ß-Blocker Use and Clinical Outcomes in Patients With COPD Following Acute Myocardial Infarction.

Importance: While ß-blockers are associated with decreased mortality in cardiovascular disease (CVD), exacerbation-prone patients with chronic obstructive pulmonary disease (COPD) who received metoprolol in the Beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease (BLOCK-COPD) trial experienced increased risk of exacerbations requiring hospitalization. However, the study excluded individuals with established indications for the drug, raising questions about the overall risk and benefit in patients with COPD following acute myocardial infarction (AMI). Objective: To investigate whether ß-blocker prescription at hospital discharge is associated with increased risk of mortality or adverse cardiopulmonary outcomes in patients with COPD and AMI. Design, Setting, and Participants: This prospective, longitudinal cohort study with 6 months of follow-up enrolled patients aged 35 years or older with COPD who underwent cardiac catheterization for AMI at 18 BLOCK-COPD network hospitals in the US from June 2020 through May 2022. Exposure: Prescription for any ß-blocker at hospital discharge. Main Outcomes and Measures: The primary outcome was time to the composite outcome of death or all-cause hospitalization or revascularization. Secondary outcomes included death, hospitalization, or revascularization for CVD events, death or hospitalization for COPD or respiratory events, and treatment for COPD exacerbations. Results: Among 3531 patients who underwent cardiac catheterization for AMI, prevalence of COPD was 17.1% (95% CI, 15.8%-18.4%). Of 579 total patients with COPD and AMI, 502 (86.7%) were prescribed a ß-blocker at discharge. Among the 562 patients with COPD included in the final analysis, median age was 70.0 years (range, 38.0-94.0 years) and 329 (58.5%) were male; 553 of the 579 patients (95.5%) had follow-up information. Among those discharged with ß-blockers, there was no increased risk of the primary end point of all-cause mortality, revascularization, or hospitalization (hazard ratio [HR], 1.01; 95% CI, 0.66-1.54; P = .96) or of cardiovascular events (HR, 1.11; 95% CI, 0.65-1.92; P = .69), COPD-related or respiratory events (HR, 0.75; 95% CI, 0.34-1.66; P = .48), or treatment for COPD exacerbations (rate ratio, 1.01; 95% CI, 0.53-1.91; P = .98). Conclusions and Relevance: In this cohort study, ß-blocker prescription at hospital discharge was not associated with increased risk of adverse outcomes in patients with COPD and AMI. These findings support use of ß-blockers in patients with COPD and recent AMI.

Interim Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccines Against COVID-19-Associated Hospitalization Among Adults Aged ≥18 Years with Immunocompromising Conditions - VISION Network, September 2023-February 2024.

In September 2023, CDC's Advisory Committee on Immunization Practices recommended updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccination for all persons aged ≥6 months to prevent COVID-19, including severe disease. As with past COVID-19 vaccines, additional doses may be considered for persons with immunocompromising conditions, who are at higher risk for severe COVID-19 and might have decreased response to vaccination. In this analysis, vaccine effectiveness (VE) of an updated COVID-19 vaccine dose against COVID-19-associated hospitalization was evaluated during September 2023-February 2024 using data from the VISION VE network. Among adults aged ≥18 years with immunocompromising conditions, VE against COVID-19-associated hospitalization was 38% in the 7-59 days after receipt of an updated vaccine dose and 34% in the 60-119 days after receipt of an updated dose. Few persons (18%) in this high-risk study population had received updated COVID-19 vaccine. All persons aged ≥6 months should receive updated 2023-2024 COVID-19 vaccination; persons with immunocompromising conditions may get additional updated COVID-19 vaccine doses ≥2 months after the last recommended COVID-19 vaccine.

Influenza vaccine effectiveness against influenza-A-associated emergency department, urgent care, and hospitalization encounters among U.S. adults, 2022-2023.

BACKGROUND: The 2022-2023 United States influenza season had unusually early influenza activity with high hospitalization rates. Vaccine-matched A(H3N2) viruses predominated, with lower levels of A(H1N1)pdm09 activity also observed. METHODS: Using the test-negative design, we evaluated influenza vaccine effectiveness (VE) during the 2022-2023 season against influenza-A-associated emergency department/urgent care (ED/UC) visits and hospitalizations from October 2022-March 2023 among adults (age ≥18 years) with acute respiratory illness (ARI). VE was estimated by comparing odds of seasonal influenza vaccination among case-patients (influenza A test-positive by molecular assay) and controls (influenza test-negative), applying inverse-propensity-to-be-vaccinated weights. RESULTS: The analysis included 85,389 ED/UC ARI encounters (17.0% influenza-A-positive; 37.8% vaccinated overall) and 19,751 hospitalizations (9.5% influenza-A-positive; 52.8% vaccinated overall). VE against influenza-A-associated ED/UC encounters was 44% (95% confidence interval [95%CI]: 40-47%) overall and 45% and 41% among adults aged 18-64 and ≥65 years, respectively. VE against influenza-A-associated hospitalizations was 35% (95%CI: 27-43%) overall and 23% and 41% among adults aged 18-64 and ≥65 years, respectively. CONCLUSIONS: VE was moderate during the 2022-2023 influenza season, a season characterized with increased burden of influenza and co-circulation with other respiratory viruses. Vaccination is likely to substantially reduce morbidity, mortality, and strain on healthcare resources.

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.

Estimation of COVID-19 mRNA Vaccine Effectiveness and COVID-19 Illness and Severity by Vaccination Status During Omicron BA.4 and BA.5 Sublineage Periods.

Importance: Recent SARS-CoV-2 Omicron variant sublineages, including BA.4 and BA.5, may be associated with greater immune evasion and less protection against COVID-19 after vaccination. Objectives: To evaluate the estimated vaccine effectiveness (VE) of 2, 3, or 4 doses of COVID-19 mRNA vaccination among immunocompetent adults during a period of BA.4 or BA.5 predominant circulation; and to evaluate the relative severity of COVID-19 in hospitalized patients across Omicron BA.1, BA.2 or BA.2.12.1, and BA.4 or BA.5 sublineage periods. Design, Setting, and Participants: This test-negative case-control study was conducted in 10 states with data from emergency department (ED) and urgent care (UC) encounters and hospitalizations from December 16, 2021, to August 20, 2022. Participants included adults with COVID-19-like illness and molecular testing for SARS-CoV-2. Data were analyzed from August 2 to September 21, 2022. Exposures: mRNA COVID-19 vaccination. Main Outcomes and Measures: The outcomes of interest were COVID-19 ED or UC encounters, hospitalizations, and admission to the intensive care unit (ICU) or in-hospital death. VE associated with protection against medically attended COVID-19 was estimated, stratified by care setting and vaccine doses (2, 3, or 4 doses vs 0 doses as the reference group). Among hospitalized patients with COVID-19, demographic and clinical characteristics and in-hospital outcomes were compared across sublineage periods. Results: During the BA.4 and BA.5 predominant period, there were 82 229 eligible ED and UC encounters among patients with COVID-19-like illness (median [IQR] age, 51 [33-70] years; 49 682 [60.4%] female patients), and 19 114 patients (23.2%) had test results positive for SARS-CoV-2; among 21 007 hospitalized patients (median [IQR] age, 71 [58-81] years; 11 209 [53.4%] female patients), 3583 (17.1 %) had test results positive for SARS-CoV-2. Estimated VE against hospitalization was 25% (95% CI, 17%-32%) for receipt of 2 vaccine doses at 150 days or more after receipt, 68% (95% CI, 50%-80%) for a third dose 7 to 119 days after receipt, and 36% (95% CI, 29%-42%) for a third dose 120 days or more (median [IQR], 235 [204-262] days) after receipt. Among patients aged 65 years or older who had received a fourth vaccine dose, VE was 66% (95% CI, 53%-75%) at 7 to 59 days after vaccination and 57% (95% CI, 44%-66%) at 60 days or more (median [IQR], 88 [75-105] days) after vaccination. Among hospitalized patients with COVID-19, ICU admission or in-hospital death occurred in 21.4% of patients during the BA.1 period vs 14.7% during the BA.4 and BA.5 period (standardized mean difference: 0.17). Conclusions and Relevance: In this case-control study of COVID-19 vaccines and illness, VE associated with protection against medically attended COVID-19 illness was lower with increasing time since last dose; estimated VE was higher after receipt of 1 or 2 booster doses compared with a primary series alone.

Vaccine Effectiveness Against Influenza-Associated Urgent Care, Emergency Department, and Hospital Encounters During the 2021-2022 Season, VISION Network.

BACKGROUND: Following historically low influenza activity during the 2020-2021 season, the United States saw an increase in influenza circulating during the 2021-2022 season. Most viruses belonged to the influenza A(H3N2) 3C.2a1b 2a.2 subclade. METHODS: We conducted a test-negative case-control analysis among adults ≥18 years of age at 3 sites within the VISION Network. Encounters included emergency department/urgent care (ED/UC) visits or hospitalizations with ≥1 acute respiratory illness (ARI) discharge diagnosis codes and molecular testing for influenza. Vaccine effectiveness (VE) was calculated by comparing the odds of influenza vaccination ≥14 days before the encounter date between influenza-positive cases (type A) and influenza-negative and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative controls, applying inverse probability-to-be-vaccinated weights, and adjusting for confounders. RESULTS: In total, 86 732 ED/UC ARI-associated encounters (7696 [9%] cases) and 16 805 hospitalized ARI-associated encounters (649 [4%] cases) were included. VE against influenza-associated ED/UC encounters was 25% (95% confidence interval (CI), 20%-29%) and 25% (95% CI, 11%-37%) against influenza-associated hospitalizations. VE against ED/UC encounters was lower in adults ≥65 years of age (7%; 95% CI, -5% to 17%) or with immunocompromising conditions (4%; 95% CI, -45% to 36%). CONCLUSIONS: During an influenza A(H3N2)-predominant influenza season, modest VE was observed. These findings highlight the need for improved vaccines, particularly for A(H3N2) viruses that are historically associated with lower VE.

Chronic Bronchitis in COPD Patients Creates Worse Symptom Burden Regardless of the Presence of Bronchiectasis in the COPDGene Cohort.

PURPOSE: To assess whether the presence or absence of bronchiectasis has an impact on the patient-reported symptoms of chronic obstructive pulmonary disease (COPD) patients. METHODS: The study included participants from the COPD Genetic Epidemiology Study (COPDGene®) cohort with available high-resolution chest tomography reporting the presence or absence of bronchiectasis (BE+/BE-) and survey data reporting the presence or absence of chronic bronchitis symptoms (CB+/CB-). Patient symptoms based on the St George's Respiratory Questionnaire (SGRQ) were then compared for the different groups. RESULTS: The study population included 7976 participants, mean age 60, Global initiative for chronic Obstructive Lung Disease (GOLD) stages 0 to 4, 18.8% BE+, and 19.5% CB+. The presence or absence of radiographic bronchiectasis was not associated with higher frequency of chronic bronchitis (GOLD 0 group odds ratio [OR] 1.01 [0.78,1.31], GOLD 1-2 group OR 1.19 [0.95, 1.50], GOLD 3-4 group OR 1.26 [0.99, 1.60]). Similarly, CB+ participants had higher SGRQ scores than CB- participants regardless of the presence of BE. CONCLUSIONS: Across all GOLD stages, chronic bronchitis symptoms are associated with worse pulmonary symptoms and significant impairment in quality of life. For patients with chronic bronchitis, the presence or absence of bronchiectasis is not associated with a significant difference in SGRQ symptom scores. Symptoms of chronic bronchitis impose a heavy burden on patients and should be treated regardless of the presence or absence of underlying bronchiectasis.

Health Coaching in Severe COPD After a Hospitalization: A Qualitative Analysis of a Large Randomized Study.

BACKGROUND: We recently demonstrated in a randomized study the feasibility and effectiveness of telephone-based health coaching using motivational interviewing on decreasing hospital readmissions and improving quality of life at 6 and 12 months after hospital discharge. In this qualitative study, we sought to explore the health-coaching intervention as seen from the perspective of the participants who received the intervention and the coaches who delivered it. METHODS: Semistructured participant interviews (n = 24) and a focus group of all health coaches (n = 3) who participated in this study were conducted. Interviews and focus group were recorded and transcribed verbatim. Transcripts were analyzed using coding and categorizing techniques and thematic analysis. Mixed-method triangulation was used to merge quantitative and qualitative data. RESULTS: Content analysis revealed 4 predominant themes of the coaching intervention: health-coaching relationship, higher participant confidence and reassurance (most related to improvement in physical quality of life), improved health-care system access (most related to decreased hospital readmissions), and increased awareness of COPD symptoms (most related to improvement in emotional quality of life). The strongest theme was the relationship with the health coach, including coach style and motivational interviewing approach. Health coaches' focus group also noted the importance of the coaching relationship as the most significant theme. CONCLUSIONS: This study provided themes to further inform the delivery and implementation of health-coaching interventions in patients with COPD after hospital discharge. Health coaching forged partnerships and created a platform for patient engagement, which was confirmed by both participants and health coaches.

Severe polyserositis induced by the 13-valent pneumococcal conjugate vaccine: a case report.

BACKGROUND: The United States Advisory Committee on Immunization Practices recommends administration of the 13-valent pneumococcal conjugate vaccine in series with the 23-valent pneumococcal polysaccharide vaccine for prevention of pneumonia in the elderly. Reports of autoimmune or auto-inflammatory diseases as a result of pneumococcal vaccination, especially pneumococcal conjugate vaccine, are extremely rare. CASE PRESENTATION: We present a case of severe serositis in a 75-year-old Caucasian woman complicated by pericardial and pleural effusions in the setting of recent 13-valent pneumococcal conjugate vaccine vaccination and no other obvious etiology. Our patient required steroid treatment, thoracentesis, chest tube, and pericardial window and subsequently recovered to her baseline. CONCLUSIONS: To the best of our knowledge, no such reaction to the 13-valent pneumococcal conjugate vaccine has previously been documented. Although the benefits of vaccination outweigh the risks, knowledge of this potential side effect can help clinicians in diagnosis and treatment of similar patients.

High-dose oral N-acetylcysteine fails to improve respiratory health status in patients with chronic obstructive pulmonary disease and chronic bronchitis: a randomized, placebo-controlled trial.

BACKGROUND: Clinical outcomes are worse in patients with COPD and chronic bronchitis. N-acetylcysteine (NAC) is commonly prescribed for such patients but with uncertain clinical benefits. We postulated that oral NAC, at much larger doses than those ordinarily prescribed, would improve clinical outcomes in a subset of patients with COPD and chronic bronchitis. OBJECTIVE: The aim of this study was to determine whether very high-dose NAC would improve respiratory health status in patients with COPD and chronic bronchitis. METHODS: Patients with COPD and chronic bronchitis were enrolled in a randomized, controlled, double-blinded trial. Patients received oral NAC (1,800 mg) or matching placebo twice daily for 8 weeks in addition to their usual respiratory medications. The primary outcome, respiratory health status, was assessed by changes in the St George's Respiratory Questionnaire. The effects of NAC on lung function and circulating markers of oxidative stress and inflammation were also evaluated. RESULTS: We terminated the study prematurely because new external information suggested the possibility of a safety issue. Of the planned 130 patients, 51 were randomized and 45 (22 in the placebo arm and 23 in the NAC arm) completed the study. There was no statistically significant difference between changes in the St George's Respiratory Questionnaire total score, comparing NAC to placebo (adjusted mean difference, 0.1 U; 95% CI, -7.8 to 8.18 U; P=0.97). There were also no significant NAC-related improvements in any of the secondary outcomes. CONCLUSION: In this 8-week trial, we were unable to show any clinical benefit from a very high dose of NAC in patients with COPD and chronic bronchitis.

Clinical and Radiologic Disease in Smokers With Normal Spirometry.

IMPORTANCE: Airflow obstruction on spirometry is universally used to define chronic obstructive pulmonary disease (COPD), and current or former smokers without airflow obstruction may assume that they are disease free. OBJECTIVE: To identify clinical and radiologic evidence of smoking-related disease in a cohort of current and former smokers who did not meet spirometric criteria for COPD, for whom we adopted the discarded label of Global Initiative for Obstructive Lung Disease (GOLD) 0. DESIGN, SETTING, AND PARTICIPANTS: Individuals from the Genetic Epidemiology of COPD (COPDGene) cross-sectional observational study completed spirometry, chest computed tomography (CT) scans, a 6-minute walk, and questionnaires. Participants were recruited from local communities at 21 sites across the United States. The GOLD 0 group (n = 4388) (ratio of forced expiratory volume in the first second of expiration [FEV1] to forced vital capacity >0.7 and FEV1 ≥80% predicted) from the COPDGene study was compared with a GOLD 1 group (n = 794), COPD groups (n = 3690), and a group of never smokers (n = 108). Recruitment began in January 2008 and ended in July 2011. MAIN OUTCOMES AND MEASURES: Physical function impairments, respiratory symptoms, CT abnormalities, use of respiratory medications, and reduced respiratory-specific quality of life. RESULTS: One or more respiratory-related impairments were found in 54.1% (2375 of 4388) of the GOLD 0 group. The GOLD 0 group had worse quality of life (mean [SD] St George's Respiratory Questionnaire total score, 17.0 [18.0] vs 3.8 [6.8] for the never smokers; P < .001) and a lower 6-minute walk distance, and 42.3% (127 of 300) of the GOLD 0 group had CT evidence of emphysema or airway thickening. The FEV1 percent predicted distribution and mean for the GOLD 0 group were lower but still within the normal range for the population. Current smoking was associated with more respiratory symptoms, but former smokers had greater emphysema and gas trapping. Advancing age was associated with smoking cessation and with more CT findings of disease. Individuals with respiratory impairments were more likely to use respiratory medications, and the use of these medications was associated with worse disease. CONCLUSIONS AND RELEVANCE: Lung disease and impairments were common in smokers without spirometric COPD. Based on these results, we project that there are 35 million current and former smokers older than 55 years in the United States who may have unrecognized disease or impairment. The effect of chronic smoking on the lungs and the individual is substantially underestimated when using spirometry alone.

Self-reported sleep quality and acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Many patients with chronic obstructive pulmonary disease (COPD) suffer from poor sleep quality. We hypothesized that poor sleep quality in otherwise stable patients predicted exacerbations in these patients. METHODS: This is a secondary analysis of the results of a previously published randomized trial of azithromycin in 1,117 patients with moderate to severe COPD who were clinically stable on enrollment. Sleep quality was measured using the Pittsburgh Sleep Quality Index. Other quality of life indices included the Medical Outcome Study 36-item Short Form Health Survey and the St Georges Respiratory Questionnaire. Outcomes included time to first exacerbation and exacerbation rate. RESULTS: Sleep quality was "poor" (Pittsburgh Sleep Quality Index >5) in 53% of participants but was not related to age or severity of airflow obstruction. Quality of life scores were worse in "poor" sleepers than in "good" sleepers. Major classes of comorbid conditions, including psychiatric, neurologic, and musculoskeletal disease, were more prevalent in the "poor" sleepers. Unadjusted time to first exacerbation was shorter (190 versus 239 days) and exacerbation rate (1.7 versus 1.37 per year) was greater in the poor sleepers, but no differences were observed after adjusting for medications and comorbid conditions associated with poor sleep. CONCLUSION: Poor sleepers had greater exacerbation rates than did good sleepers. This appeared to be due largely to them having more, or more severe, concomitant medical conditions and taking more medications.

Healthcare utilization and costs in persons with insomnia in a managed care population.

OBJECTIVES: To better understand the direct costs of insomnia. Our study aimed to compare healthcare costs and utilization of patients diagnosed with insomnia who received care in a managed care organization with a set of matched controls. DESIGN: Our observational, retrospective cohort study compared 7647 adults with an insomnia diagnosis with an equally sized matched cohort of health plan members without an insomnia diagnosis between 2003 and 2006. We also compared a subset of patients diagnosed with and treated for insomnia with those diagnosed with insomnia but not treated. SETTING: A large Midwestern health plan with more than 600,000 members. RESULTS: Multivariate analysis was used to estimate the association between insomnia diagnosis and costs, controlling for covariates, in the baseline and follow-up periods. Although we cannot conclude a causal relationship between insomnia and healthcare costs, our analysis found that insomnia diagnosis was associated with 26% higher costs in the baseline and 46% in the 12 months after diagnosis. When comorbidities were recognized, the insomnia cohort had 80% higher costs, on average, than the matched control cohort. CONCLUSIONS: These outcomes suggest the need to look beyond the direct cost of insomnia to how its interaction with comorbid conditions drives healthcare cost and utilization.

Randomized trial of zileuton for treatment of COPD exacerbations requiring hospitalization.

RATIONALE: Leukotrienes have been implicated in the pathogenesis of acute exacerbations of COPD, but leukotriene modifiers have not been studied as a possible therapy for exacerbations. OBJECTIVE: We sought to test the safety and efficacy of adding oral zileuton (a 5-lipoxygenase inhibitor) to usual treatment for acute exacerbations of COPD requiring hospitalization. METHODS: Randomized double-blind, placebo-controlled, parallel group study of zileuton 600 mg orally, 4 times daily versus placebo for 14 days starting within 12 hours of hospital admission for COPD exacerbation. Primary outcome measure was hospital length of stay; secondary outcomes included treatment failure and biomarkers of leukotriene production. MAIN FINDINGS: Sixty subjects were randomized to zileuton and 59 to placebo (the study was stopped short of enrollment goals because of slow recruitment). There was no difference in hospital length of stay (3.75 +/- 2.19 vs. 3.86 +/- 3.06 days for zileuton vs. placebo, p = 0.39) or treatment failure (23% vs. 27% for zileuton vs. placebo, p = 0.63) despite a decline in urinary LTE(4) levels in the zileuton-treated group as compared to placebo at 24 hours (change in natural log-transformed ng/mg creatinine -1.38 +/- 1.19 vs. 0.14 +/- 1.51, p < 0.0001) and 72 hours (-1.32 +/- 2.08 vs. 0.26 +/- 1.93, p<0.006). Adverse events were similar in both groups. PRINCIPAL CONCLUSIONS: While oral zileuton during COPD exacerbations that require hospital admission is safe and reduces urinary LTE(4) levels, we found no evidence suggesting that this intervention shortened hospital stay, with the limitation that our sample size may have been insufficient to detect a modest but potentially meaningful clinical improvement.