The Relation of CFTR-Genotype and Associated Comorbidities to Development of Pulmonary Atelectasis in Cystic Fibrosis Patients

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Martin" "apellidos" => "de Vicente" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "h" "identificador" => "aff0040" ] ] ] 10 => array:3 [ "nombre" => "J." "apellidos" => "Costa Colomer" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "i" "identificador" => "aff0045" ] ] ] 11 => array:3 [ "nombre" => "R." "apellidos" => "Álvarez-Sala Walther" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 12 => array:2 [ "colaborador" => "the Spanish Working Group Atelectasis in CF" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "1" "identificador" => "fn0005" ] ] ] ] "afiliaciones" => array:9 [ 0 => array:3 [ "entidad" => "Cystic Fibrosis Unit, Department of Pulmonology, La Paz University Hospital, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Cystic Fibrosis Unit, Department of Pulmonology, Virgen del Rocio University Hospital, Sevilla, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Cystic Fibrosis Unit, Department of Pediatrics, Clinic Hospital, Valencia, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Cystic Fibrosis Unit, Department of Pediatrics, Niño Jesus Hospital, Madrid, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Cystic Fibrosis Unit, Department of Pulmonology, La Princesa University Hospital, Madrid, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Cystic Fibrosis Unit, Department of Pulmonology, Doce de Octubre University Hospital, Madrid, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Cystic Fibrosis Unit, Department of Pulmonology, Ramón y Cajal University Hospital, Madrid, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Cystic Fibrosis Unit, Department of Pediatrics, Miguel Servet Hospital, Zaragoza, Spain" "etiqueta" => "h" "identificador" => "aff0040" ] 8 => array:3 [ "entidad" => "Cystic Fibrosis Unit, Department of Pediatrics, Sant Joan de Dêu, Barcelona, Spain" "etiqueta" => "i" "identificador" => "aff0045" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "textoCompleto" => "Cystic fibrosis (CF) is the most frequent life-threatening autosomal recessive disease in Caucasians. In Spain, close to 50% are heterozygous, while 28% are homozygous for F508del (Phe.508.del).<a class="elsevierStyleCrossRef" href="#bib0105">1</a> Respiratory complications produce highest morbidity and mortality in CF patients and represent approximately 62.53% of total deaths according to the European Registry 2019.<a class="elsevierStyleCrossRef" href="#bib0105">1</a> Among these complications, atelectasias have received the least scientific attention and little medical literature addresses this complication. The estimated incidence scatters around 4–11%, being less frequent the segmental atelectasis (0.81%).<a class="elsevierStyleCrossRefs" href="#bib0110">2–4</a>No international consensus on atelectasis etiology, prognosis or treatment has been elaborated.<a class="elsevierStyleCrossRefs" href="#bib0125">5–7</a> Its etiology could be secondary to either mucus plugs<a class="elsevierStyleCrossRefs" href="#bib0140">8,9</a> or serious affectations of the pulmonary parenchyma in which, the progressive and irreversible damage of the airway would cause distortion, obstruction and bronchial dilatations.<a class="elsevierStyleCrossRefs" href="#bib0125">5,8,10,11</a> Its severity ranges from asymptomatic to major complications, depending on various unkown factors.Considering the scarcity of published works on atelectasis in CF, we have proposed to analyze whether genetics, certain CF typical respiratory of this complication and other comorbidities are associated to development of this complication.All cases of diagnosed stable CF children and adults (≥ 18 years) who suffered persistent atelectasis as a pulmonary complication, diagnosed by image techniques, with at least a two-year-follow-up of the patient after the first episode were included until December 2017 (named as cases), and in which the study variables could have been collected. Likewise, age and gender-matched control patients were enrolled (date of birth of ±three years).The following variables were assessed: CFTR-mutations (dividing them into homozygotes and heterozygotes for F508del (Phe.508del) mutation, F508del (Phe.508del) mutation with one allele pending sequencing and other different mutations), pulmonary complication such as ABPA,<a class="elsevierStyleCrossRef" href="#bib0160">12</a> hemoptysis, pneumothorax and chronic bronchial infection (CBI) before the episode of atelectasis or, as in the case of CBI, at the time of the pulmonary collapse was described, and other comorbidities related to the disease, including pancreatic insufficiency and CF-related diabetes (CFRD). We also collected pulmonary function at the time of collapse (basal), and the last one registered, and the annual decline, in both groups.The study has been approved by the Research Ethics Committee of the University La Paz University Hospital in Madrid, Spain (PI-2130). Patients were not involved.For the statistical analysis, the SPSS program, version 13, was used. The data were expressed as mean plus standard deviation or percentage of the variable. The comparison of independent quantitative variables was performed by the Mann–Whitney test, the quantitative repeated variables by the Wilcoxon test and the qualitative variables by the Chi-square test.p<0.05 was considered significant.Among a total population of 969 patients with CF attended in the included CF centers, 38 patients (3.9%), with a mean age at diagnosis of atelectasis of 20.05±12.67 years, suffered at least one episode of atelectasis. Of the 38 patients, 23 were women (60.5%), with a mean age of 24.58±11.9 years. Among the 39 controls, 26 were women (66.7%), with a mean age of 25.08±11.84 years. The pulmonary functional data are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. No significant demographic differences were identified, as well as in mutations or comorbidities (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>In contrast, comparing both groups, we found significant differences regarding pulmonary function both in the basal study data collection and in the last one. There was no significant decline of pulmonary function per year between groups (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).Remarkably, a significantly elevated frequency of atelectasis was identified in patients with history of ABPA in relation to control group (23.7% vs 2.6%, p=0.006), but not in other complications (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). However, we saw those 31 cases and 31 controls suffered CBI for one or several microorganisms, without statistical significance for the microorganisms studied (p=0.523) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).22 patients did not show radiological improvement (57.9%), 7 patients presented partial (18.4%) and 6 complete improvement (15.8%).<a class="elsevierStyleCrossRef" href="#bib0130">6</a>Within our series, a prevalence of atelectasis of 3.9% for the observational period has been estimated, like that found in other studies.<a class="elsevierStyleCrossRefs" href="#bib0110">2–4</a> Unlike other series, in which atelectasis is more frequent in children (the airways are smaller and with a greater tendency to collapse and associated with progressive structural lung disease), our average age at diagnosis of atelectasis was 20.05±12.67 years.<a class="elsevierStyleCrossRefs" href="#bib0145">9,13,14</a>In the search for correlations that may lead to possible risk factors predisposing development of atelectasis in CF, we have tried to find among our variables, if one of them could favor them.F508del (Phe.508.del) mutation homozygous is generally associated with a more severe phenotype and prognosis.<a class="elsevierStyleCrossRef" href="#bib0175">15</a> However, we did not find that this mutation was related to an increased risk of suffering this pulmonary complication, nor did we observe differences between the mutations in cases and controls (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).We clearly observed that the patients with atelectasis had a worse pulmonary function before manifestation of the complication (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). So, patients with moderate-severe pulmonary function are more prone to develop pulmonary collapses, because of intrapulmonary ventilatory differences. This finding has not been analyzed in medical bibliography until now, probably because of the scarcity of studies, which cover a small number of patients.<a class="elsevierStyleCrossRefs" href="#bib0125">5–7</a>In other published series including CF patients, it has been postulated that haemoptysis or hyperglycemia would be possible risk factors in the occurrence of atelectasis, due to possible increased viscosity of bronchial mucus.<a class="elsevierStyleCrossRef" href="#bib0120">4</a> However, we did not see differences in the comorbidities studied regarding pancreatic insufficiency or CFRD. This could be explained because both phenotypes are more linked to the F508del (Phe.508.del) mutation,<a class="elsevierStyleCrossRef" href="#bib0180">16</a> which is represented in a similar frequency in the two groups. Although we have not analyzed other complications, it has been reported that non-CF patients with severe acute pancreatitis have an increased risk to develop atelectasis.<a class="elsevierStyleCrossRef" href="#bib0185">17</a>If we refer to lung complications, we have only found significant differences in relation to ABPA. ABPA significantly predominated in patients with pulmonary atelectasis.<a class="elsevierStyleCrossRef" href="#bib0190">18</a> We attribute this to the production of sputum “plugs” due to Aspergillus-colonization and the resulting allergic reaction, which further increases sputum viscosity and mucosal edema, causing structural lung damage.<a class="elsevierStyleCrossRefs" href="#bib0195">19,20</a>Regarding airway colonization with pathogens, the cohort with atelectasis revealed a trend to more frequent airway colonization with Pseudomonas aeruginosa, followed in frequency by MSSA. However, these findings did not reach statistical significance in our cohort. This would suggest that if we included a greater number of patients, we could reach statistical significance.As study limitations, we must point out its retrospective nature and the relatively small number of included patients, and the way to obtain the control group, although we have not found differences in mutations of both groups. Being a relatively rare complication, it has been easier for us to resort to this kind of analysis, to be able to collect the largest possible number of cases in the given time.In conclusion and in relation to the variables studied, the presence of atelectasis is more frequently associated with patients who previously suffered from ABPA and who already had a moderate-severe impaired lung function. Probably, if the sample size were enlarged, we could find other variables, which would be risk factors for atelectasis as pulmonary complication in CF.We think multicentric studies should be carried out leading to international guidelines for therapy and prevention of pulmonary atelectasis in CF.FundingThis research project entitled “Repercussion of atelectasis as a pulmonary complication in cystic fibrosis” has been awarded a grant by the Neumomadrid Foundation, Madrid, Spain.Conflict of interestThe authors declare no conflict of interest in the study design, collection, analysis and interpretation of the data, as well as in the writing of the manuscript or in the publication of the results." 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"identificador" => "fn0005" ] ] "multimedia" => array:2 [ 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:2 [ "leyenda" => "pp, percent predicted; FEV1, forced expiratory volume in the first second; FVC, forced vital capacity; BMI, body mass index.-1: basal data. -2: last data (define time difference mean and SD)." "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Atelectasis (cases) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Controls \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Height (cm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">160.56±13.92 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">160.14±9.62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.900 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Weigh (kg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">51.65±17.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49.54±16.07 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.860 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BMI (kg/m2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19.89±3.98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20.42±3.72 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.582 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ppFVC -1 (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">66.0±24.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">87.78±21.97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.0014 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ppFEV1 -1 (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49.02±22.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75.55±27.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.040 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FEV1/FVC -1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">65.98±18.45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">71.0±15.36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.20 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ppFVC -2 (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">72.18±24.58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">90.12±22.55 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.020 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ppFEV1 -2 (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">61.74±29.45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75.38±27.57 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.040 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FEV1/FVC -2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">61.0±12.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">72.7±15.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Annual worsening ppFVC/year \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.90±6.91 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.54±6.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.810 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Annual worsening ppFEV1/year \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.49±6.22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.60±4.64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.390 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Annual worsening FEV1/FVC/year \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.17±8.22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.51±1.72 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.63 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Pulmonary function test." ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Controls \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Cases \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mutations</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Homozigous F508del \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (33.3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (18.4%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="4" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.348</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Heterozygous F508del \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 (41%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 (55.3%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">F508del/unknown \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (12.8%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (7.9%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Others \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (12.8%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (18.4%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pancreatic insufficiency \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26 (66.7%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23 (60.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.373 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cystic fibrosis-related diabetes (CFRD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (12.8%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (18.4%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.359 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hemoptysis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (7.7%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (13.2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.341 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Embolization \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (5.1%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (10.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.325 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ABPA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2.6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (23.7%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.006 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pneumothorax \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (5.2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.253 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Chronic bronquial infection (CBI) (last data collection) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">31 (79.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">31 (81.6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.52 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Methicillin-Sensitive Staphylococcus aureus (MSSA) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 (51.3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (31.6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.064 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Methicillin-Resistant Staphylococcus aureus (MRSA) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (12.8%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (10.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.517 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pseudomonas aeruginosa \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 (61.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 (50%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.215 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Stenotrophomonas maltophilia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (12.8%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (10.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.517 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Achromobacter xylosoxidans \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (5.1%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (10.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.325 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Non-tuberculous mycobacterias \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (7.7%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (10.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.485 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mycobacterium tuberculosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Others \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (20.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (28.9%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.277 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">*Aspergillus spp. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (10.3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (7.9%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">*Candida spp. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2.6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (5.3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">*Haemophilus spp. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (7.7%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (2.6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Other variables analyzed." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:20 [ 0 => array:3 [ "identificador" => "bib0105" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "<a target="_blank" href="https://www.ecfs.eu/sites/default/files/general-content-images/working-groups/ecfs-patient-registry/ECFSPR_Report_2019_v1_23Dec2021.pdf">https://www.ecfs.eu/sites/default/files/general-content-images/working-groups/ecfs-patient-registry/ECFSPR_Report_2019_v1_23Dec2021.pdf</a>." ] ] ] 1 => array:3 [ "identificador" => "bib0110" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Unilateral air bronchogram in a patient with cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C. 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"vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/03002896/0000005800000009/v3_202304072223/S0300289622001806/v3_202304072223/en/main.assets" "Apartado" => array:4 [ "identificador" => "93866" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Scientific Letters" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/03002896/0000005800000009/v3_202304072223/S0300289622001806/v3_202304072223/en/main.pdf?idApp=UINPBA00003Z&text.app=https://archbronconeumol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289622001806?idApp=UINPBA00003Z"]

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Scientific Letter

The Relation of CFTR-Genotype and Associated Comorbidities to Development of Pulmonary Atelectasis in Cystic Fibrosis Patients

M. Martínez-Redondoa, C. Prados Sáncheza,

Corresponding author

conchaprados@gmail.com

Corresponding author.

, F. García-Rioa, E. Quintana Gallegob, S. Castillo Corullónc, A. Salcedo Posadasd, R. Girón Morenoe, M.T. Martínez Martínezf, L. Máiz Carrog, C. Martin de Vicenteh, J. Costa Colomeri, R. Álvarez-Sala Walthera, the Spanish Working Group Atelectasis in CF 1

a Cystic Fibrosis Unit, Department of Pulmonology, La Paz University Hospital, Madrid, Spain

b Cystic Fibrosis Unit, Department of Pulmonology, Virgen del Rocio University Hospital, Sevilla, Spain

c Cystic Fibrosis Unit, Department of Pediatrics, Clinic Hospital, Valencia, Spain

d Cystic Fibrosis Unit, Department of Pediatrics, Niño Jesus Hospital, Madrid, Spain

e Cystic Fibrosis Unit, Department of Pulmonology, La Princesa University Hospital, Madrid, Spain

f Cystic Fibrosis Unit, Department of Pulmonology, Doce de Octubre University Hospital, Madrid, Spain

g Cystic Fibrosis Unit, Department of Pulmonology, Ramón y Cajal University Hospital, Madrid, Spain

h Cystic Fibrosis Unit, Department of Pediatrics, Miguel Servet Hospital, Zaragoza, Spain

i Cystic Fibrosis Unit, Department of Pediatrics, Sant Joan de Dêu, Barcelona, Spain

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prognosis or treatment has been elaborated&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">5&#8211;7</span></a> Its etiology could be secondary to either mucus plugs<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">8&#44;9</span></a> or serious affectations of the pulmonary parenchyma in which&#44; the progressive and irreversible damage of the airway would cause distortion&#44; obstruction and bronchial dilatations&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">5&#44;8&#44;10&#44;11</span></a> Its severity ranges from asymptomatic to major complications&#44; depending on various unkown factors&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Considering the scarcity of published works on atelectasis in <span class="elsevierStyleItalic">CF</span>&#44; we have proposed to analyze whether genetics&#44; certain <span class="elsevierStyleItalic">CF</span> typical respiratory of this complication and other comorbidities are associated to development of this complication&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">All cases of diagnosed stable CF children and adults &#40;&#8805; 18 years&#41; who suffered persistent atelectasis as a pulmonary complication&#44; diagnosed by image techniques&#44; with at least a two-year-follow-up of the patient after the first episode were included until December 2017 &#40;named as cases&#41;&#44; and in which the study variables could have been collected&#46; Likewise&#44; age and gender-matched control patients were enrolled &#40;date of birth of &#177;three years&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The following variables were assessed&#58; <span class="elsevierStyleItalic">CFTR</span>-mutations &#40;dividing them into homozygotes and heterozygotes for F508del &#40;Phe&#46;508del&#41; mutation&#44; F508del &#40;Phe&#46;508del&#41; mutation with one allele pending sequencing and other different mutations&#41;&#44; pulmonary complication such as <span class="elsevierStyleItalic">ABPA</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">12</span></a> hemoptysis&#44; pneumothorax and chronic bronchial infection &#40;<span class="elsevierStyleItalic">CBI</span>&#41; before the episode of atelectasis or&#44; as in the case of <span class="elsevierStyleItalic">CBI</span>&#44; at the time of the pulmonary collapse was described&#44; and other comorbidities related to the disease&#44; including pancreatic insufficiency and <span class="elsevierStyleItalic">CF</span>-related diabetes &#40;<span class="elsevierStyleItalic">CFRD</span>&#41;&#46; We also collected pulmonary function at the time of collapse &#40;basal&#41;&#44; and the last one registered&#44; and the annual decline&#44; in both groups&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The study has been approved by the Research Ethics Committee of the University La Paz University Hospital in Madrid&#44; Spain &#40;PI-2130&#41;&#46; Patients were not involved&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">For the statistical analysis&#44; the SPSS program&#44; version 13&#44; was used&#46; The data were expressed as mean plus standard deviation or percentage of the variable&#46; The comparison of independent quantitative variables was performed by the <span class="elsevierStyleItalic">Mann&#8211;Whitney</span> test&#44; the quantitative repeated variables by the Wilcoxon test and the qualitative variables by the <span class="elsevierStyleItalic">Chi-square test&#46;</span><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 was considered significant&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Among a total population of 969 patients with <span class="elsevierStyleItalic">CF</span> attended in the included <span class="elsevierStyleItalic">CF</span> centers&#44; 38 patients &#40;3&#46;9&#37;&#41;&#44; with a mean age at diagnosis of atelectasis of 20&#46;05<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;67 years&#44; 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There was no significant decline of pulmonary function per year between groups &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Remarkably&#44; a significantly elevated frequency of atelectasis was identified in patients with history of <span class="elsevierStyleItalic">ABPA</span> in relation to control group &#40;23&#46;7&#37; vs 2&#46;6&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;006&#41;&#44; but not in other complications &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; However&#44; we saw those 31 cases and 31 controls suffered <span class="elsevierStyleItalic">CBI</span> for one or several microorganisms&#44; without statistical significance for the microorganisms studied &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;523&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">22 patients did not show radiological improvement &#40;57&#46;9&#37;&#41;&#44; 7 patients presented partial &#40;18&#46;4&#37;&#41; and 6 complete improvement &#40;15&#46;8&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Within our series&#44; a prevalence of atelectasis of 3&#46;9&#37; for the observational period has been estimated&#44; like that found in other studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">2&#8211;4</span></a> Unlike other series&#44; in which atelectasis is more frequent in children &#40;the airways are smaller and with a greater tendency to collapse and associated with progressive structural lung disease&#41;&#44; our average age at diagnosis of atelectasis was 20&#46;05<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;67 years&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">9&#44;13&#44;14</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">In the search for correlations that may lead to possible risk factors predisposing development of atelectasis in <span class="elsevierStyleItalic">CF</span>&#44; we have tried to find among our variables&#44; if one of them could favor them&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">F508del &#40;Phe&#46;508&#46;del&#41; mutation homozygous is generally associated with a more severe phenotype and prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">15</span></a> However&#44; we did not find that this mutation was related to an increased risk of suffering this pulmonary complication&#44; nor did we observe differences between the mutations in cases and controls &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">We clearly observed that the patients with atelectasis had a worse pulmonary function before manifestation of the complication &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; So&#44; patients with moderate-severe pulmonary function are more prone to develop pulmonary collapses&#44; because of intrapulmonary ventilatory differences&#46; This finding has not been analyzed in medical bibliography until now&#44; probably because of the scarcity of studies&#44; which cover a small number of patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">5&#8211;7</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">In other published series including <span class="elsevierStyleItalic">CF</span> patients&#44; it has been postulated that haemoptysis or hyperglycemia would be possible risk factors in the occurrence of atelectasis&#44; due to possible increased viscosity of bronchial mucus&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">4</span></a> However&#44; we did not see differences in the comorbidities studied regarding pancreatic insufficiency or <span class="elsevierStyleItalic">CFRD&#46;</span> This could be explained because both phenotypes are more linked to the F508del &#40;Phe&#46;508&#46;del&#41; mutation&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">16</span></a> which is represented in a similar frequency in the two groups&#46; Although we have not analyzed other complications&#44; it has been reported that non-<span class="elsevierStyleItalic">CF</span> patients with severe acute pancreatitis have an increased risk to develop atelectasis&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">17</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">If we refer to lung complications&#44; we have only found significant differences in relation to <span class="elsevierStyleItalic">ABPA</span>&#46; <span class="elsevierStyleItalic">ABPA</span> significantly predominated in patients with pulmonary atelectasis&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">18</span></a> We attribute this to the production of sputum &#8220;plugs&#8221; due to <span class="elsevierStyleItalic">Aspergillus</span>-colonization and the resulting allergic reaction&#44; which further increases sputum viscosity and mucosal edema&#44; causing structural lung damage&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">19&#44;20</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Regarding airway colonization with pathogens&#44; the cohort with atelectasis revealed a trend to more frequent airway colonization with <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>&#44; followed in frequency by <span class="elsevierStyleItalic">MSSA</span>&#46; However&#44; these findings did not reach statistical significance in our cohort&#46; This would suggest that if we included a greater number of patients&#44; we could reach statistical significance&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">As study limitations&#44; we must point out its retrospective nature and the relatively small number of included patients&#44; and the way to obtain the control group&#44; although we have not found differences in mutations of both groups&#46; Being a relatively rare complication&#44; it has been easier for us to resort to this kind of analysis&#44; to be able to collect the largest possible number of cases in the given time&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">In conclusion and in relation to the variables studied&#44; the presence of atelectasis is more frequently associated with patients who previously suffered from <span class="elsevierStyleItalic">ABPA</span> and who already had a moderate-severe impaired lung function&#46; Probably&#44; if the sample size were enlarged&#44; we could find other variables&#44; which would be risk factors for atelectasis as pulmonary complication in <span class="elsevierStyleItalic">CF&#46;</span></p><p id="par0105" class="elsevierStylePara elsevierViewall">We think multicentric studies should be carried out leading to international guidelines for therapy and prevention of pulmonary atelectasis in <span class="elsevierStyleItalic">CF&#46;</span></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0110" class="elsevierStylePara elsevierViewall">This research project entitled &#8220;Repercussion of atelectasis as a pulmonary complication in cystic fibrosis&#8221; has been awarded a grant by the <span class="elsevierStyleGrantSponsor" id="gs1">Neumomadrid Foundation</span>&#44; Madrid&#44; Spain&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflict of interest</span><p id="par0115" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest in the study design&#44; collection&#44; analysis and interpretation of the data&#44; as well as in the writing of the manuscript or in the publication of the results&#46;</p></span></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Spanish Working Group &#8216;Atelectasis in CF&#8217;&#58; M Blanco Aparicio&#44; R Cordovilla Perez&#44; M&#46; Garc&#237;a Clemente&#44; David Iturbe Fern&#225;ndez&#44; Amparo Sol&#233; Jover&#44; Carlos J Carpio&#46;</p>"
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          "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">pp&#44; percent predicted&#59; FEV1&#44; forced expiratory volume in the first second&#59; FVC&#44; forced vital capacity&#59; BMI&#44; body mass index&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">-1&#58; basal data&#46; -2&#58; last data &#40;define time difference mean and SD&#41;&#46;</p>"
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                  \t\t\t\t">72&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#46;06&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Annual worsening ppFVC&#47;year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">1&#46;90<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;91&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;54<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;01&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;810&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Annual worsening ppFEV1&#47;year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">0&#46;49<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;22&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;60<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;64&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;390&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Annual worsening FEV1&#47;FVC&#47;year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">1&#46;17<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;22&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;51<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;63&nbsp;\t\t\t\t\t\t\n
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                  """
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Homozigous F508del&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">13 &#40;33&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">7 &#40;18&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " rowspan="4" align="char" valign="\n
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                  \t\t\t\t">0&#46;348</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Heterozygous F508del&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;41&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21 &#40;55&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>F508del&#47;unknown&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5 &#40;12&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">3 &#40;7&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Others&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;12&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;18&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">26 &#40;66&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23 &#40;60&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;373&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Cystic fibrosis-related diabetes &#40;CFRD&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">5 &#40;12&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;18&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;359&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Hemoptysis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;7&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;13&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;341&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Embolization</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;5&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;10&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;325&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">ABPA</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;23&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;006&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Pneumothorax</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;5&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;253&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Chronic bronquial infection &#40;CBI&#41; &#40;last data collection&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">31 &#40;79&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31 &#40;81&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;52&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Other variables analyzed&#46;</p>"
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Article information

ISSN: 03002896
Original language: English

DOI:10.1016/j.arbres.2022.02.009

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2024 August	100	33	133
2024 July	123	25	148
2024 June	74	28	102
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2023 March	69	38	107
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