Biomedical subjects
M R Sears
Publications and source records attributed to M R Sears.
Sheepskins and bedding in childhood, and the risk of development of bronchial asthma.
BACKGROUND: Sheepskin bedding might increase house dust mite exposure and so explain some of the increasing prevalence of severity of childhood asthma. METHODS: Relationships between use of different types of bedding, and diagnoses of asthma, symptoms of wheezing, skin prick test evidence of house dust mite sensitivity, and airway responsiveness to methacholine, were examined retrospectively in a birth cohort of children followed longitudinally to age 15 years. RESULTS: In the whole cohort, no associations were identified to suggest a causal relationship between use of any type of bedding and development of features of asthma. Although not an a priori hypothesis, we noted that among children with a family history of atopic disease, those who were house dust mite sensitive were more likely to have used an innerspring mattress (29.6% vs 10.2% who had not used an innerspring mattress, p = 0.005). CONCLUSION: In this subgroup, increased airway responsiveness and mite sensitivity were significantly associated with use of innerspring mattresses, although whether this is a causal or secondary association is not certain. Use of a sheepskin in the bed in early childhood was not an additional risk factor for the development of asthma.
Bronchodilators and bronchial hyperresponsiveness.
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Regular beta-adrenergic agonists. Evidence, not reassurance, is what is needed.
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The beta 2-agonist controversy. Observations, explanations and relationship to asthma epidemiology.
Links between frequent use of inhaled beta 2-agonists and morbidity and mortality from asthma appear probable. Two mortality epidemics followed the marketing of potent inhaled adrenergic agents. Case-control studies in New Zealand linked mortality with prescription of fenoterol, especially in severe asthma. A Saskatchewan case-control study confirmed an association of mortality with fenoterol, and also with frequent use of salbutamol (albuterol). Cardiac effects of beta 2-agonists do not cause mortality, but frequent use of these agents may increase the chronic severity of asthma, hence increasing the number of asthmatic patients at risk of death in an acute attack. Frequent use of beta 2-agonists may reduce lung function, increasing airway responsiveness, and impair control of asthma, despite use of inhaled corticosteroids. Mechanisms for this effect may include tachyphylaxis to nonbronchodilator effects, increased responsiveness to allergen, interaction with corticosteroid receptors, altered mucociliary function, differential effects of enantiomers, and masking of symptoms by beta 2-agonist use. The withdrawal of fenoterol from New Zealand in 1990 was associated with a substantial decline in morbidity and mortality. Overall, the evidence suggests that frequent use of inhaled beta 2-agonists has a deleterious effect on the control of asthma. Epidemics of mortality are explained by an increase in chronic severity of asthma following introduction of more potent beta 2-agonists. While beta 2-agonists remain essential for relief of breakthrough symptoms, long term use, particularly with high doses of potent agents, appears to be detrimental.
Bronchodilator treatment in asthma.
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Bronchodilator treatment in asthma. Increase in deaths during salmeterol treatment unexplained.
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Allergic disorders and attention deficit disorder in children.
It has been suggested that children with attention deficit disorder-hyperactivity (ADDH) are likely to show allergic disorders, and that both ADDH and allergic disorders may share a common biological background. In a large sample of children from the general population we found no association between parent, teacher, and self-reports of ADDH behaviors and a history of allergic disorders (asthma, eczema, rhinitis, and urticaria) at ages 9 or 13 years. Similarly, reports of ADDH behaviors at age 13 years were not related to level of atopic responsiveness by skin test or serum IgE levels. Our findings call into question the hypothesis that there is a relationship between ADDH and allergic disorder.
Atopy in childhood. I. Gender and allergen related risks for development of hay fever and asthma.
Reasons for the gender differences in prevalence rates for asthma remain unclear. We have examined the relationships between allergen skin-test reactions and diagnoses of hay fever and asthma in New Zealand boys and girls examined at the age of 13 years. Information on current and past wheezing, diagnosed asthma, and hay fever was obtained for 662 subjects (341 boys) of a birth cohort followed longitudinally to the age of 13 years, using a physician-administered questionnaire. Atopic status was determined by skin-prick tests to 11 common allergens. The proportion of 13-year-old boys with current asthma was 1.6 times higher and of ever-diagnosed asthma 1.4 times higher than in girls, but the prevalence of recurrent wheeze (> or = three episodes per year) not diagnosed as asthma, or of hay fever, was not significantly different between the sexes. The prevalence of diagnosed asthma increased with increasing numbers of positive skin tests, but hay fever without asthma was little affected above one positive skin-test. Boys had a greater prevalence of any positive skin-test (50.1% vs 37.1%), two or more positive tests (29.3% vs 21.8%), and responses to house dust mite (34.0% vs 23.1%) and cat (14.7% vs 11.2%). Gender differences for asthma became insignificant when adjusted for skin-test responsiveness to house dust mite and/or cat. The proportion of children with diagnosed asthma increased with increasing size of weals to house dust mite and cat dander. Gender differences in allergen sensitivities partly explain the gender differences in diagnosed asthma in children. In both sexes, risk of asthma was primarily associated with sensitization to indoor allergens (house dust mite and cat), and was related to the magnitude of the skin-test response, while the risk of hay fever was primarily associated with grass pollen sensitivity.
Atopy in childhood. II. Relationship to airway responsiveness, hay fever and asthma.
While airway hyperresponsiveness is usually associated with a diagnosis of asthma or symptoms of wheezing, some individuals with rhinitis show airway hyperresponsiveness as do some with no symptoms whatsoever. We have studied the correlations between symptoms, airway hyperresponsiveness and atopy as determined by skin-prick tests in a cohort of New Zealand children. A total of 662 members of a birth cohort were studied at age 13 years using a respiratory questionnaire, skin-prick tests to 11 common allergens, and an abbreviated validated methacholine challenge test to determine airway responsiveness. Airway hyperresponsiveness (methacholine PC20 FEV1 < or = 8 mg/ml) was strongly correlated with reported asthma and current wheezing (P<0.0001) and also with atopy, especially to house dust mite and cat (P<0.0001). As weal size for both house dust mite and cat increased, so did the proportion of children with airway hyperresponsiveness. All children with diagnosed asthma and airway hyperresponsiveness were atopic. Skin-test reactions to house dust mite and cat were strongly correlated with any degree of measurable airway responsiveness (PC20 FEV1 < or = 25 mg/ml) in children with rhinitis (P<0.00001), and remained significantly correlated even in children without current asthma, without asthma ever and without rhinitis (P<0.001). Atopy is a major determinant of airway hyperresponsiveness in children, not only in those with reported histories of asthma and wheezing, but also in the absence of any history suggesting asthma and rhinitis.
Atopy in childhood. III. Relationship with pulmonary function and airway responsiveness.
The relationship between atopy and pulmonary function in children, and how these relate directly or indirectly to airway hyperresponsiveness, is uncertain. We have examined these relationships in a sample of 13-year-old children. A questionnaire on respiratory symptoms, skin-prick tests to 11 common allergens, spirometry and an abbreviated methacholine challenge test were completed by 662 members (341 boys) of a birth cohort of New Zealand children followed longitudinally to age 13. There was a significant relationship between the presence and degree of atopy, and baseline pulmonary function. Low FEV1/VC ratios were associated with a greater likelihood of airway responsiveness, not only in subjects with diagnosed asthma, but also in the full cohort and in the sub-group of 426 children who denied asthma or current wheeze. The relationships between baseline FEV1/VC and airway responsiveness were stronger in atopic than in non-atopic children, with the strongest relationships in children sensitive to house dust mite and/or cat dander. In the presence of atopy, progressively lower levels of lung function were strongly associated with a higher prevalence of airway responsiveness (P<0.001). In non-atopic subjects, only those with the most impaired lung function (FEV1/VC < 75%) showed any substantive prevalence of airway responsiveness. The relationship between the degree of atopy and the FEV1/VC ratio, although significant in univariate analysis, became completely non-significant after accounting for airway responsiveness. In 13-year-old children, atopy, especially to house dust mite and cat dander, was correlated with pulmonary function expressed as FEV1/VC ratio. Airway responsiveness likewise correlated with impaired baseline lung function. The apparent relationship of lung function to atopy occurred primarily as a result of the relationship between atopy and airway responsiveness. Atopy and impaired lung function were additive factors predicting airway responsiveness.
The definition and diagnosis of asthma.
Asthma defies precise definition, despite several carefully worded statements. Perhaps the most concise and useful description of asthma is "variable airflow obstruction". The diagnosis is made by recognition of a patterns of one or more characteristic symptoms including wheeze, cough, chest tightness and dyspnoea, and is best confirmed by evidence of variable or reversible airflow obstruction accompanying symptoms.
Regular inhaled beta agonist in asthma: effects on exacerbations and lung function.
BACKGROUND: A comparison of the effects of regular upsilon as needed inhaled beta agonist treatment on the control of asthma in the last 16 weeks of each of two 24 week treatment periods has been reported. This paper presents additional information on exacerbations of asthma and trends in lung function, airways hyperresponsiveness to methacholine, and bronchodilator responsiveness during the entire 24 week periods of regular or as needed beta agonist treatment. METHODS: Subjects undertook a year long randomised, double blind crossover study of regular upsilon as needed inhaled beta agonist treatment. Fenoterol (400 micrograms) or matching placebo was inhaled as a dry powder four times daily for 24 weeks, then subjects crossed over to the alternative regimen. Treatment with inhaled corticosteroids was used by 50 of the 64 subjects in constant doses throughout the study. Symptoms, peak expiratory flow rates, and drug use were recorded daily, spirometry was performed every four weeks, and methacholine and bronchodilator responsiveness were measured every eight weeks. RESULTS: Exacerbations of asthma symptoms occurred earlier and more often during regular treatment with fenoterol and four of five severe exacerbations requiring admission to hospital occurred during the period of regular treatment. Prebronchodilator forced expiratory volume in one second (FEV1) was on average 0.15 litres lower (95% confidence interval (95% CI) 0.11-0.19) and vital capacity (VC) 0.12 litres lower (95% CI 0.08-0.16) than during the placebo period. Morning peak flow rates were significantly lower and evening peak flow rates significantly higher, with an increase in diurnal variation from 9.8% (95% CI 6.9-12.8) to 17.5% (95% CI 13.8-21.3) during regular treatment. Geometric mean concentration of methacholine causing a 20% fall in FEV1 from the value after saline (PC20) decreased significantly from 1.63 to 1.15 mg/ml, indicating increased bronchial hyperresponsiveness during regular treatment. Response to bronchodilator, as measured by the % increase in postbronchodilator FEV1 related to prebronchodilator FEV1, was maintained with no evidence for tachyphylaxis. CONCLUSION: Chronic use of inhaled fenoterol resulted in more exacerbations, a significant decline in baseline lung function, and an increase in airway responsiveness to methacholine in asthmatic subjects, but did not alter bronchodilator responsiveness. These findings support the previous report that regular inhaled beta agonist treatment is deleterious in the long term control of asthma.
Sex differences in hypokalaemic and electrocardiographic effects of inhaled terbutaline.
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An alternative method for comparing and describing methacholine response curves.
Tests of nonspecific airway hyperresponsiveness are frequently used in the study of asthma both in the clinical settings and in epidemiologic studies. However, standard methods for characterizing individual tests and comparing results between subgroups have not been established. The most frequently used method of characterizing response curves is to report the dose that results in a 20% fall in FEV1 from the initial or baseline FEV1 value (PD20FEV1). Other investigators have suggested using the response slopes. In this study we demonstrate an alternative method of analysis that uses all of each subject's response data, makes comparisons between subgroups, and can include explanatory covariables. This approach is demonstrated using methacholine challenge data obtained in New Zealand children at 9 and 11 yr of age. The results showed significant differences between the mean dose-response curves of wheezers and nonwheezers, that responsiveness increased with the frequency of reported wheeze, and that initial pulmonary function and serum IgE are significantly related to responsiveness. These factors were not always significant using more traditional methods of analysis, indicating an increased sensitivity with this method of analysis.
Beta-agonists and bronchial asthma.
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