Pulmonary pharmacology & therapeutics
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Both chronic cough and chronic pain are critical clinical issues in which a large number of patients remain unsatisfied with available treatments. These conditions have considerable effects on sufferers' quality of life, who often show co-morbidities such as anxiety and depression. There is therefore a pressing need to find new effective therapies. ⋯ There is a substantial literature around mechanisms of chronic pain which is likely to be useful in advancing knowledge about the pathologies of chronic cough. Here we compare the basic pain and cough pathways, in addition to the clinical features and possible pathophysiologies of each; including mechanisms of peripheral and central sensitisation which may underlie symptoms such as hyperalgesia and allodynia, and hypertussitvity and allotussivity. Due to the substantial overlap that emerges, it is likely that therapies may be effective over both areas.
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Pulm Pharmacol Ther · Feb 2013
ReviewEmerging mediators of airway smooth muscle dysfunction in asthma.
Phenotypic changes in airway smooth muscle are integral to the pathophysiological changes that constitute asthma - namely inflammation, airway wall remodelling and bronchial hyperresponsiveness. In vitro and in vivo studies have shown that the proliferative, secretory and contractile functions of airway smooth muscle are dysfunctional in asthma. These functions can be modulated by various mediators whose levels are altered in asthma, derived from inflammatory cells or produced by airway smooth muscle itself. In this review, we describe the emerging roles of the CXC chemokines (GROs, IP-10), Th17-derived cytokines (IL-17, IL-22) and semaphorins, as well as the influence of viral infection on airway smooth muscle function, with a view to identifying new opportunities for therapeutic intervention in asthma.
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Pulm Pharmacol Ther · Aug 2012
ReviewCommonalities between the pro-fibrotic mechanisms in COPD and IPF.
COPD and IPF are two chronic lung diseases which are characterized by a decline in lung function, resulting in significant morbidity and mortality. Both of these diseases are more commonly associated with an aging population and the duration for which the disease has been underlying is often unknown. Significant matrix deposition occurs, resulting in either non-reversible airways obstruction in the case of COPD and impaired gas exchange and parenchymal consolidation in IPF. ⋯ Moreover, in the extreme fibrotic setting of IPF, the remodelling is sometimes associated with uncontrolled wound healing responses. As wound healing is a critical aspect to maintaining tissue function and homeostasis, targeting this process directly may result in safety concerns. This review therefore describes some of the recent advances in ascertaining pathways promoting lung fibrosis that may be amenable to therapeutic intervention in both COPD and IPF.
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Pulm Pharmacol Ther · Aug 2012
ReviewCigarette smoke-induced inflammation and respiratory host defense: Insights from animal models.
While the devastating impact of tobacco on human health is well established, and efforts to reduce its prevalence are ongoing, over 1 billion people continue to smoke. Emerging evidence suggests that cigarette smoking distorts lung immune homeostasis, compromising respiratory host defense. ⋯ In this article, we discuss mechanisms by which cigarette smoke elicits inflammatory processes and how smoking impacts respiratory host defense against viral and bacterial agents. Elucidating cigarette smoke's impacts on lung immune homeostasis will contribute to our understanding of the pathogenesis of chronic obstructive pulmonary disease COPD.
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Pulm Pharmacol Ther · Oct 2011
ReviewThe dynamic face of respiratory research: understanding the effect of airway disease on a lung in constant motion.
The lungs are in a constant state of motion. The dynamic nature of tidal breathing, whereby cycles of pressure changes across the lungs cause the chest wall, lung tissue and airways to repeatedly expand and contract, ventilates the lung tissue and allows respiration to occur. However, these regular cycles of tidal inspirations and expirations are punctuated by breaths of differing volumes, most particularly periodic deep inspirations. ⋯ On the other hand, DI bronchoprotection is completely absent in asthma. Although the mechanisms behind these abnormalities remain unclear, the inability for deep inspirations to both protect against and fully reverse bronchoconstriction in patients with asthma appears critical in the development of airway hyperresponsiveness. As such, determining the pathophysiology responsible for the malfunction of deep inspirations in asthma remains critical to understanding the disease and is likely to pave the way for novel therapeutic targets.