A Concise Review of Pulmonary Sarcoidosis

Article · October 2010with61 Reads
DOI: 10.1164/rccm.201006-0865CI · Source: PubMed
This is an update on sarcoidosis, focusing on etiology, diagnosis, and treatment. In the area of etiopathogenesis, we now have a better understanding of the immune response that leads to the disease as well as genetic factors that modify both the risk for the disease and its clinical outcome. Several groups have also identified possible agents as a cause for sarcoidosis. Although none of these potential causes has been definitely confirmed, there is increasing evidence to support that one or more infectious agents may cause sarcoidosis, although this organism may no longer be viable in the patient. The diagnosis of sarcoidosis has been significantly aided by new technology. This includes the endobronchial ultrasound, which has been shown to increase the yield of needle aspiration of mediastinal and hilar lymph nodes. The positive emission tomography scan has proven useful for selecting possible biopsy sites by identifying organ involvement not appreciated by routine methodology. It has also helped in assessing cardiac involvement. The biologic agents, such as the anti-tumor necrosis factor antibodies, have changed the approach to refractory sarcoidosis. There is increasing evidence that the clinician can identify which patient is most likely to benefit from such therapy. As new and more potent antiinflammatory agents have been developed, it is clear that there are other factors that burden the patient with sarcoidosis, including fatigue and sarcoidosis-associated pulmonary hypertension. There have been several recent studies demonstrating treatment options for these problems.
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    • HP was diagnosed by the presence of compatible clinical manifestations with a non-necrotizing granulomatous interstitial bronchiolocentric pneumonitis [11]. The diagnosis of sarcoidosis was made on the basis of the compatible clinical pictures and histologic demonstration of noncaseating granulomas [12, 13] The diagnosis of HP and sarcoidosis needed exclusion of other diseases capable of producing a similar histologic picture: Biopsy tissues were subjected to special stains (acid fast bacilli stain and Gömöri methenamine silver stain) to rule out microorganisms and fungi. IPF patients were evaluated using serial FVC and DLCO measurements .
    [Show abstract] [Hide abstract] ABSTRACT: Background Idiopathic pulmonary fibrosis (IPF) is characterized by the complex interaction of cells involved in chronic inflammation and fibrosis. Global gene expression of a homogenous cell population will identify novel candidate genes. Methods Gene expression of fibroblasts derived from lung tissues (8 IPF and 4 controls) was profiled, and ontology and functional pathway were analyzed in the genes exhibiting >2 absolute fold changes with p-values < 0.05. CCL8 mRNA and protein levels were quantified using real-time PCR and ELISA. CCL8 localization was evaluated by immunofluorescence staining. Results One hundred seventy eight genes differentially expressed and 15 genes exhibited >10-fold change. Among them, 13 were novel in relation with IPF. CCL8 expression was 22.8-fold higher in IPF fibroblasts. The levels of CCL8 mRNA and protein were 3 and 9-fold higher in 14 IPF fibroblasts than those in 10 control fibroblasts by real-time PCR and ELISA (p = 0.022 and p = 0.026, respectively). The CCL8 concentrations in BAL fluid was significantly higher in 86 patients with IPF than those in 41 controls, and other interstitial lung diseases including non-specific interstitial pneumonia (n = 22), hypersensitivity pneumonitis (n = 20) and sarcoidosis (n = 19) (p < 0.005, respectively). Cut-off values of 2.29 pg/mL and 0.43 pg/mL possessed 80.2 and 70.7% accuracy for the discrimination of IPF from NC and the other lung diseases, respectively. IPF subjects with CCL8 levels >28.61 pg/mL showed shorter survival compared to those with lower levels (p = 0.012). CCL8 was expressed by α-SMA-positive cells in the interstitium of IPF. Conclusions Transcriptome analysis identified several novel IPF-related genes. Among them, CCL8 is a candidate molecule for the differential diagnosis and prediction of survival. Electronic supplementary material The online version of this article (doi:10.1186/s12931-016-0493-6) contains supplementary material, which is available to authorized users.
    Full-text · Article · Dec 2017
    • We demonstrated previously that after in vitro stimulation of PBMCs with FCWAs alone, the secretion of TNF-?, IL- 6, IL-10 and IL-12 was higher in patients with sarcoidosis compared to healthy subjects [20]. These cytokines have all been implicated in the immunopathogenesis of sarcoidosis [1,[23][24][25]. Since FCWAs and LPS might have a synergistic effect on the immune responses of patients with sarcoidosis, we investigated in the present study the in vitro synthesis of inflammatory cytokines in PBMCs after co-stimulation with FCWAs and LPS.
    [Show abstract] [Hide abstract] ABSTRACT: Background Composition of organic dust is very complex, involving particles of microbial, animal and plant origin. Several environmental exposure studies associate microbial cell wall agents in organic dust with various respiratory symptoms and diseases. The aim of the present study was to investigate the in vitro effects of the co-exposure of fungal cell wall agents (FCWAs) and bacterial lipopolysaccharide (LPS) on inflammatory immune responses of peripheral blood mononuclear cells (PBMCs) from patients with pulmonary sarcoidosis. MethodsPBMCs from 22 patients with pulmonary sarcoidosis and 20 healthy subjects were isolated and stimulated in vitro with FCWAs (soluble and particulate (1???3)-?-D-glucan, zymosan and chitosan) and/or LPS. Subsequently, cytokines were measured by ELISA and the mRNA expression of dectin-1, toll-like receptor 2 (TLR2), TLR4 and mannose receptor (MR) was analysed by real-time RT-PCR. ResultsPatients with sarcoidosis had a significantly higher secretion of inflammatory cytokines tumour necrosis factor-alpha (TNF-?), interleukin-6 (IL-6), IL-10 and IL-12 (1.7-fold, 2.0-fold, 2.2-fold, and 2.8-fold, respectively; all p?<?0.05) after in vitro co-stimulation of PBMCs with FCWAs and LPS. We showed that PBMCs from patients with sarcoidosis had a higher baseline mRNA expression of dectin-1, TLR2, TLR4 and MR (6-fold, 11-fold, 18-fold, and 4-fold, respectively). Furthermore, we found a reduced expression of dectin-1, TLR2 and TLR4 after stimulation with FCWAs and/or LPS, although the reduction was significantly weaker in patients than in healthy subjects. Conclusions In conclusion, co-stimulation with FCWAs and LPS of PBMC from patients with sarcoidosis caused a weaker reduction of dectin-1, TLR2, TLR4 receptors expression, which could increase the sensitivity of PBMCs, leading to excessive inflammatory cytokine responses and result in the development or progression of pulmonary sarcoidosis.
    Full-text · Article · Dec 2016
    • Sarcoidosis is an idiopathic granulomatous disease that can affect every organ system, most commonly the lungs, which are involved in over 90% of cases.[1, 2] There are numerous clinical manifestations of pulmonary sarcoidosis, including pulmonary nodules, fibrotic lung disease, airway hyperreactivity, mucosal nodules and plaques, bronchostenosis, and bronchiectasis.[3] The most common cause of bronchiectasis in sarcoidosis is traction bronchiectasis and has been reported in up to 40% of patie
    [Show abstract] [Hide abstract] ABSTRACT: Sarcoidosis is an idiopathic disease that most commonly involves the lungs and is characterized by granulomatous inflammation. Bronchiectasis is one pulmonary manifestation of sarcoidosis, although it is almost always observed as traction bronchiectasis in the setting of fibrotic lung disease. A 50-year-old woman was evaluated for chronic cough and bronchiectasis with a small amount of peripheral upper lobe honeycombing and no significant pulmonary fibrosis or lymphadenopathy. After an extensive laboratory and imaging evaluation did not identify a cause of her bronchiectasis, bronchoscopy was performed to assess for primary ciliary dyskinesia and revealed a diffuse cobblestone appearance of the airway mucosa. Endobronchial biopsies and lymphocyte subset analysis of bronchoalveolar lavage fluid were consistent with a diagnosis of sarcoidosis. We believe endobronchial sarcoidosis should be included in the differential diagnosis of patients presenting with bronchiectasis.
    Full-text · Article · Nov 2016
    • Serum ACE and vitamin D levels are often elevated. Biopsy shows non-caseating granulomas, but this is not a pathognomonic finding; other entities such as rheumatoid arthritis, foreign-body reactions (including inhalational diseases) and fungal infection must be excluded [1, 2]. Although musculoskeletal complaints are commonly associated with sarcoidosis, radiographically apparent bone disease is uncommon and is rarely seen at presentation.
    [Show abstract] [Hide abstract] ABSTRACT: We report a case of fulminant sarcoidosis in a 28-year-old man presenting with skin nodules, multifocal small and large joint arthralgias, and blurred vision. Characteristic bone, soft tissue, articular, and CNS findings were evident on multimodality imaging. Bony abnormalities included near-complete destruction of a distal phalanx, “lace-like” lucent lesions, erosive arthritis, lytic lesions with and without sclerotic margins, and bone marrow replacement visible only on MRI. The extent of bony disease at time of presentation was unusual. We review the widely varying reported prevalence of imaging findings of bony sarcoidosis in the literature, and discuss reasons for this variability. We found that musculoskeletal findings at US and MRI were less specific than radiographic and CT findings, but were useful in quantifying extent of disease.
    Article · Sep 2016
    • BALF = bronchoalveolar lavage fluid. macrophages and CD4+ T cells participate in the influx of mononuclear cells into the alveoli that often precedes sarcoid granuloma formation in the lung (Baughman et al., 2011; Jones, 2002). Diagnostic studies have reported highly variable sensitivity and specificity when using the CD4/CD8 ratio, prompting us to perform what we believe to be the first meta-analysis to assess the available evidence on the diagnostic usefulness of this ratio in sarcoidosis.
    [Show abstract] [Hide abstract] ABSTRACT: Background: The usefulness of bronchoalveolar lavage fluid (BALF) CD4/CD8 ratio for diagnosing sarcoidosis has been reported in many studies with variable results. Therefore, we performed a meta-analysis to estimate the overall diagnostic accuracy of BALF CD4/CD8 ratio based on the bulk of published evidence. Methods: Studies published prior to June 2015 and indexed in PubMed, OVID, Web of Science, Scopus and other databases were evaluated for inclusion. Data on sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were pooled from included studies. Summary receiver operating characteristic (SROC) curves were used to summarize overall test performance. Deeks's funnel plot was used to detect publication bias. Results: Sixteen publications with 1885 subjects met our inclusion criteria and were included in this meta-analysis. Summary estimates of the diagnostic performance of the BALF CD4/CD8 ratio were as follows: sensitivity, 0.70 (95%CI 0.64-0.75); specificity, 0.83 (95%CI 0.78-0.86); PLR, 4.04 (95%CI 3.13-5.20); NLR, 0.36 (95%CI 0.30-0.44); and DOR, 11.17 (95%CI 7.31-17.07). The area under the SROC curve was 0.84 (95%CI 0.81-0.87). There was no evidence of publication bias. Conclusion: Measuring the BALF CD4/CD8 ratio may assist in the diagnosis of sarcoidosis when interpreted in parallel with other diagnostic factors.
    Full-text · Article · Apr 2016
    • Stage II is defined by adenopathy plus pulmonary infiltrates, stage III by pulmonary infiltrates alone and stage IV includes radiographic evidence of pulmonary fibrosis. More recently stage 0 has been added when the chest roentgenogram shows none of these abnormal- ities [2]. Bronchoscopic procedures are most often done for detection of granulomas because the lung and hilar or mediastinal lymph nodes are the most affected sites in sarcoidosis [3].
    [Show abstract] [Hide abstract] ABSTRACT: Sarcoidosis is a chronic systemic granulomatous disorder of unknown etiology, which most commonly presents with bilateral hilar adenopathy and pulmonary infiltrates. Fiberoptic bronchoscopic procedures are the most important tools for the diagnosis sarcoidosis. Purpose: A retrospective study was done to evaluate the efficacy and safety of bronchoscopic diagnostic procedures in pulmonary sarcoidosis. Patients and methods: This retrospective study was done by reviewing the records of the bronchoscopic procedures and pathological reports performed between May 2012 and September 2015 to assess the diagnostic yield, and safety and bronchoscopic procedures (TBNA, EBB and TBLB) of cases of sarcoidosis done in the bronchoscopy unit of Chest Department, Mansoura University. We included adult patients with mediastinal lymphadenopathy with or without diffuse pulmonary infiltrate with suspected sarcoidosis with indicated fiberoptic bronchoscopy and excluded patients unfit for FOB with uncorrectable bleeding diathesis, patients with uncontrolled cardiac comorbidities and respiratory failure. The diagnostic yield and complications were the endpoints of our study. Results: Regarding the diagnostic yield, TBNA showed the diagnosis of 4 out of 8 patients (50%) in stage I and 3 out of 5 patients (60%) in stage II. In all the studied cases, TBNA showed the diagnosis of 7 out of 13 patients (53.8%). EBB showed the diagnosis of 2 out of 2 (100%) in stage I, 1 out of 2 patients (50%) in stage II and 1 out of 2 patients (50%) in stage III. In all the studied cases, EBB showed the diagnosis of 4 out of 6 patients (66.7%). TBLB∕EBB showed the diagnosis of 6 out of 12 patients (50%) in stage II and diagnosis of 4 out of 7 patients (57%) in stage III. In all the studied cases, TBLB∕EBB showed the diagnosis of 10 out of 19 patients (52.6%). Pneumothorax developed only in 4 patients (12%), hemoptysis developed in 5 patients (16%) and no procedure related mortality. Conclusion: The bronchoscopic diagnostic procedures (TBNA, EBB and TBLB) are effective and safe in the diagnosis of pulmonary sarcoidosis.
    Full-text · Article · Apr 2016
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