Sarah Sungurlu, DO Assistant Professor of Medicine Division of Pulmonary and Critical Care Medicine
Learning Objectives
• Characterize disease phenotypes, exacerbation risks, and treatable traits
• Discuss recent clinical trial evidence and guideline updates
• Tailor maintenance regimens for patients with COPD to reflect disease severity, minimize exacerbation risks, and account for comorbidities and patient preferences
• Learn how to educate patients with COPD
Chronic Obstructive Pulmonary Disease
2025 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Definition
• Heterogeneous lung condition characterized by chronic respiratory symptoms (dyspnea, cough, sputum production, exacerbations)
–Due to abnormalities of the airways (bronchitis, bronchiolitis) and/or alveoli (emphysema) that cause persistent, often progressive airflow obstruction
• Focuses on patient characteristics and removes etiology to emphasize COPD factors beyond tobacco
• In low- and middle-income countries, nonsmoking COPD may be responsible to 60%-70% of cases
14.2M Americans diagnosed with COPD(2021)1
791K emergency department visits annually in the US2
3rd leading cause of US hospital readmissions3
6th leading cause of death in the US2,a
K, thousand; M, million. aIncludes all chronic lower respiratory diseases. 1. Lin C, et al. Int J Chron Obstruct Pulmon Dis. 2023;18:1511–1524; 2. CDC. https://www.cdc.gov/nchs/fastats/copd.htm. Accessed January 14, 2025; 3. Press VG, et al. Ann Am Thorac Soc. 2019;16(2):161-170; 4. Boers E, et al. JAMA Netw Open. 2023;6(12):e2346598. Globally, incidence projected to increase by 23% from 2020 to 2050.4
Acute Exacerbations of COPD (AECOPD) Prevalence and Impact
2to3
AECOPD are experienced on average by patients each year1
1.34 1.79 ✓Decreased lung function, physiologic deterioration, and increased airway/ systemic inflammation2 ✓Large reductions in QoL, physical fitness, and increased morbidity2 ✓Incremental increases in mortality risk following each AECOPD1 50% of AECOPD are NOT reported by patients3;
HR of acute CV EVENTS within 30-days following 1st AECOPD1
HR of ALL-CAUSE MORTALITY within 30 days following 1st AECOPD1
Call to Action
• Recognize patients with symptoms potentially indicative of COPD and assess for the disease
• Recommend appropriate treatment strategies based on disease severity and predominant symptoms
• Regularly reevaluate patients using validated assessment tools
• Adjust and escalate pharmacologic and nonpharmacologic treatment approaches in patients with uncontrolled symptoms and/or frequent exacerbations
COPD DIAGNOSIS & ASSESSMENT
Heterogeneous
• Definition of Emphysema: abnormal enlargement of airways distal to terminal bronchioles due to destruction of their walls without obvious fibrosis
• Definition of Chronic Bronchitis: chronic productive cough for at least 3 consecutive months in 2 consecutive years
–Mucous gland enlargement and hyperplasia of goblet cells are hallmarks of chronic bronchitis
Chronic Obstructive Pulmonary Disease (COPD)
Role of Spirometry
• Diagnosis cannot be made without proven fixed obstruction
• Can help with therapeutic options depending on severity of airflow obstruction
• Can help with differential diagnosis
2025 report. https://goldcopd.org/2025-gold-report/. Accessed January 14, 2025.
Radiology
• Chest X-ray
–Hyperinflation
–Flattened diaphragm
–Increased retrosternal airspace
–Bullae
• Chest CT
–Emphysema
–Bullae
–Pulmonary vascular changes suggestive of pulmonary hypertension
–Utility for lung cancer screening, differential diagnoses, and LVR
GOLD ABE Assessment Tool
Spirometrically confirmed diagnosis
Assessment of airflow obstruction
Assessment of symptoms/risk of exacerbations
≥2 moderate exacerbations or ≥1 leading to hospitalization
0 or 1 moderate exacerbation (not leading to hospitalization)
Modified British Medical Research Council Questionnaire (mMRC)
Please mark the box that applies to you (one box only)
mMRC Grade 0 I only get breathless with strenuous exercise
mMRC Grade 1
mMRC Grade 2
I get short of breath when hurrying on the level or walking up a slight hill
I walk slower than people of the same age on the level because of breathlessness, or I have to stop for breath when walking on my own pace on the level
mMRC Grade 3
mMRC Grade 4
I stop for breath after walking about 100 meters or after a few minutes on the level
I am too breathless to leave the house or I am breathless when dressing or undressing
Because COPD impacts patients beyond dyspnea, comprehensive assessment is recommended.
COPD Assessment Test (CAT)
Patient-Administered Self-Assessment Tool
I never cough I cough all the time
I have no phlegm (mucus) in my chest at all
My chest does not feel tight at all
When I walk up a hill or one flight of stairs, I am not breathless
I am not limited doing any activities at home
I am confident leaving my home despite my lung condition
My chest is completely full of phlegm (mucus)
My chest feels very tight
When I walk up a hill or one flight of stairs, I am very breathless
I am very limited doing activities at home
I am not at all confident leaving my home because of my lung condition
I sleep soundly I don’t sleep soundly because of my lung condition
I have lots of energy I have no energy at all
Initial Pharmacologic Treatment 2025 GOLD Report
Group E
LABA + LAMAa (consider LABA+LAMA+ICSa if blood eos ≥300 cells/µL)
Group A Group B
LABA + LAMAa A bronchodilator
mMRC 0-1; CAT <10
SYMPTOMS
mMRC ≥2; CAT ≥10
ICS, inhaled corticosteroids; LABA, long-acting β-agonist; LAMA, long-acting muscarinic antagonists.
aSingle inhaler therapy may be more convenient and effective than multiple inhalers; single inhalers improve adherence to treatment. GOLD, 2025 report. https://goldcopd.org/2025-gold-report/. Accessed January 14, 2025.
COPD EXACERBATION RISK & MANAGEMENT
• Previous exacerbations • Severe/very severe airflow limitation • Smoking/exposure to irritants • Older age • Chronic mucus secretion • Poor exercise capacity • Significant comorbidities
Exacerbation Etioendophenotypes1
Exacerbation defined as:2 “an event characterized by increased dyspnea and/or cough and sputum that worsens in <14 days”
AECOPD Severity Assessment
COPD patient with suspected AECOPD
Confirm AECOPD diagnosis and episode severity
Severity Variable thresholds to determine severity
• Dyspnea VAS <5
• RR <24 breaths/min
Mild (default)
• HR <95 bpm
• Resting SaO2 ≥92% breathing ambient air (or patient’s usual oxygen prescription)AND change ≤3% (when known)
• CRP <10 mg/L (if obtained)
• Dyspnea VAS ≥5
• RR ≥24 breaths/min
Moderate (meets at least 3 of 5)a
• HR ≥95 bpm
• Resting SaO2 <92% breathing ambient air (or patient’s usual oxygen prescription)AND/OR change >3% (when known)
• CRP ≥10 mg/L
aIf obtained, ABG may show hypoxemia (PaO2 ≤60 mm Hg) and/or hypercapnia (PaCO2 >45 mm Hg) but NO acidosis (pH <7.35)
• Dyspnea, RR, HR, SaO2 and CRP same as moderate
Consider differential diagnosis
• Heart failure
• Pneumonia
• Pulmonary embolism
Appropriate testing and treatment
Severe
• ABG show new onset/worsening hypercapnia and acidosis (PaCO2 >45 mm Hg and pH <7.35)
https://goldcopd.org/2025-gold-report/. Accessed January 14, 2025.
Determine etiology: viral testing, sputum culture, other
AECOPD Management
• REDUCE trial: shorter course of systemic steroids yields equal length to next exacerbation1
• Steroids shorten recovery time, reduce risk of treatment failure, and reduce risk of early relapse
• Preferred dosing of prednisone 40 mg for 5 days
–Oral prednisone is equally effective to intravenous administration if oral access is available and intact –Widely varying practices regarding the dose of systemic corticosteroids in ICU mechanically ventilated patients (low dose <240 mg/day)2 Leuppi JD, et al. JAMA. 2013;309(21):2223-2231 2. Kiser TH, et al. Am J Respir Crit Care Med. 2014;189(9):1052-64.
When Do We Use Antibiotics In A COPD Exacerbation?
• Controversial, but some evidence of benefit with antibiotics in absence of pneumonia
– Most exacerbations are triggered by viral infection. Bacterial infection or environmental factors can also trigger
– To reduce overexposure to antibiotics, suggest use of antibiotics if increase in dyspnea, sputum volume, and sputum purulence
• Sputum purulence more specific
• Or require mechanical ventilation (invasive or noninvasive)
• Duration: 5 days
• Choice: should be based on local resistance pattern (macrolide, tetracycline, amoxicillin)
– If frequent exacerbations or require mechanical ventilation recommend sputum culture
Management of Exacerbations
• Inhaled bronchodilators:
–Increase dose and/or frequency of short-acting bronchodilator
–Combine SABA and short-acting anticholinergics as initial bronchodilator for acute exacerbation
–Use spacers or nebulizer when appropriate
• Oxygen therapy: use minimum flow rate to maintain SpO2 (or PaO2) at an acceptable level, as high FiO2 can result in worsening hypercapnia
• Noninvasive ventilation: first mode for acute respiratory failure to improve gas exchange, reduce work of breathing/need for intubation, decrease hospitalization duration, and improve survival
Hospital Discharge & Follow-up
• Reassess oxygen needs
• PFTs are recommended at 8-12 weeks of discharge (baseline conditions) to establish diagnosis
• Can have significant improvement in FEV1 > 8 weeks after acute exacerbation
• Can consider acute spirometry in hospitalized patient or shortly after discharge to try to reduce overdiagnosis GOLD, 2025 report. https://goldcopd.org/2025-gold-report/. Accessed January 14, 2025.
Reducing Readmissions Across Montefiore
• Transitional care excellence team consult for all COPD and pneumonia discharges
• Discharge pathway includes:
– Education and supervision/correction of inhaler technique
– Medication optimization (inhalers, smoking cessation)
– Assessment and recommendations for comorbidity management
– Telephonic follow-up within 2 days of discharge
– Post discharge appointment within 14 days
– AND MORE!
Transitional Care Excellence
• Multidisciplinary team of pharmacists, nurse practitioners, and research associates that drives and supports continuity of care and collaboration across the health system
–Responsible for the delivery of patient-centered transitional care interventions
• Mission: safely transition patients from hospital to next point of care
• Vision: innovate hospital medicine through an acute and chronic care continuum model that holistically encompasses multimorbidity disease management and social determinants of health
Following Discharge for a COPD Exacerbation…
… the 30-day readmission rate is 23%
… the 5-year rehospitalization risk is44%
… the 5-year mortality rate is 55%
Admissions for COPD exacerbations have an estimated mortality rate of 10% 1. Shah T, et al. Chest. 2016;150(4):916-926; 2. Portillo EC, et al. Fed Pract. 2018;35(11):30-36; 3. GOLD, 2025 report. https://goldcopd.org/2025-gold-report/. Accessed January 14, 2025.
Mortality relates to patient age, presence of acidotic respiratory failure, the need for ventilatory support, and comorbidities.
Readmissions at Montefiore
Montefiore Einstein
Interventions That Reduce Frequency of AECOPD
2025 GOLD COPD Report
Class Agent
Bronchodilators LABAs; LAMAs; LABA + LAMA
Corticosteroidcontaining regimens
LABA + ICS
LABA + LAMA + ICS
Evidence Also Supporting Reduced Mortality
Single inhaler triple compared to dual LABD relative risk reduction: IMPACT HR 0.72 (95% CI: 0.53, 0.99); ETHOS HR 0.51 (95% Cl: 0.33, 0.80)
Anti-inflammatory Roflumilast; dupilumab
Anti-infectives Vaccines; long-term macrolides
Mucoregulators N-acetylcysteine; carbocysteine, erdosteine
Smoking cessation
Others
Pulmonary rehabilitation
Lung volume reduction
Vitamin D
Shielding measures
HR for usual care group compared to intervention group (smoking cessation)
HR 1.18 (95% Cl:1.02, 1.37)
Old trials: RR 0.28 (95% Cl: 0.10, 0.84)
New trials: RR 0.68 (95% Cl: 0.28, 1.67)
ADJUSTING THERAPY
Blood Eosinophils
& ICS Benefit on AECOPD
Relationship between blood eosinophil counts and effects of ICS on exacerbation prevention in COPD patients
Low Likelihood of Benefit
High Likelihood of Benefit
Triple Inhaled Combination Therapy RCT Clinical Evidence
2,3 Budesonide/ glycopyrrolate/ formoterol fumarate (BGF)
0.91/year vs FF/VI, 1.07/year (RR, 0.85) & UMEC/VI, 1.21/year (RR 0.75)
HR 0.72 vs UMEC/VI FF/UMEC/VI HR 0.89 vs FF/VI
1.08/year vs GF, 1.42/year (RR, 0.76) & BF, 1.24/year (RR 0.87)
BID, twice daily; QD, once daily; DPI, dry powder inhaler; HR, hazard ratio; pMDI, pressurized MDI; RR, rate ratio. aSymptomatic patients (CAT ≥10) with a history of frequent (≥2 moderate AECOPD) and/or severe AECOPD (≥1 requiring hospitalization).
HR 0.51 vs GF
HR 0.72 vs BF
1. Lipson DA, et al. Am J Respir Crit Care Med. 2020;201(12):1508-1516; 2. Rabe KF, et al. N Engl J Med. 2020;383(1):35-48; 3. Martinez FJ, et al. Am J Respir Crit Care Med. 2021;203(5):553–564.
Factors to Consider When Adding ICS to LABD
STRONGLY
FAVORS USE
•History of hospitalization(s) for AECOPDa
•≥2 moderate AECOPD per yeara
•Blood eos ≥300 cells/µL
•History of, or concomitant, asthma
FAVORS USE
•1 moderate AECOPD per yeara
•Blood eos 100 to <300 cells/µL
AGAINST USE
•Repeated pneumonia events
•Blood eos <100 cells/µL
•History of mycobacterial infection
(Note the scenario is different when considering ICS withdrawal).
aDespite appropriate long-acting bronchodilator maintenance therapy.
Blood eosinophils should be seen as a continuum, quoted values represent approximate cut-points; eosinophil counts are likely to fluctuate. GOLD, 2025 report. https://goldcopd.org/2025-gold-report/. Accessed January 14,, 2025.
Patient currently on LABA + ICS
•No current exacerbations
•Previous positive treatment responsea Consider changing to LABA + LAMA
Continue treatment
aPatient previously had exacerbations and responded to LABA + ICS treatment. GOLD, 2025 report. https://goldcopd.org/2025-gold-report/. Accessed January 14, 2025. No relevant exacerbation history Current exacerbations
Adjust
or
Escalate Therapy?
Factors to Consider
• Review proper use of (compliance to) prescription medicine, eg, correct inhalation maneuvers
• Adherence issues, eg cost, adverse events
• Current symptoms and exacerbation history
• Clinical tools
– Spirometry, blood eosinophils, 6-min walking distance, SGRQ, mMRC, and CAT
SGRQ, St. George's Respiratory Questionnaire. GOLD, 2025 report. https://goldcopd.org/2025-gold-report/. Accessed January 14, 2025.
Review
•Symptoms
•Dyspnea
•Exacerbations
•Escalate
•Switch inhaler device or molecules
•De-escalate Adjust
Assess
•Inhaler technique and adherence
•Nonpharmacological approaches (including pulmonary rehabilitation and self-management education)
2025 GOLD Report Recommendations
Algorithm for Follow-up Pharmacologic Treatment – Exacerbations
aSingle inhaler therapy may be more convenient and effective than multiple inhalers; single inhalers improve adherence to trea tment. Consider de-escalation of ICS if pneumonia or other considerable sideeffects. In case of blood eos ≥300 cells/µL, de-escalation is more
gold-report/. Accessed January 14, 2025.
Latest Maintenance Medications
Dupilumab – Exacerbation Pathway
• IL-4Rα biologic; 300 mg SQ, Q2W (single-dose prefilled syringe or pen) • BOREAS P3 study
– N=939 patients with a blood eos ≥300 cell/µL and an elevated exacerbation risk despite use of triple therapy
– Significantly improved lung function and health status; decreased risk for AECOPD
2025 GOLD Report Recommendations
Algorithm for Follow-up Pharmacologic Treatment – Dyspnea
LABA or LAMA
LABA + LAMAa
• Consider switching inhaler device or molecules
• Implement or escalate nonpharmacologic treatment(s)
• Consider adding ensifentrine
• Investigate (and treat) other causes of dyspnea
aSingle inhaler therapy may be more convenient and effective than multiple inhalers; single inhalers improve adherence to trea tment. Consider de-escalation of ICS if pneumonia or other considerable side effects. In case of blood eos ≥300 cells/µL, de-escalation is more likely to be associated with the development of exacerbations.
Exacerbations refers to the number of exacerbations per year. GOLD, 2025 report. https://goldcopd.org/2025 -gold-report/. Accessed January 14, 2025.
Latest Maintenance Medications
Ensifentrine – Dyspnea Pathway
•Dual phosphodiesterase-3 and -4 (PDE3/4) inhibitor; 3 mg/2.5 mL inhalation suspension, Q12H
•ENHANCE 1 and ENHANCE 2 P3 studies
– N=760 and N=789 patients aged 40–80 years with moderate to severe symptomatic COPD
– Exclusion: patients with history of AECOPD in the last 3 months were excluded
– Not designed to assess impact on top of dual LABA/LAMA or triple ICS/LABA/LAMA; thus, difficult to position in algorithms
– Ensifentrine significantly improved lung function, dyspnea, and health status
ENHANCE Program Baseline Characteristics (mITT)
Endpoint: ENHANCE Trials
Latest Maintenance Medications
Ensifentrine – Dyspnea Pathway
•Dual phosphodiesterase-3 and -4 (PDE3/4) inhibitor; 3 mg/2.5 mL inhalation suspension, Q12H
•ENHANCE 1 and ENHANCE 2 P3 studies
– N=760 and N=789 patients aged 40–80 years with moderate to severe symptomatic COPD
– Exclusion: patients with history of AECOPD in the last 3 months were excluded
– Not designed to assess impact on top of dual LABA/LAMA or triple ICS/LABA/LAMA; thus, difficult to position in algorithms
– Ensifentrine significantly improved lung function, dyspnea, and health status
The Impact of Delaying Step-up Therapy
A Retrospective Study of Triple Inhaled Therapy AECOPD Rates
The Impact of Delaying Step-up Therapy
A Retrospective Study of Triple Inhaled Therapy
PATIENT EDUCATION AND NONPHARMACOLOGIC TREATMENT OPTIONS
Selection and Proper Use of Delivery Devices What? When? How?
Up to 60% of patients with COPD are noncompliant to the prescribed regimen; only 1 out of 10 patients with an MDI performs all essential steps correctly.
• How deeply can patients inhale?
• How long can patients hold their breath?
• Do patients have the dexterity to use the device?
• What are the manual instructions for MDI? DPI? SMI? Nebulizer?
• How do you clean the device?
• How do you know when the device is empty?
Reducing Exacerbation Risk Nonpharmacologic Interventions
• Smoking cessation
• Pulmonary rehabilitation
• Vaccines –Updated guidance in the 2025 GOLD Report
• Education and self-management (COPD action plan, physical activity)
Smoking cessation is the only evidence-based intervention proven to slow down the accelerated decline in lung function.
Budde J, et al. Chronic Obstr Pulm Dis. 2019;6(2):129-131; Ramsey SC, Hobbs FDR. Proc Am Thorac Soc. 2006;3(7):635-640; Mantero M, et al. Int J Chron Obstruct Pulmon Dis. 2017;12:2687-2693; GOLD, 2025 report. https://goldcopd.org/2025-gold-report/. Accessed January 14, 2025; van Eerd EAM, et al. NPJ Prim Care Respir Med. 2017;27(1):41.
Pulmonary Rehabilitation (PR)
• Benefits:
✓Improves dyspnea, fatigue, emotional function (symptoms of anxiety and depression), health status, and exercise tolerance in stable patients
✓Reduces hospitalization among patients who have had a recent exacerbation (≤4 weeks from prior hospitalization)
✓Evidence supporting reduced mortality
✓Cost-effective
• Indicated in all patents with relevant symptoms and/or at high risk for AECOPD
• Optimal benefits: 6-8–week programs
LESS THAN 1% of patients receive PULMONARY REHAB following hospitalization
• Barriers: accessibility, availability, uptake 1. GOLD, 2025 report. https://goldcopd.org/2025-gold-report/. Accessed January 14,2025; 2. Griffiths TL, et al. Lancet. 2000;355(9201):362-368; 3. McCarthy B, et al. Cochrane Database Syst Rev. 2015(2):CD003793; 4. Maddocks M, et al. Respirology. 2015;20(3):395-404; 5. University of Michigan. https://www.michiganmedicine.org/health-lab/less-1-copd-patients-receive-pulmonary-rehab-following-hospitalization/. Accessed January 14, 2025.
Wakefield Pulmonary Rehab Program
Montefiore PR Information for Pulmonary Providers
What are the referral criteria for PR from pulmonary providers?
• COPD
– Pulmonologist diagnosis of COPD
PLUS
– GOLD E disease or GOLD B disease with high preintervention likelihood of benefit from pulmonary rehabilitation
• Pre- or post-lung transplant
• Interstitial lung disease with high preintervention likelihood of benefit from PR
• Pulmonary hypertension with high preintervention likelihood of benefit from PR
Education and Self-Management
• Encourage communication with health care professionals
• Increase/maintain physical activity
• Practice expiration exercises that facilitate sputum excretion and reduce exhaustion due to coughing
• Nutritional support and healthy diet
• Adequate sleep
• Written COPD action plan –includes avoiding triggers, monitoring symptoms, constant information
My COPD Action Plan
GOLD, 2025 report. https://goldcopd.org/2025-gold-report/. Accessed January 14, 2025; COPD Foundation. https://www.copdfoundation.org/Learn-More/Educational-MaterialsResources/Downloads.aspx#MyCOPDActionPlan. Accessed January 14, 2025.
GUIDANCE ON REFERRING PATIENTS WITH COPD TO PULMONOLOGY
SPECIALTY
Who, When, Where, and How?
Key Factors to Consider Upon Referral
• Severity of symptoms
– Progressive dyspnea that significantly impacts daily activities
– Frequent or severe COPD exacerbations requiring hospitalization
– Persistent cough with significant sputum production
• Medication management
– Inadequate symptom control despite maximal tolerated dose of standard treatment
– Need for complex medication regimens or combination therapies
• Diagnostic uncertainty
– Suspected underlying conditions that may contribute to COPD symptoms, eg, pulmonary hypertension, bronchiectasis
• Pulmonary function tests (PFTs)
– Severely decreased FEV1/FVC ratio indicating significant airflow obstruction
• Patient factors
– Desire to participate in pulmonary rehabilitation
– Difficulty managing self-care related to COPD
– Significant psychological impact from COPD symptoms
What Should I Include in My Referral?
• Detailed medical history –eg, smoking status and COPD exacerbations
• Current medications and dosages
• Recent pulmonary function test results
• Relevant clinical findings –eg, chest exam and oxygen saturation levels
• Specific concerns or questions regarding patient’s COPD management
Watson JS, et al. Br J Gen Pract. 2020;70(693):e274–e284.
Summary
• COPD is a common and chronic disease that can be managed effectively
• Key objectives of management are alleviation of symptoms and prevention of exacerbations, in both short-term and long-term treatment
• Exacerbations significantly increase patient morbidity and risk of death
• Pharmacologic and nonpharmacologic management strategies can reduce the risk of exacerbations and mortality
• Evidence-based guidelines for COPD management are also available and regularly updated by the GOLD committee
• Simple and reliable questionnaires (eg, CAT, mMRC) should be routinely used to assess symptoms, risk of exacerbations, and patient health status
• Maintenance therapy should be matched to individual patient needs
• Supportive clinician and patient resources are available
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