Validation of 2D Force Measurement Roller Ski and Practical Application.

Several methods could be used to measure the forces from skis or roller skis in cross-country skiing. Equipment that could measure medio-lateral forces may be of good help for investigating the relevant skating techniques. The aim of this study was to validate a pair of newly designed two-dimensional force measurement roller skis. The vertical and medio-lateral forces which were perpendicular to the body of the roller ski could be measured. Forces were resolved into the global coordinate system and compared with the force components measured by a force plate. A static and dynamic loading situation for the force measurement roller ski was performed to reveal the validity of the system. To demonstrate whether the force measurement roller ski would affect roller skiing performance on a treadmill, a maximum speed test with the V2 technique was performed by using both normal and force measurement roller skis. The force-time curves obtained by these two different force measurement systems were shown to have high similarity (coefficient of multiple correlations > 0.940). The absolute difference for the forces in the X and Z directions over one push-off cycle was 3.9−33.3 N. The extra weight (333 g) of the force measurement roller ski did not affect the performance of the skiers. Overall, the newly designed two-dimensional force measurement roller ski in this study is valid for use in future research during daily training for skate skiing techniques.

Prospective study confirms that bronchiolitis in early infancy increases the risk of reduced lung function at 10-13 years of age.

AIM: This study evaluated children hospitalised for bronchiolitis at less than six months of age to see if they had reduced lung function in early adolescence. METHODS: We have prospectively followed 166 children hospitalised for infant bronchiolitis in 2001-2004 at Tampere University Hospital, Finland. At 10-13 years of age, flow-volume spirometry was measured in 89 cases and 108 controls without infant bronchiolitis from the local population register. Parameters of flow-volume spirometry before and after bronchodilation were analysed. RESULTS: Forced expiratory volume in one second/forced vital capacity (FEV1/FVC) after bronchodilation was lower in cases than controls. FEV1 was pathological - under the 5th percentile of the national references - in 25% of cases and 12% of controls (p = 0.020) before bronchodilation and in 18% of cases and 5% of controls (p = 0.003) after bronchodilation. FEV1/FVC was pathological in 25% of cases and 13% of controls (p = 0.034) before bronchodilation. Logistic regression, adjusted for current asthma and maternal smoking, showed that infant bronchiolitis was associated with pathological FEV1 before (odds ratio 2.4) and after (odds ratio 4.4) bronchodilation. The result was similar for positive respiratory syncytial virus cases. CONCLUSION: Reduced FEV1 after bronchodilation was found in early adolescence after infant bronchiolitis, suggesting irreversible bronchial obstruction.

Interleukin-10 gene polymorphism rs1800896 is associated with post-bronchiolitis asthma at 11-13 years of age.

AIM: Interleukin-10 (IL-10) is an anti-inflammatory cytokine that is involved with bronchiolitis and asthma. We evaluated associations between four IL-10 polymorphisms, namely rs1800871, rs1800872, rs1800890 and rs1800896, and post-bronchiolitis asthma in young adolescents. METHODS: The cohort consisted of 125 children hospitalised for bronchiolitis at Tampere University Hospital, Finland, in 2000-2004, at less than six months of age. At 11-13 years, asthma diagnoses and asthma-presumptive symptoms, allergic rhinitis and use of inhaled corticosteroids (ICS) were registered. Data on the four polymorphisms and their genotypes, haplotypes and allele frequencies were analysed in relation to asthma, allergic rhinitis and asthma medication. RESULTS: The variant IL-10 rs1800896 genotype was associated with less persistent asthma at five to seven and 11-13 years of age (4.3 versus 15.2%, p = 0.04) than the wild genotype and less ICS use during the previous 12 months (5.4 versus 18.2%, p = 0.03), as was the variant allele G. Allele A was associated with more persistent asthma and ICS use. The significant differences between the variant and wild genotypes were lost in adjusted logistic regression, but the direction of the association remained. CONCLUSION: IL-10 rs1800896 gene polymorphism was associated with post-bronchiolitis asthma at 11-13 years of age in children hospitalised for bronchiolitis at less than six months of age.

Toll-like receptor 1 and 10 gene polymorphisms are linked to postbronchiolitis asthma in adolescence.

AIM: Toll-like receptors (TLR) are innate immunity molecules and our previous studies found that TLR1 gene polymorphism was associated with postbronchiolitis asthma at one to six years of age, as was TLR10 at five to seven years of age. This study examined any associations at 11-13 years of age. METHODS: This prospective follow-up study was part of an ongoing evaluation of children admitted to Tampere University Hospital, Finland, for bronchiolitis in 2001-2004 at less than six months of age. We evaluated the association of TLR1 rs5743618 and TLR10 rs4129009 polymorphisms with asthma and asthma medication in 125 children aged 11-13 years. RESULTS: Associations were measured as adjusted odd ratios (aOR) with 95% confidence intervals (95% CI). The variant TLR1 rs5743618 (aOR 4.04, 95% CI 0.99-13.01) and TLR10 rs4129009 (aOR 7.02, 95% CI 1.56-31.53) genotypes increased the risk of needing inhaled corticosteroids (ICSs) at 11-13 years of age. The variant TLR10 genotype (aOR 7.69, 95% CI 1.35-43.95) increased the risk of persistent asthma continuing from five to seven years of age until 11-13 years of age. The results were similar when the combined genotypes were analysed. [Correction added on 3 October 2017, after online publication: The data in the variant TRL1 rs5743618 genotype were incorrect and have been corrected in this version.] CONCLUSION: Polymorphisms in both the TLR1 and TLR10 genes may increase the risk of asthma at 11-13 years after infant bronchiolitis.

IL-17A gene polymorphism rs2275913 is associated with the development of asthma after bronchiolitis in infancy.

BACKGROUND: Interleukin-17 (IL-17A) is a mainly pro-inflammatory cytokine, and IL-17 signaling implicates in the development of allergic asthma. The polymorphism rs2275913 in the promoter region of the IL-17A gene has in previous studies been associated with asthma susceptibility. The objective was to evaluate the association between IL-17A rs2275913 (-197G>A) polymorphism and post-bronchiolitis asthma and/or allergic rhinitis in a prospective 11-13 years post-bronchiolitis follow-up. METHODS: 166 previously healthy full-term infants, hospitalized for bronchiolitis at age less than 6 months, were invited to follow-up visits at the ages of 5-7 years and 11-13 years. Asthma diagnoses and presumptive symptoms, allergic rhinitis and use of inhaled corticosteroids (ICS) were registered. Blood samples for IL-17A rs2275913 (-197G>A) polymorphism were obtained during hospitalization or at the 5-7 years control visit. RESULTS: There were no significant differences between children with the wild GG and variant GA or AA genotype in the severity of bronchiolitis during hospitalization or in the outcomes until the age 5-7 years. At 11-13 years of age, children with the variant GA or AA genotype had significantly less often current asthma, use of ICSs during last 12 months or allergic rhinitis than those with the wild GG genotype. The ICS use during last 12 months retained the statistical significance in adjusted analyses (adjusted OR 0.25), whereas current asthma and allergic rhinitis marginally lost it. CONCLUSIONS: The IL-17A rs2275913 (-197G>A) polymorphism decreased the risk of post-bronchiolitis asthma at 11-13 years of age, but not earlier in life, in the present prospective, long-term follow-up study.

Marked variability observed in inpatient management of bronchiolitis in three Finnish hospitals.

AIM: Infants hospitalised for bronchiolitis undergo examinations and treatments not supported by current research evidence and we investigated practice variations with regard to Finnish children under the age of two. METHODS: This prospective, multicentre cohort study was conducted in paediatric units in three university hospitals in Finland from 2008 to 2010. Hospital medical records were reviewed to collect data on clinical course, testing and treatment. Data were analysed separately for children meeting our strict definition of bronchiolitis, aged under 12 months without a history of wheezing, and a loose definition, aged 12-23 months or with a history of wheezing. RESULTS: The median age of the 408 children was 8.1 months. Clinical management varied between the three hospitals when stratified by strict and loose bronchiolitis subgroup definitions: complete blood counts ranged from 15-95% vs 16-94%, respectively, and the other measures were chest x-ray (16-91% vs 14-72%), intravenous fluids (2-47% vs 2-41%), use of nebulised epinephrine (10-84% vs 7-50%), use of salbutamol (18-21% vs 13-84%) and use of corticosteroids (6-23% vs 60-76%). CONCLUSION: The clinical management of bronchiolitis varied considerably with regard to the three hospitals and the two definitions of bronchiolitis. A stronger commitment to evidence-based bronchiolitis guidelines is needed in Finland.

Following up infant bronchiolitis patients provided new evidence for and against the united airway disease hypothesis.

AIM: The united airway disease (UAD) hypothesis suggests that allergic rhinitis and asthma develop together. We evaluated the evidence for and against the UAD hypothesis at five to seven years of age after hospitalisation for bronchiolitis at less than six months. METHODS: This study used prospective follow-up data for 102 children hospitalised for bronchiolitis under the age of six months. We included the presence of previous and current asthma, prolonged rhinitis and skin prick tests (SPT) to common inhaled allergens and lung function by impulse oscillometry (IOS) at five to seven years of age. Bronchial hyper-reactivity (BHR) was assessed using the exercise challenge test and bronchodilation test. RESULTS: Current asthma, but not previous transient asthma, was associated with prolonged rhinitis and a positive SPT. BHR, which reflected reactive airways, but not lung function, was associated with respiratory allergy, namely the combination of current asthma, prolonged rhinitis and a positive SPT. CONCLUSION: This post-bronchiolitis follow-up study suggested an association between respiratory allergy and reactive airways at five to seven years of age, which supported the UAD hypothesis. However, previous transient asthma and a reduction in lung function reduction did not support the hypothesis.

Toll-like receptor 2 subfamily genotypes are not associated with severity of bronchiolitis or postbronchiolitis wheezing in infants.

AIM: 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. METHODS: 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. RESULTS: There were no significant associations between TLR1, TLR2 or TLR6 genotypes and severity of bronchiolitis or risk of postbronchiolitis 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% versus 41% in both the Finnish and European controls. MAF in the TLR2 gene was low (3%) in study subjects and in both controls. CONCLUSION: TLR2 subfamily gene polymorphisms were not associated with severity of bronchiolitis or risk of postbronchiolitis wheezing.

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. METHODS: 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. RESULTS: 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. CONCLUSION: High birth weight and the development of overweight may be associated with post-bronchiolitis wheezing in infancy.

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. 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.

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.

Intermittent Tiotropium Bromide for Episodic Wheezing: A Randomized Trial.

BACKGROUND AND OBJECTIVES: Options to treat and prevent episodic wheezing in children are scarce. Our objective was to assess the efficacy of intermittent tiotropium bromide treatment in early childhood episodic wheezing. METHODS: This 48-week, randomized, open-label, controlled, parallel-group trial was conducted at 4 hospitals in Finland. Children aged 6 to 35 months with 2 to 4 physician-confirmed episodes of wheeze and/or shortness of breath were considered eligible. Study participants were randomly allocated to receive 1 of 3 treatments: once-daily tiotropium bromide 5 µg for 7 to 14 days during respiratory tract infections and as-needed albuterol sulfate 0.2 mg (n = 27), twice-daily fluticasone propionate 125 µg for 7 to 14 days during respiratory tract infections and as-needed albuterol sulfate 0.2 mg (n = 25), or as-needed albuterol sulfate 0.2 mg alone (n = 28). The primary outcome was efficacy, assessed as intention-to-treat by comparing the proportion of episode-free days (the days lacking symptoms or treatments) between the treatment groups. RESULTS: The proportion of episode-free days was higher in those receiving intermittent tiotropium bromide (median 97% [interquartile range, 93% to 99%]) than in those receiving intermittent fluticasone propionate (87% [78% to 93%], P = .002), or with as-needed albuterol sulfate alone (88% [79% to 95%], P = .003). Adjustment with allergic sensitization, the baseline number of physician-confirmed episodes of wheeze and/or shortness of breath, or short-course glucocorticoid treatment in the 2 weeks before the enrollment, did not affect the result. Intervention-related adverse events were not seen. CONCLUSIONS: Intermittent tiotropium bromide treatment may be an effective alternative to current therapies for episodic wheezing. Before implementation of use, further research on safety and efficacy is indicated.

Risk factors for irreversible airway obstruction after infant bronchiolitis.

BACKGROUND: Increasing evidence shows that environmental factors in childhood play a role in development of irreversible airway obstruction. We evaluated early-life and preschool-age risk factors for irreversible airway obstruction in adolescence after bronchiolitis in infancy. METHODS: This study is a secondary analysis of data collected during prospective long-term follow-up of our post-bronchiolitis cohort. Risk factor data were collected during hospitalisation and on follow-up visits at 5-7 and 10-13 years of ages. Lung function was measured from 103 participants with impulse oscillometry at 5-7 years of age and from 89 participants with flow-volume spirometry at 10-13 years of age. RESULTS: Asthma diagnosis at <12 months of age showed a significant association with irreversible airway obstruction at 10-13 years of age independently from current asthma. Irreversible airway obstruction was less frequent in children with variant than wild genotype of the Toll-like receptor 4(TLR4) rs4986790, but the significance was lost in logistic regression adjusted for current asthma and weight status. Higher post-bronchodilator respiratory system resistance at 5 Hz and lower baseline and post-bronchodilator reactance at 5 Hz by impulse oscillometry at 5-7 years of age were associated with irreversible airway obstruction at 10-13 years of age. CONCLUSION: Asthma diagnosis during the first living year and worse lung function at preschool age increased the risk for irreversible airway obstruction at 10-13 years of age after bronchiolitis. TLR4 rs4986790 polymorphism may be protective for development of irreversible airway obstruction after bronchiolitis.

[Evidence-based methods of medicine in specialization training: a neonatologic problem as an example]. / Näyttöön perustuvan lääketieteen menetelmät erikoistumiskoulutuksessa: esimerkkinä neonatologinen ongelma.

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.

TLR5 rs5744174 gene polymorphism is associated with the virus etiology of infant bronchiolitis but not with post-bronchiolitis asthma.

BACKGROUND AND AIM: Bronchiolitis is a leading cause of hospitalization in infants and is associated with a risk of subsequent asthma. The innate immunity genes, such as those encoding toll-like receptors (TLRs), are likely to play a role in bronchiolitis and post-bronchiolitis outcome. Thus far, only one study has considered TLR5 genes in respiratory syncytial virus (RSV) bronchiolitis. The aim of this study was to investigate the association of TLR5 gene polymorphism with virus etiology and severity of bronchiolitis, and with post-bronchiolitis asthma. METHODS: We recruited 164 infants (age < 6 months) hospitalized for bronchiolitis in this study and determined TLR5 rs5744174 (C > T) single nucleotide polymorphism, virus etiology and severity markers of bronchiolitis, and presence of post-bronchiolitis asthma until age 11 to 13 years. RESULTS: RSV was detected in 113 (68.9%), rhinovirus in 19 (11.6%), and some other virus in 20 (12.2%) cases. Non-RSV etiology was more common among infants with the variant CT or TT genotype in the TLR5 rs5744174 gene than in those with the CC genotype (89.7% vs 71.7%, P = 0.03). TLR5 rs5744174 polymorphism was not associated with the need of supplementary oxygen or feeding support, with the length of hospital stay, or with post-bronchiolitis asthma at any age. CONCLUSION: The TLR5 rs5744174 variant genotype may increase the susceptibility to bronchiolitis not caused by RSV.

Impulse oscillometry at preschool age is a strong predictor of lung function by flow-volume spirometry in adolescence.

BACKGROUND: The transition from early childhood wheezing to persistent asthma is linked to lung function impairment over time. Little is known how the methods used to study lung function at different ages correlate longitudinally. METHODS: Sixty-four children with a history of hospitalization for bronchiolitis before 6 months of age were prospectively studied with impulse oscillometry (IOS) at the mean age of 6.3 years and these preschool IOS results were compared with flow-volume spirometry (FVS) measurements at mean age of 11.4 years. RESULTS: The baseline respiratory system resistance at 5 Hz (Rrs5) showed a modest statistically significant correlation with all baseline FVS parameters except FVC. The post-bronchodilator (post-BD) Rrs5 showed a modest statistically significant correlation with post-BD FEV1 and FEV1 /FVC. The bronchodilator-induced decrease in Rrs5 showed a modest statistically significant correlation with the percent increase in FEV1 . Baseline and post-BD respiratory reactance at 5 Hz (Xrs5) showed a modest statistically significant correlation with baseline and post-BD FVS parameters except post-BD FEV1 /FVC, respectively, and post-BD Xrs5 showed a strong correlation with post-BD FVC (ρ = 0.61) and post-BD FEV1 (ρ = 0.59). In adjusted linear regression, preschool Xrs5 remained as a statistically significant independent predictor of FVS parameters in adolescence; the one-unit decrease in the Z-score of preschool post-BD Xrs5 predicted 9.6% lower post-BD FEV1 , 9.3% lower post-BD FVC, and 9.7% lower post-BD MEF50 when expressed as %-predicted parameters. CONCLUSION: Persistent post-BD small airway impairment in children with a history of bronchiolitis detected with IOS at preschool age predicted FVS results measured in early adolescence.

Polymorphisms in the promoter region of IL10 gene are associated with virus etiology of infant bronchiolitis.

BACKGROUND: Bronchiolitis is the most common infection leading to hospitalization in infancy. Interleukin-10 (IL-10) is an anti-inflammatory cytokine, and in our previous study, IL10 gene rs1800896 (- 1082A/G) polymorphism was associated with viral etiology of infant bronchiolitis. The objective of this study was to evaluate the associations between IL10 single nucleotide polymorphisms (SNPs) at rs1800890 (- 3575A/T), rs1800871 (- 819C/T) or rs1800872 (- 592C/A) either alone or combined with the SNP at rs1800896 (- 1082G/A), and the etiology and severity of infant bronchiolitis. METHODS: Data on four IL10 SNPs were available from 135 full-term infants, hospitalized for bronchiolitis at age less than 6 months, and from 378 to 400 controls. Viral etiology was studied, and oxygen support, feeding support and the length of stay in hospital were recorded during bronchiolitis hospitalization. RESULTS: Infants with rhinovirus bronchiolitis had the IL10 rs1800890 variant AT or TT genotype less often (18.2%) than controls (63.3%, P = 0.03), and likewise, had the IL10 rs1800896 variant AG or GG genotype less often (27.3%) than controls (65.5%, P = 0.009). Twenty-eight infants with bronchiolitis had the variant-variant Grs1800896Trs1800890 haplotype, and none of them had rhinovirus infection. The IL10 rs1800871 or rs1800872 genotypes showed no associations with viruses. No association was found between any genotypes and bronchiolitis severity measures. CONCLUSION: IL10 rs1800890 and rs1800896 polymorphisms differed between infants with rhinovirus bronchiolitis and controls, but not between infants with respiratory syncytial virus bronchiolitis and controls.