Cheryl M. Salome

Physiology of obesity and effects on lung function

In obese people, the presence of adipose tissue around the rib cage and abdomen and in the visceral cavity loads the chest wall and reduces functional residual capacity (FRC). The reduction in FRC and in expiratory reserve volume is detectable, even at a modest increase in weight. However, obesity has little direct effect on airway caliber. Spirometric variables decrease in proportion to lung volumes, but are rarely below the normal range, even in the extremely obese, while reductions in expiratory flows and increases in airway resistance are largely normalized by adjusting for lung volumes. Nevertheless, the reduction in FRC has consequences for other aspects of lung function. A low FRC increases the risk of both expiratory flow limitation and airway closure. Marked reductions in expiratory reserve volume may lead to abnormalities in ventilation distribution, with closure of airways in the dependent zones of the lung and ventilation perfusion inequalities. Greater airway closure during tidal breathing is associated with lower arterial oxygen saturation in some subjects, even though lung CO-diffusing capacity is normal or increased in the obese. Bronchoconstriction has the potential to enhance the effects of obesity on airway closure and thus on ventilation distribution. Thus obesity has effects on lung function that can reduce respiratory well-being, even in the absence of specific respiratory disease, and may also exaggerate the effects of existing airway disease.

Longitudinal changes in atopy during a 4-year period: Relation to bronchial hyperresponsiveness and respiratory symptoms in a population sample of Australian schoolchildren

A total of 380 schoolchildren living in Belmont, New South Wales, a coastal town where the predominant aeroallergens are house dust mites, were studied on three occasions at 2-year intervals. At each study, atopy was measured by skin prick tests to 13 allergens, bronchial responsiveness was measured by histamine inhalation test, and respiratory illness history was assessed by a self-administered questionnaire to parents. The age of the group was 8 to 10 years at enrollment. We found that skin wheals less than 4 mm were not associated with respiratory or allergic illness, and therefore, we defined atopy as the presence of a skin wheal of greater than or equal to 4 mm. In the sample, 24% of the children were atopic at 8 to 10 years (early-onset atopy), and an additional 15% became atopic during the study (late-onset atopy). Both early- and late-onset atopy had a close association with hay fever. Late-onset atopy was strongly associated with inconsistent reporting of symptoms. Early-onset atopy was an important risk factor for bronchial hyperresponsiveness (BHR), diagnosed asthma, and continuing symptoms of wheeze, and was a particularly important risk factor for BHR with current wheeze in late childhood years. We conclude that atopy acquired at an early age is an important predictive factor for respiratory symptoms occurring with BHR and continuing into late childhood.

Prevalence of bronchial hyperresponsiveness and asthma in a rural adult population.

The prevalence of bronchial hyperresponsiveness in adult populations is not known. To document its prevalence and distribution and to determine the factors associated with it, a random sample of the adult population of Busselton, Western Australia, was studied. Spirometric function, bronchial responsiveness to histamine, and atopic responses to skin prick tests were measured. Respiratory symptoms were determined by questionnaire. Data were obtained from 916 subjects. Of these, 876 underwent a histamine inhalation test and bronchial hyperresponsiveness to histamine (defined as a dose of histamine provoking a 20% fall in FEV1 equal to or less than 3.9 mumol) was found in 10.5%. Another 40 subjects with poor lung function were tested with a bronchodilator and 12 were found to have bronchial hyperresponsiveness (defined as a greater than 15% increase in FEV1), making the total prevalence of bronchial hyperresponsiveness 11.4%. The prevalence of current asthma, defined as bronchial hyperresponsiveness plus symptoms consistent with asthma in the last 12 months, was 5.9%. The distribution of bronchial hyperresponsiveness in the studied population was continuous. There was a significant association between it and respiratory symptoms, atopy, smoking, and abnormal lung function (p less than 0.001 for all associations). There was no association with age, sex, or recent respiratory tract infection.

Bronchial hyperresponsiveness in two populations of Australian schoolchildren. I. Relation to respiratory symptoms and diagnosed asthma

In order to explore the relationship between bronchial hyperresponsiveness (BHR) to inhaled histamine, respiratory symptoms and diagnosed asthma in children, we undertook a cross‐sectional study of 2363 Australian schoolchildren aged 8–11 years. The methods used included a self‐administered questionnaire to parents, which was shown to have a high degree of repeatability, and a histamine inhalation test to measure bronchial responsiveness (BR). The study showed that 17.9% of children had BHR, defined as a 20% fall in FEV1 at a provoking dose of histamine (PD20 FEV1) of less than 7.8 μmol. The distribution of PD20 FEV1 appeared to be continuous. Most children with PD20 FEV1 values < 1.0μmol had symptoms of asthma. However, 6.7% of children had BHR without symptoms or a previous diagnosis of asthma and 5.6% had had a diagnosis of asthma but had no BHR. Although there was a good association between BHR and respiratory symptoms, questionnaire data of wheeze and diagnosed asthma do not reflect accurately the level of BHR in the community. We conclude that cross‐sectional studies of BR to identify children with BHR probably do not reflect the prevalence of asthma in populations of children. However, the strong association between BHR and symptoms, particularly in children with severe and moderate BHR, suggests that measurements of BR in populations are useful for defining a group of children whose airways behave differently from those of the majority. Prospective studies are needed to define the level of BHR that is associated with important sequelae.

Ventilation heterogeneity is a major determinant of airway hyperresponsiveness in asthma, independent of airway inflammation

Background: Airway hyperresponsiveness is the ability of airways to narrow excessively in response to inhaled stimuli and is a key feature of asthma. Airway inflammation and ventilation heterogeneity have been separately shown to be associated with airway hyperresponsiveness. A study was undertaken to establish whether ventilation heterogeneity is associated with airway hyperresponsiveness independently of airway inflammation in subjects with asthma and to determine the effect of inhaled corticosteroids on this relationship. Methods: Airway inflammation was measured in 40 subjects with asthma by exhaled nitric oxide, ventilation heterogeneity by multiple breath nitrogen washout and airway hyperresponsiveness by methacholine challenge. In 18 of these subjects with uncontrolled symptoms, measurements were repeated after 3 months of treatment with inhaled beclomethasone dipropionate. Results: At baseline, airway hyperresponsiveness was independently predicted by airway inflammation (partial r2 = 0.20, p<0.001) and ventilation heterogeneity (partial r2 = 0.39, p<0.001). Inhaled corticosteroid treatment decreased airway inflammation (p = 0.002), ventilation heterogeneity (p = 0.009) and airway hyperresponsiveness (p<0.001). After treatment, ventilation heterogeneity was the sole predictor of airway hyperresponsiveness (r2 = 0.64, p<0.001). Conclusions: Baseline ventilation heterogeneity is a strong predictor of airway hyperresponsiveness, independent of airway inflammation in subjects with asthma. Its persistent relationship with airway hyperresponsiveness following anti-inflammatory treatment suggests that it is an important independent determinant of airway hyperresponsiveness. Normalisation of ventilation heterogeneity is therefore a potential goal of treatment that may lead to improved long-term outcomes.

Sahaja yoga in the management of moderate to severe asthma: a randomised controlled trial

Background: Sahaja Yoga is a traditional system of meditation based on yogic principles which may be used for therapeutic purposes. A study was undertaken to assess the effectiveness of this therapy as an adjunctive tool in the management of asthma in adult patients who remained symptomatic on moderate to high doses of inhaled steroids. Methods: A parallel group, double blind, randomised controlled trial was conducted. Subjects were randomly allocated to Sahaja yoga and control intervention groups. Both the yoga and the control interventions required the subjects to attend a 2 hour session once a week for 4 months. Asthma related quality of life (AQLQ, range 0–4), Profile of Mood States (POMS), level of airway hyperresponsiveness to methacholine (AHR), and a diary card based combined asthma score (CAS, range 0–12) reflecting symptoms, bronchodilator usage, and peak expiratory flow rates were measured at the end of the treatment period and again 2 months later. Results: Twenty one of 30 subjects randomised to the yoga intervention and 26 of 29 subjects randomised to the control group were available for assessment at the end of treatment. The improvement in AHR at the end of treatment was 1.5 doubling doses (95% confidence interval (CI) 0.0 to 2.9, p=0.047) greater in the yoga intervention group than in the control group. Differences in AQLQ score (0.41, 95% CI –0.04 to 0.86) and CAS (0.9, 95% CI –0.9 to 2.7) were not significant (p>0.05). The AQLQ mood subscale did improve more in the yoga group than in the control group (difference 0.63, 95% CI 0.06 to 1.20), as did the summary POMS score (difference 18.4, 95% CI 0.2 to 36.5, p=0.05). There were no significant differences between the two groups at the 2 month follow up assessment. Conclusions: This randomised controlled trial has shown that the practice of Sahaja yoga does have limited beneficial effects on some objective and subjective measures of the impact of asthma. Further work is required to understand the mechanism underlying the observed effects and to establish whether elements of this intervention may be clinically valuable in patients with severe asthma.

Effect of therapy on bronchial hyperresponsiveness in the long‐term management of asthma

The aim of this study was to determine if prophylactic therapy leads to a reduction in the severity of bronchial hyperresponsiveness (BHR) in subjects with severe asthma. Measurements of bronchial responsiveness to histamine were made in two groups of subjects for periods up to 2 years. Thirteen subjects in the study group took regular medication and used a home monitor of airway function to determine the medication requirements needed to maintain optimal airway function. A control group of eleven subjects was managed with the same drugs but without daily monitoring and without any attempt to keep daily lung function at optimal levels. Subjects in the study group had a 10‐ to 100‐fold decrease in the severity of BHR, which was independent of the improvement in baseline lung function. All but one subject in the study group became symptom free and six were able to maintain the improvement in BHR and symptoms on reduced medication. There was no change in the severity of BHR or in the baseline lung function in the control group. It is concluded that it is possible to reduce the severity of BHR in subjects with severe asthma by the use of pharmacological agents. This reduction in severity appears to require the long‐term use of medications, including aerosol corticosteroids, with daily home monitoring to allow adjustment of the amount of treatment required.

Bronchial hyperresponsiveness in two populations of Australian schoolchildren. III. Effect of exposure to environmental allergens

Two populations of schoolchildren, one living in an area where the predominant allergens are house dust mites and the other in an area where the predominant allergens are pollens, were studied to investigate in more detail the associations between atopy, bronchial hyperresponsiveness (BHR) and symptoms of asthma. The prevalence of atopy (39%) was the same in both towns but the prevalence of BHR was higher in the inland ‘pollen’ area (19%vs 15%). Atopic children had an increased risk of having BHR and, to a lesser extent, respiratory symptoms, diagnosed asthma and hay fever. The risk of BHR was further increased in children atopic to both pollens and house dust mites, and in children with a high index of atopy (derived from the number and size of the skin reactions to four allergen groups). In addition, the relationship between atopy and BHR was quantitative in that the severity of BHR increased with the severity of atopy. We conclude that there is not a direct causal relationship between atopy and BHR but there may be a common mechanism involved in their development. It appears that, within the atopic population, the type of allergen to which the individual is sensitized, the quantity of aeroallergen present in the environment and the degree of atopy, as measured by the number and size of the skin reactions, are all factors that may interact to increase the risk of BHR.

A prospective study of bronchial hyperresponsiveness and respiratory symptoms in a population of Australian schoolchildren

To examine the relationship between bronchial hyperresponsiveness (BHR) and respiratory symptoms associated with asthma, we studied a sample of 380 schoolchildren on three occasions at 2‐yr intervals. The age of the children at the first study was 8–10 yr. Respiratory symptoms history was assessed by questionnaire, BHR was measured by a histamine inhalation test and atopy was assessed by skin‐prick tests to 13 allergens. The cumulative prevalence of BHR in this sample was 27%. The severity of BHR was categorized as severe, moderate, mild or slight. The distribution of severe, moderate and mild BHR was similar at each of the studies. At the third study, when the children were aged 12–14 yr, the prevalence of slight BHR decreased. Children with severe or moderate BHR at age 8–10 yr were atopic, reported current symptoms during the 4 yr of the study and had a high prevalence of severe or moderate BHR in later studies. In this group, 87% of children had current respiratory symptoms and 73% were using asthma medication at age 12–14 yr. In children with mild or slight BHR when first studied, the prevalence of atopy, continuing respiratory symptoms and medication use was much lower. We conclude that severe or moderate BHR is an important risk factor for ongoing morbidity and that comparisons of the prevalence of this severity of BHR in populations may be more informative than comparisons of BHR defined by present criteria.

Repeatability of peak nasal inspiratory flow measurements and utility for assessing the severity of rhinitis

Background:  The measurement of peak nasal inspiratory flow (PNIF) provides a simple, cheap, fast and readily available tool for determining the extent of nasal airway patency. However, there are questions regarding its repeatability when used to assess the degree of nasal obstruction in large populations. Therefore, this study aimed to evaluate the repeatability of PNIF measurements and to assess their association with the signs and symptoms of rhinitis.