Mucus Properties In Children With Primary Ciliary Dyskinesia

Bush, Andrew; Payne, Donald; Pike, Sarah E.; Jenkins, Gavin R.; Henke, Markus O.; Rubin, Bruce K.

doi:10.1378/chest.129.1.118

Cited by 108 publications

(89 citation statements)

References 29 publications

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Section: Overview Of Pcd-related Lung Disease: What Happens When Lungmentioning

confidence: 95%

“…Examination of sputum collected from children with PCD reveals a predominantly neutrophilic inflammation (14,15). Two studies demonstrate a remarkably similar degree of airway inflammation in small cohorts of PCD and subjects with CF (15,16), despite the generally milder pulmonary phenotype observed in PCD. There is a need to investigate local and systemic inflammation in larger cohorts of children and adults with PCD and to carefully examine the relationships between airway infection, inflammation, structural lung injury, and functional impairment.…”

Section: Overview Of Pcd-related Lung Disease: What Happens When Lungmentioning

confidence: 95%

See 1 more Smart Citation

Update of Respiratory Tract Disease in Children with Primary Ciliary Dyskinesia

Sagel¹,

Davis²,

Campisi³

et al. 2011

Proceedings of the American Thoracic Society

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Primary ciliary dyskinesia (PCD) is a rare genetic disease characterized by abnormal ciliary structure and function leading to impaired mucociliary clearance and chronic progressive sinopulmonary disease. Upper and lower respiratory tract manifestations are cardinal features of PCD. This review summarizes the current state of knowledge of respiratory tract disease in individuals with PCD and highlights the challenges in identifying and quantifying lung disease in very young children with PCD. No specific therapies are available to correct ciliary dysfunction in PCD. Treatment is not evidence based, and recommendations are largely extrapolated from cystic fibrosis and other conditions with impaired mucociliary clearance. There is a pressing need to develop and validate outcome measures, including patient-reported outcomes, that could be used to evaluate potential therapies in PCD. This review concludes with recommendations for clinical endpoints and outcome measures and a prioritized list of treatments to study in PCD clinical trials.

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Section: Overview Of Pcd-related Lung Disease: What Happens When Lungmentioning

confidence: 95%

Section: Overview Of Pcd-related Lung Disease: What Happens When Lungmentioning

confidence: 95%

Update of Respiratory Tract Disease in Children with Primary Ciliary Dyskinesia

Sagel¹,

Davis²,

Campisi³

et al. 2011

Proceedings of the American Thoracic Society

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“…In cystic fibrosis patients, it has been suggested that the viscous mucus may trap the highly reactive nitric oxide, preventing it from being exhaled freely [67,68]. Viscous mucus is a particular issue for cystic fibrosis patients but similar biophysical properties have been identified in sputum of patients with PCD [78]. The significance of this potential mechanism requires further evaluation.…”

Section: Nitric Oxide Is Trapped and Broken Down In Viscous Sputummentioning

confidence: 99%

Nitric oxide in primary ciliary dyskinesia

et al. 2012

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Nitric oxide is continually synthesised in the respiratory epithelium and is upregulated in response to infection or inflammation. Primary ciliary dyskinesia (PCD) is characterised by recurrent sinopulmonary infections due to impaired mucociliary clearance. Despite chronic infections, nasal nitric oxide in such patients is markedly reduced and is used as a screening test for this condition. These low levels were first described .15 yrs ago but the underlying mechanisms have yet to be fully elucidated. We review epithelial nitric oxide synthesis, release and measurement in the upper airways with particular reference to PCD. The key hypotheses that have been proposed to explain the low nitric oxide levels in this condition are explored and the potential benefits of augmenting airway nitric oxide levels are considered. Further work in these patients clarifying both whether the respiratory epithelium is able to biosynthesise normal levels of nitric oxide and the role played by abnormalities in the anatomy of the paranasal sinuses is essential. While nitric oxide augmentation is unlikely to be beneficial in common PCD phenotypes, it has potential in the treatment of secondary dyskinesias and may also improve treatment of bacterial infections, particularly where biofilms are implicated.

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“…Although bicarbonate secretion in the airway has been shown (22), its impact on mucus adhesion has so far been limited to studies of murine intestine (18,19). Others have suggested that CF mucus is not inherently abnormal but is altered by secondary phenomena such as inflammation and gland hyperplasia (23).…”

mentioning

confidence: 99%

A Functional Anatomic Defect of the Cystic Fibrosis Airway

Birket¹,

Chu

Liu³

et al. 2014

Am J Respir Crit Care Med

130

162

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Rationale: The mechanisms underlying cystic fibrosis (CF) lung disease pathogenesis are unknown.Objectives: To establish mechanisms linking anion transport with the functional microanatomy, we evaluated normal and CF piglet trachea as well as adult swine trachea in the presence of selective anion inhibitors.Methods: We investigated airway functional microanatomy using microoptical coherence tomography, a new imaging modality that concurrently quantifies multiple functional parameters of airway epithelium in a colocalized fashion.Measurements and Main Results: Tracheal explants from wild-type swine demonstrated a direct link between periciliary liquid (PCL) hydration and mucociliary transport (MCT) rates, a relationship frequently invoked but never experimentally confirmed. However, in CF airways this relationship was completely disrupted, with greater PCL depths associated with slowest transport rates. This disrupted relationship was recapitulated by selectively inhibiting bicarbonate transport in vitro and ex vivo. CF mucus exhibited increased viscosity in situ due to the absence of bicarbonate transport, explaining defective MCT that occurs even in the presence of adequate PCL hydration.Conclusions: An inherent defect in CF airway surface liquid contributes to delayed MCT beyond that caused by airway dehydration alone and identifies a fundamental mechanism underlying the pathogenesis of CF lung disease in the absence of antecedent infection or inflammation.

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Mucus Properties In Children With Primary Ciliary Dyskinesia

Cited by 108 publications

References 29 publications

Update of Respiratory Tract Disease in Children with Primary Ciliary Dyskinesia

Update of Respiratory Tract Disease in Children with Primary Ciliary Dyskinesia

Nitric oxide in primary ciliary dyskinesia

A Functional Anatomic Defect of the Cystic Fibrosis Airway

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