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Biomedical subjects

Anne E Tattersfield

Publications and source records attributed to Anne E Tattersfield.

17 recordsLinked to original sources
PubMed2006

Effects of rac-albuterol on arterial blood gases in patients with stable hypercapnic chronic obstructive pulmonary disease.

AIMS: Many patients with chronic obstructive pulmonary disease (COPD) are treated with high dose beta(2)-adrenoceptor agonists, which can increase ventilation/perfusion mismatching, and tremor and cardiac output, thereby increasing oxygen uptake and carbon dioxide output (VCO(2)). Patients with severe COPD and hypercapnia may be unable to increase ventilation in response to increased VCO(2), in which case arterial carbon dioxide tension (P(a)CO(2)) may rise. Our aim was to determine whether high dose nebulized rac-albuterol could increase P(a)CO(2) in patients with COPD, limited bronchodilator reversibilty and hypercapnia. METHODS: We compared 10 mg and 400 microg rac-albuterol, given in two doses 1 h apart on nonconsecutive days, in a double-blind randomized crossover study in 14 patients with severe COPD. P(a)CO(2), arterial oxygen tension (P(a)O(2)) and heart rate were measured over 120 min and change from baseline was plotted against time to obtain an area under the curve. RESULTS: Mean P(a)CO(2) fell slightly over 120 min, with no difference between treatments (0.03 kPa h(-1) (95% confidence interval 0.02, 0.04)) and only three subjects had an increase in P(a)CO(2) after high dose rac-albuterol. High dose rac-albuterol caused a greater fall in P(a)O(2)[0.1 kPa h(-1) (95% confidence interval 0, 0.2)] and increase in heart rate than the low dose, although the differences were small. CONCLUSIONS: Under stable conditions most subjects with severe COPD and hypercapnia will have a fall in P(a)CO(2) and P(a)O(2) following 10 mg rac-albuterol, suggesting that they maintain capacity to respond to any increase in VCO(2) and prevent a rise in P(a)CO(2).

Adrenergic beta-Agonists↗
PubMed2006

Plasma concentrations of inhaled corticosteroids in relation to airflow obstruction in asthma.

AIMS: To compare the pharmacokinetic profiles of beclometasone, budesonide, fluticasone and mometasone following inhalation in patients with asthma, and explore the relationship between lung function and plasma drug concentrations. METHODS: Thirty subjects with asthma and a forced expiratory volume in 1 s (FEV(1)) ranging from 36 to 138% predicted, inhaled 800 microg beclometasone, budesonide and mometasone and 1000 microg fluticasone in random order. Plasma drug concentrations were measured over 8 h and the relationship between the area under the plasma concentration-time curve (AUC(0-8)) and lung function was modelled using linear regression. Estimated AUC(0-8) values at 50 and 100% predicted FEV(1) were compared for each drug. RESULTS: Pharmacokinetic profiles differed markedly between the drugs. Correlation coefficients for the relation between FEV(1)% predicted and AUC(0-8) values for beclometasone, budesonide, fluticasone and mometasone were 0.37 (P = 0.05), 0.33 (P = 0.08), 0.25 (P = 0.2) and 0.52 (P = 0.004), respectively, and estimated AUC(0-8) values were 1.3 [95% confidence interval (CI) 1.0, 1.8], 1.3 (95% CI 1.0, 1.8), 1.4 (95% CI 0.9, 2.2) and 2.2 (95% CI 1.3, 3.5) times higher for the four drugs, respectively, at 100 compared with 50% predicted FEV(1.) CONCLUSION: The higher plasma concentrations of inhaled corticosteroids in patients with a higher FEV(1)% predicted suggests that, for any given dose, these patients will be at greater risk of developing adverse systemic effects with long-term use.

Administration, Inhalation↗
PubMed2005

Benefit versus risk for oral, inhaled, and nasal glucocorticosteroids.

Many factors affect the benefit-to-risk analysis of the use of the glucocorticosteroids in the treatment of allergic inflammation. For most patients the benefit-to-risk ratio favors topical over oral administration, but in severe disease oral administration may be required. It is clear from pharmacokinetic and pharmacodynamic studies that inhaled glucocorticosteroids in particular are absorbed into the systemic circulation and that they can have clinical adverse effects when given in high doses. Therefore, with inhaled and nasal glucocorticosteroids, the dose that will achieve the optimal benefit/risk ratio is the lowest dose that controls symptoms and prevents exacerbations requiring treatment with oral glucocorticosteroids. This optimal dose needs to be determined on an individual basis and is likely to vary as disease severity changes over time.

Administration, Inhalation↗
PubMed2005

Use of upper limb exercise to assess breathlessness in patients with cancer: tolerability, repeatability, and sensitivity.

We report the development of an arm exercise test to assess breathlessness in patients with lung cancer who are breathless at low levels of exertion. Exercise consisted of raising the arm over 40 cm, either the dominant arm only (n=10) or both arms alternating at minute intervals (n=12). Subjects breathed through a mouthpiece, and ventilation (VE) and oxygen uptake (VO(2)) were measured. Following familiarization, three tests were performed over one week to explore repeatability, and sensitivity was assessed in a fourth test. Arm exercise was generally well tolerated and increased breathlessness, VE, and VO(2). The commonest factor limiting exercise was arm fatigue, although four patients in the two-arm test also reported breathlessness. Repeatability for breathlessness score and VE was best in the two-arm test. The added resistance used to assess sensitivity could not be detected. The two-arm test offers a potential means of assessing the effects of an intervention on breathlessness and E in patients for whom a cycle or treadmill exercise test is unsuitable.

Adult↗
PubMed2004

Safety of inhaled corticosteroids.

Systemic bioavailability from the gastrointestinal tract is reduced with newer inhaled corticosteroids (ICSs) such as fluticasone, but systemic absorption still occurs via the lung. Observational studies have shown an association between ICS use and several adverse outcomes such as cataracts, glaucoma, and adrenal failure, and prospective controlled studies have confirmed a causal relationship between ICS use and bruising, reduction in bone mineral density, and reduced growth velocity. The evidence suggests that the effect of ICSs on bone mineral density is small in the short term but that patients taking moderate or high doses for long periods will be at increased risk of fractures and that this could be an appreciable public health problem. There is also evidence to suggest that the risk of long-term adverse effects is likely to differ between ICSs. The clinical message that follows is that ICSs should be used widely because they reduce the need for courses of oral corticosteroids and improve quality of life, but that they need to be managed carefully to reduce the risk of adverse effects with long-term use.

Administration, Inhalation↗
PubMed2004

A benefit-risk assessment of inhaled long-acting beta2-agonists in the management of obstructive pulmonary disease.

The two inhaled long-acting beta2-adrenoceptor agonists, salmeterol and formoterol, have been studied extensively since their introduction in the early 1990s. In this review we consider the evidence for their efficacy and safety in adults with asthma and chronic obstructive pulmonary disease (COPD), by reviewing long-term prospective studies in which these drugs have been compared with placebo or an alternative bronchodilator. We have also assessed safety, including data from postmarketing surveillance studies and case-control studies using large databases. In patients with asthma, salmeterol and formoterol increase lung function, reduce asthmatic symptoms and improve quality of life when compared with placebo. Both drugs protect against exercise-induced asthma, although some tolerance develops with regular use. Tolerance to the bronchodilator effects of formoterol has also been seen, although this is small and most of the beneficial effects are maintained long-term. Both drugs have been shown to reduce asthma exacerbations but only in studies in which most patients were taking an inhaled corticosteroid. Adding a long-acting beta2-agonist provided better control than increasing the dose of inhaled corticosteroid in several studies. Long-acting beta2-agonists also provide better asthma control than use of regular short-acting beta2-agonists and theophylline. Their relative efficacy compared with leukotriene antagonists is uncertain as yet. Formoterol appears to be at least as safe and effective as a short-acting beta2-agonist when used on an 'as required' basis. In patients with COPD, both salmeterol and formoterol offer improved lung function and reduced COPD symptoms compared with placebo, and quality of life has been improved in some studies. Some tolerance to the bronchodilating effect of salmeterol was seen in one study. Most studies have not found a significant reduction in exacerbations in COPD. Both drugs have provided greater benefit than ipratropium bromide or theophylline; there are limited data on tiotropium bromide. The long-acting beta2-agonists cause predictable adverse effects including headache, tremor, palpitations, muscle cramps and a fall in serum potassium concentration. Salmeterol can also cause paradoxical bronchospasm. There is some evidence that serious adverse events including dysrhythmias and life-threatening asthma episodes can occur; however, the incidence of such events is very low but may be increased in patients not taking an inhaled corticosteroid. Salmeterol 50 microg twice daily and formoterol 12 microg twice daily are effective and safe in treating patients with asthma and COPD. Higher doses cause more adverse effects, although serious adverse events are rare.

Administration, Inhalation↗
PubMed2003

Formoterol used as needed improves health-related quality of life in asthmatic patients uncontrolled with inhaled corticosteroids.

Clinical benefits have been shown to occur when using the long-acting beta2-agonist formoterol 4.5 microg for as-needed medication rather than terbutaline 500 microg in patients with unstable asthma taking an inhaled corticosteroid. This study compared their effects on health-related quality of life and the relation with conventional clinical indices in the same population. 362 asthmatics were randomized to use either formoterol 4.5 microg or terbutaline 500 microg as needed, both inhaled via Turbuhaler. The Asthma Quality of Life Questionnaire (AQLQ) was practised at enrolment and completed by 341 patients after randomization and at 4, 8, and 12 weeks. Clinical indices were measured at the same time points. Mean overall AQLQ scores were comparable at baseline, being 4.90 in the formoterol and 4.82 in the terbutaline group and improved during treatment by 0.41 and 0.17 units, respectively (mean difference 0.24, 95% CI 0.08, 0.39, P<0.005). Mean improvement in the symptom domain was 0.49 units when using formoterol. Correlations between changes in clinical indices and changes in AQLQ scores during the 12-week period were weak (maximum r value=0.37). When used for as-needed medication, formoterol 4.5 microg provided an improvement in asthma-specific quality of life and to a somewhat greater extent than the widely used terbutaline 500 microg. The symptom domain in AQLQ showed almost 0.5 units improvement after formoterol, a change that is considered to be clinically relevant.

Administration, Inhalation↗
PubMed2002

Inhaled corticosteroids and hip fracture: a population-based case-control study.

There is accumulating evidence that the use of inhaled corticosteroids is associated with a dose-related reduction in bone mineral density. Whether this translates to an increase in fracture is unclear. We have used the General Practice Research Database to perform a case-control analysis, including 16,341 cases of hip fracture (mean age of 79 years, 79% female, median period prescribing data 2.7 years) and 29,889 control subjects, individually matched by age, sex, and general practice. Data for all prescriptions for corticosteroids and for potential confounders, including other drug use and comorbid illnesses, were extracted, and the impact of inhaled corticosteroid exposure was analyzed using conditional logistic regression. The risk of hip fracture was associated with exposure to inhaled corticosteroids with an odds ratio of 1.26 (95% confidence interval, 1.17 to 1.36). This odds ratio was reduced after adjusting the model for annual courses of oral corticosteroids, the only confounder of note (OR 1.19; 95% CI, 1.10 to 1.28). There was a dose-response relationship between inhaled corticosteroid use and hip fracture even after adjusting for the annual number of courses of oral corticosteroids (p trend = 0.007). In older subjects, the recent use of inhaled corticosteroids is associated with a dose-related increase in hip fracture.

Accidental Falls↗
PubMed2002

The impact of oral corticosteroid use on bone mineral density and vertebral fracture.

The use of oral corticosteroids is associated with an increased risk of fracture, but there is limited information on the relationship between corticosteroid dose, bone mineral density (BMD), and fracture. We examined this relationship in a community population (more than 50 years) taking oral corticosteroids for chronic lung disease. Details of corticosteroid use and lifestyle were obtained by questionnaire, general practice records, and patient interview. BMD was assessed at the lumbar spine and femur and vertebral fracture by morphometric X-ray absorptiometry. Of the 117 patients who participated (median age, 69), 48% were female. Fifty-eight percent had osteoporosis (a T score of less than -2.5), and 61% had a vertebral fracture. The presence of vertebral fracture was related to BMD at the femoral neck, with an odds ratio of 1.6 for a 1 SD reduction in BMD. The cumulative prednisolone dose ranged from 3.4 to 175 g and was strongly associated with vertebral fracture, with the odds ratio between the highest and lowest dose quartiles being 4.4 (95% confidence interval, 1.04, 18.8). The difference in femoral neck BMD between the same dose quartiles was only modest, however (0.5 SD; 95% confidence interval, 0.09, 0.94). In patients taking long-term oral corticosteroids for chronic lung disease, the relationship between vertebral fracture risk and BMD is similar to that seen in other populations. Cumulative prednisolone dose is strongly related to fracture risk, and this effect is independent of its more modest impact on BMD.

Administration, Inhalation↗
PubMed2002

Descriptors of breathlessness in patients with cancer and other cardiorespiratory diseases.

The objective of this study was to examine the relationship between descriptors of breathlessness and its underlying cause in patients with lung cancer and cardiopulmonary diseases to see whether descriptors might be used to help determine the cause of breathlessness, particularly in patients with lung cancer. We studied 131 patients with primary or secondary lung cancer, whose breathlessness was attributed to tumor mass, pleural effusion, lung collapse, metastases, pleural thickening or lymphangitis carcinomatosis, and 130 patients with breathlessness attributed to asthma, chronic obstructive pulmonary disease (COPD), interstitial lung disease or cardiac failure. Patients selected statements (descriptors) that described the quality of their breathlessness from a 15-item questionnaire and the relationship between the descriptors and the attributed cause of breathlessness was evaluated by cluster analysis. All patient groups were characterized by more than one cluster and several clusters were shared between groups. Specific sets of clusters were associated with breathlessness due to asthma, COPD and cardiac failure, and to cancer causing collapse, metastases or pleural thickening. The association of different sets of clusters with the different diagnostic groups suggests that patients are describing qualitatively different experiences of breathlessness, but the relationship does not appear to be sufficiently robust for the questionnaire to aid differential diagnosis.

Aged↗
PubMed2002

Lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a rare disease categorized by an overgrowth of atypical smooth muscle cells (LAM cells) in the lungs and axial lymphatics, which is associated with the mesenchymal tumor angiomyolipoma. The disease occurs in women generally in their mid thirties with a prevalence approximately 1 per million in the general population but is much more frequent in women with tuberous sclerosis complex (TSC). LAM is categorized by airflow obstruction, lung cysts, recurrent pneumothorax, and pleural and abdominal chylous collections. The disease is progressive, generally resulting in respiratory failure and death. The TSC-2 gene is abnormal in LAM cells and may be responsible for their disordered growth. These cells are of an unusual phenotype, expressing smooth muscle proteins, melanoma proteins, estrogen and progesterone receptors. Although at present of unknown significance these are useful in diagnosis. Treatment is largely supportive, being directed at airflow obstruction, pneumothorax, chylous complications, and bleeding from angiomyolipomas. In patients with rapidly progressive disease, hormone manipulation is frequently tried in the form of progesterone or antiestrogen therapies although no firm evidence of their efficacy exists.

Journal Article↗
PubMedDate not supplied

Current issues with beta2-adrenoceptor agonists: historical background.

The discovery that dessicated adrenal glands had beneficial effects in asthma arose in 1900 following a vogue for studying organotherapy at the end of the 19th century. The adrenal hormone adrenaline was found to have sympathomimetic properties and was isolated and synthesized in 1901. The first nonselective beta-agonist, isoproterenol, was isolated in 1940, followed by the development of selective beta2-agonists in the 1960s and the introduction of the long-acting beta2-agonists in the 1990s. The introduction of beta2-selectivity reduced adverse effects, as did developments in inhaler technology that allowed subjects to inhale much smaller doses of drug selectively to the airways. The beta2-agonists are some of the more important drugs to have been developed in the 20th century. Excessive doses can cause problems, and attempts to maximize the benefit from beta2-agonists and to reduce adverse effects has led to considerable epidemiological, clinical, and mechanistic research over the last 50 yr.

Adrenergic beta-2 Receptor Agonists↗