Differential Non-Coding RNA Profiles for Lung Cancer Early Detection in African and White Americans.

Introduction: Lung cancer leads in cancer-related deaths. Disparities are observed in lung cancer rates, with African Americans (AAs) experiencing disproportionately higher incidence and mortality compared to other ethnic groups. Non-coding RNAs (ncRNAs) play crucial roles in lung tumorigenesis. Our objective was to identify ncRNA biomarkers associated with the racial disparity in lung cancer. Methods: Using droplet digital PCR, we examined 93 lung-cancer-associated ncRNAs in the plasma and sputum samples from AA and White American (WA) participants, which included 118 patients and 92 cancer-free smokers. Subsequently, we validated our results with a separate cohort comprising 56 cases and 72 controls. Results: In the AA population, plasma showed differential expression of ten ncRNAs, while sputum revealed four ncRNAs when comparing lung cancer patients to the control group. In the WA population, the plasma displayed eleven ncRNAs, and the sputum had five ncRNAs showing differential expression between the lung cancer patients and the control group. For AAs, we identified a three-ncRNA panel (plasma miRs-147b, 324-3p, 422a) diagnosing lung cancer in AAs with 86% sensitivity and 89% specificity. For WAs, a four-ncRNA panel was developed, comprising sputum miR-34a-5p and plasma miRs-103-3p, 126-3p, 205-5p, achieving 88% sensitivity and 87% specificity. These panels remained effective across different stages and histological types of lung tumors and were validated in the independent cohort. Conclusions: The ethnicity-related ncRNA signatures have promise as biomarkers to address the racial disparity in lung cancer.

Tobacco treatment in the setting of lung cancer screening.

PURPOSE OF REVIEW: Lung cancer screening by low-dose CT is an increasingly implemented preventive medicine tool. Screening for lung cancer is incomplete without addressing problematic tobacco use, the greatest modifiable risk factor in the development of lung cancer. This review describes recent work related to lung cancer screening and treatment of tobacco use in that context. RECENT FINDINGS: Implementation of lung cancer screening demonstrates socioeconomic disparities in terms of adherence to screening as well as likelihood of successful tobacco dependence treatment. Active tobacco dependence is a common comorbidity for patients undergoing lung cancer screening. The optimal implementation of tobacco dependence treatment in the context of lung cancer screening is still an area of active investigation. SUMMARY: Treatment of tobacco dependence at time of lung cancer screening is a major opportunity for clinicians to intervene to reduce the major modifiable risk factor for lung cancer, tobacco use. Providing comprehensive tobacco dependence treatment is most effective using combination pharmacologic and behavioral interventions. Practices providing comprehensive treatment will benefit from accurate documentation for billing and coding and supplementing with external resources such as state Quit Lines.

Incidental Pulmonary Nodules and Lung Cancer Screening.

Incidental nodules and lung cancer screening nodules are causes of concern and anxiety for the patients. Both these require diligent follow up according to their respective guidelines.

Integrating a Systematic, Comprehensive E-Cigarette and Vaping Assessment Tool into the Electronic Health Record.

BACKGROUND: Recently, the use of electronic cigarettes increased sharply, leading to increased e-cigarette, or Vaping Product Use-Associated Lung Injury (EVALI), and other acute pulmonary conditions. There is an urgent need for clinical information about e-cigarette users to identify factors that contribute to EVALI. We developed an e-cigarette/vaping assessment tool (EVAT) that was integrated into the Electronic Health Record (EHR) of a large state-wide medical system and initiated a system-wide dissemination and education to support its use. METHODS: EVAT documented current vaping status, history, and e-cigarette content (nicotine, cannabinoids, and/or flavoring). Educational materials and presentations were developed via a comprehensive literature review. EVAT utilization in the EHR was assessed quarterly. Patients' demographic data and clinical site name were also collected. RESULTS: The EVAT was built, validated, and integrated with the EHR in July 2020. Live and virtual seminars were conducted for prescribing providers and clinical staff. Asynchronous training was offered using podcasts, e-mails, and Epic tip sheets. Participants were informed about vaping harm and EVALI and instructed on the use of EVAT. As of December 31, 2022, EVAT was used 988,181 times, with 376,559 unique patients evaluated. Overall, 1,063 hospital units and affiliated ambulatory clinics used EVAT, including 64 Primary Care, 95 Pediatrics, and 874 Specialty sites. CONCLUSIONS: EVAT was successfully implemented. Continued outreach efforts are needed to further increase its usage. Education materials should be enhanced to help providers to reach youth and vulnerable populations and connect patients to the tobacco treatment resources.

Streptococcus pneumoniae promotes lung cancer development and progression.

Streptococcus pneumoniae (SP) is associated with lung cancer, yet its role in the tumorigenesis remains uncertain. Herein we find that SP attaches to lung cancer cells via binding pneumococcal surface protein C (PspC) to platelet-activating factor receptor (PAFR). Interaction between PspC and PAFR stimulates cell proliferation and activates PI3K/AKT and nuclear factor kB (NF-kB) signaling pathways, which trigger a pro-inflammatory response. Lung cancer cells infected with SP form larger tumors in BALB/C mice compared to untreated cells. Mice treated with tobacco carcinogen and SP develop more lung tumors and had shorter survival period than mice treated with the carcinogen alone. Mutating PspC or PAFR abolishes tumor-promoting effects of SP. Overabundance of SP is associated with the survival. SP may play a driving role in lung tumorigenesis by activating PI3K/AKT and NF-kB pathways via binding PspC to PAFR and provide a microbial target for diagnosis and treatment of the disease.

Education for Tobacco Use Disorder Treatment: Current State, Evidence, and Unmet Needs.

Background: Tobacco use is undertreated in the medical setting. One driver may be inadequate tobacco use disorder treatment (TUDT) training for clinicians in specialties treating tobacco-dependent patients. Objective: We sought to evaluate the current state of TUDT training for diverse professionals and how these skills are assessed in credentialing exams. Methods: We performed a focused review of current educational practices, evidence-based strategies, and accreditation exam contents focused on TUDT. Results: Among medical students, participants in reviewed studies reported anywhere from 45 minutes to 3 hours of TUDT training throughout their 4-year programs, most often in the form of didactic sessions. Similarly, little TUDT training was reported at the post-graduate (residency, fellowship, continuing medical education) levels, and reported training was typically delivered as time-based (expected hours of instruction) rather than competency-based (demonstration of mastery) learning. Multiple studies evaluated effective TUDT curricula at varied stages of training. More effective curricula incorporated longitudinal sessions and active learning, such as standardized patient encounters or proctored patient visits. Knowledge of TUDT is minimally evaluated on certification exams. For example, the American Board of Internal Medicine blueprint lists TUDT as <2% of one subtopic on both the internal medicine and pulmonary exams. Conclusion: TUDT training for most clinicians is minimal, does not assess competency, and is minimally evaluated on certification exams. Effective, evidence-based TUDT training incorporating active learning should be integrated into medical education at all levels, with attention paid to inclusion on subsequent certifying exams.

Profiling Plasma Cytokines by A CRISPR-ELISA Assay for Early Detection of Lung Cancer.

Cytokines play crucial roles in tumorigenesis and are potential biomarkers for cancer diagnosis. An Enzyme-linked Immunosorbent Assay (ELISA) is commonly used to measure cytokines but has a low sensitivity and can only detect a single target at a time. CRISPR-Associated Proteins (Cas) can ultra-sensitively and specifically detect nucleic acids and is revolutionizing molecular diagnostics. Here, we design a microplate-based CRISPR-ELISA assay to simultaneously profile multiple cytokines, in which antibodies are coupled with ssDNA to form antibody-ssDNA complexes that bridges CRISPR/Cas12a and ELISA reactions. The ssDNA triggers the Cas12a collateral cleavage activity and releases the fluorescent reporters to generate amplified fluorescent signals in the ELISA detection of cytokines. The CRISPR-ELISA assay can simultaneously measure multiple cytokines with a significantly higher sensitivity compared with conventional ELISA. Using the CRISPR-ELISA assay to profile plasma cytokines in 127 lung cancer patients and 125 cancer-free smokers, we develop a panel of plasma cytokine biomarkers (IL-6, IL-8, and IL-10) for early detection of the disease, with 80.6% sensitivity and 82.0% specificity. The CRISPR-ELISA assay may provide a new approach to the discovery of cytokine biomarkers for early lung cancer detection.

Study design for a proactive teachable moment tobacco treatment intervention among patients with pulmonary nodules.

INTRODUCTION: We developed Teachable Moment to Opt-Out of Tobacco (TeaM OUT) as a tobacco treatment intervention based on a foundation of a theoretical model of teachable moments, "naturally occurring life transitions or health events thought to motivate individuals to spontaneously adopt risk-reducing health behaviors". The TeaM OUT intervention combines a teachable moment for patients with newly detected incidental pulmonary nodules with a proactive interactive voice response (IVR) system to increase connections to evidence-based tobacco treatment interventions. METHODS: We will perform a convergent, nested observational mixed-methods study utilizing both randomized trial and observational methods to test the effectiveness and generalizability of the TeaM OUT intervention through three aims. AIM 1: Among patients recently diagnosed with a pulmonary nodule, we will utilize a pragmatic, stepped wedge randomized controlled design to evaluate the effectiveness of a proactive, teachable moment-based, tobacco treatment outreach intervention (TeaM OUT) on increasing engagement with tobacco treatment resources compared to Enhanced Usual Care. AIM 2: Using a longitudinal observational design, we will evaluate the association of receipt of the TeaM OUT intervention with seven-day point abstinence prevalence and quit motivation compared to Enhanced Usual Care. AIM 3: Qualitatively elicit perspectives from key stakeholders to inform acceptability and utility, implementation barriers and facilitators, and scalability of the TeaM OUT intervention. DISCUSSION: We are hopeful that implementation of TeaM OUT will increase the number of patients who quit using cigarettes with subsequent improvements in their health.

Exploring the effects of racial and socioeconomic factors on timeliness of lung cancer diagnosis and treatment in Baltimore Veterans.

OBJECTIVES: To characterize the effect of racial and socioeconomic factors on the timeliness of lung cancer diagnosis and treatment in a single-center Veterans Affair Medical Center (VAMC) pulmonary nodule clinic. METHODS: We conducted a single-center retrospective review of all patients seen at the Baltimore VAMC pulmonary nodule clinic between 2013 and 2019 to identify key demographic factors, measures of neighborhood socioeconomic disadvantage, cancer staging and histopathologic information, and time elapsed between diagnosis and treatment. We excluded patients with pulmonary nodules undergoing active surveillance, prior history of lung cancer, metastases of a different primary origin, insufficient followup, or who had received care outside the VHA system. RESULTS: Median times to diagnosis and treatment of lung cancer were 28 and 73 days. There were no statistically significant differences in overall timeliness of diagnosis and treatment when stratified by race or measures of neighborhood socioeconomic disadvantage. CONCLUSIONS: The authors found no differences in timeliness of lung cancer care by race and socioeconomic status within the system. Despite general adherence to national standards in timeliness of care, there continues to be a need for improvements in the operational workflows to reduce time to diagnosis and treatment for all Veterans.

The Effect of a Dedicated Lung Mass Clinic on Lung Nodule Follow Up.

Introduction: With the increased use of computed tomography (CT) imaging, lung nodules are found yearly requiring tracking and guideline directed follow up imaging. We describe the structure of a clinic dedicated to lung nodule tracking, patient education and the outcomes of lung nodule follow up. Methods: Patient electronic medical record charts were reviewed for lung nodules requiring tracking to determine if a follow up study was ordered, completed by the patient, and completed in an appropriate time frame. Patients were grouped based on referral to pulmonary clinic, lung mass clinic, or no subspecialty clinic. 700 CT reports were extracted from the electronic medical record of which 350 (50%) had lung nodules reported on CT, and 111 (15.9%) were lung nodules that additionally recommended discrete follow up in the radiologist report at the Veterans Health Administration hospital in Baltimore. Of these 111 patients, 95% were male and 5% were female. The mean age of the population was 66.3 ± 7.7 years. Results and Discussion: Patients seen in the lung mass clinic had a statistically significant higher rate of the follow up study being ordered by the provider. The lung mass clinic also had a higher percentage of patients who completed the study and completed the study within the recommended time frame, however, this was not statistically significant. Conclusion: A dedicated lung mass clinic should be considered as a method of improving lung nodule tracking with the added benefit of patient education and multidisciplinary care.

Military exposures and lung cancer in United States veterans.

Lung cancer screening begins at age 50, with yearly low dose computed tomography (LDCT) scans until age 80, for patients determined to be high risk due to tobacco smoking. Veterans serving from World War II to the Gulf War are now at the age where LDCT is recommended. This recommendation from the United States Preventative Service Task Force includes patients who have a 20-pack year tobacco history and currently smoke or quit within the last 15 years. This recommendation does not consider additional risk factors such as exposures to lung carcinogens. We discuss unique operational and occupational exposures encountered while serving in the armed forces, which may potentially increase the risk of lung cancers in the Veteran population. The additional risk of lung cancer due to military exposure history is unclear and more work is needed to identify and quantify risk at an individual level. Increasing awareness at the provider level regarding the carcinogenic exposures encountered may allow a larger population of Veterans, not meeting traditional LDCT criteria, to benefit from lung cancer screening.

Assessing calorie and protein recommendations for survivors of critical illness weaning from prolonged mechanical ventilation - can we find a proper balance?

BACKGROUND & AIMS: Survivors of critical illness requiring prolonged mechanical ventilation (PMV) are predisposed to malnutrition, muscle wasting, and weakness. There is a lack of data regarding nutrition adequacy among these patients, and although nitrogen balance has been studied as a marker of adequate protein intake in healthy individuals and acutely critically ill patients, it has not been well studied in critically ill patients with PMV. The purpose of this study was to determine if patients requiring PMV admitted to a long-term acute care hospital (LTACH) achieved registered dietitian (RD) recommended goals for energy and protein intake and if the recommendations were adequate to avoid negative nitrogen balance. METHODS: Using a retrospective, cohort study design, patients requiring PMV who had orders for 24-h urine collections for urea nitrogen (24hrUUN) were included. Energy and protein intake was calculated from chart documentation of dietary intake for the 24-h period during which patients underwent a 24hrUUN. Nitrogen intake was estimated from protein intake. Dietary intake was compared to RD-recommendations to determine the percentage of RD-recommendations achieved. Nitrogen balance was calculated as nitrogen intake minus nitrogen loss, with negative balance categorized as less than -1. RESULTS: Subjects (n = 16) were 38% male and 75% African American (mean age 61.5 ± 3.2 years; mean BMI 27.5 ± 2.5 kg/m2). Duration of LTACH hospitalization was 26.5 (6-221) days. Mean energy and protein intake was 21.7 ± 2.9 kcal/kg/d and 1.1 ± 0.1 g/kg/d, respectively, which corresponded to 86% of both RD energy and protein recommendations. Ten patients achieved a positive nitrogen balance (mean 0.9 ± 1.1 g). In addition, there was a positive linear relationship between protein intake and nitrogen balance (r = 0.59, p = 0.016). CONCLUSION: Survivors of critical illness requiring PMV achieved a high percentage of RD-recommended protein and calories, and prevented a negative nitrogen balance in a majority of patients. Increasing protein intake can prevent a negative nitrogen balance. Future studies should evaluate whether these patients are able to maintain a steady state of nitrogen intake and excretion over time and how this affects time to and/or success of weaning.

Pulmonary talcosis in the setting of cosmetic talcum powder use.

Pulmonary talcosis is a rare pneumoconiosis that is difficult to diagnose and may progress to debilitating lung disease. Four types of talcosis are described in literature: talc-silicosis and talc-asbestosis secondary to inhalation in industry workers and talc-emboli in intravenous drug users that self-inject talc-containing oral tablets. Although found in common household products, talc is overlooked as a cause of pneumoconiosis. Talcosis caused by cosmetic face powder is even rarer. Here we discuss a woman in her 50s who developed talcosis from inhalation of cutaneous cosmetics two years prior, and how comprehensive history may be crucial in diagnosing this rare disease.

Microbiota Biomarkers for Lung Cancer.

Non-small cell lung cancer (NSCLC) is the number one cancer killer and its early detection can reduce mortality. Accumulating evidences suggest an etiopathogenic role of microorganisms in lung tumorigenesis. Certain bacteria are found to be associated with NSCLC. Herein we evaluated the potential use of microbiome as biomarkers for the early detection of NSCLC. We used droplet digital PCR to analyze 25 NSCLC-associated bacterial genera in 31 lung tumor and the paired noncancerous lung tissues and sputum of 17 NSCLC patients and ten cancer-free smokers. Of the bacterial genera, four had altered abundances in lung tumor tissues, while five were aberrantly abundant in sputum of NSCLC patients compared with their normal counterparts (all p < 0.05). Acidovorax and Veillonella were further developed as a panel of sputum biomarkers that could diagnose lung squamous cell carcinoma (SCC) with 80% sensitivity and 89% specificity. The use of Capnocytophaga as a sputum biomarker identified lung adenocarcinoma (AC) with 72% sensitivity and 85% specificity. The use of Acidovorax as a sputum biomarker had 63% sensitivity and 96% specificity for distinguishing between SCC and AC, the two major types of NSCLC. The sputum biomarkers were further validated for the diagnostic values in a different cohort of 69 NSCLC cases and 79 cancer-free controls. Sputum microbiome might provide noninvasive biomarkers for the early detection and classification of NSCLC.

Autoantibodies against tumor-associated antigens in sputum as biomarkers for lung cancer.

Tumor antigens (TAs) can initiate host immune responses and produce TA-associated autoantibody (TAAbs), potential cancer biomarkers. Sputum is directly generated from the upper and lower airways, and thus can be used as a surrogate sample for the diagnosis of lung cancer based on molecular analysis. To develop sputum TAAb biomarkers for the early detection of lung cancer, the leading cause of cancer death, we probed a protein microarray containing more than 9,000 antigens with sputum supernatants of a discovery set of 30 lung cancer patients and 30 cancer-free smokers. Twenty-eight TAs with higher reactivity in sputum of lung cancer cases vs. controls were identified. The diagnostic significance of TAAbs against the TAs was determined by enzyme-linked immunosorbent assays (ELISAs) in sputum of the discovery set and additional 166 lung cancer patients and 213 cancer-free smokers (validation set). Three sputum TAAbs against DDX6, ENO1, and 14-3-3ζ were developed as a biomarker panel with 81% sensitivity and 83% specificity for diagnosis of lung cancer, regardless of stages, locations, and histological types of lung tumors. This study provides the first evidence that sputum TAAbs could be used as biomarkers for the early detection of lung cancer.

Complex obstructive lung disease - A diagnostic and management conundrum.

Rheumatoid arthritis (RA) is a common autoimmune disease most well-known for its inflammatory, destructive polyarthropathy. Extraarticular manifestations of the disease may involve the respiratory system, including interstitial lung disease, pleural disease, pulmonary vascular abnormalities, and airways disease. Smoking is highly prevalent in the RA population, and may even have a synergistic effect in disease development and progression. In the diagnosis of pulmonary disease, this presents a unique diagnostic and therapeutic challenge. We present a case of a woman in her 50s who presented for evaluation of dyspnea and was found to have obstructive lung disease. In addition to RA, she had a significant smoking history and also owned pet birds, making definitive diagnosis difficult. Ultimately, chest imaging was crucial in identifying RA-related lung disease as the root cause of her symptoms, leading to successful treatment and symptom management.

Computed Tomography Angiography-Based Pulmonary Artery Volumetry as a Diagnostic Tool for Pulmonary Hypertension.

OBJECTIVES: We evaluated use of three-dimensional pulmonary artery volumes derived from computed tomography pulmonary angiography (CTPA) in a group with pulmonary hypertension (PH) compared with healthy controls as a tool for the diagnosis of PH. METHODS: Retrospective analysis was performed of 40 CTPA scans obtained within 90 days of right heart catheterization demonstrating PH. The CTPA scans of 40 age- and sex-matched patients without cardiopulmonary disease were used as comparison. Diameters and volumes of the pulmonary arteries were compared. RESULTS: Adjusted total volume of the main, right, and left proximal pulmonary arteries (PAvol) demonstrated area under the curve of 0.918 (95% confidence interval, 0.860-0.975) for detection of PH, comparable to main pulmonary artery diameter measurement. Area under the curve values for PAvol were higher in subgroups divided by sex and PH severity. CONCLUSIONS: Volumetric analysis of the proximal pulmonary arteries using CTPA is a promising diagnostic tool for PH in a real-world cohort.

Phenotypes of Bronchopulmonary Dysplasia in Adults.

Bronchopulmonary dysplasia (BPD), first described by Northway in 1967, is a process of neonatal lung injury that is most strongly associated with prematurity. The "old" form of the disease associated with the oxidative damage and volutrauma from perinatal mechanical ventilation has been increasingly supplanted by a "new" form resulting from interrupted growth of the lung at earlier stages of fetal development. Given the significant improvement in the survival of children with BPD since the 1980s, many more of these patients are living into adulthood and are being seen in adult pulmonary practices. In this review, we present three brief vignettes of patients from our practice to introduce three of the major patterns of disease seen in adult survivors of BPD, namely, asthma-like disease, obstructive lung disease, and pulmonary hypertension. Additional factors shown to affect the lives of adult BPD survivors are also discussed. Finally, we discuss insights into the process of transitioning these complex patients from pediatric to adult pulmonary practices. As survivors of BPD enter adulthood and continue to require specialty pulmonary care, awareness of the disease's varied manifestations and responses to treatment will become increasingly important.

A Non-Coding RNA Landscape of Bronchial Epitheliums of Lung Cancer Patients.

We propose to systematically identify a non-coding RNA (ncRNA) profile of exfoliated bronchial epitheliums of sputum from lung cancer patients. Bronchial epithelial cells enriched from sputum of 32 lung cancer patients and 33 cancer-free smokers were analyzed by next-generation sequencing to comprehensively characterize the ncRNA profiles. In addition, 108 miRNAs, 88 small nucleolar RNAs, 13 piwi-interacting RNAs, 6 transfer RNAs, 4 ribosomal RNAs, 19 small nuclear RNAs, and 25 long-noncoding (lnc) RNAs displayed a significantly different level in bronchial epitheliums of sputum of lung cancer patients versus cancer-free smokers (all <0.001). PCR analysis confirmed their different expression levels in the sputum specimens. A high expression of SNHG9, an lncRNA, was validated in 78 lung tumor tissues, and the expression was inversely associated with overall survival of lung cancer patients (p = 0.002). Knockdown of SNHG9 in cancer cells reduced the cell growth, proliferation, and invasion in vitro and tumorigenesis in vivo. The multiple differentially expressed ncRNAs in bronchial epitheliums may contribute to the development and progression of lung cancer and provide potential biomarkers and therapeutic targets for the disease.