A 2-year randomised placebo-controlled trial of doxycycline for lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is characterised by lung cysts and airflow obstruction. Matrix metalloproteinases have been implicated in lung destruction in LAM. We performed a randomised, double-blind trial, comparing the matrix metalloproteinases inhibitor doxycycline with placebo on the progression of LAM.

Sirolimus therapy for angiomyolipoma in tuberous sclerosis and sporadic lymphangioleiomyomatosis: a phase 2 trial.

Purpose: Renal angiomyolipomas are a frequent manifestation of tuberous sclerosis and sporadic lymphangioleiomyomatosis (LAM). These disorders are associated with mutations of TSC1 or TSC2 that lead to overactivation of mTOR complex 1 (mTORC1), suggesting an opportunity for targeted therapy by using mTORC1 inhibitors. This study investigated the efficacy and safety of the mTORC1 inhibitor sirolimus for treatment of renal angiomyolipomas in patients with these disorders.

Quadrupling the dose of inhaled corticosteroid to prevent asthma exacerbations: a randomized, double-blind, placebo-controlled, parallel-group clinical trial.

Rationale: Asthma exacerbations are unpredictable, disruptive, and frightening, and are therefore important to prevent.

Objectives: We investigated whether a policy of quadrupling the dose of inhaled corticosteroid when asthma control starts to deteriorate reduces asthma exacerbations requiring treatment with oral corticosteroids.

Methods: A total of 403 people with asthma were given a self-management plan and randomized to take an active or placebo corticosteroid inhaler in addition to their usual asthma treatment when their PEF fell by 15% on 2 consecutive days or by 30% on 1 day.

Effect of mouth taping at night on asthma control--a randomised single-blind crossover study.

Background: Nose breathing ensures that inspired air is warm, filtered and moist and may therefore benefit patients with asthma. It features in some complementary approaches to treat asthma and is encouraged at night in the Buteyko technique by the use of mouth taping. In this pragmatic study we sought to determine whether taping the mouth at night has any effect on asthma control compared with usual breathing in patients with symptomatic asthma, since if it was effective it would be a simple intervention to implement.

Systemic and bronchodilator effects of inhaled rac-formoterol in subjects with chronic obstructive pulmonary disease: a dose-response study.

What Is Already Known About This Subject: The long-acting inhaled beta(2)-agonist formoterol has systemic effects when taken in high doses. It can be used as relief medication in asthma and there is interest in this approach in chronic obstructive pulmonary disease (COPD). Relief medication can involve high doses, and in subjects with COPD who have limited ability to bronchodilate the adverse effects can outweigh the benefits.

Poor adherence with inhaled corticosteroids for asthma: can using a single inhaler containing budesonide and formoterol help?

Background: Poor adherence with inhaled corticosteroids is an important problem in asthma management. Previous approaches to improving adherence have had limited success.

Aim: To determine whether treatment with a single inhaler containing a long-acting beta(2)-agonist and a corticosteroid for maintenance treatment and symptom relief can overcome the problem of poor adherence with inhaled corticosteroids.

Plasma concentrations of fluticasone propionate and budesonide following inhalation: effect of induced bronchoconstriction.

Aims: To determine whether and to what extent bronchoconstriction affects plasma concentrations of fluticasone and budesonide following inhalation.

Methods: Twenty people with mild asthma inhaled 1000 microg fluticasone (Accuhaler) plus 800 microg budesonide (Turbohaler) on two visits. On one occasion, prior to drug inhalation, FEV(1) was decreased by at least 25% using inhaled methacholine.

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.

Use of inhaled corticosteroids and the risk of fracture.

Background: Previous studies have found an association between the use of inhaled corticosteroids and fracture, but the extent to which this association is due to inhaled corticosteroids or to related factors, such as the severity of airflow obstruction, is disputed. We report a new approach in which we combine data on people with airflow obstruction from a large Medical Research Council study of the assessment and management of older people in the community with longitudinal data from their computerized general practice records.

Methods: Our cohort includes 1,671 study participants with a diagnosis of asthma or COPD (mean age, 80.

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.

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.

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.

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.

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.

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.

Inhaled corticosteroids, bone mineral density and fracture in older people.

The efficacy of inhaled corticosteroids in the treatment of asthma has been firmly established in a variety of settings. The majority of asthma management plans now recommend the use of inhaled corticosteroids at an early stage. This means that most patients with asthma will be prescribed an inhaled corticosteroid at some point in time and many patients with asthma will use these drugs for several years.

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.

Exposure to tricyclic and selective serotonin reuptake inhibitor antidepressants and the risk of hip fracture.

The use of tricyclic antidepressants is associated with an increased risk of hip fracture. Despite a better side effect profile, this adverse effect has also been reported for selective serotonin reuptake inhibitors. To determine whether these findings result from bias arising from the case-control method, the authors have performed a case-control analysis and a self-controlled case-series analysis using 1987-1999 diagnosis data for 16,341 cases of hip fracture and 29,889 controls drawn from the United Kingdom General Practice Research Database.