Journal Articles
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Item Immune modulating effects of continuous bioaerosol and terpene exposure over three years among sawmill workers in Norway(Nordic Association of Occupational Safety and Health (NOROSH), 2025-09-01) Straumfors A; Haugen F; Skare Ø; Eduard W; Henneberger PK; Douwes J; Ulvestad B; Nordby K-COBJECTIVES: Exposure to wood dust, resin acids, microbial and volatile components among sawmill workers may impair respiratory health, with inflammation indicated as a key mechanism. Previous, mostly cross-sectional studies have shown mixed results, and a conclusive association between wood dust exposure and chronic respiratory inflammation has therefore not yet been established. This study assessed associations between exposure to bioaerosols and volatile terpenes and serum inflammatory marker levels over three years. METHODS: Serum biomarkers and blood cell counts were analyzed based on 702 observations from 450 exposed sawmill workers and 102 observations from 65 unexposed sawmill workers in Norway at baseline and after three years. Job-exposure-matrices, based on measurements among the same cohort, were used to assess exposures for wood dust, endotoxins, resin acid, monoterpenes, fungal spores, and fungal fragments. Changes in exposures, biomarkers and cell counts over the study period, as well as group differences and potential cause-and-effect associations were assessed using linear mixed regression. RESULTS: Exposures were relatively low and below occupational limits, although variances were relatively high (GSDtot 2.1-8.3), largely driven by differences between workers (GSDbw 1.9-7.8). Serum CC-16 and mCRP were slightly higher after three years, whereas IL-1β, TNF-α and IL-10 levels were significantly lower among exposed compared with unexposed workers. Exposures positively associated with increases in biomarker levels included endotoxin with mCRP, monoterpenes with IL-10, and fungal spores with TNF-α and IL-8. Exposed workers had higher counts of total leucocytes, neutrophils, lymphocytes and basophils after three years. Several of the increased leucocyte counts were associated with concurrent increase in mCRP and IL-6 concentrations, predominantly in the exposed group. Conversely, increased CC-16 levels were associated with lower leucocyte and neutrophil counts, mainly in the unexposed group. CONCLUSION: Continuous exposure to wood dust and related components for three years appears to induce a chronic low-grade inflammatory response among sawmill workers with a shift in cytokine profiles towards a less regulated, potentially more muted immune state.Item Environmental and occupational exposure to erionite and related health risks: Progress and prospects(Oxford University Press on behalf of the British Occupational Hygiene Society, 2025-08-01) Chen G; ‘t Mannetje A; Salmond JA; Douwes JObjectives Erionite, a naturally occurring fibrous zeolite classified as a human carcinogen, is believed to be more potent than asbestos in causing mesothelioma. However, unlike asbestos, erionite has rarely been used for commercial purposes and, as a result, knowledge about exposure pathways is limited. This paper provides a narrative review of the current knowledge regarding the associations between erionite exposure, health effects and exposure circumstances. Methods Medline/PubMed and Scopus were systematically searched up to the end of 2024 using keywords related to erionite exposure and health outcomes. Results We identified 26 peer-reviewed journal articles reporting on the health effects of erionite exposure, specifically mesothelioma and lung cancer, with mesothelioma being the most extensively studied outcome. Of these, 12 studies focussed on erionite-exposed populations in Turkey, 8 examined health effects among Turkish migrants in northern Europe, and 6 investigated erionite-related health risks in North America (3 in the United States and 3 in Mexico). These studies showed a very high incidence of mesothelioma, often in relatively young individuals, from the Cappadocia region of Turkey, with well-documented environmental exposures to erionite, contributing to a high proportion of all deaths (21% to 51%) in affected villages. Evidence of lung cancer associated with erionite exposure was also found. There is also evidence of erionite exposure-associated mesothelioma in Guanajuato, central Mexico. In the United States, erionite exposure-associated health effects (not mesothelioma) have been reported among people occupationally exposed to erionite. Studies on environmental exposures have shown outdoor concentrations ranging from 0.001 f/ml to 0.3 f/ml, while indoor concentrations have ranged from 0.005 to 1.38 f/ml. Occupational exposure to erionite has been less studied, with only one study in forestry workers showing elevated exposures to erionite ranging from non-detectable to 0.36 f/cc. Erionite deposits have also been identified in other countries such as Italy and New Zealand, but exposures and associated health effects have not yet been studied in these regions. Conclusion There is clear evidence that environmental exposure to erionite in the Cappadocia region of Turkey, and Guanajuato in central Mexico are causally associated with the high mesothelioma rates observed in these areas. Evidence for other parts of the world where there is naturally occurring erionite is limited. This review has highlighted significant knowledge gaps, and advocates for further research on occupational exposure to erionite fibres and associated health effects.Item Causes and MEchanisms foR non-atopic Asthma in Children (CAMERA) study: rationale and protocol(BioMed Central Ltd, 2025-12-01) Njoroge M; Pinheiro GP; Santana CVN; Ali H; Hobbs S; Mena-Bucheli S; Romero-Sandoval N; Robertson S; Rutter CE; Davoren D; Brooks C; Douwes J; Cooper PJ; Mpairwe H; Figueiredo CA; Cruz AA; Barreto ML; Pearce N; Pembrey L; CAMERA study groupBACKGROUND: The Causes And MEchanisms foR non-atopic Asthma in children (CAMERA) study was designed to investigate risk factors and mechanisms of non-atopic asthma in children and young adults in Brazil, Ecuador, Uganda, and New Zealand. Initial epidemiological analyses using existing datasets identified and compared risk factors for both atopic and non-atopic asthma. The focus of this paper is the protocol for sample collection and analysis of clinical data on possible non-atopic mechanisms. METHODS: In each of the four centres, the CAMERA study will enroll 160 participants aged 10-28 years, equally distributed among atopic asthmatics (AA), non-atopic asthmatics (NAA), atopic non-asthmatics and non-atopic non-asthmatics. Participants will be new recruits or returning World ASthma Phenotypes (WASP) study participants. Phase I consists of skin prick tests to define atopy, a general CAMERA questionnaire that covers respiratory and general health to identify asthma cases, followed by an asthma control questionnaire for asthmatics only. Phase II consists of a stress questionnaire and the following clinical assessments: lung function, nasal cytology, blood sampling, in vitro whole blood stimulation to assess IFN-γ production, hair cortisol concentration, dry air and capsaicin challenges, plus in a subset, cold air challenges. Analyses will compare inflammatory, physiological and clinical parameters across the four groups overall and by country. DISCUSSION: Here, we present the protocol for the CAMERA study, to provide relevant methodological details for CAMERA publications and to allow other centres globally to conduct similar analyses. The findings of this mechanistic multi-centre study will inform new and phenotype-specific prevention and treatment approaches. CLINICAL TRIAL NUMBER: Not applicable.Item Sputum quality affects assessment of airway microbiology in childhood asthma(BioMed Central Ltd, 2025-12-01) Taylor SL; Brooks CR; Elms L; Manning SK; Richard A; Burmanje J; Douwes J; Rogers GBBackground: The analysis of sputum is the principal basis for characterising lower airway microbiology in those with chronic respiratory conditions. For such analysis to be informative, samples that poorly reflect the lower airways must be identified and removed. Our cross-sectional study explored the relationship between the quality of sputum samples and their microbiological content. We further investigated the impact of excluding low quality samples on observed microbiota-disease relationships in childhood asthma. Methods: Induced sputum was collected from children with or without asthma. Sputum quality was assessed according to squamous cell%, cell viability%, detection of sputum plugs, and salivary α-amylase levels. Sputum microbiota was characterised by 16S rRNA amplicon sequencing and qPCR. Results: Of 170 participants, 130 had asthma. Between 19% (32/170) and 29% (53/170) of samples were deemed to be of insufficient quality, depending on the quality criterion applied. Stratification of samples based on any of the sputum quality cut-offs resulted in significant differences in microbiota characteristics (all p < 0.05), with salivary α-amylase the least discriminant between microbiota of acceptable and unacceptable samples. The removal of 53 poor-quality samples based on ≥ 30% squamous cells identified a difference in the sputum microbiota by asthma status (p = 0.017) that was not evident otherwise, including significantly higher levels of Haemophilus and Gemella in asthma samples. Conclusions: Upper airway contamination of induced sputum samples from children is common. Exclusion of samples based on ≥ 30% squamous cells enables identification of asthma-airway microbiology relationships that are otherwise not apparent.Item Case-control study of leptospirosis in Aotearoa New Zealand reveals behavioural, occupational, and environmental risk factors(Cambridge University Press, 2025-06-02) Nisa S; Ortolani E; Vallée E; Marshall J; Collins-Emerson J; Yeung P; Prinsen G; Wright J; Quin T; Fayaz A; Littlejohn S; Baker MG; Douwes J; Benschop J; Hahné SLeptospirosis in NZ has historically been associated with male workers in livestock industries; however, the disease epidemiology is changing. This study identified risk factors amid these shifts. Participants (95 cases:300 controls) were recruited nationwide between 22 July 2019 and 31 January 2022, and controls were frequency-matched by sex (90% male) and rurality (65% rural). Multivariable logistic regression models, adjusted for sex, rurality, age, and season - with one model additionally including occupational sector - identified risk factors including contact with dairy cattle (aOR 2.5; CI: 1.0-6.0), activities with beef cattle (aOR 3.0; 95% CI: 1.1-8.2), cleaning urine/faeces from yard surfaces (aOR 3.9; 95% CI: 1.5-10.3), uncovered cuts/scratches (aOR 4.6; 95% CI: 1.9-11.7), evidence of rodents (aOR 2.2; 95% CI: 1.0-5.0), and work water supply from multiple sources - especially creeks/streams (aOR 7.8; 95% CI: 1.5-45.1) or roof-collected rainwater (aOR 6.6; 95% CI: 1.4-33.7). When adjusted for occupational sector, risk factors remained significant except for contact with dairy cattle, and slaughter without gloves emerged as a risk (aOR 3.3; 95% CI: 0.9-12.9). This study highlights novel behavioural factors, such as uncovered cuts and inconsistent glove use, alongside environmental risks from rodents and natural water sources.Item Antibiotic Use In Utero and Early Life and Risk of Chronic Childhood Conditions in New Zealand: Protocol for a Data Linkage Retrospective Cohort Study(JMIR Publications, 2025-02-28) Ram S; Corbin M; 't Mannetje A; Eng A; Kvalsig A; Baker M; Douwes JBackground: The incidence of many common chronic childhood conditions has increased globally in the past few decades, which has been suggested to be potentially attributed to antibiotic overuse leading to dysbiosis in the gut microbiome. Objective: This linkage study will assess the role of antibiotic use in utero and in early life in the development of type 1 diabetes (T1D), attention-deficit/hyperactive disorder (ADHD), and inflammatory bowel disease. Methods: The study design involves several retrospective cohort studies using linked administrative health and social data from Statistics New Zealand’s Integrated Data Infrastructure. It uses data from all children who were born in New Zealand between October 2005 and December 2010 (N=334,204) and their mothers. Children’s antibiotic use is identified for 4 time periods (at pregnancy, at ≤1 year, at ≤2 years, and at ≤5 years), and the development of T1D, ADHD, and inflammatory bowel disease is measured from the end of the antibiotic use periods until death, emigration, or the end of the follow-up period (2021), whichever came first. Children who emigrated or died before the end of the antibiotic use period are excluded. Cox proportional hazards regression models are used while adjusting for a range of potential confounders. Results: As of September 2024, data linkage has been completed, involving the integration of antibiotic exposure and outcome variables for 315,789 children. Preliminary analyses show that both prenatal and early life antibiotic consumption is associated with T1D. Full analyses for all 3 outcomes will be completed by the end of 2025. Conclusions: This series of linked cohort studies using detailed, complete, and systematically collected antibiotic prescription data will provide critical new knowledge regarding the role of antibiotics in the development of common chronic childhood conditions. Thus, this study has the potential to contribute to the development of primary prevention strategies through, for example, targeted changes in antibiotic use.Item Case-Control Study of Congenital Anomalies: Study Methods and Nonresponse Bias Assessment.(Wiley Periodicals LLC, 2025-02-20) Eng A; Mannetje AT; Ellison-Loschmann L; Borman B; Cheng S; Lawlor DA; Douwes J; Pearce NBACKGROUND: To describe the methods of a congenital anomalies case-control study conducted in New Zealand, discuss the encountered methodological difficulties, and evaluate the potential for nonresponse bias. METHODS: The potential cases (n = 2710) were New Zealand live births in 2007-2009 randomly selected from the New Zealand Congenital Anomalies Registry. The potential controls (n = 2989) included live births identified from the Maternity and Newborn Information System, frequency matched to cases by the child's year of birth and sex. Mothers were invited to complete an interview covering demographic, lifestyle, and environmental factors. Response probabilities for case and control mothers were evaluated in relation to maternal age, deprivation, occupation, and ethnicity, available from the Electoral Roll, and inverse probability weights (IPWs) for participation were calculated. Odds ratios (ORs) for key demographic and selected risk factors were estimated through unconditional logistic regression, with and without IPW. RESULTS: A total of 652 (24%) of case mothers and 505 (17%) of control mothers completed the interview. Younger and more deprived mothers were underrepresented among the participants, particularly for controls, resulting in inflated ORs of associations with congenital anomalies for younger age, Māori ethnicity, deprivation, and risk factors under study, such as blue-collar occupations and smoking, indicative of nonresponse bias. Nonresponse bias was minimized through IPW, resulting in ORs and exposure prevalence estimates similar to those based on the prerecruitment sample. CONCLUSIONS: Attaining high participation rates was difficult in this study that was conducted in new mothers, particularly for the controls. The resulting nonresponse bias was minimized through IPW.Item Investigating animals and environments in contact with leptospirosis patients in Aotearoa New Zealand reveals complex exposure pathways.(Taylor and Francis Group, 2025-02-12) Benschop J; Collins-Emerson JM; Vallee E; Prinsen G; Yeung P; Wright J; Littlejohn S; Douwes J; Fayaz A; Marshall JC; Baker MG; Quin T; Nisa SCASE HISTORY: Three human leptospirosis cases from a case-control study were recruited for in-contact animal and environment sampling and Leptospira testing between October 2020 and December 2021. These cases were selected because of regular exposure to livestock, pets, and/or wildlife, and sampling was carried out on their farms or lifestyle blocks (sites A-C), with veterinarians overseeing the process for livestock, and cases collecting environmental and wildlife samples. LABORATORY FINDINGS: Across the three sites, a total of 137 cattle, > 40 sheep, 28 possums, six dogs, six rats, three pigs and three rabbits were tested. Herd serology results on Site A, a dairy farm, showed infection with Tarassovi and Pomona; urinary shedding showed Leptospira borgpetersenii str. Pacifica. Animals were vaccinated against Hardjo, Pomona and Copenhageni. The farmer was diagnosed with Ballum. On Site B, a beef and sheep farm, serology showed infection with Pomona; animals were not vaccinated, and the farmer was diagnosed with Hardjo. On Site C, cattle were shedding L. borgpetersenii; animals were not vaccinated, and the case's serovar was indeterminate. Six wild animals associated with Sites A and C and one environmental sample from Site A were positive for pathogenic Leptospira by PCR. CONCLUSION: These findings highlight the complexity of potential exposures and the difficulty in identifying infection sources for human cases. This reinforces the need for multiple preventive measures such as animal vaccination, the use of personal protective equipment, pest control, and general awareness of leptospirosis to reduce infection risk in agricultural settings. CLINICAL RELEVANCE: Farms with unvaccinated livestock had Leptospira infections, highlighting the importance of animal vaccination. Infections amongst stock that were vaccinated emphasise the importance of best practice vaccination recommendations and pest control. Abbreviations: MAT: Microscopic agglutination test; PIC: Person in charge; PPE: Personalprotective equipmentItem Depression and anxiety at 1- and 12-months post ischemic stroke: methods for examining individual change over time.(CSIRO Publishing on behalf of the Australasian Society for the Study of Brain Impairment, 2024-12-05) Barker-Collo S; Krishnamurthi R; Nair B; Ranta A; Douwes J; Feigin V; Honan CBackground Depression is commonly studied post stroke, while anxiety is less studied. This study presents prevalence of depression and anxiety at 1- and 12-months post ischemic stroke alongside three methods for examining within-subjects change over time. Methods Participants were ischemic stroke patients of the Auckland Regional Community Stroke Study (ARCOS-V) with Hospital Anxiety and Depression Scale data at 1- (n = 343) and 12-months (n = 307). Change over time was examined using within-subjects repeated measures ANOVA, calculation of the Reliable Change Index, and a Sankey diagram of those meeting cut-off scores (>7) for caseness over time. Results Using repeated measures ANOVA, depression scores didn’t change significantly over time, while anxiety symptoms decreased significantly. When reliable change was calculated, 4.2% of individuals had reliable decreases in anxiety symptoms, while 5.7% had reliable decreases in depression symptoms. Those who had a reliable decrease in one tended to have a reliable decrease in the other. In the Sankey, the proportion of those meeting the cut-off score for anxiety did not change over time (12.8 and 12.7% at 1- and 12-months), while those meeting the cut-off for depression increased slightly (3.7–4.5%) and those meeting cut-offs for both decreased from 10.4 to 8.1%. Conclusion The three methods produced very different findings. Use of cut-off scores is common but has limitations. Calculation of clinically reliable change is recommended. Further work is needed to ensure depression and anxiety are monitored over time post-stroke, and both should be the subject of intervention efforts in both acute and late stages post-stroke.Item Dietary Fibre Intake, Adiposity, and Metabolic Disease Risk in Pacific and New Zealand European Women(MDPI (Basel, Switzerland), 2024-10-07) Renall N; Merz B; Douwes J; Corbin M; Slater J; Tannock GW; Firestone R; Kruger R; Te Morenga L; Brownlee IA; Feraco A; Armani ABACKGROUND/OBJECTIVES: To assess associations between dietary fibre intake, adiposity, and odds of metabolic syndrome in Pacific and New Zealand European women. METHODS: Pacific (n = 126) and New Zealand European (NZ European; n = 161) women (18-45 years) were recruited based on normal (18-24.9 kg/m2) and obese (≥30 kg/m2) BMIs. Body fat percentage (BF%), measured using whole body DXA, was subsequently used to stratify participants into low (<35%) or high (≥35%) BF% groups. Habitual dietary intake was calculated using the National Cancer Institute (NCI) method, involving a five-day food record and semi-quantitative food frequency questionnaire. Fasting blood was analysed for glucose and lipid profile. Metabolic syndrome was assessed with a harmonized definition. RESULTS: NZ European women in both the low- and high-BF% groups were older, less socioeconomically deprived, and consumed more dietary fibre (low-BF%: median 23.7 g/day [25-75-percentile, 20.1, 29.9]; high-BF%: 20.9 [19.4, 24.9]) than Pacific women (18.8 [15.6, 22.1]; and 17.8 [15.0, 20.8]; both p < 0.001). The main source of fibre was discretionary fast foods for Pacific women and whole grain breads and cereals for NZ European women. A regression analysis controlling for age, socioeconomic deprivation, ethnicity, energy intake, protein, fat, and total carbohydrate intake showed an inverse association between higher fibre intake and BF% (β= -0.47, 95% CI = -0.62, -0.31, p < 0.001), and odds of metabolic syndrome (OR = 0.91, 95% CI = 0.84, 0.98, p = 0.010) among both Pacific and NZ European women (results shown for both groups combined). CONCLUSIONS: Low dietary fibre intake was associated with increased metabolic disease risk. Pacific women had lower fibre intakes than NZ European women.