Understanding Severe Asthma: A Guide for Healthcare Professionals

Gina Hoots, Respiratory Therapist and Health Coach

Originally posted on https://medium.com/@ginahoots

Understanding Severe Asthma: A Guide for Healthcare Professionals

I recently had the honor of hosting an educational session on biologics for asthma control — a topic that was new to me as a respiratory therapist. The mechanisms, pathways, and drug names can be complex, so I turned to writing as a way to deepen my understanding and make sense of the information. If this blog helps your understanding, please comment!

Asthma is no longer seen as a single disease but rather an umbrella term for multiple conditions that may appear similar but have distinct underlying mechanisms. This evolving perspective has revolutionized asthma management, emphasizing the importance of identifying phenotypes (clinical presentations) and endotypes (biological pathways) to guide more precise treatments. Today, managing asthma involves much more than simply prescribing albuterol.

Phenotypes vs. Endotypes: The Key to Precision Treatment

Asthma phenotypes categorize patients based on observable characteristics, such as age of onset, allergen sensitivity, or comorbid conditions. Some common asthma phenotypes include:

  • Allergic asthma — Early-onset, often associated with IgE-mediated allergies.
  • Late-onset eosinophilic asthma — Typically non-allergic, driven by eosinophilic inflammation.
  • Aspirin-exacerbated respiratory disease (AERD) — Triggered by aspirin or NSAIDs.
  • Obesity-related asthma — More common in adults, often without clear signs of inflammation.

While phenotypes help clinicians describe asthma presentations, endotypes provide deeper insight into the biological mechanisms driving the disease. The two primary endotypes are:

  • T2-high asthma — Driven by Type 2 inflammation, involving eosinophils, IgE, and cytokines such as IL-4, IL-5, and IL-13.
  • T2-low asthma — Characterized by neutrophilic or paucigranulocytic inflammation, often linked to infections, pollution, or metabolic factors like obesity.

Understanding which endotype a patient has allows for more effective, targeted treatment strategies.

The Role of T2 Inflammation in Severe Asthma

T2 inflammation is present in 55–70% of patients with severe asthma and plays a major role in airway inflammation and obstruction. This process begins when allergens or irritants activate the immune system, leading to:

  1. TSLP activation — The cytokine thymic stromal lymphopoietin (TSLP) initiates T2 inflammation by triggering immune responses.
  2. T-helper type 2 (Th2) and innate lymphoid cells (ILC2) activation — These cells release cytokines such as IL-4, IL-5, and IL-13, driving inflammation.
  3. Eosinophilic airway inflammation and mucus overproduction — IL-5 supports eosinophil growth, while IL-13 contributes to mucus hypersecretion and airway remodeling.

Common biomarkers for T2-high asthma include:

  • Elevated blood eosinophil count (AECs) (e.g., AEC ≥150–300 cells/μL for biologic therapy eligibility)
  • Increased FeNO (fractional exhaled nitric oxide) (≥25 ppb)
  • Elevated IgE levels or positive allergen-specific IgE tests

These biomarkers help identify candidates for biologic therapies targeting specific pathways in T2 inflammation.

Non-T2 Inflammation: The Less Understood Pathway

Unlike T2-high asthma, T2-low asthma lacks eosinophilic inflammation and does not respond well to corticosteroids or biologics targeting IL-4, IL-5, or IgE. Instead, neutrophilic or paucigranulocytic inflammation is often involved, driven by factors such as:

  • Infections or pollution exposure — Triggering immune responses dominated by neutrophils.
  • Obesity or metabolic factors — Affecting airway function without classic inflammation.
  • Smoking-related airway remodeling — Leading to fixed obstruction and poor bronchodilator response.

T2-low asthma can be challenging to treat, as traditional asthma therapies are less effective. Tezepelumab (Tezspire) is the only biologic currently available that does not require biomarker testing and has shown efficacy in both T2-high and T2-low asthma.

Biologic Therapies: Matching the Right Treatment to the Right Patient

Biologic therapies have revolutionized asthma management by targeting specific inflammatory pathways. When considering a biologic, healthcare professionals should evaluate the patient’s:

  • FDA-indicated phenotype (eosinophilic asthma, allergic asthma, or OCS-dependent asthma)
  • Biomarkers (AECs, FeNO, IgE, allergen sensitivity)
  • Comorbid conditions (e.g., nasal polyps, atopic dermatitis, eosinophilic esophagitis)
  • Dosing preferences and adherence potential

The effectiveness of biologic therapies varies depending on the patient’s underlying asthma phenotype and endotype.

Table of Common Biologic Agents for Type 2 Asthma

When Is a Patient a Candidate for Biologic Therapy?

A patient with persistent symptoms despite high-dose inhaled therapy would be considered a candidate for biologic therapy. Key indicators for biologic therapy in severe asthma include:

  1. Frequent Exacerbations — Two or more asthma exacerbations per year requiring systemic corticosteroids suggest poor control and a need for a targeted approach.
  2. High Oral Corticosteroid (OCS) Use — Patients who rely on long-term OCS therapy may benefit from biologics as a steroid-sparing option.
  3. Elevated Biomarkers — Blood eosinophil count (AEC), FeNO, IgE levels, and allergen sensitivity help determine the best biologic choice.
  4. Poor Lung Function (FEV1 Reduction) — A low FEV1 despite appropriate inhaled therapy suggests uncontrolled inflammation.
  5. Comorbidities That Worsen Asthma — Conditions like nasal polyps and chronic rhinosinusitis may indicate a need for biologic therapy.

By addressing these factors, healthcare professionals can better determine the right biologic therapy for each patient.

Closing Thoughts and Call to Action

Severe asthma management has evolved significantly, moving from a generalized treatment approach to a more precise, biomarker-driven strategy. By identifying phenotypes and endotypes, selecting the most appropriate biologic therapy, and incorporating shared decision-making, healthcare professionals can provide more effective, personalized care.

As research continues to advance, staying informed about emerging treatments and best practices is crucial. Consider attending asthma-focused conferences, engaging in professional development, and following the latest clinical guidelines. The more we learn, the better we can support our patients in achieving optimal asthma control and improving their quality of life.

Embracing Change: A Look into the 2024 GOLD Guidelines for COPD

Embracing Change: A Look into the 2024 GOLD Guidelines for COP

In pulmonary medicine, keeping up with the latest advancements and evidence is crucial for providing optimal care to patients with chronic obstructive pulmonary disease (COPD).

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines provide evidence-based recommendations for COPD diagnosis, management, and prevention. First released in 1997, GOLD is a collaboration between the National Heart, Lung, and Blood Institute and the World Health Organization. GOLD’s objectives are to raise awareness of COPD, improve prevention and management, and encourage research. GOLD organizes World COPD Day on the third Wednesday of November to spread awareness. Since 2014, GOLD has been funded through the sale of reports and resources.

 

The GOLD guidelines use a combined assessment of symptoms and exacerbation risk to determine initial treatment. They propose escalating or de-escalating treatment based on symptoms like shortness of breath and frequency of flare-ups. The guidelines outline both drug and non-drug options for stable COPD, with the goals of reducing symptoms and future exacerbations. GOLD guidelines provide a framework for individualized COPD care. They aim to support clinicians and patients in achieving the best outcomes through proper diagnosis, treatment, and self management. The guidelines translate research into practical recommendations that evolve as new evidence comes to light.

In this overview of the annual revisions to the Global Initiative on Obstructive Lung Disease (GOLD) guidelines for 2024, we’ll explore key changes shaping our practice and improving patient outcomes. With over 30 years in the field, I’ve witnessed the evolution of our understanding of obstructive lung disease beyond the traditional FEV1/FVC ratio and treatment with Q4 albuterol nebs. This comprehensive 218-page document compiles volumes of research into a digestible resource for pulmonary diagnosticians worldwide and for respiratory therapists like myself.

Chapter 1: Definition and Overview

Let’s begin with the basics: understanding COPD and its implications. The GOLD 2024 report maintains the definition of COPD largely unchanged from previous years: “COPD is a heterogeneous lung condition characterized by chronic respiratory symptoms (dyspnea, cough, expectoration, and/or exacerbation) due to abnormalities of the airways (bronchitis, bronchiolitis) and/or alveoli (emphysema) that cause persistent, often progressive, airflow obstruction.” While most readers are familiar with Stage 4 / Category D / end-stage COPD presentations, new terminology and discussions have been introduced to better classify COPD. Today, we know that lung function is related to epigenetic changes in response to exposure to the environment over an individual’s lifetime. We also know that while COPD is both preventable and treatable, underdiagnosis can lead to unnecessary suffering and disease progression. This section will aim to review terminology that has changed in recent years.

 Clarification of the terms Early/Young/Mild COPD:

  • Early: Reflects the disease’s initial signs and symptoms.
  • Young: Indicates an onset at a younger age (e.g., 20-30s).
  • Mild: Describes the degree of obstruction present.

 Pre-COPD: Normal spirometry but with symptoms and risk factors present.

 PRISm: Preserved Ratio but Impaired Spirometry. Expands on individuals with low FEV1 and symptoms, despite preserved ratio, often associated with increased cardiovascular risk and potential transition to obstruction over time.

 Hyperinflation: While not a new term, hyperinflation has new importance in the 2024 document. Hyperinflation is characterized by elevated lung air volume compared to normal, associated with dyspnea, impaired exercise tolerance, and increased mortality, even in individuals with mild obstruction.

 Chapter 2: Diagnosis and Assessment

Diagnosing and assessing COPD require a comprehensive approach, and the 2024 updates provide insights into refining this process. Notable updates include clarification on pre-bronchodilator spirometry, enhanced screening methods, and updates on assessing blood eosinophil count for a more nuanced understanding of COPD diagnosis and assessment. Many charts and algorithms are presented for clarity and easy of reference.

 Spirometry Update:

  • Recommends post-dilator testing for diagnosis, clarifying that post-bronchodilator testing may not be necessary if obstruction is absent pre-dilator.
  • Ongoing follow-up is warranted if obstruction is present with responsiveness due to increased risk of developing fixed obstruction in the future.
  • Large-scale screening programs for the general public are not recommended, but screening for persons at risk for COPD is advised.

 Update: Other Diagnostic Tests

  • Lung cancer screening may offer an opportunity for COPD screening due to shared risk factors.
  • Blood eosinophil elevation is associated with responsiveness to inhaled corticosteroids.
  • Interstitial lung abnormalities are addressed, and presence of findings raise concern for poor outcomes.

 Chapter 3: Prevention and Management of COPD

Preventing symptoms and managing risks are central to COPD care, and the 2024 updates provide a roadmap for optimizing these efforts. Previously separated into two chapters, this chapter was merged to reduce redundancies. With a renewed focus on smoking cessation strategies, including pharmaceutical options, the guidelines emphasize evidence-based, holistic approaches despite challenges such as continued smoking among approximately 40% of diagnosed COPD patients.

 Smoking Cessation Update:

  • All smokers should be strongly advised to quit using supportive strategies.
  • Nicotine replacement and pharmaceutical support are widely available.
  • Cognitive behavioral therapy and goal setting are effective non-pharmaceutical strategies.

 Inhaled Medication Update:

  • Stress on individualized medication selection based on ability and choice.
  • Utilize assessment criteria, inhalation strength, breath hold, manual dexterity, and insurance coverage.
  • Emphasizes minimizing the number of devices and utilizing effective device education.
  • Discussion of factors such as once-daily dosing may create improved adherence.

 Non-Pharmacological Updates:

  • Aligns vaccination recommendations with CDC guidance.
  • Recommends the use of hospice, palliative care, and tele-health.
  • Highlights non-pharmacological therapies such as oxygen and pulmonary rehab, stressing personalized treatment approaches tailored to individual patient needs.

 Chapters 4-6: Management of Exacerbations, COPD and Comorbidities, and COVID-19 and COPD

These chapters have no major updates and continue to address the challenges posed by exacerbations, the complexity of COPD comorbidities, and the unique considerations of COPD management in relation to the COVID-19 pandemic. The chapter on co-morbidities covers an extensive list which reinforces the need to monitor patients closely as multimorbidity causes complex medical management.

 What You Can Do

  • Assess your COPD patients using the new guidelines to determine the right treatment path.
  • Educate patients on self-management, risk reduction, and the importance of medication adherence and follow-up care.
  • Follow up regularly to evaluate if treatments need adjustment to gain control of symptoms and reduce exacerbations.
  • Promote regular pulmonary rehabilitation attendance.
  • Encouraging shared responsibility is important as patients and providers together can optimize COPD management and outcomes.

 In conclusion, the 2024 updates to the GOLD guidelines for COPD reflect the latest evidence, with seven pages of references added this year alone. By embracing these updates and integrating them into our practice, we can elevate the standard of care for COPD patients, empowering them to lead healthier, more fulfilling lives. Health coaching is a relatively new area in which health care providers are uniquely positioned to make yet another positive difference on outcomes in persons with COPD. As respiratory therapists, we are at the forefront of change, driving progress and innovation in the pursuit of better respiratory health for all.