Effects of Viral Lower Respiratory Tract Infection on Lung Function in Infants With Cystic Fibrosis

Hiatt, Peter; Grace, Susan; Kozinetz, Claudia A.; Raboudi, Soufia Helioui; Treece, Denise G.; Taber, Larry H.; Piedra, Pedro A.

doi:10.1542/peds.103.3.619

Cited by 190 publications

(201 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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“…CF mice react with increased inflammation and decreased viral clearance to RSV infection (19). RSV is known to trigger exacerbations of CF lung disease (37)(38)(39) and to facilitate colonization with P. aeruginosa (40). Both cDCs and pDCs are typically activated and increase in number in response to RSV infection (41,42).…”

Section: Discussionmentioning

confidence: 99%

Low Sphingosine-1–Phosphate Impairs Lung Dendritic Cells in Cystic Fibrosis

Krause

Limberis

et al. 2013

Am J Respir Cell Mol Biol

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Dysfunction of the cystic fibrosis transmembrane regulator (CFTR) leads to chronic inflammation and infection of the respiratory tract. The role of CFTR for cells of the pulmonary immune system is only partly understood. The present study analyzes the phenotype and immune stimulatory capacity of lung dendritic cells (DCs) from CFTR knockout (CF) mice. Total numbers of conventional DCs, plasmacytoid DCs, and CD103-positive DCs were lower in CF mice compared with wild-type (WT) control mice, as was the expression of major histocompatibility complex class II molecules (MHCII), CD40, and CD86. After pulmonary infection with respiratory syncytial virus, DC numbers increased in WT mice but not in CF mice, and the T cellstimulatory capacity of CF DCs was impaired. The culture of CF lung DCs with bronchoalveolar lavage fluid (BALF) from WT mice increased the expression of MHCII, CD40, and CD86. The supplementation of CF BALF with sphingosine-1-phosphate (S1P), a mediator of immune cell migration and activation that is decreased in CF BALF, rescued the reduced expression of MHCII and CD40 in WT lung DCs and human blood DCs. These findings suggest that DCs are impaired in the CF lung, and that altered S1P affects lung DC function. These findings provide a novel link between defective CFTR and pulmonary innate immune dysfunction in CF.

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“…Early studies looking at respiratory viruses in CF relied on repeated serological testing, either alone (Petersen, Hoiby et al 1981) or in combination with viral cultures for viral detection (Wang, Prober et al 1984;Ramsey, Gore et al 1989;Pribble, Black et al 1990;Armstrong, Grimwood et al 1998;Hiatt, Grace et al 1999). These methods are relatively insensitive and more recent studies have utilised PCR based methodologies (Smyth, Smyth et al 1995;Collinson, Nicholson et al 1996;Punch, Syrmis et al 2004;Olesen, Nielsen et al 2006;).…”

Section: Viral Respiratory Infections In Cfmentioning

confidence: 99%

Viral Respiratory Tract Infections in Cystic Fibrosis

Wat¹

2012

Cystic Fibrosis - Renewed Hopes Through Research

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Effects of Viral Lower Respiratory Tract Infection on Lung Function in Infants With Cystic Fibrosis

Abstract: Infants with CF incurring respiratory virus infection are at significant risk for LRTI, for hospitalization, and for deterioration in lung function that persists months after the acute illness.

Cited by 190 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

Low Sphingosine-1–Phosphate Impairs Lung Dendritic Cells in Cystic Fibrosis

Viral Respiratory Tract Infections in Cystic Fibrosis

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