Measuring exhaled nitric oxide when diagnosing and managing asthma.

Measuring the concentration of nitric oxide in the exhaled breath may have several roles in patients with suspected or confirmed asthma: as an adjunctive test for the disease, as a test to determine whether patients with asthma are likely to respond to inhaled corticosteroids, as a way to monitor and adjust this therapy, and as a way to estimate the likelihood of exacerbations. However, it is not very sensitive or specific and should not be used by itself, but rather in conjunction with clinical signs and symptoms. The authors address the role of measuring exhaled nitric oxide in the diagnosis and management of asthma and provide guidance for its appropriate use.

Health Disparities: Interventions for Pulmonary Disease - A Narrative Review.

There is expansive literature documenting the presence of health disparities, but there are disproportionately few studies describing interventions to reduce disparity. In this narrative review, we categorize interventions to reduce health disparity in pulmonary disease within the US health care system to support future initiatives to reduce disparity. We identified 211 articles describing interventions to reduce disparity in pulmonary disease related to race, income, or sex. We grouped the studies into the following four categories: biologic, educational, behavioral, and structural. We identified the following five main themes: (1) there were few interventional trials compared with the breadth of studies describing health disparities, and trials involving patients with asthma who were Black, low income, and living in an urban setting were overrepresented; (2) race or socioeconomic status was not an effective marker of individual pharmacologic treatment response; (3) telehealth enabled scaling of care, but more work is needed to understand how to leverage telehealth to improve outcomes in marginalized communities; (4) future interventions must explicitly target societal drivers of disparity, rather than focusing on individual behavior alone; and (5) individual interventions will only be maximally effective when specifically tailored to local needs. Much work has been done to catalog health disparities in pulmonary disease. Notable gaps in the identified literature include few interventional trials, the need for research in diseases outside of asthma, the need for high quality effectiveness trials, and an understanding of how to implement proven interventions balancing fidelity to the original protocol and the need to adapt to local barriers to care.

Breaking Through Barriers: Factors That Influence Behavior Change Toward Leadership for Women in Academic Medicine.

Under-representation of women in leadership at Academic Medical Centers (AMCs) is a known challenge such that, in 2021, women made up only 28% of department chairs. AMCs are addressing the dearth of women leaders through targeted programming to create leadership pipelines of qualified women. The FLEX Leadership Development Program at the Case Western Reserve University (CWRU) School of Medicine prepares women faculty for increased leadership opportunities. FLEX includes the opportunity to leverage executive coaching to accomplish individual goals. The FLEX program has the explicit goal of increasing the number of women in visible leadership positions in academic medicine and health sciences. Semi-structured interviews were conducted with 25 graduates from seven FLEX cohorts (2012-2018). Participants reflected diversity in academic rank, terminal degree, racial/ethnic background, years of employment, and institutional affiliation. Interviews consisted of eight questions with additional probes to elicit lived experiences. Analysis consisted of two-stage open- and axial-coding of interview transcripts to understand: What factors facilitated behavior change following FLEX training? The analysis revealed five overarching themes: (1) Communication skills; (2) Self-Efficacy; (3) Networking; (4) Situational Awareness; and (5) Visioning. FLEX graduates reported achieving both personal and professional growth by drawing upon peer networks to proactively seek new leadership opportunities. These results suggest that the enduring benefits of the FLEX Program include improved communication skills, expanded situational awareness and relational capacity, greater self-efficacy and self-confidence, improved networking with an understanding of the value of networking. All these factors led FLEX graduates to have greater visibility and to engage with their colleagues more effectively. Similarly, FLEX graduates could better advocate for themselves and for others as well as paying it forward to mentor and train the next generation of faculty. Finally, participants learned to re-evaluate their goals and their career vision to be able to envision themselves in greater leadership roles. The five factors that strongly influenced behavior change provide valuable constructs for other programs to examine following leadership development training. Ongoing studies include examining successful leadership position attainment, personal goal attainment, and measuring changes in leadership self-efficacy.

Dietary patterns in patients with asthma and their relationship with asthma-related emergency room visits: NHANES 2005-2016.

RATIONALE: Extensive interdependencies exist between dietary intake, metabolic dysregulation, and asthma; however, the dietary pattern in adults with asthma remains unknown. OBJECTIVES: To evaluate the association between dietary patterns and asthma ER visits and explore the effect of the interaction between race and diet on asthma. METHODS: Using NHANES data, we compared dietary patterns between adults with asthma with and without asthma-related emergency room (ER) visits in the previous year, and between subjects of different races. The 2015 Healthy Eating Index (HEI-2015) was used to assess alignment between dietary patterns and the 2015-2020 Dietary Guideline for Americans. RESULTS: Among 1681 individuals included in the study, 193 reported asthma-related ER visit. Patients with asthma had low fruit and vegetable intake, and a low mean (SE) HEI-2015 score [52.6 (0.53)]. Individuals with asthma-related ER visits had lower vegetable consumption compared to those without (median 0.61 vs. 0.85 cup equivalents). Furthermore, non-Hispanic Blacks (NHB) reported lower amount of vegetable (median cup equivalent 0.58 vs. 0.89) and fruit intake (0.17 vs. 0.39) and had a lower HEI-2015 score (49.9 vs. 52.9) comparing to non-Hispanic Whites. No association was discovered between dietary patterns and ER visits in multivariable analysis, or significant interactions between diet and race in predicting the need for ER visits. CONCLUSIONS: Dietary patterns in adult with current asthma are frequently misaligned with current dietary guidelines. Patients with asthma-related ER visits and of NHB race had lower vegetable consumption; however, the associations disappeared in multivariable analysis. The impact of diet on asthma is not straightforward and deserves further investigation.Supplemental data for this article is available online at at www.tandfonline.com/ijas.

An Examination of the Intersection of Climate Change, the Physician Specialty Workforce, and Graduate Medical Education in the U.S.

Issue: As U.S. healthcare systems plan for future physician workforce needs, the systemic impacts of climate change, a worldwide environmental and health crisis, have not been factored in. The current focus on increasing the number of trained physicians and optimizing efficiencies in healthcare delivery may be insufficient. Graduate medical education (GME) priorities and training should be considered in order to prepare a climate-educated physician workforce. Evidence: We used a holistic lens to explore the available literature regarding the intersection of future physician workforce needs, GME program priorities, and resident education within the larger context of climate change. Our interinstitutional, transdisciplinary team brought perspectives from their own fields, including climate science, climate and health research, and medical education to provide recommendations for building a climate-educated physician workforce. Implications: Acknowledging and preparing for the effects of climate change on the physician workforce will require identification of workforce gaps, changes to GME program priorities, and education of trainees on the health and societal impacts of climate change. Alignment of GME training with workforce considerations and climate action and adaptation initiatives will be critical in ensuring the U.S. has a climate-educated physician workforce capable of addressing health and healthcare system challenges. This article offers a number of recommendations for physician workforce priorities, resident education, and system-level changes to better prepare for the health and health system impacts of climate change.

Bronchial Thermoplasty in Patients With Severe Asthma at 5 Years: The Post-FDA Approval Clinical Trial Evaluating Bronchial Thermoplasty in Severe Persistent Asthma Study.

BACKGROUND: Bronchial thermoplasty is a device-based treatment for subjects ≥ 18 years of age with severe asthma poorly controlled with inhaled corticosteroids and long-acting beta-agonists. The Post-FDA Approval Clinical Trial Evaluating Bronchial Thermoplasty in Severe Persistent Asthma (PAS2) study collected data on patients with severe asthma undergoing this procedure. RESEARCH QUESTION: What are the 5-year efficacy and safety results in patients with severe asthma who have undergone bronchial thermoplasty? STUDY DESIGN AND METHODS: This was a prospective, open-label, observational, multicenter study conducted in the United States and Canada. Subjects 18 to 65 years of age who were taking inhaled corticosteroids ≥ 1,000 µg/d (beclomethasone or equivalent) and long-acting beta-agonists ≥ 80 µg/d (salmeterol or equivalent) were included. Severe exacerbations, hospitalization, ED visits, and medication usage were evaluated for the 12 months prior to and at years 1 through 5 posttreatment. Spirometry was evaluated at baseline and at years 1 through 5 posttreatment. RESULTS: A total of 284 subjects were enrolled at 27 centers; 227 subjects (80%) completed 5 years of follow-up. By year 5 posttreatment, the proportion of subjects with severe exacerbations, ED visits, and hospitalizations was 42.7%, 7.9%, and 4.8%, respectively, compared with 77.8%, 29.4%, and 16.1% in the 12 months prior to treatment. The proportion of subjects on maintenance oral corticosteroids decreased from 19.4% at baseline to 9.7% at 5 years. Analyses of subgroups based on baseline clinical and biomarker characteristics revealed a statistically significant clinical improvement among all subgroups. INTERPRETATION: Five years after treatment, subjects experienced decreases in severe exacerbations, hospitalizations, ED visits, and corticosteroid exposure. All subgroups demonstrated clinically significant improvement, suggesting that bronchial thermoplasty improves asthma control in different asthma phenotypes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT01350336; URL: www. CLINICALTRIALS: gov.

Use of Fractional Exhaled Nitric Oxide to Guide the Treatment of Asthma: An Official American Thoracic Society Clinical Practice Guideline.

Background: The fractional exhaled nitric oxide (FENO) test is a point-of-care test that is used in the assessment of asthma. Objective: To provide evidence-based clinical guidance on whether FENO testing is indicated to optimize asthma treatment in patients with asthma in whom treatment is being considered. Methods: An international, multidisciplinary panel of experts was convened to form a consensus document regarding a single question relevant to the use of FENO. The question was selected from three potential questions based on the greatest perceived impact on clinical practice and the unmet need for evidence-based answers related to this question. The panel performed systematic reviews of published randomized controlled trials between 2004 and 2019 and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence-to-decision framework to develop recommendations. All panel members evaluated and approved the recommendations. Main Results: After considering the overall low quality of the evidence, the panel made a conditional recommendation for FENO-based care. In patients with asthma in whom treatment is being considered, we suggest that FENO is beneficial and should be used in addition to usual care. This judgment is based on a balance of effects that probably favors the intervention; the moderate costs and availability of resources, which probably favors the intervention; and the perceived acceptability and feasibility of the intervention in daily practice. Conclusions: Clinicians should consider this recommendation to measure FENO in patients with asthma in whom treatment is being considered based on current best available evidence.

Associations of Air Pollution and Pediatric Asthma in Cleveland, Ohio.

Air pollution has been associated with poor health outcomes and continues to be a risk factor for respiratory health in children. While higher particulate matter (PM) levels are associated with increased frequency of symptoms, lower lung function, and increase airway inflammation from asthma, the precise composition of the particles that are more highly associated with poor health outcomes or healthcare utilization are not fully elucidated. PM is measured quantifiably by current air pollution monitoring systems. To better determine sources of PM and speciation of such sources, a particulate matter (PM) source apportionment study, the Cleveland Multiple Air Pollutant Study (CMAPS), was conducted in Cleveland, Ohio, in 2009-2010, which allowed more refined assessment of associations with health outcomes. This article presents an evaluation of short-term (daily) and long-term associations between motor vehicle and industrial air pollution components and pediatric asthma emergency department (ED) visits by evaluating two sets of air quality data with healthcare utilization for pediatric asthma. Exposure estimates were developed using land use regression models for long-term exposures for nitrogen dioxide (NO2) and coarse (i.e., with aerodynamic diameters between 2.5 and 10 µm) particulate matter (PM) and the US EPA Positive Matrix Factorization receptor model for short-term exposures to fine (<2.5 µm) and coarse PM components. Exposure metrics from these two approaches were used in asthma ED visit prevalence and time series analyses to investigate seasonal-averaged short- and long-term impacts of both motor vehicles and industry emissions. Increased pediatric asthma ED visits were found for LUR coarse PM and NO2 estimates, which were primarily contributed by motor vehicles. Consistent, statistically significant associations with pediatric asthma visits were observed, with short-term exposures to components of fine and coarse iron PM associated with steel production. Our study is the first to combine spatial and time series analysis of ED visits for asthma using the same periods and shows that PM related to motor vehicle emissions and iron/steel production are associated with increased pediatric asthma visits.

The asthma evidence base: a call for core outcomes in interventional trials.

OBJECTIVES: Biologic therapies are emerging as an option to treat a subset of patients with severe asthma, however no direct comparison between these agents has been conducted. Furthermore, heterogeneity of outcomes in clinical trials makes it difficult to compare these agents and traditional therapies. The extent to which this heterogeneity exists has major implications for evidence-based decisions and is yet to be fully reported. We conducted a literature search to examine outcomes currently being used in clinical trials for asthma. DATA SOURCES: The Cochrane Library and Clinicaltrials.gov were searched for clinical trials of asthma interventions. STUDY SELECTIONS: We limited our search to phase 2 through 4 clinical trials in adults, as early-phase trials tend to have pharmacodynamic and pharmacokinetic endpoints as primary outcomes. Interventions for acute exacerbations were excluded. RESULTS: We identified 117 studies and subsequently identified 111 outcomes. The most prevalent outcomes were asthma control and symptom severity, FEV1, and change in ACQ scale. Twenty patient-reported outcomes instruments were identified and de-facto standard asthma outcomes and PROs were under-reported in examined literature. Existing quality of life tools did not capture the day-to-day experience or the unique treatment burden from oral corticosteroids for patient with severe asthma. Compounding the absence of trials directly comparing therapies, the significant variation we identified in outcome definitions and measurement create hurdles to effectively compare traditional and biologic therapies. CONCLUSION: With the growing number of clinical trials evaluating advanced therapies such as biologics, a wide range of primary and secondary outcomes are evaluated. A core outcome set created by relevant stakeholders is needed to collectively evaluate pooled outcomes in order to allow more meaningful comparisons of asthma therapies and to incorporate the patient experience.

Diabetes Mellitus Is Associated with Worse Outcome in Patients Hospitalized for Asthma.

BACKGROUND: Asthma is a prevalent disease with a high economic cost. More than 50% of its direct cost relates to asthma hospitalizations. Diabetes mellitus (DM) is a significant comorbidity in asthmatic patients, yet its impact on asthma-related hospitalizations is unknown. OBJECTIVE: To compare the outcome of asthma-related hospitalizations in patients with and without DM. METHODS: Using Healthcare Cost and Utilization Project Nationwide Readmissions Database, we analyzed data of all adults with index admission for asthma and with no other chronic pulmonary conditions, and compared outcomes between patients with and without DM. Weighted regression analysis was used to determine the impact of DM on hospitalization outcomes. All multivariate regression models were adjusted for patient demographics, socioeconomic status, and chronic medical comorbidities. RESULTS: A total of 717,200 asthmatic patients were included, with 202,489 (28.3%) having DM. Diabetic patients were older and had more comorbidities. When hospitalized for asthma, diabetic patients had increased hospital length of stay, cost, and risk for 30-day all-cause and asthma-related readmission. They also had a higher risk for developing nonrespiratory complications during their hospital stay compared with nondiabetic patients. The risk of mortality was similar between the 2 groups. CONCLUSIONS: Patients hospitalized for asthma with coexisting DM had increased hospital length of stay, cost, and risk for readmission. Interventions are urgently needed to reduce the risk for hospital admission and readmission in patients with coexisting DM and asthma. These interventions would have profound economic and societal impact.

The Exposome and Asthma.

This article on exposome and asthma focuses on the interaction of patients and their environments in various parts of their growth, development, and stages of life. Indoor and outdoor environments play a role in pathogenesis via levels and duration of exposure, with genetic susceptibility as a crucial factor that alters the initiation and trajectory of common conditions such as asthma. Knowledge of environmental exposures globally and changes that are occurring is necessary to function effectively as medical professionals and health advocates.

The intersection of obstructive lung disease and sleep apnea.

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) have synergistic detrimental effects. Their comorbid association leads to compromised gas exchange (hypoxia and hypercapnia) and higher rates of morbidity and death. As our understanding of the pathophysiologic processes of sleep evolves, the relationship between OSA and obstructive lung diseases such as COPD ("overlap syndrome") or asthma ("alternative overlap syndrome") has become more apparent. The pathophysiology of the combined conditions and optimal management are still being defined, but the effect on quality of life and morbidity underscore the importance of proper diagnosis and appropriately tailored management in these patients.

Systemic antioxidants and lung function in asthmatics during high ozone season: a closer look at albumin, glutathione, and associations with lung function.

BACKGROUND: Asthma is a chronic airway inflammatory disease with episodic symptoms of wheezing, chest tightness, cough, and shortness of breath. High ambient ozone levels have been associated with increased airway inflammation and asthma morbidity in prior studies. Mechanisms underlying individual susceptibility to asthma exacerbations from poor air quality are not fully understood. OBJECTIVE: As part of a panel observational study, we hypothesized that systemic antioxidant ability and antioxidant status may be associated with more stable asthma during high ozone season. METHODS: A cross sectional study was performed to evaluate the antioxidant profile in systemic circulation and its associations with clinical parameters in asthmatics and healthy controls during three summers in Atlanta, Georgia. RESULTS: In this panel of individuals with and without asthma, we found that although systemic glutathione levels were not different between the groups, serum albumin was significantly lower in the asthmatic group. Albumin also significantly correlated with lung function (%FEV(1)) and asthma quality of life scores. In a subgroup tested, plasma reduced glutathione (GSH) levels were associated with worse airways obstruction. CONCLUSION: Antioxidants GSH and albumin may have a role in maintaining lung function and asthma stability during times of poor ambient air quality.

Bronchial thermoplasty: a new treatment for severe refractory asthma.

Bronchial thermoplasty was recently approved for treating severe refractory asthma that is not well controlled by high-dose inhaled corticosteroids and long-acting bronchodilator therapy. This article reviews its indications, evidence of efficacy, and protocols.

Association of ambient ozone exposure with airway inflammation and allergy in adults with asthma.

RATIONALE: Previous studies have demonstrated associations of high ozone levels with increased epidemiologic as well as lung function measures of asthma activity. OBJECTIVES: In an observational study during the summer months, we hypothesized that higher ambient ozone levels are associated with more frequent symptoms, higher airway and systemic inflammation, as well as worse lung function in asthmatics as compared with non-asthmatic individuals. METHODS: Thirty-eight asthmatics and thirteen healthy control subjects residing in metropolitan Atlanta were enrolled during peak ozone season. Medical histories, quality-of-life questionnaires, spirometry, serum immunoglobulin (IgE), peripheral eosinophil counts, and exhaled nitric oxide (NO) were obtained during study visits. Personal ozone exposures over the 2 days before presentation were estimated based on location and activity surveys. MAIN RESULTS: Upper airway symptoms were more frequent in asthmatics. Higher levels of ozone were associated with worse airflow obstruction, lower quality of life scores, greater eosinophilia, and higher exhaled NO levels in asthmatics. Finally, both asthmatics and non-asthmatics with allergies showed associations between air quality and airway inflammation. CONCLUSIONS: In adults with asthma but not controls studied during peak ozone season, increasing ozone exposure predicted lower lung function and increased biomarkers of respiratory and systemic inflammation. These associations were enhanced in atopic participants, both with and without asthma. Importantly, the study findings were noted while atmospheric ozone levels were predominantly within the current and revised national air quality standards.

Noninvasive markers of airway inflammation in asthma.

BACKGROUND: Although airway inflammation plays a major role in the pathophysiology of asthma, quantitative markers of airway inflammation are limited in clinical practice. OBJECTIVE: To determine if levels of noninvasive markers of eosinophil-catalyzed oxidation, lipid peroxidation, and nitric oxide production are associated with asthma. METHODS: Participants were enrolled from academic medical centers participating in the Severe Asthma Research Program. Clinical characteristics, laboratory data, pulmonary function tests, and levels of the following noninvasive markers were obtained: urinary bromotyrosine, a marker of eosinophil-catalyzed oxidation; urinary F(2)-isoprostanes, markers of lipid peroxidation; and exhaled nitric oxide, a marker of airway inflammation RESULTS: Fifty-seven asthmatic participants and thirty-eight healthy participants were enrolled. Bromotyrosine, F(2)-isoprostanes, and exhaled nitric oxide were each significantly increased in asthmatic participants versus controls (p<0.01). An elevated level (greater than median) of any marker was associated with a significant 3- to 6-fold greater odds of having asthma. Participants with two or more elevated marker levels showed an 18-fold greater odds of having asthma. Relationships were also noted with airflow obstruction and bronchodilator response. CONCLUSION: Findings from this pilot study indicate that urinary levels of bromotyrosine and F(2)-isoprostanes, in addition to exhaled nitric oxide levels, are associated with asthma.

Alterations of the arginine metabolome in asthma.

RATIONALE: As the sole nitrogen donor in nitric oxide (NO) synthesis and key intermediate in the urea cycle, arginine and its metabolic pathways are integrally linked to cellular respiration, metabolism, and inflammation. OBJECTIVES: We hypothesized that arginine (Arg) bioavailability would be associated with airflow abnormalities and inflammation in subjects with asthma, and would be informative for asthma severity. METHODS: Arg bioavailability was assessed in subjects with severe and nonsevere asthma and healthy control subjects by determination of plasma Arg relative to its metabolic products, ornithine and citrulline, and relative to methylarginine inhibitors of NO synthases, and by serum arginase activity. Inflammatory parameters, including fraction of exhaled NO (Fe(NO)), IgE, skin test positivity to allergens, bronchoalveolar lavage, and blood eosinophils, were also evaluated. MEASUREMENTS AND MAIN RESULTS: Subjects with asthma had greater Arg bioavailability, but also increased Arg catabolism compared with healthy control subjects, as evidenced by higher levels of Fe(NO) and serum arginase activity. However, Arg bioavailability was positively associated with Fe(NO) only in healthy control subjects; Arg bioavailability was unrelated to Fe(NO) or other inflammatory parameters in severe or nonsevere asthma. Inflammatory parameters were related to airflow obstruction and reactivity in nonsevere asthma, but not in severe asthma. Conversely, Arg bioavailability was related to airflow obstruction in severe asthma, but not in nonsevere asthma. Modeling confirmed that measures of Arg bioavailabilty predict airflow obstruction only in severe asthma. CONCLUSIONS: Unlike Fe(NO), Arg bioavailability is not a surrogate measure of inflammation; however, Arg bioavailability is strongly associated with airflow abnormalities in severe asthma.