Assessment of Consistency of Fixed Airflow Obstruction Status during Budesonide/Formoterol Treatment and Its Effects on Treatment Outcomes in Patients with Asthma

BackgroundThe consistency of fixed airflow limitation status during treatment in patients with asthma is unknown.ObjectiveThe objective of this study was to determine the consistency of fixed airflow obstruction (FAO) status during treatment and effects on treatment response.MethodsThis post hoc analysis from a 12-week study (NCT00652002) assessed patients aged 12 years or more with moderate-to-severe asthma randomized to twice-daily budesonide/formoterol (BUD/FM) via pressurized metered-dose inhaler (pMDI) 320/9 μg, BUD pMDI 320 μg, FM 9 μg via dry-powder inhaler, or placebo. FAO status was assessed postbronchodilator at screening and after study drug administration at weeks 2, 6, and 12 via the forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) ratio < lower limit of normal (LLN) (FAO+) or ≥ LLN (FAO−). Patients with persistent FAO− and FAO+ retained their screening FAO status at all visits. Patients with inconsistent FAO changed categories at least once during the study. Assessments included early withdrawal due to predefined worsening asthma events (PAEs), lung function, and symptoms.ResultsOf 386 patients, 29% had persistent FAO+, 31% inconsistent FAO, and 40% persistent FAO−. PAEs were lowest in the FAO− group overall and with BUD/FM treatment in patients with FAO+ and inconsistent FAO. Baseline demographics and treatment responses of the inconsistent FAO group were most similar to the FAO+ group. The greatest improvements in asthma control days and use of rescue medications were seen with BUD/FM treatment, regardless of FAO status.ConclusionsApproximately one third of patients with moderate-to-severe asthma in this study had inconsistent FAO, and their treatment responses were most similar to patients with FAO+. Regardless of FAO status, patients treated with BUD/FM experienced the most improved treatment responses and fewest withdrawals due to PAEs

Benefit of switching to mepolizumab from omalizumab in severe eosinophilic asthma based on patient characteristics

Asma; Tractament de l'asma; EosinòfilsAsma; Tratamiento del asma; EosinófilosAsthma; Asthma treatment; EosinophilsBackground The OSMO study assessed the efficacy of switching to mepolizumab in patients with severe eosinophilic asthma that was uncontrolled whilst receiving omalizumab. The objective of this analysis was to assess the proportion of patients achieving pre-defined improvements in up to four efficacy outcomes and the relationship between patient baseline characteristics and treatment response. Methods This was a post hoc analysis of OSMO study data (GSK ID:204471; ClinicalTrials.gov No. NCT02654145). Patients with severe eosinophilic asthma uncontrolled by high-dose inhaled corticosteroids, other controller(s) and omalizumab subcutaneously (≥ 4 months) were switched to mepolizumab 100 mg administered subcutaneously. Endpoints included the proportion of responders—i.e. patients achieving a pre-defined clinical improvement in ≥ 1 of the following outcomes: (1) Asthma Control Questionnaire (ACQ)-5 score (≥ 0.5-points), (2) St George’s Respiratory Questionnaire (SGRQ) total score (≥ 4-points), (3) pre-bronchodilator forced expiratory volume in 1s (FEV1; ≥ 100 mL), all at Week 32, and (4) annualised rate of clinically significant exacerbations (≥ 50% reduction). Results Of the 145 patients included, 94%, 83%, 63% and 31% were responders for ≥ 1, ≥ 2, ≥ 3 and 4 outcomes, respectively; 75% and 78% were ACQ-5 and SGRQ score responders, and 50% and 69% were FEV1 and exacerbation responders. Subgroup analyses demonstrated improvements irrespective of baseline blood eosinophil count, prior omalizumab treatment regimen/duration, comorbidities, prior exacerbation history, maintenance oral corticosteroid use, ACQ-5 and SGRQ scores, and body weight/body mass index. Conclusions After switching to mepolizumab, almost all patients with uncontrolled severe eosinophilic asthma on omalizumab achieved a beneficial response in ≥ 1 clinical outcome. Improvements were observed regardless of baseline characteristics.This post hoc analysis and the parent study (GSK ID: 204471; ClinicalTrials.gov number: NCT02654145) were funded by GSK

Assessment of asthma control and asthma exacerbations in the epidemiology and natural history of asthma: outcomes and treatment regimens (TENOR) observational cohort

Patients with severe or difficult-to-treat asthma account for substantial asthma morbidity, mortality, and healthcare burden despite comprising only a small proportion of the total asthma population. TENOR, a multicenter, observational, prospective cohort study was initiated in 2001. It enrolled 4,756 adults, adolescents and children with severe or difficult-to-treat asthma who were followed semi-annually and annually for three years, enabling insight to be gained into this understudied population. A broad range of demographic, clinical, and patient self-reported assessments were completed during the follow-up period. Here, we present key findings from the TENOR registry in relation to asthma control and exacerbations, including the identification of specific subgroups found to be at particularly high-risk. Identification of the factors and subgroups associated with poor asthma control and increased risk of exacerbations can help physicians design individual asthma management, and improve asthma-related health outcomes for these patients

Catching Element Formation In The Act

Gamma-ray astronomy explores the most energetic photons in nature to address some of the most pressing puzzles in contemporary astrophysics. It encompasses a wide range of objects and phenomena: stars, supernovae, novae, neutron stars, stellar-mass black holes, nucleosynthesis, the interstellar medium, cosmic rays and relativistic-particle acceleration, and the evolution of galaxies. MeV gamma-rays provide a unique probe of nuclear processes in astronomy, directly measuring radioactive decay, nuclear de-excitation, and positron annihilation. The substantial information carried by gamma-ray photons allows us to see deeper into these objects, the bulk of the power is often emitted at gamma-ray energies, and radioactivity provides a natural physical clock that adds unique information. New science will be driven by time-domain population studies at gamma-ray energies. This science is enabled by next-generation gamma-ray instruments with one to two orders of magnitude better sensitivity, larger sky coverage, and faster cadence than all previous gamma-ray instruments. This transformative capability permits: (a) the accurate identification of the gamma-ray emitting objects and correlations with observations taken at other wavelengths and with other messengers; (b) construction of new gamma-ray maps of the Milky Way and other nearby galaxies where extended regions are distinguished from point sources; and (c) considerable serendipitous science of scarce events -- nearby neutron star mergers, for example. Advances in technology push the performance of new gamma-ray instruments to address a wide set of astrophysical questions.Comment: 14 pages including 3 figure

A Review of the Role of Inhaled Corticosteroids in the Treatment of Acute Asthma A Review of the Role of Inhaled Corticosteroids in the Treatment of Acute Asthma

Summary: Systemic corticosteroids (CSs) are generally accepted as treatment for acute exacerbations of asthma. In contrast, inhaled corticosteroids (ICs) have been used for the long-term management of asthma but are not widely accepted for the treatment of asthma exacerbations. The onset of action of ICs in acute asthma begins in 1 hour. In patients with mild to moderate exacerbation, administration of high-dose ICs may decrease the need for hospital admission and the number of symptomatic days

Oral corticosteroid-sparing effects of inhaled corticosteroids in the treatment of persistent and acute asthma.

OBJECTIVE: To review the efficacy and safety of inhaled corticosteroids (ICSs) when used to reduce daily oral corticosteroid (OCS) requirements in patients with severe persistent asthma and periodic requirements in patients with acute asthma exacerbations. DATA SOURCES: Clinical studies of the OCS-sparing effects of ICSs were located by searching MEDLINE databases from 1966 onward using the terms oral, steroid, and asthma in combination with the generic names for each marketed ICS. STUDY SELECTION: Studies reporting on the use of ICSs to reduce OCS requirements in patients with persistent and acute asthma are included. RESULTS: Clinical study results consistently show that ICSs significantly improve asthma control and reduce OCS requirements among adults, children, and infants with persistent asthma. A dose reduction or complete discontinuation of use of OCSs is possible in most patients without loss of asthma control. ICSs also can control asthma during acute asthma exacerbations and reduce the need for short courses of OCSs. With many ICSs, the reductions in OCS use are accompanied by recovery of hypothalamic-pituitary-adrenal axis function, indicating that the safety of asthma therapy is improved when OCS requirements are decreased with ICSs. Of the available ICSs that may reduce OCS needs, budesonide appears to be the most intensively studied. CONCLUSIONS: ICSs can reduce OCS requirements in adults and children with persistent asthma and during acute asthma exacerbations. The reduced systemic corticosteroid activity associated with ICS treatment improves the overall safety of asthma therapy

Efficacy and safety of as-needed albuterol/budesonide versus albuterol in adults and children aged ≥4 years with moderate-to-severe asthma: rationale and design of the randomised, double-blind, active-controlled MANDALA study

Introduction: Uncontrolled asthma is associated with substantial morbidity. While fast-acting bronchodilators provide quick relief from asthma symptoms, their use as rescue fails to address the underlying inflammation. Combining a short-acting beta2-agonist, such as albuterol (salbutamol), with an inhaled corticosteroid, such as budesonide, in a single inhaler as rescue therapy could help control both bronchoconstriction and inflammation, and reduce the risk of asthma exacerbations. Methods and analysis: The Phase 3 MANDALA study was designed to determine the efficacy of albuterol in combination with budesonide (albuterol/budesonide 180/160 µg or 180/80 µg, two actuations of 90/80 µg or 90/40 µg, respectively) versus albuterol (180 µg, two actuations of 90 µg) as rescue therapy in adult, adolescent and paediatric patients with moderate-to-severe asthma. This event-driven study enrolled symptomatic patients (3000 adults/adolescents and 100 children aged 4-11 years) who experienced ≥1 severe asthma exacerbation in the previous year and were receiving maintenance therapy for ≥3 months prior to study entry. The primary efficacy endpoint was time-to-first severe asthma exacerbation. Ethics and dissemination: The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use and Good Clinical Practice and the applicable regulatory requirements