Reduced Exercise Capacity in Adults Born at Very Low Birth Weight: A Population-based Cohort Study.

Rationale: Population-based data regarding the consequences of very low birth weight (VLBW) and bronchopulmonary dysplasia (BPD) on adult exercise capacity are limited. Objectives: To compare exercise capacity in a national VLBW cohort with term-born controls and explore factors contributing to the differences. Methods: At 26-30 years of age, 228 VLBW survivors and 100 controls underwent lung function tests, cardiopulmonary exercise testing, and assessment of resting cardiac structure and function using echocardiography. Data on self-reported physical activity were collected. Measurements and Main Results: Compared with controls, adults with VLBW demonstrated reduced oxygen uptake, work rate, and oxygen pulse at peak exercise (9.3%, 10.7%, and 10.8% lower, respectively) and earlier anaerobic threshold (all P < 0.0001), with all mean values within normal range. VLBW survivors showed reduced physical activity, impaired lung function (reduced FEV1, FEV1/FVC, and DlCO), altered left ventricular structure and function (reduced mass, size, stroke volume, and cardiac output), and reduced right atrial and ventricular size. Adjustment for the combination of three sets of covariates (physical activity with body mass index, lung function, and cardiac structure and function) explained most of the exercise group differences. Beyond the effects of physical activity and body mass index, lung function and cardiac structure and function contributed approximately equally. BPD with other prematurity-related perinatal factors (ventilation, antenatal steroids, extremely low birth weight, and extreme preterm) were not associated with a reduced exercise capacity. Conclusions: Exercise capacity was significantly reduced in adults with VLBW, which we speculate is from combined effects of impaired lung function, altered heart structure and function, and reduced physical activity. Perinatal factors including BPD were not associated with a reduced exercise capacity.

Impact of COVID-19 and lockdown on COPD admissions to Christchurch Hospital, New Zealand 2020-2021: a combined quantitative and qualitative study.

BACKGROUND: During the year following New Zealand's first COVID-19 lockdown, a 33% reduction in chronic obstructive pulmonary disease (COPD)-related admissions occurred and persisted beyond this period at Christchurch Hospital. AIM: To identify contributing factors which may have resulted in a persistent decrease in COPD hospitalisation rates at Christchurch Hospital following the 2020 COVID-19 lockdown. METHODS: Using an explanatory sequential mixed-methods research design, we (i) retrospectively analysed hospital admissions and primary healthcare access by people with COPD (n = 1358) in Canterbury before, during and after COVID lockdown (24 March 2019 to 2021) and (ii) undertook individual interviews from a sample of patients (n = 14). RESULTS: Patients who were not re-admitted following the COVID-19 lockdown had fewer general practice encounters, acute primary care access, antibiotic and prednisone prescriptions. Proportionally fewer Maori and more Pacific patients were admitted with COPD following lockdown. Positive contributing factors at a primary care level included improvements in primary care interactions and medication management. At a patient and community level, there were improvements in lifestyle, self-management practices, social support and contact precautions. However, a subgroup of patients described negative effects such as social isolation. CONCLUSION: A combination of patient, primary care and community-level factors led to an overall persistent decrease in COPD admissions following the COVID-19 lockdown. Future targeted and individualised measures focusing on these modifiable factors may decrease future COPD-related hospital admissions. The study design facilitated further explanation about factors that contributed to the persistent decrease in hospital admissions among people living with COPD and has underscored the importance of social support, patient empowerment and reduction in barriers in accessing care in admission reduction.

Symptom persistence and recovery among COVID-19 survivors during a limited outbreak in Canterbury, New Zealand: a prospective cohort study.

BACKGROUND: In Canterbury, near complete identification of coronavirus disease 2019 (COVID-19) cases during a limited outbreak provides unique insights into sequelae. AIMS: The current study aimed to measure symptom persistence, time to return to normal activity, generalised anxiety and health-related quality of life (HrQoL) among COVID-19 survivors compared with uninfected participants. METHODS: The authors conducted a prospective cohort study of people tested for COVID-19 by reverse transcriptase polymerase chain reaction of nasopharyngeal swabs from 1 March to 30 June 2020. They enrolled participants who tested positive and negative at a 1:2 ratio, and administered community-acquired pneumonia, 7-item generalised anxiety disorder (GAD-7) and HrQoL (RAND-36) questionnaires. RESULTS: The authors recruited 145 participants, 48 with COVID-19 and 97 without COVID-19. The mean time from COVID-19 testing to completing the health questionnaire was 306 days. The mean age of patients was 46.7 years, and 70% were women. Four (8%) COVID-19-positive and eight (8%) COVID-19-negative participants required hospitalisation. Fatigue (30/48 [63%] vs 13/97 [13%]; P < 0.001), dyspnoea (13/48 [27%] vs 6/97 [6%]; P < 0.001) and chest pain (10/48 [21%] vs 1/97 [1%]; P < 0.001) were persistent in those with COVID-19. Fewer COVID-19-positive participants returned to normal activity levels (35/48 [73%] vs 94/97 97%; P < 0.001), with longer times taken (median 21 vs 14 days; P = 0.007). The GAD-7 and RAND-36 scores of both groups were similar across all anxiety and HrQoL subscales. CONCLUSIONS: Persistent symptoms and longer recovery times were found in COVID-19 survivors, but not impaired generalised anxiety levels or HrQoL compared with COVID-19-uninfected participants.

Drug metabolism in severe chronic obstructive pulmonary disease: A phenotyping cocktail study.

AIMS: To evaluate the effect of severe chronic obstructive pulmonary disease (COPD) on drug metabolism by comparing the pharmacokinetics of patients with severe COPD with healthy volunteers and using the modified Inje drug cocktail. METHODS: This was a single-centre pharmacokinetic study with 12 healthy participants and 7 participants with GOLD D COPD. Midazolam 1 mg, dextromethorphan 30 mg, losartan 25 mg, omeprazole 20 mg, caffeine 130 mg and paracetamol 1000 mg were simultaneously administered and intensive pharmacokinetic sampling was conducted over 8 hours. Drug metabolism by CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP1A2, UGT1A6 and UGT1A9 in participants with COPD were compared with phenotypes in healthy controls. RESULTS: The oral clearance (95% confidence interval) in participants with COPD relative to controls was: midazolam 63% (60-67%); dextromethorphan 72% (40-103%); losartan 53% (52-55%); omeprazole 35% (31-39%); caffeine 52% (50-53%); and paracetamol 73% (72-74%). There was a 5-fold increase in AUC for omeprazole and approximately 2-fold increases for caffeine, losartan, dextromethorphan, and midazolam. The AUC of paracetamol, which is mostly glucuronidated, was increased by about 60%. CONCLUSION: Severe COPD is associated with a clinically significant reduction in oral drug clearance. This may be greater for cytochrome P450 substrates than for glucuronidated drugs. This supports reduced starting doses when prescribing for patients with severe COPD.

The New Zealand 1986 very low birth weight cohort as young adults: mapping the road ahead.

BACKGROUND: Very low birth weight (less than 1500 g) is associated with increased morbidity and costs of health care in childhood. Emerging evidence suggests these infants face a range of health and social problems as young adults. We studied all New Zealand very low birth weight infants born in 1986 (when 58% were exposed to antenatal corticosteroids) in infancy, with later follow-up at 7 to 8 years and 23 to 24 years. We now aim to assess the cohort at 26-28 years compared with controls. METHODS/DESIGN: The case sample will comprise a minimum of 250 members of the 1986 New Zealand national very low birth weight cohort (77% of survivors). Outcomes will be compared with a control group of 100 young adults born at term in 1986. Following written informed consent, participants will travel to Christchurch for 2 days of assessments undertaken by experienced staff. Medical assessments include growth measures, vision, respiratory function, blood pressure and echocardiogram, renal function, dental examination and blood tests. Cognitive and neuropsychological functioning will be assessed with standard tests, and mental health and social functioning by participant interview. A telephone interview will be conducted with a parent or significant other person nominated by the respondent to gain a further perspective on the young person's health and functioning. All those born at less than 28 weeks' gestation, plus a random subset of the cohort to a total of 150 cases and 50 controls, will be offered cranial magnetic-resonance imaging. Statistical analysis will examine comparison with controls and long-term trajectories for the very low birth weight cohort. DISCUSSION: The research will provide crucial New Zealand data on the young adult outcomes for very low birth weight infants and address gaps in the international literature, particularly regarding cardiovascular, respiratory, visual and neurocognitive outcomes. These data will inform future neonatal care, provide evidence-based guidelines for care of preterm graduates transitioning to adult care, and help shape health education and social policies for this high risk group. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612000995875 . Registered 1 October 2012.

DNA methylation patterns at birth predict health outcomes in young adults born very low birthweight.

BACKGROUND: Individuals born very low birthweight (VLBW) are at increased risk of impaired cardiovascular and respiratory function in adulthood. To identify markers to predict future risk for VLBW individuals, we analyzed DNA methylation at birth and at 28 years in the New Zealand (NZ) VLBW cohort (all infants born < 1500 g in NZ in 1986) compared with age-matched, normal birthweight controls. Associations between neonatal methylation and cardiac structure and function (echocardiography), vascular function and respiratory outcomes at age 28 years were documented. RESULTS: Genomic DNA from archived newborn heel-prick blood (n = 109 VLBW, 51 controls) and from peripheral blood at ~ 28 years (n = 215 VLBW, 96 controls) was analyzed on Illumina Infinium MethylationEPIC 850 K arrays. Following quality assurance and normalization, methylation levels were compared between VLBW cases and controls at both ages by linear regression, with genome-wide significance set to p < 0.05 adjusted for false discovery rate (FDR, Benjamini-Hochberg). In neonates, methylation at over 16,400 CpG methylation sites differed between VLBW cases and controls and the canonical pathway most enriched for these CpGs was Cardiac Hypertrophy Signaling (p = 3.44E-11). The top 20 CpGs that differed most between VLBW cases and controls featured clusters in ARID3A, SPATA33, and PLCH1 and these 3 genes, along with MCF2L, TRBJ2-1 and SRC, led the list of 15,000 differentially methylated regions (DMRs) reaching FDR-adj significance. Fifteen of the 20 top CpGs in the neonate EWAS showed associations between methylation at birth and adult cardiovascular traits (particularly LnRHI). In 28-year-old adults, twelve CpGs differed between VLBW cases and controls at FDR-adjusted significance, including hypermethylation in EBF4 (four CpGs), CFI and UNC119B and hypomethylation at three CpGs in HIF3A and one in KCNQ1. DNA methylation GrimAge scores at 28 years were significantly greater in VLBW cases versus controls and weakly associated with cardiovascular traits. Four CpGs were identified where methylation differed between VLBW cases and controls in both neonates and adults, three reversing directions with age (two CpGs in EBF4, one in SNAI1 were hypomethylated in neonates, hypermethylated in adults). Of these, cg16426670 in EBF4 at birth showed associations with several cardiovascular traits in adults. CONCLUSIONS: These findings suggest that methylation patterns in VLBW neonates may be informative about future adult cardiovascular and respiratory outcomes and have value in guiding early preventative care to improve adult health.

Breastfeeding protects against current asthma up to 6 years of age.

OBJECTIVE: To investigate the effects of breastfeeding on wheezing and current asthma in children 2 to 6 years of age. STUDY DESIGN: Infants (n=1105) were enrolled in a prospective birth cohort in New Zealand. Detailed information about infant feeding was collected using questionnaires administered at birth and at 3, 6, and 15 months. From this, durations of exclusive and any breastfeeding were calculated. Information about wheezing and current asthma was collected at 2, 3, 4, 5, and 6 years. Logistic regression was used to model associations between breastfeeding and outcomes with and without adjustment for confounders. RESULTS: After adjustment for confounders, each month of exclusive breastfeeding was associated with significant reductions in current asthma from 2 to 6 years (all, P<.03). Current asthma at 2, 3, and 4 years was also reduced by each month of any breastfeeding (all, P<.005). In atopic children, exclusive breastfeeding for ≥ 3 months reduced current asthma at ages 4, 5, and 6 by 62%, 55%, and 59%, respectively. CONCLUSION: Breastfeeding, particularly exclusive breastfeeding, protects against current asthma up to 6 years. Although exclusive breastfeeding reduced risk of current asthma in all children to age 6, the degree of protection beyond 3 years was more pronounced in atopic children.

Monitoring chloramines and bromamines in a humid environment using selected ion flow tube mass spectrometry.

The selectivity and sensitivity of selected ion flow tube mass spectrometry (SIFT-MS) for individual breath analysis of haloamines has been improved by heating the flow tube in a commercial instrument to around 106 degrees C. Data is presented showing the marked reduction in the number density of water clusters of product ions of common breath metabolites that are isobaric with the product ions from monochloramine and monobromamine that are used to monitor the haloamine concentrations. These results have direct relevance to the real-time monitoring of chloramines in drinking water, swimming pools and food processing plants. However, once the isobaric overlaps from water cluster ions are reduced at the higher temperatures, there is no conclusive evidence showing the presence of haloamines on single breath exhalations in the mid parts per trillion range from examination of the breaths of volunteers.

Vitamin D status of newborns in New Zealand.

Recognition of the important non-skeletal health effects of vitamin D has focused attention on the vitamin D status of individuals across the lifespan. To examine the vitamin D status of newborns, we measured serum levels of 25-hydroxyvitamin D (25(OH)D) in the cord blood of 929 apparently healthy newborns in a population-based study in New Zealand, a country at 41 °S latitude, with strong anti-skin cancer (sun avoidance) campaigns and without vitamin D food fortification. Randomly selected midwives in two regions recruited children. The median cord blood level of 25(OH)D was 44 nmol/l (interquartile range, 29-78 nmol/l). Overall, 19 % of newborns had 25(OH)D levels < 25 nmol/l and 57 % had levels < 50 nmol/l; only 27 % had levels of 75 nmol/l or higher, which are levels associated with optimal health in older children and adults. A multivariable ordinal logistic regression model showed that the strongest determinants of low vitamin D status were winter month of birth and non-European ethnicity. Other determinants of low cord blood 25(OH)D included longer gestational age, younger maternal age and a parental history of asthma. In summary, low levels of vitamin D are common among apparently healthy New Zealand newborns, and are independently associated with several easily identified factors. Although the optimal timing and dosage of vitamin D supplementation require further study, our findings may assist future efforts to correct low levels of 25(OH)D among New Zealand mothers and their newborn children.

Predicting corticosteroid response in chronic obstructive pulmonary disease using exhaled nitric oxide.

RATIONALE: Predicting corticosteroid response in COPD is important but difficult. Response is more likely to occur in association with eosinophilic airway inflammation, for which the fraction of exhaled nitric oxide (Fe(NO)) is a good surrogate marker. OBJECTIVES: We aimed to establish whether Fe(NO) levels would predict the clinical response to oral corticosteroid in COPD. METHODS: We performed a double-blind, crossover trial of steroid in patients with COPD. After a 4-week washout of inhaled steroids, patients received prednisone 30 mg/d or matching placebo, in random order, with an intervening 4-week washout. The predictive values of Fe(NO) for clinically significant changes in 6-minute-walk distance (6MWD), spirometry (FEV(1)), and St. George's Respiratory Questionnaire (SGRQ) were calculated. MEASUREMENTS AND MAIN RESULTS: A total of 65 patients (mean FEV(1) = 57% predicted) were randomized. With prednisone, there was a net increase of 13 m in 6MWD (P = 0.02) and 0.06 L in postbronchodilator FEV(1) (P = 0.02) compared with placebo. The change in SGRQ was not significant. Using receiver operator characteristic analysis, the area under the curve for an increase of 0.2 L in FEV(1) was 0.69 (P = 0.04) with an optimum Fe(NO) cut-point of 50 ppb. The positive and negative predictive values were 67 and 82%, respectively. FE(NO) was not a significant predictor for changes in 6MWD or SGRQ. CONCLUSIONS: Fe(NO) is a weak predictor of short-term response to oral corticosteroid in COPD, its usefulness being limited to predicting increase in FEV(1). Clinical trial registered with www.anzctr.org.au (ACTRN12605000683639).

Lung Function of Adults Born at Very Low Birth Weight.

BACKGROUND: Much remains unknown about the consequences of very low birth weight (VLBW) and bronchopulmonary dysplasia (BPD) on adult lungs. We hypothesized that VLBW adults would have impaired lung function compared with controls, and those with a history of BPD would have worse lung function than those without. METHODS: At age 26 to 30 years, 226 VLBW survivors of the New Zealand VLBW cohort and 100 term controls born in 1986 underwent lung function tests including spirometry, plethysmographic lung volumes, diffusing capacity of the lung for carbon monoxide, and single-breath nitrogen washout (SBN2). RESULTS: An obstructive spirometry pattern was identified in 35% VLBW subjects versus 14% controls, with the majority showing mild obstruction. Compared with controls, VLBW survivors demonstrated significantly lower forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity (FVC) ratio (FEV1/FVC), forced expiratory flow at 25% to 75% of FVC and higher residual volume (RV), RV/total lung capacity (TLC) ratio (RV/TLC), decreased diffusing capacity of the lung for carbon monoxide, and increased phase III slope for SBN2. The differences persisted after adjustment for sex and smoking status. Within the VLBW group, subjects with BPD showed significant reduction in FEV1, FEV1/FVC, and forced expiratory flow at 25% to 75% of FVC, and increase in RV, RV/TLC, and phase III slope for SBN2, versus subjects without. The differences remained after adjustment for confounders. CONCLUSIONS: Adult VLBW survivors showed a higher incidence of airflow obstruction, gas trapping, reduced gas exchange, and increased ventilatory inhomogeneity versus controls. The findings suggest pulmonary effects due to VLBW persist into adulthood, and BPD is a further insult on small airway function.

Detection of 2-pentylfuran in the breath of patients with Aspergillus fumigatus.

Aspergillus fumigatus produces 2-pentylfuran (2-PF) when cultured on blood agar, nutrient agar and other media. As 2-PF is not known to be produced by mammalian metabolism we hypothesized that it is detectable in breath of patients colonized or infected with A. fumigatus. Breath was tested for 2-PF from normal subjects, those undergoing chemotherapy, and adults at risk of colonization or infection with A. fumigatus because of bronchiectasis, cystic fibrosis, or immune suppression. Breath samples were collected in five L tedlar bags and analyzed by Gas Chromatography/Mass Spectroscopy (GC/MS) in MS-MS mode. 2-PF was not detected in breath 14 healthy controls, in one of 10 neutropenic subjects and 16 of 32 patients with lung disease. The sensitivity and specificity of the 2-PF breath tests when compared with recurrent isolation of aspergillus from sputum or from bronchoalveolar lavage over two months was 77% and 78% respectively. As 2-PF is not normally found in human breath its presence may reflect the active metabolism of A. fumigatus in the airways and form the basis of a new diagnostic breath test for Aspergillus infection.

Breastfeeding protects against adverse respiratory outcomes at 15 months of age.

The relationship between breastfeeding, respiratory and other allergic disorders has been controversial. Our aim was to investigate the relationships between breastfeeding, respiratory outcomes, eczema and atopy at 15 months of age in a prospective birth cohort in New Zealand. A total of 1105 children were enrolled at birth, and 1011 (91.2%) were followed up at 15 months. Logistic regression was used to model associations between breastfeeding duration and respiratory outcomes, eczema and atopy after adjusting for relevant confounding variables: ethnicity, socio-economic status, parity, body mass index, smoking in pregnancy, gender and respiratory infections in the first 3 months of life. Breastfeeding was associated with a significant reduction in the risk of adverse respiratory outcomes at 15 months. After adjustment for confounders, each month of exclusive breastfeeding reduced the risk of doctor-diagnosed asthma by 20% (odds ratio 0.80, 95% confidence interval 0.71 to 0.90), wheezing by 12% (0.88, 0.82 to 0.94) and inhaler use by 14% (0.86, 0.78 to 0.93). Associations for both exclusive and additional breastfeeding durations, and respiratory outcomes remained independently significant when modelled simultaneously. Although independently associated with all respiratory outcomes, adjusting for parental history of allergic disease or maternal history of asthma did not alter our findings. Breastfeeding was not associated with eczema or atopy at 15 months. In conclusion, there was a significant protective effect of breastfeeding on infant wheezing and other adverse respiratory outcomes that may be early indicators of asthma in New Zealand children.

Oxidative cross-linking of calprotectin occurs in vivo, altering its structure and susceptibility to proteolysis.

Calprotectin, the major neutrophil protein, is a critical alarmin that modulates inflammation and plays a role in host immunity by strongly binding trace metals essential for bacterial growth. It has two cysteine residues favourably positioned to act as a redox switch. Whether their oxidation occurs in vivo and affects the function of calprotectin has received little attention. Here we show that in saliva from healthy adults, and in lavage fluid from the lungs of patients with respiratory diseases, a substantial proportion of calprotectin was cross-linked via disulfide bonds between the cysteine residues on its S100A8 and S100A9 subunits. Stimulated human neutrophils released calprotectin and subsequently cross-linked it by myeloperoxidase-dependent production of hypochlorous acid. The myeloperoxidase-derived oxidants hypochlorous acid, taurine chloramine, hypobromous acid, and hypothiocyanous acid, all at 10 µM, cross-linked calprotectin (5 µM) via reversible disulfide bonds. Hypochlorous acid generated A9-A9 and A8-A9 cross links. Hydrogen peroxide (10 µM) did not cross-link the protein. Purified neutrophil calprotectin existed as a non-covalent heterodimer of A8/A9 which was converted to a heterotetramer - (A8/A9)2 - with excess calcium ions. Low level oxidation of calprotectin with hypochlorous acid produced substantial proportions of high order oligomers, whether oxidation occurred before or after addition of calcium ions. At high levels of oxidation the heterodimer could not form tetramers with calcium ions, but prior addition of calcium ions afforded some protection for the heterotetramer. Oxidation and formation of the A8-A9 disulfide cross link enhanced calprotectin's susceptibility to proteolysis by neutrophil proteases. We propose that reversible disulfide cross-linking of calprotectin occurs during inflammation and affects its structure and function. Its increased susceptibility to proteolysis will ultimately result in a loss of function.

The effect of ambient air pollution on respiratory health of school children: a panel study.

BACKGROUND: Adverse respiratory effects of particulate air pollution have been identified by epidemiological studies. We aimed to examine the health effects of ambient particulate air pollution from wood burning on school-age students in Christchurch, New Zealand, and to explore the utility of urine and exhaled breath condensate biomarkers of exposure in this population. METHODS: A panel study of 93 male students (26 with asthma) living in the boarding house of a metropolitan school was undertaken in the winter of 2004. Indoor and outdoor pollution data was continuously monitored. Longitudinal assessment of lung function (FEV1 and peak flow) and symptoms were undertaken, with event studies of high pollution on biomarkers of exposure (urinary 1-hydroxypyrene) and effect (exhaled breath condensate (EBC) pH and hydrogen peroxide concentration). RESULTS: Peak levels of air pollution were associated with small but statistically significant effects on lung function in the asthmatic students, but not healthy students. No significant effect of pollution could be seen either on airway inflammation and oxidative stress either in healthy students or students with asthma. Minor increases in respiratory symptoms were associated with high pollution exposure. Urinary 1-hydroxypyrene levels were raised in association with pollution events by comparison with low pollution control days. CONCLUSION: There is no significant effect of ambient wood-smoke particulate air pollution on lung function of healthy school-aged students, but a small effect on respiratory symptoms. Asthmatic students show small effects of peak pollution levels on lung function. Urinary 1-hydroxypyrene shows potential as a biomarker of exposure to wood smoke in this population; however measurement of EBC pH and hydrogen peroxide appears not to be useful for assessment of population health effects of air pollution.Some of the data presented in this paper has previously been published in Kingham and co-workers Atmospheric Environment, 2006 Jan; 40: 338-347 (details of pollution exposure), and Cavanagh and co-workers Sci Total Environ. 2007 Mar 1;374(1):51-9 (urine hydroxypyrene data).

Hair nicotine at 15 months old, tobacco exposure and wheeze or asthma from 15 months to 6 years old.

OBJECTIVE: To investigate the relationship between hair nicotine levels at 15 months of age and prior parent-reported smoking exposure, and the risk of wheezing and current asthma from 15 months to 6 years of age. STUDY DESIGN: We measured hair nicotine levels at 15 months of age in 376 of 535 infants enrolled in a prospective birth cohort in Christchurch, New Zealand. We obtained detailed information from parents about smoking exposure during pregnancy and in the home at 3 and 15 months of age. Data for demographics, wheezing, and asthma were obtained from yearly questionnaires up to age 6 years. We assessed hair nicotine levels in relation to reported smoke exposure in pregnancy and up to age 15 months, and the association between high levels of hair nicotine and annual reports of current wheeze and current asthma using multiple logistic regression. RESULTS: Hair nicotine increased with numbers of smokers and daily cigarettes smoked at home, and was also strongly associated with smoking in pregnancy. High level of hair nicotine was associated with increased risk of wheeze (Odds ratio 2.30, P = 0.001) and, though not significant, of current asthma (Odds ratio 2.02, P = 0.056) at 15 months of age, after controlling for socio-economic status, ethnicity, body mass index, respiratory infections in the first 3 months of life, and duration of exclusive breastfeeding. At older ages the associations were non-significant. CONCLUSION: In children aged 15 months hair nicotine level was related to smoking exposure, and was associated with increased risk of wheeze and asthma.

Prominent IgE-binding and cytokine-inducing capacities of a newly cloned N-terminal region of Der f 14, an apolipophorin-like house dust mite allergen.

We previously characterized a 177-kDa allergen, M-177, from Dermatophagoides farinae. Thereafter, a counterpart to M-177 for Euroglyphus maynei was cloned as Eur m 14, and its sequence revealed that two environmental allergens, Mag 1 and Mag 3, are digested fragments of M-177. The aims of this study were to clone the cDNA of Der f 14 corresponding to M-177 and to elucidate the allergenic capacities of the N-terminal fragment of Der f 14 (Der f 14-N). Recombinant allergens were produced as trigger-factor-fused proteins in Escherichia coli. Der f 14-N showed the highest IgE-binding frequency among Der f 14-derived fragments in patients allergic to house dust mite by enzyme-linked immunosorbent assay. Der f 14-N showed the highest capacity to induce cell proliferation in murine lymphocyte and human peripheral mononuclear cells among Der f 14-derived fragments. Der f 14-N induced IL-13, IFN-γ and IL-17 production more than Der f 1 and Der f 2 in mouse, and induced IL-5 and IFN-γ production at levels comparable to those of Der f 1 and Der f 2 in some patients. The high prevalence of IgE binding to the Der f 14-N indicates that it could be an important mite allergen.

The New Zealand Asthma and Allergy Cohort Study (NZA2CS): assembly, demographics and investigations.

BACKGROUND: Asthma and allergy are highly prevalent in industrialised countries. Longitudinal and cross-sectional studies have identified a number of potential risk factors for these conditions, including genetic and environmental factors, with significant gene-environment relationships. Birth cohort studies have been proposed as an important tool to explore these risk factors, particularly exposures in early life that are associated with later disease or protection from disease. This paper describes the establishment of a birth cohort in New Zealand. METHODS: A birth cohort was established in 1996 in Christchurch and Wellington and infants recruited between 1997-2001. Expectant mothers were recruited by midwives. Children and mothers have undergone assessment by serial questionnaires, environmental assessment including mould and allergen exposure, skin-prick testing, and at age six years are undergoing full assessment for the presence of asthma, atopy and allergic disease, including genetic assessment. RESULTS: A total of 1105 children have been recruited, and the retention rate at fifteen months was 91.4%. 15.2% of the children at recruitment have been identified as Maori. A positive family history of asthma, eczema or hay fever has been reported in 84% of children. All children have now been assessed at fifteen months and 685 children from the cohort have reached age six years and have completed the six year assessment. CONCLUSIONS: The cohort is fully assembled, and assessment of children is well advanced, with good retention rates. The study is well placed to address many current hypotheses about the risk factors for allergic disease and asthma.

Elevated concentrations of 1-hydroxypyrene in schoolchildren during winter in Christchurch, New Zealand.

Particulate air pollution is significantly elevated during the winter in Christchurch, New Zealand, largely attributable to use of wood burners for domestic home heating, topography, and meteorological conditions. Polycyclic aromatic hydrocarbons (PAHs) are a key component of airborne particulate matter (PM) and urinary 1-hydroxypyrene (1-OHP) has previously been used to assess exposure of people to PAHs. We examined urinary 1-OHP in Christchurch male non-smoking schoolchildren (12-18 yr) on two occasions after high pollution events (48 and 72 microg PM(10)/m(3) 24-h average) and two occasions during periods of low pollution (19 and 12 microg PM(10)/m(3)). Concentrations of urinary 1-OHP were significantly elevated in the students during high pollution events (median (mean+/-SD) 0.043 (0.051+/-0.032) and 0.042 (0.060+/-0.092) micromol OHP/mol creatinine respectively) compared with low pollution periods (median (mean+/-SD) 0.019 (0.026+/-0.032) and 0.025 (0.028+/-0.018) micromol/mol creatinine respectively). The observed 1-OHP concentrations are at the lower end of those determined in children and non-occupationally exposed adults in international studies and suggest a generally low exposure to PAHs. The increased urinary 1-OHP concentrations following nights of elevated particulate concentrations in ambient air suggest increased exposure to ambient air pollution during winter time, and could potentially be used as a biomarker of exposure in this population.