Viral Respiratory Tract Infections in Cystic Fibrosis

IntroductionCystic Fibrosis (CF) is the most commonly inherited potentially lethal disease amongst Caucasian children and young adults.In Europe, approximately 35,000 children and adults are affected by CF.The prevalence in the US and in Canada is approximately 30,000 and 3,000, respectively.CF is an autosomal recessive disorder and is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) (Riordan, Rommens et al. 1989).The main function of CFTR in many tissues is to regulate and participate in the transport of chloride ions across epithelial cell membranes.To date, more than 1,800 mutations have been described in this gene, but the most common mutation worldwide is caused by deletion of phenylalanine at position 508 (Delta F508) of the CFTR on chromosome 7.The dramatic improvement in survival from CF has taken great strides over the past 40 years with the introduction of specialist centre care, optimising nutritional status and preventing pulmonary inflammation.The median survival of children born in the 1990s is estimated to exceed 40 years of age with more than 85% of them achieving adulthood.CF is a multisystem disorder and is characterised by chronic suppurative lung disease and by exocrine pancreatic insufficiency which affects gastrointestinal function and causes restricted growth and maturation.CF also causes obstructive azoospermia and thus male infertility.However, in most individuals with CF the major burden is on the lungs.The absence of CFTR in airway epithelium leads to malfunction of chloride conductance and subsequent airway surface liquid (ASL) volume reduction, mucins are concentrated, the periciliary liquid depleted, and mucous clearance by ciliary and cough dependent mechanisms diminished, which leads to airflow obstruction and eventually bacterial colonisation.Bacteria implicated in the morbidity and mortality of CF include Pseudomonas aeruginosa, Burkholderia cepacia complex, Achromobacter xylosoxidans, Staphylococcus aureus, Haemophilus influenzae, Stenotrophomonas maltophilia and non-tuberculous mycobacteria.However despite the appropriate use of antibiotic therapy, chronic obstructive airway disease continues to develop in patients with CF and is the major cause of morbidity and mortality.However, the use of appropriate antibiotic therapy has had a limited effect in slowing the progression of pulmonary disease.As a result, recent studies have hypothesised that respiratory viral infection may be a contributing factor to pulmonary exacerbations.Respiratory viruses implicated in the respiratory exacerbations of CF include influenza A and www.intechopen.comCystic Fibrosis -Renewed Hopes Through Research 254 B, respiratory syncytial virus (RSV), parainfluenza virus (PIV) types 1 to 4, rhinovirus, metapneumovirus, coronavirus and adenovirus.The role of respiratory viruses in the aetiology of respiratory exacerbations in CF is not fully understood and may have been underestimated as many previous studies have used insensitive techniques to isolate respiratory viruses, therefore undermining their prevalence.New viral detection techniques have further enhanced the awareness of respiratory viral aetiology in CF exacerbations.A recent in vitro study illustrating the interaction of respiratory virus and P. aeruginosa may contribute to the pathogenesis of CF exacerbations.No doubt more work will be required in this area to further understand their relationship so as to allow the development of potential novel treatment.If respiratory viruses do lead to secondary bacterial infection in CF, this may rationalize the treatment of CF in future.Although there are commercially available vaccines and anti-virals for the prevention and treatment of respiratory viral infections, they are mainly limited to influenza viral infection.A number of studies are currently underway looking at the development of new vaccines and anti-virals, hopefully it will not be long before treatment becomes available for different types of respiratory viruses.This chapter will provide an overview on the epidemiology of respiratory viruses in CF, the available detection techniques for viruses and their differences in sensitivities, the clinical implications of viral infection in CF, the interaction between viruses and bacteria, and the management of viral infections.CF is the most commonly inherited, potentially lethal disease amongst Caucasian children and young adults (Mearns 1993).Pathological changes occur in all exocrine glands (Vawter and Shwachman 1979), however, in most individuals with CF the major impact is on the lungs (Oppenheimer and Esterly 1975).Chronic lung infections may start very early in the lives of patients with CF.It has been hypothesised that impaired mucociliary clearance and low airway surface liquid (ASL) volume is pivotal for the pathogenesis of lung infections.These in turn lead to impaired bacterial clearance from respiratory epithelial cells (Saiman and Siegel 2004).Pulmonary infections remain to be the greatest cause of morbidity and mortality leading to premature death in CF (Rajan and Saiman 2002).The incidence of CF in the United Kingdom is around 1 in 2500 live births and 1 in 25 of the population carry a mutation in their CF genes (Dodge, Morison et al. 1993).CF is a multisystem disorder and is characterised by chronic suppurative lung disease and by exocrine pancreatic insufficiency which affects gastrointestinal function and causes restricted growth and maturation.CF also causes obstructive azoospermia and thus male infertility.CF is an autosomal recessive disorder and is caused by mutations in the CFTR (Riordan, Rommens et al. 1989).The main function of CFTR in many tissues is to regulate and participate in the transport of chloride ions across epithelial cell membranes (Barasch and al-Awqati 1993).So far more than 1,800 mutations have been described in this gene (http://genet.sickkids.on.ca/cgi-bin/WebObjects/MUTATION), but the most common mutation worldwide is caused by deletion of phenylalanine at position 508 (Delta F508) of the CFTR on chromosome 7. www.intechopen.com How to referenceIn order to correctly reference this scholarly work, feel free to copy and paste the following: Dennis Wat (2012).Viral Respiratory Tract Infections in Cystic Fibrosis, Cystic Fibrosis -Renewed Hopes Through Research, Dr. Dinesh Sriramulu (Ed.),

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