Occupational exposures to pesticides and other chemicals: a New Zealand motor neuron disease case-control study.

OBJECTIVES: To assess associations between occupational exposures to pesticides and other chemicals and motor neuron disease (MND). METHODS: A population-based case-control study that included 319 MND cases (64% male/36% female) recruited through the New Zealand MND Association complemented with hospital discharge data, and 604 controls identified from the Electoral Roll. For each job held, a questionnaire collected information on 11 exposure categories (dust, fibres, tobacco smoke, fumes, gas, fumigants, oils/solvents, acids/alkalis, pesticides, other chemicals and animals/animal products). ORs were estimated using logistic regression adjusting for age, sex, ethnicity, socioeconomic status, education, smoking, alcohol consumption, physical activities, head/spine injury and other occupational exposures. RESULTS: Two exposure categories were associated with increased MND risks: pesticides (OR 1.70, 95% CI 1.17 to 2.48) and fumigants (OR 3.98, 95% CI 1.81 to 8.76), with risks increasing with longer exposure duration (p<0.01). Associations were also observed for: methyl bromide (OR 5.28, 95% CI 1.63 to 17.15), organochlorine insecticides (OR 3.28, 95% CI 1.18 to 9.07), organophosphate insecticides (OR 3.11, 95% CI 1.40 to 6.94), pyrethroid insecticides (OR 6.38, 95% CI 1.13 to 35.96), inorganic (copper) fungicides (OR 4.66, 95% CI 1.53 to 14.19), petrol/diesel fuel (OR 2.24, 95% CI 1.27 to 3.93) and unspecified solvents (OR 1.91, 95% CI 1.22 to 2.99). In women, exposure to textile fibres (OR 2.49, 95% CI 1.13 to 5.50), disinfectants (OR 9.66, 95% CI 1.29 to 72.44) and cleaning products (OR 3.53, 95% CI 1.64 to 7.59) were also associated with MND; this was not observed in men (OR 0.80, 95% CI 0.44 to 1.48; OR 0.72, 95% CI 0.29 to 1.84; OR 0.57, 95% CI 0.21 to 1.56, respectively). CONCLUSIONS: This study adds to the evidence that pesticides, especially insecticides, fungicides, and fumigants, are risk factors for MND.

Obesity measures in the Kiribati population: a need to reclassify body mass index cut-points.

BACKGROUND: Obesity is a public health problem in Micronesia. The objective of the study was to assess obesity, the relationship between body mass index (BMI) and body fat percentage (BF%) among adults, and determine the appropriate BMI cut-points in Kiribati. METHODS: A cross-sectional study was undertaken among 483 adults randomly selected from South Tarawa (ST) and Butaritari (BT). Weight, height, BF% and physical activity level (PAL) was measured using standard methods. Linear and quadratic regression analyses were conducted to assess the association between BF% and BMI whilst controlling for age and gender. Receiver operating characteristics (ROC) curve analyses were used to assess whether for the Kiribati population alternative BMI cut-off points for obesity are needed. RESULTS: Approximately 75% of participants were obese using standard BMI and BF% cut-offs, with the highest prevalence observed in South Tarawa. BF% was significantly (p < 0.001) and positively associated with age (males, r = 0.78; females, r = 0.67; p < 0.001) and BMI. Based on ROC-curve analyses the BMI cut-offs for predicting high BF% among I-Kiribati people were 24.5 kg/m2 for males and 32.9 kg/m2 for females. CONCLUSIONS: In conclusion, the majority of adults in Kiribati were either obese or overweight and had high BF%. We suggest that ethnic-specific BMI cut-points to define obesity for the population of Kiribati may be more appropriate than the currently used international cut-points.

Sputum basophils are increased in eosinophilic asthma compared with non-eosinophilic asthma phenotypes.

Sputum basophil numbers are increased in allergic asthmatics, but it is unclear what role airway basophils play in "TH2-low" asthma phenotypes. Using flow cytometry, we found that basophils were significantly increased in all asthmatics (n=26) compared with healthy controls (n=8) (P=0.007) with highest levels observed in eosinophilic asthma (EA); median 0.22%, IQR 0.11%-0.47%; n=14) compared with non-EA (NEA) (0.06%, 0.00%-0.20%; n=12; P<0.05). In asthmatics, basophils were positively correlated with sputum eosinophils (r=0.54; P<0.005) and inversely with sputum neutrophils (r=-0.46: P<0.05), but not with FEV1 (% predicted), FEV1 /FVC or bronchodilator reversibility. In a subgroup initially identified as inadequately controlled asthma (n=7), there was a trend (P=0.08) towards a reduction in sputum basophils following increased inhaled corticosteroid (ICS) treatment. Our findings suggest that basophils may be particularly important in eosinophilic asthma and that sputum basophil assessment could be a useful additional indicator of "TH2-high" asthma.

Problematic severe asthma in children treated at high altitude: tapering the dose while improving control.

BACKGROUND: Multidisciplinary treatment at high altitude is a possible treatment option for problematic severe asthma (PSA) in children. This management can result in the tapering of inhaled corticosteroids. AIM: Our aim was to analyze the effect of multidisciplinary treatment at high altitude, notably the ability to taper corticosteroids. To get an insight into possible factors influencing tapering, we examined whether demographic variables, disease control and quality of life at treatment entrance could predict the tapering of corticosteroids. METHODS: This prospective open-phase cohort study analyzed the data of 43 children aged 8-17 years referred to a specialized high altitude treatment centre. Lung function (FEV1, FEV1/VC), inflammation (FeNO), medication level, asthma control (ACT) and quality of life [PAQLQ(S)] were evaluated on admission and at discharge. RESULTS: Thirty-two (74%) children fulfilled PSA criteria. Three (7%) children used daily oral steroids. After 72 ± 30 (mean ± SD) days of treatment, the mean dosage of inhaled corticosteroids (ICS) could be significantly reduced from 1315 µg ± 666 budesonide equivalent to 1132 µg ± 514. Oral steroid maintenance therapy could be stopped in all patients. FeNO, asthma control and quality of life improved (p < 0.001) from admission to discharge; FEV1 was in the normal range on both occasions. Apart from ICS levels at entrance, multiple regression analyses did not show any associated factor predicting the reduction of ICS dosage during treatment. CONCLUSION: The results indicate that high altitude treatment may be a treatment option for children with PSA, but it is not possible to predict ICS tapering off from health status variables at treatment entrance.

TBX4 mutations (small patella syndrome) are associated with childhood-onset pulmonary arterial hypertension.

BACKGROUND: Childhood-onset pulmonary arterial hypertension (PAH) is rare and differs from adult-onset disease in clinical presentation, with often unexplained mental retardation and dysmorphic features (MR/DF). Mutations in the major PAH gene, BMPR2, were reported to cause PAH in only 10-16% of childhood-onset patients. We aimed to identify more genes associated with childhood-onset PAH. METHODS: We studied 20 consecutive cases with idiopathic or heritable PAH. In patients with accompanying MR/DF (n=6) array-comparative genomic hybridisation analysis was performed, with the aim of finding common deletion regions containing candidate genes for PAH. Three patients had overlapping deletions of 17q23.2. TBX2 and TBX4 were selected from this area as candidate genes and sequenced in all 20 children. After identifying TBX4 mutations in these children, we subsequently sequenced TBX4 in a cohort of 49 adults with PAH. Because TBX4 mutations are known to cause small patella syndrome (SPS), all patients with newly detected TBX4 mutations were screened for features of SPS. We also screened a third cohort of 23 patients with SPS for PAH. RESULTS: TBX4 mutations (n=3) or TBX4-containing deletions (n=3) were detected in 6 out of 20 children with PAH (30%). All living patients and two parents with TBX4 mutations appeared to have previously unrecognised SPS. In the adult PAH-cohort, one TBX4 mutation (2%) was detected. Screening in the cohort of (predominantly adult) SPS patients revealed no PAH. CONCLUSIONS: These data indicate that TBX4 mutations are associated with childhood-onset PAH, but that the prevalence of PAH in adult TBX4 mutation carriers is low.

Household dampness and microbial exposure related to allergy and respiratory health in Danish adults.

Background: Indoor dampness has consistently been associated with respiratory symptoms and exacerbations. The causal mechanisms may involve increased microbial exposures. However, the evidence regarding the influence of indoor microbial exposures under damp- and non-damp conditions on the risk of asthma and allergy has been inconclusive. Objective: The aim of this study was to investigate the association between dampness and microbial exposure with allergy and respiratory health in Danish adults using a cross-sectional design. Methods: From 1,866 participants of the Health2006 cohort, we selected three non-overlapping groups: 196 at random, 107 with confirmed atopy, and 99 without atopy. Bedroom dust was sampled using electrostatic dust fall collectors and analysed for endotoxin, ß-(1,3)-D-glucan, 19 microbial species or groups, and total fungal load. Household moisture-related problems and asthma were self-reported by questionnaire. Atopy was determined by skin-prick-testing and lung function was measured by spirometry. Results: Household moisture damage was positively associated with asthma outcomes, although this was statistically significant only in atopics for self-reported asthma (odds ratio (OR) 3.52; 95%CI 1.01-12.7). Mould odor was positively associated with wheezing (OR 6.05; 95%CI 1.19-30.7) in atopics. Inconsistent associations were found for individual microbial exposures and health outcomes. Inverse associations were observed between microbial diversity and rhinitis in the random sample and both doctor-diagnosed and self-reported asthma in non-atopics. Conclusions: In conclusion, our findings suggest that household moisture damage may increase the risk of asthma and wheeze with mould odor in atopics. In addition, asthma and allergy may be affected by the indoor microbial composition in urban domestic environments. Further studies are needed to identify and understand the causal agents and underlying mechanisms behind the potential effects of environmental microbial exposure on human health.

Farm exposure in utero may protect against asthma, hay fever and eczema.

The aim of the present study was to assess which factors contribute to the lower prevalence of allergic diseases in farmers' children, and the importance of timing of exposure. In a cross-sectional questionnaire survey, asthma symptoms, hay fever and eczema were assessed, as well as current, early and prenatal farm-related exposures in 1,333 farmers' children and 566 reference children aged 5-17 yrs. Farmers' children had a lower incidence of asthma symptoms and eczema. Current and maternal exposure during pregnancy to animals and/or grain and hay reduced the risk of asthma symptoms, hay fever and eczema. The exposure-response association for maternal exposure was nonlinear for most outcomes. After mutual adjustment, the effects of prenatal exposure remained unchanged whereas current exposure remained protective only for asthma medication, asthma ever and hay fever. Exposure during the first 2 yrs was not associated with symptoms, after controlling for prenatal exposure. A combination of prenatal and current exposure was most strongly associated with wheeze (odds ratio (OR) 0.48, 95% confidence interval (CI) 0.28-0.80), asthma medication (OR 0.50, 95% CI 0.30-0.82), asthma ever (OR 0.50, 95% CI 0.33-0.76), hay fever (OR 0.47, 95% CI 0.30-0.73) and eczema (OR 0.46, 95% CI 0.30-0.70). Prenatal exposure may contribute to the low prevalence of asthma, hay fever and eczema in farmers' children, but continued exposure may be required to maintain optimal protection.

Risk factors for symptoms of childhood asthma, allergic rhinoconjunctivitis and eczema in the Pacific: an ISAAC Phase III study.

BACKGROUND AND METHODS: Phase III of the International Study of Asthma and Allergies in Childhood (ISAAC) was conducted in eight Pacific countries, five of which (Samoa, Fiji, Tokelau, French Polynesia and New Caledonia) collected environmental questionnaire (EQ) data. We report the findings of the EQ analyses below. RESULTS: The major factors associated with current wheeze were regular margarine consumption (prevalence odds ratio [POR] 1.19, 95%CI 1.01-1.40), paracetamol use (POR 1.35, 95%CI 1.11-1.64), electric cooking (POR 1.42, 95%CI 1.11-1.80), regular exercise (POR 1.44, 95%CI 1.18-1.75) and maternal smoking (POR 1.16, 95%CI 1.01-1.33). Protective factors included having older siblings (two or more POR 0.69, 95%CI 0.58-0.82; one POR 0.86, 95%CI 0.71-1.05), and being born in the country of the survey (POR 0.74, 95%CI 0.63-0.87). Risk factors for rhinoconjunctivitis included regular consumption of meat, butter, margarine and nuts, regular exercise, regular television viewing, paracetamol use and passive smoking. Eczema was associated with regular meat, pasta and butter consumption, regular television viewing, paracetamol use and passive smoking. CONCLUSIONS: Regular meat and margarine consumption, paracetamol use, electric cooking and passive smoking are risk factors for symptoms of asthma, rhinoconjunctivitis and eczema in the Pacific. However, most of these associations were weak, and account for only a small proportion of cases.

Chlorinated persistent organic pollutants in serum of New Zealand adults, 2011-2013.

A national survey was conducted in 2011-2013 to assess serum concentrations of persistent organic pollutants (POPs) in adult New Zealanders. Participants were randomly selected from the 2010 Electoral Roll within 64 demographic strata according to 4 age groups, 4 regions, 2 ethnic groups (Maori/non-Maori) and gender. Eligible subjects (n=734) donated up to 30ml of blood, after which serum was pooled (n=49) according to demographic strata prior to analysis by GC-HRMS. Associations between demographic variables (age, region, ethnicity, gender) and serum POPs were assessed using linear regression. The weighted geometric mean (GM) of PCDD/Fs was 5.3pg/g lipid toxic equivalents using the WHO 2005 toxic equivalence factors (TEQ05), which increased by age (3.2, 4.4, 4.8, and 8.1pg/g lipid for the 19-24, 25-34, 35-49, and 50-64year age groups, respectively). The weighted GM of dioxin-like PCBs was 1.4pg TEQ05/g lipid which also increased by age (0.82, 0.86, 1.4, and 2.3pg/g lipid for the same age groups, respectively). Of the detected OCPs, the highest concentration was observed for p,p'-DDE (weighted GM, 220ng/g lipid) followed by hexachlorobenzene (HCB; 7.3ng/g lipid), beta-HCH (7.0ng/g lipid), and dieldrin (4.7ng/g lipid). For most Cl-POPs, concentrations were lowest in the youngest age group, and were similar for men and women and Maori and non-Maori. Serum Cl-POPs were, on average, 50% lower than those measured 15years earlier in 1997. This survey provides evidence of declining serum concentrations of chlorinated POPs in the New Zealand adult population. Age was the most important determinant of POPs concentrations. Body burdens of PCDD/Fs and PCBs in New Zealand are relatively low by international comparison, while for OCPs they are similar or lower compared to those reported for other developed countries.

Polybrominated diphenyl ethers and perfluorinated alkyl substances in blood serum of New Zealand adults, 2011-2013.

A national survey was conducted in 2011-2013 to assess serum concentrations of brominated flame retardants (BFRs) and perfluorinated alkyl substances (PFASs) in adult New Zealanders. Participants were randomly selected from the 2010 Electoral Roll within 64 demographic strata according to 4 age groups, 4 geographic regions, 2 ethnic groups (Maori/non-Maori) and sex. Eligible participants (n = 734; response rate of contacted individuals = 37%) donated up to 30 mL of blood, after which serum was pooled (49 pools for BFRs, 63 pools for PFASs) according to demographic strata. BFRs were analysed by GC-HRMS and PFASs by LC-MS/MS. Associations between serum BFRs and PFASs and demographic variables (age, region, ethnicity, sex) were assessed using regression analysis. The weighted geometric mean (GM) serum concentrations of BDE47, BDE99, BDE100, and BDE153 were 2.0, 0.66, 0.43, and 1.2 ng/g lipid, respectively. The weighted geometric mean (GM) serum concentrations of PFOS, PFOA, PFHxS, and PFNA were 3.4, 2.4, 1.0, and 0.66 ng/mL, respectively. The majority of BFRs showed higher serum concentrations in younger age groups. Conversely, the four PFASs showed higher serum concentrations in older age groups. Concentrations of BFRs and PFASs were generally lower in females compared to males. In New Zealand, both age and sex are important determinants of BFR and PFAS serum concentrations.

The global epidemiology of asthma in children.

Until recently, most studies reported that asthma prevalence has increased in recent decades. The best indication of what is now happening globally will be provided by Phase III of the International Study of Asthma and Allergies in Childhood (ISAAC) study. Some individual ISAAC centres in Western countries, as well as several studies in adults, have already reported no increase or even a decrease in asthma prevalence over the last 10 years. 'Established' risk factors for asthma cannot account for the global prevalence increases, the international patterns or the recent declines in prevalence in some Western countries. It seems that the 'package' of changes in the intrauterine and infant environment occurring with 'Westernisation' is causing increased susceptibility to the development of asthma and/or allergy. The 'package' includes changes in maternal diet, increased foetal growth, smaller family size, reduced infant infections, increased use of antibiotics and paracetamol and immunisation, all of which have been (inconsistently) associated with an increased risk of childhood asthma, but none of which can alone explain the increases in prevalence. It is likely that the 'package' is more than the sum of its parts, and that these social and environmental changes are all pushing our immune systems in the same direction. To know what that direction is requires that better aetiological theories of asthma are developed to replace the allergen theory, or to incorporate it as a special case. Global comparisons of asthma prevalence and assessment of time trends will continue to play a major role in this process.

Environmental determinants associated with the development of asthma in childhood.

Asthma is a common chronic respiratory disease, and many epidemiological studies have documented an increasing trend over the past few decades. Comparative studies have shown that asthma is more prevalent in Westernised societies than in rural or developing regions. Environmental factors are likely to be important in explaining such disparities and increasing trends. Although allergen exposure and atopic sensitisation have been thought to be important in the pathogenesis of asthma, recent cross-sectional and longitudinal studies suggest that allergic sensitisation is likely a marker rather than a causative factor for asthma. There is accumulating evidence confirming the role of early exposure to infections in altering the regulation of cytokine production and reduction of subsequent development of atopic disorders. The consistent finding of a lower prevalence of asthma in subjects brought up in a farming environment and the inverse relationship between microbial exposure and asthma symptoms further support the importance of early environmental exposure affecting the risk of subsequent development of asthma. Confirmation of the pathogenetic role of these environmental determinants may allow us to develop primary preventive strategies against the development of asthma and related atopic diseases.

Review of methods applicable to the assessment of mold exposure to children.

This article presents discussion of the assessment of the exposure of children to fungi, substances derived from fungi, and the environmental conditions that may lead to exposure. The principles driving investigations of fungal contamination and subsequent exposure are presented as well as guidelines for conducting these investigations. A comprehensive description of available research sampling and analysis techniques is also presented.

Beta(1-->3)-glucan in house dust of German homes: housing characteristics, occupant behavior, and relations with endotoxins, allergens, and molds.

beta(1-->3)-Glucans are potent proinflammatory agents that have been suggested to play a role in indoor-related respiratory health effects. The aim of this study was to assess whether beta(1-->3)-glucan concentrations in house dust are correlated with levels of endotoxins, allergens, and culturable mold spore counts in house dust. Further, the associations of beta(1-->3)-glucan with housing characteristics and occupant behavior were assessed. beta(1-->3)-Glucan was measured in settled house dust from living room floors of 395 homes of two German cities, Erfurt and Hamburg, with a specific enzyme immunoassay. Concentrations ranged from below the limit of detection to 19,013 microg/m(2) (22,588 microg/g dust). Concentrations per square meter were found to be correlated with endotoxins, mite and cat allergens, and culturable mold spores. Correlations were weaker when concentrations were expressed per gram of dust, indicating that variance in concentrations of all factors is largely determined by the amount of dust sampled. Associations between beta(1-->3)-glucan, housing characteristics, and occupant behavior were found for concentrations per square meter but not for concentrations per gram of dust. The following characteristics were associated with a significant increase in beta(1-->3)-glucan levels: carpets in the living room [means ratio (MR) = 1.9-2.1], keeping a dog inside (MR = 1.4), use of the home by four or more persons (MR = 1.4), use of the living room for > 180 hr/week (MR = 2.1), lower frequency of vacuum cleaning (MR = 1.6-3.0) and dust cleaning (MR = 1.2 and 1.4, respectively), and presence of mold spots during the past 12 months (MR = 1.4). We conclude that that the amount of dust sampled can be used as a proxy for hygiene and that beta(1-->3)-glucan concentrations per square meter are related to the amount of dust sampled.

Effect of exercise training and diet modification on serum lipids and lipoproteins in coronary artery disease patients treated with thiazides.

The effects of chronic exercise training and diet modification on serum lipids and lipoproteins were measured in 17 hypertensive males and 41 normotensive males with documented coronary artery disease (CAD). Exercise consisted of aerobic activities which were performed at approximately 75-85% of the symptom-limited maximum heart rate for 30-40 minutes, three times weekly for 3 months. Each participant's diet was also controlled, the recommended daily intake of fat and cholesterol was no more than 40 g/day and 200 mg/day, respectively. Significant increases in estimated VO2max and total cholesterol/high density lipoprotein (HDL) and a significant decrease in serum triglycerides were documented after training. Significant differences in serum cholesterol and triglycerides between the nondiuretic and diuretic patients were also noted. No significant changes were found in low density lipoprotein (LDL), HDL, or body weight. Vigorous aerobic training and diet modification can favorably modify the deleterious effects of diuretic medications on serum triglycerides and total cholesterol/HDL in patients with documented CAD.

Work-related symptoms in sewage treatment workers.

The aim of this study was to investigate health symptoms in sewage treatment workers. A health questionnaire was distributed among 147 sewage treatment workers. Correlating symptoms were clustered using principal component analysis and the association with self-reported exposure was assessed by calculating prevalence odds ratios (OR). Endotoxin was measured in two treatment plants. Personal endotoxin exposure was low (<10 Endotoxin Units/m(3)). Factor analysis of 29 symptoms resulted in four clusters of highly correlating symptoms: 'flu-like symptoms'; 'higher airway symptoms'; 'lower airway symptoms'; and 'neurological symptoms'. These clusters were positively associated with working with sewage, but only significant for 'flu- like symptoms' (OR=5.0; 95%CI=1.4-17.6; p<0.05) and 'neurological symptoms' (OR=4.2; 95%CI=1.5-11.7; p<0.01). Chemical exposure was associated with 'neurological symptoms' (OR=8.4; 95%CI=1.1-65.7; p<0.05). The use of daily washed working clothes was negatively associated with 'flu-like symptoms' (OR=0.3; 95%CI=0.1-0.6; p<0.01). In conclusion, sewage treatment workers develop a large variety of work-related symptoms that are not likely caused by endotoxin exposure only. Good hygienic practice at the workplace may prevent some of these symptoms

Application of the classic Limulus test and the quantitative kinetic chromogenic LAL method for evaluation of endotoxin concentration in indoor air.

The classic (gel-clot procedure) Limulus test (CLT) and the quantitative kinetic chromogenic LAL method (KQCL) used for the evaluation of bacterial endotoxin concentration in the indoor air of dwellings were compared. The scientific procedure included analyses of 40 air samples supplemented by the analysis of 20 sample duplicates (selected at random) which were taken during the fall season from 10 flats located in 3 towns of the Upper Silesian region (southern Poland). The particulate aerosol probes were sampled by Harvard impactor and Casella sampler. The same samples were analyzed in the Netherlands using the quantitative kinetic chromogenic LAL method, and in Poland using the classic Limulus test. Comparison of both methods revealed that the quantitative kinetic chromogenic LAL method was more precise, with better reproducibility (the coefficient of variation between analyses of the main probe and its duplicate was over two times smaller in the KQCL method than in the CLT method), fully automated in the phase of analysis and data reading, and faster and more effective than the classic Limulus test. Nevertheless, on the basis of the obtained results, the usefulness of the classic Limulus method for assessment of the degree of pollution of indoor air with bacterial endotoxin seems to be confirmed as in the majority of examined samples (21 out 40) the results obtained by both methods were of the same order of magnitude, and in the remaining 19 samples did exceed one order of magnitude. Thus, the data received by means of the classic Limulus test may be regarded as acceptable.

Asthma control in a random sample of New Zealand adolescent asthmatics.

Asthma control, defined by asthma symptoms and lung function, and asthma medication use, was assessed in 123 adolescent asthmatics. Sputum eosinophilia (>or= 2.5% eosinophils) and bronchial hyperresponsiveness (BHR) to hypertonic saline were also measured to assess whether these additional objective parameters might aid in determining asthma control; 54.5% of subjects had adequately controlled asthma; 50.4% of all subjects reported inhaled corticosteroid use in the preceding 12 months; however, only 22.3% reported regular use. Although BHR and median eosinophil numbers were significantly higher in the inadequately controlled asthmatics, BHR and sputum eosinophilia had poor sensitivity for detecting inadequate asthma control.