Prevalence and Impact of Respiratory Viral Infections in Young Children With Cystic Fibrosis: Prospective Cohort Study

Ewijk, Bart E. van; Zalm, Marieke M. van der; Wolfs, Tom F. W.; Fleer, A.; Kimpen, Jan L. L.; Wilbrink, B.; Ent, Cornelis K. van der

doi:10.1542/peds.2007-3139

Cited by 108 publications

(98 citation statements)

References 25 publications

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“…Indeed, RV infection in CF causes a high RV burden in the lower airways [18] and viral infections of the lower airways of CF patients lead to a risk of hospitalisation and to persistent deterioration of lung function parameters, and are related to increased lower respiratory tract morbidity in infants with CF [39,40]. Thus, cells from the lower respiratory tract are more relevant to RV-associated respiratory tract morbidity of CF infants than epithelial cells from the upper respiratory tract.…”

Section: Discussionmentioning

confidence: 99%

Novel antiviral properties of azithromycin in cystic fibrosis airway epithelial cells

et al. 2014

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Virus-associated pulmonary exacerbations, often associated with rhinoviruses (RVs), contribute to cystic fibrosis (CF) morbidity. Currently, there are only a few therapeutic options to treat virus-induced CF pulmonary exacerbations. The macrolide antibiotic azithromycin has antiviral properties in human bronchial epithelial cells. We investigated the potential of azithromycin to induce antiviral mechanisms in CF bronchial epithelial cells.Primary bronchial epithelial cells from CF and control children were infected with RV after azithromycin pre-treatment. Viral RNA, interferon (IFN), IFN-stimulated gene and pattern recognition receptor expression were measured by real-time quantitative PCR. Live virus shedding was assessed by assaying the 50% tissue culture infective dose. Pro-inflammatory cytokine and IFN-β production were evaluated by ELISA. Cell death was investigated by flow cytometry.RV replication was increased in CF compared with control cells. Azithromycin reduced RV replication seven-fold in CF cells without inducing cell death. Furthermore, azithromycin increased RV-induced pattern recognition receptor, IFN and IFN-stimulated gene mRNA levels. While stimulating antiviral responses, azithromycin did not prevent virus-induced pro-inflammatory responses.Azithromycin pre-treatment reduces RV replication in CF bronchial epithelial cells, possibly through the amplification of the antiviral response mediated by the IFN pathway. Clinical studies are needed to elucidate the potential of azithromycin in the management and prevention of RV-induced CF pulmonary exacerbations. @ERSpublications Azithromycin reduces rhinovirus load in CF bronchial cells, possibly through the induction of the interferon pathway

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Section: Discussionmentioning

confidence: 99%

Novel antiviral properties of azithromycin in cystic fibrosis airway epithelial cells

et al. 2014

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“…Viral respiratory infections seem to play an important role in conditioning the short-and long-term pulmonary morbidity of patients with cystic fibrosis (CF) because they increase the rate of hospitalization and antibiotic use (1). They are also the main trigger of recurrent pulmonary exacerbations, which cause progressive lung damage that is characteristic of the disease (2,3).…”

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confidence: 99%

Human Rhinovirus Infection in Children with Cystic Fibrosis

et al. 2014

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SUMMARY: Nasopharyngeal swabs obtained from 78 pediatric patients with cystic fibrosis (CF), including 47 with acute pulmonary exacerbation and 31 in a stable clinical condition, were evaluated for 17 respiratory viruses. Human rhinovirus (HRV) was the most frequently detected virus in patients with pulmonary exacerbation and in those who were clinically stable (21.3z vs. 12.9z; P ＝ 0.52). HRV-A was the main RV detected in patients with pulmonary exacerbations. However, no prevalence of particular HRV-A subtypes was found. This study highlights that RV is frequently found in the respiratory secretions of patients with CF and the impact of HRV-A appears higher than that of the other HRV types in patients with pulmonary exacerbations.

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“…Thus, perturbation of the barrier function may increase paracellular permeability, facilitate translocation of pathogens and their soluble products, and expose basolateral receptors. Rhinovirus (RV), which is responsible for the majority of common colds (1), also provokes acute lower respiratory symptoms in healthy individuals (7,18) and exacerbates airway diseases in patients with asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (9,32,47,50). In addition to stimulating production of proinflammatory cytokines (13,34), RV infection may also promote secondary bacterial infections by interfering with host innate defense mechanisms or by increasing the adherence of bacteria to the host mucosa (2,20,48).…”

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Rhinovirus-Induced Barrier Dysfunction in Polarized Airway Epithelial Cells Is Mediated by NADPH Oxidase 1

Comstock

Ganesan

Chattoraj

et al. 2011

J Virol

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Previously, we showed that rhinovirus (RV), which is responsible for the majority of common colds, disrupts airway epithelial barrier function, as evidenced by reduced transepithelial resistance (R T ), dissociation of zona occludins 1 (ZO-1) from the tight junction complex, and bacterial transmigration across polarized cells. We also showed that RV replication is required for barrier function disruption. However, the underlying biochemical mechanisms are not known. In the present study, we found that a double-stranded RNA (dsRNA) mimetic, poly(I:C), induced tight junction breakdown and facilitated bacterial transmigration across polarized airway epithelial cells, similar to the case with RV. We also found that RV and poly(I:C) each stimulated Rac1 activation, reactive oxygen species (ROS) generation, and Rac1-dependent NADPH oxidase 1 (NOX1) activity. Inhibitors of Rac1 (NSC23766), NOX (diphenylene iodonium), and NOX1 (small interfering RNA [siRNA]) each blocked the disruptive effects of RV and poly(I:C) on R T , as well as the dissociation of ZO-1 and occludin from the tight junction complex. Finally, we found that Toll-like receptor 3 (TLR3) is not required for either poly(I:C)-or RV-induced reductions in R T . Based on these results, we concluded that Rac1-dependent NOX1 activity is required for RV-or poly(I:C)-induced ROS generation, which in turn disrupts the barrier function of polarized airway epithelia. Furthermore, these data suggest that dsRNA generated during RV replication is sufficient to disrupt barrier function.

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Prevalence and Impact of Respiratory Viral Infections in Young Children With Cystic Fibrosis: Prospective Cohort Study

Abstract: Although there were no differences in the seasonal occurrences and distributions of polymerase chain reaction-detected respiratory viruses, acute respiratory illnesses were frequently associated with increased lower respiratory tract morbidity in young children with cystic fibrosis.

Cited by 108 publications

References 25 publications

Novel antiviral properties of azithromycin in cystic fibrosis airway epithelial cells

Novel antiviral properties of azithromycin in cystic fibrosis airway epithelial cells

Human Rhinovirus Infection in Children with Cystic Fibrosis

Rhinovirus-Induced Barrier Dysfunction in Polarized Airway Epithelial Cells Is Mediated by NADPH Oxidase 1

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