Scientific Letter
Efficacy of Double Bronchodilation (LABA+LAMA) in Patients with Chronic Obstructive Pulmonary Disease (COPD) and Lung Cancer
Análisis de la eficacia de la doble broncodilatación (LABA+LAMA) en pacientes con enfermedad pulmonar obstructiva crónica (EPOC) y cáncer de pulmón
Virginia Leiro-Fernández
, Ana Priegue Carrera, Alberto Fernández-Villar
Corresponding author
Servicio de Neumología, Hospital Álvaro Cunqueiro, EOXI Vigo, Instituto de Investigación Biomédica de Vigo, Vigo, Pontevedra, Spain
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(B) Maximum intensity projection (MIP) axial reconstruction (pulmonary parenchymal window) of left lung, showing a peripheral “tree-in-bud” pattern consisting of linear opacities forming predominantly subpleural branches (circled). See also the presence of small centrilobular nodules (arrow). (C) MIP coronal reconstruction (pulmonary parenchymal window) of the left lung, also showing the “tree-in-bud” pattern (circled). 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Both underdiagnosis of COPD and absence of treatment are common in these patients,<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1–3</span></a> and in curable cases these factors influence the choice of surgery or radiation therapy to treat LC, and affect tolerance to chemotherapy and radiation therapy.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,3</span></a> International LC guidelines recommend smoking cessation and respiratory rehabilitation, but do not make any explicit statements on intensive, short-term COPD treatment other than those given in the specific COPD guidelines.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Our aim was to study functional improvement of COPD in patients with LC after treatment with double bronchodilation (DBD) with a long-acting beta-adrenergic agent (LABA) and a long-acting muscarinic antagonist (LAMA). We conducted this prospective study in a population of outpatients seen in a lung cancer rapid diagnosis unit with spirometry performed on their first day in this unit showing forced expiratory volume in 1 second/forced vital capacity (FEV<span class="elsevierStyleInf">1</span>/FVC) ratio <70% and a post-bronchodilator predicted FEV<span class="elsevierStyleInf">1</span> <80%. Patients who were already receiving DBD treatment and those with an alternative diagnosis of bronchial asthma were excluded. The effect of DBD on lung function was evaluated at 4 weeks. The choice of the LAMA and the LABA were selected according to medical criteria and the ability and capacity of the patient to follow the treatment. Participants receiving inhaled corticosteroids before inclusion continued to receive this therapy. During this period, all other laboratory, endoscopic and imaging tests required for diagnosis, staging, and multidisciplinary therapeutic decision-making were also performed. At 4 weeks, before LC treatment in all cases, spirometry was repeated to evaluate the impact of DBD on FEV<span class="elsevierStyleInf">1</span> and FVC.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Results</span><p id="par0015" class="elsevierStylePara elsevierViewall">Thirty-seven patients with LC and COPD were included; patient characteristics are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Six had a previous diagnosis of COPD and were receiving bronchodilator treatment, none of which was DBD-based; 4 of these were fluticasone combined with salmeterol. The most commonly used LABA was indacaterol (83.8%), followed by salmeterol, vilanterol, and olodaterol. The most commonly used LAMA was glycopyrronium (51.4%), followed by aclidinium and tiotropium. After 4 weeks of DBD treatment, FEV<span class="elsevierStyleInf">1</span> increased by 200<span class="elsevierStyleHsp" style=""></span>ml (interquartile range [IQR] 40–320) and 8% (IQR 9–11) and FVC by 290<span class="elsevierStyleHsp" style=""></span>ml (IQR 75–665) and 6.5% (IQR 1.5–14) on average with respect to baseline values. In 40% of patients, FEV<span class="elsevierStyleInf">1</span> and/or FVC increased by 400<span class="elsevierStyleHsp" style=""></span>ml or more, although no response predictors or differences in LC staging were detected on a multivariate analysis. In 5 of the 10 potentially resectable patients who initially presented poor lung function, improvements in FEV<span class="elsevierStyleInf">1</span> and FVC after DBD permitted surgical resection for LC to be performed without the need for an oxygen consumption test.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">In this pilot study, we observed a notable improvement in lung function among patients with a diagnosis of COPD and LC who received DBD, allowing curative surgical interventions in a high percentage of patients.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In a study with a similar objective to ours that also explored postoperative pulmonary complications in 2 intervention groups who received DBD (formoterol+tiotropium) alone vs DBD+budesonide found comparable improvements to those described in our series in both groups, while the group that received budesonide had significantly better outcomes, including fewer postoperative complications.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> A lower incidence of postoperative complications was observed in another study of patients treated with tiotropium.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> In our study, we also found significant improvements in patients with severe COPD, in whom a small improvement in lung function can be decisive in the choice of a treatment, making surgery possible in half of the initially inoperable cases. Despite the obvious benefits of intensive bronchodilator therapy in patients with LC and COPD, no specific evidence-based recommendations are available. If we take into account the limitations of this study, namely, small sample size, lack of a control group and adjustment for the possible benefit of other treatments, our results may justify the conduct of other larger studies to clarify the benefit of DBD in the treatment and prognosis of these patients.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Results" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as: Leiro-Fernández V, Priegue Carrera A, Fernández-Villar A. Análisis de la eficacia de la doble broncodilatación (LABA+LAMA) en pacientes con enfermedad pulmonar obstructiva crónica (EPOC) y cáncer de pulmón. Arch Bronconeumol. 2016;52:622–623.</p>" ] ] "multimedia" => array:1 [ 0 => 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:3 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">CAT: COPD Assessment Test; COPD: chronic obstructive pulmonary disease; FEV<span class="elsevierStyleInf">1</span>: forced expiratory volume in 1 second; FVC: forced vital capacity; GOLD: Global Initiative for Chronic Obstructive Lung Disease; IQR: interquartile range; LC: lung cancer.</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=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Mean age in years (IQR)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 (58–67) \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"><span class="elsevierStyleItalic">Sex (men), n (%)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">34 (92) \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"><span class="elsevierStyleItalic">Smoking habit, n (%)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37 (100) \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"><span class="elsevierStyleItalic">Active smokers, n (%)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23 (62.2) \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"><span class="elsevierStyleItalic">Smoking index</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>, mean (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40 (35–60) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">LC histology, n (%)</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Adenocarcinoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21 (56.8) \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"><span class="elsevierStyleHsp" style=""></span>Squamous \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 (29.7) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">TNM staging, n (%)</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>I-IIIA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24 (65) \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"><span class="elsevierStyleHsp" style=""></span>IIIB-IV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13 (35) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">No COPD treatment, n (%)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31 (84) \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"><span class="elsevierStyleItalic">BODEX, mean (SD)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (0–3) \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"><span class="elsevierStyleItalic">CAT>10, n (%)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (16) \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"><span class="elsevierStyleItalic">Exacerbators</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>, <span class="elsevierStyleItalic">n (%)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (11) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">GOLD 2011 classification, n (%)</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22 (59.5) \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"><span class="elsevierStyleHsp" style=""></span>B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (19) \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"><span class="elsevierStyleHsp" style=""></span>C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (10.8) \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"><span class="elsevierStyleHsp" style=""></span>D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (8.1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">FEV</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">1</span></span><span class="elsevierStyleItalic">, mean (IQR)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2150 (1760–2430) \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"><span class="elsevierStyleItalic">FEV</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">1</span></span><span class="elsevierStyleItalic">%, mean (IQR)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">72 (58.5–79) \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"><span class="elsevierStyleItalic">FEV</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">1</span></span><span class="elsevierStyleItalic">ml, mean (IQR)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3730 (3220–4120) \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"><span class="elsevierStyleItalic">FVC%, mean (IQR)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">88 (75.5–96.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1260342.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Smoking index: pack-years=(number of cigarettes/day×total years smoking)/20.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Pack-years index=(number of cigarettes/day×total years smoking)/20.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Epidemiological and Clinical Characteristics.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The relationship COPD and lung cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A.L. Durham" 1 => "I.M. Adcock" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.lungcan.2015.08.017" "Revista" => array:6 [ "tituloSerie" => "Lung Cancer" "fecha" => "2015" "volumen" => "90" "paginaInicial" => "121" "paginaFinal" => "127" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26363803" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Physiologic evaluation of the patient with lung cancer being considered for resectional surgery: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Brunelli" 1 => "A.W. Kim" 2 => "K.I. Berger" 3 => "D.J. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 5 | 13 |
| 2024 October | 70 | 27 | 97 |
| 2024 September | 64 | 22 | 86 |
| 2024 August | 82 | 39 | 121 |
| 2024 July | 67 | 19 | 86 |
| 2024 June | 63 | 20 | 83 |
| 2024 May | 71 | 32 | 103 |
| 2024 April | 50 | 32 | 82 |
| 2024 March | 40 | 14 | 54 |
| 2024 February | 36 | 18 | 54 |
| 2023 March | 6 | 5 | 11 |
| 2023 February | 29 | 22 | 51 |
| 2023 January | 30 | 25 | 55 |
| 2022 December | 43 | 33 | 76 |
| 2022 November | 52 | 32 | 84 |
| 2022 October | 42 | 29 | 71 |
| 2022 September | 32 | 33 | 65 |
| 2022 August | 41 | 52 | 93 |
| 2022 July | 30 | 34 | 64 |
| 2022 June | 30 | 40 | 70 |
| 2022 May | 40 | 41 | 81 |
| 2022 April | 23 | 29 | 52 |
| 2022 March | 28 | 52 | 80 |
| 2022 February | 45 | 42 | 87 |
| 2022 January | 41 | 38 | 79 |
| 2021 December | 38 | 37 | 75 |
| 2021 November | 44 | 57 | 101 |
| 2021 October | 47 | 79 | 126 |
| 2021 September | 42 | 97 | 139 |
| 2021 August | 27 | 43 | 70 |
| 2021 July | 30 | 27 | 57 |
| 2021 June | 45 | 49 | 94 |
| 2021 May | 39 | 42 | 81 |
| 2021 April | 119 | 106 | 225 |
| 2021 March | 67 | 35 | 102 |
| 2021 February | 106 | 36 | 142 |
| 2021 January | 31 | 16 | 47 |
| 2020 December | 30 | 24 | 54 |
| 2020 November | 29 | 29 | 58 |
| 2020 October | 35 | 20 | 55 |
| 2020 September | 32 | 24 | 56 |
| 2020 August | 33 | 18 | 51 |
| 2020 July | 33 | 28 | 61 |
| 2020 June | 46 | 15 | 61 |
| 2020 May | 24 | 19 | 43 |
| 2020 April | 40 | 30 | 70 |
| 2020 March | 32 | 24 | 56 |
| 2020 February | 71 | 40 | 111 |
| 2020 January | 36 | 42 | 78 |
| 2019 December | 52 | 32 | 84 |
| 2019 November | 46 | 32 | 78 |
| 2019 October | 21 | 12 | 33 |
| 2019 September | 26 | 17 | 43 |
| 2019 August | 25 | 21 | 46 |
| 2019 July | 42 | 21 | 63 |
| 2019 June | 22 | 23 | 45 |
| 2019 May | 33 | 24 | 57 |
| 2019 April | 47 | 28 | 75 |
| 2019 March | 35 | 24 | 59 |
| 2019 February | 58 | 31 | 89 |
| 2019 January | 26 | 15 | 41 |
| 2018 December | 29 | 11 | 40 |
| 2018 November | 83 | 22 | 105 |
| 2018 October | 123 | 31 | 154 |
| 2018 September | 32 | 9 | 41 |
| 2018 May | 29 | 1 | 30 |
| 2018 April | 52 | 4 | 56 |
| 2018 March | 39 | 4 | 43 |
| 2018 February | 42 | 17 | 59 |
| 2018 January | 41 | 11 | 52 |
| 2017 December | 36 | 4 | 40 |
| 2017 November | 24 | 9 | 33 |
| 2017 October | 26 | 8 | 34 |
| 2017 September | 29 | 4 | 33 |
| 2017 August | 15 | 17 | 32 |
| 2017 July | 24 | 14 | 38 |
| 2017 June | 25 | 20 | 45 |
| 2017 May | 26 | 13 | 39 |
| 2017 April | 19 | 36 | 55 |
| 2017 March | 15 | 14 | 29 |
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