A Randomized, Placebo-Controlled, Respiratory Syncytial Virus Human Challenge Study of the Antiviral Efficacy, Safety, and Pharmacokinetics of RV521, an Inhibitor of the RSV-F Protein.

Effective treatments for respiratory syncytial virus (RSV) infection are lacking. Here, we report a human proof-of-concept study for RV521, a small-molecule antiviral inhibitor of the RSV-F protein. In this randomized, double-blind, placebo-controlled trial, healthy adults were challenged with RSV-A Memphis-37b.

Dual mechanism of action of T2 inhibitor therapies in virally induced exacerbations of asthma: evidence for a beneficial counter-regulation.

Biological agents such as omalizumab and monoclonal antibodies (mAbs) that inhibit type 2 (T2) immunity significantly reduce exacerbations, which are mainly due to viral infections, when added to inhaled corticosteroids in patients with severe asthma. The mechanisms for the therapeutic benefit of T2 inhibitors in reducing virally induced exacerbations, however, remain to be fully elucidated. Pre-clinical and clinical evidence supports the existence of a close counter-regulation of the high-affinity IgE receptor and interferon (IFN) pathways, and a potential dual mechanism of action and therapeutic benefit for omalizumab and other T2 inhibitors that inhibit IgE activity, which may enhance the prevention and treatment of virally induced asthma exacerbations.

Comparison of systemic pharmacodynamic effects of two combination pressurized metered dose inhalers that deliver salmeterol and fluticasone propionate.

Aim: The aim of this study was to test the systemic pharmacodynamic effects of the salmeterol component of two pressurized metered dose inhalers that delivered a combination of salmeterol and fluticasone propionate (SM/FP).

Methods: This was a six-way crossover study in 43 adult subjects, using a single blind design (subject blinded to product and clinical assessor blinded for all measurements). Each subject received single doses of two, six, and twelve inhalations from test and reference products that delivered SM/FP as 25/125 mcg per inhalation.

Systematic review of antibiotic resistance in acne: an increasing topical and oral threat.

Topical and oral antibiotics are routinely used to treat acne. However, antibiotic resistance is increasing, with many countries reporting that more than 50% of Propionibacterium acnes strains are resistant to topical macrolides, making them less effective. We reviewed the current scientific literature to enable proposal of recommendations for antibiotic use in acne treatment.

Comparison of serious inhaler technique errors made by device-naïve patients using three different dry powder inhalers: a randomised, crossover, open-label study.

Background: Serious inhaler technique errors can impair drug delivery to the lungs. This randomised, crossover, open-label study evaluated the proportion of patients making predefined serious errors with Pulmojet compared with Diskus and Turbohaler dry powder inhalers.

Methods: Patients ≥18 years old with asthma and/or COPD who were current users of an inhaler but naïve to the study devices were assigned to inhaler technique assessment on Pulmojet and either Diskus or Turbohaler in a randomised order.

Cost-effectiveness of fluticasone propionate in the treatment of chronic obstructive pulmonary disease: a double-blind randomized, placebo-controlled trial.

Background: Chronic obstructive pulmonary disease (COPD) is a debilitating disease and places a large financial burden on health-care systems and society. We prospectively evaluated the cost-effectiveness offluticasone propionate (FP) treatment in patients with moderate-to-severe COPD, who were symptomatic on regular bronchodilator therapy.

Methods: An economic analysis was performed in a 6-month, randomized, double-blind clinical trial comparing FP 1,000 microg/day with placebo in 281 patients aged 45-79 years with symptomatic moderate-to-severe COPD.

HPA-axis effects of nebulised fluticasone propionate compared with oral prednisolone in childhood asthma.

The aim of this study was to compare the effect of 7 days nebulised fluticasone propionate (FP) with oral prednisolone on 24-h urinary-free cortisol excretion, systemic exposure and safety. This was a randomised, double-blind, double-dummy, two-way crossover study. Thirty-one children (19 male, 12 female, mean age 8 years) with stable asthma were randomly assigned to 7 days treatment with either FP Nebules (2 x 0.

Evaluating the effects of asthma therapy on childhood growth: what can be learnt from the published literature?

The difficulties of assessing the effects of asthma therapy on childhood growth were explored in the first part of this review. In this part of the review growth studies with inhaled corticosteroids were selected that included a control group, measured height by stadiometry and were of > or = 1 yr duration. The studies were classified as type 1 (placebo control), type 2 (nonsteroidal therapy control), type 3 (comparator inhaled corticosteroid control) or type 4 ("real-life" studies with dose adjustment).

Bioavailability and metabolism of mometasone furoate: pharmacology versus methodology.

The degree of systemic exposure ofter inhalation of corticosteroids is of great clinical concern. For optimum outcome, the pulmonary deposition should be sufficiently high to produce the desired anti-inflammatory effect in the lungs, whereas the plasma concentrations due to the absorption of the corticosteroid from the lung and the gut should be minimal. Recently, it has been reported that inhaled mometasone furoate has a systemic bioavailability of less than 1%, which is much lower than other corticosteroids currently available.

Safety and biological efficacy of a lipid-CFTR complex for gene transfer in the nasal epithelium of adult patients with cystic fibrosis.

Gene transfer is an attractive option to treat the basic defect in cystic fibrosis. In a double-blind, placebo-controlled, rising-dose tolerance study in the nasal epithelium, we tested the safety and efficacy of a cationic liposome [p-ethyl-dimyristoylphosphadityl choline (EDMPC) cholesterol] complexed with an expression plasmid containing hCFTR cDNA. Eleven adult CF patients were studied in a protocol that allowed comparisons within individual subjects: vector and placebo were sprayed into alternate nostrils at intervals over 7 h.

The bronchoprotective effect of inhaled salmeterol in preschool children: a dose-ranging study.

The optimal dose of salmeterol in infants and preschool children is not known. The aim of this study was to assess the bronchoprotective effect of different doses of salmeterol using methacholine-induced wheeze in children aged <4 yrs. Children <4 yrs old with a history of recurrent wheeze underwent two methacholine challenges within 7 days.

Effect of one year treatment with inhaled fluticasone propionate or beclomethasone dipropionate on bone density and bone metabolism: a randomised parallel group study in adult asthmatic subjects.

Background: There is some concern that prolonged treatment with high doses of inhaled corticosteroids may have a detrimental effect on bone mass. The aim of this one year study was to investigate the effects of low and high doses of fluticasone propionate (FP) (400 microg/day and 750 microg/day) and beclomethasone dipropionate (BDP) (800 microg/day and 1500 microg/day) on bone mass and metabolism.

Methods: This was a multicentre, double blind, parallel group study involving 69 mild to moderate asthmatic subjects who were randomised to treatment as follows: 22 to FP400, 21 to BDP800, 13 to FP750, and 13 to BDP1500.

Oral steroid-sparing effect of two doses of nebulized fluticasone propionate and placebo in patients with severe chronic asthma.

Inhaled steroids, delivered by metered dose aerosol and dry powder inhalers, have proved effective in reducing the need for oral steroids in patients with oral steroid-dependant asthma. This randomized, double-blind study, compared the efficacy and tolerability of nebulized fluticasone propionate (FP Nebules), 2 mg b.d.

Effect of inhaled corticosteroids on bones and growth.

Inhaled corticosteroids are recognized as the most effective anti-inflammatory therapy in patients with asthma and their early introduction is recommended by national and international guidelines. Concerns have been raised about potential adverse effects of inhaled corticosteroids on bones and growth, as these appear to be more important clinically than effects on the hypothalamic-pituitary-adrenal axis, which are more commonly measured. This review examines the effects of inhaled corticosteroids on biochemical bone markers, bone density and growth in adults and children with asthma, in view of the recent availability of a substantial amount of new clinical trial data.

Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease. International COPD Study Group.

Background: The efficacy of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease (COPD) remains controversial because of a lack of placebo-controlled studies. We compared the effect of inhaled fluticasone propionate with placebo in the treatment of patients with COPD.

Methods: We used a randomised, double-blind, placebo-controlled design.

A double-blind, placebo controlled, dose ranging study to evaluate the safety and biological efficacy of the lipid-DNA complex GR213487B in the nasal epithelium of adult patients with cystic fibrosis.

Unlabelled: GTAB1001: A Double-Blind, Placebo Controlled, Dose Ranging Study to Evaluate the Safety and Biological Efficacy of the Lipid-DNA Complex GR213487B in the Nasal Epithelium of Adult Patients with Cystic Fibrosis.

Objectives: To evaluate the effectiveness of various dosages of the lipid-DNA complex GR213487B (0.4375mg and either 4.

Fluticasone propionate compared with budesonide: a double-blind trial in asthmatic children using powder devices at a dosage of 400 microg x day(-1).

The aim of this study was to compare fluticasone propionate (FP) with budesonide (BUD) at a dose of 400 microg x day(-1) in the treatment of children with asthma. Two hundred and twenty nine children with mild-to-moderate asthma, currently receiving 200-400 microg x day(-1) of inhaled corticosteroid, were randomized to receive either 400 microg x day(-1) of FP from the Diskhaler (registered trade mark of the Glaxo Group of Companies) or 400 microg x day(-1) of BUD from the Turbuhaler (registered trade mark of Astra Pharmaceuticals Ltd) for 8 weeks, in a parallel-group, double-blind, double-dummy study. Primary efficacy was assessed by measurement of daily peak expiratory flow (PEF).

Phrenic nerve and diaphragm function following open heart surgery: a prospective study with and without topical hypothermia.

In a prospective study, 100 patients undergoing open heart surgery were randomly allocated to receive ice/slush topical hypothermia for myocardial protection (Group I, n = 56) or not (Group II, n = 44). Chest radiographs, diaphragm screening, lung function and phrenic nerve conduction time were assessed pre-operatively and at 1 week and 1 month post-operatively in all patients and subsequently at 3 months, 6 months, 1 year and 2 years in all patients with radiological evidence of diaphragm paralysis. The two groups were similar in terms of age, sex, diabetes and smoking habits.

Effect of carbohydrate rich versus fat rich loads on gas exchange and walking performance in patients with chronic obstructive lung disease.

Background: High calorie intakes, especially as carbohydrate, increase carbon dioxide production (VCO2) and may precipitate respiratory failure in patients with severe pulmonary disease. Energy obtained from fat results in less carbon dioxide and thus may permit a reduced level of alveolar ventilation for any given arterial blood carbon dioxide tension (PaCO2).

Methods: Ten patients with stable severe chronic obstructive lung disease underwent a six minute walk before and 45 minutes after taking 920 kcal of a fat rich drink, an isocalorific amount of a carbohydrate rich drink, and an equal volume of a non-calorific control liquid on three separate days, in a double blind randomised crossover study.

Diaphragm paralysis following cardiac surgery: role of phrenic nerve cold injury.

Diaphragm paralysis has been reported radiologically after cardiac surgery with an incidence ranging from 30% to 75% of patients. We studied 100 consecutive patients undergoing open heart operations, half of whom received ice/slush topical hypothermia (group 1) and half of whom did not (group 2). Chest radiology and diaphragm screening were performed at 1 week, 1 month, and every 6 months thereafter in all patients with an elevated diaphragm.

Bilateral diaphragm paralysis after cardiac surgery with topical hypothermia.

Bilateral diaphragm paralysis is a rare but important complication of open heart surgery. Two cases were found among 360 prospectively studied patients undergoing open heart surgery during one year. Both patients had insulin dependent diabetes with peripheral neuropathy and this may have contributed to their diaphragm paralysis.

Reversible T-wave abnormality in severe acute asthma: an electrocardiographic sign of severity.

Reversible electrocardiographic (ECG) abnormalities are well recognized in severe acute asthma. Inferior lead T-wave abnormalities have only rarely been reported, and their frequency and significance have not been well documented. We studied 70 consecutive patients with severe acute asthma on admission to hospital and during recovery, in order to examine the frequency and natural history of such changes and to document their relationship to the severity of the attack.