C. M. Salome

Rapid method for measurement of bronchial responsiveness.

A rapid, simple method for measuring bronchial responsiveness to inhaled histamine is described. The method was used to obtain dose response curves in 50 atopic subjects with varying respiratory and nasal symptoms. The cumulative dose of histamine which caused a 20% fall in the one second forced expiratory volume (PD20-FEV1) varied between 0.046 and greater than 3.9 mumol and correlated with the severity of symptoms. The reproducibility of the PD20-FEV1, determined from duplicate measurements in 15 subjects with varying degrees of bronchial responsiveness was found to be satisfactory. When the PD20-FEV1 from this rapid method was compared with that obtained from the dosimeter method no significant difference was found. The dose delivered by this method was shown to be cumulative.

Obesity is a risk for asthma and wheeze but not airway hyperresponsiveness

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 <3.9 μmol histamine required to provoke a fall in forced expiratory volume in one second (FEV1) of 20% or more (PD20FEV1). Adjusted odds ratios (OR) were obtained by logistic regression. RESULTS After adjusting for atopy, age, sex, smoking history, and family history, severe obesity was a significant risk factor for recent asthma (OR 2.04, p=0.048), wheeze in the previous 12 months (OR 2.6, p=0.001), and medication use in the previous 12 months (OR 2.83, p=0.005), but not for AHR (OR 0.87, p=0.78). FEV1 and forced vital capacity (FVC) were significantly reduced in the group with severe obesity, but FEV1/FVC ratio, peak expiratory flow (PEF), and mid forced expiratory flow (FEF25–75) were not different from the group with normal BMI. The underweight group (BMI <18.5 kg/m2) had increased symptoms of shortness of breath, increased airway responsiveness, and reduced FEV1, FVC, PEF, and FEF25–75 with similar use of asthma medication as subjects in the normal weight range. CONCLUSIONS Although subjects with severe obesity reported more wheeze and shortness of breath which may suggest a diagnosis of asthma, their levels of atopy, airway hyperresponsiveness, and airway obstruction did not support the suggestion of a higher prevalence of asthma in this group. The underweight group appears to have more significant respiratory problems with a higher prevalence of symptoms, reduced lung function, and increased airway responsiveness without an increase in medication usage. This group needs further investigation.

Differences between asthma exacerbations and poor asthma control

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 beta2-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 beta2-adrenoceptor function between these conditions.

Asthma and atopy in overweight children

Background: Obesity may be associated with an increase in asthma and atopy in children. If so, the effect could be due to an effect of obesity on lung volume and thus airway hyperresponsiveness. Methods: Data from 5993 caucasian children aged 7–12 years from seven epidemiological studies performed in NSW were analysed. Subjects were included if data were available for height, weight, age, skin prick test results to a common panel of aeroallergens, and a measure of airway responsiveness. History of doctor diagnosed asthma, wheeze, cough, and medication use was obtained by questionnaire. Recent asthma was defined as a doctor diagnosis of asthma ever and wheeze in the last 12 months. Body mass index (BMI) percentiles, divided into quintiles per year age, were used as a measure of standardised weight. Dose response ratio (DRR) was used as a measure of airway responsiveness. Airway hyperresponsiveness was defined as a DRR of ⩾8.1. Adjusted odds ratios were obtained by logistic regression. Results: After adjusting for atopy, sex, age, smoking and family history, BMI was a significant risk factor for wheeze ever (OR = 1.06, p = 0.007) and cough (OR = 1.08, p = 0.001), but not for recent asthma (OR = 1.02, p = 0.43) or airway hyperresponsiveness (OR = 0.97 p = 0.17). In girls a higher BMI was significantly associated with higher prevalence of atopy (χ2 trend 7.9, p = 0.005), wheeze ever (χ2 trend 10.4, p = 0.001), and cough (χ2 trend 12.3, p<0.001). These were not significant in boys. Conclusions: Higher BMI is a risk factor for atopy, wheeze ever, and cough in girls only. Higher BMI is not a risk factor for asthma or airway hyperresponsiveness in either boys or girls.

The effects of body weight on airway calibre

Increased wheeze and asthma diagnosis in obesity may be due to reduced lung volume with subsequent airway narrowing. Asthma (wheeze and airway hyperresponsiveness), functional residual capacity (FRC) and airway conductance (Gaw) were measured in 276 randomly selected subjects aged 28–30 yrs. Data were initially adjusted for smoking and asthma before examining relationships between weight and FRC (after adjustment for height), and between body mass index (BMI = weight·height−2) and Gaw (after adjustment for FRC) by multiple linear regression, separately for females and males. For males and females, BMI (±95% confidence interval) was 27.0±4.6 kg·m−2 and 25.6±6.0 kg·m−2 respectively, Gaw was 0.64±0.04 L·s−1·cmH2O−1 and 0.57±0.03 L·s−1·cmH2O−1, and FRC was 85.3±3.4 and 84.0±2.9% of predicted. Weight correlated independently with FRC in males and females. BMI correlated independently and inversely with Gaw in males, but only weakly in females. In conclusion, obesity is associated with reduced lung volume, which is linked with airway narrowing. However, in males, airway narrowing is greater than that due to reduced lung volume alone. The mechanisms causing airway narrowing and sex differences in obesity are unknown.

Airway re-narrowing following deep inspiration in asthmatic and nonasthmatic subjects.

After bronchoconstriction, deep inspiration (DI) causes dilatation followed by airway re-narrowing. Re-narrowing may be faster in asthmatic than nonasthmatic subjects. This study investigated the relationship between re-narrowing and the magnitude of both DI-induced dilatation and the volume-dependence of respiratory system resistance (Rrs) during tidal breathing. In 25 asthmatic and 18 nonasthmatic subjects the forced oscillation technique was used to measure Rrs at baseline and after methacholine challenge, during 1 min of tidal breathing, followed by DI to total lung capacity (TLC) and passive return to functional residual capacity (FRC). Dilatation was measured as the decrease in Rrs between end tidal inspiration and TLC, re-narrowing as Rrs at FRC immediately after DI, as per cent Rrs at end-tidal expiration, and volume dependent tidal fluctuation as the difference between mean Rrs at end-expiration and end-inspiration. Asthmatic subjects had greater re-narrowing, less dilatation, and greater tidal fluctuations both at baseline and after challenge. Re-narrowing correlated with baseline tidal fluctuation and inversely with dilatation. Both baseline tidal fluctuation and dilatation were significant independent predictors of re-narrowing. Following deep inspiration-induced dilatation, faster airway re-narrowing in asthmatic than nonasthmatic subjects is associated not only with reduced deep inspiration-induced dilatation but also with some property of the airways that is detectable prior to challenge as an increased volume dependence of resistance.

Effect of obesity on breathlessness and airway responsiveness to methacholine in non-asthmatic subjects.

Background:Obesity is associated with increased prevalence and incidence of asthma, but the mechanism is unknown. Obesity reduces lung volumes, which can increase airway responsiveness, and increases resistive and elastic work of breathing, which can increase dyspnea.Objective:To determine if the intensity of dyspnea due to airway narrowing or if airway responsiveness is increased in obese, non-asthmatic subjects.Subjects:Twenty-three obese (BMI (body mass index) ⩾30 kg m−2) and 26 non-obese (BMI <30 kg m−2) non-asthmatic subjects, aged between 18 and 70 years.Methods:High-dose methacholine challenge was used to determine the sensitivity and the maximal response to methacholine. Respiratory system resistance (Rrs) and reactance were measured, using the forced oscillation technique, as indicators of resistive and elastic loads during challenge. Perception of dyspnea was measured by the Borg score during challenge. Static lung volumes were measured by body plethysmography.Results:Static lung volumes were reduced in the obese subjects. There were no significant differences in the sensitivity or maximal response to methacholine between obese and non-obese subjects. The magnitude of change in Rrs was similar in both groups, but obese subjects had more negative reactance after challenge (P=0.002) indicating a greater elastic load. The intensity of dyspnea was greater in obese subjects (P=0.03).Conclusions:Obesity reduces lung volumes, but does not alter the sensitivity or maximal response to methacholine. However, obese subjects have enhanced perception of dyspnea, associated with greater apparent stiffness of the respiratory system, and may therefore be at greater risk of symptoms.

House dust mite allergen avoidance: a randomized controlled trial of surface chemical treatment and encasement of bedding

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.

Exhaled nitric oxide levels in atopic children: relation to specific allergic sensitisation, AHR, and respiratory symptoms

Background: Exhaled nitric oxide (eNO), which has been proposed as a measure of airway inflammation, is increased in atopic subjects. This raises the question of whether eNO provides any additional information about airway inflammation in asthmatic subjects, other than as a marker for atopy. A study was undertaken to determine whether eNO levels in a population of atopic children are associated with sensitisation or natural exposure to specific allergens, and to examine the relationship between eNO, airway responsiveness, and current respiratory symptoms. Methods: Exhaled NO and airway responsiveness to histamine were measured in winter and in summer in 235 children aged 8–14 years who had been classified as atopic by skin prick testing. Current respiratory symptoms, defined as wheeze or cough during the month preceding the test, were measured by a parent completed questionnaire. Airway hyperresponsiveness (AHR) was defined as a dose response ratio (DRR) of >8.1 (% fall in forced expiratory volume in 1 second (FEV1)/μmol + 3). Results: Sensitisation to house dust mite was associated with raised eNO levels in winter while sensitisation to Cladosporium was associated with raised eNO levels in both winter and summer. Grass pollen sensitisation was not associated with raised eNO levels in either season. Exhaled NO correlated significantly with DRR histamine (r=0.43, p<0.001) independently of whether the children had current symptoms or not. In children with current wheeze, those with AHR had eNO levels 1.53 (95% CI 1.41 to 1.66) times higher than those without AHR (p=0.006). Neither DRR (p=1.0) nor eNO levels (p=0.92) differed significantly between children with or without persistent dry cough in the absence of wheeze. Conclusions: In atopic children, raised eNO levels are associated with sensitisation to perennial allergens, but not to seasonal allergens such as grass pollen. In this population, an increase in eNO is associated with AHR and current wheezing, suggesting that eNO is more than just a marker for atopy.

Increased airway closure is a determinant of airway hyperresponsiveness

In order to investigate whether increased airway closure is a component of airway hyperresponsiveness (AHR), airway closure was compared during induced bronchoconstriction in 62 asthmatic, 41 nonasthmatic nonobese (control) and 20 nonasthmatic obese (obese) subjects. Airway closure and airway narrowing were measured by spirometry as percentage change in forced vital capacity (%ΔFVC) and change in forced expiratory ratio (ΔFER), respectively. Multiple regression analyses were used to assess the determinants of AHR, assessed by the dose response slope (DRS). The DRS was significantly increased in asthmatics compared with controls but did not differ between obese and controls. The spirometric predictors of logDRS were baseline FER, ΔFER, body mass index (BMI) and %ΔFVC. There was a negative relationship between BMI and logDRS in the regression, suggesting a protective effect. The present findings suggest that the extent of airway closure during induced bronchoconstriction is a determinant of airway hyperresponsiveness, independent of the level of airway narrowing. However, after adjusting for airway closure, obesity appears to protect against airway hyperresponsiveness.