#500: COPD Update with Cyrus Askin

October 6, 2025 | By Paul Wurtz

Audio

Video

Transcript available via YouTube

GOLD Updates, Novel Treatments, and Managing Comorbidities in COPD Care

Level up your COPD care with practical, evidence-based strategies. Learn how to confirm airflow obstruction with spirometry (and use LLN/Z-scores thoughtfully), stage patients with the A/B/E framework, and build treatment around long-acting bronchodilation—adding ICS selectively based on exacerbations and eosinophils. We’ll highlight the nonpharmacologic moves that change outcomes (smoking cessation, vaccination, pulmonary rehab, oxygen when indicated), when to reach for add-ons (azithromycin, roflumilast), how to approach chronic hypercapnia with home NIV, and what’s new (hello, ensifentrine). Pulmonologist and longtime Curbsiders member Dr. Cyrus Askin (@Askins_Razor ) returns to share real-world pearls for diagnosing, treating, and managing comorbidities in COPD.

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Show Segments

• Intro
• Case 1
• Diagnostic Workup
• Understanding the Ratio, LLN/Z-Scores, and Equity
• Symptom abd Risk Staging (A/B/E)
• Case 2
• Foundational Care 
• Initial Inhaler Strategy 
• Progression & Hypercapnia: NIV & Adherence Counseling
• Add-On Pharmacologic Options for Frequent Exacerbators
• What’s New and Emerging
• Comorbidities and When to Refer 
• Take-Home Points Recap
• Plugs, CME, and Credits

Pearls

1. Confirm COPD with spirometry. Use post-bronchodilator FEV₁/FVC <0.70; if near the cutoff, consider lower limit of normal/Z-scores. Screen everyone with COPD for alpha-1 antitrypsin deficiency at least once.
2. Stage by symptoms and risk, not just FEV₁. Use mMRC or CAT to sort A vs B; any patient with ≥2 moderate exacerbations or ≥1 hospitalization in the past year is Group E.
3. Start with long-acting bronchodilation. LABA/LAMA is preferred first-line for most symptomatic patients. Don’t lead with ICS in COPD.
4. Add ICS (i.e., move to triple therapy) only when the phenotype fits. Think ICS when eosinophils are higher and/or exacerbations persist on LABA/LAMA; avoid routine ICS when eos are low. Teach rinse/spit and watch for pneumonia.
5. Non-pharmacologic management moves the mortality needle. Prioritize smoking cessation, vaccination, pulmonary rehab, and long-term oxygen only for severe resting hypoxemia. Pair exercise with protein-forward nutrition to fight sarcopenia.
6. Consider azithromycin for frequent exacerbators (especially ex-smokers) and roflumilast for the chronic-bronchitis phenotype; monitor QT/hearing (macrolide) and weight/GI/mood (roflumilast).
7. Chronic hypercapnia? Think home noninvasive ventilation (NIV). Reassess PaCO₂ after the flare; if still elevated, use nightly NIV (6–8 h). Fit and comfort matter; screen/treat OSA. Acclimation tip: wear the mask while relaxing in the evening.
8. Ensifentrine is a new maintenance option. A nebulized PDE3/4 inhibitor to consider when symptoms or exacerbations persist despite standard therapy.
9. Comorbidities change outcomes. Aggressively manage cardiovascular disease, screen for pulmonary hypertension (echo in advanced disease), address anxiety/depression, protect bone health, manage diabetes/metabolic syndrome, and look for OSA and bronchiectasis (add airway-clearance when present).
10. Mind the practicals—and know when to refer. Re-teach inhaler technique, simplify devices/regimens, and use cost-conscious “open triple” when needed. Refer for frequent exacerbations despite therapy, chronic hypercapnia/NIV issues, suspected pulmonary hypertension, bronchiectasis, alpha-1 deficiency, or diagnostic uncertainty.

#500 COPD Update 

Conducting the Initial Interview  

Patient History  

Cyrus likes to begin with an open-ended prompt, then drill into COPD-specific risks and mimics. Ask about cumulative inhalational exposures beyond cigarettes (occupational dusts, fumes, biomass, secondhand smoke). Clarify childhood respiratory history, recurrent infections, and any history of asthma that may “burn out” into fixed obstruction later in life (expert opinion). Elicit symptom time course (progressive exertional dyspnea, chronic cough, sputum), prior exacerbations, and functional limits. Screen for triggers, environmental air quality, and exercise tolerance. Document comorbidities that amplify symptoms or alter management, such as cardiovascular disease, anxiety/depression, osteoporosis, diabetes/metabolic syndrome, OSA, bronchiectasis (expert opinion, GOLD 2025).

Making the Diagnosis of COPD

Gold Standard: Spirometry

COPD diagnosis requires airflow obstruction on spirometry—post-bronchodilator FEV1/FVC < 0.70. The numerator (FEV1) is the forced expiratory volume in the first second; the denominator (FVC) is the six-second forced vital capacity. In obstructive disease, the early “inflection” is blunted and the ratio falls (unlike restrictive disease where the ratio stays normal). Use post-bronchodilator values to confirm fixed obstruction; in asthma there is reversibility, whereas COPD there is not (GOLD 2025).

LLN/Z-Scores and Race-Neutral GLI

GOLD 2025 still uses the simple 0.70 post-bronchodilator FEV₁/FVC cutoff for an operational diagnosis (Bowerman 2023, GOLD 2025). Around that threshold, be thoughtful: the Lower Limit of Normal (LLN) is essentially the 5th percentile for a patient’s age, sex, and height, and the Z-score tells you how many standard deviations a value sits from predicted (with Z < −1.64 typically “abnormal”). Because a fixed 0.70 can overdiagnose obstruction in older adults and miss it in younger adults, scan the report’s race-neutral Global Lung Function Initiative LLN/Z-scores for the ratio (and FEV₁) to reduce misclassification. Near-borderline results plus compatible symptoms should prompt closer follow-up, repeat testing, and clinical judgment (expert opinion Bowerman 2023, GOLD 2025).

Can COPD Be Diagnosed if Ratio ≥ 0.70? 

Generally no. If the ratio is ≥ 0.70, COPD is not established by GOLD criteria. For patients who are “close” to 0.70, consider symptoms, LLN/Z-scores, and alternative diagnoses. A therapeutic bronchodilator trial for quality-of-life benefit is reasonable in select cases (expert opinion). There is a concept of pre-COPD that is introduced in the GOLD 2025 report that can apply to some of these patients (GOLD 2025, expert opinion)

Imaging and Full Pulmonary Function Tests

Obtain a chest X-ray in most new pulmonary complaints to avoid missing masses or alternative pathology. If the illness script doesn’t fit (never-smoker, young age, occupational exposures, atypical symptoms), pursue cross-sectional imaging (non-HRCT acceptable) and full PFTs (spirometry, lung volumes, DLCO). Imaging helps identify emphysema distribution, bronchiectasis, or interstitial processes; full PFTs reveal air-trapping and diffusion limitations that refine the differential (expert opinion).

Alpha-1 Antitrypsin Deficiency

GOLD 2025 notes that the WHO recommends all patients diagnosed with COPD be screened for alpha-1 antitrypsin deficiency regardless of age or ethnicity. If the alpha-1 antitrypsin level returns low, repeat once to confirm; if persistently low, refer for phenotype/genotype confirmation and family counseling (GOLD 2025, expert opinion). Foundations can assist with access to augmentation therapy when indicated.

Staging COPD  

Symptom–Risk Framework

Classify patients into A, B, or E. Use symptom scores like the Modified Medical Research Council Dyspnea Scale (mMRC) and COPD Assessment Test (CAT). Groups A and B differentiated by symptom burden (A: mMRC 0-1, CAT < 10; B:  mMRC ≥2, CAT ≥10) with zero or one moderate exacerbations, whereas group E denotes more frequent exacerbations (≥2 moderate exacerbations or ≥1 hospitalization in the past year) regardless of symptom score. FEV1 percent predicted is less central to initial pharmacotherapy than symptom/exacerbation phenotype, yet remains prognostic and contributes to indices like BODE (BMI, obstruction, dyspnea, 6-minute walk) (GOLD 2025).

Nonpharmacologic and Foundational Care 

Vaccination & Prevention  

Providers should prioritize vaccination against influenza, pneumococcal, RSV, COVID-19, pertussis, and varicella zoster (if  ≥ 50 years old), and ensure that all age and comorbidity-associated vaccines are given per guidelines (Kwok 2025). These save lives and reduce exacerbations. Treat tobacco use with the same rigor as any chronic disease. Offer counseling plus pharmacotherapy: nicotine replacement therapy, bupropion, varenicline; newer varenicline analogs where available (GOLD 2025, expert opinion).

Pulmonary Rehabilitation & Exercise

Pulmonary rehab is an essential therapy for those with a high symptom burden and exacerbation risk (groups B and E), not an “extra.” It improves dyspnea, exercise capacity, and quality of life, and even carries a mortality benefit in some studies (GOLD 2025, Lindenauer 2020). When access is limited, encourage structured aerobic and resistance training with practical guidance and reassurance (Lindenauer 2020).

Managing Late Stage Complications

Assess at rest and with ambulation; prescribe long-term oxygen therapy in those with severe chronic hypoxemia. Screen for cachexia and low appetite. Consider protein supplementation (e.g., shakes) and pair with resistance training to blunt muscle loss (GOLD 2025).

Pharmacologic Management  

What GOLD Tells Us in 2025

The GOLD 2025 framework emphasizes tailoring initial therapy to both symptom burden and exacerbation risk:

•  Patients in Group A, who report fewer symptoms (mMRC 0–1 or CAT < 10) and have infrequent exacerbations, can be managed with a single bronchodilator. 
• In contrast, Group B patients, who have more significant symptoms (mMRC ≥ 2 or CAT ≥ 10) but no history of frequent exacerbations, should start with dual bronchodilation (LABA + LAMA) for superior symptom control. 
• Those in Group E—patients with frequent exacerbations (≥ 2 moderate or ≥ 1 hospitalization)—are also recommended to start with LABA + LAMA, with consideration of adding an ICS if blood eosinophils are ≥ 300. 

Relievers (PRN SABA)  

For minimally symptomatic patients, PRN short-acting bronchodilator (e.g., albuterol) can be reasonable, even if classic spirometric bronchodilator response is absent, given possible small-airway benefits (Riley 2019, expert opinion).

Initial Maintenance: In Practice 

A long-acting bronchodilator (LABA or a LAMA) is the first step, but many symptomatic patients feel and function better when you start with dual bronchodilation (LABA+LAMA) up front for superior symptom relief and fewer exacerbations; use the mMRC or CAT to gauge burden and decide how assertive to be (GOLD 2025). Dr. Askin reserves inhaled corticosteroids for the phenotype that benefits (i.e. those with recurrent exacerbations and a higher eosinophil signal) because ICS is not a default first-line in COPD. Device choice matters too, so pick a format the patient can actually use (pMDI vs DPI vs soft-mist), review technique in the room, and favor once-daily regimens when adherence is shaky. Albuterol (or another short-acting agent) can have a place for a reliever in many patients, while using long-acting therapy for maintenance, not rescue. If Dr. Askin starts with monotherapy, he will reassess in 4–6 weeks, checking technique, symptoms, and activity limits. Inadequate control or frequent SABA use nudges him to step up to LABA+LAMA. Along the way, he will watch for dry mouth or urinary retention with LAMAs, tremor or palpitations with LABAs, and always making sure to keep an eye on cost and formulary realities. For example, tiotropium/olodaterol and umeclidinium/vilanterol are common combinations, but any option the patient can access and use correctly is the “right” one (expert opinion, GOLD 2025).

When to Add ICS / Triple Therapy 

Many of us see patients on the newer triple therapy combination inhalers, but when are they truly indicated (expert opinion)? The answer is to add ICS to LABA+LAMA (i.e., move to triple therapy) when eosinophils are ≥300/µL, or in the 100–300/µL range with recurrent exacerbations or an allergic/asthmatic signal. ICS offers little benefit when eosinophils <100/µL and increases pneumonia risk; use deliberately and teach rinse/spit technique (GOLD 2025). Many will also move to triple therapy when exacerbations are frequent, or when patients are uncontrolled on LABA/LAMA with an exacerbation in the last year (expert opinion, Gartman 2021). Cost can be prohibitive for these triple inhalers, a cost-conscious “open triple” (generic budesonide/formoterol plus generic tiotropium) is a reasonable workaround when coverage is limited (expert opinion).

Frequent Exacerbators & Advanced Disease 

Roflumilast 

Consider in severe COPD with chronic bronchitis phenotype (low FEV1, frequent exacerbations). Side effects such as weight loss, diarrhea, and mood changes often limit use (expert opinion, GOLD 2025).

Chronic Azithromycin 

Consider for non-smokers with frequent exacerbations despite optimal inhalers. Typical regimens include 250mg daily or 500mg three times per week. Monitor QTc and hearing; obtain baseline ECG and audiology as appropriate. Avoid in active smokers (expert opinion, GOLD 2025).

Home NIV for Chronic Hypercapnia 

For chronic hypercapnia (PaCO₂ ≥52 mmHg) reassessed after stabilization from an exacerbation, NIV can reduce readmissions and improve outcomes. Counsel patients to use it nightly 6–8 hours; acclimate by wearing the interface while awake/evening TV to increase tolerance. Fit and interface comfort are critical, so partner with sleep techs and DME to optimize settings and masks (expert opinion, GOLD 2025).

Emerging & Adjunctive Therapies 

Ensifentrine 

An inhaled dual PDE3/4 inhibitor (nebulized) that provides bronchodilation and anti-inflammatory effects. Phase 3 data show modest FEV1 improvement with symptom and exacerbation benefits and a favorable safety profile. Access may require prior authorization; patient assistance programs exist (expert opinion, GOLD 2025). It is indicated for adults with moderate to severe COPD who continue to experience symptoms or exacerbations despite standard maintenance therapies (Sciurba 2024, GOLD 2025).

Biologics (dupilumab; others under study) 

Dupilumab now carries an add-on indication relevant to COPD with type-2/high-eosinophil features or asthma-COPD overlap. Other biologics used in asthma are under study; real-world benefit likely tracks with the degree of type-2 inflammation (Bhatt 2024).

Comorbidities

Cardiovascular/Metabolic

As internists, we should think beyond the lungs from day one. Cardiovascular disease is a major driver of morbidity and mortality in COPD, so treat lipids, blood pressure, diabetes, tobacco, and exercise with conviction as you normally would (expert opinion GOLD 2025). In advanced disease—or when the exam, CT, or ECG raises suspicion—use echocardiography to look for pulmonary hypertension (e.g., elevated estimated PA pressures, right-sided dilation) and loop in pulmonary if present.  Protect bone health early (steroid exposure and inactivity are common): ensure calcium/vitamin D adequacy, weight-bearing exercise, and DXA when appropriate. Address diabetes and metabolic syndrome with guideline-directed therapy.

Pulmonary, Sleep, & More

Keep lung cancer screening separate from COPD management but on the same checklist: continue annual low-dose CT when the patient remains eligible. Screen for anxiety and depression routinely; treating these improves symptoms, adherence, and quality of life; pulmonary rehab helps with this domain as well.

Sleep matters, too. Evaluate for OSA/overlap when hypercapnia, obesity, loud snoring, witnessed apneas, resistant hypertension, or daytime sleepiness are in the story; treating sleep-disordered breathing can improve daytime function and may reduce exacerbation burden. When bronchiectasis coexists (suggested by CT or by daily purulent sputum, recurrent infections, or scant hemoptysis), add airway-clearance strategies (e.g., huff cough, PEP devices, oscillatory tools, saline nebulization as tolerated) and culture-guided antibiotics. These are not standard COPD steps but are essential in that phenotype (expert opinion, GOLD 2025).

When to Refer

Cyrus tells us we should refer when stepping beyond dual long-acting bronchodilation, when exacerbations persist despite good adherence and technique, when chronic hypercapnia or suspected pulmonary hypertension is on the table, when bronchiectasis or another lung disease coexists, when alpha-1 antitrypsin deficiency is confirmed or strongly suspected, or when you’re considering macrolides, roflumilast, biologics, or home NIV. Really anytime you’re stepping out of your comfort zone as a primary care provider, referral is appropriate (expert opinion). 

Links

1. COPD Action Plan (ALA)
2. 2025 GOLD Update

Goal

Listeners will gain practical frameworks from GOLD 2025 to diagnose, classify, and manage COPD across diverse patient presentations.

Learning objectives

After listening to this episode listeners will…  

1. Differentiate COPD from other causes of chronic respiratory symptoms in nonsmokers using the GOLD 2025 framework.
2. Interpret spirometry and imaging findings in the context of GOLD 2025 updates, including evolving reference standards and their implications for health equity.
3. Apply the ABE classification to clinical cases and how it pertains to choosing treatment.
4. Formulate stepwise management strategies for COPD patients who progress despite maximal inhaler therapy using both pharmalogical and nonpharmalogical interventions.
5. Identify clinical scenarios in which patients may have overlapping or alternative lung disease and determine when referral to pulmonology is warranted.

Disclosures

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

Citation

Wurtz P, Askin C, Williams PN, Watto MF. “500 COPD Update with Cyrus Askin”. The Curbsiders Internal Medicine Podcast. thecurbsiders.com/category/curbsiders-podcast October 06, 2025.