Chest
Volume 147, Issue 3, March 2015, Pages 764-770
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Original Research: Pediatrics
Bardet Biedl Syndrome: Motile Ciliary Phenotype

https://doi.org/10.1378/chest.13-2913Get rights and content

BACKGROUND

Cilia line the surface of the respiratory tract and beat in a coordinated wave to protect the lungs against infection. Bardet Biedl Syndrome (BBS) is a rare condition attributed to cilia dysfunction. Murine models of BBS suggest a respiratory phenotype; however, no reports have studied the translation of these findings in patients.

METHODS

We assessed the clinical symptoms of motile cilia dysfunction and the histology of ciliated respiratory epithelium in patients with BBS.

RESULTS

We report an increased prevalence of neonatal respiratory distress at birth (12%), general practitioner-diagnosed asthma (21%), otitis media (33%), and rhinitis (36%) in patients with BBS. These symptoms, however, occurred at a significantly reduced prevalence compared with patients with known motile cilia dysfunction (primary ciliary dyskinesia). Respiratory epithelial assessment revealed cellular damage, significant ciliary depletion (on 60% of ciliated cells), and goblet cell hyperplasia in patients with BBS (50% goblet cells). These findings were quantifiably similar to those of patients with asthma (P> .05). Surprisingly, motile cilia function and ultrastructure were grossly normal with the exception of occasional unique inclusions within the ciliary membrane.

CONCLUSIONS

In conclusion, motile ciliary structure and function are essentially normal in patients with BBS.

Section snippets

Subjects

A retrospective review of clinical data was analyzed for all patients attending BBS clinics at Great Ormond Street and Guys Hospital who were referred for respiratory cilia function tests. Results from 46 patients were analyzed, of which 24 were men (57%). Ages ranged from < 1 year to 48 years, with an average age of 22 years.

Study Design

Respiratory history was recorded from patients with BBS and their families, concentrating on factors implicated in motile respiratory ciliary dysfunction such as

Patients With BBS Report Respiratory Symptoms

Patients with BBS report an increased prevalence of neonatal respiratory distress at birth, general practitioner (GP)-diagnosed asthma, and rhinitis compared with the general population. These symptoms, however, occurred at a significantly reduced incidence compared with patients with known motile cilia dysfunction (PCD) (Table 1).10, 11, 12, 13, 14, 15, 16

There was no increase in the reported frequency of chest infections or cough, and cough was not wet or productive. Rhinitis was reported to

Discussion

In summary, patients with BBS have a high prevalence of asthma, otitis media, and rhinitis. This is reflected in the nasal epithelial histology, which shows damaged epithelium and goblet cell hyperplasia. Respiratory motile cilia function and structure are largely normal in patients with BBS; however, a small proportion of cilia contain inclusions within the ciliary membrane, unique to BBS and visible by electron microscopy.

BBS proteins form a structure known as the BBSome, located at the base

Conclusions

In conclusion, motile ciliary structure and function were essentially normal in > 90% of cilia sampled in this BBS cohort. Patients do not have the classic clinical phenotype associated with motile ciliary dysfunction and, as a result, do not warrant associated therapies such as chest physiotherapy or prolonged antibiotic treatment for respiratory symptoms. However, we would recommend monitoring and control of asthmatic and ear, nose, and throat symptoms. When abnormalities occur, they appear

Acknowledgments

Author contributions: A. S. is guarantor of the article and takes responsibility for the content of the manuscript, including the data and analysis. A. S., P. L. B., and C. L. H. contributed to the study conception and design; A. S., M. D., and P. L. B. contributed to the acquisition and analysis of the data; and A. S., M. D., P. L. B., and C. L. H. contributed to the interpretation of the data and the writing and editing of the manuscript.

Financial/nonfinancial disclosures: The authors have

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FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study.

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