Dr Paul O'Byrne discussed new and emerging therapies for asthma.
The goals of asthma management are achieving current control and reducing future risk of exacerbations and loss of lung function (Canadian consensus guidelines for asthma management, Lougheed et Al Can Resp J 2012: 19: 127-64).
Canadian guidelines are the first to recommend following sputum eosinophilia to follow disease activity and control.
There several new monoclonal antibodies (mAb) under investigation for asthma, including molecules targeting IL-13, IL-5R, IL-4R and more.
Studies of monoclonal antibodies targeting Th2 pathways which don't identify the eosinophil phenotype have been consistently unsuccessful. Dr. Nair displayed a lengthy list of studies showing enhanced efficacy of biologic agents when patients are selected based on sputum phenotype. In contrast, those studies of monoclonal antibodies which do identify the eosinophil phenotype (even by OCS response) have typically been successful.
"Neutrophilic" sputum is often not a persistent phenotype. Neutrophilic asthma may not be a stable phenotype, it may be transient or variable phenomenon. The majority of patients with severe asthma have eosinophilic bronchitis.
The alternatives to manual sputum counts include blood biomarkers such as periostin and eosinophils, and also eosinophil proteins in sputum. There is a poor correlation between blood eosinophils and sputum eosinophils in severe asthmatics, unfortunately (Hastie 2013).
Lebrikizumab (anti-IL-13, binds to IL-4 subunit) in adults (Corren 2011) showed a modest increase in FEV1 in the high-periostin subgroup. Periostin is a biomarker for IL-13.
Tralokinumab is another anti-IL13 monoclonal antibody. It again performed better in patients with high IL-13 levels in induced sputum.
Dupilmab is an anti IL4 antibody (NEJM 2013).
Dupilumab (monoclonal against part of IL-4R) in persistent mod-severe asthma on ICS+LABA (Wenzel, NEJM 2013) was a proof of concept study. Dupilumab (anti-IL-4) used with SC weekly dosing in asthma showed effect in eosinophilic asthma. It improved symptoms, nocturnal waking, lung function, time to exacerbations, and inflammatory markers with eosinophilic asthma.
IMA-628 hMab is a humanized antibody that prevents binding to the IL-4R subunit. It blocked late phase asthmatic response.
Atropine was the first inhaled medication used for asthma, it was delivered in cigarette form! The anticholinergic tiotropium is clearly effective for patients with COPD, and is considered first line treatment. Tiotropium is a long acting anticholinergic agent used in COPD for years, it is a good bronchodilator, and improves exercise tolerance.
Tiotropium is superior to salmeterol as add-on therapy for adults with uncontrolled asthma (Peters 2010). Tiotropium was helpful in addition to combination ICS/LABA in adults with uncontrolled asthma (Kerstjens 2012).
Tiotropium is likely to be approved as third-line treatment for adults with asthma uncontrolled with ICS/LABA.
A new once a day LABA (vilanterol) paired with fluticasone is looking promising as well (Relovair ™).
Macrolides are studied for long term management of asthma Reiter published meta analysis showing improvement in symptoms but not lung function (2013). Azithromycin worked better in asthma patients with persistent neutrophils in induced sputum. Azithromycin was helpful in preventing exacerbations in noneosinophilic severe asthma (Brusselle 2013).
Pediatric asthma management
Dr. F Ducharme discussed controversies in pediatric asthma management.
Intermittent vs regular use of ICS
A meta-analysis of the RCTs compared intermittent vs regular use of ICS in children (Cochrane library 2012 CD009611) and included 4 trials, 828 kids, 498 preschoolers. Only one study used budesonide, the others used beclomethasone, and there were some dosing differences between BDP studies. The therapy was not really intermittent in most of the studies, more an evaluation of step-up treatment or increased ICS during exacerbations. Overall, there was no significant difference between maintenance and increased ICS with flares.
The @CochraneAirways meta-analysis of daily ICS vs intermittent ICS clearly favors daily ICS in pediatric asthma in all outcomes (increased asthma-free days and PEF, decreased rescue use and FeNO).
There is evidence that lung function loss in asthma may occur very early, and never fully recovers.
ICS and height
Growth suppression from ICS in kids is small but real (half inch shorter after budesonide 400 mcg in a 2013 NEJM study). Catch up occurs when ICS is stopped. Amount of suppression is molecule dependent.
There is a molecule-dependant impact of ICS on growth velocity, unclear if impacts final adult height.
There is evidence of catch-up growth in one study of inhaled fluticasone (Guilbert 2006) after 10 months despite continued ICS treatment.
Doubling vs. quadrupling ICS dose in asthma exacerbations
Another Cochrane meta-analysis of doubling ICS dose during exacerbations showed that it did not reduce need for oral steroids. A subgroup analysis of quadrupling ICS dose approached significant effect. Doubling the dose was not effective, a 4x increase 'might' be. However, Canadian asthma guidelines (2012) do not recommend 4x increase in ICS during exacerbations.
Studies showing lack of benefit to doubling ICS dose could well be due to lack of phenotyping.
Twitter summary made possible by @IgECPD @allergydoc4kidz @DrAnneEllis
Three allergists did a great job posting updates from the 2013 meeting of the Canadian Society of Allergy and Clinical Immunology (#CSACI): @IgECPD @allergydoc4kidz @DrAnneEllis. Compared to year 2011, this represents 300% growth in Twitter use by the Canadian allergists (from one to three participants, stable since 2012.
For comparison, here are the tweets from the previous #CSACI meetings: http://allergynotes.blogspot.com/search/label/CSACI
Sign up for 2014 #AAAAI Twitter list and meeting of tweeting allergists in real life (tweetup)
The AAAAI has the advantage of a larger membership base compared to #CSACI and not surprisingly ten times more allergists (30) posted Twitter updates from the 2012 #AAAAI meeting. The AAAAI is now on Twitter at @AAAAI_org
This is a list of the allergists who are planning to use Twitter to post updates from the 2014 #AAAAI meeting. The list is open for edit, please feel free to add your own info.
The list shows the availability of the allergists by date and if they are planning to attend a tweetup (meeting of people who use Twitter or are following the tweets). See you at 2014 #AAAAI meeting in sunny San Diego!
Comments from Twitter:
Dr John Weiner @AllergyNet: Just to emphasise that this summary by @DrVes of #CSACI meeting tweets on asthma is really excellent bit.ly/1acKJDf
Dr. Ellis @DrAnneEllis: @DrVes Thanks so much for your summaries of #CSACI. Will be live tweeting #ACAAI again this year as well next month :)