RATIONALE: Dysregulation of L-arginine and nitric oxide (NO) metabolism is thought to play a key role in asthma morbidity.This dysregulation is hypothesized to occur via different mechanisms based on underlying asthma endotype, however this has not been well characterized.Additionally, the impact of L-arginine dysregulation on asthma outcomes has not been well studied.We aim to better understand the association between L-arginine metabolites and asthma outcomes and to understand how L-arginine metabolism differs among patient demographics and markers of Th2 inflammation.METHODS: We analyzed baseline data from a cohort of 323 asthmatics from New York and Colorado.This cohort targeted recruitment to achieve balanced enrollment of obese and non-obese patients and late versus early onset asthma.L-arginine metabolites including L-arginine, Lcitrulline, ornithine, proline, and ADMA were measured from patient serum.The association between L-arginine metabolites and spirometry, asthma control, quality of life, systemic corticosteroid use, and emergency department utilization was evaluated using bivariate and multivariate regression analysis.RESULTS: Among the 323 participants, the median age was 49, range 21 to 76 years, with 81% female participants.The cohort was racially and ethnically diverse with 30.9% Hispanic/Latino participants, 23.1% identified as Black, 34.1% as White, and 11.9% other.Over half of the cohort (53.4%) was obese and 63.3% reported late onset asthma defined as asthma onset occurring later than 12 years of age.Spearman correlation coefficients for biomarkers and FEV1 are shown in figure 1.In multivariate models, arginine availability, measured by the ratio of arginine to ornithine and citrulline, was associated with decreased FEV1 and FVC, -0.29 (95% confidence interval -0.54, -0.06) and 0.29 (-0.57, -0.01), respectively.Arginine to ADMA (arg:ADMA), a marker for NO synthase (NOS) dysfunction, was associated with an increased odds of systemic corticosteroid use in the past year, odds ratio 0.33 (0.13, 0.83).CONCLUSIONS: This cohort of asthma patients represents a diverse patient population with representation from diverse asthma phenotypes.We find that increased arginine availability is associated with decreased spirometry and that arg:ADMA, representing less NOS impairment, was associated with increase in need for systemic corticosteroids.How these associations change among markers of Th2 inflammation needs to be further investigated in this cohort.Future studies will incorporate L-arginine metabolites into clustering studies to identify populations of asthmatics with different L-arginine signatures.These findings may help identify biomarkers that predictor asthma outcomes and possible response to novel therapies that target L-arginine metabolites.

Obesity is known to worsen asthma control.One potential mechanism by which it worsens asthma is through obstructive sleep apnea (OSA).Its prevalence is up to 2 to 3 times higher in patients with asthma and as many as 95% of patients with severe steroid dependent asthma have OSA.The inflammatory pathway generated by derangements in the metabolic pathways of L-arginine and nitric oxide (NO) may explain the negative underlying effects of OSA on asthma control.We modeled the effect of biomarkers of L-arginine metabolism and OSA on each outcome (Emergency room (ER)/steroid use, asthma control questionnaire (ACQ), and asthma quality of life questionnaire (AQLQ)) using generalized linear models, where biomarkers and their ratios were log-transformed and where confounders included metabolic syndrome criteria (MSX), asthma age, smoking status, sex, body mass index (BMI), and race.For OSA, unadjusted and adjusted regression models were fit to assess whether the relationship in question was mediated by differences in biomarker ratios or demographics.Our sample consists of 295 asthmatics who were primarily female (81.3%), with a median age of 49 (IQR: 22, range: 21-76) years.OSA was reported in 87 participants (29.5%).In patients with OSA, we observed a significantly higher mean age (mean difference = 9.56 years; p<0.001) as well as a significantly higher mean BMI (mean difference = 7.08 units; p<0.001).Further, we found that OSA prevalence was slightly higher among males (40% vs 27% in females, p = 0.071), and not discernably different among different race categories (p = 0.335).Patients in the OSA group were more likely to have utilized steroids or the ER in the last 12 months (OR=1.874,p=0.017), however this effect is somewhat mediated by differences in demographics between OSA/non-OSA participants.However, even after adjusting for differences due to demographics, patients with OSA had a significantly higher ACQ score (p=0.01) and had significantly lower AQLQ scores (p=0.001).OSA worsens asthma control.The prevalence of OSA is directly proportional to age.The increase in healthcare utilization in the OSA may be attributable differences in demographics.The observed discrepancy in asthma control for those with OSA was not mediated by markers of arginine metabolism nor by differences in other key demographic characteristics.

OBJECTIVES: To describe the evolution of a hospital at home (HaH) program to a HaH with a 30-day posthospitalization transition period (HaH-Plus) and results of a retrospective review of cases. DESIGN: After launching HaH-Plus, we used the same interdisciplinary clinical team to provide acute home-based care for a broader range of home-based acute-level services than originally conceived in the Hospital at Home model. These included a palliative care unit at home (PCUaH), an observation unit at home (OUaH), a post-acute care rehabilitation at home (RaH), and a program for the hospital averse – those patients needing to be in the hospital but who refuse. SETTING: Urban health system. PARTICIPANTS: Individuals 18 years or older residing in specified catchment area with Medicare fee-for-service or accepted Medicare/Medicaid Advantage plans requiring facility-based care. INTERVENTION: Provision of facility-based acute-level care at home to 685 participants. MEASUREMENTS: Length of stay, readmission, and mortality. RESULTS: HaH-Plus cared for 685 individuals. The PCUaH had the oldest participants (mean age 87), and all groups were predominantly female and dually eligible for Medicare and Medicaid. Diagnoses and length of stay were similar in all groups except that those in RaH had a larger group of diagnoses, than those accepted in to HaH-Plus and those in OUaH had a shorter stay. Rate of readmission was highest for RaH (19%). Mortality during the active treatment episode was highest for PCUaH and hospital averse as compared to HaH-Plus, OUaH and RaH. CONCLUSION: Providing a broader range of facilitybased care in the home has significant advantages for patients and increases the scalability of HaH. Developing a spectrum of services was possible by leveraging a robust, 24-hour HaH team. Communityand home-based care could become a greater part of the U.S. healthcare system if a platform of HaH services along with advances in technology and payment models were developed. J Am Geriatr Soc 67:596–602, 2019.

To date, Hospital at Home (HaH) care has focused on substitutive admission avoidance or early discharge models. In the context of a U.S. Federal innovation award program for the Center for Medicare and Medicaid Services, we have evolved the HaH model into a care “platform” for older adults. In addition to providing substitutive admission avoidance care, the platform includes: 1) “observation” stay at home; 2) acute palliative care at home; 3) acute care for hospital adverse patients (people who refuse hospital admission under all circumstances) at home; and 4) subacute rehabilitation care at home as a substitute for admission to inpatient subacute rehabilitation. This platform evolved in recognition of the evolving health care delivery system, the need to create greater demand for HaH resources, provide adequate patient volumes for HaH operations, and the needs and preferences of patients. Results from the first 2 years of the platform will be presented.