New US asthma guidelines

 New, but limited, US asthma guidelines were just published (see asthma guidelines 2020 jama2020 in dropbox, or doi:10.1001/jama.2020.21974)

 

Details: 

-- an expert panel of 19 people reviewed 475 references, updating six specific areas where they felt there was new information, but not 11 additional topics because they felt there was insufficient new information to update.

-- asthma exacerbations were defined as needing systemic corticosteroid use or having asthma-specific emergency department visits or hospitalizations 

-- this review focused those at least 12 years old 

 

Recommendations (for full list, see their figure): 

-- step 1 therapy (intermittent asthma): continue with as-needed short acting beta agonists (SABAs) 

-- step 2 therapy (mild persistent asthma): either daily low-dose inhaled corticosteroids (ICS) plus as-needed SABA therapy or an as-needed concomitant ICS plus SABA therapy 

    -- they did not include a review of as-needed ICS-formoterol, as recommended in the 2019 and 2020 GINA guidelines (Global Initiative for Asthma):  noting this “was not addressed in this update because this therapy was not included in the key questions formulated for the update” 

    -- in individuals with mild to moderate persistent asthma, they recommend against short-term increases in ICS doses, from individuals age 4 or older 

-- step 3 therapy (moderate persistent asthma): low-dose ICS-formoterol, as a Single Maintenance inhaler And Reliever Therapy (SMART), strong recommendation. Can also consider daily low-dose ICS plus a long-acting muscarinic antagonist (LAMA) and as-needed SABA (though elsewhere in the article they suggest adding a LABA over adding a LAMA for improved control, based on one study) 

    --SMART therapy should be limited to a maximum of 12 total puffs per day 

-- step 4 therapy: ICS-formoterol, both daily and as-needed (SMART), with alternative being daily medium-dose ICS plus LABA and as-needed SABA [note: SMART does NOT include LABAs with slower onset, such as salmeterol.  the only one tested in studies with short onset of action if formoterol. but, vilanterol is probably fine by its pharmacokinetics, per https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3085864/#:~:text=Vilanterol%20has%20a%20greater%20intrinsic,potency%20than%20indacaterol%20and%20salbutamol.&text=In%20human%20tissue%20pre%2Dconstricted,et%20al.%2C%202010b).)

    -- short-term increase in ICS dose alone for worsening asthma is not recommended 

-- step 5 therapy (moderate-severe persistent asthma): daily medium to high dose ICS-LABA plus adding a LAMA. Alternative would be daily high dose ICS-LABA and as-needed SABA; or high dose ICS plus montelukast plus as-needed SABA. If still not respond well, add systemic steroids. SMART was not included in the studies of these severe asthmatics, so no inclusion here for the update 

    -- note, LAMAs are not indicated for acute control in the emergency room setting but for long-term asthma control 

-- fractional exhaled nitric oxide testing (FeNO) is recommended to assist in diagnosis and monitoring of symptoms but not alone to diagnose or monitor asthma. FeNO is a biomarker of eosinophilic inflammation in the airway 

    -- of note, FeNO is not diagnostic of asthma, but is an adjunct to the diagnosis (asthma diagnosis largely reflects symptom and clinical course, as well as spirometry with bronchodilators)

    -- and, it should not be used in isolation to monitor asthma disease severity or to predict future exacerbations or assess exacerbation severity 

-- allergen mitigation is recommended only in individuals with exposure and relative sensitivity or symptoms; this should be allergen-specific and include multiple allergen-specific mitigation strategies 

-- subcutaneous immunotherapy is recommended as an adjunct to standard pharmacotherapy for individuals with mild to moderate allergic asthma who have symptoms and sensitization to specific allergens

    -- all patient should be assessed for exposure to allergens at home and at work, for symptoms on exposure, and if present, then for sensitization either by allergy skin testing or allergen-specific IgE 

-- sublingual immunotherapy is not recommended specifically for asthma

-- bronchial thermoplasty is not recommended as part of standard care 

 

Commentary: 

-- finally, an update of the US guidelines of 2007!!!

-- the US guidelines differed from the GINA guidelines in several respects (see GINA guidelines: http://gmodestmedblogs.blogspot.com/2019/10/new-and-improved-asthma-guidelines.html  )

    -- the US guidelines continue to use the category of intermittent asthma; GINA eliminated that because they felt that it did not reflect the fact that "intermittent" asthma sounded too mild and conceptually undercut the very real possibility of severe asthma exacerbations 

    -- the US guidelines continue to rely on short acting beta agonists (SABAs), which was dismissed in the GINA guidelines 

        -- of note, a recent sub study of the SYGMA trial found that even a single day of budesonide/formoterol vs a SABA in those with mild asthma decreased severe asthma exacerbations for the next 21 days as well as the use of oral steroids: see http://gmodestmedblogs.blogspot.com/2020/11/asthma-single-day-of.html

    -- the GINA guidelines reinforce the importance of assessing inhaler technique (these types of issues were not addressed in the US guidelines because the panel did not have were no specific questions related to this)

    -- GINA also considered sublingual allergen immunotherapy as an option when patients are symptomatic on low-dose ICS, have allergic rhinitis, are sensitized to house dust mites, and have an FEV1>70% of predicted 

    -- the US guidelines do note that studies with SMART therapy were based on the ICS primarily being budesonide or beclomethasone. Though their recommendations are just for an "ICS". It should be noted that budesonide and beclomethasone are the least absorbed systemically, and (in my humble opinion) are preferred over, for example, fluticasone (though specific studies of the relative actual clinical effects of comparing the different ICSs are lacking) 

-- also, by the way, the 2020 GINA update does suggest avoiding using nebulizers, where possible, since they may disseminate Coronavirus to other patients and health care professionals. "Pressurized metered dose inhalers via spacer is preferred for severe exacerbations, with a mouthpiece or tightly fitting face mask if required". also avoid doing spirometry for the same reason

--as noted in the enlightened editorial of the US guidelines, there have been two additional studies after the SYGMA studies, the PRACTICAL and the Novel START trials, finding in one study that in patients with intermittent to moderate persistent asthma and in the other study that in patients with intermittent to mild persistent asthma, as-needed budesonide-formoterol decreased severe exacerbations versus daily maintenance budesonide plus as-needed SABA (for editorial, see https://jamanetwork.com/journals/jama/fullarticle/2773481 ). The editorial is also noted that a recent article did demonstrate potential benefit of house dust mite sublingual immunotherapy

Limitations: 

-- though this was an extensive review, literature searches were only done until March /April 2017 with an update through October 2018 

-- they only evaluated six specific questions, elaborated in the supplementary material: the utility of FeNO measurements, allergen mitigation, ICS (specifically the effectiveness of intermittent versus controller ICS therapy, the comparative effectiveness of ICS/LABA as both controller and quick relief therapy impaired to ICS with or without LABA), LAMA effectiveness as add-on therapy, immunotherapy, bronchial thermoplasty) 

    -- this was not a complete overhaul of the asthma recommendations, only these six questions were addressed 

-- several of the studies used for these recommendations had limitations, including many where validated outcomes were not measured. In addition, several of the studies had small sample size and incomplete characterization of the patients involved. These decreased the level of certainty of several of the recommendations.

-- The guidelines were limited to individuals at least 12 years old, unlike the GINA guidelines, so still left with the 2007 guidelines for younger people (though the GINA guidelines do include younger ones)

so, this update does represent very significant changes since the 2007 guidelines, but a few comments:

-- i personally like the general approach of GINA over these US guidelines:

    -- i really agree with dropping the "intermittent" label, since it does underemphasize the potentially severe asthma exacerbations, both in the minds of patients and perhaps many clinicians.  mild asthma is still pretty frequently associated with bad exacerbations, and should be considered an important diagnosis and treated aggressively (ie, with real reinforcement that exacerbations need to be identified early and treated aggressively to avoid problems. esp with budesonide-formoterol, per the study noted above)

    -- i really think that the accumulating data on prn budesonide-formoterol is really impressive in those with mild asthma. and the SYGMA studies do suggest strongly that this inhaler used as-needed leads to better outcomes with less total exposure to inhaled ICSs

    -- there is a real concern that i have faced many times that insurers are many times reluctant to cover budesonide-formoterol as an inhaler (htough, i have been successful in many of these patients to prescribe mometasone-formoterol). And, insurers do not seem to like the concept of paying for more than one inhaler/month.  Maybe these new US guidelines will change that???

geoff

 

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