Respiratory health status of Australian veterans of the 1991 Gulf War and the effects of exposure to oil fire smoke and dust storms

BACKGROUND: Since the 1991 Gulf War concerns have been raised about the effects on veterans' health of exposures to Kuwaiti oil fire smoke and to dust storms. METHODS: A cross sectional study compared 1456 Australian Gulf War veterans with a randomly sampled military comparison group (n = 1588). A postal questionnaire asked about respiratory conditions, exposures, medications, tobacco use, demographic characteristics, and military service details. During a medical assessment, spirometric tests and a physical examination were performed and a respiratory questionnaire was administered. RESULTS: The response rate for the Gulf War veteran group was 80.5% and for the comparison group 56.8%. Australian Gulf War veterans had a higher than expected prevalence of respiratory symptoms and respiratory conditions suggesting asthma (OR 1.4; 95% CI 1.1 to 1.9) and bronchitis first diagnosed since the Gulf War (OR 1.9; 95% CI 1.2 to 3.1) but did not have poorer lung function or more ventilatory abnormalities than the comparison group. Veterans who reported exposure to oil fire smoke had slightly poorer forced vital capacity (difference between means -0.10 l; 95% CI -0.18 to -0.03) and those exposed to dust storms had a slightly better peak expiratory flow rate (difference between means 12.0 l/min; 95% CI 0.6 to 23.4) than veterans who did not report exposure. Veterans who were in the Gulf at or after the start of the oil fires had more respiratory conditions suggesting asthma (OR 1.7; 95% CI 1.0 to 2.9) than those who completed their deployment before this time. CONCLUSIONS: Increased self-reporting of respiratory symptoms, asthma, and bronchitis by veterans was not reflected in poorer lung function. The findings do not suggest major long term sequelae of exposure to oil fire smoke or dust storms.     

Effects of regular salmeterol on lung function and exercise capacity in patients with chronic obstructive airways disease.

BACKGROUND: The aim of this study was to evaluate the effects of single and chronic dosing with salmeterol on exercise capacity and lung function in patients with chronic obstructive pulmonary disease. METHODS: Twenty nine patients of mean (SE) age 64 (1.5) years, forced expiratory volume in one second (FEV1) 42(3)% of predicted, and 5-15% reversibility to salbutamol 200 micrograms were randomised to receive four weeks treatment with salmeterol 50 micrograms twice daily or placebo in a double blind crossover fashion with a one week washout period in between. Measurements of spirometric parameters, static lung volumes, and exercise capacity were made one and six hours after a single dose, and six hours after the final dose of salmeterol or placebo. RESULTS: Salmeterol produced a small increase in FEV1 at one and six hours after a single dose, and this was maintained after chronic dosing (mean difference and 95% CI versus placebo): single dosing at one hour 0.07 (95% CI 0.02 to 0.11) 1, single dosing at six hours 0.16 (95% CI 0.09 to 0.22) 1, chronic dosing at six hours 0.11 (95% CI 0.03 to 0.19) 1. The increase in forced vital capacity (FVC) was greater with salmeterol than with placebo six hours after single but not chronic dosing: single dosing at six hours 0.17 (95% CI 0.04 to 0.29) 1, chronic dosing at six hours 0.02 (95% CI -0.18 to 0.22) 1. Slow vital capacity was increased after treatment with salmeterol compared with placebo one and six hours after single but not after chronic dosing. There were no significant differences in static lung volumes or exercise capacity after single or chronic dosing with salmeterol compared with placebo. Patients reported a significantly lower Borg score for perceived exertion following the six minute walk after chronic treatment with salmeterol compared with placebo. CONCLUSIONS: Salmeterol produced a small improvement in spirometric values compared with placebo consistent with the degree of reversibility originally shown by the subjects to salbutamol 200 micrograms. This was not associated with improvements in static lung volumes or exercise capacity, but there was some symptomatic benefit in that patients were able to walk the same distance in six minutes with less perceived exertion.     

Pharmacy Asthma Care Program (PACP) improves outcomes for patients in the community

BACKGROUND: Despite national disease management plans, optimal asthma management remains a challenge in Australia. Community pharmacists are ideally placed to implement new strategies that aim to ensure asthma care meets current standards of best practice. The impact of the Pharmacy Asthma Care Program (PACP) on asthma control was assessed using a multi-site randomised intervention versus control repeated measures study design. METHODS: Fifty Australian pharmacies were randomised into two groups: intervention pharmacies implemented the PACP (an ongoing cycle of assessment, goal setting, monitoring and review) to 191 patients over 6 months, while control pharmacies gave their usual care to 205 control patients. Both groups administered questionnaires and conducted spirometric testing at baseline and 6 months later. The main outcome measure was asthma severity/control status. RESULTS: 186 of 205 control patients (91%) and 165 of 191 intervention patients (86%) completed the study. The intervention resulted in improved asthma control: patients receiving the intervention were 2.7 times more likely to improve from "severe" to "not severe" than control patients (OR 2.68, 95% CI 1.64 to 4.37; p<0.001). The intervention also resulted in improved adherence to preventer medication (OR 1.89, 95% CI 1.08 to 3.30; p = 0.03), decreased mean daily dose of reliever medication (difference -149.11 microg, 95% CI -283.87 to -14.36; p=0.03), a shift in medication profile from reliever only to a combination of preventer, reliever with or without long-acting beta agonist (OR 3.80, 95% CI 1.40 to 10.32; p=0.01) and improved scores on risk of non-adherence (difference -0.44, 95% CI -0.69 to -0.18; p=0.04), quality of life (difference -0.23, 95% CI -0.46 to 0.00; p=0.05), asthma knowledge (difference 1.18, 95% CI 0.73 to 1.63; p<0.01) and perceived control of asthma questionnaires (difference -1.39, 95% CI -2.44 to -0.35; p<0.01). No significant change in spirometric measures occurred in either group. CONCLUSIONS: A pharmacist-delivered asthma care programme based on national guidelines improves asthma control. The sustainability and implementation of the programme within the healthcare system remains to be investigated.     

Peak bone mass after exposure to antenatal betamethasone and prematurity: follow-up of a randomized controlled trial.

Small birth size is associated with reduced adult bone mass. We determined if antenatal betamethasone exposure, birth weight, or prematurity affects peak bone mass in 174 adults. Antenatal betamethasone exposure did not. Lower birth weight and prematurity predicted reduced adult height. Slower fetal growth rather than prematurity predicted lower bone mass, but this lower bone mass was appropriate for reduced adult height. INTRODUCTION: Small size at birth is reported to be associated with lower bone mass in adulthood. However, previous studies have not distinguished the relative contributions of length of gestation and fetal growth to size at birth. Fetal exposure to excess glucocorticoids has been proposed as a core mechanism underlying the associations between birth size and later disease risk. Antenatal glucocorticoids are given to pregnant women at risk for preterm delivery for the prevention of neonatal respiratory distress syndrome in their infants. We determined the relationship of antenatal exposure to betamethasone, birth weight, and prematurity to peak bone mass and femoral geometry in the adult survivors of the first randomized trial of antenatal glucocorticoids. MATERIALS AND METHODS: We studied 174 young adults (mean age, 31 years) whose mothers participated in a randomized trial of antenatal betamethasone. Mothers received two doses of intramuscular betamethasone or placebo 24 h apart. Two thirds of participants were born preterm (<37 weeks gestation). We measured indices of bone mass and size and derived estimates of volumetric density and bone geometry from DXA assessments of the lumbar spine, femur, and total body. RESULTS: There were no differences between betamethasone-exposed and placebo-exposed groups in any of the lumbar spine, femur, or total body DXA measures. There was no effect of antenatal betamethasone on adult height, although leg length was increased relative to trunk length (p = 0.002). A lighter birth weight (p 相似文献   

Inhaled fluticasone in bronchiectasis: a 12 month study

BACKGROUND: The clinical efficacy of inhaled corticosteroid (ICS) treatment has not been evaluated in bronchiectasis, despite the presence of chronic airway inflammation. METHODS: After three consecutive weekly visits, 86 patients were randomised to receive either fluticasone 500 mug twice daily (n = 43, 23F, mean (SD) age 57.7 (14.4) years) or matched placebo (n = 43, 34F, 59.2 (14.2) years) and reviewed regularly for 52 weeks in a double blind fashion. RESULTS: 35 and 38 patients in the fluticasone and placebo groups completed the study. Significantly more patients on ICS than on placebo showed improvement in 24 hour sputum volume (OR 2.5, 95% CI 1.1 to 6.0, p = 0.03) but not in exacerbation frequency, forced expiratory volume in 1 second, forced vital capacity, or sputum purulence score. Significantly more patients with Pseudomonas aeruginosa infection receiving fluticasone showed improvement in 24 hour sputum volume (OR 13.5, 95% CI 1.8 to 100.2, p = 0.03) and exacerbation frequency (OR 13.3, 95% CI 1.8 to 100.2, p = 0.01) than those given placebo. Logistic regression models revealed a significantly better response in sputum volume with fluticasone treatment than with placebo among subgroups of patients with 24 hour sputum volume <30 ml (p = 0.04), exacerbation frequency 5 (p = 0.03). CONCLUSIONS: ICS treatment is beneficial to patients with bronchiectasis, particularly those with P. aerurginosa infection.     

Lung function at one month of age as a risk factor for infant respiratory symptoms in a high risk population

BACKGROUND: Abnormal premorbid lung function is a risk factor for subsequent wheezing in children with one or no atopic parent. This study was undertaken to establish whether early lung function in high risk infants (both parents atopic) was a risk factor for respiratory symptoms in infancy and to examine the influence of maternal asthma, smoking, and allergen exposure during pregnancy on any association. METHODS: Infants were recruited from the NAC Manchester Asthma and Allergy Study cohort at birth. Partial forced expiratory flow volume technique under sedation was carried out to determine maximal flow at FRC (V'maxFRC). Children were followed prospectively and parents completed a standard respiratory questionnaire at one year of age. RESULTS: Sixty nine term infants (34 boys; 88% mothers non-smokers; no household pets) underwent respiratory function testing. Size adjusted V'maxFRC was significantly lower in infants who had recurrent wheeze during the first year of life (mean 1.3 ml/s/cm, 95% CI 0.99 to 1.60) than in those who did not (mean 2.03 ml/s/cm, 95% CI 1.71 to 2.36; p=0.01). V'maxFRC was also significantly lower in infants who had recurrent cough symptoms. In multivariate regression analysis, when adjusted for age at test, sex, maternal asthma, smoking and maternal mattress Der 1 levels, a lower size adjusted V'maxFRC score remained strongly associated with wheezing (OR 0.37, 95% CI 0.18 to 0.77, p=0.007). Maternal smoking also remained an independent risk factor (OR 29.85, 95% CI 2.46 to 362.5, p=0.008). CONCLUSION: Significantly diminished lung function was present in high risk infants who subsequently wheezed and coughed. This was independent of maternal exposure to mite allergen, asthma, and smoking during pregnancy.     

Validity of spirometric testing in a general practice population of patients with chronic obstructive pulmonary disease (COPD)

OBJECTIVE: To investigate the validity of spirometric tests performed in general practice. METHOD: A repeated within subject comparison of spirometric tests with a "gold standard" (spirometric tests performed in a pulmonary function laboratory) was performed in 388 subjects with chronic obstructive pulmonary disease (COPD) from 61 general practices and four laboratories. General practitioners and practice assistants undertook a spirometry training programme. Within subject differences in forced expiratory volume in 1 second and forced vital capacity (DeltaFEV1 and DeltaFVC) between laboratory and general practice tests were measured (practice minus laboratory value). The proportion of tests with FEV1 reproducibility <5% or <200 ml served as a quality marker. RESULTS: Mean DeltaFEV1 was 0.069 l (95% CI 0.054 to 0.084) and DeltaFVC 0.081 l (95% CI 0.053 to 0.109) in the first year evaluation, indicating consistently higher values for general practice measurements. Second year results were similar. Laboratory and general practice FEV1 values differed by up to 0.5 l, FVC values by up to 1.0 l. The proportion of non-reproducible tests was 16% for laboratory tests and 18% for general practice tests (p=0.302) in the first year, and 18% for both in the second year evaluation (p=1.000). CONCLUSIONS: Relevant spirometric indices measured by trained general practice staff were marginally but statistically significantly higher than those measured in pulmonary function laboratories. Because of the limited agreement between laboratory and general practice values, use of these measurements interchangeably should probably be avoided. With sufficient training of practice staff the current practice of performing spirometric tests in the primary care setting seems justifiable.     

Relationship between air pollution, lung function and asthma in adolescents

BACKGROUND: The interrelationships between air pollution, lung function and the incidence of childhood asthma have yet to be established. A study was undertaken to determine whether lung function is associated with new onset asthma and whether this relationship varies by exposure to ambient air pollutants. METHODS: A cohort of children aged 9-10 years without asthma or wheeze at study entry were identified from the Children's Health Study and followed for 8 years. The participants resided in 12 communities with a wide range of ambient air pollutants that were measured continuously. Spirometric testing was performed and a medical diagnosis of asthma was ascertained annually. Proportional hazard regression models were fitted to investigate the relationship between lung function at study entry and the subsequent development of asthma and to determine whether air pollutants modify these associations. RESULTS: The level of airway flow was associated with new onset asthma. Over the 10th-90th percentile range of forced expiratory flow over the mid-range of expiration (FEF(25-75), 57.1%), the hazard ratio (HR) of new onset asthma was 0.50 (95% CI 0.35 to 0.71). This protective effect of better lung function was reduced in children exposed to higher levels of particulate matter with an aerodynamic diameter <2.5 microm (PM(2.5)). Over the 10th-90th percentile range of FEF(25-75), the HR of new onset asthma was 0.34 (95% CI 0.21 to 0.56) in communities with low PM(2.5) (<13.7 microg/m(3)) and 0.76 (95% CI 0.45 to 1.26) in communities with high PM(2.5) (> or = 13.7 microg/m(3)). A similar pattern was observed for forced expiratory volume in 1 s. Little variation in HR was observed for ozone. CONCLUSION: Exposure to high levels of PM(2.5) attenuates the protective effect of better lung function against new onset asthma.     

Long term effects of azithromycin in patients with cystic fibrosis: A double blind, placebo controlled trial

BACKGROUND: Macrolides display immunomodulatory effects that may be beneficial in chronic inflammatory pulmonary diseases. The aim of the study was to document whether long term use of azithromycin may be associated with respiratory benefits in young patients with cystic fibrosis. METHODS: A multicentre, randomised, double blind, placebo controlled trial was conducted from October 2001 to June 2003. The criteria for enrollment were age older than 6 years and forced expiratory volume in 1 second (FEV1) of 40% or more. The active group received either 250 mg or 500 mg (body weight < or > or =40 kg) of oral azithromycin three times a week for 12 months. The primary end point was change in FEV1. RESULTS: Eighty two patients of mean (SD) age 11.0 (3.3) years and mean (SD) FEV1 85 (22)% predicted were randomised: 40 in the azithromycin group and 42 in the placebo group. Nineteen patients were infected with Pseudomonas aeruginosa. The relative change in FEV1 at month 12 did not differ significantly between the two groups. The number of pulmonary exacerbations (count ratio 0.50 (95% CI 0.32 to 0.79), p < 0.005), the time elapsed before the first pulmonary exacerbation (hazard ratio 0.37 (95% CI 0.22 to 0.63), p < 0.0001), and the number of additional courses of oral antibiotics were significantly reduced in the azithromycin group regardless of the infectious status (count ratio 0.55 (95% CI 0.36 to 0.85), p < 0.01). No severe adverse events were reported. CONCLUSION: Long term use of low dose azithromycin in young patients with cystic fibrosis has a beneficial effect on lung disease expression, even before infection with Pseudomonas aeruginosa.     

Occupational asthma due to low molecular weight agents: eosinophilic and non-eosinophilic variants

BACKGROUND: Despite having a work related deterioration in peak expiratory flow (PEF), many workers with occupational asthma show a low degree of within day diurnal variability atypical of non-occupational asthma. It was hypothesised that these workers would have a neutrophilic rather than an eosinophilic airway inflammatory response. METHODS: Thirty eight consecutive workers with occupational asthma induced by low molecular weight agents underwent sputum induction and assessment of airway physiology while still exposed at work. RESULTS: Only 14 (36.8%) of the 38 workers had sputum eosinophilia (>2.2%). Both eosinophilic and non-eosinophilic groups had sputum neutrophilia (mean (SD) 59.5 (19.6)% and 55.1 (18.8)%, respectively). The diurnal variation and magnitude of fall in PEF during work periods was not significantly different between workers with and without sputum eosinophilia. Those with eosinophilia had a lower forced expiratory volume in 1 second (FEV1; 61.4% v 83% predicted, mean difference 21.6, 95% confidence interval (CI) 9.2 to 34.1, p=0.001) and greater methacholine reactivity (geometric mean PD20 253 microg v 1401 microg, p=0.007). They also had greater bronchodilator reversibility (397 ml v 161 ml, mean difference 236, 95% CI of difference 84 to 389, p=0.003) which was unrelated to differences in baseline FEV(1). The presence of sputum eosinophilia did not relate to the causative agent, duration of exposure, atopy, or lack of treatment. CONCLUSIONS: Asthma caused by low molecular weight agents can be separated into eosinophilic and non-eosinophilic pathophysiological variants with the latter predominating. Both groups had evidence of sputum neutrophilia. Sputum eosinophilia was associated with more severe disease and greater bronchodilator reversibility but no difference in PEF response to work exposure.     

Increase in exhaled nitric oxide levels in patients with difficult asthma and correlation with symptoms and disease severity despite treatment with oral and inhaled corticosteroids. Asthma and Allergy Group

BACKGROUND: Patients with difficult asthma suffer chronic moderate to severe persistent asthma symptoms despite high doses of inhaled and oral corticosteroid therapy. These patients suffer a high level of treatment and disease related morbidity but little is known about the degree of airway inflammation in these patients. METHODS: Fifty two patients were examined to assess levels of exhaled nitric oxide (NO) as a surrogate marker of inflammatory activity in this condition. From this group, 26 patients were defined with severe symptoms and current physiological evidence of reversible airway obstruction requiring high dose inhaled (> or = 2000 micrograms beclomethasone dipropionate (BDP) equivalent) or oral steroid therapy to maintain disease control. RESULTS: Exhaled NO levels were higher in subjects with difficult asthma (mean 13.9 ppb, 95% CI 9.3 to 18.5) than in normal controls (7.4 ppb, 95% CI 6.9 to 7.8; p < 0.002), but lower than levels in steroid naive mild asthmatics (36.9 ppb, 95% CI 34.6 to 39.3; p < 0.001). Prednisolone treated patients had higher exhaled NO levels than patients only requiring inhaled corticosteroids (17.5 ppb, 95% CI 11.1 to 24.0 versus 7.2 ppb, 95% CI 4.6 to 9.8; p = 0.016), suggesting greater disease severity in this group. Non-compliance with prednisolone treatment was observed in 20% of patients but this did not explain the difference between the treatment groups. Exhaled NO levels were closely correlated with symptom frequency (p = 0.03) and with rescue beta agonist use (p < 0.002), but they did not correlate with lung function. CONCLUSIONS: Exhaled NO may serve as a useful complement to lung function and symptomatology in the assessment of patients with chronic severe asthma, and in the control and rationalisation of steroid therapy in these patients.     

Non-invasive ventilation assists chest physiotherapy in adults with acute exacerbations of cystic fibrosis

BACKGROUND: Chest physiotherapy is essential to the management of cystic fibrosis (CF). However, respiratory muscle fatigue and oxygen desaturation during treatment have been reported. The aim of this study was to determine whether non-invasive ventilation (NIV) during chest physiotherapy could prevent these adverse effects in adults with exacerbations of CF. METHODS: Twenty six patients of mean (SD) age 27 (6) years and forced expiratory volume in 1 second (FEV1) 34 (12)% predicted completed a randomised crossover trial comparing standard treatment (active cycle of breathing technique, ACBT) with ACBT + NIV. Respiratory muscle strength (PImax, PEmax), spirometric parameters, and dyspnoea were measured before and after treatment. Pulse oximetry (SpO2) was recorded during treatment. Sputum production during treatment and 4 and 24 hours after treatment was evaluated. RESULTS: There was a significant reduction in PImax following standard treatment that was correlated with baseline PImax (r=0.73, p<0.001). PImax was maintained following NIV (mean difference from standard treatment 9.04 cm H2O, 95% confidence interval (CI) 4.25 to 13.83 cm H2O, p=0.006). A significant increase in PEmax was observed following the NIV session (8.04 cm H2O, 95% CI 0.61 to 15.46 cm H2O, p=0.02). The proportion of treatment time with SpO2 < or =90% was correlated with FEV1 (r=-0.65, p<0.001). NIV improved mean SpO2 (p<0.001) and reduced dyspnoea (p=0.02). There were no differences in FEV1, forced vital capacity (FVC) or sputum weight, but FEF(25-75) increased following NIV (p=0.006). CONCLUSION: Reduced inspiratory muscle strength and oxygen desaturation during chest physiotherapy are associated with inspiratory muscle weakness and severity of lung disease in adults with exacerbations of CF. Addition of NIV improves inspiratory muscle function, oxygen saturation and small airway function and reduces dyspnoea.     

Lobar volume reduction surgery: a method of increasing the lung cancer resection rate in patients with emphysema

BACKGROUND: Guidelines on patient selection for lung cancer resection identify a predicted postoperative forced expiratory volume in 1 second (ppoFEV(1)) of <40% as a predictor of high risk. Experience with lung volume reduction surgery suggests that ppoFEV(1) may be underestimated in those with concomitant emphysema. METHODS: Anatomical lobectomy was performed in 29 patients with a resectable lung cancer within a poorly perfused, hyperinflated emphysematous lobe identified by radionuclide perfusion scintigraphy and computed tomographic scanning. Perioperative changes in spirometric parameters at 3 months were compared in 14 patients (group A) of mean age 69 years (range 48-78) with ppoFEV(1) <40% (mean (SD) 31.4 (7)%) and 15 patients (group B) with ppoFEV(1) >40% (mean (SD) 47 (5)%). The correlation between predicted and actual postoperative FEV(1) was also assessed. RESULTS: In group B there was a significant perioperative reduction in FEV(1) (p=0.01) but in group A FEV(1) did not change significantly after lobectomy (p=0.87); mean difference in perioperative change between groups A and B 331 ml (95% CI 150 to 510). Despite the difference in ppoFEV(1) between the groups, there was no difference in actual FEV(1) at 3 months. In-hospital mortality was 14% in group A and zero in group B, but at a median follow up of 12 (range 6-40) months there was no difference in survival between the groups. CONCLUSIONS: Selection for lung cancer resection in patients with emphysema using standard calculations of ppoFEV(1) may be misleading. The effect of lobar volume reduction allows for an extension of the selection criteria.     

Health effects of passive smoking. 9. Parental smoking and spirometric indices in children

BACKGROUND: A systematic quantitative review was conducted of the evidence relating parental smoking to spirometric indices in children. METHODS: An electronic search of the Embase and Medline databases was completed in April 1997 and identified 692 articles from which we included four studies in neonates, 42 cross-sectional studies in school aged children (22 were included in a meta-analysis), and six longitudinal studies of lung function development. RESULTS: In a pooled analyses of 21 surveys of school aged children the percentage reduction in forced expiratory volume in one second (FEV1) in children exposed to parental smoking compared with those not exposed was 1.4% (95% CI 1.0 to 1.9). Effects were greater on mid expiratory flow rates (5.0% reduction, 95% CI 3.3 to 6.6) and end expiratory flow rates (4.3% reduction, 95% CI 3.1 to 5.5). Adjustment for potential confounding variables had little effect on the estimates. A number of studies reported clear evidence of exposure response. Where exposure was explicitly identified it was usually maternal smoking. Two studies in neonates have reported effects of prenatal exposure to maternal smoking. Of five cross sectional studies that compared effects of perinatal exposure (retrospectively assessed) with current exposure to maternal smoking in later childhood, the three largest concluded that the major effect was in utero or neonatal exposure. Longitudinal studies suggest a small effect of current exposure on growth in lung function, but with some heterogeneity between studies. CONCLUSIONS: Maternal smoking is associated with small but statistically significant deficits in FEV1 and other spirometric indices in school aged children. This is almost certainly a causal relationship. Much of the effect may be due to maternal smoking during pregnancy.     

Respiratory symptoms and lung function in young adults with severe alpha(1)-antitrypsin deficiency (PiZZ)

BACKGROUND: Neonatal screening for alpha(1)-antitrypsin (AAT) deficiency was undertaken in Sweden between 1972 and 1974 when 129 infants with severe AAT deficiency (phenotype PiZ) were identified. The cohort has been followed up prospectively. METHODS: 124 PiZ subjects, still alive and still living in Sweden, were invited to a follow up examination at about 22 years of age. The check up included a clinical examination, spirometric tests, and a questionnaire on smoking habits and respiratory symptoms. RESULTS: Ninety eight subjects (97 PiZZ and 1 PiZ-) subjects attended the follow up. The mean age of the subjects was 22.5 years (range 19.8-24.8). The mean (SD) forced expiratory volume in 1 second (FEV(1)) was 98 (14)% predicted, vital capacity (VC) was 103 (14)% predicted, and the mean FEV(1)/VC ratio was 83 (7)%. Eighty six subjects had previously undergone spirometric tests. The median follow up time was 4.3 years (range 0.9-7.3). The mean annual change in FEV(1) (% predicted) was -1.2% (95% CI -2.1 to -0.3), in VC (% predicted) was -1.5% (95% CI -2.0 to -0.9), and in the FEV(1)/VC ratio (%) was -0.3% (95% CI -0.7 to 0.2). Twenty eight individuals (29%) reported recurrent wheezing. Fifteen subjects (15%) had been diagnosed by a physician as having asthma. Eighteen subjects reported that they had smoked at some time; 10 were current smokers. The mean number of pack years among the ever smokers was 3.4 (range 0.6-10.5). Ten of 18 ever-smokers and 18 of 80 non-smokers reported recurrent wheezing (p<0.01), while exertional dyspnoea was reported by six ever smokers and 11 non-smokers (p<0.05). Lung function test results did not differ significantly between ever smokers and non-smokers. CONCLUSIONS: Young PiZ adults have essentially normal lung function, but have a high prevalence of asthma symptoms. Smoking in these individuals is associated with an increased frequency of respiratory symptoms.     

Asthma control during long term treatment with regular inhaled salbutamol and salmeterol

BACKGROUND: The adverse effects of long term treatment of asthma with the short acting beta agonist fenoterol have been established in both epidemiological and clinical studies. A study was undertaken to investigate the efficacy and safety of long term treatment with salbutamol and salmeterol in patients with mild to moderate bronchial asthma. METHODS: In a two centre double dummy crossover study 165 patients were randomly assigned to receive salbutamol 400 micrograms q.i.d., salmeterol 50 micrograms b.i.d., or placebo via a Diskhaler. All patients used salbutamol as required for symptom relief. The study comprised a four week run in and three treatment periods of 24 weeks, each of which was followed by a four week washout. Asthma control was assessed by measuring mean morning and evening peak expiratory flow rate (PEFR), a composite daily asthma score, and minor and major exacerbation rates. Washout assessments included methacholine challenge and bronchodilator dose response tests. Analysis was by intention to treat. RESULTS: Data from 157 patients were analysed. Relative to placebo, the mean morning PEFR increased by 30 l/min (95% CI 26 to 35) for salmeterol but did not change for salbutamol. Evening PEFR increased by 25 l/min (95% CI 21 to 30) and 21 l/min (95% CI 17 to 26), respectively (p < 0.001). Salmeterol improved the asthma score compared to placebo (p < 0.001), but there was no overall difference with salbutamol. Only daytime symptoms were improved with salbutamol. The minor exacerbation rates were 0.29, 0.88, and 0.97 exacerbations/patient/year for salmeterol, salbutamol and placebo, respectively (p < 0.0001 for salmeterol). The corresponding major exacerbation rates were 0.22, 0.51 and 0.40, respectively (p < 0.03 for salmeterol). For salbutamol the asthma score deteriorated over time (p < 0.01), and the time spent in major exacerbation was significantly longer compared with placebo (12.3 days (95% CI 4.2 to 20.4) versus 8.4 days (95% CI 5.2 to 11.6), p = 0.02). There was no evidence of rebound deterioration in asthma control, lung function, or bronchial hyper-responsiveness following cessation of either active treatment, and no evidence of tolerance to salbutamol or salmeterol. CONCLUSIONS: Regular treatment with salmeterol is effective in controlling asthma symptoms and reduces minor more than major exacerbation rates. Salbutamol was associated with improved daytime symptoms but subtle deterioration in asthma control occurred over time. Salbutamol should therefore be used only as required.     

Inhaled and intravenous corticosteroids both attenuate chlorine gas-induced lung injury in pigs

BACKGROUND: The accidental release of chlorine gas is a constant threat in urban areas. The purpose of this randomized, blinded, controlled experiment was to examine the effects of post-injury administration of inhaled or intravenous corticosteroid in chlorine gas-injured pigs followed for 23 h. METHODS: Anaesthetized, ventilated pigs (n = 24) in the prone position were exposed to chlorine gas (400 parts per million in air) (1160 mg/m3) for 15 min, then randomly allocated to receive inhaled budesonide (BUD) and intravenous placebo, intravenous betamethasone (BETA) and inhaled placebo or inhaled and intravenous placebo. Haemodynamics, gas exchange and lung mechanics were evaluated for 23 h after exposure to chlorine gas. RESULTS: Airway and pulmonary artery pressures increased and arterial oxygenation fell sharply (from 13.5 +/- 0.8 to 6.7 +/- 0.9 kPa, P < 0.001) after chlorine gas exposure. These immediate changes were followed by a gradual improvement over 5-7 h to a stable level of dysfunction for the rest of the experiment in placebo animals. Arterial oxygen tension, pulmonary vascular resistance and airway pressure recovered faster and more completely in the budesonide and betamethasone groups than in the placebo group (P < 0.01). Lung wet weight to dry weight ratios were greater in the placebo group than in the budesonide and betamethasone groups (6.34 +/- 0.59 vs. 5.56 +/- 0.38 and 5.53 +/- 0.54, respectively, P < 0.05). There was a trend towards lower histological injury scores compared with placebo in animals that received budesonide (P = 0.05) or betamethasone (P = 0.07). CONCLUSION: Treatment of chlorine gas lung injury with nebulized budesonide or intravenous betamethasone had similar positive effects on recovery of lung function.     

Randomised, double blind, placebo-controlled trial of selenium supplementation in adult asthma

BACKGROUND: Epidemiological evidence from observational studies has suggested that blood levels and dietary intake of selenium of adults with asthma are lower than those of controls. The only previous trial of selenium supplementation in adults with asthma found no objective evidence of benefit but involved only 24 participants. METHODS: A randomised, double blind, placebo-controlled trial of selenium supplementation was performed in adults with asthma in London, UK, the majority of whom (75%) reported inhaled steroid use at baseline. 197 participants were randomised to receive either a high-selenium yeast preparation (100 microg daily, n=99) or placebo (yeast only, n=98) for 24 weeks. The primary outcome was asthma-related quality of life (QoL) score. Secondary outcomes included lung function, asthma symptom scores, peak flow and bronchodilator usage. Linear regression was used to analyse the change in outcome between the two treatment arms by "intention to treat". RESULTS: There was a 48% increase in plasma selenium between baseline and end of trial in the active treatment group but no change in the placebo group. While the QoL score improved more in the active treatment group than in the placebo group, the difference in change in score between the two groups was not significant (-0.05 (95% CI -0.19 to 0.09); p=0.47). Selenium supplementation was not associated with any significant improvement in secondary outcomes compared with placebo. CONCLUSIONS: Selenium supplementation had no clinical benefit in adults with asthma, the majority of whom were taking inhaled steroids.     

Anticholinergics in the treatment of children and adults with acute asthma: a systematic review with meta-analysis

BACKGROUND: Current guidelines recommend the use of a combination of inhaled beta(2) agonists and anticholinergics, particularly for patients with acute severe or life threatening asthma in the emergency setting. However, this statement is based on a relatively small number of randomised controlled trials and related systematic reviews. A review was undertaken to incorporate the more recent evidence available about the effectiveness of treatment with a combination of beta(2) agonists and anticholinergics compared with beta(2) agonists alone in the treatment of acute asthma. METHODS: A search was conducted of all randomised controlled trials published before April 2005. RESULTS: Data from 32 randomised controlled trials (n = 3611 subjects) showed significant reductions in hospital admissions in both children (RR = 0.73; 95% CI 0.63 to 0.85, p = 0.0001) and adults (RR = 0.68; 95% CI 0.53 to 0.86, p = 0.002) treated with inhaled anticholinergic agents. Combined treatment also produced a significant increase in spirometric parameters 60-120 minutes after the last treatment in both children (SMD = -0.54; 95% CI -0.28 to -0.81, p = 0.0001) and adults (SMD = -0.36; 95% CI -0.23 to -0.49, p = 0.00001). CONCLUSIONS: This review strongly suggests that the addition of multiple doses of inhaled ipratropium bromide to beta(2) agonists is indicated as the standard treatment in children, adolescents, and adults with moderate to severe exacerbations of asthma in the emergency setting.     

Fatty acid levels and risk of asthma in young adults

BACKGROUND: There is current interest in the possible protective effect of long chain (n-3) fatty acids from fish in chronic lung diseases such as asthma. The aim of this community based cross sectional study was to determine whether plasma long chain (n-3) fatty acids, as a measure of dietary intake, differed between 1601 young adults with and without asthma. METHODS: Subjects of mean (SD) age 34.6 (7.1) years completed a detailed respiratory questionnaire, food frequency questionnaire, skin prick testing, and lung function tests including methacholine challenge test for bronchial hyperreactivity (BHR) and had venous blood taken for analysis of plasma fatty acids. Plasma fatty acid levels (%) were analysed using multiple logistic regression with alternative definitions of asthma and atopy as the outcomes. RESULTS: Atopy was not associated with any plasma fatty acid. The n-3 polyunsaturated fatty acids and n-6:n-3 ratio were not consistently associated with asthma or atopy. The n-6 polyunsaturated fatty acid dihomo gamma-linolenic acid (DHGLA) was positively associated with current asthma (OR=1.30, 95% CI 1.06 to 1.60), asthma (OR=1.34, 95% CI 1.13 to 1.60), and doctor diagnosed asthma (OR=1.25, 95% CI 1.06 to 1.48). CONCLUSION: Plasma n-3 fatty acids are not associated with a reduced risk of asthma or atopy among young adults. The association of DHGLA with asthma warrants further research to determine a cause-effect relationship.