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registries of patients based on clinical results and natural history&#44; and population registries based on epidemiological and social welfare research and social welfare planning&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Patient registries may be created by agreement with scientific societies or based on the experience of a particular institution or expert network&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> One of the problems of this type of registry and the information they provide is that the cases are limited to those seen in participating centers&#44; leaving open the possibility of a selection bias toward more severe cases&#46; Notification of cases is voluntary&#44; limited to some experts&#44; and requires patient consent&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">At present&#44; in addition to the SEPAR&#44; the following scientific societies have reached a collaborative agreement with the ISCIII for participation in the strategy for development of patient registries within the RNER and SpainRDR&#58; Spanish Society of Pediatric Pulmonology &#40;SNEP&#41;&#44; Spanish Society of Family and Community Medicine &#40;semFYC&#41;&#44; European Network of Rare and Congenital Anemias &#40;ENERCA&#41;&#44; Spanish Society of Allergy and Clinical Immunology &#40;SEAIC&#41;&#44; Spanish Society of Pediatric Endocrinology &#40;SEEP&#41;&#44; Spanish Society of Neurology &#40;SEN&#41; and Center of Energy&#44; Environmental and Technological Research &#40;CIEMAT&#41;&#46; Negotiations are currently ongoing with another 5 societies and with other research networks such as CIBERNED&#46; Agreements have also been signed with the pharmaceutical industry and the Spanish Federation of Rare Diseases &#40;FEDER&#41; itself&#46; On an international level&#44; the IRDiRC consortium has already set in motion projects closely related with SpainRDR&#44; 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the population registry works with all the autonomous communities of Spain to collect information on all RDs&#46; To this end&#44; strategies have been developed for collecting data from various electronic sources such as the Minimum Basic Data Set &#40;CMBD&#41; that contains information on hospital discharge reports&#44; death certificates&#44; primary care sources&#44; neonatal and congenital malformation screening programs&#44; etc&#46; In the near future&#44; this information&#44; once validated and consolidated&#44; will allow us to estimate the incidence of the various diseases&#44; regional distribution&#44; prevalence and survival&#44; depending on the quality of follow-up in all cases&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Each of the 17 Spanish autonomous communities is setting up its own regional RD registry&#59; in the autonomous cities of Ceuta and Melilla&#44; 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In addition&#44; the recording of common parameters has been standardized &#40;demographic data&#44; smoking&#44; respiratory function tests&#44; blood gases and the walking test&#41; so that in the future data can be compared between registries&#46; Furthermore&#44; generic quality of life questionnaires have been added to the purely respiratory parameters to allow the impact of MRDs to be compared with other non-respiratory RDs or even with common diseases&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">All the registries include quality data related to each condition and comply with the applicable data protection legislation&#46; They will be accessible from the national registry website &#40;<a id="intr0040" class="elsevierStyleInterRef" href="https://registroraras.isciii.es/">https&#58;&#47;&#47;registroraras&#46;isciii&#46;es</a>&#41;&#44; as well as from the SEPAR website &#40;<a id="intr0045" class="elsevierStyleInterRef" href="http://www.separ.es/">www&#46;separ&#46;es</a>&#41; or from the website of the SpainRDR project &#40;<a id="intr0050" class="elsevierStyleInterRef" href="https://spainrdr.isciii.es/">https&#58;&#47;&#47;spainrdr&#46;isciii&#46;es</a>&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Each consultant committee is responsible for updating the contents of each registry&#44; and the final responsibility lies with each coordinator&#44; as representative of the consultant committee before SEPAR and the IIER&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The RNER itself does not provide funds for conducting parallel research based on registry data&#46; This type of initiative must be funded&#44; if required&#44; by the societies themselves or national or international research agencies&#46; The inclusion of the RNER in the international IRDiRC consortium will facilitate the creation of partnership agreements with similar registries in other countries&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">This brief description gives an idea of the multiple applications of the available information and the advantages of accumulating quality data for biomedical research at a time in which current technological possibilities for sharing knowledge only serve to reinforce the individual experience of professionals in the interests of improving knowledge in these areas&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Spanish Registry of Patients With Alpha-1 Antitrypsin Deficiency</span><p id="par0085" class="elsevierStylePara elsevierViewall">Alpha-1 antitrypsin &#40;AAT&#41; deficiency is the result of mutations that change the structure of the AAT protein&#44; thus affecting its function&#46; It appears mainly in the form of pulmonary emphysema&#44; liver cirrhosis&#44; and less frequently as other diseases &#40;panniculitis&#44; vasculitis&#44; etc&#46;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> There are estimated to be around 12<span class="elsevierStyleHsp" style=""></span>000 individuals with severe AAT deficiency in Spain&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">The Spanish Registry of Patients With Alpha-1 Antitrypsin Deficit &#40;REDAAT&#41; set up at the end of the 90s is part of the SEPAR chronic obstructive pulmonary disease &#40;COPD&#41; working area&#46; Since it was founded&#44; REDAAT has worked to further knowledge on AAT deficiency and awareness of this entity&#44; improve treatment of affected subjects and encourage research&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#8211;11</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">At present&#44; REDAAT resources include a consultant committee consisting of 12 pulmonologists&#44; 3 pediatrics and 3 basic researchers&#44; in addition to reference laboratory managers and computer support staff&#46; Over 300 physicians throughout Spain collaborate with this registry&#46; The main technical resource is <a id="intr0055" class="elsevierStyleInterRef" href="http://www.redaat.es/">www&#46;redaat&#46;es</a>&#44; legally part of the Respira Spanish Lung Foundation&#46; It has a public access area providing general information and a restricted access area for healthcare professionals where the form for recording patient data and real-time information on cases registered&#44; overall characteristics&#44; diagnoses and treatment can be found&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">REDAAT has collaborated actively in the Alpha One International Registry &#40;&#91;AIR&#93; <a id="intr0060" class="elsevierStyleInterRef" href="http://www.antitrypsindeficiency.org/">http&#58;&#47;&#47;www&#46;antitrypsindeficiency&#46;org</a>&#41; since its creation&#44; as well as with some other European national registries&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Since this registry has its own domain and an up-and-running database&#44; created prior to the formation of the RNER&#44; it is not integrated in this registry&#39;s platform although they do share their data&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">A summary of cases registered is shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Spanish Tracheal Stenosis Registry</span><p id="par0115" class="elsevierStylePara elsevierViewall">Two groups can defined under the term tracheal stenosis&#58; secondary benign laryngotracheal stenosis and idiopathic tracheal stenosis&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Idiopathic tracheal stenosis is a disease characterized by the development of fibrous stenotic scarring in the cricoid region and the upper third of the trachea&#44; with thickening of the submucosa but no underlying cartilage involvement&#46; It mainly affects women&#44; and the principal symptoms are dyspnea and stridor developing over a period of years&#46; Diagnosis is incompatible with a history of other upper airway stenosis that could be defined as secondary&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Incidence and prevalence are unknown&#44; as are etiology and prognostic factors&#46; No specific diagnostic and treatment guidelines are available and it has not yet been included in international RD catalogs&#46; Accumulated experience with this disease is centered mainly on the various therapeutic surgical techniques&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#8211;21</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Secondary benign laryngotracheal stenosis is usually due to one of the following causes&#58; post-intubation&#44; post-trauma&#44; inhalation of toxic smoke&#44; post-surgery&#44; infection&#44; inflammatory activity&#44; extrinsic and neurological compression&#44; and are not the focus of this registry&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">In the last 30 years&#44; the development of tracheal surgery&#44; along with other therapeutic alternatives &#40;laser&#44; dilations and tracheal prosthetic devices&#41;&#44; has meant that most of these benign laryngotracheal lesions can be treated&#44; although accumulation of experience in healthcare centers is limited by their relative rarity&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The Spanish Tracheal Stenosis Registry &#40;REET&#41; is an integral part of the SEPAR Thoracic Surgery Area&#46; Over 40 professionals have joined this registry as collaborators&#44; its database is an integral part of the RNER platform&#44; and data collection will begin in 2014&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Spanish Registry of Pulmonary Langerhans Cell Histiocytosis</span><p id="par0145" class="elsevierStylePara elsevierViewall">Pulmonary Langerhans cell histiocytosis &#40;PLCH&#41; in adults is characterized by a peribronchiolar proliferation of Langerhans histiocytes&#44; a dendritic cell involved in the immune response&#46; It primarily affects adults between 20 and 40 years of age&#44; with no preference for sex&#46; Progress is generally benign&#44; although around 30&#37; of patients have progressively deteriorating lung function&#46; It is associated with smoking&#44; with 95&#37; of patients being smokers&#44; but etiology is unknown and the exact incidence and prevalence of PLCH in adults has not been determined&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">An expert consensus paper was recently published giving recommendations on the diagnosis and treatment of this disease that is hoped to go some way toward standardizing procedures&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> The main treatment in severe cases is lung transplantation&#44; although the use of chemotherapeutic agents for treating progressive disease has been proposed&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">There are very few data in our setting on the characteristics and management of PLCH&#46; The first multicenter series was published recently&#44; showing the importance of the use of clinical guidelines in the diagnosis and treatment of the disease&#44; as mentioned above&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> Moreover&#44; the question of tobacco as a triggering factor in the disease and other potential physiopathological pathways need to be explored in further depth&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">The Spanish Registry of Pulmonary Langerhans Cell Histiocytosis &#40;REHPCL&#41; is part of the SEPAR diffuse interstitial disease integrated research program &#40;PII-EPID&#41;&#46; It consists of a consultant committee of 5 experts and the database is hosted on the RNER platform&#46; Data collection began in September 2013&#46; This registry&#44; in addition to its purely epidemiological aspect&#44; aims to develop parallel translational research projects in this disease&#44; and launched the PLCH Functional and Genetic Characterization project&#44; in which several SEPAR and IIER &#40;ISCIII&#41; investigators are actively involved&#46; The project has been funded by a grant from the Fundaci&#243;n M&#250;tua Madrile&#241;a and the PI-EPID &#40;EPID-Futuro Rech Assistance&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Spanish Lymphangioleiomyomatosis Register</span><p id="par0165" class="elsevierStylePara elsevierViewall">Lymphangioleiomyomatosis &#40;LAM&#41; is a lung disease affecting young women of childbearing potential&#46; It is characterized by abnormal growth of atypical smooth muscle cells &#40;LAM cells&#41; in the lung&#44; including the airways and the lymphatic and blood vessels&#44; leading to cyst formation and finally the destruction of the lung parenchyma&#46; Two types of LAM are distinguished&#58; a sporadic form with exclusively pulmonary involvement &#40;sporadic LAM&#41; and another associated with tuberous sclerosis complex&#44; a dominant autosomic neurocutaneous syndrome linked with TSC1 and TSC2 gene mutations&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Due to its low prevalence&#44; this disease is relatively unknown&#46; Many of the symptoms &#40;dyspnea&#44; cough&#41; are similar to those of other lung diseases such as asthma or chronic bronchitis&#44; so diagnosis is generally delayed&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">The true incidence of LAM is unknown&#46; In the United States&#44; 1300 patients are registered in the American LAM Foundation&#46; In a cross-sectional study carried out in Spain&#44; the SEPAR Diffuse Interstitial Pulmonary Disease &#40;EPID&#41; working group in collaboration with the Spanish LAM Patients Association &#40;AELAM&#41; registered 72 cases from 23 centers in 8 autonomous communities plus Andorra&#44; forming the basis of the Spanish LAM Registry &#40;RELAM&#41;&#46; The general characteristics of this registry are described in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0180" class="elsevierStylePara elsevierViewall">RELAM is an integral part of the PI-EPID and has an 8-member consultant committee&#46; The database is hosted on the RNER platform and data collection started in September 2013&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Spanish Alveolar Proteinosis Registry</span><p id="par0185" class="elsevierStylePara elsevierViewall">Pulmonary alveolar proteinosis &#40;PAP&#41; is a disease characterized by the accumulation of proteins and surfactant lipids in the alveoli&#44; causing gas exchange problems that can trigger respiratory insufficiency&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">There are 3 types of PAD&#58; autoimmune or acquired&#44; secondary and congenital&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">The autoimmune type accounts for 90&#37; of PAP in adults&#46; It generally occurs in subjects around 50&#8211;60 years of age&#44; and more often in men &#40;2&#58;1&#41;&#46; It presents with anti-granulocyte-macrophage colony stimulating factor antibodies &#40;anti-GM-CSF&#41;&#46; The secondary type&#44; that accounts for the remaining 10&#37; of PAP in adults&#44; presents at a similar age as the autoimmune type and is also more common in men &#40;1&#46;5&#58;1&#41; with hematological diseases &#40;particularly myelodysplastic syndrome&#41;&#44; respiratory infections or autoimmune diseases&#46; Anti-GM-CSF antibodies are negative and prognosis is worse than for the autoimmune type &#40;mean 2-year survival of 50&#37; and 5-year survival of 35&#37;&#41;&#46; Lastly&#44; the congenital type is known to be associated with genetic mutations coding for lung surfactant proteins&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">The general prevalence of PAP is 3&#46;7 patients per million inhabitants&#44; although this depends to some extent on the geographical regions&#44; due to association with race&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">The total number of cases in Spain is unknown&#46; The most significant results from national and international series are summarized in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">25&#8211;34</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0210" class="elsevierStylePara elsevierViewall">The Spanish Alveolar Proteinosis Registry &#40;REPA&#41; is an integral part of the SEPAR PII-EPID and its consultant committee consists of 5 pulmonologists&#46; The database is hosted on the RNER platform and cases have been registered since September 2013&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Spanish Sarcoidosis Registry</span><p id="par0215" class="elsevierStylePara elsevierViewall">Sarcoidosis is a systemic granulomatosis disease affecting mainly the lung &#40;90&#37;&#41; and lymphatic tissue&#44; but other organs can also be involved&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">Overall incidence and prevalence vary depending on the geographical region analyzed&#58; over 50&#47;100<span class="elsevierStyleHsp" style=""></span>000 cases are reported in Nordic countries&#44; while in others such as Japan or Spain&#44; prevalence of &#60;10&#47;100<span class="elsevierStyleHsp" style=""></span>000 inhabitants is reported&#44; among which L&#246;fgren syndrome is very common &#40;48&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> It mainly affects middle-aged adults&#46; Large series of patients studied in the last 30 years suggest that a combination of predisposing environmental factors and a genetic makeup susceptible to developing the disease are necessary&#44; but no conclusive studies have been published&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">37&#44;38</span></a> Several papers published point to the relevance of certain infectious agents &#40;bacteria&#44; viruses and mycoses&#41; and exposure to rural environments&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">One of the main clinical problems is to determine the existence of inflammatory activity&#46; In this respect&#44; angiotensin-converting enzyme &#40;ACE&#41; levels have been studied in most depth&#44; although hyposensitivity in delayed cutaneous hypersensitivity tests and lymphopenia have also been used&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> Patients with this disease have also been seen to have immunological dysfunction in macrophage and T-lymphocyte recognition&#44; processing and presentation of potential antigens&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">The general data from the largest series published in Spain are given in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#44; and the characteristics of the series from the Hospital Vall d&#8217;Hebron &#40;2005&#8211;2012&#41; that was the starting point of this registry are presented in <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a></p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0235" class="elsevierStylePara elsevierViewall">The Spanish Sarcoidosis Registry &#40;RESAR&#41; is an integral part of the PI-EPID and its consultant committee consists of 7 physicians&#46; The database is hosted on the RNER platform and cases have been registered since September 2013&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">Although the registries were initially developed by a small group of experts in each disease&#44; they represent a collaborative tool in which any clinician can report a case and any investigator can approach the scientific committee for permission to exploit the registered data&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Discussion</span><p id="par0245" class="elsevierStylePara elsevierViewall">This article gives information on the MRD registries developed in Spain in coordination with the RNER&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">The data gathered from the few existing cases will allow the scientific community to gain deeper insight into these diseases&#44; and it will also be of use to non-expert clinicians who&#44; if they come across a patient with one of these rare disorders&#44; can avail themselves of this up-to-date information and gain access to expert advice&#46; Access to updated and dynamic data from all over Spain will also be invaluable in helping healthcare institutions allocate care resources for patients with these rare conditions&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">Incorporation of the information in the population-based registries of each autonomous community in Spain will give a better overview of the reality of daily clinical practice than can be gleaned from voluntary registries&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">Like clinical trials&#44; quality data are essential for obtaining valid results&#46; Being observational studies&#44; registries are exposed to bias of many kinds&#44; although the most common are those affecting selection of cases and the quality of the available data&#44; particularly with regard to the principal variables &#40;accurate diagnosis and coding&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> In the RNER&#44; data from patient registries can be compared with those contributed by the autonomous community registries&#44; meaning that the representativeness of the sample and thus the validity of the results can be determined&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">The role of registries in decision-making with regard to the efficacy of treatments remains controversial&#46; Nevertheless&#44; when they contain a larger number of cases with more adverse events than a clinical trial&#44; their role in the post-approval monitoring of side effects and in the cost-benefit analysis of these treatments is essential&#44; and cannot be replaced with the traditional clinical trial design&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">43&#8211;45</span></a></p><p id="par0270" class="elsevierStylePara elsevierViewall">The RNER of the IIER &#40;ISCIII&#41; forms part of the Rare Diseases Strategy of Spanish National Health System&#46; It plays a key role in this strategy by acting as a source of information for the development and planning of social welfare policies and for research&#46; Contributions from all the autonomous communities&#44; together with input from professional societies&#44; industry and patients themselves&#44; make these registries a unique tool for maximizing synergies and provide enormous scope for international cooperation&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Authorship&#47;Collaboration</span><p id="par0275" class="elsevierStylePara elsevierViewall">Beatriz Lara&#58; preparation of the article and REDAAT administrator&#59; Manuel Posada and Ignacio Abaitua&#58; preparation of the article and responsible for the design and setting up of the RNER&#59; Genaro Gal&#225;n&#58; preparation of the article and REET coordinator&#59; Diego Castillo&#58; preparation of the article and REHPCL coordinator&#59; &#193;lvaro Casanova&#58; preparation of the article and RELAM coordinator&#59; Esteban Cano&#58; preparation of the article and REPA coordinator&#59; &#205;&#241;igo Ojanguren&#58; preparation of the article and RESAR coordinator&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conflict of Interest</span><p id="par0280" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest and have participated equally in the preparation of this paper&#46;</p></span></span>"
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          "titulo" => "National Rare Diseases Registry"
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          "identificador" => "sec0055"
          "titulo" => "Spanish Registry of Patients With Alpha-1 Antitrypsin Deficiency"
        ]
        7 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Spanish Tracheal Stenosis Registry"
        ]
        8 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "Spanish Registry of Pulmonary Langerhans Cell Histiocytosis"
        ]
        9 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Spanish Lymphangioleiomyomatosis Register"
        ]
        10 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Spanish Alveolar Proteinosis Registry"
        ]
        11 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Spanish Sarcoidosis Registry"
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          "titulo" => "Discussion"
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          "titulo" => "Authorship&#47;Collaboration"
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    "fechaRecibido" => "2013-12-02"
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          "clase" => "keyword"
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          "palabras" => array:6 [
            0 => "Registry"
            1 => "Respiratory diseases minority"
            2 => "Spanish Society of Pneumology and Thoracic Surgery"
            3 => "Instituto de Salud Carlos III"
            4 => "Research Institute for Rare Diseases"
            5 => "Spanish Rare Diseases Registry Research Network"
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            1 => "Enfermedades respiratorias minoritarias"
            2 => "Sociedad Espa&#241;ola de Neumolog&#237;a y Cirug&#237;a Tor&#225;cica"
            3 => "Instituto de Salud Carlos III"
            4 => "Instituto de Investigaci&#243;n de Enfermedades Raras"
            5 => "Red Espa&#241;ola de Registros de Enfermedades Raras para la Investigaci&#243;n"
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    "resumen" => array:2 [
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        "titulo" => "Abstract"
        "resumen" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">This report describes the general characteristics&#44; objectives&#44; and organizational aspects of the registries of minority respiratory diseases included in the National Registry of Rare Diseases of the Research Institute for Rare Diseases &#40;ISCIII&#41;&#44; in order to publicize their existence and encourage the participation of professionals&#46;</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Information is collected on the following conditions&#58; alpha-1 antitrypsin deficiency&#44; idiopathic tracheal stenosis&#44; adult pulmonary Langerhans&#8217; cell histiocytosis&#44; lymphangioleiomyomatosis&#44; alveolar proteinosis&#44; and sarcoidosis&#46;</p>"
      ]
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        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">En el presente trabajo se describen las caracter&#237;sticas generales&#44; objetivos y aspectos organizativos de los registros de enfermedades respiratorias minoritarias integrados en el Registro Nacional de Enfermedades Raras del Instituto de Investigaci&#243;n de Enfermedades Raras &#40;IIER&#41;&#44; con el objetivo de dar a conocer su existencia y fomentar la participaci&#243;n de los profesionales&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Se recoge informaci&#243;n sobre registros de las siguientes enfermedades&#58; d&#233;ficit de alfa-1 antitripsina&#44; estenosis traqueal idiop&#225;tica&#44; histiocitosis pulmonar de c&#233;lulas de Langerhans del adulto&#44; linfangioleiomiomatosis&#44; proteinosis alveolar y sarcoidosis&#46;</p>"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Lara Gallego B&#44; Abaitua Borda I&#44; Gal&#225;n Gil G&#44; Castillo Villegas D&#44; Casanova Espinosa &#193;&#44; Cano Jim&#233;nez E&#44; et al&#46; Registros de enfermedades respiratorias integrados en el Registro Nacional de Enfermedades Raras&#46; Arch Bronconeumol&#46; 2014&#59;50&#58;397&#8211;403&#46;</p>"
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Males&#47;females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">200&#47;305&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#40;mean&#44; SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55&#46;8 &#40;15&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FEV1 &#40;L&#41; &#40;mean&#44; SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;9 &#40;1&#46;33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FVC &#40;L&#41; &#40;mean&#44; SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;1&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Substitution treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&#46;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lung transplantation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;4&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mortality&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;12&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Basic Population Data of Spanish Registry of Patients With Alpha-1 Antitrypsin Deficiency Patients &#40;2001&#8211;2013&#41;&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">SD&#58; standard deviation&#59; DIPD&#58; diffuse interstitial pulmonary disease&#59; LAM&#58; lymphangioleiomyomatosis&#59; NK&#47;NA&#58; not known&#47;not applicable&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Source</span>&#58; Adapted from Ant&#243;n et al&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Patient Characteristics</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Age &#40;years&#41; mean</span> &#40;<span class="elsevierStyleItalic">SD</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">44&#46;56 &#40;11&#46;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Family history of DIPD n</span> &#40;<span class="elsevierStyleItalic">&#37;</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;1&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Tuberous sclerosis n</span> &#40;<span class="elsevierStyleItalic">&#37;</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;12&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Menopause n</span> &#40;<span class="elsevierStyleItalic">&#37;</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19 &#40;26&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Symptoms s n</span> &#40;<span class="elsevierStyleItalic">&#37;&#41;</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dyspnea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64 &#40;88&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cough&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32 &#40;44&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pneumothorax&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37 &#40;51&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No&#46; of pneumothorax&#47;patient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hemoptysis &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;11&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Renal angiomyolipoma n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28 &#40;38&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Lung transplantation n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;22&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Death n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;12&#46;5&#41;&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">Characteristics of LAM Patients&#46;</p>"
        ]
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      2 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">SD&#58; standard deviation&#59; DLCO&#58; carbon monoxide diffusion capacity&#59; FVC&#58; forced vital capacity&#59; GM-CSF&#58; granulocyte-monocyte colony stimulating factor&#59; inh&#58; inhaled&#59; BAL&#58; bronchoalveolar lavage&#59; n&#46;d&#46;&#58; no data&#59; PaO<span class="elsevierStyleInf">2</span>&#58; arterial oxygen pressure&#59; PAP&#58; pulmonary alveolar proteinosis&#59; Sat&#58; saturation&#59; sc&#58; subcutaneous&#59; HRCT&#58; high resolution computed tomography&#59; TLC&#58; total lung capacity&#46;</p>"
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              "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"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="4" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Spanish cases &#40;from 1995 to date&#41;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27&#8211;33</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="3" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Worldwide series<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24&#8211;26</span></a></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Total cases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Autoimmune form&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Secondary form&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Congenital form&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Seymour &#40;2002&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Inoue &#40;2008&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Bonella &#40;2011&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Subjects n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;42&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;42&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">410&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">248&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">70&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mean age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">24&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">32&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">36&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">39&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">51&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">43&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sex ratio &#40;M&#58;F&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#58;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#58;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#58;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#46;6&#58;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#58;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;3&#58;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Smoking habit n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Active&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">3 &#40;42&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;33&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">2 &#40;66&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">n&#46;d&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">62 &#40;29&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34 &#40;49&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ex-smoker&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">1 &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">1 &#40;33&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">n&#46;d&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">62 &#40;29&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21 &#40;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Never smoker&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;42&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">1 &#40;33&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;33&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">114 &#40;28&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">93 &#40;43&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">15 &#40;21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Days of clinical progress &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>72&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">147<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>42&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">210&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">300&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">270&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Clinical symptoms n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cough&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;66&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;66&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&#46;d&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">51 &#40;20&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">46 &#40;66&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dyspnea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">3 &#40;42&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">2 &#40;66&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;33&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n&#46;d&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">119 &#40;48&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">66 &#40;94&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Weight loss&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>PaO<span class="elsevierStyleInf">2</span> &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41; &#40;mm<span class="elsevierStyleHsp" style=""></span>Hg&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">66&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">71&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">69<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Basal oxygen saturation &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Chest HRCT n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ground glass&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4 &#40;58&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cobblestone pattern&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Definitive diagnosis n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Bronchoalveolar lavage&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Transbronchial biopsy&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Surgical biopsy&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">110 &#40;44&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">24 &#40;34&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Treatment n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Total BAL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">221&#40;54&#41;&nbsp;\t\t\t\t\t\t\n
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                  """
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>I&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>II&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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        "titulo" => "Acknowledgments"
        "texto" => "<p id="par0285" class="elsevierStylePara elsevierViewall">The authors would like to thank the Spanish Association of Patients with Alpha-1 Antitrypsin Deficiency&#44; represented by Mrs Shane Fitch and Mr Mariano Pastor&#44; and the Spanish Association of Patients with Lymphangioleoimyomatosis&#44; represented by Mrs Asunci&#243;n Valdivielso and Mrs Mar&#237;a Luz Vila&#44; for their extraordinary work&#46;</p> <p id="par0290" class="elsevierStylePara elsevierViewall">They also thank Dr Ruiz Manzano&#44; SEPAR Chairman in 2011&#44; for his invaluable support throughout the project&#44; without whom it would not have been possible&#46;</p>"
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Special article
Respiratory Diseases Registries in the National Registry of Rare Diseases
Registros de enfermedades respiratorias integrados en el Registro Nacional de Enfermedades Raras
Beatriz Lara Gallegoa,
Corresponding author
beat1135@gmail.com

Corresponding author.
, Ignacio Abaitua Bordab, Genaro Galán Gilc, Diego Castillo Villegasd,h, Álvaro Casanova Espinosae, Esteban Cano Jiménezf, Iñigo Ojanguren Arranzg, Manuel Posada de la Pazb
a Servicio de Neumología, Hospital Universitario Arnau de Vilanova, Lérida, Spain
b Instituto de Investigación en Enfermedades Raras, Instituto de Salud Carlos III, Madrid, Spain
c Servicio de Cirugía Torácica, Hospital Clínico Universitario, Valencia, Spain
d Servicio de Neumología, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
e Servicio de Neumología, Hospital del Henares, Coslada, Madrid, Spain
f Servicio de Neumología, Hospital Universitario Lucus Augusti, Lugo, Spain
g Servicio de Neumología, Hospital Universitario Vall d’Hebron, Barcelona, Spain
h Institut d’Investigació Biomèdica Sant Pau (IIB-San Pau), Barcelona, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The Spanish Society of Pulmonology and Thoracic Surgery &#40;SEPAR&#41; has a long and extensive experience in respiratory disease registries&#44; including some minority respiratory diseases &#40;MRD&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The Instituto de Salud Carlos III &#40;ISCIII&#41; also included rare diseases &#40;RD&#41; as one of these priority areas of intervention and&#44; as a result of this interest&#44; the Research Institute for Rare Diseases &#40;IIER&#41; was created in 2003&#46; The aim was to promote and conduct basic and clinical research&#44; training and support in healthcare referral and innovation in the medical care of RD&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The functions of the IIER include the identification of the magnitude of RDs&#44; establishing an epidemiological database for the retrieval of reliable information on the prevalence of these diseases and the distribution of healthcare resources allocated to their treatment&#46; For this reason&#44; in 2005 the National Rare Diseases Registry &#40;RNER&#41; was created to follow-up&#44; monitor and conduct research into patients with RDs&#44; their family members and control populations participating in research studies&#46; The registry has been supported by the Spanish Rare Diseases Registry Research Network &#40;Spain RDR&#58; <a id="intr0010" class="elsevierStyleInterRef" href="https://spainrdr.isciii.es/">https&#58;&#47;&#47;spainrdr&#46;isciii&#46;es</a>&#41;&#44; funded by the ISCIII as a network project within the International Rare Diseases Research Consortium &#40;IRDiRC&#41; &#40;<a id="intr0015" class="elsevierStyleInterRef" href="http://www.irdirc.eu/">http&#58;&#47;&#47;www&#46;irdirc&#46;eu</a>&#59; <a id="intr0020" class="elsevierStyleInterRef" href="http://ec.europa.eu/research/health/medical-research/rare-diseases/irdirc_en.html">http&#58;&#47;&#47;ec&#46;europa&#46;eu&#47;research&#47;health&#47;medical-research&#47;rare-diseases&#47;irdirc&#95;en&#46;html</a>&#41;&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The common objectives of both institutions were the driving force behind an agreement for the development of MRD registries in 2011&#44; under which a project monitoring or steering group was created&#44; each registry was assigned a leader&#44; and SEPAR appointed a coordinator to oversee the progress made in the context of the agreement&#46; The leaders of each MRD under the RNER coordinate the expert network for that disease&#46; Functions include the design of variables specific to the characteristics and evolution of the entity and the promotion of research&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">To optimize the task of coordinating disease databases within the RNER framework&#44; the leaders of each registry and the contributing pulmonologists follow a set of internal regulations based on the criteria established by SEPAR &#40;February 2013&#41; and the recommendations of the IIER itself&#44; in compliance with Spanish Data Protection Agency &#40;AEPD&#41; level 3 archive security&#46; The conditions for use of these data are also described under this regulation&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">National Rare Diseases Registry</span><p id="par0025" class="elsevierStylePara elsevierViewall">The RNER has 2 main strategic approaches&#58; registries of patients based on clinical results and natural history&#44; and population registries based on epidemiological and social welfare research and social welfare planning&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Patient registries may be created by agreement with scientific societies or based on the experience of a particular institution or expert network&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> One of the problems of this type of registry and the information they provide is that the cases are limited to those seen in participating centers&#44; leaving open the possibility of a selection bias toward more severe cases&#46; Notification of cases is voluntary&#44; limited to some experts&#44; and requires patient consent&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">At present&#44; in addition to the SEPAR&#44; the following scientific societies have reached a collaborative agreement with the ISCIII for participation in the strategy for development of patient registries within the RNER and SpainRDR&#58; Spanish Society of Pediatric Pulmonology &#40;SNEP&#41;&#44; Spanish Society of Family and Community Medicine &#40;semFYC&#41;&#44; European Network of Rare and Congenital Anemias &#40;ENERCA&#41;&#44; Spanish Society of Allergy and Clinical Immunology &#40;SEAIC&#41;&#44; Spanish Society of Pediatric Endocrinology &#40;SEEP&#41;&#44; Spanish Society of Neurology &#40;SEN&#41; and Center of Energy&#44; Environmental and Technological Research &#40;CIEMAT&#41;&#46; Negotiations are currently ongoing with another 5 societies and with other research networks such as CIBERNED&#46; Agreements have also been signed with the pharmaceutical industry and the Spanish Federation of Rare Diseases &#40;FEDER&#41; itself&#46; On an international level&#44; the IRDiRC consortium has already set in motion projects closely related with SpainRDR&#44; such as the RD-CONNECT project &#40;<a id="intr0025" class="elsevierStyleInterRef" href="http://www.rd-connect.eu/">http&#58;&#47;&#47;www&#46;rd-connect&#46;eu</a>&#41;&#46; DG SANCO of the European Commission has already approved the EPIRARE project &#40;<a id="intr0030" class="elsevierStyleInterRef" href="http://www.epirare.eu/">http&#58;&#47;&#47;www&#46;epirare&#46;eu</a>&#41;&#46; The aim of the former will be to standardize patient registries&#44; biobanks and data from &#8220;omics&#8221; research on an international level&#44; while the latter has set down the terms for the future European platform of RD registries that will be implemented in coming years in the European Commission Joint Research Center &#40;JRC&#41; in Ispra&#44; Italy&#46; The IIER is a member of both projects and is responsible for aspects such as defining the quality&#44; selection and definition of common variables for interchange and interoperability among biobanks&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">With regard to the functioning of the RNER and the SpainRDR Project&#44; the population registry works with all the autonomous communities of Spain to collect information on all RDs&#46; To this end&#44; strategies have been developed for collecting data from various electronic sources such as the Minimum Basic Data Set &#40;CMBD&#41; that contains information on hospital discharge reports&#44; death certificates&#44; primary care sources&#44; neonatal and congenital malformation screening programs&#44; etc&#46; In the near future&#44; this information&#44; once validated and consolidated&#44; will allow us to estimate the incidence of the various diseases&#44; regional distribution&#44; prevalence and survival&#44; depending on the quality of follow-up in all cases&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Each of the 17 Spanish autonomous communities is setting up its own regional RD registry&#59; in the autonomous cities of Ceuta and Melilla&#44; the information is remitted to the IIER&#44; and this organization will be responsible for setting up their corresponding registries&#46; By way of these registries&#44; each of the autonomous communities will supply the data derived from the various sources to the RNER&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The RNER also offers patients the possibility to self-register&#44; that is to say&#44; any individual with a disease classified as rare or his&#47;her parents or legal guardians can register on the website&#44; provide clinical information on their disease and give informed consent for the use of their data in research&#46; The RNER can be accessed at <a id="intr0035" class="elsevierStyleInterRef" href="https://registroraras.isciii.es/">https&#58;&#47;&#47;registroraras&#46;isciii&#46;es</a>&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">To create MRD registries within the National Registry&#44; each consultant committee has identified the relevant variables for data collection&#46; In addition&#44; the recording of common parameters has been standardized &#40;demographic data&#44; smoking&#44; respiratory function tests&#44; blood gases and the walking test&#41; so that in the future data can be compared between registries&#46; Furthermore&#44; generic quality of life questionnaires have been added to the purely respiratory parameters to allow the impact of MRDs to be compared with other non-respiratory RDs or even with common diseases&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">All the registries include quality data related to each condition and comply with the applicable data protection legislation&#46; They will be accessible from the national registry website &#40;<a id="intr0040" class="elsevierStyleInterRef" href="https://registroraras.isciii.es/">https&#58;&#47;&#47;registroraras&#46;isciii&#46;es</a>&#41;&#44; as well as from the SEPAR website &#40;<a id="intr0045" class="elsevierStyleInterRef" href="http://www.separ.es/">www&#46;separ&#46;es</a>&#41; or from the website of the SpainRDR project &#40;<a id="intr0050" class="elsevierStyleInterRef" href="https://spainrdr.isciii.es/">https&#58;&#47;&#47;spainrdr&#46;isciii&#46;es</a>&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Each consultant committee is responsible for updating the contents of each registry&#44; and the final responsibility lies with each coordinator&#44; as representative of the consultant committee before SEPAR and the IIER&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The RNER itself does not provide funds for conducting parallel research based on registry data&#46; This type of initiative must be funded&#44; if required&#44; by the societies themselves or national or international research agencies&#46; The inclusion of the RNER in the international IRDiRC consortium will facilitate the creation of partnership agreements with similar registries in other countries&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">This brief description gives an idea of the multiple applications of the available information and the advantages of accumulating quality data for biomedical research at a time in which current technological possibilities for sharing knowledge only serve to reinforce the individual experience of professionals in the interests of improving knowledge in these areas&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Spanish Registry of Patients With Alpha-1 Antitrypsin Deficiency</span><p id="par0085" class="elsevierStylePara elsevierViewall">Alpha-1 antitrypsin &#40;AAT&#41; deficiency is the result of mutations that change the structure of the AAT protein&#44; thus affecting its function&#46; It appears mainly in the form of pulmonary emphysema&#44; liver cirrhosis&#44; and less frequently as other diseases &#40;panniculitis&#44; vasculitis&#44; etc&#46;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> There are estimated to be around 12<span class="elsevierStyleHsp" style=""></span>000 individuals with severe AAT deficiency in Spain&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">The Spanish Registry of Patients With Alpha-1 Antitrypsin Deficit &#40;REDAAT&#41; set up at the end of the 90s is part of the SEPAR chronic obstructive pulmonary disease &#40;COPD&#41; working area&#46; Since it was founded&#44; REDAAT has worked to further knowledge on AAT deficiency and awareness of this entity&#44; improve treatment of affected subjects and encourage research&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#8211;11</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">At present&#44; REDAAT resources include a consultant committee consisting of 12 pulmonologists&#44; 3 pediatrics and 3 basic researchers&#44; in addition to reference laboratory managers and computer support staff&#46; Over 300 physicians throughout Spain collaborate with this registry&#46; The main technical resource is <a id="intr0055" class="elsevierStyleInterRef" href="http://www.redaat.es/">www&#46;redaat&#46;es</a>&#44; legally part of the Respira Spanish Lung Foundation&#46; It has a public access area providing general information and a restricted access area for healthcare professionals where the form for recording patient data and real-time information on cases registered&#44; overall characteristics&#44; diagnoses and treatment can be found&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">REDAAT has collaborated actively in the Alpha One International Registry &#40;&#91;AIR&#93; <a id="intr0060" class="elsevierStyleInterRef" href="http://www.antitrypsindeficiency.org/">http&#58;&#47;&#47;www&#46;antitrypsindeficiency&#46;org</a>&#41; since its creation&#44; as well as with some other European national registries&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Since this registry has its own domain and an up-and-running database&#44; created prior to the formation of the RNER&#44; it is not integrated in this registry&#39;s platform although they do share their data&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">A summary of cases registered is shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Spanish Tracheal Stenosis Registry</span><p id="par0115" class="elsevierStylePara elsevierViewall">Two groups can defined under the term tracheal stenosis&#58; secondary benign laryngotracheal stenosis and idiopathic tracheal stenosis&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Idiopathic tracheal stenosis is a disease characterized by the development of fibrous stenotic scarring in the cricoid region and the upper third of the trachea&#44; with thickening of the submucosa but no underlying cartilage involvement&#46; It mainly affects women&#44; and the principal symptoms are dyspnea and stridor developing over a period of years&#46; Diagnosis is incompatible with a history of other upper airway stenosis that could be defined as secondary&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Incidence and prevalence are unknown&#44; as are etiology and prognostic factors&#46; No specific diagnostic and treatment guidelines are available and it has not yet been included in international RD catalogs&#46; Accumulated experience with this disease is centered mainly on the various therapeutic surgical techniques&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#8211;21</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Secondary benign laryngotracheal stenosis is usually due to one of the following causes&#58; post-intubation&#44; post-trauma&#44; inhalation of toxic smoke&#44; post-surgery&#44; infection&#44; inflammatory activity&#44; extrinsic and neurological compression&#44; and are not the focus of this registry&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">In the last 30 years&#44; the development of tracheal surgery&#44; along with other therapeutic alternatives &#40;laser&#44; dilations and tracheal prosthetic devices&#41;&#44; has meant that most of these benign laryngotracheal lesions can be treated&#44; although accumulation of experience in healthcare centers is limited by their relative rarity&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The Spanish Tracheal Stenosis Registry &#40;REET&#41; is an integral part of the SEPAR Thoracic Surgery Area&#46; Over 40 professionals have joined this registry as collaborators&#44; its database is an integral part of the RNER platform&#44; and data collection will begin in 2014&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Spanish Registry of Pulmonary Langerhans Cell Histiocytosis</span><p id="par0145" class="elsevierStylePara elsevierViewall">Pulmonary Langerhans cell histiocytosis &#40;PLCH&#41; in adults is characterized by a peribronchiolar proliferation of Langerhans histiocytes&#44; a dendritic cell involved in the immune response&#46; It primarily affects adults between 20 and 40 years of age&#44; with no preference for sex&#46; Progress is generally benign&#44; although around 30&#37; of patients have progressively deteriorating lung function&#46; It is associated with smoking&#44; with 95&#37; of patients being smokers&#44; but etiology is unknown and the exact incidence and prevalence of PLCH in adults has not been determined&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">An expert consensus paper was recently published giving recommendations on the diagnosis and treatment of this disease that is hoped to go some way toward standardizing procedures&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> The main treatment in severe cases is lung transplantation&#44; although the use of chemotherapeutic agents for treating progressive disease has been proposed&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">There are very few data in our setting on the characteristics and management of PLCH&#46; The first multicenter series was published recently&#44; showing the importance of the use of clinical guidelines in the diagnosis and treatment of the disease&#44; as mentioned above&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> Moreover&#44; the question of tobacco as a triggering factor in the disease and other potential physiopathological pathways need to be explored in further depth&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">The Spanish Registry of Pulmonary Langerhans Cell Histiocytosis &#40;REHPCL&#41; is part of the SEPAR diffuse interstitial disease integrated research program &#40;PII-EPID&#41;&#46; It consists of a consultant committee of 5 experts and the database is hosted on the RNER platform&#46; Data collection began in September 2013&#46; This registry&#44; in addition to its purely epidemiological aspect&#44; aims to develop parallel translational research projects in this disease&#44; and launched the PLCH Functional and Genetic Characterization project&#44; in which several SEPAR and IIER &#40;ISCIII&#41; investigators are actively involved&#46; The project has been funded by a grant from the Fundaci&#243;n M&#250;tua Madrile&#241;a and the PI-EPID &#40;EPID-Futuro Rech Assistance&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Spanish Lymphangioleiomyomatosis Register</span><p id="par0165" class="elsevierStylePara elsevierViewall">Lymphangioleiomyomatosis &#40;LAM&#41; is a lung disease affecting young women of childbearing potential&#46; It is characterized by abnormal growth of atypical smooth muscle cells &#40;LAM cells&#41; in the lung&#44; including the airways and the lymphatic and blood vessels&#44; leading to cyst formation and finally the destruction of the lung parenchyma&#46; Two types of LAM are distinguished&#58; a sporadic form with exclusively pulmonary involvement &#40;sporadic LAM&#41; and another associated with tuberous sclerosis complex&#44; a dominant autosomic neurocutaneous syndrome linked with TSC1 and TSC2 gene mutations&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Due to its low prevalence&#44; this disease is relatively unknown&#46; Many of the symptoms &#40;dyspnea&#44; cough&#41; are similar to those of other lung diseases such as asthma or chronic bronchitis&#44; so diagnosis is generally delayed&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">The true incidence of LAM is unknown&#46; In the United States&#44; 1300 patients are registered in the American LAM Foundation&#46; In a cross-sectional study carried out in Spain&#44; the SEPAR Diffuse Interstitial Pulmonary Disease &#40;EPID&#41; working group in collaboration with the Spanish LAM Patients Association &#40;AELAM&#41; registered 72 cases from 23 centers in 8 autonomous communities plus Andorra&#44; forming the basis of the Spanish LAM Registry &#40;RELAM&#41;&#46; The general characteristics of this registry are described in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0180" class="elsevierStylePara elsevierViewall">RELAM is an integral part of the PI-EPID and has an 8-member consultant committee&#46; The database is hosted on the RNER platform and data collection started in September 2013&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Spanish Alveolar Proteinosis Registry</span><p id="par0185" class="elsevierStylePara elsevierViewall">Pulmonary alveolar proteinosis &#40;PAP&#41; is a disease characterized by the accumulation of proteins and surfactant lipids in the alveoli&#44; causing gas exchange problems that can trigger respiratory insufficiency&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">There are 3 types of PAD&#58; autoimmune or acquired&#44; secondary and congenital&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">The autoimmune type accounts for 90&#37; of PAP in adults&#46; It generally occurs in subjects around 50&#8211;60 years of age&#44; and more often in men &#40;2&#58;1&#41;&#46; It presents with anti-granulocyte-macrophage colony stimulating factor antibodies &#40;anti-GM-CSF&#41;&#46; The secondary type&#44; that accounts for the remaining 10&#37; of PAP in adults&#44; presents at a similar age as the autoimmune type and is also more common in men &#40;1&#46;5&#58;1&#41; with hematological diseases &#40;particularly myelodysplastic syndrome&#41;&#44; respiratory infections or autoimmune diseases&#46; Anti-GM-CSF antibodies are negative and prognosis is worse than for the autoimmune type &#40;mean 2-year survival of 50&#37; and 5-year survival of 35&#37;&#41;&#46; Lastly&#44; the congenital type is known to be associated with genetic mutations coding for lung surfactant proteins&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">The general prevalence of PAP is 3&#46;7 patients per million inhabitants&#44; although this depends to some extent on the geographical regions&#44; due to association with race&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">The total number of cases in Spain is unknown&#46; The most significant results from national and international series are summarized in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">25&#8211;34</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0210" class="elsevierStylePara elsevierViewall">The Spanish Alveolar Proteinosis Registry &#40;REPA&#41; is an integral part of the SEPAR PII-EPID and its consultant committee consists of 5 pulmonologists&#46; The database is hosted on the RNER platform and cases have been registered since September 2013&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Spanish Sarcoidosis Registry</span><p id="par0215" class="elsevierStylePara elsevierViewall">Sarcoidosis is a systemic granulomatosis disease affecting mainly the lung &#40;90&#37;&#41; and lymphatic tissue&#44; but other organs can also be involved&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">Overall incidence and prevalence vary depending on the geographical region analyzed&#58; over 50&#47;100<span class="elsevierStyleHsp" style=""></span>000 cases are reported in Nordic countries&#44; while in others such as Japan or Spain&#44; prevalence of &#60;10&#47;100<span class="elsevierStyleHsp" style=""></span>000 inhabitants is reported&#44; among which L&#246;fgren syndrome is very common &#40;48&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> It mainly affects middle-aged adults&#46; Large series of patients studied in the last 30 years suggest that a combination of predisposing environmental factors and a genetic makeup susceptible to developing the disease are necessary&#44; but no conclusive studies have been published&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">37&#44;38</span></a> Several papers published point to the relevance of certain infectious agents &#40;bacteria&#44; viruses and mycoses&#41; and exposure to rural environments&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">One of the main clinical problems is to determine the existence of inflammatory activity&#46; In this respect&#44; angiotensin-converting enzyme &#40;ACE&#41; levels have been studied in most depth&#44; although hyposensitivity in delayed cutaneous hypersensitivity tests and lymphopenia have also been used&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> Patients with this disease have also been seen to have immunological dysfunction in macrophage and T-lymphocyte recognition&#44; processing and presentation of potential antigens&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">The general data from the largest series published in Spain are given in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#44; and the characteristics of the series from the Hospital Vall d&#8217;Hebron &#40;2005&#8211;2012&#41; that was the starting point of this registry are presented in <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a></p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0235" class="elsevierStylePara elsevierViewall">The Spanish Sarcoidosis Registry &#40;RESAR&#41; is an integral part of the PI-EPID and its consultant committee consists of 7 physicians&#46; The database is hosted on the RNER platform and cases have been registered since September 2013&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">Although the registries were initially developed by a small group of experts in each disease&#44; they represent a collaborative tool in which any clinician can report a case and any investigator can approach the scientific committee for permission to exploit the registered data&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Discussion</span><p id="par0245" class="elsevierStylePara elsevierViewall">This article gives information on the MRD registries developed in Spain in coordination with the RNER&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">The data gathered from the few existing cases will allow the scientific community to gain deeper insight into these diseases&#44; and it will also be of use to non-expert clinicians who&#44; if they come across a patient with one of these rare disorders&#44; can avail themselves of this up-to-date information and gain access to expert advice&#46; Access to updated and dynamic data from all over Spain will also be invaluable in helping healthcare institutions allocate care resources for patients with these rare conditions&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">Incorporation of the information in the population-based registries of each autonomous community in Spain will give a better overview of the reality of daily clinical practice than can be gleaned from voluntary registries&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">Like clinical trials&#44; quality data are essential for obtaining valid results&#46; Being observational studies&#44; registries are exposed to bias of many kinds&#44; although the most common are those affecting selection of cases and the quality of the available data&#44; particularly with regard to the principal variables &#40;accurate diagnosis and coding&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> In the RNER&#44; data from patient registries can be compared with those contributed by the autonomous community registries&#44; meaning that the representativeness of the sample and thus the validity of the results can be determined&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">The role of registries in decision-making with regard to the efficacy of treatments remains controversial&#46; Nevertheless&#44; when they contain a larger number of cases with more adverse events than a clinical trial&#44; their role in the post-approval monitoring of side effects and in the cost-benefit analysis of these treatments is essential&#44; and cannot be replaced with the traditional clinical trial design&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">43&#8211;45</span></a></p><p id="par0270" class="elsevierStylePara elsevierViewall">The RNER of the IIER &#40;ISCIII&#41; forms part of the Rare Diseases Strategy of Spanish National Health System&#46; It plays a key role in this strategy by acting as a source of information for the development and planning of social welfare policies and for research&#46; Contributions from all the autonomous communities&#44; together with input from professional societies&#44; industry and patients themselves&#44; make these registries a unique tool for maximizing synergies and provide enormous scope for international cooperation&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Authorship&#47;Collaboration</span><p id="par0275" class="elsevierStylePara elsevierViewall">Beatriz Lara&#58; preparation of the article and REDAAT administrator&#59; Manuel Posada and Ignacio Abaitua&#58; preparation of the article and responsible for the design and setting up of the RNER&#59; Genaro Gal&#225;n&#58; preparation of the article and REET coordinator&#59; Diego Castillo&#58; preparation of the article and REHPCL coordinator&#59; &#193;lvaro Casanova&#58; preparation of the article and RELAM coordinator&#59; Esteban Cano&#58; preparation of the article and REPA coordinator&#59; &#205;&#241;igo Ojanguren&#58; preparation of the article and RESAR coordinator&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conflict of Interest</span><p id="par0280" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest and have participated equally in the preparation of this paper&#46;</p></span></span>"
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          "identificador" => "sec0055"
          "titulo" => "Spanish Registry of Patients With Alpha-1 Antitrypsin Deficiency"
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          "identificador" => "sec0015"
          "titulo" => "Spanish Tracheal Stenosis Registry"
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          "titulo" => "Spanish Registry of Pulmonary Langerhans Cell Histiocytosis"
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          "titulo" => "Spanish Lymphangioleiomyomatosis Register"
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          "titulo" => "Spanish Alveolar Proteinosis Registry"
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          "titulo" => "Spanish Sarcoidosis Registry"
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          "clase" => "keyword"
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            0 => "Registry"
            1 => "Respiratory diseases minority"
            2 => "Spanish Society of Pneumology and Thoracic Surgery"
            3 => "Instituto de Salud Carlos III"
            4 => "Research Institute for Rare Diseases"
            5 => "Spanish Rare Diseases Registry Research Network"
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            1 => "Enfermedades respiratorias minoritarias"
            2 => "Sociedad Espa&#241;ola de Neumolog&#237;a y Cirug&#237;a Tor&#225;cica"
            3 => "Instituto de Salud Carlos III"
            4 => "Instituto de Investigaci&#243;n de Enfermedades Raras"
            5 => "Red Espa&#241;ola de Registros de Enfermedades Raras para la Investigaci&#243;n"
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        "titulo" => "Abstract"
        "resumen" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">This report describes the general characteristics&#44; objectives&#44; and organizational aspects of the registries of minority respiratory diseases included in the National Registry of Rare Diseases of the Research Institute for Rare Diseases &#40;ISCIII&#41;&#44; in order to publicize their existence and encourage the participation of professionals&#46;</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Information is collected on the following conditions&#58; alpha-1 antitrypsin deficiency&#44; idiopathic tracheal stenosis&#44; adult pulmonary Langerhans&#8217; cell histiocytosis&#44; lymphangioleiomyomatosis&#44; alveolar proteinosis&#44; and sarcoidosis&#46;</p>"
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        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">En el presente trabajo se describen las caracter&#237;sticas generales&#44; objetivos y aspectos organizativos de los registros de enfermedades respiratorias minoritarias integrados en el Registro Nacional de Enfermedades Raras del Instituto de Investigaci&#243;n de Enfermedades Raras &#40;IIER&#41;&#44; con el objetivo de dar a conocer su existencia y fomentar la participaci&#243;n de los profesionales&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Se recoge informaci&#243;n sobre registros de las siguientes enfermedades&#58; d&#233;ficit de alfa-1 antitripsina&#44; estenosis traqueal idiop&#225;tica&#44; histiocitosis pulmonar de c&#233;lulas de Langerhans del adulto&#44; linfangioleiomiomatosis&#44; proteinosis alveolar y sarcoidosis&#46;</p>"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Lara Gallego B&#44; Abaitua Borda I&#44; Gal&#225;n Gil G&#44; Castillo Villegas D&#44; Casanova Espinosa &#193;&#44; Cano Jim&#233;nez E&#44; et al&#46; Registros de enfermedades respiratorias integrados en el Registro Nacional de Enfermedades Raras&#46; Arch Bronconeumol&#46; 2014&#59;50&#58;397&#8211;403&#46;</p>"
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        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">SD&#58; standard deviation&#59; FEV1&#58; forced expiratory volume in first second&#59; FVC&#58; forced vital capacity&#59; L&#58; liters&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">n&#61;505&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Males&#47;females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">200&#47;305&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#40;mean&#44; SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55&#46;8 &#40;15&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FEV1 &#40;L&#41; &#40;mean&#44; SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;9 &#40;1&#46;33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FVC &#40;L&#41; &#40;mean&#44; SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;1&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Substitution treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&#46;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lung transplantation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;4&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mortality&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;12&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab546869.png"
              ]
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Basic Population Data of Spanish Registry of Patients With Alpha-1 Antitrypsin Deficiency Patients &#40;2001&#8211;2013&#41;&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">SD&#58; standard deviation&#59; DIPD&#58; diffuse interstitial pulmonary disease&#59; LAM&#58; lymphangioleiomyomatosis&#59; NK&#47;NA&#58; not known&#47;not applicable&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Source</span>&#58; Adapted from Ant&#243;n et al&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Patient Characteristics</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Age &#40;years&#41; mean</span> &#40;<span class="elsevierStyleItalic">SD</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44&#46;56 &#40;11&#46;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Family history of DIPD n</span> &#40;<span class="elsevierStyleItalic">&#37;</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;1&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Tuberous sclerosis n</span> &#40;<span class="elsevierStyleItalic">&#37;</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;12&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Menopause n</span> &#40;<span class="elsevierStyleItalic">&#37;</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19 &#40;26&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Symptoms s n</span> &#40;<span class="elsevierStyleItalic">&#37;&#41;</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dyspnea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64 &#40;88&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cough&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32 &#40;44&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pneumothorax&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37 &#40;51&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No&#46; of pneumothorax&#47;patient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hemoptysis &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;11&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Renal angiomyolipoma n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28 &#40;38&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Lung transplantation n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;22&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Death n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;12&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab546871.png"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Characteristics of LAM Patients&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">SD&#58; standard deviation&#59; DLCO&#58; carbon monoxide diffusion capacity&#59; FVC&#58; forced vital capacity&#59; GM-CSF&#58; granulocyte-monocyte colony stimulating factor&#59; inh&#58; inhaled&#59; BAL&#58; bronchoalveolar lavage&#59; n&#46;d&#46;&#58; no data&#59; PaO<span class="elsevierStyleInf">2</span>&#58; arterial oxygen pressure&#59; PAP&#58; pulmonary alveolar proteinosis&#59; Sat&#58; saturation&#59; sc&#58; subcutaneous&#59; HRCT&#58; high resolution computed tomography&#59; TLC&#58; total lung capacity&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="4" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Spanish cases &#40;from 1995 to date&#41;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27&#8211;33</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="3" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Worldwide series<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24&#8211;26</span></a></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Total cases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Autoimmune form&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Secondary form&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Congenital form&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Seymour &#40;2002&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Inoue &#40;2008&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Bonella &#40;2011&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Subjects n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;42&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">410&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mean age&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">24&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">32&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">36&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">39&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">43&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sex ratio &#40;M&#58;F&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;3&#58;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " colspan="8" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Smoking habit n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Active&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">1 &#40;33&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;66&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">62 &#40;29&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">34 &#40;49&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ex-smoker&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">1 &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;33&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">62 &#40;29&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">21 &#40;30&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Never smoker&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">3 &#40;42&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">1 &#40;33&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">1 &#40;33&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">114 &#40;28&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">15 &#40;21&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Days of clinical progress &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">58&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>72&#46;4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">147<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>42&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&#46;3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">210&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">300&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">270&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Clinical symptoms n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cough&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;66&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">2 &#40;66&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">1 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">n&#46;d&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">51 &#40;20&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">46 &#40;66&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dyspnea&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">3 &#40;42&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;66&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;33&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Weight loss&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>TLC &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41; &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>DLCO &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41; &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>PaO<span class="elsevierStyleInf">2</span> &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41; &#40;mm<span class="elsevierStyleHsp" style=""></span>Hg&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">69<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Basal oxygen saturation &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Chest HRCT n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ground glass&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cobblestone pattern&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Definitive diagnosis n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Bronchoalveolar lavage&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Transbronchial biopsy&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Surgical biopsy&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">110 &#40;44&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">24 &#40;34&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Treatment n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Total BAL&nbsp;\t\t\t\t\t\t\n
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                  """
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                    0 => array:2 [
                      "titulo" => "Registros de enfermedades respiratorias en Espa&#241;a&#58; fundamentos y organizaci&#243;n"
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                          "etal" => true
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                            0 => "B&#46; Lara"
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                      "doi" => "10.1016/j.cct.2008.09.002"
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                        "tituloSerie" => "Contemp Clin Trials"
                        "fecha" => "2009"
                        "volumen" => "30"
                        "paginaInicial" => "55"
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        "titulo" => "Acknowledgments"
        "texto" => "<p id="par0285" class="elsevierStylePara elsevierViewall">The authors would like to thank the Spanish Association of Patients with Alpha-1 Antitrypsin Deficiency&#44; represented by Mrs Shane Fitch and Mr Mariano Pastor&#44; and the Spanish Association of Patients with Lymphangioleoimyomatosis&#44; represented by Mrs Asunci&#243;n Valdivielso and Mrs Mar&#237;a Luz Vila&#44; for their extraordinary work&#46;</p> <p id="par0290" class="elsevierStylePara elsevierViewall">They also thank Dr Ruiz Manzano&#44; SEPAR Chairman in 2011&#44; for his invaluable support throughout the project&#44; without whom it would not have been possible&#46;</p>"
        "vista" => "all"
      ]
    ]
  ]
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Article information
ISSN: 15792129
Original language: English
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