Asthma Management Guidelines

Benjamin D. Francisco, PhD, PNP, AE-C Professor, Pulmonary Medicine & Allergy University of Missouri School of Medicine, Department of Child Health

In December of 2020, the National Heart, Lung and Blood Institute published updates to 2007 Expert Panel Report 3 (EPR-3) asthma guidelines (https://www.nhlbi.nih.gov/health-topics/ guidelines-for-diagnosis-management-of-asthma). Rather than issuing an entirely new set of guidelines, the committee identified six topics for which new evidence warranted critical reviews. Updated topics include: 1) use inhaled corticosteroids for intermittent or worsening asthma symptoms; 2) sublingual and subcutaneous immunotherapy; 3) modification of indoor trigger exposure; 4) longacting muscarinic antagonists; 5) use of fractional exhaled nitric oxide (FeNO) in asthma management; and 6) bronchial thermoplasty. The greatest change comes in revised therapy steps for the treatment of asthma. For ready access to documents that will be useful in your practice go to: https://www.nhlbi.nih.gov/health-topics/ asthma-management-guidelines-2020-updates/digital-toolkit. The “Clinician’s Guide” is a readable 16 page synopsis of the 19 recommendations contained in the 2020 Updates, including the new therapy steps. “At-a Glance” guide only includes tables with annotations for the 6 therapy steps by age group (0-4, 5-11, 12 and older). You will probably want to print this document for quick reference when prescribing. Another useful resource found at the digital toolkit URL above is a set of fact sheets that summarize the 2020 Updates in language patients and staff will be able to understand. A brief overview of the 2020 Updates is discussed below in order of topics most likely to redefine best asthma practices. Italicized text indicates a direct quote from the 2020 Updates.

One of the most debated aspects of asthma care is when and how to use inhaled corticosteroids (ICS). Advocates for intermittent ICS use have previously lacked support from expert guidelines. A related polarizing discussion has been the effectiveness of increasing ICS dose when asthma is not controlled. The 2020 Updates recommend intermittent ICS use for two age groups, 0-4 years and 12 years and older, under specific conditions.

• In children ages 0-4 years with recurrent wheezing, a short (7-10 day) course of daily inhaled corticosteroids along with an as-needed short-acting bronchodilator (such as albuterol sulfate) is recommended at the start of a respiratory tract infection (conditional recommendation, high certainty of evidence).

• People ages 12 and older with mild persistent asthma may benefit from inhaled corticosteroids with a short-acting bronchodilator for quick relief. Treatment may include inhaled corticosteroids daily or as needed when asthma gets worse (conditional recommendation, moderate certainly of evidence).

Stepping up ICS dose during times when symptoms are present (loss of control) is recommended for ages 4 and older with moderate to severe asthma only when an ICS/formoterol inhaler is in use.

• For people ages 4 and older with moderate to severe persistent asthma, the preferred treatment is a single inhaler that contains an inhaled corticosteroid and the bronchodilator formoterol. This should be used as both a daily asthma controller and quick-relief therapy (Strong recommendation, high certainty of evidence for individuals 12 years and older, moderate certainty of evidence for individuals 4-11 years)

Herein lies the most consequential change in asthma treatment dubbed the SMART plan. Single Maintenance and Reliever Therapy (SMART) is an approach whereby the same inhaler used for daily therapy can be used for additional doses when symptoms are present (Bisgaard, Le Roux et al. 2006). This is a departure from the traditional two inhaler strategy – one for control and another for quick relief (usually albuterol). SMART is recommended based on well-designed clinical trials over the last decade that compared outcomes for three treatment arms: 1) SMART plan (using an inhaler containing an ICS with formoterol), 2) fixed dose ICS/LABA group and 3) an ICS only treatment group. The SMART group had fewer asthma exacerbations, used less ICS over months and grew better. It is important to note only formoterol was studied in these trials. The SMART recommendation does not apply to ICS/LABA inhalers containing other LABAs, such as salmeterol. Currently in the US one generic and two branded ICS/formoterol inhalers are available: budesonide/formoterol, also branded as Symbicort™ and Dulera™ (mometasone and formoterol). Practical considerations for adopting a SMART plan for appropriate patients include insurance restrictions, out of pocket costs and access. When a one puff twice daily regimen is appropriate and effective these barriers are minimized. Since available ICS/formoterol MDI inhalers are dispensed with 120 usable puffs, with a one puff twice daily regimen an inhaler should last 2 months in the absence of the need to take PRN doses. During periods of breakthrough symptoms taking additional puffs would probably not exhaust supply for the month’s regular BID regimen. It is important to state the PRN regimen on the prescription to avoid denials for a one per month supply. However, with a 2 puff BID regimen more than one inhaler will be required monthly if the patient is perfectly adherent and has symptomatic days requiring extra doses. Pharmacists and insurers have had mixed responses to SMART plans, as might be expected during early adoption. Some insurers have authorized more than one ICS/formoterol inhaler per month, while others respond with denials. Meanwhile using higher ICS formulations with a one puff twice daily regimen is expedient and has the result of lowering total out of pocket costs for many families. Access is an issue when the ICS/formoterol inhaler remains at home and the patient is at school or work. Transporting the ICS/formoterol inhaler might predispose to temperature extremes that can degrade the drugs and forgetting to return home with the inhaler for routine evening and morning doses.

In summary, formoterol has an onset of action similar to albuterol with fewer adrenergic effects and potentially much longer duration of action, making this drug suitable for symptom relief. When an ICS is combined with formoterol and the SMART plan is used by patients, symptoms are managed while simultaneously stepping up the ICS dose and delivering an anti-inflammatory boost that likely addresses an underlying airway provocation. For safety with this “sliding scale” approach, maximum daily doses of ICS/formoterol must be specified – up to 8 puffs per day for patients 4-11 years of age and up to 12 puffs per day for 12 years and older were found to be safe and effective. It is important to also note the number of days this approach may be used before prompting a call for follow-up at the clinic. High numbers of daily doses are not intended for weeks of use. Alternative diagnoses and treatments must be considered when episodes are prolonged.

Another important change in asthma therapy steps is the use of long-acting muscarinic antagonists (LAMA). Whereas ipratropium has long been an important medication in asthma management (Rodrigo and Castro-Rodriguez 2005) expert guidelines did not previously recommend use of more recently available LAMAs. Four recommendations in the 2020 Focused Update address use of LAMAs:

• If inhaled corticosteroids alone do not control asthma, a health care provider may add a long-acting bronchodilator such as a long-acting beta2-agonist (LABA) or LAMA.

• For children under 12 and most people ages 12 and older with asthma that is not controlled by an inhaled corticosteroid alone, adding a LABA rather than a LAMA to an inhaled corticosteroid is preferred (conditional recommendation, moderate certainly of evidence).

• For people 12 years old and older, if a LABA cannot be used, a LAMA may be used with inhaled corticosteroid treatment instead of continuing the inhaled corticosteroid alone (conditional recommendation, moderate certainly of evidence).

• For people 12 years old and older whose asthma is not controlled with an inhaled corticosteroid plus a LABA, adding a LAMA is recommended (conditional recommendation, moderate certainly of evidence).

An important consideration when applying these recommendations is the cost and inhaler types of LAMAcontaining medications. Currently, these are only available in Respimat (a soft mist inhaler - SMI) or dry power inhalers (DPI). A major challenge in asthma care is promoting good inhalation technique so patients actually inhale aerosol droplets or particles deeply into the lungs and fully benefit from the medication. Mixing inhaler types introduces the high likelihood that patients will not practice optimal inhalation technique. For example, a patient using albuterol MDI (SABA), Breo Elipta DPI (ICS and LABA) and Spiriva Respimat SMI (LAMA) would have to learn three different inhaler techniques. If an ICS/LABA/LAMA DPI is used by a patient, a DPI albuterol would likely be the best choice to keep the inhaler type and inhalation technique consistently DPI.

Another controversial aspect of asthma care has been the role of immunotherapy. Two recommendations address this topic:

• Allergy shots, known as subcutaneous immunotherapy, are recommended for people who have allergic asthma and whose symptoms worsen after exposure to certain allergens (conditional recommendation, moderate certainly of evidence).

• Sublingual immunotherapy, which involves placing liquid drops or tablets containing allergens under your tongue, is not recommended for the treatment of allergic asthma (conditional recommendation, moderate certainly of evidence).

These recommendations seem to limit and focus the role of immunotherapy in asthma treatment. Subcutaneous immunotherapy (SCIT) is recommended for allergic asthma when there is an historical relationship between exposure and worsening symptoms, not merely because sensitivity to aeroallergens has been demonstrated by prick testing or Immunocaps. Sublingual immunotherapy (SLIT) is not recommended for treatment of allergic asthma.

A related topic is the role of environmental abatement in the home and school as a primary approach to reduce the expression of asthma and need for therapeutics. The following recommendations emphasize a multicomponent approach when there is known sensitization to specific perennial allergens.

• For people with asthma who are sensitive to indoor substances (such as house dust mites), using multiple strategies to reduce the allergen is recommended (such as air purifiers, HEPA vacuum cleaners, and pillow and mattress covers that prevent dust mites from going through them). Using only one strategy often does not improve asthma outcomes (conditional recommendation, moderate certainly of evidence).

• Integrated pest management is recommended for those who are allergic and exposed to cockroaches, mice, or rats (conditional recommendation, low certainly of evidence)

• These strategies are not recommended for people who are not allergic to indoor substances (conditional recommendation, low certainly of evidence).

Use of fractional expired nitric oxide in the management of asthma has remained controversial despite this technology becoming widely available and less expensive. The 2020 Focused Updates include two related recommendations:

• FeNO testing in individuals ages 5 and older is recommended when either the diagnosis or the approach to therapy is uncertain (conditional recommendation, moderate certainly of evidence).

• FeNO testing should not be used alone to assess asthma control or predict the course of the ailment. In children ages 4 years and younger who have recurrent episodes of wheezing, FeNO measurement does not reliably predict the future development of asthma (strong recommendation, low certainly of evidence).

These recommendations seem unlikely to significantly change clinical practice. Repeated measures over time of forced expiratory volume in one second (FEV1) for adults, FEV1 percent predicted for growing children (5 years and older) or complete spirometry remain the gold standard for objective assessment of asthma (Global Lung Initiative reference values for FEV1 available at http://gligastransfer.org.au/calcs/spiro.html ).

Finally, the emergence of bronchial thermoplasty warranted a critical review and the following recommendations:

• Most individuals ages 18 years and older with uncontrolled, moderate to severe persistent asthma should not undergo bronchial thermoplasty because the benefits are small, the risks are moderate, and the long-term outcomes are uncertain (conditional recommendation, low certainly of evidence).

• Some individuals with moderate to severe persistent asthma who have troublesome symptoms may be willing to accept the risks of bronchial thermoplasty and, therefore, might choose this intervention after shared decision making with their health care provider (conditional recommendation, low certainly of evidence).

References found on page 31.