Respiratory viral infections and interaction with bacteria in children with cystic fibrosis

Abstract

Cystic fibrosis (CF) is one of the most common lethal autosomal recessive disorders in the Caucasian population. Mutations of the cystic fibrosis transregulator membrane gene cause the body to produce thick, sticky mucus. In the lungs this results in obstruction of the airways associated with chronic inflammation, bacterial colonization and recurrent infections of the lungs, which finally leads to irreversible damage and early death . Aggressive treatment of bacterial infections has been one of the most important factors in dramatic improvement of life expectancy in patients with CF. Further improvement of survival in CF might be achieved by focusing on other sources of respiratory infections, such as viruses. Viruses are known to play an important role in the morbidity of other chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). In addition, it is suggested that viral infection might facilitate bacterial infections. Until now, the role of respiratory viral infections and its interaction with bacteria in CF was elucidated only partially. We speculated that respiratory viruses can play an important role in CF lung disease. Although the exposure to viruses is equal in CF patients and controls, the impact of respiratory viruses, even of “common colds”, on clinical symptoms is in CF patients far beyond the virus-related morbidity in healthy controls. We add detailed data that children with CF have prolonged and more severe episodes of lower respiratory tract complaints. Mainly patient-related factors seem to explain the higher susceptibility for respiratory viral infections. New clinical evidence is presented that rhinovirus is detected more frequently and for longer periods in patients with CF. We suggest that a higher viral replication due to an impaired anti-viral defense causes increased viral loads in CF patients. Furthermore, we demonstrate virus-associated bacterial colonization in CF. Virus-related respiratory illnesses are frequently associated with P. aeruginosa acquisition in both children with CF and healthy controls, but lead to persistent infection only in CF. Increased binding of bacteria under influence of viral infection could be one of the mechanisms explaining this phenomenon. We describe that P. aeruginosa binding to epithelial cells is strongly enhanced by RSV infection. In addition, RSV possibly acts as a coupling agent between bacteria and cells and the increased binding can be effectively blocked by heparin. This thesis shows that respiratory viruses play indeed an important role in CF lung disease, either directly or through interaction with bacteria. It adds new data to limited earlier findings concerning the role of respiratory viral infections in CF. Our findings might have important clinical implications. New data in this thesis indicate that it is feasible to detect P. aeruginosa colonization by oropharyngeal cultures at home. This might be helpful in early detection of new bacterial colonization, for example in preventing chronic colonization. Current treatment strategies of pulmonary symptoms in CF are mainly aimed at treating bacterial infections with antibiotics and sputum evacuation. Our results which underline the importance of respiratory viral infections might suggest new therapeutic strategies to further improve prognosis of patients with CF.