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Asthma and allergic disease impact millions of patients and are associated with high costs. Up to 30% of all medical care involves wasted spending. Across the spectrum of care provided by the allergist-immunologist, there are opportunities to improve value and reduce medical waste. Several examples highlight this reality. Evidence suggests that most patients may receive cost-effective care in the management of chronic spontaneous urticaria without the need for laboratory testing. For patients with asthma, although a single maintenance and reliever therapy approach may be cost-effective, insurance-mandated therapy changes are not, and may harm patients. Biologics may be very effective in improving asthma control but are too expensive for this indication-as demonstrated by cost-effectiveness analyses and highlighted by the Institute of Clinical and Economic Review, which concluded that the value-based price for asthma biologics ranges between $6500 and 14,3000 per year. Early introduction may prevent food allergy, but screening before first introduction is neither necessary nor cost-effective, although early salvage food oral immunotherapy may result in improved quality of life and cost savings. Evidence does not support the presence of allergic disease as a risk factor for anaphylaxis to coronavirus disease 2019 vaccination, and risk-stratified vaccination approaches do not appear cost-effective. Allergen immunotherapy is a very cost-effective treatment option. The practice of allergy-immunology has continued to evolve in recent years and can provide a leading example of high-value practice.

Purpose To describe the socioeconomic and healthcare-related effects of the COVID-19 pandemic, and willingness to receive a free COVID-19 vaccine, among African American/Black (AA/B) and Hispanic/Latinx (H/L) adults with asthma currently enrolled in a large trial. Methods The present analysis is a sub-study of the PeRson EmPowered Asthma RElief (PREPARE) study, a pragmatic study of 1201 AA/B and H/L adults with asthma. A monthly questionnaire was completed by a subset of PREPARE participants (n = 325) during May–August, 2020. The 5-item questionnaire assessed self-reported impact of COVID-19 on respondents’ ability to obtain asthma medications, medical care quality, employment, income and ability to pay bills; and willingness to get a free COVID-19 vaccine. Bivariate analysis and multivariate logistic regression were performed to investigate factors associated with vaccine hesitancy. Results Of 325 survey respondents (25% AA/B, 75% H/L), the majority reported no impact of COVID-19 on medical care or ability to get asthma medications. Approximately half of employed respondents experienced a lower level of employment or job loss, and approximately half reported having difficulty paying bills during the pandemic. Thirty-five percent of respondents reported unwillingness and 31% reported being somewhat likely to receive a free COVID-19 vaccine. AA/B race/ethnicity and poorer reported physical health were associated with a higher likelihood of COVID-19 vaccine hesitancy. Conclusion AA/B and H/L adults with asthma may experience changes in the quality of their asthma care and increased socioeconomic stressors as a result of the COVID-19 pandemic and may be hesitant or unwilling to receive a COVID-19 vaccine.

Asthma COPD Overlap has consistently reported to be associated with an increase burden of disease but the impact on lung function decline and mortality varies by study. The prevalence increases with age but the relationship with gender also varies with the study population. The variability in the prevalence and clinical characteristics of ACO is linked to differences in how chronic obstructive pulmonary disease (COPD) and asthma are defined, including diagnostic criteria (spirometry-based vs. clinical or symptom-based diagnoses vs. claims data), the population studied, the geographic region and environment and a consensus approach to the diagnosis of ACO is needed to allow meaningful and consistent epidemiologic information to be generated about this condition.

Background Hypogammaglobulinemia (serum IgG levels Research Question To determine the relationship between hypogammaglobulinemia and the risk of hospitalization in patients with COPD. Study Design and Methods Serum IgG levels were measured on baseline samples from four COPD cohorts (n = 2,259): Azithromycin for Prevention of AECOPD (MACRO, n = 976); Simvastatin in the Prevention of AECOPD (STATCOPE, n = 653), Long-Term Oxygen Treatment Trial (LOTT, n = 354), and COPD Activity: Serotonin Transporter, Cytokines and Depression (CASCADE, n = 276). IgG levels were determined by immunonephelometry (MACRO; STATCOPE) or mass spectrometry (LOTT; CASCADE). The effect of hypogammaglobulinemia on COPD hospitalization risk was evaluated using cumulative incidence functions for this outcome and deaths (competing risk). Fine-Gray models were performed to obtain adjusted subdistribution hazard ratios (SHR) related to IgG levels for each study and then combined using a meta-analysis. Rates of COPD hospitalizations per person-year were compared according to IgG status. Results The overall frequency of hypogammaglobulinemia was 28.4%. Higher incidence estimates of COPD hospitalizations were observed among participants with low IgG levels compared with those with normal levels (Gray's test, P Interpretation Hypogammaglobulinemia is associated with a higher risk of COPD hospital admissions.

Background Although inhaled therapy reduces exacerbations among patients with COPD, the effectiveness of providing inhaled treatment per risk stratification models remains unclear. Research Question Are inhaled regimens that align with the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy associated with clinically important outcomes? Study Design and Methods We conducted secondary analyses of Long-term Oxygen Treatment Trial (LOTT) data. The trial enrolled patients with COPD with moderate resting or exertional hypoxemia between 2009 and 2015. Our exposure was the patient-reported inhaled regimen at enrollment, categorized as either aligning with, undertreating, or potentially overtreating per the 2017 GOLD strategy. Our primary composite outcome was time to death or first hospitalization for COPD. Additional outcomes included individual components of the composite outcome and time to first exacerbation. We generated multivariable Cox proportional hazard models across strata of GOLD-predicted exacerbation risk (high vs low) to estimate between-group hazard ratios for time to event outcomes. We adjusted models a priori for potential confounders, clustered by site. Results The trial enrolled 738 patients (73.4% men; mean age, 68.8 years). Of the patients, 571 (77.4%) were low risk for future exacerbations. Of the patients, 233 (31.6%) reported regimens aligning with GOLD recommendations; most regimens (54.1%) potentially overtreated. During a 2.3-year median follow-up, 332 patients (44.9%) experienced the composite outcome. We found no difference in time to composite outcome or death among patients reporting regimens aligning with recommendations compared with undertreated patients. Among patients at low risk, potential overtreatment was associated with higher exacerbation risk (hazard ratio, 1.42; 95% CI, 1.09-1.87), whereas inhaled corticosteroid treatment was associated with 64% higher risk of pneumonia (incidence rate ratio, 1.64; 95% CI, 1.01-2.66). Interpretation Among patients with COPD with moderate hypoxemia, we found no difference in clinical outcomes between inhaled regimens aligning with the 2017 GOLD strategy compared with those that were undertreated. These findings suggest the need to reevaluate the effectiveness of risk stratification model-based inhaled treatment strategies.

Black and Latinx patients bear a disproportionate burden of asthma. Efforts to reduce the disproportionate morbidity have been mostly unsuccessful, and guideline recommendations have not been based on studies in these populations.In this pragmatic, open-label trial, we randomly assigned Black and Latinx adults with moderate-to-severe asthma to use a patient-activated, reliever-triggered inhaled glucocorticoid strategy (beclomethasone dipropionate, 80 μg) plus usual care (intervention) or to continue usual care. Participants had one instructional visit followed by 15 monthly questionnaires. The primary end point was the annualized rate of severe asthma exacerbations. Secondary end points included monthly asthma control as measured with the Asthma Control Test (ACT; range, 5 [poor] to 25 [complete control]), quality of life as measured with the Asthma Symptom Utility Index (ASUI; range, 0 to 1, with lower scores indicating greater impairment), and participant-reported missed days of work, school, or usual activities. Safety was also assessed.Of 1201 adults (603 Black and 598 Latinx), 600 were assigned to the intervention group and 601 to the usual-care group. The annualized rate of severe asthma exacerbations was 0.69 (95% confidence interval [CI], 0.61 to 0.78) in the intervention group and 0.82 (95% CI, 0.73 to 0.92) in the usual-care group (hazard ratio, 0.85; 95% CI, 0.72 to 0.999; P = 0.048). ACT scores increased by 3.4 points (95% CI, 3.1 to 3.6) in the intervention group and by 2.5 points (95% CI, 2.3 to 2.8) in the usual-care group (difference, 0.9; 95% CI, 0.5 to 1.2); ASUI scores increased by 0.12 points (95% CI, 0.11 to 0.13) and 0.08 points (95% CI, 0.07 to 0.09), respectively (difference, 0.04; 95% CI, 0.02 to 0.05). The annualized rate of missed days was 13.4 in the intervention group and 16.8 in the usual-care group (rate ratio, 0.80; 95% CI, 0.67 to 0.95). Serious adverse events occurred in 12.2% of the participants, with an even distribution between the groups.Among Black and Latinx adults with moderate-to-severe asthma, provision of an inhaled glucocorticoid and one-time instruction on its use, added to usual care, led to a lower rate of severe asthma exacerbations. (Funded by the Patient-Centered Outcomes Research Institute and others; PREPARE ClinicalTrials.gov number, NCT02995733.).

Hispanic/Latinx (HL) ethnicity encompasses racially and culturally diverse subgroups. Studies suggest that Puerto Ricans (PR) may bear greater asthma-related morbidity than Mexicans, but these were conducted in children or had limited clinical characterization.This study sought to determine whether disparities in asthma morbidity exist among HL adult subgroups.Adults with moderate-severe asthma were recruited from US clinics, including from Puerto Rico, for the Person Empowered Asthma Relief (PREPARE) trial. Considering the shared heritage between PR and other Caribbean HL (Cubans and Dominicans [Camp;D]), the investigators compared baseline self-reported clinical characteristics between Caribbean HL (CHL) (PR and Camp;D: n = 457) and other HLs (OHL) (Mexicans, Spaniards, Central/South Americans; n = 141), and between CHL subgroups (Camp;D [n = 56] and PR [n = 401]). This study compared asthma morbidity measures (self-reported exacerbations requiring systemic corticosteroids, emergency department/urgent care (ED/UC) visits, hospitalizations, health care utilization) through negative binomial regression.CHL compared to OHL were similar in age, body mass index, poverty status, blood eosinophils, and fractional exhaled nitric oxide but were prescribed more asthma controller therapies. Relative to OHL, CHL had significantly increased odds of asthma exacerbations (odds ratio [OR]: 1.84; 95% CI: 1.4-2.4), ED/UC visits (OR: 1.88; 95% CI: 1.4-2.5), hospitalization (OR: 1.98; 95% CI: 1.06-3.7), and health care utilization (OR: 1.91; 95% CI: 1.44-2.53). Of the CHL subgroups, PR had significantly increased odds of asthma exacerbations, ED/UC visits, hospitalizations, and health care utilization compared to OHL, whereas Camp;D only had increased odds of exacerbations compared to OHL. PR compared to Camp;D had greater odds of ED/UC and health care utilization.CHL adults, compared with OHL, adults reported nearly twice the asthma morbidity; these differences are primarily driven by PR. Novel interventions are needed to reduce morbidity in this highly impacted population.

Asthma disproportionately affects African American/Black (AA/B) and Hispanic/Latinx (H/L) patients and individuals with low socioeconomic status (SES), but the relationship between SES and asthma morbidity within these racial/ethnic groups is inadequately understood.To determine the relationship between SES and asthma morbidity among AA/B and H/L adults with moderate to severe asthma using multidomain SES frameworks and mediation analyses.We analyzed enrollment data from the PeRson EmPowered Asthma RElief randomized trial, evaluating inhaled corticosteroid supplementation to rescue therapy. We tested for direct and indirect relationships between SES and asthma morbidity using structural equation models. For SES, we used a latent variable defined by poverty, education, and unemployment. For asthma morbidity, we used self-reported asthma exacerbations in the year before enrollment (corticosteroid bursts, emergency room/urgent care visits, or hospitalizations), and Asthma Control Test scores. We tested for mediation via health literacy, perceived stress, and self-reported discrimination. All models adjusted for age, sex, body mass index, ethnicity, and comorbidities.Among 990 AA/B and H/L adults, low SES (latent variable) was directly associated with hospitalizations (β = 0.24) and worse Asthma Control Test scores (β = 0.20). Stress partially mediated the relationship between SES and increased emergency room/urgent care visits and worse asthma control (β = 0.03 and = 0.05, respectively). Individual SES domains were directly associated with asthma morbidity. Stress mediated indirect associations between low educational attainment and unemployment with worse asthma control (β = 0.05 and = 0.06, respectively).Lower SES is directly, and indirectly through stress, associated with asthma morbidity among AA/B and H/L adults. Identification of stressors and relevant management strategies may lessen asthma-related morbidity among these populations.

Despite decades of effort to drive quality improvement, many health care organizations still struggle to optimize their performance on quality metrics. The advent of publicly reported quality rankings and ratings allows for greater visibility of overall organizational performance, but has not provided a roadmap for sustained improvement in these assessments. Most quality training programs have focused on developing knowledge and skills in pursuit of individual and project-level improvements. To date, no training program has been associated with improvements in overall organization-level, publicly reported measures. In 2012, the Institute for Health care Quality, Safety, and Efficiency was launched, which is an integrated set of quality and safety training programs, with a focus on leadership development and support of performance improvement through data analytics and intensive coaching. This effort has trained nearly 2000 individuals and has been associated with significant improvement in organization-level quality rankings and ratings, offering a framework for organizations seeking systematic, long-term improvement.

Background: Poor communication and coordination between primary care providers (PCPs) and subspecialty providers (SPs) results in fragmented care and patient dissatisfaction. Project CORE was initiated in 2011 to enhance communication and coordination between PCPs and adult SPs in 5 academic medical centers (AMCs) through enhanced referral (ER) processes and asynchronous electronic consultations (ECs). We sought to apply that model in a large childrens hospital as part of a global initiative to improve access to care and enhance …

Asthma is a complex syndrome with multiple phenotypes and endotypes. Asthma exacerbations are not only the clearest indictor of the morbidity of asthma and of the risk for mortality due to asthma, but also comprise a significant amount of the cost to care for poorly controlled asthma. There continues to be significant disparity in the prevalence, mortality, and morbidity due to asthma. Patients with asthma who suffer recurrent exacerbations are considered to have exacerbation-prone asthma (EPA). Efforts to characterize patients with frequent exacerbations show that the etiology is likely multifactorial. Research to determine the intrinsic risk factors for EPA include studies of both genetic and inflammatory biomarkers. External factors contributing to exacerbations have been extensively reviewed and include viral infection, environmental exposures, air pollution, and psychosocial and economic barriers to optimizing health. It is likely that EPA occurs when patients who have an increased underlying intrinsic/biological risk are placed in a given exposome (environments with a variety of exposures and triggers including allergens, pollution, stress, barriers, and occupational exposures). It is the social construct combined with underlying biology that frequently drives an EPA phenotype.

Background Discordance between physicians' and patients' perceptions of asthma control may negatively impact symptom control, treatment, and outcomes. Objective To evaluate concordance between physicians' and patients' perceptions of overall asthma control and the association between perceived overall control and individual components of control. Methods U.S. survey data (Dec 2015–Feb 2016; Apr–Aug 2018) from the Respiratory Disease Specific Programme were analyzed. Physicians recorded patient disease characteristics and their perception of patients' asthma control. Patients' perception of control was assessed using the Asthma Control Test; responses were compared with level of symptom control per the Global Initiative for Asthma criteria and Work Productivity and Impairment questionnaire responses. Agreement and association were assessed by weighted kappa (κ) and Spearman rho (ρ), respectively. Results The study included 1,288 patients. Concordance between physician-perceived and patient-perceived asthma control in the prior 4 weeks was moderate (κ = 0.4951). Association between physicians' overall perception of asthma control and patients' overall Asthma Control Test score was also moderate (ρ = 0.5450). However, 61.5% of patients with self-reported, well-controlled asthma had shortness of breath 1 to 2 times/wk, 45.6% had 1 to 2 night-time awakenings/wk, and patients reported a mean (SD) daily activity impairment of 17.5% (16.2%). Only 21.8% of patients with self-reported, well-controlled asthma were classified as such by Global Initiative for Asthma symptom criteria. Conclusions Patients' self-assessment of overall control does not accurately characterize the true level of control; thus, patients and physicians may benefit from working together to assess the individual components of asthma control to achieve better disease management, treatment decisions, and improved outcomes.

The introduction of specific humanized monoclonal antibodies over the past 20 years has dramatically changed the treatment of allergic diseases. At present, 5 mAbs are licensed for treating moderate to severe allergic and eosinophilic asthma, atopic dermatitis, chronic spontaneous urticaria, chronic sinusitis with nasal polyps, and eosinophilic granulomatosis with polyangiitis. Given the high costs of biologics, understanding their cost-effectiveness is critical. As new biologics are developed and new indications are approved for existing biologics, the use of biologics for allergic diseases will increase. Conducting cost-effectiveness evaluations in parallel to efficacy and effectiveness trials will help patients, providers, payers, and policymakers in decision making.

BackgroundAlthough inhaled therapy reduces exacerbations among patients with COPD, the effectiveness of providing inhaled treatment per risk stratification models remains unclear.Research questionAre inhaled regimens that align with the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy associated with clinically important outcomes?Study design and methodsWe conducted secondary analyses of Long-term Oxygen Treatment Trial (LOTT) data. The trial enrolled patients with COPD with moderate resting or exertional hypoxemia between 2009 and 2015. Our exposure was the patient-reported inhaled regimen at enrollment, categorized as either aligning with, undertreating, or potentially overtreating per the 2017 GOLD strategy. Our primary composite outcome was time to death or first hospitalization for COPD. Additional outcomes included individual components of the composite outcome and time to first exacerbation. We generated multivariable Cox proportional hazard models across strata of GOLD-predicted exacerbation risk (high vslow) to estimate between-group hazard ratios for time to event outcomes. We adjusted models a priori for potential confounders, clustered by site.ResultsThe trial enrolled 738 patients (73.4%men; mean age, 68.8 years). Of the patients, 571 (77.4%) were low risk for future exacerbations. Of the patients, 233 (31.6%) reported regimens aligning with GOLD recommendations; most regimens (54.1%) potentially overtreated. During a 2.3-year median follow-up, 332 patients (44.9%) experienced the composite outcome. We found no difference in time to composite outcome or death among patients reporting regimens aligning with recommendations compared with undertreated patients. Among patients at low risk, potential overtreatment was associated with higher exacerbation risk (hazard ratio, 1.42; 95%CI, 1.09-1.87), whereas inhaled corticosteroid treatment was associated with 64%higher risk of pneumonia (incidence rate ratio, 1.64; 95%CI, 1.01-2.66).InterpretationAmong patients with COPD with moderate hypoxemia, we found no difference in clinical outcomes between inhaled regimens aligning with the 2017 GOLD strategy compared with those that were undertreated. These findings suggest the need to reevaluate the effectiveness of risk stratification model-based inhaled treatment strategies.

Background Frequency of moderate and severe chronic obstructive pulmonary disease exacerbations is an important endpoint in clinical trials, but makes them large and lengthy when powered to evaluate it. We aimed to develop a composite endpoint (COPDCompEx) that could predict treatment effect on exacerbations, enabling the design of shorter early phase clinical trials requiring fewer patients. Methods In this post hoc analysis, data from 20 randomized controlled trials were used to develop and test COPDCompEx. Diary events were tested against predefined threshold values for peak expiratory flow, reliever medication use, and symptoms. A COPDCompEx event was defined as first occurrence of a diary event, a moderate or severe exacerbation, or a study dropout. Ratios of event frequency, treatment effect and future trial sample size were compared between COPDCompEx and moderate and severe exacerbations. Findings At 3 months, the proportion of patients experiencing COPDCompEx events increased over 3-fold versus exacerbations alone. All components contributed to COPDCompEx event rate. Treatment effects at 3 months were closely matched between COPDCompEx and exacerbations, and the large net gain in power substantially reduced the required sample size. Interpretation COPDCompEx may be used to predict treatment effect on moderate and severe exacerbations of chronic obstructive pulmonary disease. This may enable the design of shorter Phase 2 clinical trials requiring fewer patients when compared with current exacerbation studies, with exacerbations as a key Phase 3 endpoint. This would, therefore, allow more efficient decision-making with reduced burden and risk to study participants.

Exacerbations account for much of the morbidity in asthma. In a large intervention study, we sought to test the hypothesis that a Black adult exacerbation-prone phenotype - a group of Black people with asthma who are at high risk of repeat exacerbation within one year - exists in asthma independent of clinical control.We analyzed exacerbation risk factors in 536 self-identified Black Americans with asthma eligible for, or on, Step 3 National Asthma Education and Prevention Program (NAEPP) therapy who participated in a randomized 6-18 month trial of tiotropium versus long acting beta agonist as add-on therapy to inhaled corticosteroids. Exacerbations were defined as events treated by oral or systemic corticosteroids. Clinical control was assessed by a validated asthma control questionnaire (ACQ5).Exacerbations became more likely with loss of clinical control. The mean baseline ACQs for exacerbators and non-exacerbators were 2.41 and 1.91, respectively (p 0.001). The strongest independent factor associated with exacerbations across all ACQ levels was an exacerbation in the preceding year (adjusted OR 3.26; p 0.001). The severity of prior exacerbations did not correlate with the likelihood of a future exacerbation. Lower baseline FEV1/FVC was also associated with increased risk of exacerbations.Even though exacerbations increase with loss of clinical control, an exacerbation susceptibility phenotype exists in Black adults with asthma, independent of clinical control. This phenotype requires precision therapeutic targeting.

Woo Jin Kim,1 Jae-Joon Yim,2 Deog Kyeom Kim,3 Myung Goo Lee,4 Anne L Fuhlbrigge,5 Pawel Sliwinski,6 Iwona Hawrylkiewicz,6 Emily S Wan,7,8 Michael H Cho,7,8 Edwin K Silverman7,8 1Department of Internal Medicine and Environmental Health Center, Kangwon National University Hospital, Chuncheon, 2Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul National University College of Medicine, Seoul, 3Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, 4Division of Pulmonary, Allergy and Critical Care Medicine, Hallym University Chuncheon Sacred Heart Hospital, Chuncheon, Korea; 5Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, CO, USA; 62nd Department of Respiratory Medicine, Institute of Tuberculosis and Lung Diseases, Warsaw, Poland; 7Channing Division of Network Medicine, 8Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, MA, USA Purpose: Chronic obstructive pulmonary disease (COPD), characterized by irreversible airflow obstruction, is a major cause of morbidity and mortality worldwide. However, geographic differences in the clinical characteristics of severe COPD patients have not been widely studied. Methods: We recruited a total of 828 severe COPD cases from three continents. Subjects in Poland were enrolled by the Institute of Tuberculosis and Lung Diseases in Warsaw; subjects in Korea participated at several university hospitals in Korea; and subjects in USA were enrolled at two clinics affiliated with academic medical centers. All subjects were over the age of 30 with at least 10 pack-years of cigarette smoking history. Cases manifested severe to very severe airflow obstruction with post-bronchodilator forced expiratory volume in 1 second (FEV1)

Summary Background Occurrence of severe asthma exacerbations are the cornerstone of the evaluation of asthma management, but severe asthma exacerbations are rare events. Therefore, trials that assess drug efficacy on exacerbations are done late in clinical development programmes. We aimed to establish an endpoint capturing clinically relevant deteriorations (diary events) that, when combined with severe exacerbations, create a composite outcome (CompEx). CompEx needs to strongly mirror results seen with the severe exacerbation-validated outcome, to allow the design of clinical trials of shorter duration and that include fewer patients than trials assessing severe exacerbations. Methods Data from 12 asthma trials of 6 months or 12 months duration and, with standardised collection of exacerbations and diary card variables, were used to construct and test CompEx. The study populations had a mean age of 35–53 years, 59–69% were female, and had a mean FEV 1 percentage of predicted normal of 63–84%. With data from five trials, we established a series of diary events based on peak expiratory flow (P), reliever use (R), symptoms (S), awakenings (A), and threshold values for change from baseline and slopes to assess trends. For the development phase, we evaluated different variable combinations and deterioration criteria to select the most robust algorithm to define a diary event for the composite outcome. We defined a composite outcome, CompEx, as first occurrence of a diary event or a severe exacerbation. We assessed the performance of CompEx in seven trials by comparing the event frequency, treatment effect (hazard ratio; HR), and the sample size needed for future trials for the CompEx versus episodes of severe exacerbations. Findings CompEx (based on PRS) was the algorithm that best fulfilled our two-set criteria. When censored at 3 months, CompEx resulted in 2·8 times more events than severe exacerbations, and while preserving the treatment effect observed on severe exacerbations (CompEx over severe exacerbation average HR 1·01). The increased number of events, together with the sustained treatment effect, resulted in a large net gain in power, with a 67% mean reduction in the number of patients required in a drug trial for severe exacerbations. In six of seven comparisons tested, CompEx reduced the sample size needed by at least 50%. Validation of independent test populations confirmed the ability of CompEx to increase event frequencies, preserve treatment effect, and reduce the number of patients needed. Interpretation CompEx is a composite outcome for evaluation of new asthma therapies. CompEx allows design of shorter trials that require fewer patients than studies of severe exacerbations, while preserving the ability to show a treatment effect compared with severe exacerbations. Funding AstraZeneca.

Hypogammaglobulinemia (serum IgG levels 7.0 g/L) has been associated with increased risk of COPD exacerbations but has not yet been shown to predict hospitalizations.To determine the relationship between hypogammaglobulinemia and the risk of hospitalization in patients with COPD.Serum IgG levels were measured on baseline samples from four COPD cohorts (n = 2,259): Azithromycin for Prevention of AECOPD (MACRO, n = 976); Simvastatin in the Prevention of AECOPD (STATCOPE, n = 653), Long-Term Oxygen Treatment Trial (LOTT, n = 354), and COPD Activity: Serotonin Transporter, Cytokines and Depression (CASCADE, n = 276). IgG levels were determined by immunonephelometry (MACRO; STATCOPE) or mass spectrometry (LOTT; CASCADE). The effect of hypogammaglobulinemia on COPD hospitalization risk was evaluated using cumulative incidence functions for this outcome and deaths (competing risk). Fine-Gray models were performed to obtain adjusted subdistribution hazard ratios (SHR) related to IgG levels for each study and then combined using a meta-analysis. Rates of COPD hospitalizations per person-year were compared according to IgG status.The overall frequency of hypogammaglobulinemia was 28.4%. Higher incidence estimates of COPD hospitalizations were observed among participants with low IgG levels compared with those with normal levels (Gray's test, P .001); pooled SHR (meta-analysis) was 1.29 (95% CI, 1.06-1.56, P = .01). Among patients with prior COPD admissions (n = 757), the pooled SHR increased to 1.58 (95% CI, 1.20-2.07, P .01). The risk of COPD admissions, however, was similar between IgG groups in patients with no prior hospitalizations: pooled SHR = 1.15 (95% CI, 0.86-1.52, P =.34). The hypogammaglobulinemia group also showed significantly higher rates of COPD hospitalizations per person-year: 0.48 ± 2.01 vs 0.29 ± 0.83, P .001.Hypogammaglobulinemia is associated with a higher risk of COPD hospital admissions.

Introduction: Differences between patient and physician perceptions of control and the impact of asthma may negatively affect symptomatic control. Aims: To investigate whether the physician’s perception of asthma control is consistent with the patient. Methods: Patient and physician data from two US cross-sectional surveys (2016 & 2018) conducted by Adelphi were analysed. Physicians completed forms including a 5-point scale for perceived asthma control in the past 4 weeks. Corresponding patients completed a questionnaire that included the ACT and the same 5-point scale and timeframe to assess their perceived asthma control. Concordance was assessed by a weighted Kappa (κ) statistic and associations by Spearman’s Rho. Results: 1288 patients were included (mean age 42.7 years; 40.4% male). 89% of patients received maintenance treatment. Patients’ asthma was evaluated by the physician to be completely (15.1%), well (47.4%), somewhat (30.4%), poorly (6.6%) or not at all (0.6%) controlled. Corresponding patient evaluation was 16.8%, 46.4%, 29.3%, 6.3%, 1.2% respectively. Agreement was moderate (88.7%, κ=0.495). Stratification by GINA treatment steps 1-5 gave κ statistics of 0.362, 0.504, 0.516, 0.440, 0.466 respectively. Associations between physician-perception of control and ACT score were also moderate (rho=0.545). Conclusion: While there is generally good agreement between physicians’ and patients’ perception of asthma control, the kappa statistic revealed only a moderate level of concordance. Despite this, over one-third of patients’ asthma was not well controlled. Further understanding of the factors that impact concordance may translate into better asthma control for patients.

Background Asthma prevalence, morbidity, and mortality disproportionately impact African American/Black (AA/B) and Hispanic/Latinx (H/L) communities. Adherence to daily inhaled corticosteroid (ICS), recommended by asthma guidelines in all but the mildest cases of asthma, is generally poor. As-needed ICS has shown promise as a patient-empowering asthma management strategy, but it has not been rigorously studied in AA/B or H/L patients or in a real-world setting. Design and Aim The PeRson EmPowered Asthma RElief (PREPARE) Study is a randomized, open-label, pragmatic study which aims to assess whether a patient-guided, reliever-triggered ICS strategy called PARTICS (Patient-Activated Reliever-Triggered Inhaled CorticoSteroid) can improve asthma outcomes in AA/B and H/L adult patient populations. In designing and implementing the study, the PREPARE research team has relied heavily on advice from AA/B and H/L Patient Partners and other stakeholders. Methods PREPARE is enrolling 1200 adult participants (600 AA/Bs, 600H/Ls) with asthma. Participants are randomized to PARTICS + Usual Care (intervention) versus Usual Care (control). Following a single in-person enrollment visit, participants complete monthly questionnaires for 15 months. The primary endpoint is annualized asthma exacerbation rate. Secondary endpoints include asthma control; preference-based quality of life; and days lost from work, school, or usual activities. Discussion The PREPARE study features a pragmatic design allowing for the real-world assessment of a patient-centered, reliever-triggered ICS strategy in AA/B and H/L patients. Outcomes of this study have the potential to offer powerful evidence supporting PARTICS as an effective asthma management strategy in patient populations that suffer disproportionately from asthma morbidity and mortality.

BACKGROUND Long-term treatment with supplemental oxygen has unknown efficacy in patients with stable chronic obstructive pulmonary disease (COPD) and resting or exercise-induced moderate desaturation. METHODS We originally designed the trial to test whether long-term treatment with supplemental oxygen would result in a longer time to death than no use of supplemental oxygen among patients who had stable COPD with moderate resting desaturation (oxyhemoglobin saturation as measured by pulse oximetry [Spo2], 89 to 93%). After 7 months and the randomization of 34 patients, the trial was redesigned to also include patients who had stable COPD with moderate exercise-induced desaturation (during the 6-minute walk test, Spo2 ≥80% for ≥5 minutes and

Unplanned early rehospitalization (UER), defined as an unscheduled admission within 30 days of a hospital discharge, is associated with graft loss and recipient mortality in some solid organ transplants but has not been investigated in lung transplant. In this retrospective study, we collected socio-demographic and clinical factors to determine predictors and outcomes of UER in the first year following lung transplantation. There were 193 patients who underwent lung transplantation and survived to discharge during the 7.9-year study period. There were 116 (60.1%) patients with at least one UER. Infections (32.8%) and post-surgical complications (11.8%) were the most common reasons for UER. On multivariate analysis, the strongest predictor of having an UER was discharge to a long-term acute care facility (odds ratio: 3.01, 95% confidence interval [CI] 1.46-6.20; P=.003). Patients with any UER in the first year following transplantation had worse adjusted survival (hazard ratio: 1.89, 95% CI 1.02-3.50; P=.04). It is unclear, however, to what extent UERs reflect preventable outcomes. Further large-scale, prospective research is needed to identify the extent to which certain types of UER are modifiable and to define patients at high-risk for preventable UER.

BACKGROUND: Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction.METHODS: We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma.RESULTS: Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (PCONCLUSIONS: Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.).

BACKGROUND: Although ambient air pollution has been linked to reduced lung function in healthy children, longitudinal analyses of pollution effects in asthmatic patients are lacking.OBJECTIVE: We sought to investigate pollution effects in a longitudinal asthma study and effect modification by controller medications.METHODS: We examined associations of lung function and methacholine responsiveness (PC20) with ozone, carbon monoxide (CO), nitrogen dioxide, and sulfur dioxide concentrations in 1003 asthmatic children participating in a 4-year clinical trial. We further investigated whether budesonide and nedocromil modified pollution effects. Daily pollutant concentrations were linked to ZIP/postal code of residence. Linear mixed models tested associations of within-subject pollutant concentrations with FEV1 and forced vital capacity (FVC) percent predicted, FEV1/FVC ratio, and PC20, adjusting for seasonality and confounders.RESULTS: Same-day and 1-week average CO concentrations were negatively associated with postbronchodilator percent predicted FEV1 (change per interquartile range, -0.33 [95% CI, -0.49 to -0.16] and -0.41 [95% CI, -0.62 to -0.21], respectively) and FVC (-0.19 [95% CI, -0.25 to -0.07] and -0.25 [95% CI, -0.43 to -0.07], respectively). Longer-term 4-month CO averages were negatively associated with prebronchodilator percent predicted FEV1 and FVC (-0.36 [95% CI, -0.62 to -0.10] and -0.21 [95% CI, -0.42 to -0.01], respectively). Four-month averaged CO and ozone concentrations were negatively associated with FEV1/FVC ratio (P < .05). Increased 4-month average nitrogen dioxide concentrations were associated with reduced postbronchodilator FEV1 and FVC percent predicted. Long-term exposures to sulfur dioxide were associated with reduced PC20 (percent change per interquartile range, -6% [95% CI, -11% to -1.5%]). Treatment augmented the negative short-term CO effect on PC20.CONCLUSIONS: Air pollution adversely influences lung function and PC20 in asthmatic children. Treatment with controller medications might not protect but rather worsens the effects of CO on PC20. This clinical trial design evaluates modification of pollution effects by treatment without confounding by indication.

As the COVID-19 health crisis continues to reshape healthcare, systems across the country face increasing pressure to adapt their models of care to expand access to care, while also improving efficiency and quality in the face of limited resources. Consequently, many have shown a growing interest and receptivity to the expansion of telehealth models to help meet these demands. Electronic consultations (eConsults) are a telehealth modality that allow for a non-face-to-face asynchronous consultation between a primary care provider (PCP) and a specialist aimed at facilitating specialist input without the need for a patient visit. The aim of this case study is to describe eConsults, how they differ from traditional in person models of care and other models of telemedicine and to review the evidence related to the effectiveness of eConsults by PCPs and clinicians from multiple specialties at the University of Colorado School of Medicine. We have worked to develop an infrastructure, delivery system integration, and care model adaptations that aim to improve delivery system performance by ensuring proper care in appropriate settings and lowering costs through reduced utilization. Lastly, we have increased care coordination, improved collaboration and better care transitions through strengthening of relationships between community-based PCPs and academic medical center-based specialists. This work has resulted in cost savings to patients and positive provider satisfaction.

BACKGROUND: Little is known about specialist-specific variations in guideline agreement and adoption. OBJECTIVE: To assess similarities and differences between allergists and pulmonologists in adherence to cornerstone components of the National Asthma Education and Prevention Program’s Third Expert Panel Report (EPR-3). METHODS: Self-reported guideline agreement, self-efficacy and adherence were assessed in allergists (n=134) and pulmonologists (n=99) in the 2012 National Asthma Survey of Physicians. Multivariate models were used to assess if physician and practice characteristics explained bivariate associations between specialty and “almost always” adhering to recommendations (i.e., ≥75% of the time). RESULTS: Allergists and pulmonologists reported high guideline self-efficacy and moderate guideline agreement. Both groups “almost always” assessed asthma control (66.2%, SE 4.3), assessed school/work asthma triggers (71.3%, SE 3.9), and endorsed inhaled corticosteroids use (95.5%, SE 2.0). Repeated assessment of inhaler technique, use of asthma action/treatment plans and spirometry were lower (39.7%, SE 4.0, 30.6%, SE 3.6, 44.7%, SE 4.1, respectively). Compared to pulmonologists, more allergists almost always performed spirometry (56.6% vs 38.6%, P=.06), asked about nighttime awakening (91.9% vs 76.5%, P=.03) and ED visits (92.2% vs 76.5%, P=0.03), assessed home triggers (70.5% vs 52.6%, P=.06) and performed allergy testing (61.8% vs 21.3%, P

Background Underuse of guideline-recommended inhaled corticosteroids (ICS) controller therapy is a risk factor for greater asthma burden. ICS concomitantly-used with rescue inhalers [Patient-Activated Reliever-Triggered ICS(‘PARTICS’)] reduced asthma exacerbations in efficacy trials, but whether PARTICS is effective in pragmatic trials is unknown. Objective We conducted this pilot to determine the feasibility of executing a large-scale pragmatic PARTICS trial and to improve study protocols. Methods Four sites recruited 33 Hispanic or Black persistently asthmatic adults, randomized them ∼3:1 to intervention or usual care, and followed them for 12 weeks. All participants received asthma guideline-based educational videos; intervention participants received video-based instructions on implementing PARTICS plus usual medications. The study involved one randomization visit and monthly questionnaires. Timely questionnaire responses (+/-2 weeks) were monitored. Participants underwent qualitative phone interviews to assess self-reported adherence to PARTICS and understand barriers to completing study procedures. Results Timely questionnaire response rates were 61%, 64%, 70% at 4, 8 and 12 weeks, respectively. Self-reported adherence to PARTICS was 76% [95%CI 58-94%(n=21)], 88% [95%CI 72-100%(n=16)], and 62% [95%CI 36-88%(n=13)] at weeks 1, 6, and 12, respectively. Barriers to completing study procedures included difficulties with questionnaire access, remembering to use ICS and rescue inhalers together, and obtaining refills. Only 22% of participants recognized their short-acting bronchodilator as “reliever” or “rescue”. Conclusion Recruitment was feasible within the allocated period. Adherence to PARTICS was incomplete, questionnaire completion was suboptimal, and common rescue inhaler nomenclature usage was limited. We have modified the full study protocol to attempt to improve adherence to PARTICS and minimize barriers to study procedures.

Background: Chronic obstructive pulmonary disease (COPD) patients enrolled into the Long-term Oxygen Treatment Trial had hypoxemia at rest, hypoxemia on exertion, or hypoxemia both at rest and on exertion. We hypothesized that patients with different patterns of hypoxemia may have significant differences in clinical features. Methods: All patients had COPD and oxygen saturation measured by pulse oximetry (blood oxygenation [SpO2]) at rest and during the 6-minute walk test (6MWT). Hypoxemia at rest was defined as resting SpO2 between 89-93%. SpO2 1 minute) was exclusionary. Results: Of 738 patients studied, 133 (18.0%) had mild-moderate hypoxemia at rest only, 319 (43.2%) had hypoxemia on exertion only, and 286 (38.8%) had hypoxemia at both rest and exertion. Patients with hypoxemia at rest only were more likely to be current smokers, had higher body mass index (BMI) and a higher incidence of self-reported diabetes. Patients with hypoxemia on exertion only were more severely obstructed compared to the other groups. General and disease-specific quality of life scores were similarly impaired in all groups. Quality of well-being scores were more impaired in those with hypoxemia at rest only. Conclusions: COPD patients with mild-moderate hypoxemia have distinct clinical characteristics based on the pattern of oxygen desaturation at rest and with exertion.

Background FEV1 as a percentage of predicted (FEV1%pred) is commonly measured in asthma clinical studies; however, reports vary on its association with asthma control instruments evaluating symptoms. Objective Assess the association between FEV1%pred and Asthma Control Questionnaire (ACQ) scores in a managed-care population with persistent asthma. Methods Retrospective analysis of survey responses and spirometry results of patients (aged ≥12 years) with persistent asthma from the Observational Study of Asthma Control and Outcomes was done. Eligible patients received 4 identical surveys including the 5-item ACQ (ACQ-5)/6-item ACQ (ACQ-6) and completed spirometry in parallel. Longitudinal analyses, comparisons of change over time, and fixed- and random-effects regression analyses were conducted, with/without adjustment for covariates. Results There were 1748 survey responses with valid spirometry results. In unadjusted models, coefficients for ACQ-5/ACQ-6 scores were not statistically significant and coefficient of determination (R2) was low (0.03). When adjusted for covariates, ACQ-5 and ACQ-6 scores were significantly associated with FEV1%pred (P Conclusions The weak and statistically insignificant association between FEV1%pred and ACQ-5/ACQ-6 scores in unadjusted models suggests a high degree of unexplained variation between these measures. Results support the use of both symptoms and pulmonary function, rather than relying on one measure alone, to assess asthma control in clinical care and outcomes studies.

Rationale Characteristics associated with adherence to long-term oxygen therapy (LTOT) in COPD remain unclear. Objectives To identify patient characteristics at the time of oxygen initiation associated with its adherence. Methods We conducted a secondary analysis of data from 359 COPD participants assigned to oxygen in the Long-term Oxygen Treatment Trial. Participants were prescribed continuous (n = 214) or intermittent (n = 145) oxygen based on desaturation patterns at study entry. At the time of initial prescription, participants rated their perceived readiness, confidence, and importance to use oxygen on a 0–10 scale (0 = not at all, 10 = very much). During follow-up, they self-reported average hours per day of use (adherence). Adherence was averaged over short-term (0–30 days), medium-term (months 9–12), and long-term (month 13 to last follow-up) intervals. Multivariable logistic regression models explored characteristics associated with high adherence (≥16 h/day [continuous] or ≥8 h/day [intermittent]) during each time interval. Results Participant readiness, confidence, and importance at the time of oxygen initiation were associated with high short- and medium-term adherence. For each unit increase in baseline readiness, the odds of high short-term adherence increased by 21% (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.05–1.40) and 94% (OR 1.94, 95% CI 1.45–2.59) in the continuous and intermittent groups, respectively. In both groups, high adherence in the medium-term was associated with high adherence in the long-term (continuous, OR 12.49, 95% CI 4.90–31.79; intermittent, OR 38.08, 95% CI 6.96–208.20). Conclusions Readiness, confidence, and importance to use LTOT at initiation, and early high adherence, are significantly associated with long-term oxygen adherence.

Objective: Symptom free days are a widely used patient-reported outcome (PRO) in asthma clinical trials. We assessed the internal consistency of one instrument for this PRO, the Symptom Fre...

Pharmacogenomic tests that predict which asthma patients are likely to respond to βTo identify the clinical and economic circumstances under which a pharmacogenomic test that predicts response to βWe synthesized published data on clinical and economic outcomes in adults 18-35 to project 10-year costs, quality-adjusted life years and cost-effectiveness of pharmacogenomic testing for βPharmacogenomic testing for βPharmacogenomic testing for β

Asthma is a common chronic disease without cure. Our understanding of asthma onset, pathobiology, classification, and management has evolved substantially over the past decade; however, significant asthma-related morbidity and excess healthcare use and costs persist. To address this important clinical condition, the NHLBI convened a group of extramural investigators for an Asthma Research Strategic Planning workshop on September 18–19, 2014, to accelerate discoveries and their translation to patients. The workshop focused on (1) in utero and early-life origins of asthma, (2) the use of phenotypes and endotypes to classify disease, (3) defining disease modification, (4) disease management, and (5) implementation research. This report summarizes the workshop and produces recommendations to guide future research in asthma.

Summary Background Lung transplant is the only available therapy for patients with advanced lung disease. The goal of this study was to examine the prevalence, origin, management and outcome of lung cancer in recipients of lung transplant at our institution. Methods After institutional review board approval, we conducted a retrospective chart review of all lung transplantations in our institution from January 1990 until June 2012. Results The prevalence of lung cancer in the explanted lung was 6 (1.2%) of 462 and all cases were in subjects with lung fibrosis. All 4 subjects with lymph node involvement died of causes related to the malignancy. Nine (1.9%) of 462 patients were found to have bronchogenic carcinoma after lung transplant. The most common location was in the native lung in recipients of a single lung transplant (6 out of 9 patients). In one case, the tumor originated in the allograft and was potentially donor related. The median time to diagnosis after lung transplant was 28 months with a range from 9 months to 10 years. Median survival was 8 months, with tumors involving lymph nodes or distant metastases associated with a markedly worse prognosis (median survival 7 months) than stage I disease (median survival 27 months). Conclusions The prevalence of lung cancer in lung transplant recipients is low. Using accepted donor screening criteria, donor derived malignancy is exceptionally rare. While stage I disease is associated with improved survival in this cohort, survival is still not comparable to that of the general population, likely influenced by the need for aggressive immune suppression.

The Long-Term Oxygen Treatment Trial demonstrated that long-term supplemental oxygen did not reduce time to hospital admission or death for patients who have stable chronic obstructive pulmonary disease and resting and/or exercise-induced moderate oxyhemoglobin desaturation, nor did it provide benefit for any other outcome measured in the trial. Nine months after initiation of patient screening, after randomization of 34 patients to treatment, a trial design amendment broadened the eligible population, expanded the primary outcome, and reduced the goal sample size. Within a few years, the protocol underwent minor modifications, and a second trial design amendment lowered the required sample size because of lower than expected treatment group crossover rates. After 5.5 years of recruitment, the trial met its amended sample size goal, and 1 year later, it achieved its follow-up goal. The process of publishing the trial results brought renewed scrutiny of the study design and the amendments. This article expands on the previously published design and methods information, provides the rationale for the amendments, and gives insight into the investigators' decisions about trial conduct. The story of the Long-Term Oxygen Treatment Trial may assist investigators in future trials, especially those that seek to assess the efficacy and safety of long-term oxygen therapy. Clinical trial registered with clinicaltrials.gov (NCT00692198).