Therapeutic use of heparin and derivatives beyond anticoagulation in patients with bronchial asthma or COPD

In this review, we identify potential targets for the therapeutic effects of heparin in asthma and chronic obstructive pulmonary disease (COPD), consider the safety and delivery modalities of this therapeutic approach. Specifically, we point to the anti-inflammatory, antioxidant and mucolytic effects of unfractionated heparin with potential to modify disease progression in COPD and asthma when administered via the inhaled route. Inhaled heparin may represent an effective add-on therapy in COPD and asthma patient groups, especially when taking into consideration the relative deficiency in endogenous heparin reported in asthma patients

Endothelial activation and increased heparan sulfate expression in cystic fibrosis

Rationale: Pulmonary disease in cystic fibrosis (CF) is characterized by an exaggerated interleukin (IL)-8–driven, neutrophilic, inflammatory response to infection. Binding of IL-8 to heparan sulfate (HS)–containing proteoglycans (HSPG) facilitates binding of the chemokine to its specific receptor, stabilizes and prolongs IL-8 activity, and protects it from proteolysis. We hypothesized that increased expression of HSPG contributes to the sustained inflammatory response in CF bronchial tissue.Objectives: Our objectives were to analyze the distribution and abundance of IL-8 and HS, in intact and cleaved forms, in bronchial tissue from adult patients with CF or chronic obstructive pulmonary disease (COPD) and a control group without inflammatory airway disease.Methods: Immunostaining and quantitative image analysis were applied to ethanol-fixed and paraffin-embedded tissue obtained at transplant in patients with CF or COPD, or postmortem in the control group.Measurements and Main Results: Quantitative immunohistochemical analysis demonstrated significant disease-related differences. Intact HS was significantly more abundant in epithelial and endothelial basement membranes in CF than in COPD or the control group. Conversely, cleaved HS was significantly more abundant in COPD than the other groups. More IL-8–positive blood vessels were observed in CF and COPD compared with the control group, whereas more extensive IL-8 expression in the epithelium was observed in CF compared with COPD.Conclusions: Sustained neutrophil recruitment in the CF airway may therefore be related not only to increased IL-8 expression but also to the increased stability and prolonged activity and retention of IL-8 when it is bound to HSPG in bronchial tissue