Inhaled heparin is effective in exacerbations of asthma

Bendstrup, K.E.; Jensen, Jesper K.

doi:10.1053/rmed.1999.0677

Cited by 29 publications

(17 citation statements)

References 6 publications

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“…As noted in Results, reproducible systemic levels of drug could be readily achieved with low interanimal variability. Notably, a number of studies, primarily involving instillation of heparin, have delivered heparin doses to patients that are Ͼ100 times those used here, and these studies reported no adverse events, further supporting the possibility of pulmonary delivery of heparin as a viable clinical strategy (24,32,33).…”

Section: Discussionsupporting

confidence: 54%

Delivery of therapeutic levels of heparin and low-molecular-weight heparin through a pulmonary route

Zhao

Liu

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Although heparin and low-molecular-weight heparins (LMWH) have been widely used clinically as anticoagulants, their broader use has been limited by the lack of noninvasive delivery methods for this class of molecules. In this study, we demonstrate an efficient, rapid, and reproducible delivery system for heparin through the lungs that is not confined to particles of a certain geometric or aerodynamic diameter. Importantly, blood levels after intrapulmonary administration of either heparin or LMWH were comparable to that of s.c. administration but are characterized by a more rapid onset of action (t 1/2 ‫؍‬ 40 min vs. 2.5 h, respectively). Furthermore, we show in animal models, that inhaled heparin species efficiently inhibit diseases such as thrombosis and emphysema, and that the repetitive inhalation of formulated LMWH results in no observable toxicity from the delivery of reproducible systemic levels of heparin or LMWH.

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Section: Discussionsupporting

confidence: 54%

Delivery of therapeutic levels of heparin and low-molecular-weight heparin through a pulmonary route

Zhao

Liu

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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“…Previous studies in both animal models and in humans with asthma have shown a benefit of heparin in ameliorating antigen-induced hyperreactivity (1,5,11). This is thought to be because of the ability of this compound to displace the cationic protein MBP from M 2 muscarinic receptors (6).…”

Section: Discussionmentioning

confidence: 99%

Eosinophil adhesion to cholinergic nerves via ICAM-1 and VCAM-1 and associated eosinophil degranulation

Sawatzky

Kingham

Court

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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In vivo, eosinophils localize to airway cholinergic nerves in antigen-challenged animals, and inhibition of this localization prevents antigen-induced hyperreactivity. In this study, the mechanism of eosinophil localization to nerves was investigated by examining adhesion molecule expression by cholinergic nerves. Immunohistochemical and functional studies demonstrated that primary cultures of parasympathetic nerves express vascular cell adhesion molecule-1 (VCAM-1) and after cytokine pretreatment with tumor necrosis factor-α and interferon-γ intercellular adhesion molecule-1 (ICAM-1). Eosinophils adhere to these parasympathetic neurones after cytokine pretreatment via a CD11/18-dependent pathway. Immunohistochemistry and Western blotting showed that a human cholinergic nerve cell line (IMR-32) expressed VCAM-1 and ICAM-1. Inhibitory experiments using monoclonal blocking antibodies to ICAM-1, VCAM-1, or CD11/18 and with the very late antigen-4 peptide inhibitor ZD-7349 showed that eosinophils adhered to IMR-32 cells via these adhesion molecules. The protein kinase C signaling pathway is involved in this process as a specific inhibitor-attenuated adhesion. Eosinophil adhesion to IMR-32 cells was associated with the release of eosinophil peroxidase and leukotriene C4. Thus eosinophils adhere to cholinergic nerves via specific adhesion molecules, and this leads to eosinophil activation and degranulation; this may be part of the mechanism of eosinophil-induced vagal hyperreactivity.

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“…4 These effects may be the underlying mechanism in the reduction of exercise-, histamineand allergen-induced bronchoconstriction. 6 These preliminary results indicate significantly decreased endogenous heparin levels in the asthmatic patient, thereby potentially decreasing anti-inflammatory effects. As it is not clear whether the decreased levels of heparin are a result of the medication (in particular β 2 -agonists) being administered, or a manifestation of the disease itself, our research is an ongoing endeavour to clarify this aspect.…”

Section: Resultsmentioning

confidence: 81%

Endogenous heparin levels in the controlled asthmatic patient

Davids¹,

Ahmed²,

Oberholster³

et al. 2010

S Afr Med J

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Levels of circulating endogenous heparin in patients with diseases associated with inflammatory processes, such as asthma, are still unknown. Since heparin displays antiinflammatory properties, it is expected that the inhibitory effects on inflammatory mediators are reduced at low levels of endogenous heparin. 1 We present evidence supporting the hypothesis that asthmatic patients have lower levels of circulating endogenous heparin than healthy individuals have.Since 1955, endogenous plasma heparin has been demonstrated to be a normal constituent of blood, with concentrations ranging from 153 to 177 mIU/ml, and its levels were found to be independent of gender or age.2 Discrepancies in the concentrations of endogenous heparin reported by various research groups are thought to result from the different quantitative methods or isolation procedures used.

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Inhaled heparin is effective in exacerbations of asthma

Cited by 29 publications

References 6 publications

Delivery of therapeutic levels of heparin and low-molecular-weight heparin through a pulmonary route

Delivery of therapeutic levels of heparin and low-molecular-weight heparin through a pulmonary route

Eosinophil adhesion to cholinergic nerves via ICAM-1 and VCAM-1 and associated eosinophil degranulation

Endogenous heparin levels in the controlled asthmatic patient

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