Budesonide/Formoterol or Budesonide/Albuterol as Anti-Inflammatory Reliever Therapy for Asthma.

Overuse of reliever as short-acting beta-agonist and associated underuse of controller as inhaled corticosteroid (ICS) administered via separate inhalers results in worse asthma outcomes. Such discordance can be obviated by combining both controller and reliever in the same inhaler. So-called anti-inflammatory reliever (AIR) therapy comprises the use of a single inhaler containing an ICS such as budesonide (BUD) in conjunction with a reliever as either albuterol (ALB) or formoterol (FORM), to be used on demand, with variable dosing driven by asthma symptoms in a flexible patient-centered regimen. Global guidelines now support the use of BUD-ALB as AIR therapy to reduce exacerbations, either on its own in mild asthma or in conjunction with fixed-dose maintenance ICS-long-acting beta-agonist in moderate to severe asthma. Using BUD-FORM on its own allows patients to seamlessly move in an intuitive flexible fashion between AIR and maintenance and reliever therapy, by stepping up and down the dosing escalator across a spectrum of asthma severities. Head-to-head clinical studies are indicated to compare BUD-FORM versus BUD-ALB as AIR in mild asthma, and also BUD-FORM as maintenance and reliever therapy versus BUD-ALB as AIR plus maintenance ICS-long-acting beta-agonist in moderate to severe asthma. Patients should be encouraged to make an informed decision in conjunction with their health care professional regarding the best therapeutic option tailored to their individual needs, which in turn is likely to result in long-term compliance and associated optimal asthma control.

Should Airway Hyper-Responsiveness Be Included in the Definition of Clinical Remission With Biologic Therapy in Severe Asthma.

Airway hyper-responsiveness (AHR) is a tenet of the persistent asthma phenotype along with reversible airway obstruction and type 2 (T2) inflammation. Indirect acting challenges such as mannitol are more closely related to the underlying T2 inflammatory process as compared with direct challenges. In this review article, we summarise the current literature and explore the future role of mannitol AHR in clinical remission with biologics.

Randomized controlled trial of triple versus dual inhaler therapy on small airways in smoking asthmatics.

BACKGROUND: Smoking worsens underlying asthma inflammation and also induces resistance to inhaled corticosteroids (ICS). Small airways dysfunction measured by impulse oscillometry (IOS) is associated with worse control. OBJECTIVES: We investigated the effects on small airways of adding long-acting beta-agonist (LABA) alone or with long-acting muscarinic antagonist (LAMA) to ICS in asthmatic smokers. METHODS: Sixteen current smokers were enrolled: mean age 44 year, FEV1 84%, FEF25-75 47%, R5 158%, ACQ 1.69, 20 pack year . Patients were converted to a reference ICS as HFA-BDP during initial run-in at median dose of 800 µg/day. Open label olodaterol 5 µg od (OLO) or olodaterol 5 µg/tiotropium 5 µg od (OLO/TIO) was added to HFA-BDP for median duration of 3 weeks in a randomized cross over design, including run-in and washout periods on HFA-BDP. IOS and spirometry were measured after each treatment (BDP/OLO/TIO or BDP/OLO) and at baseline after run-in and washout (BDP). RESULTS: After chronic dosing, IOS outcomes at trough except for R20 were all significantly improved with OLO/TIO compared to OLO. For the primary end-point of total airway resistance (as R5), the mean difference (95%CI) at trough was 0.06 (0.015-0.10) kPa/l/s, peripheral airways resistance (as R5-R20) 0.03 (0.003-0.06) kPa/l/s, peripheral lung reactance area (as AX) 0.38 (0.08-0.68) kPa/l and resonant frequency (as RF) 2.28 (0.45-4.12) Hz. FEF25-75 at trough was also better with OLO/TIO vs TIO: 0.93 (0.86 - 0.95) l/s while FEV1 was not different. CONCLUSIONS: ICS/LABA/LAMA was superior to ICS/LABA on trough small airway outcomes in asthma patients who smoke.

Emerging pharmacotherapy for COVID-19.

Broadly speaking, pharmacological treatments for COVID-19 can be divided into those acting on upstream pathways early on in the disease process via suppression of viral replication or by inhibiting cell entry, and those acting on downstream pathways later on via selective attenuation of the adaptive immune cytokine-mediated inflammatory response. The antiviral drug remdesivir has been shown to shorten duration of disease while interferon beta-1b may speed up viral clearance. The results with hydroxychloroquine have thus far been rather disappointing. Trials with selective cytokine blockers including anti-interleukin-1 (anti-IL-1) and anti-interleukin-6 (anti-IL-6), have shown some promise in more severe cases, with further confirmation being required from large-scale phase-3 randomised controlled trials. The likelihood is that combination therapy addressing both upstream and downstream pathways may be required to prevent progression of severe COVID-19 infection in susceptible older patients with comorbidities and we believe further studies are now warranted to specifically target such at-risk groups who are more prone to worse outcomes.