Aspergillus Serologic Findings and Clinical Outcomes in Patients With Bronchiectasis: Data From the European Bronchiectasis Registry

J Pollock; P C Goeminne; S Aliberti; E Polverino; M L Crichton; F C Ringshausen; R Dhar; M Vendrell; P R Burgel; C S Haworth; A De Soyza; J De Gracia; A Bossios; J Rademacher; A Grünewaldt; M McDonnell; D Stolz; O Sibila; M van der Eerden; P Kauppi; A T Hill; R Wilson; A Amorim; O Munteanu; R Menendez; A Torres; T Welte; F Blasi; W Boersma; J S Elborn; M Shteinberg; K Dimakou; James D Chalmers; M R Loebinger; EMBARC Registry Investigators

doi:10.1016/j.chest.2024.06.3843

Aspergillus Serologic Findings and Clinical Outcomes in Patients With Bronchiectasis: Data From the European Bronchiectasis Registry

Chest. 2024 Oct 24:S0012-3692(24)05400-X. doi: 10.1016/j.chest.2024.06.3843. Online ahead of print.

Authors

J Pollock¹, P C Goeminne², S Aliberti³, E Polverino⁴, M L Crichton¹, F C Ringshausen⁵, R Dhar⁶, M Vendrell⁷, P R Burgel⁸, C S Haworth⁹, A De Soyza¹⁰, J De Gracia¹¹, A Bossios¹², J Rademacher⁵, A Grünewaldt¹³, M McDonnell¹⁴, D Stolz¹⁵, O Sibila¹⁶, M van der Eerden¹⁷, P Kauppi¹⁸, A T Hill¹⁹, R Wilson²⁰, A Amorim²¹, O Munteanu²², R Menendez²³, A Torres²⁴, T Welte⁵, F Blasi²⁵, W Boersma²⁶, J S Elborn²⁷, M Shteinberg²⁸, K Dimakou²⁹, James D Chalmers³⁰, M R Loebinger²⁰; EMBARC Registry Investigators

Affiliations

¹ Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee.
² Department of Respiratory Disease, VITAZ Hospital, Sint-Nikolaas, Belgium.
³ IRCCS Humanitas Research Hospital, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy.
⁴ Department of Pneumology, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Thorax Institute, Institute of Biomedical Research August Pi I Sunyer, University of Barcelona, Barcelona, Spain.
⁵ Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School, Hannover, Germany; Biomedical Research in End-Stage and Obstructive Lung Disease Hannover, German Center for Lung Research, Hannover, Germany; European Reference Network on Rare and Complex Respiratory Diseases, Frankfurt am Main, Germany.
⁶ Department of Pulmonology, C. K. Birla Hospitals, Kolkata, India.
⁷ Department of Pulmonology, Dr Trueta University Hospital, Girona Biomedical Research Institute (IDIBGI), University of Girona, Girona, Spain.
⁸ Department of Respiratory Medicine and French Cystic Fibrosis National Reference Center, Hôpital Cochin, AP-HP and Université Paris Cité, Inserm U1016, Institut Cochin, Paris, France.
⁹ Cambridge Centre for Lung Infection, Royal Papworth Hospital and University of Cambridge, Cambridge.
¹⁰ Population and Health Science Institute, Newcastle University and NIHR Biomedical Research Centre for Ageing, Freeman Hospital, Newcastle.
¹¹ Department of Respiratory Medicine, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
¹² Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden; Division of Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
¹³ Department of Respiratory Medicine and Allergology, University Hospital Frankfurt, Frankfurt am Main, Germany.
¹⁴ Department of Respiratory Medicine, Galway University Hospital, Galway, Ireland.
¹⁵ Department of Pneumology, Medical Center - University of Freiburg, Baden-Württemberg, Germany.
¹⁶ Servicio de Neumología, Hospital Clínic, University of Barcelona, Barcelona, Spain; CIBER de Enfermedades Respiratorias, ISCIII, Madrid, Spain.
¹⁷ Department of Respiratory Medicine, Erasmus Medical Center, Rotterdam.
¹⁸ Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
¹⁹ Department of Respiratory Medicine, Royal Infirmary of Edinburgh, Edinburgh, Scotland.
²⁰ Royal Brompton and Harefield Hospitals and National Heart and Lung Institute, Imperial College London, London, England.
²¹ Department of Pulmonology, Centro Hospitalar Universitário S. João and Faculty of Medicine, University of Porto, Porto, Portugal.
²² Pneumology/Allergology Division, University of Medicine and Pharmacy Nicolae Testemitanu, Medpark International Hospital, Chisinau, Moldova.
²³ Department of Pneumology, Hospital Universitario y Politécnico La Fe-Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
²⁴ Instituto Clínico de Respiratorio, IDIBAPS, Hospital Clínic, University of Barcelona, Barcelona, Spain.
²⁵ Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
²⁶ Department of Pulmonary Diseases, Northwest Clinics, Alkmaar, The Netherlands.
²⁷ Faculty of Medicine, Health and Life Sciences, Queen's University, Belfast, Northern Ireland.
²⁸ Pulmonology Institute and CF Center, Carmel Medical Center, Haifa, Israel.
²⁹ 5th Respiratory Medicine Department, General Hospital for Chest Diseases of Athens SOTIRIA, Athens, Greece.
³⁰ Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee. Electronic address: j.chalmers@dundee.ac.uk.

PMID: 39461553
DOI: 10.1016/j.chest.2024.06.3843

Abstract

Background: Aspergillus species cause diverse clinical manifestations in bronchiectasis including allergic bronchopulmonary aspergillosis (ABPA), Aspergillus sensitization (AS), and raised IgG indicating exposure to or infection with Aspergillus.

Research question: What are the prevalence and clinical significance of Aspergillus-associated conditions in individuals with bronchiectasis?

Study design and methods: Patients with bronchiectasis enrolled into the European Bronchiectasis Registry from 2015 through 2022 with laboratory testing for Aspergillus lung disease (total IgE, IgE specific to Aspergillus or Aspergillus skin test, or IgG specific to Aspergillus and blood eosinophil counts) were included for analysis. Modified International Society for Human and Anima Mycology ABPA working group criteria (2021) were used to define ABPA.

Results: Nine thousand nine hundred fifty-three patients were included. Six hundred eight patients (6.1%) were classified as having ABPA, 570 patients (5.7%) showed AS, 806 patients (8.1%) showed raised Aspergillus-specific IgG without AS, 184 patients (1.8%) showed both AS and had raised Aspergillus-specific IgG levels, and 619 patients (6.2%) demonstrated eosinophilic bronchiectasis (elevated eosinophil counts without evidence of Aspergillus lung disease). The remaining 72% showed negative Aspergillus serologic findings. Patients with ABPA, AS, or raised Aspergillus-specific IgG demonstrated more severe disease, with worse lung function and more frequent exacerbations at baseline. During long-term follow-up, patients with raised Aspergillus-specific IgG experienced higher exacerbation frequency and more severe exacerbations. AS was associated with increased exacerbations and hospitalizations only in patients not receiving inhaled corticosteroids (ICS).

Interpretation: Aspergillus lung disease is common in bronchiectasis. Raised IgG levels to Aspergillus are associated with significantly worse outcomes, whereas ABPA and AS are associated with severe disease and exacerbations with a risk that is attenuated by ICS use.

Keywords: aspergillus; bronchiectasis; exacerbations; fungi; prognosis.