severe asthma treatment

new guidelines (they just keep comin'...), this time on defn, eval and treatment of severe asthma (see asthma severe treatment euro resp j 2014, or DOI: 10.1183/09031936.002020), put out by combo of european respiratory society and american thoracic society. main points:

definition: severe asthma (approx 5-10% of asthmatics) = asthma requiring high dose inhaled steroids (ICS) plus second controller (eg ICS plus long-acting b-agaonist (LABA) or leukotriene modifier/theophylline) for the past year and/or systemic steroids (>50% of the time in the past year) to control, or remains uncontrolled despite this therapy (uncontrolled = poor symptom control, or >=2 bursts of systemic steroids in past yr, or at least one hospitalization in past yr, or FEV1<80% after appropriate bronchodilator withhold.  only after confirm asthma dx -- see evaluation section

[there is an extensive section on phenotyping asthmatic kids and adults, which seems to reflect age of onset, gender, severity, proneness to exacerbation, and presents some data on differentiating different phenotypes (eg, whether there is an inflam response, and if so, presence of eosinophils or neutrophils), and some info on different genetics (eg IL4 or IL6 pathways and receptors)/epigenetics.   pretty interesting stuff, which reinforces that asthma is a myriad of different conditions lumped together, and that this knowledge may ultimately determine different treatment approaches.  but, will leave this for you to pursue in the document, if interested]

evaluation: 

    1. make sure it is asthma (misdiagnosis as uncontrolled asthma found in 12-30%). evaluate sx, triggers, environmental/occup factors. one of common misdiagnoses is respiratory sx related to obesity. they have a table (Table 6) of diseases that can masquerade as asthma in kids (eg, vocal cord dysfunction, bronchiolitis, reflux/microaspiration, foreign body, etc), and in adults (vocal cord dysfunction, copd, panic attacks, chf, etc). pfts with and without bronchodilators (esp after withholding b-agonists) needed for diagnosis. they do recommend that a high resolution chest CT be done in kids and adults with severe asthma and atypical asthma presentation, eg rapid decline in lung function, lots of mucous, etc (low quality evidence).

    2. assess comorbidities: nonadherence to rx is most common (32-56%) as cause of "severe asthma", but comorbidities can make asthma worse (eg, rhinosinusitis, nasal polyps, obesity, smoking, OSA, aspirin, anxiety/depression, etc). GERD is included in list, though role is probably over-rated and anti-reflux rx not help so much.

    3. there are some broad phenotypic aspects that can help. for example, those with early-onset allergic phenotype (may respond to anti-IL5 or anti-IL13 therapies), later onset obese phenotype (responds to weight loss more than obese, early onset asthma), late onset eosinophilic phenotype. they have a table (Table 9) with specifically targeted, mostly monoclonal antibody therapies for different phenotypes)

therapy:

    1. there is often a relative ICS insensitivity, such that oral steroids are needed regularly (or IM triamcinolone), though there is less asthma responsiveness in those with obesity, smoking, low vitamin D levels, and non-eosinophilic (esp, it seems, in those with neutrophilic) asthma. there are some novel drugs in the wings for those with corticosteroid insensitivity

    2. there are some people who do respond to high-dose ICS (eg fluticasone 500 mcg in kids, or >500 mcg in adults -- their table 4 has the list), though in pts with moderate asthma, increasing to these doses is not effective

    3. adding LABA to ICS is helpful, and is often more helpful than increasing ICS in patients with moderate asthma (those with severe asthma should already be on high dose ICS). i have sent out prior studies showing that African-Americans in general are more likely to be resistant to the effects of b-agonists (short or long-acting), perhaps related to b-adrenoreceptor genotypes. anticholinergics (eg, ipratropium, tiotropium), though usually less helpful than b-agonists, may be very useful in people resistant to b-agonists, and can be added to ICS and LABA.

    4. low dose theophylline can help (this sort of fell off the charts several years ago, was revived some with the COPD/GOLD guidelines, and i have found that it helps some people a lot, both with asthma and COPD)

    5. they recommend treatment guided by clinical symptoms, though recommend sputum eosinophil counts done in experienced centers is helpful in adults (low quality evidence) but not in kids. they recommend against using FeNO (exhaled nitric oxide fraction) measurements. consider omalizumab in adults and kids (low qual evidence) if severe allergic (IgE-dependent) asthma, if not controlled on regular meds.  not use methotrexate, macrolide antibiotics (in spite of recent study in NEJM on azithromycin). only use antifungals if documented allergic bronchopulmonary aspergillosis (low quality evidence). bronchial thermoplasty may be useful (low quality evidence) in specialized sites. no suggestions about cromoglycates (cromolyn).

so, adds a little to the current approach. highlights importance of accurate diagnosis, including PFTs, and the approach to asthmatic phenotypes, which reinforces the conception of asthma as a variety of unrelated diseases with common clinical presentation, is useful and is opening the door to more specific targeted therapies.