Differences in L-arginine metabolism and asthma morbidity among asthma patients with and without obstructive sleep apnea.

BACKGROUND: Imbalance in L-arginine and nitric oxide (NO) metabolism has been implicated in the pathophysiology of asthma and obstructive sleep apnea (OSA), and both diseases impact the other's morbidity. We sought to determine whether L-arginine/NO metabolism differs between adults with asthma with or without comorbid OSA, and its association with asthma morbidity. METHODS: This is a cross-sectional study of 322 adults with asthma recruited in Denver, CO and New York City, NY. Data were collected on OSA status, spirometry, and metrics of asthma control and morbidity. L-Arginine metabolites were quantified in patient serum. Bivariate analyses and multiple regression were performed to determine differences between L-arginine metabolism, OSA and association with asthma morbidity. RESULTS: Among the 322 participants, 92 (28.5%) had OSA. The cohort was 81.6% female, 23.4% identified as Black and 30.6% as Latino. Patients with asthma and OSA had significantly higher serum concentrations of NO synthase inhibitor asymmetric dimethylarginine (ADMA) (p-value = 0.019), lower L-arginine to ornithine ratios (p-value = 0.003), and increased ornithine (p-value = 0.001) and proline levels (p-value < 0.001) compared to those without OSA. In adjusted models, OSA was associated with worse asthma control, adjusted mean difference in asthma control questionnaire of 0.36 (95% confidence interval [CI]: 0.06 to 0.65), and asthma quality of life questionnaire, adjusted mean difference: - 0.53 (95% CI: - 0.85 to - 0.21), after adjusting for relevant covariates including body mass index and L-arginine metabolites. CONCLUSIONS: Adults with asthma and OSA had increased ADMA, an inhibitor of nitric oxide synthase, and greater metabolism of L-arginine via the arginase pathway compared to those with asthma alone, indicating a possible shared pathophysiological mechanism of these diseases.

Noninvasive Ventilation Use in Critically Ill Patients with Acute Asthma Exacerbations.

Rationale: Noninvasive ventilation decreases the need for invasive mechanical ventilation and mortality among patients with chronic obstructive pulmonary disease but has not been well studied in asthma.Objectives: To assess the association between noninvasive ventilation and subsequent need for invasive mechanical ventilation and in-hospital mortality among patients admitted with asthma exacerbation to the ICU.Methods: We performed a retrospective cohort study using administrative data collected during 2010-2017 from 682 hospitals in the United States. Outcomes included receipt of invasive mechanical ventilation and in-hospital mortality. Generalized estimating equations, propensity-matched models, and marginal structural models were used to assess the association between noninvasive ventilation and outcomes.Measurements and Main Results: The study population included 53,654 participants with asthma exacerbation. During the study period, 13,540 patients received noninvasive ventilation (25.2%; 95% confidence interval [CI], 24.9-25.6%), 14,498 underwent invasive mechanical ventilation (27.0%; 95% CI, 26.7-27.4%), and 1,291 died (2.4%; 95% CI, 2.3-2.5%). Among those receiving noninvasive ventilation, 3,013 patients (22.3%; 95% CI, 21.6-23.0%) required invasive mechanical ventilation after first receiving noninvasive ventilation, 136 of whom died (4.5%; 95% CI, 3.8-5.3%). Across all models, the use of noninvasive ventilation was associated with a lower odds of receiving invasive mechanical ventilation (adjusted generalized estimating equation odds ratio, 0.36; 95% CI, 0.32-0.40) and in-hospital mortality (odds ratio, 0.48; 95% CI 0.40-0.58). Those who received noninvasive ventilation before invasive mechanical ventilation were more likely to have comorbid pneumonia and severe sepsis.Conclusions: Noninvasive ventilation use during asthma exacerbation was associated with improved outcomes but should be used cautiously with acute comorbid conditions.

Histopathologic Analysis of Surgically Resected Lungs of Patients with Non-tuberculous Mycobacterial Lung Disease: a Retrospective and Hypothesis-generating Study.

Non-tuberculous mycobacterial lung disease (NTM-LD) is most commonly due to species within the Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MAbC). Surgical lung resection, typically a lobectomy or segmentectomy, is occasionally undertaken for individuals with recalcitrant but localized NTM-LD. Since the growth characteristics of MAC (slow growers) and MAbC (rapid growers) as well as their drug susceptibility patterns are significantly different, the objective of this study is to characterize and compare the histopathologic features of the resected lungs due to these two major NTM groups. From 1996 to 2017, 356 patients with NTM-LD due to MAC (n=270), MAbC (n=54), or both (n=32) underwent a total of 404 lobar resections (with the lingula counted as a separate lobe) at the University of Colorado Hospital. We analyzed by microscopy the existing surgical lung tissue sections for bronchiolitis, bronchiolectasis, bronchiectasis, non-necrotizing granuloma (airway, parenchymal, and total), necrotizing granuloma (airway, parenchymal, and total), peri-airway fibrosis, fibrous pleuritis, and lymphoid follicles. There were no significant differences in the presence or absence of most of the histopathologic features of surgically removed lungs due to MAC, MAbC, or both MAC + MAbC. However, there were significantly more necrotizing granulomas (airway, parenchymal, and total) and fibrous pleuritis in MAC compared to MAbC lung diseases. Since necrotizing granulomas may be a sign of inadequate control of the infection, we posit that their presence may be an indication of increased chronicity, increased virulence of MAC compared to MAbC, and/or impaired host immunity against the NTM. Futures studies to determine the root cause of such differences in histopathologic findings in MAC versus MAbC lung disease may spawn new leads on differential pathogenic mechanisms with different NTM, with the goal of aiming for more targeted therapy against both the NTM and the lung damage induced by them.

Social Support Networks and HIV/STI Risk Behaviors Among Latino Immigrants in a New Receiving Environment.

The objectives of this study were to: (1) describe the quantity and quality of social support networks of Latino immigrants living in a new receiving environment, and (2) determine the role such networks play in their HIV/STI risk behaviors, including substance use. Double incentivized convenience sampling was used to collect egocentric social support network data on 144 Latino immigrants. Latent class analysis was used for data reduction and to identify items best suited to measure quality and quantity of social support. Moderate and high quantity and quality of social support were protective of HIV/STI sexual risk behavior compared to low quantity and quality of support, after adjustment for gender, years in New Orleans and residing with family. Neither measure of social support was associated with binge drinking. The findings suggest that increased quantity and quality of social support decrease HIV/STI sexual risk behaviors but do not influence binge drinking. Interventions that improve the quantity and quality of social support are needed for Latino immigrants.

The impact of cannabis use proximal to sleep and cannabinoid metabolites on sleep architecture.

STUDY OBJECTIVES: Cannabis is a common sleep aid, however the effects of its use prior to sleep are poorly understood. This study aims to determine the impact of non-medical whole plant cannabis use three hours prior to sleep and measured cannabis metabolites on polysomnogram measures. METHODS: This is a cross-sectional study of 177 healthy adults who provided detailed cannabis use history, underwent a one-night home sleep test (HST) and had measurement of eleven plasma and urinary cannabinoids, quantified using mass spectroscopy, the morning after the HST. Multivariable models were used to assess the relationship between cannabis use proximal to sleep, which was defined as use three hours before sleep, and individual HST measurements. Correlation between metabolite concentrations and polysomnogram measures were assessed. RESULTS: In adjusted models, cannabis use proximal to sleep was associated with increased wake after sleep onset (median 60.5 versus 45.8 minutes), rate ratio 1.59 (1.22, 2.05), and increased proportion of stage one sleep (median 15.2% versus 12.3%), effect estimate 0.16 (0.06, 0.25). Compared to non-users, frequent cannabis users (>20 days per month) also had increased wake after sleep onset and stage one sleep, in addition to increased REM latency and decreased percent sleep efficiency. Delta-9 tetrahydrocannabinol metabolites correlated with these HST measures. CONCLUSIONS: Cannabis use proximal to sleep was associated with minimal changes in sleep architecture. Its use wasn't associated with measures of improved sleep including increased sleep time or efficiency and may be associated with poor quality sleep through increase wake onset and stage 1 sleep.

Patterns and predictors of multiple sexual partnerships among newly arrived Latino migrant men.

Multiple sexual partnerships (MSP), both concurrent and serial short gap, are thought to increase the risk of HIV and sexually transmitted infection (STI) acquisition and transmission. In this study we evaluate potential individual and environmental risk factors for engaging in MSP in a cohort of newly arrived Latino migrant men (LMM) in New Orleans, LA, USA. Participants were surveyed at three time points over a nine-month period to examine factors associated with MSP. Of the 113 men, 32.5 % reported ever MSP. In 290 observations, 19.5 % of men had concurrent, and 15.0 % had serial short gap partnerships in at least one interviews. Substance was associated with MSP, OR (95 % CI) 2.00 (1.16, 3.45) whereas belonging to a community organization was found to be protective, OR 0.32 (0.17, 0.59). Interventions to reduce substance use and promote social connection are needed to prevent a potential HIV/STI epidemic in this population.

Integrated models of education and service involving community-based health care for underserved populations: Tulane student-run free clinics.

OBJECTIVES: Throughout the United States numerous models of local programs, including student-run clinics, exist to address the issue of access to care. The role of these clinics in serving the local community and contributing to medical education has been documented only in limited detail, however. The purpose of this article is to describe the clinic models, patient demographics, and services provided by four student-run clinics in New Orleans. METHODS: This is a retrospective, multisite chart review study of adult patients examined at student-run clinics between January 1, 2010 and July 31, 2011. RESULTS: During a 19-month period, 859 patients collectively were seen at the clinics, for a total of 1455 visits. The most common reasons for seeking care were medication refills (21.6%) and musculoskeletal pain (12.0%). Counseling and health education were provided primarily for smoking cessation (9.0%), diabetes management (7.1%), and hypertension management (5.8%). Nearly one-fifth of patients were given a referral to primary care services. In the 2010-2011 academic year, 87.6% of preclinical medical students volunteered at ≥1 of these clinics and spent 4508 hours during 1478 shifts. CONCLUSIONS: This article highlights the role of student-run clinics in the community, the safety-net healthcare system, and medical education. Future directions include the establishment of a new clinic, fundraising, and prospective studies to further assess the impact of student-run clinics.

Extracorporeal Membrane Oxygenation for Refractory Asthma Exacerbations With Respiratory Failure.

BACKGROUND: Asthma exacerbations with respiratory failure (AERF) are associated with hospital mortality of 7% to 15%. Extracorporeal membrane oxygenation (ECMO) has been used as a salvage therapy for refractory AERF, but controlled studies showing its association with mortality have not been performed. RESEARCH QUESTION: Is treatment with ECMO associated with lower mortality in refractory AERF compared with standard care? STUDY DESIGN AND METHODS: This is a retrospective, epidemiologic, observational cohort study using a national, administrative data set from 2010 to 2020 that includes 25% of US hospitalizations. People were included if they were admitted to an ECMO-capable hospital with an asthma exacerbation, and were treated with short-acting bronchodilators, systemic corticosteroids, and invasive ventilation. People were excluded for age < 18 years, no ICU stay, nonasthma chronic lung disease, COVID-19, or multiple admissions. The main exposure was ECMO vs No ECMO. The primary outcome was hospital mortality. Key secondary outcomes were ICU length of stay (LOS), hospital LOS, time receiving invasive ventilation, and total hospital costs. RESULTS: The study analyzed 13,714 patients with AERF, including 127 with ECMO and 13,587 with No ECMO. ECMO was associated with reduced mortality in the covariate-adjusted (OR, 0.33; 95% CI, 0.17-0.64; P = .001), propensity score-adjusted (OR, 0.36; 95% CI, 0.16-0.81; P = .01), and propensity score-matched models (OR, 0.48; 95% CI, 0.24-0.98; P = .04) vs No ECMO. Sensitivity analyses showed that mortality reduction related to ECMO ranged from OR 0.34 to 0.61. ECMO was also associated with increased hospital costs in all three models (P < .0001 for all) vs No ECMO, but not with decreased ICU LOS, hospital LOS, or time receiving invasive ventilation. INTERPRETATION: ECMO was associated with lower mortality and higher hospital costs, suggesting that it may be an important salvage therapy for refractory AERF following confirmatory clinical trials.

Association between Substance Misuse and Outcomes in Critically III Patients with Pneumonia.

Rationale: In patients with pneumonia requiring intensive care unit (ICU) admission, alcohol misuse is associated with increased mortality, but the relationship between other commonly misused substances and mortality is unknown. Objectives: We sought to establish whether alcohol misuse, cannabis misuse, opioid misuse, stimulant misuse, or misuse of more than one of these substances was associated with differences in mortality among ICU patients with pneumonia. Methods: This was a retrospective cohort study of hospitals participating in the Premier Healthcare Database between 2010 and 2017. Patients were included if they had a primary or secondary diagnosis of pneumonia and received antibiotics or antivirals within 1 day of admission. Substance misuse related to alcohol, cannabis, stimulants, and opioids, or more than one substance, were identified from the International Classification of Diseases (Ninth and Tenth Editions). The associations between substance misuse and in-hospital mortality were the primary outcomes of interest. Secondary outcomes included the measured associations between substance misuse disorders and mechanical ventilation, as well as vasopressor and continuous paralytic administration. Analyses were conducted with multivariable mixed-effects logistic regression modeling adjusting for age, comorbidities, and hospital characteristics. Results: A total of 167,095 ICU patients met inclusion criteria for pneumonia. Misuse of alcohol was present in 5.0%, cannabis misuse in 0.6%, opioid misuse in 1.5%, stimulant misuse in 0.6%, and misuse of more than one substance in 1.2%. No evidence of substance misuse was found in 91.1% of patients. In unadjusted analyses, alcohol misuse was associated with increased in-hospital mortality (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.06-1.19), whereas opioid misuse was associated with decreased in-hospital mortality (OR, 0.46; 95% CI, 0.39-0.53) compared with no substance misuse. These findings persisted in adjusted analyses. Although cannabis, stimulant, and more than one substance misuse (a majority of which were alcohol in combination with another substance) were associated with lower odds for in-hospital mortality in unadjusted analyses, these relationships were not consistently present after adjustment. Conclusions: In this study of ICU patients hospitalized with severe pneumonia, substance misuse subtypes were associated with different effects on mortality. Although administrative data can provide epidemiologic insight regarding substance misuse and pneumonia outcomes, biases inherent to these data should be considered when interpreting results.

Asthma and Three Colinear Comorbidities: Obesity, OSA, and GERD.

Asthma is a complex disease with heterogeneous phenotypes and endotypes that are incompletely understood. Obesity, obstructive sleep apnea, and gastroesophageal reflux disease co-occur in patients with asthma at higher rates than in those without asthma. Although these diseases share risk factors, there are some data suggesting that these comorbidities have shared inflammatory pathways, drive the development of asthma, or worsen asthma control. This review discusses the epidemiology, pathophysiology, management recommendations, and key knowledge gaps of these common comorbidities.

A Meta-Analysis of the Efficacy of Behavioral Interventions to Reduce Risky Sexual Behavior and Decrease Sexually Transmitted Infections in Latinas Living in the United States.

The objective of this meta-analysis was to determine the effect of behavioral interventions in reducing risky sexual behavior and incident sexually transmitted infections (STI) among Latina women living in the United States. Studies were found by systematically searching the MEDLINE, EMBASE, and PsychInfo databases without language restriction. Two independent reviewers screened abstracts and full texts of articles to find randomized control trials testing the effects of behavioral interventions aimed at changing risky sexual behavior among Latinas. Articles were selected using prespecified inclusion criteria. Two independent reviewers extracted data from the included trials in duplicate using a standardized data extraction form. Six randomized control trials met the inclusion criteria for a total of 2,909 participants. Using random effects models with inverse variance weighting, we found a protective effect of the behavioral intervention on reported risky sexual behavior (odds ratio = 0.52; 95% confidence interval = 0.42, 0.64) and on incident nonviral STI (odds ratio = 0.65; 95% confidence interval = 0.46, 0.93). Behavioral interventions targeted toward Latina populations are effective in reducing risky sexual behaviors and incident STI and should be considered by policymakers as a potential tool for HIV/STI prevention in this population.