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Irreversible airway obstruction assessed by high-resolution computed tomography (HRCT), exhaled nitric oxide (FENO), and biological markers in induced sputum in patients with asthma

Erfassung einer irreversiblen Atemwegsobstruktion durch hochauflösende Computertomographie (HRCT), ausgeatmetes NO (FENO) und biologische Marker im induzierten Sputum bei Patienten mit Asthma bronchiale

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Summary

Objective

The objective of this study was to explore the significance of assessing irreversible airway obstruction (IAO) in asthma patients by high-resolution computed tomography (HRCT), biological markers in induced sputum, and exhaled nitric oxide (FENO).

Methods

The study was conducted in 34 patients with IAO, 46 patients with reversible airway obstruction (RAO), 40 patients who did not have airway obstruction (NAO), and 40 healthy subjects serving as controls. These patients received a step therapy for at least 3 months based on the guidelines for the prevention and treatment of asthma. After achieving complete or partial control of asthma, HRCT, lung function, FENO, and chemokine levels in induced sputum were measured.

Results

The airway wall area (WA; %) correlated with forced expiratory volume-1 (FEV-1(L); r = −0.67, p < 0.0001), and significant differences in bronchial wall thickening (BWT) of the LEVEL E generation airways were observed between the asthma and control groups (p < 0.01). FENO levels correlated with FEV-1 (%) in the IAO group (r = 0.49, p = 0.01). The levels of matrix metalloproteases-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in asthma patients with IAO, RAO, and NAO were significantly higher than those in the controls (p < 0.05). The level of neutrophilia in the sputum from the IAO group was higher than that from the RAO, NAO and control groups.

Conclusion

Asthma patients with IAO have an increased BWT. Airway measurements with HRCT scans appear to be valuable in the evaluation of airway remodeling in asthma patients with IAO.

Zusammenfassung

Ziel

der Studie war es, die Bedeutung der Erfassung einer irreversiblen Atemwegsobstruktion (IAO) bei Pati-enten mit Asthma bronchiale durch eine HRCT, durch biologische Marker im induzierten Sputum und durch Messung des ausgeatmeten NO zu evaluieren.

Methodik

Die Studie wurde an 34 Patienten mit IAO, 46 Patienten mit reversibler Atemwegsobstruktion (RAO), 40 Patienten ohne Atemwegsobstruktion (NAO) und 40 gesunden Kontrollpersonen durchgeführt. Die Patienten erhielten zumindest 3 Monate lang eine Stu-f­entherapie entsprechend den Leitlinien zur Prävention und Behandlung von Asthma bronchiale. Nach Erreichen einer kompletten oder partiellen Kontrolle des Asthmas wurde eine HRCT, eine Lungenfunktionsprüfung, sowie eine Messung der FENO und von Chemokinen im induzierten Sputum durchgeführt.

Ergebnisse

Die Atemwegswandfläche (WA, %) kor­relierte mit den FEV-1 Werten (r = −0,67, p < 0,0001). Weiters wurden signifikante Unterschiede zwischen der Kontrolle und den Asthmapatienten in den Verdickungen der Bronchialwand (BWT) der LEVEL E Generation Atemwege beobachtet (p < 0,001). In der Gruppe der Patienten mit IAO korrelierten die FENO Werte mit den FEV-1 (%) Werten (r = 0,49, p = 0,01). Die Werte der Matrix Metalloprotease-9 (MMP-9) und des Gewebsinhibitors der Matrix Metalloproteinase-1 (TIMP-1) waren bei allen Patienten signifikant höher als bei den Kon­trollen (p < 0,05). Der Grad der Neutrophilie im Sputum war bei den Patienten mit IAO höher als bei den Patienten mit RAO, mit NAO beziehungsweise als bei den Kontrollpersonen.

Schlussfolgerungen

Asthmapatienten mit IAO haben eine erhöhte BWT. Die Messung der Atemwege mittels HRCT scheint bei der Evaluation des Remodelings der Atemwege von Asthmapatienten mit IAO wertvoll zu sein.

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References

  1. Vonk J, Jongepier H, Panhuysen C, Schouten J, Bleecker E, Postma D. Risk factors associated with the presence of irreversible airflow limitation and reduced transfer coefficient in patients with asthma after 26 years of follow up. Thorax. 2003;58(4):322–7.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  2. Bateman ED, Boushey HA, Bousquet J, Busse WW, Clark TJH, Pauwels RA, et al. Can guideline-defined asthma control be achieved? The gaining optimal asthma control study. Am J Respir Crit Care Med. 2004;170(8):836–44. PubMed PMID: WOS:000224404800005.

    Article  PubMed  Google Scholar 

  3. Alving K, Weitzberg E, Lundberg JM. Increased amount of nitric oxide in exhaled air of asthmatics. Eur Respir J. 1993;6(9):1368–70. PubMed PMID: MEDLINE:7507065.

    PubMed  CAS  Google Scholar 

  4. Kharitonov SA, Yates D, Robbins RA, Logan-Sinclair R, Shinebourne EA, Barnes PJ. Increased nitric oxide in exhaled air of asthmatic patients. Lancet. 1994;343(8890):133–5. PubMed PMID: MEDLINE:7904001.

    Article  PubMed  CAS  Google Scholar 

  5. Boulet LP, Belanger M, Carrier G. Airway responsiveness and bronchial-wall thickness in asthma with or without fixed air-flow obstruction. Am J Respir Crit Care Med. 1995;152(3):865–71. PubMed PMID: WOS:A1995RT88700003.

    Article  PubMed  CAS  Google Scholar 

  6. Mattos W, Lim S, Russell R, Jatakanon A, Chung KF, Barnes PJ. Matrix metalloproteinase-9 expression in asthma: effect of asthma severity, allergen challenge, and inhaled corticosteroids. Chest. 2002;122(5):1543–52.

    Article  PubMed  CAS  Google Scholar 

  7. Vignola AM, Riccobono L, Mirabella A, Profita M, Chanez P, Bellia V, et al. Sputum metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio correlates with airflow obstruction in asthma and chronic bronchitis. Am J Respir Crit Care Med. 1998;158(6):1945–50.

    Article  PubMed  CAS  Google Scholar 

  8. Elkington P, O’Kane C, Friedland J. The paradox of matrix metalloproteinases in infectious disease. Clin Exp Immunol. 2005;142(1):12–20.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  9. Group ES. The ENFUMOSA cross-sectional European multicentre study of the clinical phenotype of chronic severe asthma. Eur Respir J. 2003;22(3):470–7.

  10. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, November 1986. Am Rev Respir Dis. 1987;136(1):225–44. PubMed PMID: MEDLINE:3605835.

  11. Recommendations for standardized procedures for the on-line and off-line measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide in adults and children-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. Am J Resp Crit Care. 1999;160(6):2104–17. PubMed PMID: MEDLINE:10588636.

  12. King GG, Muller NL, Whittall KP, Xiang QS, Pare PD. An analysis algorithm for measuring airway lumen and wall areas from high-resolution computed tomographic data. Am J Respir Crit Care Med. 2000;161(2):574–80. PubMed PMID: WOS:000085376000038.

    Article  PubMed  CAS  Google Scholar 

  13. Pavord I, Pizzichini M, Pizzichini E, Hargreave F. The use of induced sputum to investigate airway inflammation. Thorax. 1997;52(6):498–501.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  14. Paganin F, Vignola AM, Senéterre E, Bruel JM, Chanez P, Bousquet J. Heterogeneity of airways obstruction in asthmatic patients using high-resolution computed tomography. Chest. 1995;107(3 Suppl.):145S–6S.

    Article  PubMed  CAS  Google Scholar 

  15. Saglani S, Papaioannou G, Khoo L, Ujita M, Jeffery P, Owens C, et al. Can HRCT be used as a marker of airway remodelling in children with difficult asthma. Respir Res. 2006;7:46.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  16. Gupta S, Siddiqui S, Haldar P, Raj JV, Entwisle JJ, Wardlaw AJ, et al. Qualitative analysis of high-resolution CT scans in severe asthma. Chest. 2009;136(6):1521–8. PubMed PMID: WOS:000272742900014.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Gono H, Fujimoto K, Kawakami S, Kubo K. Evaluation of airway wall thickness and air trapping by HRCT in asymptomatic asthma. Eur Respir J. 2003;22(6):965–71. PubMed PMID: WOS:000187009900020.

    Article  PubMed  CAS  Google Scholar 

  18. Little S, Sproule M, Cowan M, Macleod K, Robertson M, Love J, et al. High resolution computed tomographic assessment of airway wall thickness in chronic asthma: reproducibility and relationship with lung function and severity. Thorax. 2002;57(3):247–53.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  19. de González AB, Darby S. Risk of cancer from diagnostic X-rays: estimates for the UK and 14 other countries. Lancet. 2004;363(9406):345–51.

  20. Vignola A, Paganin F, Capieu L, Scichilone N, Bellia M, Maakel L, et al. Airway remodelling assessed by sputum and high-resolution computed tomography in asthma and COPD. Eur Respir J. 2004;24(6):910–7.

    Article  PubMed  CAS  Google Scholar 

  21. Hayakawa T. Tissue inhibitors of metalloproteinases and their cell growth-promoting activity. Cell Struct Funct. 1994;19(3):109.

    Article  PubMed  CAS  Google Scholar 

  22. Roche WR, Williams JH, Beasley R, Holgate S. Subepithelial fibrosis in the bronchi of asthmatics. Lancet. 1989;1(8637):520–4.

    Article  PubMed  CAS  Google Scholar 

  23. Riccobono L, Mirabella A, Bonanno A, Vignola AM, Profita M, Paterno A, et al. MMP-9/TIMP-1 ratio and the resolution of airway inflammation in asthma. Am J Respir Crit Care Med. 1999;159(3):A325-A 325. PubMed PMID: WOS:000082237101767.

  24. Arron JR, Choy DF, Audusseau S, Hamid Q, Harris JM, Grp BS. Disconnect between sputum neutrophilia and indices of mucosal inflammation in severe asthma. J Allergy Clin Immunol. 2012;129(2):AB61-AB 61. PubMed PMID: WOS:000301133400235.

  25. Smith AD, Cowan JO, Filsell S, McLachlan C, Monti-Sheehan G, Jackson P, et al. Diagnosing asthma: comparisons between exhaled nitric oxide measurements and conventional tests. Am J Resp Crit Care Med. 2004;169(4):473–8.

    Article  PubMed  Google Scholar 

  26. Deykin A, Massaro AF, Drazen JM, Israel E. Exhaled nitric oxide as a diagnostic test for asthma: online versus offline techniques and effect of flow rate. Am J Resp Crit Care. 2002;165(12):1597–601.

    Article  Google Scholar 

  27. Dupont LJ, Demedts MG, Verleden GM. Prospective evaluation of the validity of exhaled nitric oxide for the diagnosis of asthma. Chest. 2003;123(3):751–6.

    Article  PubMed  CAS  Google Scholar 

  28. Woo S-I, Lee J-H, Kim H, Kang J-W, Sun Y-H, Hahn Y-S. Utility of fractional exhaled nitric oxide (FENO) measurements in diagnosing asthma. Respir Med. 2012;106(8):1103–9. PubMed PMID: WOS:000306381300004.

    Article  PubMed  Google Scholar 

  29. Delgado-Corcoran C, Kissoon N, Murphy SP, Duckworth LJ. Exhaled nitric oxide reflects asthma severity and asthma control. Pediatric Crit Care Med. 2004;5(1):48–52.

    Article  Google Scholar 

  30. Moore WC, Peters SP. Severe asthma: an overview. J Allergy Clin Immun. 2006;117(3):487–94.

    Article  PubMed  Google Scholar 

  31. Bernstein JA, Davis B, Alvarez-Puebla MJ, Levin L, Olaguibel JM. Is exhaled nitric oxide a useful adjunctive test for assessing asthma? J Asthma. 2009;46(9):955–60.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Zhang Lanlan and Jin Gang for their assistance in preparing and revising this manuscript, Cao Zhi Gang for his assistance with data analysis, and Zhang Lanlan and Cui Yali for data collection and figure preparation.

Funding

The authors received no specific funding for this study.

Conflict of interest

The authors declare that there are no actual or potential conflicts of interest in relation to this article.

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Shen Baozhong and Liu Chuntao contributed equally to this article.

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Zhang, L., Gang, J., Zhigang, C. et al. Irreversible airway obstruction assessed by high-resolution computed tomography (HRCT), exhaled nitric oxide (FENO), and biological markers in induced sputum in patients with asthma. Wien Klin Wochenschr 126, 515–523 (2014). https://doi.org/10.1007/s00508-014-0568-7

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