Research can help in the development of tests to estimate the evolution of the disease, the biggest cause of hospital admission in the first year of life
Research carried out at Unicamp identified genetic factors associated with the severity of acute viral bronchiolitis. The study, supported by FAPESP, has results published in the March 1st edition of the magazine Gene.
“Detecting genetic associations in cases of acute viral bronchiolitis is the first step towards developing tests capable of identifying the possible clinical outcome of each patient diagnosed with the disease shortly after entering the emergency room,” he said. Fernando Augusto de Lima Marson, researcher at the Faculty of Medical Sciences (FCM) at Unicamp and one of the authors of the article.
The study coordinator, Professor José Dirceu Ribeiro, also from FCM-Unicamp, highlights that there are several risk factors that promote the onset of acute viral bronchiolitis, such as prematurity, history of lung disease and passive smoking. “On the other hand, there is a very relevant percentage of patients who do not fit into any risk factor. The question is to explain, in these cases, the evolution of the disease to its most serious form,” he said.
The new study sought to relate genetic factors to the most serious forms of acute viral bronchiolitis in patients who are not in risk groups.
Ribeiro recalls that the disease is the most common in the first year of life and also the biggest cause of hospital admissions during this period worldwide. It is an infection of the respiratory tract that particularly affects the bronchioles.
In most cases, acute viral bronchiolitis is mild and without major consequences. Still, between 1% and 3% of patients require hospitalization. Of these, some patients will require oxygen inhalation. Even fewer will go to the intensive care unit to receive mechanical ventilation.
To investigate the existence of possible genetic factors that influence the severity of cases, researchers studied 181 children who were admitted over two years to three hospitals in the Campinas region. They were diagnosed with acute viral bronchiolitis and all had to receive oxygen. The screening was carried out at the Unicamp, State of Sumaré and Vera Cruz hospitals.
First, samples of secretion were collected from the nose to determine the type of virus causing acute bronchiolitis in each of them. As expected, most cases were caused by respiratory syncytial virus (RSV). More specifically, RSV infection accounted for 69,9% of patients, while 26,5% were rhinovirus infections, the second main cause.
At the same time, the researchers carried out an assessment of the 181 children to find out which ones fell into one or more risk groups for acute viral bronchiolitis. The results of the screening were revealing. 131 children (or 72% of the total) were not part of any risk group.
Molecular biology and statistical techniques were used to study and compare the patients' DNA. The search was for specific genetic markers, in particular the identification of variations in the DNA sequence called single nucleotide polymorphisms (known by the acronym in English SNP). SNPs constitute 90% of all variations in the human genome.
By working the data statistically, the prognoses of the disease were compared between patients and the frequency of polymorphisms was compared between them and also with a control group, made up of 536 healthy people (between 19 and 26 years old), invited randomly and with no history of lung diseases.
The frequencies of polymorphisms in patients for each type of virus were also analyzed, such as RSV subtypes A and B and rhinovirus, as well as possible cases of viral co-detection identified.
“Our study focused on genetic factors that could be associated with the severity of acute viral bronchiolitis. We showed that there is a relationship between the patient's genetic predisposition and the severity of the disease. To our knowledge, this is the first study worldwide to show this in this level of detail, including a large number of genetic variants,” said Marson.
Some genes are in fact associated with the presence of specific viruses that cause the disease. Unicamp researchers observed the association between the SNP rs2107538*CCL5 and bronchiolitis caused by RSV and RSV subtype A viruses and between the SNP rs1060826*NOS2 and bronchiolitis caused by rhinovirus.
“The SNPs rs4986790*TLR4, rs1898830*TLR2 and rs2228570*VDR were associated with very serious cases of the disease, those that progressed to death. rs7656411*TLR2 was associated with the need for oxygen inhalation, as well as rs352162*TLR9, rs187084*TLR9 and rs2280788*CCL5 were associated with cases requiring admission to an intensive care unit. Finally, rs1927911*TLR4, rs352162*TLR9 and rs2107538*CCL5 were associated with patients requiring mechanical ventilation,” said Marson.
The study authors highlight that the results need to be replicated by other research groups. Even so, they consider the results to be quite encouraging.
“Medicine is moving towards developing therapies tailored to each patient. In this sense, the identification of SNPs associated with the disease can represent a target for genetic therapies, creating treatments and management for precision and preventive medicine, respectively”, said Marson.
ARTICLE
The article Association between single nucleotide polymorphisms in TLR4, TLR2, TLR9, VDR, NOS2 and CCL5 genes with acute viral bronchiolitis (doi: https://doi.org/10.1016/j.gene.2017.12.022), by Alfonso Eduardo Alvarez, Fernando Augusto Lima Marson, Carmen Sílvia Bertuzzo, Juliana Cristina Santiago Bastos, Emilio Carlos Elias Baracat, Marcelo Barciel Brandão, Antônia Teresinha Tresoldi, Mariana Tresoldi das Neves Romaneli, Celize Cruz Bresciani Almeida, Therezinha de Oliveira, Patricia Godano Schlodtmann, Ester Corrêa, Maria Luísa Ferreira de Miranda, Marcelo Conrado dos Reis, José Vicente De Pieri, Clarice Weis Arns and José Dirceu Ribeiro, is published in www.sciencedirect.com/science/article/pii/S0378111917310752.