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M R Sears

Publications and source records attributed to M R Sears.

At least 19 recordsLinked to original sources
PubMed1996

The beta-agonist controversy.

After many years of increasing morbidity and mortality, several avenues of scientific investigation now appear to be converging to offer an explanation for the asthma paradox and indicate that regular or long-term use of short-acting inhaled beta-agonist drugs is inappropriate. Pharmacoepidemiologic studies indicate a strong association between increased beta-agonist use and asthma deaths, which does not appear entirely related to confounding by severity. Clinical data, although still limited, show little evidence for symptomatic or functional improvement during long-term beta-agonist therapy and, in many instances, reveal significant adverse effects. Related investigations offer evidence of potential plausible mechanisms, notably increased bronchial responsiveness to inhaled allergen, to explain these findings. A radical revision of the therapeutic use of these drugs in asthma has been prompted by these findings. Beta-agonist drugs remain essential for the management of acute severe attacks. They are also useful on demand for the relief of breakthrough symptoms and for prophylaxis of exercise-induced symptoms. In chronic asthma, however, adequate anti-inflammatory therapy is the treatment of choice. Long-term treatment with short-acting beta-agonist, even in the presence of seemingly adequate anti-inflammatory therapy, may be associated with deterioration of asthma over the long-term. The effects of long-acting beta-agonists remain under review. To date, there are no data that clearly indicate a deleterious effect, and many clinical trials show benefits in symptom control and improved lung function associated with their regular use. The significance of tachyphylaxis remains to be defined. Their current role is still somewhat unclear, but they have been successfully used in subjects in whom, despite the use of moderate doses of inhaled corticosteroid, short-acting bronchodilator is still frequently required. The use of twice-daily long-acting beta-agonist appears preferable to frequent use of short-acting beta-agonists.

Adrenergic beta-Agonists↗
PubMed1996

Elevated B cells in sputum of asthmatics. Close correlation with eosinophils.

Sputum examination is a useful noninvasive method to study airway inflammation. We investigated the reproducibility and validity of the measurements of lymphocyte subsets in the sputum of 11 stable patients with asthma and 10 nonasthmatic smokers. Sputum was dispersed with 0.1% dithiothreitol. A differential cell count was made with Wright's stain. Aliquots were stained with antibodies to CD19 (B cells), CD3 (T cells), CD4 (helper), CD8 (suppressor), and the activation marker CD25 (IL2 receptor) on T-cell subsets and were assayed by flow cytometry. Sputum from patients with asthma compared with nonasthmatic subjects had more eosinophils (mean +/- SEM, 32.5 +/- 8.5 versus 1.3 +/- 0.5%, p < 0.01) and a higher proportion of lymphocytes that were B cells (16.2 +/- 3.2 versus 4.0 +/- 1.0%, p < 0.01), and these correlated closely with the eosinophils (r = 0.8, p < 0.01). Patients with asthma also had more activated T-helper cells (39.3 +/- 4.6 versus 9.0 +/- 9.0%, p = 0.05), but the comparison was limited to two smokers because of macrophage autofluorescence. The repeatability of measurements of helper T-cells (R = 0.94), suppressor T cells (R = 0.88), and activated helper T cells (R = 0.77) was good; repeatability of measurements of T and B cells could not be examined because these were reciprocals of each other. Asthmatic sputum has different lymphocyte profiles than sputum from nonasthmatic smoking control subjects. The results demonstrate a potential importance of antibody-producing lymphocytes in the airway and their relation to sputum eosinophilia in asthma.

Adult↗
PubMed1995

Relations of bronchial responsiveness to allergy skin test reactivity, lung function, respiratory symptoms, and diagnoses in thirteen-year-old New Zealand children.

BACKGROUND: Many factors have been found to relate univariately to bronchial responsiveness (BR), but their independent relationships are often unclear because many are interrelated. OBJECTIVE: The purpose of this study was to present a multivariate analysis of the closeness of the association of various factors that are related univariately to BR, including allergy skin tests. METHODS: The results of methacholine challenge were transformed into a continuous variable (BRindex), which has a nearly Gaussian distribution. With stepwise multiple regression, the closeness of the association of the independent variables with BRindex was evaluated. RESULTS: Of the 11 skin tests applied, four showed independent relationships to BRindex (mite, cat, dog, and Aspergillus species). The sizes of these skin test reactions were correlated with BRindex, and their sum appeared to maximize the overall correlation of allergy skin tests with BRindex (r = 0.516). The lowness of the ratio of forced expiratory volume in 1 second to vital capacity and of percent predicted forced expiratory volume in 1 second added significantly to the skin tests in correlating with BRindex, (multiple r = 0.621). Adding diagnoses and symptoms increased the multiple r to 0.685. CONCLUSIONS: The size of the reactions to the four skin tests noted above showed much closer correlations with BR than total serum IgE had shown at age 11, and the relationship was present in asthmatic and nonasthmatic subjects.

Adolescent↗
PubMed1995

Exacerbations of asthma without sputum eosinophilia.

BACKGROUND: Sputum analysis provides a non-invasive method of examining the airway secretions of subjects with asthma in order to better understand the inflammatory process. Increased proportions of eosinophils are generally seen in the sputum of subjects with asthma, especially when there is an exacerbation. An unexpected observation in the sputum of subjects with mild exacerbations of asthma is reported. METHODS: Thirty four consecutive subjects with symptoms consistent with a mild exacerbation of asthma were recruited for a treatment study. Inclusion criteria required persistent symptoms of chest tightness, dyspnoea, or wheezing for two weeks (without spontaneous improvement or alteration in dose of inhaled corticosteroid) and a forced expiratory volume in one second (FEV1) that was reversible to more than 75% predicted or known best to ensure the exacerbation was mild. Sputum (spontaneous or induced with hypertonic saline) from all subjects was examined for differential cell counts. Eosinophilic sputum was defined as > or = 4% eosinophils on two occasions or > 10% eosinophils once. Clinical characteristics, sputum differential counts, and measurements of airways obstruction were compared between the subjects with and without sputum eosinophilia. RESULTS: Almost half of the subjects (16 of 34) considered to have mildly uncontrolled asthma had no sputum eosinophilia. In comparison with the subjects who had sputum eosinophilia the non-eosinophilic group had less airways obstruction (FEV1% predicted 88% v 70%) and less severe airways hyperresponsiveness (PC20 methacholine 0.45 mg/ml v 0.13 mg/ml). There was no difference between the groups in the type or prevalence of symptoms, history of recent infections, smoking, relevant allergen exposure, or use of inhaled corticosteroid. CONCLUSIONS: Symptoms of mildly uncontrolled asthma are not always associated with eosinophilic airways inflammation as measured by sputum analysis. The causes and treatment of the non-eosinophilic condition require further investigation.

Adolescent↗
PubMed1995

The effect of size and age of subject on airway responsiveness in children.

Methodologies used to assess airway responsiveness (AR) in children administer the same dosage schedule to all children despite the great range in the size of subjects. The aim of this study was to examine the hypothesis that the level of AR is size dependent within same-age cohorts and between different ages. Among a birth cohort of 1,037 New Zealand children participating in a longitudinal study, 818 had at least two measurements of airway responsiveness between ages 9 and 15 yr. Each child performed spirometry and a four-dose methacholine inhalation test. A continuous slope index of methacholine responsiveness was computed. AR slope indexes were analyzed using longitudinal methods, which included an indicator variable for subjects who reported having any wheeze. AR was lowest in both males and females in the upper quartile for height than those in the lower quartile, independently of age. AR tended to be higher (responded to lower concentrations of methacholine) in boys than girls and to decline with age among wheezers. The greater level of responsiveness in smaller or younger children could be explained by these individuals having received a dose of methacholine that was relatively large for their size.

Adolescent↗
PubMed1995

Relation of the course of bronchial responsiveness from age 9 to age 15 to allergy.

Bronchial responsiveness to methacholine was measured in a birth cohort of New Zealand children at ages 9, 11, 13, and 15. Overall bronchial hyperresponsiveness (BHR) decreased with age. While the response at age 9 was significantly related to responsiveness, symptom severity, and low lung function at age 15, these relationships were much closer when bronchial response levels after age 9 were taken into account. Also, among children who were unresponsive to methacholine at age 15, those with previous BHR had more frequent wheeze and lower lung function than those whose previous tests were all unresponsive. Both the overall tendency to BHR and the tendency to retain BHR were closely related to high serum IgE levels (determined at age 11) and to positive allergy skin tests (determined at age 13). These evidences of allergy, closely related to the severity and course of methacholine response, appeared to be important determinants of the frequency of wheeze and the degree of impairment of lung function at the end of follow-up. In view of the variability in BHR, a single estimate of bronchial responsiveness taken at an arbitrary point in time may not be an accurate index of the overall tendency to BHR.

Adolescent↗
PubMed1995

Increased peak flow variability in children with asymptomatic hyperresponsiveness.

The relevance of increased methacholine airway responsiveness detected in children with no current or past symptoms of asthma is not known. We wished to determine whether the presence of airway hyperresponsiveness in asymptomatic children is also associated with abnormal variability of peak expiratory flow (PEF). In 12 asymptomatic children with methacholine hyperresponsiveness, we examined the diurnal variation of peak expiratory flow (PEF) and response to inhaled bronchodilator. Twelve asthmatic children with a comparable range of methacholine hyperresponsiveness, and 12 normal children without methacholine responsiveness, were used as positive and negative controls. The children were aged 11 (range 9-14) yrs. The mean diurnal variation of PEF in those children with asymptomatic hyperresponsiveness was increased at 9.3%, to a degree comparable to the symptomatic asthmatic children (10.7%), and greater than the normal children (5.7%). Methacholine stimulated airway constriction was associated with symptoms in subjects from each group, indicating that the children were capable of perceiving airway constriction. We conclude that asymptomatic children with methacholine airway hyperresponsiveness have other evidence of mild variable airflow obstruction with increased diurnal PEF variability, and can perceive airflow limitation. The lack of symptoms in the children with airway hyperresponsiveness could be due to an insufficient stimulus to cause symptomatic obstruction, or the absence of eosinophilic airway inflammation, which may be a requirement for the development of symptomatic airway hyperresponsiveness.

Adolescent↗
PubMed1994

Asthma control.

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Albuterol↗
PubMed1994

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.

Allergens↗