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. 2003 Dec;58(12):1066–1070. doi: 10.1136/thorax.58.12.1066

Idiopathic chronic cough: association with organ specific autoimmune disease and bronchoalveolar lymphocytosis

S Birring 1, C Brightling 1, F Symon 1, S Barlow 1, A Wardlaw 1, I Pavord 1
PMCID: PMC1746533  PMID: 14645977

Abstract

Background: We have recently reported a strong association between organ specific autoimmune disease and idiopathic chronic cough and have suggested that cough may be caused by airway inflammation secondary to aberrant homing of activated lymphocytes to the lung. An immunopathological study was undertaken to test the hypothesis that idiopathic chronic cough is associated with lymphocytic airway inflammation.

Methods: Bronchoscopy, bronchial biopsies, bronchoalveolar lavage (BAL), and peripheral blood and BAL flow cytometry were performed in 19 patients with idiopathic chronic cough, 14 with explained chronic cough, and 11 normal subjects.

Results: Organ specific autoimmune disease or positive autoantibodies were present in eight of the 19 patients with idiopathic cough, in one of the 14 patients with explained cough, and in one of the 11 normal subjects. Median BAL fluid differential lymphyocyte counts were significantly higher in patients with idiopathic cough (10.0%) than in normal subjects (6.3%, 95% confidence interval of difference 1.5 to 11.9, p = 0.01) or patients with explained cough (5.2%, 95% CI of difference 2.0 to 10.4, p = 0.001). There were no differences in bronchial biopsy T lymphocyte counts between the groups. The mean (SE) proportion of CD3+ peripheral blood mononuclear cells expressing CD4 was significantly higher in normal subjects than in patients with idiopathic cough (69 (3)% v 58 (3)%, mean difference 11%, 95% CI of difference 2 to 20, p<0.02) but not than those with explained chronic cough (63 (2)%). There were no differences in BAL T lymphocyte phenotype between groups.

Conclusion: BAL fluid lymphocytosis occurs in some patients with idiopathic chronic cough. The association of idiopathic chronic cough with organ specific autoimmune disease raises the possibility that this might be caused by lymphocyte homing from the primary site of autoimmune inflammation or the result of an autoimmune process in the lung.

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Selected References

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  1. Baxter Alan G., Smyth Mark J. The role of NK cells in autoimmune disease. Autoimmunity. 2002 Feb;35(1):1–14. doi: 10.1080/08916930290005864. [DOI] [PubMed] [Google Scholar]
  2. Birring S. S., Morgan A. J., Prudon B., McKeever T. M., Lewis S. A., Falconer Smith J. F., Robinson R. J., Britton J. R., Pavord I. D. Respiratory symptoms in patients with treated hypothyroidism and inflammatory bowel disease. Thorax. 2003 Jun;58(6):533–536. doi: 10.1136/thorax.58.6.533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Birring S. S., Prudon B., Carr A. J., Singh S. J., Morgan M. D. L., Pavord I. D. Development of a symptom specific health status measure for patients with chronic cough: Leicester Cough Questionnaire (LCQ). Thorax. 2003 Apr;58(4):339–343. doi: 10.1136/thorax.58.4.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Birring Surinder S., Brightling Christopher E., Bradding Peter, Entwisle James J., Vara Dhiraj D., Grigg Jonathan, Wardlaw Andrew J., Pavord Ian D. Clinical, radiologic, and induced sputum features of chronic obstructive pulmonary disease in nonsmokers: a descriptive study. Am J Respir Crit Care Med. 2002 Oct 15;166(8):1078–1083. doi: 10.1164/rccm.200203-245oc. [DOI] [PubMed] [Google Scholar]
  5. Boulet L. P., Milot J., Boutet M., St Georges F., Laviolette M. Airway inflammation in nonasthmatic subjects with chronic cough. Am J Respir Crit Care Med. 1994 Feb;149(2 Pt 1):482–489. doi: 10.1164/ajrccm.149.2.8306050. [DOI] [PubMed] [Google Scholar]
  6. Brightling C. E., Symon F. A., Birring S. S., Wardlaw A. J., Robinson R., Pavord I. D. A case of cough, lymphocytic bronchoalveolitis and coeliac disease with improvement following a gluten free diet. Thorax. 2002 Jan;57(1):91–92. doi: 10.1136/thorax.57.1.91. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brightling C. E., Ward R., Goh K. L., Wardlaw A. J., Pavord I. D. Eosinophilic bronchitis is an important cause of chronic cough. Am J Respir Crit Care Med. 1999 Aug;160(2):406–410. doi: 10.1164/ajrccm.160.2.9810100. [DOI] [PubMed] [Google Scholar]
  8. Brightling C. E., Ward R., Wardlaw A. J., Pavord I. D. Airway inflammation, airway responsiveness and cough before and after inhaled budesonide in patients with eosinophilic bronchitis. Eur Respir J. 2000 Apr;15(4):682–686. doi: 10.1034/j.1399-3003.2000.15d10.x. [DOI] [PubMed] [Google Scholar]
  9. Brightling Christopher E., Symon Fiona A., Birring Surinder S., Bradding Peter, Pavord Ian D., Wardlaw Andrew J. TH2 cytokine expression in bronchoalveolar lavage fluid T lymphocytes and bronchial submucosa is a feature of asthma and eosinophilic bronchitis. J Allergy Clin Immunol. 2002 Dec;110(6):899–905. doi: 10.1067/mai.2002.129698. [DOI] [PubMed] [Google Scholar]
  10. Britten K. M., Howarth P. H., Roche W. R. Immunohistochemistry on resin sections: a comparison of resin embedding techniques for small mucosal biopsies. Biotech Histochem. 1993 Sep;68(5):271–280. doi: 10.3109/10520299309105629. [DOI] [PubMed] [Google Scholar]
  11. Gabbay E., Tarala R., Will R., Carroll G., Adler B., Cameron D., Lake F. R. Interstitial lung disease in recent onset rheumatoid arthritis. Am J Respir Crit Care Med. 1997 Aug;156(2 Pt 1):528–535. doi: 10.1164/ajrccm.156.2.9609016. [DOI] [PubMed] [Google Scholar]
  12. Green Ruth H., Brightling Christopher E., McKenna Susan, Hargadon Beverley, Parker Debbie, Bradding Peter, Wardlaw Andrew J., Pavord Ian D. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet. 2002 Nov 30;360(9347):1715–1721. doi: 10.1016/S0140-6736(02)11679-5. [DOI] [PubMed] [Google Scholar]
  13. Inui N., Chida K., Suda T., Nakamura H. TH1/TH2 and TC1/TC2 profiles in peripheral blood and bronchoalveolar lavage fluid cells in pulmonary sarcoidosis. J Allergy Clin Immunol. 2001 Feb;107(2):337–344. doi: 10.1067/mai.2001.112273. [DOI] [PubMed] [Google Scholar]
  14. Irwin R. S., Madison J. M. The diagnosis and treatment of cough. N Engl J Med. 2000 Dec 7;343(23):1715–1721. doi: 10.1056/NEJM200012073432308. [DOI] [PubMed] [Google Scholar]
  15. Lee S. Y., Cho J. Y., Shim J. J., Kim H. K., Kang K. H., Yoo S. H., In K. H. Airway inflammation as an assessment of chronic nonproductive cough. Chest. 2001 Oct;120(4):1114–1120. doi: 10.1378/chest.120.4.1114. [DOI] [PubMed] [Google Scholar]
  16. Mackay I. R. Science, medicine, and the future: Tolerance and autoimmunity. BMJ. 2000 Jul 8;321(7253):93–96. doi: 10.1136/bmj.321.7253.93. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. McGarvey L. P., Forsythe P., Heaney L. G., MacMahon J., Ennis M. Bronchoalveolar lavage findings in patients with chronic nonproductive cough. Eur Respir J. 1999 Jan;13(1):59–65. doi: 10.1183/09031936.99.13105999. [DOI] [PubMed] [Google Scholar]
  18. McGarvey L. P., Heaney L. G., Lawson J. T., Johnston B. T., Scally C. M., Ennis M., Shepherd D. R., MacMahon J. Evaluation and outcome of patients with chronic non-productive cough using a comprehensive diagnostic protocol. Thorax. 1998 Sep;53(9):738–743. doi: 10.1136/thx.53.9.738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pavord I. D., Pizzichini M. M., Pizzichini E., Hargreave F. E. The use of induced sputum to investigate airway inflammation. Thorax. 1997 Jun;52(6):498–501. doi: 10.1136/thx.52.6.498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sharif Shaya, Arreaza Guillermo A., Zucker Peter, Delovitch Terry L. Regulatory natural killer T cells protect against spontaneous and recurrent type 1 diabetes. Ann N Y Acad Sci. 2002 Apr;958:77–88. doi: 10.1111/j.1749-6632.2002.tb02949.x. [DOI] [PubMed] [Google Scholar]
  21. Tiroke A. H., Bewig B., Haverich A. Bronchoalveolar lavage in lung transplantation. State of the art. Clin Transplant. 1999 Apr;13(2):131–157. doi: 10.1034/j.1399-0012.1999.130201.x. [DOI] [PubMed] [Google Scholar]
  22. Wahlström J., Berlin M., Lundgren R., Olerup O., Wigzell H., Eklund A., Grunewald J. Lung and blood T-cell receptor repertoire in extrinsic allergic alveolitis. Eur Respir J. 1997 Apr;10(4):772–779. [PubMed] [Google Scholar]
  23. Wallaert B., Colombel J. F., Tonnel A. B., Bonniere P., Cortot A., Paris J. C., Voisin C. Evidence of lymphocyte alveolitis in Crohn's disease. Chest. 1985 Mar;87(3):363–367. doi: 10.1378/chest.87.3.363. [DOI] [PubMed] [Google Scholar]
  24. Wallaert B., Prin L., Hatron P. Y., Ramon P., Tonnel A. B., Voisin C. Lymphocyte subpopulations in bronchoalveolar lavage in Sjögren's syndrome. Evidence for an expansion of cytotoxic/suppressor subset in patients with alveolar neutrophilia. Chest. 1987 Dec;92(6):1025–1031. doi: 10.1378/chest.92.6.1025. [DOI] [PubMed] [Google Scholar]
  25. Wright J. L., Cagle P., Churg A., Colby T. V., Myers J. Diseases of the small airways. Am Rev Respir Dis. 1992 Jul;146(1):240–262. doi: 10.1164/ajrccm/146.1.240. [DOI] [PubMed] [Google Scholar]

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