Pulmonary manifestations and prognosis of a cohort of patients with interstitial lung disease and positive to anti-Th/To autoantibodies.

INTRODUCTION: Th/To autoantibody may be relevant in evaluating patients with interstitial lung disease (ILD) because the clinical diagnosis of systemic sclerosis (SSc) may not be evident. The study's objective was to describe manifestations and evolution of pulmonary function in a cohort of ILD patients positive for Th/To autoantibodies. METHODS: ILD patients positive for anti-Th/To autoantibody were enrolled in this protocol. Baseline clinical features were registered, and survival analysis was performed to identify risk factors associated with worse survival. RESULTS: Fifty-two patients positive for anti-Th/To autoantibodies with ILD were included. Only 21% of the patients fulfilled the ACR/EULAR 2013 systemic sclerosis classification criteria, and 63.4% fulfilled the IPAF ATS/ERS 2015 criteria. Twenty-five percent of the patients died during follow-up. Respiratory failure was the principal cause of death. Twenty-nine patients (56%) were positive for other hallmark SSc autoantibodies. The most frequent HRCT pattern was nonspecific interstitial pneumonia (NISP). Survival was strongly associated to the systolic pulmonary arterial pressure (sPAP), male sex and the extent of fibrosis in HRCT; besides, patients positive for other hallmark SSc autoantibodies had worse survival compared to those positive only to anti-Th/To. Seventy-six percent of them behaved as fibrotic progressive pulmonary disease, with an absolute decline of the FVC of at least 5%. CONCLUSIONS: Only a small proportion of ILD patients positive for Th/To meet the criteria to be classified as SSc; however, most met criteria for IPAF. A high proportion of patients behave as progressive fibrotic pulmonary disease. Survival is associated with sPAP, the extent of lung disease, and the presence of other hallmark SSc autoantibodies.

Complicaciones y re intervenciones de las cintas transobturadoras y retropúbicas en el Hospital Militar Central, Bogotá 2015-2020 / Complications and re-interventions of transobturator and retropubic tapes at Hospital Militar Central, Bogotá 2015-2020

la incontinencia urinaria (IU), se define por la Sociedad Internacional de Continencia, como la perdida involuntaria de orina, una condición potencialmente tratable con disminución de la calidad de vida de las mujeres en diferentes aspectos, entre ellos la salud sexual con su pareja y su bienestar social. Se han descrito que solo el 44,9 % de las mujeres consultan, teniendo mayores tasas de depresión y ansiedad. El objetivo de esta investigación fue determinar la aparición de complicaciones intraoperatorias y posoperatorias con la realización de cintas transobturadora y retropúbica en el Hospital Militar Central en Bogotá durante el periodo 2015 al 2020. Se realizó un estudio observacional, descriptivo, retrospectivo de corte longitudinal, en el Hospital Militar Central en Bogotá; se incluyeron todas las pacientes con diagnósticos de incontinencia urinaria, tanto de esfuerzo, como de urgencias y/o mixtas, intervenidas con cintas medios uretrales libres de tensión por vía retropúbica o transobturadora. Las complicaciones posteriores al procedimiento quirúrgico la más prevalente fue el dolor con un 96,8 %, seguida de infección urinaria o expulsión de la banda con un 8,6 %; entre otras complicaciones menos frecuentes como hematomas, dispareunia y abscesos. La mayoría de las pacientes obtuvieron una adecuada respuesta clínica en el postoperatorio, el 77 % no requirió ningún manejo adicional. Las cintas mediouretrales, proporcionan un buen resultado con una baja incidencia de complicaciones quirúrgicas y recidiva, con mejoría de la calidad de vida de la paciente frente a su patología de incontinencia urinaria.

The International Continence Society defines urinary incontinence (UI) as the involuntary loss of urine, a potentially treatable condition with a decrease in the quality of life of women in different aspects, including sexual health with their partner and their social well-being. It has been described that only 44.9% of women consult, having higher rates of depression and anxiety. The objective of this research was to determine the occurrence of intraoperative and postoperative complications with the performance of transobturator and retropubic taping at the Central Military Hospital in Bogota during the period 2015 to 2020. An observational, descriptive, retrospective, retrospective. All patients with diagnoses of urinary incontinence, both stress, emergency, and/or mixed, operated with tension-free mid-urethral tapes by retropubic or transobturator route were included. The most prevalent complications after the surgical procedure were pain (96.8 %), followed by urinary tract infection or expulsion of the band (8.6 %), among other less frequent complications such as hematomas, dyspareunia, and abscesses. Most patients obtained an adequate clinical response in the postoperative period, 77 % did not require additional management. Mediourethral tapes provide a good result with a low incidence of surgical complications and recurrence, improving the patient's quality of life concerning her urinary incontinence pathology.

a incontinência urinária (IU) é definida pela Sociedade Internacional de Continência como a perda involuntária de urina, uma condição potencialmente tratável com uma diminuição na qualidade de vida das mulheres em diferentes aspectos, incluindo a saúde sexual com seu parceiro e seu bem-estar social. Foi relatado que apenas 44,9% das mulheres consultam, apresentando taxas mais altas de depressão e ansiedade. O objetivo desta pesquisa foi determinar a ocorrência de complicações intraoperatórias e pós-operatórias com fita transobturatória e retropúbica no Hospital Militar Central de Bogotá, Colômbia, durante o período de 2015 a 2020. Foi realizado um estudo observacional, descritivo, retrospectivo de corte longitudinal no Hospital Militar Central de Bogotá, incluindo todos os pacientes diagnosticados com incontinência urinária, tanto de esforço, de emergência e/ou mista, operados com slings mediouretrais sem tensão via retropúbica ou transobturatória. As complicações mais prevalentes após o procedimento cirúrgico foram dor (96,8%), seguida de infecção do trato urinário ou expulsão da faixa (8,6%), entre outras complicações menos frequentes, como hematomas, dispareunia e abscessos. A maioria dos pacientes teve uma resposta clínica adequada no pós-operatório e 77% não precisaram de nenhum tratamento adicional. Os slings mediouretrais proporcionam um bom resultado com baixa incidência de complicações cirúrgicas e recorrência, com melhora na qualidade de vida da paciente com relação à sua patologia de incontinência urinária.

Lung Ultrasound Characteristics in Neonates With Positive Real Time Polymerase Chain Reaction for SARS-CoV-2 on a Tertiary Level Referral Hospital in Mexico City.

Introduction: Acute respiratory syndrome secondary to SARS-CoV-2 virus infection has been declared a pandemic since December 2019. On neonates, severe presentations are infrequent but possible. Lung ultrasound (LUS) has been shown to be useful in diagnosing lung involvement and following up patients, giving more information, and reducing exposure compared to traditional examination. Methods: LUS was performed after the diagnosis of SARS-CoV-2 infection with respiratory Real Time Polymerase Chain Reaction RT-PCR with portable equipment protected with a silicone sleeve. If hemodynamic or cardiology consultation was necessary, a prepared complete ultrasound machine was used. Ten regions were explored (anterior superior and inferior, lateral, and posterior superior and inferior, right and left), and a semiquantitative score (LUSS) was calculated. Disease severity was determined with a pediatric modified score. Results: Thirty-eight patients with positive RT-PCR were admitted, 32 (81%) of which underwent LUS. Included patients had heterogenous diagnosis and gestational ages as expected on a referral neonatal intensive care unit (NICU) (median, ICR: 36, 30-38). LUS abnormalities found were B-line interstitial pattern 90%, irregular/interrupted/thick pleural line 88%, compact B-lines 65%, small consolidations (≤5 mm) 34%, and extensive consolidations (≥5 mm) 37%. Consolidations showed posterior predominance (70%). LUSS showed a median difference between levels of disease severity and ventilatory support (Kruskal-Wallis, p = 0.001) and decreased with patient improvement (Wilcoxon signed-rank test p = 0.005). There was a positive correlation between LUSS and FiO2 needed (Spearman r = 0.72, p = 0.01). The most common recommendation to the attending team was pronation (41%) and increase in positive end expiratory pressure (34%). Five patients with comorbidities died. A significant rank difference of LUSS and FiO2 needed between survivors and non-survivors was found (Mann-Whitney U-test, p = 0.005). Conclusion: LUS patterns found were like the ones described in other series (neonatal and pediatrics). Eighty-eight percent of the studies were performed with handheld affordable equipment. While there is no specific pattern, it varies according to gestational age and baseline diagnosis LUS, which were shown to be useful in assessing lung involvement that correlated with the degree of disease severity and respiratory support.

An Open-label Study With Pirfenidone on Chronic Hypersensitivity Pneumonitis.

BACKGROUND: Chronic hypersensitivity pneumonitis (cHP) represents a severe lung disease often evolving to fibrosis with the subsequent destruction of the lung parenchyma. There are no approved therapies with confirmed efficacy to deal with this disease. METHODS: We performed an open-label, proof of concept study, to evaluate the efficacy and safety of pirfenidone added to immunosuppressive drugs on the treatment of cHP. We included 22 patients assigned to two groups: Group 1, nine patients that received prednisone plus azathioprine and Group 2, thirteen patients, received prednisone plus azathioprine and pirfenidone (ClinicalTrials.gov identifier NCT02496182). There were no significant imbalances in clinically relevant baseline characteristics between two study groups. RESULTS: After 1 year of treatment, inclusion of pirfenidone was not associated with improved forced vital capacity (primary end-point). A not significant tendency to show higher improvement of diffusion capacity of the lung for carbon monoxide (DLCO) was observed in the group receiving pirfenidone (p=0.06). Likewise, a significant improvement in the total score on the SGRQ was found in the group 2 (p=0.02) without differences in other two questionnaires related to quality of life (ATAQ-IPF and EQ-5D-3L). HRCT showed a decrease of the ground glass attenuation without changes in the fibrotic lesions and without differences between both groups. CONCLUSIONS: These findings suggest that the addition of pirfenidone to the anti-inflammatory treatment in patients with chronic HP may improve the outcome with acceptable safety profile. However, prospective randomized double-blind, placebo-controlled trials in largest cohorts are needed to validate its efficacy.

Follow up of Patients with Eagle-Barett (Prune Belly) Syndrome Treated with Single-Stage Abdominoplasty and Total Genitourinary Tract Reconstruction / Seguimiento de pacientes con síndrome de Eagle-Barret (prune belly) tratados con abdominoplastia en un solo tiempo y reconstrucción total del tracto genitourinario

Introduction The Prune Belly Syndrome (PBS) is the deficiency or congenital hypoplasia of the abdominal muscles accompanied with disorders of the urinary tract. The surgical treatment for the uropathy of the PBS seeks to correct the anatomical defects that induce damage to the urinary tract, including the improvement of the bladder emptying. The correction of the abdominal wall defect must be considered as an important part of the treatment. Objective To describe of the most relevant clinic characteristics and outcomes of a group of eight patients with PBS managed with abdominoplasty and reconstructive urologic surgery. Methods Retrospective review of the medical charts of patients with PBS at Hospital Universitario San Ignacio, Hospital Militar Central of Bogotá, Clinica Infantil Colsubsidio and Fundación Oftalmológica Ardila Lulle of Bucaramanga, (Colombia) that were managed with reconstructive surgery of the urinary tract and Monfort technique abdominoplasty (between 2006 and 2016) by one of the authors (JPN). The evaluated variables included: phenotypic appearance, renal function, bowel movements, and urinary tract infection (UTI) episodes. These variables as well as the abdominal wall aspect, were evaluated postoperatively. Results There were 11 patients identified with PBS between 2006 and 2016. Eight (8) of them underwent reconstructive urologic surgery, orchidopexy and Monfort technique abdominoplasty. After the procedures, none of the patients presented deterioration of the renal function, and they reported a better quality of the stools according to the Bristol scale; there were also less episodes of UTI. The phenotypic aspect of the abdominal wall was qualified as satisfactory in all cases. Conclusions Reconstructive urologic surgery and abdominoplasty in patients with PBS is an excellent choice of management that reduces the number of UTIs, improves bowel movements according to the Bristol scale, and preserves the renal function. This management approach also improves the phenotypic aspect of the abdominal wall. All of this leads to higher survival rate and better quality of life.

Introducción El Síndrome de Prune Belly (SPB) es la deficiencia o hipoplasia congénita de los músculos abdominales acompañada de desórdenes del tracto genitourinario. El manejo quirúrgico de la uropatía del SPB busca corregir los defectos anatómicos que inducen daño al tracto urinario, incluyendo la mejora del vaciamiento vesical. La corrección del defecto de la pared abdominal debe considerarse como una parte importante del manejo. Objetivos Describir las características clínicas más relevantes y el desenlace de un grupo de 8 pacientes con SPB manejados con abdominoplastia y cirugía urológica reconstructiva. Materiales y Métodos Revisión retrospectiva de las historias clínicas de los pacientes con SPB del Hospital Universitario San Ignacio, Hospital Militar Central de Bogotá, Clínica Infantil Colsubsidio, y Fundación Oftalmológica Carlos Ardila Lulle de Bucaramanga (Colombia), manejados con cirugía reconstructiva de las vías urinarias y abdominoplastia tipo Monfort entre los años 2008 y 2016 por uno de los autores (JPN). Las variables incluidas fueron: aspecto fenotípico, función renal, hábito intestinal y características de las deposiciones, y episodios de infección urinaria. El desenlace de estas variables y el aspecto de la pared abdominal fueron evaluados en el postoperatorio. Resultados se identificaron 11 pacientes con SPB entre 2006 y 2016. Ocho (8) fueron sometidos a cirugía reconstructiva de las vías urinarias, orquidopexia y abdominoplastia tipo Monfort. Después de los procedimientos, ninguno de los pacientes presentó deterioro de la función renal; los pacientes refieren mejor calidad de las deposiciones según la escala de Bristol; se presentaron menos episodios de infección de vías urinarias. El aspecto fenotípico fue calificado como satisfactorio en todos los casos. Conclusiones La cirugía urológica reconstructiva acompañada de abdominoplastia en pacientes con SPB es una excelente forma de manejo que reduce el número de infecciones urinarias, mejora la calidad del hábito intestinal según la escala de Bristol, y conserva la función renal. Este manejo mejora además el aspecto fenotípico de la pared abdominal. Todo esto lleva a una mayor sobrevida y mejor calidad de vida.

Abdominal trauma: experience of 4961 cases in Western Mexico.

INTRODUCTION: Trauma is a leading cause of morbimortality in the world. Intraabdominal compartment is the third most affected anatomical region and bleeding from this origin is difficult to identify, therefore the importance to predict possible lesions to the abdominal cavity. OBJECTIVE: To describe and analyze the sociodemographic profile and injuries found in patients with abdominal trauma in a western hospital in Mexico. METHOD: Consecutive patients included in the local registry GDL-SHOT were analyzed. RESULTS: From 4961 patients, 91.4% were men, with a mean age of 28.7 years. Regarding the mechanism of trauma, 39.7% were stab wounds, 33% blunt abdominal trauma and 27.3% gunshots. The most affected organs were: small bowel (20.9%), liver (18.2%), and colon (14.2%). The mean hospital stay was 6.95 days with a mortality of 6.74%. CONCLUSION: In Mexico, abdominal trauma represents an important cause of morbidity and mortality, especially in young patients. We found an important amount of penetrating trauma.

INTRODUCCIÓN: El trauma es una de las principales causas de morbimortalidad en el mundo. El abdomen es, en frecuencia, la tercera región anatómica más afectada, y el compartimento intraabdominal es un sitio de hemorragia difícil de identificar, por lo que cobra importancia el conocimiento de las posibles lesiones tras un traumatismo. OBJETIVOS: Describir y analizar el perfil sociodemográfico y las lesiones encontradas en pacientes con trauma abdominal en un hospital de referencia del occidente de México. MÉTODO: Se seleccionaron para su análisis los pacientes incluidos en el registro hospitalario local GDL-SHOT. RESULTADOS: De 4961 pacientes, el 91.4% fueron hombres, con un promedio de edad de 28.7 años. Respecto al mecanismo, el 39.7% correspondió a arma blanca, el 33% a trauma cerrado y el 27.3% a arma de fuego. Los órganos más afectados fueron el intestino delgado (20.9%), el hígado (18.2%) y el colon (14.2%). La estancia hospitalaria promedio fue de 6.95 días, con una mortalidad del 6.74%. CONCLUSIONES: En México, el trauma abdominal representa una causa importante de morbimortalidad, en especial en pacientes jóvenes, y predomina el mecanismo penetrante; el manejo más común es no conservador. La frecuencia de lesiones encontradas es discordante con la literatura de otros países y predominan las de vísceras huecas, probablemente por la diferencia en los mecanismos implicados.

Morphologic diversity of chronic pigeon breeder's disease: clinical features and survival.

Morphology in chronic HP is characterized by bronchiolocentric mononuclear inflammation, poorly formed granulomas and variable degree of fibrosis. However, recent findings suggest that this disease may present different pathologic patterns. In this study we evaluated the clinical behavior and survival of patients with pigeon breeder's disease according to the pathologic pattern. One-hundred ten biopsies were classified as "typical" (n = 58), non-specific interstitial pneumonia (NSIP)-pattern (n = 22), usual interstitial pneumonia (UIP)-like (n = 10), mixed pattern (n = 9), organizing pneumonia (OP)-pattern (n = 3), airway-centered interstitial fibrosis (ACIF)-pattern (n = 3), and non-classified (n = 5). Clinical features and survival were compared between patients with "typical", NSIP, and UIP patterns. There were no statistical differences between the groups in age, gender, time of symptoms, smoking, clubbing, and PaO(2). By the one-way ANOVA test we found differences in the percent of lymphocytes in bronchoalveolar lavage (BAL; p < 0.002) and in the forced vital capacity (p < 0.05) between the 3 groups. After Bonferroni correction the difference in BAL lymphocytes remained significant among the UIP-like and the typical pattern (36.1 ± 22.9 versus 64.6 ± 20.9, p = 0.001). UIP-like patients exhibited the worst survival rate (HR: 4.19; 95% CI: 1.66-14.47; p < 0.004) while NSIP-like pattern showed the best survival (HR: 0.18; 95% CI: 0.04-0.82; p < 0.03). Multivariate Cox regression analysis revealed that patients with a UIP-like pattern retained a significantly worse survival (HR: 3.4 (IC 95%: 1.15-10.29; p < 0.03), and mortality for the NSIP group was best and approached statistical significance (p = 0.07). These findings demonstrate that a variety of histopathologic and imaging patterns are seen in PBD, and the presence of a UIP-like pattern confers the worst prognosis.

Idiopathic pulmonary fibrosis and emphysema: decreased survival associated with severe pulmonary arterial hypertension.

BACKGROUND: It has been suggested that the presence of emphysema modifies the outcome of patients with idiopathic pulmonary fibrosis (IPF). In this article we compare clinical features, smoking history, pulmonary function, estimated systolic pulmonary artery pressure (eSPAP), and mortality in IPF with emphysema vs IPF without emphysematous changes. METHODS: A cohort of 110 IPF patients was evaluated. Clinical data were collected from clinical charts. High-resolution CT (HRCT) scans were examined by an expert blinded to clinical data, and patients were classified into the following two groups: patients with IPF with emphysema; and patients with IPF without emphysema. The Kaplan-Meier method, log-rank test, and Cox regression model were used for statistical analyses. RESULTS: The prevalence of emphysema in the IPF cohort was 28% (31 of 110 patients). IPF with emphysema was significantly associated with male gender (odds ratio [OR], 18; 95% confidence interval [CI], 2.7 to 773.7; p = 0.0003), and smoking (OR, 3.8; 95% CI, 1.36 to 11.6; p = 0.004). Patients with IPF and emphysema had a higher mean (+/- SD) decrease in oxygen saturation during rest and exercise (16.3 +/- 6.7% vs 13.5 +/- 4.6%, respectively; p = 0.04), a higher mean fibrosis HRCT scan score (1.75 +/- 0.36 vs 1.55 +/- 0.38, respectively; p = 0.015), a higher eSPAP (82 +/- 20 vs 57 +/- 15 mm Hg, respectively; p < 0.0001), and lower median survival time (25 vs 34 months, respectively; p = 0.01) than patients with IPF without emphysema. The Cox regression model showed that the two most important variables associated with mortality were FVC < 50% predicted (hazard ratio [HR], 2.6; 95% CI, 1.19 to 5.68; p = 0.016) and eSPAP >or= 75 mm Hg (HR, 2.25; 95% CI, 1.12 to 4.54; p = 0.022). CONCLUSIONS: IPF patients with emphysema exhibited higher mortality compared with those with IPF without emphysema. This dire prognosis seems to be at least partially associated with the development of severe pulmonary arterial hypertension.

Functional diversity of T-cell subpopulations in subacute and chronic hypersensitivity pneumonitis.

RATIONALE: Hypersensitivity pneumonitis (HP) exhibits a diverse outcome. Patients with acute/subacute HP usually improve, whereas patients with chronic disease often progress to fibrosis. However, the mechanisms underlying this difference are unknown. OBJECTIVES: To examine the T-cell profile from patients with subacute HP and chronic HP. METHODS: T cells were obtained by bronchoalveolar lavage from 25 patients with subacute HP, 30 patients with chronic HP, and 8 control subjects. T-cell phenotype and functional profile were evaluated by flow cytometry, cytometric bead array, and immunohistochemistry. MEASUREMENTS AND MAIN RESULTS: Patients with chronic HP showed higher CD4+:CD8+ ratio (median, 3.05; range, 0.3-15; subacute HP: median, 1.3; range, 0.1-10; control: median, 1.3; range, 0.7-2.0; P < 0.01), and a decrease of gammadeltaT cells (median, 2.0; range, 0.5-3.4; subacute HP: median, 10; range, 4.8-17; control: median, 15; range, 5-19; P < 0.01). Patients with chronic HP exhibited an increase in the terminally differentiated memory CD4+ and CD8+ T-cell subsets compared with patients with subacute HP (P < 0.05). However, memory cells from chronic HP showed lower IFN-gamma production and decreased cytotoxic activity by CD8+ T lymphocytes. Chronic HP displayed a Th2-like phenotype with increased CXCR4 expression (median, 6%; range, 1.7-36, vs. control subjects: median, 0.7%; range, 0.2-1.4; and subacute HP: median, 2.2%; range, 0.1-5.3; P < 0.01), and decreased CXCR3 expression (median, 4.3%; range, 1.4-25%, vs. subacute HP: median, 37%; range, 4.9-78%; P < 0.01). Likewise, supernatants from antigen-specific-stimulated cells from chronic HP produced higher levels of IL-4 (80 +/- 63 pg/ml vs. 25 +/- 7 pg/ml; P < 0.01), and lower levels of IFN-gamma (3,818 +/- 1671 pg/ml vs. 100 +/- 61 pg/ml; P < 0.01) compared with subacute HP. CONCLUSIONS: Our findings indicate that patients with chronic HP lose effector T-cell function and exhibit skewing toward Th2 activity, which may be implicated in the fibrotic response that characterizes this clinical form.

Accelerated variant of idiopathic pulmonary fibrosis: clinical behavior and gene expression pattern.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterized by the insidious onset of dyspnea or cough. However, a subset of patients has a short duration of symptoms with rapid progression to end-stage disease. In this study, we evaluated clinical and molecular features of "rapid" and "slow" progressors with IPF. METHODS AND FINDINGS: 26 patients with <6 months of symptoms before first presentation [rapid progressors] and 88 patients with >24 months of symptoms [slow progressors] were studied. Survival was analyzed by the Kaplan-Meyer method and proportional hazard's model. Lung microarrays and tissue proteins were measured in a subset of patients. No differences were found in age, physiologic impairment and bronchoalveolar lavage (BAL) cellular profile. There were more males (OR = 6.5; CI:1.4-29.5; p = 0.006) and smokers (OR = 3.04; CI:1.1-8.3; p = 0.04) in the rapid progressors group. Survival from the beginning of symptoms was significantly reduced in rapid progressors (HR = 9.0; CI:4.48-18.3; p<0.0001) and there was a tendency for decreased survival from the time of diagnosis (HR = 1.5; CI:0.81-2.87; p = 0.18). We identified 437 differentially expressed genes. Lungs of rapid progressors overexpressed genes involved in morphogenesis, oxidative stress, migration/proliferation, and genes from fibroblasts/smooth muscle cells. Upregulation of two of these genes, adenosine-2B receptor and prominin-1/CD133, was validated by immunohistochemistry and were expressed by alveolar epithelial cells. BAL from rapid progressors showed a >2-fold increase of active matrix metalloproteinase-9, and induced a higher fibroblast migration compared with slow progressors and controls [238+/-98% versus 123+/-29% (p<0.05) and 30+/-17% (p<0.01)]. CONCLUSIONS/SIGNIFICANCE: A subgroup of IPF patients, predominantly smoking males, display an accelerated clinical course and have a gene expression pattern that is different from those with slower progression and longer survival. These findings highlight the variability in the progression of IPF, and may explain, in part, the difficulty in obtaining significant and reproducible results in studies of therapeutic interventions in patients with IPF.

Local and circulating microchimerism is associated with hypersensitivity pneumonitis.

RATIONALE: Hypersensitivity pneumonitis (HP) is a lymphocytic alveolitis provoked by exposure to a variety of antigens. However, the disease occurs in only a subset of exposed individuals, suggesting that additional factors may be involved. Microchimerism has been implicated in the pathogenesis of autoimmune diseases, especially in those showing increased incidence after childbearing age. OBJECTIVES: To evaluate the presence of circulating and local microchimeric cells in female patients with HP. METHODS: Male microchimerism was examined in 103 patients with HP, 30 with idiopathic pulmonary fibrosis (IPF), and 43 healthy women. All of them had given birth to at least one son, with no twin siblings, blood transfusions, or transplants. Microchimerism was examined by dot blot hybridization (peripheral blood), and by fluorescence in situ hybridization in bronchoalveolar lavage cells and lungs. MEASUREMENTS AND MAIN RESULTS: Blood microchimerism was found in 33% of the patients with HP in comparison with 10% in those with IPF (p = 0.019) and 16% in healthy women (p = 0.045). Patients with HP with microchimerism showed a significant reduction of diffusing capacity of carbon monoxide (Dl(CO); 53.5 +/- 11.9% vs. 65.2 +/- 19.7%; p = 0.02) compared with patients with HP without microchimerism. In bronchoalveolar lavage cells, microchimerism was detected in 9 of 14 patients with HP compared with 2 of 10 patients with IPF (p = 0.047). Cell sorting revealed that microchimeric cells were either macrophages or CD4+ or CD8+ T cells. Male microchimeric cells were also found in the five HP lungs examined by fluorescence in situ hybridization. CONCLUSIONS: Our findings (1) demonstrate that patients with HP exhibit increased frequency of fetal microchimerism, (2) confirm the multilineage capacity of microchimeric cells, and (3) suggest that microchimeric cells may increase the severity of the disease.