Effect of Indomethacin on Bronchorrhea in Patients with Chronic Bronchitis, Diffuse Panbronchiolitis, or Bronchiectasis

Abstract

Excessive production of sputum is one of the major symptoms in patients with chronic airway diseases. Because endogenous prostaglandins may play a role in the regulation of airway secretions, blockade of cyclooxygenase pathway with indomethacin could decrease respiratory tract fluid and mucus by inhibiting Cl secretion and glandular secretion and by enhancing Na absorption across airway mucosa. To test this hypothesis, we studied the effect of inhaled indomethacin on bronchorrhea in patients with chronic bronchitis, diffuse panbronchiolitis, and bronchiectasis in a double-blind, placebo-controlled fashion. Patients who inhaled 2 ml of indomethacin (1.2 micrograms/ml) three times a day for 14 days showed a decrease in the amount of sputum, from 189 +/- 19 to 95 +/- 21 g/day (p less than 0.001) and an increase in the solid component of sputum without alterations in parameters of systemic inflammatory responses. Although pulmonary function remained unchanged, perceived dyspnea was improved so that Borg's ratio scale was decreased from 7.1 +/- 0.5 to 4.5 +/- 0.4 (p less than 0.01). Adverse effects, including hypotension and bronchoconstriction, were not observed. The reduction of sputum was accompanied by a significant decrease in the concentrations of prostaglandin (PG)E2, PGF2 alpha, thromboxane B2, and 6-oxo-PGF1 alpha in the sputum. Thus, indomethacin inhalation may be of value in reducing bronchorrhea sputum, probably through the inhibition of PG-dependent airway secretions.

Mediators of Chronic Obstructive Pulmonary Disease

“…However, PGE 2 also has potentially detrimental effects in stimulating mucus secretion and expression of mucin genes (MUC5AC, MUCB) (Borchers et al, 1999) and in sensitizing and activating airway sensory nerves to enhance coughing (Stone et al, 1992;Lee et al, 2002). Inhalation of the nonselective COX inhibitor indomethacin is reported to reduce mucus hypersecretion in patients with COPD (Tamaoki et al, 1992), but long-term trials of COX inhibitors (and in particular COX-2 inhibitors)…”

p38 and EGF receptor kinase-mediated activation of the phosphatidylinositol 3-kinase/Akt pathway is required for Zn2+-induced cyclooxygenase-2 expression

“…In contrast, COX-2 is undetectable or present at very low levels under basal conditions but is rapidly induced by mitogenic and inflammatory stimuli in a wide variety of cell types (35,42). COX-dependent pathways are centrally involved in a large array of physiological and pathophysiological processes in the lung, such as the regulation of pulmonary vascular tone (32), vascular and interstitial tissue remodeling (8,50), the regulation of capillary endothelial and alveolar epithelial permeability (12,43), the control of bronchial mucous secretion and transport (15,16,44), and the regulation of bronchial tone including the pathogenesis of bronchial asthma and chronic obstructive lung disease (4,45).…”

Aerosol Medications for Treatment of Mucus Clearance Disorders

“…23 Aerosolized indomethacin has been shown to decrease hypersecretion in subjects with chronic bronchitis, diffuse panbronchiolitis, or bronchiectasis, although the mechanism of action is not clearly known. 24 …”