Clinical risk factors and blood protein biomarkers of 10-year pneumonia risk.

BACKGROUND: Chronic inflammation may increase susceptibility to pneumonia. RESEARCH QUESTION: To explore associations between clinical comorbidities, serum protein immunoassays, and long-term pneumonia risk. METHODS: Framingham Heart Study Offspring Cohort participants ≥65 years were linked to their Centers for Medicare Services claims data. Clinical data and 88 serum protein immunoassays were evaluated for associations with 10-year incident pneumonia risk using Fine-Gray models for competing risks of death and least absolute shrinkage and selection operators for covariate selection. RESULTS: We identified 1,370 participants with immunoassays and linkage to Medicare data. During 10 years of follow up, 428 (31%) participants had a pneumonia diagnosis. Chronic pulmonary disease [subdistribution hazard ratio (SHR) 1.87; 95% confidence interval (CI), 1.33-2.61], current smoking (SHR 1.79, CI 1.31-2.45), heart failure (SHR 1.74, CI 1.10-2.74), atrial fibrillation/flutter (SHR 1.43, CI 1.06-1.93), diabetes (SHR 1.36, CI 1.05-1.75), hospitalization within one year (SHR 1.34, CI 1.09-1.65), and age (SHR 1.06 per year, CI 1.04-1.08) were associated with pneumonia. Three baseline serum protein measurements were associated with pneumonia risk independent of measured clinical factors: growth differentiation factor 15 (SHR 1.32; CI 1.02-1.69), C-reactive protein (SHR 1.16, CI 1.06-1.27) and matrix metallopeptidase 8 (SHR 1.14, CI 1.01-1.30). Addition of C-reactive protein to the clinical model improved prediction (Akaike information criterion 4950 from 4960; C-statistic of 0.64 from 0.62). CONCLUSIONS: Clinical comorbidities and serum immunoassays were predictive of pneumonia risk. C-reactive protein, a routinely-available measure of inflammation, modestly improved pneumonia risk prediction over clinical factors. Our findings support the hypothesis that prior inflammation may increase the risk of pneumonia.

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

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

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

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

Clinical risk factors and blood protein biomarkers of 10-year pneumonia risk.

Background: Chronic inflammation may increase susceptibility to pneumonia. Research Question: To explore associations between clinical comorbidities, serum protein immunoassays, and long-term pneumonia risk. Methods: Framingham Heart Study Offspring Cohort participants ≥65 years were linked to their Centers for Medicare Services claims data. Clinical data and 88 serum protein immunoassays were evaluated for associations with 10-year incident pneumonia risk using Fine-Gray models for competing risks of death and least absolute shrinkage and selection operators for covariate selection. Results: We identified 1,370 participants with immunoassays and linkage to Medicare data. During 10 years of follow up, 428 (31%) participants had a pneumonia diagnosis. Chronic pulmonary disease [subdistribution hazard ratio (SHR) 1.87; 95% confidence interval (CI), 1.33-2.61], current smoking (SHR 1.79, CI 1.31-2.45), heart failure (SHR 1.74, CI 1.10-2.74), atrial fibrillation/flutter (SHR 1.43, CI 1.06-1.93), diabetes (SHR 1.36, CI 1.05-1.75), hospitalization within one year (SHR 1.34, CI 1.09-1.65), and age (SHR 1.06 per year, CI 1.04-1.08) were associated with pneumonia. Three baseline serum protein measurements were associated with pneumonia risk independent of measured clinical factors: growth differentiation factor 15 (SHR 1.32; CI 1.02-1.69), C-reactive protein (SHR 1.16, CI 1.06-1.27) and matrix metallopeptidase 8 (SHR 1.14, CI 1.01-1.30). Addition of C-reactive protein to the clinical model improved prediction (Akaike information criterion 4950 from 4960; C-statistic of 0.64 from 0.62). Conclusions: Clinical comorbidities and serum immunoassays were predictive of pneumonia risk. C-reactive protein, a routinely-available measure of inflammation, modestly improved pneumonia risk prediction over clinical factors. Our findings support the hypothesis that prior inflammation may increase the risk of pneumonia.

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

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

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

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

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

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

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

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

High miR203a-3p and miR-375 expression in the airways of smokers with and without COPD.

Smoking is a leading cause of chronic obstructive pulmonary disease (COPD). It is known to have a significant impact on gene expression and (inflammatory) cell populations in the airways involved in COPD pathogenesis. In this study, we investigated the impact of smoking on the expression of miRNAs in healthy and COPD individuals. We aimed to elucidate the overall smoking-induced miRNA changes and those specific to COPD. In addition, we investigated the downstream effects on regulatory gene expression and the correlation to cellular composition. We performed a genome-wide miRNA expression analysis on a dataset of 40 current- and 22 ex-smoking COPD patients and a dataset of 35 current- and 38 non-smoking respiratory healthy controls and validated the results in an independent dataset. miRNA expression was then correlated with mRNA expression in the same patients to assess potential regulatory effects of the miRNAs. Finally, cellular deconvolution analysis was used to relate miRNAs changes to specific cell populations. Current smoking was associated with increased expression of three miRNAs in the COPD patients and 18 miRNAs in the asymptomatic smokers compared to respiratory healthy controls. In comparison, four miRNAs were lower expressed with current smoking in asymptomatic controls. Two of the three smoking-related miRNAs in COPD, miR-203a-3p and miR-375, were also higher expressed with current smoking in COPD patients and the asymptomatic controls. The other smoking-related miRNA in COPD patients, i.e. miR-31-3p, was not present in the respiratory healthy control dataset. miRNA-mRNA correlations demonstrated that miR-203a-3p, miR-375 and also miR-31-3p expression were negatively associated with genes involved in pro-inflammatory pathways and positively associated with genes involved in the xenobiotic pathway. Cellular deconvolution showed that higher levels of miR-203a-3p were associated with higher proportions of proliferating-basal cells and secretory (club and goblet) cells and lower levels of fibroblasts, luminal macrophages, endothelial cells, B-cells, amongst other cell types. MiR-375 expression was associated with lower levels of secretory cells, ionocytes and submucosal cells, but higher levels of endothelial cells, smooth muscle cells, and mast cells, amongst other cell types. In conclusion, we identified two smoking-induced miRNAs (miR-375 and miR-203a-3p) that play a role in regulating inflammation and detoxification pathways, regardless of the presence or absence of COPD. Additionally, in patients with COPD, we identified miR-31-3p as a miRNA induced by smoking. Our identified miRNAs should be studied further to unravel which smoking-induced inflammatory mechanisms are reactive and which are involved in COPD pathogenesis.

Risk Factors for Lung Cancer in an Underrepresented Safety-Net Screening Cohort.

INTRODUCTION/BACKGROUND: The USPSTF (United States Preventive Services Task Force) guidelines suggest criteria centering on smoking status and age to select patients for lung cancer screening. Despite the significant advances in screening with low-dose computed tomography (LDCT), cancer detection rate is low (1.1%), highlighting the need to investigate possible ways to refine the current lung cancer screening strategy. Our aim was to determine clinical risk factors predictive of lung cancer in an urban safety-net hospital. MATERIALS AND METHODS: We performed a retrospective chart review of 2847 patients who received LDCT screening for lung cancer between 3/1/2015 and 12/31/2019. Patient demographics and medical history were collected. A bivariate logistic regression was used to evaluate predictors of lung cancer. RESULTS: Compared to the National Lung Cancer Screening Trial (NLST) population, our screening cohort had significantly more African Americans (38.2% vs. 4.5%, P < .0001), more obesity (32.7% vs. 28.3%, P < .0001), and higher rates of chronic obstructive pulmonary disease (COPD) (45.9% vs. 5.0%, P < .0001). The strongest predictors of lung cancer were COPD (odds ratio [OR] = 2.14, P < .0001) and a family history of lung cancer (OR = 2.77, P < .0001). Age (OR = 1.04, P< .001) and pack years (OR = 1.01, P< .001) were less predictive. CONCLUSION: A diagnosis of COPD and family history of lung cancer were most predictive of lung cancer in a screening cohort at our urban safety-net hospital. Future studies should focus on whether inclusion of these additional risk-factors improves proportion of lung cancer detected via screening.

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

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

Lung Cancer Risk in Suspicious Lung Nodules With Negative Positron Emission Tomography.

BACKGROUND: Lung CT Screening Reporting and Data System (LungRADS) Category 4 represents lung nodules with the highest likelihood of cancer. For LungRADS-4 lesions, if positron emission tomography (PET) is negative, no uniform guideline currently exists on subsequent follow-up, particularly whether the surveillance interval can be extended. We sought to investigate the incidence of cancer, our surveillance practice, and any clinical factors associated with cancer in this patient subset. METHODS: We retrospectively stratified LungRADS-4 patients screened at our institution from March 2015 to February 2019 into subgroups: PET positive, PET negative, and no PET performed. PET negativity was defined as the absence of a radiologist's suspicion or a maximum standardized uptake value at or below the mediastinal value. RESULTS: Of the 191 LungRADS-4 patients identified, 67 (35.1%) met the criteria for PET negativity. Cancer was diagnosed in 28.8% of the entire cohort (55/191), 77.8% of the PET-positive subgroup (35/45), 22.4% of the PET-negative subgroup (15/67), and 6.3% of the no PET subgroup (5/79). The most common follow-up modality after a negative PET was a computed tomography (47/67, 70.1%), with a median interval of 3.1 months. Clinical variables including nodule location/size, chronic obstructive pulmonary disease, family history of lung cancer, pack-years, and number of years quit in former smokers were not significantly associated with greater cancer risk among the PET-negative subgroup. CONCLUSIONS: For LungRADS-4/PET-negative lesions the cancer risk remained high despite a lack of activity on PET. As such we believe the current surveillance practice of continuing to follow LungRADS-4/PET-negative patients as LungRADS-4 patients is appropriate.

Redlining, structural racism, and lung cancer screening disparities.

OBJECTIVE: The objective of this study was to understand the effect of historical redlining (preclusion from home loans and wealth-building for Black Americans) and its downstream factors on the completion of lung cancer screening in Boston. METHODS: Patients within our institution were identified as eligible for lung cancer screening on the basis of the United State Preventive Service Task Force criteria and patient charts were reviewed to determine if patients completed low-dose computed tomography screening. Individual addresses were geocoded and overlayed with original 1930 Home Owner Loan Corporation redlining vector files. Structural equation models were used to estimate the odds of screening for Black and White patients, interacted with sex, in redlined and nonredlined areas. RESULTS: Black patients had a 44% lower odds of screening compared with White (odds ratio [OR], 0.66; 95% CI, 0.52-0.85). With race as a mediator, Black patients in redlined areas were 61% less likely to undergo screening than White patients (OR, 0.39; 95% CI, 0.24-0.64). Similarly, in redlined areas Black women had 61% (OR, 0.39; 95% CI, 0.21-0.73) and Black men 47% (OR, 0.53; 95% CI, 0.29-0.98) lower odds of screening compared with White men in redlined areas. CONCLUSIONS: Despite higher rates of lung cancer screening in redlined areas, Black race mediated worse screening rates in these areas, suggesting racist structural factors contributing to the disparities in lung cancer screening completion among Black and White patients. Furthermore, these disparities were more apparent in Black women, suggesting that racial and gender intersectional discrimination are important in lung cancer screening completion.

Qualitative coronary artery calcification scores and risk of all cause, COPD and pneumonia hospital admission in a large CT lung cancer screening cohort.

BACKGROUND: Patients at high-risk for lung cancer and qualified for CT lung cancer screening (CTLS) are at risk for numerous cardio-pulmonary comorbidities. We sought to examine if qualitatively assessed coronary artery calcifications (CAC) on CTLS exams could identify patients at increased risk for non-cardiovascular events such as all cause, COPD and pneumonia related hospitalization and to verify previously reported associations between CAC and mortality and cardiovascular events. STUDY DESIGN AND METHODS: Patients (n = 4673) from Lahey Hospital and Medical Center who underwent CTLS from January 12, 2012 through September 30, 2017 were included with clinical follow-up through September 30, 2019. CTLS exams were qualitatively scored for the presence and severity of CAC at the time of exam interpretation using a four point scale: none, mild, moderate, and marked. Multivariable Cox regression models were used to evaluate the association between CT qualitative CAC and all-cause, COPD-related, and pneumonia-related hospital admissions. RESULTS: 3631 (78%) of individuals undergoing CTLS had some degree of CAC on their baseline exam: 1308 (28.0%), 1128 (24.1%), and 1195 (25.6%) had mild, moderate and marked coronary calcification, respectively. Marked CAC was associated with all-cause hospital admission and pneumonia related admissions HR 1.48; 95% CI 1.23-1.78 and HR 2.19; 95% 1.30-3.71, respectively. Mild, moderate and marked CAC were associated with COPD-related admission HR 2.30; 95% CI 1.31-4.03, HR 2.17; 95% CI 1.20-3.91 and HR 2.27; 95% CI 1.24-4.15. CONCLUSION: Qualitative CAC on CTLS exams identifies individuals at elevated risk for all cause, pneumonia and COPD-related hospital admissions.

Management Strategies to Promote Follow-Up Care for Incidental Findings: A Scoping Review.

BACKGROUND: Incidentalomas, or unexpectedly identified masses, are frequently identified in diagnostic imaging studies. Incidentalomas may require timely follow-up care to determine if they are benign, disease-causing, or malignant lesions; however, many incidentalomas do not receive diagnostic workup. The most effective strategies to manage incidentalomas and optimal metrics for judging the efficacy of these strategies remain unclear. OBJECTIVE: To identify management strategies used to promote guideline-concordant follow-up for incidentalomas and commonly reported performance metrics associated with these strategies. DATA SOURCES: We searched peer-reviewed literature for incidentaloma management studies published between 2003 and 2020. DATA EXTRACTION AND SYNTHESIS: Data extraction included anatomical location, imaging modality, clinical setting, management strategy characteristics, and metrics used to assess the management strategy. Eligible studies were analyzed qualitatively to describe strategies and metrics. RESULTS: In all, 15 studies met inclusion criteria. Four types of interventions designed to promote guideline-concordant follow-up care for incidentalomas were identified: (1) physical or verbal guideline reminders (n = 3); (2) electronic guideline references (n = 4); (3) enhanced radiology templates (n = 3); (4) restructured clinical and communication pathways (n = 5). Strategy efficacy was assessed by measuring rates of patients who received recommended follow-up care (n = 6) or had care recommendations documented in clinical records (n = 5). Few studies measured diagnostic outcomes associated with incidentalomas. CONCLUSIONS: Most management strategies target changes in radiologists' behavior. Few studies address barriers to improving incidentaloma follow-up from interpretation to patient education of findings and care delivery. Hybrid effectiveness-implementation studies are needed to better address workflow barriers and rigorously evaluate care delivery outcomes.

Identifying a nasal gene expression signature associated with hyperinflation and treatment response in severe COPD.

Hyperinflation contributes to dyspnea intensity in COPD. Little is known about the molecular mechanisms underlying hyperinflation and how inhaled corticosteroids (ICS) affect this important aspect of COPD pathophysiology. To investigate the effect of ICS/long-acting ß2-agonist (LABA) treatment on both lung function measures of hyperinflation, and the nasal epithelial gene-expression profile in severe COPD. 117 patients were screened and 60 COPD patients entered a 1-month run-in period on low-dose ICS/LABA budesonide/formoterol (BUD/F) 200/6 one inhalation b.i.d. Patients were then randomly assigned to 3-month treatment with either a high dose BDP/F 100/6 two inhalations b.i.d. (n = 31) or BUD/F 200/6 two inhalations b.i.d. (n = 29). Lung function measurements and nasal epithelial gene-expression were assessed before and after 3-month treatment and validated in independent datasets. After 3-month ICS/LABA treatment, residual volume (RV)/total lung capacity (TLC)% predicted was reduced compared to baseline (p < 0.05). We identified a nasal gene-expression signature at screening that associated with higher RV/TLC% predicted values. This signature, decreased by ICS/LABA treatment was enriched for genes associated with increased p53 mediated apoptosis was replicated in bronchial biopsies of COPD patients. Finally, this signature was increased in COPD patients compared to controls in nasal, bronchial and small airways brushings. Short-term ICS/LABA treatment improves RV/TLC% predicted in severe COPD. Furthermore, it decreases the expression of genes involved in the signal transduction by the p53 class mediator, which is a replicable COPD gene expression signature in the upper and lower airways.Trial registration: ClinicalTrials.gov registration number NCT01351792 (registration date May 11, 2011), ClinicalTrials.gov registration number NCT00848406 (registration date February 20, 2009), ClinicalTrials.gov registration number NCT00158847 (registration date September 12, 2005).

Patient characteristics associated with adherence to pulmonary nodule guidelines.

BACKGROUND: While pulmonary nodule guidelines provide follow-up recommendations based on nodule size and malignancy risk, these are inconsistently followed in clinical practice. In this study, we sought to identify patient characteristics associated with guideline-concordant nodule follow-up. METHODS: We conducted a retrospective cohort study of patients diagnosed with a pulmonary nodule between 2011 and 2014 at Boston Medical Center. Appropriate nodule follow-up evaluation was based upon the 2005 Fleischner Society Guidelines. In primary analysis, we compared patients with guideline-concordant follow-up to those with delayed or absent follow-up. In secondary analysis, we compared those with any follow-up to those without follow-up as well as the rate of guideline-concordant follow-up in patients seen by a pulmonologist. RESULTS: Of 3916 patients diagnosed with a pulmonary nodule, 1117 were included for analysis. Overall, 598 (53.5%) patients received guideline-concordant follow-up. Lower rates of guideline concordance were seen in patients of Hispanic ethnicity (OR 0.60, 95% CI 0.36-1.00), while higher rates were seen for nodules 7-8 mm (OR 1.55, 95% CI 1.02-2.35) and nodules >8 mm (OR 1.49, 95% CI 1.01-2.20). Having a history of COPD (OR 1.75, 95% CI 1.26-2.43), and being seen by a pulmonologist (OR 1.97, 95% CI 1.51-2.58) were also associated with guideline concordance. Among patients seen by a pulmonologist, 62.2% received guideline-concordant follow-up. CONCLUSION: Overall rates of pulmonary nodule follow-up are low. Patient ethnicity, COPD history, nodule size and involvement of a pulmonologist may impact follow-up rates and are potential targets for implementation interventions to improve pulmonary nodule follow-up.