Abstract IL-33, a new member of the IL-1 cytokine family, promotes Th2 inflammation, but evidence on the implications of this cytokine in asthma is lacking. IL-33 would be mainly expressed by structural cells, but whether proinflammatory cytokines modulate its expression in airway smooth muscle cells (ASMC) is unknown. Endobronchial biopsies were obtained from adults with mild (n = 8), moderate (n = 8), severe (n = 9), asthma and from control subjects (n = 5). Immunocytochemistry, laser-capture microdissection, reverse transcriptase, and real-time quantitative PCR were used for determining IL-33 expression in the lung tissues. ASMC isolated from resected lung specimens were cultured with proinflammatory cytokines and with dexamethasone. IL-33 expression by ASMC was determined by PCR, ELISA, and Western blotting. Higher levels of IL-33 transcripts are detected in biopsies from asthmatic compared with control subjects, and especially in subjects with severe asthma. ASMC show IL-33 expression at both protein and mRNA levels. IL-33 and TNF-α transcript levels correlate in the lung tissues, and TNF-α up-regulates IL-33 expression by cultured ASMC in a time- and dose-dependent manner. IFN-γ also increases IL-33 expression and shows synergistic effect with TNF-α. Dexamethasone fails to abolish TNF-α-induced IL-33 up-regulation. IL-33 expression increases in bronchial biopsies from subjects with asthma compared with controls, as well as subjects with asthma severity. ASMC are a source of the IL-33 cytokine. Our data propose IL-33 as a novel inflammatory marker of severe and refractory asthma.
BACKGROUND: Several sets of Canadian guidelines for the diagnosis and management of asthma have been published over the past 15 years. Since the last revision of the 1999 Canadian Asthma Consensus Report, important new studies have highlighted the need to incorporate new information into the asthma guidelines. OBJECTIVES: To review the literature on adult asthma management published between January 2000 and June 2003; to evaluate the influence of the new evidence on the recommendations made in the 1999 Canadian Asthma Consensus Guidelines and its 2001 update; and to report new recommendations on adult asthma management. METHODS: Three specific topics for which new evidence affected the previous recommendations were selected for review: initial treatment of asthma, add-on therapies in the treatment of asthma and asthma education. The resultant reviews were discussed in June 2003 at a meeting under the auspices of the Canadian Thoracic Society, and recommendations for adult asthma management were reviewed. RESULTS: The present report emphasises the importance of the early introduction of inhaled corticosteroids in symptomatic patients with mild asthma; stresses the benefit of adding additional therapy, preferably long-acting beta 2 -agonists, to patients incompletely controlled on low doses of inhaled corticosteroids; and documents the essential role of asthma education. CONCLUSION: The present report generally supports many of the previous recommendations published in the 1999 Canadian Asthma Consensus Report and provides higher levels of evidence for a number of those recommendations.
Abstract Background Guidelines for the diagnosis and management of asthma have been published over the last 15 years; however, there has been little focus on issues relating to asthma in childhood. Since the last revision of the 1999 Canadian Asthma Consensus Report, important new studies, particularly in children, have highlighted the need to incorporate new information into the asthma guidelines. The objectives of this article are to review the literature on asthma published between January 2000 and June 2003 and to evaluate the influence of new evidence on the recommendations made in the 1999 Canadian Asthma Consensus Report and its 2001 update, with a major focus on pediatric issues. Methods The diagnosis of asthma in young children and prevention strategies, pharmacotherapy, inhalation devices, immunotherapy, and asthma education were selected for review by small expert resource groups. The reviews were discussed in June 2003 at a meeting under the auspices of the Canadian Network For Asthma Care and the Canadian Thoracic Society. Data published through December 2004 were subsequently reviewed by the individual expert resource groups. Results This report evaluates early-life prevention strategies and focuses on treatment of asthma in children, emphasizing the importance of early diagnosis and preventive therapy, the benefits of additional therapy, and the essential role of asthma education. Conclusion We generally support previous recommendations and focus on new issues, particularly those relevant to children and their families. This document is a guide for asthma management based on the best available published data and the opinion of health care professionals, including asthma experts and educators.
BACKGROUND: Pharmaceutical industry‐sponsored research has been shown to be biased toward reporting positive results. Frequent industry participation in trials assessing the efficacy of inhaled corticosteroid (ICS) and long‐acting beta 2 ‐agonist (LABA) combination treatment makes assessing industry influence difficult and warrants an assessment of specific potential publication bias in this area. OBJECTIVE: To describe the frequency of industry involvement in ICS/LABA trials and explore associations among significant outcomes, type of industry involvement and type of primary outcome. METHODS: A systematic review of trials comparing ICS/LABA combination therapy with ICS monotherapy for asthma was conducted. Data concerning the type of industry sponsorship, primary outcome and statistical results were collected. Comparisons between type of sponsorship and significant results were analyzed using Pearson’s χ 2 test and relative risk. RESULTS: Of 91 included studies (median year of publication 2005 [interquartile range 1994 to 2008]), 86 (95%) reported pharmaceutical involvement. Author affiliation was reported in 49 of 86 (57%), and 19 of 86 (22%) were industry‐reported trials without full publications. The remainder were published journal articles. Studies with a first or senior author affiliated with industry were 1.5 times more likely to report statistically significant results for the primary outcome compared with studies with other types of industry involvement. Pulmonary measures were 1.5 times more likely to be statistically significant than were measures of asthma control. CONCLUSIONS: The potential biases identified were consistent with other research focused on author role and industry involvement, and suggest that degree of bias may vary with type of affiliation.
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