A double-blind placebo-controlled study of the effect of inhaled beclomethasone dipropionate for 2 years in patients with nonasthmatic chronic obstructive pulmonary disease.

Treatment of chronic obstructive pulmonary disease (COPD) with inhaled and oral corticosteroids is common, although their exact role is unclear. Previous studies suggest these drugs may reduce decline in lung function in this group of patients. We report a study investigating the effect of inhaled beclomethasone diproprionate (BDP) on lung function and symptoms in a group of patients with COPD. Treatment was given for 2 years, and the decline in FEV1 in individual patients calculated over this period. Ninety-eight patients were randomized for the study, 59 completing 2 years of treatment. Patients withdrawn had more severe airflow obstruction. Decline in FEV1, measured both prior to and after bronchodilator, was less in patients receiving inhaled BDP, although the differences failed to reach statistical significance except in a subgroup of patients with more severe airflow obstruction. Exacerbation rates were also reduced by inhaled BDP, but again the differences failed to reach conventional levels of statistical significance. The results of this study are consistent with previous published work, but further insight into the long-term role of corticosteroids in COPD await the publication of large studies which have recently been completed. Although the changes seen in this study and others are numerically small, the rate of decline in FEV1 returned to normal levels expected from age-related decline, and hence such treatment combined with other strategies may well have a significant role in the long-term treatment of this condition.

Is high-dose fluticasone propionate via a metered-dose inhaler and Volumatic as efficacious as nebulized budesonide in adult asthmatics?

The efficacy and tolerability of fluticasone propionate (FP) 2 mg daily via a metered-dose inhaler and Volumatic (Glaxo Wellcome) spacer device was compared with nebulized budesonide (nBUD), 2 and 4 mg daily, in a multi-centre, open-label, cross-over study of adult asthmatics. Patients received, in random order, either 4 weeks of treatment with FP followed by 4 weeks of treatment with nBUD, or vice versa, with an intervening 4 week 'wash-out' period between treatments. Thirty patients completed the study, of whom 24 were evaluable. In terms of the primary efficacy parameter, change in mean morning peak expiratory flow (PEF) (l min-1) from baseline to the fourth week of each treatment period, FP was more effective than nBUD [mean difference (FP-nBUD) 21.1 l min-1, P = 0.007, 95% CI (6.5, 35.7)]. Sub-group analysis demonstrated FP to be superior to the 4 mg nBUD [mean treatment difference (FP-nBUD) 42.9 l min-1, P = 0.026, 95% CI (7.1, 78.8)] and at least as efficacious as the 2 mg nBUD sub-group [mean treatment difference (FP-nBUD) 10.2 l min-1, P = 0.211, 95% CI (-6.5, 26.9)]. Furthermore, larger reductions in diurnal variation were observed during FP treatment [mean treatment difference (FP-nBUD) -4.4 percentage points, P = 0.028, 95% CI (-8.4, -0.5)]. There was no significant difference between the treatments for the proportion of symptom-free 24 h periods. Of those expressing a preference, significantly more patients found FP via a metered-dose inhaler and spacer device both easier to administer (78%, P = 0.007) and more convenient to take (76%, P = 0.008) than nebulized budesonide. In addition, cost per patient analysis showed that nebulized budesonide was from 1.7 to 3.5 times more expensive than FP.

Health, employment, and financial outcomes in workers with occupational asthma.

OBJECTIVE: To study the health, employment, and financial outcome of occupational asthma. DESIGN: A follow study of workers with confirmed occupational asthma. SETTING: A specialist occupational lung disease clinic. SUBJECTS: All workers had a diagnosis of occupational asthma made at least one year earlier. Diagnosis was confirmed by serial peak expiratory flow measurement, specific bronchial provocation testing, or specific immunology. MAIN OUTCOME MEASURES: Respiratory symptoms, medication, pulmonary function, employment state, and financial position. RESULTS: 112 of a total of 140 eligible workers were followed up. 32% of patients remained exposed to the causative agent. These workers had more symptoms at follow up than those removed and a greater number were taking inhaled steroids. Continued exposure was also associated with a fall in % predicted forced expiratory volume in one second (FEV1) of 3% compared with that at presentation. Their median loss of annual income due to occupational asthma was 35%. Those removed from exposure were worse off financially (median loss 54% of annual income), had fewer respiratory symptoms than the group who remained exposed, and their % predicted FEV1 had improved by 4.6%. Statutory compensation and that obtained by common law suits did not match the loss of earnings due to the development of occupational asthma. Of the workers removed from exposure, those who no longer complained of breathlessness had been diagnosed significantly earlier after the onset of their first symptom (48 v 66 months, p = 0.001) and had a significantly higher FEV1 at presentation (90% v 73% predicted, p = 0.008) compared with those who were still breathless. They had developed symptoms earlier after first exposure (48 v 66 months, p > 0.05) and had been removed from exposure sooner (eight v 12 months, p > 0.05). CONCLUSION: Removal from exposure after diagnosis of occupational asthma is beneficial in terms of symptoms and lung function, but is associated with a loss of income. Early diagnosis is important for symptomatic improvement after removal from exposure. Inadequate compensation may contribute to the workers' decision to remain exposed after diagnosis.

Effects of high dose inhaled beclomethasone dipropionate, 750 micrograms and 1500 micrograms twice daily, and 40 mg per day oral prednisolone on lung function, symptoms, and bronchial hyperresponsiveness in patients with non-asthmatic chronic airflow obstruction.

BACKGROUND: The effect of treatment with inhaled corticosteroids in patients with non-asthmatic chronic airflow obstruction is still disputed. Whether any physiological improvements seen are accompanied by changes in bronchial responsiveness and symptoms and quality of life is also still unclear. METHODS: A sequential placebo controlled, blinded parallel group study investigating the effect of three weeks of treatment with inhaled beclomethasone dipropionate (BDP), 750 micrograms or 1500 micrograms twice daily, and oral prednisolone, 40 mg per day, was carried out in 105 patients with severe non-asthmatic chronic airflow obstruction (mean age 66 years, mean forced expiratory volume in one second (FEV1) 1.05 litres [40% predicted], geometric mean PD20 0.52 mumol). End points assessed were FEV1, forced vital capacity (FVC), and peak expiratory flow (PEF), bronchial responsiveness to inhaled histamine, and quality of life as measured by a formal quality of life questionnaire. RESULTS: Both doses of BDP produced equivalent, small, but significant improvements in FEV1 (mean 48 ml), FVC (mean 120 ml), and PEF (mean 12.4 l/min). The addition of oral prednisolone to the treatment regime in two thirds of the patients did not produce any further improvement in these parameters. Inhaled BDP produced a treatment response in individual patients (defined as an improvement in FEV1, FVC, or mean PEF of at least 20% compared with baseline values) more commonly than placebo (34% v 15%). The two doses of BDP were equally effective in this respect and again no further benefit of treatment with oral prednisolone was noted. Treatment with BDP for up to six weeks did not affect bronchial responsiveness to histamine. Small but significant improvements were seen in dyspnoea during daily activities, and the feeling of mastery over the disease. CONCLUSIONS: High dose inhaled BDP is an effective treatment for patients with chronic airflow obstruction not caused by asthma. Both objective and subjective measures show improvement. Unlike asthma, no improvement in bronchial responsiveness was detected after six weeks of treatment.

A prospective audit of the value of fibre optic bronchoscopy in adults admitted with community acquired pneumonia.

We audited our practice of bronchoscoping patients admitted with community acquired pneumonia to detect latent underlying abnormalities. Fifty-five bronchoscopies were performed immediately after clinical recovery in 64 sequential patients without obvious underlying carcinoma. Five (9.1%) showed abnormalities (four carcinomas and one mild tracheal stenosis). The detection rate of abnormalities and the number of unnecessary bronchoscopies would be improved if only those patients aged 50 years or over who were current or ex-smokers were bronchoscoped. In this group 13.9% (5/36) had an underlying abnormality. The cost implications of such a policy of early bronchoscopy are discussed and compared with traditional follow-up.

Response to corticosteroids in chronic airflow obstruction: relationship to emphysema and airways collapse.

We have studied the relationship between emphysema and airways collapse, and response to corticosteroids in patients with chronic airflow obstruction. One hundred and seven patients completed a placebo-controlled trial comparing 2 wks treatment with oral prednisolone 40 mg.day-1 to inhaled beclomethasone dipropionate 500 micrograms t.d.s. Response to corticosteroids was defined on the basis of changes in forced expiratory volume in one second (FEV1), and/or forced vital capacity (FVC), and/or mean peak expiratory flow (PEF) after treatment. Patients were categorized as those with physiologically defined emphysema (carbon monoxide transfer coefficient (KCO) less than 70% predicted and total lung capacity greater than 120% predicted), and those with pressure dependent airways collapse on the flow-volume loop (ratio of inspiratory to expiratory flow at 50% vital capacity [I:E50] greater than 10). The response to placebo showed a significant order effect, probably due to a carry-over effect of active treatment of at least 3 wks. Hence, the efficacy of active treatment over placebo in the subgroups defined was assessed by analysis of data generated from the first treatment phase of the trial. The presence or absence of physiologically defined emphysema did not affect the response to oral prednisolone. Inhaled beclomethasone dipropionate, however, was less effective in the emphysema group. Pressure dependent airways collapse did not affect the response to either prednisolone or beclomethasone. However, when data from all three treatment phases were analysed there was no significant difference in the response to either drug in any of the subgroups defined.(ABSTRACT TRUNCATED AT 250 WORDS)

Measures of reversibility in response to bronchodilators in chronic airflow obstruction: relation to airway calibre.

A study was carried out to examine the independence from starting prebronchodilator FEV1 of four indices commonly used to express airflow (FEV1) reversibility in response to bronchodilators. In 121 patients with chronic airflow obstruction with a mean prebronchodilator FEV1 of 1.81 (43.9% of predicted values) the change in FEV1 expressed as a percentage of the patient's predicted FEV1 was the least dependent on starting FEV1. Reversibility, expressed as a percentage of the prebronchodilator value or as a percentage of the maximal possible increase (predicted minus starting FEV1) was correlated with starting FEV1.

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

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.

Time course of response to oral and inhaled corticosteroids in non-asthmatic chronic airflow obstruction.

One hundred and twenty one patients considered on clinical grounds to have non-asthmatic chronic airflow obstruction completed a double blind, crossover trial comparing oral prednisolone 40 mg per day with inhaled beclomethasone dipropionate 500 micrograms thrice daily, each given for 14 days, with a 14 day washout period between treatments. The time course of response was analysed for the 57 occasions where there was a significant increase in mean daily peak expiratory flow (PEF) over the treatment period. Mean daily PEF was still rising at day 14 on 12 occasions. After withdrawal of treatment mean daily PEF remained above pretreatments levels for more than two weeks in half the responses analysed. The peak response occurred earlier with inhaled beclomethasone (median 9.5 (range 3-14) days) than with oral prednisolone (median 12 (range 1-14) days), though both treatments produced a response that was sustained for a similar period. The results suggest that a trial of treatment with corticosteroids in this group of patients should last more than 14 days, and that in a study with a crossover design the washout period should be longer than two weeks.

Association between risk factors for coronary heart disease in schoolboys and adult mortality rates in the same localities.

Risk factors for coronary heart disease were compared in fifth year boys (15-16 years old) from two schools that were chosen from localities with a fourfold difference in adult mortality from coronary heart disease. One school was in an underprivileged urban locality in the area of increased incidence of heart disease ('high risk') and the other in a semi-rural affluent locality with an incidence of heart disease similar to the national average ('low risk'). Smoking, hypertension, hypercholesterolaemia, obesity, physical fitness, and inactivity were evaluated as risk factors for coronary heart disease. Smoking, increased body fat, poor diet, and physical inactivity were found increased among pupils from the school in the high risk area compared with those in the low risk area. Lipids, maximum oxygen uptake, and hypertension were similar in both schools. The risk of coronary heart disease seems to reflect the adult mortality rates in the area. To reduce the overall incidence of coronary heart disease, health education should be directed towards prevention of smoking, improving diets, and increasing amounts of activity among school children, with special attention directed toward children in regions where there is a high mortality from coronary heart disease among adults.

The twenty-metre shuttle-running test: a combined test for maximal oxygen uptake and exercise-induced asthma?

A maximal multistage 'twenty-metre shuttle-running test' has already been developed to estimate maximal oxygen uptake (VO2 max). This field test requires little equipment or expertise, can be performed simultaneously by several subjects, and is widely used in physical education lessons. The present study assessed the potential for this test to provoke exercise-induced asthma in 73 schoolboys, aged 15-16 years. Measurements of the forced expiratory volume in one second (FEV1) were made at rest and 10 min after the twenty-metre shuttle-running test; exercise-induced asthma was defined as greater than a 10% fall in FEV1 after exercise. The pupils achieved 73 +/- 19 shuttles (mean +/- SD) giving a VO2 max of 47.0 +/- 5.3 ml kg-1 min-1. Exercise-induced asthma was documented in eight pupils (11%); two were known asthmatics who, despite taking pre-exercise B2 agonist treatment, had sharp falls in FEV1 (-25.4 and -25.6%); two had previously experienced occasional chest tightness or wheeze with exercise (-16.5 and -13.2% fall FEV1); but four were asymptomatic, with no previous asthmatic symptoms (-20.0, -18.2, -15.3 and -11.4% fall FEV1). This study has demonstrated the potential of the twenty-metre shuttle-running test to provoke exercise induced-asthma, and may therefore be a useful clinical test to assess for exercise-induced asthma when an estimate of VO2 max would also be helpful. Furthermore, physical education teachers should take basic precautions when using this test.(ABSTRACT TRUNCATED AT 250 WORDS)

Occupational asthma due to soft corrosive soldering fluxes containing zinc chloride and ammonium chloride.

Two cases of occupational asthma due to soft corrosive soldering fluxes used in metal jointing are described in which the diagnosis was based on work related deterioration in daily peak expiratory flow rate and positive responses in bronchial provocation tests. Both fluxes contained ammonium chloride and zinc chloride. Occupational asthma provoked by these agents has not previously been reported.

Transfer factor for carbon monoxide in patients with diabetes with and without microangiopathy.

The transfer coefficient (KCO) was significantly lower in diabetic patients with microangiopathy than in a matched group without this complication. This may reflect microangiopathy in the pulmonary circulation.

Occupational asthma due to oil mists.

Twenty five patients who were exposed to oil mists at their place of work were investigated for possible work related asthma. Serial peak expiratory flow recordings showed 13 to have definite work related asthma, seven equivocal work related asthma, and three asthma unrelated to work; two had normal recordings. Subjects with work related asthma often produced different patterns of peak flow response during the working week; patterns also varied between patients. Six of these patients had bronchial tests with oil from their place of work. Three had asthma induced by exposure to unused (clean) soluble oil and one reacted to used but not to clean oil. The challenge tests in the remaining two gave inconclusive results. It is concluded that occupational asthma due to oil mists is common, the peak flow response is heterogeneous, and the provoking agent within the oil may vary from worker to worker.

Roentgenographic signs of cervical injury.

The injured cervical spine may be completely examined without patient movement by positioning the X-ray tube relative to the injured patient. The prevertebral soft tissue in the cervical area is extremely important in the evaluation of injury, and a thickness of 5 mm or more at the level of the anterior inferior border of the body of C3 is indirect evidence of osseous injury. In hyperextension rotation cervical spine injuries the pillar view should always be taken. Anterior displacement of one vertical body upon another may be normal or secondary to trauma. Straightening or reversal of the cervical ordotic curve may be normal for the individual.