Correspondence
Is chronic obstructive pulmonary disease a protective factor in SARS-CoV-2 infection? The importance of bronchodilator treatment
¿Es la enfermedad pulmonar obstructiva crónica un factor protector en la infección por SARS-CoV-2? La importancia del tratamiento broncodilatador
R. Boixedaa,b,c,
, L. Campinsd, J. Juanolab,e,f, L. Forcea,f, on behalf of the COCOHMAT group 1
Corresponding author
a Servicio de Medicina Interna, Hospital de Mataró, Consorci Sanitari del Maresme (CSDM), Mataró, Barcelona, Spain
b Grup d’Estudi al Maresme de la Pneumònia Adquirida en la Comunitat i la MPOC (GEMP@C), Mataró, Barcelona, Spain
c Universidad de Barcelona, CIBERES Barcelona, Barcelona, Spain
d Servicio de Farmacia, Hospital de Mataró, CSDM, Mataró, Barcelona, Spain
e Servicio de Neumología, Hospital de Mataró, CSDM, Mataró, Barcelona, Spain
f Escola de Ciències de la Salut, Tecnocampus, Universitat Pompeu Fabra, Barcelona, Spain
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La importancia del tratamiento broncodilatador" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Globally, viruses play an important role in exacerbations of chronic obstructive pulmonary disease (COPD). In a systematic review of infections in patients with COPD that required hospital admission, it was observed that the rhinovirus, respiratory syncytial virus (RSV), and influenza virus were the most prevalent agents, followed by parainfluenza and coronavirus. Coronavirus is the most frequent upper respiratory tract infection and is predominant during the winter months.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In a study conducted in Spain, 26% of patients admitted during the flu season presented with COPD as a comorbidity.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Other authors have reported a somewhat lower prevalence of COPD in patients with the flu (17.3%) and an even lower prevalence of COPD in patients with RSV infection (7.6%).<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> There are also studies which have evaluated the presence of COPD as a comorbidity in other coronavirus infections such as SARS, with a rate of 6%,<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> and MERS, with a rate of 13%.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In regard to the current SARS-CoV-2 pandemic, it was initially considered that people with chronic lung diseases could be more prone to presenting with symptoms of the infection or to developing a more severe infection. However, published case series show a low prevalence of patients with COPD: 6.6% in the United States of America,<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> 3% in Italy,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> and just 1.4% in China.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">This low prevalence could give rise to different interpretations. First, the strict lockdown imposed by public health authorities could explain that these patients, who are supposedly more vulnerable to SARS-CoV-2 infection, had closely followed social distancing protocols, thus decreasing the risk of contact.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Second, there could be a protective effect that is not well established in the physiopathology of chronic respiratory disease, with a different immune response that could prevent infection in these patients or condition milder symptoms. One piece of data in favor of this protection against infection can be concluded from the study by Mehta et al.,<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> which analyzes factors associated with a positive result on a SARS-CoV-2 diagnostic test in a sample of 184,772 people. Of the total number of tests, 1735 (9.4%) were positive whereas in patients with COPD, only 114 (6.4%) were positive (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span> .001). Therefore, it seems that COPD as a comorbidity is associated with a lower probability of having COVID-19.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Third, it has been hypothesized that baseline inhaled treatments, such as inhaled corticosteroids and bronchodilators, could have a protective effect against SARS-CoV-2 infection. <span class="elsevierStyleItalic">In vitro</span> studies on inhaled corticosteroids (budesonide), either alone or in combination with other bronchodilators (glycopyrronium bromide and formoterol), have demonstrated a suppression of HCoV-229E coronavirus replication.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Likewise, another study on inhaled corticosteroids that included just 3 patients, conducted in Japan and without a control group, observed a lower requirement for ventilatory support.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> On this matter, a systematic review was recently published on the possible protective effect of inhaled corticosteroids; it was unable to establish either a beneficial or detrimental effect of this treatment.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Similarly, in an Italian study on a cohort of patients with COVID-19, patients with SARS-CoV-2 infection were compared to the general population. No influence on progress related to either short- or long-term inhaled corticosteroids or beta-adrenergic agonists was noted.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Tiotropium bromide is one of the main treatments for COPD and is usually used in approximately 30% of patients treated in primary care.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Recent studies have demonstrated how tiotropium reduces neutrophils and macrophages as well as IL-6 and gamma interferon levels in the airways of rats exposed to tobacco smoke and infected with the A/PR/8/34 (H1N1) influenza virus. The effect was greater than what was observed with fluticasone and roflumilast.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> This potential anti-inflammatory effect with cytokine inhibition in animal models could explain a greater protective effect of tiotropium versus other inhaled therapies in SARS-CoV-2 infection.</p><p id="par0045" class="elsevierStylePara elsevierViewall">We have analyzed the prevalence of COPD in patients treated for COVID-19 in our center, specifically evaluating their baseline treatment with inhalers as a potential protective factor against SARS-CoV-2 infection.</p><p id="par0050" class="elsevierStylePara elsevierViewall">A retrospective, observational study was carried out in the Mataró Hospital which identified patients hospitalized with a clinical and/or microbiological diagnosis of SARS-CoV-2 from March 10 to April 22, 2020. A diagnosis of COPD was established when the physician had recorded it on the medical record or when a compatible spirometry was available. Treatments with inhaled corticosteroids and anticholinergics were also recorded.</p><p id="par0055" class="elsevierStylePara elsevierViewall">During the study period, 487 patients were identified. Of them, 78 (16%) had a clinical diagnosis and 409 (84%) had a microbiological diagnosis of SARS-CoV-2 infection. Of the patients identified, 62.2% were men. The mean age was 64.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>15.1 years and the overall mortality rate was 20.5%. Of all patients, 25 had a diagnosis of COPD (5.1%), 17 of which (68%) had spirometric confirmation. Within the group of patients with COPD, the mean age was 72.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>9.1 years and they had a greater mortality rate of 44%.</p><p id="par0060" class="elsevierStylePara elsevierViewall">We compared the baseline treatment of patients with COPD in our COVID-19 cohort with other published series of patients with hospital admission due to COPD exacerbation related to other respiratory pathogens or those in stable clinical condition. We did not note any differences in the use of inhaled corticosteroids between both groups. However, the use of tiotropium was significantly lower in patients with COPD who had been hospitalized for COVID-19 in relation to other cohorts of patients with stable COPD and without SARS-CoV-2 infection and controlled in primary care (12% vs. 29.5% and 31.7%, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span> .03) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">The analysis of our cohort of patients with SARS-CoV-2 confirms a low prevalence of patients with COPD (5.1%). These patients were older (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span> .02), had greater mortality (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span> .03), and there was a low percentage of patients treated with tiotropium (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span> .034).</p><p id="par0070" class="elsevierStylePara elsevierViewall">Given the discordance in the available information, large studies are needed that evaluate the presence of COPD and baseline treatments as possible protective factors against SARS-CoV-2 infection, with special attention paid to treatment with tiotropium, which appeared to have a protective effect in our study.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Likewise, it seems necessary to evaluate different prognostic factors that allow for confirming whether presence of COPD is associated with a worse disease prognosis or if there are other confounding factors that explain this higher mortality, such as age or the establishment of therapeutic limitations related to the comorbidity itself or the healthcare resources available in the context of a pandemic.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-07-09" "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as: Boixeda R, Campins L, Juanola J, Force L. ¿Es la enfermedad pulmonar obstructiva crónica un factor protector en la infección por SARS-CoV-2? La importancia del tratamiento broncodilatador. Rev Clin Esp. 2020;220:526–529.</p>" ] 1 => array:3 [ "etiqueta" => "1" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">In Appendix A the remaining members of the COCOHMAT (COhort COvid of the Hospital de MATaró) group are listed.</p>" "identificador" => "fn0005" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0080" class="elsevierStylePara elsevierViewall">ABS Cirera-Molins (Joaquim Oyon, Mariona Ferrer, Antonia Llinares, Astrid Arkesteijn, Amaia Erraiz, Tatiana Rejon, Evora Igual, Mireia Carmona, Axel Muñoz, Patricia Prado, Andrea Ventura), Cardiology Department (Berta Ferreiro), Endocrinology Department (Elena Guanyabens), Pharmacy Department (Laia Pérez, Azhara Sanchez, Javier Delgado, Marc Bitlloch), Geriatrics Department (Nicolás Morón, Franz Sancho, Adrian Oller, Cristina Borrellas), Hematology Department (Esther Plensa), Internal Medicine Department (Raquel Arànega, Carlos Lopera, Laia Arbonés, Javier Fernández, Ainhoa Rex, Marta Parra, Aleix Serrallonga, María Fernanda Solano, María Larrousse, Montserrat Mauri, Concepció Falgà, Sandra Bacca, Paula Fernández, Laura Pacho, Miquel Martin), Pulmonology Department (Alejandro Robles, Xavier Vilà, Laura Ovejero, Pilar Ortega), Oncology Department (Susana Martínez, Irene Ortiz), Pediatrics Department (Anna Vidal, Pamela Calderón, Julio Baena, Ingrid Badia), Rehabilitation Department (Adrián Ruiz).</p>" "etiqueta" => "Appendix A" "titulo" => "Members of the COCOHMAT (COhorte COvid del Hospital de MATaró) Group" "identificador" => "sec0005" ] ] ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0085" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The data are shown in absolute values (percentage).</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">AC: anticholinergics; IC: inhaled corticosteroids; COPD: chronic obstructive pulmonary disease; LTAC: long-term anticholinergics.</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"> \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">Patients \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">IC \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">AC \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">LTAC \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">Tiotropium \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"><span class="elsevierStyleItalic">Severe SARS-CoV-2 infection</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"> \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"> \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"> \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"> \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"> \t\t\t\t\t\t\n \t\t\t\t</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">Boixeda et al. (Mataró Hospital) \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">25 \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">16 (64) \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">17 (68) \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 (44) \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">3 (12)<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</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"><span class="elsevierStyleItalic">Severe COPD exacerbation</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"> \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"> \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"> \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"> \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"> \t\t\t\t\t\t\n \t\t\t\t</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">Casas-Mendez et al.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</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">465 \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">293 (63) \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">363 (77.5) \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">158 (33.9) \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">– \t\t\t\t\t\t\n \t\t\t\t</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"><span class="elsevierStyleItalic">Stable COPD</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"> \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"> \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"> \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"> \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"> \t\t\t\t\t\t\n \t\t\t\t</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">Morros et al.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</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">3837 \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">2224 (57.9) \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">1763 (45) \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">– \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">1134 (29.5)<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</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">De Oliveira et al.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</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">180 \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">167 (92.8) \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">– \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">– \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">57 (31.7)<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2531994.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="npar0005"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span> .03.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Treatment with inhaled corticosteroids and anticholinergics in patients with COPD in series of patients hospitalized due to SARS-CoV-2, severe exacerbation of COPD, and patients in the stable phase (primary care).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The relevance of respiratory viral infections in the exacerbations of chronic obstructive pulmonary disease- A systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "W.A.R. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 1 | 0 | 1 |
| 2024 October | 24 | 0 | 24 |
| 2024 September | 20 | 0 | 20 |
| 2024 August | 27 | 0 | 27 |
| 2024 July | 20 | 5 | 25 |
| 2024 June | 12 | 1 | 13 |
| 2024 May | 17 | 0 | 17 |
| 2024 April | 13 | 0 | 13 |
| 2024 March | 12 | 0 | 12 |
| 2024 February | 5 | 0 | 5 |
| 2024 January | 15 | 0 | 15 |
| 2023 December | 16 | 0 | 16 |
| 2023 November | 17 | 0 | 17 |
| 2023 October | 19 | 0 | 19 |
| 2023 September | 16 | 0 | 16 |
| 2023 August | 15 | 2 | 17 |
| 2023 July | 17 | 1 | 18 |
| 2023 June | 16 | 0 | 16 |
| 2023 May | 17 | 3 | 20 |
| 2023 April | 12 | 1 | 13 |
| 2023 March | 21 | 6 | 27 |
| 2023 February | 8 | 4 | 12 |
| 2023 January | 14 | 9 | 23 |
| 2022 December | 21 | 4 | 25 |
| 2022 November | 28 | 10 | 38 |
| 2022 October | 24 | 5 | 29 |
| 2022 September | 13 | 7 | 20 |
| 2022 August | 15 | 7 | 22 |
| 2022 July | 18 | 8 | 26 |
| 2022 June | 16 | 7 | 23 |
| 2022 May | 22 | 3 | 25 |
| 2022 April | 25 | 6 | 31 |
| 2022 March | 27 | 7 | 34 |
| 2022 February | 15 | 9 | 24 |
| 2022 January | 24 | 5 | 29 |
| 2021 December | 11 | 5 | 16 |
| 2021 November | 5 | 2 | 7 |
| 2021 October | 1 | 7 | 8 |
| 2021 September | 3 | 4 | 7 |
| 2021 August | 1 | 3 | 4 |
| 2021 July | 2 | 2 | 4 |
| 2021 June | 0 | 9 | 9 |
| 2021 May | 1 | 3 | 4 |
| 2021 April | 5 | 14 | 19 |
| 2021 March | 7 | 7 | 14 |
| 2021 February | 11 | 6 | 17 |
| 2021 January | 19 | 9 | 28 |
| 2020 December | 41 | 11 | 52 |
| 2020 November | 33 | 22 | 55 |
| 2020 October | 83 | 18 | 101 |
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