Gerard Ryan

Lung Function, Respiratory Symptoms, and Mortality: Results from the Busselton Health Study

PURPOSE This study examines the association between lung function [percentage predicted FEV, (forced expiratory volume in 1 s)] and respiratory symptoms (asthma, bronchitis, wheeze, dyspnea) and mortality from all causes; coronary heart disease, stroke, cancer, and respiratory disease in a cohort of 2,100 men and 2,177 women in the Busselton Health Study followed for 20-26 years for mortality. METHODS A total of 840 men and 637 women died during the follow-up period, and Cox proportional hazards regression was used to assess the relationships between risk factors and mortality. RESULTS Lung function was significantly and independently predictive of mortality from all causes, coronary heart disease, cancer, and respiratory disease in both men and women, and of mortality from stroke in women. There was evidence that, among men, the association was stronger in current and former smokers as compared to those who never smoked. After adjustment for age, smoking, lung function, coronary heart disease, blood pressure, treatment for hypertension, total cholesterol, body mass index, and alcohol consumption, dyspnea was significantly related to total mortality in men and women and to respiratory disease mortality in men, and asthma was significantly related to respiratory disease mortality in women. CONCLUSIONS Lung function is associated with mortality from many diseases independent of smoking and respiratory symptoms. Although most respiratory symptoms are associated with smoking and lung function, after controlling for smoking and lung function, only dyspnea is associated with mortality from nonrespiratory causes.

Decline in lung function and mortality: the Busselton Health Study.

BACKGROUND: There is a direct association between level of lung function, measured by forced expiratory volume in 1 second (FEV1) and mortality rates. A low FEV may result from an increased decline in FEV1 with age, which may be an independent predictor of mortality. OBJECTIVE: To examine the association between decline in FEV1 and mortality in a cohort from a community health study. SETTING AND METHODS: From five cross sectional studies in Busselton between 1969 and 1981 a cohort of 751 men and 940 women was identified who had three assessments of lung function over a six year period and had other health related data collected. Each subjects average FEV1 and decline in FEV1 (litre/year) were calculated from these three measurements. Mortality follow up to December 1995 was obtained. Cause of death was taken as the certified cause of death from the death certificate using ICD9 categories. RESULTS: The average decline in FEV1 was 0.04 litre per year (SD = 0.07) for men and 0.03 litre per year (SD = 0.06) for women. Average FEV1 was significantly associated with all cause and cardiovascular disease mortality in both sexes. In women there was a significant association between decline in FEV1 and death from all causes, after adjusting for average FEV1, age, smoking, coronary heart disease, and cardiovascular disease risk factors; a 0.05 litre per year increase in the rate of decline of FEV1 increased the risk of death for all causes by 1.23 (95% confidence interval 1.06, 1.44). In men the effect of decline in FEV1 on death rate was less; for all men the hazard ratio for a 0.05 litre/year greater decline in FEV1 was 1.19 (0.99, 1.21). CONCLUSION: Decline in lung function, measured by FEV1 is a predictor of death, independent of average FEV1 and risk factors for cardiovascular disease.

Familial aggregation and heritability of adult lung function: results from the Busselton Health Study

Decreased spirometric indices are characteristic of asthma and other respiratory diseases. The aim of this study was to investigate the genetic and environmental components of variance of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) measured in adulthood in an Australian population-based sample of 468 Caucasian nuclear families. The inter-relationships of the genetic determinants of these traits with asthma and atopic rhinitis were also investigated. Serial cross-sectional studies were conducted in the town of Busselton in Western Australia between 1966 and 1981 and follow-up of previous attendees was undertaken in 1995. Data from each subject included in this study were from a single survey in adulthood (25-60 yrs of age) when the subject was as close to age 45 yrs as possible. Multivariate analysis suggested that FEV1 and FVC levels were associated with age, sex, height, tobacco smoke exposure, asthma and atopic rhinitis. After adjustment for relevant covariates, FEV1 levels had a narrow-sense heritability (h2N) of 38.9% (SE 9.1%). FVC levels had an h2N of 40.6% (SE 8.9%). Extended modelling demonstrated little overlap in the genetic determinants of asthma or atopic rhinitis and either FEV1 or FVC levels. The results of this study were consistent with the existence of important genetic determinants of adult lung function that are independent of asthma or other atopic disease, cigarette smoking, height, age or sex.

Testing airway responsiveness using inhaled methacholine or histamine

Abstract Airway responsiveness assessed using histamine and methacholine is safe, reproducible and relatively easily undertaken in adults and children. Results are similar for methacholine and histamine although methacholine is better tolerated. Responsiveness is increased in children and the elderly, and in women compared to men, possibly due to body size effects. Baseline lung function confounds the interpretation of airway responsiveness and may explain the effect of smoking in most studies. Results are most usefully expressed as the provocative dose producing a 20% fall in FEV1 (PD20FEV1) or the dose‐response slope (DRS). When technical factors are controlled the reproducibility of the test is from one to two doubling doses. Measurements of airway responsiveness have been widely used in clinical and research practice. However, assessing their value in diagnosing asthma is limited by the lack of a gold standard for the definition of asthma. Using a cut‐off value of 8 mg/mL or 8 μmol for PD20, the tests will discriminate asthmatic from non‐asthmatic subjects (based on questionnaire definitions of asthma) with a sensitivity of around 60% and a specificity of around 90%. These properties of the test result in positive and negative predictive values of 86% and 69% when the prevalence of asthma is high (50%– as in the clinical setting) and 40% and 95% when the prevalence of asthma is low (10%, as in general population studies). In the usual clinical setting, assessing the significance of atypical or non‐specific symptoms, the tests are of intermediate value in predicting the presence of asthma and less useful in excluding asthma. The additional benefit of testing airway responsiveness to measuring peak flows or to a trial of therapy has yet to be fully assessed. Testing of airway responsiveness may be of value in assessing occupational asthma, asthma severity and the effects of potential sensitizers or treatments. In research, tests of airway responsiveness are more useful for excluding cases of asthma. In population studies, they serve as an objective marker of abnormal airway function which may be genetically determined and, like allergy, are strongly associated with asthma. The predictive value of airway hyperresponsiveness for the development of airway disease is yet to be clearly established. In epidemiology the benefits of measuring airway responses must be weighed against the added inconvenience and cost that is incurred.

Mortality and airflow obstruction in asthma: a 17-year follow-up study

Background: Asthma is associated with fixed airflow obstruction and an increased risk of death. The aim of this study was to relate asthma mortality and airflow obstruction to severity of asthma in a cohort of patients with chronic asthma studied over a 17‐year period.

Associations between asthma history, atopy, and non‐specific bronchial responsiveness in young adults

In 105 subjects taken from a student population and aged between 15 and 30 there was a strong positive association between the presence of the atopic state, defined by skin tests, and a high level of non‐specific bronchial responsiveness to methacholine (χ2= 10·5, d.f. = 2, P= 0·01). Regression analysis showed a history of asthma, and the symptom of wheeze, to be predominantly predicted by the degree of bronchial responsiveness (R2= 31%), with only a minor independent contribution from the degree of atopy (R2 a furthur 5%). The genetic or other reasons for the association between bronchial responsiveness and atopy may have importance in understanding the aetiology of allergic asthma.

Cystic fibrosis in Australia, 2009: results from a data registry

Objectives: To describe the demographics, clinical features and outcomes among people with cystic fibrosis (CF) in Australia and to estimate incidence of the disease.

SPECT ventilation perfusion scanning with the addition of low-dose CT for the investigation of suspected pulmonary embolism

Single‐photon emission computed tomography (SPECT) ventilation perfusion (V/Q) scanning with low‐dose computed tomography (LDCT) is an emerging imaging technique for investigation of suspected pulmonary embolism (PE). We aimed to estimate diagnostic utility of the combined technique using results from all patients referred in 2009 compared with final diagnosis and 6‐month follow‐up status. PE was diagnosed in 28 of 106 patients (26%), including in 2 of 80 (2%) with negative SPECT V/Q and LDCT. The estimated negative predictive value of SPECT V/Q for PE was 97%. LDCT was abnormal in 43 (41%) patients, including 41 patients who had negative SPECT V/Q. In 29 (27%) patients, LDCT provided information on alternative pathologies that accounted for presenting symptoms, and the combined technique had a diagnostic yield of 52%.

Variability of the plateau response to methacholine in subjects without respiratory symptoms.

BACKGROUND--Interpretation of measurements of limited maximal airway narrowing, or plateau response, requires knowledge of its variability within subjects and between methods. METHODS--The repeatability of the plateau response to inhaled methacholine with a dosimeter (D) method (maximal dose 210 mumol) and a tidal breathing (T) method (730 mumol), and the agreement of the two methods, were measured in 16 subjects with mild or no asthma. Two tests by each method (D1,D2,T1,T2) were performed in random order over four consecutive days, with a third dosimeter (D3) test one week later. The dose producing a decrease in forced expiratory volume in one second (FEV1) of 10% (PD10) and the plateau were calculated from each dose-response curve. RESULTS--A plateau was reached in all five tests in 12 subjects and in all tests except D3 in 14 subjects. PD10 was inversely related to the plateau (r = -0.95 for D, r = -0.77 for T). The 95% ranges for differences between two determinations of the plateau in a subject were +/- 11.9% (change in FEV1), +/- 19.2%, and +/- 20.3%, estimated from D1-2 and 1-3, and T1-2 tests, respectively. From the same tests the 95% ranges for the difference of a single determination from an individuals true mean value were +/- 8.3%, +/- 13.6%, and +/- 14.3%. The limits of agreement between methods indicated that 95% of the measurements of the plateau by tidal breathing ranged from 15.2% below to 13.3% above those obtained by dosimeter. There was no significant bias between methods. Tachyphylaxis over 24 hours occurred with PD10 but not with the plateau response. CONCLUSIONS--The plateau response is a subject characteristic which is independent of the method of inhalation challenge testing. Repeatability of the plateau is low in this group of subjects with low airway responsiveness.

Increased perception of airway narrowing in patients with ild asthma

Abstract To compare the perception of airway narrowing of nonasthmatic subjects with those having wheeze or mild asthma (doctor‐diagnosed), the relationship between FEV1 and breathlessness was examined in 123 subjects from a general population sample. Scores for breathlessness, using the Borg scale, were recorded before and after inhaling incremental doses of methacholine to a maximal dose of 196 mcmol or a maximum change in FEV1 of 50%. A history of asthma symptoms, including wheeze in the previous 12 months, and doctor‐diagnosed asthma was obtained by questionnaire. At any given level of FEV1 there was wide variation in Borg scores between subjects, however median Borg scores and the mean slope of Borg score on FEVI was greater in the asthmatic subjects or those with wheeze compared with nonasthmatic subjects or those without wheeze. In both nonasthmatic and asthmatic subjects, those with airway hyperresponsiveness had increased maximum symptom scores and maximum changes in FEVI, but similar Borg scores relative to change in FEVI, compared with those without hyperresponsiveness. We conclude that the perception of mild and moderate degrees of airway narrowing varies widely between individuals but is increased in subjects with a history of mild asthma or wheeze in the last 12 months, independently of airway responsiveness.