Dr. Ellis @DrAnneEllis Professor Stephen Holgate - Asthma - Inflammation is the Symptom not the Cause.
Epithelial injury and airway remodeling are a common feature of even mild asthma.
Beyond allergen exposure, there are many other environmental factors contributing to airway inflammation in asthma - air pollution (especially diesel exhaust) tops the list. Air pollution now accepted as a causal factor in asthma development, symptoms and mortality. Ambient black carbon particles reach the fetal side of the human placenta.
Holgate: the asthmatic epithelium behaves like a non-healing wound.
Gene signatures from the airways of "wheezers" vs non atopic control show predominant presence of Type 2 inflammation pathways as well as repair molecules.
Targeting alarmins such as TSLP, IL25 and 33 may be the future as you are striking at the "top of the chain" rather than all the downstream effects.
Kevin Parks MD @kparksmd Stephen Holgate MD on asthma: the airway epithelium is damaged by irritants, infections, and allergens - suggesting that epithelial targets may be a more optimistic therapeutic paradigm in asthma. Holgate making a good case for epithelium as a cause.
Dr. Ellis @DrAnneEllis Starting off the day with my favorite speaker ever. Dr. Paul O'Byrne - Dean of
@MacHealthSci and asthma expert and scholar and gentleman!
Drs Hurd and Lenfant founded GINA - 25 years ago- A strategy document, not a guideline - meant to be used anywhere in the world.
GINA describes the control-based asthma management cycle - Diagnosis first - must confirm it is actually asthma one is trying to treat.
GINA describes asthma management from Step 1 to 5 - Step 1 and 2 are the biggest group of patients who can/should be managed by primary care.
The biggest problem with Asthma management? Despite the safety of inhaled corticosteroids, adherence to therapy is abysmal - 40% of patients in one study never filled more than one refill of the ICS/LABA there were given.
Short acting beta agonists (SABAs) are the most widely used asthma medication worldwide - despite the fact that SABAs have been shown to worsen asthma control, enhance EIB, promote airway inflammation and overuse is associated with increased mortality.
SYMGA trials, published in @NEJM aimed to show the efficacy and safety of using an ICS paired with a fast acting LABA - to be used on an add needed basis.
Regular use of budesonide led to more well controlled asthma weeks compared to PRN Symbicort - but adherence in the trial was 80% - not real world experience. No difference in exacerbations between PRN Symbicort and regular budesonide. More important finding IMO!
Michael R. Rupp, MD @Docallergy Study showed that at 1 year patients with moderate asthma less than 10% filled Rx as directed. ADHERENCE IS KEY!
Dr. Ellis @DrAnneEllis Benefit in Asthma exacerbation risk for PRN Symbicort was seen with an 83% reduction in steroid exposure.
Patients in SYGMA 1 used, typically, 1 dose of reliever every 2 weeks - almost no one used the maximum 8 inhalations per day. Not a single patient who used 8 inhalations of Symbicort per day went on to have a severe exacerbation compared to 9% of patients using the same amount of SABA.
The PRACTICAL study from New Zealand completely mirrored the results of the SYGMA2 Study (but was government funded rather than via @AstraZenecaCA). Exacerbations were significantly reduced by PRN Symbicort.
These trials led to GINA making one of the largest changes in their recommendations. As needed low dose ICS/formoterol now the prefered reliever medication for asthma - across all Steps - not just mild/moderate.
Implications for practice - Adherence to maintenance therapy is poor, overuse of SABAs worsen most asthma outcomes, Symbicort 80 mcg reliever therapy that contains an ICS is superior to SABAs for all asthma outcomes. Off label in USA.