To evaluate the relationship between airway structure and function in patients with chronic bronchitis treated with metered cryospray (MCS).

To identify the molecular and cellular targets of MCS treatment and determine the mechanistic relationship to airways remodelling in patients with chronic bronchitis. Phenotype, characterise and correlate clinical, physiological, histological and molecular parameters in patients with chronic bronchitis.

Inclusion Criteria:

Each Subject must meet the following criteria to be enrolled in the study:

1. Males and females ≥40 to <80 years of age.
2. Subject is able to read, understand, and sign a written Informed Consent in order to participate in the study.
3. Subject has a diagnosis of CB and COPD and has been symptomatic for a minimum of two years. (Chronic Bronchitis is defined clinically as chronic productive cough for 3 months in each of 2 successive years in a patient in whom other causes of productive cough have been excluded).
4. Subject is classified as having moderate or severe (GOLD stage 2-3) airflow obstruction defined by a post-bronchodilator of =>30% FEV1 to <80% predicted with a baseline FEV1/FVC of <0.70.
5. Subject has a COPD assessment tool (CAT) score of ≥10.
6. Subject is being treated according to current medically accepted treatment guidelines without successful resolution of chronic bronchitis and agrees to continue maintenance pulmonary/COPD medications (as defined per GOLD Standard for medications) for the duration of the study (subject must be on a regime of pulmonary medications for a minimum of 2 weeks prior to enrolment into the study).
7. Smoking history of at least 10 pack years.
8. Non-smoking for a minimum of 2 months prior to consent and agrees to continue not smoking for the duration of the study.
9. Subject is able to adhere to and undergo 4 bronchoscopic procedures (5 for control subjects accepting cross over option), in the opinion of the investigator or per hospital guidelines.
10. For women of childbearing potential: non-pregnant, non-lactating, and agree to practice an adequate birth control method (abstinence, combination barrier and spermicide, or hormonal) for the duration of the study.

Exclusion Criteria:

A potential subject who meets any of the following criteria will be excluded from participation in this study:

1. Subject has had an acute pulmonary infection, exacerbation or pneumonia requiring medical treatment (with antibiotics and/or steroids) within 6 weeks of initially planned study bronchoscopy.
2. Diagnosis of asthma with an onset before 30 years of age.
3. Subject has Alpha-1 antitrypsin deficiency.
4. Subject has other origins of respiratory disease aside from chronic bronchitis and COPD.
5. Subject is using e-cigarettes, vaping or taking any oral or inhaled substances not prescribed by a physician.
6. Subject has untreatable or life-threatening arrhythmias, or history of inability to adequately oxygenate during a bronchoscopy, or has acute respiratory failure with hypercapnia.
7. Subject has bullous emphysema characterized as large bullae >30 millimetres on HRCT; or subject has stenosis in the tracheobronchial system, tracheobronchomegaly, trachea-bronchomalacia, amyloidosis or cystic fibrosis.
8. Subject has clinically significant bronchiectasis
9. Subject has had a transplant procedure (any).
10. Subject has a known mucosal tear, has undergone prior lung surgery such as pneumonectomy, lobectomy, bullectomy, or lung volume reduction surgery, bronchial thermoplasty, rheoplasty or cryotherapy.
11. Subject has had a prior lung device procedure, including emphysema stent(s) implanted, lung coils, valves, lung denervation or other devices for emphysema.
12. Subject is unable to temporarily discontinue use of anticoagulant therapy: warfarin, Coumadin, LMWH, heparin, clopidrogel (or equal).
13. Subject has a serious medical condition, such as: uncontrolled coagulopathy or bleeding disorder, congestive heart failure, uncontrolled angina, myocardial infarction in the past year, renal failure, liver disease, cerebrovascular accident within the past 6 months, uncontrolled diabetes, uncontrolled hypertension, autoimmune disease or uncontrolled gastric reflux.
14. Subject has or is receiving chemotherapy or active radiation therapy within the past 6 months or is expected to receive chemotherapy during participation in this study.
15. Subject is or has been in another clinical investigational study within 6 weeks of enrolment.
16. Subject has known sensitivity to medication required to perform bronchoscopy (such as lidocaine, atropine, and benzodiazepines).

Sham controlled.