Research letter
Understanding symptoms variability in outpatients with AECOPD
Ana Oliveiraa,b,c, Alda Marquesb,c,
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amarques@ua.pt
Corresponding author. Senior Lecturer, Lab 3R – Respiratory Research and Rehabilitation Laboratory, School of Health Sciences, University of Aveiro (ESSUA), Agras do Crasto - Campus Universitário de Santiago, Edifício 30, 3810-193 Aveiro, Portugal
Corresponding author. Senior Lecturer, Lab 3R – Respiratory Research and Rehabilitation Laboratory, School of Health Sciences, University of Aveiro (ESSUA), Agras do Crasto - Campus Universitário de Santiago, Edifício 30, 3810-193 Aveiro, Portugal
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Senior Lecturer, Lab 3R – Respiratory Research and Rehabilitation Laboratory, School of Health Sciences, University of Aveiro (ESSUA), Agras do Crasto - Campus Universitário de Santiago, Edifício 30, 3810-193 Aveiro, Portugal" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1652 "Ancho" => 2083 "Tamanyo" => 126072 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Correlations between changes from T1 to T3 in A) modified Borg scale – dyspnoea (MBS.d) and forced expiratory volume in 1 second (FEV1); B) modified Borg scale – fatigue (MBS.f) and FEV1; C) modified British Medical Research Council questionnaire (mMRC) and quadriceps muscle strength (QMS); D) Cough, assessed with the numerical scale, and QMS.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Symptoms are the cornerstone for diagnosing acute exacerbations of chronic obstructive pulmonary disease (AECOPD), however little information is available on their variability during these events and on their relationships with objective clinical measures. This study explored changes in patients’ symptoms and their relationships with objective clinical measures during AECOPD.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Methods</span><p id="par0010" class="elsevierStylePara elsevierViewall">A longitudinal observational study was conducted with thirty-six outpatients with AECOPD (24 males; 68.4±9.9 years; forced expiratory volume in one second (FEV<span class="elsevierStyleInf">1</span>) 50.7±20.4%predicted) recruited from the urgent care of a Central hospital. Patients attended to 4 assessments: until 48<span class="elsevierStyleHsp" style=""></span>hours of the urgent care visit (T1), 8 days (T2), 15 days (T3) and 45 days (T4) after the hospital visit. Patients’ prescriptions included only pharmacological treatment and consisted in antibiotics (n=16; 44.4%), beta-adrenergic agonists (n=2; 5.6%), cholinergic antagonists (n=3; 8.3%), associations of bronchodilators with cholinergic antagonists (n=7; 19.4%), anti-inflammatory drugs (n=1; 2.8%), xanthines (n=1; 2.8%) and expectorants (n=6; 16.7%).</p><p id="par0015" class="elsevierStylePara elsevierViewall">Activities-related dyspnoea (modified British Medical Research Council questionnaire – mMRC), dyspnoea and fatigue at rest (modified Borg Scale – MBS), cough, sputum and wheezing symptoms (11-point numerical scale) were registered in each assessment. FEV<span class="elsevierStyleInf">1</span>, using a portable spirometer, and quadriceps muscle strength (QMS), using a handheld dynamometer, were also collected.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The number of participants presenting symptoms, the severity of symptoms, FEV<span class="elsevierStyleInf">1</span> and QMS were compared among T1, T2, T3 and T4 using the Cochran or Friedman tests, respectively. Changes in symptoms were correlated with changes in FEV<span class="elsevierStyleInf">1</span> and QMS using the Spearman's correlation coefficient.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Results</span><p id="par0025" class="elsevierStylePara elsevierViewall">Dyspnoea and cough were the most reported symptoms at the onset of AECOPD. The number of patients with dyspnoea at rest, assessed with the MBS (MBS>0), decreased significantly from T1 to T4 (22 vs. 16 vs. 15 vs. 13; p=0.040) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). No significant differences were observed in the number of patients presenting activities-related dyspnoea, fatigue at rest, cough, sputum and wheezing symptoms. During the time course of the AECOPD, participants presented significantly more i) activities-related dyspnoea in T1, than in T3 (p=0.001) and T4 (p=0.028); ii) dyspnoea at rest in T1 than in T4 (p=0.016); iii) cough in T1 than in T2 (p=0.001), T3 (p<0.001) and T4 (p<0.001) and iii) wheezing in T1 than in T4 (p=0.022) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Changes occurring between T1 and T3 in mMRC correlated inversely with changes in QMS (r<span class="elsevierStyleInf">s</span>=-0.41; p=0.013) whilst changes in cough (r<span class="elsevierStyleInf">s</span>=0.47; p=0.021) correlated positively with QMS. Changes in MBS – dyspnoea (r<span class="elsevierStyleInf">s</span>=-0.47; p=0.004) and fatigue (r<span class="elsevierStyleInf">s</span>=-0.34; p=0.046) correlated inversely with changes in FEV<span class="elsevierStyleInf">1</span> (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). No further correlations were found.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Discussion</span><p id="par0035" class="elsevierStylePara elsevierViewall">Dyspnoea and cough were the most reported symptoms at the onset of AECOPD.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> Dyspnoea was the most prevalent symptom. Its time-recovery matched previous reports (i.e, 6 to 30 days).<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> Cough was the symptom reported with the highest severity and the first to improve after treatment initiation. In COPD cough is the most common symptom for which individuals seek medical attention and is a cardinal symptom in upper tract infections,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> one of the most common causes of AECOPD. Our results support the need of increasing awareness about cough severity and behaviour. Recognising the cough pattern may aid to guide patients’ monitoring and interventions, reduce need for hospitalisation, recurrence of AECOPD and, consequently, costs and morbidity related with these events.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Differences in wheezing were only detected 45 days after the onset of the exacerbation, which differs from previous reports using computerised respiratory sound analysis (i.e., improvements 15 days after the AECOPD).<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Lack of agreement between subjective and objective measures have already been reported for other outcomes, such as cough,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> and highlights the need for incorporating both patient-reported and clinical outcome measures in the assessment of patients with AECOPD.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Similar to other studies, associations between improvements in dyspnoea and higher expiratory flow rates were found, possibly due to the inflammatory aetiology of the acute exacerbation itself (i.e., reduction in inflammation during recovery from the AECOPD may influence the reduction of dyspnoea and increase expiratory flow rates) and/or reductions in lung hyperinflation.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Nevertheless, both inflammation and hyperinflation were not directly studied in the present research and thus interpretations should be made carefully. A relationship between dyspnoea and QMS was also found, as previously reported in stable patients with COPD, due to the “downward disease spiral” of increased dyspnoea, decreased physical activity and deconditioning of locomotor muscles.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> During AECOPD, this downward spiral may be even more prominent as patients severely decrease their activities.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The positive correlation found between changes in cough severity and QMS was unexpected. Whilst cough severity showed significant improvements at day 15 of the AECOPD, QMS remained statistically unchanged during the same period, with 36% of the patients exhibiting decreases in their QMS. Similar results have been found in hospitalised patients, where QMS decreased during the first 8 days of hospitalisation for AECOPD and only recovered at day 90.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Thus, although both outcomes improved during an AECOPD, their timing of improvement differs, which may explain the positive correlation found between changes at T3-T1 between these two outcomes. Studies describing the pattern of QMS recovery in outpatients with AECOPD are needed to confirm these results and aid developing timely and personalised interventions.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Despite the novel findings in symptoms behaviour during AECOPD, this study has some limitations that need to be acknowledged. Treatment of exacerbations was not standardised, but rather prescribed according to the physician best judgment. Although the effects of therapies were not of interest in this study, it must be acknowledged that different combination of treatments might influence the recovery times and outcomes of individual patients. Characterisation of symptoms lack other important features, such as sputum purulence. These data can contribute to infer about the nature of the AECOPD (i.e., infective - viral and/or bacterial - or non-infective) and about the suitability of treatments prescribed. It is thus recommended to add sputum purulence to data collection in future study protocols.</p><p id="par0060" class="elsevierStylePara elsevierViewall">In sum, this study showed that: i) dyspnoea is the most representative symptom at the onset of an AECOPD; ii) severity of cough is the first symptom to improve during the course of an AECOPD, and iii) changes in symptoms were correlated with FEV<span class="elsevierStyleInf">1</span> and QMS, which are predictors of COPD hospitalisations and mortality. Our findings evidence that timely management of symptoms is essential for patients’ recovery and should encourage health professionals to perform a comprehensive evaluation of outpatients with AECOPD using both patients reported symptoms and objective clinical outcome measures.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Conflict of interest statement</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Methods" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Results" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "Conflict of interest statement" ] 4 => array:2 [ "identificador" => "xack391634" "titulo" => "Acknowledgments" ] 5 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1652 "Ancho" => 2083 "Tamanyo" => 126072 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Correlations between changes from T1 to T3 in A) modified Borg scale – dyspnoea (MBS.d) and forced expiratory volume in 1 second (FEV1); B) modified Borg scale – fatigue (MBS.f) and FEV1; C) modified British Medical Research Council questionnaire (mMRC) and quadriceps muscle strength (QMS); D) Cough, assessed with the numerical scale, and QMS.</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="spar0015" class="elsevierStyleSimplePara elsevierViewall">Legend: Values are shown as number or median [interquartile range]; significant difference at p<0.05; * different from T1.</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">FEV<span class="elsevierStyleInf">1</span>, forced expiratory volume in one second; mMRC, modified British Medical Research Council questionnaire; MBS.d, modified Borg scale – dyspnoea; MBS.f, modified Borg scale – fatigue; NS, numerical scale; QMS, quadriceps muscle strength.</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="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">AECOPD (T1) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">8 days (T2) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">15 days (T3) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">45 days (T4) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p-value \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FEV<span class="elsevierStyleInf">1</span>, L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.9 [0.7-1.4] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.9 [0.7-1.3] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.1 [0.7-1.6] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.2 [0.8-1.6] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.075 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">QMS, kgf \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12.2<br>[9.2-20.1] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13.9<br>[10.9-18.6] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13.2<br>[11.2-21.8] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17.8*<br>[13.3-24.7] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">p<0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">No. patients (mMRC>0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.091 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">mMRC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.0 [2.0-3.0] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.0 [2.0-2.8] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.0 [1.0-2.0]* \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.5 [1.0-2.0]* \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">p<0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">No. patients (MBS.d>0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13* \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.040 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">MBS - dyspnoea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.0 [0.0-4.0] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.0 [0.0-2.8] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.0 [0.0-2.8] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.0 [0.0-1.8]* \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">p=0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">No. patients (MBS.f>0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.249 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">MBS - fatigue \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.0 [0.0-3.0] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.0 [0.0-3.0] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.0 [0.0-3.0] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.0 [0.0-2.0] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">p=0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">No. patients (NS.cough>0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.056 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cough \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.0 [6.0-10.0] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.0[2.0-5.0]* \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.0 [2.0-5.0]* \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.0 [0.0-4.0]* \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">p<0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">No. patients (NS.sputum>0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.392 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sputum \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.0 [2.0-7.5] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.0 [1.5-6.0] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.0 [2.0-4.0] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.0 [0.5-5.0] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">p=0.061 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">No. patients (NS.wheezeing>0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.183 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Wheezing \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.0 [2.5-10.0] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.0 [1.0-8.0] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.0 [0.0-5.5] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.0 [0.0-4.0]* \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">p=0.006 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1959766.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Clinical variables and symptoms variability during the course of an AECOPD.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "T.A. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 12 | 6 | 18 |
| 2024 October | 50 | 35 | 85 |
| 2024 September | 34 | 29 | 63 |
| 2024 August | 58 | 36 | 94 |
| 2024 July | 52 | 30 | 82 |
| 2024 June | 54 | 37 | 91 |
| 2024 May | 51 | 28 | 79 |
| 2024 April | 40 | 33 | 73 |
| 2024 March | 51 | 26 | 77 |
| 2024 February | 32 | 26 | 58 |
| 2024 January | 25 | 21 | 46 |
| 2023 December | 25 | 24 | 49 |
| 2023 November | 36 | 51 | 87 |
| 2023 October | 30 | 43 | 73 |
| 2023 September | 25 | 34 | 59 |
| 2023 August | 26 | 21 | 47 |
| 2023 July | 32 | 27 | 59 |
| 2023 June | 22 | 24 | 46 |
| 2023 May | 48 | 31 | 79 |
| 2023 April | 30 | 16 | 46 |
| 2023 March | 97 | 29 | 126 |
| 2023 February | 82 | 35 | 117 |
| 2023 January | 34 | 22 | 56 |
| 2022 December | 74 | 23 | 97 |
| 2022 November | 78 | 55 | 133 |
| 2022 October | 71 | 51 | 122 |
| 2022 September | 50 | 36 | 86 |
| 2022 August | 61 | 48 | 109 |
| 2022 July | 78 | 57 | 135 |
| 2022 June | 55 | 34 | 89 |
| 2022 May | 67 | 40 | 107 |
| 2022 April | 75 | 63 | 138 |
| 2022 March | 74 | 50 | 124 |
| 2022 February | 59 | 40 | 99 |
| 2022 January | 89 | 43 | 132 |
| 2021 December | 50 | 41 | 91 |
| 2021 November | 49 | 38 | 87 |
| 2021 October | 51 | 49 | 100 |
| 2021 September | 41 | 42 | 83 |
| 2021 August | 43 | 31 | 74 |
| 2021 July | 42 | 26 | 68 |
| 2021 June | 42 | 29 | 71 |
| 2021 May | 43 | 44 | 87 |
| 2021 April | 121 | 88 | 209 |
| 2021 March | 60 | 41 | 101 |
| 2021 February | 34 | 27 | 61 |
| 2021 January | 43 | 20 | 63 |
| 2020 December | 24 | 13 | 37 |
| 2020 November | 34 | 22 | 56 |
| 2020 October | 38 | 41 | 79 |
| 2020 September | 40 | 34 | 74 |
| 2020 August | 23 | 29 | 52 |
| 2020 July | 45 | 29 | 74 |
| 2020 June | 27 | 25 | 52 |
| 2020 May | 40 | 39 | 79 |
| 2020 April | 55 | 22 | 77 |
| 2020 March | 41 | 29 | 70 |
| 2020 February | 25 | 14 | 39 |
| 2020 January | 28 | 26 | 54 |
| 2019 December | 47 | 28 | 75 |
| 2019 November | 32 | 17 | 49 |
| 2019 October | 31 | 21 | 52 |
| 2019 September | 39 | 20 | 59 |
| 2019 August | 48 | 22 | 70 |
| 2019 July | 38 | 32 | 70 |
| 2019 June | 39 | 26 | 65 |
| 2019 May | 33 | 24 | 57 |
| 2019 April | 46 | 45 | 91 |
| 2019 March | 52 | 45 | 97 |
| 2019 February | 92 | 73 | 165 |
| 2019 January | 102 | 52 | 154 |
| 2018 December | 34 | 34 | 68 |
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