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Randomised controlled trials (RCTs) are universally considered as the gold standard for evaluating the efficacy of treatments. Their main strength is that, through randomisation, they avoid any major imbalance between compared groups: therefore, observed outcome differences between groups at the end of the trial are most likely related to treatment effects. Since they are inherently prospective by design, they also permit stability throughout the study to ensure that all conditions remain optimal to test the hypothesis of interest. These include high-quality follow-up, reinforced adherence, etc . Consequently, these studies can reach the highest level of internal validity, provided that all quality standards are followed, such as those defined by CONSORT guidelines [1]. This document has been Endorsed by the International Primary Care Respiratory Group and the World Allergy Organization. The authors wish to thank the Respiratory Effectiveness Group Team (Michael Walker, CEO and Supporter Liaison, Naomi Launders, Senior Scientific Researcher and Sarah Lucas, Researcher) and Oversight Committee (Keith Allan, Trevor Lambert and Nick May).

The European Respiratory Society (ERS) will hold its annual International Congress this year in Munich, Germany. The ERS congress has been growing and evolving over the last 10 years, with attendance soaring to a steady 20 000. The congress is home to all stakeholders in respiratory medicine including researchers, clinicians, allied professionals and industy. More recently, working together with the European Lung Foundation (ELF), patients and policy makers have started to attend the congress and play a key role in discussions and activities. Each year the ERS congress is becoming more diverse and more relevant to all key players in the field, but clearly it has limitations as in order to attend the congress people have to travel, which is not always possible. With this in mind, in 2014, we want to make sure that the ERS congress, and all of us who take part in it, will have a bigger impact than previously realised, not just on those attending the ERS congress, but to a truly global audience. Figures from the latest edition of the European Lung White Book [1] give the startling message that one in eight Europeans currently die from a lung condition. Lung diseases, over the past two decades, have been a globally important cause of death and disability, and are set to remain as such. However the nature of lung …

Theophylline (dimethylxanthine) has been used to treat airway diseases for more than 80 years. It was originally used as a bronchodilator, but the relatively high doses required are associated with frequent side effects, so its use declined as inhaled β2-agonists became more widely used. More recently it has been shown to have antiinflammatory effects in asthma and chronic obstructive pulmonary disease (COPD) at lower concentrations. The molecular mechanism of bronchodilatation is inhibition of phosphodiesterase (PDE)3, but the antiinflammatory effect may be due to inhibition of PDE4 and histone deacetylase-2 activation, resulting in switching off of activated inflammatory genes. Through this mechanism, theophylline also reverses corticosteroid resistance, and this may be of particular value in severe asthma and COPD, wherein histone deacetylase-2 activity is reduced. Theophylline is given systemically (orally as slow-release preparations for chronic treatment and intravenously for acute exacerbations of asthma). Efficacy is related to blood concentrations, which are determined mainly by hepatic metabolism, which may be increased or decreased in several diseases and by concomitant drug therapy. Theophylline is now usually used as an add-on therapy in patients with asthma not well controlled on inhaled corticosteroids with or without long-acting β2-agonists and in patients with COPD with severe disease not controlled by bronchodilator therapy. Side effects are related to plasma concentrations and include nausea, vomiting, and headaches due to PDE inhibition and at higher concentrations to cardiac arrhythmias and seizures due to adenosine A1-receptor antagonism. In the future, low-dose theophylline may be useful in reversing corticosteroid resistance in COPD and severe asthma.

Glucocorticoids are by far the most effective therapy currently available for asthma therapy, and inhaled glucocorticoids have become the mainstay of modern asthma therapy (I). Indeed, asthma may be defined clinically as airway obstruction that im­ proves with steroids. Oral steroids are still essential for the con­ trol of asthma exacerbations, but their chronic use in the control of asthma has sharply declined with the introduction of inhaled steroids. Inhaled steroids give effective control of asthma and are largely free of the side effects associated with maintenance treatment with oral steroids. The recognition that airways inflam­ mation is present even in the mildest of asthmatic patients has lead to the introduction of inhaled steroids at a much earlier stage in therapy. Inhaled steroids are effective in all types of asthma and at all ages. The only limitation to their use is side effects, but recent evidence suggests that this is not a problem for most patients. Although steroids are the most effective therapy known for asthma, their precise mechanism of action is not yet understood. Important advances have been made in elucidating some of the molecular and cellular actions of steroids that are relevant to their antiasthma effects (2). There have recently been important ad­ vances in understanding the molecular mechanisms of steroid action, largely through the application of molecular biology tech­ niques (3). MOLECULAR MECHANISMS

Tuberculosis of the thyroid gland occurs only rarely. Since extrapulmonary tuberculosis is now seen relatively more frequently the existence of this condition should be recognized. The cases of two patients with tuberculosis involving the thyroid are presented. The first, an Asian immigrant, presented with a painless goitre with no evidence of turberculosis elsewhere. The second was an English woman who presented with hypothyroidism due to destruction of the thyroid by tuberculosis, and who subsequently died with disseminated tuberculosis; this is the only case to report the association between myxoedema and tuberculous thyroiditis. Other manifestations of thyroid tuberculosis and the pathologic types are discussed.