Sputum inflammatory, neural, and remodeling mediators in eosinophilic and noneosinophilic asthma.

BACKGROUND: Neural and remodeling mechanisms may play a role in asthma, particularly noneosinophilic asthma (NEA). OBJECTIVE: To assess sputum mediators associated with neural, remodeling, and inflammatory mechanisms in eosinophilic asthma (EA), NEA, and participants without asthma. METHODS: A total of 111 participants with and 62 without asthma (14-21 years old) underwent sputum induction, exhaled nitric oxide, atopy, and spirometry tests. There were 24 mediators measured in sputum using enzyme-linked immunosorbent assay or bead array. Eosinophilic asthma (n = 52) and NEA (n = 59) were defined using a sputum eosinophil level cut-point of greater than or equal to 2.5%. RESULTS: Elevated levels of nociceptin (median: 39.1 vs 22.4 ng/mL, P = .03), periostin (33.8 vs 9.4 ng/mL, P = .01), and ECP; (220.1 vs 83.7 ng/mL, P = .03) were found in patients with asthma compared with those without asthma. Nociceptin was elevated in EA (54.8 vs 22.4 ng/mL, P = .02) compared with participants without asthma. Eosinophilic asthma had higher levels of inflammatory mediators (ECP: 495.5 vs 100.3 ng/mL, P ≤ .01; interleukin-1ß: 285.3 vs 209.3 pg/mL, P = .03; histamine: 5805.0 vs 3172.5 pg/mL, P < .01) and remodeling mediators (VEGF-A); 3.3 vs 2.5 ng/mL, P = .03; periostin: 47.7 vs 22.1 ng/mL, P = .04) than NEA. Whereas macrophages were associated with neural mediators, for example, neurokinin A (r = 0.27, P = .01) and nociceptin (r = 0.30, P = .02), granulocytes were associated with inflammatory and remodeling mediators (eg, ECP and VEGF-A correlated with neutrophils (r = 0.53 and r = 0.33, respectively, P < .01) and eosinophils (r = 0.53 and r = 0.29 respectively, P ≤ .01). CONCLUSION: Elevated levels of nociceptin and inflammatory and remodeling markers were found in EA, but no evidence for neural and remodeling pathways was found in NEA. Neural and remodeling mechanisms seem to coexist with inflammation.

Heart rate variability as a marker of autonomic nervous system activity in young people with eosinophilic and non-eosinophilic asthma.

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 (LFµs2; representing increased sympathetic nervous system (SNS) activity) was found in asthmatics who used ß-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 ß-agonist medication.

Viruses associated with acute respiratory infection in a community-based cohort of healthy New Zealand children.

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.

Retrofitting home insulation reduces incidence and severity of chronic respiratory disease.

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.

Damp mouldy housing and early childhood hospital admissions for acute respiratory infection: a case control study.

INTRODUCTION: A gap exists in the literature regarding dose-response associations of objectively assessed housing quality measures, particularly dampness and mould, with hospitalisation for acute respiratory infection (ARI) among children. METHODS: A prospective, unmatched case-control study was conducted in two paediatric wards and five general practice clinics in Wellington, New Zealand, over winter/spring 2011-2013. Children aged <2 years who were hospitalised for ARI (cases), and either seen in general practice with ARI not requiring admission or for routine immunisation (controls) were included in the study. Objective housing quality was assessed by independent building assessors, with the assessors blinded to outcome status, using the Respiratory Hazard Index (RHI), a 13-item scale of household quality factors, including an 8-item damp-mould subscale. The main outcome was case-control status. Adjusted ORs (aORs) of the association of housing quality measures with case-control status were estimated, along with the population attributable risk of eliminating dampness-mould on hospitalisation for ARI among New Zealand children. RESULTS: 188 cases and 454 controls were studied. Higher levels of RHI were associated with elevated odds of hospitalisation (OR 1.11/unit increase (95% CI 1.01 to 1.21)), which weakened after adjustment for season, housing tenure, socioeconomic status and crowding (aOR 1.04/unit increase (95% CI 0.94 to 1.15)). The damp-mould index had a significant, adjusted dose-response relationship with ARI admission (aOR 1.15/unit increase (95% CI 1.02 to 1.30)). By addressing these harmful housing exposures, the rate of admission for ARI would be reduced by 19% or 1700 fewer admissions annually. CONCLUSIONS: A dose-response relationship exists between housing quality measures, particularly dampness-mould, and young children's ARI hospitalisation rates. Initiatives to improve housing quality and to reduce dampness-mould would have a large impact on ARI hospitalisation.

Developments in the mechanisms of allergy in 2018 through the eyes of Clinical and Experimental Allergy, Part I.

In the first of two linked articles, we describe the development in the mechanisms underlying allergy as described by Clinical & Experimental Allergy and other journals in 2018. Experimental models of allergic disease, basic mechanisms and clinical mechanisms are all covered.

Understanding group A streptococcal pharyngitis and skin infections as causes of rheumatic fever: protocol for a prospective disease incidence study.

BACKGROUND: Group A Streptococcal (GAS) infections cause the autoimmune disease acute rheumatic fever (ARF), which can progress to chronic rheumatic heart disease (RHD). Treating pharyngitis caused by GAS with antibiotics is important in preventing ARF. However, it is difficult to distinguish these infections from GAS carriers. There is growing evidence for GAS skin infections as a cause of ARF. This study will identify the incidence of true GAS pharyngitis and serological responses to GAS skin infections. The effectiveness of antibiotics for these conditions will be explored, and modifiable risk factors. Serum antibody titres indicating the upper limits of normal (ULN for ASO/ADB antibodies) will be established alongside carriage rates in asymptomatic children. METHODS: This is a prospective disease incidence study, with an associated case-control study. The study population includes 1000 children (5-14 years) from Auckland, New Zealand, 800 of whom have visited their healthcare professional, resulting in a throat or skin swab for GAS, and 200 who are asymptomatic. The conditions of interest are GAS throat swab positive pharyngitis (n = 200); GAS carriage (n = 200); GAS negative throat swab (n = 200); GAS skin infections (n = 200); and asymptomatic controls (n = 200). All participants, except asymptomatic controls, will have acute and convalescent serological testing for ASO/ADB titres (collected < 9 days, and 2-4 weeks following symptom onset, respectively), alongside viral PCR from throat swabs. Asymptomatic controls will have ASO/ADB titres measured in one blood specimen and a throat swab for microbial culture. Caregivers of children will be interviewed using a questionnaire and any GAS isolates identified will be emm typed. The persistence of GAS antibodies will also be investigated. DISCUSSION: Findings from this study will fill critical gaps in scientific knowledge to better understand the pathophysiology of ARF, improve clinical management of GAS infections, and design more effective ARF prevention programmes. In particular it will measure the incidence of true, serologically confirmed GAS pharyngitis; assess the immune response to GAS skin infections and its role as a cause of ARF; examine the effectiveness of oral antibiotics for treating GAS pharyngitis and carriage; and identify whether risk factors for GAS infections might provide intervention points for reducing ARF.

Daily decision-making about food during pregnancy: a New Zealand study.

Pregnancy has always been a life-changing event for women and their families, but societal concern about pregnancy and motherhood has become intense in the digital age. The role of health promotion agencies and others supplying health-related resources about lifestyle behaviours is both important and in need of scrutiny. Ever increasing advice for pregnant women, their families and health professionals, abounds. This study of decision making during pregnancy investigated how women made everyday decisions during pregnancy about food and drink, as well as dietary supplements and medications, alcohol and recreational drugs. This qualitative interview study was a side-arm to a double-blind randomized, placebo-controlled trial conducted with pregnant women in Wellington New Zealand, 2013-2016. Data from interviews with 20 women were analysed using inductive thematic analysis. In relation to decision-making about lifestyle behaviours, five themes emerged-Information about food; Wanted and unwanted advice; Worry, anxiety and indecision; Making daily decisions about food; Changes in decision making over time. Participating women talked more about food selection and restriction advice than any other lifestyle topic. Analysis demonstrated concern about information accuracy and overload from multiple, diverse sources. Women described learning how to assess resource credibility, how to develop decision-making skills, and who to trust. The study raises important questions about how the health information environment, despite best intentions, can be confusing or potentially harmful. The study underlines the continued importance of the role health professionals have in not only interpreting information to discuss individualized advice, but also in empowering pregnant women to develop lifestyle-related decision-making skills.

Endotoxin, cat, and house dust mite allergens in electrostatic cloths and bedroom dust.

Environmental exposure to endotoxin, Fel d I (cat) allergen and Der p I (house dust mite) allergen have been associated with asthma symptoms and have been measured in the environment using various sampling methods, including the electrostatic dust collector. The objectives of this study were to investigate whether levels of endotoxin and allergens were detectable in electrostatic dust collectors and to examine the correlation of allergen and endotoxin levels between electrostatic dust collectors and vacuum sampling methods (floor dust and mattress dust). Electrostatic cloths, bedroom floor dust and mattress dust samples from a subset of 60 homes were randomly selected from the Health of Occupants of Mouldy Homes study for allergen and endotoxin analysis. Fel d I and Der p I allergens were analyzed by double monoclonal antibody ELISA and endotoxin by the kinetic Limulus amoebocyte lysate assay. An enhanced ELISA method was used to analyze Der p I in the electrostatic cloths. Endotoxin was detected in all samples, however Fel d I and Der p I were not detected in all electrostatic dust collector samples (detection in 53% and 15% of cloths respectively). No correlations were found between cloth and dust samples for endotoxin or Der p I, but moderate-to-strong correlations were found between all three sampling methods for Fel d I (rs = 0.612-0.715, p < 0.001). Poor correlation was found between floor dust and mattress dust samples for Der p I (rs = 0.256, p = 0.048). Electrostatic dust collectors may provide a way to measure airborne dust and allergen. Given the moderate-to-low correlations with vacuum dust sampling, this may present a unique measurement system which, when collected alongside traditional vacuum dust sampling, could provide additional exposure measures. Further studies are required to correlate endotoxin and allergen levels measured by electrostatic dust collector with air sampling and to explore the relationships between these bioaerosols, environmental factors and asthma.

Effects of Lactobacillus rhamnosus HN001 in early life on the cumulative prevalence of allergic disease to 11 years.

BACKGROUND: In a two-centre randomized placebo-controlled trial of Lactobacillus rhamnosus HN001 (HN001) (6 × 109 colony-forming units [cfu]) or Bifidobacterium lactis HN019 (HN019) (9 × 109 cfu) taken daily from 35-week gestation to 6 months' post-partum in mothers while breastfeeding and from birth to age 2 years in infants, we showed that HN001 significantly protected against eczema development at 2, 4 and 6 years and atopic sensitization at 6 years. There was no effect of HN019. We report here the findings for 11 year outcomes. METHODS: At age 11 years, eczema was defined as previously using the UK Working Party's Diagnostic Criteria. Asthma, wheeze, hay fever and rhinitis were defined based on the International Study of Asthma and Allergies in Childhood (ISAAC) questions. Atopic sensitization was defined as one or more positive responses (mean wheal diameter ≥3 mm) to a panel of food and aeroallergens. Analysis was intention-to-treat using hazard ratios to assess probiotic effects on the 11-year lifetime prevalence and relative risks for point or 12-month prevalence at 11 years. RESULTS: Early childhood HN001 supplementation was associated with significant reductions in the 12-month prevalence of eczema at age 11 years (relative risk [RR] = 0.46, 95% CI 0.25-0.86, P = 0.015) and hay fever (RR = 0.73, 95% CI 0.53-1.00, P = 0.047). For the lifetime prevalence, HN001 was associated with a significant reduction in atopic sensitization (hazard ratio [HR] = 0.71, 95% CI 0.51-1.00, P = 0.048), eczema (HR = 0.58, 95% CI 0.41-0.82, P = 0.002) and wheeze (HR = 0.76, 95% CI 0.57-0.99, P = 0.046). HN019 had no significant effect on these outcomes. CONCLUSION: This is the first early probiotic intervention to show positive outcomes for at least the first decade of life across the spectrum of allergic disease.

Maternal supplementation alone with Lactobacillus rhamnosus HN001 during pregnancy and breastfeeding does not reduce infant eczema.

BACKGROUND: In a randomized placebo-controlled trial, we previously found that the probiotic Lactobacillus rhamnosus HN001 (HN001) taken by mothers from 35 weeks of gestation until 6 months post-partum if breastfeeding and their child from birth to age 2 years halved the risk of eczema during the first 2 years of life. We aimed to test whether maternal supplementation alone is sufficient to reduce eczema and compare this to our previous study when both the mother and their child were supplemented. METHODS: In this 2-centre, parallel double-blind, randomized placebo-controlled trial, the same probiotic as in our previous study (HN001, 6 × 109 colony-forming units) was taken daily by mothers from 14-16 weeks of gestation till 6 months post-partum if breastfeeding, but was not given directly to the child. Women were recruited from the same study population as the first study, where they or their partner had a history of treated asthma, eczema or hay fever. RESULTS: Women were randomized to HN001 (N = 212) or placebo (N = 211). Maternal-only HN001 supplementation did not significantly reduce the prevalence of eczema, SCORAD ≥ 10, wheeze or atopic sensitization in the infant by 12 months. This contrasts with the mother and child intervention study, where HN001 was associated with reductions in eczema (hazard ratio (HR): 0.39, 95% CI 0.19-0.79, P = .009) and SCORAD (HR = 0.61, 95% 0.37-1.02). However, differences in the HN001 effect between studies were not significant. HN001 could not be detected in breastmilk from supplemented mothers, and breastmilk TGF-ß/IgA profiles were unchanged. CONCLUSION: Maternal probiotic supplementation without infant supplementation may not be effective for preventing infant eczema.

Indoor visible mold and mold odor are associated with new-onset childhood wheeze in a dose-dependent manner.

Evidence is accumulating that indoor dampness and mold are associated with the development of asthma. The underlying mechanisms remain unknown. New Zealand has high rates of both asthma and indoor mold and is ideally placed to investigate this. We conducted an incident case-control study involving 150 children with new-onset wheeze, aged between 1 and 7 years, each matched to two control children with no history of wheezing. Each participant's home was assessed for moisture damage, condensation, and mold growth by researchers, an independent building assessor and parents. Repeated measures of temperature and humidity were made, and electrostatic dust cloths were used to collect airborne microbes. Cloths were analyzed using qPCR. Children were skin prick tested for aeroallergens to establish atopy. Strong positive associations were found between observations of visible mold and new-onset wheezing in children (adjusted odds ratios ranged between 1.30 and 3.56; P ≤ .05). Visible mold and mold odor were consistently associated with new-onset wheezing in a dose-dependent manner. Measurements of qPCR microbial levels, temperature, and humidity were not associated with new-onset wheezing. The association between mold and new-onset wheeze was not modified by atopic status, suggesting a non-allergic association.

Early pregnancy probiotic supplementation with Lactobacillus rhamnosus HN001 may reduce the prevalence of gestational diabetes mellitus: a randomised controlled trial.

The study aims to assess whether supplementation with the probiotic Lactobacillus rhamnosus HN001 (HN001) can reduce the prevalence of gestational diabetes mellitus (GDM). A double-blind, randomised, placebo-controlled parallel trial was conducted in New Zealand (NZ) (Wellington and Auckland). Pregnant women with a personal or partner history of atopic disease were randomised at 14-16 weeks' gestation to receive HN001 (6×109 colony-forming units) (n 212) or placebo (n 211) daily. GDM at 24-30 weeks was assessed using the definition of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) (fasting plasma glucose ≥5·1 mmol/l, or 1 h post 75 g glucose level at ≥10 mmol/l or at 2 h ≥8·5 mmol/l) and NZ definition (fasting plasma glucose ≥5·5 mmol/l or 2 h post 75 g glucose at ≥9 mmol/l). All analyses were intention-to-treat. A total of 184 (87 %) women took HN001 and 189 (90 %) women took placebo. There was a trend towards lower relative rates (RR) of GDM (IADPSG definition) in the HN001 group, 0·59 (95 % CI 0·32, 1·08) (P=0·08). HN001 was associated with lower rates of GDM in women aged ≥35 years (RR 0·31; 95 % CI 0·12, 0·81, P=0·009) and women with a history of GDM (RR 0·00; 95 % CI 0·00, 0·66, P=0·004). These rates did not differ significantly from those of women without these characteristics. Using the NZ definition, GDM prevalence was significantly lower in the HN001 group, 2·1 % (95 % CI 0·6, 5·2), v. 6·5 % (95 % CI 3·5, 10·9) in the placebo group (P=0·03). HN001 supplementation from 14 to 16 weeks' gestation may reduce GDM prevalence, particularly among older women and those with previous GDM.

Lens Opacity and Hydrogen Sulfide in a New Zealand Geothermal Area.

PURPOSE: Hydrogen sulfide (H2S) is a highly toxic gas with well-established, acute irritation effects on the eye. The population of Rotorua, New Zealand, sited on an active geothermal field, has some of the highest ambient H2S exposures in the world. Evidence from ecological studies in Rotorua has suggested that H2S is associated with cataract. The purpose of the present study was, using more detailed exposure characterization, clinical examinations, and anterior eye photography, to more directly investigate this previously reported association. METHODS: Enrolled were 1637 adults, ages 18 to 65, from a comprehensive Rotorua primary care medical register. Patients underwent a comprehensive ophthalmic examination, including pupillary dilation and lens photography to capture evidence of any nuclear opacity, nuclear color, and cortical and posterior subcapsular opacity. Photographs were scored for all four outcomes on the LOCS III scale with decimalized interpolation between the exemplars. H2S exposure for up to the last 30 years was estimated based on networks of passive samplers set out across Rotorua and knowledge of residential, workplace, and school locations over the 30 years. Data analysis using linear and logistic regression examined associations between the degree of opacification and nuclear color or cataract (defined as a LOCS III score ≥2.0) in relation to H2S exposure. RESULTS: No associations were found between estimated H2S exposures and any of the four ophthalmic outcome measures. CONCLUSIONS: Overall, results were generally reassuring. They provided no evidence that H2S exposure at the levels found in Rotorua is associated with cataract. The previously found association between cataract and H2S exposure in the Rotorua population seems likely to be attributable to the limitations of the ecological study design. These results cannot rule out the possibility of an association with cataract at higher levels of H2S exposure.

The experiences of pregnant women in an interventional clinical trial: Research In Pregnancy Ethics (RIPE) study.

There is increasing global pressure to ensure that pregnant women are responsibly and safely included in clinical research in order to improve the evidence base that underpins healthcare delivery during pregnancy. One supposed barrier to inclusion is the assumption that pregnant women will be reluctant to participate in research. There is however very little empirical research investigating the views of pregnant women. Their perspective on the benefits, burdens and risks of research is a crucial component to ensuring effective recruitment. The Research In Pregnancy Ethics (RIPE) study set out to ascertain the views of pregnant women about research participation using an inductive thematic analysis. We conducted semi-structured interviews with 20 women who had participated in a double-blind randomised placebo controlled trial in Wellington (New Zealand) while pregnant. Our results show that at least some pregnant women recognise the value and importance of research during pregnancy. The women we interviewed were deeply invested in the research process and outcomes. Key motivations for participating were altruism, playing a valuable civic role and the importance of research. The main perceived burdens related to inconvenience and time commitment. For some women, possible randomization to the placebo arm was regarded as a burden or disadvantage.

Combination Nicotine Metered Dose Inhaler and Nicotine Patch for Smoking Cessation: A Randomized Controlled Trial.

INTRODUCTION: In order to replicate the rewarding effects of smoking, nicotine replacement therapies must deliver nicotine via the pulmonary route. We aimed to measure the efficacy of a simple pressurized metered dose inhaler containing nicotine combined with a nicotine patch for smoking cessation. METHODS: Double-blind randomized placebo-controlled, parallel group trial conducted at the University of Otago, Wellington, New Zealand. Five-hundred two adults (≥18 years) who smoked at least nine cigarettes per day, with a Fagerström Test for Nicotine Dependence ≥3 who wanted to quit, were randomized (1:1). INTERVENTIONS: active nicotine pressurized metered dose inhaler (pMDI) plus active nicotine patch, versus placebo pMDI plus active nicotine patch. Subjects were instructed to use the aerosols for 6 months when they felt an urge to smoke and the patches daily for 5 months, reduce their smoking and quit by the end of the fourth week. Subjects were followed for 7 months. The primary outcome was prolonged 6 month not smoked on 7 consecutive days, analyzed by intention-to-treat. RESULTS: For the primary outcome, 78/246 (31.71%) in the active group versus 46/256 (17.97%) in the control group were abstinent (odds ratio 2.12, 95% confidence interval 1.40 to 3.23). Adverse events were reported by 245/246 (99.6%) and 247/256 (96.5%) subjects in the active and control groups, respectively. Mild coughing which decreased with regular use was common with the nicotine aerosols. CONCLUSION: Inhaled nicotine from a metered dose inhaler combined with a nicotine patch substantially improves abstinence for 6 months amongst adult nicotine dependant smokers wanting to quit. IMPLICATIONS: In 2012, we published a systematic review of the use nicotine by inhalation in this journal. At that time we were unable to find any studies that had measured the effects of nicotine delivery by pMDI on smoking cessation, and we are not aware of any since 2012. Our study is the first to look at nicotine by pMDI in smoking cessation. The present trial demonstrates that a simple nonproprietary nicotine inhaler, using relatively inexpensive standard technology, increases smoking cessation rates over and above nicotine patch therapy, and could usefully enhance nicotine replacement in smoking cessation treatment.

The Probiotics in Pregnancy Study (PiP Study): rationale and design of a double-blind randomised controlled trial to improve maternal health during pregnancy and prevent infant eczema and allergy.

BACKGROUND: Worldwide there is increasing interest in the manipulation of human gut microbiota by the use of probiotic supplements to modify or prevent a range of communicable and non-communicable diseases. Probiotic interventions administered during pregnancy and breastfeeding offer a unique opportunity to influence a range of important maternal and infant outcomes. The aim of the Probiotics in Pregnancy Study (PiP Study) is to assess if supplementation by the probiotic Lactobacillus rhamnosus HN001 administered to women from early pregnancy and while breastfeeding can reduce the rates of infant eczema and atopic sensitisation at 1 year, and maternal gestational diabetes mellitus, bacterial vaginosis and Group B Streptococcal vaginal colonisation before birth, and depression and anxiety postpartum. METHODS/DESIGN: The PiP Study is a two-centre, randomised, double-blind placebo-controlled trial in Wellington and Auckland, New Zealand. Four hundred pregnant women expecting infants at high risk of allergic disease will be enrolled in the study at 14-16 weeks gestation and randomised to receive either Lactobacillus rhamnosus HN001 (6 × 10(9) colony-forming units per day (cfu/day)) or placebo until delivery and then continuing until 6 months post-partum, if breastfeeding. Primary infant outcomes are the development and severity of eczema and atopic sensitisation in the first year of life. Secondary outcomes are diagnosis of maternal gestational diabetes mellitus, presence of bacterial vaginosis and vaginal carriage of Group B Streptococcus (at 35-37 weeks gestation). Other outcome measures include maternal weight gain, maternal postpartum depression and anxiety, infant birth weight, preterm birth, and rate of caesarean sections. A range of samples including maternal and infant faecal samples, maternal blood samples, cord blood and infant cord tissue samples, breast milk, infant skin swabs and infant buccal swabs will be collected for the investigation of the mechanisms of probiotic action. DISCUSSION: The study will investigate if mother-only supplementation with Lactobacillus rhamnosus HN001 in pregnancy and while breastfeeding can reduce rates of eczema and atopic sensitisation in infants by 1 year, and reduce maternal rates of gestational diabetes mellitus, bacterial vaginosis, vaginal carriage of Group B Streptococcus before birth and maternal depression and anxiety postpartum. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registration: ACTRN12612000196842. Date Registered: 15/02/12.

Collaborating with a social housing provider supports a large cohort study of the health effects of housing conditions.

BACKGROUND: Despite the importance of adequate, un-crowded housing as a prerequisite for good health, few large cohort studies have explored the health effects of housing conditions. The Social Housing Outcomes Worth (SHOW) Study was established to assess the relationship between housing conditions and health, particularly between household crowding and infectious diseases. This paper reports on the methods and feasibility of using a large administrative housing database for epidemiological research and the characteristics of the social housing population. METHODS: This prospective open cohort study was established in 2003 in collaboration with Housing New Zealand Corporation which provides housing for approximately 5% of the population. The Study measures health outcomes using linked anonymised hospitalisation and mortality records provided by the New Zealand Ministry of Health. RESULTS: It was possible to match the majority (96%) of applicant and tenant household members with their National Health Index (NHI) number allowing linkage to anonymised coded data on their hospitalisations and mortality. By December 2011, the study population consisted of 11,196 applicants and 196,612 tenants. Half were less than 21 years of age. About two-thirds identified as Maori or Pacific ethnicity. Household incomes were low. Of tenant households, 44% containing one or more smokers compared with 33% for New Zealand as a whole. Exposure to household crowding, as measured by a deficit of one or more bedrooms, was common for applicants (52%) and tenants (38%) compared with New Zealanders as whole (10%). CONCLUSIONS: This project has shown that an administrative housing database can be used to form a large cohort population and successfully link cohort members to their health records in a way that meets confidentiality and ethical requirements. This study also confirms that social housing tenants are a highly deprived population with relatively low incomes and high levels of exposure to household crowding and environmental tobacco smoke.

Differential effects of two probiotics on the risks of eczema and atopy associated with single nucleotide polymorphisms to Toll-like receptors.

BACKGROUND: There is strong evidence to support a genetic predisposition to eczema and more recently studies have suggested that probiotics might be used to prevent eczema by modifying the expression of putative allergy-associated genes. The aim of this present study was to investigate whether two probiotics, Lactobacillus rhamnosus HN001 (HN001) and Bifidobacterium animalis subsp. lactis HN019 (HN019), can modify the known genetic predisposition to eczema conferred by genetic variation in the Toll-like receptor (TLR) genes in a high-risk infant population. METHODS: We selected 54 SNPs in the Toll-like receptor genes. These SNPs were analysed in 331 children of sole European ancestry as part of a double-blind, randomized, placebo-controlled trial examining the effects of HN001 and HN019 supplementation on eczema development and atopic sensitization. RESULTS: The data showed that 26 TLR SNPs interacted with HN001 resulting in a significantly reduced risk of eczema, 18 for eczema severity as defined by SCORAD ≥ 10 and 20 for atopic sensitization compared to placebo. There were only two SNPs that interacted with HN019 resulting in a reduced risk of eczema, eczema severity or atopy. CONCLUSIONS: This is the first study to show that the negative impact of specific TLR genotypes may be positively affected by probiotic supplementation. HN001 exhibits a much stronger effect than HN019 in this respect.

Reduced primary care respiratory infection visits following pregnancy and infancy vitamin D supplementation: a randomised controlled trial.

AIM: To determine whether vitamin D supplementation reduces primary care visits for acute respiratory infection (ARI). METHODS: A randomised, double-blind, placebo-controlled trial was conducted in New Zealand and powered to determine the vitamin D dose needed to achieve normal vitamin D status during infancy. Healthy pregnant women, from 27 weeks' gestation to birth, and their infants, from birth to age 6 months, were assigned to placebo or one of the two dosages of daily oral vitamin D3 . Woman/infant pairs were randomised to placebo/placebo, 1000 IU/400 IU or 2000 IU/800 IU. For this ad hoc analysis, the primary care records of enrolled children were audited to age 18 months. RESULTS: Two hundred and sixty pregnant women were randomised to placebo (n = 87), lower-dose (n = 87) or higher-dose (n = 86) vitamin D3 . In comparison with the placebo group (99%), the proportion of children making any ARI visits was smaller in the higher-dose (87%, p = 0.004), but not the lower-dose vitamin D3 group (95%, p = 0.17). The median number of ARI visits/child was less in the higher-dose vitamin D3 group from age 6-18 months (placebo 4, lower dose 3, higher dose 2.5; p = 0.048 for higher-dose vitamin D3 vs. placebo). CONCLUSION: Vitamin D3 supplementation during pregnancy and infancy reduces primary care visits for ARI during early childhood.