Incidence and clinical impact of respiratory viruses in adults with cystic fibrosis

Flight, W.G.; Bright-Thomas, R.J.; Tilston, Peter; Mutton, Kenneth J.; Guiver, Malcolm; Morris, Julie; Webb, A K; Jones, Andrew M.

doi:10.1136/thoraxjnl-2013-204000

Cited by 109 publications

(119 citation statements)

References 31 publications

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“…Because of the difficulties associated with the culture of viruses, clinical virology has already validated multiple molecular techniques such as sputum PCR and DNA sequencing for routine use (33). We have shown that CF sputum DNA isolated using a clinically accredited, automated protocol for respiratory virus diagnosis (20) serves as a clinically valid template for bacterial diversity analysis in CF. Linking of virology diagnostic resources with CF bacteriology should be exploited in future to allow the evaluation of the respiratory microbiome in day-to-day clinical practice.…”

Section: Discussionmentioning

confidence: 99%

“…Sputum specimens for culture-independent analysis were transported within 24 h to the regional virology laboratory in Manchester for processing as described previously (20). After liquefaction and dilution in extraction buffer within a containment level 3 laboratory (a standard precaution against unknown tuberculosis cases within respiratory specimens), sputum samples were processed in an extraction-dedicated containment level 2 laboratory.…”

Section: Methodsmentioning

confidence: 99%

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Rapid Detection of Emerging Pathogens and Loss of Microbial Diversity Associated with Severe Lung Disease in Cystic Fibrosis

et al. 2015

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f Respiratory infection in cystic fibrosis (CF) is polymicrobial, but standard sputum microbiology does not account for the lung microbiome or detect changes in microbial diversity associated with disease. As a clinically applicable CF microbiome surveillance scheme, total sputum nucleic acids isolated by a standard high-throughput robotic method for accredited viral diagnosis were profiled for bacterial diversity using ribosomal intergenic spacer analysis (RISA) PCR. Conventional culture and RISA were performed on 200 paired sputum samples from 93 CF adults; pyrosequencing of the 16S rRNA gene was applied to 59 patients to systematically determine bacterial diversity. Compared to the microbiology data, RISA profiles clustered into two groups: the emerging nonfermenting Gram-negative organisms (eNFGN) and Pseudomonas groups. Patients who were culture positive for Burkholderia, Achromobacter, Stenotrophomonas, and Ralstonia clustered within the eNFGN group. Pseudomonas group RISA profiles were associated with Pseudomonas aeruginosa culture-positive patients. Sequence analysis confirmed the abundance of eNFGN genera and Pseudomonas within these respective groups. Low bacterial diversity was associated with severe lung disease (P < 0.001) and the presence of Burkholderia (P < 0.001). An absence of Streptococcus (P < 0.05) occurred in individuals with lung function in the lowest quartile. In summary, nucleic acids isolated from CF sputum can serve as a single template for both molecular virology and bacteriology, with a RISA PCR rapidly detecting the presence of dominant eNFGN pathogens or P. aeruginosa missed by culture (11% of cases). We provide guidance for how this straightforward CF microbiota profiling scheme may be adopted by clinical laboratories. C ystic fibrosis (CF) is an inherited condition characterized by chronic endobronchial infection leading eventually to respiratory failure (1). Traditional culture-based microbiological techniques readily identify pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus, which are common and typical of CF infection (2). Other CF pathogens, such as Burkholderia cepacia complex and emerging pathogens such as Achromobacter, Stenotrophomonas, Ralstonia, and Pandoraea species, are a challenge for conventional microbiology due to their taxonomic complexity (2). These emerging non-Pseudomonas, nonfermenting Gram-negative (eNFGN) species present multiple problems for people with CF, including innate antibiotic resistance, uncertain pathogenic outcome, and potential for transmission, and are possible contraindicators for subsequent lung transplantation (3).CF therapy has evolved to optimize the prevention and suppression of bacterial infections known to be associated with clinical deterioration, such as P. aeruginosa (4, 5) or B. cepacia complex (6). Recent culture-independent analysis of CF infection revealed the presence of considerable bacterial diversity (collectively known as the CF microbiota) that is not captured by standard culture (7). Facultative and obl...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Rapid Detection of Emerging Pathogens and Loss of Microbial Diversity Associated with Severe Lung Disease in Cystic Fibrosis

et al. 2015

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“…It is estimated that 31-61% of pulmonary exacerbations in CF patients are triggered by respiratory viruses [1,2]. The most predominant viruses exacerbating CF lung disease are human rhinoviruses (RVs), which are detected in up to 70% of virus-induced CF exacerbations [3,4]. There are, to date, only a few therapeutic options to treat or prevent virus-induced CF exacerbations.…”

Section: Introductionmentioning

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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“…Rhinovirus (RV) accounts for the vast majority of virus-associated pulmonary CF exacerbations [5][6][7]. To date, therapeutic options to prevent CF pulmonary deteriorations induced by viruses are rare.…”

Section: Introductionmentioning

confidence: 99%

Vitamin D represses rhinovirus replication in cystic fibrosis cells by inducing LL-37

et al. 2015

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Vitamin D has immunomodulatory properties in the defence against pathogens. Its insufficiency is a widespread feature of cystic fibrosis (CF) patients, which are repeatedly suffering from rhinovirus (RV)-induced pulmonary exacerbations.To investigate whether vitamin D has antiviral activity, primary bronchial epithelial cells from CF children were pre-treated with vitamin D and infected with RV16. Antiviral and anti-inflammatory activity of vitamin D was assessed. RV and LL-37 levels were measured in bronchoalveolar lavage (BAL) of CF children infected with RV.Vitamin D reduced RV16 load in a dose-dependent manner in CF cells (

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Incidence and clinical impact of respiratory viruses in adults with cystic fibrosis

Cited by 109 publications

References 31 publications

Rapid Detection of Emerging Pathogens and Loss of Microbial Diversity Associated with Severe Lung Disease in Cystic Fibrosis

Rapid Detection of Emerging Pathogens and Loss of Microbial Diversity Associated with Severe Lung Disease in Cystic Fibrosis

Novel antiviral properties of azithromycin in cystic fibrosis airway epithelial cells

Vitamin D represses rhinovirus replication in cystic fibrosis cells by inducing LL-37

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