Interstitial lung disease preceding primary biliary cirrhosis in a male patient
a Department of Pulmonary Medicine, Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal
b Department of Anatomic Pathology, G.B. Morgagni L. Pierantoni General Hospital, Forlí, Italy
c Department of Radiology, G.B. Morgagni L. Pierantoni General Hospital, Forlí, Italy
d Department of Diseases of the Thorax, G.B. Morgagni L. Pierantoni General Hospital, Forlí, Italy
Read
12925
Timeswas read the article
3171
Total PDF
9754
Total HTML
Share statistics
array:20 [ "pii" => "X0873215915339518" "issn" => "08732159" "doi" => "10.1016/j.rppnen.2015.02.008" "estado" => "S300" "fechaPublicacion" => "2015-07-01" "documento" => "article" "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Rev Port Pneumol. 2015;21:214-7" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 5070 "formatos" => array:3 [ "EPUB" => 247 "HTML" => 3679 "PDF" => 1144 ] ] "itemSiguiente" => array:16 [ "pii" => "X0873215915339526" "issn" => "08732159" "doi" => "10.1016/j.rppnen.2015.02.007" "estado" => "S300" "fechaPublicacion" => "2015-07-01" "documento" => "article" "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Rev Port Pneumol. 2015;21:218-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 3857 "formatos" => array:3 [ "EPUB" => 239 "HTML" => 2690 "PDF" => 928 ] ] "en" => array:9 [ "idiomaDefecto" => true "titulo" => "Prognostic value of plasma D-dimer level in adults with community-acquired pneumonia: A prospective study" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "218" "paginaFinal" => "219" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "320v21n04-90433952fig1.jpg" "Alto" => 1703 "Ancho" => 1500 "Tamanyo" => 268623 ] ] "descripcion" => array:1 [ "en" => "Receiver operating characteristic curves for CURB-65 (dotted spaced line: AUC, 0,669; 95%CI, 0,53 to 0,81), CURB-65 and D-dimer levels (continue line: AUC: 0,689; 95%CI, 0,55 to 0,83), d-dimer level (dashed line: AUC, 0,513; 95% CI, 0,39 to 0,64) and for PSI (dotted line: AUC 0,548; 95% CI 0,38 to 0,71)." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Joana Clemente Duarte, Ana Tavares e Castro, Raquel Silva, Lurdes Correia, Adélia Simão, Armando Carvalho" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Joana Clemente" "apellidos" => "Duarte" ] 1 => array:2 [ "nombre" => "Ana Tavares e" "apellidos" => "Castro" ] 2 => array:2 [ "nombre" => "Raquel" "apellidos" => "Silva" ] 3 => array:2 [ "nombre" => "Lurdes" "apellidos" => "Correia" ] 4 => array:2 [ "nombre" => "Adélia" "apellidos" => "Simão" ] 5 => array:2 [ "nombre" => "Armando" "apellidos" => "Carvalho" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X0873215915339526?idApp=UINPBA00004E" "url" => "/08732159/0000002100000004/v0_201604141144/X0873215915339526/v0_201604141145/en/main.assets" ] "itemAnterior" => array:16 [ "pii" => "X087321591533950X" "issn" => "08732159" "doi" => "10.1016/j.rppnen.2014.08.003" "estado" => "S300" "fechaPublicacion" => "2015-07-01" "documento" => "article" "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Rev Port Pneumol. 2015;21:209-13" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 4633 "formatos" => array:3 [ "EPUB" => 236 "HTML" => 3203 "PDF" => 1194 ] ] "en" => array:11 [ "idiomaDefecto" => true "titulo" => "Asthma control in the Portuguese National Asthma Survey" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "209" "paginaFinal" => "213" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "320v21n04-90433950fig1.jpg" "Alto" => 2388 "Ancho" => 3286 "Tamanyo" => 682551 ] ] "descripcion" => array:1 [ "en" => "Relationship between CARAT and mini-AQLQ scores ( <span class="elsevierStyleItalic">n</span> = 274); (A) ARQoL by asthma control groups; Scatterplots show the correlation between (B) CARAT global score and ARQoL; (C) CARAT superior airways subscore and ARQoL; (D) CARAT inferior airways subscore and ARQoL. In A the horizontal line represents the Mini-AQLQ cut-off of 5.4 based on previous study; <span class="elsevierStyleSup">11</span> NCA: non-controlled asthma; CA: Controlled asthma. In (B, C and D) the vertical lines represent the Mini-AQLQ cut-off of 5.4 <span class="elsevierStyleSup">11</span> and the horizontal lines represent the CARAT cut-offs; <span class="elsevierStyleSup">9</span> (B) global score cut-off of 24; (C) superior airways subscore cut-off of 8 and (D) the CARAT inferior subscore cut-off of 16. The scatterplots are divided into four quadrants, the inferior left corresponds to participants with non-controlled disease and more impairments and the upper right to participants with controlled disease and less impairments." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A. Sá-Sousa, R. Amaral, M. Morais-Almeida, L. Araújo, L.F. Azevedo, A. Bugalho-Almeida, J. Bousquet, J.A. Fonseca" "autores" => array:8 [ 0 => array:2 [ "Iniciales" => "A." "apellidos" => "Sá-Sousa" ] 1 => array:2 [ "Iniciales" => "R." "apellidos" => "Amaral" ] 2 => array:2 [ "Iniciales" => "M." "apellidos" => "Morais-Almeida" ] 3 => array:2 [ "Iniciales" => "L." "apellidos" => "Araújo" ] 4 => array:2 [ "Iniciales" => "L.F." "apellidos" => "Azevedo" ] 5 => array:2 [ "Iniciales" => "A." "apellidos" => "Bugalho-Almeida" ] 6 => array:2 [ "Iniciales" => "J." "apellidos" => "Bousquet" ] 7 => array:2 [ "Iniciales" => "J.A." "apellidos" => "Fonseca" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X087321591533950X?idApp=UINPBA00004E" "url" => "/08732159/0000002100000004/v0_201604141144/X087321591533950X/v0_201604141145/en/main.assets" ] "en" => array:14 [ "idiomaDefecto" => true "titulo" => "Interstitial lung disease preceding primary biliary cirrhosis in a male patient" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "214" "paginaFinal" => "217" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "I. Franco, A. Dubini, S. Piciucchi, G. Casoni, V. Poletti" "autores" => array:5 [ 0 => array:4 [ "Iniciales" => "I." "apellidos" => "Franco" "email" => array:1 [ 0 => "ines.franco@chvng.min-saude.pt" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor1" ] ] ] 1 => array:3 [ "Iniciales" => "A." "apellidos" => "Dubini" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] 2 => array:3 [ "Iniciales" => "S." "apellidos" => "Piciucchi" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "affc" ] ] ] 3 => array:3 [ "Iniciales" => "G." "apellidos" => "Casoni" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "affd" ] ] ] 4 => array:3 [ "Iniciales" => "V." "apellidos" => "Poletti" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "affd" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Department of Pulmonary Medicine, Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] 1 => array:3 [ "entidad" => "Department of Anatomic Pathology, G.B. Morgagni L. Pierantoni General Hospital, Forlí, Italy" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] 2 => array:3 [ "entidad" => "Department of Radiology, G.B. Morgagni L. Pierantoni General Hospital, Forlí, Italy" "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "affc" ] 3 => array:3 [ "entidad" => "Department of Diseases of the Thorax, G.B. Morgagni L. Pierantoni General Hospital, Forlí, Italy" "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "affd" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "<span class="elsevierStyleSup">*</span>" "correspondencia" => "Corresponding author. ines.franco@chvng.min-saude.pt" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "320v21n04-90433951fig1.jpg" "Alto" => 711 "Ancho" => 975 "Tamanyo" => 194839 ] ] "descripcion" => array:1 [ "en" => "Chest computed tomography showing multifocal and peripheral areas of consolidation and ground glass, with perilobular pattern and halo sign." ] ] ] "textoCompleto" => "<a name="sec0005" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Introduction</span><p class="elsevierStylePara">Primary biliary cirrhosis (PBC) is a chronic autoimmune disorder of unknown etiology. It affects predominantly middle-aged women and is characterized by progressive immune-mediated destruction of the small- and medium-sized intrahepatic bile ducts causing cholestasis and cirrhosis.<a href="#bib25" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">, </span><a href="#bib26" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">, </span><a href="#bib27" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">3</span></a> PBC is often associated to other autoimmune diseases<a href="#bib25" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">, </span><a href="#bib28" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">, </span><a href="#bib29" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">5</span></a> and figures prominently among the primary autoimmune hepatobiliary diseases (AHD) with pulmonary involvement.<a href="#bib29" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">5</span></a> Cases of coexistent PBC and subclinical alveolitis, lymphoid interstitial pneumonia, organizing pneumonia, interstitial fibrosis, nonspecific interstitial pneumonia, granulomatous lung disease (GLD)<a href="#bib29" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">, </span><a href="#bib30" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">6</span></a> and, more recently, acute fibrinous and organizing pneumonia<a href="#bib31" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">7</span></a> have been described. The prevalence of GLD related to PBC<a href="#bib25" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">, </span><a href="#bib32" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">, </span><a href="#bib33" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">9</span></a> is not known, although it seems to be rare. In all reported cases, pulmonary sarcoid reaction was diagnosed during the course of PBC in women. Alternatively, interstitial lung disease (ILD) as the initial manifestation of PBC in males, to the best of the author's knowledge, has not been previously reported, and its clinical features are unknown.</p><p class="elsevierStylePara">This is a case of a male patient who first developed GLD and then met diagnostic criteria of PBC which later was present and the literature about this topic is discussed.</p><a name="sec0010" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Case report</span><p class="elsevierStylePara">A 47-year-old male, office worker, smoker (23 pack-years) and without comorbidities, presented with subacute onset of fatigue, nonproductive cough and fever. He had been an emigrant in South America 10 years ago. Pulmonary auscultation revealed bilateral crackles in lower zones, otherwise the physical examination was unremarkable. Laboratory tests showed eosinophilia (850/μL) and mild elevation of C-reactive protein (7.9 mg/dL). Bilateral opacities were observed in chest radiography and chest computed tomography, subsequently performed, showed multifocal bilateral and peripheral areas of consolidation and ground glass with perilobular pattern and halo sign (<a href="#f0005" class="elsevierStyleCrossRefs">Figure 1</a>). Arterial blood gases were within normal range. Signs or symptoms of connective tissue disease or drug toxicity were absent and exposure history was negative. Immunological study revealed only positive antimitochondrial antibody (AMA). Due to that result and in order to exclude autoimmune liver disease, liver ultrasound was performed revealing no changes. Bronchoscopy also showed no macroscopic changes. Bronchoalveolar lavage (BAL) of right B9 segment was performed and cytological analysis revealed normal total cell count for a smoker (320 × 10<span class="elsevierStyleSup">6</span>/L), with 35% lymphocytes, 10% neutrophils, 3% eosinophils, 52% macrophages and normal CD4/CD8 ratio of 1.9. Microbiological analysis of BAL fluid was negative. Due to eosinophilia and his previous history of emigration in South America, the hypothesis of chronic pulmonary paragonimiasis was considered but research of <span class="elsevierStyleItalic">Paragonimus westermani</span> on BAL was negative. Transbronchial cryobiopsy of right B9 was carried out and histological examination showed poorly formed non caseous granulomas occupying terminal bronchioles and alveolar space, associated to interstitial lympho-plasmocitary infiltrate (<a href="#f0010" class="elsevierStyleCrossRefs">Figure 2</a>). Values of pulmonary function testing were within the normal range, except DLCO (66%) that was slightly decreased. The diagnostic hypothesis of idiopathic GLD was assumed and the patient started oral prednisolone (40 mg/day) therapy, presenting clinical and functional (DLCO 79%) improvement and resolution of pulmonary consolidations.</p><a name="f0005" class="elsevierStyleCrossRefs"></a><p class="elsevierStylePara"><img src="320v21n04-90433951fig1.jpg" alt="Chest computed tomography showing multifocal and peripheral areas of consolidation and ground glass, with perilobular pattern and halo sign."></img></p><p class="elsevierStylePara">Figure 1. Chest computed tomography showing multifocal and peripheral areas of consolidation and ground glass, with perilobular pattern and halo sign.</p><a name="f0010" class="elsevierStyleCrossRefs"></a><p class="elsevierStylePara"><img src="320v21n04-90433951fig2.jpg" alt="Poorly formed granulomas occupying alveolar spaces (A) (H&E high power), associated to interstitial lympho-plasmocitary infiltrate, (B) (H&E high power)."></img></p><p class="elsevierStylePara">Figure 2. Poorly formed granulomas occupying alveolar spaces (A) (H&E high power), associated to interstitial lympho-plasmocitary infiltrate, (B) (H&E high power).</p><p class="elsevierStylePara">Two years after ILD diagnosis, and still under oral prednisolone (10 mg/week), the patient presented fatigue, pruritus and biochemical evidence of cholestasis. Ultrasonography of liver showed signs of cirrhosis. The diagnosis of PBC was made considering positive AMA and the cholestatic pattern of liver enzymes, according to the criteria proposed by American Association of Study of Liver Diseases.<a href="#bib45" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">21</span></a> Ursodeoxycholic acid (13 mg/kg/day) was started. At this time it was possible to associate ILD with the primary autoimmune hepatobiliary disease (AHD).</p><a name="sec0015" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Discussion</span><p class="elsevierStylePara">AHD carries the potential to induce or be associated with ILD and PBC figures prominently among the primary AHD with pulmonary involvement, maybe because it is the most frequent and widely studied.<a href="#bib29" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">5</span></a> In a prospective study, 15.7% of PBC patients had concomitant ILD and 53.6% of them had respiratory symptoms.<a href="#bib30" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">6</span></a> There is increasing evidence of autoimmune pathophysiology occurring within the hepatopulmonary axis that may lead to clinically evident disease.<a href="#bib29" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">5</span></a> Coexistent extrahepatic autoimmune disease arises in 70–85% of PBC patients,<a href="#bib29" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">, </span><a href="#bib34" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">10</span></a> with 41% having more than 1 concurrent autoimmune process.<a href="#bib29" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">5</span></a> Shen et al.<a href="#bib30" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">6</span></a> demonstrated that Raynaud phenomenon and association with other connective tissue diseases were risk factors for PBC patients to develop ILD.</p><p class="elsevierStylePara">The diagnosis of PCB must fulfill at least 2 out of 3 of the following criteria: (1) chronic cholestasis with elevated alkaline phosphatase and/or gamma-glutamyl transpeptidase for at least 6 months, (2) the presence of serum AMA (titer ≥ 1:40), and (3) a histopathological study of a liver specimen biopsy indicating PCB.<a href="#bib27" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">3</span></a> In this case, although liver biopsies were not performed, the presence of AMA and biochemical evidence of cholestasis established the diagnosis of PBC. Serum AMA are widely accepted as the diagnostic hallmark of PBC, found in 90–95% of patients and less than 1% of normal controls, with a very high specificity,<a href="#bib27" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">, </span><a href="#bib35" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">11</span></a> and may precede disease onset by several years,<a href="#bib26" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">2</span></a> as in the case here described. Metcalf et al.<a href="#bib36" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">12</span></a> showed that before the advent of any clinical or biomedical criteria, individuals positive for AMA do have PBC. In this setting, it seems right that patients with interstitial lung disease, positive AMA and absence of liver dysfunction, should have their liver function tests monitored, given the high probability of developing PBC.</p><p class="elsevierStylePara">PBC overwhelmingly affects females, with a female to male ratio estimated as 10 to 1.<a href="#bib26" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">2</span></a> Epidemiological studies estimate that approximately 7–11% of PBC patients are male.<a href="#bib37" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">13</span></a> The reasons underlying the low incidence of PBC in males are largely unknown. A role of fetal microchimerism, sexual hormones or X chromosome linked defects has been proposed.<a href="#bib26" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">2</span></a> There does not appear to be any histological, serological, or biochemical differences between male and female PBC, although the symptoms may differ, with males being at higher risk of life-threatening complications such as gastrointestinal bleeding and hepatocellular carcinoma and autoimmune associated conditions being more common in female.<a href="#bib37" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">13</span></a><span class="elsevierStyleSup">, </span><a href="#bib38" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">14</span></a></p><p class="elsevierStylePara">The major noninfectious causes of GLD are sarcoidosis, hypersensitivity pneumonitis, granulomatosis with polyangiitis, aspiration pneumonia, common variable immunodeficiency, berylliosis, drug-induced lung diseases and talc granulomatosis.<a href="#bib39" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">15</span></a><span class="elsevierStyleSup">, </span><a href="#bib40" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">16</span></a><span class="elsevierStyleSup">, </span><a href="#bib41" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">17</span></a><span class="elsevierStyleSup">, </span><a href="#bib42" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">18</span></a> GLD is rarely found in association with PBC and to date, all the published clinical reports have described cases of female gender.<a href="#bib25" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">, </span><a href="#bib32" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">, </span><a href="#bib33" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">9</span></a> It is not uncommon to observe hepatic noncaseating epithelioid granulomas in PBC, particularly in early-stage disease,<a href="#bib43" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">19</span></a> suggesting a similar pathway on the hepatic inflammatory activity of PBC and pulmonary granulomatous damage. Wallaert et al.<a href="#bib44" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">20</span></a> demonstrated that subclinical alveolar inflammation comprising T-lymphocytes and activated alveolar macrophages mimicking sarcoid alveolitis is present in a high proportion of PBC patients. Also Spiteri et al.<a href="#bib45" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">21</span></a> suggested that the immune mechanisms involved in the formation of granulomas are similar to that of sarcoidosis. In this case, despite lymphocytic alveolitis, radiologic findings were not suggestive of sarcoidosis (no mediastinal adenopathies or small nodules were present), granulomas were poorly differentiated (unlike the well-formed granulomas of sarcoidosis) and CD4/CD8 ratio was normal, making the diagnosis of pulmonary sarcoidosis less probable.</p><p class="elsevierStylePara">Some authors described cases of ILD preceding connective tissue disease as rheumatoid arthritis and Sjögren's syndrome.<a href="#bib46" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">22</span></a><span class="elsevierStyleSup">, </span><a href="#bib47" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">23</span></a><span class="elsevierStyleSup">, </span><a href="#bib48" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">24</span></a> The time interval from prodromal respiratory symptoms to connective tissue disease ranged between 0.5 and 24 months in the cases of rheumatoid arthritis and 36 months in the patient with Sjögren's syndrome. In our patient, GLD preceded PBC diagnosis by around 24 months. It is not known whether treatment with corticosteroids masked or delayed the onset of liver disease.</p><p class="elsevierStylePara">The data on the treatment of the lung disease in the course of PBC are limited.<a href="#bib25" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">1</span></a> GLD seems to be a steroid responsive condition. In all reported cases of GLD associated to PBC, and also in this case, clinical and radiological improvements were obtained with corticosteroid therapy. Apart from corticosteroids, other immunosuppressive medications, i.e. azathioprine, cyclophosphamide, methotrexate and cyclosporine, have also been used.</p><a name="sec0020" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Ethical disclosures</span><a name="sec0025" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Protection of human and animal subjects</span><p class="elsevierStylePara">The authors declare that no experiments were performed on humans or animals for this study.</p><a name="sec0030" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Confidentiality of data</span><p class="elsevierStylePara">The authors declare that they have followed the protocols of their work center on the publication of patient data and that all the patients included in the study received sufficient information and gave their written informed consent to participate in the study.</p><a name="sec0035" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Right to privacy and informed consent</span><p class="elsevierStylePara">The authors have obtained the written informed consent of the patients or subjects mentioned in the article. The corresponding author is in possession of this document.</p><a name="sec0040" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Conflicts of interest</span><p class="elsevierStylePara">The authors declare that there are no conflicts of interest.</p><p class="elsevierStylePara">Received 26 January 2015 <br></br>Accepted 20 February 2015 </p><p class="elsevierStylePara">Corresponding author. ines.franco@chvng.min-saude.pt</p>" "pdfFichero" => "320v21n04a90433951pdf001.pdf" "tienePdf" => true "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec640982" "palabras" => array:5 [ 0 => "Primary biliary cirrhosis" 1 => "Primary autoimmune hepatobiliary diseases" 2 => "Granulomatous lung disease" 3 => "Interstitial lung disease" 4 => "Transbronchial cryobiopsy" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle"> Abstract</span><br/><p class="elsevierStylePara"> A 47-year-old male was admitted with subacute onset of dry cough and fever. Chest tomography demonstrated multifocal areas of consolidation and ground glass attenuation. Cytological analysis of bronchoalveolar lavage revealed lymphocytosis and eosinophilia and anatomopathological exam of transbronchial cryobiopsy showed poorly formed non-caseous granulomas associated to interstitial lympho-plasmocitary infiltrate. The diagnosis of idiopathic granulomatous lung disease (GLD) was assumed and the patient started oral prednisolone, presenting clinical, functional and radiological improvement. Two years later, the patient was diagnosed with primary biliary cirrhosis (PBC). At this time, it was possible to associate GLD with the autoimmune hepatobiliary disease.</p><p class="elsevierStylePara"> Clinical, epidemiological and pathological aspects of this uncommon case of interstitial lung disease as first presentation of PBC in a male patient are discussed.</p>" ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "320v21n04-90433951fig1.jpg" "Alto" => 711 "Ancho" => 975 "Tamanyo" => 194839 ] ] "descripcion" => array:1 [ "en" => "Chest computed tomography showing multifocal and peripheral areas of consolidation and ground glass, with perilobular pattern and halo sign." ] ] 1 => array:8 [ "identificador" => "fig2" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "320v21n04-90433951fig2.jpg" "Alto" => 609 "Ancho" => 1600 "Tamanyo" => 1197855 ] ] "descripcion" => array:1 [ "en" => "Poorly formed granulomas occupying alveolar spaces (A) (H&E high power), associated to interstitial lympho-plasmocitary infiltrate, (B) (H&E high power)." ] ] 2 => array:6 [ "identificador" => "fig3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "descripcion" => array:1 [ "en" => "Chest computed tomography showing multifocal and peripheral areas of consolidation and ground glass, with perilobular pattern and halo sign." ] ] 3 => array:6 [ "identificador" => "fig4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "descripcion" => array:1 [ "en" => "Poorly formed granulomas occupying alveolar spaces (A) (H&E high power), associated to interstitial lympho-plasmocitary infiltrate, (B) (H&E high power)." ] ] ] "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:24 [ 0 => array:3 [ "identificador" => "bib25" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Interstitial lung disease in patients with primary biliary cirrhosis. Pneumonol Alergol Pol. 2012; 80(5):471-81." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Interstitial lung disease in patients with primary biliary cirrhosis." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Bartosiewicz M" 1 => "Siemion-Szcześniak I" 2 => "Jędrych M" 3 => "Radwan-Röhrenschef P" 4 => "Lewandowska K" 5 => "Langfort R" 6 => "et-al." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Pneumonol Alergol Pol. " "fecha" => "2012" "volumen" => "80" "paginaInicial" => "471" "paginaFinal" => "481" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22926910" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib26" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Update on primary biliary cirrhosis. Dig Liver Dis. 2010; 42(6):401-8." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Update on primary biliary cirrhosis." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Invernizzi P" 1 => "Selmi C" 2 => "Gershwin ME." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.dld.2010.02.014" "Revista" => array:6 [ "tituloSerie" => "Dig Liver Dis. " "fecha" => "2010" "volumen" => "42" "paginaInicial" => "401" "paginaFinal" => "408" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20359968" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib27" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "AASLD practice guidelines – primary biliary cirrhosis. 2009." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "AASLD practice guidelines – primary biliary cirrhosis." "idioma" => "es" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Lindor KD" 1 => "Gershwin ME" 2 => "Poupon R" 3 => "Kaplan M" 4 => "Bergasa NV" 5 => "Heathcote EJ." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:2 [ "titulo" => "AASLD practice guidelines – primary biliary cirrhosis." "fecha" => "2009" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib28" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Connective tissue diseases in primary biliary cirrhosis: a population-based cohort study. World J Gastroenterol. 2013; 19(31):5131-7." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Connective tissue diseases in primary biliary cirrhosis: a population-based cohort study." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Wang L" 1 => "Zhang FC" 2 => "Chen H" 3 => "Zhang X" 4 => "Xu D" 5 => "Li YZ" 6 => "et-al." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3748/wjg.v19.i31.5131" "Revista" => array:6 [ "tituloSerie" => "World J Gastroenterol. " "fecha" => "2013" "volumen" => "19" "paginaInicial" => "5131" "paginaFinal" => "5137" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23964148" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib29" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Pulmonary manifestations of primary autoimmune hepatobiliary disease. Clin Pulm Med. 2005; 12:232-45." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Pulmonary manifestations of primary autoimmune hepatobiliary disease." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Allan P" 1 => "Powers Ch" 2 => "Morris M." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Clin Pulm Med. " "fecha" => "2005" "volumen" => "12" "paginaInicial" => "232" "paginaFinal" => "245" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib30" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Primary biliary cirrhosis complicated with interstitial lung disease: a prospective study in 178 patients. J Clin Gastroenterol. 2009; 43(7):676-9." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Primary biliary cirrhosis complicated with interstitial lung disease: a prospective study in 178 patients." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Shen M" 1 => "Zhang F" 2 => "Zhang X." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MCG.0b013e31818aa11e" "Revista" => array:6 [ "tituloSerie" => "J Clin Gastroenterol. " "fecha" => "2009" "volumen" => "43" "paginaInicial" => "676" "paginaFinal" => "679" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19247207" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib31" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Acute fibrinous and organising pneumonia. BMJ Case Rep. 2012; 20:2012." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Acute fibrinous and organising pneumonia." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Guimarães C" 1 => "Sanches I" 2 => "Ferreira C." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "BMJ Case Rep. " "fecha" => "2012" "volumen" => "20" "paginaInicial" => "2012" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib32" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Primary biliary liver cirrhosis and granulomatous pulmonar infiltrates. Schweiz Med Wochenschr. 1986; 116(33):1098-102." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Primary biliary liver cirrhosis and granulomatous pulmonar infiltrates." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Hoffmann R" 1 => "Germann EJ" 2 => "Schmidt U" 3 => "Jenss H." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Schweiz Med Wochenschr. " "fecha" => "1986" "volumen" => "116" "paginaInicial" => "1098" "paginaFinal" => "1102" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3764386" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib33" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Mottled chest radiograph and gas transfer defect in chronic liver disease. Thorax. 1972; 27:315-23." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Mottled chest radiograph and gas transfer defect in chronic liver disease." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Stanley N" 1 => "Woodgate D." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Thorax. " "fecha" => "1972" "volumen" => "27" "paginaInicial" => "315" "paginaFinal" => "323" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/5039446" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib34" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Primary biliary cirrhosis. Lancet. 2003; 362:53." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Primary biliary cirrhosis." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Talwaker J" 1 => "Lindor K." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(03)13808-1" "Revista" => array:5 [ "tituloSerie" => "Lancet. " "fecha" => "2003" "volumen" => "362" "paginaInicial" => "53" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12853201" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib35" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Autoantibodies in primary biliary cirrhosis: recent progress in research on the pathogenetic and clinical significance. World J Gastroenterol. 2014; 20(10):2606-12." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Autoantibodies in primary biliary cirrhosis: recent progress in research on the pathogenetic and clinical significance." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Yamagiwa S" 1 => "Kamimura H" 2 => "Takamura M" 3 => "Aoyagi Y." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3748/wjg.v20.i10.2606" "Revista" => array:6 [ "tituloSerie" => "World J Gastroenterol. " "fecha" => "2014" "volumen" => "20" "paginaInicial" => "2606" "paginaFinal" => "2612" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24627596" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib36" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Natural history of early primary biliary cirrhosis. Lancet. 1996; 348(9039):1399-402." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Natural history of early primary biliary cirrhosis." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Metcalf JV" 1 => "Mitchison HC" 2 => "Palmer JM" 3 => "Jones DE" 4 => "Bassendine MF" 5 => "James OF." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(96)04410-8" "Revista" => array:6 [ "tituloSerie" => "Lancet. " "fecha" => "1996" "volumen" => "348" "paginaInicial" => "1399" "paginaFinal" => "1402" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8937278" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib37" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Sex differences associated with primary biliary cirrhosis. Clin Dev Immunol. 2012; 2012:610504." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Sex differences associated with primary biliary cirrhosis." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Smyk DS" 1 => "Rigopoulou EI" 2 => "Pares A" 3 => "Billinis C" 4 => "Burroughs AK" 5 => "Muratori L" 6 => "et-al." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1155/2012/610504" "Revista" => array:5 [ "tituloSerie" => "Clin Dev Immunol. " "fecha" => "2012" "volumen" => "2012" "paginaInicial" => "610504" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22693524" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib38" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Primary biliary cirrhosis in men. Gut. 1986; 27(11):1373-6." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Primary biliary cirrhosis in men." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Lucey MR" 1 => "Neuberger JM" 2 => "Williams R." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Gut. " "fecha" => "1986" "volumen" => "27" "paginaInicial" => "1373" "paginaFinal" => "1376" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3792920" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib39" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Granulomatous lung disease: an approach to the differential diagnosis. Arch Pathol Lab Med. 2010; 134(5):667-90." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Granulomatous lung disease: an approach to the differential diagnosis." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Mukhopadhyay S" 1 => "Gal AA." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1043/1543-2165-134.5.667" "Revista" => array:6 [ "tituloSerie" => "Arch Pathol Lab Med. " "fecha" => "2010" "volumen" => "134" "paginaInicial" => "667" "paginaFinal" => "690" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20441499" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib40" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Granulomatous interstitial lung diseases. Rev Prat. 2014; 64(7):946-8." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Granulomatous interstitial lung diseases." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Valeyre D" 1 => "Musungayi JM." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rev Prat. " "fecha" => "2014" "volumen" => "64" "paginaInicial" => "946" "paginaFinal" => "948" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25362776" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib41" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Incidence and aetiologies of pulmonary granulomatous inflammation: a decade of experience. Respirology. 2015; 20(1):115-21." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Incidence and aetiologies of pulmonary granulomatous inflammation: a decade of experience." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Nazarullah A" 1 => "Nilson R" 2 => "Maselli DJ" 3 => "Jagirdae J." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/resp.12410" "Revista" => array:6 [ "tituloSerie" => "Respirology. " "fecha" => "2015" "volumen" => "20" "paginaInicial" => "115" "paginaFinal" => "121" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25351289" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib42" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "The role of transbronchial lung biopsy for the diagnosis of diffuse drug-induced lung disease: a case series of 44 cases. Sarcoidosis Vasc Diffuse Lung Dis. 2008; 25(1):36-45." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "The role of transbronchial lung biopsy for the diagnosis of diffuse drug-induced lung disease: a case series of 44 cases." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Romagnoli M" 1 => "Bigliazzi C" 2 => "Casoni G" 3 => "Chilosi M" 4 => "Carloni A" 5 => "Dubini A" 6 => "et-al." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Sarcoidosis Vasc Diffuse Lung Dis. " "fecha" => "2008" "volumen" => "25" "paginaInicial" => "36" "paginaFinal" => "45" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19070259" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib43" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "The immunopathology of liver granulomas in primary biliary cirrhosis. J Autoimmun. 2012; 39(3):216-21." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "The immunopathology of liver granulomas in primary biliary cirrhosis." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "You Z" 1 => "Wang Q" 2 => "Bian Z" 3 => "Liu Y" 4 => "Han X" 5 => "Peng Y" 6 => "et-al." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaut.2012.05.022" "Revista" => array:6 [ "tituloSerie" => "J Autoimmun. " "fecha" => "2012" "volumen" => "39" "paginaInicial" => "216" "paginaFinal" => "221" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22727562" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib44" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Primary biliary cirrhosis: subclinical inflammatory alveolitis in patients with normal chest roentgenograms. Chest. 1986; 90:842-8." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Primary biliary cirrhosis: subclinical inflammatory alveolitis in patients with normal chest roentgenograms." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Wallaert B" 1 => "Bonniere P" 2 => "Prin L" 3 => "Cortot A" 4 => "Tonnel AB" 5 => "Voisin C." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Chest. " "fecha" => "1986" "volumen" => "90" "paginaInicial" => "842" "paginaFinal" => "848" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3490957" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib45" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Immunological features of lung lavage cells from patients with primary biliary cirrhosis may reflect those seen in pulmonary sarcoidosis. Gut. 1990; 31:208-12." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Immunological features of lung lavage cells from patients with primary biliary cirrhosis may reflect those seen in pulmonary sarcoidosis." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Spiteri M" 1 => "Johnson M" 2 => "Epstein O" 3 => "Sherlock S" 4 => "Clarke S" 5 => "Poulter L." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Gut. " "fecha" => "1990" "volumen" => "31" "paginaInicial" => "208" "paginaFinal" => "212" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2311980" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib46" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Organizing pneumonia preceding rheumatoid arthritis. Case Rep Pulmonol. 2014; 2014:758619." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Organizing pneumonia preceding rheumatoid arthritis." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Kinoshita Y" 1 => "Sakamoto A" 2 => "Hidaka K." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1155/2014/758619" "Revista" => array:5 [ "tituloSerie" => "Case Rep Pulmonol. " "fecha" => "2014" "volumen" => "2014" "paginaInicial" => "758619" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24600522" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib47" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Organising pneumonia can be the inaugural manifestation in connective tissue diseases, including Sjogren's syndrome. Eur Respir Rev. 2010; 19(116):161-3." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Organising pneumonia can be the inaugural manifestation in connective tissue diseases, including Sjogren's syndrome." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Henriet AC" 1 => "Diot E" 2 => "Marchand-Adam S" 3 => "de Muret A" 4 => "Favelle O" 5 => "Crestani B" 6 => "et-al." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1183/09059180.00002410" "Revista" => array:6 [ "tituloSerie" => "Eur Respir Rev. " "fecha" => "2010" "volumen" => "19" "paginaInicial" => "161" "paginaFinal" => "163" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20956186" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib48" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Case of interstitial lung disease with anti-EJ and anti-CCP antibodies preceding rheumatoid arthritis. Respir Investig. 2012; 50(2):66-9." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Case of interstitial lung disease with anti-EJ and anti-CCP antibodies preceding rheumatoid arthritis." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Tomioka H" 1 => "Kaneko M" 2 => "Kogata Y" 3 => "Katsuyama E" 4 => "Ishikawa S" 5 => "Fujii T." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.resinv.2012.04.003" "Revista" => array:6 [ "tituloSerie" => "Respir Investig. " "fecha" => "2012" "volumen" => "50" "paginaInicial" => "66" "paginaFinal" => "69" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22749253" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/08732159/0000002100000004/v0_201604141144/X0873215915339518/v0_201604141145/en/main.assets" "Apartado" => array:4 [ "identificador" => "18139" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Casos clínicos" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/08732159/0000002100000004/v0_201604141144/X0873215915339518/v0_201604141145/en/320v21n04a90433951pdf001.pdf?idApp=UINPBA00004E&text.app=https://journalpulmonology.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X0873215915339518?idApp=UINPBA00004E" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 19 | 5 | 24 |
| 2024 October | 133 | 29 | 162 |
| 2024 September | 208 | 26 | 234 |
| 2024 August | 226 | 49 | 275 |
| 2024 July | 230 | 50 | 280 |
| 2024 June | 146 | 51 | 197 |
| 2024 May | 123 | 43 | 166 |
| 2024 April | 142 | 49 | 191 |
| 2024 March | 106 | 32 | 138 |
| 2024 February | 103 | 33 | 136 |
| 2024 January | 104 | 37 | 141 |
| 2023 December | 94 | 17 | 111 |
| 2023 November | 96 | 41 | 137 |
| 2023 October | 99 | 48 | 147 |
| 2023 September | 85 | 37 | 122 |
| 2023 August | 93 | 25 | 118 |
| 2023 July | 101 | 27 | 128 |
| 2023 June | 72 | 25 | 97 |
| 2023 May | 94 | 32 | 126 |
| 2023 April | 99 | 32 | 131 |
| 2023 March | 132 | 20 | 152 |
| 2023 February | 97 | 31 | 128 |
| 2023 January | 98 | 33 | 131 |
| 2022 December | 118 | 29 | 147 |
| 2022 November | 150 | 47 | 197 |
| 2022 October | 112 | 46 | 158 |
| 2022 September | 67 | 37 | 104 |
| 2022 August | 78 | 42 | 120 |
| 2022 July | 81 | 53 | 134 |
| 2022 June | 78 | 37 | 115 |
| 2022 May | 87 | 44 | 131 |
| 2022 April | 99 | 49 | 148 |
| 2022 March | 110 | 60 | 170 |
| 2022 February | 107 | 39 | 146 |
| 2022 January | 77 | 48 | 125 |
| 2021 December | 51 | 39 | 90 |
| 2021 November | 71 | 34 | 105 |
| 2021 October | 85 | 52 | 137 |
| 2021 September | 62 | 40 | 102 |
| 2021 August | 67 | 27 | 94 |
| 2021 July | 92 | 26 | 118 |
| 2021 June | 69 | 32 | 101 |
| 2021 May | 77 | 43 | 120 |
| 2021 April | 228 | 74 | 302 |
| 2021 March | 147 | 26 | 173 |
| 2021 February | 91 | 42 | 133 |
| 2021 January | 103 | 28 | 131 |
| 2020 December | 65 | 13 | 78 |
| 2020 November | 102 | 36 | 138 |
| 2020 October | 67 | 25 | 92 |
| 2020 September | 150 | 31 | 181 |
| 2020 August | 89 | 31 | 120 |
| 2020 July | 120 | 28 | 148 |
| 2020 June | 107 | 34 | 141 |
| 2020 May | 113 | 27 | 140 |
| 2020 April | 91 | 7 | 98 |
| 2020 March | 112 | 15 | 127 |
| 2020 February | 112 | 33 | 145 |
| 2020 January | 98 | 21 | 119 |
| 2019 December | 122 | 36 | 158 |
| 2019 November | 108 | 24 | 132 |
| 2019 October | 115 | 23 | 138 |
| 2019 September | 123 | 24 | 147 |
| 2019 August | 187 | 24 | 211 |
| 2019 July | 189 | 26 | 215 |
| 2019 June | 166 | 11 | 177 |
| 2019 May | 173 | 16 | 189 |
| 2019 April | 193 | 33 | 226 |
| 2019 March | 251 | 28 | 279 |
| 2019 February | 208 | 7 | 215 |
| 2019 January | 216 | 23 | 239 |
| 2018 December | 111 | 6 | 117 |
| 2018 November | 50 | 0 | 50 |
| 2018 October | 35 | 9 | 44 |
| 2018 September | 33 | 6 | 39 |
| 2018 August | 29 | 23 | 52 |
| 2018 July | 40 | 18 | 58 |
| 2018 June | 33 | 19 | 52 |
| 2018 May | 32 | 18 | 50 |
| 2018 April | 45 | 20 | 65 |
| 2018 March | 47 | 21 | 68 |
| 2018 February | 22 | 15 | 37 |
| 2018 January | 16 | 15 | 31 |
| 2017 December | 39 | 16 | 55 |
| 2017 November | 23 | 21 | 44 |
| 2017 October | 25 | 12 | 37 |
| 2017 September | 15 | 20 | 35 |
| 2017 August | 21 | 25 | 46 |
| 2017 July | 20 | 8 | 28 |
| 2017 June | 24 | 21 | 45 |
| 2017 May | 34 | 11 | 45 |
| 2017 April | 13 | 1 | 14 |
| 2017 March | 19 | 4 | 23 |
| 2017 February | 15 | 5 | 20 |
| 2017 January | 15 | 4 | 19 |
| 2016 December | 11 | 4 | 15 |
| 2016 November | 17 | 3 | 20 |
| 2016 October | 19 | 7 | 26 |
| 2016 September | 23 | 15 | 38 |
| 2016 August | 9 | 3 | 12 |
| 2016 July | 14 | 14 | 28 |
| 2016 June | 0 | 11 | 11 |
| 2016 May | 0 | 7 | 7 |
| 2016 April | 25 | 21 | 46 |
| 2016 March | 49 | 28 | 77 |
| 2016 February | 57 | 32 | 89 |
| 2016 January | 43 | 34 | 77 |
| 2015 December | 57 | 33 | 90 |
| 2015 November | 39 | 28 | 67 |
| 2015 October | 43 | 25 | 68 |
| 2015 September | 55 | 35 | 90 |
| 2015 August | 138 | 101 | 239 |
| 2015 July | 115 | 110 | 225 |
Show all
