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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Idiopathic pulmonary fibrosis &#40;IPF&#41; is a disease that occurs more often in men&#44; with a reported male&#58;female ratio of between 1&#46;6&#58;1 and 2&#58;1&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">1&#44;2</span></a> Previous studies indicate that the course of IPF may be more benign in women&#44; an observation which could be based on differences in gene expression&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">3&#8211;5</span></a> Given that these studies were conducted prior to the publication of the current diagnostic criteria&#44; and without taking into account the variable of autoantibodies&#44; patients with diagnoses other than IPF might have been included&#46; We believed&#44; then&#44; that a new study comparing the progress of these patients according to gender could provide valuable information&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">For this reason&#44; we decided to perform this retrospective cohort study in patients with a diagnosis of IPF &#40;according to the 2011 ATS&#47;ERS&#47;JPS&#47;ALAT&#41;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a> seen in a multidisciplinary clinic specializing in interstitial lung diseases &#40;ILD&#41;&#46; Patients were recruited between March 2012 and July 2015&#46; The main study outcome variable was time from date of diagnosis to date of all-cause death or lung transplantation&#46; The main study exposure variable was sex&#46; The following variables were analyzed to avoid potential confusion between sex and the outcome variable&#58; age&#44; smoking&#44; time of dyspnea in months&#44; the development of acute exacerbations &#40;defined according to current international recommendations&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a> rheumatoid factor &#40;RF&#41; by nephelometry&#44; and antinuclear antibodies &#40;ANA&#41; by indirect immunofluorescence&#46; Other study variables included previous treatment with triple therapy &#40;systemic corticosteroids&#44; azathioprine&#44; and N-acetylcisteine&#41; before attending our clinic&#44; and use of pirfenidone&#46; Results were communicated according to the indications of the STROBE initiative&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Time of death or transplantation was estimated using Kaplan&#8211;Meier methods&#46; The rates of events between the sexes at 18 months were studied using survival estimators and 95&#37; confidence intervals&#44; and compared using the log rank test&#46; A multivariate Cox model was applied&#44; using sex as the first independent variable&#46; Variables that were significant in the univariate analysis and those considered clinically relevant were included&#46; Both crude and adjusted HR and their 95&#37; CI were reported&#46; A <span class="elsevierStyleItalic">P</span>-value of &#60;&#46;05 was considered statistically significant&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The study included 86 patients&#44; of which 21 were women &#40;24&#46;4&#37;&#41;&#46; Mean &#40;SD&#41; age was 65&#46;4 &#40;9&#41; years&#46; When characteristics were compared by sex&#44; the prevalence of smoking was higher among men &#40;84&#46;6&#37; vs 59&#46;1&#37;&#44; <span class="elsevierStyleItalic">P</span>&#60;&#46;01&#41;&#46; No significant differences in age&#44; baseline forced vital capacity &#40;FVC&#37;&#41;&#44; time since onset of dyspnea&#44; or percentage of patients with positive ANA or RF were found at diagnosis&#46; No differences were observed in the time of administration or proportion of patients who received triple therapy prior to attending our clinic&#44; nor in the percentage of patients who received pirfenidone or had an acute exacerbation&#46; In the analysis of time to death or transplantation&#44; overall all-cause mortality was 38&#46;4&#37; &#40;33&#47;86&#41;&#44; 35&#46;4&#37; &#40;23&#47;65&#41; in men&#44; and 47&#46;6&#37; &#40;10&#47;21&#41; in women&#46; Median survival was 34&#46;03 months in women and 36&#46;06 months in men&#46; Four patients received a lung transplant &#40;3 men&#41; and the indication for transplantation was established at the time of diagnosis&#46; When survival at 18 months was compared by sex&#44; no statistically significant differences were observed&#44; with rates of 0&#46;75 &#40;95&#37; CI&#44; 0&#46;61&#8211;0&#46;85&#41; in men and 0&#46;71 &#40;95&#37; CI&#44; 0&#46;44&#8211;0&#46;87&#41; in women &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;88&#41;&#46; In the Cox univariate analysis &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; treatment with pirfenidone was associated with longer survival&#44; but this effect disappeared after adjusting for the remaining variables included&#46; In the Cox multivariate analysis&#44; the only variable that showed statistical significance was baseline FVC&#37; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">In our study&#44; we found no significant differences when the survival of patients with IPF was compared by sex&#46; Treatment with pirfenidone was significantly associated with better survival in the univariate analysis&#44; but this effect disappeared in the multivariate analysis&#44; although it maintained a trend toward statistical significance&#46; This may be explained by the fact that patients who received pirfenidone had baseline FVC&#8805;50&#37; predicted value&#46; Our study has some limitations&#46; It is a retrospective study conducted in a single center&#46; Moreover&#44; with the exception of ANA and RF&#44; other antibodies were not routinely analyzed&#46; However&#44; all patients were evaluated by the clinical immunology department&#44; which ruled out the presence of an autoimmune disease by additional tests and determination of specific antibodies &#40;e&#46;g&#46;&#44; citrullinated peptide antibodies or myospecific antibodies&#41;&#44; when necessary&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a> Previous studies indicate that the female sex is associated with better survival in IPF&#44; and was considered a factor for good prognosis in a score proposed by a group of researchers&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">4&#44;10</span></a> However&#44; these studies were performed using the ATS&#47;ERS criteria from the year 2000&#46; A recent study showed that of 60 patients who met diagnostic criteria in the year 2000&#44; only 46 met the current diagnostic criteria&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a> suggesting that approximately 25&#37; of patients with IPF according to previous criteria could have had another IPD&#46; This is of interest&#44; given the differences in survival between IPF and other ILD&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a> Chronic hypersensitivity pneumonitis may be confused with IPF&#44; which is relevant&#44; since it has a more benign disease course&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a> Autoimmune diseases are more common in women<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">13</span></a> and may present a pattern of usual interstitial pneumonia indistinguishable from IPF&#44;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">14&#44;15</span></a> and generally associated with better survival&#46; We believe that including autoantibodies in a survival analysis according to sex in patients with IPF is of crucial importance&#46; Our study has been the first to include this adjustment variable and to use current diagnostic criteria to analyze the relationship between sex and survival in patients with IPF&#46; As the patients included in our study meet the current criteria of IPF&#44; and were evaluated by a specialist multidisciplinary group&#44; we believe that our results are valid and can be extrapolated to other populations&#46; However&#44; prospective studies are needed to confirm our results&#46;</p></span>"
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Scientific Letter
The Influence of Sex on Prognosis of Patients With Idiopathic Pulmonary Fibrosis in a Retrospective Cohort
Influencia del género en el pronóstico de pacientes con fibrosis pulmonar idiopática en una cohorte retrospectiva
Fabián Matías Caro
Corresponding author
fabiancarodoc@gmail.com

Corresponding author.
, María Laura Alberti, Martín Eduardo Fernández, Francisco Paulin
Consultorio multidisciplinario de enfermedades pulmonares intersticiales, Hospital de Rehabilitación Respiratoria «María Ferrer», Buenos Aires, Argentina

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