Two-year evolution of nitrogen lung clearance index in patients with primary ciliary dyskinesia

Hintergrund Primary ciliary dyskinesia (PCD) is a rare genetic disease caused by mutations in various genes encoding for any of the many polypeptide species within the axoneme (central core) of cilia or of sperm flagella, for other proteins that are present in the ciliary membrane and matrix or for proteins needed for the proper assembly of cilia. Ciliary dysfunction leads to impaired mucociliary clearance, which results in chronic bronchitis and progressive structural lung damage. The multiple-breath washout (MBW)-derived lung clearance index (LCI) is an objective parameter of lung function, sensitive to small airway obstruction and ventilation inhomogeneity. Longitudinal data on LCI in PCD is scarce. This study aims to examine the LCI in PCD over a two-year period.

Methoden All patients diagnosed with PCD according to ATS/ERS guidelines were included in this prospective observational study when at least two MBW tests in a 24 ± 3 months interval were available without pulmonary exacerbation (PEX) in the preceding four weeks. Over the course of two years LCI, percent predicted forced expiratory volume in one second (ppFEV1), and quality of life (QoL) were measured, sputum and information about PEX collected at routine quarterly visits. Nitrogen MBW was performed with the Exhalyzer D device (Eco Medics AG, Duernten, Switzerland) in awake patients. Only measurements with at least two acceptable trials as defined by the ERS were included. QoL was assessed with the QOL-PCD questionnaire. The data were collected from 2020 until 2023.

Ergebnisse 35 patients were included in the final analysis. Mean age at baseline was 21.9 ± 16.5 (range 0.3 – 64.2) years. 17 (48.6 %) participants were minors. There was no significant change in LCI or ppFEV1 between baseline and follow-up after one and two years. Mean LCI at these times was 10.2 ± 3.1, 9.8 ± 2.0, and 10.3 ± 3.0 (p = 0.11 and p = 0.54 vs. baseline, respectively). Mean ppFEV1 at these times was 73.8 ± 20.7, 78.9 ± 19.0, and 71.9 ± 21.2 (p = 0.57 and p = 0.31 vs. baseline, respectively).

Schlussfolgerung LCI remained stable in PCD patients over the course of two years. This is in line with and extends former findings on disease progression in PCD. ppFEV1 also remained stable. Considering the vast time patients spend under the disease, even longer follow-up intervals are warranted.

Interessenskonflikte

No author received grants, funding or payment regarding this study. Outside of this work, the authors report the following sources for potential conflicts of interest. All other authors have nothing to declare. J. Röhmel reports payment for presentations at educational events from Vertex Pharmaceuticals (VP), grants and clinical study remuneration from VP, INSMED, Medical Research Council / UK, the German Federal Ministry for Education and Research (BMBF), and Mukoviszidose e.V. (MEV; German Cystic Fibrosis Association). S. Gräber reports grants from the German Research Foundation (DFG), BMBF, MEV, the Christiane Herzog Foundation (CHF), and VP as well as personal fees from Chiesi GmbH and VP. E. Steinke reports funding from the Junior Clinician Scientist Program of Berlin Institute of Health at Charité Berlin. M. Mall reports funding from DFG and BMBF, grants from VP, personal fees for consultancy or participation in advisory boards from Boehringer Ingelheim, Arrowhead Pharmaceuticals, VP, Santhera, Enterprise Therapeutics, Antabio, Kither Biotech, Abbvie, Galapagos, Sterna Biologicals, Prieris, Recode, Splisense and Pari. He was member of the board and vice-president of the European Cystic Fibrosis Society from 2014 to 2020. M. Stahl reports funding from DFG, grants from VP, MEV, the German Center for Lung Research (DZL), CHF, and payment for work on an advisory board from VP. She is elected, unpaid secretary of the group on paediatric cystic fibrosis of Assembly 7 of the ERS.

Publication History

Article published online:
22 February 2024