Renato Tetelbom Stein

Risk factors for Pseudomonas aeruginosa colonization in cystic fibrosis patients.

In an attempt to study the association between Pseudomonas aeruginosa colonization and clinical factors present before colonization, we studied 502 patients who attended our cystic fibrosis (CF) clinic between 1975 and 1988 and who were not colonized with P. aeruginosa before the study period. Twelve percent of the patients became colonized with P. aeruginosa before the age of 1 year and 44% by the age of 7 years. In a birth cohort followed from diagnosis during the study period, 23% were colonized with P. aeruginosa before age 1 year and 67% before age 7 years. Early P. aeruginosa colonization was associated with early diagnosis of CF. Presence of meconium ileus, gastrointestinal symptoms and pancreatic insufficiency at the time of diagnosis was also associated with early colonization. There was no association between the presence of respiratory symptoms at the time of diagnosis and age at first P. aeruginosa colonization. In families in which more than one sibling had CF, the age of P. aeruginosa acquisition was similar in the first colonized and the subsequently colonized siblings. In the year before the colonization patients with P. aeruginosa who were older than 1 year had higher rates of hospitalization and spent more days in hospital compared with patients without P. aeruginosa. In conclusion most P. aeruginosa colonization occurs at a younger age than previously reported. Early age at diagnosis and presence of CF-associated gastrointestinal abnormalities increase the likelihood of earlier colonization of P. aeruginosa.

The burden of single virus and viral coinfections on severe lower respiratory tract infections among preterm infants: a prospective birth cohort study in Brazil.

Background: Respiratory syncytial virus (RSV) is associated with severe lower respiratory tract infection (LRTI), especially in preterm infants. Other viruses, co-detected with RSV, may play a role in the severity of respiratory outcomes. Methods: This prospective epidemiologic study of severe LRTI incidence among children born ⩽35 weeks gestational age at 3 sites in Brazil (2008–2010) followed a birth cohort for 1 year post-enrollment. Nasal washes from subjects with LRTI were tested for respiratory viruses using polymerase chain reaction. The primary outcome was the incidence of severe LRTI requiring hospitalization associated with RSV infection. Secondary outcomes included identification of viruses associated with LRTI, alone or coinfections, and risk factors associated with severe LRTI. Results: Among 303 subjects, 176 (58.1%) experienced LRTI. Among these subjects, 162 had samples tested using polymerase chain reaction; 27.8% (45/162) experienced severe LRTI. More subjects with severe LRTI were infected with RSV (30/45, 66.7%) than with other viruses. RSV was present in 33.1% (143/432) of LRTI events tested, 57.3% (82/143) were coinfections. RSV was the virus most frequently associated with severe LRTIs (34/56 events, 60.7%); 50% (17/34 events) single and 50% coinfections. Significantly longer hospital stays were associated with LRTI events involving RSV coinfections compared with RSV single infections (P = 0.012). Infants with severe LRTIs had significantly lower mean RSV-IgG levels at study entry compared with those with nonsevere or no LRTIs (P < 0.05). Conclusions: This study confirms the association of RSV alone or as a coinfection with severe LRTI and reinforces the importance of providing adequate prophylaxis for susceptible infants.

A Network Flow Approach to Predict Protein Targets and Flavonoid Backbones to Treat Respiratory Syncytial Virus Infection

Background. Respiratory syncytial virus (RSV) infection is the major cause of respiratory disease in lower respiratory tract in infants and young children. Attempts to develop effective vaccines or pharmacological treatments to inhibit RSV infection without undesired effects on human health have been unsuccessful. However, RSV infection has been reported to be affected by flavonoids. The mechanisms underlying viral inhibition induced by these compounds are largely unknown, making the development of new drugs difficult. Methods. To understand the mechanisms induced by flavonoids to inhibit RSV infection, a systems pharmacology-based study was performed using microarray data from primary culture of human bronchial cells infected by RSV, together with compound-proteomic interaction data available for Homo sapiens. Results. After an initial evaluation of 26 flavonoids, 5 compounds (resveratrol, quercetin, myricetin, apigenin, and tricetin) were identified through topological analysis of a major chemical-protein (CP) and protein-protein interacting (PPI) network. In a nonclustered form, these flavonoids regulate directly the activity of two protein bottlenecks involved in inflammation and apoptosis. Conclusions. Our findings may potentially help uncovering mechanisms of action of early RSV infection and provide chemical backbones and their protein targets in the difficult quest to develop new effective drugs.