Chronic Airway Disease, Mucus Rheology and Exacerbations

The main objective of this trial is to compare the exacerbation number over 12 months of follow-up between a group of patients with COPD treated according to standardized management (azithromycin prescribed in the event of severe sputum according to the CASA-Q score , standardized comparator arm) and a similar group in which azithromycin is prescribed based on mucus rheology (experimental arm) or CASA-Q.

The secondary objectives are to compare between the 2 arms:

* exacerbation number according to their severity (observed throughout the duration of the study);
* the evolution of the symptoms, the rheology of the sputum, and the pulmonary function (measurements repeated every three months);
* medication consumption and adverse events (monitored throughout the duration of the study);
* patient trajectories during follow-up;
* the overall clinical improvement at the end of the study and the evolution of the quality of life (measurements repeated every 3 months);
* the change in biomarkers of interest (baseline versus end of study).

Eligibility Criteria:
Inclusion Criteria:

* Subjets between 40 - 85 years (included)
* Written and signed informed consent form
* Subjects must be able to attend all planned visits and comply with all test procedures
* Beneficiary of or affiliated with the French social security system
* Man or woman with chronic obstructive pulmonary disease for at least 1 year defined according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria and validated by the clinical investigator
* Optimal treatment according to GOLD class severity C or D recommendations
* \>=3 exacerbation (regardless of severity: mild-moderate-severe) or ≥ 1 severe exacerbations (requiring hospitalization) in the past 12 months
* Spontaneous or induced sputum production
* Electrocardiogram: corrected distance between Q and T waves (QTC) \<450 ms in men, QTC \<470 ms in women
* Normal audiogram for age or absence of contraindication to azithromycin for long course according to Oto-Rhino-Laryngological specialist opinion

Exclusion Criteria:

* Pregnancy or breastfeeding
* Patients who are prisoners or under other forms of judicial protection
* Patients under any form of guardianship
* Participation in another interventional protocol, (current or during the month preceding inclusion)
* Received azithromycin in the past 3 months
* Patient whose primary diagnosis is bronchial dilation based on CT scan documentation
* Known hypersensitivity to azithromycin, erythromycin, any other macrolide, ketolide or any of the excipients of the azithromycin-based specialty used
* Concomitant use of medication contraindicated with azithromycin (dihydroergotamine, ergotamine, cisapride, colchicine)
* Other respiratory diseases or associated lung infections
* Severe hepatic insufficiency and severe cholestasis (a liver biological test will be carried out if clinical suspicion)
* Renal impairment with creatinine clearance \< 40 mL/min
* Patients with hematological malignancies who have undergone allogeneic hematopoietic stem cell transplantation
* Patients with galactose intolerance, Lapp lactase deficiency or glucose or galactose malabsorption syndrome (rare hereditary disease) due to the presence of lactose in the specialty Zithromax.