RESUMEN
OBJECTIVE: This study was undertaken to describe the spectrum of lung computed-tomography (CT) findings in children with pulmonary Langerhans cell histiocytosis (PLCH) and to evaluate for this population the CT-scan nodule and cyst scores proposed by adult pulmonologists at diagnosis and during follow-up. METHODS: Among 175 children with PLCH identified in the French national population-based Langerhans cell histiocytosis cohort, 60 were retrospectively selected by the availability of CT for a central review by three pediatric radiologists. These 60 patients are representative of childhood PLCH for almost all clinical aspects, except a lower percentage of risk organ involvement (38% vs 54%; P = 0.05). RESULTS: The 60 children's chest CT scans (n = 218) were reviewed. At diagnosis, 63% of them had nodules, 53% had cysts, and 29% had both. The percentages of patients with nodules or cysts increased from diagnosis to peak disease activity, respectively, from 63% to 73% and from 53% to 66%. The costophrenic angle was involved in 71%. Patients with pneumothorax (25%) had a higher median cyst score. Alveolar consolidation was observed in 34%. Patients with low CT-scan nodule and cyst scores had no long-term pulmonary sequelae. CONCLUSIONS: Well-known characteristics of adult PLCH (nodules and cysts) were observed in children. The chest CT scores proposed by adult pulmonologists could easily be applied to childhood PLCH. Lesions in children, unlike those in adults, are frequently located near the costophrenic angles. Alveolar consolidation might be considered an atypical feature of childhood PLCH.
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Quistes/diagnóstico , Histiocitosis de Células de Langerhans/diagnóstico , Enfermedades Pulmonares/diagnóstico , Radiografía Torácica/métodos , Tomografía Computarizada por Rayos X/métodos , Niño , Preescolar , Quistes/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Histiocitosis de Células de Langerhans/diagnóstico por imagen , Humanos , Lactante , Enfermedades Pulmonares/diagnóstico por imagen , Masculino , Pronóstico , Estudios RetrospectivosRESUMEN
Lower-respiratory-tract (LRT) amyloidosis has rarely been investigated. Our study presents characteristics, outcomes and survival of LRT amyloidosis. This multicenter retrospective study, from 1995 to 2017, included 73 patients with amyloidosis and LRT involvement. Respiratory patterns were: tracheobronchial (n = 17), nodular (n = 10), interstitial (n = 14) or composite (several respiratory involvements, n = 32). Interstitial and composite patterns were associated with multi-organ amyloidosis (n = 37, 80%) while tracheobronchial and nodular patterns were associated with organ-limited amyloidosis (n = 21, 78%). Amyloid light chain (AL) amyloidosis was diagnosed in 43 patients (59%), mainly of lambda type (n = 33, 77%). Smokers' proportion was higher in tracheobronchial (71%) and nodular (90%) patterns than in interstitial (14%) and composite (34%) patterns. The B-cell neoplasms involved 15 patients (21%), solid neoplasms 8 (11%), connective tissue diseases 8 (11%) and multiple myeloma 6 (8%). The B-cell and solid neoplasms were most prevalent in nodular pattern. Median follow-up was 4.4 years (2.2-8.9). Twenty-four patients died, mostly from respiratory infection. Survival at 1, 5, 10 years was respectively 88%, 70% and 54% for multi-organ amyloidosis, 96%, 89% and 69% for organ-limited amyloidosis (P = .125). Tracheobronchial and nodular patterns survival was better than in other respiratory patterns (P = .039). Death risk factors (multivariate analysis) were: cardiac localization (hazard-ratio [HR] 4.3 [95% confidence interval 1.6-11.5]; P = .004), age (HR 2.1 [1.2-3.7]; P = .008) and dyspnea at diagnosis (HR 4.0 [1.3-12.3]; P = .014). Various LRT amyloidosis patterns depend on smoking habits, organ-limited or multi-organ extension and comorbidities. They are associated with a different survival, which is also predicted by age, cardiac localization and dyspnea at presentation.
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Amiloidosis/epidemiología , Sistema Respiratorio/patología , Adulto , Anciano , Proteínas Amiloidogénicas/análisis , Amiloidosis/diagnóstico por imagen , Amiloidosis/patología , Amiloidosis/terapia , Comorbilidad , Femenino , Estudios de Seguimiento , Volumen Espiratorio Forzado , Francia/epidemiología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias/epidemiología , Especificidad de Órganos , Tomografía de Emisión de Positrones , Pronóstico , Modelos de Riesgos Proporcionales , Sistema Respiratorio/diagnóstico por imagen , Estudios Retrospectivos , Fumar/epidemiología , Tomografía Computarizada por Rayos XRESUMEN
AIMS: Non-infectious pulmonary complications (NIPCs) occur frequently following allogeneic haematopoietic stem cell transplantation (HSCT). As there is no consensus on the description of the related pulmonary pathological lesions, pathologist reports and clinical conclusions are largely inconsistent in routine practice. The aim of our study was to provide an accurate overview of post-allogeneic HSCT NIPCs from a large number of lung biopsies. METHODS AND RESULTS: We reviewed 61 lung biopsies in patients with an NIPC, including 51 surgical lung biopsies, four post-mortem biopsies and six lung explants. We found both bronchiolar (n = 59) and alveolar/interstitial pathologies (n = 27). We describe two types of bronchiolar lesions: bronchiolectasies (n = 37) and fibrous and cellular lesions with luminal narrowing (n = 43). We found a wide spectrum of airway/interstitial pathologies that were labelled using the terminology of the 2013 American Thoracic Society and European Respiratory Society (ATS/ERS) classification of idiopathic interstitial pneumonias (IIPs), including the following: organising pneumonia (OP, n = 8), non-specific interstitial pneumonia (NSIP, n = 9), diffuse alveolar damage (DAD, n = 6), lymphoid interstitial pneumonia (LIP, n = 1) and pleuroparenchymal fibroelastosis (PPFE, n = 2), as well as one instance of associated PPFE and NSIP. CONCLUSIONS: Interstitial pathology was associated with bronchiolar lesions in 41% of the cases reviewed (n = 25). Lung airway and interstitial inflammation was still present in lung explants from patients who underwent lung transplantation for post-allogeneic HSCT end-stage respiratory insufficiency. Herein, we describe a wide spectrum of pathological lung lesions encountered in post-allogeneic HSCT NIPCs.
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Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/patología , Pulmón/patología , Complicaciones Posoperatorias/patología , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
The objective of the study was to estimate the prevalence and incidence of interstitial lung diseases (ILDs) in Seine-Saint-Denis, a multi-ethnic county of Greater Paris, France.Patients with ILDs were identified between January and December 2012 by using several sources; all potentially involved medical specialists from public and private hospitals, community-based pulmonologists and general practitioners, and the Social Security system. Diagnoses were validated centrally by an expert multidisciplinary discussion.1170 ILD cases were reported (crude overall prevalence: 97.9/105 and incidence: 19.4/105/year). In the 848 reviewed cases, the most prevalent diagnoses were sarcoidosis (42.6%), connective tissue diseases associated ILDs (CTDs-ILDs) (16%), idiopathic pulmonary fibrosis (IPF) (11.6%), and occupational ILDs (5.0%), which corresponded to a crude prevalence of 30.2/105 for sarcoidosis, 12.1/105 for CTDs-ILDs and 8.2/105 for IPF. The prevalence of fibrotic idiopathic interstitial pneumonias, merging IPF, nonspecific interstitial pneumonia and cases registered with code J84.1 was 16.34/105 An adjusted multinomial model demonstrated an increased risk of sarcoidosis in North Africans and Afro-Caribbeans and of CTDs-ILDs in Afro-Caribbeans, compared to that in Europeans.This study, with a comprehensive recruitment and stringent diagnostic criteria, emphasises the importance of secondary ILDs, particularly CTDs-ILDs and the relatively low prevalence of IPF, and confirms that sarcoidosis is a rare disease in France.
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Enfermedades del Tejido Conjuntivo/epidemiología , Fibrosis Pulmonar Idiopática/epidemiología , Sarcoidosis Pulmonar/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Etnicidad , Femenino , Humanos , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Paris/epidemiología , Prevalencia , Distribución por Sexo , Adulto JovenRESUMEN
AIMS: The association between lung cancer and idiopathic pulmonary fibrosis (IPF) is well known, but the significance of this association is poorly understood. Bronchiolar honeycomb cysts have been proposed as possible precursors for the development of carcinoma, but limited evidence in support of this hypothesis is available. The aim of this study was to investigate this hypothesis analysing a series of carcinomas arising in IPF by immunohistochemistry. METHODS AND RESULTS: Thirty-three lung carcinomas arising in patients with IPF were analysed with a panel of immunohistochemical markers. The antibodies included those against pneumocyte markers [thyroid transcription factor 1 (TTF1), napsin-A, and surfactant protein A], the goblet cell marker mucin 5AC, markers of basal/squamous cell differentiation [cytokeratin (CK) 5/6 and ΔN-p63], and markers related to enteric differentiation (CDX2, mucin 2, CK20, and villin). A series of 100 consecutive lung adenocarcinomas arising in smokers without IPF were investigated as controls. All carcinomas arising in IPF patients were peripherally located on imaging analysis. The diagnoses were: eight squamous cell carcinomas, 20 adenocarcinomas, three small-cell carcinomas (including one composite small-cell carcinoma and adenocarcinoma), and two large-cell carcinomas. Among adenocarcinomas, a 'pneumocyte' profile (TTF1/napsin-A/SPA1-triple-positive) was observed in seven of 20 (35% versus 84% in non-IPF controls, P = 0.0001). The remaining 13 adenocarcinomas (65%) showed rare histotypes: four invasive mucinous adenocarcinomas (20% in IPF patients versus 1% in non-IPF controls, P = 0.002), seven tumours (35%) that were characterized by variable expression of markers of enteric differentiation, and two tumours (10%) that showed a peculiar basaloid component. CONCLUSIONS: The immunohistochemical characterization of carcinomas arising in IPF patients shows striking divergence from that in non-IPF smokers. The prevalence of rare entities showing bronchiole-related markers is in line with the hypothesis that these tumours arise from transformed small airways in honeycomb lung areas where abnormal bronchiolar proliferation takes place.
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Carcinoma/patología , Fibrosis Pulmonar Idiopática/complicaciones , Neoplasias Pulmonares/patología , Carcinoma/etiología , Humanos , Neoplasias Pulmonares/etiologíaRESUMEN
In common variable immunodeficiency, lung manifestations are related to different mechanisms: recurrent pneumonias due to encapsulated bacteria responsible for diffuse bronchiectasis, diffuse infiltrative pneumonia with various patterns, and lymphomas, mostly B cell extranodal non-Hodgkin type. The diagnosis relies on significant serum Ig deficiency and the exclusion of any primary or secondary cause. Histopathology may be needed. Immunoglobulin (IgG) replacement is crucial to prevent infections and bronchiectasis. IgG4-related respiratory disease, often associated with extrapulmonary localizations, presents with solitary nodules or masses, diffuse interstitial lung diseases, bronchiolitis, lymphadenopathy, and pleural or pericardial involvement. Diagnosis relies on international criteria including serum IgG4 dosage and significantly increased IgG4/IgG plasma cells ratio in pathologically suggestive biopsy. Respiratory amyloidosis presents with tracheobronchial, nodular, and cystic or diffuse interstitial lung infiltration. Usually of AL (amyloid light chain) subtype, it may be localized or systemic, primary or secondary to a lymphoproliferative process. Very rare other diseases due to nonamyloid IgG deposits are described. Among the various lung manifestations of dysregulated states of humoral immunity, this article covers only those associated with the common variable immunodeficiency, IgG4-related disease, amyloidosis, and pulmonary light-chain deposition disease. Autoimmune connective-vascular tissue diseases or lymphoproliferative disorders are addressed in other chapters of this issue.
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Amiloidosis/complicaciones , Inmunodeficiencia Variable Común/complicaciones , Enfermedades Pulmonares/etiología , Pulmón/inmunología , Humanos , Inmunidad HumoralAsunto(s)
Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/fisiopatología , Neoplasias Pulmonares/cirugía , Melaninas , Neoplasias de Células Epitelioides Perivasculares/diagnóstico , Neoplasias de Células Epitelioides Perivasculares/fisiopatología , Neoplasias de Células Epitelioides Perivasculares/cirugía , Femenino , Humanos , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Idiopathic, nonspecific interstitial pneumonia (NSIP) is most often associated with various clinical disorders, including connective tissue diseases (CTDs) and chronic hypersensitivity pneumonitis (cHP). Emerging evidence also suggests that "idiopathic" NSIP may be the lung manifestation of undifferentiated CTD (UCTD). However, whether or not NSIP outcome is influenced by the underlying cause remains uncertain. This retrospective study included 127 biopsy-proven NSIP patients (65 women, mean ± sd age 55 ± 12 years). Survivals were estimated using a Kaplan-Meier curve and compared using the log-rank test. Multivariate analyses were based on a Cox model. 15 (11.8%) patients had cHP, 29 (22.8%) had CTD, 32 (25.2%) satisfied the Kinder criteria for UCTD and 51 (40.1%) had idiopathic NSIP. At the end of follow-up (mean ± sd 64 ± 54 months), a difference in survival was observed between aetiological groups (p=0.002). Survival was better for UCTD than for idiopathic NSIP (p=0.020) and similar to that observed for CTD. cHP survival tended to be poorer than that of idiopathic NSIP (p=0.087) and was an independent predictor of mortality (hazard ratio 2.17, 95% CI 1.05-4.47; p=0.035). NSIP outcome is influenced by its cause. cHP exhibits the highest mortality. UCTD does not differ from CTD supporting the concept of autoimmune NSIP, with a prognosis that is better than that of idiopathic NSIP.
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Alveolitis Alérgica Extrínseca , Enfermedades del Tejido Conjuntivo , Neumonías Intersticiales Idiopáticas , Pulmón , Adulto , Anciano , Alveolitis Alérgica Extrínseca/complicaciones , Alveolitis Alérgica Extrínseca/diagnóstico , Alveolitis Alérgica Extrínseca/inmunología , Autoanticuerpos/sangre , Biopsia , Causas de Muerte , Enfermedades del Tejido Conjuntivo/complicaciones , Enfermedades del Tejido Conjuntivo/diagnóstico , Enfermedades del Tejido Conjuntivo/inmunología , Diagnóstico Diferencial , Femenino , Francia/epidemiología , Humanos , Neumonías Intersticiales Idiopáticas/diagnóstico , Neumonías Intersticiales Idiopáticas/etiología , Neumonías Intersticiales Idiopáticas/inmunología , Neumonías Intersticiales Idiopáticas/mortalidad , Estimación de Kaplan-Meier , Pulmón/diagnóstico por imagen , Pulmón/patología , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Pronóstico , Modelos de Riesgos Proporcionales , Pruebas de Función Respiratoria/métodos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodosRESUMEN
The 1930 International Labour Office Conference on silicosis in Johannesburg was a turning point in the history of silicosis and in the recognition of the associated pathologic patterns. Since 1930, pneumoconioses such as silicosis have become much rarer in developed countries and can now be diagnosed at an early stage based on clinical and radiologic criteria. However, in spite of these advances, pathologists must remember to look for silica in tissues, particularly when clinical and radiologic findings are more uncertain. Furthermore, nowadays pathologists essentially observe silicotic lesions as incidental findings adjacent to lung cancers. In addition to identifying the characteristic lesions, pathologists must also try to identify their causative agent, in the case of crystalline silica firstly by using polarized light examination, followed as appropriate by more sophisticated devices. Finally, pathologists and clinicians must always keep in mind the various implications of exposure to silica compounds in a wide range of diseases.
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Pulmón/patología , Patología/historia , Dióxido de Silicio , Silicosis/historia , Líquido del Lavado Bronquioalveolar , Broncoscopía , Congresos como Asunto , Diagnóstico Diferencial , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Neoplasias Pulmonares/patología , Microscopía de Polarización , Neumoconiosis/historia , Neumoconiosis/patología , Silicosis/patología , Silicotuberculosis/historia , Silicotuberculosis/patología , Tuberculosis/historia , Tuberculosis/patologíaRESUMEN
Histiocytoses are rare disorders of unknown origin with highly heterogeneous prognosis. BRAF mutations have been observed in Langerhans cell histiocytosis (LCH). We investigated the frequency of BRAF mutations in several types of histiocytoses. Histology from 127 patients with histiocytoses were reviewed. Detection of BRAF(V600) mutations was performed by pyrosequencing of DNA extracted from paraffin embedded samples. Diagnoses of Erdheim-Chester disease (ECD), LCH, Rosai-Dorfman disease, juvenile xanthogranuloma, histiocytic sarcoma, xanthoma disseminatum, interdigitating dendritic cell sarcoma, and necrobiotic xanthogranuloma were performed in 46, 39, 23, 12, 3, 2, 1, and 1 patients, respectively. BRAF status was obtained in 93 cases. BRAF(V600E) mutations were detected in 13 of 24 (54%) ECD, 11 of 29 (38%) LCH, and none of the other histiocytoses. Four patients with ECD died of disease. The high frequency of BRAF(V600E) in LCH and ECD suggests a common origin of these diseases. Treatment with vemurafenib should be investigated in patients with malignant BRAF(V600E) histiocytosis.
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Enfermedad de Erdheim-Chester/epidemiología , Histiocitosis de Células no Langerhans/clasificación , Histiocitosis de Células no Langerhans/epidemiología , Mutación/genética , Proteínas Proto-Oncogénicas B-raf/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Erdheim-Chester/genética , Femenino , Estudios de Seguimiento , Francia/epidemiología , Histiocitosis de Células no Langerhans/genética , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Pronóstico , Estudios Prospectivos , Adulto JovenRESUMEN
AIMS: Although histological non-specific interstitial pneumonia (NSIP) is concisely defined, overlap with other patterns is described. While most frequently idiopathic, NSIP is seen in various clinical contexts such as connective tissue diseases (CTDs) and chronic hypersensitivity pneumonitis (cHP). This study was designed to determine if NSIP could be separated into subgroups based on minor histological features and to correlate these subgroups with clinical associations and survival. METHODS AND RESULTS: One hundred and thirty-six patients with biopsy-proven NSIP were included [clinical diagnosis: CTDs (23%), cHP (12%), idiopathic (65%)]. In addition to the agreed NSIP criteria, seven subgroups were identified: essential NSIP and six overlap subgroups according to superimposed minor histological features. Interobserver concordance resulted in the following consensus: essential NSIP (36%), usual interstitial pneumonia (UIP) overlap (26%), cHP overlap (10%), organizing pneumonia (OP) overlap (6%), organizing diffuse alveolar damage (DAD) overlap (10%), desquamative interstitial pneumonia overlap (7%) and lymphoid interstitial pneumonia overlap (2%). OP overlap was associated with CTDs (P = 0.04) and cHP overlap with a cHP clinical diagnosis (P = 0.02). Survival was different between subgroups (P = 0.0002). Organizing DAD overlap exhibited poorer survival at 5 years (32%), followed by UIP overlap (57%). Independent predictors of mortality were organizing DAD overlap (HR = 4.99, 95% CI = 2.15-11.58, P = 0.0002), UIP overlap (HR = 2.11, 95% CI = 1.12-3.99, P = 0.02) and a clinical diagnosis of cHP (HR = 2.17, 95% CI = 1.05-4.47, P = 0.035). CONCLUSIONS: Non-specific interstitial pneumonia subdivision into pathological subgroups is clinically relevant from a prognostic and causal perspective.
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Enfermedades Pulmonares Intersticiales/clasificación , Enfermedades Pulmonares Intersticiales/patología , Adulto , Anciano , Femenino , Humanos , Inflamación/patología , Enfermedades Pulmonares Intersticiales/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Alveolos Pulmonares/patología , Fibrosis Pulmonar/patologíaAsunto(s)
Biomarcadores , Análisis Mutacional de ADN , Predisposición Genética a la Enfermedad , Histiocitosis/diagnóstico , Histiocitosis/genética , Mutación , Análisis Mutacional de ADN/métodos , Análisis Mutacional de ADN/normas , Humanos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Sarcoidosis is a systemic disease of unknown cause characterized by the formation of immune granulomas which most often involve the lung and the lymphatic system. Sarcoidosis may encompass numerous different clinical presentations. Typical presentations often prompt a rapid diagnosis while in 25 to 50% of cases, diverse and less typical presentations may lead to delayed diagnosis. The mediastinopulmonary sphere is involved in 85 to 95% of cases, associated with extrapulmonary localizations in half of cases while extrapulmonary localizations without lung involvement may be seen in 5 to 15% of cases. Bilateral hilar lymphadenopathy is the most typical sign at chest radiography. Computed tomography (CT) is essential face for atypical manifestations of the disease to avoid confusion with differential diagnoses and, sometimes, comorbidities. CT typically evidences diffuse pulmonary perilymphatic micronodules, with a perilobular and fissural distribution and upper and posterior predominance, even when an atypical CT pattern is predominant. CT allows deciphering pulmonary lesions in cases of pulmonary fibrosis, pulmonary hypertension, and airflow limitation. Pulmonary function tests generally correlate with the overall disease process. Forced vital capacity is the simplest and most accurate parameter to reflect the impact of pulmonary sarcoidosis. Cardiopulmonary exercise testing helps in understanding the mechanism behind dyspnea of uncertain origin. Endoscopic transbronchial needle aspiration is an extra tool to support diagnosis in addition to more classical biopsy means. Bronchoalveolar lavage (BAL) may be used for individual patients while it is not really decisive for the diagnosis of sarcoidosis for most patients. Diagnosis relies on compatible clinical and radiological presentation, evidence of noncaseating granulomas and exclusion of other diseases with a similar presentation or histology. The probability of diagnosis at presentation is variable from case to case and may often be reinforced with time. Some investigations are mandatory at diagnosis to assess organ involvement and disease activity. However, there are important variations in diagnostic work-up due to diverse expressions of sarcoidosis and differences in clinical practices among physicians.
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Granuloma/diagnóstico , Sarcoidosis Pulmonar/diagnóstico , Sarcoidosis/diagnóstico , Lavado Broncoalveolar/métodos , Diagnóstico Diferencial , Prueba de Esfuerzo/métodos , Granuloma/patología , Humanos , Pruebas de Función Respiratoria , Sarcoidosis/fisiopatología , Sarcoidosis Pulmonar/fisiopatología , Tomografía Computarizada por Rayos X/métodos , Capacidad VitalRESUMEN
The aim of the present study was to investigate to what extent interstitial lung disease (ILD) in common variable immunodeficiency disorder (CVID)-associated granulomatous disease (GD) is similar to pulmonary sarcoidosis 20 patients with CVID/GD were included in a retrospective study conducted by the Groupe Sarcoïdose Francophone. Medical records were centralised. Patients were compared with 60 controls with sarcoidosis. Clinical examination showed more frequent crackles in patients than controls (45% versus 1.7%, respectively; p<0.001). On thoracic computed tomography scans, nodules (often multiple and with smooth margins), air bronchograms and halo signs were more frequent in patients than controls (80% versus 42%, respectively; p=0.004) as well as bronchiectasis (65% versus 23%, respectively; p<0.001). The micronodule distribution was perilymphatic in 100% of controls and in 42% of patients (p<0.001). Bronchoalveolar lavage analysis showed lower T-cell CD4/CD8 ratios in patients than in controls (mean ± sd 1.6 ± 1.1 versus 5.3 ± 4, respectively; p<0.01). On pathological analysis, nodules and consolidations corresponded to granulomatous lesions with or without lymphocytic disorders in most cases. Mortality was higher in patients than controls (30% versus 0%, respectively) and resulted from common variable immunodeficiency complications. ILD in CVID/GD presents a specific clinical picture and evolution that are markedly different from those of sarcoidosis.
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Inmunodeficiencia Variable Común/diagnóstico , Granuloma/diagnóstico , Enfermedades Pulmonares Intersticiales/diagnóstico , Sarcoidosis Pulmonar/diagnóstico , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Niño , Inmunodeficiencia Variable Común/complicaciones , Femenino , Granuloma/complicaciones , Humanos , Enfermedades Pulmonares Intersticiales/complicaciones , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
Next generation sequencing analysis is crucial for therapeutic decision in various solid tumor contexts. The sequencing method must remain accurate and robust throughout the instrument lifespan allowing the biological validation of patients' results. This study aims to evaluate the long-term sequencing performances of the Oncomine Focus assay kit allowing theranostic DNA and RNA variants detection on the Ion S5XL instrument. We evaluated the sequencing performances of 73 consecutive chips over a 21-month period and detailed the sequencing data obtained from both quality controls and clinical samples. The metrics describing sequencing quality remained stable throughout the study. We showed that an average of 11 × 106 (±0.3 × 106) reads were obtained using a 520 chip leading to an average of 6.0 × 105 (±2.6 × 105) mapped reads per sample. Of 400 consecutive samples, 95.8 ± 16% of amplicons reached the depth threshold of 500X. Slight modifications of the bioinformatics workflow improved DNA analytical sensitivity and allowed the systematic detection of expected SNV, indel, CNV, and RNA alterations in quality controls samples. The low inter-run variability of DNA and RNA-even at low variant allelic fraction, amplification factor, or reads counts-indicated that our method was adapted to clinical practice. The analysis of 429 clinical DNA samples indicated that the modified bioinformatics workflow allowed detection of 353 DNA variants and 88 gene amplifications. RNA analysis of 55 clinical samples revealed 7 alterations. This is the first study showing the long-term robustness of the Oncomine Focus assay in clinical routine practice.
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BACKGROUND: The present article is an English-language version of the French National Diagnostic and Care Protocol, a pragmatic tool to optimize and harmonize the diagnosis, care pathway, management and follow-up of lymphangioleiomyomatosis in France. METHODS: Practical recommendations were developed in accordance with the method for developing a National Diagnosis and Care Protocol for rare diseases of the Haute Autorité de Santé and following international guidelines and literature on lymphangioleiomyomatosis. It was developed by a multidisciplinary group, with the help of patient representatives and of RespiFIL, the rare disease network on respiratory diseases. RESULTS: Lymphangioleiomyomatosis is a rare lung disease characterised by a proliferation of smooth muscle cells that leads to the formation of multiple lung cysts. It occurs sporadically or as part of a genetic disease called tuberous sclerosis complex (TSC). The document addresses multiple aspects of the disease, to guide the clinicians regarding when to suspect a diagnosis of lymphangioleiomyomatosis, what to do in case of recurrent pneumothorax or angiomyolipomas, what investigations are needed to make the diagnosis of lymphangioleiomyomatosis, what the diagnostic criteria are for lymphangioleiomyomatosis, what the principles of management are, and how follow-up can be organised. Recommendations are made regarding the use of pharmaceutical specialties and treatment other than medications. CONCLUSION: These recommendations are intended to guide the diagnosis and practical management of pulmonary lymphangioleiomyomatosis.
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Angiomiolipoma , Neoplasias Pulmonares , Linfangioleiomiomatosis , Esclerosis Tuberosa , Humanos , Linfangioleiomiomatosis/diagnóstico , Linfangioleiomiomatosis/terapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/genética , Esclerosis Tuberosa/diagnóstico , Esclerosis Tuberosa/terapia , Esclerosis Tuberosa/genética , Pulmón , Angiomiolipoma/tratamiento farmacológicoRESUMEN
BACKGROUND: Since the latest 2017 French guidelines, knowledge about idiopathic pulmonary fibrosis has evolved considerably. METHODS: Practical guidelines were drafted on the initiative of the Coordinating Reference Center for Rare Pulmonary Diseases, led by the French Language Pulmonology Society (SPLF), by a coordinating group, a writing group, and a review group, with the involvement of the entire OrphaLung network, pulmonologists practicing in various settings, radiologists, pathologists, a general practitioner, a health manager, and a patient association. The method followed the "Clinical Practice Guidelines" process of the French National Authority for Health (HAS), including an online vote using a Likert scale. RESULTS: After a literature review, 54 guidelines were formulated, improved, and then validated by the working groups. These guidelines addressed multiple aspects of the disease: epidemiology, diagnostic procedures, quality criteria and interpretation of chest CT scans, lung biopsy indication and procedures, etiological workup, methods and indications for family screening and genetic testing, assessment of the functional impairment and prognosis, indication and use of antifibrotic agents, lung transplantation, management of symptoms, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are intended to guide the diagnosis and practical management of idiopathic pulmonary fibrosis.
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Fibrosis Pulmonar Idiopática , Trasplante de Pulmón , Humanos , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/epidemiología , Fibrosis Pulmonar Idiopática/terapia , Pulmón/patología , Pronóstico , Tomografía Computarizada por Rayos X/métodosRESUMEN
Sarcoidosis is characterized by extensive local inflammation (granuloma, cytokine secretion) associated with anergy (poor response to antigens in vitro and in vivo). We postulated that this paradoxical situation would correspond to a disequilibrium between effector and regulatory T lymphocytes (T reg cells). We show that CD4+CD25(bright)FoxP3+ cells accumulate at the periphery of sarcoid granulomas, in bronchoalveolar lavage fluid, and in peripheral blood of patients with active disease. These cells exhibited powerful antiproliferative activity, yet did not completely inhibit TNF-alpha production. Sarcoidosis is therefore associated with a global T reg cell subset amplification whose activity would be insufficient to control local inflammation. At the same time, peripheral T reg cells exert powerful antiproliferative activity that may account for the state of anergy. Altogether, these findings advance our conceptual understanding of immune regulation in a way that resolves the immune paradox of sarcoidosis and permit us to envisage a profound clinical impact of T reg cell manipulation on immunity.
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Sarcoidosis Pulmonar/inmunología , Linfocitos T Reguladores/inmunología , Adulto , Anciano , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Proliferación Celular , Células Cultivadas , Técnicas de Cocultivo , Femenino , Factores de Transcripción Forkhead/metabolismo , Granuloma/metabolismo , Granuloma/patología , Humanos , Inmunidad Innata , Interferón gamma/metabolismo , Interleucina-2/metabolismo , Masculino , Persona de Mediana Edad , Receptores de Antígenos de Linfocitos T/biosíntesis , Receptores de Antígenos de Linfocitos T/genética , Receptores CXCR3 , Receptores de Quimiocina/biosíntesis , Receptores de Quimiocina/genética , Sarcoidosis Pulmonar/metabolismo , Sarcoidosis Pulmonar/patología , Linfocitos T Reguladores/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
In locally advanced non-small-cell lung cancer (NSCLC), mediastinal staging is the cornerstone of the therapeutic decision and echoendoscopy is the most practiced exam to assess the lymph node involvement. We describe a rare case of endobronchial involvement by cells originating from a metastatic lymph node after endobronchial ultrasound (EBUS). A 64-year-old man was diagnosed with a squamous cell lung cancer with mediastinal nodal involvement proven by EBUS. The patient received neoadjuvant chemotherapy with partial response and was scheduled for a lobectomy. Before surgery, a fibroscopy was performed which demonstrated a 1-cm polypoid lesion settled on the internal face of the main right bronchus corresponding to the EBUS puncture site. The histological analysis confirmed tumoral cell in this lesion. The patient was rejected for surgery and undergo chemoradiation. This case highlights the need for a careful endoscopic control before surgical resection in case of prior positive EBUS followed by an interval of time.