Cystic fibrosis – Comparison between patients in paediatric and adult age

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Resende, A. Todo-Bom, C. Loureiro, A. Mota Pinto, B. Oliveiros, L. Mesquita, H.C. Silva" "autores" => array:7 [ 0 => array:2 [ "nombre" => "E.P." "apellidos" => "Resende" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Todo-Bom" ] 2 => array:2 [ "nombre" => "C." "apellidos" => "Loureiro" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Mota Pinto" ] 4 => array:2 [ "nombre" => "B." "apellidos" => "Oliveiros" ] 5 => array:2 [ "nombre" => "L." "apellidos" => "Mesquita" ] 6 => array:2 [ "nombre" => "H.C." "apellidos" => "Silva" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173511516300872?idApp=UINPBA00004E" "url" => "/21735115/0000002300000001/v1_201701210027/S2173511516300872/v1_201701210027/en/main.assets" ] "en" => array:18 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Cystic fibrosis – Comparison between patients in paediatric and adult age" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "17" "paginaFinal" => "21" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "V. Santos, A.V. Cardoso, C. Lopes, P. Azevedo, F. Gamboa, A. Amorim" "autores" => array:6 [ 0 => array:4 [ "nombre" => "V." "apellidos" => "Santos" "email" => array:1 [ 0 => "vferreirads@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "A.V." "apellidos" => "Cardoso" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "C." "apellidos" => "Lopes" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "P." "apellidos" => "Azevedo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "F." "apellidos" => "Gamboa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 5 => array:3 [ "nombre" => "A." "apellidos" => "Amorim" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Pulmonology Department, Centro Hospitalar de São João, EPE, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Pulmonology Department, Centro Hospitalar de Lisboa Norte – Hospital de Santa Maria, Lisboa, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Pulmonology Department, Hospitais da Universidade de Coimbra – Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Faculty of Medicine of Porto University, Portugal" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "textoCompleto" => "IntroductionCystic fibrosis (CF) is the most common autosomal recessive disease affecting 1 in 2500 newborns among Caucasians.<a class="elsevierStyleCrossRef" href="#bib0155">1</a>Its incidence is well documented in Europe where 1 in 2000–3000 newborns are affected.<a class="elsevierStyleCrossRef" href="#bib0160">2</a> In Portugal, the incidence is apparently lower it is estimated at 1:6000 live births.<a class="elsevierStyleCrossRef" href="#bib0165">3</a> Currently, however, there are only about 300 CF patients (approximately one-third of whom are adults) in follow-up in specialized centres, fewer than expected considering the incidence value above.The gene responsible for CF encodes a protein of 1400 amino acids, which functions as a chloride-transport-channel located in the apical epithelial cells, thereby regulating the movement of solute and H2O.<a class="elsevierStyleCrossRefs" href="#bib0170">4–6</a> It was identified in 1989<a class="elsevierStyleCrossRefs" href="#bib0185">7–9</a> and since then, more than 2000 disease-associated mutations have been described.<a class="elsevierStyleCrossRef" href="#bib0200">10</a>The most common mutation, which is termed delF508 as a phenylalanine-residue at position 508 is absent, is present in approximately 70% of defective cystic-fibrosis-transmembrane-conductance-regulator (CFTR) alleles.<a class="elsevierStyleCrossRef" href="#bib0200">10</a>CF is a highly variable disease and patients are diagnosed with different presentations. Symptoms appear in the first year of life in the great majority of cases but may appear later, even in adulthood with considerable variation in severity and rate of progression.<a class="elsevierStyleCrossRef" href="#bib0170">4</a>The gold-standard laboratory method for diagnosing CF is the sweat test but there are other methods such as genetic analysis or the determination of nasal transepithelial potential difference.<a class="elsevierStyleCrossRefs" href="#bib0205">11,12</a> Since 2013 a pilot screening programme for CF, applied to all newborns, has been running in Portugal.Patients are diagnosed when at least one of these tests positive, identification is associated with one or more phenotypic characteristics, a positive neonatal screening or family history.<a class="elsevierStyleCrossRef" href="#bib0210">12</a>Although CF is usually discovered early in life, in recent decades it is no longer an exclusively paediatric disease. The number of adults with CF continues to increase, while the number of children has remained relatively stable over the past decade. In 2013, adults comprised 49.7% of the CF population, compared with 29.2% in 1986.<a class="elsevierStyleCrossRef" href="#bib0215">13</a> This increase may be due to increased survival, secondary to effective treatment, more diagnostic capabilities with the inclusion of milder forms of the disease, greater availability and improved genetic testing, using more specific and sensitive diagnostic criteria, as well as increased sensitivity to the possibility of medical diagnosis.<a class="elsevierStyleCrossRefs" href="#bib0220">14,15</a>The first adult CF diagnosis was made in 1946.<a class="elsevierStyleCrossRef" href="#bib0230">16</a> Since that time, a number of case studies of adults receiving a diagnosis have been reported, and the incidence of delayed diagnosis is expected to increase.There are a number of reasons for diagnosis as adults. Firstly, mild expression of the disease, absent symptoms or unusual presentations may delay a patient seeking medical attention.<a class="elsevierStyleCrossRefs" href="#bib0235">17–19</a> Secondly, the common perception of CF as a disease exclusive to childhood leads to it not being recognized in adults, especially when the presenting symptoms are atypical.<a class="elsevierStyleCrossRefs" href="#bib0250">20,21</a>We have found that patients presenting in adulthood appear to be different to patients presenting in childhood. Research has established that, as a group, those diagnosed as adults have variable and atypical presentations, and often have milder disease,<a class="elsevierStyleCrossRefs" href="#bib0260">22,23</a> better, long-term prognosis,<a class="elsevierStyleCrossRefs" href="#bib0265">23,24</a> better lung function, higher rates of pancreatic sufficiency, fewer complications, and longer life expectancy than adults diagnosed in childhood.<a class="elsevierStyleCrossRefs" href="#bib0270">24–26</a>There is a growing need to identify differences between the groups but there are no published data in Portugal.The objectives of this study were: (1) to characterize the adult CF Portuguese population, comparing patients who were diagnosed before and after 18 years of age; (2) to determine differences between the two groups regarding demographic characteristics and variables related to CF; and (3) to investigate potential diagnostic and therapeutic implications of these differences.MethodsA retrospective analysis of clinical records of patients followed in the three main specialized adult centres in Portugal (Porto, Coimbra and Lisbon) between January 01 and December 31, 2012.All patients were diagnosed with CF according to the diagnostic criteria in their consensus statement.These patients were assigned to one of two groups: those diagnosed at <18 years old (Group1 – G1) and those diagnosed at ≥18 years old (Group2 – G2).Several variables were evaluated (demographic, diagnostic, genetic, mortality, health status, and other related variables) after which the two groups were compared.The patients were analysed into CFTR mutation classes, and according to these, were subdivided into severe (classes I, II or III) or mild (patients with at least one allele from class IV to VI).Statistical analysis was performed using SPSS Statistics 19.0.ResultsEighty-nine patients with CF were identified, 55 (61.8%) diagnosed at age <18 years of age (G1) and 34 (38.2%) at age ≥18 years of age (G2).Forty-one patients (46%) were male and 48 (54%) were female. Gender distribution was similar in both groups (G1 vs. G2: women 54.5% vs. 52.9%, men 45.5% vs. 47.1%).The average age was 31.3±9.0 years. There were statistically significant differences in relation to current age, and the average age of patients in G2 was older (38.3±8.4 vs. 26.8±6.1 years, p<0.001).All of the included patients were Caucasian.The median age at diagnosis was 13, and 34 (38.2%) were diagnosed in adulthood.Over one-half of adults were women, yet men were more likely to receive a late diagnosis (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>There were significant associations between age at diagnosis and the condition suggesting the diagnosis (respiratory and digestive symptoms), as noted in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Although respiratory symptoms (recurrent/acute respiratory infections, cough, haemoptysis) were the most frequent clinical manifestations leading to the diagnosis in all patients, this is particularly evident when patients are diagnosed as adults (G2 vs. G1: 75.9% vs. 42.6%; p=0.005). Patients in G1 showed a greater variability in conditions suggesting the diagnosis, and digestive symptoms that most frequently lead to diagnosis (G1 vs. G2: 44.7% vs. 17.2%; p=0.014). In G2, 3.4% of patients were diagnosed due to fertility problems and failure to thrive was observed only in G1. Furthermore, respiratory symptoms were more frequent in female patients (70.7% vs. 37.1%, p=0.003) whereas digestive symptoms were the most frequent in males (54.3% vs. 17.1%, p<0.001).All patients studied were genotyped. The most frequent mutation identified was delF508 (54.9%), 27 patients (30.3%) were homozygous and 41 (46.1%) heterozygous. The second most common mutation was R334W (12.7%). There was a greater percentage of patients homozygous for the mutation delF508 in G1 (43.6% vs. 8.8%, p=0.02) as illustrated in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>. Greater heterogeneity of mutations in the G2 has been verified; significantly higher percentages of patients in G2 were either heterozygous for delF508 or did not carry the allele (91.2% vs. 56.4%, respectively).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>According to CFTR mutation classes, 40 (46.5%) had CFTR mutation classes I, II or III (severe) and 46 patients (53.5%) had at least one allele from classes IV–VI (mild).Thirty-six patients (66.7%) showed severe mutation classes in G1, compared with 4 patients (11.8%) in G2 (p<0.001).Considering pancreatic function, 39 patients (97.5%) with severe CFTR mutation classes presented pancreatic insufficiency vs. 9 patients (19.6%) with mild CFTR mutation classes (p<0.001).The average value of FEV1 was 58.8±28.9%, 23 patients (25.8%) with FEV1>80% and 26 (29.2%) <40%, 3 of which <20%. The assessment of respiratory function showed a higher severity in G1, with patients in G2 attaining slightly higher mean percentage predicted of FVC and FEV1 scores; there was not a significant difference in FVC and FEV1 values between groups (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>Thus, despite being considerably older (about 12 years difference), the G2 patients presented results of lung function tests which were similar to the G1.Forty-nine patients (56%) had exocrine pancreatic insufficiency and 8 of these also had CF-related diabetes and were on insulin therapy. A higher rate of pancreatic insufficiency was found in G1 and this difference was significant (74.1% vs. 27.3%, p<0.001). Pancreatic function is closely related to the genotype. All patients with delF508 homozygous had pancreatic dysfunction.The average value of body-mass-index (BMI) was 20.9±4.1kg/m2. Forty-one patients (46.1%) had BMI<20 and 14 (15.7%) were obese (BMI>25).Assessment of BMI showed a higher level of this variable in G1 and this difference was statistically significant (20.1±3.4 vs. 22.2±4.8, p=0.018).In culture result analysis, lung transplant patients (14) were excluded and therefore only 75 patients were considered. The most common microbiological isolates were Pseudomonas aeruginosa (Pa) in 49 patients (55.1%) and methicillin-sensitive-Staphylococcus-aureus (MSSA) in 50 (56.2%). Most of the patients had fewer than three microbiological isolates and more than two germs isolated. Regarding differences between microbiological isolation and age at diagnosis (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>), Pa and MSSA were the most frequently isolated microorganisms in both groups (G1 vs. G2: Pa: 60.0% vs. 47.1%, p=0.33; MSSA: 58.2% vs. 52.9%, p=0.792). Burkholderia cepacia was isolated only in G1 (12.7% vs. 0%, p=0.041).Lung transplantation rate was higher in G2 (G2 vs. G1: 20.6% vs. 12.7%, p=0.490).Fourteen-patients were hospitalized for complications. Hospital admissions rate was higher in G1 (G1 vs. G2: 44.0% vs. 17.6%, p=0.148). Two-patients (2.2%) died due to lung transplant rejection and sepsis of pulmonary origin. Mortality rate was higher in G1 (G2 vs. G1: 0% vs. 3.6%, p=0.522).DiscussionIn consideration of the fact that diagnosis of CF in adulthood is possible and appears to be increasing,<a class="elsevierStyleCrossRef" href="#bib0280">26</a> this study explored issues dealing with late diagnosis, with the objective of identifying any possible differences in clinical presentation of CF between patients diagnosed before and after 18 years of age.In this study adults who received late diagnosis of CF have unique characteristics that suggest particular needs in terms of treatment and support; they experienced fewer complications and fewer hospital admissions than those who received diagnosis under 18 years of age, in whom respiratory (p=0.148) and pancreatic (p<0.001) involvement was less severe and had a significantly better nutritional status (p=0.018).Significant association between age at diagnosis and the condition suggesting the diagnosis was found, in spite of the fact that respiratory symptoms were the most frequent manifestations leading to the diagnosis in all patients; this is particularly evident when the diagnosis is made in adulthood.The study also found a greater percentage of homozygous delF508 among patients diagnosed earlier in life than in those diagnosed in adulthood, and this difference was statistically significant. It is recognized that homozygosity for delF508 mutation is associated with a high systemic repercussion of CF, a high level of pancreatic insufficiency and a low BMI. On the other hand, the greater heterogeneity in mutations of patients with a late diagnosis found in this study could be responsible for the greater variance in conditions leading to diagnosis and the overall better indexes of health in this group; it is a fact that patients diagnosed in adulthood had fewer hospitalizations and experience fewer complications than those diagnosed early in life and most of them were pancreatic sufficient, which is closely related to the type of CFTR mutation associated.<a class="elsevierStyleCrossRefs" href="#bib0285">27,28</a>In the study, as is common in the literature, most of those diagnosed early in life present with a combination of gastrointestinal and pulmonary symptoms, while in the late diagnosis group of patients most were diagnosed due to recurrent pulmonary infections and gastrointestinal symptoms were less frequent.<a class="elsevierStyleCrossRef" href="#bib0275">25</a>The acquisition of infectious agents is an important environmental modifier which determines course and prognosis of most patients with CF. Furthermore, patients who are infected experience a more rapid decline of lung function than their non- infected peers.<a class="elsevierStyleCrossRef" href="#bib0295">29</a> Although no significant difference between age at diagnosis and culture results was found, and there was not a significant difference in FVC and FEV1 values between groups, there was a higher percentage of microbiological isolations in G1 patients, and the assessment of respiratory function showed a greater severity in these patients.No significant differences were found between groups in terms of transplantation and mortality rates.The above results provide empirical support that supports the argument that patients with a late diagnosis of CF are different from those who receive early diagnosis.ConclusionsIn summary, this study is the first description of the Portuguese adult CF population and the first to examine two distinct populations on the basis of age at diagnosis, which is particularly important, since it gives us a better understanding of real life.A significant percentage of our patients were diagnosed in adulthood, which highlights the need for diagnostic suspicion in a patient with chronic lung disease and atypical symptoms. In the study performed, a 10 years longer lifetime was detected in patients diagnosed in adulthood. This difference may be associated with higher frequency of homozygosity for the mutation delF508 found in patients diagnosed early in life which is usually associated to a higher systemic repercussion of CF and a higher level of pancreatic insufficiency cases and lower BMI.The results suggest that patients diagnosed in the paediatric age group have characteristics that distinguish them from those diagnosed in adulthood, which may have implications in terms of diagnosis, prognosis and life expectancy.Ethical responsibilitiesProtection of human and animal subjectsThe authors declare that no experiments were performed on humans or animals for this study.Confidentiality of dataThe authors declare that no patient data appear in this article.Right to privacy and informed consentThe authors declare that no patient data appear in this article.Conflicts of interestThe authors have no conflicts of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres792782" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:1 [ "identificador" => "abst0005" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec791271" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:2 [ "identificador" => "sec0010" "titulo" => "Methods" ] 4 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 5 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 6 => array:2 [ "identificador" => "sec0025" "titulo" => "Conclusions" ] 7 => array:3 [ "identificador" => "sec0030" "titulo" => "Ethical responsibilities" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0040" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0045" "titulo" => "Right to privacy and informed consent" ] ] ] 8 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflicts of interest" ] 9 => array:2 [ "identificador" => "xack265523" "titulo" => "Acknowledgments" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-10-19" "fechaAceptado" => "2016-07-22" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec791271" "palabras" => array:5 [ 0 => "Cystic fibrosis" 1 => "Cystic fibrosis diagnosis" 2 => "Cystic fibrosis in childhood" 3 => "Cystic fibrosis adult" 4 => "Cystic fibrosis late diagnosis" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians. Although most cases are diagnosed in childhood, diagnosis in adults is apparently increasing. ObjectiveEvaluate the adult population with CF, comparing patients who were diagnosed before and after 18 years of age. MethodsRetrospective analysis of patients followed in three main medical centres in Portugal in 2012. Comparison of two groups: G1 – patients diagnosed at <18 years and G2 – patients diagnosed at ≥18 years. Results89 adults were identified: 61.8% in G1, 38.2% in G2. Gender distribution was similar in both groups. Average age in G2 was higher (38.3±8.4 vs. 26.8±6.1 years, p<0.001). Respiratory symptoms most frequently led to CF diagnosis in all patients, mainly in adulthood. There was a greater percentage of patients homozygous for the mutation delF508 in G1 (43.6 vs. 8.8%, p=0.02). Respiratory and pancreatic function, and body mass index (BMI) showed a higher severity in G1 (G1 vs. G2: FEV1: 54.6±27.3 vs. 29.9±64.6%, p=0.177; pancreatic insufficiency 72.7 vs. 26.5%, p<0.001; BMI 20.2±3.4 vs. 22.2±4.8, p=0.018). Pseudomonas aeruginosa and methicillin-sensitive Staphylococcus aureus were the most frequently isolated microorganisms. Lung transplantation rate was higher in G2 (20.6 vs. 10.9%, p=0.231) while mortality rate was higher in G1 (0 vs. 3.6%, p=0.261). Hospital admission rate was higher in G1 as well as mortality rate. ConclusionThe results suggest that patients with CF diagnosed in childhood have characteristics that distinguish them from those diagnosed in adulthood, and these differences may have implications for diagnosis, prognosis and life expectancy." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusion" ] ] ] ] "multimedia" => array:4 [ 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 [ "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">Gender \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">Group G1 (<18 years), % (n=55) \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">Group G2 (≥18 years), % (n=34) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Male (n=41) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">61.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">39.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Female (n=48) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">62.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1325762.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "p-Value 0.884." ] ] ] "descripcion" => array:1 [ "en" => "Association between age at diagnosis and gender in patients with CF.<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a>" ] ] 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:2 [ "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">Presentation forms<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \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">Group G1 (<18 years), % (n=55) \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">Group G2 (≥18 years), % (n=34) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p-Value \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Respiratory symptoms \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">75.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.005 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Digestive symptoms \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">44.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.014 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Family screening \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.283 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Failure to thrive malnutrition \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.283 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Infertility \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.382 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1325761.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "More than one condition may have been present." ] ] ] "descripcion" => array:1 [ "en" => "Association between age at diagnosis and condition suggesting diagnosis." ] ] 2 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "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">Genotype \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">Group G1 (<18 years), % (n=55) \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">Group G2 (≥18 years), % (n=34) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">delF508 Homozygous \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">43.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">delF508 Heterozygous \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">55.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Others mutations \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1325763.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "a" "nota" => "p=0.02." ] ] ] "descripcion" => array:1 [ "en" => "Association between genotype delF508 and age at diagnosis.<a class="elsevierStyleCrossRef" href="#tblfn0015">a</a>" ] ] 3 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "tablatextoimagen" => array:2 [ 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">Lung function \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">Group G1 (<18 years)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \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">n \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">Group G2 (≥18 years)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \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">n \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p-Value \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FEV1% predicted \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">54.6 (27.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">65.6 (30.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.148 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FVC % predicted \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">72.1 (31.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">85.6 (29.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.197 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1325765.png" ] ] 1 => 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">Microbiological results \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">Group G1 (<18 years)<a class="elsevierStyleCrossRef" href="#tblfn0025">b</a> \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">n \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">Group G2 (≥18 years)<a class="elsevierStyleCrossRef" href="#tblfn0025">b</a> \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">n \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p-Value \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pseudomonas aeruginosa \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">47.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.33 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Burkholderia cepacia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.041 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Methicillin-sensitive Staphylococcus aureus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">58.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">52.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.792 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Methicillin-resistant Staphylococcus aureus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.728 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Achromobacter baumannii \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Aspergillus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.094 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nontuberculosis mycobacterium \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1325764.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "a" "nota" => "Results given as mean (SD)." ] 1 => array:3 [ "identificador" => "tblfn0025" "etiqueta" => "b" "nota" => "Results given as %." ] ] ] "descripcion" => array:1 [ "en" => "Association between lung function and microbiological result with age at diagnosis." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:29 [ 0 => array:3 [ "identificador" => "bib0155" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:6 [ "editores" => "A.BushE.W.F.W.AltonJ.C.DaviesU.GriesenbachA.Jaffe" "paginaInicial" => "2" "paginaFinal" => "10" "serieVolumen" => "vol. 34" "serieTitulo" => "Cystic fibrosis in the 21st century. Prog Respir Res" "serieFecha" => "2006" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0160" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The molecular genetic epidemiology of cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "WHO" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:1 [ "fecha" => "2004" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0165" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The prevalence of cystic fibrosis in the European Union" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "P.M. Farrell" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jcf.2008.03.007" "Revista" => array:6 [ "tituloSerie" => "J Cyst Fibros" "fecha" => "2008" "volumen" => "7" "paginaInicial" => "450" "paginaFinal" => "453" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18442953" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0170" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Guidelines for the diagnosis and management of cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "F.A. Abreu" 1 => "J.A. Dodge" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:2 [ "fecha" => "1996" "editorial" => "World Health Organization" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0175" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Expression of the cystic fibrosis gene in human foetal tissues" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A.E. Trezise" 1 => "J.A. Chambers" 2 => "C.J. Wardle" 3 => "S. Gould" 4 => "A. Harris" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Hum Mol Genet" "fecha" => "1993" "volumen" => "2" "paginaInicial" => "213" "paginaFinal" => "218" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7684639" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0180" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The cystic fibrosis transmembrane conductance regulator: an intriguing protein with pleiotropic functions" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. Vankeerberghen" 1 => "H. Cuppens" 2 => "J.J. Cassiman" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Cyst Fibros" "fecha" => "2002" "volumen" => "1" "paginaInicial" => "13" "paginaFinal" => "29" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15463806" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0185" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.R. Riordan" 1 => "J.M. Rommens" 2 => "B. Kerem" 3 => "N. Alon" 4 => "R. Rozmahel" 5 => "Z. Grzelczak" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Science" "fecha" => "1989" "volumen" => "245" "paginaInicial" => "1066" "paginaFinal" => "1073" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2475911" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0190" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Identification of the cystic fibrosis gene: chromosome walking and jumping" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.M. Rommens" 1 => "M.C. Iannuzzi" 2 => "B. Kerem" 3 => "M.L. Drumm" 4 => "G. Melmer" 5 => "M. Dean" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Science" "fecha" => "1989" "volumen" => "245" "paginaInicial" => "1059" "paginaFinal" => "1065" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2772657" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0195" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genotype–phenotype correlation in cystic fibrosis patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M. Ferrari" 1 => "L. Cremonesi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Ann Biol Clin (Paris)" "fecha" => "1996" "volumen" => "54" "paginaInicial" => "235" "paginaFinal" => "241" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0200" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mechanisms of disease: cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S.M. Rowe" 1 => "S. Miller" 2 => "E.J. Sorscher" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMra043184" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2005" "volumen" => "352" "paginaInicial" => "1992" "paginaFinal" => "2001" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15888700" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0205" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cystic fibrosis: a 2002 update" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "B.M. Orenstein" 1 => "G.B. Winnie" 2 => "H. Altman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1067/mpd.2002.120269" "Revista" => array:6 [ "tituloSerie" => "J Pediatr" "fecha" => "2002" "volumen" => "140" "paginaInicial" => "156" "paginaFinal" => "164" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11865265" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0210" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cystic fibrosis: terminology and diagnostic algorithms" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. De Boeck" 1 => "M. Wilschanski" 2 => "C. Castellani" 3 => "C. Taylor" 4 => "H. Cuppens" 5 => "J. Dodge" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thx.2005.043539" "Revista" => array:6 [ "tituloSerie" => "Thorax" "fecha" => "2006" "volumen" => "61" "paginaInicial" => "627" "paginaFinal" => "635" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16384879" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0215" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "titulo" => "Cystic Fibrosis Foundation: Patient Registry Annual Data Report to the Center Directors 2013" ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "2014" "editorial" => "Cystic Fibrosis Foundation" "editorialLocalizacion" => "Bethesda, Maryland" ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0220" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cystic fibrosis adult care: consensus conference report" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J.R. Yankaskas" 1 => "B.C. Marshall" 2 => "B. Sufian" 3 => "R.H. Simon" 4 => "D. Rodman" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Chest" "fecha" => "2004" "volumen" => "125" "numero" => "Suppl." "paginaInicial" => "1S" "paginaFinal" => "39S" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14734689" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0225" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Manifestations of cystic fibrosis diagnosed in adulthood" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A.N. Jerry" 1 => "M.R. David" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Curr Opin Pulm Med" "fecha" => "2005" "volumen" => "11" "paginaInicial" => "513" "paginaFinal" => "518" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16217177" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0230" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cystic fibrosis of the pancreas in an adult" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "H.K. Hellerstein" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ohio Med J" "fecha" => "1946" "volumen" => "42" "paginaInicial" => "616" "paginaFinal" => "617" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20986203" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0235" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acute presentation of cystic fibrosis in an adult" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "K.R. Gardiner" 1 => "B. Cranley" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Postgrad Med J" "fecha" => "1989" "volumen" => "65" "paginaInicial" => "471" "paginaFinal" => "472" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2602238" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0240" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Newly diagnosed cystic fibrosis in middle and later life" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "B. Hunt" 1 => "D.M. Geddes" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Thorax" "fecha" => "1984" "volumen" => "40" "paginaInicial" => "23" "paginaFinal" => "26" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3918355" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0245" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cystic fibrosis in an adult" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "S. Fiel" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Emerg Med" "fecha" => "1988" "volumen" => "20" "paginaInicial" => "109" "paginaFinal" => "121" ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0250" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cystic fibrosis in adults" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J. Godby" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Miss State Med Assoc" "fecha" => "1985" "volumen" => "26" "paginaInicial" => "161" "paginaFinal" => "163" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4009708" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0255" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Typical cystic fibrosis in an elderly woman" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C.T. Su" 1 => "B. Beanblossom" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Med" "fecha" => "1989" "volumen" => "86" "paginaInicial" => "701" "paginaFinal" => "703" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2729321" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0260" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A cystic fibrosis mutation associated with mild lung disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.H. Gan" 1 => "H.J. Veeze" 2 => "A.M. van den Ouweland" 3 => "D.J. Halley" 4 => "H. Scheffer" 5 => "A. van der Hout" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "N Engl J Med" "fecha" => "1995" "volumen" => "333" "paginaInicial" => "93" "paginaFinal" => "99" ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0265" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical manifestations of cystic fibrosis among patients with diagnosis in adulthood" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M. Gilljam" 1 => "L. Ellis" 2 => "M. Corey" 3 => "J. Zielenski" 4 => "P. Durie" 5 => "D.E. Tullis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1378/chest.126.4.1215" "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "2004" "volumen" => "126" "paginaInicial" => "1215" "paginaFinal" => "1224" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15486385" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0270" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genetic and clinical features of patients with cystic fibrosis diagnosed after the age of 16 years" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "K.H. Gan" 1 => "W.P. Geus" 2 => "W. Bakker" 3 => "C.B. Lamers" 4 => "H.G. Heijerman" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Thorax" "fecha" => "1995" "volumen" => "50" "paginaInicial" => "1301" "paginaFinal" => "1304" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8553305" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0275" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cystic fibrosis diagnosed in adult patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "T.J. McWilliams" 1 => "M.L. Wilsher" 2 => "J. Kolbe" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "N Z Med J" "fecha" => "2000" "volumen" => "113" "paginaInicial" => "6" "paginaFinal" => "8" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10738492" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0280" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Health status and sociodemographic characteristics of adults receiving a cystic fibrosis diagnosis after age 18 years" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "E. Widerman" 1 => "L. Millner" 2 => "W. Sexauer" 3 => "S. 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Tsui" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Hum Genet" "fecha" => "1992" "volumen" => "50" "paginaInicial" => "1178" "paginaFinal" => "1184" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1376016" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0295" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genetic and environmental modifiers of cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "B. Tummler" 1 => "F. 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Original article

Cystic fibrosis – Comparison between patients in paediatric and adult age

V. Santosa,

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vferreirads@gmail.com

Corresponding author.

, A.V. Cardosoa, C. Lopesb, P. Azevedob, F. Gamboac, A. Amorima,d

a Pulmonology Department, Centro Hospitalar de São João, EPE, Portugal

b Pulmonology Department, Centro Hospitalar de Lisboa Norte – Hospital de Santa Maria, Lisboa, Portugal

c Pulmonology Department, Hospitais da Universidade de Coimbra – Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal

d Faculty of Medicine of Porto University, Portugal

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Cystic fibrosis &#40;CF&#41; is the most common autosomal recessive disease affecting 1 in 2500 newborns among Caucasians&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Its incidence is well documented in Europe where 1 in 2000&#8211;3000 newborns are affected&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a> In Portugal&#44; the incidence is apparently lower it is estimated at 1&#58;6000 live births&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> Currently&#44; however&#44; there are only about 300 CF patients &#40;approximately one-third of whom are adults&#41; in follow-up in specialized centres&#44; fewer than expected considering the incidence value above&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The gene responsible for CF encodes a protein of 1400 amino acids&#44; which functions as a chloride-transport-channel located in the apical epithelial cells&#44; thereby regulating the movement of solute and H<span class="elsevierStyleInf">2</span>O&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">4&#8211;6</span></a> It was identified in 1989<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">7&#8211;9</span></a> and since then&#44; more than 2000 disease-associated mutations have been described&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The most common mutation&#44; which is termed delF508 as a phenylalanine-residue at position 508 is absent&#44; is present in approximately 70&#37; of defective cystic-fibrosis-transmembrane-conductance-regulator &#40;CFTR&#41; alleles&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">CF is a highly variable disease and patients are diagnosed with different presentations&#46; Symptoms appear in the first year of life in the great majority of cases but may appear later&#44; even in adulthood with considerable variation in severity and rate of progression&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The gold-standard laboratory method for diagnosing CF is the sweat test but there are other methods such as genetic analysis or the determination of nasal transepithelial potential difference&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">11&#44;12</span></a> Since 2013 a pilot screening programme for CF&#44; applied to all newborns&#44; has been running in Portugal&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Patients are diagnosed when at least one of these tests positive&#44; identification is associated with one or more phenotypic characteristics&#44; a positive neonatal screening or family history&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Although CF is usually discovered early in life&#44; in recent decades it is no longer an exclusively paediatric disease&#46; The number of adults with CF continues to increase&#44; while the number of children has remained relatively stable over the past decade&#46; In 2013&#44; adults comprised 49&#46;7&#37; of the CF population&#44; compared with 29&#46;2&#37; in 1986&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a> This increase may be due to increased survival&#44; secondary to effective treatment&#44; more diagnostic capabilities with the inclusion of milder forms of the disease&#44; greater availability and improved genetic testing&#44; using more specific and sensitive diagnostic criteria&#44; as well as increased sensitivity to the possibility of medical diagnosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">14&#44;15</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The first adult CF diagnosis was made in 1946&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a> Since that time&#44; a number of case studies of adults receiving a diagnosis have been reported&#44; and the incidence of delayed diagnosis is expected to increase&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">There are a number of reasons for diagnosis as adults&#46; Firstly&#44; mild expression of the disease&#44; absent symptoms or unusual presentations may delay a patient seeking medical attention&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">17&#8211;19</span></a> Secondly&#44; the common perception of CF as a disease exclusive to childhood leads to it not being recognized in adults&#44; especially when the presenting symptoms are atypical&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">20&#44;21</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">We have found that patients presenting in adulthood appear to be different to patients presenting in childhood&#46; Research has established that&#44; as a group&#44; those diagnosed as adults have variable and atypical presentations&#44; and often have milder disease&#44;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">22&#44;23</span></a> better&#44; long-term prognosis&#44;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">23&#44;24</span></a> better lung function&#44; higher rates of pancreatic sufficiency&#44; fewer complications&#44; and longer life expectancy than adults diagnosed in childhood&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">24&#8211;26</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">There is a growing need to identify differences between the groups but there are no published data in Portugal&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The objectives of this study were&#58; &#40;1&#41; to characterize the adult CF Portuguese population&#44; comparing patients who were diagnosed before and after 18 years of age&#59; &#40;2&#41; to determine differences between the two groups regarding demographic characteristics and variables related to CF&#59; and &#40;3&#41; to investigate potential diagnostic and therapeutic implications of these differences&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Methods</span><p id="par0070" class="elsevierStylePara elsevierViewall">A retrospective analysis of clinical records of patients followed in the three main specialized adult centres in Portugal &#40;Porto&#44; Coimbra and Lisbon&#41; between January 01 and December 31&#44; 2012&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">All patients were diagnosed with CF according to the diagnostic criteria in their consensus statement&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">These patients were assigned to one of two groups&#58; those diagnosed at &#60;18 years old &#40;Group1 &#8211; G1&#41; and those diagnosed at &#8805;18 years old &#40;Group2 &#8211; G2&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Several variables were evaluated &#40;demographic&#44; diagnostic&#44; genetic&#44; mortality&#44; health status&#44; and other related variables&#41; after which the two groups were compared&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">The patients were analysed into CFTR mutation classes&#44; and according to these&#44; were subdivided into severe &#40;classes I&#44; II or III&#41; or mild &#40;patients with at least one allele from class IV to VI&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Statistical analysis was performed using SPSS Statistics 19&#46;0&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="par0100" class="elsevierStylePara elsevierViewall">Eighty-nine patients with CF were identified&#44; 55 &#40;61&#46;8&#37;&#41; diagnosed at age &#60;18 years of age &#40;G1&#41; and 34 &#40;38&#46;2&#37;&#41; at age &#8805;18 years of age &#40;G2&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Forty-one patients &#40;46&#37;&#41; were male and 48 &#40;54&#37;&#41; were female&#46; Gender distribution was similar in both groups &#40;G1 vs&#46; G2&#58; women 54&#46;5&#37; vs&#46; 52&#46;9&#37;&#44; men 45&#46;5&#37; vs&#46; 47&#46;1&#37;&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The average age was 31&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;0 years&#46; There were statistically significant differences in relation to current age&#44; and the average age of patients in G2 was older &#40;38&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;4 vs&#46; 26&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;1 years&#44; <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">All of the included patients were Caucasian&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">The median age at diagnosis was 13&#44; and 34 &#40;38&#46;2&#37;&#41; were diagnosed in adulthood&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Over one-half of adults were women&#44; yet men were more likely to receive a late diagnosis &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall">There were significant associations between age at diagnosis and the condition suggesting the diagnosis &#40;respiratory and digestive symptoms&#41;&#44; as noted in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">Although respiratory symptoms &#40;recurrent&#47;acute respiratory infections&#44; cough&#44; haemoptysis&#41; were the most frequent clinical manifestations leading to the diagnosis in all patients&#44; this is particularly evident when patients are diagnosed as adults &#40;G2 vs&#46; G1&#58; 75&#46;9&#37; vs&#46; 42&#46;6&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;005&#41;&#46; Patients in G1 showed a greater variability in conditions suggesting the diagnosis&#44; and digestive symptoms that most frequently lead to diagnosis &#40;G1 vs&#46; G2&#58; 44&#46;7&#37; vs&#46; 17&#46;2&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;014&#41;&#46; In G2&#44; 3&#46;4&#37; of patients were diagnosed due to fertility problems and failure to thrive was observed only in G1&#46; Furthermore&#44; respiratory symptoms were more frequent in female patients &#40;70&#46;7&#37; vs&#46; 37&#46;1&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#41; whereas digestive symptoms were the most frequent in males &#40;54&#46;3&#37; vs&#46; 17&#46;1&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">All patients studied were genotyped&#46; The most frequent mutation identified was delF508 &#40;54&#46;9&#37;&#41;&#44; 27 patients &#40;30&#46;3&#37;&#41; were homozygous and 41 &#40;46&#46;1&#37;&#41; heterozygous&#46; The second most common mutation was R334<span class="elsevierStyleHsp" style=""></span>W &#40;12&#46;7&#37;&#41;&#46; There was a greater percentage of patients homozygous for the mutation delF508 in G1 &#40;43&#46;6&#37; vs&#46; 8&#46;8&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41; as illustrated in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46; Greater heterogeneity of mutations in the G2 has been verified&#59; significantly higher percentages of patients in G2 were either heterozygous for delF508 or did not carry the allele &#40;91&#46;2&#37; vs&#46; 56&#46;4&#37;&#44; respectively&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">According to CFTR mutation classes&#44; 40 &#40;46&#46;5&#37;&#41; had CFTR mutation classes I&#44; II or III &#40;severe&#41; and 46 patients &#40;53&#46;5&#37;&#41; had at least one allele from classes IV&#8211;VI &#40;mild&#41;&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Thirty-six patients &#40;66&#46;7&#37;&#41; showed severe mutation classes in G1&#44; compared with 4 patients &#40;11&#46;8&#37;&#41; in G2 &#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="par0155" class="elsevierStylePara elsevierViewall">Considering pancreatic function&#44; 39 patients &#40;97&#46;5&#37;&#41; with severe CFTR mutation classes presented pancreatic insufficiency vs&#46; 9 patients &#40;19&#46;6&#37;&#41; with mild CFTR mutation classes &#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="par0160" class="elsevierStylePara elsevierViewall">The average value of FEV<span class="elsevierStyleInf">1</span> was 58&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>28&#46;9&#37;&#44; 23 patients &#40;25&#46;8&#37;&#41; with FEV<span class="elsevierStyleInf">1</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>80&#37; and 26 &#40;29&#46;2&#37;&#41; &#60;40&#37;&#44; 3 of which &#60;20&#37;&#46; The assessment of respiratory function showed a higher severity in G1&#44; with patients in G2 attaining slightly higher mean percentage predicted of FVC and FEV<span class="elsevierStyleInf">1</span> scores&#59; there was not a significant difference in FVC and FEV<span class="elsevierStyleInf">1</span> values between groups &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0165" class="elsevierStylePara elsevierViewall">Thus&#44; despite being considerably older &#40;about 12 years difference&#41;&#44; the G2 patients presented results of lung function tests which were similar to the G1&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Forty-nine patients &#40;56&#37;&#41; had exocrine pancreatic insufficiency and 8 of these also had CF-related diabetes and were on insulin therapy&#46; A higher rate of pancreatic insufficiency was found in G1 and this difference was significant &#40;74&#46;1&#37; vs&#46; 27&#46;3&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Pancreatic function is closely related to the genotype&#46; All patients with delF508 homozygous had pancreatic dysfunction&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">The average value of body-mass-index &#40;BMI&#41; was 20&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;1<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#46; Forty-one patients &#40;46&#46;1&#37;&#41; had BMI<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>20 and 14 &#40;15&#46;7&#37;&#41; were obese &#40;BMI<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>25&#41;&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Assessment of BMI showed a higher level of this variable in G1 and this difference was statistically significant &#40;20&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;4 vs&#46; 22&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;8&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;018&#41;&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">In culture result analysis&#44; lung transplant patients &#40;14&#41; were excluded and therefore only 75 patients were considered&#46; The most common microbiological isolates were <span class="elsevierStyleItalic">Pseudomonas aeruginosa &#40;Pa&#41;</span> in 49 patients &#40;55&#46;1&#37;&#41; and <span class="elsevierStyleItalic">methicillin-sensitive-Staphylococcus-aureus &#40;MSSA&#41;</span> in 50 &#40;56&#46;2&#37;&#41;&#46; Most of the patients had fewer than three microbiological isolates and more than two germs isolated&#46; Regarding differences between microbiological isolation and age at diagnosis &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#44; <span class="elsevierStyleItalic">Pa</span> and <span class="elsevierStyleItalic">MSSA</span> were the most frequently isolated microorganisms in both groups &#40;G1 vs&#46; G2&#58; <span class="elsevierStyleItalic">Pa</span>&#58; 60&#46;0&#37; vs&#46; 47&#46;1&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;33&#59; <span class="elsevierStyleItalic">MSSA</span>&#58; 58&#46;2&#37; vs&#46; 52&#46;9&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;792&#41;&#46; <span class="elsevierStyleItalic">Burkholderia cepacia</span> was isolated only in G1 &#40;12&#46;7&#37; vs&#46; 0&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;041&#41;&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Lung transplantation rate was higher in G2 &#40;G2 vs&#46; G1&#58; 20&#46;6&#37; vs&#46; 12&#46;7&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;490&#41;&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Fourteen-patients were hospitalized for complications&#46; Hospital admissions rate was higher in G1 &#40;G1 vs&#46; G2&#58; 44&#46;0&#37; vs&#46; 17&#46;6&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;148&#41;&#46; Two-patients &#40;2&#46;2&#37;&#41; died due to lung transplant rejection and sepsis of pulmonary origin&#46; Mortality rate was higher in G1 &#40;G2 vs&#46; G1&#58; 0&#37; vs&#46; 3&#46;6&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;522&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Discussion</span><p id="par0200" class="elsevierStylePara elsevierViewall">In consideration of the fact that diagnosis of CF in adulthood is possible and appears to be increasing&#44;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a> this study explored issues dealing with late diagnosis&#44; with the objective of identifying any possible differences in clinical presentation of CF between patients diagnosed before and after 18 years of age&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">In this study adults who received late diagnosis of CF have unique characteristics that suggest particular needs in terms of treatment and support&#59; they experienced fewer complications and fewer hospital admissions than those who received diagnosis under 18 years of age&#44; in whom respiratory &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;148&#41; and pancreatic &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; involvement was less severe and had a significantly better nutritional status &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;018&#41;&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Significant association between age at diagnosis and the condition suggesting the diagnosis was found&#44; in spite of the fact that respiratory symptoms were the most frequent manifestations leading to the diagnosis in all patients&#59; this is particularly evident when the diagnosis is made in adulthood&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">The study also found a greater percentage of homozygous delF508 among patients diagnosed earlier in life than in those diagnosed in adulthood&#44; and this difference was statistically significant&#46; It is recognized that homozygosity for delF508 mutation is associated with a high systemic repercussion of CF&#44; a high level of pancreatic insufficiency and a low BMI&#46; On the other hand&#44; the greater heterogeneity in mutations of patients with a late diagnosis found in this study could be responsible for the greater variance in conditions leading to diagnosis and the overall better indexes of health in this group&#59; it is a fact that patients diagnosed in adulthood had fewer hospitalizations and experience fewer complications than those diagnosed early in life and most of them were pancreatic sufficient&#44; which is closely related to the type of CFTR mutation associated&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">27&#44;28</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">In the study&#44; as is common in the literature&#44; most of those diagnosed early in life present with a combination of gastrointestinal and pulmonary symptoms&#44; while in the late diagnosis group of patients most were diagnosed due to recurrent pulmonary infections and gastrointestinal symptoms were less frequent&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">25</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">The acquisition of infectious agents is an important environmental modifier which determines course and prognosis of most patients with CF&#46; Furthermore&#44; patients who are infected experience a more rapid decline of lung function than their non- infected peers&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a> Although no significant difference between age at diagnosis and culture results was found&#44; and there was not a significant difference in FVC and FEV<span class="elsevierStyleInf">1</span> values between groups&#44; there was a higher percentage of microbiological isolations in G1 patients&#44; and the assessment of respiratory function showed a greater severity in these patients&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">No significant differences were found between groups in terms of transplantation and mortality rates&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">The above results provide empirical support that supports the argument that patients with a late diagnosis of CF are different from those who receive early diagnosis&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusions</span><p id="par0240" class="elsevierStylePara elsevierViewall">In summary&#44; this study is the first description of the Portuguese adult CF population and the first to examine two distinct populations on the basis of age at diagnosis&#44; which is particularly important&#44; since it gives us a better understanding of real life&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">A significant percentage of our patients were diagnosed in adulthood&#44; which highlights the need for diagnostic suspicion in a patient with chronic lung disease and atypical symptoms&#46; In the study performed&#44; a 10 years longer lifetime was detected in patients diagnosed in adulthood&#46; This difference may be associated with higher frequency of homozygosity for the mutation delF508 found in patients diagnosed early in life which is usually associated to a higher systemic repercussion of CF and a higher level of pancreatic insufficiency cases and lower BMI&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">The results suggest that patients diagnosed in the paediatric age group have characteristics that distinguish them from those diagnosed in adulthood&#44; which may have implications in terms of diagnosis&#44; prognosis and life expectancy&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Ethical responsibilities</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Protection of human and animal subjects</span><p id="par0255" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Confidentiality of data</span><p id="par0260" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Right to privacy and informed consent</span><p id="par0265" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflicts of interest</span><p id="par0270" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Cystic fibrosis &#40;CF&#41; is the most common autosomal recessive disease in Caucasians&#46; Although most cases are diagnosed in childhood&#44; diagnosis in adults is apparently increasing&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Evaluate the adult population with CF&#44; comparing patients who were diagnosed before and after 18 years of age&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Retrospective analysis of patients followed in three main medical centres in Portugal in 2012&#46; Comparison of two groups&#58; G1 &#8211; patients diagnosed at &#60;18 years and G2 &#8211; patients diagnosed at &#8805;18 years&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">89 adults were identified&#58; 61&#46;8&#37; in G1&#44; 38&#46;2&#37; in G2&#46; Gender distribution was similar in both groups&#46; Average age in G2 was higher &#40;38&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;4 vs&#46; 26&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;1 years&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Respiratory symptoms most frequently led to CF diagnosis in all patients&#44; mainly in adulthood&#46; There was a greater percentage of patients homozygous for the mutation delF508 in G1 &#40;43&#46;6 vs&#46; 8&#46;8&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&#46; Respiratory and pancreatic function&#44; and body mass index &#40;BMI&#41; showed a higher severity in G1 &#40;G1 vs&#46; G2&#58; FEV1&#58; 54&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>27&#46;3 vs&#46; 29&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>64&#46;6&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;177&#59; pancreatic insufficiency 72&#46;7 vs&#46; 26&#46;5&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#59; BMI 20&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;4 vs&#46; 22&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;8&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;018&#41;&#46; <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> and <span class="elsevierStyleItalic">methicillin-sensitive Staphylococcus aureus</span> were the most frequently isolated microorganisms&#46; Lung transplantation rate was higher in G2 &#40;20&#46;6 vs&#46; 10&#46;9&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;231&#41; while mortality rate was higher in G1 &#40;0 vs&#46; 3&#46;6&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;261&#41;&#46; Hospital admission rate was higher in G1 as well as mortality rate&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The results suggest that patients with CF diagnosed in childhood have characteristics that distinguish them from those diagnosed in adulthood&#44; and these differences may have implications for diagnosis&#44; prognosis and life expectancy&#46;</p></span>"
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                  \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">Gender&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">Group G1 &#40;&#60;18 years&#41;&#44; &#37;<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>55&#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">Group G2 &#40;&#8805;18 years&#41;&#44; &#37;<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>34&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">62&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37&#46;5&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Association between age at diagnosis and gender in patients with CF&#46;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></p>"
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                  \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">Presentation forms<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&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">Group G1 &#40;&#60;18 years&#41;&#44; &#37;<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>55&#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">Group G2 &#40;&#8805;18 years&#41;&#44; &#37;<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>34&#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>-Value&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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Respiratory symptoms&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">75&#46;9&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;005&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Digestive symptoms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">44&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&#46;2&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;014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Family screening&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;4&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;283&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Failure to thrive malnutrition&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&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;283&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Infertility&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;4&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;382&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Association between age at diagnosis and condition suggesting diagnosis&#46;</p>"
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                  \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">Genotype&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">delF508 Homozygous&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&#46;8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">55&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Others mutations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Association between genotype delF508 and age at diagnosis&#46;<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a></p>"
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                  \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">Lung function&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FEV<span class="elsevierStyleInf">1</span>&#37; predicted&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">65&#46;6 &#40;30&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">34&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;148&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FVC &#37; predicted&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">72&#46;1 &#40;31&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">85&#46;6 &#40;29&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20&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;197&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22&#46;2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;0&nbsp;\t\t\t\t\t\t\n
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            0 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:1 [
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:6 [
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                        "paginaInicial" => "2"
                        "paginaFinal" => "10"
                        "serieVolumen" => "vol&#46; 34"
                        "serieTitulo" => "Cystic fibrosis in the 21st century&#46; Prog Respir Res"
                        "serieFecha" => "2006"
                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0160"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The molecular genetic epidemiology of cystic fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "WHO"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2004"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The prevalence of cystic fibrosis in the European Union"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "P&#46;M&#46; Farrell"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jcf.2008.03.007"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Cyst Fibros"
                        "fecha" => "2008"
                        "volumen" => "7"
                        "paginaInicial" => "450"
                        "paginaFinal" => "453"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18442953"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Guidelines for the diagnosis and management of cystic fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "F&#46;A&#46; Abreu"
                            1 => "J&#46;A&#46; Dodge"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:2 [
                        "fecha" => "1996"
                        "editorial" => "World Health Organization"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Expression of the cystic fibrosis gene in human foetal tissues"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "A&#46;E&#46; Trezise"
                            1 => "J&#46;A&#46; Chambers"
                            2 => "C&#46;J&#46; Wardle"
                            3 => "S&#46; Gould"
                            4 => "A&#46; Harris"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Hum Mol Genet"
                        "fecha" => "1993"
                        "volumen" => "2"
                        "paginaInicial" => "213"
                        "paginaFinal" => "218"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7684639"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0180"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "The cystic fibrosis transmembrane conductance regulator&#58; an intriguing protein with pleiotropic functions"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46; Vankeerberghen"
                            1 => "H&#46; Cuppens"
                            2 => "J&#46;J&#46; Cassiman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Cyst Fibros"
                        "fecha" => "2002"
                        "volumen" => "1"
                        "paginaInicial" => "13"
                        "paginaFinal" => "29"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15463806"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            6 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Identification of the cystic fibrosis gene&#58; cloning and characterization of complementary DNA"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;R&#46; Riordan"
                            1 => "J&#46;M&#46; Rommens"
                            2 => "B&#46; Kerem"
                            3 => "N&#46; Alon"
                            4 => "R&#46; Rozmahel"
                            5 => "Z&#46; Grzelczak"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Science"
                        "fecha" => "1989"
                        "volumen" => "245"
                        "paginaInicial" => "1066"
                        "paginaFinal" => "1073"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2475911"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
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              "identificador" => "bib0190"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Identification of the cystic fibrosis gene&#58; chromosome walking and jumping"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;M&#46; Rommens"
                            1 => "M&#46;C&#46; Iannuzzi"
                            2 => "B&#46; Kerem"
                            3 => "M&#46;L&#46; Drumm"
                            4 => "G&#46; Melmer"
                            5 => "M&#46; Dean"
                          ]
                        ]
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                    ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Science"
                        "fecha" => "1989"
                        "volumen" => "245"
                        "paginaInicial" => "1059"
                        "paginaFinal" => "1065"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2772657"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0195"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Genotype&#8211;phenotype correlation in cystic fibrosis patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46; Ferrari"
                            1 => "L&#46; Cremonesi"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Ann Biol Clin &#40;Paris&#41;"
                        "fecha" => "1996"
                        "volumen" => "54"
                        "paginaInicial" => "235"
                        "paginaFinal" => "241"
                      ]
                    ]
                  ]
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              ]
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              "etiqueta" => "10"
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                    0 => array:2 [
                      "titulo" => "Mechanisms of disease&#58; cystic fibrosis"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "S&#46;M&#46; Rowe"
                            1 => "S&#46; Miller"
                            2 => "E&#46;J&#46; Sorscher"
                          ]
                        ]
                      ]
                    ]
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                    0 => array:2 [
                      "doi" => "10.1056/NEJMra043184"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2005"
                        "volumen" => "352"
                        "paginaInicial" => "1992"
                        "paginaFinal" => "2001"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15888700"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0205"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cystic fibrosis&#58; a 2002 update"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "B&#46;M&#46; Orenstein"
                            1 => "G&#46;B&#46; Winnie"
                            2 => "H&#46; Altman"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1067/mpd.2002.120269"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Pediatr"
                        "fecha" => "2002"
                        "volumen" => "140"
                        "paginaInicial" => "156"
                        "paginaFinal" => "164"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11865265"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0210"
              "etiqueta" => "12"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cystic fibrosis&#58; terminology and diagnostic algorithms"
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                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46; De Boeck"
                            1 => "M&#46; Wilschanski"
                            2 => "C&#46; Castellani"
                            3 => "C&#46; Taylor"
                            4 => "H&#46; Cuppens"
                            5 => "J&#46; Dodge"
                          ]
                        ]
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                    0 => array:2 [
                      "doi" => "10.1136/thx.2005.043539"
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2006"
                        "volumen" => "61"
                        "paginaInicial" => "627"
                        "paginaFinal" => "635"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16384879"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
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                    0 => array:1 [
                      "titulo" => "Cystic Fibrosis Foundation&#58; Patient Registry Annual Data Report to the Center Directors 2013"
                    ]
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                        "fecha" => "2014"
                        "editorial" => "Cystic Fibrosis Foundation"
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            13 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cystic fibrosis adult care&#58; consensus conference report"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "J&#46;R&#46; Yankaskas"
                            1 => "B&#46;C&#46; Marshall"
                            2 => "B&#46; Sufian"
                            3 => "R&#46;H&#46; Simon"
                            4 => "D&#46; Rodman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2004"
                        "volumen" => "125"
                        "numero" => "Suppl&#46;"
                        "paginaInicial" => "1S"
                        "paginaFinal" => "39S"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14734689"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Manifestations of cystic fibrosis diagnosed in adulthood"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46;N&#46; Jerry"
                            1 => "M&#46;R&#46; David"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Opin Pulm Med"
                        "fecha" => "2005"
                        "volumen" => "11"
                        "paginaInicial" => "513"
                        "paginaFinal" => "518"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16217177"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cystic fibrosis of the pancreas in an adult"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "H&#46;K&#46; Hellerstein"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Ohio Med J"
                        "fecha" => "1946"
                        "volumen" => "42"
                        "paginaInicial" => "616"
                        "paginaFinal" => "617"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20986203"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Acute presentation of cystic fibrosis in an adult"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "K&#46;R&#46; Gardiner"
                            1 => "B&#46; Cranley"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Postgrad Med J"
                        "fecha" => "1989"
                        "volumen" => "65"
                        "paginaInicial" => "471"
                        "paginaFinal" => "472"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2602238"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Newly diagnosed cystic fibrosis in middle and later life"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "B&#46; Hunt"
                            1 => "D&#46;M&#46; Geddes"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "1984"
                        "volumen" => "40"
                        "paginaInicial" => "23"
                        "paginaFinal" => "26"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3918355"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cystic fibrosis in an adult"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "S&#46; Fiel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Emerg Med"
                        "fecha" => "1988"
                        "volumen" => "20"
                        "paginaInicial" => "109"
                        "paginaFinal" => "121"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cystic fibrosis in adults"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "J&#46; Godby"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Miss State Med Assoc"
                        "fecha" => "1985"
                        "volumen" => "26"
                        "paginaInicial" => "161"
                        "paginaFinal" => "163"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4009708"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Typical cystic fibrosis in an elderly woman"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "C&#46;T&#46; Su"
                            1 => "B&#46; Beanblossom"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Med"
                        "fecha" => "1989"
                        "volumen" => "86"
                        "paginaInicial" => "701"
                        "paginaFinal" => "703"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2729321"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A cystic fibrosis mutation associated with mild lung disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46;H&#46; Gan"
                            1 => "H&#46;J&#46; Veeze"
                            2 => "A&#46;M&#46; van den Ouweland"
                            3 => "D&#46;J&#46; Halley"
                            4 => "H&#46; Scheffer"
                            5 => "A&#46; van der Hout"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "1995"
                        "volumen" => "333"
                        "paginaInicial" => "93"
                        "paginaFinal" => "99"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical manifestations of cystic fibrosis among patients with diagnosis in adulthood"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46; Gilljam"
                            1 => "L&#46; Ellis"
                            2 => "M&#46; Corey"
                            3 => "J&#46; Zielenski"
                            4 => "P&#46; Durie"
                            5 => "D&#46;E&#46; Tullis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1378/chest.126.4.1215"
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2004"
                        "volumen" => "126"
                        "paginaInicial" => "1215"
                        "paginaFinal" => "1224"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15486385"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Genetic and clinical features of patients with cystic fibrosis diagnosed after the age of 16 years"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "K&#46;H&#46; Gan"
                            1 => "W&#46;P&#46; Geus"
                            2 => "W&#46; Bakker"
                            3 => "C&#46;B&#46; Lamers"
                            4 => "H&#46;G&#46; Heijerman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "1995"
                        "volumen" => "50"
                        "paginaInicial" => "1301"
                        "paginaFinal" => "1304"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8553305"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cystic fibrosis diagnosed in adult patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "T&#46;J&#46; McWilliams"
                            1 => "M&#46;L&#46; Wilsher"
                            2 => "J&#46; Kolbe"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "N Z Med J"
                        "fecha" => "2000"
                        "volumen" => "113"
                        "paginaInicial" => "6"
                        "paginaFinal" => "8"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10738492"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Health status and sociodemographic characteristics of adults receiving a cystic fibrosis diagnosis after age 18 years"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "E&#46; Widerman"
                            1 => "L&#46; Millner"
                            2 => "W&#46; Sexauer"
                            3 => "S&#46; Fiel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2000"
                        "volumen" => "118"
                        "paginaInicial" => "427"
                        "paginaFinal" => "433"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10936136"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Independent genetic determinants of pancreatic and pulmonary status in cystic fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "G&#46; Santis"
                            1 => "L&#46; Osborne"
                            2 => "R&#46;A&#46; Knight"
                            3 => "M&#46;E&#46; Hodson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "1990"
                        "volumen" => "336"
                        "paginaInicial" => "1081"
                        "paginaFinal" => "1084"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1977977"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Genetic determination of exocrine pancreatic function in cystic fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; Kristidis"
                            1 => "D&#46; Bozon"
                            2 => "M&#46; Corey"
                            3 => "D&#46; Markiewicz"
                            4 => "J&#46; Rommens"
                            5 => "L&#46;C&#46; Tsui"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Hum Genet"
                        "fecha" => "1992"
                        "volumen" => "50"
                        "paginaInicial" => "1178"
                        "paginaFinal" => "1184"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1376016"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0295"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Genetic and environmental modifiers of cystic fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "B&#46; Tummler"
                            1 => "F&#46; Stanke"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "ERS Monogr"
                        "fecha" => "2014"
                        "volumen" => "64"
                        "paginaInicial" => "47"
                        "paginaFinal" => "64"
                      ]
                    ]
                  ]
                ]
              ]
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Article information

ISSN: 21735115
Original language: English

DOI:10.1016/j.rppnen.2016.07.002

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