Barriers and facilitators to lung cancer screening and follow-up.

Two randomized trials have shown that lung cancer screening (LCS) with low dose computed tomography (LDCT) reduces lung cancer mortality in patients at high-risk for lung malignancy by identifying early-stage cancers, when local cure and control is achievable. The implementation of LCS in the United States has revealed multiple barriers to preventive cancer care. Rates of LCS are disappointingly low with estimates between 5%-18% of eligible patients screened. Equally concerning, follow-up after baseline screening is far lower than that of clinical trials (44-66% v >90%). To optimize the benefits of LCS, programs must identify and address factors related to LCS participation and follow-up while concurrently recognizing and mitigating barriers. As a relatively new screening test, the most effective processes for LCS are uncertain. Therefore, LCS programs have adopted a wide range of approaches without clearly established best practices to guide them, particularly in rural and resource-limited settings. In this narrative review, we identify barriers and facilitators to LCS, focusing on those studies in non-clinical trial settings - reflecting "real world" challenges. Our goal is to identify effective and scalable LCS practices that will increase LCS participation, improve adherence to follow-up, inform strategies for quality improvement, and support new research approaches.

Racial Differences in Adherence to Lung Cancer Screening Follow-up: A Systematic Review and Meta-analysis.

BACKGROUND: In 2013, the United States Preventive Services Taskforce instituted recommendations for annual lung cancer screening (LCS) with low-dose chest CT imaging for high-risk individuals. LCS reduces lung cancer mortality, with greater reduction observed in Black participants in clinical trials. Although racial disparities in lung cancer mortality have been well documented, less is known about disparities in LCS participation and adherence to follow-up in clinical practice. RESEARCH QUESTION: What is the association between race and adherence to LCS follow-up? STUDY DESIGN AND METHODS: A systematic review was conducted through a search of published studies in MEDLINE, PubMed, EMBASE, Web of Science, and Cumulative Index to Nursing and Allied Health Literature Database from database inception through October 2020. We included studies that examined rates of adherence to LCS follow-up and compared rates by race. Studies were pooled using random-effects meta-analysis. RESULTS: We screened 18,300 titles and abstracts, and 229 studies were selected for full-text review. Nine studies met inclusion criteria; seven were included in the meta-analysis. Median adherent follow-up rate was 37% (range, 16%-82%). Notable differences among the studies included the proportion of the Black population (range, 4%-47%) and the structure of the LCS programs. The meta-analyses showed lower adherence to LCS follow-up in the Black population (OR, 0.67; 95% CI, 0.55-0.80). This disparity persisted across all malignancy risk levels determined by initial screening results. INTERPRETATION: Lower adherence to LCS follow-up in Black compared with White patients occurs despite the higher potential lung cancer mortality benefit. Literature specifically addressing race-related barriers to LCS adherence remains limited. To ensure equity in LCS benefits, greater outreach to eligible Black patients should be implemented through increased physician education and use of screening program coordinators to focus on this patient population. TRIAL REGISTRY: PROSPERO; No.: CRD42020214213; URL: http://www.crd.york.ac.uk/PROSPERO.

Underutilization of Pulmonary Function Testing in Veterans Hospitalized for Chronic Obstructive Pulmonary Disease Exacerbation: Who are We Missing?

Pulmonary function testing (PFT) is required to diagnose chronic obstructive pulmonary disease (COPD) but is completed for only 30-50% of patients with the disease. We determined patient factors associated with decreased likelihood for PFT acquisition (i.e. underutilization) in the United States Veterans Affairs (VA) health care system.We performed a retrospective analysis of Veterans who survived a VA-based COPD hospitalization between 2012 and 2015. COPD was identified using International Classification of Disease (ICD)-9 codes. Our primary outcome was PFT acquisition, using Current Procedural Terminology (CPT) codes any time prior to the index hospitalization. We compared patients with and without PFTs and used logistic regression to identify associations with PFT underutilization.Of the 48,888 Veterans included, 78% underwent PFTs prior to hospitalization. Patients without PFTs were younger and more likely to be: women (4.2% vs. 3.6%; p = 0.01), nonwhite (22% vs. 19%; p < 0.0001), and current smokers (66% vs 61%; p < 0.0001). PFT acquisition was less likely in Veterans with alcohol and drug use disorders. Using logistic regression, Veterans who were women (Odds Ratio (OR) = 1.17 [95% confidence limit 1.03-1.32]), nonwhite (OR 1.12 [1.06-1.20]), and with a history of alcohol (OR = 1.07 [1.00-1.14]) or drug use disorders (OR = 1.15 [1.06-1.24]) were less likely to undergo PFTs.Though most Veterans hospitalized for COPD had PFTs prior to admission, PFTs are underutilized in Veterans who are: women, younger, nonwhite, and have alcohol or drug use disorders. These groups may be "at-risk" for delayed diagnosis or substandard COPD quality care.

Spirometry, Static Lung Volumes, and Diffusing Capacity.

BACKGROUND: Spirometric Z-scores from the Global Lung Initiative (GLI) rigorously account for age-related changes in lung function and are thus age-appropriate when establishing spirometric impairments, including a restrictive pattern and air-flow obstruction. However, GLI-defined spirometric impairments have not yet been evaluated regarding associations with static lung volumes (total lung capacity [TLC], functional residual capacity [FRC], and residual volume [RV]) and gas exchange (diffusing capacity). METHODS: We performed a retrospective review of pulmonary function tests in subjects ≥40 y old (mean age 64.6 y), including pre-bronchodilator measures for: spirometry (n = 2,586), static lung volumes by helium dilution with inspiratory capacity maneuver (n = 2,586), and hemoglobin-adjusted single-breath diffusing capacity (n = 2,508). Using multivariable linear regression, adjusted least-squares means (adjLSMeans) were calculated for TLC, FRC, RV, and hemoglobin-adjusted single-breath diffusing capacity. The adjLSMeans were expressed with and without height-cubed standardization and stratified by GLI-defined spirometry, including normal (n = 1,251), restrictive pattern (n = 663), and air-flow obstruction (mild, [n = 128]; moderate, [n = 150]; and severe, [n = 394]). RESULTS: Relative to normal spirometry, restrictive-pattern had lower adjLSMeans for TLC, FRC, RV, and hemoglobin-adjusted single-breath diffusing capacity (P ≤ .001). Conversely, relative to normal spirometry, mild, moderate, and severe air-flow obstruction had higher adjLSMeans for FRC and RV (P < .001). However, only mild and moderate air-flow obstruction had higher adjLSMeans for TLC (P < .001), while only moderate and severe air-flow obstruction had higher adjLSMeans for RV/TLC (P < .001) and lower adjLSMeans for hemoglobin-adjusted single-breath diffusing capacity (P < .001). Notably, TLC (calculated as FRC + inspiratory capacity) was not increased in severe air-flow obstruction (P ≥ .11) because inspiratory capacity decreased with increasing air-flow obstruction (P < .001), thus opposing the increased FRC (P < .001). Finally, P values were similar whether adjLSMeans were height-cubed standardized. CONCLUSIONS: A GLI-defined spirometric restrictive pattern is strongly associated with a restrictive ventilatory defect (decreased TLC, FRC, and RV), while GLI-defined spirometric air-flow obstruction is strongly associated with hyperinflation (increased FRC) and air trapping (increased RV and RV/TLC). Both spirometric impairments were strongly associated with impaired gas exchange (decreased hemoglobin-adjusted single-breath diffusing capacity).

A rare 'incidentaloma' found on low-dose CT screening for lung cancer: 'scanner beware'.

Screening for lung cancer with low-dose computed tomography (LDCT) has been shown to reduce mortality and has been recommended by the U.S. Preventive Services Task Force for adults 55 to 80 years of age with a 30 pack-year smoking history who are either current smokers or those that quit within 15 years. However, the overwhelming majority of abnormalities detected are not from malignancy. We report a case of pulmonary Langerhans' cell histiocytosis, here-to-fore thought of as extremely uncommon, and make readers aware that this may be increasingly found as LDCT is more widely adopted.

Evaluations of Implementation at Early-Adopting Lung Cancer Screening Programs: Lessons Learned.

BACKGROUND: Guidelines recommend lung cancer screening (LCS), and it is currently being adopted nationwide. The American College of Chest Physicians advises inclusion of specific programmatic components to ensure high-quality screening. However, little is known about how LCS has been implemented in practice. We sought to evaluate the experience of early-adopting programs, characterize barriers faced, and identify strategies to achieve successful implementation. METHODS: We performed qualitative evaluations of LCS implementation at three Veterans Administration facilities, conducting semistructured interviews with key staff (n = 29). Guided by the Promoting Action on Research Implementation in Health Services framework, we analyzed transcripts using principals of grounded theory. RESULTS: Programs successfully incorporated most recommended elements of LCS, although varying in approaches to patient selection, tobacco treatment, and quality audits. Barriers to implementation included managing workload to ensure appropriate evaluation of pulmonary nodules detected by screening and difficulty obtaining primary care "buy-in." To manage workload, programs used nurse coordinators to actively maintain screening registries, held multidisciplinary conferences that generated explicit management recommendations, and rolled out implementation in a staged fashion. Successful strategies to engage primary care providers included educational sessions, audit and feedback of local outcomes, and assisting with and assigning clear responsibility for nodule evaluation. Capitalizing on pre-existing relationships and including a designated program champion helped facilitate intradisciplinary communication. CONCLUSIONS: Lung cancer screening implementation is a complex undertaking requiring coordination at many levels. The insight gained from evaluation of these early-adopting programs may inform subsequent design and implementation of LCS programs.

The effect of a lung cancer care coordination program on timeliness of care.

BACKGROUND: Timeliness of care improves patient satisfaction and might improve outcomes. The CCCP was established in November 2007 to improve timeliness of care of NSCLC at the Veterans Affairs Connecticut Healthcare System (VACHS). PATIENTS AND METHODS: We performed a retrospective cohort analysis of patients diagnosed with NSCLC at VACHS between 2005 and 2010. We compared timeliness of care and stage at diagnosis before and after the implementation of the CCCP. RESULTS: Data from 352 patients were analyzed: 163 with initial abnormal imaging between January 1, 2005 and October 31, 2007, and 189 with imaging conducted between November 1, 2007 and December 31, 2010. Variables associated with a longer interval between the initial abnormal image and the initiation of therapy were: (1) earlier stage (mean of 130 days for stages I/II vs. 87 days for stages III/IV; P < .0001); (2) lack of cancer-related symptoms (145 vs. 60 days; P < .0001); (3) presence of more than 1 medical comorbidity (123 vs. 82; P = .0002); and (4) depression (126 vs. 98 days; P = .029). The percent of patients diagnosed at stages I/II increased from 32% to 48% (P = .006) after establishment of the CCCP. In a multivariate model adjusting for stage, histology, reason for imaging, and presence of primary care provider, implementation of the CCCP resulted in a mean reduction of 25 days between first abnormal image and the initiation of treatment (126 to 101 days; P = .015). CONCLUSION: A centralized, multidisciplinary, hospital-based CCCP can improve timeliness of NSCLC care, and help ensure that early stage lung cancers are diagnosed and treated.

Upper extremity deep vein thrombosis.

Upper extremity deep vein thrombosis (UEDVT) is associated with significant morbidity and mortality. The susceptible populations and risk factors for UEDVT are well-known. The presenting symptoms can be subtle, and therefore objective testing is necessary for diagnosis. The optimal diagnostic strategy has not been determined, and more than one test may be required to exclude the diagnosis. Proper treatment reduces the occurrence of complications, and treatment should include long-term anticoagulation if the patient has no contraindications. This article discusses the risk factors, pathogenesis, diagnosis, complications, and management of UEDVT.

IL-18 is induced and IL-18 receptor alpha plays a critical role in the pathogenesis of cigarette smoke-induced pulmonary emphysema and inflammation.

Th1 inflammation and remodeling characterized by local tissue destruction coexist in pulmonary emphysema and other diseases. To test the hypothesis that IL-18 plays an important role in these responses, we characterized the regulation of IL-18 in lungs from cigarette smoke (CS) and room air-exposed mice and characterized the effects of CS in wild-type mice and mice with null mutations of IL-18Ralpha (IL-18Ralpha(-/-)). CS was a potent stimulator and activator of IL-18 and caspases 1 and 11. In addition, although CS caused inflammation and emphysema in wild-type mice, both of these responses were significantly decreased in IL-18Ralpha(-/-) animals. CS also induced epithelial apoptosis, activated effector caspases and stimulated proteases and chemokines via IL-18Ralpha-dependent pathways. Importantly, the levels of IL-18 and its targets, cathepsins S and B, were increased in pulmonary macrophages from smokers and patients with chronic obstructive lung disease. Elevated levels of circulating IL-18 were also seen in patients with chronic obstructive lung disease. These studies demonstrate that IL-18 and the IL-18 pathway are activated in CS-exposed mice and man. They also demonstrate, in a murine modeling system, that IL-18R signaling plays a critical role in the pathogenesis of CS-induced inflammation and emphysema.

High rate of negative results of tuberculin and QuantiFERON tests among individuals with a history of positive skin test results.

OBJECTIVES: To evaluate individuals at high risk for tuberculosis exposure who had a history of a positive tuberculin skin test (TST) result in order to determine the prevalence of unsuspected negative TST results. To confirm these findings with the QuantiFERON-TB test (QFT), an in vitro whole-blood assay that measures tuberculin-induced secretion of interferon-gamma. METHODS: This survey was conducted from November 2001 through December 2003 at 3 sites where TST screening is regularly done. Detailed histories and reviews of medical records were performed. TSTs were placed and read by 2 experienced healthcare workers, and blood was drawn for QFT. Any subject with a negative result of an initial TST during the study (induration diameter, <10 mm) underwent a second TST and a second QFT. The TST-negative group comprised individuals for whom both TSTs had an induration diameter of <10 mm. The confirmed-negative group comprised individuals for whom both TSTs yielded no detectable induration and results of both QFTs were negative. RESULTS: A total of 67 immunocompetent subjects with positive results of a previous TST were enrolled in the study. Of 56 subjects who completed the TST protocol, 25 (44.6%; 95% confidence interval [CI], 31.6%-57.6%) were TST negative (P<.001). Of 31 subjects who completed the TST protocol and the QFT protocol, 8 (25.8%; 95% CI, 10.4%-41.2%) were confirmed negative (P<.005). CONCLUSIONS: A significant proportion of subjects with positive results of a previous TST were TST negative in this study, and a subset of these were confirmed negative. These individuals' TST status may have reverted or may never have been positive. It will be important in future studies to determine whether such individuals lack immunity to tuberculosis and whether they should be considered for reentry into tuberculosis screening programs.

Pulmonary impairment and disability.

Respiratory disorders, including occupational and environmental lung diseases, are prevalent. Physicians are frequently called upon to determine impairment and aid in the assessment of disability caused by these conditions, either as the treating physician or as an independent medical examiner. In this article we reviewed the role of physicians in determining the presence and severity of pulmonary disorders. A comprehensive clinical assessment and appropriate standardized tests, to objectively characterize the severity of impairment, are the key elements of the evaluation. This assessment may also include the physician's opinion regarding causative factors. Finally, disability determination is made by nonclinicians, through administrative means, based on the degree of impairment and a review of circumstances specific to the individual. Knowledge of these components of disability evaluation will help physicians to better serve their patients and supply appropriate data to the adjudicating system.