Is it recommended to continue Long-Acting Beta Agonists (LABAs) and Long-Acting Muscarinic Antagonists (LAMAs) in patients with Chronic Obstructive Pulmonary Disease (COPD) exacerbation?

Continuation of LABAs and LAMAs During COPD Exacerbation

Yes, LABAs and LAMAs should be continued during COPD exacerbations as part of maintenance therapy, while adding short-acting bronchodilators and systemic corticosteroids for acute management.

Rationale for Continuation

The evidence strongly supports maintaining long-acting bronchodilators during acute exacerbations:

• Long-acting bronchodilators are maintenance therapy, not acute rescue medications. They provide sustained bronchodilation that remains beneficial even during exacerbations 1.

• LABA/LAMA combinations demonstrate superior efficacy in preventing subsequent exacerbations and improving patient-reported outcomes compared to single bronchodilators or LABA/ICS combinations, particularly in high-risk patients 1, 2.

• Discontinuing maintenance therapy during exacerbations increases the risk of prolonged recovery time and subsequent exacerbations 1.

Management Algorithm During Exacerbation

Acute Phase Treatment

• Continue current LABA/LAMA maintenance therapy at the prescribed dose 1.
• Add short-acting bronchodilators (short-acting beta-agonists and/or short-acting muscarinic antagonists) for acute symptom relief 1.
• Initiate systemic corticosteroids for moderate to severe exacerbations 1.
• Consider antibiotics if there are signs of bacterial infection (increased sputum purulence, volume, or dyspnea) 1.

Post-Exacerbation Reassessment

After the acute exacerbation resolves, reassess the maintenance regimen:

For patients on LABA/LAMA who experienced an exacerbation:

• If blood eosinophils ≥300 cells/μL or history of asthma-COPD overlap: Escalate to LABA/LAMA/ICS triple therapy 1.

• If chronic bronchitis phenotype with FEV1 <50% predicted: Consider adding roflumilast to LABA/LAMA 1.

• If former smoker with recurrent exacerbations: Consider adding macrolide therapy (e.g., azithromycin) to LABA/LAMA, weighing risks of antimicrobial resistance and cardiac effects 1.

For patients already on triple therapy (LABA/LAMA/ICS) who continue to exacerbate:

• Add macrolide maintenance therapy if a former smoker, with moderate certainty of benefit in reducing exacerbation rates 1.
• Add roflumilast if chronic bronchitic phenotype present 1.

Critical Caveats

Do Not Discontinue During Exacerbation

• Stopping LABA/LAMA during exacerbations removes the foundation of bronchodilation and may worsen outcomes 1.
• The Canadian Thoracic Society weakly recommends against stepping down from LABA/LAMA/ICS to LABA/LAMA in high-risk patients, as withdrawal may increase exacerbation risk, particularly in those with eosinophils ≥300 cells/μL 1.

Avoid Common Errors

• Do not use LABAs or LAMAs as rescue medications for acute symptom relief—they have delayed onset of action 1, 3.
• Do not initiate LABA/LAMA for the first time during acute deterioration—wait until the patient is stabilized 3.
• Do not add ICS indiscriminately after exacerbations without considering eosinophil counts or asthma overlap, as ICS increases pneumonia risk without clear benefit in low-eosinophil patients 1, 4.

Phenotype-Specific Considerations

High eosinophil phenotype (>4% or >300 cells/μL):

• These patients benefit most from ICS addition to LABA/LAMA after exacerbations 4.
• LABA/ICS shows effectiveness only in this subgroup compared to LAMA monotherapy 4.

Low eosinophil phenotype (<2% or <200 cells/μL):

• LAMA initiation or continuation is preferred over ICS-containing regimens due to pneumonia risk without exacerbation benefit 4.
• Consider non-ICS add-on therapies (roflumilast, macrolides) for recurrent exacerbations 1, 5.

Chronic bronchitis phenotype:

• Roflumilast addition to LABA/LAMA reduces exacerbations in patients with FEV1 <50% predicted and history of hospitalization for exacerbation 1.
• High-dose mucolytic agents may provide additional benefit 5.

Evidence Strength

The recommendation to continue LABA/LAMA during exacerbations is supported by:

• Level A evidence from GOLD guidelines for long-acting bronchodilators as cornerstone therapy 1.
• Strong consensus across American Thoracic Society, European Respiratory Society, and Canadian Thoracic Society guidelines 2, 6.
• FDA labeling explicitly states LABA/LAMA combinations are not indicated for acute deterioration but are for long-term maintenance 3.