BridgeCOPD

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 chronic obstructive pulmonary disease (COPD) to reflect disease severity, minimize exacerbation risks, and account for comorbidities and patient preferences • Learn how to educate patients with COPD

COPD, chronic obstructive pulmonary disease.

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

Global Initiative for Chronic Obstructive Lung Disease (GOLD), 2025 report. https://goldcopd.org/2025-gold-report/. Accessed January 14, 2025.

COPD by the Numbers NY State

US 14.2M

Adults diagnosed with COPD (2021)1

869K

Adults diagnosed with COPD (2021)6

6.5%

COPD prevalence1

5.5%

COPD prevalence6

791K

Annual ED visits2

133K

Annual ED visits7

$24B

Annual cost of COPD treatment4

$2.2B

Annual cost of COPD treatment6

247K

Medicare hospitalizations5

10,382

Medicare hospitalizations6

B, billion; K, thousand; M, million. 1. Liu Y, wt al. MMWR Morb Mortal Wkly Rep. 2023;72:1250-1256; 2. National Center for Health Statistics. 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. Shah CH, et al. Appl Health Econ Health Policy. 2023;21(6):915-924; 5. Centers for Disease Control and Prevention (CDC). https://www.cdc.gov/cdi/indicatordefinitions/chronic-obstructive-pulmonarydisease.html#:~:text=In%202020%2C%20there%20were%20247%2C314,with%20COPD%20as%20any%20diagnosis.&text=In%20addition%2C%20COPD%20coexists%20with,that%20have%20high%20hospitalization%20rates.; 6. American Lung Association. https://www.lung.org/getmedia/6289ff19-cef1-4f47-8b70-fdba2764cac3/2023-COPD-State-Briefs-New-York.pdf. Accessed March 15, 2025; 7. NY State Department of Health. https://nyshc.health.ny.gov/web/nyapd/emergency-department-visits-in-new-York. Accessed March 17, 2025.

Today’s COPD Patient – in NY Compared to adults without COPD, those diagnosed with COPD in NY reported:1 Indicator

COPD

Comparison

No COPD

Currently smoking

32.6%

10.8%

Having less than a high school education

18.6%

12.4%

Earning less than $15,000 in household income

13.4%

7.2%

Receiving a flu vaccination

56.8%

45.9%

Receiving a pneumococcal vaccination

58.1%

27.4%

Average number of a bad mental health days in the last month

15.1

10.9

Rates of COPD in NY are HIGHEST among adults who are/have2… q living with disabilities q current cigarette smokers q covered by Medicare q ≥ 65 years of age

q not in the labor force q former smokers q frequent mental distress q low socioeconomic status (SES)

1. American Lung Association. https://www.lung.org/getmedia/6289ff19-cef1-4f47-8b70-fdba2764cac3/2023-COPD-State-Briefs-New-York.pdf. Accessed March 15, 2025; 2. Behavioral Risk Factor Surveillance System (BRFSS). https://www.health.ny.gov/statistics/brfss/reports/docs/2022-22_brfss_copd.pdf. Accessed March 15, 2025.

SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS)

Participants residing in the most-disadvantaged neighborhoods had a:

• 56% higher rate of COPD exacerbation • 98% higher rate of severe COPD exacerbation • 1.6-point higher CAT score • 3.1 points higher SGRQ • 24.6 meters less six-minute walk distance. . .

Compared with participants living in the least-disadvantaged neighborhoods.

In addition to SES, neighborhood disadvantage has a major impact on COPD outcomes.

SPIROMICS is a multicenter prospective cohort study that has enrolled geographically diverse patients with COPD, along with smokers without COPD and non-smokers, across 12 US sites. Participants were aged 40 to 80 years old at enrollment and provided current home addresses. Galiatsatos P, et al. Inter J Chron Obstruct Pulmon Dis. 2020;15:981-993.

Acute Exacerbations of COPD (AECOPD) Prevalence and Impact

2 to 3 1.34 1.79

AECOPD are experienced on average by patients each year1

ü Decreased lung function, physiologic deterioration, and increased airway/ systemic inflammation2

HR of acute CV EVENTS within 30-days following 1st AECOPD1

ü Large reductions in QoL, physical fitness, and increased morbidity2

HR of ALL-CAUSE MORTALITY within 30 days following 1st AECOPD1

ü Incremental increases in mortality risk following each AECOPD1

50% of AECOPD are NOT reported by patients3; often only seeking medical help when they reach a crisis point.4 CV, cardiovascular; HR, hazard ratio; QoL, quality of life. 1. Daniels K, et al. Int J Chron Obstruct Pulmon Dis. 2024;19:225–241; 2. Wedzicha JA, Wilkinson T. Proc Am Thorac Soc. 2006;3(3):218-221; 3. Evensen AE. Am Fam Physician. 2010;81(5):607-613; 4. Williams V, et al. NPJ Prim Care Respir Med. 2014;24:14062.

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

Mitzner W. N Engl J Med. 2011;365(17):1637-1639; Braman S. Chest. 2015;129(1):104S–115S.

Chronic Obstructive Pulmonary Disease (COPD)

Normal

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

GOLD, 2025 report. https://goldcopd.org/2025-gold-report/. Accessed January 14, 2025.

Obstructive pathology

FEV1/FVC <LLN

Severity of obstruction

FEV1 Z-score

Mild

-1.65 to -2.50

Moderate

-2.50 to-4.00

Severe

Less than -4.00

125

Percent Normal TLC

IRV 100

VC

ERV

IRV

75

TV

VC 50

TV

FRC

ERV 25

RV FRC

RV 0 Normal

Obstructive

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 CT, computed tomography; LVR, lung volume reduction.

GOLD ABE Assessment Tool Assessment of airflow obstruction Grade

FEV1 (% predicted)

GOLD 1

≥80%

GOLD 2

50% - 79%

GOLD 3

30% - 49%

GOLD 4

<30%

Assessment of symptoms/risk of exacerbations Exacerbation history (per year)

Spirometrically confirmed diagnosis Postbronchodilator FEV1/FVC <0.70

≥2 moderate exacerbations or ≥1 leading to hospitalization

0 or 1 moderate exacerbation (not leading to hospitalization)

Group E Group A

Group B

mMRC 0-1; CAT <10

mMRC ≥2; CAT ≥10

Symptoms CAT, COPD assessment test; FEV1 , forced expiratory volume in 1 second; FVC, forced vital capacity; mMRC, modified Medical Research Council.

GOLD, 2025 report. https://goldcopd.org/2025-gold-report/. Accessed January 14, 2025.

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

q

mMRC Grade 1

I get short of breath when hurrying on the level or walking up a slight hill

q

mMRC Grade 2

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

q

mMRC Grade 3

I stop for breath after walking about 100 meters or after a few minutes on the level

q

mMRC Grade 4

I am too breathless to leave the house or I am breathless when dressing or undressing

q

Because COPD impacts patients beyond dyspnea, comprehensive assessment is recommended.

GOLD, 2025 report. https://goldcopd.org/2025-gold-report/. Accessed January 14, 2025.

COPD Assessment Test (CAT) Patient-Administered Self-Assessment Tool I never cough I have no phlegm (mucus) in my chest at all

0 1 2 3 4 5 0 1 2 3 4 5

I cough all the time My chest is completely full of phlegm (mucus)

My chest does not feel tight at all

0 1 2 3 4 5

My chest feels very tight

When I walk up a hill or one flight of stairs, I am not breathless

0 1 2 3 4 5

When I walk up a hill or one flight of stairs, I am very breathless

I am not limited doing any activities at home

0 1 2 3 4 5

I am very limited doing activities at home

I am confident leaving my home despite my lung condition

0 1 2 3 4 5

I am not at all confident leaving my home because of my lung condition

I sleep soundly I have lots of energy

0 1 2 3 4 5

I don’t sleep soundly because of my lung condition I have no energy at all

0 1 2 3 4 5

Total Score

A total score of 10 or greater is indicative of COPD symptoms that are clinically significant (low 0–9, medium 10–20, and high 20–40 impact).

Jones PW, et al. Eur Respir J. 2009;34(3):648-654.

Initial Pharmacologic Treatment EXACERBATION HISTORY

2025 GOLD Report

≥2 moderate exacerbations or ≥1 leading to hospitalization 0 or 1 moderate exacerbation (not leading to hospital admission)

Group E LABA + LAMAa (consider LABA+LAMA+ICSa if blood eos ≥300 cells/µL)

Group A

Group B

A bronchodilator

LABA + LAMAa

mMRC 0-1; CAT <10

mMRC ≥2; CAT ≥10 SYMPTOMS

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

Evaluating Patients’ Risk for AECOPD • Previous exacerbations • Severe/very severe airflow limitation • Smoking/exposure to irritants • Older age • Chronic mucus secretion • Poor exercise capacity • Significant comorbidities The strongest predictor for COPD exacerbations is

A PREVIOUS HISTORY OF EXACERBATIONS. Budde J, et al. Chronic Obstr Pulm Dis. 2019;6(2):129-131; Ramsey S, Hobbs SD. 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; Sirois C, et al. COPD. 2019;16(3-4):234-239; Hurst JR, et al. N Engl J Med. 2010;363(12):1128-1138.

Exacerbation Etioendophenotypes1 Viruses Bacteria

Smoke

T1 inflammation

Etiotype

Pollution

T2 inflammation

Endotype Treatment Nonadherence

Multimorbidity Underrecognized etiologies

T17 inflammation

Adaptive Immunity

Severity

Frequency

Phenotype

Pauciinflammatory

T regulatory

Time Course

Symptom complex

Temporal clustering

Innate Immunity

Exacerbation defined as:2

Cardinal features2

“an event characterized by increased dyspnea and/or cough and sputum that worsens in <14 days”

• Increased dyspnea • Sputum volume • Sputum purulence

1. Bhatt SP, et al. Am J Respir Crit Care Med. 2023;208(10):1026–1041; 2. GOLD, 2025 report. https://goldcopd.org/2025-gold-report/. Accessed January 14, 2025.

• Increased airway inflammation • Gas trapping

AECOPD Severity Assessment COPD patient with suspected AECOPD Confirm AECOPD diagnosis and episode severity Severity

Mild (default)

Moderate (meets at least 3 of 5)a

Variable thresholds to determine severity • Dyspnea VAS <5 • RR <24 breaths/min • 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 • 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 a

If obtained, ABG may show hypoxemia (PaO2 ≤60 mm Hg) and/or hypercapnia (PaCO2 >45 mm Hg) but NO acidosis (pH <7.35)

Severe

Consider differential diagnosis • Heart failure • Pneumonia • Pulmonary embolism Appropriate testing and treatment Determine etiology: viral testing, sputum culture, other

• Dyspnea, RR, HR, SaO2 and CRP same as moderate • ABG show new onset/worsening hypercapnia and acidosis (PaCO2 >45 mm Hg and pH <7.35)

ABG, arterial blood gas; CRP, C-reactive protein; HR, heart rate; PaCO2, partial pressure of carbon dioxide in arterial blood; RR, respiratory rate; SaO2, oxygen saturation of arterial blood; VAS, visual analog scale.

GOLD, 2025 report. https://goldcopd.org/2025-gold-report/. Accessed January 14, 2025.

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 FiO2, fraction of inspired oxygen; PaO2, partial pressure of oxygen; SABA, short-acting β2-agonist; SpO2, oxygen saturation.

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 is 44% … the 5-year mortality rate is 55% Admissions for COPD exacerbations have an estimated mortality rate of 10% Mortality relates to patient age, presence of acidotic respiratory failure, the need for ventilatory support, and comorbidities.

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.

Readmissions at Montefiore

Montefiore Einstein

Interventions That Reduce Frequency of AECOPD 2025 GOLD COPD Report

Class

Agent

Bronchodilators

LABAs; LAMAs; LABA + LAMA

Evidence Also Supporting Reduced Mortality

LABA + ICS Corticosteroidcontaining regimens

LABA + LAMA + ICS

Anti-inflammatory

Roflumilast; dupilumab

Anti-infectives

Vaccines; long-term macrolides

Mucoregulators

N-acetylcysteine; carbocysteine, erdosteine

Others

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)

Smoking cessation

HR for usual care group compared to intervention group (smoking cessation) HR 1.18 (95% Cl:1.02, 1.37)

Pulmonary rehabilitation

Old trials: RR 0.28 (95% Cl: 0.10, 0.84) New trials: RR 0.68 (95% Cl: 0.28, 1.67)

Lung volume reduction Vitamin D Shielding measures CI, confidence interval; LABD, long-acting bronchodilator; RR, rate ratio. GOLD, 2025 report. https://goldcopd.org/2025-gold-report/. Accessed January 14, 2025.

ADJUSTING THERAPY

Blood Eosinophils & ICS Benefit on AECOPD Relationship between blood eosinophil counts and effects of ICS on exacerbation prevention in COPD patients High Likelihood of Benefit

ICS Response

Low Likelihood of Benefit

100

Singh D, et al. Eur Respir J. 2019;53(5):1900164.

Blood Eosinophils, cells/µL

300

Triple Inhaled Combination Therapy RCT Clinical Evidence

Treatment Effect on AECOPD, Moderate or Severe

IMPACT1

Dose

Fluticasone furoate/ umeclidinium/ vilanterol (FF/UMEC/VI)

DPI 100/62.5/25 µg QD

FF/UMEC/VI, 0.91/year vs FF/VI, 1.07/year (RR, 0.85) & UMEC/VI, 1.21/year (RR 0.75)

ETHOS2,3

Agent

Budesonide/ glycopyrrolate/ formoterol fumarate (BGF)

pMDI 320/18/9.6 µg BID

BGF, 1.08/year vs GF, 1.42/year (RR, 0.76) & BF, 1.24/year (RR 0.87)

Treatment Effect on Mortalitya FF/UMEC/VI HR 0.72 vs UMEC/VI FF/UMEC/VI HR 0.89 vs FF/VI

BGF HR 0.51 vs GF BGF HR 0.72 vs BF

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).

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.

Managing Patients Who Were Previously Started on ICS/LABA Due to Previous GOLD Guidelines Patient currently on LABA + ICS • No current exacerbations • Previous positive treatment responsea Low symptom load

High symptom load

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

Consider changing to LABA + LAMA

Consider changing to LABA + LAMA + ICS

Current exacerbations

Blood eos <100 cells/µL

Blood eos ≥100 cells/µL

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

Adjust • Escalate • Switch inhaler device or molecules • De-escalate

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 LABA or LAMA if blood eos<300

LABA + LAMAa

if blood eos ≥300 if blood eos ≥100

LABA + LAMA + ICSa

if blood eos <100 if blood eos ≥300

Roflumilast FEV1 <50% and chronic bronchitis

Azithromycin preferentially in former smokers

Dupilumab chronic bronchitis

If both dyspnea and exacerbation treatable traits are present, use the exacerbation pathway. aSingle inhaler therapy may be more convenient and effective than multiple inhalers; single inhalers improve adherence to treatment. Consider de-escalation of ICS if pneumonia or other considerable sideeffects. 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/2025gold-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

Cumulative Mean No. of Events

Moderate or Severe COPD Exacerbations 1.0 Placebo

0.8 0.6 0.4

Dupilumab

0.2 0 BL 4 8 12 16 20 24 28 32 36 40 44 48 52

Week

LS Mean Change From Baseline, liters

– 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 0.20

Prebronchodilator FEV1 Dupilumab

0.15 0.10 0.05 0 BL 4

Placebo 8 12

BL, baseline; IL, interleukin; LS, least squares; R, receptor; SQ, subcutaneous; Q2W, every 2 weeks. Bhatt SP, et al. N Engl J Med. 2023;389(3):205-214.

24

Week

36

44

52

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 treatment.

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

Characteristic Age, mean Gender, male, % Moderate COPD, % Severe COPD, % % predicted FEV1 mean Chronic bronchitis, % Emphysema, % Both chronic bronchitis and emphysema, % AECOPD ≤15 month of screening, % Current smokers, % Background meds: YES, % • LAMA • LAMA/ICS • LABA • LABA/ICS

Ensifentrine n=477

Placebo n=283

Ensifentrine n=498

Placebo n=291

65 57 62 38 53 81 41

65 59 58 42 52 76 52

65 49 53 46 51 65 61

65 47 49 51 50 65 62

22

28

26

27

25 56 69 32 0.8 19 18

27 58 68 27 2 16 23

21 55 55 34 0.2 7 15

21 55 55 31 0 8 16

Primary Endpoint: ENHANCE Trials

Week 12 Average Change From Baseline: FEV1 AUC0-12h

ENHANCE Program Baseline Characteristics (mITT)

100

Placebo

80

61

60

Ensifentrine 48

40 20 0

+87 mL

+94 mL

-20 -40

-26

-60 ENHANCE-1 Trial

AUC, area under the plasma drug concentration-time curve; mITT, modified intent-to-treat; Q12H, every 12 hours. Anzueto A, et al. Am J Respir Crit Care Med. 2023;208(4):406-416.

-46 ENHANCE-2 Trial

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-1 Trial Treatment

Annualized Event Rate LS, mean

Rate Ratio

Placebo (n=283)

0.41 (0.27, 0.63)

—

Ensifentrine 3 mg (n=477)

0.26 (0.17, 0.40)

0.64 (0.40, 1.00)

ENHANCE-2 Trial

Exacerbation P Rate Value Reduction

Treatment

Annualized Event Rate LS, mean

Rate Ratio

—

Placebo (n=291)

0.42 (0.30, 0.57)

—

—

36%

Ensifentrine 3 mg (n=498)

0.24 (0.18, 0.32)

0.57 (0.38, 0.87)

43%

0.05

Protocol-specified pooled analysis of exacerbation rate: rate ratio 0.59 (95% Cl: 0.43-0.80); 41% reduction in rate, P<0.05.

Anzueto A, et al. Am J Respir Crit Care Med. 2023;208(4):406-416.

Exacerbation P Rate Value Reduction

<0.05

The Impact of Delaying Step-up Therapy A Retrospective Study of Triple Inhaled Therapy AECOPD Rates

0.4

Prompt cohort

AECOPD Rates

0.33

Delayed cohort

0.3

0.2

0.1

0.21

0.20

64.7% increase in AECOPD rates

0.11

95.1% increase in AECOPD rates 0 Hospitalization

ED Visit

.

Exacerbation rates were significantly higher in the delayed cohort compared with the prompt cohort.

P<0.0001 for all comparisons. Triple therapy was defined as patients with ≥1 overlapping day(s) supply of LAMA and ICS/LABA prescription, including combination products.

Bogart M, et al. Respir Med. 2018;145:138-144.

The Impact of Delaying Step-up Therapy A Retrospective Study of Triple Inhaled Therapy Costs 35,000

Costs, $

30,000

$32,100

Prompt cohort Delayed cohort

$26,200

25,000 20,000 15,000 10,000 5,000

$10,300

22.8% higher all-cause medical costs

$6,220

66.3% higher COPD-related medical costs

0 COPD-Related Medical Costs

All-Cause Medical Costs

.

Costs were significantly higher in the delayed cohort compared with the prompt cohort.

P<0.0001 for all comparisons. Triple therapy was defined as patients with ≥1 overlapping day(s) supply of LAMA and ICS/LABA prescription, including combination products.

Bogart M, et al. Respir Med. 2018;145:138-144.

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?

DPI, dry powder inhaler; MDI, metered dose inhaler; SMI, soft mist inhaler.

Miles MC, et al. Ther Adv Respir Dis. 2013;7(2):81-86; Restrepo RD, et al. Int J Chron Obstruct Pulmon Dis. 2008;3(3):371-384.

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: ü Improves dyspnea, fatigue, emotional function (symptoms of anxiety and depression), health status, and exercise tolerance in stable patients LESS THAN 1% ü Reduces hospitalization among patients who have had of patients receive a recent exacerbation (≤4 weeks from prior hospitalization) PULMONARY REHAB ü Evidence supporting reduced mortality following hospitalization ü Cost-effective • Indicated in all patents with relevant symptoms and/or at high risk for AECOPD • Optimal benefits: 6-8–week programs

• Barriers: accessibility, availability, uptake

Physical activity is a STRONG predictor of MORTALITY. 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.

What COPD Patient/Clinician Resources Would Be Valuable to You?

For links to patient education videos and other clinical resources, please visit our Clinical Resource Center at www.ExchangeCME.com

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

Watson JS, et al. Br J Gen Pract. 2020;70(693):e274–e284.

• 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

CLINICAL RESOURCE CENTER

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https://ExchangeCME.com/COPDBridgeResources