Graeme P. Currie

British guideline on the management of asthma: A national clinical guideline

These guidelines have been replaced by British Guideline on the Management of Asthma. A national clinical guideline. Superseded By 2012 Revision Of 2008 Guideline: British Guideline on the Management of Asthma. Thorax 2008 May; 63(Suppl 4): 1–121.

Long-Acting Bronchodilator or Leukotriene Modifier as Add-on Therapy to Inhaled Corticosteroids in Persistent Asthma?

Despite the widespread use of inhaled corticosteroids, many asthmatic patients experience persistent symptoms. In such individuals, the addition of a long-acting beta2-agonist (LABA) is frequently more effective than doubling the dose of inhaled corticosteroid. However, the role of additional therapy with a leukotriene receptor antagonist (LTRA) as an alternative to an LABA has been the focus of attention in recent studies. In order to determine the overall efficacy of the pharmacologic armamentarium used in asthma, it is imperative that a combination of end points, including lung function, airway hyperresponsiveness, effects on underlying inflammation, symptoms, and more long-term sequelae such as exacerbations, are assessed. This evidence-based systematic review outlines the pharmacologic properties of LABAs and LTRAs and the importance of evaluating end points in addition to lung function when assessing these drugs. We also highlight the results of all published studies that have performed direct comparisons of both LABAs and LTRAs as add-on therapy to inhaled corticosteroids.

Difficult to treat asthma in adults

#### Summary points There is no universally accepted definition of difficult asthma. However, it is reasonable to consider it present when people have persistent symptoms and frequent exacerbations, despite being treated at steps 4 or 5 of the British Thoracic Society and Scottish Intercollegiate Guideline Network (BTS/SIGN) guidelines (fig 1⇓).1 Such patients typically receive high dose inhaled steroids (≥800 µg beclometasone equivalent), a long acting β2 agonist, plus add-on treatment. The prevalence of difficult asthma is uncertain, but it may account for 5-10% of adults with asthma.2 Morbidity and health costs are disproportionately high in these patients,w1 and they are at greater risk of fatal and near fatal exacerbations.w2 In addition, frequent, intermittent, or continuous courses of oral prednisolone (plus regular high dose inhaled steroids) increase the risk of steroid related adverse effects. #### Sources and selection criteria All authors performed a comprehensive search of articles published up to January 2009 using PubMed and Medline. Keywords and phrases used were “asthma”, “exacerbations”, “symptoms”, “difficult asthma”, “lung function”, “diagnosis”, “bronchial hyper-responsiveness”, “nitric oxide”, “sputum eosinophils”, “treatment”, “monitoring”, “inhaled steroids”, “long acting β2 agonists”, “leukotriene receptor antagonists”, “bronchial thermoplasty”, “immunoglobulin E therapy”, and “tumour necrosis factor”. Fig 1 Simplified diagram of the pharmacological management of chronic asthma in adults1 w1 Several key questions must be considered before prescribing add-on treatments and higher …

Recent developments in asthma management

Asthma is a common chronic heterogeneous condition with several characteristic features (%fig 1). It can present in early childhood as well as in adulthood, and it varies markedly in severity, clinical course, subsequent disability, and response to treatment. In common with other atopic disorders such as allergic rhinitis, atopic dermatitis, and food allergy, the prevalence of asthma has risen over the past few decades in both developed and developing countries.1 The increasing burden of asthma in primary and secondary care has led to extensive research into its genetics, pathophysiology, and treatment. In this review, we highlight some of the recent developments in the clinical management of asthma and identify key areas in which further research is needed. Fig 1 The key components of asthma We did a comprehensive literature search using Medline, Clinical Evidence, the Cochrane Library, and Embase. We used the following keywords in the search: acute asthma, chronic asthma, leucotriene receptor antagonist, long acting β2 agonist, inhaled corticosteroid, action plans, allergen, diet, magnesium, vitamin, Buteyko, anti-immunoglobulin E, and interleukin. We selected and extracted recent articles from 2000 onwards that we felt to be of relevance or interest to practising clinicians, as well as choosing topics that we were aware of being potentially important. All the authors are respiratory physicians with an interest in airways disease. ### Non-pharmacological management #### Allergen avoidance Atopy and asthma are separate conditions with differing genetic and epidemiological associations. Although atopic sensitisation increases the likelihood of asthma, this is not an absolute association. Allergen avoidance is commonly recommended in patients with asthma, especially those who show type 1 hypersensitivity to common aeroallergens.1 2 However, a surprising lack of evidence based data exists to substantiate the effectiveness of this approach. Several major studies have specifically evaluated allergen avoidance and its impact on asthma control. In a double blind randomised placebo …

Does Bronchial Hyperresponsiveness in Asthma Matter

Bronchial hyperresponsiveness is a fundamental component of the asthmatic inflammatory process causing airway narrowing on exposure to a bronchoconstrictor stimulus. This in turn causes patients to experience symptoms of breathlessness, chest tightness, cough and wheeze. Bronchial challenge tests can be performed in the laboratory to establish the degree of bronchial hyperresponsiveness to both direct and indirect stimuli. The extent to which asthma pharmacotherapy attenuates bronchial hyperresponsiveness is therefore an important measure of efficacy. This review article discusses the effects of inhaled and oral asthma treatment upon bronchial hyperresponsiveness and highlights how, in conjunction with conventional measures of asthma control, it can be used as an aid to optimally manage patients.

The expanding role of leukotriene receptor antagonists in chronic asthma

OBJECTIVE To provide a comprehensive review of studies that evaluate the effects of leukotriene receptor antagonists in adult chronic asthma. DATA SOURCES A literature search using MEDLINE, Clinical Evidence, and the Cochrane Library was performed using the following keywords: randomized controlled trial, asthma, cysteinyl leukotriene, leukotriene receptor antagonist, antileukotriene, montelukast, zafirlukast, pranlukast, inflammation, lung function, exacerbations, and symptoms. STUDY SELECTION Relevant peer-reviewed articles (mostly randomized controlled trials, meta-analyses, and reviews) published up to July 2006 were selected and extracted. RESULTS Leukotriene receptor antagonists are beneficial across a range of asthma severities and may have a particular role in exercise-induced asthma, aspirin-sensitive asthma, and individuals with concomitant allergic rhinitis. CONCLUSION In the management of chronic asthma, leukotriene receptor antagonists have emerged as a useful oral nonsteroidal anti-inflammatory adjunct both as monotherapy and in combination with other classes of drugs. Monitoring their effects in terms of lung function alone may result in clinicians missing beneficial effects on inflammatory biomarkers, airway hyperresponsiveness, and exacerbations.

An overview of how asbestos exposure affects the lung

#### Summary points People exposed to asbestos often develop lung disease in later life; manifestations include benign, malignant, or diffuse interstitial lung disease. This evidence based review covers who is considered to be at risk, different ways that exposure to asbestos affect the lung, and matters relating to compensation. Because many doctors in primary and secondary care encounter patients who have been exposed to asbestos, they need to be aware of how different people can be affected. #### Sources and selection criteria We comprehensively searched articles published up to February 2009 using PubMed and Medline. Key words and phrases used were “asbestos”, “malignant mesothelioma”, “pleural plaques”, “pleural thickening”, “asbestosis”, “lung cancer”, “cigarette smoking”, “pleural effusions”, “compensation”, “occupation”, “chemotherapy”, “radiotherapy”, “surgery”, “treatment”, and “survival” All people who have worked with asbestos are at potential risk of asbestos related lung disease through inhalation of fibres. Asbestos is a mineral silicate that occurs naturally in various forms. It is resistant to heat and other means of destruction, which explains its extensive use during the 19th and 20th centuries. The fibrous nature of asbestos allows it to be woven into cloth or incorporated into cement materials, ceiling tiles, brake and clutch linings, pipe and boiler …

Long-Acting β2-Agonists in Asthma

Asthma is a worldwide chronic disorder that is characterised by airway inflammation and hyper-responsiveness, which results in intermittent airflow obstruction and subsequent perception of symptoms and exacerbations. Inhaled corticosteroids are a fundamental component in the prevention of the short- and long-term complications associated with inadequately controlled asthma. However, many individuals experience persistent symptoms and exacerbations despite receiving low-to-medium doses of an inhaled corticosteroid (400–800 μg/day of beclometasone or equivalent). In these symptomatic asthmatic patients, guidelines advocate the initiation of a long-acting β2-adrenoceptor agonist (LABA) as additional second-line controller therapy.The recent SMART (Salmeterol Multi-centre Asthma Research Trial) study was designed to compare the effects of add-on salmeterol 42 μg (ex-actuator) twice daily with placebo over 28 weeks in a randomised, double-blind, parallel-group fashion, with the intention to enrol 60 000 asthmatic patients. However, the study was halted prematurely because preliminary data revealed an increased mortality associated with regular use of salmeterol. Moreover, concerning rates of respiratory-related deaths, asthma-related deaths and life-threatening events were observed among African Americans, who constituted up to 18% of the study population. This in turn prompted the US FDA to announce important safety information regarding inhalers containing LABAs and advise that new labelling be produced outlining the “ small but significant risk in asthma-related deaths” associated with their regular use. This evidence-based review discusses the data from SMART and highlights potentially important drawbacks with regular use of LABAs in persistent asthma.

Phosphodiesterase 4 inhibitors in chronic obstructive pulmonary disease: a new approach to oral treatment

Chronic obstructive pulmonary disease represents a major global health care burden for both primary and secondary care providers and is the most common respiratory condition necessitating hospital admission. Short-acting bronchodilators play a vital role in immediate relief of symptoms, while inhaled long-acting bronchodilators and inhaled corticosteroids are advocated for regular use in individuals with persistent symptoms and exacerbations. Theophylline is a nonspecific phosphodiesterase inhibitor and is usually reserved for patients with ongoing symptoms despite optimum inhaled bronchodilator treatment or when difficulty is encountered with inhaler devices. However, it is often not widely used mainly due to frequency of dose-related adverse effects, numerous drug interactions and narrow therapeutic index. This in turn has lead to the development of more selective phosphodiesterase inhibitors in an attempt to create a drug which patients can use with beneficial effects but without the problems associated with theophylline. Current data do indicate that phosphodiesterase 4 inhibitors confer some benefits in chronic obstructive pulmonary disease when compared to placebo in terms of lung function, quality of life and exacerbations. They are also generally well tolerated. Further studies are required to determine fully their long-term beneficial and adverse effect profiles and ultimately where they might comfortably sit in management algorithms.

Predicting survival following non-invasive ventilation for hypercapnic exacerbations of chronic obstructive pulmonary disease

Introduction:  Non‐invasive ventilation (NIV) has revolutionised the management of hypercapnic exacerbations of chronic obstructive pulmonary disease (COPD). We wished to evaluate factors related to its overall success in the ‘real‐life’ setting.