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class="elsevierStyleTextfn">SEPAR's Voice</span>" "titulo" => "Spanish Consensus on Remission in Asthma (REMAS)" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "503" "paginaFinal" => "509" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Francisco Javier Álvarez-Gutiérrez, Francisco Casas-Maldonado, Gregorio Soto-Campos, Marina Blanco-Aparicio, Julio Delgado, Alicia Padilla Galo, Santiago Quirce, Vicente Plaza" "autores" => array:9 [ 0 => array:2 [ "nombre" => "Francisco Javier" "apellidos" => "Álvarez-Gutiérrez" ] 1 => array:2 [ "nombre" => "Francisco" "apellidos" => "Casas-Maldonado" ] 2 => array:2 [ "nombre" => "Gregorio" "apellidos" => "Soto-Campos" ] 3 => array:2 [ "nombre" => "Marina" "apellidos" => "Blanco-Aparicio" ] 4 => array:2 [ "nombre" => 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array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Factors Associated With Change in S3-NIV Score Over Time in People With Chronic Respiratory Failure Treated With Long-Term Home Noninvasive Ventilation" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "483" "paginaFinal" => "489" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 1 "multimedia" => array:5 [ "identificador" => "fig0030" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 886 "Ancho" => 1614 "Tamanyo" => 187281 ] ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Messaoud Lefouili, Nathalie Arnol, Sandra Journet, Pascal Chauderon, Dan Adler, Jean-Paul Janssens, Jean-Louis Pépin, Sébastien Bailly, Jean Christian Borel" "autores" => array:9 [ 0 => array:2 [ "nombre" => "Messaoud" "apellidos" => "Lefouili" ] 1 => array:2 [ "nombre" => "Nathalie" "apellidos" => "Arnol" ] 2 => array:2 [ "nombre" => "Sandra" "apellidos" => "Journet" ] 3 => array:2 [ "nombre" => "Pascal" "apellidos" => "Chauderon" ] 4 => array:2 [ "nombre" => "Dan" "apellidos" => "Adler" ] 5 => array:2 [ "nombre" => "Jean-Paul" "apellidos" => "Janssens" ] 6 => array:2 [ "nombre" => "Jean-Louis" "apellidos" => "Pépin" ] 7 => array:2 [ "nombre" => "Sébastien" "apellidos" => "Bailly" ] 8 => array:2 [ "nombre" => "Jean Christian" "apellidos" => "Borel" ] ] ] ] "resumen" => array:1 [ 0 => array:3 [ "titulo" => "Graphical abstract" "clase" => "graphical" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><elsevierMultimedia ident="fig0030"></elsevierMultimedia></p></span>" ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289624001650?idApp=UINPBA00003Z" "url" => "/03002896/0000006000000008/v1_202408020536/S0300289624001650/v1_202408020536/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review article</span>" "titulo" => "Effectiveness, Adherence and Safety of Home High Flow Nasal Cannula in Chronic Respiratory Disease and Respiratory Insufficiency: A Systematic Review" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "490" "paginaFinal" => "502" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Cristina Jácome, Marta Jácome, Sara Correia, Inês Flores, Patrícia Farinha, Mónica Duarte, João Carlos Winck, Javier Sayas Catalan, Salvador Díaz Lobato, Manel Luján, Cátia Caneiras" "autores" => array:11 [ 0 => array:3 [ "nombre" => "Cristina" "apellidos" => "Jácome" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Marta" "apellidos" => "Jácome" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Sara" "apellidos" => "Correia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Inês" "apellidos" => "Flores" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 4 => array:3 [ "nombre" => "Patrícia" "apellidos" => "Farinha" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 5 => array:3 [ "nombre" => "Mónica" "apellidos" => "Duarte" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 6 => array:3 [ "nombre" => "João Carlos" "apellidos" => "Winck" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">f</span>" "identificador" => "aff0030" ] ] ] 7 => array:3 [ "nombre" => "Javier" "apellidos" => "Sayas Catalan" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">g</span>" "identificador" => "aff0035" ] ] ] 8 => array:3 [ "nombre" => "Salvador" "apellidos" => "Díaz Lobato" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">h</span>" "identificador" => "aff0040" ] ] ] 9 => array:3 [ "nombre" => "Manel" "apellidos" => "Luján" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">i</span>" "identificador" => "aff0045" ] ] ] 10 => array:4 [ "nombre" => "Cátia" "apellidos" => "Caneiras" "email" => array:1 [ 0 => "ccaneiras@medicina.ulisboa.pt" ] "referencia" => array:5 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">j</span>" "identificador" => "aff0050" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">k</span>" "identificador" => "aff0055" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">l</span>" "identificador" => "aff0060" ] 3 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] 4 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:12 [ 0 => array:3 [ "entidad" => "CINTESIS@RISE, Health Research Network, Faculty of Medicine, University of Porto, Porto, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidade de Saúde Familiar Bracara Augusta, Agrupamento de Centros de Saúde (ACES) do Cávado I – Braga, Braga, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Resmed Science Centre, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Healthcare Department, Nippon Gases Portugal, Vila Franca de Xira, Portugal" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "UniC, Cardiovascular R&D Centre, Faculty of Medicine, University of Porto, Porto, Portugal" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Instituto CUF, Porto Portugal" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Servicio de Neumología, Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, Madrid, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "HLA Hospital Universitario Moncloa, Universidad Europea, Nippon Gases Healthcare, Madrid, Spain" "etiqueta" => "h" "identificador" => "aff0040" ] 8 => array:3 [ "entidad" => "Servei de Pneumologia, Parc Taulí Hospital Universitari. Institut d’Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, Sabadell, Spain" "etiqueta" => "i" "identificador" => "aff0045" ] 9 => array:3 [ "entidad" => "Microbiology Research Laboratory on Environmental Health, Institute of Environmental Health, Associate Laboratory TERRA, Faculty of Medicine, Universidade de Lisboa, Lisbon, Portugal" "etiqueta" => "j" "identificador" => "aff0050" ] 10 => array:3 [ "entidad" => "Institute of Preventive Medicine and Public Health, Faculty of Medicine, University of Lisbon, Lisbon, Portugal" "etiqueta" => "k" "identificador" => "aff0055" ] 11 => array:3 [ "entidad" => "Egas Moniz Interdisciplinary Research Center, Egas Moniz School of Health & Science, Monte da Caparica, Portugal" "etiqueta" => "l" "identificador" => "aff0060" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2100 "Ancho" => 3596 "Tamanyo" => 456524 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">PRISMA flowchart.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">In 2019, respiratory diseases accounted for three of the top 10 causes of death, resulting in more than 8 million deaths annually, with chronic obstructive respiratory disease (COPD) being the third leading cause of death.<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">1</span></a> However, other chronic respiratory diseases also contribute to this high burden. The global incidence of non–cystic fibrosis bronchiectasis ranges from 67 to 566 per 100,000 inhabitants in Europe and North America.<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">2</span></a> Between 1990 and 2013, Interstitial Lung Disease (ILD) was among the top 50 causes of global years of life lost worldwide.<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">3</span></a> In addition, regardless of the underlying chronic respiratory disease, patients experience frequent exacerbations, respiratory failure and a decrease in their quality of life.<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">4</span></a> Various forms of treatment are available to improve physiological parameters, symptoms and patient-centered outcomes, including non-invasive ventilation and oxygen therapy. In recent years, high flow nasal cannula therapy has been introduced as another innovative approach to treat some groups of respiratory patients.</p><p id="par0010" class="elsevierStylePara elsevierViewall">High flow nasal cannula (HFNC) has emerged as a home treatment for patients with chronic respiratory diseases to increase the carbon dioxide (CO<span class="elsevierStyleInf">2</span>) washout, while improving the mucociliary clearance.<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">5</span></a> HFNC provides heated and humidified gas admixture at a high flow rate (up to 60<span class="elsevierStyleHsp" style=""></span>L/min) via a wide-bore nasal cannula. This therapy was widely studied in acute respiratory failure, including COVID-19 and has been shown to reduce intubation and mortality in comparison with conventional oxygen therapy.<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">6–10</span></a> In addition, HFNC seems probably better than non-invasive ventilation in terms of dyspnea, comfort, and decreasing of respiratory rate in patients either post-extubation or during acute respiratory failure.<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">11</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In the home setting, evidence has been pooled in patients with COPD, with HFNC shown to improve health-related quality of life<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">12</span></a> and reduce the rate of exacerbations.<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">13</span></a> Other systematic reviews or meta-analysis of HFNC have shown inconsistent and conflicting results.<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">14–16</span></a> These may be due to the fact that these syntheses included heterogeneous studies, mixing acute and chronic patients, short-term and long-term treatment. To our knowledge, there is only one systematic review focusing exclusively on stable patients with COPD, but unfortunately it was based on randomized control trials only.<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">13</span></a> Adding information from real-world observational studies and other chronic respiratory diseases, such bronchiectasis and ILD, may help in clinical reasoning.<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">17</span></a> Furthermore, the adherence and safety of long-term HFNC treatment in patients with chronic respiratory diseases remains unclear.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Therefore, we aimed to conduct a systematic review of the effectiveness, adherence, and safety of HFNC in the long-term treatment of patients with chronic respiratory diseases and respiratory failure.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Study design</span><p id="par0025" class="elsevierStylePara elsevierViewall">A systematic review was conducted and reported according to PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines.<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">18</span></a> The protocol was registered at PROSPERO (CRD42023461837).</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Search strategy</span><p id="par0030" class="elsevierStylePara elsevierViewall">A comprehensive search of PubMed, Web of science, and SCOPUS databases was performed until August 8, 2023. The search strategy included 2 concept sets: ((“chronic obstructive lung disease” OR COPD OR “chronic obstructive airway disease” OR “chronic obstructive lung disease” OR “interstitial lung disease” OR “ILD” OR “bronchiectasis” OR “hypercapnic” OR “normocapnic” OR “pulmonary disease” OR “chronic respiratory insufficiency”) AND (“high-flow oxygen” OR “high flow nasal cannula” OR “high flow nasal oxygen” OR “high flow oxygen therapy” OR “nasal high flow” OR “HFNC” OR “HFNO” OR “HFOT” OR “NHF” OR “NHFT” OR “short-term nasal high-flow” OR “domiciliary high-flow nasal cannula oxygen therapy” OR “domiciliary nasal high flow therapy”). Additional searches were performed using weekly automatic updates retrieved from these databases. We also searched for relevant references in the list of references of the included studies. In addition, we manually searched published meta-analyses and systematic reviews, and the references of the included studies to identify other potentially relevant studies. No language restrictions were applied.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Eligibility criteria</span><p id="par0035" class="elsevierStylePara elsevierViewall">Inclusion criteria were studies that included patients with chronic respiratory diseases such as COPD, bronchiectasis, ILD, and others and chronic respiratory failure (Population) and provided long-term HFNC, defined as at least 4 weeks with a flow of at least 20<span class="elsevierStyleHsp" style=""></span>L/min (Intervention), which could be or not compared with other forms of respiratory support (Comparators, not mandatory). To be included, primary articles had to report outcomes such dyspnea; exacerbations, hospitalizations; peripheral oxygen saturation (SpO<span class="elsevierStyleInf">2</span>), comfort; patient experience, health-related quality of life or partial pressure of carbon dioxide (paCO<span class="elsevierStyleInf">2</span>). Randomized controlled trials (RCTs), randomized crossover studies, quasi-experimental studies, case-control studies and retrospective studies were included. Study protocols, book chapters, reviews, editorials/commentaries to articles, case reports and abstracts were excluded.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Screening, selection process and data extraction</span><p id="par0040" class="elsevierStylePara elsevierViewall">After removal of duplicate studies, the articles were screened independently by 2 reviewers (CJ and MJ) to identify relevant articles by the title and abstract using the Rayyan software.<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">19</span></a> In case of disagreement, a third researcher (CC) was consulted. The 2 reviewers (MJ and CJ) used a standardized form to independently extract data from each article, including the author's surname and year of publication, study design, sample size, participants and condition, HTF protocol, outcomes, and results. The third author (CC) was consulted in case of discrepancies.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Assessment of methodological quality and risk of bias</span><p id="par0045" class="elsevierStylePara elsevierViewall">Risk of bias and methodological quality of the included studies were independently assessed by 2 authors (MJ and CJ). The risk of bias for randomized studies was assessed using the Cochrane Collaboration's tool.<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">20</span></a> Risk of bias for observational studies was assessed using the Newcastle–Ottawa Scale (NOS).<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">21</span></a> Disagreements were resolved by discussion or by a third reviewer (CC).</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Data synthesis and analysis</span><p id="par0050" class="elsevierStylePara elsevierViewall">As the included studies were clinically heterogeneous, narrative synthesis was used to report the findings. This was considered the most appropriate approach given the heterogeneity of data between the included studies. Findings were initially draft by one researcher (CJ), then reviewed by a second researcher (MJ).</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Study selection</span><p id="par0055" class="elsevierStylePara elsevierViewall">The database search yielded 938 studies. After removing duplicate results, 526 articles were screened for relevant content. During title and abstract screening, 501 articles were excluded. Finally, 24 articles were selected for full-text screening. Two additional papers were included through manual search and screening of the reference lists of full-text articles. After excluding 8 articles, 13 articles from 10 studies were selected for qualitative analysis (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Methodological quality and risk of bias</span><p id="par0060" class="elsevierStylePara elsevierViewall">Details of the included articles are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. The 13 articles were published between 2010 and 2023, mainly in European countries (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>7).<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">22–28</span></a> The articles had different designs, namely RCTs (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>3),<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">23,29,30</span></a> randomized crossover trials (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2),<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">24,31</span></a> non-randomized crossover studies (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>3)<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">22,26,27</span></a> and retrospective studies (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2).<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">25,28</span></a> Three articles were secondary analysis of RCTs.<a class="elsevierStyleCrossRefs" href="#bib0465"><span class="elsevierStyleSup">32–34</span></a> Risk of bias in RCTs was mainly related to blinding of participants/staff, blinding of outcome assessor and incomplete data (<a class="elsevierStyleCrossRef" href="#sec0125">Supplementary Fig. 1</a>), whereas in non-randomized studies it was related to the outcome assessment and groups comparability (<a class="elsevierStyleCrossRef" href="#sec0125">Supplementary Table 2</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Study characteristics</span><p id="par0065" class="elsevierStylePara elsevierViewall">Most studies were conducted in patients with COPD (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6), 2 studies in patients with bronchiectasis, one in both COPD and bronchiectasis, and one in patients with ILD. Inclusion criteria varied among studies, but prescription of long-term oxygen therapy (LTOT) (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>5),<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">23,27–29,31</span></a> chronic respiratory failure/hypercapnia (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>4),<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">22,24,29,31</span></a> history of exacerbations/hospitalizations (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>4),<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">25,26,29,30</span></a> stable hypercapnia (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>4<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">22,24,29,31</span></a>), sputum production (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2)<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">25,30</span></a> and body mass index<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span> (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2)<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">22,24</span></a> were some of the most commonly used. The studies included a total of 701 stable patients (sample sizes from 9 to 200). The average age of the patients was 65–76 years old. The average FEV<span class="elsevierStyleInf">1</span>% predicted at baseline was 25–69%, with the lowest values found in studies with patients with COPD.</p><p id="par0070" class="elsevierStylePara elsevierViewall">HFNC was mainly compared with standard care (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>3)<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">25,27,30</span></a>; LTOT (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>3),<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">23,29,31</span></a> and VNI+LTOT (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2) and NIV (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>3).<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">22,24,28</span></a> HFNC was prescribed at flow rates between 20-60<span class="elsevierStyleHsp" style=""></span>L/min, with or without O<span class="elsevierStyleInf">2</span> supplementation. Patients were recommended to use HFNC between 2 and 8<span class="elsevierStyleHsp" style=""></span>hours/day, preferably during sleep. The effects of the intervention were evaluated both in the short-term (6 weeks, <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>4<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">22,24,27,31</span></a>) and in the long-term (1<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">23,25,28,30</span></a> and 2 years<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">26</span></a>).</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Summary of findings</span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Exacerbations</span><p id="par0075" class="elsevierStylePara elsevierViewall">Most articles used exacerbations (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>9) as an outcome measure, with 6 showing the ability of HFNC to reduce these events when compared with usual care<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">25,26,30,33</span></a> or LTOT.<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">23,29</span></a> The other three articles (2 post hoc analyses of<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">23</span></a>) also showed significant improvements in exacerbations, particularly in hypercapnic patients and those with 2 or more exacerbations per year.<a class="elsevierStyleCrossRefs" href="#bib0460"><span class="elsevierStyleSup">31,32,34</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Hospitalizations</span><p id="par0080" class="elsevierStylePara elsevierViewall">HFNC was also able to reduce the rate of hospitalizations in patients with COPD and bronchiectasis (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>7<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">23,25,26,28,30,32,34</span></a>), although not superior to LTOT,<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">23</span></a> or even usual care.<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">30</span></a> Based on non-randomized studies and considering only patients with bronchiectasis, HFNC seemed to be more beneficial than usual care.<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">25,26</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">PaCO<span class="elsevierStyleInf">2</span></span><p id="par0085" class="elsevierStylePara elsevierViewall">PaCO<span class="elsevierStyleInf">2</span> was a selected outcome in 6 articles. HFNC improved PaCO2 in patients with COPD and was shown to be superior to LTOT<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">23,31,34</span></a> or non-invasive ventilation (NIV).<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">24</span></a> This was not observed in patients with ILD.<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">27</span></a></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Health-related quality of life</span><p id="par0090" class="elsevierStylePara elsevierViewall">Quality of life was used as an outcome measure in 8 articles, 6 of which showed results in favor of HFNC in patients with COPD,<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">23,24,31</span></a> bronchiectasis,<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">25,33</span></a> or both.<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">30</span></a> Different patient-reported outcome measures were used to assess this health domain: SGRQ general or the COPD specific version,<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">23–25,30,31,33</span></a> EQ-5D-5L,<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">31</span></a> health state visual analog scale,<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">24</span></a> Severe Respiratory Insufficiency Questionnaire.<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">2</span></a></p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Lung function</span><p id="par0095" class="elsevierStylePara elsevierViewall">Lung function, specifically FEV<span class="elsevierStyleInf">1</span> and FVC, were one of the most common used outcome measures (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>9 articles). However, only two studies with long-term follow up of patients with COPD and bronchiectasis were able to demonstrate the superiority of HFNC over usual care for lung function.<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">25,30</span></a></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Other outcomes</span><p id="par0100" class="elsevierStylePara elsevierViewall">The 6MWT (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>7) and mMRC (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6) were other commonly used outcomes, with the 6MWT demonstrating the superior effect of HFNC compared to LTOT and usual care in patients with COPD and ILD<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">23,27</span></a>; and the mMRC compared to usual care patients with bronchiectasis.<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">26</span></a></p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Adherence</span><p id="par0105" class="elsevierStylePara elsevierViewall">Adherence to HFNC has been reported in 8 studies, with most reporting adherences between 5.2 and 8.6<span class="elsevierStyleHsp" style=""></span>h/day,<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">24,25,27,29,31</span></a> or a percentage of users above a certain threshold (32%<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">30</span></a> and 100%<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">26</span></a> ≥2<span class="elsevierStyleHsp" style=""></span>h, 86% 7<span class="elsevierStyleHsp" style=""></span>h/day<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">23</span></a>). In four studies HFNC was compared to NIV/LTOT, but only Bräunlich et al. showed that adherence of HFNC was superior to NIV.<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">24</span></a></p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Safety</span><p id="par0110" class="elsevierStylePara elsevierViewall">With regard to safety, 8 articles presented data on adverse events associated with HFNC, of which 3 reported no events,<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">23,25,30</span></a> and the remaining presented common non-serious events<a class="elsevierStyleCrossRefs" href="#bib0435"><span class="elsevierStyleSup">26,27,31</span></a> or showed no differences between events observed under LTOT/NIV.<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">24,29</span></a></p></span></span></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Discussion</span><p id="par0115" class="elsevierStylePara elsevierViewall">In this systematic review, we comprehensively evaluated the effectiveness, adherence and safety of HFNC therapy in stable patients with COPD, bronchiectasis and ILD with chronic respiratory failure. We found that HFNC seems more effective as a long-term strategy for reducing exacerbations and improving quality of life than usual care or other home respiratory therapies, although more robust evidence is still needed. HFNC appears to have also beneficial effects on hospitalizations, paCO<span class="elsevierStyleInf">2</span>, and lung function, while being safe and having good adherence.</p><p id="par0120" class="elsevierStylePara elsevierViewall">This review shows that HFNC is associated with a reduction in exacerbations in patients with COPD and bronchiectasis that is not inferior to NIV and greater than LTOT or usual care.<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">23,25,26,29,30,33</span></a> This is an important benefit, demonstrating that HFNC contributes to the key long-term goal of reducing the frequency and severity of exacerbations in patients with chronic respiratory diseases. In addition, the reduction appears to be more significant in both hypoxic and hypercapnic patients and in those with 2 or more exacerbations in the last year.<a class="elsevierStyleCrossRefs" href="#bib0460"><span class="elsevierStyleSup">31,32,34</span></a> HFNC can therefore be considered as an alternative to consider in a selective group: patients with COPD and frequent acute exacerbations. As exacerbations are a major determinant of health status, this effect is probably related to the observed improvement in quality of life. It is noteworthy that most of the studies showing effects on quality of life used the SGRQ and exceeded its minimal clinical important difference (MICD) of 4 units. The improvement in quality of life highlighted in this narrative synthesis is in line with meta-analytic findings from previous systematic reviews on the effects of HFNC in COPD.<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">12,13</span></a> The effectiveness of HFNC in these two health domains has also been assessed using cost-effectiveness analyses, which have shown that HFNC has the potential to provide substantial cost savings.<a class="elsevierStyleCrossRefs" href="#bib0480"><span class="elsevierStyleSup">35,36</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">HFNC improved paCO<span class="elsevierStyleInf">2</span> in patients with COPD and has shown to be superior to LTOT or NIV.<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">23,24,31,34</span></a> This finding is consistent with a previous review in patients with COPD.<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">14</span></a> Nevertheless, this improvement in paCO<span class="elsevierStyleInf">2</span> needs to be considered with caution as it may be a result of the selection process and not translate the improvement expected in real-world patients with COPD. Indeed, in 4 of the 6 studies recruiting solely patients with COPD, stable hypercapnia (defined as paCO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>45<span class="elsevierStyleHsp" style=""></span>mmHg or >50<span class="elsevierStyleHsp" style=""></span>mmHg) was one of inclusion criteria. Benefits of HFNC on hospitalizations and lung function were also found,<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">25,26,30</span></a> but this evidence comes mainly from non-randomized studies. The potential of HFNC in comparison with usual care or other home respiratory therapies in changing these outcomes needs to be further explored in future studies with larger samples and long-term follow-up. Two trials are underway that will shed light on the effect of HFNC on these outcomes.<a class="elsevierStyleCrossRefs" href="#bib0490"><span class="elsevierStyleSup">37,38</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">The effects of HFNC on exercise tolerance and dyspnea are fragile,<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">23,26,27</span></a> which may be related to the short follow-up of most studies, but also to the responsiveness of the selected outcome measures to HFNC. The MICD of the 6MWT has been estimated to be 30<span class="elsevierStyleHsp" style=""></span>m in chronic respiratory diseases,<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">39</span></a> and unless HFNC is combined with specific interventions to improve exercise tolerance, it is unlike that its benefit will be demonstrated with such a specific measure of fitness. It has already been shown that the mMRC scale is a good tool to discriminate patients in terms of their dyspnea, but is not sensitive enough to change to be useful as an outcome in clinical trials.<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">40</span></a> Future studies should therefore consider including other measures that replicate activities of daily living and associated dyspnea, such as 1-min sit to stand<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">41</span></a> and London Chest Activity of Daily Living scale.<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">42</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">The effectiveness of HFNC will be more clearly demonstrated if the patients’ perspective is considered in the design and evaluation of interventions. Unfortunately, none of the studies in this review mentioned that the design of the interventions included input from patients or carers, or assessed patient comfort or experience. Twelve participants in one of the trials included in this review and 8 relatives participated in a qualitative study addressing the experience with HFNC.<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">23</span></a> Patients reported improved sleep and more energy for daily activities and found the ease of use of the device to be a strong motivator for adherence.<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">43</span></a> Future trials evaluating the effectiveness of home-based care should consider including patient-reported outcome and experience measures.<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">44</span></a> A combination of both is essential to fully understand the performance of home respiratory therapies and to allow patient-centered comparisons. Currently, there is no specific patient-reported experience measure for this health context, and this should be a research priority.<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">45</span></a> In the meantime, a COPD-specific<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">46</span></a> and other generic<a class="elsevierStyleCrossRefs" href="#bib0540"><span class="elsevierStyleSup">47,48</span></a> measures can be used. This, together with the design of pragmatic trials that take into account patient preference and experience, will provide robust real-world evidence on the role of HFNC.</p><p id="par0140" class="elsevierStylePara elsevierViewall">Patients adhered well to HFNC, with most studies showing adherence between 5 and 8<span class="elsevierStyleHsp" style=""></span>h/day.<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">24,25,27,29,31</span></a> Unfortunately at this stage we cannot know if adherence to HFNC is better than other home respiratory therapies (LTOT/NIV) as only one study made this comparison and showed results favoring HFNC.<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">24</span></a> Nevertheless the adherence reported for HFNC seems in line with the real-world adherence to NIV<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">49</span></a> and the common cut-offs of 4–5<span class="elsevierStyleHsp" style=""></span>h/day to define good adherence.<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">50,51</span></a> The study with lower adherence (mean 1.6<span class="elsevierStyleHsp" style=""></span>h/day) was also the one in which patients were advised to use the therapy for a shorter period (2<span class="elsevierStyleHsp" style=""></span>h), which is understandable as it was one of the pioneers in testing the feasibility and safety of implementing long-term HFNC.<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">30</span></a> In addition, HFNC has been shown to be an overall safe therapy that can be deliverable at home, with adverse events similar to those known for LTOT or NIV.<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">52</span></a> The concern in reporting adverse events is a stronger point of the included studies (8 out of 10 original studies). However, the method of collecting adverse events was poorly reported, with some studies appearing to use standard collection methods, while others may have relied on spontaneous patient reporting. Future trials should improve the consistency of reporting important adverse events.<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">53</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Different HFNC protocols were used, differing mainly in the flow provided, the use of O<span class="elsevierStyleInf">2</span> and the prescribed hours per day. Most studies used flows of 20–40<span class="elsevierStyleHsp" style=""></span>L/min and recommended sessions of 6–8<span class="elsevierStyleHsp" style=""></span>h per day, preferably at night. In patients on LTOT, the supplemental oxygen flow was maintained unchanged during HFNC unless a SpO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>88% was detected. Differences may be related to the characteristics of the devices, but mainly to the lack of specific guidelines at the time the studies were conducted. The Danish guidelines published this year are pioneering,<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">5</span></a> although based mostly on narrative review of findings and expert opinion. Other clinical practice guidelines are likely to follow, ideally using the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach.<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">54</span></a> This is crucial because HFNC is already being used in routine practice, as evidenced by the two retrospective studies included in this review,<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">25,28</span></a> the number of editorials published,<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">11,55–58</span></a> and the European Respiratory Society survey on HFNC practice (although with results not yet available). Recently, three strategies or ventilatory modalities have been described related to HFNC settings.<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">55</span></a> Future studies are necessary to enhance our understanding of this technique and the impact of different HFNC settings on clinical outcomes.</p><p id="par0150" class="elsevierStylePara elsevierViewall">This systematic review has some limitations that need to be considered. Our search strategy did not include the effectiveness of HFNC in stable patients during exercise or pulmonary rehabilitation programs, for which there is also a growing body of evidence.<a class="elsevierStyleCrossRefs" href="#bib0600"><span class="elsevierStyleSup">59–61</span></a> This can be considered as a limitation of our work and should be addressed in future reviews. This review is the first attempt to gather evidence on the long-term use of HFNC in patients with different chronic respiratory diseases. As it was expected, the number of studies is still limited and most of the evidence comes from patients with COPD and bronchiectasis, with only one study including patients with ILD. This limits the ability to generalize the results to patients with chronic respiratory diseases. Different study designs were included that used different outcome measures. This prevented us from doing a meta-analysis. In addition, the included reports were generally of moderate to low quality. Future studies can use these previous works to better select the most responsive outcome measures, to substantiate their sample size estimates and to design feasible HFNC protocols. This will improve the overall quality of the evidence being produced, which will allow stronger research synthesis of the evidence with the addition of meta-analysis.</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conclusions</span><p id="par0155" class="elsevierStylePara elsevierViewall">HFNC seems more effective than usual care or other home respiratory therapies as a long-term strategy for reducing exacerbations and improving quality of life in patients with COPD and bronchiectasis. This review also showed that HFNC has good adherence levels and is safe in the home setting. Real-world pragmatic trials are nevertheless needed to better clarify the effectiveness of HFNC in patients with stable chronic respiratory diseases with chronic respiratory failure.</p></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Funding</span><p id="par1155" class="elsevierStylePara elsevierViewall">No funding was received for this work.</p></span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Conflict of interests</span><p id="par0160" class="elsevierStylePara elsevierViewall">Cristina Jácome, Marta Jácome, Mónica Duarte, João Carlos Winck, Savador Díaz Lobato, Manel Luján and Cátia Caneiras have no competing interests to declare. Sara Correia, Inês Flores and Patrícia Farinha are employees of ResMed. Javier Sayas Catalan received lecture honoraria from ResMed and Philips.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres2214962" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1856954" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study design" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Search strategy" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Eligibility criteria" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Screening, selection process and data extraction" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Assessment of methodological quality and risk of bias" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Data synthesis and analysis" ] ] ] 4 => array:3 [ "identificador" => "sec0045" "titulo" => "Results" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Study selection" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Methodological quality and risk of bias" ] 2 => array:2 [ "identificador" => "sec0060" "titulo" => "Study characteristics" ] 3 => array:3 [ "identificador" => "sec0065" "titulo" => "Summary of findings" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "sec0070" "titulo" => "Exacerbations" ] 1 => array:2 [ "identificador" => "sec0075" "titulo" => "Hospitalizations" ] 2 => array:2 [ "identificador" => "sec0080" "titulo" => "PaCO" ] 3 => array:2 [ "identificador" => "sec0085" "titulo" => "Health-related quality of life" ] 4 => array:2 [ "identificador" => "sec0090" "titulo" => "Lung function" ] 5 => array:2 [ "identificador" => "sec0095" "titulo" => "Other outcomes" ] 6 => array:2 [ "identificador" => "sec0100" "titulo" => "Adherence" ] 7 => array:2 [ "identificador" => "sec0105" "titulo" => "Safety" ] ] ] ] ] 5 => array:2 [ "identificador" => "sec0110" "titulo" => "Discussion" ] 6 => array:2 [ "identificador" => "sec0115" "titulo" => "Conclusions" ] 7 => array:2 [ "identificador" => "sec0120" "titulo" => "Funding" ] 8 => array:2 [ "identificador" => "sec0140" "titulo" => "Conflict of interests" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2024-02-16" "fechaAceptado" => "2024-05-01" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1856954" "palabras" => array:6 [ 0 => "Chronic obstructive pulmonary disease" 1 => "High-flow cannula" 2 => "High-flow nasal cannula oxygen therapy" 3 => "Hypercapnic" 4 => "Nasal high-flow" 5 => "Pulmonary disease" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The effectiveness of home high flow nasal cannula (HFNC) for the treatment of chronic respiratory failure in patients with chronic respiratory diseases (CRDs) has not been summarized. We aimed to conduct a systematic review of the effectiveness, adherence, and safety of HFNC in the long-term treatment of patients with chronic respiratory diseases and respiratory failure.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A systematic review was conducted. PubMed, Web of science, and SCOPUS were search up to August 2023. Long-term HFNC studies (≥4 weeks) reporting dyspnea; exacerbations, hospitalizations; peripheral oxygen saturation (SpO<span class="elsevierStyleInf">2</span>), comfort; patient experience, health-related quality of life or partial pressure of carbon dioxide (paCO<span class="elsevierStyleInf">2</span>) were included.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Thirteen articles (701 patients) based on 10 studies were selected: randomized control trials (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>3), randomized crossover trials (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2), crossover (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>3) and retrospective (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2) studies. COPD (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6), bronchiectasis (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2), COPD/bronchiectasis (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1) and ILD (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1) were the underlined CRDs. HFNC reduced exacerbations when compared to usual care/home respiratory therapies (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6). Quality of life outcomes were also in favor of HFNC in patients with COPD and bronchiectasis (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6). HFNC had significant effects on hospitalizations, paCO<span class="elsevierStyleInf">2</span>, and lung function. Adherence ranged from 5.2 to 8.6<span class="elsevierStyleHsp" style=""></span>h/day (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>5). Three studies reported no events, 3 non-serious events and 2 no differences compared with other home respiratory therapies.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">HFNC seems more effective than usual care or other home respiratory therapies in reducing exacerbations and improving quality of life in patients with COPD and bronchiectasis, while presenting good adherence and being safe. Its apparently superior effectiveness needs to be better studied in future real-world pragmatic trials.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0170" class="elsevierStylePara elsevierViewall">The following are the supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia><elsevierMultimedia ident="upi0010"></elsevierMultimedia></p>" "etiqueta" => "Appendix B" "titulo" => "Supplementary data" "identificador" => "sec0130" ] ] ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2100 "Ancho" => 3596 "Tamanyo" => 456524 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">PRISMA flowchart.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>: 6MWT, 6<span class="elsevierStyleHsp" style=""></span>min walking test; FEV<span class="elsevierStyleInf">1</span>, forced expiratory volume in the first second; FiO<span class="elsevierStyleInf">2</span>, fraction of inspired oxygen; FVC, forced vital capacity; GOLD, Global Initiative for Chronic Obstructive Lung Disease; HFNC, high-flow nasal cannula; IQR, interquartile range; LTOT, long-term oxygen treatment; MD, mean difference; M, median; mMRC, modified Medical Research Council scale; NIV, non-invasive ventilation; PaCO<span class="elsevierStyleInf">2</span>, partial pressure of carbon dioxide; PO<span class="elsevierStyleInf">2</span>, partial pressure of oxygen; pred predicted; PtcCO<span class="elsevierStyleInf">2</span>, transcutaneous carbon dioxide pressure; SGRQ, St George Respiratory Questionnaire; SRI, Severe Respiratory Insufficiency.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">First author, year \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Country \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Design \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Eligibility criteria \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Participants \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Intervention \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Comparator \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Follow-up period \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Outcomes \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Main results \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rea et al., 2010<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">30</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">New Zealand \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RCT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Inclusion</span>- COPD diagnosis confirmed by spirometry- Bronchiectasis confirmed by high-resolution computed tomography- ≥2 exacerbations in the previous 12 months- >5<span class="elsevierStyleHsp" style=""></span>ml daily sputum- Stable for ≥4 weeks<span class="elsevierStyleUnderline">Exclusion</span>- Bronchiectasis associated with cystic fibrosis or hypogammaglobulinaemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HFNC34 patients with stable COPD/26 patients with stable bronchiectasis66.2 (9.5) years52% maleFEV<span class="elsevierStyleInf">1</span> 44.7 (20.7)% predControl29 patients with stable COPD/19 patients with stable bronchiectasis69.0 (11) years56% maleFEV<span class="elsevierStyleInf">1</span> 45.3 (14.7)% pred \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HFNC- Flow 20–25<span class="elsevierStyleHsp" style=""></span>L/min, 37°- O<span class="elsevierStyleInf">2</span> for patients on LTOT- ≥2<span class="elsevierStyleHsp" style=""></span>h/day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Usual care \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Primary</span>Rate of exacerbations (worsening of ≥2 respiratory symptoms for ≥2 days that required antibiotics or oral prednisone)<span class="elsevierStyleUnderline">Secondary</span>Time to 1st exacerbationExacerbation daysHospital admissionsSGRQ totalLung function6MWTSputum cell countsmMRCAdherenceWillingness to useAdverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Exacerbations/patient/year</span>HFNC 2.97 vs Control 3.63, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.067<span class="elsevierStyleUnderline">Annual exacerbation days</span>HFNC 18.2 vs Control 33.5, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.045<span class="elsevierStyleUnderline">Days to 1st exacerbation</span>HFNC 52 vs Control 27, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.049<span class="elsevierStyleUnderline">Patients free of exacerbations</span>HFNC 20% vs Control 8.3%, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.043<span class="elsevierStyleUnderline">SGRQ total</span>Sig. differences (>5.9 units) favor HFCN at 3&12 months<span class="elsevierStyleUnderline">FEV</span><span class="elsevierStyleInf"><span class="elsevierStyleUnderline">1</span></span><span class="elsevierStyleUnderline">& FVC</span>Sig. differences favor HFCN at 3&12 months<span class="elsevierStyleUnderline">Other outcomes</span>No sig. differences between groups<span class="elsevierStyleUnderline">Adherence</span>1.6 (0.67)<span class="elsevierStyleHsp" style=""></span>h/day; 32% ≥2<span class="elsevierStyleHsp" style=""></span>h/day<span class="elsevierStyleUnderline">Willingness to use</span>77% wished to continue HFCN<span class="elsevierStyleUnderline">Adverse events</span>None reported \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="10" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bräunlich et al., 2015<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">22</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Germany \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Non-randomized, crossover study \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Inclusion</span>- COPD- Body mass index<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span>- Stable hypercapnia (≥50<span class="elsevierStyleHsp" style=""></span>mmHg)- Stable disease (exacerbation-free time of 6 weeks)<span class="elsevierStyleUnderline">Exclusion</span>- Hearth decompensation- Acute illness- Acute respiratory insufficiency \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 patients with COPD66.7 years64% maleFEV<span class="elsevierStyleInf">1</span> 29.7% pred \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HFNC (First)- 20<span class="elsevierStyleHsp" style=""></span>L/min with O<span class="elsevierStyleInf">2</span>- ≥5<span class="elsevierStyleHsp" style=""></span>h/day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NIV (Second)with O<span class="elsevierStyleInf">2</span>≥5<span class="elsevierStyleHsp" style=""></span>h/day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 weeks (6 weeks each arm, no washout) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Primary</span>PaCO<span class="elsevierStyleInf">2</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">PaCO</span><span class="elsevierStyleInf"><span class="elsevierStyleUnderline">2</span></span><span class="elsevierStyleUnderline">mmHg</span>HFNC 45.5 vs NIV 46.4, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0.05Spontaneous breathing 53.7 vs HFNC 45.5, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05Spontaneous breathing 53.7 vs NIV 46.4, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="10" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nagata et al., 2018<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">31</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Japan \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Randomized crossover trial \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Inclusion</span>- ≥20 years- Hypercapnia- GOLD stages 2–4- LTOT ≥16<span class="elsevierStyleHsp" style=""></span>h/day for ≥1 month<span class="elsevierStyleUnderline">Exclusion</span>- Exacerbation within 6 weeks of enrolment- Used nocturnal NIV within 6 weeks of enrolment- Active malignancy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group A (HFNC/LTOT then LTOT)13 patients with COPD73.8 (6.9) years92.3% malesFEV<span class="elsevierStyleInf">1</span> 29.44 (16.82)% predGroup B (LTOT then HFNC/LTOT)16 patients with COPD76.2 (9.3) years88% malesFEV1 29.43 (11.21)% pred \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HFNC+LTOTFlow rate 30–40<span class="elsevierStyleHsp" style=""></span>L/min with O<span class="elsevierStyleInf">2</span>Flow to maintain SpO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>88%If discomfort, minimum flow of 20<span class="elsevierStyleHsp" style=""></span>L/min≥4<span class="elsevierStyleHsp" style=""></span>h/night \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LTOTO<span class="elsevierStyleInf">2</span> 0.25–4<span class="elsevierStyleHsp" style=""></span>L/min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 weeks (6 weeks each arm, no washout) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Primary</span>SGRQ-C<span class="elsevierStyleUnderline">Secondary</span>PaCO2Nocturnal PtcCO2Exacerbations (worsening of baseline respiratory symptoms that required treatment with oral corticosteroids and/or antibiotics)PaO2SpO2EQ-5D-5LmMRCLung functionPhysical activity6MWTAdherenceAdverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">SGRQ-C</span>Total −7.8 (−11.9, −3.7), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.01Symptom −10.8 (−15.3, −6.3), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.01Activity −4.7 (−8.7, −0.6), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.03Impact −8.7 (−15, −2.5), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01<span class="elsevierStyleUnderline">PaCO</span><span class="elsevierStyleInf"><span class="elsevierStyleUnderline">2</span></span>−4.1 (−6.5, −1.7) mmHg, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.01<span class="elsevierStyleUnderline">Nocturnal PtcCO</span><span class="elsevierStyleInf"><span class="elsevierStyleUnderline">2</span></span>−5.1 (−8.4, −1.8) mmHg, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.01<span class="elsevierStyleUnderline">Exacerbations</span>HFCN<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>LTOT 0% vs LTOT 19%<span class="elsevierStyleUnderline">EQ-5D-5L</span>Score 0.05 (−0.01, 0.11), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.08VAS 7.9 (2.9, 12.9), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01<span class="elsevierStyleUnderline">Steps/day</span>−233 (−483, 16), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.07<span class="elsevierStyleUnderline">Other outcomes</span>No sig. differences observed for mMRC, PaO<span class="elsevierStyleInf">2</span>, SpO<span class="elsevierStyleInf">2</span>, Lung function, 6MWT<span class="elsevierStyleUnderline">Adherence HFNC</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleUnderline">+</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleUnderline">LTOT</span>Group A 7.1 (1.5) h/day (flow 29.2 (1.9) L/min)Group B 8.6 (2.9) h/day (flow 30.3 (4.6) L/min)<span class="elsevierStyleUnderline">Adverse events HFCN+LTOT</span>Night sweat (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>4)Nasal discharge (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1)Insomnia (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1)Skin rash (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="10" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Storgaard et al., 2018<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">23</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Denmark \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RCT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Inclusion</span>- COPD with chronic hypoxemic respiratory failure- ≥3 months LTOT<span class="elsevierStyleUnderline">Exclusion</span>- Malignant disease- Terminal nonmalignant disease- Unstable psychiatric disease- Home NIV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HFNC<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>LTOT100 patients with COPD with chronic hypoxemic respiratory failure71.0 (8.2) years44% malesFEV1 29.8 (12.6) % predLTOT100 patients with COPD with chronic hypoxemic respiratory failure70.4 (9.0) years37% malesFEV1 31.8 (12.9) % pred \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HFNC<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>LTOTFlow rate 20<span class="elsevierStyleHsp" style=""></span>L/minO<span class="elsevierStyleInf">2</span> to maintain SpO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>88%8<span class="elsevierStyleHsp" style=""></span>h/day, during sleep \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LTOT1–2<span class="elsevierStyleHsp" style=""></span>L/min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Primary</span>Exacerbations (worsening of dyspnea, cough and sputum production for >2 consecutive days leading to treatment with systemic glucocorticoids or antibiotics)<span class="elsevierStyleUnderline">Secondary</span>PaCO2PaO<span class="elsevierStyleInf">2</span>SaO<span class="elsevierStyleInf">2</span>Lung functionmMRCSGRQ6MWTBorg scaleHospitalizationMortalityAdherenceAdverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Exacerbations/patient/year</span>HFNC<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>LTOT 3.12 vs LTOT 4.95, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001<span class="elsevierStyleUnderline">Hospitalizations/patient/year</span>HFNC<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>LTOT 1.08 vs LTOT 1.22, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.373<span class="elsevierStyleUnderline">mMRC</span>HFNC+LTOT lower mean score (vs LTOT) at 3, 6, 9, 12 months (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001).<span class="elsevierStyleUnderline">SGRQ total</span>HFNC<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>LTOT lower mean score (vs LTOT) at 6 (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.002) & 12 months (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.033)<span class="elsevierStyleUnderline">PaCO</span><span class="elsevierStyleInf"><span class="elsevierStyleUnderline">2</span></span>HFNC<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>LTOT lower mean value (vs LTOT) at 12 months (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.005)<span class="elsevierStyleUnderline">6MWT</span>HFNC<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>LTOT higher mean value at 12 months (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.005)<span class="elsevierStyleUnderline">Other outcomes</span>No differences in hospitalizations, mortality, Borg, lung function, PaO<span class="elsevierStyleInf">2</span>, SaO<span class="elsevierStyleInf">2</span><span class="elsevierStyleUnderline">Adherence HFNC+LTOT</span>86% used 286 days, mean 7<span class="elsevierStyleHsp" style=""></span>h/day<span class="elsevierStyleUnderline">Adverse events</span>None reported \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="10" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bräunlich et al., 2019<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">24</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Germany \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Randomized crossover trial \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Inclusion</span>- COPD patients with chronic respiratory insufficiency- Stable daytime hypercapnia (PaCO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>50<span class="elsevierStyleHsp" style=""></span>mmHg)- ≥18<span class="elsevierStyleHsp" style=""></span>y<span class="elsevierStyleUnderline">Exclusion</span>- Exacerbation in the 4 weeks prior- NIV in the 14 days prior- Body mass index<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">94 patients with COPD65.3 (9.3) years39% malesFEV1 28.5 (10.2)% pred \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HFNC<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>LTOTFlow 20<span class="elsevierStyleHsp" style=""></span>L/minO<span class="elsevierStyleInf">2</span> not changed from baseline6<span class="elsevierStyleHsp" style=""></span>h/day, during sleep \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NIV<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>LTOT6<span class="elsevierStyleHsp" style=""></span>h/day, during sleep \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 weeks \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Primary</span>PaCO<span class="elsevierStyleInf">2</span><span class="elsevierStyleUnderline">Secondary</span>pO<span class="elsevierStyleInf">2</span>SaO<span class="elsevierStyleInf">2</span>Respiratory rateLung function6MWTBorg scaleSRISGRQVAS state of healthAdherenceAdverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">HFNC</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">+</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">LTOT vs NIV</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">+</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">LTOT</span><span class="elsevierStyleUnderline">PaCO</span><span class="elsevierStyleInf"><span class="elsevierStyleUnderline">2</span></span>MD −1.4 (−3.1, 0.4), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.12<span class="elsevierStyleUnderline">Other outcomes</span>No significant differences.<span class="elsevierStyleBold">HFNC</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">+</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">LTOT (pre vs post)</span><span class="elsevierStyleUnderline">PaCO</span><span class="elsevierStyleInf"><span class="elsevierStyleUnderline">2</span></span>MD −2.8 (95%CI −4.6, −1.1), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.002<span class="elsevierStyleUnderline">Respiratory rate</span>MD −1.4 (95%CI −2.9, −0.0), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.046<span class="elsevierStyleUnderline">SRI</span>MD 3.5 (95%CI 1.1, 5.8), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.004 (and in 3 sub-scales Respiratory Complaints, Physical Functioning, Attendant Symptoms and Sleep)<span class="elsevierStyleUnderline">SGRQ total</span>MD −6.2 (95%CI −8.9, −3.5), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001 (and all sub-scales)<span class="elsevierStyleUnderline">VAS state of health</span>MD 1 (95%CI 0.2, 1.8), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.015<span class="elsevierStyleUnderline">Other outcomes</span>No significant differences.<span class="elsevierStyleUnderline">Adherence</span>HFNC<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>LTOT 5.2 (3.3)<span class="elsevierStyleHsp" style=""></span>h/dayNIV<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>LTOT 3.9 (2.5)<span class="elsevierStyleHsp" style=""></span>h/dayDifference 1.6<span class="elsevierStyleHsp" style=""></span>h/day (95%CI 0.9, 2.4), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001<span class="elsevierStyleUnderline">Adverse events</span>Death (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2 HFNC+LTOT; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2 NIV+LTOT)Number of severe adverse events (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>17 HFNC+LTOT, <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>21 NIV+LTOT)Number of adverse events (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>33 HFNC+LTOT, <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>55 NIV+LTOT) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="10" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Weinreich, 2019<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">32</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Denmark \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Post hoc analysis of a RCT (Storgaard et al., 2018) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Inclusion</span>- COPD with chronic hypoxemic respiratory failure- ≥3 months LTOT<span class="elsevierStyleUnderline">Exclusion</span>- Malignant disease- Terminal nonmalignant disease- Unstable psychiatric disease- Home NIV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HFNC+LTOT100 patients with COPD with chronic hypoxemic respiratory failure71.0 (8.2) years44% malesFEV<span class="elsevierStyleInf">1</span> 29.8 (12.6) % predDivided in two groups:Group 0–1 exacerbation in 1year prior32 patients74 (9) years50% malesFEV<span class="elsevierStyleInf">1</span> 31.1% predGroup ≥2 exacerbations in 1year prior68 patients70 (7.6) years41% malesFEV<span class="elsevierStyleInf">1</span> 29.0 (12.2) % pred \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HFNC+LTOTFlow rate 20<span class="elsevierStyleHsp" style=""></span>L/minO<span class="elsevierStyleInf">2</span> to maintain SpO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>88%8<span class="elsevierStyleHsp" style=""></span>h/day, during sleep \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LTOT1–2<span class="elsevierStyleHsp" style=""></span>L/min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ExacerbationsHospitalizations \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Exacerbations</span>Group 0–1 –increase in number (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01)Group ≥2 – reduction in number (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.03)Group differences (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.05)<span class="elsevierStyleUnderline">Hospitalizations</span>Group 0–1 –increase in number (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01)Group ≥2 – reduction in number (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.002)Group differences pre (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.004) and during study (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001)<span class="elsevierStyleUnderline">Hospitalization days</span>Group 0–1 –increase in days (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.08)Group ≥2 – reduction in days (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.025)Group differences pre (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.003) and during study (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="10" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Storgaard et al., 2020<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">34</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Denmark \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Post hoc analysis of a RCT (Storgaard et al., 2018) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Inclusion</span>- COPD with chronic hypoxemic respiratory failure- ≥3 months LTOT- Persistent hypercapnic failure (PaCO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>6<span class="elsevierStyleHsp" style=""></span>kPa)<span class="elsevierStyleUnderline">Exclusion</span>- Malignant disease- Terminal nonmalignant disease- Unstable psychiatric disease- Home NIV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HFNC+LTOT31 patients with COPD67 years32% malesFEV<span class="elsevierStyleInf">1</span> 24.5 (8.8) % predLTOT43 patients with COPD68 years30% malesFEV<span class="elsevierStyleInf">1</span> 26.1 (6.2)% pred \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HFNC+LTOTFlow rate 20<span class="elsevierStyleHsp" style=""></span>L/minO2 to maintain SpO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>88%8<span class="elsevierStyleHsp" style=""></span>h/day, during sleep \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LTOT1–2<span class="elsevierStyleHsp" style=""></span>L/min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PaCO<span class="elsevierStyleInf">2</span>PaO<span class="elsevierStyleInf">2</span>ExacerbationsHospitalizations \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">PaCO</span><span class="elsevierStyleInf"><span class="elsevierStyleUnderline">2</span></span>HFNC+LTOT 1.3% decrease (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.624)LTOT 7% increase (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.003)<span class="elsevierStyleUnderline">Exacerbations rate/year</span>HFNC+LTOT decreased 0.15 (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.661)LTOT increased 2.2 (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001)<span class="elsevierStyleUnderline">Hospitalizations/year</span>HFNC+LTOT decreased 0.67 (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.013)LTOT increased +0.3 (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.180)<span class="elsevierStyleUnderline">Other outcomes</span>No sig. differences in PaO<span class="elsevierStyleInf">2</span> between groups \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="10" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Good et al., 2021<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">33</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">New Zealand \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Post hoc analysis of a RCT (Rea et al., 2010) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Inclusion</span>- Bronchiectasis confirmed by high-resolution computed tomography- ≥2 exacerbations in theprevious year- >5<span class="elsevierStyleHsp" style=""></span>ml daily sputum- Stable for ≥4 weeks<span class="elsevierStyleUnderline">Exclusion</span>- bronchiectasis associated with cystic fibrosis or hypogammaglobulinaemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HFNC26 patients with stable bronchiectasis63 (11.4) years42% maleFEV<span class="elsevierStyleInf">1</span> 56.5 (20.2)% predControl19 patients with stable bronchiectasis65 (13.9) years37% maleFEV<span class="elsevierStyleInf">1</span> 42.42 (15.2)% pred \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HFNC- Flow 20–25<span class="elsevierStyleHsp" style=""></span>L/min, 37°- O<span class="elsevierStyleInf">2</span> for patients on LTOT- ≥2<span class="elsevierStyleHsp" style=""></span>h/day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Usual care \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PrimaryRate of exacerbations (worseningof ≥2 respiratory symptoms for ≥2 days that required antibiotics or oral prednisone)SecondaryTime to 1<span class="elsevierStyleHsp" style=""></span>st exacerbationN of exacerbated daysSGRQLung function6MWT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Exacerbations/patient/year</span>HFNC 2.39 vs Control 3.48, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.034<span class="elsevierStyleUnderline">Annual exacerbation days</span>HFNC 10.3 vs Control 29.9, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.056<span class="elsevierStyleUnderline">Days to 1st exacerbation</span>HFNC 84 vs Control 54, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.316<span class="elsevierStyleUnderline">Patients free of exacerbations</span>HFNC 20% vs Control 8.3%, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.043<span class="elsevierStyleUnderline">SGRQ changes</span>Total HFCN −12.3 vs Control −1.2, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.028Impact HFCN −14.7 vs Control −1.6, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.018<span class="elsevierStyleUnderline">Other outcomes</span>No differences between groups for FEV<span class="elsevierStyleInf">1</span>, FVC, 6MWT, SGRQ symptoms/activity \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="10" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Crimi et al., 2022<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">25</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Italy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Retrospective case-control study \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Inclusion</span>- A diagnosis of radiologically and clinically significant bronchiectasis- Chronic cough, sputum production most days of the week and/or frequent respiratory infections- ≥1 severe exacerbation 1year prior- Optimized treatment<span class="elsevierStyleUnderline">Exclusion</span>- Cystic fibrosis- Traction bronchiectasis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HFNC20 patients with bronchiectasis70.7 (9.4) years30% malesFEV1 58.8 (18)% predControl20 patients with bronchiectasis68.6 (8.9) years30% malesFEV1 63.2 (17.7)% pred \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HFNCFlow 25–40<span class="elsevierStyleHsp" style=""></span>L/min34<span class="elsevierStyleHsp" style=""></span>°C or 37<span class="elsevierStyleHsp" style=""></span>°C (according to tolerance)O<span class="elsevierStyleInf">2</span> adjusted to maintain SpO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>≥92%6<span class="elsevierStyleHsp" style=""></span>h/day, during sleep \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Usual care \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Primary</span>Rate of exacerbations (physician determining a change in treatment in the presence of deterioration in ≥3Symptoms for ≥48<span class="elsevierStyleHsp" style=""></span>h)<span class="elsevierStyleUnderline">Secondary</span>HospitalizationsmMRCSputum colorDifficulty of mucus expectoration (VAS 1–10)SGRQLung functionSpO<span class="elsevierStyleInf">2</span>AdherenceAdverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Exacerbations</span>MD (HFNC- Control) −1.9 (95%CI −2.8, −0.9), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001<span class="elsevierStyleUnderline">Hospitalizations</span>MD −0.7 (95%CI −1.1, −0.3), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001<span class="elsevierStyleUnderline">Difficulty of mucus expectoration</span>MD −2.2 (95%CI −3.9,−0.5), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.012<span class="elsevierStyleUnderline">SGRQ total</span>MD −10.4 (95%CI −20.2,−0.6), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.039FEV<span class="elsevierStyleInf">1</span>, %predMD 6.1 (95%CI 1,11.3), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.022FVC, %predMD 4.6 (95%CI 0.8,8.3), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.019<span class="elsevierStyleUnderline">Other outcomes</span>No significant differences in mMRC and SpO<span class="elsevierStyleInf">2</span><span class="elsevierStyleUnderline">Adherence</span>6.3 (1.8) h/day<span class="elsevierStyleUnderline">Adverse events</span>No serious eventsPoor tolerance (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1)Personal reasons (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="10" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nagata et al., 2022<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">29</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Japan \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RCT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Inclusion</span>- ≥40 years- Daytime hypercapnia (PaCO<span class="elsevierStyleInf">2</span>><span class="elsevierStyleHsp" style=""></span>45<span class="elsevierStyleHsp" style=""></span>mmHg and pH><span class="elsevierStyleHsp" style=""></span>7.35)- GOLD stages 2–4- LTOT for ≥16<span class="elsevierStyleHsp" style=""></span>h/day for ≥ 1 month- ≥1 moderate/severe exacerbation 1year prior- Stable and free from a exacerbation 4 weeks prior<span class="elsevierStyleUnderline">Exclusion</span>- NIV 4 weeks prior- HFNC 1 year prior- History/suspicion of obstructive sleep apnea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HFNC+LTOT49 patients with COPD72.9 (7.4) years90% malesFEV1 25.6 (8.4)% predLTOT50 patients with COPD75.2 (6.7) years88% malesFEV<span class="elsevierStyleInf">1</span> 27.1 (8.9)% pred \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HFNC+LTOTFlow 30–40<span class="elsevierStyleHsp" style=""></span>L/minIf discomfort, minimum flow of 20<span class="elsevierStyleHsp" style=""></span>L/min37<span class="elsevierStyleHsp" style=""></span>°C (if discomfort 34<span class="elsevierStyleHsp" style=""></span>°C or 31<span class="elsevierStyleHsp" style=""></span>°C)O<span class="elsevierStyleInf">2</span> adjusted to maintain SpO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>88%>4<span class="elsevierStyleHsp" style=""></span>h/day during sleep \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LTOTLTOT alone as prescribed \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52 weeks \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Primary</span>Rate of moderate/severe exacerbations<span class="elsevierStyleUnderline">Secondary</span>Time to the 1<span class="elsevierStyleHsp" style=""></span>st exacerbationDeathmMRCSGRQPittsburgh Sleep Quality Index6MWTLung functionSpO<span class="elsevierStyleInf">2</span>Physiological parametersAdherenceAdverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Rate of moderate/severe exacerbations</span>LTOT (ref HFCN+LTOT) Adjusted mean count 2.85 (95%CI 1.48–5.47), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.002<span class="elsevierStyleUnderline">Time to 1st moderate/severe exacerbation</span>LTOT vs HFCN+LTOT, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.032<span class="elsevierStyleUnderline">SpO</span><span class="elsevierStyleInf"><span class="elsevierStyleUnderline">2</span></span>HFCN+LTOT 1.01 (0.33)% vs LTOT −0.20 (0.32)%, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.010<span class="elsevierStyleUnderline">Other outcomes</span>No significant differences.<span class="elsevierStyleUnderline">Adherence HFNC/LTOT</span>7.3 (3)<span class="elsevierStyleHsp" style=""></span>h/day (flow 28.5 (4.6) L/min)<span class="elsevierStyleUnderline">Adverse events</span>Infections and infestations: HFNC/LTOT 26.5% vs LTOT 32%Respiratory, thoracic, and mediastinal disorders: HFNC/LTOT 38.8% vs LTOT 42% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="10" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Weinreich et al., 2022<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">27</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Denmark \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Crossover study \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Inclusion criteria</span>- ILD diagnosis- prescribed ambulatory oxygen treatment or LTOT<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>12 months prior- Age ><span class="elsevierStyleHsp" style=""></span>18 years<span class="elsevierStyleUnderline">Exclusion</span> criteria- Life expectancy<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>3 months- Pneumonia/exacerbation of ILD<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>3 months prior \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 patients with ILD69 (5) years56% malesFEV1 69.9 (20)% pred \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HFNCFlow<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>L/min37<span class="elsevierStyleHsp" style=""></span>°CO<span class="elsevierStyleInf">2</span> as prescribed for LTOT/ambulatory oxygen treatment8<span class="elsevierStyleHsp" style=""></span>h/day, preferably during sleep \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No HFNC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 weeks \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6MWT (distance and time to SpO<span class="elsevierStyleInf">2</span> recovery)Lung functionPaO<span class="elsevierStyleInf">2</span>PaCO<span class="elsevierStyleInf">2</span>mMRCSGRQRichards-Campbell sleep questionnaireAdherenceAdverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">6MWT distance</span>393 (42) m vs after HFNC 441 (22) m, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.049<span class="elsevierStyleUnderline">Time to SpO</span><span class="elsevierStyleInf"><span class="elsevierStyleUnderline">2</span></span><span class="elsevierStyleUnderline">recovery</span>3.4 (3.0) min vs after HFNC 2.2 (1.1) min, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001<span class="elsevierStyleUnderline">Other outcomes</span>No significant differences.Adjusting for hours of HFNC use, mMRC (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.04) and minimum oxygen saturation during 6MWT (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01) improved.<span class="elsevierStyleUnderline">Adherence</span>6.5 (1) h/day<span class="elsevierStyleUnderline">Adverse events</span>Mild rhinorrhea (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>5)Bothered by the device heat (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>3)Exacerbation (=1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="10" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Simioli et al., 2023<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">26</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Italy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Non-randomized crossover study \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Inclusion criteria</span>- ≥18 years- Radiological evidence of bronchiectasis on HRCT- ≥2 exacerbations/hospitalizations- Smoke cessation ><span class="elsevierStyleHsp" style=""></span>3 months- Ability to use electronic devices<span class="elsevierStyleUnderline">Exclusion criteria</span>- Exacerbation 7 days prior- pO<span class="elsevierStyleInf">2</span> <<span class="elsevierStyleHsp" style=""></span>60<span class="elsevierStyleHsp" style=""></span>mmHg- LTOT ><span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>L/min- Chronic use of NIV(…) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">78 patients with bronchiectasisM 70 (IQR 60–76) years46.2% malesFEV<span class="elsevierStyleInf">1</span> 2.39 (0.87)L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HFNC (Second)Flow 35–60<span class="elsevierStyleHsp" style=""></span>L/min31–37<span class="elsevierStyleHsp" style=""></span>°CFiO2 0.21O<span class="elsevierStyleInf">2</span> not added2 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Usual care(First)12 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Primary</span>Exacerbations (warrant additional treatment (e.g., antibiotic, systemic corticosteroid, bronchodilators)<span class="elsevierStyleUnderline">Secondary</span>HospitalizationsLung functionmMRCAdherence (≥2<span class="elsevierStyleHsp" style=""></span>h/day, ≥4 days/week)Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Exacerbations/year</span>2.81 (2.15) vs 2 months 2.36 (0.69), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.982.81 (2.15) vs 2 years 0.45 (0.66), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001<span class="elsevierStyleUnderline">Hospitalizations/year</span>1.65 (2.10) vs 2 years 0.56 (0.98), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001<span class="elsevierStyleUnderline">Lung function</span>FEV<span class="elsevierStyleInf">1</span> 2.39 (0.87)L vs 2 years 2.55 (0.82)L, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.45<span class="elsevierStyleUnderline">FVC</span> 2.73 (0.88)L vs 2 years 2.84 (0.90)L, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.66<span class="elsevierStyleUnderline">mMRC</span>2.4 (0.81) vs 2 months 0.97 (0.97), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.0012.4 (0.81) vs 2 years 0.60 (0.78), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001<span class="elsevierStyleUnderline">Adherence</span>100%, 2 months 100%, 2 years 95%<span class="elsevierStyleUnderline">Adverse events</span>Minor epistaxis (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1)Interface discomfort (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1),Dysphagia (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="10" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Weinreich et al., 2023<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">28</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Denmark \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Retrospective study \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Inclusion criteria</span>- Patients with COPD- Treated with LTOT plus either long-term HFNC or NIV, in whom a 2nd add-on (NIV or HFNC) was initiated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HFNC+LTOT baseline17 patients with COPD66.8 (7.3) years35% malesFEV<span class="elsevierStyleInf">1</span> 27.1 (8.2)% predNIV+LTOT baseline16 patients with COPD68.3 (7.5) years43.8% malesFEV1 30.5 (8.8)% pred \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HFNC+LTOT baselinePrescribed according to the Danish Respiratory Society guidelines (or physician’ discretion before 2019)12 patient started also NIV (night) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NIV+LTOT baselinePrescribed according to the Danish Respiratory Society guidelines13 patients started also HFNC(day) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">∼29 months (908 (586) days) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hospitalizations \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Hospitalizations</span>HFNC+LTOT 2.5 (0.4) vs 12 months 1.5 (0.4), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.022NIV+LTOT 2.9 (0.5) vs 12 months 1.6 (0.4), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.014 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3612280.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Details of the included articles.</p>" ] ] 2 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.doc" "ficheroTamanyo" => 3988480 ] ] 3 => array:5 [ "identificador" => "upi0010" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc2.doc" "ficheroTamanyo" => 30208 ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:61 [ 0 => 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