Primary Ciliary Dyskinesia Due to Microtubular Defects is Associated with Worse Lung Clearance Index

S. Irving; M. Dixon; M. R. Fassad; E. Frost; J. Hayward; K. Kilpin; S. Ollosson; A. Onoufriadis; M. P. Patel; J. Scully; S. B. Carr; H. M. Mitchison; M. R. Loebinger; C. Hogg; A. Shoemark; A. Bush

doi:10.1007/s00408-018-0086-x

Primary Ciliary Dyskinesia Due to Microtubular Defects is Associated with Worse Lung Clearance Index

S. Irving (Lead / Corresponding author), M. Dixon, M. R. Fassad, E. Frost, J. Hayward, K. Kilpin, S. Ollosson, A. Onoufriadis, M. P. Patel, J. Scully, S. B. Carr, H. M. Mitchison, M. R. Loebinger, C. Hogg, A. Shoemark, A. Bush

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Abstract

Purpose: Primary ciliary dyskinesia (PCD) is characterised by repeated upper and lower respiratory tract infections, neutrophilic airway inflammation and obstructive airway disease. Different ultrastructural ciliary defects may affect lung function decline to different degrees. Lung clearance index (LCI) is a marker of ventilation inhomogeneity that is raised in some but not all patients with PCD. We hypothesised that PCD patients with microtubular defects would have worse (higher) LCI than other PCD patients.

Methods: Spirometry and LCI were measured in 69 stable patients with PCD. Age at testing, age at diagnosis, ethnicity, ciliary ultrastructure, genetic screening result and any growth of Pseudomonas aeruginosa was recorded.

Results: Lung clearance index was more abnormal in PCD patients with microtubular defects (median 10.24) than those with dynein arm defects (median 8.3, p = 0.004) or normal ultrastructure (median 7.63, p = 0.0004). Age is correlated with LCI, with older patients having worse LCI values (p = 0.03, r = 0.3).

Conclusion: This study shows that cilia microtubular defects are associated with worse LCI in PCD than dynein arm defects or normal ultrastructure. The patient's age at testing is also associated with a higher LCI. Patients at greater risk of obstructive lung disease should be considered for more aggressive management. Differences between patient groups may potentially open avenues for novel treatments.

Original language	English
Pages (from-to)	231-238
Number of pages	8
Journal	Lung
Volume	196
Issue number	2
Early online date	24 Jan 2018
DOIs	https://doi.org/10.1007/s00408-018-0086-x
Publication status	Published - Apr 2018

Keywords

Ciliopathy
Lung function
Paediatrics
Rare disease

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine

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© The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
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Cite this

Irving, S., Dixon, M., Fassad, M. R., Frost, E., Hayward, J., Kilpin, K., Ollosson, S., Onoufriadis, A., Patel, M. P., Scully, J., Carr, S. B., Mitchison, H. M., Loebinger, M. R., Hogg, C., Shoemark, A., & Bush, A. (2018). Primary Ciliary Dyskinesia Due to Microtubular Defects is Associated with Worse Lung Clearance Index. Lung, 196(2), 231-238. https://doi.org/10.1007/s00408-018-0086-x

@article{31e11aeae0414a978b2ab76435ba1eb0,

title = "Primary Ciliary Dyskinesia Due to Microtubular Defects is Associated with Worse Lung Clearance Index",

abstract = "Purpose: Primary ciliary dyskinesia (PCD) is characterised by repeated upper and lower respiratory tract infections, neutrophilic airway inflammation and obstructive airway disease. Different ultrastructural ciliary defects may affect lung function decline to different degrees. Lung clearance index (LCI) is a marker of ventilation inhomogeneity that is raised in some but not all patients with PCD. We hypothesised that PCD patients with microtubular defects would have worse (higher) LCI than other PCD patients.Methods: Spirometry and LCI were measured in 69 stable patients with PCD. Age at testing, age at diagnosis, ethnicity, ciliary ultrastructure, genetic screening result and any growth of Pseudomonas aeruginosa was recorded.Results: Lung clearance index was more abnormal in PCD patients with microtubular defects (median 10.24) than those with dynein arm defects (median 8.3, p = 0.004) or normal ultrastructure (median 7.63, p = 0.0004). Age is correlated with LCI, with older patients having worse LCI values (p = 0.03, r = 0.3).Conclusion: This study shows that cilia microtubular defects are associated with worse LCI in PCD than dynein arm defects or normal ultrastructure. The patient's age at testing is also associated with a higher LCI. Patients at greater risk of obstructive lung disease should be considered for more aggressive management. Differences between patient groups may potentially open avenues for novel treatments.",

keywords = "Ciliopathy, Lung function, Paediatrics, Rare disease",

author = "S. Irving and M. Dixon and Fassad, {M. R.} and E. Frost and J. Hayward and K. Kilpin and S. Ollosson and A. Onoufriadis and Patel, {M. P.} and J. Scully and Carr, {S. B.} and Mitchison, {H. M.} and Loebinger, {M. R.} and C. Hogg and A. Shoemark and A. Bush",

note = " The research is supported by the COST Action 1407 network (BEAT-PCD: Better Evidence to Advance Therapeutic Options for PCD). A.B. was supported by the NIHR Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London. Work by A.S. is an independent research funded by a postdoctoral research fellowship from the National Institute of Health Research and Health Education England, and the views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute of Health Research or the Department of Health. H.M.M. acknowledges support from the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London and was supported by Grants from Action Medical Research (GN2101), Newlife Foundation (10-11/15) and the Great Ormond Street Hospital Children{\textquoteright}s Charity. M.L received funding from Bayer Pharmaceuticals (Berlin) for an investigator lead research grant in lung clearance index.",

year = "2018",

month = apr,

doi = "10.1007/s00408-018-0086-x",

language = "English",

volume = "196",

pages = "231--238",

journal = "Lung",

issn = "0341-2040",

publisher = "Springer",

number = "2",

}

Irving, S, Dixon, M, Fassad, MR, Frost, E, Hayward, J, Kilpin, K, Ollosson, S, Onoufriadis, A, Patel, MP, Scully, J, Carr, SB, Mitchison, HM, Loebinger, MR, Hogg, C, Shoemark, A & Bush, A 2018, 'Primary Ciliary Dyskinesia Due to Microtubular Defects is Associated with Worse Lung Clearance Index', Lung, vol. 196, no. 2, pp. 231-238. https://doi.org/10.1007/s00408-018-0086-x

TY - JOUR

T1 - Primary Ciliary Dyskinesia Due to Microtubular Defects is Associated with Worse Lung Clearance Index

AU - Irving, S.

AU - Dixon, M.

AU - Fassad, M. R.

AU - Frost, E.

AU - Hayward, J.

AU - Kilpin, K.

AU - Ollosson, S.

AU - Onoufriadis, A.

AU - Patel, M. P.

AU - Scully, J.

AU - Carr, S. B.

AU - Mitchison, H. M.

AU - Loebinger, M. R.

AU - Hogg, C.

AU - Shoemark, A.

AU - Bush, A.

N1 - The research is supported by the COST Action 1407 network (BEAT-PCD: Better Evidence to Advance Therapeutic Options for PCD). A.B. was supported by the NIHR Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London. Work by A.S. is an independent research funded by a postdoctoral research fellowship from the National Institute of Health Research and Health Education England, and the views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute of Health Research or the Department of Health. H.M.M. acknowledges support from the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London and was supported by Grants from Action Medical Research (GN2101), Newlife Foundation (10-11/15) and the Great Ormond Street Hospital Children’s Charity. M.L received funding from Bayer Pharmaceuticals (Berlin) for an investigator lead research grant in lung clearance index.

PY - 2018/4

Y1 - 2018/4

N2 - Purpose: Primary ciliary dyskinesia (PCD) is characterised by repeated upper and lower respiratory tract infections, neutrophilic airway inflammation and obstructive airway disease. Different ultrastructural ciliary defects may affect lung function decline to different degrees. Lung clearance index (LCI) is a marker of ventilation inhomogeneity that is raised in some but not all patients with PCD. We hypothesised that PCD patients with microtubular defects would have worse (higher) LCI than other PCD patients.Methods: Spirometry and LCI were measured in 69 stable patients with PCD. Age at testing, age at diagnosis, ethnicity, ciliary ultrastructure, genetic screening result and any growth of Pseudomonas aeruginosa was recorded.Results: Lung clearance index was more abnormal in PCD patients with microtubular defects (median 10.24) than those with dynein arm defects (median 8.3, p = 0.004) or normal ultrastructure (median 7.63, p = 0.0004). Age is correlated with LCI, with older patients having worse LCI values (p = 0.03, r = 0.3).Conclusion: This study shows that cilia microtubular defects are associated with worse LCI in PCD than dynein arm defects or normal ultrastructure. The patient's age at testing is also associated with a higher LCI. Patients at greater risk of obstructive lung disease should be considered for more aggressive management. Differences between patient groups may potentially open avenues for novel treatments.

AB - Purpose: Primary ciliary dyskinesia (PCD) is characterised by repeated upper and lower respiratory tract infections, neutrophilic airway inflammation and obstructive airway disease. Different ultrastructural ciliary defects may affect lung function decline to different degrees. Lung clearance index (LCI) is a marker of ventilation inhomogeneity that is raised in some but not all patients with PCD. We hypothesised that PCD patients with microtubular defects would have worse (higher) LCI than other PCD patients.Methods: Spirometry and LCI were measured in 69 stable patients with PCD. Age at testing, age at diagnosis, ethnicity, ciliary ultrastructure, genetic screening result and any growth of Pseudomonas aeruginosa was recorded.Results: Lung clearance index was more abnormal in PCD patients with microtubular defects (median 10.24) than those with dynein arm defects (median 8.3, p = 0.004) or normal ultrastructure (median 7.63, p = 0.0004). Age is correlated with LCI, with older patients having worse LCI values (p = 0.03, r = 0.3).Conclusion: This study shows that cilia microtubular defects are associated with worse LCI in PCD than dynein arm defects or normal ultrastructure. The patient's age at testing is also associated with a higher LCI. Patients at greater risk of obstructive lung disease should be considered for more aggressive management. Differences between patient groups may potentially open avenues for novel treatments.

KW - Ciliopathy

KW - Lung function

KW - Paediatrics

KW - Rare disease

U2 - 10.1007/s00408-018-0086-x

DO - 10.1007/s00408-018-0086-x

M3 - Article

C2 - 29368042

SN - 0341-2040

VL - 196

SP - 231

EP - 238

JO - Lung

JF - Lung

IS - 2

ER -

Primary Ciliary Dyskinesia Due to Microtubular Defects is Associated with Worse Lung Clearance Index

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Keywords

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