Evaluation of different classification methods using electronic nose data to diagnose sarcoidosis.

Electronic nose (eNose) technology is an emerging diagnostic application, using artificial intelligence to classify human breath patterns. These patterns can be used to diagnose medical conditions. Sarcoidosis is an often difficult to diagnose disease, as no standard procedure or conclusive test exists. An accurate diagnostic model based on eNose data could therefore be helpful in clinical decision-making. The aim of this paper is to evaluate the performance of various dimensionality reduction methods and classifiers in order to design an accurate diagnostic model for sarcoidosis. Various methods of dimensionality reduction and multiple hyperparameter optimised classifiers were tested and cross-validated on a dataset of patients with pulmonary sarcoidosis (n= 224) and other interstitial lung disease (n= 317). Best performing methods were selected to create a model to diagnose patients with sarcoidosis. Nested cross-validation was applied to calculate the overall diagnostic performance. A classification model with feature selection and random forest (RF) classifier showed the highest accuracy. The overall diagnostic performance resulted in an accuracy of 87.1% and area-under-the-curve of 91.2%. After comparing different dimensionality reduction methods and classifiers, a highly accurate model to diagnose a patient with sarcoidosis using eNose data was created. The RF classifier and feature selection showed the best performance. The presented systematic approach could also be applied to other eNose datasets to compare methods and select the optimal diagnostic model.

Diagnostic and Staging Value of Serum Angiotensin-Converting Enzyme in Sarcoidosis.

OBJECTIVE: To investigate the diagnostic and staging value of serum angiotensin-converting enzyme (sACE) in sarcoidosis. METHODS: Patients with suspected sarcoidosis treated in the Department of Pulmonary and Critical Care Medicine of the China-Japan Friendship Hospital from 2010 to 2020 were included. The data of sACE, erythrocyte sedimentation rate (ESR), complete blood count (CBC), lung function, bronchoalveolar lavage, and biopsy were collected. The differences between the sarcoidosis group and the nonsarcoidosis group and between different stages of sarcoidosis were compared. The receiver operating characteristic (ROC) curve analysis was used for the diagnostic test of sACE in sarcoidosis. RESULTS: A total of 84 cases with suspected sarcoidosis were included, among which 70 cases were confirmed to be sarcoidosis by biopsy. The mean value of sACE in sarcoidosis patients was 56.61 ± 30.80 U/L, which was significantly higher than that in nonsarcoidosis patients (28.07 ± 14.11 U/L, P = 0.001). The level of sACE in sarcoidosis patients with peripheral superficial lymph nodes and multiple system involvement was significantly higher than that in intrathoracic sarcoidosis patients (P = 0.009); the percentage of lymphocytes in bronchoalveolar lavage fluid (BALF) of sarcoidosis patients was 45.39 ± 22.87%, which was significantly higher than that of nonsarcoidosis patients (P < 0.001). There was no correlation between sACE and ESR (correlation coefficient = -0.167). According to ROC curve analysis, when sACE ≥ 44.0 U/L, the sensitivity of sarcoidosis diagnosis was 61.4%, the specificity was 92.9%, and the AUC was 0.819. CONCLUSION: sACE has a good specificity in the diagnosis of sarcoidosis. sACE values in patients with sarcoidosis with systemic involvement were higher than those with simple intrathoracic sarcoidosis.

Systemic Sarcoidosis with Psoriasiform Plaques and Patchy Nonscarring Alopecia.

ABSTRACT: Cutaneous sarcoidosis occurs in about one-quarter of patients with systemic disease and presents with either specific or nonspecific signs. Psoriasiform sarcoidosis is an uncommon presentation. Herein, study authors report a rare case of systemic sarcoidosis that presented with psoriasiform plaques and patchy alopecia. The main patient complaint was disfigurement from skin lesions over different areas of his body, followed by scalp alopecia and uveitis. These lesions were well-defined plaques, some oozing and others scaly. Dermoscopic examination revealed yellow-orange globular structure. A biopsy was taken; the eventual diagnosis was sarcoidosis, for which the patient received treatment with systemic steroids, resulting in improvement of all of his lesions. Physicians should suspect sarcoidosis in any patient presenting with psoriasiform skin lesions not responding to traditional psoriasis treatment.

Clinical characterization and outcomes of 85 patients with neurosarcoidosis.

To analyze the frequency and clinical phenotype of neurosarcoidosis (NS) in one of the largest nationwide cohorts of patients with sarcoidosis reported from southern Europe. NS was evaluated according to the Diagnostic Criteria for Central Nervous System and Peripheral Nervous System Sarcoidosis recently proposed by Stern et al. Pathologic confirmation of granulomatous disease was used to subclassify NS into definite (confirmation in neurological tissue), probable (confirmation in extraneurological tissue) and possible (no histopathological confirmation of the disease). Of the 1532 patients included in the cohort, 85 (5.5%) fulfilled the Stern criteria for NS (49 women, mean age at diagnosis of NS of 47.6 years, 91% White). These patients developed 103 neurological conditions involving the brain (38%), cranial nerves (36%), the meninges (3%), the spinal cord (10%) and the peripheral nerves (14%); no patient had concomitant central and peripheral nerve involvements. In 59 (69%) patients, neurological involvement preceded or was present at the time of diagnosis of the disease. According to the classification proposed by Stern et al., 11 (13%) were classified as a definite NS, 61 (72%) as a probable NS and the remaining 13 (15%) as a possible NS. In comparison with the systemic phenotype of patients without NS, patients with CNS involvement presented a lower frequency of thoracic involvement (82% vs 93%, q = 0.018), a higher frequency of ocular (27% vs 10%, q < 0.001) and salivary gland (15% vs 4%, q = 0.002) WASOG involvements. In contrast, patients with PNS involvement showed a higher frequency of liver involvement (36% vs 12%, p = 0.02) in comparison with patients without NS. Neurosarcoidosis was identified in 5.5% of patients. CNS involvement prevails significantly over PNS involvement, and both conditions do not overlap in any patient. The systemic phenotype associated to each involvement was clearly differentiated, and can be helpful not only in the early identification of neurological involvement, but also in the systemic evaluation of patients diagnosed with neurosarcoidosis.

Clinical Features, Histopathology and Differential Diagnosis of Sarcoidosis.

Sarcoidosis is a chameleon disease of unknown etiology, characterized by the growth of non-necrotizing and non-caseating granulomas and manifesting with clinical pictures that vary on the basis of the organs that are mainly affected. Lungs and intrathoracic lymph nodes are the sites that are most often involved, but virtually no organ is spared from this disease. Histopathology is distinctive but not pathognomonic, since the findings can be found also in other granulomatous disorders. The knowledge of these findings is important because it could be helpful to differentiate sarcoidosis from the other granulomatous-related diseases. This review aims at illustrating the main clinical and histopathological findings that could help clinicians in their routine clinical practice.

Clinical characteristics and organ system involvement in sarcoidosis: comparison of the University of Minnesota Cohort with other cohorts.

BACKGROUND: Sarcoidosis is a systemic granulomatous disease of unknown etiology. Clinical cohort studies of different populations are important to understand the high variability in clinical presentation and disease course of sarcoidosis. The aim of the study is to evaluate clinical characteristics, including organ involvement, pulmonary function tests, and laboratory parameters, in a sarcoidosis cohort at the University of Minnesota. We compare the organ system involvement of this cohort with other available cohorts. METHODS: We conducted a retrospective data collection and analysis of 187 subjects with biopsy-proven sarcoidosis seen at a tertiary center. Organ system involvement was determined using the WASOG sarcoidosis organ assessment instrument. Clinical phenotype groups were classified using the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis criteria. RESULTS: Mean subject age at diagnosis was 45.8 ± 12.4, with a higher proportion of males (55.1%), and a higher proportion of blacks (17.1%) compared to the racial distribution of Minnesota residents (5.95%). The majority (71.1%) of subjects required anti-inflammatory therapy for at least 1 month. Compared to the A Case Control Etiologic Study of Sarcoidosis cohort, there was a higher frequency of extra-thoracic lymph node (34.2% vs. 15.2%), eye (20.9% vs. 11.8%), liver (17.6% vs. 11.5%), spleen (20.9% vs. 6.7%), musculoskeletal (9.6% vs. 0.5%), and cardiac (10.7% vs. 2.3%) involvement in our cohort. A multisystem disease with at least five different organs involved was identified in 13.4% of subjects. A restrictive physiological pattern was observed in 21.6% of subjects, followed by an obstructive pattern in 17.3% and mixed obstructive and restrictive pattern in 2.2%. Almost half (49.2%) were Scadding stages II/III. Commonly employed disease activity markers, including soluble interleukin-2 receptor and angiotensin-converting enzyme, did not differ between treated and untreated groups. CONCLUSIONS: This cohort features a relatively high frequency of high-risk sarcoidosis phenotypes including cardiac and multiorgan disease. Commonly-utilized serum biomarkers do not identify subpopulations that require or do better with treatment. Findings from this study further highlight the high-variability nature of sarcoidosis and the need for a more reliable biomarker to predict and measure disease severity and outcomes for better clinical management of sarcoidosis patients.

Emerging phenotypes of sarcoidosis based on 18F-FDG PET/CT: a hierarchical cluster analysis.

Objectives: In sarcoidosis, the definition of organ involvement with traditional means appears laborious and somewhat controversial, and phenotyping by the above overlapping. 18F-FDG PET/CT defines disease extent by activity more precisely, and may result in a better understanding of sarcoidosis disease behavior and phenotypes expression. We hypothesized that 18F-FDG PET/CT could add in the phenotyping of sarcoidosis patients by unveiling in detail sites of involvement even in clinically and physiologically silent disease.Methods: This study was designed to investigate the role of 18F-FDG PET/CT in phenotyping sarcoidosis using cluster analysis by adding this new means in the routine work-up of 195 sarcoidosis patients of a single academic center.Results: 18F-FDG PET/CT succeeded to identify despite the random distribution of the disease, an ordered stratification into 4 phenotypes: I) thoracic nodal hilar-mediastinal, II) thoracic nodal hilar-mediastinal and lungs, III) an extended thoracic and extra-thoracic only nodal phenotype including inguinal-abdominal-supraclavicular stations, and IV) all the above plus systemic organs and tissues such as muscles-bones-spleen and skin.Conclusion: Though further studies are necessary to confirm findings as patterns of disease behavior; the proposed phenotypes may prove useful in the design of future studies with homogeneous cohorts facilitating in sarcoidosis patients a personalized medicine approach.

Cardiac sarcoidosis classification with deep convolutional neural network-based features using polar maps.

AIMS: The aim of this study was to determine whether deep convolutional neural network (DCNN)-based features can represent the difference between cardiac sarcoidosis (CS) and non-CS using polar maps. METHODS: A total of 85 patients (33 CS patients and 52 non-CS patients) were analyzed as our study subjects. One radiologist reviewed PET/CT images and defined the left ventricle region for the construction of polar maps. We extracted high-level features from the polar maps through the Inception-v3 network and evaluated their effectiveness by applying them to a CS classification task. Then we introduced the ReliefF algorithm in our method. The standardized uptake value (SUV)-based classification method and the coefficient of variance (CoV)-based classification method were used as comparative methods. RESULTS: Sensitivity, specificity and the harmonic mean of sensitivity and specificity of our method with the ReliefF algorithm were 0.839, 0.870 and 0.854, respectively. Those of the SUVmax-based classification method were 0.468, 0.710 and 0.564, respectively, and those of the CoV-based classification method were 0.655, 0.750 and 0.699, respectively. CONCLUSION: The DCNN-based high-level features may be more effective than low-level features used in conventional quantitative analysis methods for CS classification.

A prospective study of patients diagnosed with sarcoidosis: factors - environmental exposure, health assessment, and genetic outlooks.

This original research is a directional study that determined the habits of individuals using four analyses to find statistical significance in the data collected from the surveys of 801 qualified of 1,340 individuals who agreed to participate. Results from the self-reported diagnosis of individuals affected by sarcoidosis produced seven statistically significant indicators of future research needed. The demographics revealed a significantly greater number of women and African-Americans participants than other minorities in the United States and suggested a sense of urgency to find a cure. Most important are the seven statistically significant findings that also gave credence to the researchers' four subdiagnostic classifications. They are acute sarcoidosis (AS) and chronic sarcoidosis with limited dissemination (CSLD), while more severe cases include those with chronic sarcoidosis with full dissemination including cutaneous involvement (CSFDIC) and chronic sarcoidosis with neurosarcoidosis (CSN). The most severe sarcoidosis cases (CSN) were on the "most likely" side of every statistically significant category except drinking alcohol, and the "least likely" to participate in physical activities. Conversely, the least severe case of sarcoidosis (AS) was the opposite. The complete list of statistically significant areas was related to alcohol use, tobacco use, ciprofloxacin use, environmental exposure to metals (copper, iron), infectious diseases (candidiasis), genetics, and physical exercise. Statistically, the most crucial study needed; emerged from the Rh blood grouping of the participants.

Nationwide survey on the organ-specific prevalence and its interaction with sarcoidosis in Japan.

Previous studies attempted to characterize the subjects with sarcoidosis according to differences in sex, age, and the presence of specific organ involvement. However, significant interactions among these factors precluded a clear conclusion based on simple comparison. This study aimed to clarify the age- and sex-stratified prevalence of specific organ involvement and the heterogenous nature of sarcoidosis. Using the data of 9,965 patients who were newly registered into a database at the Ministry of Health, Labour and Welfare, Japan between 2002 and 2011, we evaluated the age- and sex-specific prevalence of the eye, lung, and skin involvement of sarcoidosis. We also attempted corresponding analysis considering multiple factors. As compared with several decades ago, the monophasic age distribution in men became biphasic, and the biphasic distribution in women, monophasic. The prevalence of pulmonary and cutaneous lesions was significantly associated with age, whereas the prevalence of ocular involvement showed a biphasic pattern. The prevalence of bilateral hilar lymphadenopathy was significantly higher, whereas the prevalence of diffuse lung shadow was significantly lower, in subjects with ocular involvement than those without ocular involvement. Corresponding analysis visually clarified the complex interactions among factors. Our results contribute to a better understanding of the heterogeneous features of sarcoidosis.

Endobronchial Ultrasound-guided Transbronchial Needle Aspiration Using 19-G Needle for Sarcoidosis.

BACKGROUND: Flexible bronchoscopy with endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) is increasingly being used to obtain pathology specimens for diagnosis of sarcoidosis. There is wide variation in reported diagnostic yield in literature. New TBNA needles are available in the market but data are lacking about their diagnostic yield especially for sarcoidosis. This study reports the diagnostic yield of bronchoscopy with EBUS-TBNA using ViziShot FLEX 19-G needle in a series of patients with suspected sarcoidosis. METHODS: This is a retrospective chart review for diagnostic yield of the 19-G EBUS-TBNA needle for suspected sarcoidosis. RESULTS: Eighty-six EBUS bronchoscopies were performed, 15 were done with clinical suspicion of sarcoidosis. The 19-G needle was used for all cases of suspected sarcoidosis. The procedure was diagnostic of sarcoidosis in 14 (93.3%) patients by TBNA with 1 nondiagnostic bronchoscopy. Procedural diagnostic yield was 93.3%. Eighty-five percent (28/33) of sampled lymph nodes were positive for noncaseating granulomas. The yield of transbronchial lung biopsy (TBLB) and endobronchial lung biopsy was 38% (5/13) and 43% (6/14), respectively. TBLB and endobronchial lung biopsy did not add to the diagnostic yield of the procedure. No significant adverse events were noted. CONCLUSION: This series reports a higher diagnostic yield than most other published studies and opens platform for direct comparison of each available needle. It also adds to the safety data for this larger needle. In addition, it raises doubt into utility of TBLB for diagnosis of sarcoidosis, which can increase the procedural complications.

Enhanced CD8+ cytolytic T cell responses in the peripheral circulation of patients with sarcoidosis and non-Löfgren's disease.

BACKGROUND: The role of CD4+ T cells in the immunopathogenesis of pulmonary sarcoidosis is well-established, while less is known about the phenotype and function of CD8+ cytolytic T cells (CTLs). METHODS: CD8+ CTLs were explored in peripheral blood and bronchoalveolar lavage (BAL) samples obtained from up to 25 patients with sarcoidosis and 25 healthy controls. The proportion of CTLs was assessed by the expression of cytolytic effector molecules perforin, granzyme B and granulysin in CD8+ T cells, using flow cytometry. Cytolytic function in blood lymphocytes was assessed using a standard 51Cr-release assay. Patients with Löfgren´s syndrome (LS) and an acute disease onset, were compared to non-LS patients with an insidious onset. RESULTS: Higher proportions of peripheral CD8+ CTLs expressing perforin and granzyme B were observed in sarcoidosis compared to healthy controls. Blood CTLs from non-LS patients had significantly higher expression of perforin, granzyme B and granulysin compared to matched BAL, while LS patients maintained lower levels of effector molecules in both compartments. Mitogen-stimulated peripheral lymphocytes from sarcoidosis patients, particularly from the non-LS group, showed a higher target cell lysis compared to controls. CONCLUSION: These results demonstrated enhanced peripheral CD8+ CTL responses in sarcoidosis, especially in non-LS patients who have an increased risk of chronic disease. Further comprehensive clinical studies are warranted to increase our understanding of CD8+ CTL responses in sarcoidosis.

Identification of Jak-STAT signaling involvement in sarcoidosis severity via a novel microRNA-regulated peripheral blood mononuclear cell gene signature.

Sarcoidosis is a granulomatous lung disorder of unknown cause. The majority of individuals with sarcoidosis spontaneously achieve full remission (uncomplicated sarcoidosis), however, ~20% of sarcoidosis-affected individuals experience progressive lung disease or cardiac and nervous system involvement (complicated sarcoidosis). We investigated peripheral blood mononuclear cell (PBMC) microRNA and protein-coding gene expression data from healthy controls and patients with uncomplicated or complicated sarcoidosis. We identified 46 microRNAs and 1,559 genes that were differentially expressed across a continuum of sarcoidosis severity (healthy control → uncomplicated sarcoidosis → complicated sarcoidosis). A total of 19 microRNA-mRNA regulatory pairs were identified within these deregulated microRNAs and mRNAs, which consisted of 17 unique protein-coding genes yielding a 17-gene signature. Pathway analysis of the 17-gene signature revealed Jak-STAT signaling pathway as the most significantly represented pathway. A severity score was assigned to each patient based on the expression of the 17-gene signature and a significant increasing trend in the severity score was observed from healthy control, to uncomplicated sarcoidosis, and finally to complicated sarcoidosis. In addition, this microRNA-regulated gene signature differentiates sarcoidosis patients from healthy controls in independent validation cohorts. Our study suggests that PBMC gene expression is useful in diagnosis of sarcoidosis.

Categorización diagnóstica según los criterios del First International Workshop on Ocular Sarcoidosis (FIWOS) en una serie de 11 pacientes / Diagnostic categorization according to the First International Workshop on Ocular Sarcoidosis (FIWOS) criteria in a series of 11 patients

Objetivo. Categorizar a los pacientes con diagnóstico de sarcoidosis ocular en el período comprendido entre 2009 y 2014. Métodos. Se revisaron las historias clínicas de los pacientes con sarcoidosis ocular y se recopilaron las variables para categorizar a los pacientes según los criterios del FIWOS. Resultados. Se encontró a un total de 11 pacientes con uveítis sarcoidea, 7 mujeres y 4 hombres, con una mediana de edad de 58 años. El patrón de panuveítis bilateral crónica fue el más frecuente en un 54,5%, seguido de la uveítis anterior crónica unilateral, con 27,2%. El diagnóstico de sarcoidosis fue definitivo en 4 pacientes (36,3%), presunto en 5 pacientes (45,4%), probable en un paciente (9%) y posible en un paciente (9%). Conclusiones. Más de la mitad de los pacientes sin biopsia confirmatoria fueron diagnosticados de sarcoidosis ocular. La panuveítis bilateral crónica y la uveítis anterior crónica fueron los patrones predominantes (AU)

Objective. Categorization of patients diagnosed with ocular sarcoidosis during the period 2009-2014. Methods. The medical records of patients with ocular sarcoidosis were reviewed and variables were collected to categorize the patients according to the criteria of the FIWOS. Results. We found 11 patients, 7 women and 4 men, with sarcoid uveitis; the median age was 58 years. Bilateral panuveitis was the most common pattern (54.5%), followed by chronic anterior uveitis (27.2%). The diagnosis of sarcoidosis was definitive in 4 patients (36.3%), presumed in 5 (45.4%), probable in 1 (9%) and possible in 1 (9%). Conclusions. Ocular sarcoidosis was diagnosed in more than half of the patients who had no confirmatory biopsy. Bilateral panuveitis and chronic anterior uveitis were the patterns most frequently observed (AU)

The influence of comorbidities on mortality in sarcoidosis: a observational prospective cohort study.

AIM: The aim of this study was to identify the frequency and prevalence of comorbidities in sarcoid patients and to assess their influence on overall mortality in the cohort of patients with sarcoidosis. MATERIALS AND METHODS: A cohort of 557 patients with histologically confirmed sarcoidosis diagnosed between 2007 and 2011 and a group of non-sarcoid controls were observed. All patients were carefully observed for comorbidities and mortality. RESULTS: 291 males (52.2%) and 266 females (47.8%) with mean age 48.4 ± 12.0 years in sarcoidosis group and a group of 100 controls with mean age (49.25 ± 10.3) were observed. The mean number of comorbidities in both groups was similar (0.9 ± 0.99 vs 0.81 ± 0.84 NS). The frequency of thyroid disease was significantly higher in sarcoidosis group comparing to controls at the time of diagnosis (OR = 3.62 P = 0.0144). During the observation period (median 58.0 months), 16 patients died (2.9%). The mean number of comorbidities was significantly higher in the groups of non-survivors as compared to survivors (2.8 ± 1.0, vs 0.8 ± 0.9), P < 0.0001. CONCLUSION: The comorbidity burden has strong impact on mortality in sarcoidosis. Thyroid diseases are more frequent in sarcoidosis than in non-sarcoid controls.

The Diagnosis, Differential Diagnosis, and Treatment of Sarcoidosis.

BACKGROUND: Sarcoidosis is a granulomatous inflammatory disease of unknown cause. Its prevalence in Germany is approximately 46 per 100 000 persons. METHODS: This article is based on pertinent publications retrieved by a selective search in PubMed. RESULTS: A presumptive diagnosis of sarcoidosis is made in any patient with a granulomatous inflammation that is not explained by any other identifiable cause, such as an infection or foreign body. Non-caseating granulomas containing epithelioid cells are its histological hallmark. Recently developed diagnostic techniques, including positron emission tomography and magnetic resonance imaging, have made it easier to detect organ involvement and to assess the activity of the disease. The pattern of organ involvement varies from patient to patient. Many patients have a systemic inflammatory reaction with subfebrile or febrile temperatures, night sweats, weight loss, diminished physical reserve, and fatigue. Sarcoidosis often resolves spontaneously. Detection of organ involvement is not necessarily an indication for treatment, but treatment is clearly needed if there is symptomatic cardiac involvement or any involvement of the central nervous system. Oral corticosteroids are the first line of treatment. Their long-term use can cause serious complications. CONCLUSION: The treatment of patients with sarcoidosis, particularly those with complicated disease courses, requires close collaboration of the primary care physician with a specialized interdisciplinary center.

From the definition of silicosis at the 1930 Johannesburg conference to the blurred boundaries between pneumoconioses, sarcoidosis, and pulmonary alveolar proteinosis (PAP).

The 1930 International Labour Office Conference on silicosis in Johannesburg identified silicosis by setting a medicolegal framework to its nosology: as with other occupational illnesses, its medical content was fixed under economic pressure. This article follows a reading of all the proceedings of this conference (debates and reports of experts) to examine their potential impact on the etiology and nosology of other diseases, specifically sarcoidosis and pulmonary alveolar proteinosis (PAP), "idiopathic" diseases in which inorganic particles may be involved. We propose renewed study of the role of inorganic particles in these diseases. To do this, we propose to mobilize detection means such as mineralogical analysis and electron microscopy and in depth interviewing that are currently seldom used in France, in order to establish diagnosis and the potential occupational and environmental origin of these diseases.

Ocular and systemic features of sarcoidosis and correlation with the International Workshop for Ocular Sarcoidosis diagnostic criteria.

PURPOSE: To describe the ocular and systemic features in biopsy proven (definite) and non-biopsy proven (clinical) ocular sarcoidosis and to compare the ocular features with those proposed by the International Workshop for Ocular Sarcoidosis (IWOS). METHODS: Retrospective chart review of 83 patients who attended a tertiary referral uveitis clinic and were diagnosed with sarcoidosis. Patients were divided into two groups based on the type of diagnosis: those who had tissue biopsy confirmed diagnosis 'definite sarcoidosis' (n= 42; 50.60 %) and those who had 'clinical sarcoidosis' (n= 41; 49.40%). Ocular and systemic manifestations, including lung function tests and bronchoalveolar lavage findings were compared in the two groups. The ocular features were also compared with the categories laid down by the International Workshop on Ocular Sarcoidosis (IWOS). RESULTS: The mean age at presentation was 38.75 years (SD=12.33), 55.42% patients were female and mean follow-up was 24.35 months (SD=18.35). Trabecular meshwork nodules and/or tent-shaped PAS (category II of IWOS) were observed more frequently in patients with biopsy proven sarcoidosis (26.19 % v/s 9.76%; p=0.08). After logistic regression analysis, the predictor coefficient curve showed area under curve of 0.7262. Lymphocytosis (38.61% and 28.02%, p=0.93) and monocytosis (55.11% and 53.83%, p=0.56) on bronchoalveolar lavage analysis was present in both the groups, highlighting presence of granulomatous disease. CONCLUSION: This study suggests high reliability for the clinical diagnosis of ocular sarcoidosis in patients with signs recommended by IWOS and that our diagnostic criteria are consistent with that of the IWOS.

What comorbidities accompany sarcoidosis? A large cohort (n=1779) patients analysis.

BACKGROUND: Sarcoidosis is a systemic granulomatous multiorgan disease with the most common manifestation is in the chest, although the granulomas can also involve all other organs causing variety of symptoms mimicking different diseases. OBJECTIVES: To evaluate the incidence of comorbidity in a large group of patients with sarcoidosis diagnosed or followed in referral center for lung diseases in Poland. PATIENTS AND METHODS: We performed a retrospective analysis in a group of 1779 patients discharged with the final diagnosis "sarcoidosis" (ICD-10: D86) from January 2008 to October 2011. RESULTS: The majority (79.2%) were diagnosed as pulmonary and/or lymph node sarcoidosis (D86.0, D86.1, D86.2). Sarcoidosis of other and combined sites (D86.8) were diagnosed in 15.8% and unspecified (D86.9) in 5.0% of patients. At least one comorbid condition was noted in 54% of the patients, most frequently arterial hypertension (22.4%), thyroid disorders (5.6%), diabetes mellitus (5.0%), COPD (4.3%) and obesity (3.3%). Using linear regression models, the associations between the number of comorbidities and age and extent of the disease were found (p<0.001). Patients with multiorgan sarcoidosis were more likely to have a comorbid condition. CONCLUSIONS: More than half of patients with sarcoidosis have a comorbid condition, which is more likely in older patients and those with multiorgan involvement.

Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) Study. Sarcoidosis Protocol.

Sarcoidosis is a systemic disease characterized by noncaseating granulomatous inflammation with tremendous clinical heterogeneity and uncertain pathobiology and lacking in clinically useful biomarkers. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study is an observational cohort study designed to explore the role of the lung microbiome and genome in these two diseases. This article describes the design and rationale for the GRADS study sarcoidosis protocol. The study addresses the hypothesis that distinct patterns in the lung microbiome are characteristic of sarcoidosis phenotypes and are reflected in changes in systemic inflammatory responses as measured by peripheral blood changes in gene transcription. The goal is to enroll 400 participants, with a minimum of 35 in each of 9 clinical phenotype subgroups prioritized by their clinical relevance to understanding of the pathobiology and clinical heterogeneity of sarcoidosis. Participants with a confirmed diagnosis of sarcoidosis undergo a baseline visit with self-administered questionnaires, chest computed tomography, pulmonary function tests, and blood and urine testing. A research or clinical bronchoscopy with a research bronchoalveolar lavage will be performed to obtain samples for genomic and microbiome analyses. Comparisons will be made by blood genomic analysis and with clinical phenotypic variables. A 6-month follow-up visit is planned to assess each participant's clinical course. By the use of an integrative approach to the analysis of the microbiome and genome in selected clinical phenotypes, the GRADS study is powerfully positioned to inform and direct studies on the pathobiology of sarcoidosis, identify diagnostic or prognostic biomarkers, and provide novel molecular phenotypes that could lead to improved personalized approaches to therapy for sarcoidosis.