abundance of vehicles and airplanes that rely on fossil fuels. We've seen that policies that drive adoption of renewable fuels, like low carbon fuel standards, decrease health risks.The American Lung Association and Environmental Defense Fund found that low carbon fuel standards, combined with statewide carbon pollution limits—such as limits on emissions from manufacturing—have helped prevent almost 90,000 cases of respiratory symptoms and 8,000 cases of asthma-related health complications. These policies also helped prevent 15,000 lost workdays.With the administration continuing to diminish the intent of the Renewable Fuel Standard (RFS), adoption of low carbon fuel policies in states becomes increasingly important in order to reduce carbon emissions and improve health.Several states have considered low carbon fuel standards this year, most notably Washington and New York. BIO and the Low Carbon Fuels Coalition (LCFC) have engaged our advocates and worked tirelessly in both states to advance these policies. However, with the impact of the COVID-19, and Washington's session standing at just 60 days ending in March, this is a battle we will continue fighting into next year.The administration's expansive issuance of small refinery exemptions granted through the RFS has upended the policy and added to the uncertainty as it deliberates whether it will abide by the court ruling that deemed many of these exemptions illegal. BIO will remain vigilant in making sure the Environmental Protection Agency administers the policy as Congress intended.As the world's economies struggle, the federal government has considered various options to boost local businesses and sectors hardest hit by the novel COVID-19—including airlines. In December, Congress passed a biodiesel tax credit extension, benefiting a few qualified producers of sustainable aviation fuels (SAF). This tax credit, however, expires in 2022.As airlines and biofuel companies across the country—many in rural communities—look to get back to normal following the COVID-19 outbreak, a long-term tax credit specifically for SAF production would significantly help in speeding up efforts. The tax credit would also put the country on a sustainable path forward as we look to reignite our economy. Further, if Congress requires airlines to reduce emissions in return for support, SAF must be part of those requirements to assist biofuel producers.Fortunately, thanks to biotechnology, both the sustainable fuels and biobased manufacturing sectors are agile and finding impactful ways to help in this crisis. Crops normally marked for biofuel production are now being used by producers to make alcohol for hand sanitizer. And using biotechnology, companies are creating renewable chemicals and enzymes more efficiently to develop cleaning products for medical devices.The priority for the foreseeable future across sectors, in Congress and States, will be protecting the U.S. population from the COVID-19 outbreak. But it is important that policies to address this and possible future outbreaks also address the impact of fuels pollution and the ability of the industrial biotech sector to help protect the nation's health.FiguresReferencesRelatedDetailsCited byIT-Enabled Sustainable Innovation and the Global Digital Divides30 August 2021 | Sustainability, Vol. 13, No. 17 Volume 16Issue 2Apr 2020 InformationCopyright 2020, Mary Ann Liebert, Inc., publishersTo cite this article:Stephanie Batchelor.Biotech Plays Critical Role in Protecting Against Coronavirus Outbreak.Industrial Biotechnology.Apr 2020.43-43.http://doi.org/10.1089/ind.2020.29207.sbaPublished in Volume: 16 Issue 2: April 17, 2020Online Ahead of Print:March 27, 2020PDF download

State Medicaid Coverage for Tobacco Cessation Treatments and Barriers to Accessing Treatments - United States, 2008-2018.

The prevalence of current cigarette smoking is approximately twice as high among adults enrolled in Medicaid (23.9%) as among privately insured adults (10.5%), placing Medicaid enrollees at increased risk for smoking-related disease and death (1). Medicaid spends approximately $39 billion annually on treating smoking-related diseases (2). Individual, group, and telephone counseling and seven Food and Drug Administration (FDA)-approved medications* are effective in helping tobacco users quit (3). Comprehensive, barrier-free, widely promoted coverage of these treatments increases use of cessation treatments and quit rates and is cost-effective (3). To monitor changes in state Medicaid cessation coverage for traditional Medicaid enrollees† over the past decade, the American Lung Association collected data on coverage of nine cessation treatments by state Medicaid programs during December 31, 2008-December 31, 2018: individual counseling, group counseling, and the seven FDA-approved cessation medications§; states that cover all nine of these treatments are considered to have comprehensive coverage. The American Lung Association also collected data on seven barriers to accessing covered treatments.¶ As of December 31, 2018, 15 states covered all nine cessation treatments for all enrollees, up from six states as of December 31, 2008. Of these 15 states, Kentucky and Missouri were the only ones to have removed all seven barriers to accessing these cessation treatments. State Medicaid programs that cover all evidence-based cessation treatments, remove barriers to accessing these treatments, and promote covered treatments to Medicaid enrollees and health care providers could reduce smoking, smoking-related disease, and smoking-attributable federal and state health care expenditures (3-7).

A more effective approach to lung cancer screening?

A more effective approach to lung cancer screening?

Editorial introductions

Editorial introductions

US EPA science advisers split on whether to tighten ozone pollution limit

A panel of science advisers is recommending that the current US air pollution limit for ground-level ozone remain at 70 ppb rather than be tightened. This might trigger a sigh of relief from operators of chemical plants that release volatile organic compounds and other substances that can form ozone in the presence of sunlight—such facilities are less likely to see tougher emission control requirements. But the American Lung Association says the existing limit puts children with asthma at risk from exposure to ozone, which can trigger lung problems. The Dec. 6 recommendation from the Environmental Protection Agency’s seven-member Clean Air Scientific Advisory Committee (CASAC) to maintain the current standard doesn’t represent a consensus. A majority of 6 endorsed an EPA draft decision to retain the current ozone standard, set in 2015. They are a business analytics consultant, who is the committee’s chair, along with scientists from regulatory agencies of four

Cluster Randomized Trial of Teens Against Tobacco Use: Youth Empowerment for Tobacco Control in El Paso, Texas

This study examines smoke-free youth partnerships implementing the Teens Against Tobacco Use model developed by the American Lung Association. This innovative tobacco prevention strategy has not been evaluated rigorously. Students used peer teaching to educate youth about tobacco use and engaged in tobacco control advocacy activities. Participating high school and middle school youth were trained to develop and deliver tobacco prevention presentations to 4th-8th grade students in schools. To evaluate the efficacy of the presentations, matched pairs of classrooms willing to have 1 presentation were randomly assigned to receive either the presentation first (intervention condition) or later in the school year (control condition). The study took place in a predominantly low-income Hispanic community. A total of 9 schools, 107 classes, and 2,257 students participated in the evaluation. Tobacco susceptibility was assessed with a brief survey administered to students in both intervention and control classrooms in 2014 and 2015 after the completion of presentations in intervention classrooms. Analyses completed in 2019 compared intervention and control classrooms on tobacco susceptibility. Intent-to-treat analyses indicated that classrooms receiving a tobacco prevention presentation had significantly lower tobacco susceptibility scores than classrooms that did not receive a presentation (12% vs 17%, p<0.01), representing a 37% reduction in the odds of tobacco susceptibility. Teens Against Tobacco Use presenters also completed tobacco retailer compliance checks and gained media coverage in advocating to regulate e-cigarettes in the same manner as other tobacco products. Findings suggest Teens Against Tobacco Use is an effective means of reducing tobacco susceptibility among 4th-8th graders in the immediate term. Longer-term outcome evaluations are needed to determine whether Teens Against Tobacco Use presentations can have a lasting impact on tobacco use. This study is registered at www.clinicaltrials.gov NCT02443025.

Mitochondrial dysfunction in human primary alveolar type II cells in emphysema

BackgroundCigarette smoke is the main risk factor of pulmonary emphysema development, which is characterized by alveolar wall destruction. Mitochondria are important for alveolar type II (ATII) cell metabolism due to ATP generation. MethodsWe isolated ATII cells from control non-smoker and smoker organ donors, and after lung transplant of patients with emphysema to determine mitochondrial function, dynamics and mitochondrial (mt) DNA damage. FindingsWe found high mitochondrial superoxide generation and mtDNA damage in ATII cells in emphysema. This correlated with decreased mtDNA amount. We also detected high TOP1-cc and low TDP1 levels in mitochondria in ATII cells in emphysema. This contributed to the decreased resolution of TOP1-cc leading to accumulation of mtDNA damage and mitochondrial dysfunction. Moreover, we used lung tissue obtained from areas with mild and severe emphysema from the same patients. We found a correlation between the impaired fusion and fission as indicated by low MFN1, OPA1, FIS1, and p-DRP1 levels and this disease severity. We detected lower TDP1 expression in severe compared to mild emphysema. InterpretationWe found high DNA damage and impairment of DNA damage repair in mitochondria in ATII cells isolated from emphysema patients, which contribute to abnormal mitochondrial dynamics. Our findings provide molecular mechanisms of mitochondrial dysfunction in this disease. FundThis work was supported by National Institutes of Health (NIH) grant R01 HL118171 (B.K.) and the Catalyst Award from the American Lung Association (K.B.).