#468: Asthma Update with Cyrus Askin

January 27, 2025 | By Matthew Watto, MD

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Transcript available via YouTube

2024 GINA Strategy, peak expiratory flow insights, SMART therapy, and other asthma pearls that will leave you breathless

Master the art of diagnosing and managing asthma with practical, evidence-based strategies. Learn how to approach the initial interview, gain comfort with key diagnostic tools like spirometry and PEF, and optimize therapy using the latest GINA report. We’re joined by Dr. Cyrus Askin, a longtime Curbsiders member returning as our guest expert to share his insights as a pulmonologist. 

X profile (formerly twitter):  @Askins_Razor 

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Show Segments

• Intro
• Case
• Topic
• Rapid fire questions/Picks of the Week
• Outro

Pearls

1. Avoid SABA monotherapy; prioritize ICS-formoterol as the new reliever therapy given the fast onset of formoterol. It can be used as a maintenance inhaler if more control is needed. Avoid salmeterol due to delayed onset.
2. For patients with a SABA who are  unable to obtain access to ICS-formoterol, tell them to use an ICS inhaler whenever they use their SABA. 
3. Clinical history is important. In addition to assessing asthma triggers like dust, wildfires, and pollen, ask about a  history of premature birth (before 34 weeks) as this increases the risk of bronchopulmonary dysplasia and underdeveloped terminal airways, which is a risk factor for asthma.
4. Spirometry should be used to diagnose asthma, but peak expiratory flow (PEF) can be used if spirometry is unavailable. 
5. When spirometry is normal during asymptomatic periods, use bronchoprovocation testing with methacholine to confirm airway hyperresponsiveness. This is particularly sensitive for diagnosing asthma.
6. Utilize the ACT questionnaire to assess and monitor asthma control over time. Scores below 20 suggest poorly-controlled asthma and should prompt therapy adjustments.
7. Refer early for severe or poorly-controlled asthma, asthma-COPD overlap, or obesity-associated asthma. 
8. Use personal PEF measurements to assist in creating an asthma action plan, which can aid in diagnosing and triaging asthma exacerbations.
9. Encourage healthy weight management, regular exercise, routine vaccination, and pulmonary rehabilitation to improve asthma outcomes.
10. Refer to the 2024 GINA Report for comprehensive guidance, as it provides detailed instructions for care of patients with asthma and covers most scenarios encountered in clinical practice.

#468 Asthma Update

Conducting the Initial Interview

Patient History

After leading with an open ended question, Dr. Askin considers these asthma-specific questions when taking a history:  

• Are the symptoms associated with any environmental triggers?
• Do they fluctuate with the climate or pollen count?
• Most smartphones measure an air quality index (AQI) which can be used to monitor for triggers
• Ask about any associations with dust or wildfires (if relevant geographically)
• Is there any association with physical activity?
• Do they have a family history of asthma or other lung diseases?
• Childhood history is important: being born prematurely (before 34 weeks) can be a risk factor for lack of terminal airway development and bronchopulmonary dysplasia  
• Ask about any childhood symptoms. Did they have a diagnosis of childhood asthma? We don’t fully understand why some people have symptoms of asthma in childhood that abate as the patient gets older (expert opinion). 

Making the Diagnosis of Asthma 

Gold Standard: Spirometry 

The hallmark of asthma is obstructive airway disease seen on spirometry with reversibility with a bronchodilator. Both are needed – a reduction in FEV1/FVC can be seen in a variety of obstructive lung diseases, and thus the diagnosis on asthma hinges on airway responsiveness to a bronchodilator once this obstruction is demonstrated. Additionally, reductions in FEF 25-75% (forced expiratory flow between 25% and 75% of FVC) can indicate obstruction in medium-sized airways, a hallmark of asthma in its early stages.

For patients who are not experiencing symptoms, they may need bronchoprovocation testing with methacholine, as normal spirometry during an asymptomatic period does not rule out asthma (Shin 2023). In patients with normal PFTs, spirometry should be performed with a methacholine challenge to assess for airway hyperactivity. Here, a baseline is obtained (without methacholine) followed by methacholine in increasing doses. This is then followed by a bronchodilator to evaluate for airway reversibility. Note: The bronchodilator is not administered before methacholine, as it interferes with the response. Therefore, if both bronchoprovocation testing and bronchodilator responsiveness are assessed on the same day, bronchoprovocation testing must be performed first. If exercise-induced bronchoconstriction is suspected, a similar process can be conducted using an exercise test. This approach is highly sensitive for diagnosing asthma (Yurdakul 2005, expert opinion). 

Caveat: Pregnant Patients

In pregnant patients, spirometry results may be confounded, though it can still be attempted in some cases. In these patients, upfront treatment may also be considered. As a reminder, the ‘rule of thirds’ describes how asthma control during pregnancy typically changes: one-third of patients improve, one-third worsen, and one-third remain unchanged (expert opinion).

Spirometry – Is It Always Necessary?

Spirometry is the gold standard for diagnosing obstructive airway diseases, including asthma, and should be performed whenever possible (GINA 2024). In some situations, such as employment requirements for military or police work, a confirmed diagnosis may be essential (expert opinion). However, in cases where asthma history is strongly suggestive and spirometry is logistically challenging or unavailable, particularly in resource-limited settings, empiric treatment with an inhaled corticosteroid (ICS) combined with formoterol as both a diagnostic and therapeutic approach may be considered. Though it is not the standard of care, it could be reasonable to use in practice, for example, in patients unable to produce valid spirometry results (e.g., due to excessive coughing). Empiric therapy in such cases might help alleviate symptoms and guide further management (expert opinion).

Peak Expiratory Flow (PEF) Testing

The best role for PEF testing is in a patient who has already been diagnosed with asthma and is using PEF to monitor their asthma control over time (expert opinion). However, a potential use for PEF is in resource limited settings where spirometry may not be available (GINA 2024). For diagnostic purposes, variability in PEF—such as a diurnal variation greater than 20% or improvement following bronchodilator use—strongly supports reversible airway obstruction that is typical of asthma. If using for diagnosis, follow these steps (GINA 2024):

• Conduct PEF readings twice daily over two weeks.
• Assess for >10% variability (highest of three readings BID with good technique).
• Use the same flow meter consistently to reduce variability.

As with spirometry, reversibility after bronchodilator administration is consistent with a diagnosis of asthma. To perform a bronchodilator challenge in a patient using PEF:

• Administer 200-400 mcg albuterol.
• Measure PEF after 10-15 minutes.
• A >20% increase in PEF suggests reversible airway obstruction.

Takeaway:  If relying on PEF, then the subjective threshold to initial an inhaled corticosteroid (ICS) should likely be lower – and the risk/benefit ratio would probably favor starting empiric therapy in patients with highly suggestive clinical features of asthma who do not fully meet diagnostic criteria on PEF. Again, try to do spirometry if possible in these patients (expert opinion). 

Staging Asthma

Focusing on the patient experience regarding their asthma can often be more effective than getting too bogged down trying to stage their symptoms. Dr. Askin suggests putting people into three “buckets” that exist on a spectrum:

1. Do they only have symptoms in certain circumstances?
2. Do they always have symptoms, but the symptoms are mild?
3. Are they always short of breath such that it interferes with their daily life?

While staging can be helpful and should not be ignored, grouping patients this way is accomplishes the same goal as does staging, which is to create a framework in which you can effectively manage a patient in front of you. Focus on the patient experience, assess how badly it is affecting their life, and this will likely steer you in the right direction (expert opinion). 

The Asthma Control Test 

It can be difficult to assess a patient’s symptomatology over time, thus using an objective measure like the asthma control test (ACT) can be helpful in practice (expert opinion). The ACT is a simple, validated questionnaire designed to assess asthma control in patients (aged 12 and older) over the past four weeks. It consists of five questions addressing daytime symptoms, nighttime awakenings, activity limitations, rescue inhaler use, and the patient’s perception of control, with a total score ranging from 5 to 25. Scores of 20 or above indicate well-controlled asthma, while lower scores (19 or lower) suggest not well-controlled or poorly-controlled asthma. The ACT is a valuable tool in clinical practice for establishing a baseline, monitoring asthma control over time, and guiding treatment adjustments (Soler 2019). 

Asthma Management

Formoterol (with ICS) as the New Albuterol

Current evidence demonstrates that  ICS-formoterol as needed is superior to as-needed albuterol with maintenance ICS (Beasley 2019). Many providers practicing today learned that albuterol rescue inhalers were a cornerstone of asthma management, especially for those with mild asthma (expert opinion). This view is now considered outdated due to its association with increased exacerbations and suboptimal symptom control. Current evidence and guidelines emphasize the importance of combining a fast-onset bronchodilator (usually formoterol) with ICS. This addresses the underlying pathophysiology of asthma and combats the inflammation while also providing rapid symptom relief, reducing the need for systemic steroids, and improving long-term outcomes. Transitioning patients from albuterol monotherapy to ICS-formoterol or an ICS paired with a separate bronchodilator is now the standard of care. Issues with tachyphylaxis (decreasing response to repeated SABA use) further limit its utility (O’Byrne 2018, Bateman 2018, Beasley 2019, GINA 2024, expert opinion).

 Using an ICS with formoterol leads to reliable and impressive symptom control, reductions in exacerbations, and lower doses of corticosteroids over time (Bateman 2021). Remember that not all LABAs are created equal. Formoterol in particular should be used because it has a quick onset (5-10 minutes) and can last for up to 12 hours. Salmeterol, on the other hand, takes roughly two hours to become effective, making it undesirable to use for rescue inhaler purposes. Do not use SABA monotherapy — this is an outdated practice not supported by current evidence and guidelines (GINA 2024). 

There are no head to head trials comparing formoterol-ICS with albuterol-ICS, and as a result there is no compelling reason to use albuterol-ICS in place of what is already proven effective in formoterol-ICS. There is recent data to suggest that albuterol-ICS is better than albuterol alone, however (Papi 2022). Thus, a potential use for the albuterol-ICS combination could be in a patient who is already on albuterol monotherapy and are unwilling to give it up in place of formoterol. In this patient, adding the ICS to albuterol could allow the patient to experience the benefits of ICS without giving up albuterol; the primary shift in asthma management focuses on moving away from SABA monotherapy rather than placing excessive emphasis on the choice of beta agonist (expert opinion).

In summary: ICS-formoterol offers superior symptom control, reduces exacerbations, and lowers overall corticosteroid use over time. Formoterol is the preferred bronchodilator due to its rapid onset of action and long duration, making it more effective than alternatives like salmeterol, which has a delayed onset and is unsuitable for quick relief (O’Byrne 2018, Bateman 2018, Beasley 2019, GINA 2024, expert opinion).

Practical Application

For intermittent symptoms triggered by unavoidable factors (e.g., exercise), take 2 puffs with a spacer 15 minutes before exposure and repeat if symptoms persist with a maximum of 12 puffs per day (NAEPPCC 2020).

For mild-to-moderate asthma, use as-needed (PRN) ICS-formoterol therapy per GINA’s stepwise approach (GINA 2024, expert opinion). Transition to Maintenance And Reliever Therapy (MART) if symptoms worsen, with adjustments based on the Asthma Control Test (ACT) score or patient-reported control. MART typically involves 2 puffs BID for maintenance and additional doses PRN (NAEPPCC 2020).

Reliever therapy (e.g., budesonide/formoterol or BUD/FORM) is for patients with episodic symptoms, while MART is ideal for consistent symptoms like nocturnal awakenings or frequent exacerbations. For highly symptomatic patients (e.g., frequent ED visits), start with high-dose therapy and step down once control is achieved (GINA 2024, expert opinion).

Cost-Conscious Options

For patients unable to afford combination ICS-formoterol inhalers (e.g. BUD/FORM), separate ICS and fast-onset bronchodilator inhalers (such as albuterol or formoterol) can be used together. This approach maintains the benefits of combining ICS with bronchodilators while avoiding the outdated and less effective practice of SABA monotherapy (GINA 2024, expert opinion).

Montelukast

Montelukast is frequently used as an oral adjunctive medication for asthma, particularly for patients with allergic asthma, exercise-induced bronchoconstriction, or aspirin-sensitive asthma. It is also effective in managing cough-variant asthma, even as monotherapy according to recent studies (Yi 2022). The biggest concerns when using this medication are with respect to neuropsychiatric side effects, such as depression, anxiety, and suicidal thoughts, which led to an FDA black box warning (Umetsu 2021). A recent 2023 meta-analysis was unable to confirm the increased risk of suicidal thoughts, nonetheless it is important to factor these side effects into you treatment decisions and counseling of patients (Lo 2023 expert opinion). While there is no role for montelukast as monotherapy in asthma, except possibly cough-variant asthma, it can be used in select patients as adjunctive therapy alongside their ICS-LABA inhaler. Note that, in the absence of asthma (e.g., seasonal allergies), montelukast is not used (GINA 2024, expert opinion). 

Theophylline

Theophylline is not used much anymore because of its narrow therapeutic window and significant side effects. While GINA still mentions it as an option in resource-limited settings, it’s mostly seen as a last-resort choice and rarely comes into play in modern practice. Safer and more effective options, like ICS/LABA combinations and biologics, have taken its place, so most clinicians trained in the last decade have little to no experience with it (GINA 2024, expert opinion).

Optimizing Therapy

Key considerations include ensuring the patient is taking the medication correctly and deliberately. Using a spacer can enhance drug delivery by facilitating slow, deep inhalation and allowing the medication to collect in the chamber before reaching the lungs effectively. This is particularly important for maintenance therapy, where a spacer can also reduce side effects like thrush. For patients prioritizing portability, selecting a reliever inhaler that fits easily in their pocket may improve adherence.

When patients report persistent symptoms or side effects, reassessing the steroid dose is essential. The starting dose of ICS-formoterol typically ranges from 80 to 160 micrograms, adjusted based on symptom severity. A significant portion of the efficacy of ICS is achieved at lower doses, roughly equivalent to the effect of 5 mg of prednisone, with minimal systemic side effects such as thrush or cavities. However, every patient is unique, and responses may vary, making it important to tailor dosing. The classic approach involves starting at a lower dose and stepping up to a higher dose if symptoms persist, while also being mindful of potential cardiac side effects from the LABA component at higher doses (Lan 2024, GINA 2024, expert opinion).

Nonpharmacologic Measures

Dr. Askin mentions several key measures to improve symptoms of asthma aside from medications:

• Supporting healthy weight management for patients with overweight or obesity to improve overall well-being and asthma control (Juel 2012).
• Encourage regular conditioning and strength training to improve respiratory health. Reframe the term “exercise-induced asthma” as Asthma with an Exertional Trigger so that patients do not feel deterred from exercising (expert opinion).
• Identity and eliminate triggers whenever possible.
• Place referrals for and encourage patients to utilize pulmonary rehabilitation (Zampogna 2020).
• Encourage patients to keep track of their symptoms and triggers in a symptom journal (expert opinion).
• Stay up to date with vaccines, including influenza, RSV, COVID-19, and pneumonia, as indicated as this plays a vital role in preventing respiratory infections that can exacerbate asthma (Vasileiou 2020, expert opinion).

Asthma Exacerbations

PEF and Asthma Action Plans

In contrast to using PEF for making the diagnosis of asthma, it can be particularly useful to establish a baseline. This can aid in identifying exacerbations and further characterizing those exacerbations using PEF zones. For example, telling patients this what to do if feeling short of breath:

• Green Zone: 100-80% of personal best or predicted. Asthma is well-controlled. Continue maintenance therapy as prescribed.
• The Yellow Zone, defined as 50-80% of a patient’s best or predicted PEF, signals worsening symptoms and requires prompt action. Management includes increasing the frequency of BUD/FORM inhaler use or switching to nebulized therapies for 48 hours. Systemic steroids may be considered based on the patient’s specific needs. A follow-up assessment should be scheduled to evaluate symptom progression and adjust treatment. Antibiotics are generally not recommended unless there is clear evidence of a bacterial infection, such as pneumonia.
• The Red Zone, with PEF below 50% of a patient’s best or predicted, signals a serious asthma flare that needs urgent attention. Start immediate treatment with bronchodilators and systemic steroids, and encourage the patient to go to the emergency department for further care. If they are set on managing at home, make sure to document everything carefully and check in often (expert opinion).

Asthma action plans should reference the patient’s personal best PEF to define zones and include clear, written instructions on when to escalate care. Plans should emphasize that patients should reach out to their healthcare provider early in the course during yellow or red zone exacerbations. Even when patients have optimal access to care, action plans are valuable for educating them about symptom progression, reducing unnecessary ED visits by empowering patients to initiate early interventions after prompt detection of exacerbations (Couri 2019, GINA 2024, expert opinion).

Emergency Department

Besides the Red Zone on PEF, Dr. Askin mentions additional factors that should prompt ED referral, including speaking in short sentences (4-5 words) or showing any signs of severe respiratory distress. Emergency departments have become highly effective at managing asthma, reducing the need for inpatient admissions. Patients requiring admission often present with complications or severe, refractory symptoms. Always be sure to rule out conditions like acute decompensated heart failure or bacterial infections that may mimic or complicate asthma exacerbations (expert opinion).

Azithromycin

Azithromycin is a potential adjunctive therapy for severe asthma due to its immunomodulatory effects. It reduces pro-inflammatory cytokines and may inhibit airway remodeling by limiting fibroblast and smooth muscle proliferation, making it a physiologically plausible option for improving symptoms of asthma (Gibson 2019).

Studies have demonstrated that long-term, low-dose azithromycin reduced exacerbations and improved quality of life in patients with severe asthma; azithromycin increased asthma remission rates in adults with persistent, uncontrolled asthma, benefiting both eosinophilic and noneosinophilic subtypes (Gibson 2019, Rhoades 2024). 

Persistent Asthma Symptoms

Specialist Referral

Within the 2024 GINA report, the color-coded recommendations on page 144 offer practical insights into treatment strategies and criteria for specialist referral. Early referral is particularly important for patients with severe or poorly-controlled asthma, those requiring advanced phenotyping for biologic therapies, or those with complex presentations, such as asthma-COPD overlap or obesity-associated asthma (GINA 2024, expert opinion).

Comprehensive Workup

The workup for persistent, uncontrolled asthma can be initiated by the primary care provider or deferred to the specialist, depending on individual practice patterns. It often includes a CBC with eosinophils and a high-resolution CT to assess for structural causes. It is also important to ensure that alternative diagnoses are not being missed, so consider a pro-BNP, ANCA testing, and echocardiography to assess for common mimickers (GINA 2024, expert opinion). 

Asthma Phenotypes

High Type 2 (T2) inflammation is associated with allergic conditions such as eczema, allergic rhinitis, and food or drug allergies. It is characterized by elevated type-2 helper T cells and is often identified through increased eosinophil levels in sputum or blood. This allergic inflammation is driven by cytokines such as IL-4, IL-5, and IL-13, which serve as targets for biologic therapies. Patients with T2-high asthma generally respond well to inhaled corticosteroids (ICS) and, in refractory cases, to biologics targeting specific mediators in the inflammatory pathway (Miller 2021, GINA 2024, expert opinion).

Patients with low T2 asthma lack significant biomarkers of inflammation and often respond poorly to biologics. Emerging treatments, like tezepelumab, which targets upstream mediators, show some potential (Menzies-Gow 2021). Specific subtypes, such as cough-variant asthma, may benefit from montelukast (Yi 2022), while adult-onset asthma and asthma with persistent airflow limitation require careful evaluation for possible asthma-COPD overlap (Freiler 2015). Obesity-associated asthma presents further challenges in diagnosis and treatment due to its unique pathophysiology (Miller 2021, GINA 2024, expert opinion).

Links

1. Asthma Action Plan (CDC); Spanish Version (AAFA)
2. 2024 GINA Strategy

Goal

Listeners will feel confident assessing asthma symptoms in clinic and prescribing first-line therapies per the latest guidelines. 

Learning objectives

After listening to this episode listeners will…  

1. Review comprehensive asthma strategies during a clinic encounter, including history taking, physical exam, diagnostic testing, and counseling on asthma action plans.
2. Discuss key updates from the GINA 2024 report: including peak expiratory flow, and modern asthma management such as SMART (or MART) therapy.
3. Guide patients through individualized treatment options, considering access, cost, and indications for biologic therapy and specialty referral.
4. Counsel patients, including athletes, on managing asthma triggers such as exercise-induced bronchoconstriction and occupational asthma.
5. Gain comfort managing asthma exacerbations in the outpatient setting.

Disclosures

Dr. Askin reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures. 

Citation

Wurtz P, Askin C, Williams PN, Watto MF. “468 Asthma Update with Cyrus Askin”. The Curbsiders Internal Medicine Podcast. thecurbsiders.com/category/curbsiders-podcast January 27, 2025.