Electronic diaries for asthma.
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Adolescent↗
Biomedical subjects
G K Crompton
Publications and source records attributed to G K Crompton.
Glucocorticoid resistance in asthma.
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Asthma↗
Pulmonary eosinophilia with systemic features: therapy and prognosis.
Of 65 patients presenting with pulmonary eosinophilia to one Respiratory Unit during a 20-year period, 12 (18%) had systemic features associated with their pulmonary disease. Eleven had fever, three night sweats, three arthralgia, three vasculitic rashes and two weight loss. Anaemia, myalgia, peripheral neuropathy, mononeuritis, pericardial effusion and photosensitivity rash were each recorded in single patients. None had evidence of hypersensitivity to drugs, helminthes or other allergens. Ten of the 12 patients could be classified as cryptogenic pulmonary eosinophilia and two as Churg Strauss syndrome. Ten were female. The maximum recorded eosinophil counts were higher in the 12 patients with systemic features compared with the remaining 53 patients [mean (SD) 5613 (3883) vs. 2359 (3046) x 10(6) 1(-1), P < 0.02], whereas both asthma and recurrent episodes of eosinophilia were significantly less common. Steroid therapy achieved a good clinical response and radiological clearing in the majority of patients. All 12 patients were treated with prolonged duration oral prednisolone [mean (SEM) dose 8.5 (3.8) mg day-1 duration 5.5 (1.3) years]. The two patients with Churg Strauss syndrome required azathioprine in addition to long-term prednisolone. There were no deaths and currently four patients are off all steroids and six receive less than 5 mg day-1. During a median follow-up period of 11 years, there was no significant decline in FEV1 or VC, measured as percent predicted values. Persistent radiographic abnormalities consistent with fibrosis or bronchiectasis were not seen.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
High dose inhaled steroid therapy and the cortisol stress response to acute severe asthma.
Systemic absorption of inhaled corticosteroids taken in high doses (> or = 1500 micrograms beclomethasone dipropionate or budesonide daily), may cause suppression of the hypothalamo-pituitary-adrenal axis. Patients taking long-term high dose inhaled steroid therapy might therefore be at risk of adrenal crisis at times of stress. Plasma cortisol levels were measured in 24 adults with severe acute asthma who had not received treatment with systemic corticosteroids prior to hospital attendance. Seven were not taking inhaled steroids, four were taking 600-1200 micrograms and 13 were taking 1500-2400 micrograms beclomethasone dipropionate or budesonide daily. Plasma cortisol levels in these 13 (median 594 nmol l-1, interquartile range 399-620 nmol l-1) were similar to levels in those taking lower dose/no inhaled steroids (median 512 nmol l-1, interquartile range 287-1050 nmol l-1): there was no relationship between inhaled steroid dose and cortisol level. Nine of the 24 patients failed to achieve plasma cortisol values > 500 nmol l-1 (the normal response to an insulin stress test). When compared with the remaining 15, they had less severe asthma as indicated by higher arterial oxygen tension (P < 0.01) and peak expiratory flow (P < 0.03). Patients taking long-term high dose inhaled corticosteroids appear to be able to mount an appropriate adrenocortical response to the stress of severe acute asthma.
Acute Disease↗
Breath-actuated inhalers in chronic asthma: comparison of Diskhaler and Turbohaler for delivery of beta-agonists.
An open, randomized, cross-over study was performed to compare the efficacy and acceptability of two breath-actuated inhalers, the Turbohaler (T) and Diskhaler (D), for delivery of beta-agonists. Thirty six adults with chronic asthma requiring beta-agonists four times daily were treated with terbutaline 500 micrograms via T and salbutamol 400 micrograms via D four times daily, each period lasting four weeks. Additional bronchodilator via pressurized aerosol was permitted as required. Peak expiratory flow (PEF) was recorded in the morning (before and after beta-agonist) and in the evening. The mean morning PEF was higher during the first two weeks using T (295 l.min-1) than whilst using D (281 l.min-1, p < 0.01), but this difference did not persist during the second two weeks and there were no differences in post-bronchodilator PEF or rescue beta-agonist use. After four weeks, > 90% of patients used both inhaler devices efficiently and they were equally acceptable in terms of ease of use and convenience to carry. The Diskhaler and Turbohaler achieve similar clinical efficacy for delivery of beta-agonists.
Administration, Inhalation↗
Hypothalamo-pituitary-adrenal axis suppression in asthmatic adults taking high dose beclomethasone dipropionate.
Inhaled corticosteroids control symptoms of chronic asthma in most patients. Use of drugs such as beclomethasone dipropionate (BDP) and budesonide is being encouraged as the importance of airways inflammation in asthma is increasingly appreciated. Beclomethasone dipropionate is used in doses of up to 2000 micrograms daily (equivalent to eight puffs of Beclorforte inhaler) and the Data Sheet warns that systemic absorption sufficient to cause suppression of the hypothalamo-pituitary-adrenal (HPA) axis may occur in some patients taking 2000 micrograms. HPA suppression to an extent which is clinically relevant has not been reported in asthmatic adults taking lower doses of BDP. We report six cases of HPA hypofunction occurring in patients on long-term treatment with BDP, in a dose of 1500 micrograms daily. Patients taking BDP in a dose of 1500 micrograms daily might be at risk of adrenal crisis and should carry steroid cards unless HPA function has been assessed and found normal.
Adult↗
Proinflammatory cytokines in acute asthma.
Cytokine-mediated interactions between monocytes/macrophages, lymphocytes, and eosinophils may be important in regulation of airway inflammation in asthma. Peripheral blood cytokine concentrations were measured in twenty adults with severe, acute asthma, ten with mild asthma (intermittent inhaled beta-agonists), twelve with chronic asthma (high-dose inhaled steroids), and in sixteen healthy subjects. Interleukin-1 beta, tumour necrosis factor, and interferon gamma were not detected in most subjects. Granulocyte macrophage colony-stimulating factor concentrations were higher in patients with severe asthma than in healthy subjects (median 179 vs 80 pg/ml; 95% confidence interval for difference 16-168; p = 0.009). Plasma concentrations of soluble interleukin-2 receptor (sIL-2R) were similar in all asthma groups (geometric mean in severe acute group 570 U/ml, mild group 559 U/ml, and chronic group 560 U/ml) and higher than those in healthy controls (361 U/ml, p less than 0.01). Sequential sIL-2R measurements were done in fifteen of the patients with severe acute asthma. There was no difference between baseline concentrations and those after 2 days of steroid treatment but by day 7 they had fallen significantly (ratio day 7/day 3 = 0.74, [95% CI 0.67-0.82]; p less than 0.001); however, there was no correlation with improvement in peak expiratory flow. This study provides further evidence for T-lymphocyte activation in asthma but shows that plasma sIL-2R is not a useful marker of disease activity.
Acute Disease↗
Cutaneous vasoconstrictor response to glucocorticoids in asthma.
The aim of the study was to find out whether asthma patients whose airways obstruction is sensitive (CS) or resistant (CR) to corticosteroid treatment also differ in their cutaneous vasoconstrictor response to a potent topical glucocorticoid. Corticosteroid resistance was defined by failure of forced expiratory volume in 1 s (FEV1) and peak expiratory flow rate to improve by at least 15% after a 2-week trial of corticosteroids (prednisolone 20 mg daily for 1 week, then 40 mg daily for 1 week) despite more than 15% improvement with inhaled beta agonists. Beclomethasone dipropionate in concentrations of 3 micrograms/ml, 10 micrograms/ml, 30 micrograms/ml, and 100 micrograms/ml was applied to forearm skin; the site was occluded under plastic and the degree of blanching assessed after 18 h. CS asthmatic subjects (n = 31), asthma patients with mild airways obstruction (n = 26), asthma patients taking long-term prednisolone (n = 13), and healthy volunteers showed similar vasoconstrictor responses. In CR asthmatic subjects (n = 15), the response (expressed in terms of either blanching intensity or the proportion of patients showing a positive response) was significantly lower than that in the CS group at concentrations of 3 micrograms/ml (p less than 0.01), 10 micrograms/ml (p less than 0.01), and 30 micrograms/ml (p less than 0.05), but not at 100 micrograms/ml. This resistance to glucocorticoids in the skin, together with reported evidence of glucocorticoid resistance in peripheral blood leucocytes, suggests a general defect in the ability of tissues to respond to glucocorticoids in CR asthma.
Administration, Oral↗
Hypothalamo-pituitary-adrenal axis suppression in asthmatics inhaling high dose corticosteroids.
The frequency of hypothalamo-pituitary-adrenal (HPA) axis suppression in asthmatics taking high dose (greater than 1000 micrograms daily) inhaled corticosteroids is unknown. HPA function was studied in 78 adult asthmatics taking long-term inhaled corticosteroids (median dose 1600 micrograms, range 1200-2650 micrograms daily). All patients except one were using metered dose aerosols; 15 were using large volume spacer devices. Median duration of high dose therapy was 13 months (range 1-54). Sixty-nine patients were taking beclomethasone dipropionate (1500 micrograms, n = 36; 2000 micrograms, n = 26, greater than 2000 micrograms, n = 7) and nine budesonide (1200 micrograms, n = 2; 1600 micrograms, n = 6; 1800 micrograms, n = 1). Four patients, all of whom were taking greater than 2000 micrograms beclomethasone dipropionate, were taking 200-400 micrograms of their total dose intranasally. Twenty-six patients had discontinued long term systemic corticosteroid treatment (at least 5 mg prednisolone daily, or equivalent, for a minimum of 6 months) between 7 months and 22 years prior to assessment. All patients had measurements of 9 am serum cortisol and 24-h urine free cortisol excretion and a short tetracosactrin test. Subnormal results were: 9 am cortisol less than 190 nmol l-1; rise in serum cortisol in response to tetracosactrin less than 200 nmol l-1 and/or achieved cortisol less than 500 nmol l-1; urine free cortisol less than 80 nmol 24 h-1. Hypothalamo-pituitary-adrenal suppression was defined as subnormal results in at least two of the three tests. Tests were performed at least 2 weeks after completion of any short course prednisolone treatments. Suppression was found in 16 (20.5%) patients (1500 micrograms, n = 6; 1600 micrograms, n = 1; 2000 micrograms, n = 7; 2400 micrograms, n = 2). Risk factors identified for this suppression were: (a) previous requirement for long-term systemic corticosteroids (10/26, chi 2 = 6.1, P less than 0.02); and (b) increasing duration of high dose inhaled therapy (median 28.5 months in suppressed vs. 12 months in normal, P less than 0.05). No clear relationship was identified between HPA function and dose, even when corrected for body surface area and there was no relationship between suppression and number of short courses of prednisolone in the preceding 12 months. Screening tests of HPA function should be performed in all asthmatics taking greater than or equal to 1500 micrograms inhaled corticosteroid daily. Unless function has been shown to be normal, all patients taking these doses should carry steroid cards.
Administration, Intranasal↗
Screening for hypothalamo-pituitary-adrenal axis suppression in asthmatics taking high dose inhaled corticosteroids.
High dose inhaled corticosteroids may cause suppression of the hypothalamo-pituitary-adrenal (HPA) axis. Several tests are available to screen for this suppression but it is not clear which is the most useful. HPA function was assessed in 78 adult asthmatics inhaling long-term, high dose (median 1600 micrograms; range 1200-2650 micrograms) beclomethasone dipropionate (n = 69) or budesonide (n = 9). Screening tests performed in all patients were 9 am serum cortisol, short tetracosactrin test and 24-h urine free cortisol excretion. Eleven patients also underwent insulin stress tests. Subnormal results were: 9 am cortisol less than 190 nmol l-1; urine free cortisol less than 80 nmol 24 h-1; rise in cortisol in response to tetracosactrin or hypoglycaemia less than 200 nmol l-1 and/or achieved cortisol less than 500 nmol l-1. HPA suppression (defined as subnormal results of at least two of the three initial tests and/or subnormal response to hypoglycaemia), was found in 16 patients. In the 11 patients who underwent insulin stress tests, results of all initial tests were normal in three, one test was abnormal in three and two tests were abnormal in four patients. All three tests were abnormal in the remaining patient. The response to hypoglycaemia was normal in the three patients whose screening tests were all normal; HPA suppression was present in seven patients and one patient had a borderline result. Close correlation was observed between the maximum cortisol during hypoglycaemia and both urine free cortisol (rs = 0.84; P = 0.001) and post-tetracosactrin cortisol (r = 0.75; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Inhalation↗
The use of a new breath-actuated inhaler by patients with severe airflow obstruction.
The ability of patients with severe airflow limitation (forced expiratory volume in one second less than 1.0 l or peak expiratory flow rate less than 200 l.min.1) to use a new breath-actuated inhaler (BAI) was assessed. One hundred and fifty six patients attending two respiratory units entered and completed the study. Subjects were instructed how to use the device and after attempting to trigger the BAI had flow-volume loops measured. One hundred and fifty one (97%) were able to actuate the inhaler on their first (146) or second (5) attempt. The five unsuccessful patients did not have the most severe airways obstruction. It is concluded that this new device, which is actuated at low inspiratory flow rates, can be used by patients with severe airflow limitation and represents an important advance in inhaler technology.
Adult↗
The adult patient's difficulties with inhalers.
Fifty percent or less of adult patients can be expected to be able to use the conventional metered dose inhaler (MDI) efficiently if the only tuition they receive is the manufacturer's instruction pamphlet and a high proportion of patients should be expected to develop a poor inhalation technique unless their ability to use an MDI is checked regularly. Because of these problems I believe that the future of the conventional MDI is limited. The new generation of inhalation devices have exciting design features and are undoubtedly better than established inhalation systems in that they are as effective and much easier to use. When these new devices are all available for the delivery of bronchodilators and corticosteroids there is no doubt that many patients will benefit. They should be prescribed in preference to the MDI for all patients whose ability to use a conventional pressurized inhaler is not routinely assessed prior to the institution of therapy and at regular intervals thereafter.
Adult↗
Potentiation of cisplatin by alpha-interferon in advanced non-small cell lung cancer (NSCLC): a phase II study.
Studies in experimental human lung cancer models have suggested that interferon may enhance significantly the response to some cytotoxic drugs. We have performed a phase II study of cisplatin (100 mg/m2 q.21 or 28 days) and alpha-2 interferon (3 or 5 MU three times weekly) in 68 patients with advanced non-small cell lung cancer and good performance status. As toxicity was acceptable, the dose of interferon and schedule of cisplatin were increased at the midpoint of the study. 46% (11/24) of patients with squamous carcinoma responded and an overall partial response rate of 30% was attained in 60 evaluable patients. There was no potentiation of haematological, renal or neurological toxicity but nausea and vomiting were severe. These results suggest that the combination has activity in this usually refractory disease.
Adult↗
Do large volume spacer devices reduce the systemic effects of high dose inhaled corticosteroids?
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.
Administration, Inhalation↗
Nebulized or intravenous beta 2 adrenoceptor agonist therapy in acute asthma?
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Administration, Inhalation↗
Treatment for acute asthma in the ambulance.
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Adult↗
Comparison of terbutaline via the Nebuhaler and salbutamol via the Volumatic: theory and practice.
The bronchodilating efficacy of terbutaline (250 micrograms.puff) inhaled via the Nebuhaler and salbutamol (100 micrograms.puff) inhaled via the Volumatic has been studied in 30 patients with reversible obstructive airways disease in a randomized crossover study. The salbutamol/Volumatic combination produced significantly greater bronchodilatation than terbutaline/Nebuhaler (one puff, p less than 0.001; eight puffs, p less than 0.01). The findings are discussed with particular reference to the theories of spacer action.
Albuterol↗
Respiratory impairment in inflammatory bowel disease: does it vary with disease activity?
Serial assessments of respiratory function were made in 44 patients with inflammatory bowel disease. Pulmonary function tests were performed at the initial assessment and after three months to see if abnormality was associated with alteration in disease activity, drug therapy or with evidence of immunological disturbance. Fourteen patients (32%) had some abnormality of respiratory function when first investigated. Seven (16%) had a reduced gas transfer factor but these abnormalities were not related to disease activity, drug therapy or any immunological variable. Elevation of both functional residual capacity and residual volume was found in nine (20%) patients at the initial assessment. These abnormalities appeared to be associated with active inflammatory bowel disease and in four of these patients lung volumes returned to normal at 3 months when the bowel disease was in remission.
Adolescent↗