A silent revolution: phenotyping asthma for personalised medicine
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Chung" "autores" => array:1 [ 0 => array:4 [ "Iniciales" => "K.F." "apellidos" => "Chung" "email" => array:1 [ 0 => "f.chung@imperial.ac.uk" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:3 [ "entidad" => "National Heart and Lung Institute, Imperial College London, London, United Kingdom" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] ] "textoCompleto" => "<p class="elsevierStylePara">A silent revolution is taking place in asthma. Although it has been known to clinicians for a while that asthma presents in various guises and forms, the value of such knowledge has remained very much a pastime of clinicians in categorising asthma. Various clinical forms of asthma have been described such as aspirin-sensitive asthma, late-onset non-atopic asthma with an indolent course, early-onset asthma in childhood and severe asthma. However, only recently, with the application of cluster analysis, a statistical technique to grouping sets of data that have a degree of closeness has there been real progress made in defining phenotypes. Clustering requires approaches that will group a set of objects depending on degree of closeness to each other so that objects in the same group are more similar to each other than those in other groups (or clusters). It is a major test of explanatory data mining, and a common technique for statistical data analysis used in many fields including more recently the determination of phenotypes of asthma dependent on disease characteristics. Of the many clustering algorithms in use, the most commonly applied to asthma phenotyping has been connectivity models such as hierarchical clustering based on distance connectivity or k-means algorithm base by single mean cluster. Thus, in one of the first clustering analyses from the NIH-funded Severe Asthma Research Project (SARP), the use of Ward's minimum variance hierarchical clustering method using 17 composite clinical and physiological variables derived from 63 separate binary questions applied to an adolescent and adult cohort of mild to severe asthma of 726 subjects led to the definition of five clusters of asthma.<a href="#bib1" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">1</span></a> In their tree analysis, subjects could be assigned to five clusters that ranged from milder to more severe disease, using only three variables: baseline FEV<span class="elsevierStyleInf">1</span>, post-bronchodilator FEV<span class="elsevierStyleInf">1</span> and age of onset of asthma.</p><p class="elsevierStylePara">In the current issue of the Portuguese Journal of Pulmonology, Loreiro and colleagues report the first cluster analysis applied to a cohort of Portuguese patients using Ward's clustering method (<span class="elsevierStyleItalic">Loreiro et al. Cluster analysis in phenotyping a Portuguese population. Rev Port Pneumol 2015; in press</span>). They describe five clusters that were differentiated by age of onset of asthma, gender predominance, body mass index, symptoms of asthma, allergic status and presence of eosinophilia. The interesting clusters of the Portuguese cohort are particularly those related to the onset of disease. Early onset clusters include either those with mild allergic asthma or those with allergic brittle asthma, while late onset asthma was associated with severe asthma either with chronic airflow obstruction and eosinophilic inflammation, or highly symptomatic obese women with non-eosinophilic inflammation. One can start to see clusters associated with eosinophilic inflammation, particularly with chronic airflow obstruction.</p><p class="elsevierStylePara">It is reassuring that these clusters derived from a relatively small number of asthmatic participants (total of 57) do have similarities with those previously described in the SARP cohort<a href="#bib1" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">1</span></a> and in the Leicester cohort.<a href="#bib2" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">2</span></a> In fact, the late onset severe asthma cluster with eosinophilia is also described in a later analysis of SARP that included sputum eosinophilia.<a href="#bib3" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">3</span></a> This reproducibility provides some support to the validity of the clustering approach. It would have been strengthened if these clusters were replicated in a separate independent cohort. Overall, one wonders with the availability of multiple national and international cohorts of asthma whether a large analysis of all these cohorts together to produce a meta-cluster analysis should not be entertained. This would need international collaboration for which there should be great enthusiasm.</p><p class="elsevierStylePara">The value of these cluster analyses is whether these will help the clinicians in terms of precision/personalised medicine, particularly when it applies to severe asthma.<a href="#bib4" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">4</span></a> By defining these five clusters, could we now programme different treatment paradigms specific for each cluster?<a href="#bib5" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">5</span></a> However, in order to reach this stage, we need to have some understanding the mechanisms underlying asthma and add mechanistic biomarkers to the cluster analysis to see how these biomarkers distribute across the cluster, which is the process of determining the endotypes of asthma.<a href="#bib6" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">6</span></a> For example, if Cluster 5 of the Portuguese cohort is associated with eosinophilic inflammation, and perhaps part of this population is associated with a Th2 high expression, new treatments based on suppressing activity of Th2 cytokines such as IL-4, IL-5 and IL-13 might be beneficial.<a href="#bib7" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">7</span></a> On the other hand, Cluster 4 patients could be more appropriately treated by blocking non-Th2 pathways, but these pathways remain to be defined. Much more molecular phenotyping will be needed before reaching this stage of defining clusters with an accurate precision. Clustering with the use of <span class="elsevierStyleItalic">omics</span> data (transcriptome, metabolome, lipidome, microbiome and proteome) is the most promising route of getting to the endotypes that will be more useful in pinpointing the ‘right’ treatment for the ‘right’ patient, an approach that has been taken by the European Unbiased BIOmarkers in PREDiction of respiratory disease outcomes (U-BIOPRED) project.<a href="#bib8" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">8</span></a></p><p class="elsevierStylePara">At the end of the day, with the complexity of the analysis of omics data with clinical and physiological data backed by sophisticated bioinformatics analyses, the objective has to be to provide clinically-relevant phenotypes or more precisely endotypes, that will help optimise and provide targeted treatments, the whole basis of precision/personalised medicine.</p>" "pdfFichero" => "320v21n06a90445965pdf001.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:8 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 8 | 16 |
| 2024 October | 47 | 41 | 88 |
| 2024 September | 61 | 25 | 86 |
| 2024 August | 66 | 38 | 104 |
| 2024 July | 42 | 38 | 80 |
| 2024 June | 44 | 29 | 73 |
| 2024 May | 44 | 27 | 71 |
| 2024 April | 46 | 31 | 77 |
| 2024 March | 45 | 28 | 73 |
| 2024 February | 35 | 23 | 58 |
| 2024 January | 35 | 20 | 55 |
| 2023 December | 27 | 25 | 52 |
| 2023 November | 28 | 36 | 64 |
| 2023 October | 26 | 36 | 62 |
| 2023 September | 30 | 28 | 58 |
| 2023 August | 29 | 17 | 46 |
| 2023 July | 35 | 29 | 64 |
| 2023 June | 23 | 16 | 39 |
| 2023 May | 79 | 30 | 109 |
| 2023 April | 35 | 22 | 57 |
| 2023 March | 52 | 15 | 67 |
| 2023 February | 34 | 20 | 54 |
| 2023 January | 32 | 16 | 48 |
| 2022 December | 47 | 20 | 67 |
| 2022 November | 64 | 32 | 96 |
| 2022 October | 44 | 30 | 74 |
| 2022 September | 30 | 31 | 61 |
| 2022 August | 32 | 31 | 63 |
| 2022 July | 31 | 42 | 73 |
| 2022 June | 27 | 27 | 54 |
| 2022 May | 37 | 39 | 76 |
| 2022 April | 35 | 31 | 66 |
| 2022 March | 29 | 49 | 78 |
| 2022 February | 32 | 25 | 57 |
| 2022 January | 26 | 33 | 59 |
| 2021 December | 29 | 46 | 75 |
| 2021 November | 37 | 39 | 76 |
| 2021 October | 33 | 40 | 73 |
| 2021 September | 20 | 29 | 49 |
| 2021 August | 24 | 17 | 41 |
| 2021 July | 25 | 23 | 48 |
| 2021 June | 22 | 18 | 40 |
| 2021 May | 35 | 28 | 63 |
| 2021 April | 60 | 79 | 139 |
| 2021 March | 64 | 21 | 85 |
| 2021 February | 42 | 18 | 60 |
| 2021 January | 44 | 9 | 53 |
| 2020 December | 24 | 7 | 31 |
| 2020 November | 40 | 14 | 54 |
| 2020 October | 36 | 19 | 55 |
| 2020 September | 58 | 15 | 73 |
| 2020 August | 59 | 24 | 83 |
| 2020 July | 103 | 17 | 120 |
| 2020 June | 84 | 23 | 107 |
| 2020 May | 72 | 17 | 89 |
| 2020 April | 90 | 21 | 111 |
| 2020 March | 69 | 17 | 86 |
| 2020 February | 63 | 55 | 118 |
| 2020 January | 123 | 21 | 144 |
| 2019 December | 77 | 18 | 95 |
| 2019 November | 71 | 16 | 87 |
| 2019 October | 88 | 27 | 115 |
| 2019 September | 80 | 19 | 99 |
| 2019 August | 99 | 12 | 111 |
| 2019 July | 107 | 9 | 116 |
| 2019 June | 95 | 9 | 104 |
| 2019 May | 108 | 10 | 118 |
| 2019 April | 125 | 25 | 150 |
| 2019 March | 115 | 18 | 133 |
| 2019 February | 120 | 13 | 133 |
| 2019 January | 154 | 29 | 183 |
| 2018 December | 76 | 3 | 79 |
| 2018 November | 23 | 5 | 28 |
| 2018 October | 26 | 9 | 35 |
| 2018 September | 22 | 7 | 29 |
| 2018 August | 28 | 23 | 51 |
| 2018 July | 28 | 19 | 47 |
| 2018 June | 39 | 14 | 53 |
| 2018 May | 49 | 23 | 72 |
| 2018 April | 69 | 19 | 88 |
| 2018 March | 66 | 18 | 84 |
| 2018 February | 47 | 17 | 64 |
| 2018 January | 50 | 21 | 71 |
| 2017 December | 52 | 19 | 71 |
| 2017 November | 20 | 22 | 42 |
| 2017 October | 19 | 22 | 41 |
| 2017 September | 42 | 13 | 55 |
| 2017 August | 42 | 19 | 61 |
| 2017 July | 27 | 19 | 46 |
| 2017 June | 33 | 14 | 47 |
| 2017 May | 33 | 22 | 55 |
| 2017 April | 22 | 2 | 24 |
| 2017 March | 27 | 9 | 36 |
| 2017 February | 18 | 9 | 27 |
| 2017 January | 21 | 9 | 30 |
| 2016 December | 34 | 14 | 48 |
| 2016 November | 32 | 18 | 50 |
| 2016 October | 27 | 17 | 44 |
| 2016 September | 19 | 17 | 36 |
| 2016 August | 28 | 32 | 60 |
| 2016 July | 30 | 49 | 79 |
| 2016 May | 1 | 0 | 1 |
| 2016 April | 34 | 2 | 36 |
| 2016 March | 25 | 23 | 48 |
| 2016 February | 34 | 36 | 70 |
| 2016 January | 87 | 55 | 142 |
| 2015 December | 91 | 77 | 168 |
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