The new BTS/SIGN asthma guidelines: where evidence leads the way.
Explore the source record for details and available documents.
Asthma↗
Biomedical subjects
B G Higgins
Publications and source records attributed to B G Higgins.
Environmental exposure to air pollution and allergens and peak flow changes.
Laboratory-based studies have shown that ozone and nitrogen dioxide can potentiate the effect of allergen in sensitized asthmatic subjects, but it is not known whether this interaction is important under natural exposure conditions. Thirty-five subjects with clinical diagnoses of asthma or chronic obstructive pulmonary disease and with a provocative dose causing a 20% fall in forced expiratory volume in one second methacholine <12.25 micromol (using the Yan method) kept peak expiratory flow (PEF) records for a 4-week period during late summer, with concurrent measurement of spore and pollen counts and pollution levels. Multiple regression analysis was then used to determine the effect on PEF of aeroallergen, and of the interaction between aeroallergen and pollutant levels. A statistically significant interaction was demonstrated between total spore count and ozone, but not nitrogen dioxide. Mean PEF fell in association with increasing spore count (same-day and 24-h lag level) and PEF variability increased with increasing spore count (24-h lag level only); both changes were greater the higher the prior ozone level. These results suggest that ozone can potentiate the effect of aeroallergens in subjects with bronchial hyperreactivity under natural exposure conditions. However, the effect was small, and the clinical significance of the interaction requires further study.
Adult↗
Issues at the interface between primary and secondary care in the management of common respiratory disease. 3: Providing better asthma care: what is there left to do?
Explore the source record for details and available documents.
Asthma↗
Current asthma management.
Explore the source record for details and available documents.
Adrenal Cortex Hormones↗
Pleural sarcoidosis: a rare presentation.
Sarcoidosis is a chronic disorder of unknown aetiology which causes tissue injury and granuloma formation in many organs. Although over 80% of cases have intrathoracic disease at presentation, pleural sarcoidosis remains an unusual manifestation. A case of sarcoidosis presenting with a discrete pleural mass is reported.
Adult↗
Functional upper airways obstruction: two patients with persistent symptoms.
Functional upper airways obstruction is caused by vocal cord dysfunction and classically occurs in paroxysms closely resembling acute asthmatic attacks. We present two cases in which the symptoms and signs of the vocal cord dysfunction demonstrate very little variability with time. We suggest that as part of this disorder, a syndrome of chronic unremitting symptoms may occur.
Adolescent↗
Asthmatic bronchial hyperresponsiveness varies with ambient levels of summertime air pollution.
It is widely believed that the mechanisms of action of outdoor air pollutants are the same as those found in the laboratory, although few studies have attempted to clarify this issue. This study investigates the relationship of asthmatic bronchial hyperresponsiveness (BHR), a marker of airway inflammation, and pulmonary function to ambient levels of summertime air pollution. Thirty eight nonsmoking adult asthmatic subjects underwent repeated measurement of methacholine BHR, using Yan's method, at differing levels of air pollution (O3, SO2, NO2, smoke) during summer 1993. A total of 109 evaluable tests were performed: 31 subjects completed three or more challenge tests, and seven managed two. Levels of all pollutants remained within current World Health Organization (WHO) Guidelines for Health. Changes in BHR were found to correlate significantly with changes in the levels of 24 h mean SO2, NO2 and smoke; 48 h mean NO2 and smoke; 24 h lag NO2; although the effect was only small, accounting for approximately 10% of the variability in within-subject BHR between visits. Twenty four hour lag NO2 was also associated with forced vital capacity (FVC). In conclusion, in subjects with asthma, methacholine bronchial hyperresponsiveness varies with ambient levels of summertime air pollution. This suggests that changes in airway inflammation underlie the increased respiratory morbidity known to accompany pollution episodes.
Adolescent↗
Geographical and social class effects on asthma mortality in England and Wales.
To determine whether asthma mortality is influenced by geographical or social factors, a retrospective analysis of deaths from asthma in England and Wales between 1979-1987 was performed. Death rates in the 15 Regional Health Authority areas of England and Wales were stratified by sex, age group (0-4, 5-34, 35-64, and > 64 years), and occupational social class. Detailed analysis was restricted to subjects aged 5-64 years because adequate social class data was only available over this age range. Death rates were higher in manual occupational groups (social class IIIb-V) than in non-manual occupations (social class I-IIIa), but on further analysis this effect was confined to males aged 35-64 years. In younger subjects (5-34 years), mortality was higher in the south of the country, and this difference was significant in males (P < 0.05). In older subjects (35-64 years), mortality in both sexes was significantly higher in the north of the country. This study demonstrates that mortality is not evenly distributed between social classes or regions of the country.
Adolescent↗
Effects of air pollution on symptoms and peak expiratory flow measurements in subjects with obstructive airways disease.
BACKGROUND: Evidence from laboratory studies suggests that air pollution can produce bronchoconstriction and respiratory symptoms in selected subjects, but the relevance of these findings to exposure to natural pollution is unclear. This study was performed to determine whether air pollution at typical levels found in the UK has demonstrable effects on respiratory function and symptoms in subjects with airways disease. METHODS: Seventy five adult patients with diagnoses of asthma or chronic obstructive pulmonary disease (COPD) were studied for a period of four weeks during which they kept records of their peak expiratory flow (PEF) rates, symptoms (wheeze, dyspnoea, cough, throat and eye irritation), and bronchodilator use. Thirty six patients in whom the provocative dose of methacholine causing a 20% fall in FEV1 was below 12.25 mumol were classified as reactors. Ambient air pollution was measured with absorption spectroscopy. RESULTS: There were modest but significant increases in PEF variability, bronchodilator use, and wheeze with increasing sulphur dioxide levels; bronchodilator use, dyspnoea, eye irritation, and minimum PEF readings were related to ozone levels. In the subgroup of reactors falls in mean and minimum peak flow and increases in wheeze, dyspnoea, and bronchodilator use were associated with increases in levels of both sulphur dioxide and ozone. Some associations were seen with pollution levels on the same day, but for others the pollution effects appeared to be delayed by 24 or 48 hours. Pollution levels did not breach the WHO guide levels during the course of the study. CONCLUSIONS: Increases in environmental levels of ozone and sulphur dioxide are associated with adverse changes in peak flow measurements and both ocular and respiratory symptoms in subjects with obstructive airways disease. Although the peak flow and symptom changes were modest, they occurred at pollution levels below current WHO guide levels.
Adult↗
Factors affecting peak expiratory flow variability and bronchial reactivity in a random population sample.
BACKGROUND: Bronchial reactivity measurements are widely used in epidemiological studies to provide an objective marker of asthma. There are, however, several potential advantages of measuring peak expiratory flow (PEF) variability instead, particularly in large studies. PEF variability and bronchial reactivity were compared in a population sample to assess the relationships of the two measurements to factors known to be associated with airways disease, and to compare their response rates. METHODS: Subjects aged 18-65 were randomly selected from the electoral register of an administrative area in eastern England and randomised to attend either for a bronchial challenge test measuring the provocative dose of methacholine producing a 20% fall in FEV1 (PD20), or to measure PEF at two hourly intervals during waking hours for one week. Skin tests with common allergens were performed and a smoking history obtained. PEF variability was expressed as the amplitude % mean (highest - lowest x 100/mean). RESULTS: A total of 273 subjects (69%) collected a PEF meter but a completed record sheet was returned by only 247 (62%); this was still significantly more than the 202 subjects (54%) who attended for and successfully completed a challenge test. Amplitude % mean was higher in women than in men (9.7% v 8.5%). In multiple regression analysis amplitude % mean increased significantly with age, mean skin weal diameter, and with current smoking. The odds of having a PD20 below 24.5 mumol increased with mean skin weal diameter and were greater in current smokers. Neither age nor sex had a significant effect on bronchial reactivity but there were significant interactions between age and the effects of both smoking and atopy. CONCLUSIONS: The higher response rate associated with the use of PEF variability measurement, and the association with factors implicated in the pathogenesis of airways disease, suggest that PEF variability would be a useful measurement to employ in epidemiological studies.
Adolescent↗
Comparison of PD20 with two alternative measures of response to histamine challenge in epidemiological studies.
Bronchial responsiveness to histamine or methacholine provides a useful objective measure for epidemiological studies of airways disease, but most people in a community population do not have a 20% fall in forced expiratory volume in one second (FEV1) with the highest dose administered. Histamine challenge data were analysed to compare the repeatability. Normality and separation of symptom groups of the early dose-response slope with provocative dose producing a 20% fall in FEV1 (PD20). Tests were continued until a 20% fall in FEV1 occurred, or 4 mumol had been given. Data were available for 510 randomly selected subjects, and for an additional 283 with wheeze. A repeat test was obtained in 104 individuals. PD20 was estimated by curve fitting, with extrapolation to 8 mumol. Least-squares slope of percentage decline in FEV1 on histamine dose was calculated, using all the measured points and two-point slope as the fall from the post-saline measurement to the maximum cumulative dose divided by the maximum dose. Log transformation of PD20 and shifted reciprocal transformations of slope produced constant variance. Over all subjects the three measures had similar repeatability; in subjects with PD20 > 8 mumol the intraclass correlation for two-point slope was only 0.26, but was 0.66 for least-squares slope. Neither measure of slope was normally distributed, but the distribution of log(PD20) was consistent with a censored normal distribution. In conclusion, least-squares slope is preferable to two-point slope for epidemiological studies.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Effect of oral lithium on bronchial reactivity in asthma.
1. Recognition that inositol phospholipid-derived second messengers are involved in the initiation and maintenance of airway smooth muscle contraction raises the possibility of new therapeutic approaches to the treatment of asthma. We anticipated that lithium, through its effects on cell signal transduction and ion-transport pathways, would be likely to protect the airways against constrictor stimuli. 2. We carried out a randomized, double-blind study of lithium carbonate in asthmatic patients. 3. After a 1 week run-in period, 27 patients were allocated lithium carbonate (800 mg) or placebo for 21 days with measurement of forced expiratory volume in 1 s, the dose of histamine causing a 20% fall in the forced expiratory volume in 1 s and serum lithium concentration on days 3, 7, 14 and 21. 4. Twenty-one patients completed the study (10 on lithium, 11 on placebo). Mean serum lithium levels for patients on active treatment were in the therapeutic range on all four occasions. 5. Lithium did not alter the forced expiratory volume in 1 s (P = 0.8) or the twice-daily peak expiratory flow (P = 0.15). It did, however, reduce histamine reactivity (the maximum difference between lithium and placebo was 1.2 doubling doses of histamine on day 21; 95% confidence interval 0.2-2.2 doubling doses), improve symptom scores (P less than 0.05) and reduce usage of beta-adrenoceptor agonist inhalers (P less than 0.05). 6. We conclude that lithium reduces bronchial reactivity in airway smooth muscle; this finding raises new therapeutic possibilities for the treatment of asthma.
Administration, Oral↗
Comparison of bronchial reactivity and peak expiratory flow variability measurements for epidemiologic studies.
Inclusion of a standardized measurement of airway function is important in epidemiologic studies of asthma to facilitate comparison between different studies. Bronchial reactivity is widely used in such studies, but measurement of peak expiratory flow (PEF) variability has a number of potential advantages. We compared PEF variability with methacholine challenge tests in a community population sample. Subjects selected at random (n = 95) and on the basis of having experienced wheeze in the last 12 months (n = 130) performed a challenge test with methacholine to a maximum dose of 12.25 mumol and made serial PEF recordings every 2 h for a week. PEF variability was expressed as mean daily maximum amplitude as a percentage of the mean (amplitude % mean). Increased bronchial reactivity and PEF variability were arbitrarily defined as values above the 10th or below the 90th percentiles in the random sample. A measurement of amplitude % mean was available from all 225 subjects, whereas only 115 (51%) had a measurable PD20 methacholine. PD20 measurements correlated weakly but significantly with amplitude % mean (r = -0.44, p less than 0.001). Increased values of both bronchial reactivity and PEF variability were related to the presence of respiratory symptoms in the week before testing. Asthma was more strongly related to increased bronchial reactivity than to PEF variability. Both measurements showed a strong association with atopy and the intraclass correlation coefficients (ratio of between-subject to total variance) were similar for both.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Effect of salbutamol and ipratropium bromide on airway calibre and bronchial reactivity in asthma and chronic bronchitis.
Bronchial reactivity to agonists such as histamine is seen in both chronic bronchitis and asthma, two conditions with different pathological changes in the airways. Salbutamol, when given acutely, reduces bronchial reactivity in patients with asthma, but the mechanism has not been clarified. To determine whether the effect of salbutamol depends on the pathological changes underlying the increased reactivity, we have compared the effect of salbutamol and ipratropium on bronchial reactivity in nine patients with asthma and ten with chronic bronchitis. Each drug was given on separate days in increasing doses (5, 100, 750, 1,000 micrograms) according to a double-blind, randomized design. Changes in forced expiratory volume in one second (FEV1) and specific airways conductance (sGaw) were measured after each dose, and the provocative concentration of histamine causing a 20% fall in the FEV1 (PD20) was determined after the last dose. Salbutamol and ipratropium were equipotent in the asthmatic subjects and caused a similar maximal increase in FEV1 (0.58 and 0.57 l) and sGaw (0.166 and 0.154 s-1.kPa-1). The two drugs also produced similar changes in the patients with chronic bronchitis, although the maximum response to both drugs was smaller (FEV1 0.29 and 0.32 l; sGaw 0.056 and 0.060 s-1.kPa-1; p less than 0.05). Despite differences in bronchodilatation the increase in histamine PD20 following salbutamol was similar in the asthmatic and bronchitic subjects (2.26 and 1.90 doubling doses (DD)) and greater in both groups (p less than 0.05) than the change in PD20 with ipratropium (0.84 and 0.56 DD).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The distribution of peak expiratory flow variability in a population sample.
Although serial peak expiratory flow (PEF) measurements are often used to assess the variability of airflow obstruction, the range of values to be expected in the general population has never been defined, nor is there any consensus as to how PEF variability should be expressed. We have compared PEF recordings made by 121 subjects selected at random from the population of a small town (Group A) and 221 subjects selected because of wheeze in the last year (Group B). Subjects were asked to record PEF every 2 h during waking hours for 7 days using a mini-Wright peak flow meter. Seven indices of PEF variability were derived for each subject and the range for each index determined. All indices showed a positively skewed distribution in the random sample. Two variability indices, standard deviation percent mean and amplitude percent mean, provided the greatest separation between subjects with both a diagnosis of asthma and wheeze in the last year and subjects with neither feature and also provided the highest intra-class correlation coefficients. We conclude that amplitude percent mean and standard deviation percent mean provide the best means of expressing PEF variability for epidemiological purposes, but that amplitude percent mean is more easily derived and appears to be the index of choice. PEF variability has a continuous distribution in the general population and no clear-cut division between asthmatic and nonasthmatic subjects can be defined.
Adolescent↗
Influence of inhaled terbutaline on bronchial responsiveness.
Explore the source record for details and available documents.
Airway Resistance↗
Rebound increase in bronchial responsiveness after treatment with inhaled terbutaline.
To investigate whether cessation of regular beta-agonist treatment results in an increase in bronchial responsiveness, two double-blind, randomised crossover studies were done. Subjects with mild asthma were investigated to determine the course of change in bronchial responsiveness, measured as the provocative dose (PD20) of histamine that caused a 20% fall in forced expiratory volume in 1 s after short-term and longer term treatment with an inhaled beta-agonist. In the first study in 8 subjects, 500 and 2000 micrograms terbutaline thrice in 1 day protected against histamine-induced bronchoconstriction, and the increase in PD20 compared with placebo remained high throughout the day and overnight. In the second study 8 subjects received placebo or terbutaline 750 micrograms thrice daily for 14 days. The protection afforded by terbutaline against histamine-induced bronchoconstriction on day 14 was less than that on day 1 by 40% in the morning and 82% in the afternoon. On day 15 PD20 was lower after stopping terbutaline than placebo, with a maximum difference of 1.5 (95% CI 0.6-2.5) doubling-doses of histamine 23 h after the end of treatment. Thus treatment with terbutaline for 1 day did not result in any rebound increase in bronchial responsiveness. Treatment for 2 weeks impaired the ability of terbutaline to protect against histamine-induced bronchoconstriction, and was followed by a rebound increase in bronchial responsiveness after cessation of treatment.
Adolescent↗
Comparison of histamine and methacholine for use in bronchial challenge tests in community studies.
Measurement of bronchial reactivity is widely used in epidemiological surveys. Histamine has been compared with methacholine inhalation challenge in two samples of adults from a small town to determine which is the better agent for use in community studies. Increasing doses of histamine and methacholine were given, up to a maximum of 4 and 12 mumol respectively, according to the method of Yan et al, the provocative dose of agonist causing a 20% fall in FEV1 (PD20) being measured. More subjects had a measurable PD20 with methacholine than with histamine, both in a random sample of 108 subjects (25 v 11 subjects, p less than 0.01) and in an additional 95 subjects selected because of wheeze in the last 12 months (67 v 48 subjects, p less than 0.01). Side effects were mild with both agents but histamine caused voice change in more subjects (21% v 11%). Repeatability was assessed in a further group of subjects with wheeze in the last year. The 95% range for a single estimation of PD20 in subjects with a measured PD20 on at least one occasion was +/- 2.5 doubling doses for histamine (n = 25) and +/- 2.1 doubling doses for methacholine (n = 33). Thus methacholine has advantages over histamine for community studies of bronchial reactivity as it is possible to use doses that produce more PD20 measurements with fewer side effects.
Adolescent↗