Editorial
The Post-truth Behind the Asthma-COPD Overlap and the Orbit of Mercury: Lessons From the CHACOS Study
La posverdad detrás del solapamiento entre asma y EPOC y la órbita de Mercurio. Lecciones del estudio CHACOS
a Servicio de Neumología, Hospital Lucus Augusti, Lugo, Spain
b Servicio de Neumología, Hospital Universitario Virgen del Rocío, Sevilla, Spain
c CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain
d Servicio de Neumología, Hospital Universitario Son Espases-IdISBa, Palma de Mallorca, Baleares, Spain
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"apellidos" => "Cosío" "email" => array:1 [ 0 => "borja.cosio@ssib.es" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Servicio de Neumología, Hospital Lucus Augusti, Lugo, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Neumología, Hospital Universitario Virgen del Rocío, Sevilla, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Neumología, Hospital Universitario Son Espases-IdISBa, Palma de Mallorca, Baleares, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La posverdad detrás del solapamiento entre asma y EPOC y la órbita de Mercurio. Lecciones del estudio CHACOS" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The overlap between asthma and chronic obstructive pulmonary disease (COPD) in the same patient is one of the current challenges of research into respiratory diseases. Briefly, there are 2 distinct interpretations of this overlap that are not necessarily exclusive. One is that 2 different diseases (COPD and asthma) co-exist in the same patient; and the other is that the patient has only 1 of the diseases, but presents clinical features which departs from the conventional conception of COPD or asthma.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a> This debate has led to the publication of a wide range of diagnostic criteria for identifying these patients.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The initial hypothesis of the CHACOS study (Characterization of ACO in Spain), sponsored by the Society of Pulmonology and Thoracic Surgery (SEPAR) and funded by the Instituto de Salud Carlos III and Chiesi Spain, was that if COPD and asthma coincided in the airway of the same patient, this would cause an inflammatory process in which the biological characteristics of each entity would merge. The objective, then, was to find unique clinical or functional features or biomarkers that would help differentiate ACO patients from those with COPD or asthma and chronic airflow obstruction (CAFO). CHACOS was a cross-sectional study in which investigators from 23 hospitals participated. In total, 292 patients >40 years of age with post-bronchodilator FEV<span class="elsevierStyleInf">1</span>/FVC <70%, were included, 94 of whom were non-smokers with asthma, 89 had COPD, and 109 were classified as having ACO, according to 2 criteria: CAFO in smoking asthmatics (44 patients) or COPD with eosinophilia ≥200<span class="elsevierStyleHsp" style=""></span>cells/μL (65 patients), which we called “eosinophilic COPD”.</p><p id="par0015" class="elsevierStylePara elsevierViewall">An initial analysis was performed<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> which showed that the clinical history of ACO patients did not differ significantly (symptoms measured by the Asthma Control Test and COPD Assessment Test or previous exacerbations) from patients with COPD or asthma. However, when patients were reclassified according to their inflammatory pattern as “Th2-high” (≥300<span class="elsevierStyleHsp" style=""></span>eosinophils/μL in blood or ≥3% in sputum), or “Th2-low”, 2 groups of CAFO patients emerged that did show different clinical characteristics. Consequently, this new categorization helped select patients who were candidates for treatments aimed at specific inflammatory patterns, such as inhaled corticosteroids or biological agents.</p><p id="par0020" class="elsevierStylePara elsevierViewall">In a second study, we investigated the value and interactions of blood biomarkers of systemic inflammation (IL-6, IL-8, TNF-α, IL-17) and Th2 inflammation (periostin, IL-5, and IL-13) in patients with asthma, COPD, and ACO. A network analysis and a principal component analysis showed the inflammatory pattern of ACO to be a mixture of the patterns observed in asthma and COPD, but no single biomarkers nor any combination of biomarkers were identified that could accurately differentiate ACO from asthma or COPD.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">These results suggest that the ACO group (as defined in the CHACOS study) is too heterogeneous and artificial. Indeed, when the characteristics of the 2 categories included under the definition of ACO are compared, significant differences are observed, inferring a wide biological variability in the ACO group, a mishmash that includes patients with eosinophilic, neutrophilic, and mixed endotypes.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">A recent consensus definition of ACO includes the 2 categories mentioned above: the smoking asthmatic who develops CAFO, and the patient with eosinophilic COPD: ≥300<span class="elsevierStyleHsp" style=""></span>cells/μL in blood or a “strongly positive” bronchodilator test (≥15% and 400<span class="elsevierStyleHsp" style=""></span>ml).<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> The CHACOS study population once again clearly demonstrates that patients with a diagnosis of ACO according to the criteria of this new consensus are indistinguishable from non-smoking asthmatics or COPD patients without eosinophilia.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> This finding strongly challenges the adequacy of the current algorithm, and even questions the existence of a specific phenotype with perceptible clinical characteristics, even if it provides a reasonable classification of candidates for treatment with inhaled corticosteroids.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Consequently, the results of the CHACOS study support the idea that the conventional diagnostic categories based on clinical presentation are valid for differentiating clear cases of asthma (“pure Th2” inflammation) and COPD (“pure Th1” inflammation). They are, however, insufficient for identifying patient groups who exhibit mixed or atypical inflammatory or clinical features. This, then, calls for a paradigm shift in the evaluation of obstructive airway diseases that combines biological mechanisms with clinical features, and which helps identify treatable characteristics in an appropriate clinical and biological context.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">These about-turns are not unusual in science. Newton's equations predict fairly accurately the value of the gravitational interaction between the planets of the solar system and, in addition, how they orbit the sun. Since the end of the 19th century and the beginning of the 20th century, certain astronomical measurements established that the orbit of Mercury was shifting about 5600 arcseconds per century, a phenomenon known as “precession”. However, Newton's equations predict a precession of 5557 arcseconds per century; in other words, there is a discrepancy of 43 arcseconds per century. Einstein resolved this inaccuracy with the theory of General Relativity, creating a new paradigm that contributed to the advancement of science. In the case of CAFO, the paradigm shift may come when personalized medicine is used to cross-reference the biological, clinical, and social factors of each specific patient. In the meantime, it seems reasonable to take a pragmatic attitude towards the complexity of these diseases and to tailor treatments to those traits that can be treated, with the application of medical techniques oriented to the singularities of each specific patient.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> We believe that the collaborative effort generated during the CHACOS study must continue, and that the scientific community must examine whether this new point of view provides an objective advantage for patients, by conducting a clinical trial in which only patients with CAFO and a Th2-high profile are treated with inhaled corticosteroids (or other anti-inflammatory drugs).</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Pérez de Llano L, López-Campos JL, Cosío BG. La posverdad detrás del solapamiento entre asma y EPOC y la órbita de Mercurio. Lecciones del estudio CHACOS. Arch Bronconeumol. 2018;54:175–176.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "What pulmonologists think about the asthma-COPD overlap syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Miravitlles" 1 => "B. Alcázar" 2 => "F.J. Alvarez" 3 => "T. Bazús" 4 => "M. Calle" 5 => "C. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 5 | 1 | 6 |
| 2024 October | 28 | 24 | 52 |
| 2024 September | 44 | 12 | 56 |
| 2024 August | 80 | 37 | 117 |
| 2024 July | 53 | 31 | 84 |
| 2024 June | 52 | 26 | 78 |
| 2024 May | 91 | 26 | 117 |
| 2024 April | 41 | 27 | 68 |
| 2024 March | 41 | 18 | 59 |
| 2024 February | 38 | 23 | 61 |
| 2023 August | 4 | 0 | 4 |
| 2023 March | 10 | 3 | 13 |
| 2023 February | 48 | 25 | 73 |
| 2023 January | 28 | 18 | 46 |
| 2022 December | 49 | 23 | 72 |
| 2022 November | 48 | 21 | 69 |
| 2022 October | 55 | 39 | 94 |
| 2022 September | 33 | 26 | 59 |
| 2022 August | 28 | 43 | 71 |
| 2022 July | 32 | 34 | 66 |
| 2022 June | 27 | 37 | 64 |
| 2022 May | 34 | 43 | 77 |
| 2022 April | 37 | 26 | 63 |
| 2022 March | 59 | 24 | 83 |
| 2022 February | 32 | 22 | 54 |
| 2022 January | 44 | 34 | 78 |
| 2021 December | 30 | 38 | 68 |
| 2021 November | 33 | 37 | 70 |
| 2021 October | 39 | 50 | 89 |
| 2021 September | 20 | 47 | 67 |
| 2021 August | 33 | 40 | 73 |
| 2021 July | 30 | 30 | 60 |
| 2021 June | 36 | 39 | 75 |
| 2021 May | 34 | 33 | 67 |
| 2021 April | 93 | 61 | 154 |
| 2021 March | 44 | 29 | 73 |
| 2021 February | 22 | 17 | 39 |
| 2021 January | 26 | 15 | 41 |
| 2020 December | 22 | 19 | 41 |
| 2020 November | 21 | 21 | 42 |
| 2020 October | 28 | 14 | 42 |
| 2020 September | 21 | 10 | 31 |
| 2020 August | 26 | 14 | 40 |
| 2020 July | 42 | 29 | 71 |
| 2020 June | 26 | 14 | 40 |
| 2020 May | 23 | 12 | 35 |
| 2020 April | 31 | 13 | 44 |
| 2020 March | 13 | 6 | 19 |
| 2020 February | 31 | 20 | 51 |
| 2020 January | 35 | 13 | 48 |
| 2019 December | 32 | 15 | 47 |
| 2019 November | 32 | 21 | 53 |
| 2019 October | 13 | 11 | 24 |
| 2019 September | 21 | 11 | 32 |
| 2019 August | 36 | 19 | 55 |
| 2019 July | 17 | 14 | 31 |
| 2019 June | 24 | 11 | 35 |
| 2019 May | 32 | 12 | 44 |
| 2019 April | 40 | 15 | 55 |
| 2019 March | 36 | 11 | 47 |
| 2019 February | 31 | 24 | 55 |
| 2019 January | 44 | 13 | 57 |
| 2018 December | 40 | 20 | 60 |
| 2018 November | 51 | 39 | 90 |
| 2018 October | 81 | 27 | 108 |
| 2018 September | 9 | 0 | 9 |
| 2018 April | 1 | 2 | 3 |
| 2018 March | 0 | 1 | 1 |
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