The relationship of 25-hydroxyvitamin D values and risk of fracture: a population-based retrospective cohort study.

Our study investigates 25-hydroxyvitamin D levels and fracture risk using population-level data. 25-Hydroxyvitamin D values < 12, 12-19, and > 50 ng/mL were not associated with increased risk of fractures overall compared with values 20-50 ng/mL. Severely low levels may be associated with increased risk of osteoporotic fracture, particularly of the wrist. INTRODUCTION: Studies of the relationship between serum 25-hydroxyvitamin D (25(OH)D) levels and fracture risk have been inconsistent. We hypothesized that high 25(OH)D concentrations (> 50 ng/mL) would be associated with increased risk of fracture. METHODS: We identified all adult patients living in Olmsted County, Minnesota, between January 1, 2005 and December 31, 2011, who had at least one 25(OH)D measurement. Fracture outcomes were retrieved starting 30 days after 25(OH)D measurement and until patients' final clinical visit as an Olmsted County resident, December 31, 2014, or death. Data were analyzed using Cox proportional hazard regression. RESULTS: Of 11,002 individuals with a 25(OH)D measurement, 5.8% had a 25(OH)D value ˂ 12 ng/mL, and 5.1% had a value > 50 ng/mL. Compared with subjects with 25(OH)D values 20-50 ng/mL (reference group), values < 12, 12-19, and > 50 ng/mL displayed no association with overall fracture risk. After adjusting for a prior diagnosis of osteoporosis/osteopenia, only individuals with values ˂ 12 ng/mL had increased risk of any osteoporotic fracture (aHR = 1.41; 95% CI 1.05-1.89) and wrist fracture (aHR = 2.11; 95% CI 1.27-3.48) compared with the reference group. Compared with the reference group, values ˂ 12 ng/mL were associated with increased risk of any fracture (aHR = 1.35; 95% CI 1.01-1.80), osteoporotic fracture (aHR = 2.18; 95% CI 1.44-3.31), and wrist fracture (aHR = 2.39; 95% CI 1.19-4.81) in subjects without a prior diagnosis of osteoporosis/osteopenia, but not in those with a prior diagnosis of osteoporosis/osteopenia. CONCLUSION: Severely low 25(OH)D levels may be associated with increased risk of osteoporotic fracture, particularly of the wrist, but 25(OH)D values > 50 ng/mL were not associated with increased fracture risk.

Usefulness of asthma predictive index in ascertaining asthma status of children using medical records: An explorative study.

BACKGROUND: Frequent wheezing in original asthma predictive index (API) was defined by parental report of recurrent wheezing within 1 year during the first 3 years of life. The nature of frequent wheezing in children, particularly aged over 3 years, has not been studied. We aimed to assess the frequency and interval of wheezing to define frequent wheezing in ascertaining asthma for children using medical records. METHODS: Among children who participated in a previous study (n = 427), all wheezing episodes documented in medical records were collected for children who had ≥2 wheezing episodes PLUS met one major criterion or two minor criteria of API. We compared the distribution of known risk factors for asthma between subjects having two consecutive wheezing episodes with shorter interval (≤1 year) compared to those with longer interval (1 to 3 years). RESULTS: A total of 62 children met API at median age of 2.3 years. During follow-up period (median age: 11.3 years), a total of 198 wheezing episodes were observed. 81% of wheezing intervals were within 3 years from the earlier wheezing episode, including 60% within 1 year. Children who met API based on 1-year interval (n = 40) vs 1- to 3-year interval (n = 13) appeared to be similar in regard to the known risk factors for asthma. CONCLUSIONS: Our exploratory study finding suggests that children who had frequent wheezing episodes with longer interval (<3 years) need to be considered to be determined as asthma cases when API is applied to retrospective medical records. Prospective studies with a larger sample size need to replicate this finding.

Influence of HLA-DR polymorphism and allergic sensitization on humoral immune responses to intact pneumococcus in a transgenic mouse model.

Asthma is independently associated with HLA-DR3 and increased risks of pneumococcal diseases. We aimed to determine whether HLA-DR polymorphism (HLA-DRB1*03), sensitization to house dust mite (HDM), or their interaction affects humoral immune responses to pneumococcal polysaccharide and protein antigens of intact pneumococci. Induction of serum titers of anti-pneumococcal polysaccharide and anti-surface protein IgM and IgG in response to immunization with intact pneumococci (Pn) serotype 14 was determined using humanized HLA-DR3 and DR2 transgenic mice. Transgenic mice were sensitized by injecting HDM and challenged with intranasal HDM. Mice were subsequently immunized with heat-killed Pn14 at day 24. Serum titers of anti-phosphorylcholine (PC) IgM and IgG, anti-pneumococcal polysaccharide, capsular type 14 (PPS14) IgM and IgG, and anti-pneumococcal surface protein A (PspA) IgG were measured. We included a total of 44 mice (22 DR3 and 22 DR2 mice) and half of mice in each group were sensitized with HDM (i.e. 22 HDM-sensitized and 22 control mice). HDM-sensitized mice, irrespective of HLA-DR polymorphism, had significantly lower humoral immune responses. HLA-DR3 mice, irrespective of HDM sensitization, elicited a significantly lower anti-PC IgG response. In contrast, the anti-PspA IgG response was higher in DR3 relative to DR2 mice. The effect of HDM sensitization on lowering humoral immune responses to Pn14 was observed in DR3 mice regardless of the nature of the antigen, whereas such decreases were observed only for the anti-PPS14 IgG and anti-PC IgM responses in DR2 mice. HDM sensitization lowered humoral immune responses to intact pneumococcus and this effect was significantly modified by the HLA-DR polymorphism.