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Journal of Clinical Immunology

, Volume 34, Issue 1, pp 68–75 | Cite as

Activity, Severity and Impact of Respiratory Disease in Primary Antibody Deficiency Syndromes

  • John R. Hurst
  • Sarita Workman
  • Davinder S. Garcha
  • Suranjith L. Seneviratne
  • Jamanda A. Haddock
  • Bodo Grimbacher
Original Research

Abstract

Purpose

Some patients with primary antibody deficiency (PAD) syndromes develop bronchiectasis. In immunocompetent patients with bronchiectasis, key clinico-pathophysiological relationships exist between exacerbation frequency, lung function, health-status, infection and inflammation. It is not known whether such relationships are present in PAD. It is also not known how local and systemic inflammation in PAD compares with that in immunocompetent (non-PAD) bronchiectasis patients.

Method

We assessed symptoms, exacerbation frequency, health-status, lung function, CT, airway and systemic inflammation and infection in 33 PAD patients and 20 immunocompetent controls with bronchiectasis.

Results

Despite less severe airflow obstruction, PAD patients had similar health-status impairment and greater airway (sputum log10 IL-6 2.71 vs. 1.81 pg/ml, p = 0.001) and greater systemic inflammation than immunocompetent bronchiectasis controls (serum log10 CRP 0.77 vs. 0.36 mg/l, p = 0.001).

In PAD, cross-sectional markers of disease severity (CT and lung function) did not relate to inflammatory markers of disease activity, however there was a relationship between FEV1 decline rate and systemic inflammation (IL-6; r = 0.42, p = 0.036) and the magnitude of the systemic inflammatory response was related to that in the airway. Correlation between generic SF36 and respiratory SGRQ questionnaires (r = −0.79, p < 0.001) suggests that much health-status impairment in PAD relates to respiratory involvement. Health-status was associated with dyspnoea (rho = 0.77, p < 0.001), respiratory infection frequency (rho = 0.48, p = 0.016), lung function (FEV1: r = −0.60, p = 0.001) and rate of lung function decline (r = 0.41, p = 0.047).

Conclusion

The major findings of this analysis are that in patients with PAD, cross-sectional markers of disease severity such as lung function and CT extent of disease do not reflect disease activity as assessed by airway and systemic inflammation. In addition, there is a relationship between the rate of progression of lung disease and the severity of the systemic inflammatory response which itself is related to that in the airway. Much of the quality of life impact in PAD relates to respiratory involvement, specifically the severity of airflow obstruction, respiratory exacerbation frequency and dyspnoea. Finally, patients with PAD had greater airway and systemic inflammation than a control population with non-PAD bronchiectasis which may suggest a dysregulated airway immune response.

Keywords

CVID XLA immunodeficiency bronchiectasis respiratory 

Notes

Acknowledgements

We wish to thank the PAD and control bronchiectasis patients who have given freely of their time to support our research. We acknowledge contributions from the Royal Free Hospital Lung Function Unit, and Departments of Clinical Chemistry, Haematology and Microbiology in monitoring our patients and providing assays on their clinical samples. Finally, we thank Mr Raymond Sapsford, Laboratory Manager in the Centre for Respiratory Medicine, UCL, for processing the blood and sputum specimens for storage.

No specific funding was received for the study.

Conflicts of Interest

The Authors declare that they have no conflicts of interest to declare.

References

  1. 1.
    Pasteur MC, Bilton D, Hill AT. British Thoracic Society Bronchiectasis non-CF Guideline Group. British Thoracic Society guideline for non-CF bronchiectasis. Thorax. 2010;65 Suppl 1:i1–i58.PubMedCrossRefGoogle Scholar
  2. 2.
    Buckley RH. Pulmonary complications of primary immunodeficiencies. Paediatr Respir Rev. 2004;5(Suppl A):225–33.CrossRefGoogle Scholar
  3. 3.
    Eijkhout HW, van Der Meer JW, Kallenberg CG, Weening RS, van Dissel JT, Sanders LA, et al. The effect of two different dosages of intravenous immunoglobulin on the incidence of recurrent infections in patients with primary hypogammaglobulinemia. A randomized, double-blind, multicenter crossover trial. Ann Intern Med. 2001;135:165–74.PubMedCrossRefGoogle Scholar
  4. 4.
    Oksenhendler E, Gérard L, Fieschi C, Malphettes M, Mouillot G, Jaussaud R, et al. Infections in 252 patients with common variable immunodeficiency. Clin Infect Dis. 2008;46:1547–54.PubMedCrossRefGoogle Scholar
  5. 5.
    Howard V, Greene JM, Pahwa S, Winkelstein JA, Boyle JM, Kocak M, et al. The health status and quality of life of adults with X-linked agammaglobulinemia. Clin Immunol. 2006;118:201–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Litzman J, Freiberger T, Grimbacher B, Gathmann B, Salzer U, Pavlík T, et al. Mannose-binding lectin gene polymorphic variants predispose to the development of bronchopulmonary complications but have no influence on other clinical and laboratory symptoms or signs of common variable immunodeficiency. Clin Exp Immunol. 2008;153:324–30.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Aghamohammadi A, Allahverdi A, Abolhassani H, Moazzami K, Alizadeh H, Gharagozlou M, et al. Comparison of pulmonary diseases in common variable immunodeficiency and X-linked agammaglobulinaemia. Respirology. 2010;15:289–95.PubMedCrossRefGoogle Scholar
  8. 8.
    Resnick ES, Moshier EL, Godbold JH, Cunningham-Rundles C. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood. 2012;119:1650–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Cole PJ. Inflammation: a two-edged sword–the model of bronchiectasis. Eur J Respir Dis Suppl. 1986;147:6–15.PubMedGoogle Scholar
  10. 10.
    Angrill J, Agustí C, De Celis R, Filella X, Rañó A, Elena M, et al. Bronchial inflammation and colonization in patients with clinically stable bronchiectasis. Am J Respir Crit Care Med. 2001;164:1628–32.PubMedCrossRefGoogle Scholar
  11. 11.
    Martínez-García MA, Soler-Cataluña JJ, Perpiñá-Tordera M, Román-Sánchez P, Soriano J. Factors associated with lung function decline in adult patients with stable non-cystic fibrosis bronchiectasis. Chest. 2007;132:1565–72.PubMedCrossRefGoogle Scholar
  12. 12.
    Wilson CB, Jones PW, O’Leary CJ, Cole PJ, Wilson R. Validation of the St. George’s respiratory questionnaire in bronchiectasis. Am J Respir Crit Care Med. 1997;156:536–41.PubMedCrossRefGoogle Scholar
  13. 13.
    Martínez-García MA, Perpiñá-Tordera M, Román-Sánchez P, Soler-Cataluña JJ. Quality-of-life determinants in patients with clinically stable bronchiectasis. Chest. 2005;128:739–45.PubMedCrossRefGoogle Scholar
  14. 14.
    Warley AR, Finnegan OC, Nicholson EM, Laszlo G. Grading of dyspnoea and walking speed in cardiac disease and in chronic airflow obstruction. Br J Dis Chest. 1987;81:349–55.PubMedCrossRefGoogle Scholar
  15. 15.
    Jenkinson C, Coulter A, Wright L. Short form 36 (SF36) health survey questionnaire: normative data for adults of working age. BMJ. 1993;306:1437–40.PubMedCrossRefGoogle Scholar
  16. 16.
    Bhalla M, Turcios N, Aponte V, Jenkins M, Leitman BS, McCauley DI, et al. Cystic fibrosis: scoring system with thin-section CT. Radiology. 1991;179:783–8.PubMedGoogle Scholar
  17. 17.
  18. 18.
    Garcha DS, Thurston SJ, Patel AR, Mackay AJ, Goldring JJ, Donaldson GC, et al. Changes in prevalence and load of airway bacteria using quantitative PCR in stable and exacerbated COPD. Thorax. 2012;67:1075–80.PubMedCrossRefGoogle Scholar
  19. 19.
    Nolan T, Hands RE, Ogunkolade W, Bustin SA. SPUD: a quantitative PCR assay for the detection of inhibitors in nucleic acid preparations. Anal Biochem. 2006;351:308–10.PubMedCrossRefGoogle Scholar
  20. 20.
    Gregersen S, Aaløkken TM, Mynarek G, Kongerud J, Aukrust P, Frøland SS, et al. High resolution computed tomography and pulmonary function in common variable immunodeficiency. Respir Med. 2009;103:873–80.PubMedCrossRefGoogle Scholar
  21. 21.
    Lacasse Y, Goldstein R, Lasserson TJ, Martin S. Pulmonary rehabilitation for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2006;4, CD003793.PubMedGoogle Scholar
  22. 22.
    Chen Y, Stirling RG, Paul E, Hore-Lacy F, Thompson BR, Douglass JA. Longitudinal decline in lung function in patients with primary immunoglobulin deficiencies. J Allergy Clin Immunol. 2011;127:1414–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Donaldson GC, Seemungal TA, Bhowmik A, Wedzicha JA. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax. 2002;57:847–52.PubMedCrossRefGoogle Scholar
  24. 24.
    Thickett KM, Kumararatne DS, Banerjee AK, Dudley R, Stableforth DE. Common variable immune deficiency: respiratory manifestations, pulmonary function and high-resolution CT scan findings. QJM. 2002;95:655–62.PubMedCrossRefGoogle Scholar
  25. 25.
    Roberts HR, Wells AU, Milne DG, Rubens MB, Kolbe J, Cole PJ, et al. Airflow obstruction in bronchiectasis: correlation between computed tomography features and pulmonary function tests. Thorax. 2000;55:198–204.PubMedCrossRefGoogle Scholar
  26. 26.
    Pereira AC, Kokron CM, Romagnolo BM, Yagi CS, Saldiva PH, Lorenzi Filho G, et al. Analysis of the sputum and inflammatory alterations of the airways in patients with common variable immunodeficiency and bronchiectasis. Clinics (Sao Paulo). 2009;64:1155–60.CrossRefGoogle Scholar
  27. 27.
    Loebinger MR, Bilton D, Wilson R. Upper airway 2: bronchiectasis, cystic fibrosis and sinusitis. Thorax. 2009;64:1096–101.PubMedCrossRefGoogle Scholar
  28. 28.
    Rose MA, Schubert R, Schmitt-Grohe S, Reichenbach J, Zielen S. Immunoglobulins and inflammatory cytokines in nasal secretions in humoral immunodeficiencies. Laryngoscope. 2006;116:239–44.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • John R. Hurst
    • 1
  • Sarita Workman
    • 2
  • Davinder S. Garcha
    • 1
  • Suranjith L. Seneviratne
    • 2
    • 3
  • Jamanda A. Haddock
    • 4
  • Bodo Grimbacher
    • 2
    • 3
  1. 1.UCL Respiratory MedicineUniversity College LondonLondonUK
  2. 2.Department of Clinical ImmunologyRoyal Free London NHS Foundation TrustLondonUK
  3. 3.UCL Centre for ImmunodeficiencyUniversity College LondonLondonUK
  4. 4.Department of RadiologyRoyal Free London NHS Foundation TrustLondonUK

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