The Breathing Life Lung Centre awarded €3 Million Research grant

Question? Could you confirm details of the recent grant from the European Union and what impact this has made to the new lung centre.

Dr Yiallouros ( Head of the Breathing Life Lung Centre )

'The Breathing Life Lung Centre research focuses on the associations of respiratory diseases with environmental and modern lifestyle changes. In collaboration with colleagues from the Cyprus International Institute and the Harvard School of Public Health we study the effects of particulate matter and other air pollutants on respiratory diseases through assessment of the time trends of hospital admissions and mortality, proximity of children's residence to main roads and power plants. The trends in childhood asthma and allergic sensitization in Cyprus have also been a central focus of our activities. We have been conducting large scale population studies of the relationships between obesity and asthma and systemic and airway inflammation looking how body fat and associated factors such as diet, adipokines, micronutrients, vitamin D are related to severity of asthma, lung function and levels of systemic and airway inflammation. We have also developed an interest in studies of cilia motility and ultra-structure and the epidemiology of primary ciliary dyskinesia in Cyprus and Europe'.

The two most recent awarded research grants were:

a) ''The Relation of Vitamin D Status with Asthma and Atopy in Adolescents in Cyprus''. The project investigated in a cohort of 930 adolescents the effect of modern affluent life style in Cyprus, including increasing obesity, reduced sunlight exposure and compromised vitamin D status on asthma, wheezing, lung function, and allergic sensitization. Dr Yiallouros was the Principal Investigator of the project which ran in period 2010-2012 and was awarded with the amount of 160,000 euros by the Cyprus Research Promotion Foundation. Dr Ourania Kolokotroni, Specialist Paediatrician (MRCPch), worked as a Research Fellow on this project and is now completing her doctoral thesis on the data created by the project.

b) "BESTCILIA - Better Experimental Screening and Treatment for Primary Ciliary Dyskinesia". This project will run for the period 2012-2015 and is funded with 3 million Euros by EU FP7 under the action HEALTH.2012.2.4.4-2 on Observational trials in rare diseases. Dr Yiallouros is the leader of Work Package 3 titled "Introduction of Standardized Diagnostic Testing for PCD in countries with limited health care expenditures" and is funded with 260,000 euros. Mr Panayiotis Kouis, Biologist BSc, MSc, has been employed as a research fellow for this project and is going to develop his doctoral thesis on the data to be created from the project.

A summary of the rationale and aims of the BEST CILIA project is copied below:
Aim: To characterize the clinical course and improve the diagnosis and treatment of Primary Ciliary Dyskinesia (PCD).

Primary Ciliary Dyskinesia1 [OMIM No 244400 (] is a rare, genetically heterogeneous disorder that affects approximately 1 in 20,000 individuals. It results from dysfunction of small hair-like organelles (cilia), which are responsible to clean our upper and lower airways. It causes severe, chronic destructive airway disease with progressive loss of lung function. Additional health burden results from chronic ENT problems impairing hearing. In addition many other organ systems such as the cardiovascular (congenital heart defects) and reproductive system (infertility) can be affected. In a recent survey conducted in more than 1,000 patients in 26 countries throughout Europe, the age at diagnosis and the risk factors for late diagnosis were determined. Adjusted age at diagnosis ranged from 4.8 yrs to 6.8 yrs and strongly correlated with the country's percent of gross national product spent on health. Thus, PCD in children is under-diagnosed and diagnosed too late, particularly in countries with low health expenditures. Disorders of dysmotile cilia have been poorly studied. Due to the lack of evidence-based treatment guidelines, most therapeutic strategies for PCD are derived from protocols and research in other respiratory disorders, notably cystic fibrosis (CF). However, this strategy is unsafe as PCD exhibits a different pathophysiology. Although unproven, clinical experience and observational reports suggest that early diagnosis is important for the preservation of pulmonary function, quality of life and life expectancy; appropriate studies to validate this hypothesis are lacking. Additionally, in rare diseases such as CF, evidence-based guidelines and treatment strategies have been developed, whereas in PCD, neither evidence-based guidelines exist nor have orphan drugs been studied or are available. Accordingly, diagnostic and management strategies for PCD vary widely between and within countries in Europe.

In Europe, there are marked discrepancies between countries in the availability of PCD diagnostic services. Thus, in order to fulfil the aim to improve clinical practice in PCD care, we will generate standard operation procedures (SOPs) and introduce standardized diagnostic testing in countries where this is not available at the moment. In other genetic disorders, the diagnosis can be established using genetics exclusively. However, due to extensive genetic heterogeneity, only ~50% of PCD cases can currently be determined by large-scale DNA sequencing efforts. Thus, additional studies must first identify the majority of genetic defects before this method can be useful as a routine diagnostic tool. In our proposal, we will evaluate the whole spectrum of PCD diagnostics recommended by the ERS PCD task force: nasal NO (nNO) measurement, high speed videomicroscopy (HVM), transmission electron microscopy (TEM) and even high resolution immunofluorescence (IF) microscopy in difficult cases. We therefore will be able to achieve the highest diagnostic standard. Our results will aid the implementation of state-of-the-art diagnostic standards in Europe and the USA. PCD is a rare disease with no orphan drug available. Currently, all treatment is off-label. In order to generate the first evidence-based knowledge, we will conduct a randomized controlled multicentre trial evaluating the effectiveness and adverse events of azithromycin (AZN) as maintenance prophylactic therapy for a period of 6 months because of its potential beneficial properties with respect to anti-infection (covers whole range of bacteria encountered in PCD pulmonary infection), quorum sensing inhibition and anti-inflammation. Particular attention will be given to appropriate outcome measures in this trial: The primary outcome will be the pulmonary exacerbation rate. Secondary outcomes include pulmonary function parameters and PCD-specific quality of life. To this purpose, we will newly develop and validate PCD-specific, age adjusted healthrelated quality of life questionnaires (HRQoLQs). BESTCILIA has been designed in close consultation with patient organizations, notably the Dutch, German, Swiss, Polish and US American patient support groups assuring that the patient perspective is considered in all aspects of our project. The patient organizations are also involved in dissemination activities to ensure recruitment of patients for the registry and the clinical trial, to spread new knowledge and to guarantee the wide and rapid uptake of developed guidelines. PCD is a rare congenital disease manifesting in early childhood and progressing throughout adulthood. Therefore, our proposal will cover both adult and child health aspects.