Race Adjustment of Pulmonary Function Tests in the Diagnosis and Management of COPD: A Scoping Review.

Aim: Increasing evidence suggests that the inclusion of self-identified race in clinical decision algorithms may perpetuate longstanding inequities. Until recently, most pulmonary function tests utilized separate reference equations that are race/ethnicity based. Purpose: We assess the magnitude and scope of the available literature on the negative impact of race-based pulmonary function prediction equations on relevant outcomes in African Americans with COPD. Methods: We performed a scoping review utilizing an English language search on PubMed/Medline, Embase, Scopus, and Web of Science in September 2022 and updated it in December 2023. We searched for publications regarding the effect of race-specific vs race-neutral, race-free, or race-reversed lung function testing algorithms on the diagnosis of COPD and COPD-related physiologic and functional measures. Joanna Briggs Institute (JBI) guidelines were utilized for this scoping review. Eligibility criteria: The search was restricted to adults with COPD. We excluded publications on other lung disorders, non-English language publications, or studies that did not include African Americans. The search identified publications. Ultimately, six peer-reviewed publications and four conference abstracts were selected for this review. Results: Removal of race from lung function prediction equations often had opposite effects in African Americans and Whites, specifically regarding the severity of lung function impairment. Symptoms and objective findings were better aligned when race-specific reference values were not used. Race-neutral prediction algorithms uniformly resulted in reclassifying severity in the African Americans studied. Conclusion: The limited literature does not support the use of race-based lung function prediction equations. However, this assertion does not provide guidance for every specific clinical situation. For African Americans with COPD, the use of race-based prediction equations appears to fall short in enhancing diagnostic accuracy, classifying severity of impairment, or predicting subsequent clinical events. We do not have information comparing race-neutral vs race-based algorithms on prediction of progression of COPD. We conclude that the elimination of race-based reference values potentially reduces underestimation of disease severity in African Americans with COPD.

Social and Biological Determinants in Lung Cancer Disparity.

Lung cancer remains a leading cause of death in the United States and globally, despite progress in treatment and screening efforts. While mortality rates have decreased in recent years, long-term survival of patients with lung cancer continues to be a challenge. Notably, African American (AA) men experience significant disparities in lung cancer compared to European Americans (EA) in terms of incidence, treatment, and survival. Previous studies have explored factors such as smoking patterns and complex social determinants, including socioeconomic status, personal beliefs, and systemic racism, indicating their role in these disparities. In addition to social factors, emerging evidence points to variations in tumor biology, immunity, and comorbid conditions contributing to racial disparities in this disease. This review emphasizes differences in smoking patterns, screening, and early detection and the intricate interplay of social, biological, and environmental conditions that make African Americans more susceptible to developing lung cancer and experiencing poorer outcomes.

Returning incidentally discovered Hepatitis C RNA-seq results to COPDGene study participants.

The consequences of returning infectious pathogen test results identified incidentally in research studies have not been well-studied. Concerns include identification of an important health issue for individuals, accuracy of research test results, public health impact, potential emotional distress for participants, and need for IRB permissions. Blood RNA-sequencing analysis for non-human RNA in 3984 participants from the COPDGene study identified 228 participants with evidence suggestive for hepatitis C virus (HCV) infection. We hypothesized that incidentally discovered HCV results could be effectively returned to COPDGene participants with attention to the identified concerns. In conjunction with a COPDGene Participant Advisory Panel, we developed and obtained IRB approval for a process of returning HCV research results and an HCV Follow-Up Study questionnaire to capture information about previous HCV diagnosis and treatment information and participant reactions to return of HCV results. During phone calls following the initial HCV notification letter, 84 of 124 participants who could be contacted (67.7%) volunteered that they had been previously diagnosed with HCV infection. Thirty-one of these 124 COPDGene participants were enrolled in the HCV Follow-Up Study. Five of the 31 HCV Follow-Up Study participants did not report a previous diagnosis of HCV. For four of these participants, subsequent clinical HCV testing confirmed HCV infection. Thus, 30/31 Follow-Up Study participants had confirmed HCV diagnoses, supporting the accuracy of the HCV research test results. However, the limited number of participants in the Follow-Up Study precludes an accurate assessment of the false-positive and false-negative rates of the research RNA sequencing evidence for HCV. Most HCV Follow-Up Study participants (29/31) were supportive of returning HCV research results, and most participants found the process for returning HCV results to be informative and not upsetting. Newly diagnosed participants were more likely to be pleased to learn about a potentially curable infection (p = 0.027) and showed a trend toward being more frightened by the potential health risks of HCV (p = 0.11). We conclude that HCV results identified incidentally during transcriptomic research studies can be successfully returned to research study participants with a carefully designed process.

COPDGene® 2019: Redefining the Diagnosis of Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality. Present-day diagnostic criteria are largely based solely on spirometric criteria. Accumulating evidence has identified a substantial number of individuals without spirometric evidence of COPD who suffer from respiratory symptoms and/or increased morbidity and mortality. There is a clear need for an expanded definition of COPD that is linked to physiologic, structural (computed tomography [CT]) and clinical evidence of disease. Using data from the COPD Genetic Epidemiology study (COPDGene®), we hypothesized that an integrated approach that includes environmental exposure, clinical symptoms, chest CT imaging and spirometry better defines disease and captures the likelihood of progression of respiratory obstruction and mortality. METHODS: Four key disease characteristics - environmental exposure (cigarette smoking), clinical symptoms (dyspnea and/or chronic bronchitis), chest CT imaging abnormalities (emphysema, gas trapping and/or airway wall thickening), and abnormal spirometry - were evaluated in a group of 8784 current and former smokers who were participants in COPDGene® Phase 1. Using these 4 disease characteristics, 8 categories of participants were identified and evaluated for odds of spirometric disease progression (FEV1 > 350 ml loss over 5 years), and the hazard ratio for all-cause mortality was examined. RESULTS: Using smokers without symptoms, CT imaging abnormalities or airflow obstruction as the reference population, individuals were classified as Possible COPD, Probable COPD and Definite COPD. Current Global initiative for obstructive Lung Disease (GOLD) criteria would diagnose 4062 (46%) of the 8784 study participants with COPD. The proposed COPDGene® 2019 diagnostic criteria would add an additional 3144 participants. Under the new criteria, 82% of the 8784 study participants would be diagnosed with Possible, Probable or Definite COPD. These COPD groups showed increased risk of disease progression and mortality. Mortality increased in patients as the number of their COPD characteristics increased, with a maximum hazard ratio for all cause-mortality of 5.18 (95% confidence interval [CI]: 4.15-6.48) in those with all 4 disease characteristics. CONCLUSIONS: A substantial portion of smokers with respiratory symptoms and imaging abnormalities do not manifest spirometric obstruction as defined by population normals. These individuals are at significant risk of death and spirometric disease progression. We propose to redefine the diagnosis of COPD through an integrated approach using environmental exposure, clinical symptoms, CT imaging and spirometric criteria. These expanded criteria offer the potential to stimulate both current and future interventions that could slow or halt disease progression in patients before disability or irreversible lung structural changes develop.

Potential Racial Disparities Using Current Lung Cancer Screening Guidelines.

RATIONALE: The current age threshold for lung cancer screening targets individuals beginning at age 55. These guidelines were developed based on results from the National Lung Cancer Screening Trial where only 4.4% of the enrollees were African American, when they represent 12.3% of US population. African Americans were also found to have higher incidence and younger onset of lung cancer. We hypothesized that implementation of screening at age 55 would not detect a substantial fraction of early onset lung cancer cases in African American population. OBJECTIVES: We used Surveillance, Epidemiology, and End Results (SEER) Program data to determine the frequency of early-onset lung cancers and to assess the stage at diagnosis in a biracial sample. METHODS: Microscopically confirmed lung cancer (primary site code C 34) cases were identified using SEER 18 registry (2004-2014). Early-onset cancers were defined as cancers diagnosed in persons aged 45 to 54 years. Cases were stratified by race and age groups. Comparisons were evaluated with chi-square tests. RESULTS: 468,403 lung cancers were diagnosed during this period. Nearly 9% of all lung cancers were early onset, with increased frequency in African Americans vs. Whites, 14.2 vs. 8.2%, p < 0.05. Age-adjusted incidence rates were significantly higher in African Americans with highest percent difference noted for age group 50-54. African Americans were more likely to be diagnosed at advanced stages of lung cancer compared to Whites. CONCLUSIONS: We conclude that the current age threshold for lung cancer screening may potentially miss a considerable number of lung cancer cases in African Americans. Further studies are needed to determine the appropriateness of screening age criteria for African Americans.

Tobacco smoking in China: a pulmonary health crisis.

PURPOSE OF REVIEW: China's economy has had tremendous growth through the principle of command economy, where profitable private industries become government-owned and managed. The tobacco industry, which generates 10% of the annual governmental income from the country's over 300 million smokers, serves as a prime example. The present review takes an in-depth look at how the success of the government's tobacco industry has caused a pulmonary health crisis for the country with the world's largest population; and in turn, poses a threat to global lung health. RECENT FINDINGS: China's emergence as a world leader has allowed insight to the nation's health system. Recent studies have shown that China has the highest prevalence and the worst outcomes of smoking related pulmonary diseases such as chronic obstructive pulmonary disease. Similarly, the rates of lung cancer have grown exponentially over the last decade with China now accounting for 36% of annual new cases globally. The burden of disease is detrimental to the health system, places financial hardship on patients, and threatens the economy and work force. SUMMARY: The present review should serve as a call for research, preventive health initiatives, and governmental policy to reform tobacco production, social acceptance, and use.

Study Design and Rationale: A Multicenter, Prospective Trial of Electromagnetic Bronchoscopic and Electromagnetic Transthoracic Navigational Approaches for the Biopsy of Peripheral Pulmonary Nodules (ALL IN ONE Trial).

BACKGROUND: Pulmonary nodules are a common but difficult issue for physicians as most identified on imaging are benign but those identified early that are cancerous are potentially curable. Multiple diagnostic options are available, ranging from radiographic surveillance, minimally invasive biopsy (bronchoscopy or transthoracic biopsy) to more invasive surgical biopsy/resection. Each technique has differences in diagnostic yield and complication rates with no established gold standard. Currently, the safest approach is bronchoscopic but it is limited by variable diagnostic yields. Percutaneous approaches are limited by nodule location and complications. With the recent advent of electromagnetic navigation (EMN), a combined bronchoscopic and transthoracic approach is now feasible in a single, staged procedure. Here, we present the study design and rationale for a single-arm trial evaluating a staged approach for the diagnosis of pulmonary nodules. METHODS: Participants with 1-3 cm, intermediate to high-risk pulmonary nodules will undergo a staged approach with endobronchial ultrasound (EBUS) followed by EMN-bronchoscopy (ENB), then EMN-transthoracic biopsy (EMN-TTNA) with the procedure terminated at any stage after a diagnosis is made via rapid onsite cytopathology. We aim to recruit 150 EMN participants from eight academic and community settings to show significant improvements over other historic bronchoscopic guided techniques. The primary outcome is overall diagnostic yield of the staged approach. CONCLUSION: This is the first study designed to evaluate the diagnostic yield of a staged procedure using EBUS, ENB and EMN-TTNA for the diagnosis of pulmonary nodules. If effective, the staged procedure will increase minimally invasive procedural diagnostic yield for pulmonary nodules.

Features of COPD as Predictors of Lung Cancer.

BACKGROUND: Lung cancer is a leading cause of death and hospitalization for patients with COPD. A detailed understanding of which clinical features of COPD increase risk is needed. METHODS: We performed a nested case-control study of Genetic Epidemiology of COPD (COPDGene) Study subjects with and without lung cancer, age 45 to 80 years, who smoked at least 10-pack years to identify clinical and imaging features of smokers, with and without COPD, that are associated with an increased risk of lung cancer. The baseline evaluation included spirometry, high-resolution chest CT scanning, and respiratory questionnaires. New lung cancer diagnoses were identified over 8 years of longitudinal follow-up. Cases of lung cancer were matched 1:4 with control subjects for age, race, sex, and smoking history. Multiple logistic regression analyses were used to determine features predictive of lung cancer. RESULTS: Features associated with a future risk of lung cancer included decreased FEV1/FVC (OR, 1.28 per 10% decrease [95% CI, 1.12-1.46]), visual severity of emphysema (OR, 2.31, none-trace vs mild-advanced [95% CI, 1.41-3.86]), and respiratory exacerbations prior to study entry (OR, 1.39 per increased events [0, 1, and ≥ 2] [95% CI, 1.04-1.85]). Respiratory exacerbations were also associated with small-cell lung cancer histology (OR, 3.57 [95% CI, 1.47-10]). CONCLUSIONS: The degree of COPD severity, including airflow obstruction, visual emphysema, and respiratory exacerbations, was independently predictive of lung cancer. These risk factors should be further studied as inclusion and exclusion criteria for the survival benefit of lung cancer screening. Studies are needed to determine if reduction in respiratory exacerbations among smokers can reduce the risk of lung cancer.

Low-dose spiral CT screening and evaluation of the solitary pulmonary nodule.

Lung cancer screening using helical low-dose computerized tomography (LDCT) increased drastically after publication of a successful well-designed prospective randomized screening study, the National Lung Screening Trial. This increase in screening has led to a significant increase in the diagnosis of solitary pulmonary nodules (SPNs). Some of these lesions are early cancers, and their removal can potentially prevent a lung cancer death. Some have the histologic appearance of a cancer but will never progress and cause harm. Some are non-neoplastic and are best observed. The number of lesions detected with LDCT is so great that algorithms are being developed for more efficient evaluation and management of SPNs. This article will discuss current tools, approaches, and concerns regarding patient care in this setting.

Lung cancer disparities in African Americans: health versus health care.

African Americans with lung cancer have disproportionately worse outcomes than other ethnic groups. The incidence of lung cancer in blacks has remained well above the rates seen for the general population and the 5-year and overall survival rates for blacks with lung cancer are among the lowest of all racial groups. Many studies have focused on socioeconomic status of African Americans as the sole cause of these disparities. Other stu-dies, however, have identified additional factors related to risks for poor outcomes in blacks with lung cancer. This article reviews data on these risks and their relationships to the health and health care of African Americans with lung cancer.

Hemoptysis, anemia and respiratory failure: a rare initial presentation of acute leukemia.

Leukemic pulmonary infiltration, as an initial presentation of acute leukemia, is rare and poses a therapeutic dilemma. Leukemic infiltrate of the lung may be unrecognized, as patients can present with cough, fever and localized roentgenographic infiltrate, all suggestive of bacterial pneumonia. Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) with distinct clinicopathologic features, such as: younger age of patients, shorter duration of symptoms before diagnosis, pulmonary infiltration with atypical promyelocytes and bleeding tendency due to disseminated intravascular coagulation (DIC). APL can become rapidly fatal if not treated early in its course. We report a case of APL with diffuse pulmonary infiltration and abnormal complete blood count. He was initially diagnosed and treated as an outpatient for community-acquired pneumonia. The patient returned with worsening pulmonary infiltrate, abnormal peripheral smear and respiratory failure, resulting in death within three months of his initial presentation. As evidenced by this case, acute leukemia should be considered in the differential diagnosis for pulmonary infiltrate and abnormal hematological findings.