RICERCA ITALIANA     

Non-invasive methods to assess biological and mechanistic bases of respiratory diseases: clinical and epidemiological applications.

Università degli Studi di Parma

Abstract

Respiratory disorders are a leading cause of death worldwide, and further increase in mortality is expected in the near future. In Europe, respiratory diseases rank second (after cardiovascular diseases) in terms of mortality, incidence, prevalence and costs. Whereas there has been a substantial reduction of infective lung diseases, such as tuberculosis and pneumonia, over the last decades there has been a progressive increase of inflammatory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Chronic respiratory disorders, particularly asthma and COPD are becoming a leading medical problem worldwide.
The concept that inflammation leads to bronchial hyper-responsiveness, airflow limitation and mucus hypersecretion in chronic pulmonary diseases, especially asthma and chronic obstructive pulmonary disease (COPD) has led to a widening search for the types of inflammatory cells and mediators that are responsible for the cascade of events linking the initial stimulus to the final abnormality in airway function.
In the last few years, such non invasive techniques as induced sputum analysis and exhaled nitric oxide (NO) measurement have been successfully introduced in the evaluation of asthma and COPD. Recently, analysis of exhaled breath condensate (EBC) has been introduced among the techniques to evaluate airways inflammation. EBC is very easy to perform, non-invasive, can be repeated within short period of time also in ventilated subjects >>>

Principal Investigator

Antonio MUTTI Università degli Studi di PARMA

Research Objectives

Relying on the collaboration of researchers with different background (Occupational Medicine, Respiratory Medicine, Toxicology, Industrial Hygiene), the present research project is aimed at:

a) validation of inflammatory and/or oxidative stress biomarkers present in EBC, both by intra assay evaluation (reproducibility, sensitivity and accuracy) and by their correlation with clinical and functional parameters. Both diagnostic and prognostic validity of EBC analysis in lung diseases will be assessed, particularly for those mediators known to be specific for asthma and COPD and sensitive to inflammatory changes;

b) validation of noninvasive methods (exhaled air and EBC collection) applicable to the study of lung response in subjects with asthma and COPD, either at steady state and after inhaled stimula with allergens and pollutants;

c) development of noninvasive methods to assess target tissue dose and early lung events in healthy subjects exposed to pneumotoxic substances;

d) comparison between biological results obtained by EBC analysis and those obtained by standard techniques (induced sputum analysis and exhaled NO measurement) as well as by clinical-functional parameters;

e) application of the most sensitive, selective and specific reference analytical techniques (LC-MS/MS, GC-MS, ICP-MS) for a better understanding of molecular mechanisms leading to lung damage.

Timescale

24 months

National and international background

Respiratory disorders are a leading cause of death worldwide, and further increase in mortality is expected in the near future. In Europe, respiratory diseases rank second (after cardiovascular diseases) in terms of mortality, incidence, prevalence and costs (1-3). Whereas there has been a substantial reduction of infective lung diseases, such as tuberculosis and pneumonia, over the last decades there has been a progressive increase of inflammatory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Chronic respiratory disorders, particularly asthma and COPD are becoming a leading medical problem worldwide (4).

COPD is the 4th cause of death in the USA, its incidence being increasing despite the decreasing prevalence of smokers. In Italy, an estimated 2.6 million men and women have COPD, and the disease causes around 18 000 deaths each year. In addition to mortality, morbidity from COPD results in substantial use of secondary healthcare resources. The burden of COPD in Italy may be due to the underdiagnosis of the disease by healthcare professionals, particularly in the early stages of the disease, and a lack of awareness among physicians of recommended treatment practices (4).

Undoubtedly, the most important risk factor in the development of COPD is cigarette smoking. The effects of cigarette smoke on the lung are manifold. Cigarette smoke has been found to attract inflammatory cells into the lungs and stimulates the >>>