Editorial
Evidence-based oxygen therapy: Missed and future opportunities
Oxigenoterapia baseada na evidência: Oportunidades perdidas e futuras
Y. Lacasse
, S. Bernard, F. Maltais
Corresponding author
Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec (Hôpital Laval), 2725 Chemin Ste-Foy, Québec, Québec, G1V 4G5, Canada
Read
942
Timeswas read the article
510
Total PDF
432
Total HTML
Share statistics
array:24 [ "pii" => "S2173511512000978" "issn" => "21735115" "doi" => "10.1016/j.rppnen.2012.10.001" "estado" => "S300" "fechaPublicacion" => "2012-11-01" "aid" => "115" "copyright" => "Sociedade Portuguesa de Pneumologia" "copyrightAnyo" => "2012" "documento" => "simple-article" "crossmark" => 0 "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "edi" "cita" => "Rev Port Pneumol. 2012;18:257-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 3594 "formatos" => array:3 [ "EPUB" => 237 "HTML" => 2372 "PDF" => 985 ] ] "itemSiguiente" => array:20 [ "pii" => "S217351151200053X" "issn" => "21735115" "doi" => "10.1016/j.rppnen.2012.06.002" "estado" => "S300" "fechaPublicacion" => "2012-11-01" "aid" => "101" "copyright" => "Sociedade Portuguesa de Pneumologia" "documento" => "article" "crossmark" => 0 "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Rev Port Pneumol. 2012;18:260-6" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 5292 "formatos" => array:3 [ "EPUB" => 278 "HTML" => 3478 "PDF" => 1536 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Silicosis in sandblasters of shipyard <span class="elsevierStyleItalic">versus</span> silicosis in stone carvers in Brazil: A comparison of imaging findings, lung function variables and cardiopulmonary exercise testing parameters" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "260" "paginaFinal" => "266" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Silicose em jateadores de areia de estaleiro <span class="elsevierStyleItalic">versus</span> silicose em escultores de pedra no Brasil: uma comparação dos achados de imagem, função pulmonar e teste de exercício cardiopulmonar" ] ] "contieneResumen" => array:2 [ "en" => true "pt" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1215 "Ancho" => 1542 "Tamanyo" => 50536 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Box plots (median, 1st and 3rd quartiles, minimum and maximum) of peak oxygen uptake (peak VO<span class="elsevierStyleInf">2</span>) according to the type of workers exposed to silica dust. Significant difference (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.0001) was found between the sandblasters and stone carvers.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A.J. Lopes, W. Costa, T. Thomaz Mafort, A. de Sá Ferreira, S.L. Silveira de Menezes, F. Silva Guimarães" "autores" => array:6 [ 0 => array:2 [ "nombre" => "A.J." "apellidos" => "Lopes" ] 1 => array:2 [ "nombre" => "W." "apellidos" => "Costa" ] 2 => array:2 [ "nombre" => "T." "apellidos" => "Thomaz Mafort" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "de Sá Ferreira" ] 4 => array:2 [ "nombre" => "S.L." "apellidos" => "Silveira de Menezes" ] 5 => array:2 [ "nombre" => "F." "apellidos" => "Silva Guimarães" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "pt" => array:9 [ "pii" => "S0873215912000773" "doi" => "10.1016/j.rppneu.2012.04.006" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "pt" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0873215912000773?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S217351151200053X?idApp=UINPBA00004E" "url" => "/21735115/0000001800000006/v1_201305151609/S217351151200053X/v1_201305151609/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2173511512000899" "issn" => "21735115" "doi" => "10.1016/j.rppnen.2012.09.001" "estado" => "S300" "fechaPublicacion" => "2012-11-01" "aid" => "116" "documento" => "simple-article" "crossmark" => 0 "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "edi" "cita" => "Rev Port Pneumol. 2012;18:255-6" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 3173 "formatos" => array:3 [ "EPUB" => 232 "HTML" => 1879 "PDF" => 1062 ] ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Love is not thanked" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "255" "paginaFinal" => "256" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "O amor não se agradece" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "C.R. Cordeiro" "autores" => array:1 [ 0 => array:2 [ "nombre" => "C.R." "apellidos" => "Cordeiro" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "pt" => array:9 [ "pii" => "S0873215912001146" "doi" => "10.1016/j.rppneu.2012.09.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "pt" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0873215912001146?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173511512000899?idApp=UINPBA00004E" "url" => "/21735115/0000001800000006/v1_201305151609/S2173511512000899/v1_201305151609/en/main.assets" ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Evidence-based oxygen therapy: Missed and future opportunities" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "257" "paginaFinal" => "259" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Y. Lacasse, S. Bernard, F. Maltais" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Y." "apellidos" => "Lacasse" "email" => array:1 [ 0 => "Yves.Lacasse@med.ulaval.ca" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "S." "apellidos" => "Bernard" ] 2 => array:2 [ "nombre" => "F." "apellidos" => "Maltais" ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec (Hôpital Laval), 2725 Chemin Ste-Foy, Québec, Québec, G1V 4G5, Canada" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Oxigenoterapia baseada na evidência: Oportunidades perdidas e futuras" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Two landmark trials conducted more than 30 years ago provided scientific evidence that, under very specific circumstances, long-term oxygen therapy (LTOT) may prolong life.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> These two trials targeted patients with chronic obstructive pulmonary disease (COPD) and severe daytime hypoxemia documented by direct arterial blood gas measurement.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Although the survival benefits of LTOT in COPD are real, home oxygen is not a panacea. In the British Medical Research Council's trial, 500 days elapsed before any effect of LTOT on survival appeared, when compared to no oxygen therapy at all.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Overall, at 5-year follow-up, those who received oxygen had improved survival: 19 of 42 (42%) had died, compared to 30 of the 45 control patients (66%). The difference (24%) corresponds to a number needed to treat (NNT) of 5, which means that 5 patients must receive oxygen during 5 years in order to prevent one death over the same period. Similarly, the American Nocturnal Oxygen Therapy trial randomly assigned patients to receive oxygen for either 12<span class="elsevierStyleHsp" style=""></span>h a day (nocturnal group) or 24<span class="elsevierStyleHsp" style=""></span>h a day (continuous group).<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The latter group actually received oxygen for an average of 19<span class="elsevierStyleHsp" style=""></span>h a day. All received oxygen therapy during sleep. At 24 months, the overall mortality in the continuous group was 22.4%, whereas it was 40.8% in the nocturnal group (absolute difference: 18.4%; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01). The corresponding NNT was therefore 6.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The good news from both trials was that “oxygen saves lives”. From this moment, oxygen therapy became a standard of care, and confirmatory trials would be considered by many as unethical. Unfortunately, beyond survival, the effects of LTOT on quality of life remain largely unexplored in randomized controlled trials. Both the British and the American trials were conducted before the era of quality-of-life questionnaires. Although suggestion from uncontrolled studies has been made that oxygen therapy improves quality of life,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> clinical experience rather suggests that LTOT may limit the patients’ ability to remain active and may be detrimental to the rehabilitation process.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Thereafter, oxygen therapy gained widespread acceptance by official organizations for treatment of most chronic cardio-respiratory conditions complicated by severe hypoxemia, even if proof of efficacy is lacking. These conditions now largely go beyond COPD and include, among others, cystic fibrosis,<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> interstitial lung diseases,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> and pulmonary arterial hypertension.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> In only rare exceptions (such as obesity hypoventilation<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> and chronic heart failure<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>), the indication of oxygen in patients with severe hypoxemia is questioned. Also, new indications of oxygen therapy in COPD (such as nocturnal oxygen therapy in patients with isolated nocturnal oxygen desaturation, or ambulatory oxygen to correct exercise-induced desaturation) have emerged. To these extended indications of home oxygen, one must add that, even in COPD, inappropriate prescriptions of home oxygen therapy are not unusual.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Oxygen is everywhere.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Home oxygen therapy is very expensive. For instance, in the Canadian cohort of the Confronting COPD Survey (3265 individuals; mean age: 63 years; 44% female), oxygen therapy accounted for 17% of the entire annual direct costs of COPD care.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Also, home oxygen therapy imposes sacrifices on patients and their families. It is therefore surprising that it is so readily accepted by patients, health care professionals and payers, despite the lack of evidence to support its use in most circumstances. Why is that so? In addition to being safe and readily available, the problem with oxygen is that its prescription always makes sense: if oxygen desaturation exists, its correction should help.</p><p id="par0030" class="elsevierStylePara elsevierViewall">This reasoning was common before the introduction of “evidence-based medicine”, when the study and understanding of basic mechanisms of disease and pathophysiologic principles were considered sufficient to guide clinical practice.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> A famous example proved the contrary. Since ventricular arrhythmias are an important cause of death following acute myocardial infarction, their suppression was expected to decrease mortality. The Cardiac Arrhythmia Suppression trial (CAST) was stopped early after patients allocated to receive potent anti-arrhythmic drugs were found to have an increased mortality rate when compared to those receiving placebo.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Similar examples, although less dramatic, exist in the field of oxygen therapy. For instance, although oxygen corrects oxygen desaturation and improves walked distance in patients with COPD and exercise-induced desaturation in laboratory testing,<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> other trials have failed to demonstrate any long-term benefit.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14–17</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Before the introduction of “evidence-based medicine”, another assumption guiding clinical practice was that unsystematic observations from clinical experience were a valid way of building and maintaining knowledge about the efficacy of treatment.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Clinicians’ memory is often selective. The observations they recall are often anecdotal and limited to their best or worst experiences. In the case of oxygen therapy, bad experiences seldom occur. The consequence is that prescriptions of home oxygen therapy are well anchored into clinical practice and almost never challenged.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Twenty years ago, a shift of paradigm operated. Evidence-based medicine was put forward.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Evidence based medicine is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> The assumptions of the new paradigm were then described as follows: (1) the study and understanding of mechanisms of disease are necessary but insufficient guides for clinical practice; (2) systematic observations increase the confidence clinicians can have in knowledge about efficacy of treatments; (3) understanding certain rules of evidence is necessary to correctly interpret the medical literature.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">This new paradigm guided us in the development and implementation of the International Nocturnal Oxygen (INOX) trial, a multi-centre, randomized, placebo-controlled trial of nocturnal oxygen therapy in COPD (ClinicalTrtials.gov id: <a href="ctgov:NCT01044628">NCT01044628</a>). Prior observations suggested that nocturnal oxygen desaturation may accelerate the natural progression of COPD toward its end stages of severe hypoxemia, right heart failure, and death.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20,21</span></a> Until recently, it was often recommended in Canada (and elsewhere around the world) that nocturnal oxygen be considered if desaturation occurs for protracted periods. However, current evidence from two small randomized controlled trials<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22,23</span></a> and their meta-analysis<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> does not support this recommendation. The cost-effectiveness of nocturnal oxygen is unknown. The INOX trial, in which 4 clinical sites in Portugal (Matosinhos, Vila Nova de Gaia, Coimbra and Lisboa) participate, is intended to address this important clinical question.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Of note, even when data from randomized trials exist, its translation into clinical practice may be problematic. This is seen especially in the case of negative trials. Our experience with a randomized trial of ambulatory oxygen in oxygen-dependent patients with COPD illustrates this situation.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> In a one-year, randomized, three-period, crossover trial, we allocated 24 patients to one of the 6 possible sequences generated by 3 interventions: (1) standard therapy (home oxygen therapy with an oxygen concentrator only); (2) standard therapy plus as-needed ambulatory oxygen; (3) standard therapy plus ambulatory compressed air. The comparison of ambulatory oxygen vs. ambulatory compressed air was double blind. The main outcomes were quality of life, exercise tolerance and daily duration of exposure to oxygen. The trial was stopped prematurely after a planned interim analysis. On average, the patients used few ambulatory cylinders and ambulatory oxygen had no effect at all on any of the outcomes. Our results did not support the widespread provision of ambulatory oxygen to patients with oxygen-dependent COPD.</p><p id="par0055" class="elsevierStylePara elsevierViewall">The results of our trial challenged the recommendation that active patients receiving LTOT should have both stationary and mobile systems of oxygen delivery.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26,27</span></a> The sample size of our trial was small. However, for both quality of life and exercise capacity, the 95% confidence intervals around the mean treatment effect included zero (i.e., no effect) and excluded what is usually considered as the minimal clinically important difference, a clear demonstration that the negative results were not from a lack of power to detect a clinically significant difference. We rather interpreted the negative results as a real indication of no benefit from ambulatory oxygen under the circumstances of the study. Our results were recently confirmed by a related trial.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> However, we are still facing clinicians’ reluctance, even in our own institution, to limit the prescriptions of ambulatory oxygen in oxygen-dependent COPD patients.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Home oxygen therapy still offers a multitude of research opportunities in COPD.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> The INOX trial is only one of them. The effects of home oxygen therapy in most cardiopulmonary conditions (including interstitial lung diseases, cystic fibrosis, pulmonary arterial hypertension and chronic heart failure) remain unexplored. Randomized trials represent the most powerful method to address these important clinical questions. Cost-effectiveness analyses are also needed. Suggestion has been made that multicenter clinical research networks should be established to perform such clinical trials.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> Such efforts are challenging as they require time, money and commitment from all investigators to bring the clinical trials to their ends. However, this investment is certainly worth it for the patients and those who will have to financially support LTOT.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts 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:30 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Report of the Medical Research Council Working Party" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "Medical Research Council Working Party" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "1981" "volumen" => "1" "paginaInicial" => "681" "paginaFinal" => "686" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2882097" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Nocturnal Oxygen Therapy Trial Group" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "Nocturnal Oxygen Therapy Trial Group" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann Intern Med" "fecha" => "1980" "volumen" => "93" "paginaInicial" => "391" "paginaFinal" => "398" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6776858" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of long-term oxygen therapy on quality of life and survival in chronic airflow limitation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A.J. Crockett" 1 => "J.M. Cranston" 2 => "J.R. Moss" 3 => "J.H. Alpers" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Monaldi Arch Chest Dis" "fecha" => "1999" "volumen" => "54" "paginaInicial" => "193" "paginaFinal" => "196" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10394840" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cystic fibrosis adult care: consensus conference report" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J.R. Yankaskas" 1 => "B.C. Marshall" 2 => "B. Sufian" 3 => "R.H. Simon" 4 => "D. Rodman" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "2004" "volumen" => "125" "paginaInicial" => "1S" "paginaFinal" => "39S" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14734689" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interstitial lung disease guideline: the British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Bradley" 1 => "H.M. Branley" 2 => "J.J. Egan" 3 => "M.S. Greaves" 4 => "D.M. Hansell" 5 => "N.K. Harrison" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thx.2008.101691" "Revista" => array:8 [ "tituloSerie" => "Thorax" "fecha" => "2008" "volumen" => "63" "numero" => "Suppl. 5" "paginaInicial" => "v1" "paginaFinal" => "v58" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18757459" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0168827805006975" "estado" => "S300" "issn" => "01688278" ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Medical therapy for pulmonary arterial hypertension: updated ACCP evidence-based clinical practice guidelines" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "D.B. Badesch" 1 => "S.H. Abman" 2 => "G. Simonneau" 3 => "L.J. Rubin" 4 => "V.V. McLaughlin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1378/chest.06-2674" "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "2007" "volumen" => "131" "paginaInicial" => "1917" "paginaFinal" => "1928" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17565025" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recent advances in obesity hypoventilation syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "B. Mokhlesi" 1 => "A. Tulaimat" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1378/chest.07-0027" "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "2007" "volumen" => "132" "paginaInicial" => "1322" "paginaFinal" => "1336" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17934118" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): the Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Swedberg" 1 => "J. Cleland" 2 => "H. Dargie" 3 => "H. Drexler" 4 => "F. Follath" 5 => "M. Komajda" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/ehi204" "Revista" => array:6 [ "tituloSerie" => "Eur Heart J" "fecha" => "2005" "volumen" => "26" "paginaInicial" => "1115" "paginaFinal" => "1140" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15901669" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Appropriateness of domiciliary oxygen delivery" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G.H. Guyatt" 1 => "D.A. McKim" 2 => "P. Austin" 3 => "R. Bryan" 4 => "J. Norgren" 5 => "B. Weaver" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "2000" "volumen" => "118" "paginaInicial" => "1303" "paginaFinal" => "1308" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11083678" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The burden of COPD in Canada: results from the Confronting COPD survey" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "K.R. Chapman" 1 => "J. Bourbeau" 2 => "L. Rance" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Respir Med" "fecha" => "2003" "volumen" => "97" "numero" => "Suppl. C" "paginaInicial" => "S23" "paginaFinal" => "S31" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12647940" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evidence-based medicine. A new approach to teaching the practice of medicine" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "Evidence-Based Medicine Working Group" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "JAMA" "fecha" => "1992" "volumen" => "268" "paginaInicial" => "2420" "paginaFinal" => "2425" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1404801" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. The Cardiac Arrhythmia Suppression Trial (CAST) Investigators" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "The Cardiac Arrhythmia Suppression Trial (CAST) Investigators" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM198908103210629" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "1989" "volumen" => "321" "paginaInicial" => "406" "paginaFinal" => "412" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2473403" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A systematic review of randomized controlled trials examining the short-term benefit of ambulatory oxygen in COPD" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J.M. Bradley" 1 => "T. Lasserson" 2 => "S. Elborn" 3 => "J. Macmahon" 4 => "B. O’Neill" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1378/chest.06-0180" "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "2007" "volumen" => "131" "paginaInicial" => "278" "paginaFinal" => "285" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17218587" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ambulatory oxygen improves quality of life of COPD patients: a randomised controlled study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Eaton" 1 => "J.E. Garrett" 2 => "P. Young" 3 => "W. Fergusson" 4 => "J. Kolbe" 5 => "S. Rudkin" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Eur Respir J" "fecha" => "2002" "volumen" => "20" "paginaInicial" => "306" "paginaFinal" => "312" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12212960" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S001650850700399X" "estado" => "S300" "issn" => "00165085" ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Exertional oxygen of limited benefit in patients with chronic obstructive pulmonary disease and mild hypoxemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "C.F. McDonald" 1 => "C.M. Blyth" 2 => "M.D. Lazarus" 3 => "I. Marschner" 4 => "C.E. Barter" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/ajrccm.152.5.7582304" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "1995" "volumen" => "152" "paginaInicial" => "1616" "paginaFinal" => "1619" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7582304" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of oxygen on health quality of life in patients with chronic obstructive pulmonary disease with transient exertional hypoxemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M.L. Nonoyama" 1 => "D. Brooks" 2 => "G.H. Guyatt" 3 => "R.S. Goldstein" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.200702-308OC" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2007" "volumen" => "176" "paginaInicial" => "343" "paginaFinal" => "349" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17446339" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A randomised trial of domiciliary, ambulatory oxygen in patients with COPD and dyspnoea but without resting hypoxaemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.P. Moore" 1 => "D.J. Berlowitz" 2 => "L. Denehy" 3 => "J.J. Pretto" 4 => "D.J. Brazzale" 5 => "K. Sharpe" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thx.2009.132522" "Revista" => array:6 [ "tituloSerie" => "Thorax" "fecha" => "2011" "volumen" => "66" "paginaInicial" => "32" "paginaFinal" => "37" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20880870" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evidence-based medicine" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "G.H. Guyatt" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Ann Intern Med" "fecha" => "1991" "volumen" => "114" "numero" => "Suppl. 2 ACP J Club" "paginaInicial" => "A-16" ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evidence based medicine: what it is and what it isn’t" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "D.L. Sackett" 1 => "W.M. Rosenberg" 2 => "J.A. Gray" 3 => "R.B. Haynes" 4 => "W.S. Richardson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "BMJ" "fecha" => "1996" "volumen" => "312" "paginaInicial" => "71" "paginaFinal" => "72" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8555924" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical hypoxia: causes, consequences, and correction" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "D.C. Flenley" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Lancet" "fecha" => "1978" "volumen" => "1" "paginaInicial" => "542" "paginaFinal" => "546" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2893965" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0140673605177010" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The origins of cor pulmonale; a hypothesis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A.J. Block" 1 => "P.G. Boysen" 2 => "J.W. Wynne" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "1979" "volumen" => "75" "paginaInicial" => "109" "paginaFinal" => "110" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/421540" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A double-blind trial of nocturnal supplemental oxygen for sleep desaturation in patients with chronic obstructive pulmonary disease and a daytime PaO<span class="elsevierStyleInf">2</span> above 60<span class="elsevierStyleHsp" style=""></span>mm Hg" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "E.C. Fletcher" 1 => "R.A. Luckett" 2 => "S. Goodnight-White" 3 => "C.C. Miller" 4 => "W. Qian" 5 => "C. Costarangos-Galarza" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/ajrccm/145.5.1070" "Revista" => array:6 [ "tituloSerie" => "Am Rev Respir Dis" "fecha" => "1992" "volumen" => "145" "paginaInicial" => "1070" "paginaFinal" => "1076" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1586049" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A randomized trial of nocturnal oxygen therapy in chronic obstructive pulmonary disease patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Chaouat" 1 => "E. Weitzenblum" 2 => "R. Kessler" 3 => "C. Charpentier" 4 => "M. Enrhart" 5 => "R. Schott" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Eur Respir J" "fecha" => "1999" "volumen" => "14" "paginaInicial" => "1002" "paginaFinal" => "1008" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10596681" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Domiciliary oxygen for chronic obstructive pulmonary disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.M. Cranston" 1 => "A.J. Crockett" 2 => "J.R. Moss" 3 => "J.H. Alpers" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Cochrane Database Syst Rev" "fecha" => "2005" "paginaInicial" => "CD001744" ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Randomised trial of ambulatory oxygen in oxygen-dependent COPD" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Y. Lacasse" 1 => "R. Lecours" 2 => "C. Pelletier" 3 => "R. Begin" 4 => "F. Maltais" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1183/09031936.05.00113504" "Revista" => array:6 [ "tituloSerie" => "Eur Respir J" "fecha" => "2005" "volumen" => "25" "paginaInicial" => "1032" "paginaFinal" => "1038" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15929958" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "B.R. Celli" 1 => "W. MacNee" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Eur Respir J" "fecha" => "2004" "volumen" => "23" "paginaInicial" => "932" "paginaFinal" => "946" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15219010" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chronic obstructive pulmonary disease. National clinical guideline on management of chronic obstructive pulmonary disease in adults in primary and secondary care" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "National Institute for Clinical Excellence (NICE)" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Thorax" "fecha" => "2004" "volumen" => "59" "numero" => "Suppl. 1" "paginaInicial" => "1" "paginaFinal" => "232" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15041752" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Influence of lightweight ambulatory oxygen on oxygen use and activity patterns of COPD patients receiving long-term oxygen therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Casaburi" 1 => "J. Porszasz" 2 => "A. Hecht" 3 => "B. Tiep" 4 => "R.K. Albert" 5 => "N.R. Anthonisen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3109/15412555.2011.630048" "Revista" => array:6 [ "tituloSerie" => "COPD" "fecha" => "2012" "volumen" => "9" "paginaInicial" => "3" "paginaFinal" => "11" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22292592" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term oxygen treatment in chronic obstructive pulmonary disease: recommendations for future research: an NHLBI workshop report" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "T.L. Croxton" 1 => "W.C. Bailey" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.200507-1161WS" "Revista" => array:7 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2006" "volumen" => "174" "paginaInicial" => "373" "paginaFinal" => "378" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16614349" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0016508502004572" "estado" => "S300" "issn" => "00165085" ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical research in chronic obstructive pulmonary disease: needs and opportunities" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "T.L. Croxton" 1 => "G.G. Weinmann" 2 => "R.M. Senior" 3 => "R.A. Wise" 4 => "J.D. Crapo" 5 => "A.S. Buist" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.200207-756WS" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2003" "volumen" => "167" "paginaInicial" => "1142" "paginaFinal" => "1149" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12684252" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735115/0000001800000006/v1_201305151609/S2173511512000978/v1_201305151609/en/main.assets" "Apartado" => array:4 [ "identificador" => "9716" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Editorials" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735115/0000001800000006/v1_201305151609/S2173511512000978/v1_201305151609/en/main.pdf?idApp=UINPBA00004E&text.app=https://journalpulmonology.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173511512000978?idApp=UINPBA00004E" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 9 | 4 | 13 |
| 2024 October | 23 | 27 | 50 |
| 2024 September | 24 | 26 | 50 |
| 2024 August | 48 | 30 | 78 |
| 2024 July | 27 | 34 | 61 |
| 2024 June | 26 | 26 | 52 |
| 2024 May | 28 | 37 | 65 |
| 2024 April | 29 | 24 | 53 |
| 2024 March | 30 | 31 | 61 |
| 2024 February | 19 | 36 | 55 |
| 2024 January | 17 | 23 | 40 |
| 2023 December | 15 | 22 | 37 |
| 2023 November | 17 | 30 | 47 |
| 2023 October | 13 | 24 | 37 |
| 2023 September | 17 | 36 | 53 |
| 2023 August | 19 | 25 | 44 |
| 2023 July | 20 | 24 | 44 |
| 2023 June | 18 | 18 | 36 |
| 2023 May | 17 | 26 | 43 |
| 2023 April | 16 | 7 | 23 |
Show all
