Acute otitis media (AOM) and respiratory tract infections are common in early childhood and are major contributors to antibiotic use. The oral probiotic Streptococcus salivarius K12 has demonstrated antimicrobial and immunomodulatory activity in vitro, and preventive effects in children with recurrent AOM. We aim to determine the efficacy of S. salivarius K12 in preventing AOM in the general infant population. We conducted a multicentre, double-blind, randomised, placebo-controlled trial in Wellington and Christchurch, New Zealand. Children were enrolled at 3–6 months of age, their households were randomised 1:1, and daily study product was given from age 6 to 24 months. The primary outcome was the rate of doctor-recorded AOM. Secondary outcomes included time to first AOM episode, respiratory infections, antibiotic prescribing and healthcare utilisation. Analyses were by intention to treat using mixed-effects negative binomial regression adjusted for region and, for the primary outcome, prior AOM, with random effects for general practice and family. A total of 428 children were randomised by household and 368 (86

BACKGROUND:Various observational studies have suggested that infants and young children who regularly sleep in synthetic bedding materials are more likely to experience wheezing and asthma, while children who use feather duvets and/or feather pillows are less likely to wheeze. METHODS:In Wellington, New Zealand, we conducted a three-armed, parallel, randomised trial of 460 infants who were assigned to use different bedding materials: synthetic, wool or feather bedding in the form of sleepsacks from 3 months of age to 2 years of age to test the hypothesis that children exposed to feather materials are less likely to develop wheezing. Pregnant women were recruited before birth. Parents were unaware of the primary research hypothesis and were told this was a study of child warmth and wheezing. We have reported wheezing (parental and GP), a variety of respiratory health parameters and atopic status at 2 years. RESULTS:One hundred and forty-seven infants received a synthetic sleepsack, 150 wool and 144 feather. We have found no significant differences in reported or doctor-diagnosed wheezing or other respiratory health measures by bedding material used. For frequency of wheezing presentation at GP surgery, there was a significant increased rate for children using feather materials compared to synthetic, relative rate 2.00 (95% CI: 1.14, 3.52). CONCLUSION:This study does not support earlier observational studies that suggest higher rates of wheezing for children using synthetic bedding or lower rates for feather materials, at least for early childhood wheezing. Our study suggests that the explanation for the observational study findings may lie in selection bias, where the parents of at-risk children avoid feather bedding materials.

Purpose:Aotearoa New Zealand (NZ) homes are cold by international standards, with many failing to achieve temperatures recommended by WHO housing and health guidelines. Despite strong evidence of seasonal exacerbations in Chronic Obstructive Pulmonary Disease (COPD), there has been little examination of the effect of household warmth, or housing quality on COPD outcomes. The Warm Homes for Elder New Zealanders (WHEZ) study aimed to see if subsidising electricity costs would improve the health outcomes of older people with COPD. Previous analysis showed a modest, typically 2-10% dependent on prior usage, increase in electricity use among the subsidised households. Patients and Methods:Participants aged over 55 with doctor-diagnosed COPD were recruited from three regional centres, and where possible their dwelling was insulated after enrolment. A single-blinded randomised controlled trial of the effect of an electricity voucher (NZ$500) on health care usage during winter was carried out in three locations across New Zealand. The primary outcome was exacerbations treated with antibiotics, and/or corticosteroids. The Clinical Trial Registration is NCT01627418. Of the 520 participants assigned to a wave, partial or better data was achieved for 424; 215 of those were randomised to the early intervention group, and 209 to receive the intervention later. Results:Despite the modest increase in energy use by study households, reported previously, there was no significant difference between study arms in the frequency of exacerbation of COPD (0.089, p=0.5875, 95% CI -1.406-1.584) nor hospitalisations. An exploratory analysis suggested a lower mortality among participants assigned to receive the intervention first (OR 0.310, p=0.0175, 95% CI 0.118-0.815). Conclusion:This study showed little effect of winter electricity vouchers on exacerbations of COPD. However, such vouchers increased energy use and may have reduced overall mortality. A larger study, particularly with susceptible subpopulations, is recommended to examine this mortality impact further.

This paper reflects on the influences and outcomes of He Kāinga Oranga/Housing and Health Research Programme over 25 years, and their impact on housing and health policy in Aotearoa and internationally. Working in partnership particularly with Māori and Pasifika communities, we have conducted randomised control trials which have shown the health and broad co-benefits of retrofitted insulation, heating and remediation of home hazards, which have underpinned government policy in the Warm Up NZ-Heat Smart programme and the Healthy Homes Standards for rental housing. These trials have been included as evidence in the WHO Housing and Health Guidelines and led to our designation as a WHO Collaborating Centre on Housing and Wellbeing. We are increasingly explicitly weaving Māori frameworks, values and processes with traditional Western science.

Aim: To observe upper respiratory tract infection (URTI) symptoms, rhinovirus levels and compliance with daily carrageenan nasal spray. Methods: 102 adults were randomized to carrageenan or saline placebo three times daily for 8 weeks and URTI symptoms were recorded. A control group (n = 42) only recorded URTI symptoms. Participants collected nasal swabs when symptomatic. Results: Regular daily carrageenan prophylaxis resulted in consistent but nonsignificant reductions in URTI symptoms versus the placebo group. Saline placebo decreased and increased some cold symptoms compared with no treatment. Conclusion: Daily prophylactic administration of antiviral carrageenan may not significantly reduce URTI symptoms. Due to low compliance, use in a population with specific reasons to avoid URTIs may be more appropriate. Disease-specific outcomes may be more useful than symptom reporting.

Objective An imbalance in autonomic nervous system (ANS) activity may play a role in asthma, but it is unclear whether this is associated with specific pathophysiology. This study assessed ANS activity by measuring heart rate variability (HRV) in eosinophilic (EA) and non-eosinophilic asthma (NEA) and people without asthma. Methods HRV, combined hypertonic saline challenge/sputum induction, exhaled nitric oxide (FeNO), skin prick tests to measure atopy, and spirometry tests were conducted in teenagers and young adults (14-21 years) with (n = 96) and without (n = 72) generally well-controlled asthma. HRV parameters associated with sympathetic and parasympathetic ANS branches were analyzed. EA and NEA were defined using a 2.5% sputum eosinophil cut-point. Airway hyperreactivity (AHR) was defined as >= 15% reduction in FEV1 following saline challenge. Results HRV parameters did not differ between asthmatics and non-asthmatics or EA and NEA. They were also not associated with markers of inflammation, lung function or atopy. However, increased absolute low frequency (LF mu s(2); representing increased sympathetic nervous system (SNS) activity) was found in asthmatics who used beta-agonist medication compared to those who did not (median: 1611, IQR 892-3036 vs 754, 565-1592; p < 0.05) and increased normalized low frequency (LF nu) was found in those with AHR compared to without AHR (64, 48-71 vs 53, 43-66; p < 0.05). Conclusion ANS activity (as measured using HRV analysis) is not associated with pathophysiology or inflammatory phenotype in young asthmatics with generally well-controlled asthma. However, enhanced SNS activity can be detected in asthmatics with AHR or who use beta-agonist medication.

Background Group A streptococcal (GAS) infections can trigger an immune-mediated response resulting in acute rheumatic fever (ARF). The role of social and environmental risk factors for GAS pharyngitis and skin infections are not well understood. This study aimed to identify factors associated with GAS pharyngitis and skin infections, and to determine if these are the same as those for ARF. Methods A case-control study, including 733 children aged 5-14 years, was undertaken between March 2018 and October 2019 in Auckland, New Zealand. Healthy controls (n =190) and symptomatic cases including GAS pharyngitis (n = 210), GAS seronegative carriers (n = 182), and GAS skin infections (n = 151) were recruited. Trained interviewers administered a comprehensive, pre-tested, face-to-face questionnaire. Findings Multivariable analysis identified strong associations between barriers to accessing primary healthcare and having GAS pharyngitis (adjusted OR 3 center dot 3; 95% CI 1 center dot 8-6 center dot 0), GAS carriage (aOR 2 center dot 9; 95% CI 1 center dot 5-6 center dot 0) or a GAS skin infection (aOR 3 center dot 5; 95% CI 1 center dot 6-7 center dot 6). Children who had GAS skin infections were more likely than all other groups to report living in a crowded home (aOR 1 center dot 9; 95% CI 1 center dot 0-3 center dot 4), have Maori or Pacific grandparents (aOR 3 center dot 0; 95% CI 1 center dot 2-7 center dot 6), a family history of ARF (aOR 2 center dot 2; 95% CI 1 center dot 1-4 center dot 3), or having a previous diagnosis of eczema (aOR 3 center dot 9; 95% CI 2 center dot 2-6 center dot 9). Interpretation Reducing barriers to accessing primary healthcare (including financial restrictions, the inability to book an appointment, lack of transport, and lack of childcare for other children) to treat GAS pharyngitis and skin infections could potentially reduce these infections and lead to a reduction in their sequelae, including ARF. These strategies should be co-designed and culturally appropriate for the communities being served and carefully evaluated. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Acute respiratory infections (ARIs) are a major cause of morbidity among children. Respiratory viruses are commonly detected in both symptomatic and asymptomatic periods. The rates of infection and community epidemiology of respiratory viruses in healthy children needs further definition to assist interpretation of molecular diagnostic assays in this population. Children otherwise healthy aged 1 to 8 years were prospectively enrolled in the study during two consecutive winters, when ARIs peak in New Zealand. Parents completed a daily symptom diary for 8 weeks, during which time they collected a nasal swab from the child for each clinical ARI episode. A further nasal swab was collected by research staff during a clinic visit at the conclusion of the study. All samples were tested for 15 respiratory viruses commonly causing ARI using molecular multiplex polymerase chain reaction assays. There were 575 ARIs identified from 301 children completing the study, at a rate of 1.04 per child-month. Swabs collected during an ARI were positive for a respiratory virus in 76.8% (307 of 400), compared with 37.3% (79 of 212) of swabs collected during asymptomatic periods. The most common viruses detected were human rhinovirus, coronavirus, parainfluenza viruses, influenzavirus, respiratory syncytial virus, and human metapneumovirus. All of these were significantly more likely to be detected during ARIs than asymptomatic periods. Parent-administered surveillance is a useful mechanism for understanding infectious disease in healthy children in the community. Interpretation of molecular diagnostic assays for viruses must be informed by understanding of local rates of asymptomatic infection by such viruses.

To assess whether retrofitting home insulation can reduce the risk of respiratory disease incidence and exacerbation, a retrospective cohort study was undertaken using linked data from a national intervention program. The study population was made up of 1 004 795 residents from 205 001 New Zealand houses that received an insulation subsidy though a national Energy Efficiency and Conservation Authority program. A difference-in-difference model compared changes in the number of prescriptions dispensed for respiratory illness post- insulation to a control population over the same timeframe. New prescribing of chronic respiratory disease medication at follow-up was used to compare incidence risk ratios between intervention and control groups. Chronic respiratory disease incidence was significantly lower in the intervention group at follow-up: odds ratio 0.90 (95% CI: 0.86-0.94). There was also a 4% reduction in medication dispensed for treating exacerbations of chronic respiratory disease symptoms in the intervention group compared with the control group: relative rate ratio (RRR) 0.96 (95% CI: 0.96-0.97). There was no change in medication dispensed to prevent symptoms of chronic respiratory disease RRR: 1,00 (95% CI: 0.99-1.00). These findings support home insulation interventions as a means of improving respiratory health outcomes.

Aims: To assess the role of neural and remodelling pathways, alongside inflammatory mechanisms, in eosinophilic (EA) and non-eosinophilic asthma (NEA). Methods: 111 asthmatics and 62 non-asthmatics (14-21 years) underwent sputum induction testing. Twenty-four mediators were measured in supernatant. EA (n=52) and NEA (n=59) were defined using a sputum eosinophil cut-point of 2.5%. Results: Elevated levels of nociceptin (median: 39.1 vs 22.4 ng/mL, p=0.03), periostin (33.8 vs 9.4 pg/mL, p=0.01), and eosinophil cationic protein (ECP; 220.1 vs 83.7 ng/mL, p=0.03) were found in asthmatics compared to non-asthmatics. Nociceptin was elevated in EA (54.8 vs 22.4 ng/mL, p=0.02) but not NEA (27.8 vs 22.4 ng/mL, p=0.22). EA had higher levels of inflammatory (ECP: 496 vs 100.3 ng/mL, p=<0.01; interleukin-1β: 286 vs 209.3 pg/mL, p=0.03; histamine: 5805 vs 3173 pg/mL, p=<0.01) and remodelling (vascular endothelial growth factor: VEGF; 3.3 vs 2.5 ng/mL, p=0.03; periostin: 47.7 vs 22.1 pg/mL, p=0.04) mediators compared to NEA. Whilst macrophage counts were correlated with neural mediators such as neurokinin A (r=0.27, p=0.01), nociceptin (r=0.30, p=0.02), and nerve growth factor-β: NGF-β; r=0.19, p=0.04), granulocytes correlated with inflammatory and remodelling mediators; e.g., ECP and VEGF correlated with neutrophils (r=0.53 & r=0.33 respectively, p≤0.01) and eosinophils (r=0.53& r=0.29 respectively, p≤0.01). Conclusions: Inflammatory cells/mediators were often associated with neural and remodelling mediators, suggesting that these mechanisms coexist with inflammation. Neural and remodelling pathways may not play a role in NEA, but nociceptin may be important in EA.

Objectives: Rates of acute rheumatic fever, a sequelae of group A Streptococcal (GAS) infection, remain unacceptably high in Indigenous M a over line ori and Pacific children in New Zealand. This prospective study aimed to describe GAS antibody titres in healthy children (5-14 years) by ethnicity, and to determine how paired titres vary with GAS culture positive and negative pharyngitis, and GAS skin infections. Methods: Analysis included 887 children (32% M a over line ori, 36% Pacific, 33% European/Other) from Auckland, New Zealand. Cases comprise 772 children who had a sore throat or skin infection, which resulted in a swab taken for culture. Healthy controls were asymptomatic ( N = 154) and matched by age, ethnicity and region. All participants had a serum sample, with a second sample collected from cases only. Sera were analysed for anti-streptolysin O (ASO) and anti-DNase-B (ADB) antibodies. Results: Healthy M a over line ori and Pacific children had higher GAS antibody titres than healthy European/Other children. Children with GAS-positive sore throat had the highest mean ASO titres and children with GASpositive skin infection had the highest mean ADB titres. When a two-fold increase or an upper limit of normal cut-off (ASO 450 IU/ml, ADB 400 U/ml) was applied to titres from children with GAS-positive sore throat, 62.1% were classified as having serologically confirmed GAS pharyngitis and 37.9% had GAS detected without serological response. Conclusions: Elevated ASO titres were associated with GAS pharyngitis and elevated ADB titres were associated with GAS skin infections in New Zealand children. Higher ASO/ADB titres in healthy M a over line ori and Pacific children could indicate a greater prior exposure to GAS infections. (c) 2021 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

AimsTo evaluate the effect of the probioticLactobacillus rhamnosusHN001 and/or cereal enriched with oat-derived beta-glucan (OBG) on metabolic and mental health outcomes when administered to adults with pre-diabetes.Design2×2 factorial design randomised, parallel-groups placebo-controlled; double-blinded for probiotic, single-blinded for cereals.ParticipantsCommunity-dwelling adults aged 18–80 years with pre-diabetes: glycated haemoglobin (HbA1c) 41–49 mmol/mol.InterventionsCapsules containingLactobacillus rhamnosus(HN001) (6×109colony-forming units/day), or placebo capsules; and cereal containing 4 g/day OBG or calorie-matched control cereal, taken daily, for 6 months. Study groups were: (A) HN001 capsules+OBG cereal; (B) HN001 capsules+control cereal; (C) placebo capsules+OBG cereal and (D) placebo capsules+control cereal.Outcome measuresPrimary outcome: HbA1cat 6 months. Secondary outcomes: fasting plasma glucose, fasting insulin, homeostatic model assessment of insulin resistance, fasting lipids, blood pressure, body weight, waist circumference, body mass index and mental well-being.Results153 participants were randomised. There was complete HbA1coutcome data available for 129 participants. At 6 months the mean (SD) HbA1cwas 45.9 (4.4) mmol/mol, n=66 for HN001, and 46.7 (4.3) mmol/mol, n=63 for placebo capsules; 46.5 (4.0) mmol/mol, n=67 for OBG and 46.0 (4.6) mmol/mol n=62 for control cereal. The estimated difference between HN001-placebo capsules was −0.83, 95% CI −1.93 to 0.27 mmol/mol, p=0.63, and between OBG-control cereals −0.17, 95% CI −1.28 to 0.94 mmol/mol, p=0.76. There was no significant interaction between treatments p=0.79. There were no differences between groups or significant interactions between treatments for any of the secondary outcomes.ConclusionsThis study found no evidence of clinical benefit from the supplementation with either HN001 and/or cereal containing 4 g OBG on HbA1cand all secondary outcomes relevant to adults with pre-diabetes.Trial registration numberAustralian New Zealand Clincial Trials Registry number ACTRN12617000990325

The World Health Organization (WHO) recommends minimum indoor temperatures of 18 degrees C to maintain health. In a study of 152 children's bedrooms in Wellington, New Zealand we aimed to establish the costs of following WHO advice, using standard heaters over eight weeks of autumn to spring to investigate household factors and heating behaviours that significantly increase heating costs. During the heating intervention a mean children's bedroom temperature of 20 degrees C (range of 17-23 degrees C) was achieved, over a mean period of 12.2 h per night, using on average 6.33 kWh per night. Five factors significantly affected energy use: keeping children's bedroom doors fully open, having three or more intervention weeks in mid-winter, presence of mould, housing built pre-1978, and the bedroom having two or more exterior walls. These data have important implications for the New Zealand Winter Energy Payment (WEP) policy, supporting low income households. Based on figures from this study, the projected cost to heat one child's bedroom (NZ$58 per month) equates to 46% of the 2021 WEP. The current WEP is insufficient to cover the costs of heating living areas and more than one child's bedroom and should be adjusted for number of children and climatic region.

Introduction Prediabetes is the asymptomatic precursor to type two diabetes mellitus, a significant and growing public health problem in New Zealand (NZ). Little is known about how general practitioners (GPs) and nurses view prediabetes care, and similarly little is known about how people with prediabetes view their condition and care. Aim This study aimed to investigate the views of NZ GPs and nurses, and people with prediabetes about prediabetes and its management. Methods This was a mixed qualitative methods study that is part of a randomised control trial of a prediabetes intervention. Results Three key themes emerged from the health professional data (GPs and nurses) and another three themes emerged from people with prediabetes data. GPs and nurses were uncertain about the progression of prediabetes; they felt prediabetes was not a priority and they were unsure about what to advise. People with prediabetes were uncertain about the diagnosis and information given to them; they were unsure about what to do about prediabetes and they found lifestyle change hard. Discussion GPs, nurses and people with prediabetes, expressed much uncertainty, but also some certainty about prediabetes. All were certain that prediabetes is common and increasing and that sustained lifestyle change was very difficult. But uncertainty prevailed about whether, in reality, prediabetes could be stopped, who would be most likely to benefit from lifestyle interventions and how best to achieve these. Older Māori and Pacific women were keen to promote lifestyle change and this appeared best done through Māori and Pacific peoples’ organisations by means of co-designed interventions.

ABSTRACT Background: Neural mechanisms may play an important role in non-eosinophilic asthma. This study compared airway sensory nerve reactivity, using capsaicin challenge, in eosinophilic and non-eosinophilic asthma and non-asthmatics. Methods: Thirty-eight asthmatics and nineteen non-asthmatics (aged 14-21 years) underwent combined hypertonic saline challenge/sputum induction, exhaled nitric oxide (FeNO), atopy, and spirometry tests, followed by capsaicin challenge. Eosinophilic (EA) and non-eosinophilic asthma (NEA) were defined using a sputum eosinophil cut-point of 2.5%. Airway hyperreactivity (AHR) was defined as a ≥15% drop in FEV1 during saline challenge. Sensory nerve reactivity was defined as the lowest capsaicin concentration that evoked 5 (C5) coughs. Results: Non-eosinophilic asthmatics (n=20) had heightened capsaicin sensitivity (lower C5) compared to non-asthmatics (n=19) (geometric mean C5: 58.3μM, 95% confidence interval 24.1-141.5 vs 193.6μM, 82.2-456.0; p<0.05). There was a similar (but non-significant) difference in capsaicin sensitivity in NEA compared with EA (n=18), (58.3μM, 24.1-141.5 vs 191.0μM, 70.9-514.0; p=0.07). FEV1 was significantly reduced from baseline following capsaicin inhalation in both asthmatics and non-asthmatics but no differences were found between subgroups. No associations with capsaicin sensitivity and atopy, sputum eosinophils, blood eosinophils, asthma control, or treatment were observed. Conclusion: Non-eosinophilic asthma, but not eosinophilic asthma, showed enhanced capsaicin sensitivity compared with non-asthmatics. Sensory nerve reactivity may therefore play an important role in the pathophysiology of non-eosinophilic asthma.

We have previously shown that probiotic supplementation with Lactobacillus rhamnosus HN001 (HN001) led to a reduced incidence of gestational diabetes mellitus (GDM). Here we investigate whether HN001 supplementation resulted in alterations in fasting lipids, insulin resistance, or bile acids (BAs) during pregnancy. Fasting plasma samples collected at 24–30 weeks’ gestation, from 348 women randomised at 14–16 weeks’ gestation to consume daily probiotic HN001 (n = 172) or a placebo (n = 176) were analysed for lipids, insulin, glucose and BAs. Women supplemented with HN001 had lower fasting glucose compared with placebo (p = 0.040), and lower GDM. Significant differences were found in fasting insulin, HOMA-IR, low density lipoprotein-cholesterol (LDL-c), high density lipoprotein (HDL)-c, triglycerides, total cholesterol, and BAs by GDM status. Lower fasting conjugated BAs were seen in women receiving HN001. A significant decrease of glycocholic acid (GCA) was found in older (age ≥ 35) women who received HN001 (p = 0.005), while GDM women showed significant reduced taurodeoxycholic acid (TDCA) (p = 0.018). Fasting conjugated BA was positively correlated with fasting glucose (r = 0.136, p = 0.020) and fasting insulin (r = 0.113, p = 0.036). Probiotic HN001 supplementation decreases conjugated BAs and might play a role in the improvement of glucose metabolism in women with pregnancy.

In order to assess the colonization efficacy of the oral probiotic Streptococcus salivarius K12, a rapid method for specific detection and enumeration of the strain was developed. Here, we describe a two-step TaqMan (TM) quantitative PCR assay using primer-probe combinations targeting genes of the locus encoding the lantibiotic bacteriocin salivaricin B.