Search

Asthma and obesity are both complex conditions characterized by chronic inflammation, and obesity-related severe asthma has been associated with differences in the microbiome. However, whether the airway microbiome and microbiota-immune response relationships differ between obese persons with or without non-severe asthma is unestablished.To compare the airway microbiome and microbiota-immune mediator relationships between obese and non-obese subjects, with and without mild-moderate asthma.We performed cross-sectional analyses of the airway (induced sputum) microbiome and cytokine profiles from blood and sputum, employing 16S rRNA gene and ITS region sequencing to profile bacteria and fungi, and multiplex immunoassays. Analysis tools included QIIME2, linear discriminant analysis effect size (LEfSe), Piphillin, and SParse InversE Covariance Estimation for Ecological Association Inference (SPIEC-EASI).Obesity, irrespective of asthma status, was associated with significant differences in sputum bacterial community structure and composition (unweighted Unifrac PERMANOVA, p=0.02), including a higher relative abundance of Prevotella, Gemella, and Streptococcus species. Among asthmatic subjects, additional differences in sputum bacterial composition and fungal richness were identified between obese and non-obese individuals. Correlation network analyses demonstrated differences between obese and non-obese asthma in relationships between cytokine mediators, and these together with specific airway bacteria, involving blood PAI-1, sputum IL1-β, GM-CSF, IL-8, TNF-α, and several Prevotella species.Obesity itself is associated with an altered sputum microbiome, which further differs in those with mild-moderate asthma. The distinct differences in airway microbiota and immune marker relationships in obese asthma suggest potential involvement of airway microbes that may impact mechanisms or outcomes of obese asthma.

To describe clinical outcomes in patients with severe asthma (SA) by common sociodemographic determinants of health: sex, race, ethnicity, and age.CHRONICLE is an observational study of subspecialist-treated, United States adults with SA receiving biologic therapy, maintenance systemic corticosteroids, or uncontrolled by high-dosage inhaled corticosteroids with additional controllers. For patients enrolled between February 2018 and February 2020, clinical characteristics and asthma outcomes were assessed by sex, race, ethnicity, age at enrollment, and age at diagnosis. Treating subspecialists reported exacerbations, exacerbation-related emergency department visits, and asthma hospitalizations from 12 months before enrollment through the latest data collection. Patients completed the St. George's Respiratory Questionnaire and the Asthma Control Test at enrollment.Among 1884 enrolled patients, the majority were female (69%), reported White race (75%), non-Hispanic ethnicity (69%), and were diagnosed with asthma as adults (60%). Female, Black, Hispanic, and younger patients experienced higher annualized rates of exacerbations that were statistically significant compared with male, White, non-Hispanic, and older patients, respectively. Black, Hispanic, and younger patients also experienced higher rates of asthma hospitalizations. Female and Black patients exhibited poorer symptom control and poorer health-related quality of life.In this contemporary, real-world cohort of subspecialist-treated adults with SA, female sex, Black race, Hispanic ethnicity, and younger age were important determinants of health, potentially attributable to physiologic and social factors. Knowledge of these disparities in SA disease burden among subspecialist-treated patients may help optimize care for all patients.Supplemental data for this article is available online at at www.tandfonline.com/ijas .

Njira Lugogo,1 Bradley E Chipps,2 Reynold A Panettieri Jr,3 Frank Trudo,4 Christopher S Ambrose5 1University of Michigan, Ann Arbor, MI, USA; 2Capital Allergy & Respiratory Disease Center, Sacramento, CA, USA; 3Rutgers, The State University of New Jersey, New Brunswick, NJ, USA; 4AstraZeneca, Wilmington, DE, USA; 5AstraZeneca, Gaithersburg, MD, USACorrespondence: Christopher S Ambrose, BioPharmaceuticals Medical, AstraZeneca, One MedImmune Way, Gaithersburg, MD, 20878, USA, Tel +1 301-398-4454, Email chris.ambrose@astrazeneca.comAbstract: There is growing recognition of the adverse consequences of maintenance systemic corticosteroid (mSCS) therapy in severe asthma (SA). The objective of this study was to describe the prevalence of potential adverse effects of long-term mSCS therapy in adults with specialist-confirmed SA in the United States (US). CHRONICLE is an ongoing, noninterventional, observational study of US adults with SA treated by allergists/immunologists and pulmonologists. Once enrolled, patients’ duration of mSCS therapy was reported by sites based on medical record review. For patients enrolled between February 2018 and February 2021, the prevalence of SCS-associated conditions was evaluated among those with no reported history of mSCS use, or mSCS use with < 2 years or ≥ 2 years cumulative duration. Prevalence and incidence estimates were adjusted for age and smoking history. Of 2793 patients enrolled, 311 and 231 had mSCS use for < 2 and ≥ 2 years, respectively. In adjusted analyses, adrenal insufficiency, pneumonia, type 2 diabetes, osteoporosis/osteopenia, congestive heart failure, coronary artery disease, hypertension, anxiety, and depression were statistically significantly associated with any mSCS use. By duration, mSCS use ≥ 2 years was associated with osteopenia/osteoporosis, coronary artery disease, adrenal insufficiency, and diabetes-related neuropathy; mSCS use < 2 years was associated with depression and osteopenia/osteoporosis, and diagnoses of depression, anxiety, and hypertension during the 12 months prior to enrollment. Overall, among patients with specialist-confirmed SA, mSCS use was associated with a high prevalence of multiple adverse conditions. Healthcare professionals should employ mSCS-sparing treatment strategies to avoid these negative consequences.Keywords: duration, steroids, diabetes, pneumonia, osteoporosis

Asthma remains a substantial health burden, despite continued treatment advances. Patients with mild or moderate asthma, even those with intermittent symptoms, are at risk for severe or fatal exacerbations. Use of short-acting beta2-agonist (SABA)-only rescue therapy is associated with an increased risk of exacerbations, beginning at about the second fill annually. Systemic corticosteroids have shortterm and long-term adverse effects, and long-term adverse effects are driven by cumulative lifetime doses starting at 0.5 to 1.0 g. Expert opinion on the use of SABA only for rescue therapy differs, but recent evidence suggests that a fast-acting bronchodilator combined with inhaled corticosteroids (ICS) is more effective at reducing the risk of exacerbations than SABA alone. There is a window of opportunity just prior to an asthma exacerbation during which use of fast-acting bronchodilator + ICS may play a significant role in mitigating the risk of exacerbation. Patients may respond better to a combination inhaler of a fast-acting bronchodilator and an ICS as needed for rescue therapy or as part of a maintenance and rescue therapy paradigm, rather than attempting to use separate inhalers. However, there is currently no fixed-dose, fast-acting bronchodilator + ICS approved in the United States for as-needed use.

Multiple biologics are now available for severe asthma (SA) treatment and can improve outcomes for patients. However, few available data describe the real-world use and effectiveness of multiple approved biologics, including biologic switching, among subspecialists in the United States.To evaluate biologic use and associated exacerbation outcomes in a large cohort of subspecialist-treated US adults with SA.CHRONICLE is an ongoing, noninterventional study of subspecialist-treated US adults with SA receiving biologics, maintenance systemic corticosteroids, or those persistently uncontrolled by high-dose inhaled corticosteroids with additional controllers. For enrolled patients, sites report asthma exacerbations and medication use starting 12 months before enrollment. For patients enrolled between February 2018 and February 2021, biologic use and exacerbation outcomes before and after biologic initiation are described.Among 2793 enrolled patients, 66% (n = 1832) were receiving biologics. The most used biologic (gt; 1 biologic use per patient allowed) was omalizumab (47%), followed by benralizumab (27%), mepolizumab (26%), dupilumab (18%), and reslizumab (3%). Overall, 16% of patients had biologic switches, 13% had stops, and 89% had ongoing biologic use. Patients starting and switching biologics experienced a 58% (1.80 vs 0.76 per patient-year) and 49% (1.47 vs 0.75 per patient-year) reduction in exacerbations, respectively (both Plt; .001), with a numerically greater reduction observed among those starting non-anti-immunoglobulin E biologics compared with anti-immunoglobulin E.Real-world starting and switching of biologic therapies for SA were associated with meaningful reductions in exacerbations. With increasing biologic options available, individualized approaches to therapy may improve patient outcomes.ClinicalTrials.gov identifier: NCT03373045.

Several chronic conditions have been associated with a higher risk of severe coronavirus disease 2019 (COVID-19), including asthma. However, there are conflicting conclusions regarding risk of severe disease in this population.To understand the impact of asthma on COVID-19 outcomes in a cohort of hospitalized patients and whether there is any association between asthma severity and worse outcomes.We identified hospitalized patients with COVID-19 with confirmatory polymerase chain reaction testing with (n = 183) and without asthma (n = 1319) using International Classification of Diseases, Tenth Revision, codes between March 1 and December 30, 2020. We determined asthma maintenance medications, pulmonary function tests, highest historical absolute eosinophil count, and immunoglobulin E. Primary outcomes included death, mechanical ventilation, intensive care unit (ICU) admission, and ICU and hospital length of stay. Analysis was adjusted for demographics, comorbidities, smoking status, and timing of illness in the pandemic.In unadjusted analyses, we found no difference in our primary outcomes between patients with asthma and patients without asthma. However, in adjusted analyses, patients with asthma were more likely to have mechanical ventilation (odds ratio, 1.58; 95% confidence interval [CI], 1.02-2.44; P = .04), ICU admission (odds ratio, 1.58; 95% CI, 1.09-2.29; P = .02), longer hospital length of stay (risk ratio, 1.30; 95% CI, 1.09-1.55; P.003), and higher mortality (hazard ratio, 1.53; 95% CI, 1.01-2.33; P = .04) compared with the non-asthma cohort. Inhaled corticosteroid use and eosinophilic phenotype were not associated with considerabledifferences. Interestingly, patients with moderate asthma had worse outcomes whereas patients with severe asthma did not.Asthma was associated with severe COVID-19 after controlling for other factors.

RationaleProgressive lung function (LF) decline in patients with asthma contributes to worse outcomes. Asthma exacerbations are thought to contribute to this decline; however, evidence is limited with mixed results.MethodsThis historical cohort study of a broad asthma patient population in the Optimum Patient Care Research Database, examined asthma patients with 3+eligible post-18th birthday peak expiratory flow rate (PEF) records (primary analysis) or records of forced expiratory flow in 1 s (FEV1) (sensitivity analysis). Adjusted linear growth models tested the association between mean annual exacerbation rate (AER) and LF trajectory.ResultsWe studied 1 09 182 patients with follow-up ranging from 5 to 50 years, of which 75 280 had data for all variables included in the adjusted analyses. For each additional exacerbation, an estimated additional −1.34 L/min PEF per year (95% CI −1.23 to –1.50) were lost. Patients with AERs >2/year and aged 18–24 years at baseline lost an additional −5.95 L/min PEF/year (95% CI −8.63 to –3.28) compared with those with AER 0. These differences in the rate of LF decline between AER groups became progressively smaller as age at baseline increased. The results using FEV1 were consistent with the above.ConclusionTo our knowledge, this study is the largest nationwide cohort of its kind and demonstrates that asthma exacerbations are associated with faster LF decline. This was more prominent in younger patients but was evident in older patients when it was related to lower starting LF, suggesting a persistent deteriorating phenotype that develops in adulthood over time. Earlier intervention with appropriate management in younger patients with asthma could be of value to prevent excessive LF decline.