As part of our ongoing seminar series, the Centre of Excellence in Severe Asthma hosted Prof. Charles Irvin, for a webinar on “Physiological Phenotyping of Airways Responsiveness in Asthma” on 04 May 2017.
Presentation Summary:
Asthma leads to variable airflow obstruction and airway hyperresponsiveness. The processes that cause these changes are complex. Processes also vary between people. As a result, a one-size-fits all treatment approach is unlikely to be successful.
Prof. Irvin presents findings from a range of clinical trials. Findings highlight differences in response to therapy. In part, differences are explained by patient characteristics. For example, race, body mass and smoking status all effect treatment response.
Lung function assessments also demonstrate differences between people with asthma. In some patients, airway hyperresponsiveness is caused by airway narrowing. However, in other patients reduced lung function results from airway closure.
Differences between patients result from different disease processes. These differences have implications on our understanding of asthma pathogenesis and on treatment strategies.
Key Points:
- Historically, asthma was thought to be a neural disorder triggering muscle bronchospasm in the lungs
- Current hypotheses suggest a key role for inflammation in asthma pathophysiology
- Asthma pathophysiology is very complex, involving a range of cells types and mediators
- Inflammation is highly variable within and between individuals with asthma
- Disease severity and duration are likely to have effects of lung function
- Therapy must be personalised and targeted to the active disease processes in the individual patient
- In a trial of influenza vaccine safety in children and adults with asthma, vaccination had no effect on asthma exacerbation rates compared to control
- However, exacerbation rates were very high (~30% of patients over 2-weeks)
- In a trial of theophylline and montelukast, both therapies were effective only in patients not already taking inhaled corticosteroids (ICS) therapy
- Patient characteristics predicted response to treatment (montelukast effective in Caucasian populations; theophylline in African-Americans, people with low BMI and smokers)
- Obese patients with asthma had worse exacerbations after theophylline treatment, suggesting different disease processes in this population
- Obesity has effects on lung function
- Increased BMI is associated with increased airway hyperreactivity in obese asthmatics
- Weight loss following bariatric surgery improved airway hyperresponsiveness, but changes were highly variable between patients
- Different phenotypes are observed in lung function assessments
- Airway hyperreactivity is associated with airway narrowing in some patients, while airway closure occurs in others
- Airway closure is prevalent in asthma populations and associated with slightly reduced lung function, across a range of clinical trials
- Rates of airway closure are increased in obese individuals
- Treating patients with a “one-size-fits all” approach frequently does not work
- Detailed patient phenotyping is required to inform the use of targeted therapy
About Prof. Charles Irvin:
Prof. Charles Irvin is Director of the Vermont Lung Center and Professor of Medicine; Molecular Physiology & Biophysics at the University of Vermont. His scientific career has focused on understanding the mechanisms of airways dysfunction of the patient with asthma.
Using a multidisciplinary approach including: cell and molecular biology, animal models and systems, transgenic models, physiology, imaging and clinical trial studies, he and his colleagues are attempting to understand the pathophysiological basis of asthma in order to both better diagnose and treat asthma patients.
He has trained 20+ postdoctoral fellows and mentored numerous junior faculty, the vast majority now successfully engaged in research careers.
Prof. Irvin’s travel was supported by AstraZeneca.
