Asthma: Outpatient Management

Background 

Asthma is an immune-mediated, inflammatory disease characterized by intermittent and reversible lower airway obstruction due to smooth muscle constriction and airway narrowing. 

Current immunological theory is that early-life exposures may shape the development of a child’s immune system to favor either a Th-1(non-allergic) or Th-2 (allergic) lymphocyte predominance. 

Once a child is sensitized, an exposure will cause the airways to release mediators that damage the epithelium. 

Th2 lymphocytes trigger the release of cytokines (IL-4, IL-5, IL-9, 1L-10, IL-13) → stimulate IgE production, mast cells, basophils, and eosinophils → mediate inflammation via histamine, prostaglandins, and leukotrienes. 

Triggers

A broad range of triggers has been identified that can make asthma worse. Trigger exposure may occur on a chronic or episodic basis. Identifying and avoiding asthma triggers is essential to preventing asthma flare-ups.

• Respiratory viruses (most common trigger in children)
• Irritants: 
  • Burned substances: tobacco smoke, marijuana, candles, incense, wood/charcoal fires
  • Air pollution 
  • Chemicals in some cleaning products
  • Particles in the air (construction sites, perfumes, paints, soaps)
• Allergens:
  • Perennial allergens: mold spores, cockroaches, rodents, dust mites, pet dander
  • Seasonal allergens: tree, weed, and grass pollens
• Weather (rapid changes in temperature, extreme hot or extreme cold)
• Strong emotions (laughing, crying, anger)
• Exercise (rare, and likely over-diagnosed; exercise-induced symptoms are more suggestive of poorly-controlled asthma) 

Perennial allergens tend to particularly affect health disparities in inner city populations.

Diagnosis

A diagnosis of asthma is largely clinical!

• Diagnosis is based on recurrence and patterns of symptoms (wheeze, cough, post-tussive emesis, shortness of breath, night-time waking, chest tightness)
  • Cannot diagnose asthma with first episode of cough or wheeze
  • Need to ask how often symptoms are occurring and under what circumstances

“Not all that wheezes is asthma”

• ⅓ of toddlers will wheeze at some point, but only 40% go on to develop asthma
• Other causes of wheezing: viral infections, foreign bodies, anatomic abnormalities

No specific age cut-off for asthma diagnosis!

• Need to be able to establish a pattern of recurrent respiratory symptoms over time; difficult to do in a very young child

Things that increase likelihood of asthma: 

• Family history of asthma or atopy (allergic rhinitis, atopic dermatitis, food allergy)
• Personal history of atopic dermatitis, food or environmental allergies
  • Food allergy = risk for more severe, life-threatening asthma
• Symptoms responsive to short-acting beta agonist (SABA)

Pulmonary Function Tests (PFTs)

• Diagnostic confirmation of asthma:
  • Demonstration of variable expiratory airflow limitation (variable obstruction)
  • Documentation of reversible obstruction with bronchodilators
• Spirometry generally used for children over 5-6 years of age, adolescents, and adults 
• Per GINA guidelines, we should check PFTs before treating for asthma whenever possible, as it is more difficult to make the diagnosis after treatment is initiated  

PFTs in Asthma:

• Important numbers to look for in suspected asthma: 
  • FEV1: total volume of air a patient is able to exhale in the first second during maximal effort
  • FVC: total volume of air a patient is able to exhale during maximal effort
  • FEV1/FVC = proportion of forced vital capacity that can be expired in 1 second
• Demonstration of variable expiratory airflow limitation (obstructive defect):
  • FEV1 <80% predicted
  • Low FEV1/FVC ratio (<70% predicted for adults, <85% predicted for patients 5-18 years-old)
  • Predicted value based on age, sex, height, and race?!
  • “Variability” can be demonstrated at different visits, in home monitoring, etc.
• Documentation of reversible obstruction with bronchodilators: 
  • Spirometry should be performed before and after administration of a bronchodilator
  • Reversible = Increase in FEV1 or FVC ≥12% from baseline
• Flow volume loops: 

Other Tests: 

• Impulse oscillometry
  • Allows for passive measurement of lung function
  • Good for young kids (<5yo) who are less able to participate in spirometry (generally available in pulmonology offices)
• Methacholine challenge
  • Used for bronchial provocation (creates airway hyperresponsiveness)
  • Not commonly used in children; typically used in adults when there are clinical features suggestive of asthma but spirometry is normal or no significant response to asthma medications
  • Sensitive, but not specific (can also be seen with allergic rhinitis, CF, COPD, and BPD)

Predictive Indices: 

• Asthma Predictive Index (API) and Modified API
  • Applied to children 3 years and younger with wheezing episodes
  • Helps determines likelihood of a patient going on to develop childhood asthma
  • Specificity is good, but not sensitivity (might miss some children that will develop asthma); however, the negative predictive value is high

• Pediatric Asthma Risk Score (PARS)
  • Positive predictive value of 67% and a negative predictive value of 76%

Assessing Severity

Assessing asthma severity differs by guideline:

• NAEPP (2007): <4yo, 5-11yo, ≥12yo
• GINA (2021): “Asthma severity is assessed retrospectively, after at least 2-3 months of treatment, from the level of treatment required to control symptoms and exacerbations. It is important to distinguish between severe asthma and asthma that is uncontrolled.”

In general, before starting a controller medication, asthma severity can be assessed by the following questions:

• How often do you wake at night due to breathing difficulty?
• How often do you need to use albuterol as a rescue inhaler? (Prior to exercise to prevent onset of symptoms does not count)
• Interfering with normal activity?
• How often many times in the last year have you had an exacerbation requiring oral steroids?

After treatment initiation, we can ask these same questions to assess control. 

Once on medications, we determine severity by medication type and dose required for control. 

Outpatient Management

The goal of asthma therapy is to suppress the inflammatory cascade from the top down, starting with avoidance of precipitants, then an anti-inflammatory medication (typically an inhaled corticosteroid) to reduce downstream reactivity. 

In this way, optimizing care should start at the most fundamental level—avoidance of precipitants and non-pharmacologic methods prior to initiating/escalating pharmacotherapy.

• A key step in pharmacotherapy is assessing adherence and reviewing the proper technique of inhalers. 

Global Initiative for Asthma (GINA) 

Landmark changes in asthma management! 

For safety, GINA no longer recommends SABA-only treatment in adults or adolescents: 

• “There is a lack of evidence for the safety or efficacy of SABA-only treatment. Historic recommendations for SABA-only treatment were based on the assumption that patients with mild asthma would not benefit from ICS.” (2021 guideline, page 63)
• “Although inhaled SABAs are highly effective for the quick relief of asthma symptoms, patients whose asthma is treated with SABA alone (compared with ICS) are at increased-risk of asthma-related death (Evidence A) and urgent asthma-related healthcare (Evidence A), even if they have good symptom control. The risk of asthma exacerbations and mortality increases incrementally with higher SABA use, including in patients treated with SABA alone. One long-term study of regular SABA in patients with newly diagnosed asthma showed worse outcomes and lower lung function than in patients who were treated with daily low dose ICS from the start.” (2021 guideline, page 64)

GINA recommends that ALL adults and adolescents with asthma should receive ICS-containing controller treatment. 

• ICS may be regular daily treatment, or as-needed low-dose ICS-formoterol.

Single inhaler Maintenance And Reliever Therapy (SMART)

• Because of the rapid onset of action of formoterol, a combination ICS-formoterol inhaler can be used both for daily controller therapy and for quick relief of symptoms, a recommended strategy referred to as SMART (Single inhaler Maintenance and Reliever Therapy).
  • There is only one such combination product in the US: budesonide-formoterol (Symbicort)

GINA – Track 1 for Adults/Adolescents

How is it used? 

• When a patient at any treatment step has asthma symptoms, they use low dose ICS-formoterol in a single inhaler for symptom relief.
• In Steps 3–5, patients also take ICS-formoterol as their daily controller treatment. Together, this is called ‘maintenance and reliever therapy’ or ‘MART’ 

When should it not be used?

• ICS-formoterol should not be used as the reliever in patients prescribed a different ICS-LABA for their controller therapy; in this case, Track 2 should be utilized and SABAs are recommended for rescue therapy. 

GINA – Track 2 for Adults/Adolescents

How is it used?

• When a patient uses SABA PRN in Step 1, patients are instructed to take low dose ICS at the same time in a combination inhaler or with the ICS taken right after the SABA.
• In the remaining steps, patient takes ICS controller regularly and SABA alone PRN. 

When should it not be used?

• Before prescribing SABA PRN, consider adherence to prescribed ICS-containing controller (if not, then patient will be at higher risk of exacerbations and more likely to benefit from combination inhaler script)

Add-on therapies: 

• Long-Acting Muscarinic Antagonist (LAMA)
  • ICS-LABA-LAMA (triple combinations), recommended for age >18yo
  • Add on tiotropium in a separate inhaler (age >6yo)
• Leukotriene Receptor Antagonist (LTRA)
  • Montelukast (*2020 black box warning for suicidal thoughts/actions)
• Azithromycin
  • 3 days weekly dosing only by specialist referral (reduces exacerbations in patients taking high dose ICS-LABA)
• Biologic therapies
  • Omalizumab (anti-IgE)
  • Benralizumab, mepolizumab, resliuzmab (anti-IL5)
  • Biologic therapies should be considered on reassessment of blood eosinophils (even if low at first assessment)

GINA updates – 2021

GINA does not distinguish between intermittent and mild persistent asthma because this historical definition was arbitrary and based on an untested assumption that patients with symptoms twice a week or less would not benefit from ICS. 

Severe asthma is defined as asthma that requires high dose LABA to remain controlled or is uncontrolled despite high dose LABA. 

• Guidance about COVID-19 and asthma (see below)
• Mild and severe asthma definitions
  • Intermittent vs mild persistent asthma = no longer distinguishing, further definition will be addressed in next set of GINA guidelines
  • Severe asthma = escalation to high dose ICS-LABA to remain controlled or is uncontrolled despite high dose LABA
• Consider documenting severity by describing treatment escalation
  • Ex: :”patient controlled on medium dose ICS-LABA” as opposed to “patient with moderate severe asthma”

Asthma & COVID-19

CDC offers guidance on COVID-19 for certain conditions, including moderate-to-severe asthma. 

• Are people with asthma at higher risk for COVID or severe COVID-19?
  • Asthma does not appear to be a strong risk factor for acquiring COVID-19 or to increase the risk of more severe disease or death for the majority of patients. 
• Are people with asthma at higher risk for COVID-19 related death?
  • If well-controlled, then no. But yes in patients with recent use of ICS or hospitalized patients with severe asthma. 
• Are there any changes recommended for routine asthma management?
  • Not really—avoid nebulizers where possible to reduce risk of spreading virus; MDI with a spacer is preferred. 
• Are people with asthma safe to receive COVID-19 vaccination?
  • YES!!

Blog post based on Med-Peds Forum talk by Lindsey Mahoney and Vivian Shi, PGY4