Thoughtful prescription of inhaled medication has the potential to reduce inhaler-related greenhouse gas emissions by 85.

Introduction: Both physicians and patients are increasingly aware of the environmental impacts of medication. The shift of treatment paradigm towards MART-treatment (Maintenance and Reliever Therapy) in asthma affects the treatment-related emissions. The carbon footprint of inhaled medication is also tied to the type of the device used.

A randomised phase 2a study to investigate the effects of blocking interleukin-33 with tozorakimab in patients hospitalised with COVID-19: ACCORD-2.

Background: Increased serum interleukin (IL)-33 predicts poor outcomes in patients hospitalised with coronavirus disease 2019 (COVID-19). We examined the efficacy and safety of tozorakimab, a monoclonal antibody that neutralises IL-33, in improving outcomes in ACCORD-2 (EudraCT: 2020-001736-95).

Methods: ACCORD-2 was an open-label, phase 2a study in adults hospitalised with COVID-19.

Blood transcriptomic signature in type-2 biomarker-low severe asthma and asthma control.

Background: Patients with type-2 (T2) cytokine-low severe asthma often have persistent symptoms despite suppression of T2 inflammation with corticosteroids.

Objectives: We sought to analyze whole blood transcriptome from 738 samples in T2-biomarker-high/-low patients with severe asthma to relate transcriptomic signatures to T2 biomarkers and asthma symptom scores.

Methods: Bulk RNA-seq data were generated for blood samples (baseline, week 24, week 48) from 301 participants recruited to a randomized clinical trial of corticosteroid optimization in severe asthma.

Inhaled nebulised unfractionated heparin (UFH) for the treatment of hospitalised patients with COVID-19: A randomised controlled pilot study.

There is a strong scientific rationale to use nebulised unfractionated heparin (UFH) in treating patients with COVID-19. This pilot study investigated whether nebulised UFH was safe and had any impact on mortality, length of hospitalisation and clinical progression, in the treatment of hospitalised patients with COVID-19. This parallel group, open label, randomised trial included adult patients with confirmed SARS-CoV-2 infection admitted to two hospitals in Brazil.

A Randomized Trial of a Composite T2-Biomarker Strategy Adjusting Corticosteroid Treatment in Severe Asthma: A Post Hoc Analysis by Sex.

Background: Approximately 5% to 10% of patients with asthma have severe disease, with a consistent preponderance in females. Current asthma guidelines recommend stepwise treatment to achieve symptom control with no differential treatment considerations for either sex.

Objective: To examine whether patient sex affects outcomes when using a composite T2-biomarker score to adjust corticosteroid (CS) treatment in patients with severe asthma compared with standard care.

Exacerbation Profile and Risk Factors in a Type-2-Low Enriched Severe Asthma Cohort: A Clinical Trial to Assess Asthma Exacerbation Phenotypes.

The past 25 years have seen huge progress in understanding of the pathobiology of type-2 (T2) asthma, identification of measurable biomarkers, and the emergence of novel monoclonal antibody treatments. Although present in a minority of patients with severe asthma, very little is known about the mechanisms underlying T2-low asthma, making it a significant unmet need in asthma research. The objective of this study was to explore the differences between study exacerbators and nonexacerbators, to describe physiological changes at exacerbation in those who are T2 and T2 at the time of exacerbation, and to evaluate the stability of inflammatory phenotypes when stable and at exacerbation.

Mortality after admission with pneumonia is higher than after admission with an exacerbation of COPD.

https://bit.ly/3LyhnnC

Effects of switching from a metered dose inhaler to a dry powder inhaler on climate emissions and asthma control: post-hoc analysis.

Objective: To compare the effects of switching from a pressurised metered dose inhaler (pMDI)-based to a dry powder inhaler (DPI)-based maintenance therapy versus continued usual care on greenhouse gas emissions (carbon dioxide equivalents, COe) and asthma control.

Methods: This post-hoc analysis was based on a subset of 2236 (53%) patients from the Salford Lung Study in Asthma who at baseline were using a pMDI-based controller therapy. During the study patients were randomised to fluticasone furoate/vilanterol (FF/VI) via the ELLIPTA DPI (switched from pMDI to DPI) (n=1081) or continued their usual care treatment (n=1155), and were managed in conditions close to everyday clinical practice.

The environmental impact of inhaled therapy: making informed treatment choices.

When selecting the best inhaler and drug combination for a patient with respiratory disease, a number of factors should be considered. While efficacy and safety of medical treatments are always a priority, in recent years the environmental impacts of all aspects of life have become an increasingly necessary consideration and inhaled therapies are no exception. The carbon footprint of an item, individual or organisation is one of the most important and quantifiable environmental impacts, assessed by the amount of greenhouse gases (often expressed in terms of carbon dioxide equivalents) generated throughout the life cycle.

The environmental impact of inhalers for asthma: A green challenge and a golden opportunity.

The propellants in metered-dose inhalers (MDIs) are powerful greenhouse gases, which account for approximately 13% of the NHS's carbon footprint related to the delivery of care. Most MDI use is in salbutamol relievers in patients with poorly controlled disease. The UK lags behind Europe in this regard, with greater reliance on salbutamol MDI and correspondingly greater greenhouse gas emissions, roughly treble that of our European neighbours.

Factors affecting adherence with treatment advice in a clinical trial of patients with severe asthma.

Background: Understanding why patients with severe asthma do not follow healthcare provider (HCP) advice to adjust treatment is critical to achieving personalised disease management.

Methods: We reviewed patient choice to follow HCP advice to adjust asthma treatment in a UK-based randomised, controlled, single-blind (study participant), multicentre, parallel group 48-week clinical study comparing biomarker-directed treatment adjustment with standard care in severe asthma.

Results: Of 1572 treatment advisories (291 participants), instructions were followed in 1377 cases (87.

A phase 2 multiple ascending dose study of the inhaled pan-JAK inhibitor nezulcitinib (TD-0903) in severe COVID-19.

https://bit.ly/35Xs1Rf

Safety data in randomised real-world evidence studies: Salford Lung Study learnings.

Evidence to support clinical decision making must be based on safety data that have been captured, analysed and interpreted in a robust and reliable way. Randomised real-world evidence (RRWE) studies provide the opportunity to evaluate the use of medicines in patients and settings representative of routine clinical practice. However, elements that underpin the design of RRWE studies can have a significant impact upon the analysis, interpretation and implications of safety data.

A Randomized Controlled Trial to Assess the Effect of Lidocaine Administered via Throat Spray and Nebulization in Patients with Refractory Chronic Cough.

Background: Refractory chronic cough (RCC) is a debilitating condition for which there are no licensed treatments. Lidocaine is a nonselective inhibitor of voltage-gated sodium channels with potential antitussive effects, but randomized placebo-controlled studies evaluating its efficacy in RCC are lacking.

Objective: To investigate the efficacy of nebulized lidocaine and lidocaine throat spray versus matched placebos in RCC.

Composite type-2 biomarker strategy versus a symptom-risk-based algorithm to adjust corticosteroid dose in patients with severe asthma: a multicentre, single-blind, parallel group, randomised controlled trial.

Background: Asthma treatment guidelines recommend increasing corticosteroid dose to control symptoms and reduce exacerbations. This approach is potentially flawed because symptomatic asthma can occur without corticosteroid responsive type-2 (T2)-driven eosinophilic inflammation, and inappropriately high-dose corticosteroid treatment might have little therapeutic benefit with increased risk of side-effects. We compared a biomarker strategy to adjust corticosteroid dose using a composite score of T2 biomarkers (fractional exhaled nitric oxide [FENO], blood eosinophils, and serum periostin) with a standardised symptom-risk-based algorithm (control).

The Effect of Pain Conditioning on Experimentally Evoked Cough: Evidence of Impaired Endogenous Inhibitory Control Mechanisms in Refractory Chronic Cough.

The pathophysiology of refractory chronic cough (RCC) is unclear. We hypothesised that endogenous inhibitory control mechanisms, such as those activated by noxiousstimuli inducing pain (conditioned pain modulation (CPM)), may be capable of inhibiting coughing and urge to cough evoked by inhaled capsaicin. Furthermore, these mechanisms may be impaired in patients with RCC.

Association of bacterial load in drinking water and allergic diseases in childhood.

Background: Treatment of drinking water may decrease microbial exposure.

Objective: To investigate whether bacterial load in drinking water is associated with altered risk of allergic diseases.

Methods: We recruited 1,110 schoolchildren aged 6-16 years between 2011 and 2013 in Požega-Slavonia County in Croatia, where we capitalized on a natural experiment whereby individuals receive drinking water through public mains supply or individual wells.

Impact of socioeconomic status on participation and outcomes in the Salford Lung Studies.

COPD and asthma prevalence is associated with socioeconomic status (or "deprivation"), yet deprivation is rarely considered in typical large-scale efficacy randomised controlled trials that recruit highly selected patient populations. In this analysis of the Salford Lung Studies in COPD and asthma (two 12-month, open-label, effectiveness randomised controlled trials conducted in UK primary care), we evaluated the impact of patient deprivation on clinical outcomes with initiating fluticasone furoate/vilanterol continuing usual care. Patients were categorised into deprivation quintiles based on postcode and a countrywide database of indices of deprivation, and trial outcomes by quintile were assessed.

Real-World Data and Randomised Controlled Trials: The Salford Lung Study.

Traditional efficacy double-blind randomised controlled trials (DBRCTs) measure the benefit a treatment produces under near-ideal test conditions in highly selected patient populations; however, the behaviour of patients and investigators in such trials is highly controlled, highly compliant and adherent, and non-representative of routine clinical practice. Pragmatic effectiveness trials measure the benefit a treatment produces in patients in everyday "real-world" practice. Ideally, effectiveness trials should recruit patients as similar as possible to those who will ultimately be prescribed the medicine, and create freedom within the study design to allow normal behaviours of patients and healthcare professionals (HCPs) to be expressed.