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Background: Although many children with asthma may have a remission as they grow and other children who did not have asthma may develop asthma in adult life, knowledge about the factors that influence the onset and prognosis of asthma during adolescence and young adulthood is very limited. Methods: A cohort of 8–10 year old children (n=718) living in Belmont, New South Wales, Australia were surveyed six times at 2 yearly intervals from 1982 to 1992, and then again 5 years later in 1997. From this cohort, 498 subjects had between three and seven assessments and were included in the analysis. Atopy, airway hyperresponsiveness (AHR), and wheeze in the last 12 months were measured at each survey. Late onset, remission, and persistence were defined based on characteristics at the initial survey and the changes in characteristics at the follow up surveys. Results: The proportion of subjects with late onset atopy (13.7%) and wheeze (12.4%) was greater than the proportion with remission of atopy (3.2%) and wheeze (5.6%). Having atopy at age 8–12 years (OR 2.8, 95% CI 1.5 to 5.1) and having a parental history of asthma (OR 2.0, 95% CI 1.02 to 4.13) were significant risk factors for the onset of wheeze. Having AHR at age 8–12 years was a significant risk factor for the persistence of wheeze (OR 4.3, 95% CI 1.3 to 15.0). Female sex (OR 1.9, 95% CI 1.01 to 3.60) was a significant risk factor for late onset AHR whereas male sex (OR 1.9, 95% CI 1.1 to 2.8) was a significant risk factor for late onset atopy. Conclusions: The onset of AHR is uncommon during adolescence, but the risk of acquiring atopy and recent wheeze for the first time continues during this period. Atopy, particularly present at the age of 8–10 years, predicts the subsequent onset of wheeze.

Background: There are few paediatric studies of the interrelationships between inflammatory markers and asthma severity. We therefore assessed the relationships between eosinophil-associated markers, cytokines, and asthma severity in asthmatic children aged 8–12 years. Methods: Forty-five children were tested twice, 2 weeks apart. Asthma severity was measured in terms of symptoms, lung function, medication needs, and histamine responsiveness. Peripheral inflammatory markers measured included eosinophil numbers, serum ECP, IL-5, and TNF-α and mononuclear cell IL-5, and TNF-α production. Results: Histamine responsiveness was correlated with circulating eosinophils (r=0.56, P=0.0001) and serum ECP (r=0.54, P=0.003). Eosinophilia was increased in children with severe as opposed to mild airway hyperresponsiveness (P=0.02) and those who lost days at school as opposed to those who did not (P=0.01). There were no other associations between markers of asthma severity and inflammation. Children taking inhaled corticosteroids had lower serum IL-5 levels than those on β-agonists±cromolyn (mean and 95% CI: 20.5 [11.7–35.7] pg/ml vs 64.3 [26.6–155.4] pg/ml; P=0.04). Cellular IL-5 production correlated with serum TNF-α (r=0.63, P=0.0062) and IL-5 (r=−0.59, P=0.005). Conclusions: Serum levels of TNF-α and IL-5 were not related to peripheral eosinophilia and asthma severity in these children but were related to their own cellular production ex vivo. This study confirms that eosinophilia is the index of inflammation that is most closely related to the clinical severity of childhood asthma.

To determine predictors for failed reduction of inhaled corticosteroids (ICS), in 50 subjects with well-controlled asthma (age 43.7 [18–69]; 22 males) taking a median dose of 1,000 μ g ICS/d (100–3,600 μ g/d), ICS were halved every 8 wk. Airway hyperresponsiveness (AHR) to a bronchial provocation test (BPT) with histamine was measured at baseline. AHR to BPT with mannitol, spirometry, exhaled nitric oxide (eNO), and, in 31 subjects, sputum inflammatory cells were measured at baseline and at monthly intervals. Thirty-nine subjects suffered an asthma exacerbation. Seven subjects were successfully weaned off ICS. Using a Kaplan– Meier survival analysis, the significant predictors of a failure of ICS reduction were being hyperresponsive to both histamine and mannitol at baseline (p = 0.039), and being hyperresponsive to mannitol during the dose-reduction phase of the study (p = 0.02). Subjects older than 40 yr of age tended to be at greater risk of ICS reduction failure (p = 0.059). Response to mannitol and p...

BACKGROUND—A study was undertaken to assess whether the recent increases in prevalence of both asthma and obesity are linked and to determine if obesity is a risk factor for diagnosed asthma, symptoms, use of asthma medication, or airway hyperresponsiveness. METHODS—Data from 1971 white adults aged 17-73 years from three large epidemiological studies performed in NSW were pooled. Doctor diagnosis of asthma ever, history of wheeze, and medication use in the previous 12 months were obtained by questionnaire. Body mass index (BMI) in kg/m2 was used as a measure of obesity. Airway hyperresponsiveness (AHR) was defined as dose of

The object of this study was to compare the effect of standard and "low irritant" insecticide aerosols on lung function, airway hyperresponsiveness (AHR) and symptoms in asthmatic subjects. A double blind randomized, crossover study was conducted in 25 asthmatic subjects who reported sensitivity to insecticide aerosols. All subjects were exposed for 30 min, on separate occasions, to two standard insecticide formulations (A and B), one low irritant formulation (C) and a negative control aerosol. Spirometric function and chest, nose and eye symptoms were recorded during, and for 90 min after, the exposure. AHR to methacholine was measured 90 min after the exposure. Compared to the negative control, the maximum fall in forced expiratory volume in one second (FEV1) was slightly greater after standard insecticides (mean differences from control +/-95% confidence interval: aerosol A, 3.3+/-3.6%, p=0.08; aerosol B, 5.1+/-4.7%, p=0.04), AHR was significantly more severe (mean difference from control: aerosol A, 0.35+/-0.29 doubling doses, p=0.028; aerosol B, 0.52+/-0.43 doubling doses, p=0.028), and symptoms were more severe. The low irritant test aerosol (C) did not differ significantly from the negative control with respect to FEV1, AHR or symptoms. It is concluded that some insecticide aerosols trigger symptoms and falls in lung function in some people with asthma. Furthermore, these aerosols may also increase airway hyperresponsiveness, although the mechanism of this effect has not been determined. The low irritant formulation did not appear to have the same effects.

To evaluate the association between growth in height and growth in lung function, and to identify the potential temporal relationships between airway hyperresponsiveness (AHR), respiratory symptoms, and lung function growth during adolescence and young adulthood, we analyzed data collected from the Belmont cohort. Among the 718 schoolchildren initially studied at 1982 (aged 8-10 yr), 557 were studied between two times and six times at 2-yr intervals until 1992. Baseline lung function, AHR by histamine inhalation test, and recent wheeze by questionnaires, were measured at each visit. We found that between 17 and 19 yr of age, when growth in height had stopped, growth in FEV(1) was approximately 200 ml/yr in boys and 100 ml/yr in girls. Peak growth velocity of height occurred at age 13 both in boys and in girls, whereas peak growth velocity of FEV(1) occurred at the same age only in girls and 1 yr later in boys. Having AHR and recent wheeze at the previous study time were both associated with lower subsequent growth in FEV(1), but not with subsequent growth in FVC. We conclude that lung function continues to grow after the cessation of height growth and that growth in FEV(1) is reduced in subjects with AHR and/or recent wheeze.

Background The patterns of inheritance of asthma have largely been explored using data of symptom history collected by questionnaires which are subject to bias and which may therefore distort the measured relationship. Objective The purpose of this study was to examine family patterns of allergic disease using objective measurements of atopy and of airway hyperresponsiveness (AHR). Methods A large random sample of children aged 8–11 years was studied and 3 months later, their parents were also invited for study. Of the sample of 1655 children, both parents of 661 children were studied. In all subjects, respiratory illness history was measured by questionnaire, atopy by skin tests and AHR by responsiveness to histamine. Results The odds ratio for a child to have AHR if either parent had the same condition was approximately 2.0, which was the same as the odds ratio for wheeze or diagnosed asthma in the presence of the same condition in either parent. The odds ratio for atopy was smaller (approximately 1.4, NS) but the risk of a nonatopic child having AHR if the parent had AHR was 3.0 (P = 0.01). The correlation between weal size in the child and parent was poor and the severity of AHR in the child was only modestly correlated with the severity of AHR in the parent (R = 0.51, P = 0.04). Conclusion The use of objective measurements did not strengthen the association between atopic or asthmatic conditions in the parent and child, but did suggest that atopy and AHR are inherited independently.

Objective: Smokers who develop chronic airflow limitation (CAL) do not usually present for medical attention until their lung disease is well advanced. In contrast, asthmatic subjects experience acute symptoms and present for care early in the course of their disease. The aim of this study was to determine whether subjects with asthma differ from smokers with CAL in their ability to perceive acute methacholine-induced bronchoconstriction. Methodology: Thirteen subjects with diagnosed asthma and 10 current smokers with CAL, defined as forced expiratory volume in 1 s (FEV1) < 75% predicted and FEV1/forced vital capacity < 80%, with no previous diagnosis of asthma, were challenged with methacholine. Symptom severity was recorded on a Borg scale. Lung volumes were measured before challenge and after the FEV1 had fallen by 20%. Results: After methacholine falls in FEV1 were similar in the asthmatic subjects and smokers. The regression lines relating change in FEV1 to symptom score were significantly steeper in asthmatic subjects than smokers (0.13 ± 0.04, 0.03 ± 0.04, respectively, P < 0.01). At 20% fall in FEV1 there were no significant differences between asthmatic subjects and smokers in the magnitude of change of lung volumes. Conclusions: In asthmatic subjects, symptoms are closely related to change in FEV1. In smokers with CAL, symptoms change little during bronchial challenge despite large changes in FEV1. The differences in perception between the two subject groups are not due to differences in acute hyperinflation during challenge. We propose that heavy smokers may adapt to poor lung function, or may have damaged sensory nerves as a result of prolonged cigarette smoking.

Perception of the efficacy of bronchodilators in relieving airflow obstruction is a likely determinant of compliance with treatment in patients prescribed these drugs on an 'as needed' basis. This study aimed to determine whether bronchodilator-induced improvements in lung function are associated with improvements in breathing difficulty in subjects with asthma or smokers with airflow limitation. Twenty smokers with airflow limitation and 16 subjects with previously physician-diagnosed asthma received salbutamol (200 micrograms) and ipratropium bromide (80 micrograms). Spirometry and lung volumes were measured before and 40 min after bronchodilator. Subjects recorded changes in 'difficult breathing' on a visual analogue scale (VAS). After bronchodilator, forced expiratory volume in 1 s (FEV1) increased by 23.0 +/- 6.4% of baseline (mean +/- 95% CI) in smokers, and by 25.2 +/- 8.5% in the asthmatics, while VAS improved by 31 +/- 23% in smokers and 45 +/- 25% in asthmatics. However, these changes were not significantly correlated in either smokers (r = -0.04) or asthmatics (r = 0.15). In the asthmatic subjects, good perceivers (> 25% improvement in VAS) had greater improvements in lung volumes, as percentage predicted, than did poor perceivers. In the smokers, changes in lung function did not differ significantly between good and poor perceivers. Improvement in FEV1, as percentage predicted, was significantly correlated with improvement in VAS in good perceivers (asthma: r = 0.78, P < 0.01; smokers: r = 0.68, P < 0.05), but not in poor perceivers. Asthmatic subjects had good perception of improvements in lung function. However, in smokers with airflow limitation there is little correlation between improvement in lung function and sensation of breathing difficulty. In these subjects symptoms appear to be an unreliable guide for 'as needed' use of bronchodilators.

In epidemiologic studies of asthma there is a group with recent wheeze, but with no airway hyperresponsiveness (AHR), in whom it is unclear whether any significant airway abnormality exists. Exhaled nitric oxide (NO) has been proposed as a measure of airway inflammation. We measured exhaled NO in a population sample of 306 young adults who also underwent bronchial challenge with histamine or a bronchodilator test. Subjects blew into a 3-L Tedlar bag against a 2-mm-diameter resistance to close the soft palate and exclude nasal air. The NO content of expired gas from a single breath was analyzed by chemiluminescent analyzer. Exhaled NO was log-normally distributed in the population sample and duplicate measurements were highly reproducible (intraclass correlation coefficient = 0.98). Exhaled NO correlated significantly with airway responsiveness, measured as the dose-response ratio to histamine (r = 0.39, p < 0.001) and with peripheral blood eosinophils (r = 0.35, p < 0.001). Exhaled NO was significantly greater in asthmatic subjects (geometric mean, 22.2; 95% confidence intervals, 16.1 to 30.7 ppb) than in normal subjects (7.8, 7.1 to 8.4, p < 0.001) or in subjects with wheeze but no AHR (8.8, 7.5 to 10.3, p < 0.001). We conclude that exhaled NO is log-normally distributed, is highly reproducible and discriminates well among subjects, suggesting that it is both a feasible and useful measurement for epidemiologic studies of asthma. The findings suggest that wheeze in the absence of AHR is unlikely to be associated with airway inflammation.

Study objective: Cough is a common symptom in children that is frequently encountered in general practice. However, most of the information on the prevalence of persistent cough has come from studies that use different, often ambiguous, definitions for persistent cough. It is therefore important that a validated questionnaire to accurately measure persistent cough is developed and is appropriate for use in different age groups of children and in different cultures. Such a questionnaire is essential for accurately measuring the prevalence of persistent cough and the factors associated with its occurrence. Design: A parent-administered respiratory questionnaire was developed and administered twice during a 3-week interval pilot study to test repeatability. The questionnaire was then administered to a randomly selected cross-section of Australian children aged 5 to 7 years old and 8 to 11 years old (N 5 511 and N 5 654, respectively), and to 566 Nigerian children aged 8 to 11 years old. Results: The new questionnaire was reliable, with most of the questions having a k value of above 0.6. The prevalence of persistent cough was similar in younger and older Australian children, but significantly less in Nigerian children (p < 0.001). Also, persistent cough was more prevalent in children of high rather than low socioeconomic status among older Australian children (p 5 0.04). Conclusions: The newly developed questionnaire will be an important tool in epidemiological studies for measuring the prevalence, morbidity, and risk factors of persistent cough in childhood. Although our findings showed that persistent cough does not occur more frequently in younger than in older Australian children, it is more frequent in Australian than in Nigerian children. (CHEST 1999; 115:434 ‐ 439)

Summary Background Increased variation in peak expiratory flow (PEF) is characteristic of poorly controlled asthma, and measurement of diurnal variability of PEF has been recommended for assessment of asthma severity, including during exacerbations. We aimed to test whether asthma exacerbations had the same PEF characteristics as poor asthma control. Methods Electronic PEF records from 43 patients with initially poorly controlled asthma were examined for all exacerbations that occurred after PEF reached a plateau with inhaled corticosteroid treatment. Diurnal variability of PEF was compared during exacerbations, run-in (poor asthma control), and the period of stable asthma before each exacerbation. Findings Diurnal variability was 21·3% during poor asthma control and improved to 5·3% (stable asthma) with inhaled corticosteroid treatment. 40 exacerbations occurred in 26 patients over 2–16 months; 38 (95%) of exacerbations were associated with symptoms of clinical respiratory infection. During exacerbations, consecutive PEF values fell linearly over several days then improved linearly. However, diurnal variability during exacerbations (7·7%) was not significantly higher than during stable asthma (5·4%, p=0·1). PEF data were consistent with impaired response to inhaled β 2 -agonist during exacerbations but not during poorly controlled asthma. Interpretation Asthmatics remain vulnerable to exacerbations during clinical respiratory infections, even after asthma is brought under control. Calculation of diurnal variability may fail to detect important changes in lung function. PEF variation is strikingly different during exacerbations compared with poor asthma control, suggesting differences in β 2 -adrenoceptor function between these conditions.

The absence of a maximal dose-response plateau as well as gas trapping and increases in closing capacity (CC) suggest that increased airway closure is an important mechanical abnormality of asthmatic airways. We compared the extent and distribution of airway closure in 13 normal and in 23 asthmatic subjects. Airway closure (LVclosed) was measured with single-photon emission computed tomography (SPECT) and an inhaled Technegas bolus as the percentage of lung volume without Technegas (LVtrans), and with CC, using nitrogen washout. LVclosed was compared in the apical, middle and lower zones, each being of equal vertical height. Values of mean LVclosed +/- 95% confidence interval (CI) were similar in normal (30 +/- 6.0% LVtrans) and asthmatic subjects (30 +/- 7.8% LVtrans). In normal subjects, LVclosed correlated with both age (r = 0.89, p < 0. 01) and CC (r = 0.86, p < 0.01), was more extensive in the lower zone (58 +/- 18.8% LVtrans, p < 0.01) than in the middle and upper zones (17 +/- 8.7% and 26 +/- 8.2 LVtrans, respectively), and increased with age in both the middle and lower zones (r = 0.94 and r = 0.90, respectively, p < 0.01). In asthmatic subjects, LVclosed did not correlate with age; was greatest in the lower zone, intermediate in the middle zone, and lowest in the apical zone (59 +/- 13.2%, 22 +/- 5.8%, and 12 +/- 4.4% LVtrans, respectively, p < 0. 01); and correlated weakly with age in the middle zone only (r = 0. 46, p < 0.05). We conclude that there is a predictable pattern of airway closure in normal subjects and that it is primarily influenced by pulmonary elastic recoil. This pattern is lost in asthmatic subjects. This may be explained by an increased range of closing pressures and a patchy distribution of airway closure, probably secondary to allergic inflammation.

The International Union Against Tuberculosis and Lung Disease questionnaire is widely used in epidemiologic studies of adult asthma. We examined whether the symptom questions could be classified into groups that represent different "syndromes," and whether some questions are better for predicting asthma than others. We analyzed questionnaire data from a population sample of 1,527 adults aged 18 to 55 years using factor analyses to classify the 17 respiratory symptom questions into four different groups that we termed asthma, cough, breathlessness, and urgent medical visit. The urgent medical visit was a subset of asthma. These four "syndromes" had good validity when measured against airway responsiveness to histamine, atopy to common allergens, lung function, smoking status, and body mass index. Questions that predicted asthma syndrome were those that asked about wheeze at rest or following exercise, asthma attack, chest tightness, and shortness of breath at rest. Questions about cough identified a different group of subjects who apparently did not have asthma. Questions of breathlessness did not aggregate with "asthma" or with "cough syndrome." The identification of particular questions that measure different respiratory conditions is important for epidemiologic studies when short questionnaires or more precise definitions are required.

Electronic spirometers offer the prospect of paperless home monitoring, but data quality is not automatically better than from conventional monitoring. The aim of this study was to determine the extent to which the quality and processing of self-recorded spirometric data from patients with asthma complied with international guidelines for spirometry. Data were from 33 subjects with poorly controlled asthma who had completed the first 9 weeks of a clinical budesonide trial. MicroMedical DiaryCard electronic spirometers were used to record three spirometric manoeuvres in twice-daily sessions. Confounding events were recorded in a paper diary. Within-session reproducibility was calculated for forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and peak expiratory flow (PEF) during the first week of run-in and week 9 of budesonide treatment. Geometric means of within-session reproducibility (mean difference between highest and second-highest value from each session over a one-week period) for FEV1, FVC and PEF were 76 mL, 116 mL and 18 L x min(-1), respectively, during run-in. Times of spirometric sessions varied widely, with some overlap between morning and evening session times. Manoeuvre-induced falls in PEF and FEV1 occurred only as often as expected by chance. Nonasthma events including equipment faults and painful conditions caused changes in spirometric results. Home spirometric monitoring can be carried out with excellent reproducibility in patients with asthma. However, quality-control issues are complex and an accompanying paper diary remains essential.

Little is known about the effects of drugs on small airways. However, the small airways respond to constricting and dilating substances in vitro. Pathologic assessment demonstrates that small airways are inflamed, and the physiology suggests that they narrow and dilate. If after a period of treatment for asthma, all tests including the SBNT are normal, it would be safe to say that the small airways had been treated. However, we need to have some way of imaging the airways to decide whether or not there is abnormality in the small airways and to target the drugs that we are using to treat them. New ways of imaging, measuring, and performing a biopsy of the small airways are needed if we are going to make progress in this area.

We assessed the clinical and biochemical effects in asthmatic children of fish oil supplementation and a diet that increases omega-3 and reduces omega-6 fatty acids. Thirty nine asthmatic children aged 8-12 yrs participated in a double-blind, randomized, controlled trial for 6 months during which they received fish oil capsules plus canola oil and margarine (omega-3 group) or safflower oil capsules plus sunflower oil and margarine (omega-6 group). Plasma fatty acids, stimulated tumour necrosis factor alpha (TNFalpha) production, circulating eosinophil numbers and lung function were measured at baseline and after 3 and 6 months of dietary modification. Day and night symptoms, peak flow rates and medication use were recorded for 1 week prior to laboratory visits. Plasma phospholipid omega-3 fatty acids were significantly greater in the omega-3 group at 3 and 6 months compared to the omega-6 group (p

Background: Although lung diseases are a leading cause of premature mortality in Australian Aborigines, little is known about normal lung function in these people. Aim: To develop models for 'normal' spirometric function in rural Australian Aborigines. Method: A cross-sectional population-based study of four rural Aboriginal communities was performed in Queensland, Northern Territory and South Australia, Australia. We studied 261 children aged seven-19 years and 332 adults aged 20-80 years who were free of symptoms and had no clinical signs of chronic lung disease. The outcome measures were forced expiratory volume in one second (FEV 1 ) and forced vital capacity (FVC). Multiple linear regression was used to develop models for FEV 1 and FVC and comparisons were made with Caucasians and indigenous people from other countries. Results: The Aboriginal people studied had FEV 1 and FVC values that were lower (20% and 30% respectively) than those found in Caucasians of the same height, age and gender. As a consequence, they had relatively high FEV 1 /FVC ratios. Those studied also had forced expiratory volumes that were lower than those found in African Americans and other indigenous peoples. Conclusions: Apparently healthy rural Aboriginal people have low forced expiratory volumes when contrasted with Caucasians and indigenous peoples such as African Americans. More research is required to determine if this is 'normal' or a product of the suboptimal environment into which many Aboriginal people are born.

BACKGROUND: Regular, inhaled beta 2 agonists may increase airway responsiveness in asthmatic subjects. The mechanism is not known but may be via an increase in airway inflammation. A study was undertaken to examine the effect of regular inhaled salbutamol on airway responsiveness to methacholine and hypertonic saline, on the maximal response plateau to methacholine, and on inflammatory cells in induced sputum in rhinitic non-asthmatic subjects. METHODS: Thirty subjects with a baseline maximal response plateau of > 15% fall in forced expiratory volume in one second (FEV1) entered a randomised, placebo controlled, parallel trial consisting of two weeks run in, four weeks of treatment, and two weeks washout. Methacholine challenges were performed at the beginning of the run in period, before treatment, after treatment, and after washout. Hypertonic saline challenges were performed before and after treatment and induced sputum samples were collected for differential cell counting. RESULTS: There was no change in airway responsiveness, maximal response plateau to methacholine, or in induced sputum eosinophils or mast cells. The maximum fall in FEV1 after hypertonic saline increased in the salbutamol group (median change 6.0%, interquartile range (IQR) 11.0) but did not change in the placebo group (median change 1.3%, IQR 5.5). CONCLUSIONS: Regular inhaled salbutamol for four weeks increases airway responsiveness to hypertonic saline but does not alter airway responsiveness to methacholine or cells in induced sputum in non-asthmatic individuals with rhinitis. The relevance of these findings to asthmatic subjects has not been established.

Absence of a maximal dose-response plateau and mathematical modeling suggest that asthmatic airways close during bronchoconstriction. Finding segmental areas affected by closure would be important in understanding asthmatic airway function. The aim of this study was to evaluate single-photon emission computed tomography (SPECT) as a method of investigating airway closure. Simultaneous SPECT transmission and emission studies were performed on a thoracic phantom to develop analysis methodology, and on 13 normal subjects after they inhaled a Technegas bolus from residual volume (RV), to measure airway closure. Single-breath nitrogen test values and lung volumes were measured. Airway closure was defined as the percent of Technegas-free lung volume (LVclosed). The mean error +/- 95% CI of the error, as determined by transmission scan, was 1.1 ml +/- 165 ml (0.8% +/- 15% lung volume) in the phantom studies, and 112 ml +/- 419 ml (4% +/- 31% of supine functional residual capacity [FRC]) in the human studies. LVclosed correlated with closing capacity (r = 0.86, p < 0.01 ) and closing volume (r = 0.86, p < 0.01), but not with RV/total lung capacity (TLC). This study indicates that simultaneous SPECT emission and transmission scans, using a Technegas bolus, are a valid method of measuring airway closure in vivo, with the added advantage of providing three-dimensional data that allow the detection of small, discrete areas of airway closure and determination of their volumes and shapes.

To explore the natural history of asthma and its relation to allergic responses, we examined the relation between total serum IgE in early adulthood and a history of respiratory symptoms, airway hyperresponsiveness (AHR), and atopy during childhood. We studied 180 subjects aged 18-20 years who had been studied since the age of 8-10 years. We measured wheeze in the previous year by questionnaire, AHR by histamine inhalation test, atopy by skin prick tests, and serum IgE levels by immunoassay. Subjects with AHR in early adulthood had higher IgE levels (mean 257.0 IU/ml) than subjects with past AHR (mean 93.3 IU/ml) or with lifelong normal responsiveness (mean 67.6 IU/ml) (P < 0.001). Subjects who had symptoms had higher IgE levels (mean 125.9 IU/ml) than those who were lifelong asymptomatic (mean 63.1 IU/ml) (P < 0.001). Recent wheeze, AHR, and allergic sensitization all had a positive relation to serum IgE, but IgE was not more predictive of AHR than skin prick tests. The finding that young adults who are sensitized to common allergens are highly likely to have AHR even in the absence of symptoms is further evidence of the fundamental role of IgE-mediated responses in the natural history of AHR throughout childhood and into adulthood.

The aims of treating patients with asthma are to relieve symptoms, to prevent symptoms and exacerbations, and to prevent long-term deterioration in lung function. It is the role of medical practitioners to inform the patient what asthma is, and to develop a plan to achieve the aims for the individual, recognizing that asthma is frequently a chronic, lifelong disease. Most patients can be diagnosed, assessed for severity and causes, and treated in primary care practices, however, sometimes help from an asthma clinic of a specialist is required. The most important management decision is to determine whether the patient needs inhaled corticosteroids; subsequently, decisions about dose, duration and method of delivery of treatment can be tailored to the individual depending on the preferences and social conditions of the patient. The aim of this article is to present the latest strategies for the management of asthma and the simplest methods for their implementation. Important new strategies include careful assessment of the severity; immediate introduction of a plan that is tailored of the individual and aimed at the possible reversing of the disease; detailed instructions for management of exacerbations and the combined use of inhaled corticosteroids with a long-acting bronchodilator. It is becoming clear that these strategies obviate dependence on oral corticosteroids in newly diagnosed asthmatic patients. Furthermore, relatively low doses of inhaled corticosteroids can be used to maintain good control if used in conjunction with other therapies. The role of newly developed antagonists to leukotrienes is not yet known but it may well be useful in mild asthma and in special forms of the disease, such as those sensitive to aspirin. In the future, the most important strategy will be to prevent the disease.

If house dust mite allergen (Der p I) is an important cause of asthma, there should be a direct relationship between level of exposure to this allergen and asthma severity. To examine this, we studied six large random samples of children in different regions of New South Wales, Australia. We measured recent wheeze by questionnaire, airway hyperresponsiveness (AHR) by histamine inhalation test and sensitization to house dust mites by skin prick tests. Current asthma was defined as the presence of recent wheeze and AHR. We measured Der p I levels in the beds of approximately 80 children in each region. In regions where Der p I levels were high, more children were sensitized to house dust mites, and these children had significantly more AHR and recent wheeze. After adjusting for sensitization to other allergens, we found that the risk of house dust mite-sensitized children having current asthma doubled with every doubling of Der p I level. There was a modest correlation between AHR and Der p I exposure in individuals (r = 0.23, p0.03). These data suggest that house dust mite allergens are an important cause of childhood asthma and that reducing exposure to these allergens could have a large public health benefit in terms of asthma prevention.

Calculation of diurnal peak expiratory flow (PEF) variability using values before and after bronchodilator is no longer possible for many asthmatic patients because they now use beta-agonists "as needed" for symptoms rather than regularly. This study assesses the usefulness of a number of alternative PEF indices as markers of airway liability in subjects with stable, although not necessarily well-controlled, asthma. Forty-six adult subjects completed a questionnaire about symptoms and treatment in the previous 3 mo. Spirometric function and airway hyperresponsiveness (AHR) were assessed; AHR was expressed as dose response ratio (DRR) (maximal percent fall in FEV1 divided by final dose of histamine). Subjects recorded PEF morning and evening, before and after bronchodilator (if used) for 2 wk. Nine different PEF indices were calculated. Diurnal variability (amplitude percent maximum) without bronchodilator was significantly less than diurnal variability with bronchodilator. Normal indices of PEF lability were found in 42% of subjects with reduced maximal midexpiratory flow (MMEF). Most of the PEF indices correlated strongly with DRR, and less strongly with symptom score and airway obstruction. Minimum morning prebronchodilator PEF over a week (expressed as percent recent best or percent predicted) is recommended as the best PEF index of airway lability in patients with stable asthma because it correlates strongly with AHR, patients are more likely to comply with a once-daily reading, the calculation is simple, and regular use of a beta-agonist is not required.

We have calculated normal standards for lung function of Australian children and have estimated the effects on lung function of passive smoking, current asthma, past asthma, and a current respiratory infection. Three cross-sectional samples of children in school years 3-5 (aged 8-11 years) were studied. The 2765 children were from two rural regions of NSW and from the city of Sydney. Details of passive smoking and respiratory illness were collected by a questionnaire sent to parents. Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), peak expiratory flow rate (PEFR), and forced mid-expiratory flow rate (FEF25-75%) were used as measures of lung function. Airway responsiveness was assessed by histamine inhalation test. Data from 1278 "normal" children were used in regression analysis to calculate prediction models for lung function. Passive smoking was associated with reduced FEV1, PEFR, and FEF25-75%. Children with current asthma had reduced FEV1 and FEF25-75% and children with past asthma had reduced FEF25-75%. Children with a current respiratory infection had reduced FVC, FEV1, PEFR, and FEF25-75%. The effects of these deficits on the future lung function of these children is not known but is likely to be important.

Summary To test the effectiveness of a house dust mite (HDM) allergen avoidance strategy we conducted a randomized controlled trial in 35 atopic subjects with asthma, aged 13 to 60 living in Sydney — a high HDM allergen environment. After a 3 month run-in period, subjects were randomized to active allergen avoidance treatment (n= 17) or placebo (n= 18) groups and followed for 6 months. The active treatment involved placing impermeable covers over the mattress, pillows and duvet and spraying the remaining bedding, as well as the carpets and furniture, with a tannic acid/acaricidal spray. Subjects kept a daily record of symptoms and peak expiratory flow rates and had 3 monthly assessments of lung function and airway hyperresponsiveness (AHR). Dust samples were collected from the bed, the bedroom floor and the living room floor at 3 monthly intervals and 2 weeks after the treatment. Mean HDM allergen levels at baseline at these sites were, in the active group, 15.5, 9.6 and 10.2μ/g Der p I/g of fine dust, and, in the placebo group 25.7, 11.8 and 6.3μg/g. Two weeks after the allergen avoidance treatment the HDM allergen level in the beds was reduced to 29% of baseline (95% CI 16.50%, P= 0.038 compared with placebo), but was not significantly different at 3 or 6 months. There was also no significant effect of the allergen avoidance treatment on symptom scores, peak flow variability, lung function or AHR (P > 0.1). We conclude that, in a high HDM allergen environment, simple chemical treatment and encasement of bedding is not sufficient to cause a sustained, beneficial reduction in allergen levels. Effective allergen avoidance requires an active strategy to remove allergen reservoirs and control accumulating allergen within the house.

In recent years, airway responsiveness has commonly been measured in epidemiological studies using one of two methods. In one method, histamine is administered via a handheld DeVilbiss nebulizer and in the other, methacholine is administered via a dosimeter. Allergic sensitivity has commonly been measured by either the allergen droplet method or by Phazet. We wanted to assess the comparability of airway responsiveness and of allergic sensitivity measured by both methods. A total of 48 volunteers, including normal and asthmatic subjects, participated in the study. Subjects first underwent one of the two tests of airway responsiveness and allergic sensitivity, and then returned within 10 days to undergo tests using the second protocol. Commencement protocol was allocated in random order. There was good agreement between both methods for assessing airway responsiveness and for assessing allergic sensitivity. The difference for dose response ratio (DRR) between histamine and methacholine was a 1.19 (95% (CI) 0.78, 1.82) fold changes, which was not statistically significant. Agreement between allergic sensitivity methods was perfect for Alternaria tenuis, good for rye-grass (kappa = 0.71) and moderate for cat and Dermatophagoides pteronyssinus (kappa approximately 0.5). It is possible to compare data from epidemiological studies which use these methods.

The aim of the present study was to compare the severity of asthma in children and adults living in the same home environments. In winter 1991 and 1992, we studied two large random samples of children living in two different regions; and, three months later, we conducted a study of adults who lived with enrolled children. A total of 805 children and 814 adults attended in Lismore, and 850 children and 711 adults in Wagga Wagga. Questionnaires were used to measure symptom history, histamine inhalation challenge to measure airway hyperresponsiveness (AHR) and skin-prick tests to measure allergy. There was a higher prevalence of asthma in children than in adults: recent wheeze was 1.5 times higher; asthma medication use was 1.5 times higher; diagnosed asthma was 1.6 times higher; and AHR was two times higher. Current asthma (AHR and recent wheeze) was 9.5-11.3% in children and 5.4-5.6% in adults. These differences were statistically significant. In both regions, airway responsiveness was more severe in children who were sensitized to common allergens than in similarly sensitized adults. These results suggests that airways can develop protective mechanisms with age, or that recent environmental changes in factors such as allergen levels, diet or treatment practices have led to immunological changes and to increased airway responsiveness in this generation of children.

Objective : To investigate whether prevalence of asthma in children increased in 10 years. Design : Serial cross sectional studies of two populations of children by means of standard protocol. Setting : Two towns in New South Wales: Belmont (coastal and humid) and Wagga Wagga (inland and dry). Subjects : Children aged 8-10 years: 718 in Belmont and 769 in Wagga Wagga in 1982; 873 in Belmont and 795 in Wagga Wagga in 1992. Main outcome measures : History of respiratory illness recorded by parents in self administered questionnaire; airway hyperresponsiveness by histamine inhalation test; atopy by skin prick tests; counts of house dust mites in domestic dust. Results : Prevalence of wheeze in previous 12 months increased in Belmont, from 10.4% (75/718) in 1982 to 27.6% (240/873) in 1992 (P Conclusions : We suggest that exposure to higher allergen levels has increased airway abnormalities in atopic children or that mechanisms that protected airways of earlier generations of children have been altered by new environmental fators.

OBJECTIVE To describe aspects of the manifestations and management of asthma in a community setting. DESIGN Cross-sectional survey. SETTING A NSW provincial centre in October 1991. PARTICIPANTS Ninety-eight adults, identified from a population survey, with wheeze, shortness of breath, or cough, in the past year, and either airway hyperresponsiveness (AHR) or a reported doctor's diagnosis of asthma. MAIN OUTCOME MEASURES Histamine challenge test to measure AHR; asthma quality of life questionnaire (AQLQ) score (with the maximum score of 10 corresponding with lowest quality of life); need for medical attention or time off work; medical management and self-management of asthma; and the extent of beta 2-agonist use. RESULTS Of the 98 participants, 74 had had asthma diagnosed by their doctor, 34 had perennial asthma, and 30 had required medical attention or had missed work because of asthma in the preceding year. The median AQLQ score was 1.0 (interquartile range, 0.6-1.8). Inhaled steroids were used by 17 participants who accounted for 23% of those with medically diagnosed asthma, 32% of those with perennial asthma, 17% of those with moderate or severe AHR, 40% of those who had required medical attention or missed work because of asthma in the preceding year, and 31% of those with AQLQ scores in the top quartile. Only 18 participants owned a peak flow meter; seven had a written self-management plan; 18 stated they would respond to worsening asthma by starting or increasing treatment with inhaled steroids, and six would start therapy with orally administered steroids. Twelve had never used beta 2-agonists and only five had purchased more than 12 beta 2-agonist inhalers in the preceding year. CONCLUSIONS The spectrum of asthma in this community sample included many adults with mild disease and few with severe disease. Many were not managed in accordance with the recommendations of the Asthma Management Plan, but overuse of beta 2-agonists was not an important public health problem in this community.

In assessing the effectiveness of management strategies for patients with asthma, it is important to measure outcomes which are relevant to the concerns of patients. Quality of life is one such outcome which may not be adequately reflected in lung function measurements. We have developed an asthma quality of life questionnaire (the AQLQ) for this purpose. The aim of this study was to test the validity and responsiveness of the AQLQ as a measure of change. Forty four adults with asthma were assessed on two occasions 4 months apart. On each occasion subjects completed the AQLQ and the Sickness Impact Profile (SIP). Lung function and the degree of bronchial hyperresponsiveness (BHR) were measured and diary cards were used to derive a symptom score and mean daily peak flow variability. The relation of change in AQLQ scores to change in the other outcomes was assessed. Questionnaire responsiveness was assessed by comparing the change in AQLQ scores between 19 improved and 20 stable subjects. Improvement was assessed on lung function and BHR criteria. As expected, change in AQLQ score was correlated with change in symptom score ( r = 0.37, 95% CI −0.04 to 0.64) and change in BHR ( r = 0.38, 95% CI 0.06 to 0.64). The associations with change in peak flow variability ( r = 0.12, 95% CI −0.26 to 0.47) and change in SIP score ( r = 0.18, 95% CI −0.12 to 0.45) were in the expected direction but weaker than expected. The AQLQ was capable of detecting differences between improved and stable subjects ( p = 0.007). These data, in the context of the known content validity of the AQLQ, support the continued use of the AQLQ as a measure of change in adults with asthma. Further evaluation of construct validity should be incorporated into the design of clinical trials which use the AQLQ as an outcome measure.

Asthma is a major public health problem in developed countries, where it consumes a large and increasing share of scarce health resources. Ideally, medical management should be both optimal in terms of improving the patient's quality of life, and cost-effective for society. At present, there is very little information relating to costs and economic efficiency of current asthma management. Although the true total cost of asthma is unknown, current estimates suggest it is high. The main value of recent total cost estimates is that they identify the most expensive areas of asthma costs, and ideally, formal cost-effectiveness analyses should be concentrated on these areas. Asthma is still under- or inappropriately diagnosed, and undertreated. Several national and international consensus plans for the optimal management of asthma in children and adults have been published. If these inadequacies in asthma management were corrected, using current treatment recommendations, the overall cost of asthma from both the community and patient perspective should fall. The situation requires increased use of preventative medications {sodium cromoglycate (cromolyn sodium) or inhaled corticosteroids}, more widespread use of written crisis plans, more proactive medical consultations (rather than reactive or urgent consultations), further expansion of asthma education programmes, and further education of medical practitioners about the optimum management of both long term asthma and the acute exacerbation of asthma in the patient's home, the doctor's office, the hospital emergency room and the hospital inpatient setting. The increased costs associated with these measures would be more than offset by reduced expenditure on bronchodilator drugs, less widespread use of nebulisers at home and in hospitals, reduced antibiotic usage, reduced need for expensive emergency medical care and particularly reduced utilisation of hospital resources. To ensure that resources are being directed into the most cost-effective areas of asthma care, clinical trials of asthma should include utilisation of healthcare resources as an outcome measure, and estimates of the costs of the treatment under study. In addition, since the intangible cost (quality of life) is one of the most important effects of treatment from the patient's perspective, this should be more widely used as an outcome measure in clinical trials. Ultimately, prevention of asthma is the long term goal. If the hypothesis that sensitisation to house dust mite in early infancy is a major contributor to the subsequent development of asthma, then prevention may require drastic and expensive changes to current housing.

For describing bronchial responsiveness, it has been suggested that the dose-response slope (DRS), which is the linear slope of the dose-response curve, is a more useful measure of severity than the provoking dose that causes a 20% fall in FEV1 (PD20FEV1). To determine the distribution of DRS measurements and their relation to respiratory illness in adults, we have reanalyzed data collected in 1981 from a random sample of the population of Busselton, Western Australia. We measured bronchial responsiveness to histamine by the rapid method and atopy by skin prick tests to 15 common allergens. Satisfactory bronchial challenge data were recorded for 858 subjects. Subjects were classified as having asthma symptoms by self-reported history or as having chronic airflow limitation by abnormality of lung function. In normal subjects, DRS values were symmetrically distributed on a logarithmic scale so that a value that represented abnormal responsiveness could be calculated. The dose-response slope had a significant independent association with past and current asthma symptoms, smoking history, sex, atopy, and FEV1/FVC ratio but not with chronic airflow limitation. In subjects in whom a PD20FEV1 could not be measured, the DRS had a significant relation to asthma symptoms, smoking history, and FEV1/FVC. Thus, DRS values, which could be obtained for most subjects, contributed additional information to PD20FEV1 values and discriminated more accurately between groups classified according to respiratory history. These data confirm that DRS values should be used in preference to PD20FEV1 values for describing the severity of bronchial responsiveness in populations.

Methacholine dose response curves (DRC) in asthmatic subjects are characterized by a leftward shift and increased maximal response. Allergen inhalation in atopic subjects shifts the DRC to the left, but the effect on the shape is unknown. This study was designed to investigate the effect of allergen inhalation on the maximal response plateau of the methacholine DRC in 16 atopic subjects; nine had mild asthma and seven had rhinitis. They were challenged with allergen and with control solutions in a single-blind design. Methacholine challenges (up to 199 mumol) were performed at baseline and 24 h after the control and allergen challenges. A plateau of the DRC was defined as a difference of less than 5% in FEV1 between the last two or more doses. The maximal response was obtained by averaging the values on the plateau and was reached by all except one subject. Allergen inhalation induced an early asthmatic response (EAR) in all subjects and an additional late asthmatic response (LAR) in 6 subjects. In subjects with an EAR alone the maximal response to methacholine 24 h after allergen challenge was not different from control (mean difference, 2.9% fall in FEV1; p greater than 0.05). In subjects with LAR, the mean value for the maximal response increased from 28.5% after control to 36.5% after allergen (mean difference, 8.0%; p less than 0.05). Of six subjects who developed LAR two lost the plateau on the DRC after allergen challenge. We conclude that allergen inhalation increases the maximal response to methacholine in those subjects who have a LAR.

Because there is no consensus definition of asthma for epidemiology, we have examined the reliability of a questionnaire and the effect of its mode of administration on classification of asthma in children. A symptom history questionnaire was parent self-administered and then readministered within three months by a nurse. The questions of diagnosed asthma, cumulative wheeze, and recent wheeze (wheeze in the previous 12 months) were more repeatable than questions of night cough, but 7 percent of children changed diagnosed asthma category, 13 percent changed cumulative wheeze category, and 9 percent changed recent wheeze category at second questionnaire. Because the numbers who changed from symptom positive to negative roughly equalled the changes from negative to positive, prevalence estimates were not affected. Methods of measuring asthma with greater precision are urgently needed. Because of reporting bias, epidemiologic information collected by current questionnaires should be treated with some caution. (Chest 1992; 102:153–57)

A 20-item self-administered questionnaire with Likert scale responses was developed to measure quality of life in adult subjects with asthma. A total scale score together with subscale scores for breathlessness, mood disturbance, social disruption and concerns for health were calculated by addition of item scores. Items for the scale were selected by principal components analysis of the responses of 283 subjects to a preliminary pool of 69 items. In 58 subjects with stable asthma, good short term test-retest reliability was demonstrated with the intraclass correlation coefficient for the total scale being 0.80. The questionnaire was internally consistent in a sample of outpatients (Cronbach's alpha 0.92 in 77 subjects) and in a community sample with asthma (Cronbach's alpha 0.94 in 87 subjects). Weak correlations in the expected direction were seen with three medical markers of asthma severity. This supports the construct validity of the questionnaire and emphasizes that quality of life represents a separate dimension of asthma.

Although the characteristics of the histopathologic changes present in subjects who die with status asthmaticus are well documented, the structural changes present in subjects with mild to moderately severe asthma are not well described and the inflammatory changes in the large airways of subjects with chronic airflow limitation (CAL) and asthma have not been compared. Ten subjects with asthma, five taking inhaled corticosteroids and five taking beta 2-agonist aerosols, five subjects with CAL, and four subjects with no respiratory illness had four biopsies taken from airways 10 mm in diameter. The length of intact epithelium, thickness of basement membrane, and number of lymphocytes, neutrophils, eosinophils, plasma cells, monocytes, and mast cells in the lamina propria, bronchial smooth muscle, and submucosa were measured. Intact epithelium was present along 56% of the basement membrane in the asthmatic subjects, along 54% in the subjects with CAL, and along 84% in the control subjects. In the asthmatic subjects there was no direct relationship between the severity of asthma and the amount of epithelial cell loss or the number of inflammatory cells. The basement membrane was thickened in all asthmatic subjects but not in normal subjects or subjects with CAL. There was a significant increase in the number of lymphocytes, eosinophils, and mast cells in the asthmatic airways, particularly in the lamina propria, compared with the CAL subjects. There were no eosinophils or mast cells in any of the control subjects. The airways of subjects with CAL contained significantly more inflammatory cells than the control subjects. Subjects with asthma on inhaled corticosteroids had significantly fewer lymphocytes, eosinophils, and mast cells compared with subjects taking only beta 2-agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

The beds, carpets and furnishings in 15 houses were sprayed with a solution containing tannic acid and an acaricide in an attempt to reduce allergen concentrations. Dust was collected from these sites for 4 weeks following spraying and the mite allergen Der p I concentration was measured and compared with baseline concentrations. In a subgroup of houses, counts of live mites and estimates of aeroallergen were also made. Four untreated houses were monitored over the same period. In dust samples collected 3 days after spraying, the mean concentrations of Der p I in beds, carpets and furniture were 23%, 28% and 26% of the pretreatment levels. All these reductions were significant compared to untreated controls. Samples collected 4 weeks after treatment were not significantly different to baseline for each group. After the initial reduction, the rate of increase in allergen concentration was significantly greater in the spray-only beds than in the beds which had been both sprayed and fitted with occlusive covers. Both aeroallergen and live mites continued to be detected in houses after treatment with the spray. These studies suggest that such sprays are only temporarily effective when applied at the manufacturer's recommended volumes and additional approaches are required to control the bulk of allergens in houses.

The nature of the relationship between airway hyperresponsiveness (AHR) and atopy (specific IgE to aeroallergens) is unknown and one of the most important questions about asthma. Is AHR a consequence of airway inflammation caused by allergic or other responses or is it a separately inherited state? It is clear from epidemiological studies that these two abnormalities are linked. However, not all allergic (atopic) people have AHR and not all airway-hyperresponsive people are allergic. Furthermore, there is some suggestion that the risk factors for the two abnormalities are different. In Australian children, there has been little increase in the prevalence of atopy but AHR and symptoms have increased so that more of the atopic group now have asthma (1). The data suggest that over the years between 1982 and 1992 in atopic children, the risk factors for AHR have increased or that protective factors have been lost. There have been almost no other studies of atopic status and AHR in randomly selected populations over a period of time to determine if this is happening elsewhere. This article outlines what is known, what is partially known, and the important questions that need to be answered.

To describe bronchial responsiveness in populations, the dose-response slope (DRS), which is the linear slope of the dose-response curve, may be a more useful measure of severity than the provoking dose that causes a 20% fall in FEV1 (PD20 FEV1). To examine the distribution of DRS measurements and their relation to respiratory symptoms in children, we have analyzed data collected during a population study designed to measure the prevalence of bronchial hyper-responsiveness and respiratory symptoms. In this study, respiratory symptom history was measured by a self-administered questionnaire to parents and bronchial responsiveness was measured using the rapid inhalation method. Of 1,217 children studied, DRS values were obtained for 1,203 children who had technically satisfactory bronchial challenge data. In asymptomatic children, DRS values were distributed symmetrically on a logarithmic scale. The geometric mean DRS was reliable measure of the central position of the curve, and 1.96 standard deviations only slightly underestimated the 95% interval. In children with recent wheeze, the distribution was skewed toward larger DRS values. Mean DRS values were significantly different between groups determined according to symptom frequency. It appears that DRS values are more useful than PD20 FEV1 values in epidemiologic studies of respiratory illness in children because a value that relates well to symptom history can be calculated for the entire sample. The major advantages are that the measurement more clearly discriminates between symptom severity groups and that a value that represents abnormal responsiveness can be calculated.

Peak expiratory flow varies throughout the day in normal subjects, and this diurnal variation is increased in people with asthma.1 Current asthma guidelines recommend that diurnal variability of the peak expiratory flow rate should be calculated when diagnosing asthma and assessing its severity,2–7 including during exacerbations.34 Diurnal variability of peak flow has been used as a marker of airway responsiveness,8 9 particularly in epidemiological studies,10 11 and as an outcome measure in clinical asthma trials.12 However, there are problems associated with its use. #### Summary points Variation in peak flow over days or weeks provides helpful information about asthma control Asthma guidelines recommend that diurnal peak flow variability is calculated to provide an index of airway lability These calculations are too time consuming for normal clinical practice Factors such as the time of recording or recent use of β2 agonist drugs result in minor changes in peak flow, but can cause large errors in diurnal variability Diurnal variability may fail to detect important changes in lung function An alternative, simpler index of peak flow variation such as the lowest morning peak flow expressed as percentage of the patient's personal best peak flow value should be evaluated for inclusion in asthma guidelines Although diurnal variability in peak flow has been included in asthma guidelines for many years, doctors in primary and secondary care settings rarely use it, because of the cumbersome calculations involved. Several alternative equations may be used. The most common are the amplitude percentage mean ((maximum—minimum)/mean) or the amplitude percentage maximum ((maximum—minimum)/maximum), calculated for each day, and then averaged over a period of 1 to 2 weeks.13 Determining the amplitude percentage mean from as few as 7 days of twice daily peak flow readings for one patient (see fig 1) is …

The severity of airway inflammation in patients with asthma is best assessed by combining several tests of bronchial responsiveness. The prognostic significance of bronchial responsiveness is unknown, but indirect evidence suggests that those with moderate and severe asthma rarely remit spontaneously and permanently. Assessment of severity is crucial to the rational management of all patients with asthma. Severity can be used as a guide to both short- and long-term management.

In this study, we examined two groups of patients with chronic airflow limitation (CAL) separated according to their awake, stable arterial CO2 level. The aim was to identify factors that may contribute to the development of chronic hypercapnic respiratory failure. Patients with obstructive sleep apnea were excluded from the study. Detailed lifetime histories of smoking, alcohol, and snoring were obtained from all patients together with measurements of lung function and of upper airway size. Thirty-three patients with FEV1 less than 1.5 L were studied, of whom 19 were eucapnic and 14 were hypercapnic. Both groups had a similar degree of chronic airflow limitation and similar lung volumes and DLCO. The hypercapnic group had more hypopneas and desaturated more severely during sleep. The greatest differences between the groups were in their alcohol consumptions, snoring histories, and upper airway dimensions. The eucapnic patients were characterized by lower lifetime alcohol intake, minimal snoring, and large upper airway size. In contrast, the hypercapnic patients were characterized by excessive lifetime alcohol consumption, habitual snoring over many years, and a small upper airway size. Our findings suggest that chronic, heavy alcohol use and upper airway dysfunction are important factors in the development of hypercapnic respiratory failure.