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Supplementary Materials 1: Patient Participant Focus Group Questions

Supplementary Materials 2: Healthcare Personnel Interview Questions

Although lung cancer screening (LCS) with annual low-dose chest CT has been shown to reduce lung cancer deaths, it remains underutilized. Northern Plains American Indian and Alaska Native (AI/AN) communities experience extreme lung cancer disparities, and little is known about the acceptance and adoption of LCS in these groups. We conducted interviews with healthcare professionals and focus groups with patients in an urban Minnesota community clinic serving AI/AN. Data collection took place during winter 2019–2020. Indigenous researchers collected and analyzed the data for emergent themes using simultaneous collaborative consensus with a LCS researcher. Participants reported some similar barriers to LCS as previous studies reported but also shared some new insights into traditional ways of knowing and recommendations for effectively implementing this evidence-based preventive care service. Lung screening is largely acceptable to patients and healthcare personnel in an AI/AN–serving community clinic. We identified barriers as previously reported in other populations but also identified some unique barriers and motivators. For example, the concept of the seven generations may provide motivation to maintain one's health for future generations while providing additional support during screening for persons traumatized by the Western medicine health system may facilitate increased screening uptake.Prevention Relevance:Secondary prevention of lung cancer through screening is potentially lifesaving considering that overall survival of lung cancer is 20% at 5 years but curable if detected at an early stage. This work provides insight into culturally tailored approaches to implementing the service in individuals at high risk of the disease.

Supplementary Materials 3: Lung Cancer Brochure developed from this work

BACKGROUND: Smokers manifest varied phenotypes of pulmonary impairment. RESEARCH QUESTION: Which pulmonary phenotypes are associated with coronary artery disease (CAD) in smokers? STUDY DESIGN AND METHODS: We analyzed data from the University of Pittsburgh COPD Specialized Center for Clinically Oriented Research (SCCOR) cohort (n = 481) and the Genetic Epidemiology of COPD (COPDGene) cohort (n = 2,580). Participants were current and former smokers with > 10 pack-years of tobacco exposure. Data from the two cohorts were analyzed separately because of methodologic differences. Lung hyperinflation was assessed by plethysmography in the SCCOR cohort and by inspiratory and expiratory CT scan lung volumes in the COPDGene cohort. Subclinical CAD was assessed as the coronary artery calcium score, whereas clinical CAD was defined as a self-reported history of CAD or myocardial infarction (MI). Analyses were performed in all smokers and then repeated in those with airflow obstruction (FEV(1) to FVC ratio, < 0.70). RESULTS: Pulmonary phenotypes, including airflow limitation, emphysema, lung hyperinflation, diffusion capacity, and radiographic measures of airway remodeling, showed weak to moderate correlations (r < 0.7) with each other. In multivariate models adjusted for pulmonary phenotypes and CAD risk factors, lung hyperinflation was the only phenotype associated with calcium score, history of clinical CAD, or history of MI (per 0.2 higher expiratory and inspiratory CT scan lung volume; coronary calcium: OR, 1.2; 95% CI, 1.1-1.5; P = .02; clinical CAD: OR, 1.6; 95% CI, 1.1-2.3; P = .01; and MI in COPDGene: OR, 1.7; 95% CI, 1.0-2.8; P = .05). FEV(1) and emphysema were associated with increased risk of CAD (P < .05) in models adjusted for CAD risk factors; however, these associations were attenuated on adjusting for lung hyperinflation. Results were the same in those with airflow obstruction and were present in both cohorts. INTERPRETATION: Lung hyperinflation is associated strongly with clinical and subclinical CAD in smokers, including those with airflow obstruction. After lung hyperinflation was accounted for, FEV(1) and emphysema no longer were associated with CAD. Subsequent studies should consider measuring lung hyperinflation and examining its mechanistic role in CAD in current and former smokers.

The 2016 SCCT/STR guideline for coronary artery calcification (CAC) scoring on non-cardiac chest CT (NCCT) scans explicitly calls for the reporting of CAC. Whether the publication of the 2016 SCCT/STR guideline has had any impact on CAC reporting in lung cancer screening (LCS) scans has not been investigated. Consecutive patients with a LCS scan were identified from the University of Minnesota LCS registry and evaluated for CAC reporting in 3 separate cohorts: 6 months before, 6 months after, and 1 year after the publication of the 2016 SCCT/STR guideline. Scans were evaluated for CAC and quantified using the Agatston method. CAC reporting, downstream testing and initiation of preventive therapy were assessed. Among 614 patients (50% male, mean age 64.1 ± 6.0 years), CAC was present in 460 (74.9%) with a median Agatston score of 62 (IQR 0, 230). Of these, 196 (31.9%) had a CAC score of 1–100, 125 (20.4%) had 101–300, and 118 (19.2%) had > 300. Overall, CAC was reported in 325 (70.7%) patients with CAC present. CAC reporting relative to publication of the 2016 SCCT/STR guideline was as follows: 6 months prior—74.1%, 6 months after—64.6%, and 1 year after—77.5%. In the 308 patients with a new diagnosis of sub-clinical CAD based on CAC presence, 6 (1.9%) patients were referred to cardiology, and 15 (4.9%) patients underwent testing for obstructive CAD. Only 6 (1.9%) and 9 (2.9%) patients were newly started on aspirin and statin respectively. CAC detected incidentally on lung cancer screening CT scans is prevalent, and rarely acted upon clinically. CAC reporting is fairly high, and publication of the 2016 SCCT/STR guideline for CAC scoring on NCCT scans did not have any significant impact on CAC reporting.

American Indians and Alaska Natives experience higher lung cancer mortality than other races in Minnesota. We compared rates of standard-of-care genetic mutation testing in this group compared to non-Native controls. No significant difference was identified; further resources should therefore be focused on other potential contributing factors, such as commercial tobacco use and other social determinants of health. BACKGROUND: American Indians and Alaska Natives (AI/AN) continue to experience extreme lung cancer health disparities. The state of Minnesota is home to over 70,000 AI/AN, and this population has a 2-fold increase in lung cancer mortality compared to other races within Minnesota. Genetic mutation testing in lung cancer is now a standard of high-quality lung cancer care, and EGFR mutation testing has been recommended for all adenocarcinoma lung cases, regardless of smoking status. However, genetic testing is a controversial topic for some AI/AN. PATIENTS AND METHODS: We performed a multisite retrospective chart review funded by the Minnesota Precision Medicine Grand Challenge as a demonstration project to examine lung cancer health disparities in AI/AN. We sought to measure epidemiology of lung cancer among AI receiving diagnosis or treatment in Minnesota cancer referral centers as well as rate of EGFR testing. The primary outcome was the rate of EGFR mutational analysis testing among cases and controls with nonsquamous, non—small-cell lung cancer. We secured collaborations with 5 health care systems covering a diverse geographic and demographic population. RESULTS: We identified 200 cases and 164 matched controls from these sites. Controls were matched on histology, smoking status, sex, and age. In both groups, about one third of subjects with adenocarcinoma received genetic mutation testing. CONCLUSION: There was no significant difference in mutation testing in AI compared to non-AI controls at large health care systems in Minnesota. These data indicate that other factors are likely contributing to the higher mortality in this group.

Lung cancer screening (LCS) combined with smoking cessation intervention is currently recommended for older individuals with a history of heavy smoking. Tailoring tobacco treatment for this patient population of older, people who smoke (PWS) may improve cessation rates while efficiently using limited smoking cessation resources. Although some older people who smoke will need more intensive treatment to achieve sustained abstinence, others may be successful with less intensive treatment. A framework to identify themBaseline demographic, smoking, and health data are reported from a randomized clinical trial of longitudinal smoking cessation interventions delivered in the setting of LCS. Candidate variables were factor analyzed to identify latent factors, or constructs, to identify subgroups of older participants among the heterogenous population of older people who smoke.We identified three factor-derived constructs: self-reported health status, heaviness of smoking, and nicotine dependence. Nicotine dependence was moderately correlated with both of the other two factors.This factor analysis of baseline participant characteristics identified a set of latent constructs - based on a few practical clinical variables -- that can be used to classify the heterogenous population of older people who smoke to identify. We propose this framework to identify subgroups of people who smoke who might successfully quit with less intense treatment at the time of lung cancer screening.

RATIONALE: Multiple studies have demonstrated an increased risk of chronic obstructive pulmonary disease (COPD) in heterozygous carriers of the AAT (alpha-1 antitrypsin) Z allele. However, it is not known if MZ subjects with COPD are phenotypically different from noncarriers (MM genotype) with COPD. OBJECTIVES: To assess if MZ subjects with COPD have different clinical features compared with MM subjects with COPD. METHODS: Genotypes of SERPINA1 were ascertained by using whole-genome sequencing data in three independent studies. We compared outcomes between MM subjects with COPD and MZ subjects with COPD in each study and combined the results in a meta-analysis. We performed longitudinal and survival analyses to compare outcomes in MM and MZ subjects with COPD over time. MEASUREMENTS AND MAIN RESULTS: We included 290 MZ subjects with COPD and 6,184 MM subjects with COPD across the three studies. MZ subjects had a lower FEV(1)% predicted and greater quantitative emphysema on chest computed tomography scans compared with MM subjects. In a meta-analysis, the FEV(1) was 3.9% lower (95% confidence interval [CI], −6.55% to −1.26%) and emphysema (the percentage of lung attenuation areas

Rationale: Increasing awareness of the prevalence and significance of Preserved Ratio Impaired Spirometry (PRISm), alternatively known as restrictive or Global Initiative for Chronic Obstructive Lu...

The 2016 SCCT/STR guideline for coronary artery calcification (CAC) scoring on non-cardiac chest CT (NCCT) scans explicitly calls for the reporting of CAC. Whether the publication of the 2016 SCCT/STR guideline has had any impact on CAC reporting in lung cancer screening (LCS) scans has not been investigated. Consecutive patients with a LCS scan were identified from the University of Minnesota LCS registry and evaluated for CAC reporting in 3 separate cohorts: 6 months before, 6 months after, and 1 year after the publication of the 2016 SCCT/STR guideline. Scans were evaluated for CAC and quantified using the Agatston method. CAC reporting, downstream testing and initiation of preventive therapy were assessed. Among 614 patients (50% male, mean age 64.1 ± 6.0 years), CAC was present in 460 (74.9%) with a median Agatston score of 62 (IQR 0, 230). Of these, 196 (31.9%) had a CAC score of 1-100, 125 (20.4%) had 101-300, and 118 (19.2%) had300. Overall, CAC was reported in 325 (70.7%) patients with CAC present. CAC reporting relative to publication of the 2016 SCCT/STR guideline was as follows: 6 months prior-74.1%, 6 months after-64.6%, and 1 year after-77.5%. In the 308 patients with a new diagnosis of sub-clinical CAD based on CAC presence, 6 (1.9%) patients were referred to cardiology, and 15 (4.9%) patients underwent testing for obstructive CAD. Only 6 (1.9%) and 9 (2.9%) patients were newly started on aspirin and statin respectively. CAC detected incidentally on lung cancer screening CT scans is prevalent, and rarely acted upon clinically. CAC reporting is fairly high, and publication of the 2016 SCCT/STR guideline for CAC scoring on NCCT scans did not have any significant impact on CAC reporting.

Background Attenuation of transforming growth factor β by blocking angiotensin II has been shown to reduce emphysema in a murine model. General population studies have demonstrated that the use of angiotensin converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) is associated with reduction of emphysema progression in former smokers and that the use of ACEis is associated with reduction of FEV1 progression in current smokers. Research Question Is use of ACEi and ARB associated with less progression of emphysema and FEV1 decline among individuals with COPD or baseline emphysema? Methods Former and current smokers from the Genetic Epidemiology of COPD Study who attended baseline and 5-year follow-up visits, did not change smoking status, and underwent chest CT imaging were included. Adjusted linear mixed models were used to evaluate progression of adjusted lung density (ALD), percent emphysema (%total lung volume Results Over 5 years of follow-up, compared with nonusers, ACEi and ARB users with COPD showed slower ALD progression (adjusted mean difference [aMD], 1.6; 95% CI, 0.34-2.9). Slowed lung function decline was not observed based on phase 1 medication (aMD of FEV1 % predicted, 0.83; 95% CI, –0.62 to 2.3), but was when analysis was limited to consistent ACEi and ARB users (aMD of FEV1 % predicted, 1.9; 95% CI, 0.14-3.6). No effect modification by smoking status was found for radiographic outcomes, and the lung function effect was more pronounced in former smokers. Results were similar among participants with baseline emphysema. Interpretation Among participants with spirometry-confirmed COPD or baseline emphysema, ACEi and ARB use was associated with slower progression of emphysema and lung function decline. Trial Registry ClinicalTrials.gov ; No.: NCT00608764; URL: www.clinicaltrials.gov

Increasing American Indian/Alaska Native (AI/AN) representation in genetic research is critical to ensuring that personalized medicine discoveries do not widen AI/AN health disparities by only benefiting well-represented populations. One reason for the under-representation of AIs/ANs in research is warranted research distrust due to abuse of some AI/AN communities in research. An approach to easing the tension between protecting AI/AN communities and increasing the representation of AI/AN persons in genetic research is community-based participatory research. This approach was used in a collaboration between a tribe and academic researchers in efforts to increase AI/AN participation in genetic research. From the lessons learned, the authors propose recommendations to researchers that may aid in conducting collaborative and respectful research with AI/AN tribes/communities and ultimately assist in increasing representation of AIs/ANs in personalized medicine discoveries.

Contains fulltext : 220761.pdf (Publisher’s version ) (Open Access) Rationale: The decades-long progression of chronic obstructive pulmonary disease (COPD) renders identifying different trajectories of disease progression challenging.Objectives: To identify subtypes of patients with COPD with distinct longitudinal progression patterns using a novel machine-learning tool called "Subtype and Stage Inference" (SuStaIn) and to evaluate the utility of SuStaIn for patient stratification in COPD.Methods: We applied SuStaIn to cross-sectional computed tomography imaging markers in 3,698 Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1-4 patients and 3,479 controls from the COPDGene (COPD Genetic Epidemiology) study to identify subtypes of patients with COPD. We confirmed the identified subtypes and progression patterns using ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) data. We assessed the utility of SuStaIn for patient stratification by comparing SuStaIn subtypes and stages at baseline with longitudinal follow-up data.Measurements and Main Results: We identified two trajectories of disease progression in COPD: a "Tissue-->Airway" subtype (n = 2,354, 70.4%), in which small airway dysfunction and emphysema precede large airway wall abnormalities, and an "Airway-->Tissue" subtype (n = 988, 29.6%), in which large airway wall abnormalities precede emphysema and small airway dysfunction. Subtypes were reproducible in ECLIPSE. Baseline stage in both subtypes correlated with future FEV1/FVC decline (r = -0.16 [P < 0.001] in the Tissue-->Airway group; r = -0.14 [P = 0.011] in the Airway-->Tissue group). SuStaIn placed 30% of smokers with normal lung function at elevated stages, suggesting imaging changes consistent with early COPD. Individuals with early changes were 2.5 times more likely to meet COPD diagnostic criteria at follow-up.Conclusions: We demonstrate two distinct patterns of disease progression in COPD using SuStaIn, likely representing different endotypes. One third of healthy smokers have detectable imaging changes, suggesting a new biomarker of "early COPD."

Purpose Screening for lung cancer with low-dose computed tomography is endorsed by the US Preventive Services Task Force, but many eligible patients have yet to be offered screening. Major barriers to the implementation of screening are physician and system related—the requirement for a detailed smoking history, including pack-years, to determine eligibility. We conducted this pilot to determine the feasibility of lung cancer screening (LCS) promotion that would offer screening to eligible persons and patient completion of smoking history to estimate the size of the population of former smokers who may be eligible for LCS in a single health care system. Patients and Methods Two hundred participants were randomly selected from former smokers who were seen at the University of Minnesota Health in the past 2 years and assigned to control (usual care) and electronic promotion, stratified by age. Electronic messages to promote LCS were sent to an intervention group, including a link to complete a detailed smoking history in the electronic health record. Results Of 99 participants, 66 (67%) in the intervention group read the message, 24 (36%) of 66 responded, and 19 (79%) of 24 respondents completed the smoking history. Ten intervention participants and 13 usual care participants were eligible for screening on the basis of pack-year history. Four eligible participants underwent screening in the intervention group compared with one participant in the usual care group. Conclusion Electronic promotion may help identify patients who are eligible for LCS but will not reliably reach all patients because of low response rates. In this sample of former smokers, the majority are ineligible for LCS on the basis of pack-year history. Electronic methods can improve documentation of smoking history.

PLUTO will conduct a sequential, multiple assignment, randomized trial to inform the choice and delivery of smoking cessation treatments for smokers in the setting of lung cancer screening, including for smokers who respond both incompletely (any smoking after quit date) and completely to first-line treatment (4 or 8 weeks of counseling with nicotine replacement therapy). Currently, there is little evidence to guide the development of adaptive interventions in tobacco cessation. SMART designs, such as the one we propose, are an ideal experimental design to assess different adaptive intervention strategies. Adaptive interventions for smoking cessation in the context of lung cancer screening have high potential for dissemination and impact. The USPSTF recommends annual low-dose CT screening for patients at high risk Recommendation (Grade B)4; private insurance coverage is mandated for USPSTF Grade A or B recommendations. The Affordable Care Act (ACA) mandates coverage of preventative services including smoking cessation treatment. The ACA requires coverage of at least 2 quit attempts/year, 4 counseling sessions of at least 10 minutes, and all Food and Drug Administration (FDA) approved tobacco cessation meds for a 90 day treatment regimen when prescribed by a health care provider (7 medications: 5 forms of NRT, bupropion, and varenicline).74 Effective smoking cessation treatment, delivered in the context of lung cancer screening programs, may augment the mortality benefit of imaging studies. The novel tobacco treatment system we plan – identification of smokers by using the EMR and proactive invitation to treatment coupled with lung cancer screening – is an opportunity to engage a new cohort of smokers with mechanisms in place to implement delivery of care. Thus, the PLUTO trial takes advantage of a new clinical practice development: recommendation for annual lung cancer screening based on age and smoking history. Strengths are an innovative study design and sequential random assignment of treatment conditions in addition to the main comparative effectiveness outcome that allows more rigorous measurement of effects than a standard randomized controlled trial would afford. The information about timing of assessment, optimal intervention components, and intensity of treatment are ripe for dissemination.

Lung cancer staging remains a moving target. Since the first TNM staging system was established by Mountain and colleagues there have been seven revisions (1,2). A jaded viewer may understandably feel that these revisions have proven to be refinements more than paradigm shifts.

Asthma-COPD overlap (ACO) is a common clinical syndrome, yet there is no single objective definition. We hypothesized that immunoglobulin E (IgE) measurements could be used to refine the definition of ACO. In baseline plasma samples from 2870 participants in the COPD Genetic Epidemiology (COPDGene(®)) study, we measured total IgE levels and specific IgE levels to 6 common allergens. Compared to usual chronic obstructive pulmonary disease (COPD), participants with ACO (based on self-report of asthma) had higher total IgE levels (median 67.0 versus 42.2 IU/ml) and more frequently had at least one positive specific IgE (43.5% versus 24.5%). We previously used a strict definition of ACO in participants with COPD, based on self-report of a doctor’s diagnosis of asthma before age 40. This strict ACO definition was refined by the presence of atopy, determined by total IgE > 100 IU/ml or at least one positive specific IgE, as was the broader definition of ACO based on self-reported asthma history. Participants with all 3 ACO definitions were younger (mean age 60.0–61.3 years), were more commonly African American (36.8%–44.2%), had a higher exacerbation frequency (1.0–1.2 in the past year), and had more airway wall thickening on quantitative analysis of chest computed tomography (CT) scans. Among participants with ACO, 37%–46% did not have atopy; these individuals had more emphysema on chest CT scan. Based on associations with exacerbations and CT airway disease, IgE did not clearly improve the clinical definition of ACO. However, IgE measurements could be used to subdivide individuals with atopic and non-atopic ACO, who might have different biologic mechanisms and potential treatments.

Rationale: The American Thoracic Society (ATS)/European Respiratory Society defines a positive bronchodilator response (BDR) by a composite of BDR in either forced expiratory volume in 1 second (FEV(1)) and/or forced vital capacity (FVC) greater than or equal to 12% and 200 ml (ATS-BDR). We hypothesized that ATS-BDR components would be differentially associated with important chronic obstructive pulmonary disease (COPD) outcomes. Objectives: To examine whether ATS-BDR components are differentially associated with clinical, functional, and radiographic features in COPD. Methods: We included subjects with COPD enrolled in the COPDGene study. In the main analysis, we excluded subjects with self-reported asthma. We categorized BDR into the following: 1) No-BDR, no BDR in either FEV(1) or FVC; 2) FEV(1)-BDR, BDR in FEV(1) but no BDR in FVC; 3) FVC-BDR, BDR in FVC but no BDR in FEV(1); and 4) Combined-BDR, BDR in both FEV(1) and FVC. We constructed multivariable logistic, linear, zero-inflated negative binomial, and Cox hazards models to examine the association of BDR categories with symptoms, computed tomography findings, change in FEV(1) over time, respiratory exacerbations, and mortality. We also created models using the ATS BDR definition (ATS-BDR) as the main independent variable. Results: Of 3,340 COPD subjects included in the analysis, 1,083 (32.43%) had ATS-BDR, 182 (5.45%) had FEV(1)-BDR, 522 (15.63%) had FVC-BDR, and 379 (11.34%) had Combined-BDR. All BDR categories were associated with FEV(1) decline compared with No-BDR. Compared with No-BDR, both ATS-BDR and Combined-BDR were associated with higher functional residual capacity %predicted, greater internal perimeter of 10 mm, and greater 6-minute-walk distance. In contrast to ATS-BDR, Combined-BDR was independently associated with less emphysema (adjusted beta regression coefficient, −1.67; 95% confidence interval [CI], −2.68 to −0.65; P = 0.001), more frequent respiratory exacerbations (incidence rate ratio, 1.25; 95% CI, 1.03–1.50; P = 0.02) and severe exacerbations (incidence rate ratio, 1.34; 95% CI, 1.05–1.71; P = 0.02), and lower mortality (adjusted hazards ratio, 0.76; 95% CI, 0.58–0.99; P = 0.046). Sensitivity analysis that included subjects with self-reported history of asthma showed similar findings. Conclusions: BDR in both FEV(1) and FVC indicates a COPD phenotype with asthma-like characteristics, and provides clinically more meaningful information than current definitions of BDR.

Background Chronic bronchitis (CB) increases risk of COPD exacerbations. We have shown that the St. George's Respiratory Questionnaire (SGRQ) CB definition identifies patients with a similar clinical phenotype as classically defined CB. Whether the SGRQ CB definition is a predictor of future COPD exacerbations is unknown. Methods We analyzed 7,557 smokers with normal spirometry and Global Initiative for Chronic Obstructive Lung Disease stage 1-4 COPD in the Genetic Epidemiology of COPD study with longitudinal follow-up data on exacerbations. Subjects were divided into classic CB+ or classic CB–, using the classic definition. In addition, subjects were divided into SGRQ CB+ or SGRQ CB–. Exacerbation frequency and severe exacerbation frequency were determined in each group. Multivariable linear regressions were performed for exacerbation frequency with either classic CB or SGRQ CB and relevant covariates. Results There were 1,434 classic CB+ subjects and 2,290 SGRQ CB+ subjects. The classic CB+ group had a greater exacerbation frequency compared with the classic CB– group (0.69 ± 1.26 vs 0.36 ± 0.90 exacerbations per patient per year; P Conclusions The SGRQ CB definition identified more subjects at risk for future exacerbations than the classic CB definition. SGRQ CB was at least a similar if not better predictor of future exacerbations than classic CB.

Purpose A common pattern of recurrence in lung cancer after receiving full dose external beam radiation therapy (EBRT) to targeted sites is isolated mediastinal and hilar recurrence (IMHR). Treatment options for these patients are limited to palliative radiation, chemotherapy, and/or best supportive care. We describe our experience with treating IMHR with bronchoscopic endobronchial ultrasound (EBUS) guided intratumoral injection of cisplatin (ITC). Methods Patients treated between Jan 2009–September 2014 with ITC for IMHR were included. Patient demographics, tumor histology, size, concurrent therapy, location, number of sites treated, treatment sessions, and encounters were abstracted. Responses were analyzed on follow-up scans 8–12 weeks after the last treatment session using RECIST 1.1 criteria. Locoregional recurrence, progression-free survival (PFS), and overall survival were measured. Results 50 sites were treated in 36 patients (19 males, 17 females) with mean age 61.9 ± 8.5 years. Eight sites treated on subsequent encounters were excluded and one patient had an unevaluable response, leaving 35 patients and 41 sites for final analysis. 24/35 (69%) had complete or partial response (responders), whereas 11/35 (31%) had stable or progressive disease (non-responders). There were no significant differences in response based on histology, size, and concurrent therapy. Median survival for the group was 8 months (95% CI of 6–11 mo). Responders had significantly higher survival and PFS than non-responders. Two patients treated with concurrent EBRT, developed broncho-mediastinal fistula. Conclusion EBUS guided intratumoral cisplatin for IMHR appears to be safe and effective, and may represent a new treatment paradigm for this patient population.

Spirometric Volumes and Breathlessness Across Levels of Airflow Limitation : The COPDGene Study.

BACKGROUND:Eosinophilic airway inflammation in patients with chronic obstructive pulmonary disease (COPD) is associated with exacerbations and responsivity to steroids, suggesting potential shared mechanisms with eosinophilic asthma. However, there is no consistent blood eosinophil count that has been used to define the increased exacerbation risk. OBJECTIVE:We sought to investigate blood eosinophil counts associated with exacerbation risk in patients with COPD. METHODS:Blood eosinophil counts and exacerbation risk were analyzed in patients with moderate-to-severe COPD by using 2 independent studies of former and current smokers with longitudinal data. The Genetic Epidemiology of COPD (COPDGene) study was analyzed for discovery (n=1,553), and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study was analyzed for validation (n=1,895). Asubset of the ECLIPSE study subjects were used to assess the stability of blood eosinophil counts over time. RESULTS:COPD exacerbation risk increased with higher eosinophil counts. An eosinophil count threshold of 300cells/μL or greater showed adjusted incidence rate ratios for exacerbations of 1.32 in the COPDGene study (95% CI, 1.10-1.63). The cutoff of 300cells/μL or greater was validated for prospective risk of exacerbation in the ECLIPSE study, with adjusted incidence rate ratios of 1.22 (95% CI, 1.06-1.41) using 3-year follow-up data. Stratified analysis confirmed that the increased exacerbation risk associated with an eosinophil count of 300cells/μL or greater was driven by subjects with a history of frequent exacerbations in both the COPDGene and ECLIPSE studies. CONCLUSIONS:Patients with moderate-to-severe COPD and blood eosinophil counts of 300cells/μL or greater had an increased risk exacerbations in the COPDGene study, which was prospectively validated in the ECLIPSE study.

Rationale: Malignant airway obstruction is commonly found in patients with lung cancer and is associated with significant morbidity and mortality. Relieving malignant obstruction may improve symptoms, quality of life, and life expectancy.Objectives: The objective of this study was to analyze our experience with bronchoscopic endobronchial intratumoral injection of cisplatin for malignant airway obstruction.Methods: We conducted a retrospective analysis of patients with malignant airway obstruction treated with bronchoscopic intratumoral injection of cisplatin. Patient characteristics, histology, degree of airway obstruction, procedural methods, treatment cycles, performance status, and therapeutic outcomes were evaluated. Tumor response was analyzed based on bronchoscopic measurements performed on completion the of final treatment session. Adverse events and overall survival were abstracted.Measurements and Main Results: Between January 2009 and September 2014, 22 patients (10 men, 12 women; mean age ± SD...

National recommendations for lung cancer screening for former and current smokers aged 55-80 years with a 30-pack-year smoking history create demand to implement efficient and effective systems to offer smoking cessation on a large scale. These older, high-risk smokers differ from participants in past clinical trials of behavioral and pharmacologic interventions for tobacco dependence. There is a gap in knowledge about how best to design systems to extend reach and treatments to maximize smoking cessation in the context of lung cancer screening. Eight clinical trials, seven funded by the National Cancer Institute and one by the Veterans Health Administration, address this gap and form the SCALE (Smoking Cessation within the Context of Lung Cancer Screening) collaboration. This paper describes methodological issues related to the design of these clinical trials: clinical workflow, participant eligibility criteria, screening indication (baseline or annual repeat screen), assessment content, interest in stopping smoking, and treatment delivery method and dose, all of which will affect tobacco treatment outcomes. Tobacco interventions consider the "teachable moment" offered by lung cancer screening, how to incorporate positive and negative screening results, and coordination of smoking cessation treatment with clinical events associated with lung cancer screening. Unique data elements, such as perceived risk of lung cancer and costs of tobacco treatment, are of interest. Lung cancer screening presents a new and promising opportunity to reduce morbidity and mortality resulting from lung cancer that can be amplified by effective smoking cessation treatment. SCALE teamwork and collaboration promise to maximize knowledge gained from the clinical trials.

Screening for lung cancer with low-dose CT has evolved rapidly in recent years since the National Lung Screening Trial (NLST) results. Subsequent professional and governmental organization guidelines have shaped policy and reimbursement for the service. Increasingly available guidance describes eligible patients and components necessary for a high-quality lung cancer screening program; however, practical instruction and implementation experience is not widely reported. We launched a lung cancer screening program in the face of reimbursement and guideline uncertainties at a large academic health center. We report our experience with implementation, including challenges and proposed solutions. Initially, we saw less referrals than expected for screening, and many patients referred for screening did not clearly meet eligibility guidelines. We educated primary care providers and implemented system tools to encourage referral of eligible patients. Moreover, in response to the Centers for Medicare & Medicaid Services (CMS) final coverage determination, we report our programmatic adaptation to meet these requirements. In addition to the components common to all quality programs, individual health delivery systems will face unique barriers related to patient population, available resources, and referral patterns.

e18595Background: Although smoking history is classically quantified as pack-years (packages of cigarettes per day smoked times the number of years smoked), there is no standard for eliciting this ...

e18915Background: Widespread adoption of lung cancer screening (LCS) with low-dose computed tomography (LDCT) is an opportunity to save lives. However, one risk of screening is undergoing unnecessa...

All bronchoscopists will encounter, at some point, central airway obstruction (CAO) and will face the problem of documenting its severity. Axial imaging is suggested as the gold standard for assessing CAO, but anecdotal evidence indicates that many bronchoscopists use visual estimation. The prevalence and reliability of this method have not been extensively studied.This study aimed to determine bronchoscopists' opinions about assessing CAO and to assess the variability of visual estimation.All 438 members of the American Association of Bronchology and Interventional Pulmonology were invited to participate in an online questionnaire. In addition to reporting opinions and practice in measuring CAO, participants estimated degree of obstruction for 10 bronchoscopic photos of abnormal central airway lesions using a sliding scale from 0 to 100%.Responses were obtained from 118 individuals with varied interventional bronchoscopy experience. Most participants reported using visual estimation of CAO (91%) and largely by numeric estimates (87%). A total of 55 participants volunteered additional methods they employed, and their comments reflected discontent with the dependability of those. When shown the same 10 bronchoscopic photos, estimates varied considerably, with very large ranges of responses for all images. Most (86%) agreed that measurement of airway narrowing should be standardized.Although limited by sample size and static photos of abnormal airways, this study supports the tenet that most bronchoscopists use a subjective and variable method of estimating CAO, which is anecdotally pervasive in the absence of a clinically practical alternative.

BACKGROUND Alveolar-pleural fistula with persistent air leak is a common problem causing significant morbidity, prolonged hospital stay, and increased health-care costs. When conventional therapy fails, an alternative to prolonged chest-tube drainage or surgery is needed. New bronchoscopic techniques have been developed to close the air leak by reducing the flow of air through the leak. The objective of this study was to analyze our experience with bronchoscopic application of a synthetic hydrogel for the treatment of such fistulas. METHODS We conducted a retrospective study of patients with alveolar-pleural fistula with persistent air leaks treated with synthetic hydrogel application via flexible bronchoscopy. Patient characteristics, underlying disease, and outcome of endoscopic treatment were analyzed. RESULTS Between January 2009 and December 2013, 22 patients (14 men, eight women; mean age ± SD, 62 ± 10 years) were treated with one to three applications of a synthetic hydrogel per patient. The primary etiology of persistent air leak was necrotizing pneumonia (n = 8), post-thoracic surgery (n = 6), bullous emphysema (n = 5), idiopathic interstitial pneumonia (n = 2), and sarcoidosis (n = 1). Nineteen patients (86%) had complete resolution of the air leak, leading to successful removal of chest tube a mean (± SD) of 4.3 ± 0.9 days after last bronchoscopic application. The procedure was very well tolerated, with two patients coughing up the hydrogel and one having hypoxemia requiring bronchoscopic suctioning. CONCLUSIONS Bronchoscopic administration of a synthetic hydrogel is an effective, nonsurgical, minimally invasive intervention for patients with persistent pulmonary air leaks secondary to alveolar-pleural fistula.