G. Ian Town

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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

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.