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Laura Hatzler,
Valentina Panetta,
Susanne Lau,
Petra Wagner,
Renate L Bergmann,
Sabina Illi,
Karl E Bergmann,
Thomas Keil,
Stephanie Hofmaier,
Alexander Rohrbach,
Carl Peter Bauer,
Ute Hoffman, Johannes Forster,
Fred Zepp,
Antje Schuster,
Ulrich Wahn,
Paolo Maria Matricardi
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ABSTRACT: IgE sensitization against grass pollen is a cause of seasonal allergic rhinitis.
We sought to investigate the evolution at the molecular level and the preclinical predictive value of IgE responses against grass pollen.
The German Multicentre Allergy Study examined a birth cohort born in 1990. A questionnaire was administered yearly, and blood samples were collected at 1, 2, 3, 5, 6, 7, 10, and 13 years of age. Grass pollen-related seasonal allergic rhinitis (SARg) was diagnosed according to nasal symptoms in June/July. Serum IgE antibodies to Phleum pratense extract and 8 P pratense molecules were tested with immune-enzymatic singleplex and multiplex assays, respectively.
One hundred seventy-seven of the 820 examined children had SARg. A weak monomolecular/oligomolecular IgE response to P pratense was observed very frequently before SARg onset. These initial IgE responses increased in concentration and molecular complexity during the preclinical and clinical process. A typical progression of IgE sensitization was observed: Phl p 1 (initiator in >75% of cases); then Phl p 4 and Phl p 5; then Phl p 2, Phl p 6, and Phl p 11; and then Phl p 12 and Phl p 7. At age 3 years, IgE sensitization predicted SARg by age 12 years (positive predictive value, 68% [95% CI, 50% to 82%]; negative predictive value, 84% [95% CI, 80% to 87%]). At this preclinical prediction time, the number of recognized molecules and the serum levels of IgE to P pratense were significantly lower than at 3 or more years after SARg onset.
The IgE response against grass pollen molecules can start years before disease onset as a weak monosensitization or oligosensitization phenomenon. It can increase in serum concentration and complexity through a "molecular spreading" process during preclinical and early clinical disease stages. Testing IgE sensitization at a preclinical stage facilitates prediction of seasonal allergic rhinitis at its molecular monosensitization or oligosensitization stage.
The Journal of allergy and clinical immunology 07/2012; 130(4):894-901.e5. · 9.17 Impact Factor
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ABSTRACT: IntroductionSurveillance systems for acute respiratory infections (ARI) in children currently are often limited in terms of the panel
of pathogens and the age range investigated or are only syndromic and at times only active in the winter season.
MethodsWithin PID-ARI.net, a research network for ARI in children in Germany, an active, year-round surveillance system was formed
in three regions from north to south for population-based analysis. Children from birth to 16 years of age were included and
up to 19 noncolonizing airway pathogens were tested for with multiplex RT-PCR.
ResultsIn the 10-year period from July 1996 to June 2006, a total of 18,899 samples were tested. The positive rate increased with
the size of the test panel to up to 72.9%. Picornaviruses (35–39%), paramyxoviruses (23–28%) and orthomyxoviruses (5.8–12.5%)
comprised the highest fraction. Reoviruses and Legionella pneumophila were not found at all and Chlamydia pneumoniae and Bordetella parapertussis only rarely. Respiratory syncytial virus and parainfluenza virus (PIV) type 3 were anticyclical in rhythmicity with metapneumovirus
and PIV1 and PIV2. The age medians per pathogen depended predominantly upon the attack rate and interepidemic intervals.
ConclusionActive surveillance systems for ARI are superior to passive systems. They should be pathogen-specific and comprehensive for
viruses and bacteria and age ranges. They should be population-based and multilevel to avoid bias. The impact of atypical
bacteria in children was highly overestimated in earlier studies.
European Journal of Pediatrics 04/2012; 166(9):957-966. · 1.88 Impact Factor
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ABSTRACT: This observational, prospective study was undertaken to estimate the burden of rotavirus (RV) gastroenteritis (GE) leading to general practitioner (GP)/family paediatrician (FP) visits among children aged <5 years in Czech Republic, Germany, Italy, Poland, Spain and the UK. Children aged <5 years presenting with acute GE provided stool samples for rapid RV testing. RV+ samples were confirmed and typed by RT-PCR. Demographic and clinical data were collected for all RVGE episodes. Transmission patterns among other household children aged <5 years were also assessed. From November 2005 to May 2007, excluding data from the UK, 497/3,813 (13.0%) children aged <5 years presenting with acute GE to GP/FP and tested were RV+ by PCR. Most RVGE cases (69.1%) occurred in children aged <2 years, occurred between December and May (93.1%) and were moderate or severe by Vesikari score (92.9%). RV strain distribution varied between countries: G9P[8] was the most common type in Poland (54/76) and Spain (172/196), G1P[8] was predominant in the Czech Republic (56/64) and Italy (46/107), and G4P[8] and G1P[8] both prevailed in Germany (17/54 and 13/54, respectively). A total of 24/122 (19.7%) children aged <5 years resident in the same household as a PCR+ study participant also developed RVGE. Conclusion. This multinational epidemiological study in Europe shows that RV is easily transmitted among household children, with RVGE burden highest among children aged <2 years accessing primary healthcare for acute GE.
European Journal of Pediatrics 02/2011; 170(2):213-22. · 1.88 Impact Factor
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ABSTRACT: To assess whether breastfeeding protects against acute gastroenteritis (AGE) due to rotavirus (RV) infection compared to RV-negative AGE (RV-) in children age 0-12 months. Data from a community-based study of children with AGE from 30 pediatric practices in Germany, Switzerland, and Austria were evaluated. A case-control design was conducted with RV-positive AGE (RV+) cases and RV- AGE as controls. Odds ratios and 95% confidence intervals were estimated using log-linear regression models adjusting for child's age, family size, number of siblings, child care attendance, and nationality. A total of 1,256 stool samples were collected from infants with AGE; 315 (25%) were RV+ and 941 RV-. Being breastfed in the period of disease inception reduced the risk of AGE due to RV+ (OR, 0.53; 95% CI, 0.37-0.76). In infants 0-6 months of age, the protective effect was stronger (OR, 0.33; 95% CI, 0.19-0.55) than in 7-12-month-old children. Our study adds to the evidence of a protective concurrent effect of breastfeeding against rotavirus infection in infants, particularly in children 6 months and younger. Breastfeeding is important to diminish rotavirus-related gastroenteritis in infants before vaccination can be introduced.
European Journal of Pediatrics 12/2010; 169(12):1471-6. · 1.88 Impact Factor
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ABSTRACT: The disease burden caused by recently identified respiratory viruses like HCoV-NL63 is unknown.
We determined the burden of disease due to HCoV-NL63 infections using the population-based PRI.DE cohort of children under the age of 3 with lower respiratory tract infections (LRTIs).
In total 1756 respiratory samples, from hospitalized children or children who visited the outpatient clinic, were tested for HCoV-NL63. Sampling covered a period of 2 years and the frequency of infection in different years was compared to other Western European studies that tested for this virus in 2 or more consecutive years.
Sixty-nine samples were HCoV-NL63 positive, 35 were with high loads, and of these 25 were single HCoV-NL63 infections. Based on the number of children with high HCoV-NL63 infection and no additional infection, the overall annual incidence in outpatients was 7 per 1000 children per year (95% confidence interval (CI) 3-13 per 1000 children per year), which can be extrapolated to an absolute number of 16,929 visits to the physician due to an HCoV-NL63 infection in Germany per year. The estimated hospitalization rate is 22 per 100,000 children (95% CI: 7-49 per 100,000 children per year). This number reflects 522 HCoV-NL63 children in Germany per year. A large year-to-year difference in HCoV-NL63 infection frequency was observed. Combining these data with those of other studies in Western Europe revealed that HCoV-NL63 infections follow a 2-year inter-epidemic period with peaks of infection in the winters of 2000/2001, 2002/2003 and 2004/2005 (p<0.0001).
HCoV-NL63 infection in children below 3 years of age often requires a visit to the physician in an outpatient clinic, especially during peak-years, but hospitalizations are relatively infrequent.
Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 03/2010; 48(2):104-8. · 3.12 Impact Factor
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Johannes Forster,
Alfredo Guarino,
Nathalie Parez,
Fernando Moraga,
Enriqueta Román,
Olivier Mory,
Alberto E Tozzi,
Ana López de Aguileta,
Ulrich Wahn,
Clive Graham,
Reinhard Berner,
Titus Ninan,
Celia Barberousse,
Nadia Meyer,
Montse Soriano-Gabarró
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ABSTRACT: Rotavirus is the leading cause of acute gastroenteritis requiring hospitalization in young children. Data on the burden of rotavirus gastroenteritis are needed to guide recommendations for rotavirus vaccine use. This study was undertaken to estimate the burden of rotavirus gastroenteritis in European children <5 years of age.
This prospective, study was conducted in 12 hospitals in France, Germany, Italy, Spain, and the United Kingdom. A sample of all children aged <5 years presenting to emergency departments or hospitalized because of community-acquired acute gastroenteritis was enrolled for parental interview and stool collection. Acute gastroenteritis was defined as diarrhea (>/=3 loose stools per 24 hours) for <14 days. Rotavirus was detected by enzyme-linked immunosorbent assay and typed by reverse-transcriptase polymerase chain reaction.
Between February 2005 and August 2006, 3734 children with community-acquired acute gastroenteritis were recruited and retained for analysis (55.9% via the emergency department, 41.8% hospitalized). Of the 2928 community-acquired acute gastroenteritis cases for which stool samples were available, 43.4% were rotavirus-positive by enzyme-linked immunosorbent assay (32.8% emergency department, 56.2% hospitalized). Of these rotavirus gastroenteritis cases 80.9% occurred in children aged <2 years and 15.9% among infants aged <6 months. Acute gastroenteritis was more severe in rotavirus-positive subjects (Vesikari score >/= 11 in 53.3% compared with 31.0% of rotavirus-negative subjects). All 1271 rotavirus-positive strains were genotyped (G1P[8]: 40.3%; G9P[8]: 31.2%; G4P[8]: 13.5%; G3P[8]: 7.1%).
Rotavirus gastroenteritis places high demands on European health care systems, accounting for 56.2% of hospitalizations and 32.8% of emergency department visits because of community-acquired acute gastroenteritis in children aged <5 years. Most community-acquired rotavirus gastroenteritis occurs in children aged <2 years, and a high proportion occurs in infants aged <6 months. Cases were also observed among very young infants <2 months of age. Rotavirus vaccination is expected to have a major impact in reducing morbidity and the pressure on hospital services in Europe.
PEDIATRICS 04/2009; 123(3):e393-400. · 4.47 Impact Factor
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ABSTRACT: Acute respiratory tract infections (ARI) in children are often treated with antibiotics even without evidence of bacterial infection. Serum procalcitonin (PCT) is elevated in bacterial but not in viral infections.
We performed a retrospective analysis of children in the PID-ARI.net study on respiratory infections to address the question of whether plasma PCT could potentially distinguish between bacterial infections requiring antibiotic therapy and viral ARI. We analysed data on 327 children who had been included in the German PID-ARI.net study and in whom nasopharyngeal aspirates had been analysed with a 19-valent multiplex reverse transcription-polymerase chain reaction-enzyme-linked immunosorbent assay for viral and atypical bacterial pathogens. Serum PCT was determined using a quantitative immunoassay (BRAHMS Kryptor PCTsensitive, Henningsdorf, Germany). We then focussed specifically on those children who were treated with antibiotics and therefore had been suspected of having bacterial infection but who had a serum PCT level lower than 0.1 ng/ml.
Out of 327 children, 132 had serum PCT levels below 0.1 ng/ml. Of these 132, 38 children had been treated with antibiotics. After exclusion of 26 patients (with critical illnesses, antibiotics on admission or for reasons other than ARI), 12 children remained for further evaluation. Of these 12 children, four had atypical pneumonia; four others had positive virus testing, and, in the last four, the aetiology of ARI remained unknown; evidence of bacterial infection could not be detected in any.
Taken the results of this retrospective analysis, serum PCT values below 0.1 ng/ml might be a marker to identify children with acute respiratory tract infection in whom antibiotic treatment could be withheld. However, only a prospective intervention trial will prove the general safety of this limit.
European Journal of Pediatrics 01/2009; 168(9):1117-24. · 1.88 Impact Factor
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Johannes Forster
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ABSTRACT: Since 2000 there has been sufficient evidence that chest X-rays are unnecessary in infants and children with uncomplicated lower respiratory tract infection. The reason is that neither the diagnosis nor the first therapeutic decisions will be influenced by the result of this procedure, and especially so if children have been infected with the respiratory syncytial virus. However, epidemiological studies in Germany reveal an ongoing use of chest X-ray in these cases. This might suggest that the X-ray images are taken as "proof" of pneumonia, which indeed pays off in the German DRG (Diagnosis Related Groups) system since hospitals receive a higher reimbursement for RSV pneumonia than for RSV bronchiolitis.
Zeitschrift für Evidenz Fortbildung und Qualität im Gesundheitswesen 01/2009; 103(6):364-6.
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ABSTRACT: Because of their important role in the pathophysiology of severe RSV infection, IFNs represent an ideal group of candidate genes for determining RSV disease severity. We studied 14 polymorphisms within 7 genes involved in IFNs signalling. Our study populations consisted of 156 infants with severe RSV infection and 296 healthy control children. None of the genes showed association with severe RSV infection in children. Thus, despite the involvement of different IFNs in the pathophysiology of RSV infection, genetic variants in IFNG and related genes might not alter the risk for the development of severe RSV-associated diseases.
Archives of Virology 11/2008; 153(11):2133-7. · 2.11 Impact Factor
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ABSTRACT: Tumor necrosis factor (TNF-) is a proinflammatory cytokine that is important in the innate host defence and thus in the defence of infectious agents. However, in excess it provokes the development of chronic inflammatory diseases. The aim of this study was to test association of TNF with severe RSV bronchiolitis as example of an infectious disease and asthma as representative for a chronic inflammatory condition. The following study populations were genotyped for 4 polymorphisms within TNF-β (rs909253) and TNF- (rs1799964, rs1799724, rs1800629): 322 asthmatic children, 151 children with severe respiratory syncytial virus (RSV) bronchiolitis and 270 controls. Furthermore, serum TNF- levels were measured by a FlowCytomix Assay. Asthma showed association with two TNF- polymorphisms as well as with TNF haplotpyes (p = 0.0050). In contrast, RSV bronchiolitis was associated with TNF haplotypes (p < 0.00001) but not with any single polymorphism. In addition, TNF- serum levels correlated with rs1799724 (p = 0.034). A genetically mediated up-regulation of TNF- expression might provoke a pronounced inflammation of the airways and thus a more severe course of RSV infection as well as the onset of asthma. It remains to be elucidated whether severe RSV bronchiolitis starts TNF- upregulation and is one first step in the direction to asthma later in life, or whether both dieases are independent from each other and supported by TNF- upregulation.
Pediatric Allergy and Immunology 09/2008; 20(2):157 - 163. · 2.46 Impact Factor
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ABSTRACT: Tumor necrosis factor (TNF-)alpha is a proinflammatory cytokine that is important in the innate host defence and thus in the defence of infectious agents. However, in excess it provokes the development of chronic inflammatory diseases. The aim of this study was to test association of TNF with severe RSV bronchiolitis as example of an infectious disease and asthma as representative for a chronic inflammatory condition. The following study populations were genotyped for 4 polymorphisms within TNF-beta (rs909253) and TNF-alpha (rs1799964, rs1799724, rs1800629): 322 asthmatic children, 151 children with severe respiratory syncytial virus (RSV) bronchiolitis and 270 controls. Furthermore, serum TNF-alpha levels were measured by a FlowCytomix Assay. Asthma showed association with two TNF-alpha polymorphisms as well as with TNF haplotypes (p = 0.0050). In contrast, RSV bronchiolitis was associated with TNF haplotypes (p < 0.00001) but not with any single polymorphism. In addition, TNF-alpha serum levels correlated with rs1799724 (p = 0.034). A genetically mediated up-regulation of TNF-alpha expression might provoke a pronounced inflammation of the airways and thus a more severe course of RSV infection as well as the onset of asthma. It remains to be elucidated whether severe RSV bronchiolitis starts TNF-alpha upregulation and is one first step in the direction to asthma later in life, or whether both diseases are independent from each other and supported by TNF-alpha upregulation.
Pediatric Allergy and Immunology 09/2008; 20(2):157-63. · 2.46 Impact Factor
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ABSTRACT: A rapid and reliable diagnosis of respiratory syncytial virus (RSV) infection in childhood is very important for clinical management. In this study we compared a rapid antigen test (enzyme immunoassay, EIA) for the detection of RSV with a reverse transcriptase polymerase chain reaction (RT-PCR) [19-valent multiplex RT-PCR enzyme-linked immunosorbent assay (ELISA)] to assess the diagnostic performance. Furthermore the diagnostic value of the EIA in terms of age and season relation was analyzed. A total of 400 nasopharyngeal or tracheal secretions from pediatric patients with clinical signs of lower respiratory tract infection were included. The specimen had to be taken in a standardized manner within 72 h after admission. Specimens were tested in parallel with the EIA and the multiplex RT-PCR ELISA. The RT-PCR technique was used as the target assay. The EIA reached a sensitivity of 58% and a specificity of 90% for all samples tested. For patients < [corrected] 1 year the post-test probability for a positive EIA was 91% during the RSV season; a negative test result decreased disease probability from 53 to 25%. For older patients a positive test raised disease probability from 23 to 45% during the RSV season. Negative test results did not markedly change disease probability.
European Journal of Pediatrics 08/2008; 167(7):745-9. · 1.88 Impact Factor
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Nadina Karaolis-Danckert,
Anette E Buyken,
Michael Kulig,
Anja Kroke, Johannes Forster,
Wolfgang Kamin,
Antje Schuster,
Claudia Hornberg,
Thomas Keil,
Renate L Bergmann,
Ulrich Wahn,
Susanne Lau
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ABSTRACT: It is unclear which exposures may cause or modify the adverse effect of rapid weight gain on fat mass development in term children whose birth weight is appropriate-for-gestational age (AGA).
To determine which intrauterine or postnatal exposures increase the risk of or modify the effect of rapid weight gain on body fat percentage (BF%) and body mass index (BMI) trajectories between 2 and 6 y of age.
Term AGA singletons (n = 370) from the German Multicenter Allergy Study (MAS-90), a longitudinal birth cohort study, with repeated anthropometric measurements until 6 y, and data on breastfeeding status, exposure to smoking during pregnancy, and maternal anthropometric and socioeconomic characteristics were included in this analysis.
A shorter gestation [multivariate-adjusted odds ratio (OR): 5.12; 95% CI: 2.22, 11.82; P = 0.0001], being firstborn (OR: 2.01; 95% CI: 1.10, 3.69; P = 0.02), and having been bottle-fed (OR: 3.02; 95% CI: 1.68, 5.43; P = 0.0002) all significantly increased a child's risk of gaining weight rapidly, whereas a larger BMI at birth was protective (OR: 0.54; 95% CI: 0.38, 0.77; P = 0.0006). Multilevel model analyses showed that rapid growers exposed to tobacco in utero subsequently gained more BF% between 2 and 6 y than did rapid growers who had not been exposed (beta +/- SE: 0.78 +/- 0.28%/y; P = 0.005). Similarly, change in BF% was greater in rapid growers with an overweight mother than in those with a normal-weight mother (1.01 +/- 0.30%/y; P = 0.0007).
The occurrence of rapid weight gain between birth and 2 y and the magnitude of its effect on BF% development in AGA children is influenced by both intrauterine and postnatal exposures.
American Journal of Clinical Nutrition 06/2008; 87(5):1356-64. · 6.67 Impact Factor
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ABSTRACT: Toll like receptors (TLRs) are an essential part of the innate immune response. So far, ten different TLRs were identified in humans. They recognize a wide range of microbial and viral pathogens. Infection by respiratory syncytial virus (RSV) is still a major health problem, about 2% of all children are hospitalised due to RSV bronchiolitis during their first 2 years of live. TLR4 has already been described in association with RSV associated diseases by us and others. Thus we were interested whether other TLRs are also involved in the genetics of severe RSV infection. We genotyped 19 polymorphisms in the autosomal TLRs, these are TLR1, 2, 3, 5, 6, 9 and 10. Association analyses by the Armitage's Trend test revealed weak association of one TLR9 promoter polymorphism with RSV infection (p = 0.013). In addition, association was found with TLR10 haplotypes (p = 0.024). We conclude from our data--that--although we can not rule out a minor involvement of TLR9 polymorphism and TLR10 haplotypes--TLRs other than TLR4 do not play a major role in the genetics of severe RSV associated diseases. Future studies should focus on additional genes of the innate immune response.
Disease markers 02/2008; 25(1):59-65. · 1.64 Impact Factor
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ABSTRACT: Respiratory syncytial virus (RSV) is a major cause of bronchiolitis in infants. During the course of RSV infection, predominant T helper cell (TH) 2 response is associated with disease progression, whereas predominant TH1 reaction provides convalescence. Interleukin (IL)-18 plays an important role in adjusting the TH1/TH2 immune response to viral infections. Thus, we tested the hypothesis that polymorphisms in IL-18 were associated with severe RSV-associated diseases.
We chose to study the promotor polymorphisms -607A/C (rs1946518) and -137G/C (rs187238), the 2 exon polymorphisms 113T/G (rs360718) and 127C/T (rs360717), and 2 intron polymorphisms 5304A/G (rs795467) and 133G/C (rs360721) within the IL-18 gene. Genotyping was performed on 154 children with severe RSV infection as defined by strict clinical criteria and on 270 controls. Statistical analyses of single polymorphisms made use of the Armitage's trend test, haplotypes were calculated with FASTEHPLUS and FAMHAP.
-133G/C showed association with severe RSV infection (P = 0.043). The association was further supported by haplotype analyses with all 6 polymorphisms (P < 0.00001 for association with RSV).
This study indicates possible involvement of IL-18 in the determination of severe RSV-associated diseases. Defining the genetic basis of RSV bronchiolitis might help us in identifying new drug targets for a more specific therapy. In addition, it might enable an early identification of children at risk for RSV bronchiolitis and thus make a selective prevention feasible.
The Pediatric Infectious Disease Journal 01/2008; 26(12):1094-8. · 3.58 Impact Factor
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ABSTRACT: Surveillance systems for acute respiratory infections (ARI) in children currently are often limited in terms of the panel of pathogens and the age range investigated or are only syndromic and at times only active in the winter season.
Within PID-ARI.net, a research network for ARI in children in Germany, an active, year-round surveillance system was formed in three regions from north to south for population-based analysis. Children from birth to 16 years of age were included and up to 19 noncolonizing airway pathogens were tested for with multiplex RT-PCR.
In the 10-year period from July 1996 to June 2006, a total of 18,899 samples were tested. The positive rate increased with the size of the test panel to up to 72.9%. Picornaviruses (35-39%), paramyxoviruses (23-28%) and orthomyxoviruses (5.8-12.5%) comprised the highest fraction. Reoviruses and Legionella pneumophila were not found at all and Chlamydia pneumoniae and Bordetella parapertussis only rarely. Respiratory syncytial virus and parainfluenza virus (PIV) type 3 were anticyclical in rhythmicity with metapneumovirus and PIV1 and PIV2. The age medians per pathogen depended predominantly upon the attack rate and interepidemic intervals.
Active surveillance systems for ARI are superior to passive systems. They should be pathogen-specific and comprehensive for viruses and bacteria and age ranges. They should be population-based and multilevel to avoid bias. The impact of atypical bacteria in children was highly overestimated in earlier studies.
European Journal of Pediatrics 10/2007; 166(9):957-66. · 1.88 Impact Factor
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ABSTRACT: The effect of cow's milk consumption on childhood asthma has been debated for several years. This study attempts to provide further insight into this association through the use of a longitudinal study design. Newborns from parents with atopic history were recruited from Germany, Austria, and England (n = 696). For five repeated ascertainments, information was collected on cow's milk exposure, incidence of doctor-diagnosed asthma, and confounders. Generalized estimation equations, incorporating different models (concurrent, delayed, combined, and reverse causation), were used to determine this association. No association between cow's milk consumption and childhood asthma was found for the concurrent effects model (OR = 0.81, 95% confidence interval [CI]: 0.55, 1.20). In the delayed effects model, the direction of the association varied with time of follow-up. Thus, we stratified by period, which resulted in a significant protective delayed effect at 36 months (OR = 0.18, 95% CI = 0.06, 0.49). However, reverse causation negated this finding since the presence of asthma in prior months led to a reduction in further exposure to cow's milk (OR = 0.40, 95% CI = 0.16, 0.99). Hence, cow's milk consumption does not protect against childhood asthma. The apparent protection of cow's milk against asthma may result from parents of asthmatic children avoiding cow's milk, rather than actual prophylaxis.
Journal of Asthma 04/2007; 44(2):99-105. · 1.52 Impact Factor
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ABSTRACT: Surfactant proteins (SP) are important for the innate host defence and essential for a physiological lung function. Several linkage and association studies have investigated the genes coding for different surfactant proteins in the context of pulmonary diseases such as chronic obstructive pulmonary disease or respiratory distress syndrome of preterm infants. In this study we tested whether SP-B was in association with two further pulmonary diseases in children, i. e. severe infections caused by respiratory syncytial virus and bronchial asthma.
We chose to study five polymorphisms in SP-B: rs2077079 in the promoter region; rs1130866 leading to the amino acid exchange T131I; rs2040349 in intron 8; rs3024801 leading to L176F and rs3024809 resulting in R272H. Statistical analyses made use of the Armitage's trend test for single polymorphisms and FAMHAP and FASTEHPLUS for haplotype analyses.
The polymorphisms rs3024801 and rs3024809 were not present in our study populations. The three other polymorphisms were common and in tight linkage disequilibrium with each other. They did not show association with bronchial asthma or severe RSV infection in the analyses of single polymorphisms. However, haplotypes analyses revealed association of SP-B with severe RSV infection (p = 0.034).
Thus our results indicate a possible involvement of SP-B in the genetic predisposition to severe RSV infections in the German population. In order to determine which of the three polymorphisms constituting the haplotypes is responsible for the association, further case control studies on large populations are necessary. Furthermore, functional analysis need to be conducted.
BMC Pulmonary Medicine 02/2007; 7:6. · 1.33 Impact Factor
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ABSTRACT: Surfactant protein C is part of the surfactant complex lining up the alveoles and thereby inhibiting collapse of the airways. In addition it is involved in innate immune responses. Rare polymorphisms within surfactant protein C have been linked to sporadic paediatric lung diseases, like proteinosis or interstitial lung diseases. One study in the Finnish population described association of common polymorphisms with neonatal respiratory syndrome. Other common lung diseases have not yet been investigated for association with this gene. The aim of this study was to test surfactant protein C for association with bronchial asthma and with severe respiratory syncytial virus associated diseases in infancy. The two common amino acid variants Asn138Thr and Asn186Ser were genotyped on 322 children with asthma, 131 children with severe respiratory syncytial virus associated diseases and 270 controls. Statistical analyses of single polymorphisms made use of the Armitage's trend test; haplotypes were calculated with FAMHAP and FASTEHPLUS. Polymorphisms were in Hardy-Weinberg equilibrium and in tight linkage equilibrium in all populations. Single polymorphisms showed no association with the diseases, however, surfactant protein C haplotypes were associated with severe respiratory syncytial virus associated diseases (p = 0.013). Furthermore, an inverse haplotype distribution was found between children with asthma and respiratory syncytial virus infection (p = 0.00025). The results of our study might suggest opposing roles of surfactant Protein C in the genetic predisposition for respiratory syncytial virus associated diseases vs. asthma. The causal mechanism for this observation has still to be shown.
Pediatric Allergy and Immunology 01/2007; 17(8):572-7. · 2.46 Impact Factor
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ABSTRACT: A longitudinal study of health care-associated transmission of rotaviruses (RVs) in pediatric inpatients 0-48 months old in Austria, Germany, and Switzerland showed that almost one third of all cases occurred in patients 2 months old or younger. The effectiveness of vaccination against RV from 2 months of age onward remains to be evaluated.
Infection Control and Hospital Epidemiology 07/2006; 27(6):633-5. · 3.67 Impact Factor
