Vitamin D Status Over Time and Cognitive Function in Norwegian Older Adults: A Prospective Cohort of the HUNT Study.

BACKGROUND: There is conflicting evidence regarding the association between vitamin D status and cognitive function in population studies. The use of one-time vitamin D measurement in cognitive health studies may not reflect long-term vitamin D status in the body. OBJECTIVE: We aimed to examine the relationship of vitamin D status measured over time with the risk of neurocognitive disorders (NCDs) in Norwegian older adults. DESIGN: Prospective cohort study. SETTING: Regional, Trøndelag Health Study. PARTICIPANTS: This study followed a random cohort of 717 participants from HUNT2 (1995-97) and HUNT3 (2006-08) to HUNT4 70+ (2017-19). The mean age at HUNT4 70+ was 77.7 years. METHODS: Seasonal-standardized serum 25-hydroxyvitamin D [25(OH)D] levels in HUNT2 and HUNT3 were averaged and used as either a categorical variable (<50 and ≥50 nmol/L) or a continuous variable (per 25 nmol/L decrease). In the cohort aged 70 years or over (HUNT4 70+), NCDs consisting of mild cognitive impairment (MCI) and dementia were diagnosed by clinical experts according to the DSM-5 criteria. Logistic and linear regression models were used to estimate odds ratios (ORs) and regression coefficients (beta) with 95% confidence intervals (CIs) to assess the relationship between 25(OH)D levels and the risk of NCDs or the Montreal Cognitive Assessment (MoCA) score. RESULTS: In total, 347 (48.4%) had NCDs in HUNT4, with 33.3% having MCI and 15.1% having dementia. Compared with participants with serum 25(OH)D ≥50 nmol/L, those with 25(OH)D <50 nmol/L had a similar risk of NCDs (OR 1.05, 95% CI 0.76 to 1.46). No association was observed with the risk of MCI (OR 1.01, 95% CI 0.71 to 1.44) or dementia (OR 1.16, 95% CI 0.70 to 1.92), respectively. In a subsample of participants evaluated with the MoCA (n=662), a 25 nmol/L decrease in serum 25(OH)D was not associated with a change in MoCA score (beta 0.33, 95% CI -0.17 to 0.85). CONCLUSION: Vitamin D insufficiency defined by two times measurements of serum 25(OH)D with a 10-year interval was not associated with the risk of NCDs in a cohort of older Norwegian adults. Future studies utilizing multiple vitamin D measurements with a longer follow-up duration and larger sample size are warranted.

No association between circulating concentrations of vitamin D and risk of lung cancer: an analysis in 20 prospective studies in the Lung Cancer Cohort Consortium (LC3).

Background: There is observational evidence suggesting that high vitamin D concentrations may protect against lung cancer. To investigate this hypothesis in detail, we measured circulating vitamin D concentrations in prediagnostic blood from 20 cohorts participating in the Lung Cancer Cohort Consortium (LC3). Patients and methods: The study included 5313 lung cancer cases and 5313 controls. Blood samples for the cases were collected, on average, 5 years before lung cancer diagnosis. Controls were individually matched to the cases by cohort, sex, age, race/ethnicity, date of blood collection, and smoking status in five categories. Liquid chromatography coupled with tandem mass spectrometry was used to separately analyze 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] and their concentrations were combined to give an overall measure of 25(OH)D. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for 25(OH)D as both continuous and categorical variables. Results: Overall, no apparent association between 25(OH)D and risk of lung cancer was observed (multivariable adjusted OR for a doubling in concentration: 0.98, 95% CI: 0.91, 1.06). Similarly, we found no clear evidence of interaction by cohort, sex, age, smoking status, or histology. Conclusion: This study did not support an association between vitamin D concentrations and lung cancer risk.

Serum 25-hydroxyvitamin D levels and self-reported allergic rhinitis in Norwegian adults - The HUNT Study.

BACKGROUND: The role of low vitamin D status in the development of allergic rhinitis is unclear. We aimed to investigate the relationship between serum 25-hydroxyvitamin D [25(OH)D] and incidence of allergic rhinitis in adults. METHODS: The study included a random sample from an adult population who participated in the second and third surveys of the Nord-Trøndelag Health Study (HUNT) in Norway (HUNT2, 1995-1997 and HUNT3, 2006-2008). Serum 25(OH)D levels were measured in blood samples collected at baseline. Among 1351 adults who did not report allergic rhinitis at baseline, incident allergic rhinitis was identified by participant report of having or having had allergic rhinitis or hay fever at follow-up. Adjusted odds ratios (AOR) and 95% confidence intervals (CI) were calculated after adjustment for age, smoking, physical activity, socioeconomic status, family history of allergy, body mass index, and season. The analyses were stratified by sex due to its significant interaction with 25(OH)D levels (P < 0.02). RESULTS: Over an average of 11 years, 9% of men and 15% of women developed allergic rhinitis. Among men, serum 25(OH)D level <50 nM was associated with an increased risk of incident allergic rhinitis (AOR 2.55; 95% CI 1.01-6.49); each 25 nM reduction in 25(OH)D level was associated with an AOR of 1.84 (95% CI 1.18-2.87). In women, however, the association was opposite, with AOR being 0.83 (95% CI 0.66-1.05) for each 25 nM reduction in serum 25(OH)D level. CONCLUSIONS: Vitamin D appears to play different roles in the development of allergic rhinitis among men and women.

The associations of anxiety and depression symptoms with weight change and incident obesity: The HUNT Study.

OBJECTIVE: To investigate the associations of anxiety and depression symptoms with weight change and incident obesity in men and women. DESIGN: We conducted a prospective cohort study using the Norwegian Nord-Trøndelag Health Study (HUNT). SUBJECTS: The study cohort included 25 180 men and women, 19-55 years of age from the second survey of the HUNT (1995-1997). MEASUREMENTS: Anxiety and depression symptoms were measured using the Hospital Anxiety and Depression Scale. Weight change was determined for the study period of an average 11 years. Incident obesity was new-onset obesity classified as having a body mass index of 30.0 kg m(2) at follow-up. The associations of anxiety or depression with weight change in kilograms (kg) was estimated using linear regression models. Risk ratios (RRs) for incident obesity associated with anxiety or depression were estimated using log-binomial regression. RESULTS: In men, any anxiety or depression was associated with an average 0.81 kg (95% confidence interval (CI) 0.27-1.34) larger weight change after 11 years compared with those without such symptoms (mean weight change: 5.04 versus 4.24 kg). Women with any anxiety or depression had an average 0.98 kg (95% confidence interval (CI) 0.49-1.47) larger weight change compared with those without such symptoms (mean weight change: 5.02 versus 4.04 kg). Participants with any anxiety or depression had a significantly elevated cumulative incidence of obesity (men: RR 1.37, 95% CI 1.13-1.65; women: RR 1.18, 95% CI 1.00-1.40). CONCLUSION: We found that symptoms of anxiety and depression were associated with larger weight change and an increased cumulative incidence of obesity in both men and women.

Antibiotic use in early life and development of allergic diseases: respiratory infection as the explanation.

BACKGROUND: Early antibiotic use has been postulated to increase the development of allergic disease. Antibiotic use results from infection. Early infection may play a confounding role in the relationship between antibiotic use and allergic disease. OBJECTIVE: We aimed to investigate the relationship between antibiotic use during the first year of life and the development of allergic diseases in a birth cohort study, and also to carefully address the confounding effect of early respiratory infection. METHODS: Three thousand three hundred and six children were included in this study who participated in investigations at all occasions of 2 months, 1, 4 and 8 years of age. Data on antibiotic use and respiratory infections were collected at the age of 1 year. Diagnoses of allergic diseases at 4 and 8 years of age were derived from the follow-up questionnaires. RESULTS: During the first year of life, 43% (n=1420) of the children received antibiotics and 32% (n=1046) of the children had at least one type of respiratory infection among pneumonia, bronchitis and otitis. In univariate logistic regression analysis and after adjustment for early life factors, antibiotic use during the first year of life was associated with wheeze, asthma, eczema and food hypersensitivity at 4 years of age. After adjustment for the above respiratory infections during the first year of life, only the associations with wheeze and asthma at age 4 years remained statistically significant. These associations became non-significant in a subgroup analysis in children without early allergic signs. At age 8 years, antibiotic use during the first year of life was significantly associated with wheeze and eczema after adjustment for early life factors. The significant associations at age 8 years faded away following further adjustment for the respiratory infections. CONCLUSION: Our study indicated that the association between early antibiotic use and later allergic disease could at least partially be explained by early respiratory infection.

Fast food consumption counters the protective effect of breastfeeding on asthma in children?

BACKGROUND: Fast food consumption and childhood asthma have rapidly increased in recent decades. During the same period there has been an increased rate of prolonged breastfeeding. OBJECTIVE: To evaluate if fast food consumption was associated with asthma in children, and if the proposed protective effect of breastfeeding on asthma was altered by fast food consumption. METHODS: This case-control study included 246 children with allergist-diagnosed asthma and 477 non-asthmatic controls at age 8-10 years. Information on fast food consumption and exclusive breastfeeding was obtained from questionnaire data. The association between asthma and fast food consumption was evaluated. Asthma in relation to exclusive breastfeeding was also evaluated, taking into account fast food consumption as a modifying factor. RESULTS: Children with asthma were more likely to consume fast food than children without asthma [crude odds ratio (OR) 1.70, 95% confidence interval (CI) 1.23-2.34]. In comparison to prolonged exclusive breastfeeding (> or =12 weeks), asthma was positively associated with short-term exclusive breastfeeding (<12 weeks) in children who never or occasionally consumed fast food (crude OR 1.84, 95% CI 1.09-3.11), but not in children who frequently consumed fast food (crude OR 1.07, 95% CI 0.72-1.61). The P-value for this interaction (0.109) was borderline. Children with high fast food consumption who were exclusively breastfed <12 weeks as infants, had greater than a twofold risk of asthma compared with infants who had been exclusively breastfed for a longer time period and who did not become high consumers of fast food in later childhood. These findings were not affected after final adjustment of confounders and covariates. CONCLUSION: Fast food consumption is associated with asthma in children and potentially counteracts the protective effect of prolonged breastfeeding on asthma. This may explain the paradoxical phenomenon of parallel increased rates of prolonged breastfeeding and asthma in children. 556-561.

Symptoms to pollen and fruits early in life and allergic disease at 4 years of age.

BACKGROUND: The predictive value of reported early symptoms to pollen or fruits on later allergic disease is unclear. Our aim is to evaluate if symptoms to pollen and/or to fruits early in life are associated with allergic disease and sensitization to pollen at 4 years. METHODS: The study included 3619 children from the Barn (Children), Allergy, Milieu, Stockholm, Epidemiology project (BAMSE) birth cohort. Reported symptoms of wheeze, sneeze or rash to birch, grass or weed, symptoms (vomiting, diarrhea, rash, facial edema, sneeze, or wheeze) to fruits including tree-nuts at 1 or 2 years of age, and definitions of asthma, rhinitis and eczema at 4 years were derived from questionnaire data. Sensitization to pollen allergens was defined as allergen-specific IgE-antibodies to any pollen (birch/timothy/mugwort) > or =0.35 kU(A)/l. RESULTS: At 1 or 2 years of age, 6% of the children were reported to have pollen-related symptoms, 6% had symptoms to fruits, and 1.4% to both pollen and fruits. Children with symptoms to both pollen and fruits at 1 or 2 years of age had an increased risk for sensitization to any pollen allergen at age 4 (OR(adj) = 4.4, 95% CI = 2.1-9.2). This group of children also had a substantially elevated risk for developing any allergic disease (asthma, rhinitis, or eczema) at 4 years irrespective of sensitization to pollen (OR(adj) = 8.6, 95% CI = 4.5-16.4). CONCLUSIONS: The prevalence of reported symptoms to pollen and fruits is very low in early childhood. However, children with early symptoms to both pollen and fruits appear to have a markedly elevated risk for allergic disease.

Infrequent milk consumption plus being overweight may have great risk for asthma in girls.

BACKGROUND: Inadequate milk consumption and being overweight are each associated with asthma symptoms in children. Milk consumption has been inversely related to childhood overweight. Thus, being overweight may be a pathway or a confounder in milk-asthma relationship. A combination of both factors may be associated with greater risk of asthma than one factor alone. METHODS: This study included 246 children with allergist-diagnosed asthma and 477 nonasthmatic controls at the age of 8-10 years. Information on milk consumption during the last 12 months was obtained from questionnaires. Being overweight was defined as body mass index > or =85th percentile. Being overweight as a possible pathway or confounder was formally tested. The odds ratio (OR) for combined infrequent milk consumption and being overweight in asthmatic vs nonasthmatic children was determined in multivariate logistic regression analyses. RESULTS: There was a significant interaction between milk consumption and sex of the child in relation to asthma. Asthma was significantly associated with infrequent milk consumption in girls (crude OR 2.11, 95% CI 1.05-4.24) but not in boys. The asthma-milk relation in girls was neither mediated by being overweight (p(mediation tests) = 0.27) nor was the relationship confounded by being overweight (a 9% change in coefficient). Asthmatic girls had 3.6 times increased odds of having combination of infrequent milk consumption and being overweight than nonasthmatic girls (adjusted OR 3.64, 95% CI 1.18-11.24). Asthma was not associated with either factor or with absence of the other in girls. CONCLUSION: Infrequent milk consumption plus being overweight may have great risk for asthma in girls.

Urinary inflammatory mediators and inhalation of hypertonic saline in children.

BACKGROUND: The inflammatory mechanisms of hypertonic saline-induced bronchoconstriction are not well understood. METHODS: Seventeen asthmatics with (n=11) and without bronchial hyperresponsiveness (BHR) (n=6) and 18 randomly selected nonatopic nonasthmatic controls without BHR were evaluated by urine samples collected before and 1 h after hypertonic saline provocation test. Histamine, 11beta-PGF2alpha, and LTE4 were analysed by enzyme immunoassay (EIA) and eosinophil protein X (EPX) by radioimmunoassay (RIA). RESULTS: The levels of leukotriene E4 (LTE4) increased significantly after the challenge tests, both in the asthmatics (median: 354 pg/mg pre-challenge vs. 628 pg/mg post-challenge; P=0.05) and in the controls (median: 294 pg/mg pre-challenge vs. 460 pg/mg post-challenge; P <0.01). The levels of histamine also increased significantly in the latter (median: 299 micromol/mg pre-challenge vs. 569 micromol/mg post-challenge; P=0.03). However, the levels of 11beta-PGF2alpha and EPX did not change significantly after the challenge tests either in the asthmatics or in the controls. CONCLUSIONS: The inhalation of hypertonic saline increased urinary excretion of LTE4 both in the asthmatics and in the controls. The slight increase of leukotrienes was enough to induce airway obstruction in some of the asthmatics, because of the hyperresponsiveness in their airways.

High body mass index, asthma and allergy in Swedish schoolchildren participating in the International Study of Asthma and Allergies in Childhood: Phase II.

AIM: To assess the relationship between high body mass index (BMI) and asthma and atopic manifestations in 12-y-old children. METHODS: The relationship between high BMI and asthma symptoms was studied in 457 sixth-grade children, with (n = 161) and without (n = 296) current wheeze. High BMI was defined as > or = 75th percentile of gender-specific BMI reference values for Swedish children at 12 y of age; overweight as a subgroup of high BMI was defined as > or = 95th percentile. Children with a BMI < 75th percentile served as controls. Questionnaires were used to assess asthmatic and allergic symptoms, and bronchial hyperresponsiveness was assessed by hypertonic saline provocation tests. RESULTS: Current wheeze was associated with high BMI after adjustment for confounding factors (adjusted OR 1.7, 95% CI 1.0-2.5) and overweight had an even more pronounced effect (adjusted OR 1.9, 95% CI 1.0-3.6). In addition, asthma severity was associated with high BMI, as evaluated by the number of wheezing episodes during the previous 12 mo among the wheezing children (adjusted OR 2.0, 95% CI 1.0-4.0). There was also an association between high BMI and the presence of eczema in wheezing children (adjusted OR 2.2, 95% CI 1.0-4.6). However, high BMI was not significantly associated with hay fever, positive skin prick tests or bronchial hyperresponsiveness. CONCLUSION: The study confirms and extends a previously observed relationship between BMI and the presence of wheezing and asthma.

Wheezing in relation to atopy and environmental factors in Estonian and Swedish schoolchildren.

BACKGROUND: The prevalence of asthma and allergic diseases is significantly lower in post socialist Eastern Europe than in Western industrialized countries. The reason for this difference is largely unknown. Different types of childhood wheezing could be related to different risk factors. OBJECTIVE: To compare the prevalence of respiratory symptoms, asthma and atopic diseases among Estonian and Swedish schoolchildren and to evaluate characteristics for wheezing in the two countries. METHODS: In a prevalence study, population-based random samples of 10-11-year-old schoolchildren in Tallinn (n = 979), Estonia and in Linköping (n = 911) and Ostersund (n = 1197), Sweden were studied by a parental questionnaire and skin prick tests (SPT). All 275 children with wheeze in the past 12 months and 710 randomly selected controls within the original cohorts were invited to a case-control study involving a parental questionnaire, examination for flexural dermatitis and bronchial challenge with hypertonic saline. The study adhered to the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II protocol. RESULTS: The prevalence of current wheezing was similar (8-10%) in the three centres, while diagnosed asthma and atopic symptoms were more common in Sweden and cold-related respiratory symptoms were more prevalent in Estonia. Frequent wheezing was more common in Sweden than in Estonia (but significantly so only in Ostersund). Wheezing children in Sweden had a high rate of positive SPT (49% in Linköping and 58% in Ostersund) bronchial hyper-responsiveness (BHR) (48% in Linköping and Ostersund) and anti-asthmatic treatment (63% in Linköping and 81% in Ostersund). In Estonia, the proportion of wheezing children with positive SPT, BHR and anti-asthmatic treatment was only 26%, 13% and 17%, respectively. Domestic crowding was inversely related to wheezing in one of the study areas (Ostersund). The mean baseline forced expiratory volume in one second (FEV1) was higher in Estonia than in Sweden, both in wheezing and non-wheezing children. CONCLUSIONS: Our study suggested that although wheezing symptoms were equally common in Estonia and Sweden, they were less severe in Estonia. More frequent symptoms and a high rate of atopy, BHR and anti-asthmatic medication characterized wheezing children in Sweden. In contrast, BHR, atopy and medication were uncommon among wheezing children in Estonia.