Indoor particulate matter concentrations and air cleaner intervention association with biomarkers in former smokers with COPD.

BACKGROUND: Indoor pollutants have been associated with worse clinical outcomes in chronic obstructive pulmonary disease (COPD). Elevated biomarkers are associated with ambient pollution exposure, however the association with indoor pollution remains unclear. METHODS: Former smokers with spirometry-confirmed COPD were randomized to portable air cleaner or placebo. Indoor particulate matter (PM2.5, PM10, and ultrafine particles [UFP; PM<0.1]) and biomarkers were measured longitudinally at pre-specified intervals and course PM fraction (PM10-2.5) was calculated. Biomarkers were categorized based on associations with biologic mechanisms: inflammation (white blood cell count, interleukin [IL]-6, IL-8, IL-1ß, tumor necrosis factor-α, interferon-γ, serum amyloid A), platelet activation (P-selectin, CD40 ligand [CD40L], 11-dehdydro-thromboxane-B2 [11dTxB2]), endothelial dysfunction (Vascular Cell Adhesion Molecule [VCAM]-1, Intercellular Adhesion Molecule [ICAM]-1), and oxidative stress (thiobarbituric acid reactive substances [TBARS], 8-hydroxydeoxyguanosine, 8-isoprostane). Associations between PM concentrations and each biomarker were analyzed using multivariable linear mixed models. An intention-to-treat analysis was performed to evaluate the air cleaner intervention on the biomarker levels longitudinally. RESULTS: Fifty-eight participants were randomized to each group. Finer PM was more strongly associated with higher IL-8 (mean difference per doubling: UFP 13.9% [p = 0.02], PM2.5 6.8% [p = 0.002], PM10-2.5 5.0% [p = 0.02]) while interferon-γ was associated with UFP and IL-1ß with PM10-2.5. UFP and PM2.5 were associated with elevated levels of the oxidative stress biomarkers TBARS and 8-isoprostane respectively. For platelet activation markers, UFP was associated with higher 11dTxB2 while PM2.5 was associated with higher P-selectin and CD40L. Pollutants were not associated with biomarkers of endothelial dysfunction. In intention-to-treat analysis there was no association of the air cleaner intervention with any of the biomarkers. DISCUSSION: Among former smokers with COPD, elevated levels of indoor air pollutants, particularly ultrafine particles (PM<0.1), were associated with elevated biomarkers of inflammation, platelet activation, and oxidative stress. However, an air cleaner intervention that reduced PM did not significantly reduce biomarker levels.

Indoor Air Pollution and Impaired Cardiac Autonomic Function in Chronic Obstructive Pulmonary Disease.

Rationale: Indoor air pollution represents a modifiable risk factor for respiratory morbidity in chronic obstructive pulmonary disease (COPD). The effects of indoor air pollution, as well as the impact of interventions to improve indoor air quality, on cardiovascular morbidity in COPD remain unknown. Objectives: To determine the association between indoor particulate matter (PM) and heart rate variability (HRV), a measure of cardiac autonomic function tied to cardiovascular morbidity and mortality, as well as the impact of household air purifiers on HRV. Methods: Former smokers with moderate-severe COPD were recruited from a 6-month randomized controlled trial of a portable air cleaner intervention to undergo paired assessment of both in-home PM and HRV using 24-hour Holter monitoring at up to five time points. Primary outcomes were HRV measures tied to cardiovascular morbidity (standard deviation of normal-to-normal intervals [SDNN] and root mean square of successive differences between normal-to-normal intervals [RMSSD]). Measurements and Results: Eighty-five participants contributed 317 HRV measurements. A twofold increase in household PM ⩽2.5 µm in aerodynamic diameter was associated with decreases in SDNN (ß, -2.98% [95% confidence interval (CI), -5.12 to -0.78]) and RMSSD (ß, -4.57% [95% CI, -10.1 to -1.60]). The greatest effects were observed with ultrafine particles (<100 nm) (RMSSD; ß, -16.4% [95% CI, -22.3 to -10.1]) and among obese participants. Participants randomized to the active air cleaner saw improvements in RMSSD (ß, 25.2% [95% CI, 2.99 to 52.1]), but not SDNN (ß, 2.65% [95% CI, -10.8 to 18.1]), compared with the placebo group. Conclusions: This is the first U.S. study to describe the association between household PM and cardiac autonomic function among individuals with COPD, as well as the potential cardiovascular health benefits of household air cleaners.

Evaluation of Calibration Approaches for Indoor Deployments of PurpleAir Monitors.

Low-cost air quality monitors are growing in popularity among both researchers and community members to understand variability in pollutant concentrations. Several studies have produced calibration approaches for these sensors for ambient air. These calibrations have been shown to depend primarily on relative humidity, particle size distribution, and particle composition, which may be different in indoor environments. However, despite the fact that most people spend the majority of their time indoors, little is known about the accuracy of commonly used devices indoors. This stems from the fact that calibration data for sensors operating in indoor environments are rare. In this study, we sought to evaluate the accuracy of the raw data from PurpleAir fine particulate matter monitors and for published calibration approaches that vary in complexity, ranging from simply applying linear corrections to those requiring co-locating a filter sample for correction with a gravimetric concentration during a baseline visit. Our data includes PurpleAir devices that were co-located in each home with a gravimetric sample for 1-week periods (265 samples from 151 homes). Weekly-averaged gravimetric concentrations ranged between the limit of detection (3 µg/m3) and 330 µg/m3. We found a strong correlation between the PurpleAir monitor and the gravimetric concentration (R>0.91) using internal calibrations provided by the manufacturer. However, the PurpleAir data substantially overestimated indoor concentrations compared to the gravimetric concentration (mean bias error ≥ 23.6 µg/m3 using internal calibrations provided by the manufacturer). Calibrations based on ambient air data maintained high correlations (R ≥ 0.92) and substantially reduced bias (e.g. mean bias error = 10.1 µg/m3 using a US-wide calibration approach). Using a gravimetric sample from a baseline visit to calibrate data for later visits led to an improvement over the internal calibrations, but performed worse than the simpler calibration approaches based on ambient air pollution data. Furthermore, calibrations based on ambient air pollution data performed best when weekly-averaged concentrations did not exceed 30 µg/m3, likely because the majority of the data used to train these models were below this concentration.

Racial Segregation and Respiratory Outcomes among Urban Black Residents with and at Risk of Chronic Obstructive Pulmonary Disease.

Rationale: Racial residential segregation has been associated with worse health outcomes, but the link with chronic obstructive pulmonary disease (COPD) morbidity has not been established.Objectives: To investigate whether racial residential segregation is associated with COPD morbidity among urban Black adults with or at risk of COPD.Methods: Racial residential segregation was assessed using isolation index, based on 2010 decennial census and baseline address, for Black former and current smokers in the multicenter SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study), a study of adults with or at risk for COPD. We tested the association between isolation index and respiratory symptoms, physiologic outcomes, imaging parameters, and exacerbation risk among urban Black residents, adjusting for established COPD risk factors, including smoking. Additional mediation analyses were conducted for factors that could lie on the pathway between segregation and COPD outcomes, including individual and neighborhood socioeconomic status, comorbidity burden, depression/anxiety, and ambient pollution.Measurements and Main Results: Among 515 Black participants, those residing in segregated neighborhoods (i.e., isolation index ⩾0.6) had worse COPD Assessment Test score (ß = 2.4; 95% confidence interval [CI], 0.7 to 4.0), dyspnea (modified Medical Research Council scale; ß = 0.29; 95% CI, 0.10 to 0.47), quality of life (St. George's Respiratory Questionnaire; ß = 6.1; 95% CI, 2.3 to 9.9), and cough and sputum (ß = 0.8; 95% CI, 0.1 to 1.5); lower FEV1% predicted (ß = -7.3; 95% CI, -10.9 to -3.6); higher rate of any and severe exacerbations; and higher percentage emphysema (ß = 2.3; 95% CI, 0.7 to 3.9) and air trapping (ß = 3.8; 95% CI, 0.6 to 7.1). Adverse associations attenuated with adjustment for potential mediators but remained robust for several outcomes, including dyspnea, FEV1% predicted, percentage emphysema, and air trapping.Conclusions: Racial residential segregation was adversely associated with COPD morbidity among urban Black participants and supports the hypothesis that racial segregation plays a role in explaining health inequities affecting Black communities.

Contribution of Individual and Neighborhood Factors to Racial Disparities in Respiratory Outcomes.

Rationale: Black adults have worse health outcomes compared with white adults in certain chronic diseases, including chronic obstructive pulmonary disease (COPD).Objectives: To determine to what degree disadvantage by individual and neighborhood socioeconomic status (SES) may contribute to racial disparities in COPD outcomes.Methods: Individual and neighborhood-scale sociodemographic characteristics were determined in 2,649 current or former adult smokers with and without COPD at recruitment into SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study). We assessed whether racial differences in symptom, functional, and imaging outcomes (St. George's Respiratory Questionnaire, COPD Assessment Test score, modified Medical Research Council dyspnea scale, 6-minute-walk test distance, and computed tomography [CT] scan metrics) and severe exacerbation risk were explained by individual or neighborhood SES. Using generalized linear mixed model regression, we compared respiratory outcomes by race, adjusting for confounders and individual-level and neighborhood-level descriptors of SES both separately and sequentially.Measurements and Main Results: After adjusting for COPD risk factors, Black participants had significantly worse respiratory symptoms and quality of life (modified Medical Research Council scale, COPD Assessment Test, and St. George's Respiratory Questionnaire), higher risk of severe exacerbations and higher percentage of emphysema, thicker airways (internal perimeter of 10 mm), and more air trapping on CT metrics compared with white participants. In addition, the association between Black race and respiratory outcomes was attenuated but remained statistically significant after adjusting for individual-level SES, which explained up to 12-35% of racial disparities. Further adjustment showed that neighborhood-level SES explained another 26-54% of the racial disparities in respiratory outcomes. Even after accounting for both individual and neighborhood SES factors, Black individuals continued to have increased severe exacerbation risk and persistently worse CT outcomes (emphysema, air trapping, and airway wall thickness).Conclusions: Disadvantages by individual- and neighborhood-level SES each partly explain disparities in respiratory outcomes between Black individuals and white individuals. Strategies to narrow the gap in SES disadvantages may help to reduce race-related health disparities in COPD; however, further work is needed to identify additional risk factors contributing to persistent disparities.

Disparities in access to food and chronic obstructive pulmonary disease (COPD)-related outcomes: a cross-sectional analysis.

BACKGROUND: Millions of Americans are living in food deserts in the United States, however the role of the local food environment on COPD has not been studied. The aim of this study is to determine the association between food deserts and COPD-related outcomes. METHOD: In this cross-sectional analysis we linked data collected from SPIROMICS (SubPopulations and InteRmediate Outcome Measures in COPD Study) between 2010 and 2015 and food desert data, defined as an underserved area that lacks access to affordable healthy foods, from the Food Access Research Atlas. COPD outcomes include percentage of predicted forced expiratory volume in one second (FEV1%), St. George's Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT), 6-min walk distance test (6MWD), exacerbations, and air trapping. We used generalized linear mixed models to evaluate the association between living in food deserts and respiratory outcomes, adjusting for age, gender, race, education, income, marital status, BMI, smoking status, pack years, and urban status RESULTS: Among 2713 participants, 22% lived in food deserts. Participants living in food deserts were less likely to be white and more likely to have a lower income than those who did not live in food deserts. In the adjusted model controlling for demographics and individual income, living in food deserts was associated lower FEV1% (ß = - 2.51, P = 0.046), higher air trapping (ß = 2.47, P = 0.008), worse SGRQ (ß = 3.48, P = 0.001) and CAT (ß = 1.20, P = 0.003) scores, and 56% greater odds of severe exacerbations (P = 0.004). Results were consistent when looking at food access alone, regardless of whether participants lived in low income areas. CONCLUSIONS: Findings suggest an independent association between food desert and food access alone with COPD outcomes. Health program planning may benefit from addressing disparities in access to food.

Rural Residence and Poverty Are Independent Risk Factors for Chronic Obstructive Pulmonary Disease in the United States.

RATIONALE: In developing countries, poor and rural areas have a high burden of chronic obstructive pulmonary disease (COPD), and environmental pollutants and indoor burning of biomass have been implicated as potential causal exposures. Less is known about the prevalence of COPD in the United States with respect to urban-rural distribution, poverty, and factors that uniquely contribute to COPD among never-smokers. OBJECTIVES: To understand the impact of urban-rural status, poverty, and other community factors on COPD prevalence nationwide and among never-smokers. METHODS: We studied a nationally representative sample of adults in the National Health Interview Survey 2012-2015, with data linkage between neighborhood data from the U.S. Census's American Community Survey and the National Center for Health Statistics Urban-Rural Classification Scheme. The main outcome was COPD prevalence. MEASUREMENTS AND MAIN RESULTS: The prevalence of COPD in poor, rural areas was almost twice that in the overall population (15.4% vs. 8.4%). In adjusted models, rural residence (odds ratio [OR], 1.23; P < 0.001) and census-level poverty (OR, 1.12; P = 0.012) were both associated with COPD prevalence, as were indicators of household wealth. Among never-smokers, rural residence was also associated with COPD (OR, 1.34; P < 0.001), as was neighborhood use of coal for heating (OR, 1.09; P < 0.001). CONCLUSIONS: In a nationally representative sample, rural residence and poverty were risk factors for COPD, even among never-smokers. The use of coal for heating was also a risk factor for COPD among never-smokers. Future disparities research to elucidate contributors to COPD development in poor and rural areas, including assessments of heating sources and environmental pollutants, is needed.

Changes in Spirometry Interpretative Strategies: Implications for Classifying COPD and Predicting Exacerbations.

BACKGROUND: Recent guidelines for spirometry interpretation recommend both race-neutral reference equations and use of z score thresholds to define severity of airflow obstruction. RESEARCH QUESTION: How does the transition from race-specific to race-neutral equations impact severity classifications for patients with COPD when using % predicted vs z score thresholds, and do changes in severity correspond to clinical risk? STUDY DESIGN AND METHODS: This retrospective cohort study included Black and White patients with COPD and available spirometry from the Johns Hopkins Health System. Global Lung Function Initiative (GLI) 2012 (race-specific) equations and GLI Global (race-neutral) equations were used to determine FEV1 % predicted and z score values. Patients were classified as having mild, moderate, or severe disease according to % predicted or z score thresholds. Associations between a change in severity classification from race-specific to race-neutral with COPD exacerbations and all-cause hospitalizations were evaluated using logistic regression. RESULTS: This cohort included 13,324 patients, of whom 9,232 patients (69.3%) were White (mean age, 65.7 years) and 4,092 patients (30.7%) were Black (mean age, 61.1 years). More Black than White patients showed a change in severity classification between approaches when using % predicted thresholds (20.2% vs 6.1%; P < .001), but not with z score thresholds (12.6% vs 12.3%; P = .68). An increased severity classification with a race-neutral approach was associated with increased risk of exacerbation when using z score thresholds (OR, 2.34; 95% CI, 1.51-3.63), but not when using % predicted thresholds (OR, 1.08; 95% CI, 0.61-1.93). A decreased severity classification with a race-neutral approach was associated with lower risk of exacerbation with both % predicted (OR, 0.49; 95% CI, 0.28-0.87) and z score (OR 0.67; 95% CI, 0.50-0.90) thresholds. INTERPRETATION: The proportions of Black and White individuals reclassified were similar with z score thresholds, and changes in severity corresponded to clinical risk with z scores. These results support recent recommendations for use of race-neutral equations and z score thresholds for spirometry interpretation.

Influence of Impaired Diffusing Capacity and Sleep-disordered Breathing on Nocturnal Hypoxemia and Health Outcomes in Men with and without Human Immunodeficiency Virus.

Rationale: Nocturnal hypoxemia is common in sleep-disordered breathing (SDB) and is associated with increased morbidity and mortality. Although impaired diffusing capacity of the lung for carbon monoxide (DlCO) is associated with daytime hypoxemia, its influence on SDB-related nocturnal hypoxemia is not known. Objectives: To characterize the effects of DlCO impairment on SDB-related nocturnal hypoxemia and associated health outcomes. Methods: Data from a multicenter cohort of men with and without human immunodeficiency virus (HIV) infection, with concomitant measures of DlCO and home-based polysomnography (n = 544), were analyzed. Multivariable quantile regression models characterized associations between DlCO and several measures of SDB-related hypoxemia (e.g., total sleep time with oxygen saturation as measured by pulse oximetry [SpO2] < 90% [T90]). Structural equation models were used to assess associations of impaired DlCO and SDB-related hypoxemia measures with prevalent hypertension and type 2 diabetes. Results: DlCO impairment (<80% predicted) was associated with sleep-related hypoxemia. Participants with severe SDB (apnea-hypopnea index ⩾ 30 events/h) and impaired DlCO had higher T90 (median difference, 15.0% [95% confidence interval (CI), 10.3% to 19.7%]) and average SDB-related desaturation (median difference, 1.0 [95% CI, 0.5 to 1.5]) and lower nadir SpO2 (median difference, -8.2% [95% CI, -11.4% to -4.9%]) and average SpO2 during sleep (median difference, -1.1% [95% CI, -2.1% to -0.01%]) than those with severe SDB and preserved DlCO. Higher T90 was associated with higher adjusted odds of prevalent hypertension (odds ratio, 1.39 [95% CI, 1.14 to 1.70]) and type 2 diabetes (odds ratio, 1.25 [95% CI, 1.07 to 1.46]). Conclusions: DlCO impairment in severe SDB was associated with sleep-related hypoxemia, prevalent hypertension, and type 2 diabetes. Assessment of SDB should be considered in those with impaired DlCO to guide testing and risk stratification strategies.

Urine and Plasma Markers of Platelet Activation and Respiratory Symptoms in COPD.

Introduction: Antiplatelet therapy has been associated with fewer exacerbations and reduced respiratory symptoms in chronic obstructive pulmonary disease (COPD). Whether platelet activation is associated with respiratory symptoms in COPD is unknown. Methods: Former smokers with spirometry-confirmed COPD had urine 11-dehydro-thromboxane B2 (11dTxB2), plasma soluble CD40L (sCD40L), and soluble P-selectin (sP-selectin) repeatedly measured during a 6- to 9-month study period. Multivariate mixed-effects models adjusted for demographics, clinical characteristics, and medication use evaluated the association of each biomarker with respiratory symptoms, health status, and quality of life. Results: Among 169 participants (average age 66.5±8.2 years, 51.5% female, 47.5±31 pack years, forced expiratory volume in 1 second percent predicted 53.8±17.1), a 100% increase in 11dTxB2 was associated with worse respiratory symptoms reflected by higher scores on the COPD Assessment Test (ß 0.77, 95% confidence interval [CI]: 0.11-1.4) and Ease of Cough and Sputum Clearance Questionnaire ß 0.77, 95%CI: 0.38-1.2, worse health status (Clinical COPD Questionnaire ß 0.13, 95%CI: 0.03-0.23) and worse quality of life (St George's Respiratory Questionnaire ß 1.9, 95%CI: 0.39-3.4). No statistically significant associations were observed for sCD40L or sP-selectin. There was no consistent statistically significant effect modification of the relationship between urine 11dTxB2 and respiratory outcomes by history of cardiovascular disease, subclinical coronary artery disease, antiplatelet therapy, or COPD severity. Conclusions: In stable moderate-severe COPD, elevated urinary11dTxB2, a metabolite of the platelet activation product thromboxane A2, was associated with worse respiratory symptoms, health status, and quality of life.

Decreased Cardiac Autonomic Function is Associated with Higher Exacerbation Risk and Symptom Burden in Chronic Obstructive Pulmonary Disease.

Current measures of chronic obstructive pulmonary disease (COPD) severity, including lung function, do not fully explain symptom burden, and there is a need to identify predictors of exacerbation risk and morbidity. Autonomic dysfunction may be implicated in both cardiovascular and respiratory morbidity in COPD and convey risk for exacerbations. Heart rate variability (HRV) is a marker of cardiac autonomic function that is predictive of cardiovascular health and has promise as a non-invasive COPD biomarker. The CLEAN AIR Heart study provided an opportunity to investigate the association between HRV and COPD morbidity among former smokers with moderate-severe COPD. Eighty-five participants, contributing 305 HRV measurements, underwent repeated clinical assessments over 4 study periods that included a 24-Holter monitoring assessment of HRV. HRV measures of interest were standard deviation of normal-to-normal intervals, (SDNN) (overall HRV) and root-mean-square of successive differences (RMSSD) (parasympathetic function). Exacerbation risk was assessed using negative binomial models, and mixed-effects models analyzed associations between HRV and symptoms. Decreases in SDNN (incidence rate ratio [IRR]1.40; 95% confidence interval [CI] 1.13 to1.74) and RMSSD (IRR 1.60; 95% CI 1.07 to 2.37) were associated with severe exacerbation risk. Decreases in SDNN were associated with higher St George's Respiratory Questionnaire scores, COPD Assessment Test scores, and chronic bronchitis symptoms. Findings demonstrate that HRV is associated with COPD symptom burden and exacerbation risk. HRV may represent an important biomarker with the potential to identify high-risk COPD populations.

Brief Report: HIV Is Associated With Impaired Pulmonary Diffusing Capacity Independent of Emphysema.

BACKGROUND: HIV is associated with accelerated decline in lung function and increased risk for chronic obstructive pulmonary disease (COPD). Recently, there has been growing attention toward the impairment in the diffusing capacity of the lungs for carbon monoxide (DLCO), a marker of pulmonary gas exchange, observed among persons living with HIV. Although increased emphysema can contribute to the DLCO impairment observed, other factors may drive this association. METHODS: Using cross-sectional data from the Study of HIV in the Etiology of Lung Disease, we studied the association between HIV and DLCO independent of emphysema. We also analyzed the joint influence of HIV and COPD on DLCO impairment. An analysis was conducted among 339 participants (229 with HIV) with lung function and chest CT imaging data. Multivariable regression models were generated with percent predicted DLCO and odds of DLCO impairment as outcomes. RESULTS: After adjusting for confounders, including emphysema severity, HIV was associated with lower DLCO (ß -4.02%; P = 0.020) and higher odds of DLCO impairment (odds ratio 1.93; P = 0.017). Even among those without COPD, HIV was independently associated with lower DLCO (ß -3.89%; P = 0.049). Compared with HIV-uninfected participants without COPD, those with both HIV and COPD experienced the greatest impairment in DLCO (ß -14.81; P < 0.001). CONCLUSIONS: HIV is associated with impaired pulmonary gas exchange independent of emphysema severity. Our data also suggest a potentially additive influence between HIV and COPD on DLCO impairment. Further studies should investigate the other factors, including pulmonary vascular disease, which may contribute to DLCO impairment among persons living with HIV.

Cognitive Dysfunction, Psychiatric Distress, and Functional Decline After COVID-19.

BACKGROUND: There is a limited understanding of the cognitive and psychiatric sequelae of COVID-19 during the post-acute phase, particularly among racially and ethnically diverse patients. OBJECTIVE: We sought to prospectively characterize cognition, mental health symptoms, and functioning approximately four months after an initial diagnosis of COVID-19 in a racially and ethnically diverse group of patients. METHODS: Approximately four months after COVID-19 diagnosis, patients in the Johns Hopkins Post-Acute COVID-19 Team Pulmonary Clinic underwent a clinical telephone-based assessment of cognition, depression, anxiety, trauma, and function. RESULTS: Most Johns Hopkins Post-Acute COVID-19 Team patients assessed were women (59%) and members of racial/ethnic minority groups (65%). Of 82 patients, 67% demonstrated ≥1 abnormally low cognitive score. Patients requiring intensive care unit (ICU) stays displayed greater breadth and severity of impairment than those requiring less intensive treatment. Processing speed (35%), verbal fluency (26%-32%), learning (27%), and memory (27%) were most commonly impaired. Among all patients, 35% had moderate symptoms of depression (23%), anxiety (15%), or functional decline (15%); 25% of ICU patients reported trauma-related distress. Neuropsychiatric symptoms and functional decline did not differ by post-ICU versus non-ICU status and were unrelated to global cognitive composite scores. CONCLUSIONS: At approximately 4 months after acute illness, cognitive dysfunction, emotional distress, and functional decline were common among a diverse clinical sample of COVID-19 survivors varying in acute illness severity. Patients requiring ICU stays demonstrated greater breadth and severity of cognitive impairment than those requiring less intensive treatment. Findings help extend our understanding of the nature, severity, and potential duration of neuropsychiatric morbidity after COVID-19 and point to the need for longitudinal assessment of cognitive and mental health outcomes among COVID-19 survivors of different demographic backgrounds and illness characteristics.

Rapid Design and Implementation of Post-COVID-19 Clinics.

Survivors of COVID-19 are a vulnerable population, with complex needs because of lingering symptoms and complications across multiple organ systems. Those who required hospitalization or intensive care are also at risk for post-hospital syndrome and post-ICU syndromes, with attendant cognitive, psychological, and physical impairments, and high levels of health care utilization. Effective ambulatory care for COVID-19 survivors requires coordination across multiple subspecialties, which can be burdensome if not well coordinated. With growing recognition of these needs, post-COVID-19 clinics are being created across the country. We describe the design and implementation of multidisciplinary post-COVID-19 clinics at two academic health systems, Johns Hopkins and the University of California-San Francisco. We highlight components of the model which should be replicated across sites, while acknowledging opportunities to tailor offerings to the local institutional context. Our goal is to provide a replicable framework for others to create these much-needed care delivery models for survivors of COVID-19.

Haemoglobin as a biomarker for clinical outcomes in chronic obstructive pulmonary disease.

In COPD, anaemia is associated with increased morbidity, but the relationship between haemoglobin over its entire observed range and morbidity is poorly understood. Such an understanding could guide future therapeutic targeting of haemoglobin in COPD management. Leveraging the COPDGene study, we conducted a cross-sectional analysis of haemoglobin from COPD participants, examining symptoms, quality of life, functional performance, and acute exacerbations of COPD (AECOPD). Haemoglobin was analysed both as a continuous variable and categorised into anaemia, normal haemoglobin, and polycythaemia groups. Fractional polynomial modelling was used for continuous analyses; categorical models were multivariable linear or negative binomial regressions. Covariates included demographics, comorbidities, emphysema, diffusing capacity, and airflow obstruction. From 2539 participants, 366 (14%) were identified as anaemic and 125 (5%) as polycythaemic. Compared with normal haemoglobin, anaemia was significantly associated with increased symptoms (COPD Assessment Test score: p=0.006, modified Medical Research Council (mMRC) Dyspnoea Score: p=0.001); worse quality of life (St. George's Respiratory Questionnaire (SGRQ) score: p<0.001; Medical Outcomes Study Short Form 36-item Questionnaire (SF-36) General Health: p=0.002; SF-36 Physical Health: p<0.001), decreased functional performance (6-min walk distance (6MWD): p<0.001), and severe AECOPD (p=0.01), while polycythaemia was not. Continuous models, however, demonstrated increased morbidity at both ends of the haemoglobin distribution (p<0.01 for mMRC, SGRQ, SF-36 Physical Health, 6MWD, and severe AECOPD). Evaluating interactions, both diffusing capacity and haemoglobin were independently associated with morbidity. We present novel findings that haemoglobin derangements towards either extreme of the observed range are associated with increased morbidity in COPD. Further investigation is necessary to determine whether haemoglobin derangement drives morbidity or merely reflects systemic inflammation, and whether correcting haemoglobin towards the normal range improves morbidity.