Lungenfunktion, Lung Clearance Index und bronchiale Entzündung bei Kindern und Jugendlichen mit Bronchiolitis obliterans

Zusammenfassung

Einleitung Die Bronchiolitis obliterans (BO) ist eine sehr seltene, chronische Lungenerkrankung, die vereinzelt nach schweren Atemwegsinfektionen oder als Folge von Stammzell- und Lungentransplantation auftritt. Ziel der Arbeit war es, die Lungenfunktion und die bronchiale Entzündung bei BO-Patienten im Jugend- und Kindesalter zu untersuchen. Zudem sollte das Potenzial des LCI in der Diagnostik dieser Patienten untersucht werden.

Methoden Es wurden 16 BO-Patienten (Alter: Median 16,7; 9,6 – 25,3 Jahre) und 17 gesunde Probanden (Alter: Median 16,6; 7,6 – 25,0 Jahre) untersucht. Neben der Untersuchung der Lungenfunktion (FVC, FEV₁, MEF₂₅, RV und RV/TLC) mittels Bodyplethysmografie erfolgte eine Reversibilitätstestung nach Gabe von 400 µg Salbutamol. Die Bestimmung des LCI erfolgte mittels Multiple Breath Washout (MBW)-Methode. Zusätzlich wurde die Zellverteilung und das Zytokinprofil (IL-1ß, IL-6, IL-8, TNF-α) mittels Cytometric Bead Array (CBA) im induzierten Sputum analysiert.

Ergebnisse FVC, FEV₁ und MEF₂₅ der BO-Patienten waren signifikant niedriger, das RV und die RV/TLC jedoch signifikant erhöht im Vergleich zur Kontrollgruppe. Eine bronchiale Reversibilität zeigte sich bei 3 Patienten. Der LCI war bei den BO-Patienten gegenüber der Kontrollgruppe signifikant erhöht (Median 10,24 vs. 7,1) und korrelierte signifikant mit dem MEF₂₅ (p < 0,0001). Im induzierten Sputum fand sich eine signifikante Erhöhung der Gesamtzellzahl, der neutrophilen Granulozyten sowie von IL-6 und IL-8 (p < 0.01).

Schlussfolgerung Die Lungenfunktion ist bei Kindern und Jugendlichen mit BO stark eingeschränkt. Zudem erwies sich der LCI als sensitiver und reproduzierbarer Marker zur Beurteilung der obstruktiven Beeinträchtigung der kleinen Atemwege. Im induzierten Sputum ist eine von Neutrophilen dominierte bronchiale Entzündung nachweisbar.

Abstract

Introduction Bronchiolitis obliterans (BO) is a rare and severe pulmonary disease which can occur due to airway infection or as a result of stem cell or lung transplantation. Our goal was to study the lung function and airway inflammation among BO patients. Furthermore, we examined the potential of the lung clearance index (LCI) for BO diagnostics among that group.

Methods 16 BO patients (age: 16.7; 9.6 – 25.3 years) and 17 healthy controls (age: 16.6; 7.6 – 25.0 years) participated in the study. Lung function parameters (FVC, FEV₁, MEF₂₅, RV und RV/TLC) as well as airway reversibility after administration of 400 µg salbutamol was investigated. The lung clearance index was determined using the multiple-breath washout method (MBW). Additionally, induced sputum was analyzed for cytology and cytokine levels (IL-1ß, IL-6, IL-8, TNF-α) using the cytometric bead array (CBA).

Results BO patients had significantly lower FVC, FEV₁ and MEF₂₅ but increased RV and RV/TLC. Airway reversibility was observed in 3 patients. The LCI was significantly higher among BO patients compared to the healthy control group (median 10.24 vs. 7.1). Apart from a massive airway inflammation indicated by elevated numbers of total cells and neutrophils, the CBA analysis showed increased levels of IL-6 and IL-8 (p < 0.01).

Discussion In BO patients, lung function in childhood and adolescence is severely impaired. Furthermore, we were able to demonstrate the sensitivity and reproducibility of LCI and its value for the evaluation of small airway obstruction. In induced sputum, a neutrophil-dominated airway inflammation is detectable.

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