Editorial
Translational research in acute respiratory distress syndrome
Investigación traslacional sobre el síndrome de dificultad respiratoria aguda
P. Cardinal-Fernandez
Department of Emergency, Hospital Universitario HM Sanchinarro, Madrid, Spain
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EPLS, early protective lung strategy; EPHS, early protective hemodynamic strategy. <span class="elsevierStyleItalic">C</span><span class="elsevierStyleInf">dyn</span>, dynamic compliance of respiratory system; <span class="elsevierStyleItalic">R</span><span class="elsevierStyleInf">awi</span>, inspiratory airway resistance; <span class="elsevierStyleItalic">R</span><span class="elsevierStyleInf">awe</span>, expiratory airway resistance; WOB, total inspiratory work of breathing (*<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 compared to baseline by two-way analysis of variance for repeated measures; <span class="elsevierStyleSup">#</span><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 compared to one hour by two-way analysis of variance for repeated measures).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A. Gil Cano, M. Gracia Romero, M.I. Monge García, P. Guijo González, J. Ruiz Campos" "autores" => array:5 [ 0 => array:2 [ "nombre" => "A." "apellidos" => "Gil Cano" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Gracia Romero" ] 2 => array:2 [ "nombre" => "M.I." "apellidos" => "Monge García" ] 3 => array:2 [ "nombre" => "P." "apellidos" => "Guijo González" ] 4 => array:2 [ "nombre" => "J." "apellidos" => "Ruiz Campos" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S021056911630184X" "doi" => "10.1016/j.medin.2016.08.008" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S021056911630184X?idApp=WMIE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S217357271730053X?idApp=WMIE" "url" => "/21735727/0000004100000003/v1_201704120039/S217357271730053X/v1_201704120039/en/main.assets" ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Translational research in acute respiratory distress syndrome" "tieneTextoCompleto" => true "saludo" => "Dear Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "133" "paginaFinal" => "134" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "P. Cardinal-Fernandez" "autores" => array:1 [ 0 => array:3 [ "nombre" => "P." "apellidos" => "Cardinal-Fernandez" "email" => array:1 [ 0 => "pablocardinal@hotmail.com" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Department of Emergency, Hospital Universitario HM Sanchinarro, Madrid, Spain" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Investigación traslacional sobre el síndrome de dificultad respiratoria aguda" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Translational research (TR) or “bench to bedside research” is defined as the “process of transformation of knowledge through successive fields of research from a basic science discovery to public health impact”.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a> TR should be considered a type of pragmatic and patient-centered research, whose main aim is to reduce the time lag between the problem identification and its solution.</p><p id="par0010" class="elsevierStylePara elsevierViewall">In TR, the first step is to have a clear definition of the disease and the problem. Recently, the importance of linking clinical manifestations (syndrome) to pathological findings with the aim to define a specific disease has been highlighted.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">2,3</span></a> Identifying physiopathological mechanisms that link this relation (clinical–pathological) allows to understand the disease, identify subcategories and recognize therapeutic targets. In reference to the problem, it sometimes seems that identifying it is an easy or fast process, but nothing could be furthest from the truth. Selecting the problem implies the answer to the following questions: (a) Is it possible to address the problem with the intellectual, logistic and economic resources available for the researcher? (feasibility) and (b) which scientific, social and economic impact could the research have? (interest or relevance).</p><p id="par0015" class="elsevierStylePara elsevierViewall">The second step is to enunciate the hypothesis. In several cases, experiments in humans are not possible. However, animal models allow us to partially simulate certain human conditions. In other words, animal models are a simplification of the human reality that permits to focus the attention on a specific event (or a few events) and reduces the influence of confusion factors. How similar to the human disease the animal model should be mainly depends on which question researchers want to answer. In all experimental conditions, it is necessary to have a reference by which to assess the efficacy of an intervention. This reference, which is indeed more important than the intervention itself, derives from at least two groups: controls and sham. The former are animals that only differ from the experimental group in that they receive a placebo. All the animals are prepared similarly [e.g. anesthesiated, operated, etc.], but then the researcher randomizes each one to the intervention or placebo groups. The latter are animals on which investigators apply the same preparation than on the control group, but which do not receive any intervention nor placebo. On the one hand, the control group allows to know the specific effect of the intervention since both groups share the same confusion variables. On the other, the sham group ensures that the scientific data reflect the effect of the experiment itself, and this is not merely a consequence of the procedure. Finally, if preclinical studies are positive and there is enough evidence in favor of the new treatment (or solution for the problem), this should be evaluated at the bedside and, if effective, incorporated to the clinical practice.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Acute respiratory distress syndrome (ARDS) is a cataclysmic syndrome. Diffuse alveolar damage (DAD), the histological hallmark for the acute phase,<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a> is present in only 48% of ARDS patients.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> Furthermore, it has been recently demonstrated that patients with ARDS and DAD present a different outcome from patients with ARDS but without DAD.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">5,6</span></a> One of the most important problems in relation to ARDS is the lack of effective pharmacological treatments, despite positive results in preclinical studies. This dissonance may be due to the fact that animal models do not represent ARDS or that the population on which the treatment is tried out is incorrect.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">7</span></a> For example, clinical trials are not designed to demonstrate the effectiveness of a treatment in a random sample of the general population because the effect of an intervention is over targets (e.g. molecules, pathophysiologic pathways or anatomical structures) which should be present in the sample in which the intervention is evaluated. For that reason, it is only possible to lump patients who share the same. However, when the target is present only in a subset of patients, the population has to be splinted and the intervention must be tried out only on the subgroup which presents the target. Enrichment is the word used to describe the procedure of selecting subgroups of patients in which detection of an intervention effect is more likely than it would be in an unselected population.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">7</span></a> Biomarkers are currently the most useful way to enrich a specific population.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In this issue of <span class="elsevierStyleItalic">Medicina Intensiva</span>, Cano et al.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">9</span></a> use an elegant translational experiment to address the effect of a restrictive versus a liberal strategy of fluid management in a two-hit rabbit model of lung injury. Despite both strategies influence the outcome (wet and dry lung weight ratio [WW/DW]) several differences are evident. The liberal arm is associated to a decrease in the dynamic compliance and a bigger increase in WW/DW, as well as in the corrected aortic flow time than the restrictive strategy. Likewise, a trend to increase the total inspiratory work of breath, expiratory airway resistance and histology lung injury is reported in association to the liberal arm. On the contrary, the cardiac index is significantly reduced only in the restrictive arm. As a conclusion, Cano et al.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">9</span></a> mentioned that preemptive hemodynamic intervention by restricting the administration of fluids significantly slowed the progression of pulmonary edema and the decrease in pulmonary compliance. These interesting results provide a physiopathological explanation for the finding of the clinical study <span class="elsevierStyleItalic">Fluid and Catheter Treatment Trial (FACTT)</span>,<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">10</span></a> which included 1001 ALI/ARDS patients. The FACTT study found that the conservative fluid protocol improves several secondary end-points but not the primary end-point (60 days mortality).<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">10</span></a> As it was mentioned earlier on,<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> less than a half of FACTT participants could have been expected to present the ARDS histological hallmark (DAD) and the rest, a group of heterogeneous entities such as pulmonary embolism, fibrosis or atelectasis.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> For this reason, based on the results of Cano et al.,<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">9</span></a> an intriguing question is what would have happened if the FACTT cohort had been enriched in DAD? In other words, was the effect of restrictive fluid in the FACTT study diluted by the lack of enrichment in DAD? One of the targets for restrictive fluid protocol may be the disrupted alveolar capillary barrier function.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">11</span></a> But, is this target shared by ARDS patients with and without DAD? This question should have a direct impact on the design of future ARDS studies since it could determine which patients could be lumped and which patients should be splinted.</p><p id="par0030" class="elsevierStylePara elsevierViewall">As a conclusion, Cano et al.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">9</span></a> use a refined animal model to explain what had been observed at the bedside with ARDS patients. This can be regarded as a clear example of TR, which could be considered one of the most powerful strategies to accelerate the long and winding process from “bench to beside”.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interest</span><p id="par0035" class="elsevierStylePara elsevierViewall">The author express that don’t have conflict of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:11 [ 0 => array:3 [ "identificador" => "bib0060" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Translational research: understanding the continuum from bench to bedside" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "B.C. Drolet" 1 => "N.M. Lorenzi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Transl Res J Lab Clin Med" "fecha" => "2011" "volumen" => "157" "paginaInicial" => "1" "paginaFinal" => "5" "itemHostRev" => array:3 [ "pii" => "S0090429509023504" "estado" => "S300" "issn" => "00904295" ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0065" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acute Respiratory Distress: from syndrome to disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "P. Cardinal-Fernandez" 1 => "E. Correger" 2 => "J. Villanueva" 3 => "F. Rios" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Med Int/Soc Esp Med Int Unidades Coronarias" "fecha" => "2016" "volumen" => "40" "paginaInicial" => "169" "paginaFinal" => "175" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0070" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The ten diseases that are not true diseases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "P.O. Depuydt" 1 => "J.P. Kress" 2 => "J.I. 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A preemptive hemodynamic intervention by restricting the administration of fluids attenuates pulmonary edema progression in oleic-induced lung injury. <span class="elsevierStyleItalic">Med Int/Soc Esp Med Intensiva Unidades Coronarias</span> 2016." ] ] ] 9 => array:3 [ "identificador" => "bib0105" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comparison of two fluid-management strategies in acute lung injury" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "L. National Heart" 1 => "N. Blood Institute Acute Respiratory Distress Syndrome Clinical Trials" 2 => "H.P. Wiedemann" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa062200" "Revista" => array:7 [ "tituloSerie" => "N Engl J Med" "fecha" => "2006" "volumen" => "354" "paginaInicial" => "2564" "paginaFinal" => "2575" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16714767" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0302283811012309" "estado" => "S300" "issn" => "03022838" ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0110" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The acute respiratory distress syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M.A. Matthay" 1 => "L.B. Ware" 2 => "G.A. Zimmerman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI60331" "Revista" => array:7 [ "tituloSerie" => "J Clin Invest" "fecha" => "2012" "volumen" => "122" "paginaInicial" => "2731" "paginaFinal" => "2740" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22850883" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S1470204508702031" "estado" => "S300" "issn" => "14702045" ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735727/0000004100000003/v1_201704120039/S2173572717300528/v1_201704120039/en/main.assets" "Apartado" => array:4 [ "identificador" => "406" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Editorial" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735727/0000004100000003/v1_201704120039/S2173572717300528/v1_201704120039/en/main.pdf?idApp=WMIE&text.app=https://medintensiva.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173572717300528?idApp=WMIE" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 2 | 4 | 6 |
| 2024 October | 34 | 40 | 74 |
| 2024 September | 27 | 22 | 49 |
| 2024 August | 39 | 28 | 67 |
| 2024 July | 33 | 25 | 58 |
| 2024 June | 48 | 38 | 86 |
| 2024 May | 29 | 32 | 61 |
| 2024 April | 48 | 33 | 81 |
| 2024 March | 30 | 19 | 49 |
| 2024 February | 28 | 32 | 60 |
| 2024 January | 24 | 36 | 60 |
| 2023 December | 23 | 30 | 53 |
| 2023 November | 25 | 28 | 53 |
| 2023 October | 24 | 25 | 49 |
| 2023 September | 38 | 34 | 72 |
| 2023 August | 31 | 7 | 38 |
| 2023 July | 38 | 25 | 63 |
| 2023 June | 22 | 19 | 41 |
| 2023 May | 34 | 33 | 67 |
| 2023 April | 38 | 17 | 55 |
| 2023 March | 81 | 29 | 110 |
| 2023 February | 55 | 33 | 88 |
| 2023 January | 28 | 16 | 44 |
| 2022 December | 67 | 38 | 105 |
| 2022 November | 55 | 29 | 84 |
| 2022 October | 67 | 30 | 97 |
| 2022 September | 58 | 27 | 85 |
| 2022 August | 46 | 31 | 77 |
| 2022 July | 41 | 27 | 68 |
| 2022 June | 64 | 26 | 90 |
| 2022 May | 48 | 38 | 86 |
| 2022 April | 59 | 49 | 108 |
| 2022 March | 41 | 55 | 96 |
| 2022 February | 31 | 44 | 75 |
| 2022 January | 30 | 34 | 64 |
| 2021 December | 45 | 48 | 93 |
| 2021 November | 32 | 47 | 79 |
| 2021 October | 45 | 77 | 122 |
| 2021 September | 31 | 37 | 68 |
| 2021 August | 27 | 48 | 75 |
| 2021 July | 22 | 32 | 54 |
| 2021 June | 27 | 29 | 56 |
| 2021 May | 32 | 42 | 74 |
| 2021 April | 49 | 40 | 89 |
| 2021 March | 84 | 25 | 109 |
| 2021 February | 46 | 17 | 63 |
| 2021 January | 38 | 18 | 56 |
| 2020 December | 40 | 14 | 54 |
| 2020 November | 25 | 20 | 45 |
| 2020 October | 41 | 27 | 68 |
| 2020 September | 32 | 23 | 55 |
| 2020 August | 30 | 15 | 45 |
| 2020 July | 21 | 16 | 37 |
| 2020 June | 24 | 24 | 48 |
| 2020 May | 18 | 12 | 30 |
| 2020 April | 18 | 5 | 23 |
| 2020 March | 18 | 14 | 32 |
| 2020 February | 34 | 47 | 81 |
| 2020 January | 18 | 24 | 42 |
| 2019 December | 14 | 32 | 46 |
| 2019 November | 19 | 24 | 43 |
| 2019 October | 20 | 13 | 33 |
| 2019 September | 14 | 19 | 33 |
| 2019 August | 20 | 12 | 32 |
| 2019 July | 24 | 22 | 46 |
| 2019 June | 16 | 12 | 28 |
| 2019 May | 38 | 28 | 66 |
| 2019 April | 14 | 14 | 28 |
| 2019 March | 14 | 26 | 40 |
| 2019 February | 14 | 26 | 40 |
| 2019 January | 17 | 21 | 38 |
| 2018 December | 15 | 18 | 33 |
| 2018 November | 32 | 50 | 82 |
| 2018 October | 63 | 24 | 87 |
| 2018 September | 21 | 13 | 34 |
| 2018 August | 22 | 8 | 30 |
| 2018 July | 26 | 13 | 39 |
| 2018 June | 22 | 8 | 30 |
| 2018 May | 12 | 5 | 17 |
| 2018 April | 28 | 6 | 34 |
| 2018 March | 29 | 4 | 33 |
| 2018 February | 17 | 7 | 24 |
| 2018 January | 37 | 16 | 53 |
| 2017 December | 14 | 5 | 19 |
| 2017 November | 17 | 10 | 27 |
| 2017 October | 21 | 11 | 32 |
| 2017 September | 22 | 13 | 35 |
| 2017 August | 21 | 13 | 34 |
| 2017 July | 5 | 2 | 7 |
| 2017 April | 1 | 2 | 3 |
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