Ciliary dysfunction and ultrastructural abnormalities are features of severe asthma

Thomas, Biju; Rutman, Andrew; Hirst, Robert A.; Haldar, Pranabashis; Wardlaw, Andrew J.; Bankart, John; Brightling, Christopher E.; O’Callaghan, Christopher

doi:10.1016/j.jaci.2010.05.046

Cited by 166 publications

(142 citation statements)

References 42 publications

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“…In a recent study we used transmission electron microscopy (TEM) to show cilia loss is a feature of patients with severe asthma [14]. To determine whether RSV infection also led to cilia loss, we obtained three additional samples from healthy control subjects (median (range) age 29 (24-58) years) by brushing the bronchus intermedius (by flexible bronchoscopy), and cultured and infected the ciliated cells as before.…”

Section: Transmission Electron Microscopymentioning

confidence: 99%

Ciliary dyskinesia is an early feature of respiratory syncytial virus infection

Smith

Kulkarni

Radhakrishnan

et al. 2013

European Respiratory Journal

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Respiratory syncytial virus is a major cause of respiratory disease. There are conflicting accounts of the response of human epithelial cells to respiratory syncytial virus and a lack of data on its effect on ciliary function. Our aim was to study the early stages of respiratory syncytial virus infection of primary human basal and ciliated cultures.Using high speed videomicroscopy, we found that ciliary beat frequency was unaffected by respiratory syncytial virus infection over 72 h; however, ciliary dyskinesia significantly increased within 24 h of infection (p,0.05). Transmission electron microscopy revealed that ultrastructural abnormalities were confined to ciliated cells, including increased cilia loss and mitochondrial damage. Confocal immunofluorescence microscopy showed that respiratory syncytial virus antigen gradually spread from the cell surface to the ciliary tip of infected cells over 3 days. Interestingly, ciliated cultures secreted fewer viruses than basal (progenitor) cell cultures and produced a chemokine response focused on recruitment of neutrophils.This study highlights differences in infection models and underscores the need to explore further the role of ciliated cells in the establishment of respiratory syncytial virus infection.Increased ciliary dyskinesia combined with ciliary loss and epithelial damage is likely to result in reduced mucociliary clearance early in the infective process. @ERSpublications Increased ciliary dyskinesia with ciliary loss and epithelial damage can result in reduced mucociliary clearance

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Section: Transmission Electron Microscopymentioning

confidence: 99%

Ciliary dyskinesia is an early feature of respiratory syncytial virus infection

Smith

Kulkarni

Radhakrishnan

et al. 2013

European Respiratory Journal

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“…This aggravates clinical symptoms and contributes to the disease burden of asthma. Ciliary function is an important factor for the mucociliary clearance (8,9). However, studies on ciliary function in asthma are scarce.…”

mentioning

confidence: 99%

Effect of TH2 cytokines and interferon gamma on beat frequency of human respiratory cilia

et al. 2016

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Background:In asthmatic airways secondary ciliary dyskinesia contributes to impaired mucociliary clearance. To investigate underlying mechanisms, we studied the effects of cytokines associated with asthma phenotype on the ciliary beat frequency (CBF) in a cell culture model of ciliated human respiratory epithelial cells. Methods: Nasal respiratory epithelial cells of 21 patients were used to prepare multicellular cells (spheroids) in the presence of the T helper (TH) 2 cytokines interleukin (IL)-4, IL-5, IL-9 and IL-13, and the TH1 cytokine interferon gamma (IFN-γ). CBF was determined by high-speed video microscopy. results: Addition of IL-4 and IL-13 and IL-4 + IL-13 decreased the mean CBF by 17, 21, and 22%, respectively, compared with untreated controls. Addition of IL-5 and IL-9 lead to an increase in mean CBF (20 and 10%, respectively). Lower concentrations of IFN-γ (0.1 and 1 ng/ml) decreased mean CBF and higher concentrations (10 ng/ml) increased CBF by 6%. Addition of IFN-γ to IL-13 reversed the effect of IL-13 on the CBF of spheroids. conclusion: Cytokines directly influence the ciliary function of respiratory epithelium and contribute to the impaired mucociliary clearance in asthmatic disease. Our study encourages further research to investigate IFN-γ as a treatment option in diseases with impaired mucociliary clearance like asthma.

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“…Subjects with severe asthma had a significantly lower number of ciliated cells and higher dyskinesia and cilia immotility indices, compared to healthy controls or those with mild or moderate asthma. 22 Ciliary disorientation and a reduction in mean cilia beat frequency were found in subjects with moderate and severe asthma. 22 Mucus hypersecretion and airways inflammation limit air flow during exacerbations of asthma.…”

Section: Impairment Of Secretion Clearance and Pulmonary Diseasementioning

confidence: 99%

“…22 Ciliary disorientation and a reduction in mean cilia beat frequency were found in subjects with moderate and severe asthma. 22 Mucus hypersecretion and airways inflammation limit air flow during exacerbations of asthma. Typically, as bronchodilator and anti-inflammatory agents reverse the air-flow limitations, secretion clearance functions are restored.…”

Section: Impairment Of Secretion Clearance and Pulmonary Diseasementioning

confidence: 99%

Airway Clearance Therapy: Finding the Evidence

Volsko

2013

Respir Care

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Disease processes can impair ciliary function, alter secretion production and mucus rheology, and interfere with the cough reflex. Airway clearance therapy has been a cornerstone of therapy aimed at minimizing the devastating effects of airway obstruction, infection, and inflammation due to mucus stasis on the conducting airways and lung parenchyma. Although challenges to performing clinical studies evaluating the effectiveness of airway clearance therapeutic modalities exist, resources are available in the literature. In addition to device evaluations and original clinical research, the expert opinion, systematic reviews, and evidence-based practice guidelines can be found. These tools can be used to develop protocols and pathways to guide our practice. Monitoring and reporting patient, process, and financial outcomes are essential steps germane to the implementation of evidence-based care.

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Ciliary dysfunction and ultrastructural abnormalities are features of severe asthma

Cited by 166 publications

References 42 publications

Ciliary dyskinesia is an early feature of respiratory syncytial virus infection

Ciliary dyskinesia is an early feature of respiratory syncytial virus infection

Effect of TH2 cytokines and interferon gamma on beat frequency of human respiratory cilia

Airway Clearance Therapy: Finding the Evidence

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