[Show abstract][Hide abstract] ABSTRACT: Aim:
Toll-like receptors (TLR) play a crucial role in innate immunity, protecting the host from pathogens such as viruses. Genetic variations in TLRs have been associated with the severity of viral bronchiolitis in infancy and with the later occurrence of post-bronchiolitis asthma. The aim of the present study was to evaluate if there are any exploratory associations between TLR gene polymorphisms and lung function at 5 to 7 years of age in former bronchiolitis patients.
We performed impulse oscillometry (IOS) at the median age of 6.3 years for 103 children who had been hospitalized for bronchiolitis at less than six months of age. The main parameters evaluated were airway resistance and reactance at 5Hz in baseline and post-exercise measurements. Data on single nucleotide polymorphisms (SNP) of TLR1 rs5743618, TLR2 rs5743708, TLR6 rs5743810 and TLR10 rs4129009 (TLR2 subfamily) and TLR3 rs3775291, TLR4 rs4986790, TLR7 rs179008, TLR8 rs2407992 and TLR 9 rs187084 were available for analyses.
The TLR4 rs4986790 wild genotype A/A was associated with a greater Rrs5 response (0.72 vs. -0.42, p = 0.03) to exercise. In TLR6 rs5743810, the minor allele T was associated with greater Rrs5 response (0.80 vs. -0.03, p = 0.04) to exercise. In TLR7 rs179008, the major allele A was associated with baseline decline in dRrs/df (-1.03 vs 0.61, p = 0.01) and increased Fres (2.28 vs. 0.89, p = 0.01) in girls.
Among the nine studied TLRs, only TLR7 rs179008 showed some exploratory associations with post-bronchiolitis lung function deficiency, and polymorphisms of TLR4 rs4986790, and TLR6 rs5743810 in particular, with airway reactivity. These findings call for further confirmatory studies.
[Show abstract][Hide abstract] ABSTRACT: In 169 Finnish infants hospitalized for bronchiolitis at age <6 months in 2008-2010, nasopharyngeal aspirates were tested by PCR for Bordetella pertussis and 16 viruses. Respiratory viruses were detected in 89% (71% with RSV), but no infant had B. pertussis. The latter finding may reflect a positive effect from the broadening of the Finnish pertussis vaccination program in 2005.
No preview · Article · Nov 2015 · The Pediatric Infectious Disease Journal
[Show abstract][Hide abstract] ABSTRACT: Aim:
Interleukin-10 (IL-10) has been associated with wheezing and asthma in children and the genetic variation of the IL-10 cytokine production may be linked to post-bronchiolitis lung function. We used impulse oscillometry (IOS) to evaluate the associations of IL10 polymorphisms with lung function at a median age of 6.3 years in children hospitalised for bronchiolitis before six months of age.
We performed baseline and post-exercise IOS on 103 former bronchiolitis patients. Data on single nucleotide polymorphisms (SNP) of IL10 rs1800896 (-1082G/A), rs1800871 (-819C/T), rs1800872 (-592C/A) were available for 99 children and of IL10 rs1800890 (-3575T/A) for 98 children.
IL10 rs1800896, rs1800871 and rs1800872 combined genotype AA+CT+CA and carriage of haplotype ATA, respectively, were associated with higher resistance and lower reactance in baseline IOS in adjusted analyses. At IL10 rs1800890, the A/A-genotype and carriers of A-allele were associated with lower reactance in baseline IOS. There were no significant associations between the studied SNPs and airway hyper-reactivity to exercise.
Low-IL-10-producing polymorphisms in the IL-10 encoding gene were associated with obstructive lung function parameters, suggesting an important role for IL-10 in development of lung function deficit in early bronchiolitis patients.
[Show abstract][Hide abstract] ABSTRACT: Objective:
To determine whether hospital length-of-stay (LOS) for bronchiolitis is influenced by the causative virus: respiratory syncytial virus (RSV) or rhinovirus.
This prospective study was carried out in 3 university hospitals in Finland during 2 consecutive winter seasons. We enrolled consecutive children <2 years of age hospitalized with an attending physician's diagnosis of bronchiolitis. All enrolled children were included in the primary analysis. A parallel analysis was also conducted using a stricter definition for bronchiolitis (age <12 months and no history of wheeze). Polymerase chain reaction was used to test the nasopharyngeal aspirate samples for multiple respiratory pathogens.
The median age of the 408 children was 8 months, 73% had no history of wheeze and their median hospital LOS was 2 days. 144 (35%) children had RSV only and 92 (23%) children rhinovirus only infections. Children with rhinovirus only had shorter duration of prehospital symptoms, higher disease severity score at entry and more often a history of wheezing (all P ≤ 0.001). Controlling for 7 demographic and clinical characteristics, those with rhinovirus only had shorter hospital LOS when compared with children with RSV only (adjusted odds ratio: 0.45; 95% confidence interval: 0.22-0.92; P = 0.03). The rhinovirus only finding was similar in the subset of 206 children with stricter diagnosis (adjusted odds ratio: 0.30; 0.06-1.49; P = 0.14).
Hospital LOS is associated with rhinovirus etiology of bronchiolitis. Our data call attention to the importance of both RSV and rhinovirus testing in clinical research.
No preview · Article · Aug 2014 · The Pediatric Infectious Disease Journal
[Show abstract][Hide abstract] ABSTRACT: Toll-like receptors (TLR´s) 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.
TLR1rs5743618, TLR2rs5743708 and TLR6rs5743810 SNP´s of 133 children who had been hospitalized for bronchiolitis at <6months of age were analyzed. Doctor-diagnosed asthma and atopy as well as their occurrence during the first six years of life were evaluated during a follow-up visit.
At the mean age of 6.4 years, asthma was present in 17 (13%) patients, there was asthma diagnosis during the first six 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 1-6 years of age (vs. 13(38%) of those with G/T or T/T genotypes; p=0.04). In addition, 11/60 children (18%) with TLR6 rs5743810 C/T vs. 36/73(49%) of other genotypes had atopic eczema at follow-up. Only two children (8%) with wild genotype in all investigated SNP´s had asthma during the first six years of life (vs. 30% in those with variant genotype of TLR1, TLR2 and/or TLR6).
In this study we demonstrated that TLR1 rs5743618 was associated with asthma and atopic eczema during the first six years of life after early bronchiolitis. In addition, TLR6 rs5743810 was associated with present atopy at preschool age.
No preview · Article · Jan 2014 · The Pediatric Infectious Disease Journal
[Show abstract][Hide abstract] ABSTRACT: Expression of toll-like receptor (TLR) 2 subfamily genes, including genes encoding TLR1, TLR2, TLR6 and TLR10, have been connected to allergy and asthma. This controlled study investigated the association of TLR1, TLR2 and TLR6 gene polymorphisms with clinical characteristics and subsequent wheezing in young infants with bronchiolitis.
In all, 129 full-term infants hospitalised for bronchiolitis at the age of <6 months were clinically followed-up until a mean age of 18 months. Genotyping of the TLR1 T1805G, TLR2 G2258A and TLR6 C745T polymorphisms was carried out by pyrosequencing and in 318 healthy, Finnish controls.
There were no significant associations between TLR1, TLR2 or TLR6 genotypes and severity of bronchiolitis or risk of post-bronchiolitis wheezing. TLR6 polymorphism was associated with allergy in univariate analyses. Minor allele frequency (MAF) in the TLR1 gene (17%) in the hospitalised children was similar to our Finnish controls, but different to European controls from other studies. MAF in the TLR6 gene was 50% vs. 41% in both the Finnish and European controls. MAF in the TLR2 gene was low (3%) in study subjects and in both controls.
TLR2 subfamily gene polymorphisms were not associated with severity of bronchiolitis or risk of post-bronchiolitis wheezing. This article is protected by copyright. All rights reserved.
No preview · Article · Sep 2013 · Acta Paediatrica
[Show abstract][Hide abstract] ABSTRACT: 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.
: To evaluate the association between the TLR3 L412F polymorphism and viral findings, clinical characteristics and subsequent wheezing in young infants with bronchiolitis.
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.
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).
Preliminary evidence was found that TLR3 L412F gene polymorphism may be associated with bronchiolitis leading to hospitalization and postbronchiolitis wheezing.
[Show abstract][Hide abstract] ABSTRACT: 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.
Methods: In all, 205 infants were hospitalized for bronchiolitis at <6 months of age. Asthma and allergy were studied from a total of 166 children at 6.4 years (mean). A total of 141 (85%) frozen whole blood samples were available for MBL genotyping and MBL2 gene mutations were determined on pyrosequencing for detection of three single-nucleotide polymorphisms.
Results: Ninety-five children (67.4%) had the wild-type MBL genotype A/A and 46 had A/O or O/O genotypes. Asthma was present in 16 children (11.3%) at 5–7 years of age. Nine children (19.6%) with non-AA genotype had asthma (vs 7.4% of those with genotype AA, P= 0.03). The result remained significant after adjustment for age, gender and atopy. There were no significant associations between MBL genotypes and asthma at any age before the study. Atopic dermatitis, allergic rhinitis or paternal and/or maternal asthma had no significant associations with MBL genotypes.
Conclusions: The variant non-A/A MBL genotype is associated with asthma after bronchiolitis in infancy, but not earlier than at 5–7 years of age.
No preview · Article · Apr 2012 · Pediatrics International
[Show abstract][Hide abstract] ABSTRACT: 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.
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).
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.
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.
Full-text · Article · Mar 2012 · Allergology International
[Show abstract][Hide abstract] ABSTRACT: 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.
In all, 127 full-term infants hospitalized for bronchiolitis at age <6 months have been followed up until the mean age of 1.5 years. The weights and lengths of the infants were measured on admission to hospital and at the control visit. Birth weights were obtained from the hospital records.
Both occurrence and recurrence of post-bronchiolitis wheezing were associated with birth weight >4000 g and the recurrence of post-bronchiolitis wheezing with WFL >110% at age 1.5 years. The associations were robust to adjustments with gender and allergy. Higher weight gain from birth to hospitalization at age <6 months was associated with wheezing in the subgroup of children with birth weight >4000 g.
High birth weight and the development of overweight may be associated with post-bronchiolitis wheezing in infancy.
No preview · Article · Jul 2011 · Acta Paediatrica
[Show abstract][Hide abstract] ABSTRACT: Asthma risk is lower after wheezing associated with respiratory syncytial virus (RSV) than with non-RSV infection in infancy. RSV is the main wheezing-associated virus in infants aged <6 months. We evaluated the outcome of children hospitalised for bronchiolitis at <6 months of age, with special focus on viral aetiology and early risk factors. Out of 205 infants hospitalised for bronchiolitis at <6 months of age, 127 (62%) attended a control visit at a mean age of 6.5 yrs and the parents of an additional 39 children were interviewed by telephone. Thus, follow-up data collected by identical structured questionnaires were available from 166 (81%) children. Viral aetiology of bronchiolitis, studied on admission by antigen detection or PCR, was demonstrable in 97% of cases. Current asthma was present in 21 (12.7%) children: 8.2% in the 110 former RSV patients versus 24% in non-RSV patients (p=0.01). 45 (27%) children had ever had asthma. In adjusted analyses, atopic dermatitis, non-RSV bronchiolitis and maternal asthma were independently significant early-life risk factors for asthma. The risk of asthma was lower after RSV bronchiolitis than after bronchiolitis caused by other viruses in children hospitalised at <6 months of age.
Full-text · Article · Jun 2011 · European Respiratory Journal
[Show abstract][Hide abstract] ABSTRACT: Preliminary evidence suggests that viral-pertussis coinfections are common in nonvaccinated infants.
Bordetella pertussis infection was studied by polymerase chain reaction in nasopharyngeal aspirates in 142 infants <6 months of age, who were admitted for bronchiolitis. Viral etiology,documented by antigen detection or polymerase chain reaction in nasopharyngeal aspirate, was respiratory syncytial virus (RSV) in 105, rhinovirus in 8, influenza A virus in 8, and other viruses in 10 cases. Only 11 samples were negative.
B. pertussis infection was found in 12 (8.5%) cases, being coinfection with RSV in 8 (67%) cases (7.6% of all RSV infections). In a retrospective analysis, RSV-pertussis coinfections and sole RSV infections did not differ for the presence of cough. Preliminary evidence was found that a history of coughing spells was associated with B. pertussis identification.
Coinfection with B. pertussis was present in 8.5% of <6-month-old infants, who were hospitalized for viral bronchiolitis. To avoid underdiagnosis, pertussis should be considered in all nonvaccinated infants admitted for lower respiratory tract infection.
No preview · Article · Nov 2010 · The Pediatric Infectious Disease Journal
[Show abstract][Hide abstract] ABSTRACT: Cytokine and TLR4 polymorphisms and their association with the infection history of 129 children hospitalized for bronchiolitis during the first 6 months of life were analyzed. The carriers of IFNG +874 T/A allele A had fewer infections and use of inhaled corticosteroids and the carriers of TLR4+896 A/G allele G were more likely to need tympanostomy than noncarriers.
No preview · Article · Sep 2009 · The Pediatric Infectious Disease Journal
[Show abstract][Hide abstract] ABSTRACT: One of the objectives of the qualification of medical specialists is familiarization to the scientific literature of the future special field. We describe a training project, in which doctors specializing in pediatrics collected and evaluated the current scientific data on the closure of the arterial duct in premature infants. Main emphasis in the article is put on the setting of the questions to be elucidated, acquisition of the required information, evaluation of the degree of evidence, and how reliably these questions can be answered on the basis of the current information. We recommend arranging evidence-based medical training for specializing doctors.
No preview · Article · Jan 2009 · Duodecim; lääketieteellinen aikakauskirja