MINI-SYMPOSIUM: RESPIRATORY VIRUSES – PART IIRespiratory virus infections in cystic fibrosis
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INTRODUCTION
Cystic fibrosis (CF) is the most common lethal inherited disorder in Caucasian populations. In the UK, the incidence of CF is around one in 2500 live births, with one in 25 of the general population carrying a CF gene mutation.1 It is also the most frequent cause of chronic suppurative lung disease and gastrointestinal disease in children and young adults of Caucasian descent. It is an autosomal-recessive disease caused by mutations of a gene located on the long arm of chromosome 7.2 The gene
EPIDEMIOLOGY OF RESPIRATORY VIRUSES
The relationship between respiratory viral infection and asthma has long been recognised. It is estimated that 85% of asthma attacks in children11 and 44% in adults12 in the community are caused by respiratory viral infections. The relationship between respiratory virus infection and CF is less clear, although this is probably due to only a few prospective studies having been reported.13., 14., 15., 16., 17., 18. Most studies have been hampered by a limited use of control subjects and the lack
ROLE OF RESPIRATORY VIRUSES IN CYSTIC FIBROSIS
The impact of respiratory viral infections in patients with CF is far greater than in healthy individuals, being associated with prolonged hospitalisations.7 Although the lungs are normal at birth, altered airway clearance with viscous respiratory secretions, airway plugging, inflammation and increased bronchial tone further predispose to infections.
Only a handful of studies have prospectively assessed the impact of respiratory virus infections in exacerbations of CF, and they have shown
DETECTION OF RESPIRATORY VIRUSES
Viruses possess either RNA or DNA, but not both. It is therefore essential to know the structure of each individual respiratory virus in order to develop molecular techniques identifying nucleic acid (Table 1). PCR is now a widely used technique for the detection of viruses. It is more sensitive than the conventional culture and microscopy method. The latter requires 106 virions to be present in a sample and is more time consuming, taking up to 2–3 weeks for positive isolations. It is therefore
VIRAL RESPIRATORY INFECTIONS IN CYSTIC FIBROSIS
Early studies relied on repeated serological testing, either alone15 or in combination with viral isolation.13., 17., 18., 27., 30. These methods are relatively insensitive and more recent studies have utilised PCR-based methodologies, albeit only to picornaviruses.14., 18. There are also likely to be differences in the populations studied as the prognosis for CF has improved with each successive birth cohort.
It is now nearly 20 years since Wang et al.27 described the relationship between
BACTERIAL AND VIRAL INTERACTION IN CYSTIC FIBROSIS
Of potentially greater significance is the observation that initial bacterial infections might be facilitated by respiratory viral infections, in particular RSV.7., 15. In a 25-year retrospective review from the Danish CF clinic, first isolation of P. aeruginosa was most likely between October and March,31 the peak of the RSV season. These findings must be cautioned by design of the study and there are a number of other possible agents that would broadly fit the RSV season, notably influenza
PREVENTION AND TREATMENT OF RESPIRATORY VIRUSES
Therapeutic measures to prevent or treat respiratory viral infections in CF include vaccination, specific antiviral antibodies and antiviral agents. There is greatest experience with influenza vaccine, yet there is no evidence from randomised studies that influenza vaccine given to patients with CF is beneficial.43 Palivizumab, a mouse-human IgG monoclonal antibody preparation, has been shown to reduce the rate of RSV-associated hospitalisation in premature infants.44 The results of an ongoing
SUMMARY
Respiratory virus infections have pronounced and long-lasting effects on patients with CF, resulting in significant declines in FVC, FEV1 and Shwachman score, significantly increasing both the frequency and the duration of hospitalisation. Deleterious effects on patients with CF have been reported for most viruses studied but the effects of RSV and influenza appear the greatest. There is a body of circumstantial evidence to suggest that respiratory virus infections may facilitate bacterial
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Cited by (40)
High prevalence of Merkel cell polyomavirus is associated with dysregulation in transcript levels of TLR9 and type I IFNs in a large cohort of CF patients from the Italian (Lazio) reference center for cystic fibrosis
2022, Microbial PathogenesisCitation Excerpt :Beside the role as respiratory pathogen, MCPyV infection in the respiratory tract mucosal cells may cause a dysregulation in the innate immune sensing and response to other microorganisms. The impact of respiratory viruses has been only recently recognized in CF patients [38]. Increased respiratory symptoms, decline of respiratory function, higher frequency and duration of hospitalization have been reported in CF for HRV, RSV and Influenza A/B viruses [39,40]; however microbiological and clinical implication of respiratory viruses in CF remains still a poorly understood issue.
Pseudomonas aeruginosa Cif protein enhances the ubiquitination and proteasomal degradation of the transporter associated with antigen processing (TAP) and reduces major histocompatibility complex (MHC) class I antigen presentation
2014, Journal of Biological ChemistryCitation Excerpt :Accordingly, we suggest these combined actions of the P. aeruginosa Cif virulence factor promote the establishment of polymicrobial infections in the lungs of patients with cystic fibrosis, chronic obstructive pulmonary disease, and bronchiectasis and provide a novel explanation for the clinical observation that patients infected with P. aeruginosa who acquire a viral infection have a higher viral load and a longer duration of viral infection than patients who are not simultaneously infected with P. aeruginosa (5, 62–65).