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Patient understanding of chest low-dose CT (LDCT) scan results for lung cancer screening (LCS) may impact outcomes.What are patient- and clinician-identified gaps in understanding and communication of LCS results and how might communication be improved through a patient-oriented tool?We performed a mixed-methods study of participants recruited from a multisite LCS program to understand knowledge gaps after receiving LCS results and to guide development of a commonly asked questions (CAQ) after LCS information sheet. Initial patient surveys assessed understanding and reactions to LCS results (n = 190). We then conducted patient interviews and focus group discussions (n = 31) to understand experiences receiving LDCT scan results and reactions to results letters and the proposed CAQ; we also interviewed clinicians (n = 6) for feedback on these resources. We summarized survey responses and used thematic analysis to identify major themes in focus groups and interviews.Of 190 survey respondents (43% response rate), although 88% agreed that they "understood" their LCS results, only 55% reported understanding what a lung nodule is. Approximately two-thirds thought it was "very important" to receive more information regarding lung nodules and incidental lung and heart disease. In interviews and focus groups, although patients believed that brief results letters for normal LDCT scan results generally were acceptable, most found letters explaining abnormal LDCT scan and incidental findings to be concerning and not a substitute for discussion with their clinician. Nearly all patients expressed that the CAQ sheet provided helpful information on nodules, provided results reporting and incidental findings, and helped them form questions to ask their clinicians.We identified patient-reported information needs regarding LCS results and developed a CAQ information sheet that was refined with patient and clinician input. The CAQ may represent a simple and feasible way to improve LCS results reporting and to augment clinician-patient discussions.

Although the harmful effects of smoking after a cancer diagnosis have been clearly demonstrated, many patients continue to smoke cigarettes during treatment and beyond. The NCCN Guidelines for Smoking Cessation emphasize the importance of smoking cessation in all patients with cancer and seek to establish evidence-based recommendations tailored to the unique needs and concerns of patients with cancer. The recommendations contained herein describe interventions for cessation of all combustible tobacco products (eg, cigarettes, cigars, hookah), including smokeless tobacco products. However, recommendations are based on studies of cigarette smoking. The NCCN Smoking Cessation Panel recommends that treatment plans for all patients with cancer who smoke include the following 3 tenets that should be done concurrently: (1) evidence-based motivational strategies and behavior therapy (counseling), which can be brief; (2) evidence-based pharmacotherapy; and (3) close follow-up with retreatment as needed.

Annual lung cancer screening (LCS) has mortality benefits for eligible participants; however, studies demonstrate low adherence to follow-up LCS.What are patients' perspectives on barriers and facilitators to adherence to annual LCS?Forty participants enrolled in the University of Washington/Seattle Cancer Care Alliance LCS program completed a demographic questionnaire and a semistructured interview based on the Tailored Implementation in Chronic Diseases framework to determine attitudes, barriers, and facilitators to longitudinal LCS. Interviews were coded using principles of framework analysis to identify and compare themes between adherent and nonadherent participants.The 40 participants underwent initial LCS in 2017 with negative results. Seventeen were adherent to follow-up annual LCS, whereas 23 were not. Seven overall themes emerged from qualitative analysis, which are summarized as follows: (1) screening experiences are positive and participants have positive attitudes toward screening; (2) provider recommendation is a motivator and key facilitator for most patients; (3) many patients are influenced by personal factors and symptoms and do not understand the importance of asymptomatic screening; (4) common barriers to longitudinal screening include cost, insurance coverage, accessibility, and other medical conditions; (5) patients have variable preferences about how they receive their screening results, and many have residual questions about their results and future screening; (6) reminders are an important facilitator of annual screening; and (7) most patients think a navigator would be beneficial to the screening process, with different aspects of navigation thought to be most helpful. Those who were not adherent more commonly reported individual barriers to screening, competing health concerns, and less provider communication.Key facilitators (eg, patient reminders, provider recommendations) may improve long-term screening behavior, and a number of barriers to the screening process could be addressed through patient navigation.

Shared decision making (SDM) is an important part of lung cancer screening (LCS) that includes discussing the risks and benefits of screening, potential outcomes, patient eligibility and willingness to participate, tobacco cessation, and tailoring a strategy to an individual patient. More than other cancer screening tests, eligibility for LCS is nuanced, incorporating the patient's age as well as tobacco use history and overall health status. Since comorbidities and multimorbidity (ie, 2 or more comorbidities) impact the risks and benefits of LCS, these topics are a fundamental part of decision-making. However, there is currently little evidence available to guide clinicians in addressing comorbidities and an individual's "appropriateness" for LCS during SDM visits. Therefore, this literature review investigates the impact of comorbidities and multimorbidity among patients undergoing LCS. Based on available evidence and guideline recommendations, we identify comorbidities that should be considered during SDM conversations and review best practices for navigating SDM conversations in the context of LCS. Three conditions are highlighted since they concomitantly portend higher risk of developing lung cancer, potentially increase risk of screening-related evaluation and treatment complications and can be associated with limited life expectancy: chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and human immunodeficiency virus infection.

Objectives The relationship between marijuana use and markers of chronic lung disease in people living with HIV (PLWH) is poorly understood. Methods We performed a cross-sectional analysis of the Examinations of HIV-Associated Lung Emphysema (EXHALE) study, including 162 HIV-positive patients and 138 participants without HIV. We modelled marijuana exposure as: (i) current daily or weekly marijuana smoking vs. monthly or less often; or (ii) cumulative marijuana smoking (joint-years). Linear and logistic regression estimated associations between marijuana exposure and markers of lung disease, adjusted for tobacco smoking and other factors. Results In PLWH, current daily or weekly marijuana use was associated with a larger forced vital capacity (FVC), larger total lung capacity and increased odds of radiographic emphysema compared with marijuana non-smokers in adjusted models; these associations were not statistically significant in participants without HIV. Marijuana joint-years were associated with higher forced expiratory volume in 1 s and FVC in PLWH but not with emphysema. Conclusions In PLWH, marijuana smoking was associated with higher lung volumes and potentially with radiographic emphysema. No consistently negative associations were observed between marijuana and measures of chronic lung health.

BACKGROUND Chronic inflammation, innate immune activation, T-cell imbalance and endothelial activation have been linked with lung diseases. We sought to determine whether markers of these pathophysiologic pathways were associated with spirometry and chest computed tomography (CT) abnormalities among adolescents living with HIV (ALWH). SETTING Coptic Hope Center for Infectious Diseases in Nairobi, Kenya. METHODS We performed a cross-sectional study of ALWH (10-19 years old). Participants underwent chest CT, spirometry, and venipuncture for serum biomarkers. We also collected demographic, anthropometric, T-cell subset, antiretroviral therapy, and exposure data. We compared characteristics and biomarkers by airflow obstruction [postbronchodilator FEV1/FVC z-score (zFEV1/FVC) < -1.64]. We used multivariable linear regression to determine associations of log10-transformed biomarkers and chest CT abnormalities with lower postbronchodilator zFEV1/FVC (airflow limitation). We performed exploratory principal components analysis on biomarkers, and determined associations of factors with postbronchodilator zFEV1/FVC and chest CT abnormalities. RESULTS Of 47 participants with acceptable quality spirometry, 21 (45%) were female, median age was 13 years and 96% had perinatally-acquired HIV. Median CD4 was 672 cells/µL. Overall, 28% had airflow obstruction and 78% had a chest CT abnormality; airflow obstruction was associated with mosaic attenuation (P = 0.001). Higher endothelial activation (sVCAM-1, sICAM-1), inflammation and innate immune activation (serum amyloid-A, sTREM-1, sCD163), and T-cell imbalance (lower CD4/CD8) markers were associated with airflow limitation. Factors comprising endothelial and innate immune activation were associated with airflow limitation. CONCLUSIONS Endothelial activation, innate immune activation, T-cell imbalance, and chronic inflammation are associated with airflow limitation and obstruction, providing insights into chronic lung disease pathophysiology among ALWH.

RATIONALE Adherence to follow-up lung cancer screening (LCS) in real-world settings is suboptimal. Patient understanding of screening results and anticipated follow-up may be crucial to adherence. OBJECTIVE To determine patient-factors associated with identification of follow-up recommendations as a measure of patient understanding of screening results after LCS , and to determine whether misidentification of follow-up is associated with lower adherence to recommendations. METHODS We performed a prospective study of patients in the University of Washington/Seattle Cancer Care Alliance LCS registry who underwent an initial LCS exam between June 2017- September 2019. We mailed potential participants a survey following initial LCS exam, with additional data abstracted from the electronic health record and LCS registry. Participants were asked to identify the timing and next step for their follow-up, with answers corresponding to Lung-RADS recommendations. We examined associations between incorrect identification of recommended follow-up and patient-level characteristics, self-perceived benefit/harm of LCS, LCS knowledge, Lung-RADS score, and patient-reported method of LCS results communication (letter, telephone or in-person). We used multivariable logistic regression to evaluate associations with incorrect identification of recommendations and assessed incorrect identification of recommendations as a potential mechanism for poor adherence in a separate regression model. RESULTS One-hundred eighty-eight participants completed the survey (response rate 44%); 47% misidentified their follow-up recommendation. Those with lung-RADS scores ≥3 had higher odds of incorrectly identifying follow-up recommendations compared to those with scores

Chronic obstructive pulmonary disease (COPD) is common in people living with HIV (PLWH). We sought to evaluate the appropriateness of COPD diagnosis and management in PLWH, comparing results to HIV-uninfected persons. We conducted a cross-sectional analysis of Veterans enrolled in the Examinations of HIV-Associated Lung Emphysema study, in which all participants underwent spirometry at enrollment and reported respiratory symptoms on self-completed surveys. Primary outcomes were misdiagnosis and under-diagnosis of COPD, and the frequency and appropriateness of inhaler prescriptions. Misdiagnosis was defined as having an International Classification of Diseases (ICD)-9 diagnosis of COPD without spirometric airflow limitation (post-bronchodilator forced expiratory volume in 1-second [FEV1]/Forced vital capacity [FVC]

Highlights • The incidence of idiopathic pneumonia syndrome (IPS) is declining in a modern cohort of allogeneic hematopoietic cell transplantation (HCT) recipients. • Total body irradiation dose remains a significant risk factor for IPS development. • IPS is a rare but substantial cause of post-HCT morbidity and mortality., Our current knowledge of idiopathic pneumonia syndrome (IPS) predates improved specificity in the diagnosis of IPS and advances in hematopoietic cell transplantation (HCT) and critical care practices. In this study, we describe and update the incidence, risk factors, and outcomes of IPS. We performed a retrospective cohort study of all adults who underwent allogeneic HCT at the Fred Hutchinson Cancer Research Center between 2006 and 2013 (n = 1829). IPS was defined using the National Heart, Lung, and Blood Institute consensus definition: multilobar airspace opacities on chest imaging, absence of lower respiratory tract infection, and hypoxemia. We described IPS incidence and mortality within 120 and 365 days after HCT. We examined conditioning intensity (nonmyeloablative versus myeloablative with high-dose total body irradiation [TBI] versus myeloablative with low-dose TBI) as an IPS risk factor in a time-to-event analysis using Cox models, controlled for age at transplant, HLA matching, stem cell source, and pretransplant Lung function Score (a combined measure of impairment in Forced Expiratory Volume in the first second (FEV1) and Diffusion capacity for carbon monoxide (DLCO)). Among 1829 HCT recipients, 67 fulfilled IPS criteria within 120 days (3.7%). Individuals who developed IPS were more likely to be black/non-Hispanic versus other racial groups and have severe pulmonary impairment but were otherwise similar to participants without IPS. In adjusted models, myeloablative conditioning with high-dose TBI was associated with increased risk of IPS (hazard ratio, 2.5; 95% confidence interval, 1.2 to 5.2). Thirty-one patients (46.3%) with IPS died within the first 120 days of HCT and 47 patients (70.1%) died within 365 days of HCT. In contrast, among the 1762 patients who did not acquire IPS in the first 120 days, 204 (11.6%) died within 120 days of HCT and 510 (29.9%) died within 365 days of HCT. Our findings suggest that although the incidence of IPS may be declining, it remains associated with post-transplant mortality. Future study should focus on early detection and identifying pathologic mediators of IPS to facilitate timely, targeted therapies for those most susceptible to lung injury post-HCT.

Background Lung cancer screening (LCS) is effective at reducing mortality for high-risk smokers. Mortality benefits go beyond early cancer detection, because shared decision-making (SDM) may present a “teachable moment” to reinforce cessation and provide resources. Research Question How well is smoking cessation performed during LCS SDM encounters, and what patient and provider characteristics are associated with smoking cessation assistance? Study Design and Methods This is a retrospective cohort study of current smokers participating in initial LCS SDM through a multisite program in Seattle, Washington, between 2015-2018. The LCS tracking database and electronic health record were reviewed for demographics, comorbidity data, and clinical encounter information. The primary outcome was provision of a smoking cessation resource, defined as referral to cessation resources, recommendation for nicotine replacement, or prescription for cessation medication. Participant and provider factor associations with the outcome were evaluated using χ2 testing and multivariable logistic regression. Results Most of the 423 study participants were men (70%), with a median age of 61 (IQR, 58-66) years and median of 50 (41-72) pack-years of smoking. Only 26% of encounters had documentation consistent with SDM. Thirty-nine percent of participants received at least one smoking cessation resource, and only 5% received both counseling referrals and medication. In a multivariable model, the provision of any smoking cessation resource was half as likely in participants with higher levels of comorbidity (Charlson Index >2; OR, 0.53; 95% CI, 0.31-0.81), and half as likely if the ordering provider was not the patient’s PCP or their specialist (OR, 0.55; 95% CI, 0.32-0.96). Interpretation Overall provision of smoking cessation resources was moderate during SDM encounters for LCS, and lower in patients with more comorbidities and when not performed by the patient’s PCP or specialist. Interventions are needed to improve smoking cessation counseling and resource utilization at the time of LCS encounters.

Background: There are well-documented disparities in lung cancer outcomes across populations. Lung cancer screening (LCS) has the potential to reduce lung cancer mortality, but for this benefit to be realized by all high-risk groups, there must be careful attention to ensuring equitable access to this lifesaving preventive health measure.Objectives: To outline current knowledge on disparities in eligibility criteria for, access to, and implementation of LCS, and to develop an official American Thoracic Society statement to propose strategies to optimize current screening guidelines and resource allocation for equitable LCS implementation and dissemination.Methods: A multidisciplinary panel with expertise in LCS, implementation science, primary care, pulmonology, health behavior, smoking cessation, epidemiology, and disparities research was convened. Participants reviewed available literature on historical disparities in cancer screening and emerging evidence of disparities in LCS.Results: Existing LCS guidelines do not consider racial, ethnic, socioeconomic, and sex-based differences in smoking behaviors or lung cancer risk. Multiple barriers, including access to screening and cost, further contribute to the inequities in implementation and dissemination of LCS.Conclusions: This statement identifies the impact of LCS eligibility criteria on vulnerable populations who are at increased risk of lung cancer but do not meet eligibility criteria for screening, as well as multiple barriers that contribute to disparities in LCS implementation. Strategies to improve the selection and dissemination of LCS in vulnerable groups are described.

Despite a known mortality benefit, lung cancer screening (LCS) implementation has been unexpectedly slow. New programs face barriers to implementation, which may include lack of clinician engagement or beliefs that the intervention is not beneficial.To evaluate diverse clinician perspectives on their views of LCS and their experience with LCS implementation and processes.We performed a qualitative study of clinicians participating in LCS. Clinicians were drawn from three medical centers, representing diverse specialties and practice settings. All participants practiced at sites with formal lung cancer screening programs. We performed semi-structured interviews with probes designed to elicit opinions of LCS, perceived evidence gaps, and recommendations for improvements. Transcribed interviews were iteratively reviewed and coded using directed content analysis.Participants (n=24) included LCS coordinators, pulmonologists, physician and non-physician primary care providers (PCPs), a surgeon, and a radiologist. Most clinicians expressed that the evidence supporting LCS was adequate to support clinical adoption, though most PCPs had little direct knowledge and based decisions on local recommendations or endorsement by the US Preventative Services Task Force (USPSTF). Many PCPs endorsed lack of knowledge of eligibility requirements and screening strategy (e.g. annual while eligible). Clinicians with more lung cancer screening knowledge, including several PCPs, identified a number of gaps in the current evidence that tempered enthusiasm, including: unclear ideal screening interval, populations with high cancer risk that do not qualify under USPSTF, indications to stop screening, and the role of serious comorbidities. Support for centralized programs and LCS coordinators was strong, but not uniform. Clinicians were frustrated by time limitations during a patient encounter, costs to the patient, and issues with insurance coverage. Many gaps in informatics support were identified. Clinicians recommended working to improve informatics support, continuing to clarify clinician responsibilities, and working on increasing public awareness of LCS.Despite working within programs that have adopted many recommended care processes to support LCS, clinicians identified a number of issues in providing high-quality LCS. Many of these issues are best addressed by improved support of LCS within the electronic health record and continued education of staff and patients.

This population-based cohort study examines associations of voriconazole and other antifungal medications with risk of keratinocyte carcinomas in recipients of lung transplants., Key Points Question What is the association between voriconazole, an antifungal used to treat aspergillosis infections, and the risk of keratinocyte carcinomas among recipients of lung transplants? Findings In a population-based cohort study of 9599 non-Hispanic white recipients of 9793 lung transplants in the United States (2007-2016) with linkage to pharmacy claims, increasing cumulative voriconazole exposure was associated with an increased risk of cutaneous squamous cell carcinoma. Meaning These findings suggest that physicians caring for lung transplant recipients at high risk for aggressive keratinocyte carcinomas should limit voriconazole exposure when possible and encourage skin protection behaviors and more frequent cancer screenings., Importance The antifungal medication voriconazole is used to prevent and treat aspergillosis, a major cause of mortality among recipients of lung transplants (hereinafter referred to as lung recipients). Small studies suggest that voriconazole increases risk of cutaneous squamous cell carcinoma (SCC). Objective To examine associations of voriconazole and other antifungal medications with risk of keratinocyte carcinomas (SCC and cutaneous basal cell carcinoma [BCC]) in lung recipients. Design, Setting, and Participants This population-based cohort study included non-Hispanic white patients (n = 9599) who underwent lung transplant in the United States from January 1, 2007, to December 31, 2016, identified through the national Scientific Registry of Transplant Recipients with data linkable to pharmacy claims. Data were analyzed from March 1, 2018, to February 13, 2019. Exposures Antifungal medication use, including voriconazole, itraconazole, posaconazole, and other antifungals, was ascertained from pharmacy claims and treated as a time-varying exposure (assessed every 30 days). Cumulative antifungal exposure was calculated as the total number of exposed months. Main Outcomes and Measures Primary outcomes were the first SCC or BCC reported to the transplant registry by transplant centers. Follow-up began at transplant and ended at SCC or BCC diagnosis, transplant failure or retransplant, death, loss to follow-up, or December 31, 2016. Cox proportional hazards regression models were used to estimate adjusted hazard ratios (AHRs) for each antifungal medication. Results Among the 9793 lung transplants in 9599 recipients included in the analysis, median age at transplant was 59 (interquartile range [IQR], 48-65) years, 5824 (59.5%) were male, and 5721 (58.4%) reported ever smoking. During a median follow-up of 3.0 (IQR, 1.4-5.0) years after transplant, 1031 SCCs (incidence, 322 per 10 000 person-years) and 347 BCCs (incidence, 101 per 10 000 person-years) were reported. Compared with lung recipients with no observed voriconazole use, those with 1 to 3 months of voriconazole use experienced increased AHR for SCC of 1.09 (95% CI, 0.90-1.31); 4 to 7 months, 1.42 (95% CI, 1.16-1.73); 8 to 15 months, 2.04 (95% CI, 1.67-2.50); and more than 15 months, 3.05 (95% CI, 2.37-3.91). Ever itraconazole exposure was associated with increased SCC risk (AHR, 1.20; 95% CI, 1.00-1.45). For BCC, risk was not associated with voriconazole use but was increased with itraconazole use (AHR, 1.74; 95% CI, 1.27-2.37) or posaconazole use (AHR, 1.55; 95% CI, 1.00-2.41). Conclusions and Relevance In this study, voriconazole use was associated with increased SCC risk among lung recipients, especially after prolonged exposure. Further research evaluating the risk-benefit ratio of shorter courses or alternative medications in transplant recipients at high risk for SCC should be considered.

Objective: Lung cancer is the leading cause of non-AIDS-defining cancer deaths among HIV-infected individuals. Although lung cancer screening with low-dose computed tomography (LDCT) is endorsed by multiple national organizations, whether HIV-infected individuals would have similar benefit as uninfected individuals from lung cancer screening is unknown. Our objective was to determine the benefits and harms of lung cancer screening among HIV-infected individuals. Design: We modified an existing simulation model, the Lung Cancer Policy Model, for HIV-infected patients. Data sources: Veterans Aging Cohort Study, Kaiser Permanente Northern California HIV Cohort, and medical literature. Target population : HIV-infected current and former smokers. Time horizon : Lifetime. Perspective : Population. Intervention: Annual LDCT screening from ages 45, 50, or 55 until ages 72 or 77 years. Main outcome measures: Benefits assessed included lung cancer mortality reduction and life-years gained; harms assessed included numbers of LDCT examinations, false-positive results, and overdiagnosed cases. Results of base-case analysis: For HIV-infected patients with CD4+ cell count at least 500 cells/μl and 100% antiretroviral therapy adherence, screening using the Centers for Medicare & Medicaid Services criteria (age 55–77, 30 pack-years of smoking, current smoker or quit within 15 years of screening) would reduce lung cancer mortality by 18.9%, similar to the mortality reduction of uninfected individuals. Alternative screening strategies utilizing lower screening age and/or pack-years criteria increase mortality reduction, but require more LDCT examinations. Limitations: Strategies assumed 100% screening adherence. Conclusion: Lung cancer screening reduces mortality in HIV-infected patients with CD4+ cell count at least 500 cells/μl, with a number of efficient strategies for eligibility, including the current Centers for Medicare & Medicaid Services criteria.

Objective Lung cancer screening may benefit HIV-infected (HIV) smokers because of an elevated risk of lung cancer, but may have unique harms because of HIV-specific risk factors for false-positive screens. This study seeks to understand whether inflammatory biomarkers and markers of chronic lung disease are associated with noncalcified nodules at least 4 mm (NCN) in HIV compared with uninfected patients. Design This is a cohort study of Examinations of HIV-Associated Lung Emphysema (EXHALE), including 158 HIV and 133 HIV-uninfected participants. Methods Participants underwent a laboratory assessment [including measurement of D-dimer, interleukin 6, and soluble CD14 (sCD14)], chest computed tomography (CT), and pulmonary function testing. We created multivariable logistic regression models to determine predictors of NCN in the participants stratified by HIV status, with attention to semiqualitative scoring of radiographic emphysema, markers of pulmonary function, and inflammatory biomarkers. Results Of the 291 participants, 69 had NCN on chest CT. As previously reported, there was no difference in prevalence of these nodules by HIV status. Emphysema and elevated sCD14 demonstrated an association with NCN in HIV participants independent of smoking status, CD4 cell count, HIV viral load, and pulmonary function. Conclusion Emphysema and sCD14, a marker of immune activation, was associated with a higher prevalence of NCN on chest CT in HIV participants. Patients with chronic immune activation and emphysema may be at higher risk for both false-positive findings and incident lung cancer, thus screening in this group requires further study to understand the balance of benefits and harms.

Rationale: Lung cancer screening with low-dose chest computed tomography decreases mortality for high-risk current or former smokers. Lifetime smoking intensity (cigarette pack-years), an essential...

Background Lung cancer screening, despite its proven mortality benefit, remains vastly underutilized. Previous studies examined knowledge, attitudes, and beliefs to better understand the reasons underlying the low screening rates. These investigations may have limited generalizability because of traditional participant recruitment strategies and examining only subpopulations eligible for screening. The current study used crowdsourcing to recruit a broader population to assess these factors in a potentially more general population. Methods A 31-item survey was developed to assess knowledge, attitudes, and beliefs regarding screening among individuals considered high risk for lung cancer by the United States Preventive Services Task Force. Amazon's crowdsourcing platform (Mechanical Turk) was used to recruit subjects. Results Among the 240 respondents who qualified for the study, 106 (44%) reported knowledge of a screening test for lung cancer. However, only 36 (35%) correctly identified low-dose CT scanning as the appropriate test. A total of 222 respondents (93%) reported believing that early detection of lung cancer has the potential to save lives, and 165 (69%) were willing to undergo lung cancer screening if it was recommended by their physician. Multivariable regression analysis found that knowledge of lung cancer screening, smoking status, chronic pulmonary disease, and belief in the efficacy of early detection of lung cancer were associated with willingness to screen. Conclusions Although a minority of individuals at high risk for lung cancer are aware of screening, the majority believe that early detection saves lives and would pursue screening if recommended by their primary care physician. Health systems may increase screening rates by improving patient and physician awareness of lung cancer screening.

Pulmonary complications remain among the most frequent causes of morbidity and mortality for individuals with HIV despite the advent of antiretroviral therapy (ART) and improvement in its efficacy and availability. The prevalence of non-infectious pulmonary diseases is rising in this population, reflecting both an increase in smoking and the independent risk associated with HIV. The unique mechanisms of pulmonary disease in these patients remain poorly understood, and direct effects of HIV, genetic predisposition, inflammatory pathways, and co-infections have all been implicated. Lung cancer, chronic obstructive pulmonary disease (COPD), and pulmonary hypertension are the most prevalent non-infectious pulmonary diseases in persons with HIV, and the risk of each of these diseases is higher among HIV-infected (HIV+) persons than in the general population. This review discusses the latest advances in the literature on these important complications of HIV infection.

Lung cancer screening with low-dose chest CT has been demonstrated to reduce lung cancer mortality among a subset of high-risk current and former smokers. Despite randomized trial evidence and widespread guideline recommendations, uptake of lung cancer screening among currently eligible individuals remains poor. Recent studies estimate that less than 5% of all eligible individuals have undergone screening. Moreover, inappropriate screening of ineligible individuals seems to be common, and among those who have been screened, follow-up may also be poor. In this review, the authors examine recent studies demonstrating the current state of suboptimal implementation of lung cancer screening. The authors also introduce both patient- and provider-facing evidence-based interventions that may improve implementation of screening. These include tailored navigation interventions to overcome patient barriers throughout the screening care continuum and interventions to improve the identification of eligible individuals for providers. Further evidence on best practices around the implementation of lung cancer screening is essential to ensure that recent evidence can be translated into practice to improve the early detection of lung cancer for high-risk individuals.

Author(s): Triplette, Matthew; Justice, Amy; Attia, Engi F; Tate, Janet; Brown, Sheldon T; Goetz, Matthew Bidwell; Kim, Joon W; Rodriguez-Barradas, Maria C; Hoo, Guy W Soo; Wongtrakool, Cherry; Akgun, Kathleen; Crothers, Kristina | Abstract: OBJECTIVE:Aging people living with HIV (PLWH) face an increased burden of comorbidities, including chronic obstructive pulmonary disease (COPD). The impact of COPD on mortality in HIV remains unclear. We examined associations between markers of COPD and mortality among PLWH and uninfected study participants. DESIGN:Longitudinal analysis of the Examinations of HIV-Associated Lung Emphysema (EXHALE) cohort study. METHODS:EXHALE includes 196 PLWH and 165 uninfected smoking-matched study participants who underwent pulmonary function testing and computed tomography (CT) to define COPD and were followed. We determined associations between markers of COPD with mortality using multivariable Cox regression models, adjusted for smoking and the Veterans Aging Cohort Study (VACS) Index, a validated predictor of mortality in HIV. RESULTS:Median follow-up time was 6.9 years; the mortality rate was 2.7/100 person-years among PLWH and 1.7/100 person-years among uninfected study participants (P = 0.11). The VACS Index was associated with mortality in both PLWH and uninfected study participants. In multivariable models, pulmonary function and CT characteristics defining COPD were associated with mortality in PLWH: those with airflow obstruction (forced expiratory volume in 1 s/ forced vital capacity l0.7) had 3.1 times the risk of death [hazard ratio 3.1 (95% confidence interval 1.4-7.1)], compared with those without; those with emphysema (g10% burden) had 2.4 times the risk of death [hazard ratio 2.4 (95% confidence interval 1.1-5.5)] compared with those with ≤ 10% emphysema. In uninfected subjects, pulmonary variables were not significantly associated with mortality, which may reflect fewer deaths limiting power. CONCLUSION:Markers of COPD were associated with greater mortality in PWLH, independent of the VACS Index. COPD is likely an important contributor to mortality in contemporary PLWH.

Lung cancer screening has a mortality benefit to high-risk smokers, but implementation remains suboptimal. Providers represent the key entry point to screening, and an understanding of provider perspectives on lung cancer screening is necessary to improve referral and overall implementation.The objective of this study was to understand knowledge, beliefs, attitudes, barriers, and facilitators to screening in a diverse group of referring pulmonologists and primary care providers.We conducted an electronic survey of primary care and pulmonary providers within a tertiary care medical center across different practice sites. The survey covered the following domains: 1) beliefs and assessment of evidence, 2) knowledge of lung cancer screening and guidelines, 3) current screening practices, 4) barriers and facilitators, and 5) demographic and practice characteristics.The 196 participants included 80% primary care clinicians and 19% pulmonologists (1% others). Forty-one percent practiced at university-based or affiliated clinics, 47% at county hospital-based clinics, and 12% at other or unidentified sites. The majority endorsed lung cancer screening effectiveness (74%); however, performance on knowledge-based assessments of screening eligibility, documentation, and nodule management was suboptimal. Key barriers included inadequate time (36%), inadequate staffing (36%), and patients having too many other illnesses to address screening (38%). Decision aids, which are used at the point of referral, were commonly identified both as important lung cancer screening clinical facilitators (51%) and as provider knowledge facilitators (59%). There were several differences by provider specialty, including primary care providers more frequently reporting time constraints and their patients having too many other illnesses to address screening as significant barriers to lung cancer screening.Providers endorsed the benefits of lung cancer screening, but there are limitations in provider knowledge of key screening components. The most frequently reported barriers to screening represent a lack of clinical time or resources to address lung cancer screening in clinical practice. Facilitators for nodule management as well as point-of-care referral materials may be helpful in reducing knowledge gaps and the clinical burden of referral. These are all modifiable factors, which could be addressed to increase screening referral. Differences in attitudes and barriers by specialty should also be considered to optimize screening implementation.

Introduction Despite known associations between obesity and cardiovascular disease, the relationship between obesity as reflected by body mass index (BMI) and angiographic coronary artery disease (CAD) is not fully understood. Moreover, this relationship has not been adequately defined in black patients, a group demonstrated to have lower rates of angiographic CAD despite higher rates of CAD risk factors, cardiovascular events, and CAD-related mortality. Methods Using an angiography database from an academic hospital, we studied patients undergoing first-time, nonemergent coronary angiography. From this cohort, we selected those without previous CAD diagnosis and with complete anthropomorphic measures and outcome data. Using models that controlled for patient demographics and CAD risk factors, we compared rates of angiographic CAD for blacks and whites by BMI. Results Black patients had higher rates of CAD risk factors, including obesity and morbid obesity. Nevertheless, black patients were less likely to have a significant stenosis than white patients. Morbid obesity was associated with significantly less CAD in both race groups. Controlling for black-white differences in BMI and the prevalence of morbid obesity did not change the odds ratio for CAD among black patients. Conclusions Racial differences in BMI and prevalence of morbid obesity do not contribute to black-white differences in CAD detected during elective angiography. The paradoxical association of morbid obesity with a lower burden of atherosclerosis may be attributed in part to the limitations of noninvasive screening in the morbidly obese and subsequent referral of patients without disease for angiography.

Objectives The prevalence of emphysema is higher among HIV-infected (HIV+) individuals compared to HIV-uninfected persons. While greater tobacco use contributes, HIV-related effects on immunity likely confer additional risk. Low peripheral blood CD4+ to CD8+ T-lymphocyte (CD4/CD8) ratio may reflect chronic inflammation in HIV and may be a marker of chronic lung disease in this population. Therefore, we sought to determine whether the CD4/CD8 ratio was associated with chronic obstructive pulmonary disease (COPD), particularly the emphysema subtype, in a cohort of HIV+ subjects. Methods We performed a cross-sectional analysis of 190 HIV+ subjects enrolled in the Examinations of HIV Associated Lung Emphysema (EXHALE) study. Subjects underwent baseline laboratory assessments, pulmonary function testing and chest computed tomography (CT) analyzed for emphysema severity and distribution. We determined the association between CD4/CD8 ratio and emphysema, and the association between CD4/CD8 ratio and pulmonary function markers of COPD. Results Mild or greater emphysema (>10% lung involvement) was present in 31% of subjects. Low CD4/CD8 ratio was associated with >10% emphysema in multivariable models, adjusting for risk factors including smoking, current and nadir CD4 count and HIV RNA level. Those with CD4/CD8 ratio 10% emphysema compared to those with a ratio >1.0 in fully adjusted models. A low CD4/CD8 ratio was also associated with reduced diffusion capacity (DLCO). Conclusions A low CD4/CD8 ratio was associated with emphysema and low DLCO in HIV+ subjects, independent of other risk factors and clinical markers of HIV. The CD4/CD8 ratio may be a useful, clinically available, marker for risk of emphysema in HIV+ subjects in the antiretroviral therapy (ART) era.

Author(s): Triplette, Matthew; Attia, Engi; Akgun, Kathleen; Campo, Monica; Rodriguez-Barradas, Maria; Pipavath, Sudhakar; Shahrir, Shahida; Wongtrakool, Cherry; Goetz, Matthew; Kim, Joon; Soo Hoo, Guy W; Brown, Sheldon T; Crothers, Kristina | Abstract: BackgroundEmphysema is more prevalent in HIV-infected (HIV+) patients independent of smoking behavior. Nonetheless, health effects of emphysema in this population are poorly understood. We determined whether emphysema is associated with a greater burden of pulmonary symptoms and a lower 6-minute walk distance (6MWD) in HIV+ compared with HIV-uninfected (HIV-) subjects.MethodsWe performed a cross-sectional analysis of 170 HIV+ and 153 HIV- subjects in the Examinations of HIV-Associated Lung Emphysema (EXHALE) cohort study. Subjects completed a self-assessment of respiratory symptoms, pulmonary function testing, and 6MWD testing as well as a chest computed tomography to determine emphysema severity. We used regression models to determine the association of emphysema with respiratory symptoms and 6MWD in HIV+ subjects and compared this to HIV- subjects.ResultsModels stratified by HIV status demonstrated an association between g10% radiographic emphysema and chronic cough and/or phlegm and 6MWD in HIV+ subjects. These associations persisted among the subset without airflow obstruction: those with emphysema had 4.2 (95% confidence interval: 1.3 to 14) times the odds of chronic cough and/or phlegm and walked 60 m (95% confidence interval: 26 to 93) less distance than those without emphysema. There was no association between g10% emphysema and symptoms or 6MWD in HIV- subjects.ConclusionsIn our cohort, g10% radiographic emphysema was associated with chronic cough and/or phlegm and lower 6MWD in HIV+ but not HIV- subjects. These findings were robust even among HIV+ subjects with milder forms of emphysema and those without airflow obstruction, highlighting the clinical impact of emphysema in these patients.

Little is known about vulnerable patients' perceptions and understanding of, and preferences for, lung cancer screening decision aids.To determine, in a low-income, racially diverse population, (1) participants' experience, preferences, and reactions to web-based and paper decision aids, and (2) their understanding of harms and benefits of lung cancer screening.We enrolled outpatients at an urban county hospital in six focus group discussions that included review of a web-based and a paper-based lung-cancer screening decision aid. Participants completed surveys before and after the focus groups.Forty-five patients participated (mean age, 61 yr; 76% current smokers; 24% former smokers); 27% had not completed high school; 50% had an annual income not exceeding $15,000; 42% were nonwhite; and 96% reported chronic illness requiring at least three health care visits yearly. Comparing the proportion with correct answers on pre- and postsurveys, participants' understanding of lung cancer screening increased, particularly of the harms of screening including the potential for false positives, extra testing, and complications. However, after conclusion of the focus groups, more than 50% believed that screening lowered the chance of getting lung cancer. Five major themes emerged from qualitative analyses. Participants (1) were not aware of the purpose of lung cancer screening; (2) wanted to know about the benefits and harms; (3) believed physicians need to communicate more effectively; (4) found decision aids helpful and influential for decision-making about screening; and (5) wanted the discussion to be personalized and tailored. Participants expressed surprise that the magnitude of their lung cancer risk and benefits of screening were lower than anticipated.Vulnerable patients find lung cancer screening decision aids helpful and generally show increased knowledge after reviewing decision aids, particularly of harms. Our results can inform future implementation efforts.

Rationale, aims and objectives Drug-eluting coronary stents (DES) rapidly dominated the marketplace in the United States after approval in 2003, but utilization rates were initially lower among African American patients. We assess whether racial differences persisted as DES diffused into practice. Methods Medicare claims data were used to identify coronary stenting procedures among elderly patients with acute coronary syndromes (ACS). Regression models of the choice of DES versus bare mental stent controlled for demographics, ACS type, co-morbidities and hospital characteristics. Diffusion was assessed in the short run (2003–2004) and long run (2007), with the effect of race calculated to allow for time-varying effects. Results The sample included 381 887 Medicare beneficiaries treated with stent insertion; approximately 5% were African American. Initially (May 2003–February 2004), African American race was associated with lower DES use compared to other races (44.3% versus 46.5%, P

Background Black patients in the United States undergoing angiography for suspected coronary artery disease (CAD) have consistently been found to have less disease than whites. As the effects of hypertension are greater in blacks than whites, and hypertensive heart disease may mimic CAD and lead to catheterization, we examined the association between race and hypertension as an explanation for the disparities in angiographic CAD. Methods Using an academic hospital's institutional database, we studied patients undergoing first-time elective angiography from 2001 to 2008. Using multivariable logistic regression with data on patient demographics, CAD risk factors, and coronary stenoses, we compared rates of angiographic disease for blacks and whites, creating models separately for patients with and without hypertension. We then tested the significance of an interaction term between race and hypertension on angiographic findings. Results We identified 1,203 black and 2,538 white patients who underwent initial elective angiography. Black patients were less likely to have a significant stenotic lesion (≥50% stenosis in the left main artery or ≥70% stenosis elsewhere) than whites (adjusted risk ratio 0.65; 95% confidence interval (CI) 0.55-0.75). Among patients with hypertension this difference was exaggerated (adjusted risk ratio 0.60; 95% CI 0.51-0.71). However, among patients without hypertension, the risk of having a significant lesion was similar in blacks and whites (adjusted risk ratio 0.97; 95% CI 0.67-1.37). The interaction term for race and hypertension was confirmed as statistically significant. Conclusions Among patients electively referred for angiography, hypertension, and its effects may contribute to the lower rate of CAD found in blacks compared to whites.

Background: Patients with acute myeloid leukemia (AML) admitted to the ICU have high in-hospital mortality, ranging from 40-70% (Halpern A, JAMA Oncology, 2017, 3; 374 and Thakkar SG, Cancer, 2008, 112; 2233). A model that considers AML-specific as well as ICU-specific variables could be of great value to identify critically ill patients likely to survive beyond hospital discharge and would help providers frame goals of care discussions. The AML Composite Model (AML-CM) was recently developed to predict early as well as late mortality after diagnosis of AML (Sorror ML, JAMA Oncology, 2017, 3:1675). The AML-CM incorporates AML cytogenetic risk, age, and comorbidity burden. It is unknown whether the AML-CM scores calculated at diagnosis of AML could add prognostic value to variables collected at the time of admission to ICU. To this end, we investigated the predictive value of AML-CM scores at diagnosis in addition to other risk factors including traditional ICU markers of illness severity collected from the time of ICU admission for prediction of 90-day mortality in patients with AML. Methods: This is a retrospective study of 218 patients with AML admitted to an ICU at one of two affiliated referral hospitals at any time during or after the initiation of chemotherapy between 2008 and 2017. We used factors from three time points: 1) initial diagnosis: sex, race, and AML-CM; 2) time of ICU admission: age, presence of relapsed or refractory disease, history of hematopoietic stem cell transplant (HCT), presence of neutropenia with ANC Results: The final study population was 217 patients, because one patient was lost to follow-up. The median age at ICU admission was 59 (range 19-83), 58% were male, and 79% were white. Mortality was 52% at 90 days. The median AML-CM was 7 (interquartile range 5-10), with 54% having AML-CM ≥7, and 46% having AML-CM The results of the univariate and multivariable analyses are listed in Table 1. The following variables were independently associated with 90-day mortality in the multivariate analysis: AML-CM ≥ 7 was associated with 3.6 times the odds of dying (95% CI 1.9-6.8, p=0.0001); IMV, 4.8 times the odds of dying (95% CI 2.2-10.5, p The AUC of the multivariable model which combined the 5 variables with statistically significant association on univariate analysis was 0.77. Based on results above, we calculated 90-day mortality rates among patients with 0 (n=39), 1 (n=84), 2 (n=75), and 3-4 (n=19) of the following factors: AML-CM ≥7, history of HCT, relapsed or resistant/refractory disease at ICU admission, and use of IMV (figure 1). Mortality rates at 90 days were 10%, 48%, 68%, and 95%, respectively. Conclusions: We identified 4 risk factors that show promise in predicting 90-day mortality after ICU admission in patients with AML: the AML-CM from time of diagnosis, history of HCT prior to ICU admission, disease status at ICU admission, and use of invasive mechanical ventilation within 24 hours of admission. Collectively, these factors can provide strong rationale to consider futility of ICU care among those with 3-4 risk factors, who represent ~9% of the population and have an extremely high risk of mortality at 90 days. Further, patients with 1-2 risk factors (73% of population) could be good candidates for early palliative care consult coincident with ICU admission given relatively high mortality risk within 90 days. Disclosures Becker: GlycoMimetics: Research Funding.

The Internet is a popular way for people to meet casual sex partners. However, online outreach remains largely unexplored to promote voluntary counseling and testing for HIV. The Student Health Action Coalition’s HIV testing program (SHAC-HIV) targets high-risk clients through tailored Internet outreach via chat rooms, social networking sites, and online forums. The SHAC-HIV model also demonstrates that nontraditional testing sites can provide low-cost, client-centered, high-quality services to support increased demand for HIV-testing services. Within the clinic, SHAC-HIV’s testing model includes four major components: (a) reliance on a team of well-trained health sciences student volunteers; (b) rapid oral-fluid HIV tests; (c) universal, consent-based testing with client-centered health education and counseling; and (d) coordinated referrals for follow-up testing, treatment, and care. This approach reaches high-risk clients as well as undiagnosed infections. In 2007, there were nine confirmed positive results out of 389 tests, yielding a 2.3% positivity rate. This positivity percentage is higher than any other nontraditional testing site in North Carolina. This article describes the SHAC-HIV outreach and vo-luntary counseling and testing program with the aim of encouraging adoption of the model by other nontraditional testing sites.

Sclerostin domain containing 1 (SOSTDC1) protein regulates processes from development to cancer by modulating activity of bone morphogenetic protein (BMP) and wingless/int (Wnt) signaling pathways. As dysregulation of both BMP and Wnt signaling has been observed in breast cancer, we investigated whether disruption of SOSTDC1 signaling occurs in breast cancer. SOSTDC1 mRNA expression levels in breast tissue were examined using a dot blot. Affymetrix microarray data on SOSTDC1 levels were correlated with breast cancer patient survival using Kaplan–Meier plots. Correlations between SOSTDC1 protein levels and clinical parameters were assessed by immunohistochemistry of a breast cancer tissue microarray. SOSTDC1 secretion and BMP and Wnt signaling were investigated using immunoblotting. We found that SOSTDC1 is expressed in normal breast tissue and this expression is reduced in breast cancer. High levels of SOSTDC1 mRNA correlated with increased patient survival; conversely, SOSTDC1 protein levels decreased as tumor size and disease stage increased. Treatment of breast cancer cells with recombinant SOSTDC1 or Wise, a SOSTDC1 orthologue, demonstrated that SOSTDC1 selectively blocks BMP-7-induced Smad phosphorylation without diminishing BMP-2 or Wnt3a-induced signaling. In conclusion, SOSTDC1 mRNA and protein are reduced in breast cancer. High SOSTDC1 mRNA levels correlate with increased distant metastasis-free survival in breast cancer patients. SOSTDC1 differentially affects Wnt3a, BMP-2, and BMP-7 signaling in breast cancer cells. These results identify SOSTDC1 as a clinically important extracellular regulator of multiple signaling pathways in breast cancer.