- Title
- Inflammatory mechanisms and treatment of obstructive airway diseases with neutrophilic bronchitis
- Creator
- Simpson, Jodie L.; Phipps, Simon; Gibson, Peter G.
- Relation
- Pharmacology and Therapeutics Vol. 124, Issue 1, p. 86-95
- Publisher Link
- http://dx.doi.org/10.1016/j.pharmthera.2009.06.004
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2009
- Description
- Obstructive airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) are major global health issues. Although considered as distinct diseases, airway inflammation is a key underlying pathophysiological process in asthma, COPD and bronchiectasis. Persistent neutrophilic airway inflammation (neutrophilic bronchitis) occurs with innate immune activation and is a feature of each of these airway diseases. Little is known about the mechanisms leading to neutrophilic bronchitis and few treatments are effective in reducing neutrophil accumulation in the airways. There is a similar pattern of inflammatory mediator release and toll like receptor 2 expression in asthma, COPD and bronchiectasis. We propose the existence of an active amplification mechanism, an effector arm of the innate immune system, involving toll like receptor 2, operating in persistent neutrophilic bronchitis. Neutrophil persistence in the airways can occur through a number of mechanisms such as impaired apoptosis, efferocytosis and mucus hypersecretion, all of which are impaired in airways disease. Impairment of neutrophil clearance results in a reduced ability to respond to bacterial infection. Persistent activation of airway neutrophils may result in the persistent activation of the innate immune system resulting in further airway insult. Current therapies are limited for the treatment of neutrophilic bronchitis; possible treatments being investigated include theophylline, statins, antagonists of pro-inflammatory cytokines and macrolide antibiotics. Macrolides have shown great promise in their ability to reduce airway inflammation, and can reduce airway neutrophils, levels of CXCL8 and neutrophil proteases in the airways. Studies also show improvements in quality of life and exacerbation rates in airways diseases.
- Subject
- neutrophil; CXCL8; asthma; COPD; macrolide; toll like receptor
- Identifier
- uon:8036
- Identifier
- http://hdl.handle.net/1959.13/916573
- Identifier
- ISSN:0163-7258
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