Association between upper and lower respiratory disease among patients with primary ciliary dyskinesia: an international study

Yin Ting Lam¹, Jean-François Papon^{2

3}, Mihaela Alexandru^{2

3

4}, Andreas Anagiotos⁵, Miguel Armengot^{6

7

8}, Mieke Boon⁹, Andrea Burgess¹⁰, Doriane Calmes¹¹, Suzanne Crowley¹², Sinan Ahmed D Dheyauldeen^{13

14}, Nagehan Emiralioglu¹⁵, Ela Erdem Eralp¹⁶, Christine van Gogh¹⁷, Yasemin Gokdemir¹⁶, Eric G Haarman¹⁸, Amanda Harris^{19

20}, Isolde Hayn²¹, Hasnaa Ismail-Koch¹⁰, Bülent Karadag¹⁶, Céline Kempeneers²², Elisabeth Kieninger²³, Sookyung Kim², Natalie Lorent^{24

25}, Ugur Ozcelik¹⁵, Charlotte Pioch²⁶, Johanna Raidt²⁷, Ana Reula^{8

28}, Jobst Roehmel^{26

29

30}, Synne Sperstad Kennelly¹², Panayiotis Yiallouros^{31

32}; EPIC-PCD team; Myrofora Goutaki^{1

23}

Affiliations

¹ Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
² Assistance Publique-Hôpitaux de Paris, Université Paris-Saclay, Hôpital Bicêtre, Service d'ORL, Le Kremlin-Bicêtre, France.
³ Faculté de Médecine, Université Paris-Saclay, Le Kremlin-Bicêtre, France.
⁴ AP-HP Département de Génétique médicale, Sorbonne Université, Inserm UMR_S933 Maladies génétiques d'expression pédiatrique, Hôpital Armand Trousseau, Paris, France.
⁵ Department of Otorhinolaryngology, Nicosia General Hospital, Nicosia, Cyprus.
⁶ Department of Otorhinolaryngology, and Primary Ciliary Dyskinesia Unit, La Fe University and Polytechnic Hospital, Valencia, Spain.
⁷ Medical School, Valencia University, Valencia, Spain.
⁸ Molecular, Cellular and Genomic Biomedicine Group, IIS La Fe, Valencia, Spain.
⁹ Department of Paediatrics, University Hospital Leuven, Leuven, Belgium.
¹⁰ Primary Ciliary Dyskinesia Centre, Southampton Children's Hospital, Southampton NHS Foundation Trust, Southampton, UK.
¹¹ Department of Pneumology, University Hospital Liège, Liège, Belgium.
¹² Paediatric Department of Allergy and Lung Diseases, Oslo University Hospital, Oslo, Norway.
¹³ Department of Otorhinolaryngology, Head and Neck Surgery, Oslo University Hospital, Oslo, Norway.
¹⁴ Faculty of Medicine, University of Oslo, Oslo, Norway.
¹⁵ Department of Pediatric Pulmonology, Hacettepe University, School of Medicine, Ankara, Turkey.
¹⁶ Department of Pediatric Pulmonology, Marmara University, School of Medicine, Istanbul, Turkey.
¹⁷ Department of Otorhinolaryngology - Head and Neck Surgery, Amsterdam UMC, Amsterdam, The Netherlands.
¹⁸ Department of Pediatric Pulmonology, Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands.
¹⁹ Southampton Children's Hospital, University of Southampton, Southampton, UK.
²⁰ Primary Ciliary Dyskinesia Centre, NIHR Respiratory Biomedical Research Centre, University of Southampton, Southampton, UK.
²¹ Department of Otorhinolaryngology, Head and Neck Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.
²² Division of Respirology, Department of Pediatrics, University Hospital Liège, Liège, Belgium.
²³ Division of Paediatric Respiratory Medicine and Allergology, Department of Paediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
²⁴ Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium.
²⁵ Department Chrometa, Laboratory of Respiratory and Thoracic Diseases, KU Leuven, Leuven, Belgium.
²⁶ Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
²⁷ Department of General Pediatrics, University Hospital Muenster, Muenster, Germany.
²⁸ Biomedical Sciences Department, CEU-Cardenal Herrera University, Castellón, Spain.
²⁹ German Centre for Lung Research (DZL), Associated Partner Site, Berlin, Germany.
³⁰ Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, Germany.
³¹ Medical School, University of Cyprus, Nicosia, Cyprus.
³² Pediatric Pulmonology Unit, Hospital "Archbishop Makarios III", Nicosia, Cyprus.

PMID: 38444659
PMCID: PMC10910353
DOI: 10.1183/23120541.00932-2023

Association between upper and lower respiratory disease among patients with primary ciliary dyskinesia: an international study

Yin Ting Lam et al. ERJ Open Res. 2024.

. 2024 Mar 4;10(2):00932-2023.

doi: 10.1183/23120541.00932-2023. eCollection 2024 Mar.

Authors

Affiliations

¹ Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
² Assistance Publique-Hôpitaux de Paris, Université Paris-Saclay, Hôpital Bicêtre, Service d'ORL, Le Kremlin-Bicêtre, France.
³ Faculté de Médecine, Université Paris-Saclay, Le Kremlin-Bicêtre, France.
⁴ AP-HP Département de Génétique médicale, Sorbonne Université, Inserm UMR_S933 Maladies génétiques d'expression pédiatrique, Hôpital Armand Trousseau, Paris, France.
⁵ Department of Otorhinolaryngology, Nicosia General Hospital, Nicosia, Cyprus.
⁶ Department of Otorhinolaryngology, and Primary Ciliary Dyskinesia Unit, La Fe University and Polytechnic Hospital, Valencia, Spain.
⁷ Medical School, Valencia University, Valencia, Spain.
⁸ Molecular, Cellular and Genomic Biomedicine Group, IIS La Fe, Valencia, Spain.
⁹ Department of Paediatrics, University Hospital Leuven, Leuven, Belgium.
¹⁰ Primary Ciliary Dyskinesia Centre, Southampton Children's Hospital, Southampton NHS Foundation Trust, Southampton, UK.
¹¹ Department of Pneumology, University Hospital Liège, Liège, Belgium.
¹² Paediatric Department of Allergy and Lung Diseases, Oslo University Hospital, Oslo, Norway.
¹³ Department of Otorhinolaryngology, Head and Neck Surgery, Oslo University Hospital, Oslo, Norway.
¹⁴ Faculty of Medicine, University of Oslo, Oslo, Norway.
¹⁵ Department of Pediatric Pulmonology, Hacettepe University, School of Medicine, Ankara, Turkey.
¹⁶ Department of Pediatric Pulmonology, Marmara University, School of Medicine, Istanbul, Turkey.
¹⁷ Department of Otorhinolaryngology - Head and Neck Surgery, Amsterdam UMC, Amsterdam, The Netherlands.
¹⁸ Department of Pediatric Pulmonology, Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands.
¹⁹ Southampton Children's Hospital, University of Southampton, Southampton, UK.
²⁰ Primary Ciliary Dyskinesia Centre, NIHR Respiratory Biomedical Research Centre, University of Southampton, Southampton, UK.
²¹ Department of Otorhinolaryngology, Head and Neck Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.
²² Division of Respirology, Department of Pediatrics, University Hospital Liège, Liège, Belgium.
²³ Division of Paediatric Respiratory Medicine and Allergology, Department of Paediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
²⁴ Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium.
²⁵ Department Chrometa, Laboratory of Respiratory and Thoracic Diseases, KU Leuven, Leuven, Belgium.
²⁶ Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
²⁷ Department of General Pediatrics, University Hospital Muenster, Muenster, Germany.
²⁸ Biomedical Sciences Department, CEU-Cardenal Herrera University, Castellón, Spain.
²⁹ German Centre for Lung Research (DZL), Associated Partner Site, Berlin, Germany.
³⁰ Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, Germany.
³¹ Medical School, University of Cyprus, Nicosia, Cyprus.
³² Pediatric Pulmonology Unit, Hospital "Archbishop Makarios III", Nicosia, Cyprus.

PMID: 38444659
PMCID: PMC10910353
DOI: 10.1183/23120541.00932-2023

Abstract

Introduction: Nearly all patients with primary ciliary dyskinesia (PCD) report ear-nose-throat (ENT) symptoms. However, scarce evidence exists about how ENT symptoms relate to pulmonary disease in PCD. We explored possible associations between upper and lower respiratory disease among patients with PCD in a multicentre study.

Methods: We included patients from the ENT Prospective International Cohort (EPIC-PCD). We studied associations of several reported ENT symptoms and chronic rhinosinusitis (defined using patient-reported information and examination findings) with reported sputum production and shortness of breath, using ordinal logistic regression. In a subgroup with available lung function results, we used linear regression to study associations of chronic rhinosinusitis and forced expiratory volume in 1 s (FEV₁) accounting for relevant factors.

Results: We included 457 patients (median age 15 years, interquartile range 10-24 years; 54% males). Shortness of breath associated with reported nasal symptoms and ear pain of any frequency, often or daily hearing problems, headache when bending down (OR 2.1, 95% CI 1.29-3.54) and chronic rhinosinusitis (OR 2.3, 95% CI 1.57-3.38) regardless of polyp presence. Sputum production associated with daily reported nasal (OR 2.2, 95% CI 1.20-4.09) and hearing (OR 2.0, 95% CI 1.10-3.64) problems and chronic rhinosinusitis (OR 2.1, 95% CI 1.48-3.07). We did not find any association between chronic rhinosinusitis and FEV₁.

Conclusion: Reported upper airway symptoms and signs of chronic rhinosinusitis associated with reported pulmonary symptoms, but not with lung function. Our results emphasise the assessment and management of upper and lower respiratory disease as a common, interdependent entity among patients with PCD.

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Conflict of interest statement

Conflict of interest: J-F. Papon reports personal fees from Sanofi, GSK, Medtronic and ALK, outside the submitted work. Conflict of interest: M. Alexandru received personal fees from Sanofi and ALK outside the submitted work. Conflict of interest: M. Boon reports grants from Forton grant (King Baudouin Foundation) 2020-J1810150-217926 for cystic fibrosis research and personal fees from Vertex outside the submitted work. Conflict of interest: N. Lorent received honoraria to her institution from GSK, INSMED and AN2 Therapeutics outside the submitted work, and a travel grant from Pfizer. Conflict of interest: J. Roehmel received grants, clinical study reimbursement from Vertex, INSMED, Medical Research Council/UK, BMBF and Mukoviszidose Institut, outside the submitted work. Conflict of interest: The other authors report no competing interests.

Figures

**FIGURE 1**
Flowchart of people who participated in the ENT (ear–nose–throat) Prospective International Cohort (EPIC)-PCD (primary ciliary dyskinesia). FEV₁: forced expiratory volume in 1 s; TEM: transmission electron microscope.

**FIGURE 2**
Association of patient-/parent-reported nasal symptoms or headache when bending down with a) shortness of breath and b) sputum production among ENT (ear–nose–throat) Prospective International Cohort (EPIC)-PCD (primary ciliary dyskinesia) participants (n=457).

**FIGURE 3**
Association of patient-/parent-reported ear pain and hearing problems with a) shortness of breath and b) sputum production among ENT (ear–nose–throat) Prospective International Cohort (EPIC)-PCD (primary ciliary dyskinesia) participants (n=457).

**FIGURE 4**
Association of chronic rhinosinusitis (CRS) with patient-/parent-reported a) shortness of breath and b) sputum production among ENT (ear–nose–throat) Prospective International Cohort (EPIC)-PCD (primary ciliary dyskinesia) participants (n=457).

See this image and copyright information in PMC

References

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Association between upper and lower respiratory disease among patients with primary ciliary dyskinesia: an international study

Affiliations

Association between upper and lower respiratory disease among patients with primary ciliary dyskinesia: an international study

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous