Selenium status and allergic disease in a cohort of New Zealand children.

BACKGROUND: New Zealand has one of the highest rates of asthma and atopy. Selenium has been implicated in the aetiology of asthma, and associations between low selenium status and asthma in New Zealand children have been reported. OBJECTIVE: The aim was to investigate the association between selenium status and allergic disease in a birth cohort of New Zealand children. METHODS: The New Zealand Asthma and Allergy Cohort Study is a prospective birth cohort in Wellington and Christchurch, involving 1105 infants born 1997-2001. During the 6-year assessment (n = 635), associations were investigated between plasma selenium (PlSe) and whole blood glutathione peroxidase activity (WBGPx) and allergy-related health outcomes including asthma, wheeze, hayfever, rhinitis, eczema and rash. RESULTS: Wellington children had greater PlSe and WBGPx than Christchurch children (P < 0.001 for both). PlSe (P = 0.004) and WBGPx (P = 0.03) were lower in children exposed to environmental smoke, but differences were no longer significant after adjustment for study location, current household smoking (5-6 years), maternal smoking during pregnancy, family history (either parent with asthma, eczema or hayfever), prioritized ethnicity (Maori, Pacific peoples, Other, European), gender, season born, number of siblings, New Zealand Deprivation Index and body mass index at 6 years. Analysis of PlSe or WBGPx as continuous variables or of quartiles of PlSe with health outcomes showed no significant associations after adjustment. Univariate analysis of quartiles of PlSe and WBGPx with persistent wheeze showed significant inverse trends (P = 0.005 for both), but these reduced after adjustment. CONCLUSIONS AND CLINICAL RELEVANCE: Our results do not support a strong association between selenium status and the high incidence of asthma in New Zealand. However, there was a modest association between lower PlSe and WBGPx activity and higher incidence of persistent wheeze.

The effects of early and late paracetamol exposure on asthma and atopy: a birth cohort.

BACKGROUND: Despite reports of positive associations between paracetamol and asthma, the nature of these associations is unclear. OBJECTIVE: We aimed to investigate the associations between infant and childhood paracetamol use and atopy and allergic disease at 5-6 years. METHODS: In a birth cohort study, we collected reported paracetamol exposure between birth and 15 months in Christchurch (n=505) and between 5 and 6 years for all participants (Christchurch and Wellington) (n=914). Outcome data for reported current asthma, reported wheeze and atopy (measured using skin prick tests) were collected at 6 years for all participants. Logistic regression models were adjusted for potential confounders, including the number of chest infections and antibiotic use. RESULTS: Paracetamol exposure before the age of 15 months was associated with atopy at 6 years [adjusted odds ratio (OR)=3.61, 95% confidence interval (CI) 1.33-9.77]. Paracetamol exposure between 5 and 6 years showed dose-dependent associations with reported wheeze and current asthma but there was no association with atopy. Compared with use 0-2 times, the adjusted OR (95% CI) were wheeze 1.83 (1.04-3.23) for use 3-10 times, and 2.30 (1.28-4.16) for use >10 times: current asthma 1.63 (0.92-2.89) for use 3-10 times and 2.16 (1.19-3.92) for use >10 times: atopy 0.96 (0.59-1.56) for use 3-10 times, and 1.05 (0.62-1.77) for use >10 times. CONCLUSION AND CLINICAL RELEVANCE: Our findings suggest that paracetamol has a role in the development of atopy, and the maintenance of asthma symptoms. Before recommendations for clinical practice can be made, randomized-controlled trials are needed to determine whether these associations are causal.

Ethnic differences in time trends in asthma prevalence in New Zealand: ISAAC Phases I and III.

SETTING: The International Study of Asthma and Allergies in Childhood (ISAAC) Phase III survey, New Zealand. OBJECTIVE: To assess the prevalence of asthma symptoms and time trends by ethnicity between ISAAC Phase I (1992-1993) and Phase III (2001-2003). DESIGN: Information on asthma symptoms and environmental exposures was collected in children aged 6-7 years (n = 10,873) and adolescents aged 13-14 years (n = 13,317). RESULTS: In children, the prevalence of current wheeze was 28.5% in Maori (prevalence odds ratio [POR] = 1.49, 95%CI 1.32-1.68), and 25.2% in Pacific Islanders (POR 1.28, 95%CI 1.07-1.54) compared with 20.7% in Europeans/Pakeha. In adolescents, 29.9% of Maori (POR = 1.13, 95%CI 1.03-1.23) and 20.8% of Pacific Islanders (POR 0.74, 95%CI 0.62-0.87) experienced current wheeze compared to 28.6% of Europeans/Pakeha. Between Phases I and III, the prevalence of current wheeze increased significantly by 0.49%/year in Pacific Islanders, increased non-significantly by 0.12%/year in Maori, and decreased significantly by 0.25%/year in Europeans/Pakeha children. In adolescents, the prevalence of current wheeze increased by 0.05%/year in Pacific Islanders and decreased by 0.33%/year in Europeans/Pakeha and by 0.07%/year in Maori. CONCLUSION: Ethnic differences in asthma symptom prevalence in New Zealand have increased. The reasons for this are unclear, but may reflect inequalities in access to health services.

Pseudomonas aeruginosa transmission is infrequent in New Zealand cystic fibrosis clinics.

Pseudomonas aeruginosa is an important pathogen in cystic fibrosis (CF). Although most patients harbour unique P. aeruginosa isolates, some clinics report patients sharing common strains. The overall importance of person-to-person transmission in P. aeruginosa acquisition and whether routine patient segregation is necessary remains uncertain. The present authors therefore investigated the extent of P. aeruginosa transmission in New Zealand CF clinics. New Zealand's seven major CF centres were assessed, combining epidemiological data with computer-assisted SalI DNA fingerprinting of 496 isolates from 102 patients. One cluster of related isolates was significantly more prevalent in the largest clinic than expected by chance. The seven patients with isolates belonging to this cluster had more contact with each other than the remaining patients attending this centre. No other convincing evidence of transmission was found in any of the other smaller clinics. Three P. aeruginosa strains believed to be transmissible between patients in Australian and British CF clinics are present in New Zealand, but there was no definite evidence they had spread. Pseudomonas aeruginosa transmission is currently infrequent in New Zealand cystic fibrosis clinics. This situation could change rapidly and ongoing surveillance is required. The current results confirm that computer-assisted SalI DNA fingerprinting is ideally suited for such surveillance.

The association of early life exposure to antibiotics and the development of asthma, eczema and atopy in a birth cohort: confounding or causality?

BACKGROUND: In general, studies reporting positive associations between antibiotic exposure and respiratory and allergic disease have been unable to determine the nature of this association. OBJECTIVE: To examine the association between antibiotic exposure in infancy and the development of asthma, eczema and atopy in early childhood. METHODS: In a birth cohort study, we collected reported antibiotic exposure before 3 months and before 15 months along with outcomes (wheeze, asthma, eczema, rash, inhaler use) at 15 months (n=1011) and 4 years (n=986). Atopy was measured using skin prick tests at 15 months. RESULTS: We found significant univariate associations of antibiotic exposure before 3 months with asthma developing between birth and 15 months [OR 2.32 (95% CI 1.45-3.69)]. After adjustment for chest infections, this association reduced (OR=1.58, 95% CI 0.96-2.60) becoming marginally significant (P=0.07). A marginally significant association of antibiotics with atopy (OR=1.44, 95% CI 0.96-2.14) in the univariate analysis also reduced after adjustment for chest infections (OR=1.36, 95% CI 0.91-2.05). There was no effect of antibiotic exposure before 15 months on asthma developing after 15 months and present between 3 and 4 years (OR=1.35 95% CI 0.85-2.14). Antibiotic exposure before 3 months was not associated with eczema and rash developing between birth and 15 months but exposure before 15 months was related to eczema [OR 1.83 (95% CI 1.10-3.05)] and rash [OR 1.61 (95% CI 1.02-2.53)] developing after 15 months and remaining present at 4 years. These effects reduced in the multivariate analysis. CONCLUSIONS: Our findings suggest that the effect of antibiotics on respiratory disease may be due to confounding by chest infections at an early age when asthma may be indistinguishable from infection.

Fatal late onset necrotising enterocolitis in a term infant: Atypical Kawasaki disease or polyarteritis nodosa of infancy?

A 3-month-old infant died following a 3-week illness that commenced with diarrhoea and vomiting, and produced progressive infarction of his small bowel. Post-mortem identified multiorgan arteritis of uncertain aetiology, giving rise to coronary artery occlusion and myocardial infarction as well as necrosis of the entire small bowel and other organs. Kawasaki disease and polyarteritis nodosa of infancy are proposed as possible aetiologies in this case.

Variations in bronchiolitis management between five New Zealand hospitals: can we do better?

OBJECTIVES: To determine the current management of bronchiolitis by five major New Zealand hospitals and to identify areas for improvement. METHODS: Lists of infants under 1 year of age admitted with bronchiolitis during 1998 were obtained from the casemix offices of the five largest New Zealand hospitals with paediatric services. Hospital records from a random sample of these admissions were reviewed. RESULTS: Out of the 409 infants admitted overnight, 8% had been born less than or=32 weeks gestation and 53% were aged younger than 6 months. Overall, 59% received oxygen, 21% had nasogastric fluids, 22% had intravenous fluids, 34% were prescribed antibiotics, 42% received bronchodilators and 60% had a chest radiograph. Respiratory secretions were collected for viral studies from 58% of infants and, in 59%, respiratory syncytial virus was detected. Significant variations in management were detected between hospitals. The overall proportion of infants requiring oxygen, intravenous or nasogastric fluids (65%) was significantly higher than that found in a 1986-1988 Christchurch study where only 25% received one or more of these interventions (P < 0.001). CONCLUSIONS: Opportunities exist to rationalize bronchiolitis management in New Zealand with potential cost savings, particularly by reducing the number of chest radiographs and prescribing of unnecessary antibiotics and bronchodilators.

Cost-effectiveness of palivizumab in New Zealand.

OBJECTIVE: To establish the preterm infant hospitalization risks from respiratory syncytial virus (RSV) in New Zealand and the net cost per hospitalization averted by palivizumab. METHODS: The 437 infants born < 32 weeks' gestation in 1997 and treated at five major neonatal units were identified. Subsequent admissions during the next 2 years for bronchiolitis, pneumonia and croup were tracked, and information collected on RSV tests performed. Data on the length of stay and hospital costs were used to calculate the potential net cost per hospitalization averted associated with the use of palivizumab and the number needed to treat (NNT) to prevent one hospitalization. RESULTS: Estimated RSV readmission risk before 1 year corrected age in infants < 32 weeks' gestation discharged home on oxygen, and those " 28 weeks' gestation, or between 29 and 31 weeks' gestation with or without chronic lung disease was 42%, 23%, 19%, 10% and 8%, respectively. The NNT with palivizumab to prevent one hospitalization ranged from six to 26 across subgroups. Mean (range) net cost per hospitalization averted was 60,000 New Zealand dollars ($28,000-$166,700). In no subgroup would prophylaxis result in net cost saving. Prophylaxis for all NZ infants " 28 weeks' gestation would cost approximately $1,090,000 net and prevent 29 hospitalizations annually, being equivalent to $37,000 net per hospitalization averted, with eight infants treated to prevent one hospitalization. Alternative assumptions about cost and efficacy failed to alter these findings. CONCLUSION: If value is placed on preventing morbidity, the priority groups for palivizumab prophylaxis are preterm infants discharged home on oxygen, followed by preterm infants of 28 weeks' gestation or less.

The burden of symptoms of asthma, allergic rhinoconjunctivitis and atopic eczema in children and adolescents in six New Zealand centres: ISAAC Phase One.

AIM: To describe the burden of symptoms of asthma, allergic rhinoconjunctivitis and atopic eczema in children in six New Zealand centres. METHODS: The International Study of Asthma and Allergies in Childhood (ISAAC) Phase One was undertaken in Auckland, Bay of Plenty, Hawke's Bay, Wellington, Nelson and Christchurch during 1992-1993. In each centre, approximately 3,000 six to seven year old children and 3,000 thirteen to fourteen year old adolescents were studied, a total of 37,592 participants. Both age groups answered written questionnaires and the adolescents a video questionnaire about asthma symptoms. RESULTS: The prevalences of symptoms were high, for asthma 25% and 30%, allergic rhinoconjunctivitis 10% and 19%, and atopic eczema 15% and 13% in each age group respectively. More than 40% of participants had symptoms in the last year of at least one condition, most commonly asthma. There were no significant differences among regions, except for six to seven year olds in Nelson who had significantly lower prevalences of some symptoms of asthma and allergic rhinoconjunctivitis. CONCLUSIONS: Asthma and allergies are common in New Zealand, with resultant morbidity and cost. However, there is little regional variation with the exception of lower rates in Nelson children. Explanations for these findings will be the subject of further studies.

Asthma survey items as predictors of respiratory problems in children 2 yrs later: a longitudinal study.

The study compared the ability of characteristics defined by an asthma survey (wheeze versus cough and asthma diagnosis versus no diagnosis) to predict later respiratory problems in a cohort of 108 schoolchildren who had reported either recent wheeze or recurrent cough in a 1987 asthma survey. The children recorded daily respiratory symptoms and peak flow from April 1989 until May 1990. The frequency and severity of lower respiratory symptom episodes and peak flow dips were compared in the wheeze and cough groups and in the diagnosed versus nondiagnosed children. The independent effects of initial wheeze, atopy, diagnosis and bronchial hyperresponsiveness (BHR) on the longitudinal outcome measures were assessed using multiple linear regression. Children with initial wheeze had more chronic symptoms and peak flow variability than those with cough alone, but wheeze had only a weak effect on frequency and severity of acute lower respiratory episodes. Children with both wheeze and atopy had more acute symptomatic episodes and more chronic symptoms than did the other children. Children with diagnosed asthma (versus no diagnosis) had significantly more frequent and severe lower respiratory exacerbations, more days symptomatic and greater peak flow variability. The predictive effects of diagnosis were independent of (and stronger than the effects of) wheeze, atopy and BHR, or combinations of these variables. The results suggest that among children who report respiratory symptoms, survey-reported wheeze on its own is a weaker marker of significant respiratory disease than is a doctor's diagnosis of asthma.

The changing face of epiglottitis in Canterbury 1970-1996.

AIM: To record changes in the epidemiology, clinical presentation and management of the potentially fatal childhood disease, epiglottitis. METHODS: The case records of 69 children presenting to Christchurch Hospital with acute epiglottitis over the last 27 years were reviewed to confirm the diagnosis and to record clinical data. RESULTS: The incidence of epiglottitis increased significantly up until 1992. Since then there have been only two cases. This decline coincides with the availability of the Haemophilus influenzae Group b vaccine from 1993. Haemophilus influenzae was cultured in 86% of children. With the emergence of ampicillin resistant strains, antimicrobial therapy has changed to cephalosporins. Changes in airway management have also occurred, with the replacement of tracheostomy by elective naso-tracheal intubation. CONCLUSIONS: The incidence of epiglottitis in New Zealand has followed trends reported overseas. The longer term implications of this declining incidence following introduction of vaccination are not known. It is important however, that doctors still know how to recognize and manage acute epiglottitis in children and adults.

The effect of season-of-response to ISAAC questions about asthma, rhinitis and eczema in children.

BACKGROUND: To examine whether responses to questions about the lifetime prevalence and 12-month period prevalence of symptoms of asthma and allergies are affected by the season in which the questions are asked. METHODS: The international Study of Asthma and Allergies in Childhood (ISAAC) Phase One was undertaken in six New Zealand centres; in three centres the effect of season was studied. Over three school terms at least 3000 children were studied in each of two age groups per centre (6-7 years; 13-14 years), one-third in each term respectively. The ISAAC standardized written questionnaires were used to identify asthma, rhinitis and eczema symptoms. The written questionnaire in the younger age group was completed by the parent/guardian. The older age group self-completed the written questionnaire and also a video questionnaire about asthma symptoms. RESULTS: The total number of respondents was 21,437, approximately half in each age group. The season of responding had no effect on the level of response to eczema questions. For the written asthma questionnaire no season-of-response effect was present for 6-7 year olds; for 13-14 year olds there was a trend to a higher rate of positive responses by those responding in winter, but in only one question did this reach statistical significance. With the video questionnaire there was a similar trend for a higher rate of positive responses when questions were asked in winter, but this did not reach statistical significance. For rhinitis symptoms there was a statistically significant season-of-response effect in both age groups with two questions; the fewest positive responses by the winter responders. CONCLUSIONS: There was no significant effect of season-of-response to questions on eczema symptoms, and most questions on asthma symptoms. There was a season-of-response effect on responses to questions on rhinitis symptoms suggesting a recall bias relating to recency of symptoms.

The relationship between upper respiratory infections and hospital admissions for asthma: a time-trend analysis.

We have shown that viruses are associated with 80 to 85% of asthma exacerbations in school-age children in the community. We hypothesize that viral infections are also associated with severe attacks of asthma precipitating hospital admissions. To investigate this, we conducted a time-trend analysis, comparing the seasonal patterns of respiratory infections and hospital admissions for asthma in adults and children. During a 1-yr study in the Southampton area of the United Kingdom, 108 school-age children monitored upper and lower respiratory symptoms and took peak expiratory flow rate (PEFR) recordings. From children reporting a symptomatic episode or a decrease in PEFR, samples were taken for detection of viruses and atypical bacteria. A total of 232 respiratory viruses and four atypical bacteria were detected. The half-monthly rates of upper respiratory infection were compared with the half-monthly rates for hospital admissions for asthma (International Classification of Diseases [ICD] code 493) for the same time period for the hospitals serving the areas from which the cohort of schoolchildren was drawn. The relationships of upper respiratory infections and hospital admissions for asthma with school attendance were studied. Strong correlations were found between the seasonal patterns of upper respiratory infections and hospital admissions for asthma (r = 0.72; p < 0.0001). This relationship was stronger for pediatric (r = 0.68; p < 0.0001) than for adult admissions (r = 0.53; p < 0.01). Upper respiratory infections and admissions for asthma were more frequent during periods of school attendance (87% of pediatric and 84% of total admissions), than during school holiday periods (p < 0.001). These relationships remained significant when allowance was made for linear trend and seasonal variation using multiple regression analysis (p < 0.01). Not surprisingly, school attendance, because it is a major factor in respiratory virus transmission, was found to be a major confounding variable in children. This study demonstrates that upper respiratory viral infections are strongly associated in time with hospital admissions for asthma in children and adults. Rhinoviruses were the major pathogen implicated, and the majority of viral infections and asthma admissions occurred during school attendance.

Adaptive resistance to tobramycin in Pseudomonas aeruginosa lung infection in cystic fibrosis.

Aminoglycoside antibiotics have been shown to induce adaptive resistance in Pseudomonas aeruginosa in vitro and in a mouse model of infection, but adaptive resistance has not been described in human infections. Seven patients with cystic fibrosis were treated with inhaled tobramycin to determine whether adaptive resistance occurred in P. aeruginosa in their sputum. In three patients who had not recently taken antibiotics, 80 mg tobramycin was administered by nebuliser and resulting peak sputum tobramycin concentrations were 90-240 mg/L (elimination half-life 1.9-2.1 h). Adaptive resistance was detected in P. aeruginosa 1-4 h after the dose of tobramycin. Moderate resistance was present at 24 h and full susceptibility returned between 24 and 48 h. In four other patients on long-term twice-daily inhaled aminoglycoside treatment, adaptive resistance was present before, and 4 h after, 80 mg of tobramycin administered by nebuliser. The presence and time course of adaptive resistance in humans may have implications for improving aminoglycoside dosing regimens.

Are non-allergenic environmental factors important in asthma?

OBJECTIVE: To review the roles of viral respiratory tract infections, environmental tobacco smoke and air pollution in asthma. DATA SOURCES: MEDLINE (1992-1995) searches were conducted for publications on asthma, environmental tobacco smoke, ozone, nitrogen dioxide and particulates. STUDY SELECTION: Representative original experimental and epidemiological studies and reviews of viral infections in asthma. DATA SYNTHESIS: Respiratory virus infections are the most common and important trigger of asthma attacks in children and probably also in adults. Their role in promoting development of asthma is not so clear. Exposure to environmental tobacco smoke is almost certainly responsible for some cases of childhood asthma, and can also trigger symptoms of bronchoconstriction in adults with asthma. Exposure to ozone or nitrogen dioxide is associated with symptoms, impaired lung function, bronchial hyperresponsiveness and hospital presentations for asthma. These pollutants may also act as cofactors in the development of allergen-specific bronchial hyperresponsiveness. CONCLUSIONS: Research on preventing upper respiratory viral infections may reduce asthma morbidity. The move to non-smoking workplaces is welcome, but new interventions are needed to prevent young women taking up smoking and subsequently exposing their children. The ambient air quality guideline for ozone should be revised and a health-based guideline for respirable particulates introduced.

Prevalence of childhood asthma symptoms in an industrial suburb of Christchurch.

AIM: In response to community concern about the possible respiratory effects of emissions from a fertiliser plant, a study was carried out to determine whether the prevalence of asthma symptoms in 5-8 yr old children in an industrial suburb of Christchurch (Hornby) was the same as in the rest of Christchurch. METHODS: A sample of 646 children aged 5-8 years in Hornby was compared with 1183 6-7 year old children randomly selected from schools throughout the Christchurch metropolitan area. The Christchurch sample was part of the International Study of Asthma and Allergies in Childhood (ISAAC) carried out during 1993. ISAAC questionnaires on respiratory symptoms with some additional questions about smoking and pets were answered by the caregivers of the children sampled. RESULTS: Response rates were 97% in Hornby and 94% in Christchurch. Of the sample, 29% (Hornby) and 27% (Christchurch) had 'wheeze in the last 12 months' while 45% of Hornby and 44% of Christchurch children had 'ever wheezed', 28% had 'ever had asthma'. Significantly more children in Hornby (44%) were exposed to passive smoking compared to Christchurch (29%). Indoor pets were present in 73% and 67% of homes, respectively. CONCLUSION: There was no evidence of an increase in asthma symptoms reported in children in the industrial area of Hornby.

Community study of role of viral infections in exacerbations of asthma in 9-11 year old children.

OBJECTIVE: To study the association between upper and lower respiratory viral infections and acute exacerbations of asthma in schoolchildren in the community. DESIGN: Community based 13 month longitudinal study using diary card respiratory symptom and peak expiratory flow monitoring to allow early sampling for viruses. SUBJECTS: 108 Children aged 9-11 years who had reported wheeze or cough, or both, in a questionnaire. SETTING: Southampton and surrounding community. MAIN OUTCOME MEASURES: Upper and lower respiratory viral infections detected by polymerase chain reaction or conventional methods, reported exacerbations of asthma, computer identified episodes of respiratory tract symptoms or peak flow reductions. RESULTS: Viruses were detected in 80% of reported episodes of reduced peak expiratory flow, 80% of reported episodes of wheeze, and in 85% of reported episodes of upper respiratory symptoms, cough, wheeze, and a fall in peak expiratory flow. The median duration of reported falls in peak expiratory flow was 14 days, and the median maximum fall in peak expiratory flow was 81 l/min. The most commonly identified virus type was rhinovirus. CONCLUSIONS: This study supports the hypothesis that upper respiratory viral infections are associated with 80-85% of asthma exacerbations in school age children.