Chest X-ray Stage Research Articles

Osteoporosis and major fragility fractures (MOF) in sarcoidosis patients: association with disease severity

BackgroundThe reports on bone mineral loss or major osteoporosis fracture (MOF) in sarcoidosis are scarce and have conflicting outcomes. This study aimed to evaluate the prevalence and risk factors of MOF in sarcoidosis patients.MethodsIn a single-center cohort of 382 patients with sarcoidosis (55.8 ± 11.6 years) we evaluated bone mineral density at lumbar spine, at femoral neck and at total hip and the presence of MOF. Lung function measurements including diffusion capacity for carbon monoxide (DLCO) were assessed. Chest X-rays were performed and radiological staging was done by Scadding score.ResultsNinety patients (23.6%) with sarcoidosis have history of a MOF. BMD T-scores were lower in sarcoidosis with MOF with respect to those without MOF, but the difference was statistically significant only for BMD at femoral neck (p < 0.05). Moreover, BMD values at total hip was positively correlated with DLCO (%) (p < 0.001). Prevalence of MOF was higher in patients with sarcoidosis with lung parenchymal involvement (radiological stages 2–4) than in patients with sarcoidosis in chest X-ray stages 0 and 1 (28.3 vs 19.2% respectively, p < 0.05). Moreover, multiple regression analyses showed that X-ray Scadding score was positively associated with MOF.ConclusionsThis study shows that MOF represent a common and important complication in patients with moderate/severe sarcoidosis. The chest X-ray evaluation and the pulmonary function test could allow to define the risk of MOF in sarcoidosis patients.

Association between sarcoidosis and HLA polymorphisms in a Czech population from Central Europe: focus on a relationship with clinical outcome and treatment.

Sarcoidosis is an immune-mediated systemic disease with unknown etiology affecting the lung predominantly. The clinical manifestation of sarcoidosis is rather diverse ranging from Löfgren's syndrome to fibrotic disease. Also, it differs among patients with distinct geographical and ethnic origins, consistent with environmental and genetic factors' role in its pathogenesis. Of those, the polymorphic genes of the HLA system have been previously implicated in sarcoidosis. Therefore, we have performed an association study in a well-defined cohort of Czech patients aiming to define how variation in HLA genes, may contribute to disease origin and development. Total of the 301 Czech unrelated sarcoidosis patients were diagnosed according to international guidelines. In those, HLA typing was performed using next-generation sequencing. The allele frequencies at six HLA loci (HLA-A,-B,-C,-DRB1,-DQA1, and -DQB1) observed in the patients were compared with HLA allele distribution determined in 309 unrelated healthy Czech subjects; sub-analyses of relationships between HLA and distinct sarcoidosis clinical phenotypes were performed. Associations were assessed by two-tailed Fischer's exact test with correction for multiple comparisons. We report two variants, HLA-DQB1*06:02, and HLA-DQB1*06:04, as risk factors for sarcoidosis, and three variants, HLA-DRB1*01:01, HLA-DQA1*03:01, and HLA-DQB1*03:02 as protective factors. HLA-B*08:01, HLA-C*07:01, HLA-DRB1*03:01, HLA-DQA1*05:01, and HLA-DQB1*02:01 variants associated with Löfgren's syndrome, a more benign phenotype. HLA- DRB1*03:01 and HLA-DQA1*05:01 alleles were connected with better prognosis-chest X-ray (CXR) stage 1, disease remission, and non-requirement of corticosteroid treatment. The alleles HLA-DRB1*11:01 and HLA-DQA1*05:05 are associated with more advanced disease represented by the CXR stages 2-4. HLA-DQB1*05:03 associated with sarcoidosis extrapulmonary manifestation. In our Czech cohort, we document some associations between sarcoidosis and HLA previously described in other populations. Further, we suggest novel susceptibility factors for sarcoidosis, such as HLA-DQB1*06:04, and characterize associations between HLA and sarcoidosis clinical phenotypes in Czech patients. Our study also extends the role of the 8.1 ancestral haplotype (HLA-A*01:01∼HLA-B*08:01∼HLA-C*07:01∼HLA-DRB1*03:01∼HLA-DQA1*05:01∼HLA-DQB1*02:01), already implicated in autoimmune diseases, as a possible predictor of better prognosis in sarcoidosis. The general translational application of our newly reported findings for personalized patient care should be validated by an independent study from another, international referral center.

Epidemiology, prevalence, and associated factors of oral candidiasis in HIV patients from southwest Iran in post-highly active antiretroviral therapy era.

BackgroundOral candidiasis (OC) is one of the most common opportunistic fungal infections among people living with HIV/AIDS (PLWHA). The prevalence of OC and Candida profiles among HIV-infected patients might be changing in the era of Highly Active Antiretroviral Therapy (HAART). This study aimed to identify Candida spp., determine OC prevalence and associated risk factors for PLWHA.Materials and methodsOral candidiasis prevalence was explored in oral swabs of 276 patients who referred for consultation at Behavioral Diseases Counseling Center (BDCC). Clinical symptoms, culture and molecular assays were used for OC detection. In statistical analysis, we assessed socio-demographic characteristics, clinical information and treatment history of some infections.ResultsThe overall prevalence of OC was 41%. Candida albicans (64.6%) was the most common species, followed by C. glabrata (26.5%) and C. dubliniensis (19.5%). Candida famata, C. africana, and C. stellatoidea as the first fungi isolated from OC in PLWHA from southwest Iran. In 36.3% of patients, mixed cultures of more than one species were observed. Body mass index (BMI) (OR = 0.947; CI = 0.89–0.99; p = 0.045) and CD4 count ≤ 200 cells/mm3 (OR = 4.365; CI = 1.73–10.98; p = 0.002) were the predictors of OC in the final model of multiple logistic regression analysis. Education level, addiction status, sexual behaviors, chest X-ray, other infections and WHO clinical stage were other important risk factors for OC.ConclusionOral candidiasis remains a significant opportunistic infection in post-HAART era among PLWHA. Despite the increasing prevalence of NAC species, C. albicans (64.6%) was still the predominant species. Our results showed that low BMI with OC indicates treatment failure (i.e., failure to increase CD4 count or suppress viral load). Also, low CD4 counts (≤200 cells/mm3) in HIV patients show an impaired immune status, and our findings emphasize that OC can be a clinical indicator of HIV infection in individuals who do not know their HIV status or have failed treatment.

Sarcoidosis related to checkpoint and BRAF/MEK inhibitors in melanoma.

Therapy for advanced melanoma has deeply changed in the last decade with the introduction of checkpoint and BRAF/MEK inhibitors. Granulomatous reactions have been reported related to these drugs. We performed a systematic review of all the cases described in the medical literature by the search (("Melanoma"[Mesh]) AND ("Sarcoidosis"[Mesh] OR "Granuloma"[Mesh])). Ninety-one patients under immunotherapy were included in the analyses. The time from the initiation of the immunotherapy until the onset of sarcoidosis or sarcoid-like reaction (SLR) was 7.1months (SD 9). Peripheral lymph nodes as the mode of onset were seen more frequently in patients under CTLA-4 inhibitors (p=.016) whereas in patients under BRAF/MEK inhibitors used to be in the form of specific skin lesions (p=.006). Chest X-ray stage I-II was the rule in the CTLA-4 and PD-1 groups. On the contrary, stage 0 accounted for 80% of the patients in the BRAF/MEK group examined for pulmonary involvement. Specific skin involvement was the most common manifestation apart from pulmonary involvement. It was more frequent in patients under BRAF/MEK inhibitors and especially in the form of papules. Splenic involvement was found also more frequently in patients under CTLA-4 inhibitors. Specific treatment for sarcoidosis/SLR was prescribed in 50 patients (58.8%), without differences among groups. Almost all patients presented a good prognosis independently of the decision made regarding their previous immunotherapy. CONCLUSION: Physicians should bear in mind the possibility of sarcoidosis/SLR after the initiation of checkpoint or BRAF/MEK inhibitors in patients diagnosed with advanced melanoma, especially in the form of skin involvement and mediastinal and peripheral lymph nodes. It is important to achieve an accurate diagnosis to rule out the possibility of cancer involvement. What to do with these drugs is yet to be clarified. It seems reasonable to prioritize cancer treatment so it is not mandatory to stop these drugs.

Comparison of lymphocyte immune phenotypes in bronchoalveolar lavage of non-smoking patients with sarcoidosis and other interstitial lung diseases

Bronchoalveolar lavage (BAL) as complementary method is still used as ancillary tool in diagnosis of interstitial lung diseases. Tobacco smoking has been described to affect the BAL lavage cellular profile. To our knowledge, only few reports have so far investigated CD3+CD4+ and CD3+CD8+ lymphocyte subsets in non-smoking sarcoidosis patients additionally stratified according to CXR stage, and compared them to other non-smoking patients with interstitial lung diseases (ILDs). We compared lymphocytes immune phenotypes, subsets, with CD3+, CD3+CD4+ and CD3+CD8+ cell markers, in the non-smoking subjects (n=297) including the patients with pulmonary sarcoidosis (S), idiopathic pulmonary fibrosis (IPF) (n=22), hypersensitivity pneumonitis (HP) (n=15), other interstitial idiopathic pneumonias (OIIPs) (n=39). According to prognosis, the patients with S were divided into four groups: 18 patients with Löfgren's syndrome (LS) in chest X-ray (CXR) ≤1 stage, 64 patients without LS in CXR ≤1 stage, 113 patients in CXR 2 stage and 26 patients with advanced CXR ≥3 stage. After the use of false discovery rate (FDR) correction, relative numbers (%) of CD3+, CD3+CD4+, CD3+CD8+ and CD3+CD4/CD3+CD8 ratio showed the most significant differences between the non-smokers with S (both with/without LS) and the non-smokers with other ILDs (IPF, OIIPs, HP). These lymphocytes subsets were further altered in the non-smokers with CXR stage 2 compared to the non-smokers with other ILDs (IPF, OIIPs, HP). We did not observe any differences in these lymphocyte subsets and CD3+CD4+/CD3+CD8+ ratio between the non-smokers with advanced sarcoidosis stage (CXR ≥3) and the non-smokers with IPF. Our data on the non-smokers confirmed the presence of the typical BAL cellular profile in sarcoidosis. The BAL cellular profile was helpful namely for differentiation of less advanced sarcoidosis. Its definite diagnostic utility should be the subject of further clinical studies with large numbers of the well characterized patients taking into consideration other clinical factors influencing BAL cellular profile, such as smoking or treatment.

Study on prevalence of left ventricular diastolic dysfunction in chronic obstructive pulmonary disease

Background: Left ventricular diastolic dysfunction (LVD) is very common in chronic obstructive pulmonary disease (COPD) patients. The aim of the present study was to LVD function in COPD patients using echocardiogram and to detect the presence of LVD dysfunction in all stages of COPD.Methods: This was an observational study done at Institute of Internal Medicine, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai, during the period from March 2015 to August 2015. The study included 100 patients with COPD. All patients were subjected to chest X-ray, electrocardiogram, pulmonary function test (PFT) and echocardiogram.Results: The results showed the prevalence rate of LVD dysfunction in 80% patients with COPD. There was a good significant correlation between age (p&lt;0.001), status of smoking (p&lt;0.05), chest X-ray findings (p&lt;0.001) and stages of COPD (p&lt;0.001) with incidence of LVD in study population.Conclusions: High prevalence of LVD dysfunction was noticed in patients with COPD. Hence patients with COPD should undergo routine examinations timely to prevent the incidence of associated cardiovascular complications.

Lung cancer stage-shift following a symptom awareness campaign

BackgroundLung cancer outcomes in the UK are worse than in many other developed nations. Symptom awareness campaigns aim to diagnose patients at an earlier stage to improve cancer outcomes.MethodsAn early...

Annexin A11 (ANXA11) gene polymorphisms are associated with sarcoidosis in a Han Chinese population: a case–control study

ObjectivesTo further identify the single-nucleotide polymorphisms (SNPs) that contribute to the genetic susceptibility to sarcoidosis, we examined the potential association between sarcoidosis and 15 SNPs of the ANXA11 gene.DesignA case–control...

Serial chitotriosidase measurements in sarcoidosis – Two to five year follow-up study

Chitotriosidase (CTO) is a human chitinolytic enzyme secreted by activated macrophages and polymorphonuclear neutrophils. Albeit not specific for sarcoidosis, it is increased in over 90% of patients with active disease. The aims of this study were to correlate CTO measurements with clinical assessment of sarcoidosis and to test CTO as a marker of sarcoidosis relapse. 95 patients were followed-up for 24-60 months. Serial CTO measurements were performed every 3-6 months and correlated to clinical symptoms, lung function (FVC and DLco) and chest X-ray. In 38 patients clinical outcome status (COS) at 5 years was determined. Initial CTO levels were significantly higher in patients with impaired FVC/DLco (p=0.011 for both) but there was no correlation with standard chest X-ray stages. Patients with Loefgren's syndrome had significantly lower initial and control CTO level compared to other patients (p=0.011 and p=0.001, respectively). At follow-up there was a positive correlation of CTO and deterioration of clinical symptoms (p<0.001), chest X-ray (p<0.001) and FVC/DLco (p=0.012 and p=0.086, respectively). Control CTO levels were significantly lower in no disease groups versus minimal or persistent disease group as defined by COS (p=0.003 and p<0.001, respectively). At relapse CTO increased for 100% or more from baseline value in 12/14 patients. It was shown that CTO correlates with certain sarcoidosis phenotypes (Loefgren's syndrome, COS) and that serial measurements of CTO correlate with clinical symptoms, chest radiographs and lung function.

Sarcoidosis-associated pulmonary hypertension

Pulmonary hypertension is a serious complication of sarcoidosis. This review discusses clinical characteristics of patients with sarcoid-associated pulmonary hypertension (SAPH) and pitfalls in the diagnosis, and highlights potential therapies. SAPH is common in patients with advanced disease, but it can occur in patients with minimal disease burden. Risk factors for SAPH include restrictive lung physiology, hypoxemia, advanced Scadding chest X-ray stage, and low carbon monoxide diffusion capacity. Echocardiogram is a good initial screening tool in the diagnosis of pulmonary hypertension, but right heart catheterization is necessary to confirm the diagnosis. Treatment with pulmonary vasodilators, including endothelin antagonists, can lead to improvements in pulmonary hemodynamics in some patients but may not improve their exercise capacity. Forced vital capacity is an important predictor of exercise performance in patients with SAPH. Clinical observations and response to specific therapies for pulmonary hypertension suggest the presence of different SAPH phenotypes. Patients who complain of persistent dyspnea should be screened for the presence of pulmonary hypertension. The prognosis of SAPH is poor and it is prudent to consider referral of these patients for lung transplantation. In some patients with SAPH, treatment with anti-inflammatory agents and pulmonary vasodilators can lower pulmonary arterial pressures, improve dyspnea and functionality, and enhance overall quality of life.

HRCT findings of pulmonary sarcoidosis; relation to pulmonary function tests

BackgroundChest-X-ray has several limitations in detecting the extent of pulmonary disease in sarcoidosis. It might not reflect the degree of pulmonary involvement in patients with sarcoidosis when compared to computed tomography of the thorax. We aimed to investigate the HRCT findings of pulmonary sarcoidosis and to find out the existence of possible relations between HRCT findings and PFTs. In addition, we aimed to investigate the accordance between HRCT findings and conventional chest-X-ray staging of pulmonary sarcoidosis.Method45 patients with sarcoidosis with a mean age 29.7+/− 8.4 years were evaluated. Six of them were female and 39 were male. The type, distribution and extent of the parameters on HRCT/CTs were evaluated and scored. Chest-X-rays were evaluated for the stage of pulmonary sarcoidosis. Correlations were investigated between HRCT/CT parameter scores, Chest X-Ray stages and pulmonary function parameters.ResultsNodule, micronodule, ground glass opacity and consolidation were the most common HRCT findings. There were significant correlations between pulmonary function parameters, HRCT pattern scores, and chest-X-ray stages. A significant correlation between chest-x-ray score and total HRCT score was found.ConclusionsPulmonary sarcoidosis patients might have various pulmonary parenchymal changes on HRCT. Thorax HRCT was superior to chest-X-ray in detecting pulmonary parenchymal abnormalities. The degree of pulmonary involvement might be closely related to the loss of pulmonary function measured by PFTs. Chest-X-ray is considered to have a role in the evaluation of pulmonary sarcoidosis.

HRCT findings of pulmonary sarcoidosis; relation to pulmonary function tests

Background: Chest-X-ray has several limitations in detecting the extent of pulmonary disease in sarcoidosis. It might not reflect the degree of pulmonary involvement in patients with sarcoidosis when compared to computed tomography of the thorax. We aimed to investigate the HRCT findings of pulmonary sarcoidosis and to find out the existence of possible relations between HRCT findings and PFTs. In addition, we aimed to investigate the accordance between HRCT findings and conventional chest-X-ray staging of pulmonary sarcoidosis. Method: 45 patients with sarcoidosis with a mean age 29.7+/− 8.4 years were evaluated. Six of them were female and 39 were male. The type, distribution and extent of the parameters on HRCT/CTs were evaluated and scored. Chest-X-rays were evaluated for the stage of pulmonary sarcoidosis. Correlations were investigated between HRCT/ CT parameter scores, Chest X-Ray stages and pulmonary function parameters. Results: Nodule, micronodule, ground glass opacity and consolidation were the most common HRCT findings. There were significant correlations between pulmonary function parameters, HRCT pattern scores, and chest-X-ray stages. A significant correlation between chest-x-ray score and total HRCT score was found. Conclusions: Pulmonary sarcoidosis patients might have various pulmonary parenchymal changes on HRCT. Thorax HRCT was superior to chest-X-ray in detecting pulmonary parenchymal abnormalities. The degree of pulmonary involvement might be closely related to the loss of pulmonary function measured by PFTs. Chest-X-ray is considered to have a role in the evaluation of pulmonary sarcoidosis.

Inflammatory activity assessment by F18 FDG-PET/CT in persistent symptomatic sarcoidosis

Establishing inflammatory activity in sarcoidosis patients with persistent disabling symptoms is important. Whole body F(18)-FDG PET/CT (PET) appeared to be a sensitive method to detect inflammatory activity in newly diagnosed symptomatic sarcoidosis. The aim was to assess the presence of inflammatory activity using PET in sarcoidosis patients with unexplained persistent disabling symptoms and the association between PET findings and serological inflammatory markers. Sarcoidosis patients who underwent a PET between June 2005 and June 2010 (n = 89), were retrospectively included. All PET scans were examined and positive findings were classified as thoracic and/or extrathoracic. As serological markers of inflammatory activity angiotensin-converting enzyme (ACE), soluble interleukin-2 receptor (sIL-2R), and neopterin were considered. In 65/89 (73%) of the studied patients PET was positive, 52 of them (80%) had serological signs of inflammatory activity. In 14/15 patients with a Chest X-ray stage IV PET was positive. In 80% of the PET positive patients extrathoracic inflammatory activity was found. Sensitivity of combined serological inflammatory markers for the presence of inflammatory activity as detected by PET was 80%, specificity 100%, positive predictive value 100%, negative predictive value 65%. The majority of sarcoidosis patients with persistent disabling symptoms, even those with radiological stage IV, had PET positive findings with remarkably 80% extrathoracic lesions. In 20% PET was positive without signs of serological inflammatory activity. PET appeared to be of additional value to assess inflammatory activity in patients with persistent symptoms in the absence of signs of serological inflammatory activity and to detect extrathoracic lesions.

Systemic oxidative stress in patients with pulmonary sarcoidosis

Background A local redox imbalance has been reported in pulmonary sarcoidosis. However, so far no study has described a systemic redox imbalance in this context. The aim of the present study was to evaluate the systemic oxidative stress in patients with sarcoidosis and determine its relationship to treatment and indices of disease severity. Methods 35 patients with histologically proven pulmonary sarcoidosis and 13 healthy volunteers were included in the study. All patients were studied during a stable phase of their disease. Systemic oxidative stress was quantified in serum with the use of a commercially available spectrophotometric method (D-ROM test) which determines overall oxidative stress, by measuring total hydroperoxides. Oxidative stress was expressed in conventional units, i.e. Carratelli Units (UCarr), where 1 UCarr corresponds to 0.8 mg/L H 2O 2. Results Serum oxidative stress levels were significantly higher in patients with sarcoidosis compared to those of normal subjects (390 ± 25 vs 300 ± 18 UCarr respectively, p = 0.04). Patients not receiving systemic corticosteroids had higher levels of oxidative stress compared to steroid-treated patients (461.5 ± 38 vs 315 ± 20, p < 0.01) and compared to controls (461.5 ± 38 vs 300 ± 18 UCarr, p < 0.01). Oxidative stress did not correlate with diffusion lung capacity (DLCO), partial arterial oxygen tension (PaO 2), MRC dyspnoea scale or chest X-ray stage. Conclusions Systemic oxidative stress is increased in patients with stable pulmonary sarcoidosis who do not receive systemic corticosteroids. This finding suggests a sustained oxidative burden even when clinical, functional and radiological criteria indicate disease stability.

Protein levels of CC chemokine ligand (CCL)15, CCL16 and macrophage stimulating protein in patients with sarcoidosis

The objective of this study was to assess protein levels for candidate cytokines, chemokines, growth factors, matrix metalloproteinases and their inhibitors in bronchoalveolar lavage fluid (BALF) in patients with polar forms of pulmonary sarcoidosis, i.e. Löfgren's syndrome (LS) and more advanced chest X-ray (CXR) stage III disease. Twenty-four inflammatory molecules were analysed in unconcentrated BALF samples from 10 sarcoidosis patients with CXR stage III and 10 patients with LS by semiquantitative protein array. Four novel molecules [CC chemokine ligand (CCL)15, CCL16, macrophage migration inhibitory factor (MIF) and macrophage stimulating protein (MSP)], detected for the first time in association with sarcoidosis, were then quantified by enzyme-linked immunosorbent assay in a second cohort of 68 sarcoidosis patients and 17 control subjects. The protein levels of CCL15, CCL16, CCL24, CXCL8, CXCL9, CXCL10, interleukin-16, MIF, MSP and matrix metallopeptidase 1 were increased in CXR stage III patients when compared with patients with LS. CCL15 and MSP up-regulation in CXR stage III patients in comparison with LS patients and controls was confirmed by enzyme-linked immunosorbent assay. Moreover, MSP was associated with treatment requirement (P = 0.001) and CCL15 was elevated in patients with disease progression at 2-year follow-up (P = 0.016). CCL16 levels were increased in sarcoidosis versus controls (P < 0.05), but no difference was observed between patient subgroups. MIF up-regulation was not confirmed in a larger patient group. In conclusion, chemokines CCL15, CCL16 and MSP were found elevated for the first time in BALF from sarcoidosis patients; our results showed that CCL15 and MSP may affect disease course.

Uveitis with Biopsy-proven Sarcoidosis in Chinese—A Study of 60 Patients in a Uveitis Clinic Over a Period of 20 Years

The aim of this study was to assess the clinical features of uveitis with biopsy-proven sarcoidosis in Chinese patients. This was a retrospective study of uveitis patients with biopsy-proven sarcoidosis who consecutively visited the uveitis clinic of Taipei Veterans General Hospital from 1986 to 2005. Medical records were reviewed to obtain demographic data, initial symptoms, biopsy sites, pulmonary conditions detected by chest X-ray and manifestations of uveitis. From 2002 onwards, patients also received chest computed tomography (CT). A total of 60 uveitis patients with biopsy-proven sarcoidosis were identified. Forty-four patients (73%) were found in the last 4 years. Female predominance with a male-to-female ratio of 1:6.5 was found. The most common initial symptom was uveitis in 41 patients (68%). The most common positive biopsy sites were mediastinal lymph nodes, lung, conjunctiva and skin. Twenty (90.9%) of 22 patients with chest X-ray stage 0 showed >or= stage 1 on CT. The mean age at uveitis onset was 47.7+/-14.7 years (range, 21-76 years), with no gender difference (p=0.913). A peak incidence was found in the 6th decade of life. There was bilateral eye involvement in 54 patients (90%). Frequency of the manifestations of uveitis showed isolated anterior uveitis in 2 patients (3.3%), isolated posterior uveitis in 8 patients (13.3%), intermediate and posterior uveitis (i.e. anterior uveitis sparing) in 16 patients (26.7%), and panuveitis in 34 patients (56.7%). A marked increase was noted since 2002. One of the causes is the performance of chest CT. Chest CT is useful to discover mediastinal lymphadenopathy and other lesions suggestive of sarcoidosis, as well as to help guide tissue confirmation in patients with peculiar uveitis features indicative of sarcoidosis. Female predominance and peak incidence of uveitis onset in the 6th decade of life were found. The posterior segment was the most common localization of uveitis in biopsy-proven sarcoidosis in Chinese.

Differences in Clinical Findings between Caucasians and African Americans with Biopsy-Proven Sarcoidosis

To study the prevalence of ocular manifestations in African American and Caucasian patients with biopsy-proven sarcoidosis at the initial ophthalmic examination and to determine the relationship between angiotensin-converting enzyme (ACE) levels, chest x-ray findings, and ocular signs of sarcoidosis. Retrospective, cross-sectional, observational study. Eighty-one consecutive patients with biopsy-proven sarcoidosis seen at the Doheny Eye Institute from January 1989 through April 2005. Medical records were reviewed to obtain demographic data, biopsy site, initial ocular findings, pulmonary symptoms, and results of serum ACE levels and chest x-rays. Associations between ACE level/chest x-ray stages and ocular manifestations related to sarcoidosis were obtained from these data. Ocular manifestations related to sarcoidosis. Of the 81 patients, 35 were Caucasian; 29 were African American; and the remaining 17 were Hispanic, Asian Indian, and other races. Female patients were older than males (P = 0.05). Sixty-five (80%) of the 81 patients had ocular manifestations related to sarcoidosis. Thirty-three patients (40.7%) had uveitis, 12 (14.8%) had adnexal granulomas, and 25 (30.8%) had keratoconjunctivitis sicca. Of the 33 patients with uveitis, 22 presented with nongranulomatous inflammation. There was no significant association between ocular manifestations related to sarcoidosis and serum ACE levels (P = 0.43) or chest x-ray stage (P>0.99). Of the 29 African American patients, 26 (89.7%) had ocular manifestations related to sarcoidosis, compared with 24 (68.6%) of the 35 Caucasians (P = 0.12). The African American patients were younger (mean age, 44.4 years) than the Caucasian patients (mean age, 52.0) (P = 0.003) and had higher mean ACE levels (P = 0.003). A significantly high proportion of African American males presented with uveitis (P = 0.005), and a significantly high proportion of African American females presented with adnexal granulomas (P = 0.05). The present study reveals that patients with sarcoidosis can present initially with clinical features of nongranulomatous uveitis. Relative to Caucasians, African American patients with sarcoidosis tend to be younger when they first present to the ophthalmologist and to present with uveitis and/or adnexal granuloma. Serum ACE levels and chest x-ray stages may not help predict the occurrence of ocular changes in sarcoidosis.

Protein Profiles of Bronchoalveolar Lavage Fluid from Patients with Pulmonary Sarcoidosis

Pulmonary sarcoidosis is a multisystem granulomatous disease with various clinical phenotypes. So far, there has been little information on protein patterns (PPs) of bronchoalveolar lavage fluid (BALF) from patients with sarcoidosis and no data are available on PPs in clinical disease subtypes. To investigate the PP of BALF from patients with pulmonary sarcoidosis, to evaluate whether PPs reflect disease course as assessed by chest X-ray (CXR), and to compare PPs between patients with/without Löfgren's syndrome. Surface-enhanced laser desorption/ionization-time-of-flight mass spectroscopy was applied to investigate PPs in unconcentrated BALF from 65 patients (CXR stage I, n = 32; CXR stage II, n = 22, CXR stage III, n = 11) and 23 healthy control subjects. The Mann-Whitney U test was used to detect differentially expressed protein peaks. After reversed-phase fractionation, peptide fingerprint mapping and immunodepletion were used to identify deregulated (up-regulated or down-regulated) proteins. Forty differentially expressed protein entities (2.75-185.62 kD) were detected in patients with pulmonary sarcoidosis versus control subjects (p < 0.05). Whereas 13 peaks (33%) were present across all CXR stages, 27 (67%) were specific for particular CXR stages. Comparison of PPs between CXR stage I patients with or without Löfgren's syndrome revealed 25 differentially expressed peaks. The total number of deregulated peaks and also of those associated with sarcoidosis as a whole were markedly lower in patients with Löfgren's syndrome in comparison with other sarcoid phenotypes. Human serum albumin, alpha1-antitrypsin, and protocadherin-2 precursor were identified from sarcoidosis-associated PP. Surface-enhanced laser desorption/ionization-time-of-flight mass spectroscopy enables determination of protein patterns in sarcoid BALF and allows detection of protein patterns linked to a particular disease course.

Finite Paths are Universal

The type and mode of presentation of pulmonary sarcoidosis (radiologic stage, activity) influence alveolar lymphocyte number and subsets as well as other inflammatory cells. To investigate the variations in alveolar cells, lymphocyte subsets and NK-cells in different radiological stages of active pulmonary sarcoidosis. 85 untreated, newly diagnosed patients (32 male, 53 female), median age 47.2+/-14.7 years were investigated. Patients were classified into chest x-ray stages (33 stage I, 27 stage II, 14 stage III and 11 stage IV disease). Bronchoalveolar lavage was performed with 4 portions of 50 mL. Total cells and cell differentials were counted, while CD3+, CD4+, CD8+, CD19+, CD3-CD16/56+ (NK-cells) and CD3+CD16/56+ (NKT-cells) were determined by flow cytometry. Lymphocytosis was high in all stages. Significant differences were found in: a) CD4 between stages I and II and I and IV. b) CD8 between stages I and IV and c) NK and NKT cells between stages I and III. Variations were observed in alveolar cells and lymphocyte subsets in different stages of pulmonary sarcoidosis. Cells exhibiting cytotoxic activity were increased with stage progression, CD8 from stage I to IV, NK and NKT cells from stage I to III. These cells may be involved in the inflammatory process regulating granuloma formation.

Expression of macrophage inflammatory protein-3 beta/CCL19 in pulmonary sarcoidosis.

In this study, messenger RNA (mRNA) expression for novel T lymphocyte chemoattractants, leukotactin-1, macrophage inflammatory protein (MIP)-3 alpha and MIP-3 beta was investigated in bronchoalveolar lavage fluid (BALF) cells from patients with sarcoidosis, a T cell-mediated disease with typical CD4+ lymphocyte alveolitis. Of these three chemokines, only MIP-3 beta mRNA was upregulated in sarcoidosis, and therefore, protein levels of this chemokine, its pharmacologic regulation, and association with disease clinical course were explored. MIP-3 beta protein concentrations were elevated in BALF from sarcoid patients compared with control subjects (p = 0.001) and in patients with chest X-ray stage II chemokine protein levels were increased compared with stage I (p = 0.003). MIP-3 beta protein was associated predominantly with alveolar macrophages and correlated with BALF lymphocytes and T cell subsets. mRNA expression for the MIP-3 beta receptor, CC chemokine receptor 7, was increased in sarcoidosis and correlated with MIP-3 beta protein levels. MIP-3 beta mRNA and protein expression in BALF cells was suppressed by dexamethasone and cyclosporine A in vitro. In conclusion, MIP-3 beta is implicated in T lymphocyte recruitment in sarcoidosis, is associated with disease progression, and is downregulated by drugs used for sarcoidosis treatment. This novel chemokine, therefore, represents a candidate for studies of sarcoidosis pathobiologic mechanisms.