Pub Date : 2007-10-01DOI: 10.1177/1753465807082374
J. Tkáč, S. Man, D. Sin
Chronic obstructive pulmonary disease (COPD) is a highly prevalent chronic lung condition, affecting ∼10% of adults over the age of 40 years in the western world. Research over the past 10 years has shown that COPD is more than just a lung disorder; it affects other end-organs including the cardiovascular and the musculoskeletal systems, making it a multi-component, multi-system disease. COPD increases the risk for ischemic heart disease, stroke, osteoporosis, cachexia, and muscle weakness by two to threefold, independent of other factors such as smoking and age. The mechanisms by which COPD affects these end-organs, however, are unclear. In this paper, we review some of the common and serious extra-pulmonary manifestations of COPD and the potential mechanisms by which they can be linked with COPD.
{"title":"Review: Systemic consequences of COPD","authors":"J. Tkáč, S. Man, D. Sin","doi":"10.1177/1753465807082374","DOIUrl":"https://doi.org/10.1177/1753465807082374","url":null,"abstract":"Chronic obstructive pulmonary disease (COPD) is a highly prevalent chronic lung condition, affecting ∼10% of adults over the age of 40 years in the western world. Research over the past 10 years has shown that COPD is more than just a lung disorder; it affects other end-organs including the cardiovascular and the musculoskeletal systems, making it a multi-component, multi-system disease. COPD increases the risk for ischemic heart disease, stroke, osteoporosis, cachexia, and muscle weakness by two to threefold, independent of other factors such as smoking and age. The mechanisms by which COPD affects these end-organs, however, are unclear. In this paper, we review some of the common and serious extra-pulmonary manifestations of COPD and the potential mechanisms by which they can be linked with COPD.","PeriodicalId":364194,"journal":{"name":"Theraputic Advances in Respiratory Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127767337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-10-01DOI: 10.1177/1753465807082373
P. Montuschi
Analysis of exhaled breath condensate (EBC) is a noninvasive method for studying the composition of airway lining fluid and has the potential for assessing lung inflammation. EBC is mainly formed by water vapor, but also contains aerosol particles in which several biomolecules including leukotrienes, 8-isoprostane, prostaglandins, hydrogen peroxide, nitric oxide-derived products, and hydrogen ions, have been detected in healthy subjects. Inflammatory mediators in EBC are detected in healthy subjects and some of them are elevated in patients with different lung diseases. Analysis of EBC is completely noninvasive, is particularly suitable for longitudinal studies, and is potentially useful for assessing the response to pharmacological therapy. Identification of selective profiles of biomarkers of lung diseases might also have a diagnostic value. However, EBC analysis currently has important limitations. The lack of standardized procedures for EBC analysis and validation of some analytical techniques makes it difficult comparison of results from different laboratories. Analysis of EBC is currently more useful for relative measures than for quantitative assessment of inflammatory mediators. Reference analytical techniques are required to provide definitive evidence for the presence of some inflammatory mediators in EBC and for their accurate quantitative assessment in this biological fluid. Several methodological issues need to be addressed before EBC analysis can be considered for clinical applications. However, further research in this area is warranted due to the relative lack of noninvasive methods for assessing lung inflammation.
{"title":"Review: Analysis of exhaled breath condensate in respiratory medicine: methodological aspects and potential clinical applications","authors":"P. Montuschi","doi":"10.1177/1753465807082373","DOIUrl":"https://doi.org/10.1177/1753465807082373","url":null,"abstract":"Analysis of exhaled breath condensate (EBC) is a noninvasive method for studying the composition of airway lining fluid and has the potential for assessing lung inflammation. EBC is mainly formed by water vapor, but also contains aerosol particles in which several biomolecules including leukotrienes, 8-isoprostane, prostaglandins, hydrogen peroxide, nitric oxide-derived products, and hydrogen ions, have been detected in healthy subjects. Inflammatory mediators in EBC are detected in healthy subjects and some of them are elevated in patients with different lung diseases. Analysis of EBC is completely noninvasive, is particularly suitable for longitudinal studies, and is potentially useful for assessing the response to pharmacological therapy. Identification of selective profiles of biomarkers of lung diseases might also have a diagnostic value. However, EBC analysis currently has important limitations. The lack of standardized procedures for EBC analysis and validation of some analytical techniques makes it difficult comparison of results from different laboratories. Analysis of EBC is currently more useful for relative measures than for quantitative assessment of inflammatory mediators. Reference analytical techniques are required to provide definitive evidence for the presence of some inflammatory mediators in EBC and for their accurate quantitative assessment in this biological fluid. Several methodological issues need to be addressed before EBC analysis can be considered for clinical applications. However, further research in this area is warranted due to the relative lack of noninvasive methods for assessing lung inflammation.","PeriodicalId":364194,"journal":{"name":"Theraputic Advances in Respiratory Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133181400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-10-01DOI: 10.1177/1753465807080740
L. Fernandes, P. Henry, R. Goldie
Asthma is a complex inflammatory disease of the airways involving reversible bronchoconstriction. Chronic obstructive pulmonary disease is typified by inflammation and airflow limitation that has an irreversible component. There is now substantial evidence that Rho kinase is involved in many of the pathways that contribute to the pathologies associated with these respiratory diseases including bronchoconstriction, airway inflammation, airway remodelling, neuromodulation and exacerbations due to respiratory tract viral infection. Indeed the Rho kinase inhibitor Y-27632 causes bronchodilatation and reduces pulmonary eosinophilia trafficking and airways hyperresponsiveness. Furthermore, accumulating evidence suggests that inhibition of Rho kinase could have a major beneficial impact on symptoms and disease progression in asthma and COPD by modulating several other systems and processes. Thus, the Rho kinase pathway may indeed be a worthwhile therapeutic target in the treatment of asthma and chronic obstructive pulmonary disease.
{"title":"Review: Rho kinase as a therapeutic target in the treatment of asthma and chronic obstructive pulmonary disease","authors":"L. Fernandes, P. Henry, R. Goldie","doi":"10.1177/1753465807080740","DOIUrl":"https://doi.org/10.1177/1753465807080740","url":null,"abstract":"Asthma is a complex inflammatory disease of the airways involving reversible bronchoconstriction. Chronic obstructive pulmonary disease is typified by inflammation and airflow limitation that has an irreversible component. There is now substantial evidence that Rho kinase is involved in many of the pathways that contribute to the pathologies associated with these respiratory diseases including bronchoconstriction, airway inflammation, airway remodelling, neuromodulation and exacerbations due to respiratory tract viral infection. Indeed the Rho kinase inhibitor Y-27632 causes bronchodilatation and reduces pulmonary eosinophilia trafficking and airways hyperresponsiveness. Furthermore, accumulating evidence suggests that inhibition of Rho kinase could have a major beneficial impact on symptoms and disease progression in asthma and COPD by modulating several other systems and processes. Thus, the Rho kinase pathway may indeed be a worthwhile therapeutic target in the treatment of asthma and chronic obstructive pulmonary disease.","PeriodicalId":364194,"journal":{"name":"Theraputic Advances in Respiratory Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134098006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-10-01DOI: 10.1177/1753465807081747
M. Cazzola, M. Matera
Several studies suggested an association between the regular use of β2-agonists and asthma deaths. Whether this association represents adverse effects of β -agonist use or is entirely due to disease severity is a matter of ongoing debate. Previous literature indicates that confounding by poor asthma control may explain the apparent deleterious effects of inhaled β2-agonists. Tolerance to nonbronchodilator effects of β2-agonists may account for the increase in reactivity to indirect bronchoconstrictor challenges and explain why some studies have demonstrated enhanced bronchoconstriction in patients with asthma after regular β 2-agonist therapy. Nonetheless, the salmeterol multi-centre asthma research trial (SMART) found more asthma deaths (13 vs 3) and life-threatening asthma events (37 vs 22) in the salmeterol-treated asthmatic patients, although it was documented that among African-Americans, 5 times as many deaths and near-deaths from asthma occurred in those given salmeterol than in those given placebo, and among patients with asthma not using an inhaled corticosteroid (ICS) as a preventive (controller) medication, again more deaths and near-deaths from asthma occurred in those given salmeterol than in those given placebo. Only 38% of the African-Americans who participated in the study used an ICS. As a result of the findings from the SMART, FDA issued a public health advisory to highlight that long-acting β2-agonists (LABAs) should not be the first medicine used to treat asthma. LABAs should be added to the asthma treatment plan only if other medicines, including the use of low-or-medium dose ICSs, do not control asthma. However, despite all of the concerns raised by the SMART, inhaled β2-agonists remain the most effective bronchodilators available for the immediate relief of asthma symptoms and, as such, remain an important component of asthma management. Obviously, there are concerns about LABA treatment as monotherapy for asthma. Patients with asthma should be initiated and maintained on sufficiently high doses of ICSs and only patients whose asthma cannot be controlled should receive additional LABAs on a regular basis.
{"title":"Review: Safety of long-acting β2 -agonists in the treatment of asthma","authors":"M. Cazzola, M. Matera","doi":"10.1177/1753465807081747","DOIUrl":"https://doi.org/10.1177/1753465807081747","url":null,"abstract":"Several studies suggested an association between the regular use of β2-agonists and asthma deaths. Whether this association represents adverse effects of β -agonist use or is entirely due to disease severity is a matter of ongoing debate. Previous literature indicates that confounding by poor asthma control may explain the apparent deleterious effects of inhaled β2-agonists. Tolerance to nonbronchodilator effects of β2-agonists may account for the increase in reactivity to indirect bronchoconstrictor challenges and explain why some studies have demonstrated enhanced bronchoconstriction in patients with asthma after regular β 2-agonist therapy. Nonetheless, the salmeterol multi-centre asthma research trial (SMART) found more asthma deaths (13 vs 3) and life-threatening asthma events (37 vs 22) in the salmeterol-treated asthmatic patients, although it was documented that among African-Americans, 5 times as many deaths and near-deaths from asthma occurred in those given salmeterol than in those given placebo, and among patients with asthma not using an inhaled corticosteroid (ICS) as a preventive (controller) medication, again more deaths and near-deaths from asthma occurred in those given salmeterol than in those given placebo. Only 38% of the African-Americans who participated in the study used an ICS. As a result of the findings from the SMART, FDA issued a public health advisory to highlight that long-acting β2-agonists (LABAs) should not be the first medicine used to treat asthma. LABAs should be added to the asthma treatment plan only if other medicines, including the use of low-or-medium dose ICSs, do not control asthma. However, despite all of the concerns raised by the SMART, inhaled β2-agonists remain the most effective bronchodilators available for the immediate relief of asthma symptoms and, as such, remain an important component of asthma management. Obviously, there are concerns about LABA treatment as monotherapy for asthma. Patients with asthma should be initiated and maintained on sufficiently high doses of ICSs and only patients whose asthma cannot be controlled should receive additional LABAs on a regular basis.","PeriodicalId":364194,"journal":{"name":"Theraputic Advances in Respiratory Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129758807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-10-01DOI: 10.1177/1753465807082692
M. Miravitlles
Exacerbations may produce permanent impairment in lung function and health status in patients with COPD. Up to 70% of episodes have a bacterial etiology, being of mixed viral infection in some cases. The new, more active antibiotics have demonstrated better eradication of bacteria in the airways and, consequently, prolongation of the time to the next exacerbation. However, the ability of bacteria to develop resistance to the antibiotics currently used warrants novel research into new families of antimicrobials, and the adoption of new strategies such as the prevention of exacerbations, nebulized antibiotic treatment or the use of antibiotics in combination.
{"title":"Review: Do we need new antibiotics for treating exacerbations of COPD?","authors":"M. Miravitlles","doi":"10.1177/1753465807082692","DOIUrl":"https://doi.org/10.1177/1753465807082692","url":null,"abstract":"Exacerbations may produce permanent impairment in lung function and health status in patients with COPD. Up to 70% of episodes have a bacterial etiology, being of mixed viral infection in some cases. The new, more active antibiotics have demonstrated better eradication of bacteria in the airways and, consequently, prolongation of the time to the next exacerbation. However, the ability of bacteria to develop resistance to the antibiotics currently used warrants novel research into new families of antimicrobials, and the adoption of new strategies such as the prevention of exacerbations, nebulized antibiotic treatment or the use of antibiotics in combination.","PeriodicalId":364194,"journal":{"name":"Theraputic Advances in Respiratory Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114283984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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