The field of acute exacerbations in chronic respiratory disease is challenging: definitions of acute exacerbations differ amongst the diseases and their severity has proven difficult to define. The Guest Editors of this Monograph tackle this challenging area by bringing together articles from internationally recognised experts in the field of acute exacerbations in chronic lung diseases. The book is separated into three sections: the first considers the definition, severity and consequences of exacerbations in each disease; the second looks at exacerbation triggers; and the third discusses the treatment and prevention of exacerbations using pharmacological and non-pharmacological interventions. The book's structure allows comparisons between the definitions, short- and long-term consequences, triggers and therapeutic management of different respiratory diseases. It serves as a complete reference that raises awareness about the importance of acute exacerbations in patients with chronic lung diseases.
- ERS Monograph
- Page 1AbstractAlberto Papi, Research Centre on Asthma and COPD, Dept of Medical Sciences, University of Ferrara, Via Rampari di S. Rocco, 27-44121 Ferrara, Italy. E-mail: ppa@unife.it
Asthma is one of the most common chronic respiratory diseases worldwide. The natural history of the disease is punctuated by episodes of symptom worsening, termed exacerbations. These play an important role in the natural history of the disease, in terms of their effect on morbidity and mortality and because of the economic healthcare burden. Exacerbations are generally acute or subacute in presentation and may, in some cases, represent the initial presentation of bronchial asthma. Clinically, it is important to understand and recognise the risk factors involved in triggering an acute event. When facing a patient with suspected exacerbated asthma, clinicians must first exclude a diagnosis other than asthma and then identify potential risks for asthma-related death and assess the clinical severity of the manifestations. Proper asthma management and treatment should primarily aim to prevent and reduce, and possibly eradicate, exacerbation episodes.
Cite as: Morandi L, Bellini F, Papi A. Asthma: definition, severity and impact of pulmonary exacerbations. In: Burgel P-R, Contoli M, López-Campos JL, eds. Acute Exacerbations of Pulmonary Diseases (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 1–12 [https://doi.org/10.1183/2312508X.0015516].
- Page 13AbstractJohn R. Hurst, UCL Respiratory, University College London, London WC1E 6BT, UK. E-mail: j.hurst@ucl.ac.uk
This chapter reviews approaches to the definitions, severity and impact of exacerbations in COPD. The “clinical diagnosis of exclusion” approach to COPD exacerbation, used in daily practice, contrasts with the symptom-based and healthcare utilisation definitions of exacerbation employed in clinical trials. There are strengths and weaknesses to these different definitions that should be considered when interpreting research. There remains no biomarker of exacerbation, in part because exacerbations are heterogeneous events. What is loosely called “exacerbation severity” is in fact a composite of the severity of the underlying COPD and the severity of the exacerbation insult. There are several scores that may aid the prediction of poor outcomes at exacerbation. Exacerbations affect lung function, health status, the timing of future exacerbations and mortality, and therefore the exacerbation-susceptible “frequent-exacerbator” phenotype experiences a particular burden of disease. Exacerbations also contribute significantly to healthcare expenditure. Prevention and mitigation of exacerbations are therefore key goals of COPD management.
Cite as: Simons SO, Hurst JR. COPD: definition, severity and impact of pulmonary exacerbations. In: Burgel P-R, Contoli M, López-Campos JL, eds. Acute Exacerbations of Pulmonary Diseases (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 13–24 [https://doi.org/10.1183/2312508X.10015616].
- Page 25AbstractPatrick A. Flume, Medical University of South Carolina, 96 Jonathan Lucas Street, Room 816-CSB, MSC 630, Charleston, SC, USA. E-mail: flumepa@musc.edu
Pulmonary exacerbations are common events in patients with CF lung disease. Although we lack a consensus definition, they are generally defined as worsening of the daily respiratory and systemic symptoms, often with an acute drop in pulmonary function. For a myriad of reasons, described here, the current best definition of a pulmonary exacerbation is the physician's decision to treat for that indication. The problem with this definition is demonstrated by the variability among clinicians. Issues with other attempts at a definition are also reviewed here. Similarly, there are hurdles to establishing the severity of an exacerbation, as treatment decisions such as hospitalisation are influenced by factors other than worse illness. Exacerbations are associated with multiple adverse outcomes, including loss of lung function, high financial burden and even mortality. Understanding the causes of exacerbations and development of therapies to prevent them are of utmost importance.
Cite as: Flume PA, VanDevanter DR. Cystic fibrosis: definition, severity and impact of pulmonary exacerbations. In: Burgel PR, Contoli M, López-Campos JL, eds. Acute Exacerbations of Pulmonary Diseases (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 25–37 [https://doi.org/10.1183/2312508X.10015716].
- Page 38AbstractJames D. Chalmers, Division of Molecular and Clinical Medicine, University of Dundee, Dundee DD1 9SY, UK. E-mail: jchalmers@dundee.ac.uk
Exacerbations of bronchiectasis are common, with European data suggesting that the average patient experiences two exacerbations per year. Exacerbations have been associated with worse QoL, lung function decline and increased mortality. Exacerbations are highly heterogeneous, presenting most frequently with increasing cough and sputum production, but also commonly with breathlessness, wheeze, malaise and systemic features. There is a lack of research into the causes of bronchiectasis exacerbations, but antibiotic therapy is currently recommended for all exacerbations because of the high frequency of bacterial infection in the disease. Exacerbations are the primary end-point for the majority of late-phase bronchiectasis clinical trials, although these have been limited by the lack of a standardised definition. The EMBARC (European Multicentre Bronchiectasis Audit and Research Collaboration) network, in collaboration with colleagues from the USA, Australasia and South Africa, has recently generated a consensus definition of exacerbations, which should help to standardise outcomes. Exacerbations are key events in the natural history of bronchiectasis. There is an urgent need for further research into the causes, optimal management and outcomes of bronchiectasis exacerbations.
Cite as: Finch S, Dicker AJ, Chalmers JD. Non-cystic fibrosis bronchiectasis: definition, severity and impact of pulmonary exacerbations. In: Burgel P-R, Contoli M, López-Campos JL, eds. Acute Exacerbations of Pulmonary Diseases (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 38–57 [https://doi.org/10.1183/2312508X.10015816].
- Page 58AbstractChristopher J. Ryerson, Dept of Medicine and Centre for Heart Lung Innovation, University of British Columbia and St Paul's Hospital, Vancouver, BC, Canada. E-mail: Chris.Ryerson@hli.ubc.ca
A recent international working group has suggested redefining AE of IPF (AE-IPF) as an acute, clinically significant respiratory deterioration characterised by evidence of new widespread alveolar abnormality. These revised diagnostic criteria consist of: 1) previous or concurrent diagnosis of IPF, 2) acute worsening or development of dyspnoea typically of <1 month duration, 3) CT with new bilateral ground-glass opacity and/or consolidation superimposed on a background pattern consistent with a usual interstitial pneumonia pattern and 4) deterioration not fully explained by cardiac failure or fluid overload. This represents a major change from the previous definition and diagnostic criteria, most significantly in no longer requiring AEs to be idiopathic. Historically, the annual incidence of AE-IPF ranges between 1% and 20%, and AEs have an in-hospital mortality of 27–65%. Multicentre registries and networks are necessary to revisit the epidemiology of AE using the revised definition, further define the risk factors for AE, and develop both preventative and therapeutic management approaches.
Cite as: Tanizawa K, Collard HR, Ryerson CJ. IPF: definition, severity and impact of pulmonary exacerbations. In: Burgel P-R, Contoli M, López-Campos JL, eds. Acute Exacerbations of Pulmonary Diseases (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 58–65 [https://doi.org/10.1183/2312508X.10015916].
- Page 66AbstractIsabella Annesi-Maesano, EPAR – UPMC INSERM UMR-S 1136, Paris 6, Medical School Saint-Antoine, 27 rue Chaligny, 75571 Paris Cedex 12, France. E-mail: isabella.annesi-maesano@inserm.fr
Major threats causing AEs of pulmonary diseases include exposure to chemical air pollutants and biocontaminants, including allergens. The impact of chemical air pollutants on asthma attacks and COPD exacerbation is well established. The impact of airborne allergens is also well documented in the case of asthma and for rhinitis attacks and aggravation. Recently, an association has also been found between air pollution and IPF exacerbations. The modalities of action are different. The lag period (time between the exposure event and aggravation) is short (up to few hours or days) for both allergens and chemical air pollution in the case of asthma, and longer in the case of chemical pollutants for COPD and IPF. Whether a combination of air pollution and allergens is associated with a higher risk of pulmonary disease aggravation than exposure to each individually needs to be elucidated. The role of prevention has been promoted, but is often difficult in practice.
Cite as: Annesi-Maesano I. Chemical air pollution and allergen exposure. In: Burgel P-R, Contoli M, López-Campos JL, eds. Acute Exacerbations of Pulmonary Diseases (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 66–75 [https://doi.org/10.1183/2312508X.10016016].
- Page 76AbstractSebastian L. Johnston, Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, Norfolk Place, London W2 1PG, UK. E-mail: s.johnston@imperial.ac.uk
Respiratory virus infections are the most common human infectious disease syndrome. Overwhelming epidemiological, clinical and experimental evidence indicates that respiratory viruses are the major triggers of AEs in patients with chronic airway diseases such as asthma, COPD, CF and interstitial lung disease. Nevertheless, treatments for respiratory viruses (other than influenza virus) have yet to be developed, and therefore the enormous burden of disease associated with respiratory virus infection in these chronic airway diseases remains unaddressed. This failure to develop antiviral therapies needs to be addressed by both the scientific community and the pharmaceutical industry if the morbidity and mortality of virus-induced exacerbations are to be reduced in the future.
Cite as: Ritchie AI, Mallia P, Johnston SL. Viral infection. In: Burgel P-R, Contoli M, López-Campos JL, eds. Acute Exacerbations of Pulmonary Diseases (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 76–96 [https://doi.org/10.1183/2312508X.10016116].
- Page 97AbstractSanjay Sethi, Clinical and Translational Research Center, Room 6045A, 875 Ellicott Street, Buffalo, NY 14203, USA. E-mail: ssethi@buffalo.edu
There is a wide range in the importance of bacteria as a trigger of exacerbations of respiratory disease, from a limited role in asthma and IPF to a dominant role in CF and bronchiectasis, with an intermediate role in COPD. Conventional techniques to understand bacterial infection, such as culture and antibody response studies, are being replaced with new methods, such as microbiome and immuno-inflammatory profiling, with consequent new insights and a rethinking of traditional concepts. The trend is towards recognition of a more substantial role for bacteria in exacerbations and even in stable disease pathogenesis than previously thought, with an appreciation that infections are often polymicrobial and that changes in microbial community composition can cause disruption of the stable homeostatic state leading to exacerbations. Future studies are likely to contribute further changes to our understanding in this area, with innovative therapeutic implications.
Cite as: Provost KA, Frederick CA, Sethi S. Bacterial infection. In: Burgel P-R, Contoli M, López-Campos JL, eds. Acute Exacerbations of Pulmonary Diseases (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 97–113 [https://doi.org/10.1183/2312508X.10016216].
- Page 114AbstractFrits M.E. Franssen, Dept of Development and Education, Center of Expertise for Chronic Organ Failure (CIRO), Hornerheide 1, 6085 NM Horn, The Netherlands. E-mail: fritsfranssen@ciro-horn.nl
The inflammatory responses and triggers of COPD exacerbations are heterogeneous, and these events are increasingly recognised as episodes with enhanced risks. As exacerbation diagnosis is based on symptoms rather than objective measures, other pathologies may mimic its presentation. Myocardial infarction and heart failure are common in exacerbating patients, and those with elevated cardiac biomarkers have increased odds for mortality. In additional to traditional risk factors, other or enhanced risk factors may contribute to the observed increase in cardiovascular risk during exacerbations. Furthermore, a high prevalence of pulmonary embolism has been observed in COPD patients with exacerbation, mainly in those with absence of lower respiratory tract infection symptoms or other obvious aetiologies. Healthcare professionals caring for COPD patients with exacerbations should be aware of the differential diagnosis of these events and consider additional diagnostics following clinical suspicion. The current literature suggests that diagnostic algorithms and pharmacological treatment of non-COPD-related events during COPD exacerbations are comparable to stable-state and other patient groups.
Cite as: Franssen FME, Vanfleteren LEGW. Differential diagnosis and impact of cardiovascular comorbidities and pulmonary embolism during COPD exacerbations. In: Burgel P-R, Contoli M, López-Campos JL, eds. Acute Exacerbations of Pulmonary Diseases (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 114–128 [https://doi.org/10.1183/2312508X.10016316].
- Page 129AbstractArnaud Bourdin, Dept of Respiratory Disease, Hôpital Arnaud de Villeneuve, 371 Avenue du Doyen Giraud, 34295 Montpellier Cedex 5, France. E-mail: a-bourdin@chu-montpellier.fr
The typical management plan for treatment for an exacerbation of asthma has mostly remained unchanged for 20 years, with systemic steroids and bronchodilators remaining the unavoidable cornerstones for treatment. Deaths due to asthma are rare occurrences in the hospital setting, which does not provide an incentive for improvements in treatment management. However, it is thought that ∼50% of asthma deaths overall may be preventable. This has stimulated new research into the use of biologics, resulting in a promising new era where management strategies are likely to shift dramatically.
Cite as: Charriot J, Volpato M, Sueh C, et al. Asthma: treatment and prevention of pulmonary exacerbations. In: Burgel P-R, Contoli M, López-Campos JL, eds. Acute Exacerbations of Pulmonary Diseases (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 129–146 [https://doi.org/10.1183/2312508X.10016416].
- Page 147AbstractNicolas Roche, Pneumologie et Réanimation, Hôpital Cochin, 27 rue du Fbg Saint Jacques, 75014 Paris, France. E-mail: nicolas.roche@aphp.fr
COPD exacerbations are frequent events that have major short- and long-term impacts on both patients and society, making their treatment and prevention crucial issues. Recognising exacerbations in order to initiate early treatment is the first step of their management, followed by determining whether the patient can be managed at home or should be referred to the hospital. Exacerbation treatments rely on bronchodilators, antibiotics and corticosteroids, as well as oxygen therapy and ventilatory support if required. Prevention of exacerbations is based on pharmacological agents (mostly inhaled treatments, i.e. long-acting bronchodilators and corticosteroids) that should be prescribed gradually based on the patient's individualised categorisation, and on nonpharmacological measures, including smoking cessation, rehabilitation, education and integrated care. Efforts should also be directed at improving guideline implementation and standards of care in this area, to offer all patients a personalised approach.
Cite as: Roche N. COPD: treatment and prevention of pulmonary exacerbations. In: Burgel P-R, Contoli M, López-Campos JL, eds. Acute Exacerbations of Pulmonary Diseases (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 147–166 [https://doi.org/10.1183/2312508X.10016516].
- Page 167AbstractJ. Stuart Elborn, National Heart and Lung Institute, Imperial College London, Sydney Street, Chelsea, London SW3 6NP, UK. E-mail: j.elborn@imperial.ac.uk
Pulmonary exacerbations are frequent and clinically important events in the natural history of CF. The frequency of pulmonary exacerbations is associated with poor clinical outcomes. Preventing pulmonary exacerbations is a high priority in delivering optimal care for people with CF. A number of therapies have been shown to reduce pulmonary exacerbations in clinical trials, and these should be used in a targeted way in individual patients. When pulmonary exacerbations occur, treatment should be commenced promptly, and for each event, people with CF and their multidisciplinary team should consider the optimal treatment regime with new antibiotics combined with augmentation of regular therapies.
Cite as: Elborn JS. Cystic fibrosis: treatment and prevention of pulmonary exacerbations. In: Burgel P-R, Contoli M, López-Campos JL, eds. Acute Exacerbations of Pulmonary Diseases (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 167–180 [https://doi.org/10.1183/2312508X.10016616].
- Page 181AbstractMike J. Harrison, Papworth NHS Foundation Trust, Papworth Everard, Cambridge CB23 3RE, UK. E-mail: mike.harrison9@nhs.net
Prevention and treatment of exacerbations are vital for the effective management of bronchiectasis. There is a lack of clinical trials to help guide clinicians with regard to evidence-based interventions for patients with bronchiectasis. Recent clinical trial evidence supports the use of long-term oral macrolide therapy to prevent exacerbations in patients with and without chronic Pseudomonas infection. There is less robust evidence for therapies used to treat exacerbations in bronchiectasis, and for other therapies that aim to prevent exacerbations, including inhaled antibiotics. As a result, clinical practice varies significantly among clinicians. The development of large international databases should increase the evidence base for interventions. International guidelines are due to be published in 2017 that will update best-practice management of patients with bronchiectasis.
Cite as: Harrison MJ, Haworth CS. Non-cystic fibrosis bronchiectasis: treatment and prevention of pulmonary exacerbations. In: Burgel P-R, Contoli M, López-Campos JL, eds. Acute Exacerbations of Pulmonary Diseases (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 181–198 [https://doi.org/10.1183/2312508X.10016716].
- Page 199AbstractCarola Condoluci, A. Gemelli University Hospital, Catholic University of the Sacred Heart, Largo F. Vito 1, 00168 Rome, Italy. E-mail: carola.condoluci@gmail.com
AE of IPF (AE-IPF) represents episodes of acute and rapid respiratory deterioration without identifiable aetiology during the clinical course of IPF, and is burdened by a high mortality rate. It represents the leading cause of hospitalisation and death among patients with IPF. Currently available therapeutic strategies are poorly effective, and guidelines recommend best supportive care in association with high-dose steroid therapy, although the strength of the latter recommendation is weak. We review the available evidence on the treatment of AE-IPF, emphasising the therapeutic options supported by the current guidelines and describing new therapeutic approaches provided by various emerging drugs. We also examine the main points related to AE-IPF supportive care. Finally, we review the current approaches to prevention of AE-IPF.
Cite as: Condoluci C, Inchingolo R, Mastrobattista A, et al. IPF: treatment and prevention of pulmonary exacerbations. In: Burgel P-R, Contoli M, López-Campos JL eds. Acute Exacerbations of Pulmonary Diseases (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 199–223 [https://doi.org/10.1183/2312508X.10002017].
- Page 22415. The role of pulmonary rehabilitation in the prevention of exacerbations of chronic lung diseasesAbstractWim Janssens, Dept of Respiratory Diseases, KU Leuven, Herestraat 49, B-3000 Leuven, Belgium. E-mail: wim.janssens@uzleuven.be
The prevention of exacerbations and hospital admissions is of major importance in the management of COPD. Various studies, including meta-analyses, have demonstrated that pulmonary rehabilitation programmes can reduce the risk of hospital readmission and may prevent future events. At present, the heterogeneity of studies and the small number of patients involved allows only a weak recommendation for pulmonary rehabilitation programmes to reduce exacerbations in patients at risk. This chapter speculates on the mechanisms through which these potential benefits are obtained. The targeted population, the optimal moment of pulmonary rehabilitation initiation and the multidisciplinary strategies that should be implemented are also discussed. Future studies that have been adequately designed and powered to study the effect of pulmonary rehabilitation programmes on the prevention of AEs are now needed.
Cite as: Rodrigues FM, Loeckx M, Troosters T, et al. The role of pulmonary rehabilitation in the prevention of exacerbations of chronic lung diseases. In: Burgel P-R, Contoli M, López-Campos JL, eds. Acute Exacerbations of Pulmonary Diseases (ERS Monograph). Sheffield, European Respiratory Society, 2017; pp. 224–246 [https://doi.org/10.1183/2312508X.10016916].