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.

The proposal for a third medical school in New Zealand: a community-engaged graduate entry medical program.

New Zealand has a maldistributed workforce that is heavily dependent on recruiting international medical graduates. Shortages are particularly apparent in high needs communities and in general scope specialties in provincial regions. The University of Waikato in partnership with the Waikato District Health Board has proposed a third medical school for New Zealand which will concentrate on addressing the workforce needs of disadvantaged rural and provincial communities. The proposed program is a community engaged, graduate entry medical course.

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.

Asthma phenotypes: consistency of classification using induced sputum.

BACKGROUND AND OBJECTIVE: Asthma can be classified as eosinophilic or non-eosinophilic based on the cell profile of induced sputum. This classification can help determine whether corticosteroid treatment is indicated. We assessed the stability of these phenotypes over time and with different treatment regimens. METHODS: Clinically stable, non-smoking, asthmatic adults were enrolled in one of two studies. In study one, induced sputum cell counts from 28 subjects were analysed after 4 weeks without corticosteroid treatment and after 6 week treatments with placebo, regular inhaled beta-agonist, inhaled corticosteroid, and combined beta-agonist and corticosteroid. In study two, sputum from 26 subjects with non-eosinophilic asthma was analysed after 12 weeks of placebo and after four 2-week corticosteroid washouts. Sputum with <2% eosinophils was classified as non-eosinophilic. RESULTS: Sputum classification changed frequently in both studies. In study one, only one of eight participants with non-eosinophilic sputum after placebo treatment remained non-eosinophilic throughout. In study two, all of participants had at least one eosinophilic sputum sample, despite the fact that all had been non-eosinophilic at recruitment. Neutrophilic asthma was uncommon in both studies and was also inconsistent. CONCLUSIONS: The phenotypic classification of asthma changes frequently. A diagnosis of non-eosinophilic asthma should not be based on a single sputum sample.

Cord-blood 25-hydroxyvitamin D levels and risk of respiratory infection, wheezing, and asthma.

OBJECTIVE: Higher maternal intake of vitamin D during pregnancy is associated with a lower risk of wheezing in offspring. The relationship between cord-blood levels of 25-hydroxyvitamin D (25[OH]D) and childhood wheezing is unknown. We hypothesized that cord-blood levels would be inversely associated with risk of respiratory infection, wheezing, and asthma. PATIENTS AND METHODS: Cord blood from 922 newborns was tested for 25(OH)D. Parents were asked if their child had a history of respiratory infection at 3 months of age or a history of wheezing at 15 months of age and then annually thereafter. Incident asthma was defined as doctor-diagnosed asthma by the time the child was 5 years old and reported inhaler use or wheezing since the age of 4 years. RESULTS: The median cord-blood level of 25(OH)D was 44 nmol/L (interquartile range: 29-78). Follow-up was 89% at the age of 5 years. Adjusting for the season of birth, 25(OH)D had an inverse association with risk of respiratory infection by 3 months of age (odds ratio: 1.00 [reference] for ≥75 nmol/L, 1.39 for 25-74 nmol/L, and 2.16 [95% confidence interval: 1.35-3.46] for <25 nmol/L). Likewise, cord-blood 25(OH)D levels were inversely associated with risk of wheezing by 15 months, 3 years, and 5 years of age (all P < .05). Additional adjustment for more than 12 potential confounders did not materially change these results. In contrast, we found no association between 25(OH)D levels and incident asthma by the age of 5 years. CONCLUSIONS: Cord-blood levels of 25(OH)D had inverse associations with risk of respiratory infection and childhood wheezing but no association with incident asthma.

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.

Bromotyrosines in sputum proteins and treatment effects of terbutaline and budesonide in asthma.

BACKGROUND: Inhaled corticosteroids are widely used in the treatment of persistent asthma, usually combined with inhaled beta2-agonists. Previous research suggests that short-acting beta2-agonists (SABAs) may downregulate the anti-inflammatory effects of inhaled corticosteroids, thereby increasing asthma morbidity. OBJECTIVE: To determine whether 3-bromotyrosine and 3,5-dibromotyrosine levels, specific markers of eosinophil activation, reflect treatment effects on airway inflammation of inhaled corticosteroids and SABAs and support previous conclusions. METHODS: Levels of 3-bromotyrosine and 3,5-dibromotyrosine were measured in sputum supernatants using stable isotope dilution gas chromatography-mass spectrometry in a randomized, placebo-controlled, crossover study of treatment with terbutaline, budesonide, and their combination in patients with persistent asthma. Thirty-four individuals were randomized, and 28 completed the study. RESULTS: Treatment with budesonide lowered median 3-bromotyrosine levels compared with treatment with placebo, terbutaline, and budesonide-terbutaline (0.24 vs 0.64, 0.62, and 0.43 3-bromotyosine/tyrosine [mmol/mol]; P < .05) and lowered median 3,5-dibromotyrosine levels compared with placebo and terbutaline treatments (0.04 vs 0.11 and 0.07 3,5-dibromotyrosine/ tyrosine [mmol/mol], P < .05). Unlike eosinophil numbers, 3-bromotyrosine and 3,5-dibromotyrosine levels did not increase with terbutaline treatment compared with placebo treatment but were significantly raised when terbutaline was added to budesonide treatment. 3-Bromotyrosine levels correlated significantly with eosinophil cationic protein levels in all groups. CONCLUSIONS: 3-Bromotyrosine and 3,5-dibromotyrosine levels reflect treatment effects in asthma and support previous findings that SABAs impair the anti-inflammatory effects of inhaled corticosteroids. In addition to eosinophil numbers and eosinophil cationic protein levels, these modified tyrosine residues provide useful information about the inflammatory state of the airways.

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.

Risk of severe asthma episodes predicted from fluctuation analysis of airway function.

Asthma is an increasing health problem worldwide, but the long-term temporal pattern of clinical symptoms is not understood and predicting asthma episodes is not generally possible. We analyse the time series of peak expiratory flows, a standard measurement of airway function that has been assessed twice daily in a large asthmatic population during a long-term crossover clinical trial. Here we introduce an approach to predict the risk of worsening airflow obstruction by calculating the conditional probability that, given the current airway condition, a severe obstruction will occur within 30 days. We find that, compared with a placebo, a regular long-acting bronchodilator (salmeterol) that is widely used to improve asthma control decreases the risk of airway obstruction. Unexpectedly, however, a regular short-acting beta2-agonist bronchodilator (albuterol) increases this risk. Furthermore, we find that the time series of peak expiratory flows show long-range correlations that change significantly with disease severity, approaching a random process with increased variability in the most severe cases. Using a nonlinear stochastic model, we show that both the increased variability and the loss of correlations augment the risk of unstable airway function. The characterization of fluctuations in airway function provides a quantitative basis for objective risk prediction of asthma episodes and for evaluating the effectiveness of therapy.

Home management of mild to moderately severe community-acquired pneumonia: a randomised controlled trial.

OBJECTIVE: To determine whether community management of mild to moderate community-acquired pneumonia (CAP) is as effective and acceptable as standard hospital management of CAP. DESIGN: Randomised controlled trial. SETTING: Christchurch, New Zealand, primary and secondary care. PARTICIPANTS: 55 patients presenting or referred to the emergency department at Christchurch Hospital with mild to moderately severe pneumonia, assessed using a validated pneumonia severity assessment score, from July 2002 to October 2003. INTERVENTIONS: Hospital treatment as usual or comprehensive care in the home delivered by primary care teams. MAIN OUTCOME MEASURES: Primary: days to discharge, days on intravenous (IV) antibiotics, patient-rated symptom scores. Secondary: health status measured using level of functioning at 2 and 6 weeks, patient satisfaction. RESULTS: The median number of days to discharge was higher in the home care group (4 days; range, 1-14) than in the hospital groups (2 days; range, 0-10; P = 0.004). There was no difference in the number of days on IV antibiotics or on subsequent oral antibiotics. Patient-rated symptom scores at 2 and 6 weeks, median change in symptom severity from baseline to 6 weeks, and general functioning at 2 and 6 weeks did not differ between the groups. Patients in both groups were satisfied with their treatment, with a clear preference for community treatment (P < 0.001). CONCLUSIONS: Mild to moderately severe CAP can be managed effectively in the community by primary care teams. This model of comprehensive care at home can be implemented by primary care teams with suitable funding structures.

Psychopathology and illness beliefs influence COPD self-management.

OBJECTIVE: To explore the influence of psychological characteristics in Chronic Obstructive Pulmonary Disease (COPD) self-management. METHODS: Patients admitted with an exacerbation of COPD were interviewed for psychiatric symptoms, illness beliefs and self-management behaviour using a new COPD Self-Management Interview (COPD-SMI). This comprised three scenarios to mimic a future evolving exacerbation. Responses were scored for knowledge and actions (adherence) for each scenario. RESULTS: Of 47 people approached, 39 participated; 41% had panic attacks, 33% general anxiety, 35% a depression history, 31% an anxiety history and 21% an alcohol dependence history. Twenty-six (67%) had a self-management plan. When hypothetically "well" lower (poorer) COPD-SMI Knowledge Scores were associated with an alcohol dependence history (P=.025), no panic (P=.021) and males (P=.028). Those perceiving less influence over COPD had lower Action Scores during this scenario (P=.01) and the "early exacerbation" scenario (P=.05). Lower Knowledge Scores for the "early exacerbation" were associated with no panic (P=.01) and no self-management plans (P=.03). For the "severe exacerbation", lower Action Scores were associated with depression history (P=.004), panic (P=.002), higher FEV(1)% and no self-management plans (P=.005). Higher PaCO(2) was associated with lower confidence in symptom recognition, self-management ability and medical care influencing COPD. CONCLUSION: Anxiety, depression, alcohol use and illness beliefs may differentially influence self-management. Depression, previous alcohol dependence and perceived less influence over COPD inhibited self-management. Those with panic demonstrated more self-management knowledge when "well" but performed poorly on actions during the "severe exacerbation". Those with self-management plans had better knowledge and actions.

Evaluation of a PCR assay for detection of Streptococcus pneumoniae in respiratory and nonrespiratory samples from adults with community-acquired pneumonia.

Streptococcus pneumoniae is the most common cause of community-acquired pneumonia, but it is undoubtedly underdiagnosed. We used a nested PCR assay (targeting the pneumolysin gene) to detect S. pneumoniae DNA in multiple sample types from 474 adults with community-acquired pneumonia and 183 control patients who did not have pneumonia. Plasma or buffy coat samples were PCR positive in only 6 of the 21 patients with positive blood cultures for S. pneumoniae and in 12 other patients (4 of whom had no other laboratory evidence of S. pneumoniae infection). Buffy coat samples from two control patients (neither having evidence of S. pneumoniae infection), but no control plasma samples, were PCR positive. Although pneumococcal antigen was detected in the urine from 120 of 420 (29%) patients, only 4 of 227 (2%) urine samples tested were PCR positive. Overall, 256 of 318 (81%) patients had PCR-positive sputum samples, including 58 of 59 samples from which S. pneumoniae was cultured. Throat swab samples from 229 of 417 (55%) patients were PCR positive and, in those who produced sputum, 96% also had positive PCR results from sputum. Throat swabs from 73 of 126 (58%) control patients were also PCR positive. We conclude that the pneumolysin PCR assay adds little to existing diagnostic tests for S. pneumoniae and is unable to distinguish colonization from infection when respiratory samples are tested.

Eosinophils and eosinophilic cationic protein in induced sputum and blood: effects of budesonide and terbutaline treatment.

BACKGROUND: There is a need for easily measurable markers of airway inflammation to guide the use of anti-inflammatory treatment in asthma. Eosinophilic cationic protein (ECP) levels in sputum and blood correlate with clinical severity, and serial measurements of ECP have been proposed as a suitable candidate. AIMS AND METHODS: Our aim was to confirm that sputum and serum ECP measurements would provide a more sensitive indicator of responses to asthma treatment than eosinophil counts per se, in a randomized, placebo-controlled, crossover study of terbutaline, budesonide, and their combination in patients with chronic persistent asthma. We compared the changes in eosinophil counts and ECP in induced sputum and blood during each treatment period. RESULTS: Budesonide and combined treatment caused a significant reduction in sputum eosinophils (-2.7% and -2.3%, respectively, P < 0.05). Sputum eosinophils increased with terbutaline (+3.9%, P = 0.049). In contrast, the changes for sputum ECP were not significant. There was a similar treatment effect on blood eosinophils, but not for serum ECP. Correlations between sputum and blood eosinophils were significant with and without budesonide, but were nonsignificant between sputum and blood ECP during the active treatments. Correlations between sputum eosinophils and ECP, and between blood eosinophils and serum ECP were greatest during treatment with placebo or terbutaline alone: budesonide weakened or abolished these relationships. CONCLUSIONS: Compared with eosinophil counts, ECP measurements in either induced sputum or serum failed to reflect treatment-related changes in chronic asthma. We conclude that ECP is not a sensitive or reliable means of evaluating airway inflammation, and can not be recommended for assessing responses to anti-inflammatory therapy.

Eosinophil peroxidase produces hypobromous acid in the airways of stable asthmatics.

Eosinophil peroxidase and myeloperoxidase use hydrogen peroxide to produce hypobromous acid and hypochlorous acid. These powerful oxidants may damage the lungs if they are produced as part of the inflammatory response in asthma. The aim of this study was to determine if peroxidases generate hypohalous acids in the airways of individuals with stable asthma, and if they affect lung function. Sputum was induced from patients with mild to moderate asthma and from healthy controls. Eosinophil peroxidase, myeloperoxidase, chlorinated and brominated tyrosyl residues, and protein carbonyls were measured in sputum supernatants. Eosinophil peroxidase protein was significantly elevated in asthmatic subjects whereas myeloperoxidase protein was not. There was significantly more 3-bromotyrosine (Br-Tyr) in proteins from the sputum of asthmatics compared to controls (0.79 vs. 0.23 mmol Br-Tyr/mol Tyr; medians p < .0001). Levels of 3-chlorotyrosine (0.23 vs. 0.14 mmol Cl-Tyr/mol Tyr; medians p = .11) and protein carbonyls (0.347 vs. 0.339 nmol/mg protein; medians p = .56) were not significantly increased in asthmatics. Levels of 3-bromotyrosine were strongly correlated with eosinophil peroxidase protein (r = 0.79, p < .0001). There were no significant correlations between the markers of oxidative stress and lung function. We conclude that eosinophil peroxidase produces substantial amounts of hypobromous acid in the airways of stable asthmatics. Although this highly reactive oxidant is a strong candidate for exacerbating inflammatory tissue damage in the lung, its role in asthma remains uncertain.

Plasma brain natriuretic peptide after long-term treatment for heart failure in general practice.

AIM: Plasma brain natriuretic peptide (BNP) concentrations are known to have high sensitivity and specificity in the diagnosis of heart failure in newly symptomatic patients. The relationship of plasma BNP to cardiac function in stable patients on long-term established treatment for heart failure is unknown. Plasma BNP was assessed for its ability to predict echocardiographic abnormality in 100 patients receiving long-term treatment in general practice for a provisional diagnosis of heart failure. METHODS AND RESULTS: BNP >35 pmol/l had a sensitivity and specificity of 69% and 67%, respectively, for a left ventricular ejection fraction of <45%. However, 19% of patients had an LVEF of below 45% whilst BNP was below 35 pmol/l. These patients, in whom a diagnosis of heart failure had been made years previously (mean 3.9 years), were all clinically stable on treatment. CONCLUSION: These findings support the view that BNP can be restored to normal levels in well-compensated patients despite persisting significant systolic dysfunction and suggest that BNP assays may be helpful for monitoring adequacy of therapy. BNP assays will have limited utility in the diagnosis of cardiac impairment once anti-failure therapy is well established and symptoms have been abolished.

Adherence to asthma self-management plans with inhaled corticosteroid and oral prednisone: A descriptive analysis.

BACKGROUND: Asthma self-management plans (SMP) are widely recommended for use, but there is little information regarding the degree of patient adherence to their instructions. The aim of the present study was to perform a descriptive analysis of patient responses to worsening asthma with regard to using individualized SMP. METHODS: Diary data were obtained from an earlier 2 year study in which patients used regularly revised SMP in combination with daily recordings of peak expiratory flow (PEF) and symptoms to manage intercurrent asthma episodes. Based on PEF and symptom changes, the SMP contained instructions about increasing the dose of inhaled corticosteroid (ICS) or commencing oral prednisone during worsening asthma, depending on severity. Data from 165 patient diaries were analysed. First, documented responses to episodes of worsening asthma were matched against SMP instructions and adherence was determined using a priori criteria. Second, each occasion when the ICS dose was increased or prednisone was commenced was identified and changes in PEF and/or symptoms that may have led to these actions were sought. RESULTS: Adherence for increasing the ICS dose was dependent on asthma severity, ranging from 78% during severe episodes to 31% during mild short-lived events. When oral prednisone was indicated, patients were adherent on 56% of occasions. Symptoms prompted intervention more frequently than changes in PEF. Significant changes in PEF were absent on 41 and 48% of occasions for ICS dose increase and oral prednisone use, respectively. CONCLUSIONS: Adherence to asthma SMP is variable and often poor. It tends to increase in proportion to the severity and duration of an asthma episode. This underscores the importance of SMP in more severe asthma. Symptoms are more important then PEF in prompting patients to alter treatment. This ought to modify our approach in constructing individual asthma SMP.