BACKGROUND:Robotic-assisted laparoscopic surgery (RALS) in a steep Trendelenburg position creates conditions conducive to cyclical alveolar collapse when using standard lung protective ventilation settings (LPV). The magnitude of force induced by alveolar collapse and expansion is predicted to cause a localized injury, but biological evidence of perioperative atelectrauma is lacking. We hypothesized that the negative transpulmonary pressures and increased dissipated power of ventilation encountered during RALS lead to injury of the dependent (apical) lung despite the use of LPV settings. METHODS:We conducted a single-center, observational study of lung mechanics and injury in 15 subjects (8 M/7F; mean ± standard deviation: 59.5 ± 7.4 years) without lung disease undergoing RALS with LPV at an academic hospital in the United States. Subjects had a median body mass index of 32.5 kg/m2 with a range of 24.3 to 50.9 kg/m2. We continuously measured lung mechanics, including transpulmonary pressures. Bronchoalveolar lavages (BAL) were obtained from apical and anteromedial subsegments after intubation and from contralateral subsegments before extubation. During RALS, the apical lung is dependent and the anteromedial lung in nondependent. BAL analyses included total protein concentrations, proteomics, lipidomics, and leukocyte counts. RESULTS:Lung mechanics were impaired, with elevated respiratory elastance and driving pressures, and negative end-expiratory transpulmonary pressures, despite standard LPV settings (tidal volume 7.0 ± 0.8 mL/kg ideal body weight; positive end-expiratory pressure 8.7 ± 3.4 cm H2O). Increases in total protein (median [interquartile range], 131 [27-193] µg/mL), extracellular matrix components (fibulin-1: 2.1 [1.6-4.0] fold; microfibril-associated glycoprotein-4: 2.2 [1.3-4.0] fold), and procoagulants (prothrombin: 1.7 [1.3-4.8] fold; plasminogen: 3.2 [1.9-4.5] fold) were observed in apical BAL after surgery (adj. P < .001 for all), but not in anteromedial BAL (adj. P > .05). No differences in percent leukocyte composition were observed among lavages (P > .287 for all cell types). Phosphatidylglycerol abundance was increased in apical BAL after surgery in unadjusted analyses (5.8 [1.9-7.9] %, P = .021), but no changes in phospholipid abundance were noted in adjusted analysis. Increases in apical BAL total protein were positively correlated with the dissipated mechanical power of ventilation (r2 = 0.434, P = .014). CONCLUSIONS:In this focused biomechanical study, we found molecular evidence for alveolar-capillary damage in the dependent apical lobes, consistent with localized atelectrauma. Regional atelectrauma from impaired lung mechanics can occur in the positionally dependent lung while using LPV settings during RALS, most likely from insufficient end-expiratory pressure.

BACKGROUND:Obesity is associated with poorly controlled asthma. One reason for this may be the increased mitochondrial oxidative stress in obese asthma. Indeed, targeting oxidative stress reduces airway reactivity in animal models. The purpose of this trial was to investigate the potential efficacy of the mitochondrial-targeted antioxidant MitoQuinone (MitoQ) for the treatment of poorly controlled asthma in people with obesity. METHODS:A twelve week, randomized, double-masked, placebo-controlled trial of 40 mg MitoQ versus placebo in adults with obesity and poorly controlled asthma was performed. The primary outcome was change in airway reactivity, with secondary outcomes of change in asthma control, quality of life, and lung function. RESULTS:Twenty participants were randomized to MitoQ, 18 to placebo. After 12 weeks, there was no difference in change in airway reactivity to methacholine (provocative dose producing a 20% decrease in FEV1) between the group assigned to MitoQ (median change = 0.0 μg [IQR -25.5 to 1.4]) or placebo (change = -0.8 μg [IQR -57 to 0.0]), p = 0.81. There was no difference in the change in Asthma Control Test score (MitoQ 1 [IQR -1 to 2], placebo 1 [-2 to 2]), p = 0.62, or Marks Asthma Quality of Life Score (MitoQ -0.08 [IQR -0.35 to 0.10], placebo -0.05 [-0.30 to 0.15]), p = 0.80. CONCLUSION:MitoQ was well tolerated but did not improve airway reactivity, asthma control, or lung function. Targeting oxidative stress in people with obesity and poorly controlled asthma with MitoQ is unlikely to be efficacious for the treatment of asthma.

BACKGROUND:The coexistence of obesity and asthma is increasingly common and associated with poorer asthma outcomes. Weight loss has been shown to improve asthma outcomes. Although several effective weight-loss medications are available, evidence regarding their respiratory effects remains limited. OBJECTIVE:To conduct a systematic review of the respiratory adverse events (AEs) associated with weight-loss medications in general populations and specifically among individuals with asthma. METHODS:We searched Medline, Embase, Cochrane, and CINAHL, as well as trial registries, without date or language restrictions. We included randomized controlled trials, nonrandomized comparative studies, and large, single-group studies assessing the respiratory AEs of liraglutide, semaglutide, tirzepatide, orlistat, naltrexone-bupropion, phentermine-topiramate, and setmelanotide. We assessed the risk of bias in each study using design-specific, validated tools. We conducted random-effects model-based meta-analyses of risk differences for respiratory AEs, comparing active interventions and placebo. RESULTS:Our searches yielded 9,086 unique records. We included 123 studies, of which 122 studies evaluated general populations and one study specifically evaluated individuals with asthma. Overall, the randomized trials had low risk of bias. Liraglutide, semaglutide, tirzepatide, and naltrexone-bupropion were not associated with increased respiratory AEs compared with placebo. Insufficient data limited comparisons for other drugs. Respiratory events, such as upper respiratory tract infections and nasopharyngitis, were common, with nasopharyngitis incidence ranging from 4.1% (95% CI: 0.7%, 9.3%; tirzepatide, 0-6 months) to over 23.7% (95% CI: 19.6%, 28.1%; liraglutide, 13-24 months), although these were not clearly associated with doses or indications. Evidence specifically addressing individuals with asthma was sparse. CONCLUSIONS:There was no evidence of increased respiratory harm associated with weight-loss drugs compared with placebo, suggesting a reassuring respiratory safety profile in the general population. However, evidence specifically focused on individuals with asthma remains limited.

Importance:Despite strong guideline support, single maintenance and reliever therapy (SMART) for asthma is underused in the US. Limited insurance coverage of SMART-compatible inhalers remains a major barrier to its adoption. Objective:To compare the annual asthma management costs of SMART vs traditional therapy from a US health care payer perspective. Design, Setting, and Participants:This economic evaluation used a probabilistic decision-tree model with Monte Carlo simulations to compare the total asthma management costs for patients prescribed SMART vs traditional therapy, conducting analyses from September 1, 2024, to March 13, 2025. Input data were extracted through a systematic review of 6 randomized clinical trials as well as current asthma guidelines. Exposures:SMART vs traditional therapy. Main Outcomes and Measures:The main outcome was annual asthma-related costs to health care payers. Model inputs, including exacerbation rates and expected inhaler utilization, were extracted from prior randomized clinical trials. Morbidity data and medication costs were obtained from national databases and inflated to 2024 US dollars. Analyses used a 1-year time horizon and were repeated with and without quality-adjusted life-years (QALYs) considered. Results:The model includes 11 988 individuals with moderate to severe asthma who participated in the randomized clinical trials. For patients prescribed SMART, the estimated total annual cost of asthma management was $2181 (95% CI, $1606-$2939) per patient compared with $2235 (95% CI, $1595-$3267) for traditional therapy. SMART was associated with an incremental gain of 0.0006 QALYs (95% CI, 0.0003-0.0011 QALYs) per patient. SMART was less costly in 57% of simulations when QALYs were excluded, was more cost-effective in 67% of simulations when QALYs were included, and produced a mean incremental net monetary benefit of $118 (95% CI, -$344 to $663) per patient per year. Conclusions and Relevance:The findings of this economic analysis suggest that SMART was associated with modest cost savings and improved health outcomes compared with traditional asthma therapy. Given its cost-effectiveness, demonstrated effectiveness, and strong guideline endorsement, expanding insurance coverage of SMART may reduce asthma-related morbidity while lowering costs to US health care payers.

BACKGROUND:Individuals with obesity and asthma experience poor asthma-related quality of life and asthma control, and high rates of asthma-related hospitalizations. OBJECTIVE:Aerobic exercise can improve asthma control, but minimal data are available in obesity and asthma. This study evaluated feasibility and efficacy of a remote digital therapeutic exercise program in obesity and asthma. METHODS:Twenty participants with body mass index ≥30 kg/m2 and poorly controlled asthma defined as an Asthma Control Test (ACT) score of ≤19, rescue inhaler use more often than twice weekly, nocturnal asthma awakenings at least weekly, emergency department or hospital visit for asthma within 6 months, or steroid course within 6 months were enrolled in a single-arm, 12-week pilot study conducted between November 2024 and December 2025. Feasibility was defined as ≥60% of participants completing ≥50% of prescribed exercises. Efficacy was defined as ≥30% of participants experiencing an improvement in ACT of ≥3. RESULTS:Fifty percent of participants completed ≥50% of prescribed exercises, not achieving our feasibility target. Forty percent of participants achieved a ≥3-point increase in ACT. ACT scores increased significantly from a median of 16 (interquartile range: 14-19) to 20 (17-21). CONCLUSIONS:Completing ≥75 minutes of exercise weekly was attainable in 50% of participants; remote digital therapeutic exercise programs may improve physical activity levels and asthma control among individuals with obesity and poorly controlled asthma. Larger cohorts are necessary to expand upon these results.

RATIONALE:Obesity is linked to poorly controlled asthma and may impair bronchodilator response. This study examines dietary factors affecting asthma symptoms, control, and lung function. METHODS:In a multi-center, cross-sectional study of 102 individuals with obesity and poorly controlled asthma, we assessed dietary intake (Arizona Food Frequency Questionnaire), asthma symptoms and control (standardized questionnaires), and lung function (spirometry and bronchodilator response). Correlations between omega-3 and -6 fatty acids with asthma outcomes and lung function were examined using Pearson correlations and multivariate regression. RESULTS:Median age was 56 (IQR 41-64) years, and median BMI was 37 (35-42) kg/m2. Fifty-four percent were African American and 75 % were female. Median total calorie intake was 2029 (1199-3837) kcal, median total omega-3 intake was 1.07 (0.63-2.04) g, and median omega-6 intake was 24.54 (13.31-45.35) g. No significant relationship was found between fatty acid intake and asthma symptoms, asthma control, or baseline lung function. However, percent bronchodilator response was positively correlated with omega-3 fatty acids (r = 0.273, p = 0.0074). After adjusting for caloric intake, for every 1 g increase in omega-3 intake, there was a 4 % increase in percent bronchodilator response. CONCLUSIONS:Dietary intake of omega-3 fatty acids may influence bronchodilator response in patients with poorly controlled asthma and obesity. Interventions to improve overall dietary quality, such as increased omega-3 intake, may improve medication response in people with obesity and poorly controlled asthma. Future research is needed to better understand this association and determine if additional dietary factors might affect medication responses.

BACKGROUND:Obesity is associated with more severe asthma symptoms, more frequent exacerbations, and more frequent asthma-related hospitalisations compared to adults without obesity. Because the origins and expression of obesity varies between individuals, a one-size-fits-all approach to obesity management will not address the underlying cause(s), increasing the risk of treatment failure. We hypothesise that obesity-related asthma is driven by excess adiposity, poor diet quality, physical inactivity, and poor metabolic health, while an individualised obesity management intervention, utilising medical nutrition therapy and personalised physical activity prescription, will result in better asthma control. METHODS:The Individualised Diet and Exercise Intervention for Optimising Asthma Control and Lung Function (IDEAL) Study will test the first individualised obesity management approach for people with asthma. In this 16-week randomised controlled trial with 12-month follow-up, 102 adults with obesity and uncontrolled asthma will be randomised to either the IDEAL program or control group. Participants will be assessed for outcomes at baseline, 16 and 52 weeks. Participants randomised to the IDEAL Program will attend five sessions with a dietitian and physiotherapist/exercise physiologist during the 16-week intervention period. We will test the intervention effect on asthma (asthma control, lung function), inflammatory (e.g. sputum cell counts, plasma IL-6) and non-asthma outcomes (e.g. diet quality, physical activity levels, metabolic health), as well as the acceptability and cost of the intervention. CONCLUSION:This trial aims to provide people living with asthma and obesity an effective and sustainable way to help control their asthma symptoms and will assess mechanisms responsible for any improvements observed. ETHICS/REGISTRATIONS:NSW REGIS ETHICS Reference: 2023/ETH00833. UoN IBC Reference No: SP-23-92. ANZCTR Reference No: ACTRN12623000979651. Universal Trial Number: U1111-1291-8501.

INTRODUCTION:Both asthma and depression are common diseases that significantly contribute to morbidity and mortality worldwide. AREA COVERED:This review was conducted through PubMed as a search engine and discusses the similarities with respect to epidemiology, contributing factors and disease pathogenesis for both depression and asthma. The goal of this review was to assess the available evidence on the links between asthma and depression. These diseases share common epidemiologic characteristics including an increased prevalence in higher income countries, and each is an independent risk factor for development of the other. They share common risk factors including genetic, maternal, and socioeconomic factors. Common pathophysiologic mechanisms in asthma and depression include similar cytokine signaling pathways. Despite the striking similarities in terms of epidemiology, risk factors, and pathophysiologic pathways, few studies have investigated the effects of treating depression on asthma outcomes. The intersection between asthma and depression is remarkable and the available literature suggests treatment of co-morbid depression may improve asthma outcomes. Further investigation into the treatment of depression in asthma is warranted. EXPERT OPINION:Understanding the connection between depressive symptoms and asthma is important for improving asthma outcomes. High-quality studies assessing anti-depressant therapy in those with asthma and depressive symptoms are needed.

Most people with severe asthma have obesity. Metabolic dysfunction, often associated with obesity, is particularly associated with severe asthma. Mechanisms linking metabolic dysfunction with asthma, and whether improving metabolic function can affect asthma, are not known. The endocannabinoid system plays a significant role in metabolism; inhibition of cannabinoid receptor 1 (CB1R) induces weight loss and improves serum lipid profiles. We used a CB1R inverse agonist, INV-202, in a mouse model of obese asthma and investigated changes in weight, inflammation, airway reactivity, and surfactant lipids. Mice were fed low or high-fat diets (LFD, HFD), and house dust mite (HDM) extract was delivered intranasally to induce allergic airway inflammation. Mice received INV-202 by oral gavage. Airway hyperresponsiveness was measured by FlexiVent, and lung tissue cytokines were measured by ELISA. Leukocytes and lipids in the bronchoalveolar lavage fluid (BALF) were analyzed by flow cytometry and mass spectroscopy, respectively. LFD and HFD mice lost an average of 11% and 27% of their body weight, respectively. LFD mice had a 33% decrease in CCL20 in lung tissue and a 55% decrease in neutrophils in BALF. LFD and HFD mice had improvements in airway hyperresponsiveness, particularly as measured by reduced elastance. Phosphatidylglycerol in BALF increased with INV-202, which significantly correlated with compliance in LFD mice. This study supports a significant contribution of metabolic factors related to the endocannabinoid system in lung compliance and airway reactivity, in part through effects on surfactant lipid composition, and demonstrates the potential of CB1R inverse agonists to treat obese asthma.NEW & NOTEWORTHY Inhibition of the cannabinoid receptor 1, through a pharmacological inverse agonist, not only induces weight loss in a mouse model of obese asthma but also reduces airway hyperresponsiveness, particularly through decreasing elastance/increasing compliance.

RATIONALE: People with obesity and asthma experience worse asthma control and have increased rates of hospitalizations compared to lean people with asthma. Standard inhaler therapy, such as inhaled corticosteroids, are not as effective in people with obesity compared to lean people. This is thought to be due to the low lung volumes caused by obesity, which can increase airway reactivity even in the absence of asthma. Lung volumes can be increased through use of continuous positive airway pressure (CPAP). We sought to determine the efficacy of nocturnal CPAP for reducing airway reactivity in obese people both with and without asthma. METHODS: This was a two-site double-blinded randomized control trial. Participants with BMI ≥ 30 kg/m2 with (n=20) and without (n=20) asthma were randomized to 7 nights of CPAP of 10 cmH2O or sham CPAP (4cmH2O). Baseline airway physiology and response to methacholine were measured by oscillometry before and after the CPAP intervention, and compared using Student's t-test. Airway reactivity was quantified by the PC100, defined as the dose of methacholine producing a 100% increase in the area under the reactance curve from 5 Hz to the resonant frequency (Ax). The changes in ln(PC100) resulting from the intervention were compared by ANOVA. RESULTS: Control participants in both the CPAP and sham groups had similar BMI's (34.3 vs 34.1, respectively), as did the participants with asthma (BMI's of 40.1 vs 37.3, respectively). Participants with asthma had higher magnitudes of resistance and reactance, lower FEV1, and higher residual volume (percent predicted) than controls. On average, participants used CPAP for less than 5 hours per night. In the participants receiving 10 cmH2O CPAP, there were no significant differences in baseline oscillometry parameters between those with asthma versus controls, except for improved resistance at 19 Hz in participants with asthma (-0.29±0.08 vs -0.07±0.31, p=0.07). ln(PC100) increased, although non-significantly, with CPAP in controls only (1.53 [SEM 0.98] vs 0.42 [SEM 0.27]; p=0.17, respectively). CONCLUSIONS: These data suggest that nocturnal CPAP is unlikely to have a significant impact on asthma outcomes in people with obesity, and that airway reactivity in people with obesity and asthma is not related to low lung volumes. A larger, longer trial with greater adherence to CPAP and possible higher CPAP pressure may provide more power to see any small changes.

Obesity contributes to pulmonary dysfunction through poorly understood biochemical mechanisms. Chronic inflammation and altered cellular metabolism have emerged as pathological changes across organ systems in obesity, but whether similar changes occur in lungs with obesity is unknown. We collected bronchoalveolar lavage fluid (BALF) from right upper lobe and lingula pulmonary subsegments of 14 adults (7 males/7 females) with body mass indexes (BMIs) ranging from 24.3 to 50.9 kg/m2 without lung disease. Proteomes were measured using sequential window acquisition of all theoretical fragment ion spectra (SWATH) mass spectrometry. Proteomic composition and pathway enrichments were examined for the cohort and as a function of BMI. BALF proteomic compositions were consistent with earlier studies and had improved protein identification. We found minimal differences in BALF proteomes between lavage regions. Five proteins were strongly correlated with BMI (False Detection Rate/FDR-adjusted P values < 0.05) and 11 had weaker correlation (FDR-adjusted P values 0.05-0.1). These proteins included acute phase reactants and complement factors. Few proteomic differences between biological sexes were detected, but some of them coincided with BMI-related proteins. Pathway enrichments impacted by BMI included innate immunity, antifibrinolysis, oxidative stress, and lipid metabolism. The bronchoalveolar microenvironment is altered by obesity in humans without lung disease. Pathway alterations associated with BMI included coagulation and fibrinolysis, redox and oxidative stress, energy metabolism, and humoral immune function. Our data support the theory that conserved biochemical and cellular changes in obesity may be fundamental mechanisms of dysfunction in multiple tissues but the specific impact on pulmonary function or disease is not yet known.NEW & NOTEWORTHY Obesity is thought to cause deleterious changes in lung biochemistry, but data in humans are lacking. We measured the alveolar proteome in bronchoalveolar lavages from subjects with a wide range of body mass index and no lung disease. We found changes in proteins and pathways associated with increasing body mass index that are similar to pathological changes observed in other tissues and may constitute mechanisms of pulmonary dysfunction in obesity.

RATIONALE: Lung protective ventilation is the standard of care in intraoperative ventilation. However, these strategies have been shown to cause impairment in lung mechanics and may be suboptimal in patients undergoing robotic assisted laparoscopic surgery (RALS). Nonlinear mathematical descriptors of lung mechanics (volume dependent elastance %E2, and the stress index) quantify lung overdistension and/or regional collapse in acute respiratory distress syndrome. Accordingly, we used nonlinear models to understand the mechanical impairments in ventilation during RALS. METHODS: In a secondary analysis of airway and esophageal pressures and gas flows collected from 109 subjects (45/65 M/F, Age 27 to 77) with body mass index (BMI) ranging from 18 to 60 kg/m2 undergoing RALS, we calculated %E2 and the stress index at 4 surgical stages: flat after intubation, with pneumoperitoneum, in steep Trendelenburg, and after desufflation. We determined %E2 in 109 subjects (71 to 106 subjects per position) and the stress index in 48 subjects (29 to 48 subjects per position). Association between %E2 and the stress index was determined by analysis of variance (ANOVA). RESULTS: The average %E2 was -14±14 in the flat stage and averaged -11.8±16 in pneumoperitoneum and steep Trendelenburg (p<0.001) as seen in Figure 1A. The average stress index was 0.4±0.16 in the flat stage and increased to an average of 0.6±0.14 in pneumoperitoneum and steep Trendelenburg (p<0.001) as seen in Figure 1B. Both %E2 and stress index were invariant to BMI, and the two parameters were not correlated (r2=0.031, p=0.078). CONCLUSION: Our consistent finding of %E2<0 and stress index<1 suggests significant levels of lung derecruitment in our patients, despite the lack of correlation between the two parameters. Studies in animal models have shown that these parameters correlate strongly in non-injured lungs but become discordant in lung injury. While the lungs of our patients were not injured, they were operating far from normal conditions, which we speculate may have caused a similar effect due to the mechanical instabilities caused by positional depressions in lung volume.

RATIONALE: Both the Global Initiative for Asthma (GINA) and National Asthma Education and Prevention Program (NAEPP) recommend single maintenance and reliever therapy (MART) as the preferred inhaler strategy for patients with moderate-to-severe asthma as it reduces the risk of severe asthma exacerbations. Despite these guidelines, MART adoption remains low in the United States (U.S.), with clinicians and patients citing poor pharmaceutical coverage and high out-of-pocket costs as key barriers. To help inform U.S. healthcare payors’ decision making, we conducted a cost-analysis to compare the total cost of MART versus traditional therapy with and without quality-adjusted life years (QALYs) considered. METHODS: We developed a probabilistic model to evaluate the direct costs to healthcare payors of MART versus traditional inhaler therapy. Using a decision-analytic tree, we estimated annualized expenses related to: (1) asthma morbidity (including asthma-related clinical visits, systemic corticosteroid prescriptions, emergency department visits, and inpatient hospitalizations) and (2) inhaler dispensations. Estimates of asthma-related morbidity, inhaler usage, and quality of life metrics were aggregated and weighted from six randomized controlled trials of MART versus traditional inhaler therapy. Inhaler and steroid cost inputs were extracted from 2024 Micromedex® data, while clinical care costs were based on the 2022 Medical Expenditure Panel Survey (MEPS) and adjusted to 2024 prices using historical inflation rates. Monte Carlo simulations were then conducted with and without consideration of QALYs to determine the estimated cost of MART versus traditional inhaler therapy to healthcare payors. RESULTS: Without consideration of QALYs, the expected direct annualized cost to healthcare payors of MART (mean $3,081 U.S. dollars [U.S.D.]) was lower than traditional therapy (mean $3,181 U.S.D.) in 52% of simulations. With consideration of QALYs and a willingness-to-pay threshold of $100,000 per QALY, MART was cost effective in 56% of simulations, with a mean cost saving of $145 U.S.D. annually with MART. Further, MART provided a mean incremental QALY gain of 0.0079 over traditional therapy, which translated to an estimated $790 U.S.D. improvement in value annually with MART. Finally, at the current generic price of $97 U.S.D per budesonide-formoterol inhaler (based on GoodRx estimates), MART would decrease cost to healthcare payors in 84% of cases without QALYs considered. CONCLUSIONS: At current prices, MART is less costly for healthcare payors in comparison to traditional inhaler therapy with and without consideration of QALYs. These analyses may be beneficial to both healthcare payors and other stakeholders who are advocating for improved accessibility to guideline-recommended asthma management.

RATIONALE: 4G4G/4G5G SERPINE1 genotypes produce high concentrations of plasminogen activator inhibitor-1 and are associated with worse asthma outcomes. A secondary analysis of the American Lung Association (ALA) SOYA trial showed that soy isoflavones significantly reduced asthma exacerbations versus placebo among patients with 4G4G/4G5G SERPINE1 genotypes. We hypothesized that baseline characteristics predict optimal responders to soy isoflavones among this subgroup. METHODS: ALA-SOYA was a randomized controlled trial that tested the efficacy of soy isoflavones vs. placebo for reducing asthma exacerbations among adolescents and adults with symptomatic asthma. In this responder analysis among participants with 4G4G/4G5G SERPINE1 genotypes, baseline demographic and clinical characteristics were tested for effect modification of the treatment assignment (soy/placebo) on the primary outcome of annualized number of asthma exacerbations using interaction terms in negative binomial regression models, with a significance threshold of p-interaction=0.15. RESULTS: Data were available for n=168 participants. Soy reduced the annualized number of asthma exacerbations relative to placebo among patients with 4G4G/4G5G SERPINE1 genotypes (incident rate ratio (IRR)=0.37, 95% confidence interval (CI): 0.15-0.90, p=0.028). Self-reported adherence to baseline controller therapy was the only significant effect modifier of this association (interaction p=0.115), with those using inhaled corticosteroid (ICS)/long-acting beta-agonist (LABA) controller therapy at least twice weekly experiencing reductions in asthma exacerbations with soy versus placebo (IRR = 0.25, 95% CI: 0.09-0.69; p= 0.007) but not among those using ICS/LABA controller therapy less frequently (IRR = 1.33, 95% CI: 0.22-8.02; p= 0.757). CONCLUSION: Soy isoflavones reduce asthma exacerbations among patients with the 4G4G/4G5G SERPINE1 genotypes and are most effective in those with greater adherence to asthma controller therapy regimens.

People with obesity and asthma often experience poor asthma control and frequent exacerbations, and exhibit airway hyperresponsiveness (AHR) that may be mitigated by elevating lung volume. Our objective was to determine if nocturnal continuous positive airway pressure (CPAP) mitigates AHR in people with obesity, both with and without asthma. We performed a double-blinded randomized controlled trial at two centers. Participants with BMI ≥ 30 kg/m2 with (n = 20) and without (n = 20) asthma were randomized to 7 nights of CPAP of 10 cmH2O or sham CPAP (4 cmH2O). Baseline airway physiology and response to methacholine were measured by oscillometry before and after CPAP intervention. Airway responsiveness was quantified by PC100AX - the concentration of methacholine producing a 100

OBJECTIVE:Older adults with asthma (OAA) have elevated asthma morbidity rates. A six-session intervention based on self-regulation theory was shown to improve outcomes. However, wide-spread implementation was difficult due to the in-person design. Our objective was to determine the feasibility and acceptability of an updated intervention for OAA that is completely remote, includes a physician component, and utilizes shared decision-making (SDM). METHODS:A pilot study of 12 OAA with uncontrolled asthma and their asthma providers was conducted at three health centers. The remote intervention (titled SOAR) consisted of 4 sessions (2 groups and 2 individual). Asthma providers (both specialists and primary care) were sent updates of progress along with information on how to incorporate SDM into the visit. Implementation (feasibility, acceptability, and appropriateness) and clinical (asthma control, asthma quality of life, perceived control, depression, and self-confidence) outcomes were measured. RESULTS:SOAR was found to be feasible, acceptable, and appropriate, with values on validated implementation scales similar to those of in-person behavioral interventions. Asthma providers found the program helpful and intended to change care based on the updates. Asthma control scores improved significantly from baseline (14.2 to 16.8, p = 0.04), as did asthma quality of life (4.2 to 4.9, p = 0.03) and self-confidence to manage asthma (7.1 to 8.5, p = 0.02). There was no change in depression nor perceived control scores. CONCLUSION:A remote behavioral intervention appeared feasible and acceptable for OAA and their health care providers, and can improve outcomes. Larger scale implementation trials are warranted.