Airway Biopsy Results From Patients With Suspected Granulomatosis With Polyangiitis (2005-2015): Clinicopathological Correlation and Proposal of an Algorithm to Improve Diagnosis.

OBJECTIVES: The aim of this study was to review the histologic diagnostic yield of airway biopsies with a suspected granulomatosis with polyangiitis (GPA) diagnosis at a single center devoted to respiratory diseases using previously published criteria. A secondary aim was to apply the algorithm proposed by the European Medicines Agency to determine whether more biopsies were confidently identified as having GPA diagnoses. METHODS: From a total of 132 airway biopsies (2005-2015), 50 were randomly selected for second review by an expert pathologist, and previously published criteria were applied. Thereafter, antineutrophil cytoplasm autoantibody testing results and the European Medicines Agency algorithm were applied. RESULTS: Repeat review and application of the published criteria resulted in an increase from 16 to 25 diagnoses of GPA. This increased to 35 of 50 when antineutrophil cytoplasm autoantibody results and the European Medicines Agency algorithm were applied. Interobserver correlation was 57.5% among pathologists (κ = 0.19), which was likely due to missing clinical information and inadequate tissue samples. Patients with generalized disease were 2.6 times more likely to obtain diagnostic GPA airway biopsy results than those with limited disease (airway only). CONCLUSIONS: An increase in the diagnostic yield of this malady could be attained by following an algorithm that incorporates carefully retrieved clinical, endoscopic, and serologic data, coupled with systematic histopathologic sample review.

Diagnostic discrepancy between bronchoalveolar lavage and transbronchial biopsy from bronchoscopies of HIV patients with pneumonia: toward an integral diagnosis.

BACKGROUND: The key diagnostic method for the evaluation of lung diseases associated with HIV infection is bronchoscopy, with bronchoalveolar lavage (BAL) being the most commonly used sampling technique. Transbronchial biopsy (TBB) is often complementary. SETTING: This is a retrospective cross-sectional study to determine the diagnostic usefulness of bronchoscopy with simultaneous samples obtained through BAL and TBB in HIV-infected patients with pneumonia at the National Institute of Respiratory Diseases Ismael Cosío Villegas. METHODS: In this cross-sectional study (January 2014-December 2015), the diagnostic yield of bronchoscopic samples from all HIV-positive patients with pneumonia aged >18 years, from procedures performed in the Interventional Pulmonology Unit, was analyzed and recorded in its database. The diagnostic yield concordance between BAL and TBB samples was evaluated by kappa index calculation. RESULTS: A total of 198 procedures on 189 HIV-infected patients with pneumonia were performed. A total of 167/189 (88.4%) patients were male, and the mean age was 34.7 years (SD ±9.0). Overall, the diagnostic yield for either technique was 87.9% (174/198), but it was higher for TBB, its yield being 78.8% (156/198). In contrast, that of BAL was 62.1% (123/198) (P=0.001). The overall diagnostic yield concordance between TBB and BAL was insignificant (k=0.213, P<0.001). It improved for fungal infections, pneumocystosis, and tuberculosis (k=0.417, 0.583, and 0.462, respectively, all P<0.001). CONCLUSION: Our results show that the simultaneous obtainment of BAL and TBB samples is useful and complementary in the diagnosis of infections and malignancies in HIV-infected patients. Additionally, they are safe procedures in this group of patients.

Biomarkers for Predicting Malignant Pleural Mesothelioma in a Mexican Population.

Background: Diagnosis of malignant pleural mesothelioma (MPM) remains a challenge, especially when resources in pathology are limited. The study aimed to evaluate cost-effective tumor markers to predict the probability of MPM in plasma samples in order to accelerate the diagnostic workup of the tissue of potential cases. Methods: We conducted a case-control study stratified by gender, which included 75 incident cases with MPM from three Mexican hospitals and 240 controls frequency-matched by age and year of blood drawing. Plasma samples were obtained to determine mesothelin, calretinin, and thrombomodulin using enzyme-linked immunosorbent assays (ELISAs). We estimated the performance of the markers based on the area under the curve (AUC) and predicted the probability of an MPM diagnosis of a potential case based on the marker concentrations. Results: Mesothelin and calretinin, but not thrombomodulin were significant predictors of a diagnosis of MPM with AUCs of 0.90 (95% CI: 0.85-0.95), 0.88 (95% CI: 0.82-0.94), and 0.51 (95% CI: 0.41-0.61) in males, respectively. For MPM diagnosis in men we estimated a true positive rate of 0.79 and a false positive rate of 0.11 for mesothelin. The corresponding figures for calretinin were 0.81 and 0.18, and for both markers combined 0.84 and 0.11, respectively. Conclusions: We developed prediction models based on plasma concentrations of mesothelin and calretinin to estimate the probability of an MPM diagnosis. Both markers showed a good performance and could be used to accelerate the diagnostic workup of tissue samples in Mexico.

Utility of Transbronchial Lung Cryobiopsy in Non-Interstitial Diseases.

BACKGROUND: Transbronchial lung cryobiopsy (TLCB), performed with a flexible cryoprobe, is an interventional pulmonology procedure that has proved its diagnostic value for interstitial pulmonary disease. However, it has not been explored extensively as a diagnostic tool for patients with non-interstitial lung pathology, including infectious and malignant diseases. OBJECTIVE: To evaluate the diagnostic yield and safety of an interventional pulmonology approach that integrates TLCB and bronchoalveolar lavage (BAL) for the diagnosis of non-interstitial pulmonary disease. METHODS: TLCB and BAL were performed under general anesthesia through the same bronchoscopic access on 103 adult patients (including immunocompromised HIV+ individuals) with clinical/radiological evidence of non-interstitial lung disease admitted to the Interventional Pulmonology Service between May 2015 and April 2016. Samples obtained were sent to pathology and microbiology laboratories for standard diagnostic analysis. RESULTS: Samples of TLCB allowed the diagnosis of 75.7% of patients, while 39.8% were diagnosed from BAL. The global diagnostic yield from the dual sampling was 92.2%. TLCB allowed the diagnosis of 94.7% of cancer cases and 60.0% of infectious cases, while BAL samples identified 77.5% of infectious cases and 21.2% of malignant lesions. The incidence of complications was 4.9% with full recovery in all cases. CONCLUSIONS: Simultaneous TLCB and BAL constitute a safe and useful diagnostic procedure for non-interstitial pulmonary disease, with a global diagnostic yield of 92.2%. Complementary advantages of samples obtained by each technique result in a robust diagnostic strategy for infectious and malignant disease in adults, including HIV+ individuals.

Usefulness of Endobronchial Ultrasound in Patients with Human Immunodeficiency Virus Infection and Mediastinal Lymphadenopathy.

BACKGROUND: There are few published studies about the usefulness of endobronchial ultrasound (EBUS) in patients infected with human immunodeficiency virus (HIV). The clinical spectrum of likely diseases in this population is varied and differs from patients not infected with HIV. OBJECTIVE: The aim of this study was to measure the usefulness of EBUS-guided transbronchial needle aspiration (EBUS-TBNA) in HIV-infected patients with mediastinal lymphadenopathy. MATERIALS AND METHODS: We conducted an observational, cross-sectional, retrospective, descriptive study on patients with HIV infection and mediastinal lymphadenopathy who underwent EBUS-TBNA between September 2014 and April 2016. The patients' final diagnosis, regardless of the sample from which it was obtained, was considered the positive gold standard, and the absence of diagnosis was the negative. The study measured diagnostic accuracy of bronchoalveolar lavage (BAL), transbronchial biopsy (TBB), and EBUS-TBNA. RESULTS: A total of 43 procedures were performed; 79.1% (34/43) of the patients were male, and the median age was 35 years (range, 22-66). The overall diagnostic yield including all types of samples was 90.7% (39/43); the yield of BAL was 50% (21), that of TBB 61.9% (26), and that of EBUS-TBNA was 60.5% (26). The combined yield of BAL with TBB was 69.8% (30); the yield of BAL with EBUS-TBNA was 86% (37) and that of TBB with EBUS-TBNA was 88.4% (38). The highest diagnostic accuracy was 97.7% for the combination of TBB and EBUS-TBNA. CONCLUSIONS: The most common infectious diagnoses were tuberculosis, with a higher diagnostic accuracy using EBUS-TBNA than BAL. With malignancies, both EBUS-TBNA and TBB were useful. EBUS-TBNA is a minimally invasive diagnostic tool that should be considered in these patients.

Hipertensión arterial pulmonar asociada a virus de la inmunodeficiencia humana / Pulmonary arterial hypertension associated to human immunodeficiency virus

A partir de la presentación del tratamiento antirretroviral altamente efectivo, la esperanza de vida de los pacientes con virus de la inmunodeficiencia humana ha aumentado de manera significativa. En la actualidad, las causas de muerte son las complicaciones no infecciosas. Entre ellas, la hipertensión arterial pulmonar tiene una importancia especial. Es relevante la detección temprana para establecer la terapéutica con el objetivo de prevenir el desenlace fatal a futuro.

From the advent of the highly effective antiretroviral treatment, the life expectancy of patients with human immunodeficiency virus has increased significantly. At present, the causes of death are non-infectious complications. Between them, the pulmonary arterial hypertension has a special importance. It is important early detection to establish the therapeutic, with the objective of preventing a fatal outcome to future.

Overexpression of Endothelin-1 Leads to More Severe Pulmonary Complex Vascular Lesions Associated with the Human Immunodeficiency Virus.

BACKGROUND AND AIMS: Despite increase in survival of HIV patients due to highly active antiretroviral therapy (HAART), non-infectious complications are still prevalent such as presentation of lung vasculopathy, even in asymptomatic patients. Endothelin-1 (ET-1) is a potent vasoconstrictor that causes pulmonary vasculopathy. Participation of this protein in the pulmonary circulation in HIV patients has not been elucidated. In this work we studied the presence and expression of ET-1 in pulmonary complex vascular lesions associated with human immunodeficiency virus (PCVL/HIV). METHODS: We used immunohistochemistry and immunochemiluminescence (imagej) to determine the different degrees of expression of ET-1 in PCVL/HIV in comparison with non-PCVL/HIV. Reagents used were anti-endothelin-1 and an automated system. All data are presented as mean and standard deviation (SD). Differences were analyzed with one-way ANOVA; p < 0.05 was accepted as statistically significant. RESULTS: Lung tissues from 56 patients who died from complications of HIV pulmonary infection and with PCVL were studied. Histological evidence of pulmonary vasculopathy was shown as different types (proliferative, obliterative and plexiform). A statistically significant increase in ET-1 expression was observed in all PCVL/HIV tissue samples and is associated directly with different grades of severity of endothelial dysfunction. CONCLUSIONS: ET-1 has a relevant role in the pathogenesis of pulmonary vasculopathy in acquired immunodeficiency syndrome (AIDS) patients. It is necessary to determine in the future the participation of ET-1 and other mechanisms involved in PCVL/HIV.

[Pulmonary arterial hypertension associated to human immunodeficiency virus]. / Hipertensión arterial pulmonar asociada a virus de la inmunodeficiencia humana.

From the advent of the highly effective antiretroviral treatment, the life expectancy of patients with human immunodeficiency virus has increased significantly. At present, the causes of death are non-infectious complications. Between them, the pulmonary arterial hypertension has a special importance. It is important early detection to establish the therapeutic, with the objective of preventing a fatal outcome to future.

Relationship of dendritic cell density, HMGB1 expression, and tumor-infiltrating lymphocytes in non-small cell lung carcinomas.

Lung cancer is the leading cause of cancer death worldwide and non-small cell lung carcinoma (NSCLC) is the most common type of lung carcinomas. In adenocarcinomas, the most frequent histologic type of NSCLC, dendritic cells (DCs) are localized in close contact with tumor cells, and tumor-infiltrating lymphocytes (TILs) are observed in the peritumoral zones. In NSCLC, no studies investigating the density of intratumoral DCs and their impact on the density of TILs have been performed. In addition, the role of the alarmin high-mobility group box1 (HMGB1) in intratumoral DCs recruitment has not been analyzed. In the present study, a total of 82 cases of advanced stages of NSCLC were included. Tissue samples were obtained from biopsies and autopsies. DCs in biopsies or combinations of DCs and NK cells, CD3 T lymphocytes, or CD8 T lymphocytes from autopsy specimens were quantified in high power fields. Also, distribution of HMGB1 in tumor cells was detected. In lung adenocarcinomas, irrespective of subclassification, high densities of infiltrating DCs directly associated to high densities of peritumoral TILs. A 2.5-fold increase in TILs was found in specimens with high densities of infiltrating DCs compared with TILs from adenocarcinomas with low densities of infiltrating DCs. High densities of infiltrating DCs were associated with lung adenocarcinomas expressing cytoplasmic or nuclear-cytoplasmic HMGB1. Our results suggest that in adenocarcinoma patients, HMGB1 produced by tumor cells recruits DCs, which associate to an increase of TILs. Encouraging tumor-DCs-T lymphocytes interactions should improve the quality of life and survival of NSCLC patients.

Bronquiolitis folicular linfoidea posterior a infección por adenovirus / Lymphoid follicular bronchiolitis post-adenovirus infection

Introducción: La bronquiolitis folicular es una lesión pulmonar rara. Consiste en la presencia de abundantes folículos linfoides hiperplásicos con centros germinales reactivos, distribuidos a lo largo de los bronquiolos y compresión de la vía aérea pequeña intratorácica. Existen pocos informes de bronquiolitis folicular en la población pediátrica. Los datos que se conocen de esta enfermedad para esta población han sido extrapolados de estudios realizados en pacientes adultos. El tratamiento se basa en esteroides y, en general, el pronóstico es bueno. Caso clínico: Describimos el caso de una niña de 5 años de edad, con antecedente de neumonía grave a los 3 años, con adenovirus en el panel viral. Posteriormente, presentó sibilancias recurrentes y tos crónica. En la tomografía axial de tórax de alta resolución se observó un patrón en vidrio despulido, bronquiectasias, atrapamiento aéreo y atelectasia basal derecha, por lo que se realizó una biopsia de pulmón, la cual mostró bronquiolitis folicular linfoidea. Conclusiones: La bronquiolitis folicular linfoidea es una entidad poco frecuente, que requiere ser sospechada en pacientes con antecedentes de infección por adenovirus. Presenta cuadro clínico de hiperreactividad bronquial y alteraciones radiológicas con patrón en vidrio despulido, bronquiectasias y atrapamiento aéreo. La biopsia pulmonar por toracotomía es la clave para establecer el diagnóstico y el pronóstico.

Background: Follicular bronchiolitis, a rare lung injury, is characterized by abundant hyperplastic lymphoid follicles with reactive germinal centers distributed along the bronchioles with compression of the lower intrathoracic airway. In the literature there are few reports of follicular bronchiolitis in the pediatric population. Data obtained from this disease have been extracted from studies in adult patients. Treatment is based on steroids with a good prognosis. Case report: We describe the case of a 5-year-old female with a history of severe pneumonia at 3 years of age, isolating adenovirus in the viral panel. Subsequently, she had recurrent wheezing and chronic cough. High resolution thoracic computed tomography (CT) showed ground glass pattern, bronchiectasis, air trapping and right basal atelectasis. Lung biopsy was performed and reported lymphoid follicular bronchiolitis. Conclusions: Lymphoid follicular bronchiolitis is a rare entity that requires a high level of suspicion in patients with a history of adenovirus infection, clinical symptoms of bronchial hyperreactivity and radiological changes in ground glass pattern, bronchiectasis and air trapping. Lung biopsy by thoracotomy is the key for diagnosis and prognosis.

Asbestosis y mesotelioma pleural maligno / Asbestosis and malignant pleural mesothelioma

Trabajo de revisión sobre los aspectos clínicos de la asbestosis y el mesotelioma pleural en el contexto de una posible epidemia de mesotelioma pleural en los próximos 50 años. Estas enfermedades tienen como agente etiológico común a las fibras de asbesto. Se describe la historia del asbesto desde que los cipriotas lo usaron para hacer vestidos hace 5,000 años hasta su participación industrial en la década de 1870 y su prohibición al descubrirlo como causante de la asbestosis, el cáncer pulmonar y el mesotelioma pleural. Se describen las diferencias de la estructura, la química y las propiedades biológicas de los asbestos. En México se utiliza el crisotilo en un 90% para fabricar productos de fibrocemento destinados a la construcción y componentes destinados a piezas de rozamiento, de calefacción y textiles. Se analizan los aspectos clínicos, radiológicos, histológicos y funcionales de la asbestosis y el mesotelioma pleural, así como su tratamiento y prevención. Se refieren los diagnósticos diferenciales de estas enfermedades con otros padecimientos respiratorios. El periodo de latencia tanto de la asbestosis como del mesotelioma pleural varía de 20 a 40 años, por lo cual nos enfrentamos en México a una epidemia de mesotelioma pleural en los próximos 50 años. La única prevención efectiva de la asbestosis y el mesotelioma pleural maligno es la prohibición de las industrias que utilizan el asbesto.

Review article considering clinical issues of asbestosis and pleural mesothelioma in the context of a potential pleural mesothelioma outbreak in Mexico in the next 50 years. The common etiologic agent of asbestosis and pleural mesothelioma are asbestos fibers. The history of asbestos dates from 5 000 years ago when Cypriots used it to make their garments, until its industrial usage in the 1870s and its prohibition in some countries after finding its direct relationship with asbestosis, lung cancer, and pleural mesothelioma. The main structural characteristics, chemical profile, and biological properties of asbestos are described here. In Mexico, chrysotile, or white asbestos, is used in 90% of the production of fibercements for the building industry, as well as in components of friction pieces, heating and textile industries. This article analyses the clinical, radiological, histological, and functional issues of asbestosis and pleural mesothelioma; as well as their treatment and prevention. The differential diagnoses for this disease in relation to other respiratory illnesses are described. Since the latent period for both asbestosis and pleural mesothelioma is between 20 and 40 years, an outbreak of pleural mesothelioma can be expected in Mexico in the next 50 years. The only effective way to prevent asbestosis and malignant pleural mesothelioma is banning asbestos-related industries.

In situ molecular identification of the influenza A (H1N1) 2009 Neuraminidase in patients with severe and fatal infections during a pandemic in Mexico City.

BACKGROUND: In April 2009, public health surveillance detected an increased number of influenza-like illnesses in Mexico City's hospitals. The etiological agent was subsequently determined to be a spread of a worldwide novel influenza A (H1N1) triple reassortant. The purpose of the present study was to demonstrate that molecular detection of pandemic influenza A (H1N1) 2009 strains is possible in archival material such as paraffin-embedded lung samples. METHODS: In order to detect A (H1N1) virus sequences in archived biological samples, eight paraffin-embedded lung samples from patients who died of pneumonia and respiratory failure were tested for influenza A (H1N1) Neuraminidase (NA) RNA using in situ RT-PCR. RESULTS: We detected NA transcripts in 100% of the previously diagnosed A (H1N1)-positive samples as a cytoplasmic signal. No expression was detected by in situ RT-PCR in two Influenza-like Illness A (H1N1)-negative patients using standard protocols nor in a non-related cervical cell line. In situ relative transcription levels correlated with those obtained when in vitro RT-PCR assays were performed. Partial sequences of the NA gene from A (H1N1)-positive patients were obtained by the in situ RT-PCR-sequencing method. Sequence analysis showed 98% similarity with influenza viruses reported previously in other places. CONCLUSIONS: We have successfully amplified specific influenza A (H1N1) NA sequences using stored clinical material; results suggest that this strategy could be useful when clinical RNA samples are quantity limited, or when poor quality is obtained. Here, we provide a very sensitive method that specifically detects the neuraminidase viral RNA in lung samples from patients who died from pneumonia caused by Influenza A (H1N1) outbreak in Mexico City.

Elemental composition of ferruginous bodies and occupational categories: analyses and case studies in Mexico.

Inorganic fibers form part of the complex mixture of environmental pollutants in Mexico City and in general locations. Upon entering the lungs, some of those fibers are transformed into ferruginous bodies (FB) that can be used as biological markers of exposure to fibers. Hence, the objectives of this study were, first, to describe the most frequent types of FB found in the lungs, and second, to determine the elemental composition of the cores of some of those FB. A total of 264 lung samples collected from autopsies performed at the National Institutes of Health in Mexico City were analyzed. The FB were obtained by digesting the samples in commercial bleach and all the FB were then collected in 0.45 µm Millipore membranes. All the FB obtained from each case were counted directly under bright field microscopy, and then classified by morphology. Results showed from 14.5 FB/g in Category 1 (housewives), to 50.2 FB/g for samples from Category 5 (construction workers), and 152 FB/g for Category 6 (miners). Significant differences were found upon comparing samples from Categories 5/6 to Category 1 (p < 0.05). Type 1 FB were the most frequent ones seen in the samples from Categories 1 to 5. Elemental analyses of the cores of several FB found aluminosilicates, fiberglass, tremolite and amosite asbestos among others. In conclusion, residents of Mexico show exposures to a variety of fibers that induce FB including asbestos.

Mucormicosis pulmonar diseminada: informe de dos casos / Disseminated pulmonary mucormycosis: report of two cases

La mucormicosis es causada por hongos de la clase de los Zigomicetos, orden de los Mucorales, es una micosis oportunista. Los factores de riesgo son diabetes mellitus, neoplasias principalmente hematológicas, trasplante de órganos, uso de medicamentos citotóxicos e inmunosupresores. La localización pulmonar ocupa el segundo lugar en frecuencia después de la rinocerebral.Se informan dos casos: Caso 1. Hombre de 57 años de edad con diabetes mellitus de 10 años de evolución, con neumonía necrotizante, falleció y en la autopsia se encontró el lóbulo superior derecho con extensa necrosis, colonias de bacterias Gram positivas e hifas anchas no septadas que se identificaron como de Mucorales. Caso 2. Hombre de 43 años de edad diabético, cuadro neumónico con opacidad del hemitórax derecho, la gammagrafía ventilatoria-perfusoria mostró destrucción completa del pulmón derecho. Se hizo neumonectomía, el pulmón mostró lesiones semejantes al caso 1. No recibió tratamiento específico, falleció y en la autopsia no se encontraron lesiones micóticas en el pulmón izquierdo, hubo diseminación a bazo, riñones y tiroides.

Efecto citostática de la cumarina y la 7-hidroxicumarina en tres líneas celulares de adenocarcinoma pulmonar humano / Cystostatic effect of coumarin and 7-hidroxicoumarin on three human lung adenocarcinoma cell lines

Introducción: Las cumarinas son productos naturales ampliamente distribuidos en la naturaleza. En el humano el principal metabolito de la cumarina es la 7-hidroxicumarina, el cual es la forma activa del compuesto. Estos y otros compuestos relacionados presentan actividades biológicas de importancia terapéutica, entre las cuales destaca su efecto antitumoral. Objetivo: Evaluar la actividad antiproliferativa de estos dos compuestos sobre tres líneas celulares de cáncer y pulmón. Material y métodos: Se emplearon tres líneas celulares de adenocarcinomas de pulmón (SK-LU-1, 1.3.15 y 3A5A) para determinar el efecto de los fármacos utilizando experimentos de exposición única a concentraciones de 10 µg/mL a 80 µg/mL. El efecto sobre la proliferación celular se evaluó mediante ensayos de incorporación de timidina tritiada al cabo de 24 h y 48 h de exposición a los fármacos. Resultados: Se presentó un efecto inhibitorio de ambos compuestos sobre cada una de las líneas celulares estudiadas, presentando mayor actividad la 7-hidroxicumarina. La sensibilidad entre las distintas líneas celulares fue dependiente de la concentración y el tiempo de exposición. En este sentido las líneas 1.3.15 y 3A5A que fueron recientemente establecidas a partir de pacientes del INER y caracterizadas morfo e inmunofenotípicamente, presentaron mayor sensibilidad al efecto inhibitorio tanto a 24 H como a 48 H. Conclusiones: Estos resultados indican que las células tumorales de pulmón son blanco del efecto antiproliferativo de estos compuestos naturales; sin embargo, es necesario realizar un mayor número de protocolos experimentales básicos y clínicos que confirmen la utilizaciòn de la 7-hidroxicumarina sola o en combinación con la terapia que se emplea en el tratamiento del cáncer pulmonar