Follow-up pharmacologic management of COPD^*

No exacerbations and no dyspnea/low COPD impact (ie, mMRC 0 to 1 or CAT <10)^¶
Current therapy	Actions
SABA or SABA-SAMA^Δ as needed	Add LAMA (preferred) or LABA; continuing current therapy is a reasonable alternative for those with minimal symptoms
LAMA, LABA, or LAMA-LABA	Continue current therapy
LABA-ICS or LABA-LAMA-ICS	Taper or discontinue ICS dose to reduce adverse effects of ICS therapy^◊
Persistent dyspnea or high COPD impact (ie, mMRC ≥2 or CAT ≥10)^¶ with no exacerbations
Current therapy	Actions
SABA or SABA-SAMA^Δ as needed	Add LAMA-LABA
LAMA or LABA monotherapy	Change to LAMA-LABA^§
LABA-ICS	LAMA-LABA-ICS^§ LAMA-LABA if lack of response or adverse effects from ICS therapy^◊
LAMA-LABA	Trial of LAMA-LABA-ICS, in patients with blood eosinophils ≥100 cells/microL or features of concomitant asthma^¥ Add-on ensifentrine, where available^‡ Additional interventions may include low-dose theophylline, repeat pulmonary rehabilitation, and nonpharmacologic therapies^†
LAMA-LABA + ensifentrine, ±ICS	Continue maximal inhaled therapies Trial of LAMA-LABA-ICS, in patients with blood eosinophils ≥100 cells/microL or features of concomitant asthma^¥ Stop ICS, if lack of response or adverse effects from ICS^◊ Additional interventions may include low-dose theophylline, repeat pulmonary rehabilitation, and nonpharmacologic therapies^†
1 or more exacerbations in past year +/– persistent dyspnea or high COPD impact (ie, mMRC ≥2 or CAT ≥10)^¶
Current therapy	Actions
SABA or SABA-SAMA^Δ as needed	Add LAMA-LABA
LAMA or LABA monotherapy	LAMA-LABA, if blood eosinophil count <300/microL^¥ or LAMA-LABA-ICS, if blood eosinophil count ≥300/microL^¥ or hospitalization for COPD exacerbation or LABA-ICS, if blood eosinophil count ≥100/microL^§ and LAMA contraindicated
LAMA-LABA	LAMA-LABA-ICS, if blood eosinophil count ≥100/microL^¥ or Add ensifentrine (preferred), where available,^‡ or either roflumilast^¶¶ or azithromycin^ΔΔ, if blood eosinophil count <100/microL^**
LABA-ICS	LAMA-LABA-ICS^§ or LAMA-LABA^§, if adverse effects from ICS therapy^◊
LAMA-LABA-ICS	Continue LAMA-LABA-ICS Add ensifentrine (preferred), where available,^‡ or systemic therapies (roflumilast^¶¶, azithromycin^ΔΔ, or dupilumab^◊◊) Stop ICS if adverse effects from ICS therapy^◊
LAMA-LABA & ensifentrine ±ICS	Continue maximal inhaled therapy Add roflumilast^¶¶ or azithromycin^ΔΔ or dupilumab^◊◊ Stop ICS if adverse effects from ICS therapy^◊

BMI: body mass index; CAT: COPD Assessment Test; COPD: chronic obstructive pulmonary disease; FEV₁: forced expiratory volume in one second; ICS: inhaled corticosteroids (glucocorticoids); LABA: long-acting beta-agonist; LAMA: long-acting muscarinic-antagonist; mMRC: modified Medical Research Council; SABA: short-acting beta-agonist; SAMA: short-acting muscarinic-antagonist; SpO₂: pulse oxygen saturation.

* Adjustments to pharmacologic therapy for COPD are based on an assessment of dyspnea/exercise limitation (mMRC or CAT), frequency of exacerbations, and peripheral blood eosinophil counts. Follow-up visits are also an opportunity to assess and reinforce nonpharmacologic interventions for COPD, including: smoking cessation; inhaler technique and adherence to medications; administration of pneumococcal and seasonal influenza vaccinations; pulmonary rehabilitation; and nutrition counselling regarding healthy diet and normal BMI. All patients with COPD should have a rapid relief inhaler available, either a SABA or a SABA-SAMA (SABA preferred for patients using a LAMA). Refer to UpToDate content on the overview of management for stable COPD.

¶ mMRC dyspnea scale: https://www.pcrs-uk.org/mrc-dyspnoea-scale; CAT evaluates health impact of COPD: https://www.catestonline.org.

Δ SAMAs are generally not recommended to be used routinely in conjunction with LAMAs due to cumulative anticholinergic side effects and theoretical blockage of LAMA effects by the SAMA.

◊ If the blood eosinophil count ≥300 cells/microL, patients are more likely to experience exacerbations after ICS withdrawal. Close patient monitoring is required if ICS are withdrawn.

§ Ensifentrine may reasonably be added to the regimen instead of LAMA or LABA therapy if one of these agents cannot be used due to adverse effects or other contraindication.

¥ In patients with exacerbations and blood eosinophil count ≥300 cells/microL, the addition of ICS is likely to be of benefit. For patients with eosinophil counts ≥100 but <300 cells/microL, ICS may improve exacerbation rates and pulmonary function.

‡ Ensifentrine has not been well-studied as add-on therapy to both LAMA and LABA. Until further data are available, however, the distinct mechanism of action and favorable side-effect profile of this agent drive its preferred use in this setting.

† Nonpharmacologic measures (eg, oxygen therapy if SpO2 ≤88%, pulmonary rehabilitation, bronchoscopic or surgical lung volume reduction, lung transplantation) can help reduce dyspnea and exacerbations. Contributing comorbidities should be evaluated and treated. Not all patients achieve control of dyspnea or exacerbations despite optimal available pharmacotherapy.

** For patients with a blood eosinophil count <100 cells/microL, there is a low likelihood that addition of ICS will be beneficial and higher risk of pneumonia after the addition of ICS.

¶¶ Roflumilast is used for patients with chronic bronchitis and FEV₁ <50% predicted, particularly if there has been at least 1 hospitalization for an exacerbation in the past year. Potential adverse effects may limit use.

ΔΔ Azithromycin preventive therapy is more effective in patients who are not current smokers. It may lead to development of resistant organisms and may prolong the QT interval.

◊◊ Dupilumab therapy is appropriate only for patients with peripheral eosinophilia (≥300 cells/microL) or concomitant severe asthma.

Adapted in part from: Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease (2025 Report). Available at: www.goldcopd.org (Accessed on November 15, 2024).

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Follow-up pharmacologic management of COPD*

Follow-up pharmacologic management of COPD^*