Showing papers in "Thorax in 1990"

Case-control study of prescribed fenoterol and death from asthma in New Zealand, 1977-81.

Abstract: A previous New Zealand case-control study of asthma deaths in the 5-45 year age group during 1981-3 found that prescription of fenoterol (by metered dose inhaler) was associated with an increased risk of death in patients with severe asthma. One major criticism of this study was that drug data for the cases and controls came from different sources. A new case-control design has been used to evaluate the same hypothesis, with a different set of asthma deaths, the same source for drug information being used for both cases and controls. This depended on identifying deaths from asthma during 1977-81 from national mortality records, and ascertaining which patients from those who died had been admitted to a major hospital for asthma during the 12 months before death. The study was confined to this subgroup, which accounted for about 20% of all asthma deaths in the areas served by a major hospital. For each of the eligible patients who died four age matched controls were selected from patients admitted to hospital for asthma during the year that the death occurred who had also had an admission for asthma in the previous 12 months. For the 58 cases and 227 control subjects information on prescribed drugs was collected from the hospital records relating to the previous admission. The odds ratio of asthma death in patients prescribed inhaled fenoterol was 1.99 (95% confidence interval 1.12-3.55, p = 0.02). As in the previous study, subgroups defined by markers of chronic asthma severity were also considered. The inhaled fenoterol odds ratio was 2.98 (95% CI 1.15-7.70, p = 0.02) in patients prescribed three or more categories of asthma drugs, 3.91 (95% CI 1.79-8.54, p less than 0.01) in patients with a previous admission for asthma in the past 12 months, and 5.83 (95% CI 1.62-21.0, p = 0.01) in patients prescribed oral corticosteroids at the time of admission. In patients with the most severe asthma (defined by a previous admission for asthma during the past 12 months and prescribed oral corticosteroids at time of admission) the inhaled fenoterol odds ratio was 9.82 (95% CI 2.23-43.4, p less than 0.01). These findings add further support to the hypothesis that inhaled fenoterol increases the risk of death in patients with severe asthma.

Pharyngeal shape and dimensions in healthy subjects, snorers, and patients with obstructive sleep apnoea.

Abstract: To characterise the relation between pharyngeal anatomy and sleep related disordered breathing, 17 men with complaints of snoring were studied by all night polysomnography. Ten of them had obstructive sleep apnoea (mean (SD) apnoea-hypopnoea index 56.3 (41.7), age 52 (10) years, body mass index 31.4 (5.3) kg/m2); whereas seven were simple snorers (apnoea-hypopnoea index 6.7 (4.6), age 40 (17) years, body mass index 25.9 (4.3) kg/m2). The pharynx was studied by magnetic resonance imaging in all patients and in a group of eight healthy subjects (age 27 (6) years, body mass index 21.8 (2.2) kg/m2, both significantly lower than in the patients; p less than 0.05). On the midsagittal section and six transverse sections equally spaced between the nasopharynx and the hypopharynx several anatomical measurements were performed. Results showed that there was no difference between groups in most magnetic resonance imaging measurements, but that on transverse sections the pharyngeal cross section had an elliptic shape with the long axis oriented in the coronal plane in normal subjects, whereas in apnoeic and snoring patients the pharynx was circular or had an elliptic shape but with the long axis oriented in the sagittal plane. It is suggested that the change in pharyngeal cross sectional shape, secondary to a reduction in pharyngeal transverse diameter, may be related to the risk of developing sleep related disordered breathing.

A hospital study of community acquired pneumonia in the elderly.

Abstract: Studies on community acquired pneumonia in the United States in patients over the age of 65 years have shown that Gram negative bacilli account for an appreciable proportion of cases, in addition to usual pathogens such as Streptococcus pneumoniae and Haemophilus influenzae. There have been no reports of community acquired pneumonia in the elderly in the United Kingdom. We undertook such a study to determine the clinical features, aetiology, and outcome. Seventy three patients (38 men) with ages ranging from 65 to 97 (median 79) years were studied prospectively. Pneumonia was defined as an acute lower respiratory tract infection with new, previously unrecorded shadowing on a chest radiograph. Patients with severe chronic illness in whom pneumonia was an expected terminal event were excluded. Nearly all the patients (96%) had respiratory symptoms or signs but many had features that might obscure the true diagnosis of pneumonia. Over half the patients had non-respiratory symptoms and over a third had no systemic signs of infection. A pathogen was identified in 43% of patients, most commonly Streptococcus pneumoniae, Haemophilus influenzae and influenza B virus. Gram negative bacilli were not seen. The mortality rate was high (33%). Early deaths were due to infection whereas later deaths were associated with other factors, such as stroke (two patients) and pulmonary embolism (two patients). Prognostic indicators for mortality were apyrexia, systolic hypotension, increasing hypoxaemia, and new urinary incontinence. As the range of pathogens causing pneumonia was the same in the elderly in this study as in other age groups it is suggested that initial antibiotic treatment for patients in this age group should always cover S pneumoniae and H influenzae.

Relation of ventilatory impairment and of chronic mucus hypersecretion to mortality from obstructive lung disease and from all causes.

Abstract: The relation of ventilatory impairment and chronic mucus hypersecretion to death from all causes and death from obstructive lung disease (chronic bronchitis, emphysema and asthma) was studied in 13,756 men and women randomly selected from the general population of the City of Copenhagen. During the 10 year follow up 2288 subjects died. In 164 subjects obstructive lung disease was considered to be an underlying or a contributory cause of death (obstructive lung disease related death); in 73 subjects it was considered to be the underlying cause of death (obstructive lung disease death). Forced expiratory volume in one second, expressed as a percentage of the predicted value (FEV1% pred), and the presence of chronic phlegm were used to characterise ventilatory function and chronic mucus hypersecretion respectively. For mortality analysis the proportional hazards regression model of Cox was used; it included age, sex, pack years, inhalation habit, body mass index, alcohol consumption, and the presence or absence of asthma, heart disease, and diabetes mellitus as confounding factors. By comparison with subjects with an FEV1 of 80% pred or more, subjects with an FEV1 below 40% pred had increased risk of dying from all causes (relative risk (RR) = 5.0 for women, 2.7 for men), a higher risk of obstructive lung disease related death (RR = 57 for women, 34 for men), and a higher risk of obstructive lung disease death (RR = 101 for women, 77 for men). Chronic mucus hypersecretion was associated with only a slightly higher risk of death from all causes (RR = 1.1 for women, 1.3 for men). The association between chronic mucus hypersecretion and obstructive lung disease death varied with the level of ventilatory function, being weak in subjects with normal ventilatory function (for an FEV1 of 80% pred the RR was 1.2), but more pronounced in subjects with reduced ventilatory function (for an FEV1 of 40% pred the RR was 4.2). A similar though statistically non-significant trend was observed with regard to obstructive lung disease related death. This study shows that impaired lung function is very strongly related to total mortality, obstructive lung disease related mortality, and obstructive lung disease mortality and suggests that chronic mucus hypersecretion, in those with impaired ventilatory function, is also a significant risk factor for death from obstructive lung disease.

Quantification of airborne moulds in the homes of children with and without wheeze.

Abstract: A population survey of 1000 7 year old children found a significant excess of wheeze among children whose homes were reported to be mouldy (odds ratio 3.70, 95% confidence limits 2.22, 6.15). The airborne mould flora was quantified by repeated volumetric sampling during the winter in three rooms of the homes of 88 children. All of these had previously completed spirometric tests before and after a six minute free running exercise challenge. Total airborne mould counts varied from 0 to 41,000 colony forming units (CFU)/m3, but were generally in the range 50-1500 CFU/m3, much lower than the concentrations found outdoors in summer. The principal types of fungi identified are all known to be common out of doors, and most were found on at least one occasion in most of the homes. Median and geometric mean total mould counts were not related to reports of visible mould in the home, or to a history of wheeze in the index child. The heterogeneous group of non-sporing fungi (mycelia sterilia) were the only airborne fungi present at significantly higher concentrations in the homes of wheezy children (geometric mean 2.1 v 0.7 CFU/m3. A non-significant increase in total mould counts was observed in the homes of children with a 10% or greater decline in FEV1 after exercise (geometric mean 354 v 253 CFU/m3). Questionnaire reports of mould in the home may be a poor indicator of exposure to airborne spores. The total burden of inhaled mould spores from indoor sources is probably not an important determinant of wheeze among children in the general population. Although the association with mycelia sterilia could be a chance finding, these non-sporing isolates may include a potent source of allergen.

Comparison of bronchodilator responses and deposition patterns of salbutamol inhaled from a pressurised metered dose inhaler, as a dry powder, and as a nebulised solution.

Abstract: The lung dose and deposition patterns of drug delivered by dry powder inhaler are not known. The effects of inhaling 400 micrograms salbutamol delivered by dry powder inhaler (two 200 micrograms salbutamol Rotacaps), by pressurised metered dose inhaler, and by Acorn nebuliser were studied in nine subjects with chronic stable asthma. Technetium-99m labelled Teflon particles were mixed with micronised salbutamol in the pressurised metered dose inhaler and in the capsules; technetium-99m labelled human serum albumin was mixed with the salbutamol solution for the nebuliser study. The pressurised metered dose inhaler deposited 11.2% (SEM 0.8%) of the dose within the lungs; this was significantly more than the dose deposited by the dry powder inhaler (9.1% (0.6%], but did not differ significantly from the dose delivered by the nebuliser (9.9% (0.7%]. Distribution within the peripheral third of the lung was significantly greater with the nebuliser than with the other two systems; FEV1 improved to a significantly greater extent after inhalation of 400 micrograms salbutamol from the pressurised metered dose inhaler (35.6% from baseline) than from the nebuliser (25.8%) or dry powder inhaler (25.2%). Thus after inhalation of similar doses of salbutamol a larger proportion of drug was deposited within the lungs when it was inhaled from a metered dose inhaler than from a dry powder system; the nebuliser achieved the greatest peripheral deposition. The bronchodilator response seems to depend on the amount of drug within the lungs rather than its pattern of distribution.

Chemotherapy and management of tuberculosis in the United Kingdom: recommendations of the Joint Tuberculosis Committee of the British Thoracic Society.

Abstract: The number of notified cases of tuberculosis in Britain has fallen over the last 10 years but the disease still causes appreciable morbidity and mortality.' 2 There have been major changes in the staffing of thoracic medicine over the same period since the retirement of many physicians with long experience of tuberculosis. The treatment of tuberculosis depends not only on the correct prescription of effective chemotherapy regimens but also on the patient's compliance with treatment. Several studies have shown that when treatment is not supervised by thoracic physicians prescription errors and excessive or inadequate treatment occur in an appreciable proportion of patients.5 The patient's compliance is a major determinant of the success of drug treatment, and is more likely to be achieved if the most effective and shortest regimens are prescribed correctly, with treatment monitored, and adjusted if necessary, by an experienced physician. Recent studies have shown problems of compliance and default (10O,,) and drug toxicity (10°O) in adult patients in England and Wales.6 In view of the development of effective short course regimens and major changes in the staffing of the services that provide tuberculosis treatment, the Joint Tuberculosis Committee of the British Thoracic Society believes that it is now opportune to issue guidelines for the management of tuberculosis in the United Kingdom. Guidelines have been published recently by the American Thoracic Society7 and by the International Union against Tuberculosis and Lung Diseases.8 The committee considers that treatment of all cases of adult pulmonary tuberculosis should be supervised by physicians in thoracic medicine, and that the drug treatment of all forms of adult non-pulmonary tuberculosis should at the very least be supervised in conjunction with a thoracic physician. The treatment of children should be shared by a paediatrician and a thoracic physician.

Benefits and problems of a physical training programme for asthmatic patients.

Abstract: The clinical and physiological effects of a medically supervised, indoor physical training programme were investigated in 36 asthmatic subjects aged 16-40 years. After clinical evaluation, lung function assessment, and progressive incremental exercise testing subjects were randomly allocated to control and training groups. The measurements were repeated after a six week run in period and after a further three months in which those in the training group underwent an indoor training programme. The measurements made at three months were compared with those at the end of the run in period. There was no significant change in anthropometric characteristics, blood lipid profiles, or the provocative concentration of histamine causing a 20% fall in FEV1 (histamine PC20) in the group who underwent training. After training there were significant increases in mean maximal oxygen uptake (ml kg-1 min-1) from 23 (5) to 28 (6), oxygen pulse (ml/beat) from 8.8 (2.3) to 10.8 (2.4), and anaerobic threshold (1/min) from 1.11 (0.27) to 1.38 (0.33). These changes were significantly greater in the group undergoing training than in the control group. There was also a significant fall in breathlessness scores (Borg ratings), blood lactate, carbon dioxide output, and minute ventilation during submaximal exercise in the training group, with no change in the control group. The subject's motivation, the initial level of fitness, and the symptom score at the time of training were the most important factors influencing improvements in cardiorespiratory fitness. Thus submaximal physical exercise of controlled intensity, sustained for three months, produced significant improvements in fitness and cardiorespiratory performance that should be advantageous to the exercising asthmatic patient. The availability of medical supervision throughout the exercise programme appears to have contributed to the successful outcome.

Value of washings and brushings at fibreoptic bronchoscopy in the diagnosis of lung cancer.

Abstract: A retrospective study was performed to evaluate the diagnostic yield for lung cancer from histological biopsy specimens and from washings and brushings for cytological examination taken at fibreoptic bronchoscopy. The records of 680 bronchoscopies were analysed. Of 300 patients eventually diagnosed as having a malignant lesion, 188 had had biopsy, washing, and brushing. Of these, 125 had endoscopically visible tumour (group A) and 63 had no abnormal findings or abnormal findings that were not diagnostic of malignancy (group B). In group A biopsy specimens gave a positive result in 76% of cases, washings in 49.6%, and brushings in 52%; biopsy material gave the only positive result in 22.4% of cases, washings in 2.2%, and brushings in 4.8%. In group B biopsy specimens were positive in 36.5%, washings in 38.1%, and brushings in 28.6%; biopsy gave the only positive result in 11.1% of cases, washing in 9.5%, and brushing in 3.2%. Washing had a higher diagnostic yield than brushing in group B. Biopsy and cytological examination of either washings or brushings were found to give over 95% of all positive results in group A, but in group B the combination of biopsy and washing was more often successful (94.3%) than biopsy and brushing (82.8%). It is concluded that for the maximum diagnostic yield in the diagnosis of lung cancer biopsy should be combined with cytology using both washings and brushings.

Physiology and treatment of cough.

Abstract: excess secretions. It is characterised by a violent expiration, which provides the high flow rates that are required to shear away mucus and remove foreign particles from the larynx, trachea, and large bronchi. Most sensory stimuli that cause coughing also increase airway secretion, which is beneficial as this provides a vehicle for explusion of particulate matter. Cough is a very common presenting symptom in general practice and in the chest clinic. The prevalence of cough in the population depends on the prevalence of smoking and other environmental factors and in different populations has varied from 5°0 to 400%.One indication of the size of the problem is the self prescription of over the counter antitussives, which has been estimated at 75 million doses

Respiratory failure and sleep in neuromuscular disease.

Abstract: Sleep hypoxaemia in non-rapid eye movement (non-REM) and rapid eye movement (REM) sleep was examined in 20 patients with various neuromuscular disorders with reference to the relation between oxygen desaturation during sleep and daytime lung and respiratory muscle function. All the patients had all night sleep studies performed and maximum inspiratory and expiratory mouth pressures (PI and Pemax), lung volumes, single breath transfer coefficient for carbon monoxide (KCO), and daytime arterial oxygen (PaO2) and carbon dioxide tensions (PaCO2) determined. Vital capacity in the erect and supine posture was measured in 14 patients. Mean (SD) PI max at RV was low at 33 (19) cm H2O (32% predicted). Mean PE max at TLC was also low at 53 (24) cm H2O (28% predicted). Mean daytime PaO2 was 67 (16) mm Hg and PaCO2 52 (13) mm Hg (8.9 (2.1) and 6.9 (1.7) kPa). The mean lowest arterial oxygen saturation (SaO2) was 83% (12%) during non-REM and 60% (23%) during REM sleep. Detailed electromyographic evidence in one patient with poliomyelitis showed that SaO2% during non-REM sleep was maintained by accessory respiratory muscle activity. There was a direct relation between the lowest SaO2 value during REM sleep and vital capacity, daytime PaO2, PaCO2, and percentage fall in vital capacity from the erect to the supine position (an index of diaphragm weakness). The simple measurement of vital capacity in the erect and supine positions and arterial blood gas tensions when the patient is awake provide a useful initial guide to the degree of respiratory failure occurring during sleep in patients with neuromuscular disorders. A sleep study is required to assess the extent of sleep induced respiratory failure accurately.

Reduced selenium in asthmatic subjects in New Zealand.

Abstract: Selenium is an essential component of glutathione peroxidase, an enzyme that helps protect cells against oxidation damage and modulates the lipoxygenase pathway of arachidonic acid metabolism. Low selenium concentrations might therefore influence the inflammatory process in asthma by reducing the activity of glutathione peroxidase. Whole blood and plasma selenium concentrations and glutathione peroxidase activity have been measured in 56 asthmatic patients and 59 non-asthmatic control subjects in New Zealand, a country with a low dietary selenium intake and a high prevalence of asthma. When compared with control subjects the asthmatic patients had lower values for whole blood selenium concentrations (-4.9, 95% confidence interval -10.2 to 0.4 ng/ml) and glutathione peroxidase activity (-3.3, 95% CI -5.8 to -0.8 units/g Hb). There was a 1.9 and 5.8 fold increased risk of asthma in subjects with the lowest range of whole blood selenium concentration and glutathione peroxidase activity respectively (95% CI 0.6 to 5.6 and 1.6 to 21.2). Levels were lower in patients and control subjects without an atopic predisposition, but were not affected by prednisone use. Similar differences between the asthmatic and control subjects were not observed for selenium concentration or glutathione peroxidase activity measured in plasma, which reflects short term rather than long term selenium content. These findings are consistent with the hypothesis that low selenium concentrations may have a role in the pathogenesis of asthma in New Zealand.

Morphological integrity of the bronchial epithelium in mild asthma.

Abstract: In severe asthma bronchial epithelial cells are damaged and detached, and it has been proposed that such damage might lead to the bronchial hyperresponsiveness that characterises asthma. To investigate the relation between airway hyperresponsiveness and epithelial damage, biopsy specimens of the bronchial mucus membrane were obtained at fibreoptic bronchoscopy from 11 patients with mild atopic asthma and airway hyperresponsiveness (provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) less than 1.0 mg/ml), and from 17 healthy non-atopic subjects who did not have airway hyperresponsiveness (PC20 methacholine greater than 8.0 mg/ml). Observers who were blind to the presence or absence of asthma examined the biopsy specimens by light and electron microscopy. Epithelial cells, intercellular spaces, and goblet cells were counted. Intercellular junctional complexes were examined, and a semiquantitative assessment was made of ciliary loss, non-parallel central ciliary filaments, and vacuoles in ciliated cells. There were no differences between the asthmatic and healthy groups in any of these measurements. These findings indicate that airway hyperresponsiveness may be present when there is no apparent change in the structure of the bronchial epithelium.

Corticosteroid trials in non-asthmatic chronic airflow obstruction: a comparison of oral prednisolone and inhaled beclomethasone dipropionate.

Abstract: One hundred and twenty seven adults considered on clinical grounds to have non-asthmatic chronic airflow obstruction entered a randomised, double blind, placebo controlled, crossover trial comparing the physiological response to inhaled beclomethasone dipropionate 500 micrograms thrice daily with oral prednisolone 40 mg a day, both given for two weeks. One hundred and seven patients completed the study. Response was assessed as change in FEV1 and FVC measured on the last treatment day, and as change in mean peak expiratory flow (PEF) over the final seven days of treatment from home PEF recordings performed five times daily. A full response to treatment was defined as an increase in FEV or FVC, or an increase in mean daily PEF over the final seven days of treatment, of at least 20% from baseline values. An improvement in one measurement of at least 15%, or of 10% in any two measurements, was defined as a partial treatment response. Response to placebo showed a significant order effect, suggesting a carry over effect of active treatment of at least three weeks. Response to active treatment was therefore related to initial baseline values, and compared with placebo by considering responses in the first treatment phase only. A full response to oral prednisolone (16/38) was significantly more common than to placebo (3/35). The number of full responses to inhaled beclomethasone (8/34) did not differ significantly from the number responding to oral prednisolone or placebo in the first treatment phase, though full and partial responses to inhaled beclomethasone (12/34) were significantly more common than those to placebo (4/35). When all three treatment phases were considered 44/107 patients showed a full response to one or both forms of corticosteroid treatment, a response to prednisolone (39) occurring more frequently than to inhaled beclomethasone (26). Only 21 of the 44 responders showed a response to both forms of treatment. Inhaled beclomethasone dipropionate 500 micrograms thrice daily was inferior to oral prednisolone 40 mg per day, but better than placebo, in producing improvement in physiological measurements in patients thought to have nonasthmatic chronic airflow obstruction. It was, however, an effective alternative in over half of those showing a response to prednisolone.

Cystic fibrosis. 1. Pseudomonas aeruginosa infection in cystic fibrosis and its management.

Abstract: Cystic fibrosis is the most prevalent of the fatal inherited diseases in white populations. It is characterised by the triad of chronic pulmonary disease, pancreatic insufficiency, and increased concentrations of electrolytes in sweat. Most patients are treated in specialised centres and at least 40 000 are alive in Europe and the United States. Until recently cystic fibrosis was exclusively a childhood disorder (and indeed most patients are still treated in paediatric clinics), but more aggressive treatment regimens in children has resulted in prolonged survival and an improved quality of life. A median survival of 25-30 years is now common and an understanding of the molecular pathology of cystic fibrosis is likely to lead to further improvements in treatment and survival. Respiratory physicians will therefore be concerned increasingly in the care of adult patients with cystic fibrosis and the management of their chronic lung infections, the most important of which is caused State Seruminstitute by Pseudomonas aeruginosa. and University of A detailed understanding of the patho-

Jet and ultrasonic nebuliser output: use of a new method for direct measurement of aerosol output.

Abstract: Output from jet nebulisers is calibrated traditionally by weighing them before and after nebulisation, but the assumption that the weight difference is a close measure of aerosol generation could be invalidated by the concomitant process of evaporation. A method has been developed for measuring aerosol output directly by using a solute (fluoride) tracer and aerosol impaction, and this has been compared with the traditional weight loss method for two Wright, six Turbo, and four Micro-Cirrus jet nebulisers and two Microinhaler ultrasonic nebulisers. The weight loss method overestimated true aerosol output for all jet nebulisers. The mean aerosol content, expressed as a percentage of the total weight loss, varied from as little as 15% for the Wright jet nebulisers to 54% (range 45-61%) for the Turbo and Micro-Cirrus jet nebulisers under the operating conditions used. In contrast, there was no discrepancy between weight loss and aerosol output for the ultrasonic nebulisers. These findings, along with evidence of both concentrating and cooling effects from jet nebulisation, confirm that total output from jet nebulisers contains two distinct fractions, vapour and aerosol. The vapour fraction, but not the aerosol fraction, was greatly influenced by reservoir temperature within the nebuliser; so the ratio of aerosol output to total weight loss varied considerably with temperature. It is concluded that weight loss is an inappropriate method of calibrating jet nebuliser aerosol output, and that this should be measured directly.

Decline of lung function and development of chronic airflow limitation: a longitudinal study of non-smokers and smokers in Busselton, Western Australia.

Abstract: Data collected during seven population health surveys over 18 years in Busselton, Western Australia, were examined to determine the effect of smoking on lung function and to investigate the development of chronic airflow limitation. Lung function was measured and details of respiratory illness and smoking histories were collected from subjects attending surveys at three year intervals from 1966 to 1984. Data from ex-smokers and asthmatic patients (diagnosis based on answer to questionnaire) were excluded. Regression of height adjusted forced expiratory volume in one second (FEV1) on age was calculated individually for 759 non-smokers and 225 regular smokers with four or more observations. Decline in height adjusted FEV1 was similar for men and women. In smokers the rate of decline in FEV1 was greater than in non-smokers and was related to the amount smoked, to the extent that a smoker could expect a 20-30% greater rate of decline than a non-smoker of the same age. Chronic airflow limitation (defined as FEV1/FEV less than 65% or FEV1 less than 65% predicted on at least two occasions) was common, occurring in 24% of men and 18% of women who were regular smokers and in 5% of male and 8% of female non-smokers. These figures are higher than those reported in other populations, especially for women and for non-smokers. Not all chronic airflow limitation was associated with respiratory symptoms, confirming that the condition may be unrecognised until it is advanced.

Do large volume spacer devices reduce the systemic effects of high dose inhaled corticosteroids

Abstract: When used in high doses, inhaled corticosteroids may cause suppression of the hypothalamo-pituitary-adrenal axis. The influence of the mode of drug inhalation on the degree of this suppression is not clear. Hypothalamo-pituitary-adrenal function was assessed by measurement of 0900 h serum cortisol concentrations, a short tetracosactrin test, and 24 hour urine free cortisol excretion in 48 adults with asthma taking 1500-2500 micrograms beclomethasone dipropionate daily via a metered dose aerosol. Twelve patients had hypothalamo-pituitary-adrenal suppression, as judged by subnormal results from at least two of the three tests or (in one patient) by an abnormal insulin stress test response. These patients then changed to inhaling the same dose of beclomethasone dipropionate through a 750 ml spacer device (Volumatic). The endocrine tests were repeated from nine days to eight weeks later in 10 patients. Comparison with initial values showed that adding the spacing device caused an increase in the median 0900 h cortisol concentration from 126 nmol/l to 398 nmol/l, in the post-tetracosactrin cortisol concentration from 402 nmol/l to 613 nmol/l and in 24 hour urine free cortisol excretion from 54 nmol to 84 nmol. The rise in serum cortisol concentration in response to tetracosactrin did not change. Evidence of persisting hypothalamo-pituitary-adrenal axis suppression was present in only four of the 10 patients; the most pronounced improvements in function tended to occur in those who had never required long term oral corticosteroids. The results from this uncontrolled study suggest that asthmatic patients taking high dose beclomethasone dipropionate may minimise adverse effects by using a large volume spacer device.

Rib cage mechanics after median sternotomy.

Abstract: A substantial reduction in lung volumes occurs after sternotomy, but the mechanism or mechanisms are unclear. Measurements were made of lung volumes and of chest wall motion with four pairs of magnetometers (two pairs for anteroposterior rib cage, one for lateral rib cage, and one for anteroposterior abdominal dimensions) in 16 men before and one week and three months after coronary artery grafting. Reductions in all lung volumes occurred after sternotomy and were greater in the supine than in the sitting position. Supine vital capacity was reduced one week after surgery, with almost complete recovery at three months. One week after sternotomy there was a significant reduction in tidal volume from a mean (95% confidence limits) value of 0.88 (0.76-1.00) litre to 0.61 (0.52-0.70) l, and in supine rib cage displacement from 3.87 (1.96-5.78) mm to 0.44 (-0.61-1.49) mm in the lateral plane. Respiratory frequency increased from 16 (13-19) to 21 (19-24)/min. Coordination of the rib cage was assessed by measuring the difference in timing of onset of chest wall motion and airflow in four planes. At one week nine of 14 patients showed uncoordination between airflow and rib cage motion in one or more dimensions, and this was still present in three patients at three months. No loss of the temporal relation between airflow and abdominal wall motion was detected. The results suggest that reduced and uncoordinated rib cage expansion contributes to the restrictive ventilatory defect that follows median sternotomy.

Effects of lung resection on pulmonary function and exercise capacity.

Abstract: The effects of lung resection on exercise capacity and perception of symptoms were studied in 47 patients aged 39-73 (mean 58.3) years. Twenty had a pneumonectomy and 27 a lobectomy, all for lung cancer. Forced expiratory volume, maximal inspiratory and expiratory pressures, and progressive maximal one minute incremental cycle ergometer exercise performance were measured before and after surgery. Breathlessness and leg discomfort were assessed with a modified Borg scale (0-10). Mean FEV1 decreased from 79% (SD 22%) to 53% (11%) of the predicted value after pneumonectomy and from 89% (22%) to 74% (18%) after lobectomy. Exercise capacity, measured as the highest work load completed, Wmax, decreased from 78% (25%) to 58% (28%) predicted in the pneumonectomy group and from 77% (21%) to 67% (20%) in the lobectomy group. There was only a weak relation between changes in FEV1 and changes in Wmax (r = 0.54, r2 = 0.30). The slope of the relation between the intensity of dyspnoea and work load or the intensity of dyspnoea and ventilation increased significantly after pneumonectomy, but not after lobectomy. Leg discomfort increased more rapidly when related to work load after both pneumonectomy and lobectomy. After resection dyspnoea was rarely the only limiting factor at maximal exercise. It is concluded that (1) change in FEV1 is a poor predictor of change in exercise capacity after lung resection; (2) pneumonectomy results in a 25% decrease in Wmax and in an appreciable increase in dyspnoea during exercise; (3) lobectomy has little or no effect on Wmax or the intensity of postoperative dyspnoea; (4) after both pneumonectomy and lobectomy leg discomfort makes an important contribution to exercise limitation.

Prospective study of mycobacterial infections in patients with cystic fibrosis.

Abstract: Fifty four patients with cystic fibrosis, aged 3-67 years, were studied prospectively for pulmonary mycobacterial infection. Sputum smears and cultures were carried out and intradermal skin tests performed. Mycobacteria were cultured from six patients in association with clinical deterioration; four patients had positive direct smears. Mycobacterium tuberculosis, M aviumintracellulare, M kansasii, and M gordonae were isolated. There were no deaths and all improved with chemotherapy. A third of the other 48 patients had positive skin test responses (greater than 6 mm) to purified protein derivative (PPD) tuberculin and 21 to one or more antigens prepared from non-tuberculous mycobacteria. Sensitisation increased with age; before the age of 11 only one patient had a positive response to PPD tuberculin and none to any other antigen. This was less than in healthy control subjects of similar age. After age 11 the reactions in sensitised patients were stronger than in positive healthy control subjects. Our study indicates that it is important to consider mycobacterial infection in patients with cystic fibrosis who deteriorate without obvious cause.

A general practice based survey of bronchial hyperresponsiveness and its relation to symptoms, sex, age, atopy, and smoking.

Abstract: The prevalence and associations of bronchial hyperresponsiveness were investigated in a general practice population The sample was obtained by using every 12th patient on the practice age-sex register, replacing non-responders with corresponding age and sex matched individuals from up to two further 1 in 12 samples The response rate was 43%; 366 patients were studied Doubling concentrations of methacholine were given to a maximum of 32 mg/ml or until a 20% fall in forced expiratory volume in one second (FEV1) occurred (provocation concentration, PC20FEV1) Bronchial hyperresponsiveness was defined arbitrarily as a PC20FEV1 of 2 mg/ml or less (or 11 mumol cumulative dose, PD20FEV1) The prevalence of bronchial hyperresponsiveness was 23% Bronchial hyperresponsiveness was not associated with age but was more prevalent in women than men (31%:13%) It was also more common in those who had ever wheezed (39%) and in those who had had an attack of rhinitis in the preceding month (45%, p less than 01), in atopic individuals (30%), and in smokers (32%), but it was not associated with cough or dyspnoea There was a positive correlation between PC20FEV1 and resting FEV1 (r = 0288) and a negative correlation between PC20FEV1 and mean daily peak flow variability (r = -0356) Stepwise binary logistic regression analysis showed significant independent effects on PC20FEV1 for mean daily peak flow variability, gender, number of positive skin test responses, resting FEV1, and mean histamine skin weal area, but no relation with smoking or mean allergen weal area The prevalence of bronchial hyperresponsiveness was much higher than the prevalence of diagnosed asthma in the practice in 1984 (49%) Analysis of case notes of 169 individuals showed that those with bronchial hyperresponsiveness had not attended the practice more frequently for respiratory complaints during the previous five years

Relation of urinary cotinine concentrations to cigarette smoking and to exposure to other people's smoke.

Abstract: The relation of urinary cotinine measurements to tobacco consumption in smokers and to exposure to other people's smoke in non-smokers was studied in 49 smokers and 184 reported non-smokers attending a health screening centre. The median urinary cotinine concentration was 1623 ng/ml in the smokers and 6.1 ng/ml in the non-smokers. In smokers the average urinary cotinine concentration increased with reported habitual cigarette consumption; in non-smokers it increased with the reported total seven day duration of exposure to other people's tobacco smoke. Cotinine concentrations were approximately three times higher in non-smokers living with a spouse or partner who was a smoker than in those living with a non-smoker; their reported duration of exposure to tobacco smoke was also three times higher. Non-smoking subjects who were exposed to any tobacco smoke and who lived with a smoker reported 70% of their exposure to be at home (56% for men and 86% for women); the men reported more exposure at work than non-smoking men who lived with a non-smoker. This study confirms the relation of urinary cotinine to stated tobacco smoke exposure in both smokers and non-smokers and further validates the use of information on the smoking habits of the spouse or partner as a measure of tobacco smoke exposure in epidemiological studies of non-smokers.

Sex difference in the inhaled tartaric acid cough threshold in non-atopic healthy subjects.

Abstract: The threshold for cough induced by inhaled tartaric acid was measured in 71 non-atopic healthy volunteers. The cough threshold was lower in women than in men, which may be relevant to previous reports that angiotensin converting enzyme inhibitors induce cough more frequently in women than in men.

Bronchoscopic cryotherapy for advanced bronchial carcinoma.

Abstract: A prospective study was carried out to assess the value of bronchoscopic cryotherapy for palliation of inoperable bronchial carcinoma with bronchial obstruction. Symptoms, lung function, and chest radiographic and bronchoscopic findings were recorded serially before and after 81 cryotherapy sessions in 33 consecutive patients. Most patients improved in terms of overall symptoms, stridor, and haemoptysis and they had an overall improvement in dyspnoea. Objective improvement in lung function was seen in 58% of patients and the changes in lung function correlated with symptoms. Bronchoscopic evidence of relief of bronchial obstruction was seen in 77% of patients and 24% showed improvement in degree of collapse on the radiograph. There were no important complications. These results compare favourably with the results in published series of patients having laser therapy. It is concluded that bronchoscopic cryotherapy is valuable for the palliation of inoperable bronchial carcinoma.

Potassium channels and airway function: new therapeutic prospects.

Abstract: Potassium (K+) channels have long been associated with recovery of excitable cells after depolarisation and drugs that block these channels, such as tetraethylammonium and 4aminopyridine, cause an increase in excitability. In airway smooth muscle these K+ channel blocking drugs result in spontaneous action potentials and a reduced threshold of excitation,'2 which may be similar to the electrophysiological changes described in asthmatic airways.' The recent development of drugs that open K+ channels in smooth muscle has reawakened interest in potassium channels because such drugs relax airway smooth muscle and may reduce the hyperreactivity of asthma. It is now clear that there is great diversity ofK+ channels in different cells, raising the possibility that selective drugs may be developed for specific cell types, with therapeutic benefit. We review here some ofthe recent developments in understanding K+ channels in airways and the therapeutic prospects for new K+ channel activators.

Pulmonary sequelae in survivors of congenital diaphragmatic hernia.

Abstract: Nineteen survivors of congenital diaphragmatic hernia repair were compared with age and sex matched control children six to 11 years after repair. All subjects were examined clinically and underwent lung function testing. The patients also had individual lung volumes assessed radiographically and had radionuclide (krypton-81 m, technetium-99 m macroaggregates) ventilation-perfusion (V/Q) lung scans. Four patients had pectus excavatum and two had mild scoliosis. Spirometric measurements were lower in the patients than in the control subjects but only the differences in peak expiratory flow and flow at 50% of expired vital capacity were significant. The radiographic left lung volumes in patients surviving left diaphragmatic repair were larger than expected at 49.3% (SD 2%), suggesting alveolar overdistension. V/Q scans showed a mismatch in the ipsilateral lung, mean Q (40% (7%] being significantly lower than mean V (47% (6%)). In seven patients who had required ventilation for four days or more perfusion to the ipsilateral lung was significantly lower (34% (6%)) than values for the 12 patients ventilated for less than four days (43% (6%)). Survivors of right diaphragmatic repair had a better outcome in terms of relative radiographic lung volumes and V/Q distribution. More severely affected children are now surviving repair of congenital diaphragmatic herniation, with residual pulmonary abnormalities that could produce functional impairment in adult life.

Pulmonary function in healthy young adult Indians in Madras.

Abstract: Forced vital capacity, forced expiratory volume in one second, functional residual capacity, residual volume, total lung capacity, and single breath diffusing capacity measurements (effective alveolar volume, carbon monoxide transfer factor, and transfer coefficient) were measured in 247 young healthy adults (130 male, 117 female) aged 15-40 years living in Madras. Subjects were of Dravidian stock, living at sea level with rice as their staple diet. Regression equations were derived for men and women for predicting normal pulmonary function for young adults in South India. The values were similar to those reported for subjects from Western India and lower than those reported for North Indians and caucasians.

Formoterol, a new long acting beta 2 agonist for inhalation twice daily, compared with salbutamol in the treatment of asthma.

Abstract: Sixteen patients with stable chronic asthma participated in a double blind crossover study comparing the new inhaled long acting beta 2 agonist formoterol with salbutamol Inhaled (n = 15) and oral steroid (n = 1) treatment were maintained at the same daily dose throughout the study For four weeks the patients received either formoterol 24 micrograms twice daily or salbutamol 400 micrograms twice daily, plus additional puffs (with the same drug) when needed Asthma symptoms, additional puffs of beta 2 agonist, peak expiratory flow (PEF), and side effects were recorded daily During treatment with formoterol the patients used fewer additional puffs of beta 2 agonist, had better symptom scores, less disturbed sleep, more days without additional aerosol, and higher PEF both morning and evening than during salbutamol treatment Thus formoterol 24 micrograms twice daily gave long lasting bronchodilatation and asthma symptoms were well controlled with regular twice daily administration