Sunday, May 26, 2019

The Role of Inflammation in the Advancement of Chronic Obstructive

The agency of firing off in the advancement of Chronic hindering Pulmonary disease. Introduction Chronic obstructive pulmonary disease (COPD) is the collective term used for respiratory disease, including chronic bronchitis and emphysema. The disease develops slowly and is often not diagnosed until it is advanced and irreparable damage is evident (Global Initiative for Chronic Obstructive Lung Disease, 2011). The disease is characterised by airflow obstruction and lung p arnchyma.P atomic number 18nchyma, associated with emphysema, is the permanent enlargement of the air spaces distal to the terminal bronchioles, accompanied by airway wall destruction, without obvious fibrosis (Demirjian and Kamangar, 2011 Atsuyasu et al. , 2007). Airflow limitation results from loss of elastic recoil and reduced airway tethering. Chronic bronchitis leads to contract of airway calibre, increasing airway resistance. Patients may display signs of one or both of these diseases as they frequently o ccur in association with each other.Common symptoms are wheezing, coughing, shortness of breath on exertion, production of sputum and recurrent respiratory infections (Global Initiative for Chronic Obstructive Lung Disease, 2011). There are a host of triggers that exacerbates symptoms including green goddess and environmental pollutants, resulting in chronic inflammation (Kazuhiro and Barnes, 2009 Manuel et al. , 2002). Inflammation is defined as the presence of redness, swelling and pain, caused by the presence of edema fluid and the infiltration of tissues by leukocytes (Nairn & Helbert, 2002, pp15).Inflammation is a key biological result to eliminate harmful pathogens, that there is increasing evidence to suggest that chronic incendiary responses are responsible for the advancement of this disease and other chronic diseases including coronary artery disease, cancer, rheumatoid arthritis and multiple sclerosis. This re assure explores the correlation surrounded by COPD and i nflammation and the posterior effect on the systemic systems and the link with coronary heart disease (Mantovini et. al. , 2008 Mohr & Pelletier, 2005 Sattar et. al. , 2003 Powells et. al. , 2001 Danesh et. al. 2000 Murdoch & Finn, 2000). Methods Search engines used were Google Scholar and Pub Med using the keywords COPD, inflammation, disease, apoptosis, interleukin 8, cytokines, coronary heart disease and COPD. Searches were restricted to dates between 1999 and 2012. The majority of the included paper were obtained from the reference lists of other research papers. COPD riskiness factors COPD is strongly linked with repeated word picture to deleterious particles or gases and cigarette low-down has been acknowledged as a prime risk factor (Fabri et. al. , 2006 Lindberg et al. , 2005 Pauwels and Rabe. 2004, Association for Respiratory Technology & Physiology, 2000). Smokers have an extendd prevalence of respiratory and lung function abnormalities, a greater rate of decline i n FEV1 and a higher mortality rate than non-smokers (World health organisation, 2012). However, only a third of smokers develop COPD which implies that other factors such as genetics and environment are involved (Agusti, 2003). Exposure to air pollution caused by heating and cooking with bio-mass fuels in poorly ventilated lodging are major risk factors for COPD, especially in developing countries (Pauwels & Rabe, 2004).The most documented COPD genetic risk factor is the deficiency of Alpha -1-antitrypsin, a polymorphous glycoprotein which offers anti-protease protection against the serine proteinease, neutrophil elastase (Abboud & Vimalanathan, 2008 Devereux, 2006 Siafakas & Tzortzaki, 2002 Fabbri et al. , 2006). Research studies (in vitro) indicated that Alpha 1 antitrypsin as well possesses anti-inflammatory capabilities that extend beyond its anti-protease habit, including regulation of CD14 carryion (Nita, Serapinas & Janciauskiene, 2007), inhibition of TNF-? ene upregul ation (Subramaniyam, 2007) and inhibition of lipopolysaccharide energizing of monocytes and neutrophil migration (Janciauskiene et al. , 2004). Deficiency of Alpha -1-antitrypsin is associated with COPD cash advance in both smokers and non-smokers, although far greater in smokers (Bergen et al. , 2010 Fabbri et al. , 2006 Siafakas and Tzortzaki. , 2002 Foos et al. , 2002). Studies have suggested that smoking with this genetic disposition will easily increase risk of developing COPD (Kohnlein & Welte, 2008 Pauwels & Rabe, 2004 Foos et al. , 2002 Siafakas & Tzortzaki, 2002 Association forRespiratory Technology and Physiology, 2000). Pathogenesis of COPD Exposure to noxious particles triggers cytokine activation to recruit cells, which play a vital role in removing the noxious agents (Nairn & Helbert, 2007, pp22). An infiltration of neutrophils, eosinophils and CD8+ T-lymphocytes into the airways and lungs follows (Demedts et al, 2006 Mahler et al. , 2004 Sopori, 2002). High concen trations of chemokines, interleukon-8 (IL8) and tumor humiliation factor-a have been prove in patients with COPD which are potent activators and chemo-attractants of leukocyte subpopulations (Murdoch and Finn, 2000 Yamamoto et al. 1997). The interaction of chemo-attractants with leukocytes initiates a series of coordinated and cellular events, which includes phagocytosis, assoil of soluble anti-microbials and formation of reactive oxygen compounds involved in intracellular killing (Murdoch & Finn, 2000). Neutrophils and macrophages release elastase, stimulating the production of mucus to assist in ridding the airways of the irritants and subsequent waste generated by the inflammatory response (Shimizu et al. , 2000).Other processes such as neutrophil necrosis and reactive oxygen species move on contri thoe to mucus hyper secretion (Kim and Nadel, 2004 Mizgerd, 2002). When an inflammatory response is no longer needed protease inhibitor cells dampen the response. Research suggests that the inhibiting response in COPD is not triggered and chronic inflammation presides, representing a crucial tool in the pathogenesis of COPD (Demedts et al. , 2006 Hodge et al 2004). Hypersecretion of mucous can inhibit the ciliated epithelium from transporting mucus from the airways.Subsequent delays in bacteria clearance results in bacterial colonisation, which stimulates further granulocytic recruitment to the airways, escalating the inflammatory response. Chronic inflammation is linked with tissue destruction, imbalance of proteolytic and anti-proteolytic activity, hyper secretion of mucus, increased apoptotic activity and oxidative stress which contribute to the progression of COPD. Long term, chronic inflammation can result in widespread airway and parenchymal cell destruction which further contributes to disease progression (Mantovini et al. 2008 Mohr and Pelletier, 2005 Sattar et al. , 2003 Sopori, 2002 Powells et al. , 2001 Danesh et al. , 2000 Murdoch & Finn, 2000). R esearch suggests that macrophages express a markedly lower amount of toll like receptors in COPD suffers, resulting in a change magnitude recognition of microbes, facilitating damaging microbial colonisation, which may rationalise the increased amount of respiratory infections in COPD sufferers (Schneberger, 2011 Droemann et al. 2005). Infection initiates a biased release of inflammatory mediators which may escalate the pathogenesis of the disease (Gaschler et al. 2009, Ritter et al. , 2005 Sethi, 2000). oxidative stress Demedts et al, 2005 found that the dental consonant macrophages of COPD sufferers produced much higher levers of oxygen radicals and myeloperoxide which are important for the destruction of inter-cellular pathogens. Oxidant/anti-oxidant imbalance can result in the inactivation of anti-proteinases, airspace epithelial injury, increased sequestration of neutrophils in the pulmonary microvasculature, and gene expression of pro-inflammatory mediators, all of which exa cerbate the inflammatory response (MacNee, 2000 Drost et al. 2005). Emphysema like changes have been limn in the CT scans of malnourished women, suggesting that diet has an effect on lung tissue in the absence of smoking (Coxon et al. , 2004). Dietary supplementation then may be a beneficial therapeutic intervention in this condition, as antioxidants not only protect against the direct injurious make of oxidants, but fundamentally bowdlerize the inflammatory events that play an important part in the pathogenesis of COPD (Coxon et al. , 2004 MacNee, 2000). Apoptosis and COPDResearch suggests that there is increased apoptosis of epithelial cells in smokers and COPD patients. Apoptosis persisted despite smoking finis which suggests apoptosis may play a part in driving the inflammatory process and progression of the disease (Hodge et al. , 2003). Increased apoptotic alveolar epithelial and endothelial cells in the lungs not counterbalanced by proliferation and sufficient phagocytic clearance results in destruction of lung tissue and development of emphysema (Demedts et al, 2006 Kazutetsu, Naoko & Atsushi, 2003 Barnes et al. 000) Apoptosis can be induced by various stimuli, including oxidative stress, elastase and infiltrating cytoxix CD8 + T cells which are all associated with inflammation (Kazutetsu, Naoko and Atsushi, 2003). Efferocytosis allows for the removal of apoptotic material with minimal inflammation and prevents the development of secondary necrosis and ongoing inflammation. Failure of this highly conserved process may contribute to disease pathogenesis by impeding both the resolution of inflammation and the maintenance of alveolar integrity (Mukaro and Hodge, 2011 Taylor et al. , 2010 Morimoto et al, 2006 Vandivier et al, 2006).Proteolytic/Anti-proteolytic activity Mukaro and Hodge, (2011) suggests that in COPD there is an imbalance between proteolytic and anti-proteolytic activity, a prominent factor in the pathogenesis of this disease, which may contribute to lung parenchymal destruction. Research has also found that macrophages demonstrate defective phagocytic ability against common airways pathogens in COPD (Taylor et al. , 2010 Hodge et al. , 2003), The findings of Berenson et al. , (2006), supported a paradigm of defective immune responsiveness of alveolar macrophages, but found no significant differences in the blood macrophages of COPD sufferers.Taylor (2010) conceptualizes that persistence of bacteria as a consequence of defective phagocytosis may be a chronic antigenic drive for chronic inflammation. Systemic effects of COPD Chronic inflammation is present in all disease processes, mediating all stages of disease from initiation, manifestation and increment (Sompayrac 2003, pp12). Compelling epidemioligical data associate systemic inflammation to atherosclerosis, ischemic heart disease, strokes, and coronary deaths (Danesh, Whincup and Walker, 2000 Ridker, 1999).These observations have been strongly supported by experiments that show the direct effects of certain inflammatory markers, such as C-reactive protein (CRP), on the pathogenesis of plaque formation (Zwaka, Hombach and Torzewski, 2001 Lagrand, Visser & Hermens, 1999). A study by Gan, Man & Sin, 2003) found that patients with COPD were 2. 18 times much believably to have an elevated circulating c-reactive protein levels. Evidence strongly suggests that there is relationship between COPD, systemic inflammation, and cardiovascular diseases.Studies show that patients with mild-to-moderate COPD, cardiovascular disease is the lead cause of morbidity and mortality (Din and Man, 2009 Pope et al, 2003). As these diseases share similar risk factors such as smoking, increased age and inactivity, causation is unclear and is likely to be due to multiple factors, including lifestyle, environmental and genetics (Gan, 2005 Agusti et. al. 2003). Discussion Inflammation, it would appear, is a double edged sword crucial for clearance of pathogens an d recovery from injury but can also contribute to life threatening chronic diseases (Smith, 1994 Sporori, 2003).COPD is a complex condition, influenced by multiple genetic and/or environmental risks. A oscillation of low grade inflammation is the consequence, with destructive and damaging effects, resulting in mucus hyper-secretion, airway obstruction, increased elastase production and oxidative stress, which encourage further inflammation and destruction. COPD is associated with exposure to smoke or noxious gases, however inflammation may also be caused by irritation from coughing, wheezing, respiratory infections and mucus production. Most exacerbations of COPD are caused by bacterial or viral infection (Sanjay and Murphy, 2008 Sanjay 2008).Mucosal cells produce mucus, which irritates the airways causing airway obstruction. This subsequently reduces FEV1, and cough effectiveness, which contributes to the build up of bacterial mucus. Imbalance between proteolytic and anti-proteoly tic activity presides, creating an ideal environment for infection. Research suggests that macrophages express a markedly lower amount of toll like receptors in COPD suffers, resulting in a rock-bottom recognition of microbes, facilitating damaging microbial colonisation, which may explain the increased amount of respiratory infections in COPD sufferers (Schneberger,2011 Droemann et al. 005). Infection initiates a biased release of inflammatory mediators which may escalate the pathogenesis of the disease (Gaschler et al. , 2009, Ritter et al. , 2005 Sethi, 2000). Researchers have found high levels of neutrophils, macrophages and CD8+ cells in ex smokers (Lappers et al. , 2006). Thus, suggesting that inflammatory changes in COPD, although initially induced by inhalation of noxious agents, are fundamental to the disease process, rather than to the initial trigger per se (Gamble et al, 2007). Studies have shown that airway epithelial and T-cell apoptosis in COPD continues despite smok ing cessation (Lappers et al. 2006). exorbitance apoptosis results in inappropriate destruction of host tissue, leading to atrophy and tissue necrosis, which in turn further stimulates the inflammatory response and perpetuates the situation. We have already ascertained an imbalance between the proteolytic and anti-proteolytic activity and this is another factor that contributes, resulting in failure to resolve the inflammatory reaction rapidly (Hodge et al. , 2005). Un-cleared apoptotic cells may undergo secondary necrosis with discharge of injurious cells contents resulting in tissue destruction and further inflammation.Inability to remove apoptotic cells and debris created overwhelms the normal clearance mechanisms, stimulating further inflammatory responses, further contributing to COPD pathogenesis (Sanjay and Murphy, 2008 Sanjay 2008). It has been identified that the immune system may become less responsive, the longer that chronic inflammation presides, which may lead you to believe that this would initiate an inhibitory effect on the inflammatory process. However this is not the case and the inflammatory process persists, presenting as low level chronic inflammation.In access a less responsive immune system is more susceptible to infection, exacerbating the inflammatory response (Sanjay and Murphy, 2008 Sanjay 2008). There appears to be strong epidemiological links between cardiovascular disease and COPD. The same inflammatory markets are evident in both suggesting a systemic link. Both diseases share similar risk factors, so it is difficult to determine initiation of the diseases. One could also argue that the debilitating effects of COPD, which include a reduced exercise capacity, dyspnoea and deconditioning increase the risk of cardiovascular disease development.In conclusion, it appears that adaptive immune is active in the disease progression of this complex pathophysiological syndrome. Particularly elaboration and production of cytokines, chemi cal mediators and auto-antibodies, which instanter injure respiratory tissues. CD8+ mediates tissue destruction, whereas CD4 orchestrates inflammatory responses, which facilitates humoral immune responses (Gadgill and Duncan 2008). Conclusions made in this review are only valid within the boundaries of the research and papers used. References Agusti et al (2003) Systemic effects of chronic obstructive pulmonary disease.Eur Respir J 2003 21 347-360 Online. on tap(predicate) at http//www. taiss. com/gepoc/gecarp/gepubli/publdoc/010-999-agustiag-systemic-effects-chronic-obstructive-pulmonary-disease. pdf (Accessed 10 November 2011). Association for Respiratory Technology and Physiology (2000) handbook in Spirometry. 2nd Edition. Association for Respiratory Technology and Physiology. Birmingham . Barnes P. J (2000) Mechanisms in COPD, Differences from Asthma. Chest, February 2000, vol 117, no. 2, suppl 105-145. Online Available at http//www. ncbi. nlm. nih. gov/pubmed/10673467 (Acces sed 4 November 2011). Beeh, K. M. , Kornmann, O. Buhl, R. , Culpitt, S. V. , Giembycz, M. A. , Barnes, P. J. , Neutrophil chemotactic activity of sputum from patients with COPD role of interleukin 8 and leukotriene B4. Chest, 2003 123, 1240-1247 Online. Available at http//journal. publications. chestnet. org/article. aspx? articleid=1081469 (Accessed 4 November 2011). Bergin, D. A. , Reeves, E. P. , Meleady, P. , Henry, M. , McElvaney, O. J. , Carroll, T. P. , Condron, T. P. , Chotirmall, S. H. , Clynes, M. , ONeill, S. J. , McElvaney, N. G. , (2010) ? -1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8.J Clin Invest. 2010 120(12)42364250. Doi10. 1172/JCI41196 Online Available at http//www. jci. org/articles/view/41196 (Accessed 21 magisterial 2012). Brunner, T. , Mueller. C. , (2003) Apoptosis in disease about shortage and excess. Essays Biochem. 200339119-30. Online. Available at http//www. ncbi. nlm. nih. gov/pubmed/14585078 (Access ed 30 July 2012). Canavan, J. , Garrod, R. , Marshall, J. , Jackson, D. , Ansley, P. , Jewell, A. , (2007) Measurement of the acute inflammatory response to walking exercise in COPD effects of pulmonary rehabilitation. International Journal of COPD, 20072(3) 347-353.Cosio, G. , Majo, J. , Cosio, M. , (2002) Inflammation of the Airways and Lung Parenchyma in COPD. Chest. May 2002. 121(5_wuppl)160s-165S Online Available at http//www. ncbi. nlm. nih. gov/pubmed/12010846 (Accessed 5 November 2011) Danesh, J. , Whincup, P. , senior M. C. , Lennnon, L. , Thomson, A. , Appleby, P. , Gallimore, J. R. , Pepys, M. B. ,(2000) Low grade inflammation and coronary heart disease prospective study and updated meta-analyses BMJ 2000321199 online Available at http//www. bmj. com/content/321/7255/199. wide of the mark (Accessed 21 solemn 2011). Demedts, I. K. , Demoor, T. Bracke, K. R. , Joos, G. F. , Brusselle, G. G. , (2006) Role of apoptosis in the pathogenesis of COPD and pulmonary emphysema. R espiratory Research, 753. Online Available at http//www. ncbi. nlm. nih. gov/pmc/articles/PMC1501017/ (Accessed 14 November 2011). Droemann D. , Goldmann, T. , Tiedje, T. , Zabel, P. , Dalhoff, K. , Schaaf, B. , (2005) Toll like receptor 2 expression is decreased on alveolar macrophages in cigarette smokers and COPD patients. Respiratory Research 668. Online Available at from http//respiratory-research. com/contents/6/1/68 (Accessed 14 November 2011).Drost E. M. , Skwarski, K. M. , Souleda, J. , Soler, N. , Roca, J. ,Augusti, A. , MacNee, W. , (2005) Oxidative stress and airway inflammation in severe exacerbations of COPD. International Journal of Respiratory Medicine, Thorax 2005, 2930300 Online, Available at http//thorax. bmj. com/content/60/4/293. full. pdf, (Accessed 9 November 2012). Dyer, E. , Englander, H. , Kagen, D. , (2011) Treatment of Anemia in Patients with Heart Disease. Washington (DC) Department of Veteran Affairs. Gamble, E. , Grootendorst, D. C. , Hattootuwa, K. , OShaugnessy, T. , Ram, F. S. F. , Qlu, K. , Zhu, J. Vignola, A. M. , Kroegel, C. , Morell, F. , Pavord, I. D. , Rabe, K. F. , Jeffery, P. K. , Barnes, N. C. (2008) Airway Mucusal inflammation in COPD is similar in smokers and ex-smokers a pooled analysis. Eur Respir. J. 2007, 30 467-471 DOI10. 1183/09031936. 00013006 Online Available at http//www. lumc. nl/rep/1070/att/91028021319455/100316114728452. pdf. (Accessed 15 August 2012) Garrod R. , Ansley, P. , Canavan, J. , Jewell, A. , (2007) Exercise and the inflammatory response in chronic obstructive pulmonary disease (COPD) Does grooming confer anti-inflammatory properties in COPD? medical exam Hypotheses (2007) 68, 291-298. Global Initiative for Chronic Obstructive Lung Disease (2011) Global Strategy for the Diagnosis, Management, and Prevention of COPD Online Available at http//www. goldcopd. org/. (Accessed 3 November 2011). Hodge S. , Hodge, G. , Scicchitano, R. , Reynolds, P. N. , Holmes, M. , (2003) Alveolar macrophages from subjects with chronic obstructive pulmonary disease are deficient in their ability to phagocytose apoptotic airway epithelial cells. Immunology and Cell Biology (2003), 81, 289-296, Online, Available at http//65. 199. 186. 23/icb/journal/v81/n4/full/icb200342a. tml, (Accessed 7 November 2012). Hodge S. , Hodge G. , Holmes M. , Reynolds P. N. , (2005) Apoptosis in COPD. Current Respiratory Medicine reviews. Volume 1, Number 1, January 2005, pp 33-41(9). Publisher Bentham science publishers. Online, Available at http//www. ingentaconnect. com/content/ben/crmr/2005/00000001/00000001/art00004, (Accessed 24 July 2012). John M. , Hoernig S. , Doehner,W. , Okonko, D. D. , Witt, C. , Anker, S. D. (2005) Anaemia and Inflammation in COPD. Chest 2005 127 825-829. Online Available at http//www. chestjournal. chestpubs. org (Accessed 21 November 2011).Kazuhiro I. And Barnes P. J. (2008) COPD as a Disease of Accelerated Lung Aging, Chest. January 2009 one hundred thirty-five (1) 173-180. doi10. 1378/chest. 08-1419 Online, Available at http//journal. publications. chestnet. org/article. aspx? articleid=1089585 (Accessed 10 November 2012). Kim S. and Nadel J. A. (2004) Role of Neutrophils in Mucus Hypersecretion in COPD and Implications for Therapy Treatments in Respiratory Medicine, Volume 3,Number 3, 2004 , pp. 147-159(13) Online Available from http//chestjournal. chestpubs. org/content/117/5_suppl_2/386S. full (Accessed 20 November 2011).Kohnlein T. and Welte T. (2008) Alpha-1 Antitrypsin Deficiency Pathogenesis, Clinical Presentation, Diagnosis, and Treatment, The American Journal of Medicine Volume 121, Issue 1 , Pages 3-9, January 2008 Online. Available at http//www. ncbi. nlm. nih. gov/pubmed/18187064 (Accessed 29 July 2012). Lapperre T. S. , Postma, D. S. , Gosman, M. M. E. , Snoech-Stroban, J. B. , Hacken, N. H. T. , Hiemstra, P. S. , Timen, W. , Sterk, P. J. , Mauad, T. , Relation between eon of smoking cessation and bronchial inflammation in COPD. Thorax 200661 115-121 doi10. 1136/thx. 2005. 040519. Online.Available at http//thorax. highwire. org/content/21/2/115. full (Accessed 17 August 2012) Lapperre, T. S. , Postma, D. S. , Gosman, M. M. E. , Snoech-Stroban, J. B. , Hacken, N. H. T. , Hiemstra, P. S. , Timens. W. , Sterk, P. J. , Mauad, T. , Relationship between duration of smoking cessation and bronchial inflammation in COPD. Lapperre, T. S. , Postma, D. S. , Gosman, M. M. E. , Snoech-Stroban, J. B. , Hacken, N. H. T. , Hiemstra, P. S. , Timens. W. , Sterk, P. J. , Mauad, T. , Relationship between duration of smoking cessation and bronchial inflammation in COPDLapperre, T. S. , Postma, D. S. Gosman, M. M. E. , Snoech-Stroban, J. B. , Hacken, N. H. T. , Hiemstra, P. S. , Timens. W. , Sterk, P. J. , Mauad, T. , Relationship between duration of smoking cessation and bronchial inflammation in COPD. Lapperre, T. S. , Postma, D. S. , Gosman, M. M. E. , Snoech-Stroban, J. B. , Hacken, N. H. T. , Hiemstra, P. S. , Timens. W. , Sterk, P. J. , Mauad, T. , Relationship between duration of smoking cessation and bronchial inflammation in COPD. Mahler, D. A. , Huang, S. , Tabrizi, M. , Bell, G. A. , (2004) Efficacy and Safety of a Monoclonal Antibody Recognizing Interleukin-8 in COPD* A Pilot Study.CHEST. September2004126(3)926-934. doi10. 1378/chest. 126. 3. 926 September2004, Vol 126, No. 3 Online Available at http//journal. publications. chestnet. org/article. aspx? articleid=1082794 (Accessed 9 November 2012). - Mantovani, A. , Allavena, P. , Sica, A. , Balkwill, F. , (2008) Cancer-related inflammation Nature 454, 436-444 (24 July 2008) doi10. 1038/nature07205 online Available at http//www. nature. com/nature/journal/v454/n7203/abs/nature07205. html (Accessed 17 August 2012). Mizgerd J. P (2002) Molecular mechanisms of neutrophil recruitment elicited by bacteria in the lungs. Seminars in Immunology. Volume 12 Issue 2 April 2002 Pages 123-132. - Mohr,D. C. , Pelletier,D. , (2005) A temporal framework for understanding the effects of stressful life events on inflammation in patients with multiple sclerosis. Departments of Psychiatry and Neurology, University of California, San Francisco, CA 94131, USA online Available at http//www. sciencedirect. om/science/article/pii/S0889159105000620 (Accessed 17 August 2012). Murdoch C & Finn A (2000) Chemokine receptors and their role in inflammation and infectious diseases. Blood. May 15, 2000 vol 95. No. 10 3032-3043. Nadel, J. A. (2000) Role of neutrophil elastase in Hypersecretion during COPD exacerbations and proposed therapies. Chest. 2000 117, 386S-389S. Nairn R & Helbert M (2002) Immunology for Medical Students. Mosby Elsevier. Canada. Pauwels, R. A. , Buist, A. S. , Calverley, P. M. A. , Jenkins, C. R. , Hurd, S. S. , (2001) Global Strategy for the Diagnosis, Management, and Prevention of Chronic

No comments:

Post a Comment

Note: Only a member of this blog may post a comment.