Biomedical subjects

Robert J Hancox

Publications and source records attributed to Robert J Hancox.

14 recordsLinked to original sources

PubMed2006

Associations between respiratory symptoms, lung function and gastro-oesophageal reflux symptoms in a population-based birth cohort.

BACKGROUND: Several studies have reported an association between asthma and gastro-oesophageal reflux, but it is unclear which condition develops first. The role of obesity in mediating this association is also unclear. We explored the associations between respiratory symptoms, lung function, and gastro-oesophageal reflux symptoms in a birth cohort of approximately 1000 individuals. METHODS: Information on respiratory symptoms, asthma, atopy, lung function and airway responsiveness was obtained at multiple assessments from childhood to adulthood in an unselected birth cohort of 1037 individuals followed to age 26. Symptoms of gastro-oesophageal reflux and irritable bowel syndrome were recorded at age 26. RESULTS: Heartburn and acid regurgitation symptoms that were at least "moderately bothersome" at age 26 were significantly associated with asthma (odds ratio = 3.2; 95% confidence interval = 1.6-6.4), wheeze (OR = 3.5; 95% CI = 1.7-7.2), and nocturnal cough (OR = 4.3; 95% CI = 2.1-8.7) independently of body mass index. In women reflux symptoms were also associated with airflow obstruction and a bronchodilator response to salbutamol. Persistent wheezing since childhood, persistence of asthma since teenage years, and airway hyperresponsiveness since age 11 were associated with a significantly increased risk of heartburn and acid regurgitation at age 26. There was no association between irritable bowel syndrome and respiratory symptoms. CONCLUSION: Reflux symptoms are associated with respiratory symptoms in young adults independently of body mass index. The mechanism of these associations remains unclear.

Adolescent↗

PubMed2006

Adiposity, asthma, and airway inflammation.

BACKGROUND: Several studies have found obesity to be associated with an increased prevalence of asthma. For reasons that remain unclear, this association has often been reported to be stronger in women than in men. One possible explanation might be that these studies have used body mass index to identify adiposity, which might be a less reliable measure of body fat in men than in women. OBJECTIVE: We sought to explore the association between body fat percentage measured by means of bioelectrical impedance analysis and asthma, airflow obstruction, and airway inflammation in men and women. METHODS: Respiratory questionnaires, spirometry, bronchodilator response, exhaled nitric oxide level, and percentage of body fat were measured in a population-based cohort of approximately 1000 individuals at age 32 years. RESULTS: There was a significant association between the percentage of body fat and asthma in women (P = .043) but not in men (P = .75). Airflow obstruction was associated with percentage of body fat in women (P = .046), but there was an inverse association in men (P = .010). Bronchodilator responsiveness was also associated with lower body fat in men (P = .004). Airway inflammation, measured by means of exhaled nitric oxide, was not associated with body fat in either women (P = .17) or men (P = .25). CONCLUSION: Adiposity is associated with asthma and airflow obstruction in women. This does not appear to be mediated by airway inflammation. In men airflow obstruction and bronchodilator responsiveness are associated with a lower percentage of body fat. CLINICAL IMPLICATIONS: In women, but not in men, obesity is associated with asthma and airflow obstruction, but there was no association with airway inflammation.

Adipose Tissue↗

PubMed2005

Tolerance to bronchodilation during treatment with long-acting beta-agonists, a randomised controlled trial.

BACKGROUND: Regular use of beta-agonists leads to tolerance to their bronchodilator effects. This can be demonstrated by measuring the response to beta-agonist following bronchoconstriction using methacholine. However most studies have demonstrated tolerance after a period of beta-agonist withdrawal, which is not typical of their use in clinical practice. This study assessed tolerance to the bronchodilator action of salbutamol during ongoing treatment with long-acting beta-agonist. METHODS: Random-order, double-blind, placebo-controlled, crossover trial. After 1 week without beta-agonists, 13 asthmatic subjects inhaled formoterol 12 microg twice daily or matching placebo for 1 week. Eight hours after the first and last doses subjects inhaled methacholine to produce a 20% fall in FEV1. Salbutamol 100, 200 and 400 microg (cumulative dose) was then given at 5-minute intervals and FEV1 was measured 5 minutes after each dose. After a 1 week washout subjects crossed over to the other treatment. Unscheduled use of beta-agonists was not allowed during the study. The main outcome variable was the area under the salbutamol response curve. RESULTS: The analysis showed a significant time by treatment interaction indicating that the response to salbutamol fell during formoterol therapy compared to placebo. After 1 week of formoterol the area under the salbutamol response curve was 48% (95% confidence interval 28 to 68%) lower than placebo. This reduction in response remained significant when the analyses were adjusted for changes in the pre-challenge FEV1 and dose of methacholine given (p = 0.001). CONCLUSION: The bronchodilator response to salbutamol is significantly reduced in patients taking formoterol. Clinically relevant tolerance to rescue beta-agonist treatment is likely to occur in patients treated with long-acting beta-agonists.

Administration, Inhalation↗

PubMed2005

Association of television viewing during childhood with poor educational achievement.

BACKGROUND: Excessive television viewing in childhood has been associated with adverse effects on health and behavior. A common concern is that watching too much television may also have a negative impact on education. However, no long-term studies have measured childhood viewing and educational achievement. OBJECTIVE: To explore these associations in a birth cohort followed up to adulthood. DESIGN: Prospective birth cohort study. SETTING: Dunedin, New Zealand. PARTICIPANTS: Approximately 1000 unselected individuals born between April 1, 1972, and March 31, 1973. Ninety-six percent of the living cohort participated at 26 years of age. MAIN OUTCOME MEASURES: Educational achievement by 26 years of age. RESULTS: The mean time spent watching television during childhood and adolescence was significantly associated with leaving school without qualifications and negatively associated with attaining a university degree. Risk ratios for each hour of television viewing per weeknight, adjusted for IQ and sex, were 1.43 (95% confidence interval [CI], 1.24-1.65) and 0.75 (95% CI, 0.67-0.85), respectively (both, P<.001). The findings were similar in men and women and persisted after further adjustment for socioeconomic status and early childhood behavioral problems. Television viewing during childhood (ages 5-11 years) and adolescence (ages 13 and 15 years) had adverse associations with later educational achievement. However, adolescent viewing was a stronger predictor of leaving school without qualifications, whereas childhood viewing was a stronger predictor of nonattainment of a university degree. CONCLUSIONS: Television viewing in childhood and adolescence is associated with poor educational achievement by 26 years of age. Excessive television viewing in childhood may have long-lasting adverse consequences for educational achievement and subsequent socioeconomic status and well-being.

Adolescent↗

PubMed2005

C-reactive protein and cardiorespiratory fitness in young adults.

BACKGROUND: Fitness and obesity are both independently associated with cardiovascular events and mortality. C-reactive protein (CRP), a predictor of cardiovascular events is associated with obesity; but its association with cardiorespiratory fitness in early adulthood is uncertain. The aim of this study was to examine the relationship between cardiorespiratory fitness and CRP, controlling for obesity in an unselected cohort of young adults. DESIGN: A cross-sectional study in a representative birth cohort. METHODS: We measured CRP levels, cardiorespiratory fitness, anthropometric variables, blood pressure and smoking in 26-year-old men (n=400) and women (n=315). Log CRP levels were compared across cardiorespiratory fitness with adjustment for body mass index (BMI), sex, blood pressure, smoking and combined oral contraceptive use. RESULTS: Geometric mean CRP levels were higher in women (3.23 mg/l, 95% CI 2.85-3.64) compared with men (1.70 mg/l, 1.52-1.89). Regression analysis adjusting for sex and weight showed an inverse association between fitness and CRP (beta=-0.16, P<0.001). This association held after statistical controls were added for BMI, systolic blood pressure and smoking and combined oral contraceptive use (P< or =0.01). CONCLUSIONS: Cardiorespiratory fitness levels are inversely associated with CRP levels in young adults independent of obesity, blood pressure, smoking and combined oral contraceptive use in women. Physical fitness may decrease the risk of cardiovascular events by reducing inflammation.

Adult↗

PubMed2004

Rapid onset of tolerance to beta-agonist bronchodilation.

INTRODUCTION: Regular use of beta-agonists leads to tolerance to their bronchodilator effects. This is easily demonstrated if dilation is tested following methacholine challenge. It is not known how quickly tolerance develops or how long it lasts after stopping beta-agonist therapy. METHODS: Ten subjects with stable asthma were studied. Following 2 weeks without beta-agonists, methacholine was inhaled to induce a 20% reduction in FEV1. The response to inhaled salbutamol (100, 100, 200 microg at 5-min intervals) was then measured. This procedure was repeated 24 h after one dose and 24 h after 3, 7 and 14 days of inhaled formoterol 12 microg twice daily, and 3 and 5 days after formoterol was discontinued. Unscheduled use of beta-agonists was not permitted. RESULTS: Bronchodilator tolerance, assessed by a reduction of the area under the salbutamol dose-response curve, occurred after 1 dose of formoterol (28% reduction, 95% CI 12, 45%), increased up to 1 week and plateaued between 1 and 2 weeks (58% reduction, 95% CI 38, 78%). Three days after stopping formoterol, the response to salbutamol was similar to baseline (12% reduction, 95% CI -9, 33%). The first dose of formoterol provided significant bronchoprotection to methacholine (1.6 doubling doses, P=0.007). This diminished with regular treatment and by 2 weeks the PD20 methacholine was not significantly different to baseline. CONCLUSIONS: Bronchodilator tolerance occurs after a single dose and reaches a maximum after 1 week of regular formoterol. Sensitivity recovers 3 days after stopping treatment.

Adrenergic beta-Agonists↗

PubMed2004

Sex differences in the relation between body mass index and asthma and atopy in a birth cohort.

RATIONALE: Several studies have identified an association between asthma and obesity in women. It remains unclear if this association is due to genuine asthma or to symptoms caused by overweight, at what age the association develops, and whether it is confined to females. OBJECTIVE: To explore the relations between body mass index, asthma, and atopy in a birth cohort of approximately 1,000 individuals. METHODS: Information on asthma and measurements of lung function, airway responsiveness, and atopy were obtained on multiple occasions between ages 9 and 26. Associations between these outcomes and body mass index were analyzed using generalized mixed linear regression models. Further analyses adjusted for potential covariates including breastfeeding, birth order, parental asthma, and personal and family smoking history. MAIN RESULTS: Body mass index was positively associated with asthma, wheeze, asthma treatment, atopy, immunoglobulin E, and inversely with the FEV(1)/FVC ratio in females. There was no significant association with airway responsiveness to methacholine or salbutamol. There was little evidence of an association between body mass index and asthma or atopy in males. Analyses adjusting for potential covariates showed similar findings. Asthma was not associated with a raised body mass index in childhood and childhood asthma did not lead to being overweight as an adult. CONCLUSIONS: A raised body mass index is associated with asthma and atopy in women but not men. Population attributable fraction calculations estimate that 28% (95% confidence interval 7-45) of asthma developing in women after age 9 is due to overweight.

Adolescent↗

PubMed2004

Elevation of cardiac troponins in exacerbation of chronic obstructive pulmonary disease.

OBJECTIVES: To investigate the prevalence of serum troponin elevation in patients admitted to hospital with an exacerbation of chronic obstructive pulmonary disease (COPD). METHODS: We examined the records of all patients admitted to hospital for treatment of COPD for serum troponin measurement, clinical features of myocardial ischaemia, oxygenation (pulse oximetry, arterial blood gas analysis), spirometry, and duration of admission. RESULTS: Troponin elevation was observed in 58 of 235 (25%) presentations in which troponin was measured. Despite the troponin result, only seven of these 58 patients had been diagnosed with an acute coronary syndrome. New ECG evidence of ischaemia was uncommon. Patients with raised troponins tended to be older (75.7 vs 70.0 years, P = 0.001), had lower pulse oximetry (85.6% vs 89.6%, P = 0.003), were more acidotic (pH 7.34 vs 7.40, P= 0.002) and more hypercapnoeic (pCO2 58.0 vs 49.1, P = 0.04). There were no significant differences in serum creatine kinase. Patients with raised troponins had significantly longer admissions (5 vs 3 days, P = 0.001). CONCLUSIONS: Serum troponins are commonly raised in acute exacerbations of COPD and appear to reflect the severity of the exacerbation. In the majority of patients there is insufficient evidence to support the diagnosis of an acute coronary syndrome.

Age Distribution↗

PubMed2002

Beta2-agonist tolerance and exercise-induced bronchospasm.

The effect of regular inhaled beta-agonist on the treatment of exercise-induced bronchoconstriction was studied. Eight subjects with exercise-induced bronchoconstriction took 1 week each of salbutamol 200 microg qid or placebo in a random-order, double-blind, crossover study. They then withheld this treatment for 8 hours before performing a dry-air, sub-maximal exercise challenge at a work-rate previously shown to induce a 15% fall in forced expiratory volume in 1 second (FEV1). Five minutes after exercise, they inhaled salbutamol 100, 100, and 200 microg at 5-minute intervals. The mean pre-exercise FEV1 was similar on both study days. However, pretreatment for 1 week with salbutamol led to a significantly greater fall in FEV1 after exercise. The FEV1 remained lower than during the placebo arm despite the administration of salbutamol after exercise. This difference persisted 25 minutes after exercise. It is concluded that regular beta-agonist treatment leads to increased exercise-induced bronchoconstriction and a suboptimal bronchodilator response to beta-agonist. The data suggest that previous regular beta-agonist treatment may lead to a failure to respond to emergency bronchodilator treatment during an acute asthma attack and support current opinion that regular short-acting beta-agonist therapy should not be used to treat asthma.

Adolescent↗

PubMed2002

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.

Administration, Topical↗

PubMedDate not supplied

Association between child and adolescent television viewing and adult health: a longitudinal birth cohort study.

BACKGROUND: Watching television in childhood and adolescence has been linked to adverse health indicators including obesity, poor fitness, smoking, and raised cholesterol. However, there have been no longitudinal studies of childhood viewing and adult health. We explored these associations in a birth cohort followed up to age 26 years. METHODS: We assessed approximately 1000 unselected individuals born in Dunedin, New Zealand, in 1972-73 at regular intervals up to age 26 years. We used regression analysis to investigate the associations between earlier television viewing and body-mass index, cardiorespiratory fitness (maximum aerobic power assessed by a submaximal cycling test), serum cholesterol, smoking status, and blood pressure at age 26 years. FINDINGS: Average weeknight viewing between ages 5 and 15 years was associated with higher body-mass indices (p=0.0013), lower cardiorespiratory fitness (p=0.0003), increased cigarette smoking (p<0.0001), and raised serum cholesterol (p=0.0037). Childhood and adolescent viewing had no significant association with blood pressure. These associations persisted after adjustment for potential confounding factors such as childhood socioeconomic status, body-mass index at age 5 years, parental body-mass index, parental smoking, and physical activity at age 15 years. In 26-year-olds, population-attributable fractions indicate that 17% of overweight, 15% of raised serum cholesterol, 17% of smoking, and 15% of poor fitness can be attributed to watching television for more than 2 h a day during childhood and adolescence. INTERPRETATION: Television viewing in childhood and adolescence is associated with overweight, poor fitness, smoking, and raised cholesterol in adulthood. Excessive viewing might have long-lasting adverse effects on health.

Adolescent↗

PubMedDate not supplied

Recovery from bronchoconstriction and bronchodilator tolerance.

Until recently, researchers believed that tolerance or tachyphylaxis to the bronchodilator effects of beta-agonists did not occur. However, recent studies examining the recovery from bronchoconstriction have clearly shown that an impaired response to beta-agonists occurs in patients who have been using regular beta-agonist treatment. This tolerance develops with both long- and short-acting beta-agonists and is not affected by treatment with inhaled steroids. It develops rapidly, reaching a maximum within 1 wk of starting beta-agonists, and has been demonstrated after methacholine, hypertonic saline, mannitol, and exercise-induced bronchoconstriction. The observed reduction in the bronchodilator response is proportional to the severity of bronchoconstriction. Therefore, although individuals with stable asthma show little evidence of tolerance, those with severe bronchospasm have a markedly reduced bronchodilator response to beta-agonists. Almost all asthmatics show evidence of tolerance when tested in the setting of bronchoconstriction, although the extent of this tolerance varies. The reasons for this interindividual variation are not understood. Bronchodilator tolerance is difficult to study in the clinical setting because nearly every patient has used multiple doses of beta-agonist before seeking medical attention. However, there is compelling evidence that the response to rescue beta-agonist treatment is reduced in those who use regular long- or short-acting beta-agonists. The extent to which this phenomenon contributes to asthma morbidity and mortality remains to be determined.

Bronchoconstriction↗

PubMedDate not supplied

Interactions between corticosteroids and beta2-agonists.

In vitro studies have demonstrated numerous ways in which beta2-agonists and corticosteroids may interact. Together with evidence of improved control of airway diseases using a combination therapy of inhaled corticosteroids and long-acting beta-agonists compared with treatment with either drug alone, this suggests that there may be a beneficial synergy between these two classes of medication. However, a positive interaction has not been clearly demonstrated in vivo. There is little evidence that beta2-agonists enhance the anti-inflammatory actions of inhaled corticosteroids. Corticosteroids do not enhance the bronchodilator response to beta2- agonists, nor do they appear to prevent the development of tolerance during chronic beta2-agonist treatment. The evidence that high doses of corticosteroids can reverse tolerance to beta2-agonists is conflicting. Most of the clinical benefits from combinations using inhaled corticosteroids and long-acting beta-agonists to treat asthma could result from additive or complimentary effects of the drugs on different parts of the disease process. Nevertheless, there are several studies in which the combination of a long- or short-acting beta-agonist with an inhaled corticosteroid appears to have provided more than additive clinical benefits. The issue warrants further study. Combined inhaled corticosteroid/beta-agonist treatment will remain the basis of asthma management for the foreseeable future, and although the overall clinical benefit of the combination is no longer in doubt, there is more to learn about maximizing this benefit and minimizing adverse effects.

Adrenergic beta-2 Receptor Agonists↗

PubMedDate not supplied

Concluding remarks: can we explain the association of beta-agonists with asthma mortality? A hypothesis.

Beta-agonists have clearly demonstrated benefits for the treatment of both acute and chronic asthma. Therefore, it is perhaps surprising that many of the articles in this issue have focused on concerns about their safety. Much of this concern can be traced back to the "beta-agonist controversy"--the association of high-dose isoprenaline and fenoterol inhalers with asthma mortality in the 1960s and 1970s. Although a causal link was never proven, lingering doubts about the safety of beta-agonists remain. It is unclear whether a similar adverse effect is responsible for recently reported association of long-acting beta-agonists with asthma deaths. No mechanism for the beta-agonist controversy was established, but the evidence presented in this collection of articles points to a number of contributing factors. I suggest that a combination of these effects provides a plausible mechanism for the association of frequent beta-agonist use with asthma mortality. Rebound bronchoconstriction and bronchial hyperresponsiveness occur on withdrawal of regular beta-agonist treatment. Regular use of fenoterol is associated with a reduction in morning peak flow suggesting that the overnight interval between doses is sufficient to allow rebound bronchoconstriction. This has not been observed with terbutaline or salbutamol, although rebound phenomena do occur when these drugs are withdrawn for slightly longer periods. Regular use of beta-agonists also leads to tolerance to their bronchoprotective and bronchodilator effects. Tolerance becomes more apparent with worsening bronchoconstriction. In severe asthma, this could result in a poor response to emergency treatment. The combination of rebound deterioration of asthma and a poor response to beta-agonist treatment resulting from tolerance could explain the increased mortality associated with fenoterol and isoprenaline. Both effects are probably caused by downregulation of beta-receptors which occurs with all beta-agonists. Long-acing beta-agonists cause a similar degree of tolerance to short-acting beta-agonists, but avoid the problem of overnight withdrawal. Long-acting beta-agonists have also been shown to improve asthma control when taken in combination with inhaled corticosteroids. The clinical significance of tolerance in this context remains to be determined.

Adrenergic beta-Agonists↗