Combined diffusing capacity for nitric oxide and carbon monoxide as predictor of bronchiolitis obliterans syndrome following lung transplantation

Anna Winkler,Nikolaus Kneidinger,Rudolf Hatz,Rudolf A Jörres,Holger Dressel,Jürgen Behr,Kathrin Kahnert,Claus Neurohr,Thomas Radtke

doi:10.1186/s12931-018-0881-1

Abstract

BackgroundThere is a need for non-invasive parameters that are sensitive to the development of the bronchiolitis obliterans syndrome (BOS) in lung transplantation (LTx) patients. We studied whether the pulmonary diffusing capacity for inhaled nitric oxide is capable of detecting BOS stages.MethodsSixty-one LTx patients were included into this cross-sectional study (19/29/7/3/3 in BOS stages 0/0-p/1/2/3). For analysis stages 0/0-p versus 1/2/3 (“BOS binary-early”), and stages 0/0-p/1 versus 2/3 (“BOS binary-late”) were summarized. Measurements of the combined diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) were compared with spirometry and bodyplethysmography, and their relative importance was evaluated by discriminant analysis.ResultsRegarding the recognition of “BOS binary-early”, among spirometric parameters forced expiratory volume in 1 s (FEV1) was best, among bodyplethysmographic parameters airway resistance, and among diffusing parameters DLNO. Regarding “BOS binary-late”, DLNO was inferior to bodyplethysmographic parameters.ConclusionAlthough the study comprised only measurements at a single time point and no follow-up, DLNO outperformed FEV1, the time course of which is used in detecting BOS. Together with its pathophysiological plausibility, this result suggests that the measurement of DLNO, possibly over time, could be an easily applicable tool for the monitoring of LTx patients and should be evaluated in larger studies.

Highlights

There is a need for non-invasive parameters that are sensitive to the development of the bronchiolitis obliterans syndrome (BOS) in lung transplantation (LTx) patients
Cameli et al [12] investigated the role of exhaled NO and carbon monoxide as markers of pulmonary inflammation associated with acute graft rejection and lung infection in Lung transplantation (LTx) patients and found higher values of FeNO and in particular a higher alveolar concentration of nitric oxide (CalvNO) in LTx patients with BOS compared to non-BOS patients [12]
A patient was enrolled in the cohort if he or she fulfilled the following inclusion criteria: (a) the patient was the recipient of a LTx performed at the study center, and (b) the patient expressed his or her willingness to participate in individually planned follow-up assessments; and if the patient did not fulfill any of the following exclusion criteria: (a) acute infections, (b) high levels of physical exertion or food intake prior to the measurements, (c) nicotine abuse on the day of measurements, or (d) physical impairment resulting in an inability to perform two valid and reproducible Diffusing capacity for nitric oxide (DLNO)-Carbon monoxide (DLCO) measurements [13]

Summary

Introduction

There is a need for non-invasive parameters that are sensitive to the development of the bronchiolitis obliterans syndrome (BOS) in lung transplantation (LTx) patients. Cameli et al [12] investigated the role of exhaled NO (eNO) and carbon monoxide (eCO) as markers of pulmonary inflammation associated with acute graft rejection and lung infection in LTx patients and found higher values of FeNO and in particular a higher alveolar concentration of nitric oxide (CalvNO) in LTx patients with BOS compared to non-BOS patients [12] This indicates that alveolar markers might be suitable for detecting BOS, as airway inflammation and remodelling of the small airways in LTx patients with BOS could be associated with alveolar changes such as elevated levels of peripheral eNO and CalvNO [12]. This combination has been evaluated in various lung diseases but is not yet part of clinical routine [13, 14]

Methods

Results

Conclusion