Original article
Ultrasound assessment of diaphragmatic dynamics in patients with chronic obstructive pulmonary disease after treatment with indacaterol/glycopyrronium
Valoración ecográfica de la dinámica diafragmática en pacientes con enfermedad pulmonar obstructiva crónica tras tratamiento con indacaterol/glicopirronio
A.L. Wangüemert-Péreza,
, J.M. Figueira-Gonçalvesb,c, Y. Ramallo-Fariñad, S. Guanche-Dortaa, R. Golpee
Corresponding author
a Servicio de Neumología, Hospital San Juan de Dios Tenerife, Santa Cruz de Tenerife, Spain
b Servicio de Neumología, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
c Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Santa Cruz de Tenerife, Spain
d Foundation of the Canary Islands Health Research Institute (FIISC), Santa Cruz de Tenerife, Spain Health Services Research on Chronic Patients Network (REDISSEC), Madrid, Spain
e Servicio de Neumología, Hospital Universitario Lucus Augusti, Lugo, Spain
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"apellidos" => "Golpe" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Servicio de Neumología, Hospital San Juan de Dios Tenerife, Santa Cruz de Tenerife, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Neumología, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Santa Cruz de Tenerife, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Foundation of the Canary Islands Health Research Institute (FIISC), Santa Cruz de Tenerife, Spain Health Services Research on Chronic Patients Network (REDISSEC), Madrid, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Servicio de Neumología, Hospital Universitario Lucus Augusti, Lugo, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Valoración ecográfica de la dinámica diafragmática en pacientes con enfermedad pulmonar obstructiva crónica tras tratamiento con indacaterol/glicopirronio" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1596 "Ancho" => 2674 "Tamanyo" => 668299 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Diaphragmatic excursion and thickness. A) Diaphragmatic excursion during normal breathing. B) Diaphragmatic excursion during deep breathing. C) Diaphragmatic excursion during sniffing. D) Diaphragm thickness. A, B and C with convex ultrasound probe; D with linear ultrasound probe.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Air trapping in chronic obstructive pulmonary disease (COPD) is one of the most important phenomena of the disease pathophysiology as it is largely responsible for the dyspnoea that patients experience. Air trapping requires a new balance to be adopted between the elastic forces of the lungs and the ribcage, as well as changes to the situation of the respiratory muscles. These adaptations present a series of mechanical disadvantages that result in increased respiratory effort. The diaphragm, the primary muscle involved in the respiration cycle, loses its normal configuration, affecting excursion and limiting its expansion over the lower ribs<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–3</span></a>.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The use of bronchodilator therapy reduces airflow obstruction and reduces air trapping, thereby improving both diaphragmatic mobility as well as filling of the cardiac ventricles, which has a positive impact on the symptomatology of COPD patients<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4–6</span></a>. The use of dual bronchodilation has been shown to improve symptoms, quality of life, physical activity and to control flares with respect to individual components in patients with COPD with a moderate-severe degree of obstruction (including in sick individuals without prior treatment) and a higher rate of responders to treatment<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Chest ultrasound (CU) is a useful technique for assessing diaphragm function. Studies performed with short-acting bronchodilators have shown improvement in diaphragm mobility by reducing air trapping. However, to date, these changes have not been analysed following the use of long-acting bronchodilators<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4–6,8,9</span></a>.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Our hypothesis when proposing this study was that long-acting bronchodilator therapy would result in improvements in air trapping which would translate into improved diaphragmatic mobility and diaphragm thickness as measured by CU.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The objectives of the study were as follows: 1) use CU to assess changes to diaphragmatic mobility and thickness after starting bronchodilator therapy with indacaterol/glycopyrronium 85/43 mcg every 24 hours with a Breezhaler device in patients recently diagnosed with COPD; 2) analyse whether the changes that occur in diaphragmatic mobility and/or thickness following the start of bronchodilator therapy correlate with changes in the degree of dyspnoea according to the Modified Medical Research Council (mMRC) scale and with indirect air trapping markers such as forced vital capacity (FVC).</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study design</span><p id="par0030" class="elsevierStylePara elsevierViewall">Interventional prospective study with 3 months of outpatient monitoring of patients with new COPD diagnosis with moderate-very severe airflow obstruction during the period spanning 1 January to 30 June 2021. Patients underwent a CU prior to study start and after 3 months of LAMA-LABA therapy, as per the GesEPOC (Spanish COPD) guidelines<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,11</span></a>.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Study population</span><p id="par0035" class="elsevierStylePara elsevierViewall">The inclusion criteria for COPD patients were as follows: 1) patients being monitored by the pulmonology service; 2) age > 40 years; 3) active smoker or ex-smoker with a pack-year index (PY) of ≥10; 4) forced expiratory volume ratio (FEV1)/FVC in the first second of <70% after administration of 400 μg salbutamol; 5) moderate to very severe degree of air flow (moderate 50% ≤ FEV1 < 80%, severe 30% ≤ FEV1 < 50% and very severe FEV1 < 30%); 6) treatment-naïve for bronchodilator therapy in the 3 months prior to study inclusion; 7) dyspnoea with an mMRC score of ≥2; 8) absence of any respiratory exacerbations in the previous 3 months; 9) presence of pulmonary emphysema due to chest CT findings and/or diffusing capacity for carbon monoxide (DLCO) of <80%.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The exclusion criteria were as follows: low-risk COPD and COPD patients with eosinophil exacerbator phenotype with LABA/IC therapy<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,11</span></a>; no visualisation of the diaphragmatic dome in right subcostal view in CU; refusal to participate in the study; failure to comply with bronchodilator therapy during the study period; failure to attend the 3-month follow-up visit after starting treatment, and the presence of respiratory exacerbation during follow-up.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Variables</span><p id="par0045" class="elsevierStylePara elsevierViewall">Patients included in the study underwent two ultrasound assessments: the first was performed at the time of COPD diagnosis and the second 3 months after starting bronchodilator therapy with indacaterol/glycopyrronium 85/43 mcg every 24 hours with the Breezhaler device.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The variables collected were: diaphragmatic excursion (in at rest, deep, and sniff breathing) and diaphragm thickness (maximum and minimum), prior to starting bronchodilator therapy and after 3 months of therapy. The diaphragm thickening fraction was calculated for all patients (DTf = thickness at end of inspiration – thickness at end of expiration)/thickness at end of expiration × 100.</p><p id="par0055" class="elsevierStylePara elsevierViewall">The following spirometry data were collected: FEV1, FVC (expressed in absolute values and percentages with respect to the predicted value) and FEV1/FVC ratio. At visit 0, the aforementioned variables were collected after performing a bronchodilator test with salbutamol. At the follow-up visit (3 months later), the variables were obtained via forced spirometry following administration of the corresponding indacaterol/glycopyrronium 85/43 mcg treatment.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Likewise, the following was collected at visit 0: smoking history; smoking load according to the pack-year index (PY); body mass index (BMI); comorbidities (obstructive sleep apnoea, diabetes mellitus, arterial hypertension, dyslipidaemia, ischemic heart disease, cerebrovascular accident), and the Charlson comorbidity index was calculated without adjusting for age. At both visit 0 and the follow-up visit, the degree of dyspnoea was recorded as measured against the mMRC scale. None of the included patients were in a respiratory physical therapy program during the study.</p><p id="par0065" class="elsevierStylePara elsevierViewall">The ultrasound assessments and measurements were completed by a single technician with extensive CU experience. A Toshiba Xario 2007 ultrasound machine was used with a convex 3–5 Mhz probe to assess diaphragmatic excursion and a linear 5−13 MHz probe to evaluate diaphragm thickness. The images/videos were always recorded in the system.</p><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Procedure</span><p id="par0070" class="elsevierStylePara elsevierViewall">Both ultrasound examinations were performed in the following manner: the patient was instructed to lie on a bed in the supine position and the bed was placed at a 45° incline. Diaphragmatic excursion was measured first. To do so, a convex probe was placed at the subcostal level on the right side with the transducer aimed towards the diaphragmatic dome. Once the diaphragmatic dome was located, the patient was instructed to first take some normal breaths in order to assess diaphragmatic excursion during at rest breathing. The same process was carried out with the patient practising deep breathing and sniffing (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). After that, the linear probe was used at the phrenic point to measure the maximum and minimum diaphragm thickness. These measurements were used to calculate the diaphragmatic thickening fraction as described above.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Ethics committee approval</span><p id="par0075" class="elsevierStylePara elsevierViewall">The study was approved by the Nuestra Señora de la Candelaria University Hospital Ethics Committee (CODE CHUNSC_2021_53) and all the patients signed the informed consent prior to inclusion in the study.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Data analysis</span><p id="par0080" class="elsevierStylePara elsevierViewall">The study variables were subjected to descriptive analysis using mean and standard deviation for the quantitative variables and frequency and percentage for the qualitative variables. The Kolmogorov-Smirnov test was used to confirm the fit of the data to a normal distribution.</p><p id="par0085" class="elsevierStylePara elsevierViewall">To evaluate the effect of the intervention on the variables of interest, Student’s <span class="elsevierStyleItalic">t</span>-test was used for related variables if the variables followed a normal distribution. If not, the Wilcoxon signed-rank test was used. Pearson’s formula was used to study the correlation between the different variables. An alpha value of <0.05 was considered significant.</p><p id="par0090" class="elsevierStylePara elsevierViewall">The statistical package used was SPSS (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp).</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Study population characteristics</span><p id="par0095" class="elsevierStylePara elsevierViewall">A total of 30 patients were included. Their baseline characteristics are listed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. The majority were men (56.6%), with a mean age of 69.4 ± 6.2 years and BMI of 28.2 ± 3.5 kg/m<span class="elsevierStyleSup">2</span>. Of the total, 33.3% were active smokers with a mean PY of 49.8 ± 23.8. The most frequent comorbidities were: arterial hypertension (43.3%), ischaemic heart disease (43.3%), obstructive sleep apnoea (43.3%), dyslipidaemia (40%) and diabetes <span class="elsevierStyleItalic">mellitus</span> (10%).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Differences in diaphragmatic excursion in the three breathing types</span><p id="par0100" class="elsevierStylePara elsevierViewall">Diaphragmatic excursion measured during at rest breathing, deep breathing and sniffing showed improvement, with a significant increase between the two measurements (0 and 3 months of treatment) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">Pre- and post-treatment diaphragmatic excursion during at rest, deep, and sniff breathing was: 19.9 ± 7.1 mm and 26.4 ± 8.7 mm (<span class="elsevierStyleItalic">p < 0.0001) 42.5 14.1 mm and 64.5 25.9 mm (p < 0.0001) and 36.5 17.4 mm and 46.7 18.5 mm (p =  0</span><span class="elsevierStyleItalic">P</span>.012), respectively.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Differences in diaphragm thickness</span><p id="par0110" class="elsevierStylePara elsevierViewall">After 3 months of treatment, a significant improvement occurred in both maximum and minimum diaphragm thickness. (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). However, no significant differences were found with respect to the diaphragm thickening fraction formula (83.6 ± 46.9% pre-treatment vs. 78.2 ± 37.09 % post-treatment, p = 0.341). The improvement in diaphragmatic mobility via sniffing was significantly correlated (r = 0.490; p =  0.007) with a reduction in the maximum and minimum diaphragm thickness (r = 0.437; p =  0.018 and r = 0.391; p =  0.036 respectively).</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Functional respiratory tests</span><p id="par0115" class="elsevierStylePara elsevierViewall">A significant improvement in FEV1/FVC (mean %) was observed 3 months after starting bronchodilator therapy (54.9 ± 8.18 vs. 57.3 ± 9.19%; <span class="elsevierStyleItalic">p =  0</span>.024). Pre- and post-treatment FEV1% was 58.9 ± 16.0% and 61.6 ± 15.4% (p =  0.079), respectively (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). Regarding FVC %, prior to treatment this was 74.2 ± 14.7% and 81.7 ± 17.6% (<span class="elsevierStyleItalic">p =</span> 0.0001) after treatment.</p><p id="par0120" class="elsevierStylePara elsevierViewall">There was a significant positive correlation (r = 0.475; <span class="elsevierStyleItalic">p =  0</span>.009) between FVC and the difference in sniff excursion, though this correlation was not found for the diaphragmatic excursion measurements in the other two tests.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Relationship between dyspnoea and diaphragmatic excursion</span><p id="par0125" class="elsevierStylePara elsevierViewall">The patients experienced an improvement in dyspnoea after 3 months of treatment (2.03 ± 0.55 to 1.66 ± 0.54 mMRC; <span class="elsevierStyleItalic">p =</span> 0.001). No significant correlation was found between the changes in the dyspnoea scale and the increase in diaphragmatic excursion with the bronchodilator therapy (<span class="elsevierStyleItalic">p ></span> 0 .05), except for with the sniff diaphragmatic excursion (<span class="elsevierStyleItalic">p <</span> 0.03).</p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Discussion</span><p id="par0130" class="elsevierStylePara elsevierViewall">The main result of our study is that treatment with indacaterol/glycopyrronium 85/43 mcg for 3 months produced an improvement in diaphragmatic mobility as measured via CU in naïve patients with COPD and moderate to very severe obstructed airflow. This improvement in diaphragmatic mobility correlated with an improvement in FVC when using the sniff test.</p><p id="par0135" class="elsevierStylePara elsevierViewall">Dyspnoea is one of the primary symptoms of COPD and is largely due to the inspiratory muscles’ reduced capacity to perform their function, resulting in excess inspiratory workload. Various mechanisms can predispose muscle weakness in patients (including the diaphragm), such as underlying systemic inflammation, oxidative stress, chronic steroid use or hypoxemia<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12,13</span></a>. In addition, air trapping facilitates the appearance of structural changes in the diaphragm, causing it to flatten and, consequently, decreasing its excursion, creating adverse conditions for it to properly perform its function<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14,15</span></a>.</p><p id="par0140" class="elsevierStylePara elsevierViewall">In COPD, respiratory limitation during exercise is largely due to reduced ventilatory capacity caused by lung hyperinflation, which translates into reduced inspiratory capacity and ventilatory reserve<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14,15</span></a>. Therefore, one parameter used to measure air trapping, the inspiratory capacity/total lung capacity (IC/TCL) ratio, correlates well with the effort capacity measured with the 6-minute walking test<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>.</p><p id="par0145" class="elsevierStylePara elsevierViewall">Various studies have shown a relationship between diaphragmatic excursion parameters and the clinical and functional variables of COPD. Davachi et al.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> found greater diaphragmatic mobility in patients with mild obstruction with respect to those with a more severe degree of obstruction. Mekov et al.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> observed a significant correlation between the degree of dyspnoea in COPD patients and diaphragmatic excursion both at rest and following exercise. These results indicate that diaphragmatic excursion assessment techniques are promising tools for evaluating COPD patients including, perhaps, evaluating responses to therapeutic interventions.</p><p id="par0150" class="elsevierStylePara elsevierViewall">Bronchodilators are a cornerstone of pharmacological therapy for COPD<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>. Their use reduces air trapping and improves diaphragm mechanics<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>. Dual bronchodilation, compared to monotherapy, is more effective at improving pulmonary function, dyspnoea, quality of life, and exercise capacity for patients<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21,22</span></a>. Hatipoglu et al.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> found that albuterol, compared to placebo, produced an increase in inspiratory capacity accompanied by an increase in maximal and twitch transdiaphragmatic pressures.</p><p id="par0155" class="elsevierStylePara elsevierViewall">Our study analysed the effects of long-acting dual bronchodilation with indacaterol/glycopyrronium on diaphragmatic excursion and pulmonary function variables. We found that this drug, after 3 months of use, produced an increase in diaphragmatic excursion. What’s more, we found a significant relationship between this variable and FVC improvement, which indirectly points to an improvement in air trapping. It must be highlighted that this correlation was only seen in the sniff test. This test is likely the most appropriate for assessing the maximum strength of the inspiratory muscles and may be the most sensitive for detecting improvement to diaphragmatic excursion. Nevertheless, we cannot rule out that our study’s sample size may have been insufficient for detecting significant changes with the other tests.</p><p id="par0160" class="elsevierStylePara elsevierViewall">Our study also found an improvement in diaphragm thickness following the therapeutic intervention, coinciding with improved pulmonary function. This result is consistent with the study by Rittayami et al.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> which showed that, compared to healthy controls, diaphragm thickening and diaphragmatic excursion worsened as airflow obstruction declined.</p><p id="par0165" class="elsevierStylePara elsevierViewall">It must also be mentioned that our study found a certain correlation between improvement in one clinical variable (dyspnoea measured via the mMRC scale) and changes in chest excursion variables, though these were not statistically significant with the exception of the sniff test. This may be attributable to the fact that the mMRC scale may not be sensitive enough to detect minimal changes in dyspnoea, together with the sample size. Scales such as the Transition Dyspnea Index (TDI)<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> could be considered for future studies with similar characteristics.</p><p id="par0170" class="elsevierStylePara elsevierViewall">This is the first study we are aware of that analysed the effect of long-acting dual bronchodilation on diaphragmatic excursion in naïve patients with COPD. The results suggest that it could be a promising tool for researching the effect of these drugs, representing a starting point for designing assessment strategies for both clinical practise and research studies (for example, establishing comparisons between different types of drugs, or between patients with different characteristics).</p><p id="par0175" class="elsevierStylePara elsevierViewall">Nevertheless, it has some limitations, such as the single-centre nature of the study and the small sample size. In addition, it did not use tools such as plethysmography to quantify the degree of air trapping, which would have made it possible to delve with greater precision into the relationship between this significant COPD alteration and diaphragm function measurements. However, the FVC improvement, in the absence of illnesses that could cause pulmonary restriction, is an indirect measure that is reasonably indicative of improvement in air trapping. As previously mentioned, the mMRC scale may not have been sensitive enough to correlate clinical variables (dyspnoea) with diaphragm function parameters. Lastly, a single observer took the CU measurements, so any potential interindividual variability can be ruled out.</p><p id="par0180" class="elsevierStylePara elsevierViewall">Despite these limitations, the study supports the use of CU as a useful tool for real-time visual assessment of the effect of bronchodilator therapy on the respiratory mechanics of COPD patients and represents a starting point for developing future studies.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conclusion</span><p id="par0185" class="elsevierStylePara elsevierViewall">Diaphragmatic mobility improved after 3 months of treatment with indacaterol/glycopyrronium 85/43 mcg every 24 hours in patients with COPD with moderate to very severe obstruction.</p><p id="par0190" class="elsevierStylePara elsevierViewall">Progressive assessment of this mobility via CU is a promising tool for monitoring these patients, including evaluating response to therapeutic interventions.</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Funding</span><p id="par0195" class="elsevierStylePara elsevierViewall">The authors declare they have not received any funding to carry out this study.</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Conflicts of interest</span><p id="par0200" class="elsevierStylePara elsevierViewall">The authors declare that they do not have any conflicts of interest directly or indirectly related to the content of the manuscript.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1881019" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1630398" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1881020" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1630399" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study design" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Study population" ] 2 => array:3 [ "identificador" => "sec0025" "titulo" => "Variables" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Procedure" ] ] ] 3 => array:2 [ "identificador" => "sec0035" "titulo" => "Ethics committee approval" ] 4 => array:2 [ "identificador" => "sec0040" "titulo" => "Data analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0045" "titulo" => "Results" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Study population characteristics" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Differences in diaphragmatic excursion in the three breathing types" ] 2 => array:2 [ "identificador" => "sec0060" "titulo" => "Differences in diaphragm thickness" ] 3 => array:2 [ "identificador" => "sec0065" "titulo" => "Functional respiratory tests" ] 4 => array:2 [ "identificador" => "sec0070" "titulo" => "Relationship between dyspnoea and diaphragmatic excursion" ] ] ] 7 => array:2 [ "identificador" => "sec0075" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0080" "titulo" => "Conclusion" ] 9 => array:2 [ "identificador" => "sec0085" "titulo" => "Funding" ] 10 => array:2 [ "identificador" => "sec0090" "titulo" => "Conflicts of interest" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-10-02" "fechaAceptado" => "2023-01-24" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1630398" "palabras" => array:3 [ 0 => "COPD" 1 => "Ultrasound" 2 => "Diaphragmatic excursion" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1630399" "palabras" => array:3 [ 0 => "EPOC" 1 => "Ultrasonografía" 2 => "Excursión diafragmática" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Air trapping is one of the main determinants of dyspnea in patients with chronic obstructive pulmonary disease (COPD). An increase in air trapping leads to a change in the normal diaphragmatic configuration with associated functional impairment. Said deterioration improves with bronchodilator therapy. Chest ultrasound (CU) has been used to assess changes in diaphragmatic motility after short-acting bronchodilator therapy, but there are no previous studies on these changes after long-acting bronchodilator treatment.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Interventional prospective study. Patients with COPD and moderate to very severe ventilatory obstruction were included in the study. Diaphragm motion and thickness were assessed by CU before and after 3 months of treatment with indacaterol/glycopirronium 85/43 mcg.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Thirty patients were included (56.6% men, mean age: 69.4 ± 6.2 years). Pre- and post-treatment diaphragmatic mobility measured during resting breathing, deep breathing, and nasal sniffing were 19.9 ± 7.1 mm and 26.4 ± 8.7 mm (<span class="elsevierStyleItalic">p</span> < 0.0001); 42.5 ± 14.1 mm and 64.5 ± 25.9 mm (<span class="elsevierStyleItalic">p</span> < 0.0001); and 36.5 ± 17.4 mm and 46.7 ± 18.5 mm (<span class="elsevierStyleItalic">p</span> = 0.012), respectively. A significant improvement was also found in the minimum and maximum diaphragm thickness (<span class="elsevierStyleItalic">p</span> < 0.05), but there were no significant changes in the diaphragmatic shortening fraction after treatment (<span class="elsevierStyleItalic">p</span> = 0.341).</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Treatment with indacaterol/glycopyrronium 85/43 mcg every 24 hours for 3 months improved diaphragmatic mobility in patients with COPD with moderate to very severe airway obstruction. CU may be useful for assessing the response to treatment in these patients.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducción</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">El atrapamiento aéreo en la enfermedad pulmonar obstructiva crónica (EPOC) es uno de los principales responsables de la disnea en estos enfermos. Su incremento conlleva que el diafragma pierda su configuración habitual y se afecte así su funcionalidad, la cual parece mejorar tras la administración de terapia broncodilatadora. La ecografía torácica (ET) se ha utilizado para evaluar estos cambios tras el uso de broncodilatadores de acción corta, pero no hay estudios que valoren estas variaciones con el empleo de broncodilatadores de acción larga.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y métodos</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Estudio prospectivo intervencionista de 3 meses de seguimiento donde se valoró el movimiento/grosor diafragmático con ET antes y después del inicio del tratamiento con indacaterol/glicopirronio 85/43 mcg en pacientes EPOC con obstrucción moderada-muy grave al flujo aéreo.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Treinta pacientes fueron incluidos (56,6% hombres, edad media: 69,4 ± 6,2 años). La movilidad diafragmática pre y postratamiento en respiración a volumen corriente, profunda y sniff nasal fue de 19,9 ± 7,1 mm y 26,4 ± 8,7 mm (<span class="elsevierStyleItalic">p</span> < 0,0001), 42,5 ± 14,1 mm y 64,5 ± 25,9 mm (<span class="elsevierStyleItalic">p</span> < 0,0001) y 36,5 ± 17,4 mm y 46,7 ± 18,5 mm (<span class="elsevierStyleItalic">p</span> = 0,012), respectivamente. También existió una mejora significativa en el grosor diafragmático mínimo y máximo (<span class="elsevierStyleItalic">p</span> < 0,05) pero no en la fracción de engrosamiento diafragmático tras tratamiento (<span class="elsevierStyleItalic">p</span> = 0,341).</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">El tratamiento con indacaterol/glicopirronio 85/43 mcg cada 24 horas durante 3 meses mejoró la movilidad diafragmática en paciente con EPOC con obstrucción moderada-muy grave al flujo aéreo. La ET puede ser útil en la valoración de la repuesta al tratamiento de estos pacientes.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:3 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1596 "Ancho" => 2674 "Tamanyo" => 668299 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Diaphragmatic excursion and thickness. A) Diaphragmatic excursion during normal breathing. B) Diaphragmatic excursion during deep breathing. C) Diaphragmatic excursion during sniffing. D) Diaphragm thickness. A, B and C with convex ultrasound probe; D with linear ultrasound probe.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">FEV1: forced expiratory volume in one second; N: sample size; PY: pack-years; SD: standard deviation.</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "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">Variables \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">n = 30 (%) \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">Age in years, mean (SD) \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">69.4 (6.2) \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">Sex, male \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 (56.6) \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">mMRC dyspnoea, mean (SD) \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">2.03 (0.55) \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">FEV1 \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="elsevierStyleHsp" style=""></span><50% \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 (40.0) \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="elsevierStyleHsp" style=""></span>≥50%−79% \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">18 (60.0) \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">Active smoker \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">10 (33.3) \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">PY, mean (SD) \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">49.8 (23.8) \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="elsevierStyleHsp" style=""></span>≤30 \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">8 (27.6) \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="elsevierStyleHsp" style=""></span>31−60 \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 (55.2) \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="elsevierStyleHsp" style=""></span>>60 \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">5 (17.2) \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">Body mass index, mean (SD) \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">28.2 (3.5) \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">Obstructive sleep apnoea, n (%) \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">13 (43.3) \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="elsevierStyleHsp" style=""></span>Moderate \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 (20.0) \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="elsevierStyleHsp" style=""></span>Severe \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">7 (23.3) \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">Arterial hypertension, n (%) \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">13 (43.3) \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">Ischaemic heart disease, n (%) \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">13 (43.3) \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">Dyslipidaemia, n (%) \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 (40.0) \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">Type 2 diabetes mellitus, n (%) \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 (10.0) \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">Cerebrovascular accident \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">0 (0) \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">Charlson Comorbidity Index, mean (SD) \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">4.9 (1.4) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Characteristics of the chronic obstructive pulmonary disease patients included in the study.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">DLCO: diffusing capacity for carbon monoxide; FEV1: forced expiratory volume in one second; FVC: forced vital capacity; KCO: diffusing capacity for carbon monoxide adjusted for alveolar volume. Max: maximum; Min: minimum; mm: millimetres; mMRC: Modified Medical Research Council; SD: standard deviation.</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "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">Pre-intervention mean (SD) \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">Post-intervention mean (SD) \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"><span class="elsevierStyleItalic">p</span> \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">Baseline excursion (mm) \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">19.99 (7.16) \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">26.4 (8.79) \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"><0.0001 \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">Deep excursion (mm) \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">42.51 (14.19) \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">64.55 (25.91) \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">< 0.0001 \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">Sniff excursion (mm) \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">36.51 (17.45) \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">46.76 (18.58) \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">0.012 \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">Min. thickness (mm) \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">1.46 (0.51) \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">1.83 (0.74) \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">0.005 \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">Max. thickness (mm) \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">2.55 (0.82) \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 (0.76) \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">< 0.0001 \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">Diaphragmatic thickening fraction (%) \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">78.2 (37.09) \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">83.06 (46.94) \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">0.341 \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">Body mass index (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">28.2 (3.5) \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">28.8 (3.2) \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">0.216 \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">FEV1/FVC \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">54.93 (8.18) \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 (8.19) \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">0.024 \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">FEV1 %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">58.59 (16.07) \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">61.66 (15.43) \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">0.079 \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">FEV1 (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">1.58 (0.478) \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">1.62 (0.430) \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">0.400 \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">FVC %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">74.21 (14.79) \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">81.76 (17.6) \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">< 0.0001 \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">FVC (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">2.69 (0.844) \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">2.75 (0.693) \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">0.472 \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">DLCO % \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">52.07 (17.23) \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">53.38 (16.63) \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">0.363 \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">KCO % \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">64.34 (18) \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">66.38 (17.51) \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">0.049 \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">DYSPNEA mMRC, mean (SD) \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">2.03 (0.55) \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">1.66 (0.54) \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">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="\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="elsevierStyleHsp" style=""></span>0, n (%) \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">0 (0) \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">0 (0) \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="elsevierStyleHsp" style=""></span>1, n (%) \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">4 (13.3) \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 (40.0) \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="elsevierStyleHsp" style=""></span>2, n (%) \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">21 (70.0) \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">18 (60.0) \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="elsevierStyleHsp" style=""></span>3, n (%) \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">5 (16.7) \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">0 (0) \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="elsevierStyleHsp" style=""></span>4, n (%) \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">0 (0) \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">0 (0) \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></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Changes in diaphragmatic excursion/thickness and in functional respiratory tests before and after long-acting bronchodilator therapy.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:24 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diaphragmatic excursion correlates with exercise capacity and dynamic hyperinflation in COPD patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. 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