Chronic Bronchitis

Chronic bronchitis, like emphysema, is among a group of lung diseases known as chronic obstructive pulmonary disease, or COPD. Chronic bronchitis involves a long-term cough with mucus production, caused by inflammation and irritation of the bronchial tubes (airways) in the lungs. When the epithelial lining of the bronchial tubes becomes inflamed and irritated, thick mucus begins to form in them. Over time, mucus plugs up the airways of the lungs leading to narrowing and obstruction, making breathing difficult. Unlike acute bronchitis, chronic bronchitis is progressive, especially among smokers who fail to quit. People with chronic bronchitis experience recurrences or exacerbations of symptoms associated with progressive disease.  However, prolonged smoking cessation will allow the airway to heal, and treatment with an effective β-adrenergic inverse agonist may accelerate this healing.

The lining of the airway, or surface epithelium, consists of a number of different cell types, one of which is the goblet cell. The excessive mucus production and secretion associated with chronic cough is caused by goblet cell (mucous cell) metaplasia. Mucus hypersecretion is:

  • regulated by IL-13 a central inflammatory cytokine
  • a common feature of chronic bronchitis, bronchiectasis and asthma
  • induced by chronic cigarette smoking

Initial Target Indication: Patients with chronic bronchitis undergoing smoking cessation to reduce peri-operative complications (“smoking cessation”)

“Why do I cough so much when trying to quit smoking?” — is a common question smokers ask their doctors. Coughing is one of the main symptoms of smoking cessation and for many people it is the main reason for smokers not to quit. Many smokers develop a chronic cough which is exacerbated initially after smoking cessation. It generally occurs within the first two weeks of quitting, an important period of productive cough. The symptoms of chronic cough are often so severe that many smokers return to smoking to suppress the cough symptoms.

Rationale: INV102 can treat the underlying cause of chronic cough and mucus secretion which are a major barrier to smoking cessation and cause of peri-operative complications in patients with COPD. INV102 has been shown to down regulate IL-13 and the production of mucus in the lung. It is expected that INV102 will expedite healing of the airway in smokers and return to ciliated epithelium, leading to decreased cough and mucus production, which in turn leads to increased success rate in quitting. Treatment with INV102 is expected to be initiated prior to quitting allowing for a titration to a full effective dose, and the drug is expected to be used with other approved medications (e.g. Zyban®).

Further information on this trial can be found at www.clinicaltrials.gov with the identifier NCT01825122.