Disparities across the continuum of lung cancer care: a review of recent literature.

PURPOSE OF REVIEW: Lung cancer remains the leading cause of cancer mortality worldwide. Health disparities have long been noted in lung cancer incidence and survival and persist across the continuum of care. Understanding the gaps in care that arise from disparities in lung cancer risk, screening, treatment, and survivorship are essential to guiding efforts to achieve equitable care. RECENT FINDINGS: Recent literature continues to show that Black people, women, and people who experience socioeconomic disadvantage or live in rural areas experience disparities throughout the spectrum of lung cancer care. Contributing factors include structural racism, lower education level and health literacy, insurance type, healthcare facility accessibility, inhaled carcinogen exposure, and unmet social needs. Promising strategies to improve lung cancer care equity include policy to reduce exposure to tobacco smoke and harmful pollutants, more inclusive lung cancer screening eligibility criteria, improved access and patient navigation in lung cancer screening, diagnosis and treatment, more deliberate offering of appropriate surgical and medical treatments, and improved availability of survivorship and palliative care. SUMMARY: Given ongoing disparities in lung cancer care, research to determine best practices for narrowing these gaps and to guide policy change are an essential focus of future lung cancer research.

Research Priorities for Interventions to Address Health Disparities in Lung Nodule Management: An Official American Thoracic Society Research Statement.

Background: Lung nodules are common incidental findings, and timely evaluation is critical to ensure diagnosis of localized-stage and potentially curable lung cancers. Rates of guideline-concordant lung nodule evaluation are low, and the risk of delayed evaluation is higher for minoritized groups. Objectives: To summarize the existing evidence, identify knowledge gaps, and prioritize research questions related to interventions to reduce disparities in lung nodule evaluation. Methods: A multidisciplinary committee was convened to review the evidence and identify key knowledge gaps in four domains: 1) research methodology, 2) patient-level interventions, 3) clinician-level interventions, and 4) health system-level interventions. A modified Delphi approach was used to identify research priorities. Results: Key knowledge gaps included 1) a lack of standardized approaches to identify factors associated with lung nodule management disparities, 2) limited data evaluating the role of social determinants of health on disparities in lung nodule management, 3) a lack of certainty regarding the optimal strategy to improve patient-clinician communication and information transmission and/or retention, and 4) a paucity of information on the impact of patient navigators and culturally trained multidisciplinary teams. Conclusions: This statement outlines a research agenda intended to stimulate high-impact studies of interventions to mitigate disparities in lung nodule evaluation. Research questions were prioritized around the following domains: 1) need for methodologic guidelines for conducting research related to disparities in nodule management, 2) evaluating how social determinants of health influence lung nodule evaluation, 3) studying approaches to improve patient-clinician communication, and 4) evaluating the utility of patient navigators and culturally enriched multidisciplinary teams to reduce disparities.

Bronchial gene expression signature associated with rate of subsequent FEV1 decline in individuals with and at risk of COPD.

BACKGROUND: COPD is characterised by progressive lung function decline. Leveraging prior work demonstrating bronchial airway COPD-associated gene expression alterations, we sought to determine if there are alterations associated with differences in the rate of FEV1 decline. METHODS: We examined gene expression among ever smokers with and without COPD who at baseline had bronchial brushings profiled by Affymetrix microarrays and had longitudinal lung function measurements (n=134; mean follow-up=6.38±2.48 years). Gene expression profiles associated with the rate of FEV1 decline were identified by linear modelling. RESULTS: Expression differences in 171 genes were associated with rate of FEV1 decline (false discovery rate <0.05). The FEV1 decline signature was replicated in an independent dataset of bronchial biopsies from patients with COPD (n=46; p=0.018; mean follow-up=6.76±1.32 years). Genes elevated in individuals with more rapid FEV1 decline are significantly enriched among the genes altered by modulation of XBP1 in two independent datasets (Gene Set Enrichment Analysis (GSEA) p<0.05) and are enriched in mucin-related genes (GSEA p<0.05). CONCLUSION: We have identified and replicated an airway gene expression signature associated with the rate of FEV1 decline. Aspects of this signature are related to increased expression of XBP1-regulated genes, a transcription factor involved in the unfolded protein response, and genes related to mucin production. Collectively, these data suggest that molecular processes related to the rate of FEV1 decline can be detected in airway epithelium, identify a possible indicator of FEV1 decline and make it possible to detect, in an early phase, ever smokers with and without COPD most at risk of rapid FEV1 decline.

Hospitalization as an opportunity to engage underserved individuals in shared decision-making for lung cancer screening: results from two randomized pilot trials.

PURPOSE: Medicare requires tobacco dependence counseling and shared decision-making (SDM) for lung cancer screening (LCS) reimbursement. We hypothesized that initiating SDM during inpatient tobacco treatment visits would increase LCS among patients with barriers to proactively seeking outpatient preventive care. METHODS: We collected baseline assessments and performed two pilot randomized trials at our safety-net hospital. Pilot 1 tested feasibility, acceptability, and preliminary efficacy of a nurse practitioner initiating SDM for LCS during hospitalization (Inpatient SDM). We collected qualitative data on barriers encountered during Pilot 1. Pilot 2 added a community health worker (CHW) to address barriers to LCS completion (Inpatient SDM + CHW-navigation). For both studies, preliminary efficacy was an intention-to-treat analysis of LCS completion at 3 months between intervention and comparator (furnishing of LCS decision aid only) groups. RESULTS: Baseline assessments showed that patients preferred in-person LCS discussions versus self-reviewing materials; overall 20% had difficulty understanding written information. In Pilot 1, 4% (2/52) in Inpatient SDM versus 2% (1/48, comparator) completed LCS (p = 0.6), despite 89% (89/100) desiring LCS. Primary care providers noted that competing priorities and patient factors (e.g., social barriers to keeping appointments) prevented the intervention from working as intended. In Pilot 2, 50% (5/10) in Inpatient SDM + CHW-navigation versus 9% (1/11, comparator) completed LCS (p < 0.05). Many patients were ineligible due to recent diagnostic chest CT (Pilot 1: 255/659; Pilot 2: 239/527). CONCLUSIONS: Inpatient SDM + CHW-navigation shows promise to improve LCS rates among underserved patients who smoke, but feasibility is limited by recent diagnostic chest CT among inpatients. Implementing CHW-navigation in other clinical settings may facilitate LCS for underserved patients. TRAIL REGISTRATION: ClinicalTrials.gov Identifier: NCT03276806 (8 September 2017); NCT03793894 (4 January 2019).

Effect of long-term corticosteroid treatment on microRNA and gene-expression profiles in COPD.

The aim was to investigate whether microRNA (miRNA) expression is modulated by inhaled corticosteroid (ICS) treatmentWe performed genome-wide miRNA analysis on bronchial biopsies of 69 moderate/severe chronic obstructive pulmonary disease (COPD) patients at baseline and after 6- and 30-month treatment with the ICS fluticasone propionate or placebo. The effect of ICS on miRNA expression was validated in differentiated primary bronchial epithelial cultures, and functional studies were conducted in BEAS-2B cells. MiRNAs affected by ICS and their predicted targets were compared to an independent miRNA dataset of bronchial brushings from COPD patients and healthy controls.Treatment with ICS for both 6 and 30 months significantly altered the expression of four miRNAs, including miR-320d, which was increased during ICS treatment compared with placebo. The ICS-induced increase of miR-320d was confirmed in primary airway epithelial cells. MiR-320d negatively correlated targets were enriched for pro-inflammatory genes and were increased in the bronchial brushes of patients with lower lung function in the independent dataset. Overexpression of miR-320d in BEAS-2B cells dampened cigarette smoke extract-induced pro-inflammatory activity via inhibition of nuclear factor-κB.Collectively, we identified miR-320d as a novel mediator of ICS, regulating the pro-inflammatory response of the airway epithelium.

Nasal gene expression differentiates COPD from controls and overlaps bronchial gene expression.

BACKGROUND: Nasal gene expression profiling is a promising method to characterize COPD non-invasively. We aimed to identify a nasal gene expression profile to distinguish COPD patients from healthy controls. We investigated whether this COPD-associated gene expression profile in nasal epithelium is comparable with the profile observed in bronchial epithelium. METHODS: Genome wide gene expression analysis was performed on nasal epithelial brushes of 31 severe COPD patients and 22 controls, all current smokers, using Affymetrix Human Gene 1.0 ST Arrays. We repeated the gene expression analysis on bronchial epithelial brushes in 2 independent cohorts of mild-to-moderate COPD patients and controls. RESULTS: In nasal epithelium, 135 genes were significantly differentially expressed between severe COPD patients and controls, 21 being up- and 114 downregulated in COPD (false discovery rate < 0.01). Gene Set Enrichment Analysis (GSEA) showed significant concordant enrichment of COPD-associated nasal and bronchial gene expression in both independent cohorts (FDRGSEA < 0.001). CONCLUSION: We identified a nasal gene expression profile that differentiates severe COPD patients from controls. Of interest, part of the nasal gene expression changes in COPD mimics differentially expressed genes in the bronchus. These findings indicate that nasal gene expression profiling is potentially useful as a non-invasive biomarker in COPD. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT01351792 (registration date May 10, 2011), ClinicalTrials.gov registration number NCT00848406 (registration date February 19, 2009), ClinicalTrials.gov registration number NCT00807469 (registration date December 11, 2008).

Asthma-COPD overlap. Clinical relevance of genomic signatures of type 2 inflammation in chronic obstructive pulmonary disease.

RATIONALE: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and likely includes a subgroup that is biologically comparable to asthma. Studying asthma-associated gene expression changes in COPD could add insight into COPD pathogenesis and reveal biomarkers that predict a favorable response to corticosteroids. OBJECTIVES: To determine whether asthma-associated gene signatures are increased in COPD and associated with asthma-related features. METHODS: We compared disease-associated airway epithelial gene expression alterations in an asthma cohort (n = 105) and two COPD cohorts (n = 237, 171). The T helper type 2 (Th2) signature (T2S) score, a gene expression metric induced in Th2-high asthma, was evaluated in these COPD cohorts. The T2S score was correlated with asthma-related features and response to corticosteroids in COPD in a randomized, placebo-controlled trial, the Groningen and Leiden Universities study of Corticosteroids in Obstructive Lung Disease (GLUCOLD; n = 89). MEASUREMENTS AND MAIN RESULTS: The 200 genes most differentially expressed in asthma versus healthy control subjects were enriched among genes associated with more severe airflow obstruction in these COPD cohorts (P < 0.001), suggesting significant gene expression overlap. A higher T2S score was associated with decreased lung function (P < 0.001), but not asthma history, in both COPD cohorts. Higher T2S scores correlated with increased airway wall eosinophil counts (P = 0.003), blood eosinophil percentage (P = 0.03), bronchodilator reversibility (P = 0.01), and improvement in hyperinflation after corticosteroid treatment (P = 0.019) in GLUCOLD. CONCLUSIONS: These data identify airway gene expression alterations that can co-occur in asthma and COPD. The association of the T2S score with increased severity and "asthma-like" features (including a favorable corticosteroid response) in COPD suggests that Th2 inflammation is important in a COPD subset that cannot be identified by clinical history of asthma.

Gene-expression profiling of buccal epithelium among non-smoking women exposed to household air pollution from smoky coal.

In China's rural counties of Xuanwei and Fuyuan, lung cancer rates are among the highest in the world. While the elevated disease risk in this population has been linked to the usage of smoky (bituminous) coal as compared to smokeless (anthracite) coal, the underlying molecular changes associated with this exposure remains unclear. To understand the physiologic effects of smoky coal exposure, we analyzed the genome-wide gene-expression profiles in buccal epithelial cells collected from healthy, non-smoking female residents of Xuanwei and Fuyuan who burn smoky (n = 26) and smokeless (n = 9) coal. Gene-expression was profiled via microarrays, and changes associated with coal type were correlated to household levels of fine particulate matter (PM2.5) and polycyclic aromatic hydrocarbons (PAHs). Expression levels of 282 genes were altered with smoky versus smokeless coal exposure (P < 0.005), including the 2-fold increase of proinflammatory IL8 and decrease of proapoptotic CASP3. This signature was more correlated with carcinogenic PAHs (e.g. Benzo[a]pyrene; r = 0.41) than with non-carcinogenic PAHs (e.g. Fluorene; r = 0.08) or PM2.5 (r = 0.05). Genes altered with smoky coal exposure were concordantly enriched with tobacco exposure in previously profiled buccal biopsies of smokers and non-smokers (GSEA, q < 0.05). This is the first study to identify a signature of buccal epithelial gene-expression that is associated with smoky coal exposure, which in part is similar to the molecular response to tobacco smoke, thereby lending biologic plausibility to prior epidemiological studies that have linked this exposure to lung cancer risk.

Translating the transcriptome into tools for the early detection and prevention of lung cancer.

Despite advances in the management of lung cancer, this disease remains a significant global health burden with survival rates that have not significantly improved in decades. The mortality reduction achieved by low-dose helical CT (LDCT) screening of select high-risk patients is challenged by the high false positive rate of this screening modality and the potential for morbidity associated with follow-up diagnostic evaluation in patients with high risk for iatrogenic complications. The diagnostic dilemma of the indeterminate nodule incidentally identified on diagnostic or screening CT has created a need for reliable biomarkers capable of distinguishing benign from malignant disease. Furthermore, there is an urgent need to develop molecular biomarkers to supplement clinical risk models in order to identify patients at highest risk for having an early stage lung cancer that may derive the greatest benefit from LDCT screening, as well as identifying patients at high-risk for developing lung cancer that may be candidates for emerging chemopreventive strategies. Evolving bioinformatic techniques and the application of these algorithms to analyse the transcriptomic changes associated with lung cancer promise translational discoveries that can bridge these large clinical gaps. The identification of lung cancer associated transcriptomic alterations in readily accessible tissue sampling sites offers the potential to develop early diagnostic and risk stratification strategies applicable to large populations. This review summarises the challenges associated with the early detection, screening and chemoprevention of lung cancer with an emphasis on how genomic information encapsulated by the transcriptome can facilitate future innovations in these clinical settings.

Interaction of cigarette exposure and airway epithelial cell gene expression.

Cigarette smoking is responsible for lung cancer and chronic obstructive pulmonary disease (COPD), the leading cause of death from cancer and the second-leading cause of death in the United States. In the United States, 46 million people smoke, with an equal number of former smokers. Moreover, 20-25% of current or former smokers will develop either disease, and smokers with one disease are at increased risk for developing the other. There are no tools for predicting risk of developing either disease; no accepted tools for early diagnosis of potentially curable lung cancer; and no tools for defining molecular pathways or molecular subtypes of these diseases, for predicting rate of progression, or for assessing response to therapy at a biochemical or molecular level. This review discusses current studies and the future potential of measuring global gene expression in epithelial cells that are in the airway field of injury and of using the genomic information derived to begin to answer some of the above questions.

DNA methylation is globally disrupted and associated with expression changes in chronic obstructive pulmonary disease small airways.

DNA methylation is an epigenetic modification that is highly disrupted in response to cigarette smoke and involved in a wide spectrum of malignant and nonmalignant diseases, but surprisingly not previously assessed in small airways of patients with chronic obstructive pulmonary disease (COPD). Small airways are the primary sites of airflow obstruction in COPD. We sought to determine whether DNA methylation patterns are disrupted in small airway epithelia of patients with COPD, and evaluate whether changes in gene expression are associated with these disruptions. Genome-wide methylation and gene expression analysis were performed on small airway epithelial DNA and RNA obtained from the same patient during bronchoscopy, using Illumina's Infinium HM27 and Affymetrix's Genechip Human Gene 1.0 ST arrays. To control for known effects of cigarette smoking on DNA methylation, methylation and gene expression profiles were compared between former smokers with and without COPD matched for age, pack-years, and years of smoking cessation. Our results indicate that aberrant DNA methylation is (1) a genome-wide phenomenon in small airways of patients with COPD, and (2) associated with altered expression of genes and pathways important to COPD, such as the NF-E2-related factor 2 oxidative response pathway. DNA methylation is likely an important mechanism contributing to modulation of genes important to COPD pathology. Because these methylation events may underlie disease-specific gene expression changes, their characterization is a critical first step toward the development of epigenetic markers and an opportunity for developing novel epigenetic therapeutic interventions for COPD.

Airway gene expression in COPD is dynamic with inhaled corticosteroid treatment and reflects biological pathways associated with disease activity.

BACKGROUND: A core feature of chronic obstructive pulmonary disease (COPD) is the accelerated decline in forced expiratory volume in one second (FEV1). The recent Groningen and Leiden Universities study of Corticosteroids in Obstructive Lung Disease (GLUCOLD) study suggested that particular phenotypes of COPD benefit from fluticasone±salmeterol by reducing the rate of FEV1 decline, yet the underlying mechanisms are unknown. METHODS: Whole-genome gene expression profiling using the Affymetrix Gene ST array (V.1.0) was performed on 221 bronchial biopsies available from 89 COPD patients at baseline and after 6 and 30 months of fluticasone±salmeterol and placebo treatment in GLUCOLD. RESULTS: Linear mixed effects modelling revealed that the expression of 138 genes decreased, whereas the expression of 140 genes significantly upregulated after both 6 and 30 months of treatment with fluticasone±salmeterol versus placebo. A more pronounced treatment-induced change in the expression of 50 and 55 of these 278 genes was associated with a lower rate of decline in FEV1 and Saint George Respiratory Questionnaire, respectively. Genes decreasing with treatment were involved in pathways related to cell cycle, oxidative phosphorylation, epithelial cell signalling, p53 signalling and T cell signalling. Genes increasing with treatment were involved in pathways related to focal adhesion, gap junction and extracellular matrix deposition. Finally, the fluticasone-induced gene expression changes were enriched among genes that change in the airway epithelium in smokers with versus without COPD in an independent data set. CONCLUSIONS: The present study suggests that gene expression in biological pathways of COPD is dynamic with treatment and reflects disease activity. This study opens the gate to targeted and molecular phenotype-driven therapy of COPD.

Genetic regulation of gene expression in the lung identifies CST3 and CD22 as potential causal genes for airflow obstruction.

BACKGROUND: COPD is a complex chronic disease with poorly understood pathogenesis. Integrative genomic approaches have the potential to elucidate the biological networks underlying COPD and lung function. We recently combined genome-wide genotyping and gene expression in 1111 human lung specimens to map expression quantitative trait loci (eQTL). OBJECTIVE: To determine causal associations between COPD and lung function-associated single nucleotide polymorphisms (SNPs) and lung tissue gene expression changes in our lung eQTL dataset. METHODS: We evaluated causality between SNPs and gene expression for three COPD phenotypes: FEV(1)% predicted, FEV(1)/FVC and COPD as a categorical variable. Different models were assessed in the three cohorts independently and in a meta-analysis. SNPs associated with a COPD phenotype and gene expression were subjected to causal pathway modelling and manual curation. In silico analyses evaluated functional enrichment of biological pathways among newly identified causal genes. Biologically relevant causal genes were validated in two separate gene expression datasets of lung tissues and bronchial airway brushings. RESULTS: High reliability causal relations were found in SNP-mRNA-phenotype triplets for FEV(1)% predicted (n=169) and FEV(1)/FVC (n=80). Several genes of potential biological relevance for COPD were revealed. eQTL-SNPs upregulating cystatin C (CST3) and CD22 were associated with worse lung function. Signalling pathways enriched with causal genes included xenobiotic metabolism, apoptosis, protease-antiprotease and oxidant-antioxidant balance. CONCLUSIONS: By using integrative genomics and analysing the relationships of COPD phenotypes with SNPs and gene expression in lung tissue, we identified CST3 and CD22 as potential causal genes for airflow obstruction. This study also augmented the understanding of previously described COPD pathways.

Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer.

Lung cancer is the leading cause of death from cancer in the US and the world. The high mortality rate (80-85% within 5 years) results, in part, from a lack of effective tools to diagnose the disease at an early stage. Given that cigarette smoke creates a field of injury throughout the airway, we sought to determine if gene expression in histologically normal large-airway epithelial cells obtained at bronchoscopy from smokers with suspicion of lung cancer could be used as a lung cancer biomarker. Using a training set (n = 77) and gene-expression profiles from Affymetrix HG-U133A microarrays, we identified an 80-gene biomarker that distinguishes smokers with and without lung cancer. We tested the biomarker on an independent test set (n = 52), with an accuracy of 83% (80% sensitive, 84% specific), and on an additional validation set independently obtained from five medical centers (n = 35). Our biomarker had approximately 90% sensitivity for stage 1 cancer across all subjects. Combining cytopathology of lower airway cells obtained at bronchoscopy with the biomarker yielded 95% sensitivity and a 95% negative predictive value. These findings indicate that gene expression in cytologically normal large-airway epithelial cells can serve as a lung cancer biomarker, potentially owing to a cancer-specific airway-wide response to cigarette smoke.

A dynamic bronchial airway gene expression signature of chronic obstructive pulmonary disease and lung function impairment.

RATIONALE: Molecular phenotyping of chronic obstructive pulmonary disease (COPD) has been impeded in part by the difficulty in obtaining lung tissue samples from individuals with impaired lung function. OBJECTIVES: We sought to determine whether COPD-associated processes are reflected in gene expression profiles of bronchial airway epithelial cells obtained by bronchoscopy. METHODS: Gene expression profiling of bronchial brushings obtained from 238 current and former smokers with and without COPD was performed using Affymetrix Human Gene 1.0 ST Arrays. MEASUREMENTS AND MAIN RESULTS: We identified 98 genes whose expression levels were associated with COPD status, FEV1% predicted, and FEV1/FVC. In silico analysis identified activating transcription factor 4 (ATF4) as a potential transcriptional regulator of genes with COPD-associated airway expression, and ATF4 overexpression in airway epithelial cells in vitro recapitulates COPD-associated gene expression changes. Genes with COPD-associated expression in the bronchial airway epithelium had similarly altered expression profiles in prior studies performed on small-airway epithelium and lung parenchyma, suggesting that transcriptomic alterations in the bronchial airway epithelium reflect molecular events found at more distal sites of disease activity. Many of the airway COPD-associated gene expression changes revert toward baseline after therapy with the inhaled corticosteroid fluticasone in independent cohorts. CONCLUSIONS: Our findings demonstrate a molecular field of injury throughout the bronchial airway of active and former smokers with COPD that may be driven in part by ATF4 and is modifiable with therapy. Bronchial airway epithelium may ultimately serve as a relatively accessible tissue in which to measure biomarkers of disease activity for guiding clinical management of COPD.

Efficacy of Digital Outreach Strategies for Collecting Smoking Data: Pragmatic Randomized Trial.

BACKGROUND: Tobacco smoking is an important risk factor for disease, but inaccurate smoking history data in the electronic medical record (EMR) limits the reach of lung cancer screening (LCS) and tobacco cessation interventions. Patient-generated health data is a novel approach to documenting smoking history; however, the comparative effectiveness of different approaches is unclear. OBJECTIVE: We designed a quality improvement intervention to evaluate the effectiveness of portal questionnaires compared to SMS text message-based surveys, to compare message frames, and to evaluate the completeness of patient-generated smoking histories. METHODS: We randomly assigned patients aged between 50 and 80 years with a history of tobacco use who identified English as a preferred language and have never undergone LCS to receive an EMR portal questionnaire or a text survey. The portal questionnaire used a "helpfulness" message, while the text survey tested frame types informed by behavior economics ("gain," "loss," and "helpfulness") and nudge messaging. The primary outcome was the response rate for each modality and framing type. Completeness and consistency with documented structured smoking data were also evaluated. RESULTS: Participants were more likely to respond to the text survey (191/1000, 19.1%) compared to the portal questionnaire (35/504, 6.9%). Across all text survey rounds, patients were less responsive to the "helpfulness" frame compared with the "gain" frame (odds ratio [OR] 0.29, 95% CI 0.09-0.91; P<.05) and "loss" frame (OR 0.32, 95% CI 11.8-99.4; P<.05). Compared to the structured data in the EMR, the patient-generated data were significantly more likely to be complete enough to determine LCS eligibility both compared to the portal questionnaire (OR 34.2, 95% CI 3.8-11.1; P<.05) and to the text survey (OR 6.8, 95% CI 3.8-11.1; P<.05). CONCLUSIONS: We found that an approach using patient-generated data is a feasible way to engage patients and collect complete smoking histories. Patients are likely to respond to a text survey using "gain" or "loss" framing to report detailed smoking histories. Optimizing an SMS text message approach to collect medical information has implications for preventative and follow-up clinical care beyond smoking histories, LCS, and smoking cessation therapy.

Successful management of suspected propofol dependence with phenobarbital in an adult patient with COVID-19.

PURPOSE: In critically ill patients, high sedation requirements for prolonged durations are often needed to achieve ventilator synchrony, a practice that was particularly common during the early stages of the coronavirus disease 2019 (COVID-19) pandemic. We report the successful use of phenobarbital to facilitate propofol weaning after prolonged medication exposure. SUMMARY: A 64-year-old male with hypertension was admitted for the management of acute respiratory distress syndrome due to COVID-19 pneumonia. The patient received high doses of fentanyl and propofol with periods of concomitant midazolam and dexmedetomidine throughout his prolonged time on mechanical ventilation. Total days of exposure were 19 for fentanyl, 17 for propofol, 12 for midazolam, and 15 for dexmedetomidine. Upon improvement in lung function, attempts to wean the patient from propofol all failed due to symptoms such as tachypnea, tachycardia, and hypertension, with symptom resolution only upon return to the previous dose. Phenobarbital was trialed for possible propofol withdrawal syndrome, allowing for a dose reduction of 10 µg/kg/min within 2 hours of the first dose without any corresponding symptoms. The patient continued to receive intermittent doses of phenobarbital for another 36 hours until propofol was discontinued. He underwent tracheostomy shortly after weaning off all sedation and was discharged to rehab 34 days after his initial admission. CONCLUSION: Information concerning propofol withdrawal syndrome in the literature is limited. Our experience demonstrates the successful use of phenobarbital to facilitate propofol weaning after prolonged exposure.

Black Race Remains Associated with Lower Eligibility for Screening Using 2021 US Preventive Services Task Force Recommendations Among Lung Cancer Patients at an Urban Safety Net Hospital.

OBJECTIVE: To evaluate whether the revised US Preventive Services Task Force (USPSTF) criteria reduced inequities in lung cancer screening (LCS) eligibility among a racially diverse sample of patients with lung cancer. METHODS: This is a retrospective analysis of adults diagnosed with primary lung malignancies at an urban safety net hospital. For all patients and exclusively ever-smokers, χ2 tests were used to evaluate differences in LCS eligibility among socio-demographic variables using the 2013 and 2021 USPSTF criteria. Patients who were ineligible for LCS were categorized by reason for exclusion. RESULTS: Among 678 lung cancer patients (46% female, mean age 66 ± 10 years), 51% were White, and 39% were Black. Using the 2013 guidelines, White patients (57%) would have been more likely to be eligible than Black (37%) and other-race patients (35%) (P < 0.0001) at time of cancer diagnosis. Under the 2021 guidelines, White patients (68%) remained more likely to be eligible for LCS than Black (54%) and other-race patients (48%) (P = 0.0002). Among exclusively ever-smoking patients, we did not observe a significant difference in eligibility by race under the 2021 USPSTF guidelines (White [73%], Black [65%], and other-race [65%]; [P = 0.48]). Sex, ethnicity, education level, and insurance type were not associated with differential screening eligibility under either the 2013 or 2021 guidelines. CONCLUSION: The revised 2021 USPSTF LCS guidelines may not be sufficient to eliminate racial inequities in LCS eligibility among patients who go on to be diagnosed with primary lung cancer. Differential rates of lung cancer among never-smokers may contribute to this inequity.