Kirsi Nuolivirta

IL-10 Gene Polymorphism at -1082 A/G Is Associated With Severe Rhinovirus Bronchiolitis in Infants

We analyzed polymorphisms of IL‐10 −1082 G/A, IL‐18 −137 G/C, TLR4 +896 A/G, and IFNG +874 T/A in 139 infants under 6 months of age hospitalized with bronchiolitis and 400 unselected blood donors. Causative viruses were determined by PCR. Infants with bronchiolitis associated with a virus other than respiratory syncytial virus (N = 18), were more often IL‐10 −1082 allele G non‐carriers, that is, homozygous for allele A (AA) than controls (66.7% vs. 28.0%, P < 0.0001). Infants with RSV bronchiolitis did not differ from controls. This finding suggests a different pathogenic mechanism for RSV bronchiolitis as compared with wheezing associated with other viral infections, for example, rhinovirus in infants under 6 months of age. Pediatr Pulmonol. 2008; 43:391–395.

Toll-like receptor 3 L412F polymorphisms in infants with bronchiolitis and postbronchiolitis wheezing.

Background: Innate immunity receptors play a critical role in host defense. In addition, the expression of Toll-like receptors (TLRs) has been connected to allergy and asthma. Aims: To evaluate the association between the TLR3 L412F polymorphism and viral findings, clinical characteristics and subsequent wheezing in young infants with bronchiolitis. Methods: In all, 129 full-term infants hospitalized for bronchiolitis at age <6 months have been followed-up until the mean age of 1.5 years. Genotyping of the TLR3 L412F gene mutation was made by pyrosequencing. Results: TLR3 L412F gene polymorphism including the minor allele T was overrepresented (52%) in infants hospitalized with bronchiolitis. The presence of the major allele C as homozygous was associated with repeated postbronchiolitis wheezing (7.06, 95% confidence interval 2.30–21.66). Conclusion: Preliminary evidence was found that TLR3 L412F gene polymorphism may be associated with bronchiolitis leading to hospitalization and postbronchiolitis wheezing.

The association of genetic variants in toll-like receptor 2 subfamily with allergy and asthma after hospitalization for bronchiolitis in infancy.

Background: Toll-like receptors (TLRs) are a pivotal part of the innate immunity system. Variations in TLR genes have been connected to autoimmune conditions, such as allergy and asthma. The TLR2 subfamily comprises TLR1, TLR2, TLR6 and TLR 10. We hypothesized that polymorphism of the TLR2 subfamily may be associated with prevalence of post-bronchiolitic asthma and/or atopy. Methods: TLR1rs5743618, TLR2rs5743708 and TLR6rs5743810 single nucleotide polymorphisms of 133 children who had been hospitalized for bronchiolitis at <6 months of age were analyzed. Doctor-diagnosed asthma and atopy as well as their occurrence during the first 6 years of life were evaluated during a follow-up visit. Results: At the mean age of 6.4 years, asthma was present in 17 (13%) patients, there was asthma diagnosis during the first 6 years of life in 39 (29%) and current doctor-diagnosed allergic rhinitis in 57 (43%) patients. Twenty-four (24%) children with G/G genotype in TLR1 rs5743618 were diagnosed to have asthma between 1 and 6 years of age (vs. 13 (38%) of those with G/T or T/T genotypes; P = 0.04). In addition, 11/60 (18%) children with TLR6 rs5743810 C/T versus 36/73 (49%) children of other genotypes had atopic eczema at follow up. Only 2 children (8%) with wild genotype in all investigated single nucleotide polymorphisms had asthma during the first 6 years of life (vs. 30% in those with variant genotype of TLR1, TLR2 and/or TLR6). Conclusion: In this study, we demonstrated that TLR1 rs5743618 was associated with asthma and atopic eczema during the first 6 years of life after early bronchiolitis. In addition, TLR6 rs5743810 was associated with present atopy at preschool age.

Finnish guidelines for the treatment of laryngitis, wheezing bronchitis and bronchiolitis in children.

Evidence‐based guidelines are needed to harmonise and improve the diagnostics and treatment of childrens lower respiratory tract infections. Following a professional literature search, an interdisciplinary working group evaluated and graded the available evidence and constructed guidelines for treating laryngitis, bronchitis, wheezing bronchitis and bronchiolitis.

Human parechovirus type 3 and 4 associated with severe infections in young children.

Background: The symptoms observed in children with human parechovirus (HPeV) infection vary widely from asymptomatic or mild gastrointestinal infections to more severe central nervous system infections and sepsis-like disease. Many of the disease associations are, however, only suggestive. In this study, we examined the connection between HPeV and acute otitis media, lower respiratory infections and suspected central nervous system infections. Methods: An HPeV specific real-time reverese transcriptase polymerase chain reaction was used to detect HPeV RNA. We analyzed altogether 200 middle-ear fluid samples, 192 nasopharyngeal aspirates, 79 cerebrospinal fluid specimens and 50 serum and 5 fecal or fecal culture samples. Positive samples were typed by sequencing the VP1 region. Results: Seven (8%) of 85 children with suspected central nervous system infections were positive for HPeV. Of these, 4 (all in autumn 2012 and from children <3 months of age) were typed to be HPeV4, whereas 1 child had HPeV3. HPeV4 was detected from stool, serum and cerebrospinal fluid. The children with acute otitis media tested HPeV positive in 2.5% episodes. In the lower respiratory cases, HPeV was absent. Conclusions: The findings reported in this study suggest that HPeV4 can cause sepsis-like disease in young infants and be present in cerebrospinal fluid. Furthermore, this report shows that HPeV findings in children with more severe symptoms occur also in Finland.

Mannose-Binding Lectin Gene Polymorphisms in Infants with Bronchiolitis and Post-Bronchiolitis Wheezing

BACKGROUND Mannose-binding lectin (MBL) encoded by the MBL2 gene, is an important component of the innate immunity. Low levels have been linked with respiratory infections and both high and low levels with allergy and asthma. The aims of the study were to evaluate the connection between polymorphisms of the MBL2 gene and viral findings, clinical characteristics and subsequent wheezing in young infants with bronchiolitis. METHODS In all, 129 full-term infants hospitalized for bronchiolitis at age less than 6 months have been followed-up until the mean age of 1.5 years. The genotyping of the MBL2 gene mutations was made by pyrosequencing for a simultaneous detection of three single nucleotide polymorphisms (SNP). RESULTS The MBL genotypes or allele frequencies had no significant associations with clinical characteristics of bronchiolitis. The 41 children with variant genotypes were more often infected by multiple viruses (21.9%, p = 0.047) than children with wild-type A/A genotypes (9.1%). In addition, more children with variant genotypes (31.7%, p = 0.016) had used corticosteroids because of post-bronchiolitis wheezing, compared to those with wild-type A/A genotypes (13.6%). No other significant associations with viral findings or post-bronchiolitis outcomes were found. CONCLUSIONS Preliminary evidence was found that the variant non-A/A genotypes may be associated with susceptibility to multiple viral infections and more severe post-bronchiolitis wheezing requiring treatment with corticosteroids.

Lung function by impulse oscillometry at age 5–7 years after bronchiolitis at age 0–6 months

Viral bronchiolitis in infancy has been associated with increased bronchial reactivity and reduced lung function in later childhood and even in adulthood. However, lung function at preschool age is less studied, mainly due to technical difficulties. The purpose of the study was to evaluate lung function and bronchial reactivity at preschool age in children who were hospitalized for bronchiolitis in early infancy.

Polymorphism of the rs1800896 IL10 promoter gene protects children from post-bronchiolitis asthma.

Viral bronchiolitis is a major cause of hospitalization in infancy, with increased asthma risk in later childhood. However, the principal mechanisms behind post‐bronchiolitic asthma have remained unclear. Previously, different cytokine polymorphisms have been associated with asthma occurrence, but no previous follow‐up study has investigated cytokine polymorphisms in relation to post‐bronchiolitic asthma.

Association of MBL2 polymorphism with asthma after bronchiolitis in infancy.

Background:  Mannose‐binding lectin (MBL) is a component of innate immunity and has been linked with the pathogenesis of asthma. The aim of the present study was to evaluate the association of MBL genotypes with preschool asthma and allergy in children with bronchiolitis in early infancy.

Weight gain in infancy and post‐bronchiolitis wheezing

Aim:  Low birth weight, high birth weight and excessive weight gain after birth may be risk factors for asthma in childhood, but their associations with wheezing in early childhood are poorly studied. The aim of the study was to evaluate birth weight, weight gain in early infancy and overweight in infancy assessed by weight for length (WFL) as risk factors for wheezing after hospitalization for bronchiolitis in early infancy.