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Castano R.,Sacre Coeur de Montreal Hospital | Castano R.,Respiratory Research Division
Otorinolaringologia | Year: 2012

This review addresses current knowledge on early recognition, diagnosis and management of Occupational Rhinitis (OR). OR is a respiratory disease caused by exposure to allergens or irritants in the workplace. The raising interest in OR relies on the fact that this condition is more frequent than occupational asthma and has important impact on work productivity. Besides, it is regarded as an early disease in the progression to occupational asthma. The diagnosis of OR constitutes a challenge; subjects do not seek medical attention because of the presence of nasal symptoms and physicians do not inquiry about the relationship of nasal symptoms with the work environment. A comprehensive medical and occupational history is crucial to recognize OR and to identify potential causal agents. The diagnosis of OR should be confirmed by objective testing including assessment of specific sensitization and performing nasal challenge test in the laboratory to reproduce nasal symptoms with the suspected occupational agent. The basic principle of management continues to be an effective control of environmental factors by implementing effective industrial hygiene strategies to reduce the levels of exposure. Active cases of OR should be treated following current guidelines to treat allergic and nonallergic rhinitis in the general population.

Greene C.M.,Respiratory Research Division | Gaughan K.P.,Respiratory Research Division
Current Opinion in Pulmonary Medicine | Year: 2013

PURPOSE OF REVIEW: Asthma is a global disease affecting millions of people. Current treatments are largely symptomatic and, although often effective, can be associated with various side effects. microRNAs (miRNAs/miRs) are regulatory RNAs that affect protein synthesis. They represent new therapeutic targets, and medicines that target specific miRNAs may have potential in the treatment of asthma. RECENT FINDINGS: There have been a number of studies in the field of miRNA that implicate specific miRNAs in the pathophysiology of asthma. For example, studies using mouse models have identified miRNAs that are altered in response to allergen challenge. Certain miRNAs that are involved in the regulation of interleukin-13 and the TH2 response, key components of the asthmatic response, have been shown to be amenable to modulation by premiRs and antimiRs. Other studies have identified miRNAs that are implicated in bronchial smooth muscle hyperresponsiveness and proliferation. Single-nucleotide polymorphisms in miRNA responsive elements within asthma susceptibility genes, and also in miRNAs themselves, can also contribute to the asthma phenotype. SUMMARY: Developing miRNA-based medicines to treat the pulmonary manifestations of asthma could yield therapeutics with new properties that have the potential to treat both the inflammation and hyperresponsivesness associated with this disease. Copyright © 2012 Lippincott Williams &Wilkins.

Castano R.,Hopital du Sacre Coeur de Montreal | Trudeau C.,Respiratory Research Division | Ghezzo H.,Respiratory Research Division
Clinical Otolaryngology | Year: 2010

Objectives: To assess the correlation between acoustic rhinometry and visual analogue scale endpoints in the context of nasal challenge with occupational agents.Design: Prospective controlled study.Setting: University teaching hospital.Participants: Sixty-seven subjects with a history of work-related rhinitis and asthma symptoms.Main outcomes measures: Subjects underwent nasal challenge with control and specific agent on consecutive days. Nasal congestive response to challenge was monitored by acoustic rhinometry and visual analogue scale.Results: Results showed no correlation between visual analogue scale and acoustic rhinometry measurements at baseline on the control (r = -0.13, P = 0.3) and active (r = 0.14, P = 0.2) challenge days. No correlation was found between acoustic rhinometry and visual analogue scale when analysing all measurements obtained at all times after challenge with the control and active agent (control: r = 0.09, P = 0.04; active: r = 0.001, P = 0.9). The correlation between acoustic rhinometry and visual analogue scale was good and significant (r = -0.62, P = <0.01) when the analysis was restricted to cases showing a decrease in nasal volume >40% from baseline values.Conclusions: We showed that the correlation between acoustic rhinometry and subjective nasal patency was poor on steady conditions. However, a significant correlation was observed in those cases showing a greater nasal congestive response after challenge measured by acoustic rhinometry. 2010 Blackwell Publishing Ltd.

McCarthy C.,Respiratory Research Division | Saldova R.,University College Dublin | Wormald M.R.,University of Oxford | Rudd P.M.,University College Dublin | And 2 more authors.
Journal of Proteome Research | Year: 2014

Acute phase proteins (APPs) are a group of circulating plasma proteins which undergo changes quantitatively or qualitatively at the time of inflammation. Many of these APPs are glycosylated, and it has been shown that alterations in glycosylation may occur in inflammatory and malignant conditions. Changes in glycosylation have been studied as potential biomarkers in cancer and also in chronic inflammatory conditions and have been shown to correlate with disease severity in certain conditions. Serine protease inhibitors (serpins), many of which are also APPs, are proteins involved in the control of proteases in numerous pathways. Alpha-1 Antitrypsin (AAT) is the most abundant serpin within the circulation and is an APP which has been shown to increase in response to inflammation. The primary role of AAT is maintaining the protease/antiprotease balance in the lung, but it also possesses important anti-inflammatory and immune-modulating properties. Several glycoforms of AAT exist, and they possess differing properties in regard to plasma half-life and stability. Glycosylation may also be important in determining the immune modulatory properties of AAT. The review will focus on the role and importance of glycosylation in acute phase proteins with particular attention to AAT and its use as a biomarker of disease. The review describes the processes involved in glycosylation, how glycosylation changes in differing disease states, and the alterations that occur to glycans of APPs with disease and inflammation. Finally, the review explores the importance of changes in glycosylation of AAT at times of inflammation and in malignant conditions and how this may impact upon the functions of AAT. © 2014 American Chemical Society.

McGarry N.,Respiratory Research Division | Greene C.M.,Respiratory Research Division | McElvaney N.G.,Respiratory Research Division | Weldon S.,Queens University of Belfast | Taggart C.C.,Queens University of Belfast
Journal of Immunology Research | Year: 2015

Secretory Leukocyte Protease Inhibitor (SLPI) is a serine protease inhibitor produced by epithelial and myeloid cells with anti-inflammatory properties. Research has shown that SLPI exerts its anti-inflammatory activity by directly binding to NF-B DNA binding sites and, in so doing, prevents binding and subsequent transcription of proinflammatory gene expression. In the current study, we demonstrate that SLPI can inhibit TNF-α-induced apoptosis in U937 cells and peripheral blood monocytes. Specifically, SLPI inhibits TNF-α-induced caspase-3 activation and DNA degradation associated with apoptosis. We go on to show that this ability of SLPI to inhibit apoptosis is not dependent on its antiprotease activity as antiprotease deficient variants of SLPI can also inhibit TNF-α-induced apoptosis. This reduction in monocyte apoptosis may preserve monocyte function during inflammation resolution and promote infection clearance at mucosal sites. © 2015 Niamh McGarry et al.

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