High Rhinovirus Burden in Lower Airways of Children With Cystic Fibrosis

Kieninger, Elisabeth; Singer, Florian; Tapparel, Caroline; Alves, Marco P.; Latzin, Philipp; Tan, Hui-Leng; Bossley, Cara; Casaulta, Carmen; Bush, Andrew; Davies, Jane C.; Kaiser, Laurent; Regamey, Nicolas

doi:10.1378/chest.12-0954

Cited by 75 publications

(83 citation statements)

References 42 publications

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“…In accordance with previous reports [18,20,28], we found that CF bronchial cells revealed an increased viral replication compared to controls. Previously, SUTANTO et al [20] reported that the viral copy number in CF airway epithelial cells in vitro infected with RV1B is higher than in non-CF cells.…”

Section: Discussionsupporting

confidence: 93%

“…Similarly, ZHENG et al [28] identified increased in vitro viral replication in CF airway epithelial cells compared with non-CF cells infected with human parainfluenza virus 3. Interestingly, increased RV replication in CF has been confirmed in an ex vivo model using bronchoalveolar lavages from CF and control patients [18]. In our study, we further demonstrated that azithromycin treatment had antiviral properties characterised by a seven-fold reduced RV1B replication in CF bronchial cells.…”

Section: Discussionsupporting

confidence: 76%

“…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%

“…Several studies have reported a hypersusceptibility of the CF airway epithelium to respiratory viruses [18,20,28]. To confirm that CF bronchial cells are more susceptible to RV infection than controls, we assessed virus shedding into supernatants at 24 h post-infection by a TCID50 assay ( fig.…”

Section: Cf Bronchial Epithelial Cells Have An Increased Susceptibilimentioning

confidence: 99%

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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: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Cf Bronchial Epithelial Cells Have An Increased Susceptibilimentioning

confidence: 99%

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Novel antiviral properties of azithromycin in cystic fibrosis airway epithelial cells

et al. 2014

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“…The association between viral respiratory infections, in particular rhinovirus, and pulmonary exacerbations is well described [81,82]. SHAH et al [83] found no differences in the pathogenicity of individual rhinovirus groups, but virus-associated exacerbations had a greater impact on lung function, length of treatment and time to next exacerbation than exacerbations in which no rhinovirus was detected.…”

Section: Microbiologymentioning

confidence: 99%

Paediatrics in Barcelona

et al. 2014

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Respiratory Tract Cultures

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Lindsay

et al. 2023

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Specimens from the upper respiratory tract (throat specimens, nasopharyngeal swabs, and nasal discharges) can be easily obtained but are contaminated with resident microbiota. Infections of the lower respiratory tract are the sixth leading cause of mortality in the United States, with 2 to 3 million cases per year, resulting in 500,000 hospitalizations. The purpose of the culture of respiratory secretions from cystic fibrosis (CF) patients is to isolate organisms associated with CF pulmonary disease so that appropriate interventions may be taken. Tympanocentesis and culture of the middle ear fluid are valuable tools for definitive diagnosis, guiding therapy, and evaluating treatment failures. In many laboratories in areas of low endemicity, culture‐based testing specifically for Corynebacterium diphtheriae has been discontinued due to the lack of requests and limitations in media shelf life.

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High Rhinovirus Burden in Lower Airways of Children With Cystic Fibrosis

Cited by 75 publications

References 42 publications

Novel antiviral properties of azithromycin in cystic fibrosis airway epithelial cells

Novel antiviral properties of azithromycin in cystic fibrosis airway epithelial cells

Paediatrics in Barcelona

Respiratory Tract Cultures

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