Roflumilast or Azithromycin to Prevent COPD Exacerbations (RELIANCE)

Inclusion Criteria:

• Patient and treating clinician considering treatment intensification withroflumilast or azithromycin to reduce the risk of COPD exacerbations

• Age ≥ 40 years

• Current or past smoker of at least 10 pack-years

• Diagnosis by treating physician of severe COPD and associated chronic bronchitis

• Hospitalized with a diagnosis of COPD exacerbation or respiratory complications dueto COVID 19 in the past 12 months

• Current medications include inhaled Long Acting Muscarinic Antagonist (LAMA), LongActing Beta Agonist (LABA) /LAMA, or Inhaled Corticosteroids (ICS) /LABA(notepatients prescribed or using SABA, SAMA, or SABA/SAMA on a scheduled basis (e.g.,every 6 hours) are eligible since the patient is receiving functional controllertherapy);

• English or Spanish speaking

• Willing and able to provide a contact telephone number.

Exclusion Criteria:

• Unable or declines to provide informed consent;

• Declines to provide social security number, health insurance claims number or TaxPayer ID (as applicable)

• History of intolerance to azithromycin or roflumilast that the patient or patient'streating clinician considers sufficiently serious to avoid either treatment option;

• Current treatment with long-term (more than 30 days) roflumilast, azithromycin orensifentrine (previous treatment with 1 or more doses of azithromycin, roflumilastor ensifentrine is not an exclusion criterion, as long as the patient and clinicianare seeking treatment intensification options and would be willing to useazithromycin or roflumilast, as per randomized treatment assignment.)

• Known hypersensitivity to azithromycin, erythromycin, any macrolide or ketolideantibiotic;

• History of cholestatic jaundice/hepatic dysfunction associated with prior use ofazithromycin

• Moderate to severe liver impairment (Child-Pugh B or C)

• Current pregnancy

• Any other clinician-determined exclusion as per the clinician's clinical practice

• The clinicians will be provided the FDA-approved prescribing information forroflumilast and azithromycin. The prescribing information includes a list ofwarnings and precautions that identifies the potential for adverse effects and isintended to support clinical decision-making that takes into account the risks andbenefits of roflumilast and azithromycin for each patient