title: Self-reported lower respiratory tract infections and development of islet autoimmunity in children with the type 1 diabetes high-risk HLA genotype: the MIDIA study.
abstract: OBJECTIVE
  To test whether self-reported lower respiratory tract infections in early infancy predicted risk for islet autoimmunity in genetically predisposed children.
  
  
  METHODS
  The environmental triggers for type 1 diabetes (MIDIA) study recruited newborns in Norway to identify those with the human leukocyte antigen high-risk genotype DR4-DQ8/DR3-DQ2. Of 46 939 newborns genotyped, 1003 (2.1%) carried the high-risk genotype, of whom 885 children were followed longitudinally with questionnaires and blood samples for autoantibody testing at 3, 6, 9 and 12 months of age, and then annually until 4 years of age. The endpoint (autoimmunity) was defined as positivity for at least one of three autoantibodies (to insulin, glutamic acid decarboxylase (GAD) or protein tyrosine phosphatase-like protein (IA2)) on at least two consecutive samples. The parents responded in the questionnaires, whether the child had had 'pneumonia, bronchitis or respiratory syncytial virus'. Cox proportional hazards regression models with time-dependent covariates were used to estimate hazard ratios for autoimmunity using STATA 10.
  
  
  RESULTS
  Forty-two children developed autoimmunity, of whom 15 later developed type 1 diabetes. For 17 of the 42 cases (40%) 'pneumonia, bronchitis or respiratory syncytial virus' was reported (0.5-4 years of age) before or at the onset of autoimmunity. For 187 of the 843 non-cases (22%) 'pneumonia, bronchitis or respiratory syncytial virus' was reported in the same age group. The hazard ratio was 3.4 (p=0.001, 95% confidence interval: 1.6-7.1) for developing autoimmunity. The estimated hazard ratio was only marginally influenced by adjustment for potential confounding factors. No association was found for other infectious self-reported symptoms.
  
  
  CONCLUSIONS
  Self-reported lower respiratory tract infections were associated with increased risk of islet autoimmunity in early infancy.
authors: Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway. trond.rasmussen@fhi.no
authors: Trond
authors: T
authors: Rasmussen
authors: Elisabet
authors: E
authors: Witsø
authors: German
authors: G
authors: Tapia
authors: Lars C
authors: LC
authors: Stene
authors: Kjersti S
authors: KS
authors: Rønningen
mesh_terms: D015551:Autoimmunity / Q000276:immunology; D001991:Bronchitis / Q000150:complications / Q000276:immunology; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics; D015803:HLA-DR3 Antigen / Q000235:genetics; D015804:HLA-DR4 Antigen / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007328:Insulin / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D008137:Longitudinal Studies; D009664:Norway; D011014:Pneumonia / Q000150:complications / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000150:complications / Q000276:immunology; D012141:Respiratory Tract Infections / Q000150:complications* / Q000276:immunology; D012306:Risk; D057566:Self Report
chemical_list: D006683:HLA-DQ Antigens; D015803:HLA-DR3 Antigen; D015804:HLA-DR4 Antigen; D007328:Insulin; D005968:Glutamate Decarboxylase