**6. Conclusion**

*B*, including *avian flu H5N1* and *swine flu H1N1*. However, Amantadine still has a role in dealing with Oseltamivir-resistant H1N1 virus. In children and adults, early initiation of neuramini‐ dase inhibitors within 48 hours of the onset of symptoms can reduce the duration of flulike symptoms by 0.5 to 2.5 days [93]. Early use of these medications can also reduce development of complications such as pneumonia [94]. The 2009 pandemic *H1N1* virus remains susceptible to neuraminidase inhibitors, and Oseltamivir has been used extensively for treatment related to this viral infection. Resistance to Oseltamivir has been reported with *H1N1* viral infection but this is mainly restricted to immunocompromised individuals [95]. Zanamivir has a poor oral bioavailability, and intranasal application has been shown to be effective in treating experimental *influenz*a infection with the reduction in symptoms caused, virus shedding and development of otitis media [96]. Intravenous use of Peramivir or Zanamivir could be lifesaving in critically ill patients with *influenza* infection [97, 98]. However, currently the Cochrane database of systematic reviews does not recommend the routine use of neuraminidase inhibitors in influenza infection in CF because of the absence of high level evidence for the

Ribavarin, a synthetic guanosine nucleoside that has a broad spectrum of anti-viral activity, has been used for treatment of infections related to *RSV*, *metapneumovirus, and parainfluen‐ za and influenza viruses* [100]. Potential benefits of ribavarin therapy include the inhibition of RSV-specific IgE production in nasal secretions, which has been associated with the development of hypoxaemia and wheezing [101] and it has improved pulmonary func‐ tions [102]. Controlled studies also show that the use of ribavarin is effective in reducing the clinical severity score, duration of mechanical ventilation, supplemental oxygen use and days of hospitalisation [103]. Aerosolised ribavarin has been used for the treatment of *RSV*-related bronchiolitis and pneumonia. Intravenous formulation could be used for treatment of severe pneumonia, caused by infection *RSV*, *metapneumovirus*, *or parainfluen‐ za virus*, on the basis of experience in immunocompromised patients [104]. Bonney et al. have shown that *metapneumovirus* can be successfully treated with a combination of

Although *rhinovirus* is the major cause of colds, its vast amount of serotypes has made development of anti-virals against it problematic. A 90% of *rhinovirus* serotypes gain entry into epithelial cells using ICAM-1 cellular receptors, and blockade of these receptors in experi‐ mental studies has shown reduced infection severity [106], but further study is required before this treatment option becomes widely available. Macrolide antibiotics, Bafilomycin A1 and Erythromycin have been shown to inhibit ICAM-1 epithelial expression and hypotheses about their potential as anti-inflammatory agents have yet to be definitive, as clinical proof is either

Recently, an anti-rhinoviral agent known as Plecoranil, which acts by inhibiting the uncoating of Picornaviruses [108], the RV 3C protease inhibitor, Ruprintrivir[109] and soluble ICAM-1, Tremacamra[106] have shown promising results in early-stage clinical trials, but each of these medications was derailed by a combination of cost, pharmacokinetics, toxicity, drug interac‐

effectiveness of these interventions [99].

158 Cystic Fibrosis in the Light of New Research

intravenous ribavarin and immunoglobulin [105].

negative or inconclusive [107].

tions, and limited efficacy [110].

As we become increasingly knowledgeable about the impact of respiratory virus infections in the context of CF exacerbations, screening for respiratory viruses should be part of the routine investigations for any CF patients that present with exacerbation symptoms. Using the appropriate sampling method in conjunction with sensitive and specific diagnostic technology will enable us to make appropriate clinical decisions surrounding the use of anti-virals and antibiotics.

Gaining further understanding in the pathogenesis of virus-induced respiratory exacerbations in CF may allow the development of new therapeutic techniques. If viral infection does predispose to bacterial infection, then influencing the interaction between viruses and bacteria could be a next pathway to diminish respiratory morbidity in patients with CF. The develop‐ ment of novel therapies will be exciting and this may improve their quality of life and prolong the lifespan of patients with CF.

However, there are still a number of research dilemmas that remain unanswered:


Further understanding in the pathogenesis of viral infection in CF would be beneficial as this may provide insight to the above unresolved mysteries. At the moment, *influenza* vaccination and the use of neuraminidase inhibitors remain the only evidence based practice, albeit weak for the management of viral infections in CF.
