We acknowledge some study limitations First even though diff

We acknowledge some study limitations. First, even though different studies seem to be tipping toward the immune boosting hypothesis, there are also negative reports and the issue remains not yet definitely settled (Ogunjimi et al., 2013). In our study we have considered a broad range of biologically plausible scenarios, inevitable leading to a broad range of potential outcomes. Second, due to lack of data on breakthrough infection after two vaccine doses and on possible waning of immunity, the model could not be parameterised including these possible vaccine imperfections. Third, we assume that reactivation of vaccine virus occurs at the same rate as for circulating virus. In practice, reactivation after gap junctions is expected to be rarer than after natural infection but the magnitude of this difference remains largely unknown. As a consequence, our scenarios with reactivation of vaccine virus probably represent a worst case scenario with regard to HZ increase after vaccination. Finally, due to lack of information no costs or effects have been included for long-term effects of congenital varicella syndrome.
Conclusions We conclude that cost-effectiveness of varicella vaccination is strongly affected by its impact on HZ, and the time horizon for economic assessment. Although there are reports of increasing HZ incidence in populations with varicella vaccination (Goldman and King, 2013; Kelly et al., 2014), the time since the introduction of vaccination has probably been too short to draw definitive conclusions. Furthermore, evidence on vaccine VZV reactivation on the long-term is still limited (Heininger and Seward, 2006). Therefore, optimal decision-making on varicella vaccination would involve judicious and repeated weighing of the various scenarios as more evidence comes in from countries with vaccination programmes already in place.
Funding
Competing Interests All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.
Authors\' Contributions
Acknowledgements
Introduction Lung diseases pose one of the leading causes of death worldwide (World Health Organization, 2011). A large fraction of those mortality numbers is represented by chronic obstructive pulmonary disease (Zvezdin et al., 2009), of which lung emphysema is a common component. The disease is associated with inflammatory processes in lung tissue caused most commonly by smoking. In consequence, the alveolar walls necessary for gas exchange in the blood are destroyed, resulting in enlarged distal air spaces and consequently deteriorated lung function and decreased quality of life (Ley-Zaporozhan et al., 2008). Pulmonary fibrosis can be idiopathic or caused by inhalation of pollutants, infection, or adverse reactions to drugs (Bourke, 2006). In the course of this interstitial lung disease normal parenchyma is gradually replaced by connective tissue (scarring), resulting in a restricted lung and impaired gas exchange (King, 2005). The sensitivity and specificity of conventional x-ray projection radiography in diagnosing those disorders is low for mild to moderate stages (King, 2005; Washko, 2010), and lung function testing is still gold standard, while direct assessment of the microstructural changes and disease progression is only available via invasive biopsy. Attenuation-based high-resolution computed tomography (HRCT) serves for improved emphysema and fibrosis imaging, also providing information about the three-dimensional regional distribution of the disease necessary for lung volume reduction surgery (Washko et al., 2008; Criner and Mamary, 2010), but its use is limited due to the required substantial radiation dose (Washko, 2010).