Exacerbation-like events in the 12 months prior to identification of chronic respiratory conditions in a primary care population.

Initial chronic obstructive lung disease (COPD) pharmacotherapy is based on symptom burden and exacerbation history. Inclusion of inhaled cortico-steroids (ICS) is recommended only for those with a history of exacerbations. This brief report highlights that among individuals with previously unrecognized COPD about 1 in 5 have one or more exacerbation-like events and about 1 in 10 have two or more events in the prior 12 months whether or not they self-report concomitant asthma. Closer attention to prior exacerbation-like event history might lead to more guideline concordant care. In addition, there are two other groups that have impaired but non-obstructive spirometry, some with significant respiratory symptom burden who have frequencies of exacerbation-like events similar to those meeting COPD spirometry criteria. To date we have little guidance for treatment of these individuals.

The prevalence and mortality risks of PRISm and COPD in the United States from NHANES 2007-2012.

BACKGROUND: We estimated the prevalence and mortality risks of preserved ratio impaired spirometry (PRISm) and chronic obstructive pulmonary disease (COPD) in the US adult population. METHODS: We linked three waves of pre-bronchodilator spirometry data from the US National Health and Nutritional Examination Survey (2007-2012) with the National Death Index. The analytic sample included adults ages 20 to 79 without missing data on age, sex, height, BMI, race/ethnicity, and smoking status. We defined COPD (GOLD 1, 2, and 3-4) and PRISm using FEV1/FVC cut points by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). We compared the prevalence of GOLD stages and PRISm by covariates across the three waves. We estimated adjusted all-cause and cause-specific mortality risks by COPD stage and PRISm using all three waves combined. RESULTS: Prevalence of COPD and PRISm from 2007-2012 ranged from 13.1%-14.3% and 9.6%-10.2%, respectively. We found significant differences in prevalence by sex, age, smoking status, and race/ethnicity. Males had higher rates of COPD regardless of stage, while females had higher rates of PRISm. COPD prevalence increased with age, but not PRISm, which was highest among middle-aged individuals. Compared to current and never smokers, former smokers showed lower rates of PRISm but higher rates of GOLD 1. COPD prevalence was highest among non-Hispanic White individuals, and PRISm was notably higher among non-Hispanic Black individuals (range 31.4%-37.4%). We found associations between PRISm and all-cause mortality (hazard ratio [HR]: 2.3 95% CI: 1.9-2.9) and various cause-specific deaths (HR ranges: 2.0-5.3). We also found associations between GOLD 2 (HR: 2.1, 95% CI: 1.7-2.6) or higher (HR: 4.2, 95% CI: 2.7-6.5) and all-cause mortality. Cause-specific mortality risk varied within COPD stages but typically increased with higher GOLD stage. CONCLUSIONS: The prevalence of COPD and PRISm remained stable from 2007-2012. Greater attention should be paid to the potential impacts of PRISm due to its higher prevalence in minority groups and its associations with mortality across various causes including cancer.

Disease Burden and Health-Related Quality of Life (HRQoL) of Chronic Obstructive Pulmonary Disease (COPD) in the US - Evidence from the Medical Expenditure Panel Survey (MEPS) from 2016-2019.

Purpose: Chronic obstructive pulmonary disease (COPD) is a progressive disease associated with reduced life expectancy, increased morbidity, mortality, and cost. This study characterized the US COPD burden, including socioeconomic and health-related quality of life (HRQoL) outcomes. Study Design and Methods: In this retrospective, cross-sectional study using nationally representative estimates from Medical Expenditures Survey (MEPS) data (2016-2019), adults (≥18 years) living with and without COPD were identified. Adults living without COPD (control cohort) and with COPD were matched 5:1 on age, sex, geographic region, and entry year. Demographics, clinical characteristics, socioeconomic, and generic HRQoL measures were examined to include a race-stratified analysis of people living with COPD. Results: A total of 4,135 people living with COPD were identified; the matched dataset represented a weighted non-institutionalized population of 11.3 million with and 54.2 million people without COPD. Among people living with COPD, 66.3% had ≥1 COPD-related condition; 62.7% had ≥1 cardiovascular condition, compared to 33.5% and 50.5% without COPD. More people living with COPD were unemployed (56.2% vs 45.3%), unable to work due to illness/disability (30.1% vs 12.1%), had problems paying bills (16.1% vs 8.8%), reported poorer perceived health (fair/poor: 36.2% vs 14.4%), missed more working days due to illness/injury per year (median, 2.5 days vs 0.0 days), and had limitations in physical functioning (40.1% vs 19.4%) (all P<0.0001). In race-stratified analyses for people living with COPD, people self-reporting as Black had higher prevalence of cardiovascular-risk conditions, poorer socioeconomic and HRQoL outcomes, and higher healthcare expenses than White or Other races. Conclusion: Adults living with COPD had higher clinical disease burden, lower socioeconomic status, and reduced HRQoL than those without, with greater disparities among Black people living with COPD compared to White and other races. Understanding the characteristics of patients helps address care disparities and access challenges.

Low lung function in Bipolar Disorder and Schizophrenia: a hidden risk.

Introduction: People with serious mental illness (SMI), such as schizophrenia and bipolar disorder, have a higher risk of premature morbidity and mortality. In the general population, impaired lung function is associated with increased morbidity and mortality. We compared lung function between people with and without serious mental illnesses using a cross-sectional study in 9 community mental health units. Methods: Subjects aged 40-70 years with a diagnosis of schizophrenia or bipolar disorder were recruited consecutively. The controls had no psychiatric diagnosis and were not receiving any psychotropics. Spirometry was performed by a trained nurse. We used the 2021 American Thoracic Society/European Respiratory Society standards for the interpretation of the spirometry results. Results: We studied 287 subjects. People with SMI (n = 169) had lower spirometry values than those without a psychiatric diagnosis (n = 118). An abnormal spirometry pattern (36.1% vs 16.9%, p < 0.001), possible restriction or non-specific (Preserved Ratio Impaired Spirometry [PRISm]) pattern (17.8% vs 7.6%, p = 0.014), and pattern of airflow obstruction or possible mixed disorder (18.3% vs 9.3%, p = 0.033) were more frequent in people with SMI. Multivariate analyses showed that the PRISm pattern was associated with abdominal circumference (odds ratio [OR] 1.05, 95%CI 1.03-1.08) and that the pattern of airflow obstruction or possible mixed disorder was associated with smoking behavior (OR 5.15, 95%CI 2.06-15.7). Conclusion: People with SMI have impaired lung function, with up to one-third of them showing an abnormal spirometry pattern. This suggests that regular monitoring of lung function and addressing modifiable risk factors, such as tobacco use and obesity, in this population is of paramount importance.

Long-Term SGRQ Stability in a Cohort of Individuals with Alpha-1 Antitrypsin Deficiency-Associated Lung Disease.

Background: Health-related quality of life (HRQoL) assessments such as St. George's Respiratory Questionnaire (SGRQ) are often used as outcome measures to evaluate patient-perceived changes in health status among individuals with lung disease. Several factors have been linked to deterioration in SGRQ, including symptoms (dyspnea, wheezing) and exercise intolerance. Whether these findings apply to individuals with alpha-1 antitrypsin deficiency (AATD) remains incompletely studied. This longitudinal study examines the trajectory of SGRQ scores in a cohort of United States individuals with AATD-associated lung disease and defines factors associated with longitudinal change. Methods: Individuals with AATD-associated lung disease enrolled in AlphaNet, a disease management program, who had ≥3 SGRQ measurements collected between 2009 and 2019, and baseline data for clinically important variables were included in these analyses. Data collected after lung transplants were excluded. Mixed-effects model analyses were used to evaluate the changes in SGRQ total and subscale scores over time and by modified Medical Research Council (mMRC) Scale, use of oxygen, age, sex, productive cough, and exacerbation frequency at baseline. Sensitivity analyses were conducted to examine the potential effect of survivor bias. Results: Participants (n=2456, mean age 57.1±9.9 years, 47% female) had a mean SGRQ total score of 44.7±18.9 at baseline, 48% used oxygen regularly, and 55% had ≥2 exacerbations per year. The median length of follow-up was 6 (IQR 3-9) years. The SGRQ total score and subscales remained stable throughout the observation period. Age, mMRC categories, presence or absence of productive cough, frequency of exacerbations, and use of oxygen at baseline were significantly associated with the rate of change of SGRQ total (p<0.0001). Conclusion: We observed long-term stability in HRQoL and an association between the rate of change in SGRQ and baseline mMRC, exacerbation frequency, productive cough, and use of oxygen in this cohort of individuals with AATD-associated lung disease.

Severity of Airflow Obstruction Based on FEV1/FVC vs FEV1% of Predicted in the General US Population.

RATIONALE: According to GOLD, the ratio of FEV1/FVC is used to confirm airflow obstruction in COPD diagnosis, whereas FEV1% of predicted (FEV1%pred) is used for severity grading. STaging of Airflow obstruction by the FEV1/FVC Ratio (STAR) and its prediction of adverse outcomes has not been evaluated in general populations. OBJECTIVE: To compare the STAR (FEV1/FVC) versus GOLD (FEV1%pred) classification for the severity of airflow limitation in terms of exertional breathlessness and mortality in the general US population. METHODS: Severity stages according to STAR and GOLD were applied to the multi-ethnic National Health and Nutrition Examination Survey (NHANES) 2007-2012 survey including ages 18-80 years, using post-bronchodilatory FEV1/FVC<0.70 to define airflow obstruction in both staging systems. Prevalence of severity stages STAR 1-4 and GOLD 1-4 was calculated and associations with breathlessness and mortality were analyzed by multinomial logistic regression and Cox regression, respectively. RESULTS: STAR versus GOLD severity staging of airflow obstruction showed similar associations with breathlessness and all-cause mortality, regardless of ethnicity/race. In those with airflow obstruction, the correlation between the two classification systems was 0.461 (p<0.001). STAR reclassified 59% of GOLD stage 2 as having mild airflow obstruction (STAR 1). STAR 1 was more clearly differentiated from the non-obstructive compared to GOLD stage 1 in terms of both breathlessness and mortality. CONCLUSIONS: FEV1/FVC and FEV1%pred as measures of severity of airflow limitation show similar prediction of breathlessness and mortality in the adult US population across ethnicity groups. However, stage 1 differed more clearly from non-obstructive based on FEV1/FVC than FEV1%pred. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Characteristics associated with SF-36 in alpha-1 antitrypsin deficiency-associated COPD: a cross-sectional analysis.

BACKGROUND: Generic measures of health-related quality of life (HRQoL), such as the 36-Item Short Form Survey (SF-36), are widely used in assessing chronic conditions. These tools have an advantage over disease-specific instruments, as they allow comparisons across different health conditions and with the general population. In alpha-1 antitrypsin deficiency (AATD)-associated chronic obstructive pulmonary disease (COPD), HRQoL research remains scarce. This cross-sectional study evaluates the factors associated with HRQoL in a cohort of patients with AATD-associated COPD. METHODS: Our study included participants of AlphaNet (2008-2019), a health management organization for people with AATD in the US who are prescribed augmentation therapy. Norm-based SF-36 scores for the mental and physical component summary scores (MCS and PCS, mean of 50 ± 10 in the general US population) and 8 individual scales were evaluated. Individuals with lung disease and data available on ≥1 measurement on any SF-36 scale and clinically relevant characteristics such as modified Medical Research Council (mMRC) scale, exacerbation frequency, productive cough, and use of oxygen were included in these analyses. Generalized linear regression models were fit to examine the association of baseline characteristics with MCS and PCS scores. Age, sex, regular use of oxygen, exacerbation frequency, mMRC, and productive cough were included in these models. RESULTS: Participants (n=4398, mean age 57.6 [SD=10.6] years, 45.4% female) had a mean MCS score of 51.2 ± 10.8 and PCS of 36.3 ± 9.8. The average mMRC score was 2.4 ± 1.3, and 56.4% had 2 or more exacerbations per year. Overall, the physical component of SF-36 was more severely impacted compared to the mental component. In multivariable regression analyses, PCS scores were significantly associated with exacerbation frequency, mMRC, regular use of oxygen, and productive cough; MCS was associated with age, sex, exacerbation frequency, mMRC, and productive cough. CONCLUSIONS: These findings demonstrate that patient-perceived physical health is significantly impaired in this cohort of people with AATD-associated COPD compared to mental health. Longitudinal studies are needed to evaluate the change in physical and mental health status over time in this population.

Risk of Death and Cardiovascular Events Following an Exacerbation of COPD: The EXACOS-CV US Study.

Purpose: This study estimated the magnitude and duration of risk of cardiovascular events and mortality following acute exacerbations of chronic obstructive pulmonary disease (AECOPD), and whether risks varied by number and severity of exacerbation in a commercially insured population in the United States. Methods: This was a retrospective cohort study of newly diagnosed COPD patients ≥40 years old in the Healthcare Integrated Research Database from 2012 to 2019. Patients experiencing exacerbations comprised the "exacerbation cohort". Moderate exacerbations were outpatient visits with contemporaneous antibiotic or glucocorticoid administration; severe exacerbations were emergency department visits or hospitalizations for AECOPD. Follow-up started on the exacerbation date. Distribution of time between diagnosis and first exacerbation was used to assign index dates to the "unexposed" cohort. Cox proportional hazards models estimated risks of a cardiovascular event or death following an exacerbation adjusted for medical and prescription history and stratified by follow-up time, type of cardiovascular event, exacerbation severity, and rank of exacerbation (first, second, or third). Results: Among 435,925 patients, 170,236 experienced ≥1 exacerbation. Risk of death was increased for 2 years following an exacerbation and was highest during the first 30 days (any exacerbation hazard ratio (HR)=1.79, 95% CI=1.58-2.04; moderate HR=1.22, 95% CI=1.04-1.43; severe HR=5.09, 95% CI=4.30-6.03). Risks of cardiovascular events were increased for 1 year following an AECOPD and highest in the first 30-days (any exacerbation HR=1.34, 95% CI=1.23-1.46; moderate HR=1.23 (95% CI 1.12-1.35); severe HR=1.93 (95% CI=1.67-2.22)). Each subsequent AECOPD was associated with incrementally higher rates of both death and cardiovascular events. Conclusion: Risk of death and cardiovascular events was greatest in the first 30 days and rose with subsequent exacerbations. Risks were elevated for 1-2 years following moderate and severe exacerbations, highlighting a sustained increased cardiopulmonary risk associated with exacerbations.

Perspectives on Ensifentrine and Its Therapeutic Potential in the Treatment of COPD: Evidence to Date.

Ensifentrine is a novel inhalational phosphodiesterase (PDE)3 and PDE4 inhibitor which improves bronchodilation and decreases inflammatory markers by acting locally on the bronchial tissue, with minimal systemic effects. Both preclinical and clinical trials have demonstrated benefits of this therapy, including improvement in lung function and reduction in exacerbations. This therapy is currently under review by the US Food and Drug Administration with a decision expected in 2024.

Prevalence of chronic cough, its risk factors and population attributable risk in the Burden of Obstructive Lung Disease (BOLD) study: a multinational cross-sectional study.

Background: Chronic cough is a common respiratory symptom with an impact on daily activities and quality of life. Global prevalence data are scarce and derive mainly from European and Asian countries and studies with outcomes other than chronic cough. In this study, we aimed to estimate the prevalence of chronic cough across a large number of study sites as well as to identify its main risk factors using a standardised protocol and definition. Methods: We analysed cross-sectional data from 33,983 adults (≥40 years), recruited between Jan 2, 2003 and Dec 26, 2016, in 41 sites (34 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We estimated the prevalence of chronic cough for each site accounting for sampling design. To identify risk factors, we conducted multivariable logistic regression analysis within each site and then pooled estimates using random-effects meta-analysis. We also calculated the population attributable risk (PAR) associated with each of the identifed risk factors. Findings: The prevalence of chronic cough varied from 3% in India (rural Pune) to 24% in the United States of America (Lexington,KY). Chronic cough was more common among females, both current and passive smokers, those working in a dusty job, those with a history of tuberculosis, those who were obese, those with a low level of education and those with hypertension or airflow limitation. The most influential risk factors were current smoking and working in a dusty job. Interpretation: Our findings suggested that the prevalence of chronic cough varies widely across sites in different world regions. Cigarette smoking and exposure to dust in the workplace are its major risk factors. Funding: Wellcome Trust.

Guidance on Mitigating the Risk of Transmitting Respiratory Infections During Nebulization by the COPD Foundation Nebulizer Consortium.

BACKGROUND: Nebulizers are used commonly for inhaled drug delivery. Because they deliver medication through aerosol generation, clarification is needed on what constitutes safe aerosol delivery in infectious respiratory disease settings. The COVID-19 pandemic highlighted the importance of understanding the safety and potential risks of aerosol-generating procedures. However, evidence supporting the increased risk of disease transmission with nebulized treatments is inconclusive, and inconsistent guidelines and differing opinions have left uncertainty regarding their use. Many clinicians opt for alternative devices, but this practice could impact outcomes negatively, especially for patients who may not derive full treatment benefit from handheld inhalers. Therefore, it is prudent to develop strategies that can be used during nebulized treatment to minimize the emission of fugitive aerosols, these comprising bioaerosols exhaled by infected individuals and medical aerosols generated by the device that also may be contaminated. This is particularly relevant for patient care in the context of a highly transmissible virus. RESEARCH QUESTION: How can potential risks of infections during nebulization be mitigated? STUDY DESIGN AND METHODS: The COPD Foundation Nebulizer Consortium (CNC) was formed in 2020 to address uncertainties surrounding administration of nebulized medication. The CNC is an international, multidisciplinary collaboration of patient advocates, pulmonary physicians, critical care physicians, respiratory therapists, clinical scientists, and pharmacists from research centers, medical centers, professional societies, industry, and government agencies. The CNC developed this expert guidance to inform the safe use of nebulized therapies for patients and providers and to answer key questions surrounding medication delivery with nebulizers during pandemics or when exposure to common respiratory pathogens is anticipated. RESULTS: CNC members reviewed literature and guidelines regarding nebulization and developed two sets of guidance statements: one for the health care setting and one for the home environment. INTERPRETATION: Future studies need to explore the risk of disease transmission with fugitive aerosols associated with different nebulizer types in real patient care situations and to evaluate the effectiveness of mitigation strategies.

National and Local Direct Medical Cost Burden of COPD in the United States From 2016 to 2019 and Projections Through 2029.

BACKGROUND: Despite the significant burden posed by COPD to health care systems, there is a lack of up-to-date information quantifying the general COPD burden, costs, and long-term projections to various stakeholders in the United States. RESEARCH QUESTION: What are the updated state-specific and nationwide estimates of the COPD disease burden and direct costs in 2019, along with projections of COPD-attributable medical costs through 2029? STUDY DESIGN AND METHODS: A cross-sectional, retrospective study design using the 2016 to 2019 Medical Expenditure Panel Survey, 2019 American Community Survey, and 2019 Behavioral Risk Factor Surveillance System data was applied to generate COPD-attributable expenditure estimates. Cost projections for the years 2020 to 2029 were based on 2017 national population projections reported by the US Census Bureau, and all costs were adjusted to 2019 US dollars. RESULTS: In total, 4,135 people living with COPD were included; a higher proportion had other concurrent conditions such as cardiovascular-related conditions compared with people without COPD (n = 86,021). Overall, in 2019, COPD-attributable medical costs after adjusting for demographic characteristics and 19 concurrent conditions (including COPD-related and non-COPD-related conditions) were estimated at $31.3 billion, with state-specific cost estimates reporting wide variation, from $44.8 million in Alaska to $3.1 billion in Florida. Nationwide COPD-attributable medical costs borne by payer type were as follows: private insurance, $11.4 billion; Medicare, $10.8 billion; and Medicaid, $3.0 billion. Projections of national medical costs attributable to COPD are reported to increase to $60.5 billion in 2029. INTERPRETATION: Understanding the current disease and economic burden of COPD in the United States, along with the projected costs attributable to COPD in the next decade, will highlight unmet needs and gaps in care that help inform health care decision-makers in planning future actions to alleviate this disease burden.

Incidence and prevalence rates of coronary artery disease in women with and without rheumatoid arthritis in Kentucky Women's Health Registry.

Aim: To investigate the incidence and prevalence rates of coronary artery disease (CAD) in women with and without rheumatoid arthritis (RA). Methods: Data was collected from the Kentucky Women's Health Registry (2007, 2008, 2009 and 2010) with 3982, 6730, 6898 and 7944, respectively. Results: Women with RA and reported CAD were over 45 years. 10% of women with RA reported CAD, while 4% of women without RA reported CAD. The incidence of CAD in women with RA were 10, 5.2 and 3.4% while the incidence of CAD in women without RA were 2.2, 2.2 and 1.4% in 2007-2010, 2008-2010 and 2009-2010, respectively. Conclusion: The incidence and prevalence of CAD was greater in women with RA compared with women without RA.