Journal Club

Kowal et al. in Scandinavian Journal of Immunology

Link: Click here

Presenter: Ms. Natalie Niessen

Alterations in circulating monocyte surface molecule expression were assessed following allergen challenge. CD14++CD16+ monocytes were increased in responders at baseline and levels correlated with airway hyperresonsiveness. Allergen challenge reduced numbers of CD14++CD16+ monocytes.

Hunt et al. in CHEST

Link: Click here

Presenter: Dr. Michael Ramsahai

No differences were detected between pepsin levels and disease severity, asthma control, FEV1 or exacerbation frequency. ”The importance of aspiration on current asthma symptom control and exacerbation rate may be overstated.”

Smargiassi et al. in Environmental Health Perspectives

Link: Click here

Presenter: Dr. Ben Ewald

Earlier studies indicated that living near petroleum refineries resulted in increased rate of hospitalisations for respiratory symptoms, in Montreal Canada. Risks of asthma emergency department visits and hospitalisations were associated with peak sulfur dioxide levels in children in the current study.

Von Bulow et al. in Respiratory Medicine

Link: Click here

Presenter: Dr. Sarah Hiles

Systematic assessment is critical for the diagnosis of severe asthma and identification of patients eligible for targeted therapy. However, the level of diagnostic assessment performed in respiratory clinics in “the real world” remains unclear. In a retrospective, cross-sectional multicenter study in Dnemark, researchers report on assessment of 98 patients with severe asthma. A designation of severe asthma was determined by medication prescriptions. Only 54% of patients had their diagnosis confirmed objectively. Further, only 23% had a bronchial challenge test performed. Inhalation technique was assessed in 19% and adherence was confirmed in 31%. Overall, these findings indicate relatively low rates of objective assessment in a specialist setting.

Del Giacco et al. in Respiratory Medicine

Link: Click here

Presenter: Dr. Vanessa Clark

A significant association exists between anxiety and asthma, although the nature of this association remains unclear. In this study, the authors assessed asthma and mental disorders in a cohort of 96 adults with asthma, compared to control subjects. The identify a significant association between asthma and lifetime anxiety, which were associated with asthma severity (based on asthma control. Interestingly, anxiety preceded asthma in ~50% of cases, while asthma preceded anxiety in ~50% of cases, indicating a potential bidirectional relationship.

Kuo et al. in the European Respiratory Journal

Link: Click here

Presenter: Dr. Steven Maltby

We discussed a recent analysis of sputum cell transcriptomics in individuals with moderate-to-severe asthma, from the U-BIOPRED cohort. This study provided interesting insights into possible mechanistic pathways underlying disease. It identified a cohort of patients with activation of the well-studied Th2 pathway. Interestingly, the data suggested that individuals lacking Th2 pathway activation fell into two separate groups. These groups appear to have activation of pathways involved in either systemic inflammation, innate immunity and inflammasome activation or alteration of metabolic and mitochondrial pathways. These findings provide interesting insights into non-Th2 asthma, where few targeted therapeutic strategies are currently available.

We discussed presentations from the 2017 Keystone Symposium on Asthma. Key themes covered included novel epithelial and sputum gene signatures, approaches to transcriptomic analysis in asthma, mast cell gene signatures and obesity and asthma.

Andrezza Franca-Pinot et al. in Thorax

Link: Click here

Presenter: Ms. Laura Cordova Rivera

We discussed a recent clinical trial which assessed the benefits of aerobic training on features of asthma. After a 12-week program, participants had improvement in lung hyper-responsiveness, quality of life measures, exacerbations and reduced levels of some inflammatory proteins. These studies suggest a benefit of adding exercise to drug therapy in the management of moderate to severe asthma.

Eugene R Bleecker et al in Lancet

Link: Click here

Presenter: Dr. Erin Harvey

We discussed a recent clinical trial that assessed the efficacy of benralizumab (an anti-IL-5 receptor-alpha) antibody therapy for the treatment of severe asthma. A total of 1205 participants were assessed, with 798 receiving the trial drug. Treatment reduced asthma exacerbations and improved lung function (pre-bronchodilator FEV1). The treatment was also well tolerated. This study provided further evidence for the utility and safety of benralizumab, for individuals with severe asthma and increased blood eosinophil numbers.

Akke-Nynke van der Meer et al in the European Respiratory Journal

Link: Click here

Presenter: Prof. Vanessa McDonald

We discussed a recent publication that assessed the efficacy of a one-time evaluation in a severe asthma clinic on disease outcomes in a severe asthma population. After completing a 1-day assessment programme, patients were returned to standard care and followed for 1 year. This approach improved asthma control (ACQ), quality of life (AQLQ) and reduced healthcare usage (exacerbations, emergency room visits and hospitalization).

Sherif Gonem et al. Lancet Respiratory Medicine

Link: Click here

Presenter: John Harrington

We discussed a recent trial assessing the effects of fevipiprant, a new drug, on severe asthma. The trial was conducted at Glenfield Hospital (Leicester, UK). Fevipiprant is a new drug that blocks prostaglandin D2 receptor 2, which is predicted to reduce eosinophil activation and production of “Type-2” cytokines. Treatment reduced eosinophil numbers and had favorable safety. This report provides preliminary data on fevipiprant effects and supports future studies into the potential improvements in asthma symptoms.

Link: Click here

Presenter: Dr Vanessa Clark

We discussed a recent study on the impacts of a systematic assessment in severe asthma management. Data was from the United Kingdom Difficult Asthma Services. The authors demonstrated that systematic assessment significantly reduced health-care usage and hospital admissions. Further, this approach improved quality of life and asthma symptom control. The findings suggest that a systematic assessment approach could provide significant benefits for individuals with severe asthma.

Joan Sweeney et al. Thorax

Link: Click here

Presenter: Dr Steven Maltby

We discussed a recent analysis of steroid-associated comorbidity in individuals with severe asthma and the impact on health. The assessment made use of two different patient databases to determine whether steroid use was connected with increased risk of developing these conditions. The first analysis demonstrated increased risk of steroid-associated comorbidities in people with severe asthma (and steroid therapy), compared to healthy controls or participants with mild asthma. The second analysis demonstrated increased rates of comorbidity in individuals with severe asthma on regular steroid therapy, versus those with severe asthma but no steroids. Together, these analyses demonstrate an increased disease burden following steroid therapy and highlight the importance of developing new “steroid-sparing” therapies.

Alvar Agusti et al. European Respiratory Journal

Link: Click here

Presenter: Dr Krystelle Godbout

We discussed a novel, “label-free” strategy for the management of chronic airway diseases based on the identification of treatable traits. Treatable traits are recognisable features or diseases that contribute to airway disease symptoms, exacerbations or prognosis. They can be a characteristic of the airway disease itself or a comorbidity, risk factor or behavioral issue. Patients are first categorized as having a high or low probability of airway disease based on clinical evaluation, spirometry, FeNO and blood eosinophils. Then, treatable traits are identified and targeted separately by an appropriate therapy. This strategy aims at achieving individualized medicine, but is currently mostly hypothetical. Future research will help clarify its relevance and practicality in clinical practice.

Sally Wenzel et al. 2016. The Lancet

Link: Click here

Presenter: Dr Michael Fricker

We discussed results from a recent Phase 2b trial of dupilumab (an IL-4 receptor inhibiting antibody), as an add-on therapy in asthmatics with uncontrolled moderate-to-severe disease. Dupilumab targets a specific branch of the immune system, termed type 2 immunity, which contributes to disease in asthma, eczema and nasal polyposis. This trial reported findings from 750 patients (half of which were diagnosed with severe asthma) and concluded that dupilumab provides significant therapeutic benefits, by reducing exacerbation rates and improving lung function, asthma control and patient quality of life. These results provide support for dupilumab as a novel therapy for severe asthma and a further Phase 3 is now underway to assess efficacy in larger populations and support drug approval application.