The Impact of Insulin Resistance on Loss of Lung Function and Response to Treatment in Asthma.

Rationale: The role of obesity-associated insulin resistance (IR) in airflow limitation in asthma is uncertain. Objectives: Using data in the Severe Asthma Research Program 3 (SARP-3), we evaluated relationships between homeostatic measure of IR (HOMA-IR), lung function (cross-sectional and longitudinal analyses), and treatment responses to bronchodilators and corticosteroids. Methods: HOMA-IR values were categorized as without (<3.0), moderate (3.0-5.0), or severe (>5.0). Lung function included FEV1 and FVC measured before and after treatment with inhaled albuterol and intramuscular triamcinolone acetonide and yearly for 5 years. Measurements and Main Results: Among 307 participants in SARP-3, 170 (55%) were obese and 140 (46%) had IR. Compared with patients without IR, those with IR had significantly lower values for FEV1 and FVC, and these lower values were not attributable to obesity effects. Compared with patients without IR, those with IR had lower FEV1 responses to ß-adrenergic agonists and systemic corticosteroids. The annualized decline in FEV1 was significantly greater in patients with moderate IR (-41 ml/year) and severe IR (-32 ml/year,) than in patients without IR (-13 ml/year, P < 0.001 for both comparisons). Conclusions: IR is common in asthma and is associated with lower lung function, accelerated loss of lung function, and suboptimal lung function responses to bronchodilator and corticosteroid treatments. Clinical trials in patients with asthma and IR are needed to determine if improving IR might also improve lung function.

Epidemiology of Asthma: Prevalence and Burden of Disease.

Asthma, a common airway disease, results in a significant burden to both patients and society worldwide. Yet, despite global political commitment backed by the United Nations, progress to reduce the burden of asthma remains inadequate. This is particularly true in low-income countries. To date, progress has been delayed by the lack of uniform data collection, imperfect surveillance methods, inadequate resources, poor access to effective therapies, substandard asthma education, ineffective governmental policies, rapid urbanization, progressive increase in asthma prevalence, increased life expectancy and obesity rates worldwide, asthma heterogeneity and disease complexity, smoking, and environmental exposures to allergens and pollution. A thorough understanding of the challenges facing the international community is essential to define future strategies to improve the burden of asthma.

Urinary total conjugated 3-bromotyrosine, asthma severity, and exacerbation risk.

Asthma is an inflammatory disease of the airways characterized by eosinophil recruitment, eosinophil peroxidase release, and protein oxidation through bromination, which following tissue remodeling results in excretion of 3-bromotyrosine. Predicting exacerbations and reducing their frequency is critical for the treatment of severe asthma. In this study, we aimed to investigate whether urinary total conjugated bromotyrosine can discriminate asthma severity and predict asthma exacerbations. We collected urine from participants with severe (n = 253) and nonsevere (n = 178) asthma, and the number of adjudicated exacerbations in 1-yr longitudinal follow-up was determined among subjects enrolled in the Severe Asthma Research Program, a large-scale National Institutes of Health (NIH)-funded consortium. Urine glucuronidated bromotyrosine and total conjugated forms were quantified by hydrolysis with either glucuronidase or methanesulfonic acid, respectively, followed by liquid chromatography-tandem mass spectrometry analyses of free 3-bromotyrosine. Blood and sputum eosinophils were also counted. The majority of 3-bromotyrosine in urine was found to exist in conjugated forms, with glucuronidated bromotyrosine representing approximately a third, and free bromotyrosine less than 1% of total conjugated bromotyrosine. Total conjugated bromotyrosine was poorly correlated with blood (r2 = 0.038) or sputum eosinophils (r2 = 0.0069). Compared with participants with nonsevere asthma, participants with severe asthma had significantly higher urinary total conjugated bromotyrosine levels. Urinary total conjugated bromotyrosine was independently associated with asthma severity, correlated with the number of asthma exacerbations, and served as a predictor of asthma exacerbation risk over 1-yr of follow-up.

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.

Benefits of Airway Androgen Receptor Expression in Human Asthma.

Rationale: Androgens are potentially beneficial in asthma, but AR (androgen receptor) has not been studied in human airways.Objectives: To measure whether AR and its ligands are associated with human asthma outcomes.Methods: We compared the effects of AR expression on lung function, symptom scores, and fractional exhaled nitric oxide (FeNO) in adults enrolled in SARP (Severe Asthma Research Program). The impact of sex and of androgens on asthma outcomes was also evaluated in the SARP with validation studies in the Cleveland Clinic Health System and the NHANES (U.S. National Health and Nutrition Examination Survey).Measurements and Main Results: In SARP (n = 128), AR gene expression from bronchoscopic epithelial brushings was positively associated with both FEV1/FVC ratio (R2 = 0.135, P = 0.0002) and the total Asthma Quality of Life Questionnaire score (R2 = 0.056, P = 0.016) and was negatively associated with FeNO (R2 = 0.178, P = 9.8 × 10-6) and NOS2 (nitric oxide synthase gene) expression (R2 = 0.281, P = 1.2 × 10-10). In SARP (n = 1,659), the Cleveland Clinic Health System (n = 32,527), and the NHANES (n = 2,629), women had more asthma exacerbations and emergency department visits than men. The levels of the AR ligand precursor dehydroepiandrosterone sulfate correlated positively with the FEV1 in both women and men.Conclusions: Higher bronchial AR expression and higher androgen levels are associated with better lung function, fewer symptoms, and a lower FeNO in human asthma. The role of androgens should be considered in asthma management.

Muscle loss contributes to higher morbidity and mortality in COPD: An analysis of national trends.

BACKGROUND AND OBJECTIVE: COPD is the third most common cause of death worldwide and fourth most common in the United States. In hospitalized patients with COPD, mortality, morbidity and healthcare resource utilization are high. Skeletal muscle loss is frequent in patients with COPD. However, the impact of muscle loss on adverse outcomes has not been systematically evaluated. We tested the hypothesis that patients hospitalized for COPD exacerbation with, compared to those without, a secondary diagnosis of muscle loss phenotype (all ICD-9 codes associated with muscle loss including cachexia) will have higher mortality and cost of care. METHODS: The NIS database of hospitalized patients in 2011 (1 January-31 December) in the United States was used. The impact of a muscle loss phenotype on in-hospital mortality, LOS and cost of care for each of the 174 808 hospitalizations for COPD exacerbations was analysed. RESULTS: Of the subjects admitted for a COPD exacerbation, 12 977 (7.4%) had a secondary diagnosis of muscle loss phenotype. A diagnosis of muscle loss phenotype was associated with significantly higher in-hospital mortality (14.6% vs 5.7%, P < 0.001), LOS (13.3 + 17.1 vs 5.7 + 7.6, P < 0.001) and median hospital charge per patient ($13 947 vs $6610, P < 0.001). Multivariate regression analysis showed that muscle loss phenotype increased mortality by 111% (95% CI: 2.0-2.2, P < 0.001), LOS by 68.4% (P < 0.001) and the direct cost of care by 83.7% (P < 0.001) compared to those without muscle loss. CONCLUSION: In-hospital mortality, LOS and healthcare costs are higher in patients with COPD exacerbations and a muscle loss phenotype.

Cost effectiveness of bronchial thermoplasty in patients with severe uncontrolled asthma.

RATIONALE: Based on its clinical effectiveness, bronchial thermoplasty (BT) was approved by the Food and Drug Administration in 2010 for the treatment of severe persistent asthma in patients 18 years and older whose asthma is not well-controlled with inhaled corticosteroids and long-acting beta-agonist medicines. OBJECTIVE: Assess the 10 year cost-effectiveness of BT for individuals with severe uncontrolled asthma. METHODS: Using a Markov decision analytic model, the cost-effectiveness of BT was estimated. The patient population involved a hypothetical cohort of 41-year-old patients comparing BT to usual care over a 10-year time frame. The main outcome measure was cost in 2013 dollars per additional quality adjusted life year (QALY). RESULTS: Treatment with BT resulted in 6.40 QALYs and $7512 in cost compared to 6.21 QALYs and $2054 for usual care. The incremental cost-effectiveness ratio for BT at 10 years was $29,821/QALY. At a willingness to pay per QALY of $50,000, BT continues to be cost effective unless the probability of severe asthma exacerbation drops below 0.63 exacerbation per year or the cost of BT rises above $10,384 total for all three bronchoscopic procedures needed to perform thermoplasty and to cover the entire bronchial tree (baseline = $6690). CONCLUSIONS: BT is a cost-effective treatment for asthmatics at high risk of exacerbations. Continuing to follow asthmatics treated with BT beyond 5 years will help inform longer efficacy and support its cost-effectiveness.

Asthma is Different in Women.

Gender differences in asthma incidence, prevalence and severity have been reported worldwide. After puberty, asthma becomes more prevalent and severe in women, and is highest in women with early menarche or with multiple gestations, suggesting a role for sex hormones in asthma genesis. However, the impact of sex hormones on the pathophysiology of asthma is confounded by and difficult to differentiate from age, obesity, atopy, and other gender associated environmental exposures. There are also gender discrepancies in the perception of asthma symptoms. Understanding gender differences in asthma is important to provide effective education and personalized management plans for asthmatics across the lifecourse.

Nocturnal Hypoxemia Is Associated with Sarcopenia in COPD Patients.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. Our previous studies have identified that nocturnal hypoxemia causes skeletal muscle loss (i.e. sarcopenia) in in vitro models of COPD. RATIONALE: We aimed to extend our preclinical mechanistic findings by analyzing a large sleep registry to determine whether nocturnal hypoxemia is associated with sarcopenia in COPD patients. METHODS: Sleep studies from COPD patients (n=479) and control subjects without COPD (n=275) were analyzed. Patients with obstructive sleep apnea (OSA), as defined by apnea hypopnea index >5, were excluded. Pectoralis muscle cross sectional area (PMcsa) was quantified using CT scans performed within one year of the sleep study. We defined sarcopenia as less than the lowest 20% residuals for PMcsa of controls, which was adjusted for age, BMI, and stratified by sex. Youden's optimal cutpoint criteria was used to predict sarcopenia based on mean oxygen saturation (mean SaO2) during sleep. Additional measures of nocturnal hypoxemia were analyzed. Pectoralis muscle index (PMI) was defined as PMcsa normalized to BMI. RESULTS: On average, COPD males had 16.6% lower PMI than control males (1.41+0.44 vs 1.69+0.56 cm2/BMI, p<0.001), while COPD females had 9.4% lower PMI than control females (0.96+0.27 vs 1.06+0.33 cm2/BMI, p<0.001). COPD males with nocturnal hypoxemia had a 9.5% decrease in PMI versus COPD with normal O2 (1.33+0.39 vs 1.47+0.46 cm2/BMI, p<0.05), and 23.6% decrease compared to controls (1.33+0.39 vs 1.74+0.56 cm2/BMI, p<0.001). COPD females with nocturnal hypoxemia had a 11.2% decrease versus COPD with normal O2 (0.87+0.26 vs 0.98+0.28 cm2/BMI, p<0.05), and 17.9% decrease compared to controls (0.87+0.26 vs 1.06+0.33 cm2/BMI, p<0.001). These findings were largely replicated using multiple measures of nocturnal hypoxemia. CONCLUSIONS: We defined sarcopenia in the pectoralis muscle using residuals that take into account age, BMI, and sex. We found that COPD patients have lower PMI than non-COPD patients, and that nocturnal hypoxemia was associated with an additional decrease in the PMI of COPD patients. Additional prospective analyses are needed to determine a protective threshold of oxygen saturation to prevent or reverse sarcopenia due to nocturnal hypoxemia in COPD.

Novel Machine Learning Identifies 5 Asthma Phenotypes Using Cluster Analysis of Real-World Data.

BACKGROUND: Asthma classification into different subphenotypes is important to guide personalized therapy and improve outcomes. OBJECTIVES: To further explore asthma heterogeneity through determination of multiple patient groups by using novel machine learning (ML) approaches and large-scale real-world data. METHODS: We used electronic health records of patients with asthma followed at the Cleveland Clinic between 2010 and 2021. We used k-prototype unsupervised ML to develop a clustering model where predictors were age, sex, race, body mass index, prebronchodilator and postbronchodilator spirometry measurements, and the usage of inhaled/systemic steroids. We applied elbow and silhouette plots to select the optimal number of clusters. These clusters were then evaluated through LightGBM's supervised ML approach on their cross-validated F1 score to support their distinctiveness. RESULTS: Data from 13,498 patients with asthma with available postbronchodilator spirometry measurements were extracted to identify 5 stable clusters. Cluster 1 included a young nonsevere asthma population with normal lung function and higher frequency of acute exacerbation (0.8 /patient-year). Cluster 2 had the highest body mass index (mean ± SD, 44.44 ± 7.83 kg/m2), and the highest proportion of females (77.5%) and Blacks (28.9%). Cluster 3 comprised patients with normal lung function. Cluster 4 included patients with lower percent of predicted FEV1 of 77.03 (12.79) and poor response to bronchodilators. Cluster 5 had the lowest percent of predicted FEV1 of 68.08 (15.02), the highest postbronchodilator reversibility, and the highest proportion of severe asthma (44.9%) and blood eosinophilia (>300 cells/µL) (34.8%). CONCLUSIONS: Using real-world data and unsupervised ML, we classified asthma into 5 clinically important subphenotypes where group-specific asthma treatment and management strategies can be designed and deployed.

Defining and Promoting Pediatric Pulmonary Health: Developing Biomarkers for Pulmonary Health.

Children with inherited and/or acquired respiratory disorders often arrive in adolescence and adulthood with diminished lung function that might have been detected and prevented had better mechanisms been available to identify and to assess progression of disease. Fortunately, advances in genetic assessments, low-cost diagnostics, and minimally- invasive novel biomarkers are being developed to detect and to treat respiratory diseases before they give rise to loss of life or lung function. This paper summarizes the Developing Biomarkers for Pulmonary Health sessions of the National Heart, Lung, and Blood Institute- sponsored 2021 Defining and Promoting Pediatric Pulmonary Health workshop. These sessions discussed genetic testing, pulse oximetry, exhaled nitric oxide, and novel biomarkers related to childhood lung diseases.

Mitochondrial DNA Copy Number Variation in Asthma Risk, Severity, and Exacerbations.

Rationale: Although airway oxidative stress and inflammation are central to asthma pathogenesis, there is limited knowledge of the relationship of asthma risk, severity, or exacerbations to mitochondrial dysfunction, which is pivotal to oxidant generation and inflammation. Objectives: We investigated whether mitochondrial DNA copy number (mtDNA-CN) as a measure of mitochondrial function is associated with asthma diagnosis, severity, oxidative stress, and exacerbations. Methods: We measured mtDNA-CN in blood in two cohorts. In the UK Biobank (UKB), we compared mtDNA-CN in mild and moderate-severe asthmatics to non-asthmatics. In the Severe Asthma Research Program (SARP), we evaluated mtDNA-CN in relation to asthma severity, biomarkers of oxidative stress and inflammation, and exacerbations. Measures and Main Results: In UK Biobank, asthmatics (n = 29,768) have lower mtDNA-CN compared to non-asthmatics (n = 239,158) (beta, -0.026 [95% CI, -0.038 to -0.014], P = 2.46×10-5). While lower mtDNA-CN is associated with asthma, mtDNA-CN did not differ by asthma severity in either UKB or SARP. Biomarkers of inflammation show that asthmatics have higher white blood cells (WBC), neutrophils, eosinophils, fraction exhaled nitric oxide (FENO), and lower superoxide dismutase (SOD) than non-asthmatics, confirming greater oxidative stress in asthma. In one year follow-up in SARP, higher mtDNA-CN is associated with reduced risk of three or more exacerbations in the subsequent year (OR 0.352 [95% CI, 0.164 to 0.753], P = 0.007). Conclusions: Asthma is characterized by mitochondrial dysfunction. Higher mtDNA-CN identifies an exacerbation-resistant asthma phenotype, suggesting mitochondrial function is important in exacerbation risk.

Impact of Bronchiectasis on COPD Severity and Alpha-1 Antitrypsin Deficiency as a Risk Factor in Individuals with a Heavy Smoking History.

Rationale: Bronchiectasis is common among those with heavy smoking histories, but risk factors for bronchiectasis, including alpha-1 antitrypsin deficiency, and its implications for COPD severity are uncharacterized in such individuals. Objectives: To characterize the impact of bronchiectasis on COPD and explore alpha-1antitrypsin as a risk factor for bronchiectasis. Methods: SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) participants (N=914; ages 40-80 years; ≥20-pack-year smoking) had high-resolution computed tomography (CT) scans interpreted visually for bronchiectasis, based on airway dilation without fibrosis or cicatrization. We performed regression-based models of bronchiectasis with clinical outcomes and quantitative CT measures. We deeply sequenced the gene encoding -alpha-1 antitrypsin, SERPINA1, in 835 participants to test for rare variants, focusing on the PiZ genotype (Glu366Lys, rs28929474). Measurements and Main Results: We identified bronchiectasis in 365 (40%) participants, more frequently in women (45% versus 36%, p=0.0045), older participants (mean age=66[standard deviation (SD)=8.3] versus 64[SD=9.1] years, p=0.0083), and those with lower lung function (forced expiratory volume in 1 second [FEV1 ] percentage predicted=66%[SD=27] versus 77%[SD=25], p<0.0001; FEV1 to forced vital capacity [FVC] ratio=0.54[0.17] versus 0.63[SD=0.16], p<0.0001). Participants with bronchiectasis had greater emphysema (%voxels ≤-950 Hounsfield units, 11%[SD=12] versus 6.3%[SD=9], p<0.0001) and parametric response mapping functional small airways disease (26[SD=15] versus 19[SD=15], p<0.0001). Bronchiectasis was more frequent in the combined PiZZ and PiMZ genotype groups compared to those without PiZ, PiS, or other rare pathogenic variants (N=21 of 40 [52%] versus N=283 of 707[40%], odds ratio [OR]=1.97; 95% confidence interval [CI]=1.002, 3.90, p=0.049), an association attributed to White individuals (OR=1.98; 95%CI = 0.9956, 3.9; p=0.051). Conclusions: Bronchiectasis was common in those with heavy smoking histories and was associated with detrimental clinical and radiographic outcomes. Our findings support alpha-1antitrypsin guideline recommendations to screen for alpha-1 antitrypsin deficiency in an appropriate bronchiectasis subgroup with a significant smoking history.

Diabetes associated with higher health care utilization and poor outcomes after COPD-related hospitalizations.

OBJECTIVES: Readmissions after hospitalizations for acute exacerbation of chronic obstructive pulmonary disease (COPD) have a high socioeconomic burden. Comorbidities such as diabetes increase the risk for hospital readmissions, but the impact of diabetes on hospital outcomes remains unknown. The aim of this study was to evaluate the effect of complicated or uncomplicated diabetes on outcomes and health care costs related to admissions and readmissions in patients 35 years and older with an index admission for COPD. STUDY DESIGN: This was a retrospective longitudinal data analysis. We analyzed data from the Healthcare Cost and Utilization Project (HCUP) Nationwide Readmissions Database. METHODS: We analyzed the 2012-2015 HCUP Nationwide Readmissions Database and used multivariable weighted regression analyses to adjust for confounding factors. Individuals with any chronic pulmonary disease other than COPD were excluded. RESULTS: Of 1,728,931 patients hospitalized for COPD, 522,020 (30.2%) had a diagnosis of diabetes. Risk of all-cause 30-day readmission was higher among patients with complicated diabetes (adjusted odds ratio [OR], 1.15; 95% CI, 1.11-1.18) and uncomplicated diabetes (adjusted OR, 1.10; 95% CI, 1.08-1.12) compared with patients without diabetes. Diabetes was associated with longer length of stay, higher rates of hospital complications during index hospitalizations and 30-day readmissions, and a higher health care cost. Although diabetes was not associated with higher hospital mortality, routine hospital discharges were less common and the need for home health care upon discharge was higher among those with diabetes. CONCLUSIONS: Patients hospitalized for COPD and coexisting diabetes have worse clinical outcomes and higher 30-day readmissions compared with patients hospitalized for COPD without diabetes. Optimizing medical therapies and targeted interventions for both diseases is needed to alleviate disease burden to individuals and to society.

Eosinophilia Is Associated with Improved COVID-19 Outcomes in Inhaled Corticosteroid-Treated Patients.

BACKGROUND: In addition to their proinflammatory effect, eosinophils have antiviral properties. Similarly, inhaled corticosteroids (ICS) were found to suppress coronavirus replication in vitro and were associated with improved outcomes in coronavirus disease 2019 (COVID-19). However, the interplay between the two and its effect on COVID-19 needs further evaluation. OBJECTIVE: To determine the associations among preexisting blood absolute eosinophil counts, ICS, and COVID-19-related outcomes. METHODS: We analyzed data from the Cleveland Clinic COVID-19 Research Registry (April 1, 2020 to March 31, 2021). Of the 82,096 individuals who tested positive, 46,397 had blood differential cell counts obtained before severe acute respiratory syndrome coronavirus 2 testing dates. Our end points included the need for hospitalization, admission to the intensive care unit (ICU), and in-hospital mortality. The effect of eosinophilia on outcomes was estimated after propensity weighting and adjustment. RESULTS: Of the 46,397 patients included in the final analyses, 19,506 had preexisting eosinophilia (>0.15 × 103 cells/µL), 5,011 received ICS, 9,096 (19.6%) were hospitalized, 2,129 required ICU admission (4.6%) and 1,402 died during index hospitalization (3.0%). Adjusted analysis associated eosinophilia with lower odds for hospitalization (odds ratio [OR] [95% confidence interval (CI)]: 0.86 [0.79-0.93]), ICU admission (OR [95% CI]: 0.79 [0.69-0.90]), and mortality (OR [95% CI]: 0.80 [0.68-0.95]) among ICS-treated patients but not untreated ones. The correlation between absolute eosinophil count and the estimated probability of hospitalization, ICU admission, and death was nonlinear (U-shaped) among patients not treated with ICS, and negative in treated patients. CONCLUSIONS: The association between eosinophilia and improved COVID-19 outcomes depends on ICS. Future randomized controlled trials are needed to determine the role of ICS and its interaction with eosinophilia in COVID-19 therapy.

Alcohol use disorder and healthcare utilization in patients with chronic asthma and obstructive lung disease.

Alcohol use disorder (AUD) is associated with significant direct morbidity and mortality. The impact of alcohol on chronic asthma and obstructive lung disease is unknown. AUD treatment may represent a potential target to improve healthcare utilization and healthcare costs in this patient population. Utilizing data from the 2012-2015 Nationwide Readmissions Database (NRD) and Nationwide Emergency Department Sample (NEDS), patients with a primary admission diagnosis of asthma or COPD were identified. Documented substance misuse, rates of hospitalization, frequency of hospital readmission, markers of admission severity, and cost were assessed. Within the NEDS cohort, 2,048,380 patients with a diagnosis of COPD or asthma were identified. Patients with documented AUD were more likely to present with respiratory failure [OR 1.32 (1.26, 1.39); p < 0.001] and more likely to require mechanical ventilation in the emergency room [OR 1.30 (1.19, 1.42); p < 0.001]. Within the NRD cohort, 1,096,663 hospital admissions were identified, of which 4.1% had documented AUD. AUD was associated with an increased length of stay [percentage increase estimate: 5% (4,6); p < 0.001], increased hospitalization cost, and an increased likelihood of 30-day readmission in patients with a primary admission diagnosis of COPD or asthma [OR 1.24 (1.2, 1.28); p < 0.001]. AUD is associated with increased disease morbidity and healthcare utilization in patients admitted with asthma or COPD. This impact persists after adjusting for substance misuse and associated comorbidities. Identifying and treating AUD in this patient population may improve disease, patient, and health-system outcomes.

Novel Machine Learning Can Predict Acute Asthma Exacerbation.

BACKGROUND: Asthma exacerbations result in significant health and economic burden, but are difficult to predict. RESEARCH QUESTION: Can machine learning (ML) models with large-scale outpatient data predict asthma exacerbations? STUDY DESIGN AND METHODS: We analyzed data extracted from electronic health records (EHRs) of asthma patients treated at the Cleveland Clinic from 2010 through 2018. Demographic information, comorbidities, laboratory values, and asthma medications were included as covariates. Three different models were built with logistic regression, random forests, and a gradient boosting decision tree to predict: (1) nonsevere asthma exacerbation requiring oral glucocorticoid burst, (2) ED visits, and (3) hospitalizations. RESULTS: Of 60,302 patients, 19,772 (32.8%) had at least one nonsevere exacerbation requiring oral glucocorticoid burst, 1,748 (2.9%) requiring and ED visit and 902 (1.5%) requiring hospitalization. Nonsevere exacerbation, ED visit, and hospitalization were predicted best by light gradient boosting machine, an algorithm used in ML to fit predictive analytic models, and had an area under the receiver operating characteristic curve of 0.71 (95% CI, 0.70-0.72), 0.88 (95% CI, 0.86-0.89), and 0.85 (95% CI, 0.82-0.88), respectively. Risk factors for all three outcomes included age, long-acting ß agonist, high-dose inhaled glucocorticoid, or chronic oral glucocorticoid therapy. In subgroup analysis of 9,448 patients with spirometry data, low FEV1 and FEV1 to FVC ratio were identified as top risk factors for asthma exacerbation, ED visits, and hospitalization. However, adding pulmonary function tests did not improve models' prediction performance. INTERPRETATION: Models built with an ML algorithm from real-world outpatient EHR data accurately predicted asthma exacerbation and can be incorporated into clinical decision tools to enhance outpatient care and to prevent adverse outcomes.

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.