Severe obstructive disease: Similarities and differences between smoker and non-smoker patients with COPD and/or bronchiectasis

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Curva de sobrevida global dos doentes mutados versus não mutados (47 vs. 22 meses, p = 0,038). B. Curva de sobrevida após tratamento com erlotinib em doentes mutados e WT (14 vs. 6 meses, p = 0,003)." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A.S. Castro, B. Parente, I. Gonçalves, A. Antunes, A. Barroso, S. Conde, S. Neves, J.C. Machado" "autores" => array:8 [ 0 => array:2 [ "nombre" => "A.S." "apellidos" => "Castro" ] 1 => array:2 [ "nombre" => "B." "apellidos" => "Parente" ] 2 => array:2 [ "nombre" => "I." "apellidos" => "Gonçalves" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Antunes" ] 4 => array:2 [ "nombre" => "A." "apellidos" => "Barroso" ] 5 => array:2 [ "nombre" => "S." "apellidos" => "Conde" ] 6 => array:2 [ "nombre" => "S." "apellidos" => "Neves" ] 7 => array:2 [ "nombre" => "J.C." 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"apellidos" => "Rezende Gonçalves" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "M." "apellidos" => "Corso Pereira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "E.M." "apellidos" => "Figueiras Pedreira De Cerqueira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "D." "apellidos" => "Oliveira Magro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "M." "apellidos" => "Mello Moreira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 5 => array:4 [ "nombre" => "I.A." "apellidos" => "Paschoal" "email" => array:1 [ 0 => "ilma@fcm.unicamp.br" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Master, University of Campinas – UNICAMP, Campinas, SP, Brazil" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "PhD, University of Campinas – UNICAMP, Campinas, SP, Brazil" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Doença obstrutiva grave: semelhanças e diferenças entre os pacientes fumadores e não-fumadores com DPOC e/ou bronquiectasias" ] ] "textoCompleto" => "IntroductionIt is quite clear nowadays that the most frequent cause of chronic and progressive airway disease that leads to chronic respiratory failure is Chronic Obstructive Pulmonary Disease (COPD) related to tobacco use. COPD is diagnosed if poorly reversible airflow obstruction can be demonstrated by spirometry and the exposure to noxious gases is present.Poorly reversible airflow obstruction is not confined to smokers. Kohansal et al.,<a class="elsevierStyleCrossRef" href="#bib0005">1</a> in a study about the natural history of chronic airflow obstruction, analyzed the Framingham Offspring cohort, who were followed for 23 years. One third of the individuals, who continued to smoke, developed airflow obstruction during follow-up. But so did 7.4% of never-smoker males and 5.6% of never-smoker females.The classic work of Fletcher et al.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> on the natural history of COPD did not include non-smokers and therefore provides no information about the subjects who do not smoke but do have chronic airflow obstruction. In the United States, 20% of the patients who have obstruction in spirometry and 20% of those who die of COPD are non-smokers.<a class="elsevierStyleCrossRefs" href="#bib0015">3–6</a> Few studies have been performed in this group and little is known about its natural history and clinical course.Mucus hypersecretion, one of the classic features of COPD, is associated with exacerbations and both situations are related to progressive loss of airflow.<a class="elsevierStyleCrossRefs" href="#bib0035">7,8</a>On the other hand, patients with hypersecretion unrelated to COPD may present functional and clinical pictures that overlap with chronic bronchitis associated with smoking.<a class="elsevierStyleCrossRef" href="#bib0045">9</a>In addition to the symptoms and the spirometric changes, other similarities may exist between COPD and bronchiectasis from various causes: the predominant neutrophilic inflammation,<a class="elsevierStyleCrossRef" href="#bib0050">10</a> the pattern of response to bronchodilators (BD),<a class="elsevierStyleCrossRefs" href="#bib0055">11–13</a> and the findings on imaging studies.Having taken this previous data into account we decided to investigate the hypothesis that there are more similarities than differences among patients with severe chronic bronchial disease, regardless of whether they have smoking related COPD or bronchiectasis due to other causes.MethodsPatients who attended our referral outpatient clinic for chronic respiratory failure and whose spirometry showed a pre-BD FEV1<50% of predicted, and FEV1/CVF<70% were invited to participate in this study. We excluded patients with neuromuscular diseases, thoracic deformities, restrictive lung diseases, pulmonary vascular disease and those who had undergone lung resection.The study was approved by the Ethics Research Committee of our institution and all participants signed an informed consent form.Clinical data were gathered from patient files. To assess the degree of breathlessness we used the British MRC (Medical Research Council) questionnaire.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> All patients underwent spirometry before and after the use of formoterol 12mcg (Foradil®, Novartis, Brazil). Forced vital capacity (FVC) and slow vital capacity (VC) curves were performed using a flow spirometer (MicroQuark; COSMED SRL, Rome, Italy) with Brazilian reference values.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> The six-minute walk test (6MWT) was performed by the patients who had pulse oxymetry (SpO2) above 90% at rest and the procedure followed that proposed by ATS.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> Body mass index (BMI) was determined and the body composition was assessed by the bioimpedance technique (Biodynamics 310, Seattle, WA, USA). All tests were conducted during periods of clinical stability.To analyze the data we first compared smokers and non-smokers and secondly we identified two groups according to the pattern of response to BD on spirometry.When comparing smokers and non-smokers we set parameters and cutoff values for each variable: BMI≤21kg/m2,<a class="elsevierStyleCrossRefs" href="#bib0010">2,17</a> MRC>1,<a class="elsevierStyleCrossRef" href="#bib0085">17</a> resting SpO2<90%, use of long-term oxygen therapy (LTOT), FEV1<30% of predicted, inspiratory capacity (IC)<80% predicted, 6MWD<350m,<a class="elsevierStyleCrossRef" href="#bib0085">17</a> and a drop in SpO2 during the 6MWT (SpO2 final–initial)≥4%, which were considered signs of greater severity. For numerical variables [FVC, VC, LM (lean mass) in % of predicted, and lean-to-fat body mass ratio (LM/FM)], we calculated the mean and median of the two groups.For the analysis of BD response we compared two criteria: ATS/ERS [volume response (FVC) or flow response (FEV1) 200ml and 12%],<a class="elsevierStyleCrossRef" href="#bib0090">18</a> and the parameters used in the study of Paré et al.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> which were applied only when the increase in FEV1 or FVC post-BD was at least 12%. According to Paré et al. the volume response is reflected by the presence of ΔFEV1/ΔCVF<1, and flow response, ΔFEV1/ΔCVF>1, where Δ means the (post-BD−pre-BD) value.<a class="elsevierStyleCrossRef" href="#bib0095">19</a>HRCT of the thorax was performed (sections 1.5–2mm thick, 10mm intervals, at maximum inspiration and expiration)<a class="elsevierStyleCrossRef" href="#bib0100">20</a> and the following CT findings were analyzed: presence of emphysema (centrilobular, paraseptal and panlobular), bronchiectasis, and signs of disease in small airways (air trapping in expiratory scans, tree-in-bud pattern, centrilobular nodules). We also compared the number of lobes affected by bronchiectasis or emphysema.Variables with normal distribution were analyzed with the Student's t-test. Variables without normal distribution were studied with the Wilcoxon test. Categorical data were compared using Chi-square test or Fisher's exact test when necessary (SAS, version 8, significance with p<0.05).ResultsOf the 68 patients enrolled, 37 were being followed with a diagnosis of COPD and 31, of extensive bronchiectasis. Patients were diagnosed with COPD if they had chronic respiratory symptoms related to tobacco exposure of at least 10 pack-years (PY), had no history of previous respiratory disease before smoking and showed spirometric findings compatible with the disease; a patient was diagnosed with bronchiectasis if he/she had never smoked or had had a long history of chronic cough and sputum production which preceded the beginning of tobacco use, with the addition of abnormal findings on HRCT (>2 segments with bronchial dilatations).<a class="elsevierStyleCrossRef" href="#bib0105">21</a> The majority of non-smoker patients were diagnosed with bronchiectasis.Clinical features, spirometric findings and body composition of the two groups are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Among the group with the diagnosis of bronchiectasis, there were ten patients with atypical cystic fibrosis (adults, with late diagnosis and two abnormally elevated sweat chloride concentrations), two with residual lesions from tuberculosis, one with alpha-1-antitrypsin deficiency, one with a history of occupational exposure, and 18 of unknown etiology.Among 37 COPD patients the CT scans showed some type of emphysema in 29 (78.4%), and bronchiectasis in 18 (48.6%). In the group with the diagnosis of bronchiectasis, 27(87%) had bronchial dilation in more than three lobes and none were found to have emphysema on HRCT scans.Of 37 COPD patients, 30 were considered current smokers,<a class="elsevierStyleCrossRef" href="#bib0110">22</a> and seven, non-smokers (had never smoked or smoked less than 10 PY). Among the non-smokers, four had diffuse centrilobular emphysema; one patient reported a lifetime of passive smoking; and two patients had panlobular emphysema.Irrespective of the diagnosis of the COPD, smokers and non-smokers were compared based on their functional and radiological parameters (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). In spirometry, FVC and VC were found significantly smaller in non-smokers (p<0.001), and there was no significant difference between smokers and non-smokers in FEV1 and IC. In the assessment of BMI, MRC, SpO2 at rest, use of LTOT, 6MWD and bioimpedance findings there was no statistically significant difference between groups.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>HRCT scan findings associated smoking with the presence of centrilobular and paraseptal emphysema (p<0.001 and 0.017, respectively). More lobes were found with bronchiectasis in non-smokers (p<0.001) and more lobes with emphysema in smokers (p<0.001). The signs of small airways disease were more frequently found in non-smokers (p<0.001).20 patients met the ATS/ERS criteria for volume responders and 7, for flow responders; by Paré et al.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> 29 patients could be classified as volume responders and 4 patients were flow responders, respectively. Due to the low number of flow responders, only the characteristics of volume responders and non-responders were compared.There were 18 patients with FEV1<30% predicted among 29 volume responders and 12 patients with FEV1<30% predicted among 39 without volume response (p=0.010), identified by Paré et al.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> criteria.The analysis of the other clinical parameters, functional measurements, radiological findings and systemic repercussions showed no statistically significant difference between volume responders and non-responders, regardless of the criteria used.Patients were not compared by diagnosis, COPD or bronchiectasis.DiscussionWe included in this study patients with obstructive disease, defined by pre-BD FEV1/FVC<70%, and pre-BD FEV1<50% predicted, with the aim of evaluating severely ill patients. In the literature a European consensus<a class="elsevierStyleCrossRef" href="#bib0115">23</a> provides a precedent for our choice as well as relevant recent studies that have used this criteria.<a class="elsevierStyleCrossRefs" href="#bib0110">22,24,25</a>All subjects included in our study had a post-BD FEV1/FVC<70% and a post-BD FEV1<80% predicted, which is in accordance with GOLD diagnostic criteria for COPD.<a class="elsevierStyleCrossRef" href="#bib0130">26</a>Normal spirometry values following BD were an exclusion criterion and therefore asthmatic patients were not included. It was known beforehand that the two diseases that would show up in this series of patients would be COPD and bronchiectasis, which do have several characteristics in common, such as obstruction not fully reversible with BD.In our study, patients were considered smokers if they had smoked more than 10 PY.<a class="elsevierStyleCrossRef" href="#bib0110">22</a>The comparison of smokers and non-smokers with the same degree of lung function compromise (FEV1) showed that there were few differences between the groups. There was overlap in all clinical and functional parameters, except for VC and FVC which were significantly smaller in non-smokers. When systemic effects were assessed (BMI, the ratio LM/FM and 6MWT) smoking did not affect the results (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).On HRCT scans, signs of small airway disease were more frequently found in non-smokers (94.3% of the patients, p<0.001). This finding fits in with the hypothesis that bronchiolitis affecting the airways of under 2mm in diameter is a central event in the pathogenesis of bronchiectasis.<a class="elsevierStyleCrossRef" href="#bib0135">27</a>Signs of small airway involvement were also frequent in smokers and were found on HRCT scans in 57.6% of them.In 1950, Reid<a class="elsevierStyleCrossRef" href="#bib0135">27</a> published a cornerstone study on the pathology of extensive bronchiectasis. One of the most important findings was the reduction of bronchial subdivisions between the hilum and the periphery of the lung. The missing bronchi, whenever their remnants could be identified, were obliterated by fibrous tissue and all the generations of bronchi and small airways that should arise from them had completely disappeared.Hansell et al.<a class="elsevierStyleCrossRef" href="#bib0140">28</a> suggest that bronchiolitis is the initial lesion in bronchiectasis.Roberts et al.<a class="elsevierStyleCrossRef" href="#bib0105">21</a> evaluated the presence of airflow obstruction in 100 patients with bronchiectasis and also found that the presence and severity of airflow obstruction correlated with the intensity of mosaic attenuation detected on HRCT.In patients with clinical diagnosis of COPD in our study bronchiectasis was seen in the scans of 18 subjects (48.6%), a finding that is consistent with the literature in patients of equivalent severity of airway obstruction.<a class="elsevierStyleCrossRefs" href="#bib0145">29–31</a>Taking all this into account the hypothesis that smoking related chronic bronchitis and bronchiectasis share many pathogenic events is not farfetched. In fact, according to Boucher,<a class="elsevierStyleCrossRef" href="#bib0160">32</a> there are three well known causes of chronic bronchitis: two of them, cystic fibrosis and primary ciliary diskynesia, are genetically determined, and one is acquired after birth by those individuals who are susceptible, and is most commonly related to tobacco exposure. All three conditions compromise the mucociliary transport apparatus and during their course they all may lead to bronchiectasis.Considering the pattern of response to bronchodilator in patients with severe obstruction, an important finding was that using both criteria (ATS/ERS<a class="elsevierStyleCrossRef" href="#bib0090">18</a> and Paré et al.<a class="elsevierStyleCrossRef" href="#bib0095">19</a>) fewer individuals were considered volume responders by ATS/ERS criteria.What distinguishes Paré et al.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> criteria is the fact that they do not refer to absolute values; a variation of 12% in FVC and FEV1 is sufficient for the classification of an individual as a volume or flow responder. For patients like the ones in this study, with baseline volumes that are very low, “small” volume variation may represent a large variation in percentage, without reaching the 200ml required by ATS/ERS.<a class="elsevierStyleCrossRef" href="#bib0090">18</a>As expected, flow response was not significant in our sample of patients with severe bronchial obstruction.In addition to detecting a larger number of volume responder patients, Paré et al.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> criteria allowed the demonstration of an association between the severity of obstructive disease, as assessed by FEV1, and the volume response (18 patients with FEV1<30% among 29 volume responders and 12 patients with FEV1<30% among 39 without volume response, p=0.010).Schermer et al.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> analyzing BD response in 2210 COPD patients found a positive correlation between ΔFEV1 and ΔCVF with each stage: ΔFEV1 declined toward the most severe GOLD stages, while ΔCVF augmented. These findings are in agreement with ours, provided that Paré et al.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> criteria are applied to the sample.ConclusionsIn patients with severe obstruction the smoking etiology does not appear to be relevant in determining systemic complications such as hypoxemia, exercise capacity and loss of lean body mass. Bronchiectasis was found in a significant proportion of patients with severe COPD.Volume response is more common than flow response in patients with severe obstruction. The comparison of two criteria for assessing bronchodilator response showed that Paré et al. criteria are more sensitive than ATS/ERS criteria in identifying volume response in this subgroup of patients. Further studies with a larger number of patients might confirm our findings.Conflicts of interestThe authors have no conflicts of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:2 [ "identificador" => "xres547861" "titulo" => array:6 [ 0 => "Abstract" 1 => "Introduction" 2 => "Objectives" 3 => "Methods" 4 => "Results" 5 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec565729" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres547860" "titulo" => array:6 [ 0 => "Resumo" 1 => "Introdução" 2 => "Objetivos" 3 => "Métodos" 4 => "Resultados" 5 => "Conclusões" ] ] 3 => array:2 [ "identificador" => "xpalclavsec565730" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflicts of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2012-02-06" "fechaAceptado" => "2012-05-31" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec565729" "palabras" => array:6 [ 0 => "Airway obstruction" 1 => "Respiratory function tests" 2 => "Bronchitis" 3 => "Bronchiectasis" 4 => "Bronchodilator tests" 5 => "Computed tomography of the thorax" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec565730" "palabras" => array:6 [ 0 => "Obstrução das Vias Respiratórias" 1 => "Testes de Função Respiratória" 2 => "Bronquite" 3 => "Bronquiectasias" 4 => "Testes de Broncodilatador" 5 => "Tomografia de tórax" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "IntroductionPoorly reversible airflow obstruction may or may not be related to smoking. ObjectivesTo describe patients with severe obstructive lung disease including etiology, imaging, functional aspects, systemic manifestations, and the pattern of bronchodilator response. MethodsSixty-eight patients (age 55.9±13.7 years, FEV1 [forced expiratory volume in one second] 31.9±10.2% predicted) underwent spirometry, evaluation of body mass composition, 6-minute walk test, X-ray, thorax high-resolution CT scanning, and clinical evaluation. ResultsOf 68 patients enrolled, 37 had chronic obstructive pulmonary disease (COPD) and 31, extensive bronchiectasis. Among COPD patients the CT scans showed emphysema in 78.4%, and bronchiectasis in 48.6%. There were no significant differences between smokers and non-smokers, except for vital capacity, significantly smaller in non-smokers (p<0.001). We found 29 and 20 volume responders (VR) according to Paré et al. (FEV1/FVC>1=flow responder or <1=VR) and ATS/ERS criteria, respectively. According to Paré et al. criteria, there were 18 patients with FEV1<30% predicted among 29 VR, and 12 with FEV1<30% predicted among 39 without volume response (p=0.0101). ConclusionsIn patients with severe obstruction, smoking does not appear to be relevant in determining functional or systemic differences, and Paré et al. criteria can detect more VR. Bronchiectasis is a common finding in severe COPD." ] "pt" => array:2 [ "titulo" => "Resumo" "resumen" => "IntroduçãoA obstrução das vias respiratórias pouco reversível pode ou não estar relacionada com o tabagismo. ObjetivosDescrever pacientes com doença pulmonar obstrutiva grave, incluindo etiologia, aspectos dos exames de imagem, parâmetros funcionais, manifestações sistémicas, e o padrão da resposta ao broncodilatador. MétodosSessenta e oito pacientes (idades de 55,9±13,7 anos, FEV1 [volume expiratório forçado num segundo] 31,9±10,2% previsto) foram submetidos a espirometria, avaliação da composição de massa corporal, teste de caminhada de 6 minutos, radiografia, tomografia computorizadas (TAC) de alta resolução do tórax, e avaliação clínica. ResultadosDos 68 pacientes inscritos, 37 sofriam de doença pulmonar obstrutiva crónica (DPOC) e 31 de bronquiectasias extensa. Entre os pacientes com DPOC, as tomografias computadorizadas apresentaram enfisema em 78,4% e bronquietasias em 48,6%. Não existiram diferenças significativas entre os fumadores e os não-fumadores, exceto para a capacidade vital, significativamente inferior nos não-fumadores (p < 0,001). Encontramos 29 respondedores de volume (RV) pelos criterios de Paré et al. (VEF1/CVF > 1= respondedor de fluxo, se > 1 respondedor de volume), e 20 RV pelos criterios da ATS/ERS. De acordo com os critérios de Paré et al., existiam 18 pacientes com FEV1< 30% previsto entre os 29 RV, e 12 com FEV1 < 30% previsto entre os 39 sem resposta a uma prova de volume (p = 0,0101). ConclusõesEm pacientes com obstrução grave, o tabagismo não parece ser relevante na determinação de diferenças funcionais ou sistémicas, e os critérios de Paré et al. podem detetar mais RV. A bronquiectasias é uma descoberta comum em DPOC grave." ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "All data are expressed as mean±sd, except sex.BMI: body mass index; FVC: forced vital capacity; VC: slow vital capacity; FEV1: forced expiratory volume in one second; MM: mean mass." "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">All patients (n=68) \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">COPD patients (n=37) \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">Patients with bronchiectasis (n=31) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">55.9±13.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">59.8±10.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">51.3±15.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Sex (M/F) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30/38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16/21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14/17 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">BMI (kg/m2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24.0±5.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24.6±5.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23.2±4.69 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">FVC (% predicted) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">53.4±15.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">57.0±15.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">49.1±14.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">VC (% predicted) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">59.2±17.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">65.1±17.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">52.1±14.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">FVC (L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.82±0.79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.91±0.74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.71±0.84 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">FEV1 (% predicted) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">31.9±10.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30.2±9.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">34±10.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">FEV1 (L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.96±0.39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.80±0.38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.93±0.41 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Smoking (pack-years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23.1±34.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40.7±38.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.1±4.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">MM (% predicted) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">89.4±10.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">89.9±10.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">88.9±10.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab884888.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Clinical features, spirometric findings and body composition of patients." ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "FEV1: forced expiratory volume in 1s; FVC: forced vital capacity; VC: slow vital capacity; IC: inspiratory capacity." "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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables \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">Non-smokers (n=35) \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">Smokers (n=33) \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 \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">FEV1<30% predicted \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13/35 (37.1%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17/33 (51.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.2329 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Mean FVC in % predicted±sd \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">47.3±13.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">59.9±14.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Mean VC in % predicted±sd \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">51.5±13.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">67.3±17.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">IC<80% predicted \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25/35 (71.4%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21/33 (63.6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.4924 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Flattened diaphragm (lateral radiographs)<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12/32 (37.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16/25 (64%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.047 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Centrilobular emphysema<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5/35 (14.3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25/32 (78.1%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Paraseptal emphysema<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6/35 (17.1%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14/32 (43.7%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.017 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Presence of bronchiectasis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">33/35 (94.3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16/33 (48.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Air trapping or tree in bud or centrilobular nodules<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">33/35 (94.3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">19/33 (57.6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Median number of lobes with emphysema<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.0 (n=35) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.0 (n=31) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Median number of lobes with bronchiectasis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.0 (n=35) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.0 (n=33) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab884887.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "The results indicate the presence of the finding in the group analyzed. The n varies because some radiological techniques for evaluating the signal were inadequate." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "In expiratory HRCT cuts were not performed in all patients." ] ] ] "descripcion" => array:1 [ "en" => "Comparison between non-smokers and smokers." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:32 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The natural history of chronic airflow obstruction revisited. An analysis of the Framingham offspring cohort" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "R. Kohansal" 1 => "P. Martinez-Camblor" 2 => "A. Agustí" 3 => "A.S. Buist" 4 => "D.M. Mannino" 5 => "J.B. 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Original article

Severe obstructive disease: Similarities and differences between smoker and non-smoker patients with COPD and/or bronchiectasis

Doença obstrutiva grave: semelhanças e diferenças entre os pacientes fumadores e não-fumadores com DPOC e/ou bronquiectasias

J. Rezende Gonçalvesa, M. Corso Pereirab, E.M. Figueiras Pedreira De Cerqueiraa, D. Oliveira Magrob, M. Mello Moreirab, I.A. Paschoalb,

Corresponding author

ilma@fcm.unicamp.br

Corresponding author.

a Master, University of Campinas – UNICAMP, Campinas, SP, Brazil

b PhD, University of Campinas – UNICAMP, Campinas, SP, Brazil

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">It is quite clear nowadays that the most frequent cause of chronic and progressive airway disease that leads to chronic respiratory failure is Chronic Obstructive Pulmonary Disease &#40;COPD&#41; related to tobacco use&#46; COPD is diagnosed if poorly reversible airflow obstruction can be demonstrated by spirometry and the exposure to noxious gases is present&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Poorly reversible airflow obstruction is not confined to smokers&#46; Kohansal et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> in a study about the natural history of chronic airflow obstruction&#44; analyzed the Framingham Offspring cohort&#44; who were followed for 23 years&#46; One third of the individuals&#44; who continued to smoke&#44; developed airflow obstruction during follow-up&#46; But so did 7&#46;4&#37; of never-smoker males and 5&#46;6&#37; of never-smoker females&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The classic work of Fletcher et al&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> on the natural history of COPD did not include non-smokers and therefore provides no information about the subjects who do not smoke but do have chronic airflow obstruction&#46; In the United States&#44; 20&#37; of the patients who have obstruction in spirometry and 20&#37; of those who die of COPD are non-smokers&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#8211;6</span></a> Few studies have been performed in this group and little is known about its natural history and clinical course&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Mucus hypersecretion&#44; one of the classic features of COPD&#44; is associated with exacerbations and both situations are related to progressive loss of airflow&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">On the other hand&#44; patients with hypersecretion unrelated to COPD may present functional and clinical pictures that overlap with chronic bronchitis associated with smoking&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In addition to the symptoms and the spirometric changes&#44; other similarities may exist between COPD and bronchiectasis from various causes&#58; the predominant neutrophilic inflammation&#44;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> the pattern of response to bronchodilators &#40;BD&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#8211;13</span></a> and the findings on imaging studies&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Having taken this previous data into account we decided to investigate the hypothesis that there are more similarities than differences among patients with severe chronic bronchial disease&#44; regardless of whether they have smoking related COPD or bronchiectasis due to other causes&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Methods</span><p id="par0040" class="elsevierStylePara elsevierViewall">Patients who attended our referral outpatient clinic for chronic respiratory failure and whose spirometry showed a pre-BD FEV<span class="elsevierStyleInf">1</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>50&#37; of predicted&#44; and FEV<span class="elsevierStyleInf">1</span>&#47;CVF<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>70&#37; were invited to participate in this study&#46; We excluded patients with neuromuscular diseases&#44; thoracic deformities&#44; restrictive lung diseases&#44; pulmonary vascular disease and those who had undergone lung resection&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The study was approved by the Ethics Research Committee of our institution and all participants signed an informed consent form&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Clinical data were gathered from patient files&#46; To assess the degree of breathlessness we used the British MRC &#40;Medical Research Council&#41; questionnaire&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> All patients underwent spirometry before and after the use of formoterol 12<span class="elsevierStyleHsp" style=""></span>mcg &#40;Foradil<span class="elsevierStyleSup">&#174;</span>&#44; Novartis&#44; Brazil&#41;&#46; Forced vital capacity &#40;FVC&#41; and slow vital capacity &#40;VC&#41; curves were performed using a flow spirometer &#40;MicroQuark&#59; COSMED SRL&#44; Rome&#44; Italy&#41; with Brazilian reference values&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> The six-minute walk test &#40;6MWT&#41; was performed by the patients who had pulse oxymetry &#40;SpO<span class="elsevierStyleInf">2</span>&#41; above 90&#37; at rest and the procedure followed that proposed by ATS&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Body mass index &#40;BMI&#41; was determined and the body composition was assessed by the bioimpedance technique &#40;Biodynamics 310&#44; Seattle&#44; WA&#44; USA&#41;&#46; All tests were conducted during periods of clinical stability&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">To analyze the data we first compared smokers and non-smokers and secondly we identified two groups according to the pattern of response to BD on spirometry&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">When comparing smokers and non-smokers we set parameters and cutoff values for each variable&#58; BMI<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>21<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#44;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;17</span></a> MRC<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>1&#44;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> resting SpO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>90&#37;&#44; use of long-term oxygen therapy &#40;LTOT&#41;&#44; FEV<span class="elsevierStyleInf">1</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>30&#37; of predicted&#44; inspiratory capacity &#40;IC&#41;<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>80&#37; predicted&#44; 6MWD<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>350<span class="elsevierStyleHsp" style=""></span>m&#44;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> and a drop in SpO<span class="elsevierStyleInf">2</span> during the 6MWT &#40;SpO<span class="elsevierStyleInf">2</span> final&#8211;initial&#41;<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>4&#37;&#44; which were considered signs of greater severity&#46; For numerical variables &#91;FVC&#44; VC&#44; LM &#40;lean mass&#41; in &#37; of predicted&#44; and lean-to-fat body mass ratio &#40;LM&#47;FM&#41;&#93;&#44; we calculated the mean and median of the two groups&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">For the analysis of BD response we compared two criteria&#58; ATS&#47;ERS &#91;volume response &#40;FVC&#41; or flow response &#40;FEV<span class="elsevierStyleInf">1</span>&#41; 200<span class="elsevierStyleHsp" style=""></span>ml and 12&#37;&#93;&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> and the parameters used in the study of Par&#233; et al&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> which were applied only when the increase in FEV<span class="elsevierStyleInf">1</span> or FVC post-BD was at least 12&#37;&#46; According to Par&#233; et al&#46; the volume response is reflected by the presence of &#916;FEV<span class="elsevierStyleInf">1</span>&#47;&#916;CVF<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>1&#44; and flow response&#44; &#916;FEV<span class="elsevierStyleInf">1</span>&#47;&#916;CVF<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>1&#44; where &#916; means the &#40;post-BD<span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>pre-BD&#41; value&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">HRCT of the thorax was performed &#40;sections 1&#46;5&#8211;2<span class="elsevierStyleHsp" style=""></span>mm thick&#44; 10<span class="elsevierStyleHsp" style=""></span>mm intervals&#44; at maximum inspiration and expiration&#41;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> and the following CT findings were analyzed&#58; presence of emphysema &#40;centrilobular&#44; paraseptal and panlobular&#41;&#44; bronchiectasis&#44; and signs of disease in small airways &#40;air trapping in expiratory scans&#44; tree-in-bud pattern&#44; centrilobular nodules&#41;&#46; We also compared the number of lobes affected by bronchiectasis or emphysema&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Variables with normal distribution were analyzed with the Student&#39;s <span class="elsevierStyleItalic">t</span>-test&#46; Variables without normal distribution were studied with the Wilcoxon test&#46; Categorical data were compared using Chi-square test or Fisher&#39;s exact test when necessary &#40;SAS&#44; version 8&#44; significance with <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Results</span><p id="par0080" class="elsevierStylePara elsevierViewall">Of the 68 patients enrolled&#44; 37 were being followed with a diagnosis of COPD and 31&#44; of extensive bronchiectasis&#46; Patients were diagnosed with COPD if they had chronic respiratory symptoms related to tobacco exposure of at least 10 pack-years &#40;PY&#41;&#44; had no history of previous respiratory disease before smoking and showed spirometric findings compatible with the disease&#59; a patient was diagnosed with bronchiectasis if he&#47;she had never smoked or had had a long history of chronic cough and sputum production which preceded the beginning of tobacco use&#44; with the addition of abnormal findings on HRCT &#40;&#62;2 segments with bronchial dilatations&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> The majority of non-smoker patients were diagnosed with bronchiectasis&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Clinical features&#44; spirometric findings and body composition of the two groups are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">Among the group with the diagnosis of bronchiectasis&#44; there were ten patients with atypical cystic fibrosis &#40;adults&#44; with late diagnosis and two abnormally elevated sweat chloride concentrations&#41;&#44; two with residual lesions from tuberculosis&#44; one with alpha-1-antitrypsin deficiency&#44; one with a history of occupational exposure&#44; and 18 of unknown etiology&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Among 37 COPD patients the CT scans showed some type of emphysema in 29 &#40;78&#46;4&#37;&#41;&#44; and bronchiectasis in 18 &#40;48&#46;6&#37;&#41;&#46; In the group with the diagnosis of bronchiectasis&#44; 27&#40;87&#37;&#41; had bronchial dilation in more than three lobes and none were found to have emphysema on HRCT scans&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Of 37 COPD patients&#44; 30 were considered current smokers&#44;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> and seven&#44; non-smokers &#40;had never smoked or smoked less than 10 PY&#41;&#46; Among the non-smokers&#44; four had diffuse centrilobular emphysema&#59; one patient reported a lifetime of passive smoking&#59; and two patients had panlobular emphysema&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Irrespective of the diagnosis of the COPD&#44; smokers and non-smokers were compared based on their functional and radiological parameters &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; In spirometry&#44; FVC and VC were found significantly smaller in non-smokers &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; and there was no significant difference between smokers and non-smokers in FEV<span class="elsevierStyleInf">1</span> and IC&#46; In the assessment of BMI&#44; MRC&#44; SpO<span class="elsevierStyleInf">2</span> at rest&#44; use of LTOT&#44; 6MWD and bioimpedance findings there was no statistically significant difference between groups&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">HRCT scan findings associated smoking with the presence of centrilobular and paraseptal emphysema &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001 and 0&#46;017&#44; respectively&#41;&#46; More lobes were found with bronchiectasis in non-smokers &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and more lobes with emphysema in smokers &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; The signs of small airways disease were more frequently found in non-smokers &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">20 patients met the ATS&#47;ERS criteria for volume responders and 7&#44; for flow responders&#59; by Par&#233; et al&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> 29 patients could be classified as volume responders and 4 patients were flow responders&#44; respectively&#46; Due to the low number of flow responders&#44; only the characteristics of volume responders and non-responders were compared&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">There were 18 patients with FEV<span class="elsevierStyleInf">1</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>30&#37; predicted among 29 volume responders and 12 patients with FEV<span class="elsevierStyleInf">1</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>30&#37; predicted among 39 without volume response &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;010&#41;&#44; identified by Par&#233; et al&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> criteria&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">The analysis of the other clinical parameters&#44; functional measurements&#44; radiological findings and systemic repercussions showed no statistically significant difference between volume responders and non-responders&#44; regardless of the criteria used&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Patients were not compared by diagnosis&#44; COPD or bronchiectasis&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0135" class="elsevierStylePara elsevierViewall">We included in this study patients with obstructive disease&#44; defined by pre-BD FEV<span class="elsevierStyleInf">1</span>&#47;FVC<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>70&#37;&#44; and pre-BD FEV<span class="elsevierStyleInf">1</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>50&#37; predicted&#44; with the aim of evaluating severely ill patients&#46; In the literature a European consensus<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> provides a precedent for our choice as well as relevant recent studies that have used this criteria&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;24&#44;25</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">All subjects included in our study had a post-BD FEV<span class="elsevierStyleInf">1</span>&#47;FVC<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>70&#37; and a post-BD FEV<span class="elsevierStyleInf">1</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>80&#37; predicted&#44; which is in accordance with GOLD diagnostic criteria for COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Normal spirometry values following BD were an exclusion criterion and therefore asthmatic patients were not included&#46; It was known beforehand that the two diseases that would show up in this series of patients would be COPD and bronchiectasis&#44; which do have several characteristics in common&#44; such as obstruction not fully reversible with BD&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">In our study&#44; patients were considered smokers if they had smoked more than 10 PY&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">The comparison of smokers and non-smokers with the same degree of lung function compromise &#40;FEV<span class="elsevierStyleInf">1</span>&#41; showed that there were few differences between the groups&#46; There was overlap in all clinical and functional parameters&#44; except for VC and FVC which were significantly smaller in non-smokers&#46; When systemic effects were assessed &#40;BMI&#44; the ratio LM&#47;FM and 6MWT&#41; smoking did not affect the results &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">On HRCT scans&#44; signs of small airway disease were more frequently found in non-smokers &#40;94&#46;3&#37; of the patients&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; This finding fits in with the hypothesis that bronchiolitis affecting the airways of under 2<span class="elsevierStyleHsp" style=""></span>mm in diameter is a central event in the pathogenesis of bronchiectasis&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">Signs of small airway involvement were also frequent in smokers and were found on HRCT scans in 57&#46;6&#37; of them&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">In 1950&#44; Reid<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> published a cornerstone study on the pathology of extensive bronchiectasis&#46; One of the most important findings was the reduction of bronchial subdivisions between the hilum and the periphery of the lung&#46; The missing bronchi&#44; whenever their remnants could be identified&#44; were obliterated by fibrous tissue and all the generations of bronchi and small airways that should arise from them had completely disappeared&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Hansell et al&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> suggest that bronchiolitis is the initial lesion in bronchiectasis&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Roberts et al&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> evaluated the presence of airflow obstruction in 100 patients with bronchiectasis and also found that the presence and severity of airflow obstruction correlated with the intensity of mosaic attenuation detected on HRCT&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">In patients with clinical diagnosis of COPD in our study bronchiectasis was seen in the scans of 18 subjects &#40;48&#46;6&#37;&#41;&#44; a finding that is consistent with the literature in patients of equivalent severity of airway obstruction&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29&#8211;31</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">Taking all this into account the hypothesis that smoking related chronic bronchitis and bronchiectasis share many pathogenic events is not farfetched&#46; In fact&#44; according to Boucher&#44;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> there are three well known causes of chronic bronchitis&#58; two of them&#44; cystic fibrosis and primary ciliary diskynesia&#44; are genetically determined&#44; and one is acquired after birth by those individuals who are susceptible&#44; and is most commonly related to tobacco exposure&#46; All three conditions compromise the mucociliary transport apparatus and during their course they all may lead to bronchiectasis&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Considering the pattern of response to bronchodilator in patients with severe obstruction&#44; an important finding was that using both criteria &#40;ATS&#47;ERS<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> and Par&#233; et al&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#41; fewer individuals were considered volume responders by ATS&#47;ERS criteria&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">What distinguishes Par&#233; et al&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> criteria is the fact that they do not refer to absolute values&#59; a variation of 12&#37; in FVC and FEV<span class="elsevierStyleInf">1</span> is sufficient for the classification of an individual as a volume or flow responder&#46; For patients like the ones in this study&#44; with baseline volumes that are very low&#44; &#8220;small&#8221; volume variation may represent a large variation in percentage&#44; without reaching the 200<span class="elsevierStyleHsp" style=""></span>ml required by ATS&#47;ERS&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">As expected&#44; flow response was not significant in our sample of patients with severe bronchial obstruction&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">In addition to detecting a larger number of volume responder patients&#44; Par&#233; et al&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> criteria allowed the demonstration of an association between the severity of obstructive disease&#44; as assessed by FEV<span class="elsevierStyleInf">1</span>&#44; and the volume response &#40;18 patients with FEV<span class="elsevierStyleInf">1</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>30&#37; among 29 volume responders and 12 patients with FEV<span class="elsevierStyleInf">1</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>30&#37; among 39 without volume response&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;010&#41;&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">Schermer et al&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> analyzing BD response in 2210 COPD patients found a positive correlation between &#916;FEV<span class="elsevierStyleInf">1</span> and &#916;CVF with each stage&#58; &#916;FEV<span class="elsevierStyleInf">1</span> declined toward the most severe GOLD stages&#44; while &#916;CVF augmented&#46; These findings are in agreement with ours&#44; provided that Par&#233; et al&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> criteria are applied to the sample&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conclusions</span><p id="par0220" class="elsevierStylePara elsevierViewall">In patients with severe obstruction the smoking etiology does not appear to be relevant in determining systemic complications such as hypoxemia&#44; exercise capacity and loss of lean body mass&#46; Bronchiectasis was found in a significant proportion of patients with severe COPD&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">Volume response is more common than flow response in patients with severe obstruction&#46; The comparison of two criteria for assessing bronchodilator response showed that Par&#233; et al&#46; criteria are more sensitive than ATS&#47;ERS criteria in identifying volume response in this subgroup of patients&#46; Further studies with a larger number of patients might confirm our findings&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of interest</span><p id="par0230" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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        8 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Conclusions"
        ]
        9 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Conflicts of interest"
        ]
        10 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2012-02-06"
    "fechaAceptado" => "2012-05-31"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec565729"
          "palabras" => array:6 [
            0 => "Airway obstruction"
            1 => "Respiratory function tests"
            2 => "Bronchitis"
            3 => "Bronchiectasis"
            4 => "Bronchodilator tests"
            5 => "Computed tomography of the thorax"
          ]
        ]
      ]
      "pt" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palavras-chave"
          "identificador" => "xpalclavsec565730"
          "palabras" => array:6 [
            0 => "Obstru&#231;&#227;o das Vias Respirat&#243;rias"
            1 => "Testes de Fun&#231;&#227;o Respirat&#243;ria"
            2 => "Bronquite"
            3 => "Bronquiectasias"
            4 => "Testes de Broncodilatador"
            5 => "Tomografia de t&#243;rax"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span><span class="elsevierStyleSectionTitle">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Poorly reversible airflow obstruction may or may not be related to smoking&#46;</p></span> <span><span class="elsevierStyleSectionTitle">Objectives</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To describe patients with severe obstructive lung disease including etiology&#44; imaging&#44; functional aspects&#44; systemic manifestations&#44; and the pattern of bronchodilator response&#46;</p></span> <span><span class="elsevierStyleSectionTitle">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Sixty-eight patients &#40;age 55&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;7 years&#44; FEV<span class="elsevierStyleInf">1</span> &#91;forced expiratory volume in one second&#93; 31&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;2&#37; predicted&#41; underwent spirometry&#44; evaluation of body mass composition&#44; 6-minute walk test&#44; X-ray&#44; thorax high-resolution CT scanning&#44; and clinical evaluation&#46;</p></span> <span><span class="elsevierStyleSectionTitle">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Of 68 patients enrolled&#44; 37 had chronic obstructive pulmonary disease &#40;COPD&#41; and 31&#44; extensive bronchiectasis&#46; Among COPD patients the CT scans showed emphysema in 78&#46;4&#37;&#44; and bronchiectasis in 48&#46;6&#37;&#46; There were no significant differences between smokers and non-smokers&#44; except for vital capacity&#44; significantly smaller in non-smokers &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; We found 29 and 20 volume responders &#40;VR&#41; according to Par&#233; et al&#46; &#40;FEV<span class="elsevierStyleInf">1</span>&#47;FVC<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>flow responder or &#60;1<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>VR&#41; and ATS&#47;ERS criteria&#44; respectively&#46; According to Par&#233; et al&#46; criteria&#44; there were 18 patients with FEV<span class="elsevierStyleInf">1</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>30&#37; predicted among 29 VR&#44; and 12 with FEV<span class="elsevierStyleInf">1</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>30&#37; predicted among 39 without volume response &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0101&#41;&#46;</p></span> <span><span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">In patients with severe obstruction&#44; smoking does not appear to be relevant in determining functional or systemic differences&#44; and Par&#233; et al&#46; criteria can detect more VR&#46; Bronchiectasis is a common finding in severe COPD&#46;</p></span>"
      ]
      "pt" => array:2 [
        "titulo" => "Resumo"
        "resumen" => "<span><span class="elsevierStyleSectionTitle">Introdu&#231;&#227;o</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A obstru&#231;&#227;o das vias respirat&#243;rias pouco revers&#237;vel pode ou n&#227;o estar relacionada com o tabagismo&#46;</p></span> <span><span class="elsevierStyleSectionTitle">Objetivos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Descrever pacientes com doen&#231;a pulmonar obstrutiva grave&#44; incluindo etiologia&#44; aspectos dos exames de imagem&#44; par&#226;metros funcionais&#44; manifesta&#231;&#245;es sist&#233;micas&#44; e o padr&#227;o da resposta ao broncodilatador&#46;</p></span> <span><span class="elsevierStyleSectionTitle">M&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Sessenta e oito pacientes &#40;idades de 55&#44;9&#177;13&#44;7 anos&#44; FEV<span class="elsevierStyleInf">1</span> &#91;volume expirat&#243;rio for&#231;ado num segundo&#93; 31&#44;9&#177;10&#44;2&#37; previsto&#41; foram submetidos a espirometria&#44; avalia&#231;&#227;o da composi&#231;&#227;o de massa corporal&#44; teste de caminhada de 6 minutos&#44; radiografia&#44; tomografia computorizadas &#40;TAC&#41; de alta resolu&#231;&#227;o do t&#243;rax&#44; e avalia&#231;&#227;o cl&#237;nica&#46;</p></span> <span><span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Dos 68 pacientes inscritos&#44; 37 sofriam de doen&#231;a pulmonar obstrutiva cr&#243;nica &#40;DPOC&#41; e 31 de bronquiectasias extensa&#46; Entre os pacientes com DPOC&#44; as tomografias computadorizadas apresentaram enfisema em 78&#44;4&#37; e bronquietasias em 48&#44;6&#37;&#46; N&#227;o existiram diferen&#231;as significativas entre os fumadores e os n&#227;o-fumadores&#44; exceto para a capacidade vital&#44; significativamente inferior nos n&#227;o-fumadores &#40;p &#60; 0&#44;001&#41;&#46; Encontramos 29 respondedores de volume &#40;RV&#41; pelos criterios de Par&#233; et al&#46; &#40;VEF1&#47;CVF &#62; 1&#61; respondedor de fluxo&#44; se &#62; 1 respondedor de volume&#41;&#44; e 20 RV pelos criterios da ATS&#47;ERS&#46; De acordo com os crit&#233;rios de Par&#233; et al&#46;&#44; existiam 18 pacientes com FEV<span class="elsevierStyleInf">1</span>&#60; 30&#37; previsto entre os 29 RV&#44; e 12 com FEV<span class="elsevierStyleInf">1</span> &#60; 30&#37; previsto entre os 39 sem resposta a uma prova de volume &#40;p &#61; 0&#44;0101&#41;&#46;</p></span> <span><span class="elsevierStyleSectionTitle">Conclus&#245;es</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Em pacientes com obstru&#231;&#227;o grave&#44; o tabagismo n&#227;o parece ser relevante na determina&#231;&#227;o de diferen&#231;as funcionais ou sist&#233;micas&#44; e os crit&#233;rios de Par&#233; et al&#46; podem detetar mais RV&#46; A bronquiectasias &#233; uma descoberta comum em DPOC grave&#46;</p></span>"
      ]
    ]
    "multimedia" => array:2 [
      0 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">All data are expressed as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>sd&#44; except sex&#46;</p><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">BMI&#58; body mass index&#59; FVC&#58; forced vital capacity&#59; VC&#58; slow vital capacity&#59; FEV1&#58; forced expiratory volume in one second&#59; MM&#58; mean mass&#46;</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">&nbsp;\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">All patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>68&#41;&nbsp;\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">COPD patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>37&#41;&nbsp;\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">Patients with bronchiectasis &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>31&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">55&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">59&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">51&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Sex &#40;M&#47;F&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30&#47;38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16&#47;21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&#47;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">BMI &#40;kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;69&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">FVC &#40;&#37; predicted&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">53&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">57&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">49&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">VC &#40;&#37; predicted&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">59&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">65&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">52&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">FVC &#40;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;82<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;91<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;74&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;71<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">FEV<span class="elsevierStyleInf">1</span> &#40;&#37; predicted&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">31&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">34<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">FEV<span class="elsevierStyleInf">1</span> &#40;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;96<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;80<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;93<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Smoking &#40;pack-years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>34&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">40&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>38&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">MM &#40;&#37; predicted&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">89&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">89&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">88&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Clinical features&#44; spirometric findings and body composition of patients&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">FEV1&#58; forced expiratory volume in 1<span class="elsevierStyleHsp" style=""></span>s&#59; FVC&#58; forced vital capacity&#59; VC&#58; slow vital capacity&#59; IC&#58; inspiratory capacity&#46;</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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables&nbsp;\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">Non-smokers &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>35&#41;&nbsp;\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">Smokers &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>33&#41;&nbsp;\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"><span class="elsevierStyleItalic">P</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">FEV<span class="elsevierStyleInf">1</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>30&#37; predicted&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13&#47;35 &#40;37&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17&#47;33 &#40;51&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;2329&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Mean FVC in &#37; predicted<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>sd&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">47&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;5&nbsp;\t\t\t\t\t\t\n
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Article information

ISSN: 08732159
Original language: English

DOI:10.1016/j.rppneu.2012.05.003

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	9	9	18
2024 October	45	27	72
2024 September	51	20	71
2024 August	72	31	103
2024 July	35	29	64
2024 June	24	21	45
2024 May	33	25	58
2024 April	43	40	83
2024 March	39	18	57
2024 February	34	22	56
2024 January	21	28	49
2023 December	20	17	37
2023 November	32	32	64
2023 October	30	32	62
2023 September	22	29	51
2023 August	29	23	52
2023 July	27	24	51
2023 June	23	14	37
2023 May	35	21	56
2023 April	31	20	51
2023 March	61	23	84
2023 February	42	19	61
2023 January	25	28	53
2022 December	53	24	77
2022 November	48	36	84
2022 October	60	33	93
2022 September	21	34	55
2022 August	31	36	67
2022 July	29	38	67
2022 June	25	27	52
2022 May	35	34	69
2022 April	23	29	52
2022 March	25	47	72
2022 February	29	37	66
2022 January	41	42	83
2021 December	29	35	64
2021 November	36	32	68
2021 October	34	36	70
2021 September	31	32	63
2021 August	23	21	44
2021 July	34	23	57
2021 June	24	15	39
2021 May	42	32	74
2021 April	38	63	101
2021 March	92	14	106
2021 February	64	22	86
2021 January	28	18	46
2020 December	53	11	64
2020 November	47	18	65
2020 October	26	20	46
2020 September	73	17	90
2020 August	67	26	93
2020 July	87	19	106
2020 June	72	12	84
2020 May	100	27	127
2020 April	82	9	91
2020 March	62	15	77
2020 February	63	15	78
2020 January	80	13	93
2019 December	73	20	93
2019 November	97	13	110
2019 October	87	13	100
2019 September	85	20	105
2019 August	188	20	208
2019 July	203	17	220
2019 June	220	17	237
2019 May	251	11	262
2019 April	248	25	273
2019 March	248	13	261
2019 February	204	10	214
2019 January	224	25	249
2018 December	124	6	130
2018 November	36	0	36
2018 October	76	9	85
2018 September	57	8	65
2018 August	72	9	81
2018 July	77	41	118
2018 June	65	16	81
2018 May	96	14	110
2018 April	136	35	171
2018 March	171	19	190
2018 February	94	8	102
2018 January	165	21	186
2017 December	172	14	186
2017 November	83	26	109
2017 October	39	26	65
2017 September	60	29	89
2017 August	37	23	60
2017 July	43	22	65
2017 June	30	17	47
2017 May	34	11	45
2017 April	10	1	11
2017 March	21	4	25
2017 February	20	10	30
2017 January	10	3	13
2016 December	21	14	35
2016 November	20	11	31
2016 October	30	14	44
2016 September	14	4	18
2016 August	5	2	7
2016 July	7	5	12
2016 May	20	0	20
2016 April	43	1	44
2016 March	74	12	86
2016 February	83	16	99
2016 January	58	12	70
2015 December	59	5	64
2015 November	69	8	77
2015 October	96	10	106
2015 September	96	12	108
2015 August	74	4	78
2015 July	87	9	96
2015 June	88	8	96
2015 May	88	5	93
2015 April	137	11	148
2015 March	129	2	131
2015 February	131	6	137
2015 January	129	9	138
2014 December	135	13	148
2014 November	134	10	144
2014 October	254	18	272
2014 September	262	7	269
2014 August	240	17	257
2014 July	266	17	283
2014 June	220	9	229
2014 May	195	16	211
2014 April	172	17	189
2014 March	217	16	233
2014 February	207	24	231
2014 January	258	14	272
2013 December	222	15	237
2013 November	336	16	352
2013 October	286	25	311
2013 September	189	26	215
2013 August	136	20	156
2013 July	158	41	199
2013 June	126	25	151
2013 May	109	35	144
2013 April	100	55	155
2013 March	89	51	140
2013 February	97	46	143
2013 January	112	39	151

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