Editorial
Frequent or Persistent Exacerbations: Identifying the Real Problem
Agudizaciones frecuentes o persistentes: identificando el problema real
a Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Universidad de Sevilla, Sevilla, Spain
b Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain
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"referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Carmen" "apellidos" => "Calero-Acuña" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Eduardo" "apellidos" => "Márquez-Martín" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Universidad de Sevilla, Sevilla, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Agudizaciones frecuentes o persistentes: identificando el problema real" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">It is well known that exacerbations of chronic obstructive pulmonary disease (COPD) represent a health problem of the first order in the clinical presentation of the disease. Current clinical guidelines acknowledge frequent exacerbations as a significant clinical presentation that needs a specific therapeutic approach.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">For some time, clinicians have known that some patients present more exacerbations than others. However, the concept of frequent exacerbator often reflected in the guidelines was based to a large extent on the “Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points” study (ECLIPSE). This was a large multicenter observational cohort study which followed 2164 COPD patients receiving active treatment, 337 smokers with normal lung function and 245 never-smokers, for a period of 3 years. The authors analyzed the frequency of exacerbations and identified a group (12%) that had 2 or more exacerbations every year, despite active treatment, another group (23%) who were persistently exacerbation-free, and a third group (65%) with a variable number of annual exacerbations.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> This study also identified a history of previous exacerbations as the greatest isolated risk factor for predicting an exacerbation in the following year, thus establishing a pattern of clinical behavior among patients who were prone to exacerbations and consolidating the notion of a frequent exacerbator patient.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Therefore, 3 years of follow-up were needed to identify a group of patients who continue to have exacerbations despite medical treatment, and on this basis the current concept of an exacerbator patient was established. Current guidelines have simplified this concept by limiting the evaluation of the number of exacerbations to the previous year.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,3</span></a> However, in the light of the ECLIPSE study results, limiting the analysis to the number of exacerbations in the previous year may lead to a misclassification of patients by number of exacerbations.</p><p id="par0020" class="elsevierStylePara elsevierViewall">When considering this matter, it is important to scrutinize treatments and how they impact on the number of exacerbations. Currently, many treatments are available that are useful for reducing the number of exacerbations,<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> with a similar average impact. Accordingly, regardless of the debate about what treatment might be more effective depending on the type of exacerbation,<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> a patient who presented frequent exacerbations during the previous year may not constitute a major challenge for the clinician, since several effective treatments are available for reducing the rate of these events.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Our real problem is the patient who continues having exacerbations despite appropriate medical treatment, a correct inhalation technique, and good treatment adherence. The persistent exacerbator should then be defined as the patient who continues to have exacerbations despite appropriate inhaled treatment. Due to the clinical implications of exacerbations in the clinical course of COPD,<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> these patients (12% in the ECLIPSE cohort<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a>) constitute a real health problem and a major challenge to clinicians, since exacerbations are a clinical outcome which should improve with treatment.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Consequently, the diagnostic approach of the persistent exacerbator patient must be made using a systematic approach that can identify the conditions contributing to persisting exacerbations, thus enabling the physician to select the best preventive treatment possible. Because of its complexity, this process must be conducted in a specialized respiratory care setting. This systematic approach must include, but is not limited to, the following clinical considerations.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Firstly, the patient must avoid risk factors, particularly smoking which is the most significant risk factor, but also other possible factors including occupational exposures. In this respect, this clinical situation should be a motivation to help the patient advancing in the process of smoking cessation for which we have specific recommendations.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Secondly, respiratory comorbidities that may impact on the appearance of exacerbations must be evaluated. The most significant of these is probably the presence of bronchiectasis. Bronchiectasis in COPD patients is associated with frequent exacerbations, isolation of a potentially pathogenic microorganism, severe respiratory obstruction, and mortality.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> Another cause of infectious exacerbations is colonization or chronic infection of the airway, so it seems reasonable to recommend a high-resolution computed tomography scan and a microbiological study of sputum as part of the evaluation of these patients. Finally, the respiratory evaluation must include an investigation for the presence of an overlap syndrome with severe bronchial asthma<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> that might require specific treatment such as biologics.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Thirdly, potentially treatable extrapulmonary comorbidities that might be associated with the appearance of exacerbations must be studied. These include heart diseases which, given their obvious physiological relationship and symptomatic similarity to respiratory disease, can at times make it difficult to distinguish exacerbations of respiratory or cardiologic origin. Gastroesophageal reflux disease in COPD patients is associated with increased respiratory symptoms, poorer quality of life and more frequent exacerbations.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> Although the efficacy of proton pump inhibitors in the reduction of exacerbations has been questioned,<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> it seems reasonable to take this comorbidity into account in the study of the persistent exacerbator. Finally, since exacerbations are mostly caused by infections,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> immunodeficiency should also ruled out.</p><p id="par0050" class="elsevierStylePara elsevierViewall">In conclusion, there is no doubt that persistent exacerbations despite correct medical treatment are a challenge for the clinician, and must be approached systematically in a specialized respiratory medicine department. In remembrance of the famous novel of D. Miguel de Cervantes Saavedra (1547-1616), <span class="elsevierStyleItalic">The Ingenious Hidalgo Don Quixote</span>, this year we commemorate the 400th anniversary of his death, and instead of tilting at windmills when treating exacerbations, we should focus resources on identifying the real enemy, persistent exacerbators, and evaluate their determinant factors in order to offer the best preventive treatment possible in each case.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of Interests</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors state that they have no conflict of interests with regard to this manuscript.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of Interests" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Lopez-Campos JL, Calero-Acuña C, Márquez-Martín E. Agudizaciones frecuentes o persistentes: identificando el problema real. Arch Bronconeumol. 2016;52:577–578.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Spanish guideline for COPD (GesEPOC). Update 2014" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Miravitlles" 1 => "J.J. Soler-Cataluna" 2 => "M. Calle" 3 => "J. Molina" 4 => "P. Almagro" 5 => "J.A. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 6 | 3 | 9 |
| 2024 October | 52 | 26 | 78 |
| 2024 September | 55 | 19 | 74 |
| 2024 August | 91 | 36 | 127 |
| 2024 July | 57 | 20 | 77 |
| 2024 June | 85 | 33 | 118 |
| 2024 May | 77 | 30 | 107 |
| 2024 April | 65 | 32 | 97 |
| 2024 March | 41 | 16 | 57 |
| 2024 February | 33 | 20 | 53 |
| 2023 November | 1 | 0 | 1 |
| 2023 March | 6 | 4 | 10 |
| 2023 February | 59 | 28 | 87 |
| 2023 January | 46 | 22 | 68 |
| 2022 December | 64 | 35 | 99 |
| 2022 November | 65 | 18 | 83 |
| 2022 October | 51 | 40 | 91 |
| 2022 September | 50 | 26 | 76 |
| 2022 August | 61 | 45 | 106 |
| 2022 July | 56 | 54 | 110 |
| 2022 June | 86 | 35 | 121 |
| 2022 May | 84 | 27 | 111 |
| 2022 April | 61 | 31 | 92 |
| 2022 March | 64 | 44 | 108 |
| 2022 February | 40 | 23 | 63 |
| 2022 January | 57 | 36 | 93 |
| 2021 December | 53 | 36 | 89 |
| 2021 November | 60 | 49 | 109 |
| 2021 October | 54 | 51 | 105 |
| 2021 September | 51 | 46 | 97 |
| 2021 August | 46 | 33 | 79 |
| 2021 July | 46 | 31 | 77 |
| 2021 June | 85 | 35 | 120 |
| 2021 May | 54 | 30 | 84 |
| 2021 April | 187 | 89 | 276 |
| 2021 March | 95 | 24 | 119 |
| 2021 February | 53 | 29 | 82 |
| 2021 January | 43 | 19 | 62 |
| 2020 December | 44 | 19 | 63 |
| 2020 November | 38 | 14 | 52 |
| 2020 October | 42 | 21 | 63 |
| 2020 September | 35 | 6 | 41 |
| 2020 August | 40 | 13 | 53 |
| 2020 July | 32 | 26 | 58 |
| 2020 June | 36 | 7 | 43 |
| 2020 May | 48 | 11 | 59 |
| 2020 April | 32 | 17 | 49 |
| 2020 March | 24 | 14 | 38 |
| 2020 February | 67 | 19 | 86 |
| 2020 January | 33 | 16 | 49 |
| 2019 December | 32 | 16 | 48 |
| 2019 November | 30 | 21 | 51 |
| 2019 October | 10 | 6 | 16 |
| 2019 September | 11 | 11 | 22 |
| 2019 August | 23 | 16 | 39 |
| 2019 July | 19 | 13 | 32 |
| 2019 June | 14 | 17 | 31 |
| 2019 May | 31 | 19 | 50 |
| 2019 April | 37 | 16 | 53 |
| 2019 March | 23 | 20 | 43 |
| 2019 February | 32 | 20 | 52 |
| 2019 January | 25 | 14 | 39 |
| 2018 December | 26 | 8 | 34 |
| 2018 November | 54 | 17 | 71 |
| 2018 October | 56 | 22 | 78 |
| 2018 September | 19 | 10 | 29 |
| 2018 May | 15 | 1 | 16 |
| 2018 April | 58 | 6 | 64 |
| 2018 March | 31 | 8 | 39 |
| 2018 February | 53 | 7 | 60 |
| 2018 January | 98 | 9 | 107 |
| 2017 December | 62 | 8 | 70 |
| 2017 November | 29 | 7 | 36 |
| 2017 October | 23 | 9 | 32 |
| 2017 September | 28 | 23 | 51 |
| 2017 August | 30 | 16 | 46 |
| 2017 July | 23 | 13 | 36 |
| 2017 June | 36 | 11 | 47 |
| 2017 May | 30 | 20 | 50 |
| 2017 April | 33 | 15 | 48 |
| 2017 March | 15 | 9 | 24 |
| 2016 November | 1 | 1 | 2 |
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