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.

Early Evidence of Chronic Obstructive Pulmonary Disease Obscured by Race-Specific Prediction Equations.

Rationale: The identification of early chronic obstructive pulmonary disease (COPD) is essential to appropriately counsel patients regarding smoking cessation, provide symptomatic treatment, and eventually develop disease-modifying treatments. Disease severity in COPD is defined using race-specific spirometry equations. These may disadvantage non-White individuals in diagnosis and care. Objectives: Determine the impact of race-specific equations on African American (AA) versus non-Hispanic White individuals. Methods: Cross-sectional analyses of the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) cohort were conducted, comparing non-Hispanic White (n = 6,766) and AA (n = 3,366) participants for COPD manifestations. Measurements and Main Results: Spirometric classifications using race-specific, multiethnic, and "race-reversed" prediction equations (NHANES [National Health and Nutrition Examination Survey] and Global Lung Function Initiative "Other" and "Global") were compared, as were respiratory symptoms, 6-minute-walk distance, computed tomography imaging, respiratory exacerbations, and St. George's Respiratory Questionnaire. Application of different prediction equations to the cohort resulted in different classifications by stage, with NHANES and Global Lung Function Initiative race-specific equations being minimally different, but race-reversed equations moving AA participants to more severe stages and especially between the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 0 and preserved ratio impaired spirometry groups. Classification using the established NHANES race-specific equations demonstrated that for each of GOLD stages 1-4, AA participants were younger, had fewer pack-years and more current smoking, but had more exacerbations, shorter 6-minute-walk distance, greater dyspnea, and worse BODE (body mass index, airway obstruction, dyspnea, and exercise capacity) scores and St. George's Respiratory Questionnaire scores. Differences were greatest in GOLD stages 1 and 2. Race-reversed equations reclassified 774 AA participants (43%) from GOLD stage 0 to preserved ratio impaired spirometry. Conclusions: Race-specific equations underestimated disease severity among AA participants. These effects were particularly evident in early disease and may result in late detection of COPD.

Use of the Spirometric "Fixed-Ratio" Underdiagnoses COPD in African-Americans in a Longitudinal Cohort Study.

BACKGROUND: COPD diagnosis is tightly linked to the fixed-ratio spirometry criteria of FEV1/FVC < 0.7. African-Americans are less often diagnosed with COPD. OBJECTIVE: Compare COPD diagnosis by fixed-ratio with findings and outcomes by race. DESIGN: Genetic Epidemiology of COPD (COPDGene) (2007-present), cross-sectional comparing non-Hispanic white (NHW) and African-American (AA) participants for COPD diagnosis, manifestations, and outcomes. SETTING: Multicenter, longitudinal US cohort study. PARTICIPANTS: Current or former smokers with ≥ 10-pack-year smoking history enrolled at 21 clinical centers including over-sampling of participants with known COPD and AA. Exclusions were pre-existing non-COPD lung disease, except for a history of asthma. MEASUREMENTS: Subject diagnosis by conventional criteria. Mortality, imaging, respiratory symptoms, function, and socioeconomic characteristics, including area deprivation index (ADI). Matched analysis (age, sex, and smoking status) of AA vs. NHW within participants without diagnosed COPD (GOLD 0; FEV1 ≥ 80% predicted and FEV1/FVC ≥ 0.7). RESULTS: Using the fixed ratio, 70% of AA (n = 3366) were classified as non-COPD, versus 49% of NHW (n = 6766). AA smokers were younger (55 vs. 62 years), more often current smoking (80% vs. 39%), with fewer pack-years but similar 12-year mortality. Density distribution plots for FEV1 and FVC raw spirometry values showed disproportionate reductions in FVC relative to FEV1 in AA that systematically led to higher ratios. The matched analysis demonstrated GOLD 0 AA had greater symptoms, worse DLCO, spirometry, BODE scores (1.03 vs 0.54, p < 0.0001), and greater deprivation than NHW. LIMITATIONS: Lack of an alternative diagnostic metric for comparison. CONCLUSIONS: The fixed-ratio spirometric criteria for COPD underdiagnosed potential COPD in AA participants when compared to broader diagnostic criteria. Disproportionate reductions in FVC relative to FEV1 leading to higher FEV1/FVC were identified in these participants and associated with deprivation. Broader diagnostic criteria for COPD are needed to identify the disease across all populations.

Diagnosis and Detection of Sarcoidosis. An Official American Thoracic Society Clinical Practice Guideline.

Background: The diagnosis of sarcoidosis is not standardized but is based on three major criteria: a compatible clinical presentation, finding nonnecrotizing granulomatous inflammation in one or more tissue samples, and the exclusion of alternative causes of granulomatous disease. There are no universally accepted measures to determine if each diagnostic criterion has been satisfied; therefore, the diagnosis of sarcoidosis is never fully secure.Methods: Systematic reviews and, when appropriate, meta-analyses were performed to summarize the best available evidence. The evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation approach and then discussed by a multidisciplinary panel. Recommendations for or against various diagnostic tests were formulated and graded after the expert panel weighed desirable and undesirable consequences, certainty of estimates, feasibility, and acceptability.Results: The clinical presentation, histopathology, and exclusion of alternative diagnoses were summarized. On the basis of the available evidence, the expert committee made 1 strong recommendation for baseline serum calcium testing, 13 conditional recommendations, and 1 best practice statement. All evidence was very low quality.Conclusions: The panel used systematic reviews of the evidence to inform clinical recommendations in favor of or against various diagnostic tests in patients with suspected or known sarcoidosis. The evidence and recommendations should be revisited as new evidence becomes available.

Diagnosis and detection of sarcoidosis: an official American Thoracic Society Clinical Practice Guideline

The diagnosis of sarcoidosis is not standardized but is based on three major criteria: a compatible clinical presentation, finding nonnecrotizing granulomatous inflammation in one or more tissue samples, and the exclusion of alternative causes of granulomatous disease. There are no universally accepted measures to determine if each diagnostic criterion has been satisfied; therefore, the diagnosis of sarcoidosis is never fully secure. Systematic reviews and, when appropriate, meta-analyses were performed to summarize the best available evidence. The evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation approach and then discussed by a multidisciplinary panel. Recommendations for or against various diagnostic tests were formulated and graded after the expert panel weighed desirable and undesirable consequences, certainty of estimates, feasibility, and acceptability. The clinical presentation, histopathology, and exclusion of alternative diagnoses were summarized. On the basis of the available evidence, the expert committee made 1 strong recommendation for baseline serum calcium testing, 13 conditional recommendations, and best practice statement. All evidence was very low quality.The panel used systematic reviews of the evidence to inform clinical recommendations in favor of or against various diagnostic tests in patients with suspected or known sarcoidosis. The evidence and recommendations should be revisited as new evidence becomes available.

Clinical Epidemiology of COPD: Insights From 10 Years of the COPDGene Study.

The Genetic Epidemiology of COPD (COPDGene) study is a noninterventional, multicenter, longitudinal analysis of > 10,000 subjects, including smokers with a ≥ 10 pack-year history with and without COPD and healthy never smokers. The goal was to characterize disease-related phenotypes and explore associations with susceptibility genes. The subjects were extensively phenotyped with the use of comprehensive symptom and comorbidity questionnaires, spirometry, CT scans of the chest, and genetic and biomarker profiling. The objective of this review was to summarize the major advances in the clinical epidemiology of COPD from the first 10 years of the COPDGene study. We highlight the influence of age, sex, and race on the natural history of COPD, and the impact of comorbid conditions, chronic bronchitis, exacerbations, and asthma/COPD overlap.

Racial differences in quality of life in patients with COPD.

BACKGROUND: Although COPD is associated with significant health-related quality-of-life (HRQL) impairment, factors influencing HRQL in patients with COPD are not well understood, particularly in African Americans. We hypothesized that HRQL in COPD differs by race and sought to identify factors associated with those differences. METHODS: We analyzed 224 African American and 1,049 Caucasian subjects with COPD enrolled in the COPDGene (Genetic Epidemiology of COPD) Study whose conditions were classified as GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages I to IV. HRQL and symptoms were compared using the St. George Respiratory Questionnaire (SGRQ) and the modified Medical Research Council Dyspnea (MMRC) scale. We constructed a mixed-effects linear regression model for SGRQ score. RESULTS: African Americans were younger and reported fewer pack-years of smoking, more current smoking, and less attained education than Caucasians; MMRC scores were higher (P = .02) as were SGRQ scores (mean score difference, 8.4; P < .001). In a general linear model of SGRQ total score after adjusting for factors such as age, sex, and pack-years of smoking, SGRQ total score was similar for African Americans and Caucasians who reported no COPD exacerbations in the prior year. However, for subjects with exacerbations, SGRQ total score was increased to a greater relative extent for African Americans than for Caucasians (1.89 points for each exacerbation, P = .006). For hospitalized exacerbations, the effect on SGRQ total score also was greater for African Americans (4.19 points, P = .04). Furthermore, a larger percentage of African Americans reported having had at least one exacerbation that required hospitalization in the prior year (32% vs 16%, P < .001). CONCLUSION: In analyses that account for other variables that affect quality of life, HRQL is similar for African Americans and Caucasians with COPD without exacerbations but worse for African Americans who experience exacerbations, particularly hospitalized exacerbations.

Comorbid illnesses and chest radiographic severity in African-American sarcoidosis patients.

Sarcoidosis disease expression differs along racial/ethnic lines and black race has been cited as a poor prognostic factor. Besides genetic, healthcare, and socioeconomic factors, comorbid illnesses may influence sarcoidosis disease expression. We set out to investigate the association between comorbid illnesses and chest radiographic severity in a population of African-American sarcoidosis patients. The study was designed as a retrospective database analysis. The hospital and outpatient databases of the Grady Health System were searched to capture adult patients between November 1999 and December 2003 with the ICD-9 codes of 135 or 519.8, along with all associated secondary and tertiary diagnostic codes. Patient electronic pathology and radiographic reports were reviewed for tissue biopsies showing noncaseating granulomas and for chest radiographic Scadding stage. A total of 165 African-American patients were identified (64% female, 43 +/- 10 years old). Ninety percent (149/165) had comorbid illnesses. The most frequent chronic comorbid illnesses were hypertension (39%), diabetes mellitus (19%), anemia (19%), asthma (15%), gastroesophageal reflux disease (15%), depression (13%), and heart failure (10%). Females had increased frequency and clustering of chronic illnesses. Chest radiographic stages were more severe in patients with anemia, depression, and those less than 40 years old. Males, within each chronic illnesses category, had more severe CXR stages compared to females; however, significance was not achieved. We concluded that most adult patients with sarcoidosis have comorbid illnesses and these, in addition to gender differences, may influence sarcoidosis disease expression. Screening for comorbid illnesses should be an important aspect of sarcoidosis patient management.

Racial and ethnic disparities in sarcoidosis: from genetics to socioeconomics.

Sarcoidosis is a multisystem granulomatous disease of unknown cause that occurs worldwide. The clinical expression of sarcoidosis varies by race. These racial differences may be the result of genetic and socioeconomic factors. Many of these genetic associations are race-specific in that they are found in either African Americans or whites but not both. Socioeconomic differences may also explain the racial disparities between African American and white patients with sarcoidosis. Finally, the phenotypic differences be-tween races may relate to an interaction between genetics and socioeconomic factors. The influences of genetics and socioeconomic status on the development and phenotypic expression of sarcoidosis will be better understood as the mechanisms of disease development are uncovered.

Erythrocytosis in a scleroderma patient.

A 40-year-old black male with scleroderma lung disease presented with blurry vision and headache. His presenting hemoglobin was 22.3 g/dL and his serum erythropoietin level was surprisingly low. Although nocturnal hypoxemia was evident, his daytime resting arterial oxygen saturation was normal. The patient's symptoms of hyperviscosity improved after phlebotomy, as his hemoglobin gradually decreased to 18.3 g/dL. Repeat serum erythropoietin levels were in normal and high ranges. Patients with chronic interstitial lung disease and erythrocytosis could have normoxemia at rest and a normal or low serum erythropoietin level at the peak of erythrocytosis. A repeat sampling of serum erythropoietin and monitoring of oxygen saturation during sleep and exertion may help in diagnosis. Physicians should prescribe continuous oxygen therapy for patients with chronic interstitial lung disease and erythrocytosis, even if diurnal resting hypoxemia is absent.

Hospitalization for patients with sarcoidosis: 1979-2000.

BACKGROUND AND AIM: Sarcoidosis is a multi-system granulomatous disease of unknown etiology with significant racial and gender differences in disease severity, incidence, and prevalence. Primarily treated in outpatients, limited information is available on hospital outcomes in patients with sarcoidosis. The National Hospital Discharge Survey (NHDS) was analyzed over a 22-year period to determine trends in hospitalization and the impact of concurrent comorbidities. METHODS: Secondary analysis was done of the NHDS, a national survey of inpatient medical care for short stays in nonfederal facilities. RESULTS: There were a total of 750 million hospitalizations over this 22-year period, with 593,455 (0.08%) hospitalizations with a diagnosis of sarcoidosis. The number of hospitalizations increased from 22,650 in 1979 to 39,964 in 2000, and the age-adjusted rate increased from 108 per 100,000 in 1979 to 146 per 100,000 in 2000. Mean rates of hospitalization were 2.3 times higher for females than males and nine times higher for African-Americans. The mean age of patients increased over this period, particularly for white females. Cardiopulmonary diagnoses were the most frequent concurrent comorbidities. Mortality was low with an overall mortality rate of 2.3%. CONCLUSIONS: Sarcoidosis hospitalizations have increased over this time period. Hospitalization rates are highest among women and African-Americans and are frequently associated with comorbid diseases.

Catastrophic antiphospholipid syndrome in the intensive care unit.

CAPS is characterized by development of widespread microvascular thrombosis. Patients at risk are those with positive aCL or LA factor. Precipitating events, such as infection, trauma, surgical procedures, or reduction in anticoagulation therapy, may contribute to the development of CAPS. Presentation to the ICU can be dramatic, with progressive multiorgan failure and need for rapid institution of life-supporting measures. Cardiopulmonary failure has been the major contributor to mortality. A variety of therapeutic modalities have been used in an attempt to offset the widespread thrombosis and organ damage from high aCL levels. Anticoagulation therapy and high dosages of steroids seem to have a positive effect on survival.