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. 2004 Oct;59(10):892–896. doi: 10.1136/thx.2003.015768

Association of bronchial hyperresponsiveness and lung function with C-reactive protein (CRP): a population based study

S Kony 1, M Zureik 1, F Driss 1, C Neukirch 1, B Leynaert 1, F Neukirch 1
PMCID: PMC1746828  PMID: 15454657

Abstract

Background: C-reactive protein (CRP), a marker of systemic inflammation, is a powerful predictor of adverse cardiovascular events. Respiratory impairment is also associated with cardiovascular risk. Although some studies have found an inverse relationship between lung function and markers of systemic inflammation, only one study has reported a relationship between lung function and CRP levels. In contrast, little is known about the relationship between bronchial hyperresponsiveness (BHR) and systemic inflammation. The association between lung function and CRP and between BHR and CRP has been investigated.

Methods: As part of the European Community Respiratory Health Survey follow up study serum CRP levels, forced expiratory volume in 1 second (FEV1), and BHR to methacholine (⩾20% decrease in FEV1 to <4 mg methacholine) were measured in 259 adults aged 28–56 years free of cardiovascular disease or respiratory infection.

Results: Mean (SD) FEV1 (adjusted for age, sex, height, and smoking status) was lower in subjects with a high CRP level (high tertile) (3.29 (0.44) l/s v 3.50 (0.44) l/s; p<0.001) and BHR was more frequent (41.9% v 24.9%; p = 0.005) than in subjects with lower CRP levels (low+middle tertiles). Similar results were obtained when the potential confounding factors were taken into account. Similar patterns of results were found in non-smokers and in non-asthmatic subjects.

Conclusions: Increased CRP levels are strongly and independently associated with respiratory impairment and more frequent BHR. These results suggest that both respiratory impairment and BHR are associated with a systemic inflammatory process.

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Selected References

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  1. Bhatt Deepak L., Topol Eric J. Need to test the arterial inflammation hypothesis. Circulation. 2002 Jul 2;106(1):136–140. doi: 10.1161/01.cir.0000021112.29409.a2. [DOI] [PubMed] [Google Scholar]
  2. Bonafè M., Olivieri F., Cavallone L., Giovagnetti S., Mayegiani F., Cardelli M., Pieri C., Marra M., Antonicelli R., Lisa R. A gender--dependent genetic predisposition to produce high levels of IL-6 is detrimental for longevity. Eur J Immunol. 2001 Aug;31(8):2357–2361. doi: 10.1002/1521-4141(200108)31:8&#60;2357::aid-immu2357&#62;3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
  3. Burney P. G., Luczynska C., Chinn S., Jarvis D. The European Community Respiratory Health Survey. Eur Respir J. 1994 May;7(5):954–960. doi: 10.1183/09031936.94.07050954. [DOI] [PubMed] [Google Scholar]
  4. Dahl M., Tybjaerg-Hansen A., Vestbo J., Lange P., Nordestgaard B. G. Elevated plasma fibrinogen associated with reduced pulmonary function and increased risk of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001 Sep 15;164(6):1008–1011. doi: 10.1164/ajrccm.164.6.2010067. [DOI] [PubMed] [Google Scholar]
  5. Engström G., Lind P., Hedblad B., Wollmer P., Stavenow L., Janzon L., Lindgärde F. Lung function and cardiovascular risk: relationship with inflammation-sensitive plasma proteins. Circulation. 2002 Nov 12;106(20):2555–2560. doi: 10.1161/01.cir.0000037220.00065.0d. [DOI] [PubMed] [Google Scholar]
  6. Gibson P. G., Manning P. J., O'Byrne P. M., Girgis-Gabardo A., Dolovich J., Denburg J. A., Hargreave F. E. Allergen-induced asthmatic responses. Relationship between increases in airway responsiveness and increases in circulating eosinophils, basophils, and their progenitors. Am Rev Respir Dis. 1991 Feb;143(2):331–335. doi: 10.1164/ajrccm/143.2.331. [DOI] [PubMed] [Google Scholar]
  7. Griffith K. A., Sherrill D. L., Siegel E. M., Manolio T. A., Bonekat H. W., Enright P. L. Predictors of loss of lung function in the elderly: the Cardiovascular Health Study. Am J Respir Crit Care Med. 2001 Jan;163(1):61–68. doi: 10.1164/ajrccm.163.1.9906089. [DOI] [PubMed] [Google Scholar]
  8. Hole D. J., Watt G. C., Davey-Smith G., Hart C. L., Gillis C. R., Hawthorne V. M. Impaired lung function and mortality risk in men and women: findings from the Renfrew and Paisley prospective population study. BMJ. 1996 Sep 21;313(7059):711–716. doi: 10.1136/bmj.313.7059.711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Jousilahti Pekka, Salomaa Veikko, Hakala Katri, Rasi Vesa, Vahtera Elina, Palosuo Timo. The association of sensitive systemic inflammation markers with bronchial asthma. Ann Allergy Asthma Immunol. 2002 Oct;89(4):381–385. doi: 10.1016/S1081-1206(10)62039-X. [DOI] [PubMed] [Google Scholar]
  10. Kauffmann F., Frette C., Annesi I., Oryszczyn M. P., Dore M. F., Neukirch F. Relationships of haptoglobin level to FEV1, wheezing, bronchial hyper-responsiveness and allergy. Clin Exp Allergy. 1991 Nov;21(6):669–674. doi: 10.1111/j.1365-2222.1991.tb03194.x. [DOI] [PubMed] [Google Scholar]
  11. Koenig W. Inflammation and coronary heart disease: an overview. Cardiol Rev. 2001 Jan-Feb;9(1):31–35. doi: 10.1097/00045415-200101000-00007. [DOI] [PubMed] [Google Scholar]
  12. Kony Sabine, Zureik Mahmoud, Neukirch Catherine, Leynaert Benedicte, Vervloet Daniel, Neukirch Françoise. Rhinitis is associated with increased systolic blood pressure in men: a population-based study. Am J Respir Crit Care Med. 2002 Nov 21;167(4):538–543. doi: 10.1164/rccm.200208-851OC. [DOI] [PubMed] [Google Scholar]
  13. Leynaert B., Bousquet J., Henry C., Liard R., Neukirch F. Is bronchial hyperresponsiveness more frequent in women than in men? A population-based study. Am J Respir Crit Care Med. 1997 Nov;156(5):1413–1420. doi: 10.1164/ajrccm.156.5.9701060. [DOI] [PubMed] [Google Scholar]
  14. Mendall M. A., Patel P., Ballam L., Strachan D., Northfield T. C. C reactive protein and its relation to cardiovascular risk factors: a population based cross sectional study. BMJ. 1996 Apr 27;312(7038):1061–1065. doi: 10.1136/bmj.312.7038.1061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mendall M. A., Strachan D. P., Butland B. K., Ballam L., Morris J., Sweetnam P. M., Elwood P. C. C-reactive protein: relation to total mortality, cardiovascular mortality and cardiovascular risk factors in men. Eur Heart J. 2000 Oct;21(19):1584–1590. doi: 10.1053/euhj.1999.1982. [DOI] [PubMed] [Google Scholar]
  16. Minette A. Questionnaire of the European Community for Coal and Steel (ECSC) on respiratory symptoms. 1987--updating of the 1962 and 1967 questionnaires for studying chronic bronchitis and emphysema. Eur Respir J. 1989 Feb;2(2):165–177. [PubMed] [Google Scholar]
  17. O'Connor G. T., Sparrow D., Weiss S. T. A prospective longitudinal study of methacholine airway responsiveness as a predictor of pulmonary-function decline: the Normative Aging Study. Am J Respir Crit Care Med. 1995 Jul;152(1):87–92. doi: 10.1164/ajrccm.152.1.7599868. [DOI] [PubMed] [Google Scholar]
  18. Pankow J. S., Folsom A. R., Cushman M., Borecki I. B., Hopkins P. N., Eckfeldt J. H., Tracy R. P. Familial and genetic determinants of systemic markers of inflammation: the NHLBI family heart study. Atherosclerosis. 2001 Feb 15;154(3):681–689. doi: 10.1016/s0021-9150(00)00586-4. [DOI] [PubMed] [Google Scholar]
  19. Quanjer P. H., Tammeling G. J., Cotes J. E., Pedersen O. F., Peslin R., Yernault J. C. Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl. 1993 Mar;16:5–40. [PubMed] [Google Scholar]
  20. Ridker P. M., Buring J. E., Shih J., Matias M., Hennekens C. H. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation. 1998 Aug 25;98(8):731–733. doi: 10.1161/01.cir.98.8.731. [DOI] [PubMed] [Google Scholar]
  21. Ridker P. M., Cushman M., Stampfer M. J., Tracy R. P., Hennekens C. H. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997 Apr 3;336(14):973–979. doi: 10.1056/NEJM199704033361401. [DOI] [PubMed] [Google Scholar]
  22. Ridker Paul M., Rifai Nader, Rose Lynda, Buring Julie E., Cook Nancy R. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med. 2002 Nov 14;347(20):1557–1565. doi: 10.1056/NEJMoa021993. [DOI] [PubMed] [Google Scholar]
  23. Rijcken B., Schouten J. P., Xu X., Rosner B., Weiss S. T. Airway hyperresponsiveness to histamine associated with accelerated decline in FEV1. Am J Respir Crit Care Med. 1995 May;151(5):1377–1382. doi: 10.1164/ajrccm.151.5.7735588. [DOI] [PubMed] [Google Scholar]
  24. Schwartz Joel, Schindler Christian, Zemp Elisabeth, Perruchoud André P., Zellweger Jean-Pierre, Wüthrich Brunello, Leuenberger Philippe, Ackermann-Liebrich Ursula. Predictors of methacholine responsiveness in a general population. Chest. 2002 Sep;122(3):812–820. doi: 10.1378/chest.122.3.812. [DOI] [PubMed] [Google Scholar]
  25. Sherman C. B. Health effects of cigarette smoking. Clin Chest Med. 1991 Dec;12(4):643–658. [PubMed] [Google Scholar]
  26. Tsunoda Masashi, Litonjua Augusto A., Kuniak Michael P., Weiss Scott T., Satoh Toshihiko, Guevarra Lucille, Tollerud David J. Serum cytokine levels, cigarette smoking and airway responsiveness among pregnant women. Int Arch Allergy Immunol. 2003 Feb;130(2):158–164. doi: 10.1159/000069008. [DOI] [PubMed] [Google Scholar]
  27. Weiss S. T., Segal M. R., Sparrow D., Wager C. Relation of FEV1 and peripheral blood leukocyte count to total mortality. The Normative Aging Study. Am J Epidemiol. 1995 Sep 1;142(5):493–503. doi: 10.1093/oxfordjournals.aje.a117665. [DOI] [PubMed] [Google Scholar]
  28. Welle I., Bakke P. S., Eide G. E., Fagerhol M. K., Omenaas E., Gulsvik A. Increased circulating levels of alpha1-antitrypsin and calprotectin are associated with reduced gas diffusion in the lungs. Eur Respir J. 2001 Jun;17(6):1105–1111. doi: 10.1183/09031936.01.00067501. [DOI] [PubMed] [Google Scholar]
  29. Zee Robert Y. L., Ridker Paul M. Polymorphism in the human C-reactive protein (CRP) gene, plasma concentrations of CRP, and the risk of future arterial thrombosis. Atherosclerosis. 2002 May;162(1):217–219. doi: 10.1016/s0021-9150(01)00703-1. [DOI] [PubMed] [Google Scholar]
  30. Zureik M., Benetos A., Neukirch C., Courbon D., Bean K., Thomas F., Ducimetière P. Reduced pulmonary function is associated with central arterial stiffness in men. Am J Respir Crit Care Med. 2001 Dec 15;164(12):2181–2185. doi: 10.1164/ajrccm.164.12.2107137. [DOI] [PubMed] [Google Scholar]
  31. Zureik M., Kauffmann F., Touboul P. J., Courbon D., Ducimetière P. Association between peak expiratory flow and the development of carotid atherosclerotic plaques. Arch Intern Med. 2001 Jul 9;161(13):1669–1676. doi: 10.1001/archinte.161.13.1669. [DOI] [PubMed] [Google Scholar]
  32. ten Hacken N. H., Oosterhoff Y., Kauffman H. F., Guevarra L., Satoh T., Tollerud D. J., Postma D. S. Elevated serum interferon-gamma in atopic asthma correlates with increased airways responsiveness and circadian peak expiratory flow variation. Eur Respir J. 1998 Feb;11(2):312–316. doi: 10.1183/09031936.98.11020312. [DOI] [PubMed] [Google Scholar]

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