Abstract
Purpose
Bronchiolitis obliterans (BO) is an inadequately researched disease in terms of lung function as well as inflammatory profile. The short-term variation of these parameters has not been investigated. Therefore, the objective of this study was the investigation of lung function, sputum cells and cytokine profiles in BO at two visits within of four to six weeks.
Methods
Twenty patients with BO (median age = 14.6, range 8.3–24.3) performed lung function tests, airway reversibility testing and induction of sputum within four to six weeks. The cell composition in the sputum was analysed and cytokine levels of IL-1ß, IL-6 and IL-8 were determined by cytometric bead array analysis. The short-term variation was then statistically quantified and compared to that of twenty-two healthy controls. Furthermore, we compared data on short-term variation of lung function and airway inflammation with a previous investigation in these patients 10–15 months earlier.
Results
Patients with BO showed minimal variation of lung function (VCmax, FVC, FEV1, FEV1/VC, MEF25 and RV/TLC) and the inflammatory cell profile. The lung function data were significantly lower for FVC, FEV1, the Tiffeneau index and MEF25 compared to the control group, whereas RV/TLC was significantly increased. Analysis of the BO sputum cells showed a consistent neutrophil inflammation. The levels of inflammatory cytokines IL-1ß, IL-6 and IL-8 had a great variability.
Conclusions
The short-term variability of sputum neutrophilia and lung function is low in BO patients. This finding should be considered to identify successful treatment in the individual patient and could be used as endpoints for future BO-related studies.
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Abbreviations
- BO:
-
Bronchiolitis obliterans
- CBA:
-
Cytometric bead array
- VC:
-
Vital capacity
- FVC:
-
Forced vital capacity
- FEV1:
-
Forced expiratory volume in 1 second
- FEV1/VC:
-
Tiffeneau index
- MEF25:
-
25 % of the maximal expiratory flow
- RV:
-
Residual volume
- RV/TLC:
-
Residual volume expressed as percent of TLC
- IL-1ß:
-
Interleukin-1 beta
- IL-6:
-
Interleukin-6
- IL-8:
-
Interleukin-8
- HR-CT:
-
High-resolution Computer tomogram
- BAL:
-
Bronchoalveolar lavage
- hPIVs:
-
Human Parainfluenza Viruses
- NaCl:
-
Sodium Chloride
- DTT:
-
Dithiothreitol
- PBS:
-
Phosphate-buffered saline
- MAP:
-
Mitogen-activated protein
- mAb:
-
Anti-CD132
- PCR:
-
Polymerase chain reaction
- V1:
-
Visit 1
- V2:
-
Visit 2
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Acknowledgments
A grant from the Starke Lunge Foundation supported this study.
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The authors declare that they have no conflict of interest. No author has a financial relationship with a commercial entity with an interest in the subject of this manuscript.
Ethical Approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.
Informed Consent
Human guidelines of good clinical practice and the declaration of Helsinki (1964) and Edinburgh (2000) were followed in the conduct of the trial. The study was approved by the Ethics Committee of University Hospital Frankfurt am Main and registered at www.clinicaltrials.gov (NCT01633385). Informed consent was obtained from all individual participants included in the study. All the parents and all patients older than sixteen years of age provided written informed consent.
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Eckrich, J., Herrmann, E., Voss, S. et al. Short-Term Variation of Lung Function and Airway Inflammation in Children and Adolescents with Bronchiolitis Obliterans. Lung 194, 571–579 (2016). https://doi.org/10.1007/s00408-016-9907-y
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DOI: https://doi.org/10.1007/s00408-016-9907-y