Correlation of the High-Resolution Computed Tomography Patterns of Intrathoracic Sarcoidosis with Serum Levels of SAA, CA 15.3, SP-D, and Other Biomarkers of Interstitial Lung Disease.

Studies on the serum biomarkers of granulomatous inflammation and pulmonary interstitial disease in intrathoracic sarcoidosis have shown conflicting results. We postulated that differences in the concentrations of serum biomarkers can be explained by the heterogenous patterns of sarcoidosis seen on thoracic HRCT. Serum biomarker levels in 79 consecutive patients, newly diagnosed with intrathoracic sarcoidosis, were compared to our control group of 56 healthy blood donors. An analysis was performed with respect to HRCT characteristics (the presence of lymph node enlargement, perilymphatic or peribronchovascular infiltrates, ground-glass lesions, or fibrosis), CXR, and disease extent. Serum levels of CXCL9, CXCL10, CTO, and CCL18 were statistically significantly increased in all patients compared to controls. Serum levels of CA15.3 were statistically significantly increased in all patients with parenchymal involvement. SAA was increased in patients with ground-glass lesions while SP-D levels were statistically significantly increased in patients with lung fibrosis. Only SP-D and CA15.3 showed a significant correlation to interstitial disease extent. In conclusion, we found that sarcoidosis patients with different HRCT patterns of intrathoracic sarcoidosis have underlying biochemical differences in their serum biomarkers transcending Scadding stages. The stratification of patients based on both radiologic and biochemical characteristics could enable more homogenous patient selection for further prognostic studies.

How to obtain good morphology and antigen detection in the same tissue section?

Most human and animal biopsy samples are routinely embedded in paraffin since this enables the pathologist or researcher to obtain excellent morphology and simplifies storage. Nevertheless, in many cases, the antigen of interest cannot be detected in paraffin section. The alternative available for good immunohistochemistry is preparation of cryosections, which usually provide decent antigen preservation and are frequently used for immunofluorescence. However, cryosections often do not provide efficient morphological details of tissues and cells for pathologic evaluation. In order to obtain good antigen preservation and improve tissue and cell morphology after freezing, we tested three different fixations and freezing methodologies and compared them to routine formaldehyde fixation and paraffin embedding. As a model system, we selected the epithelium of the rat urinary bladder and trachea. On all samples, haematoxylin and eosin staining was performed as well as immunofluorescence with antibodies against tight junction protein ZO-1 and against intermediate filament cytokeratin 7. The best compromise between morphology and immunofluorescence was obtained with "sucrose impregnation prior to freezing" method. Moreover, this procedure is also quicker in comparison to standard paraffin section preparation. To check the clinical relevance of our study, this method was used for human biopsy samples of neoplastic urothelial and bronchial mucosa lesions. Besides good immunofluorescence results, the morphology of these samples was well preserved. We therefore propose that cryosection preparation with sucrose impregnation prior to freezing should be further exploited in other clinical and veterinary applications, since it enables good morphology and antigen preservation.

ß-glucan in the lymph nodes in sarcoidosis and in Kveim-Siltzbach test reagent.

Background: Previous studies have demonstrated a relationship between biomass of fungi exposure in the home and the risk of sarcoidosis. ß-glucan was present in the bronchial alveolar lavage fluid (BALF) of patients with sarcoidosis. The Kveim-Siltzbach test reagent (KSTR) induces a sarcoidosis specific, granulomatous, cutaneous response and was used to establish the diagnosis. To date, the granuloma-inducing component of KSTR is still unknown. The present study was undertaken to investigate the presence of ß-glucan in the lymph nodes of patients with sarcoidosis and to determine the relationship between the amounts of this agent with disease severity and to investigate the presence of ß-glucan in KSTR. Materials and methods: Lymph node aspirations were collected by transbronchial needle aspiration (TBNA) in region R4 or 7 from patients with newly diagnosed sarcoidosis. The samples were treated to isolate ß-glucan and analyzed using a Limulus-based assay. Cultures of Propionibacterium ac. and Mycobacterium gordonae as well as samples of Kveim-Siltzbach test reagent were analyzed to determine ß-glucan content. Results: A significant relationship was observed between the amount of the ß-glucan in the lymph nodes and the extent of granuloma formation in the lung parenchyma, and the size of the lymph nodes in the mediastinum (r=0.787, p=0.0001 and r=0.664, p<0.001 respectively, Spearman's test). The samples of Kveim-Siltzbach test reagent contained high levels of ß-glucan. Cultures of Propionibacterium ac. and Mycobacterium gordonae contained ß-glucan, the levels of which were lower in the Mycobacterium cultures. Comments: The results support the hypothesis that ß-glucan, and thus fungal exposure, are involved in the pathogenesis of sarcoidosis. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 130-135).

Fungal cell wall agents and bacterial lipopolysaccharide in organic dust as possible risk factors for pulmonary sarcoidosis.

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. METHODS: PBMCs from 22 patients with pulmonary sarcoidosis and 20 healthy subjects were isolated and stimulated in vitro with FCWAs (soluble and particulate (1 → 3)-ß-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. RESULTS: Patients with sarcoidosis had a significantly higher secretion of inflammatory cytokines tumour necrosis factor-alpha (TNF-α), 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.

Bronchoalveolar lavage chitotriosidase activity as a biomarker of sarcoidosis.

BACKGROUND: Chitotriosidase (CTO) was shown to be a good biomarker of sarcoidosis. Increased levels in bronchoalveolar lavage fluid (BALF) were reported and associated with more severe forms of the disease. OBJECTIVES: The aim of the study was to evaluate the value of CTO in BALF as a routine biomarker of sarcoidosis. METHODS: The study included 85 patients in 9 control subjects in whom serum and BALF CTO were measured. RESULTS: Significantly higher CTO levels were detected in BALF of sarcoidosis patients than in control subjects (p < 0.001). There was good correlation between serum and BALF CTO levels in sarcoidosis patients (Spearman's Rho 0.481, p < 0.001). Serum but not BALF CTO had good correlation with clinical parameters. Only in a group of patients with BALF CTO above upper normal range there was association of BALF CTO with impaired FVC (p = 0.020) and chest radiograph score (0-2 vs. 3-4, p = 0.016). CONCLUSIONS: In comparison to serum CTO no additional benefit of determining CTO in BAL for routine sarcoidosis workup was shown.

Frequency of IWOS Suggestive Ocular Signs in Slovenian Uveitis Patients with Confirmed Pulmonary Sarcoidosis.

PURPOSE: To investigate the prevalence of suggestive signs for ocular sarcoidosis proposed by the International Workshop on Ocular Sarcoidosis (IWOS) in patients with sarcoidosis-associated uveitis. METHODS: A retrospective study included 53 patients (77% female), with uveitis, who were seen in the period of 2010-2013 at the University Eye Hospital Ljubljana, Slovenia. All patients had confirmed pulmonary sarcoidosis based on clinical presentation, imaging and lung biopsy according to the ATS/ERS criteria. The presence of the seven clinical signs, suggested by the IWOS was determined in 47 patients with sufficient clinical data. RESULTS: Patients commonly exhibited bilaterality (79%), keratic precipitates/iris nodules (49%), and multiple chorioretinal peripheral lesions (36%). Three or more signs were observed in 40% (19/47) of patients or 79% (11/14) of patients with primary ocular involvement. CONCLUSIONS: Results add to the validation of IWOS criteria and emphasize the high percentage of at least three suggestive for ocular sarcoidosis in patients with primary ocular involvement.

Common chitotriosidase duplication gene polymorphism and clinical outcome status in sarcoidosis.

BACKGROUND: Chitotriosidase has been found to be useful as a sarcoidosis biomarker. In patients with better outcome lower values were observed. Some subjects have 24-base pair duplication in the chitotriosidase gene (CHIT1) that results in the production of inactive enzyme. This might influence the outcome of sarcoidosis and account for described observations. OBJECTIVES: The aim of this study was to correlate common CHIT1 duplication polymorphism and clinical outcome status in sarcoidosis (COS). METHODS: This retrospective study comprised 180 patients with sarcoidosis. COS at 3, 5 and 10 years was determined and correlated with CHIT1 24-base pair duplication polymorphism. CHIT1 genotyping was done by the PCR method. RESULTS: There was no significant correlation between CHIT1 24-base pair duplication polymorphism and COS at 3, 5 or 10 years but a subgroup analysis showed higher frequency of patients with Loefgren's syndrome (50% vs. 17.1%) and better COS in CHIT1 24-base pair duplication homozygotes vs. all other subjects in major COS groups (no, minimal and persistent disease) at 3 years (p=0.025) and borderline significant at 5 years (p = 0.090). CONCLUSIONS: In this study no correlation between CHIT1 24-base pair duplication polymorphism and COS was shown, but possible protective role of homozygous condition for CHIT1 24-base pair duplication polymorphism is suggested.

The effect of cardioprotective diet rich with natural antioxidants on chronic inflammation and oxidized LDL during cardiac rehabilitation in patients after acute myocardial infarction.

BACKGROUND: Chronic inflammation, the fundamental pathogenetic process of atherosclerosis, can be modified by pharmacological and non-pharmacological measures as a part of secondary prevention after acute myocardial infarction (AMI). The aim of our study was to determine the effect of diet, rich with natural antioxidants, added to physical activity (as a part of cardiac rehabilitation (CR) program) on inflammatory markers and ox-LDL, a marker of oxidative stress, closely involved in the process of chronic inflammation. METHODS: 41 male patients after AMI undergoing CR were divided into a diet group (supervised cardioprotective diet throughout the CR), and control group (CR without diet). We measured hsCRP, leucocytes, neutrophils, IL-6, oxLDL, exercise capacity and classic risk factors before and after CR program. RESULTS: Patients from the diet group presented with a significant decline in classic risk factors (BMI, waist circumference, waist to hip ratio, systolic blood pressure, heart rate, blood glucose, total cholesterol, LDL, TAG) and inflammatory markers (hsCRP, leucocytes, neutrophils) compared to control group. Furthermore, when studying nonsmokers, we observed significant decline of oxLDL in the diet group. CONCLUSIONS: The addition of cardioprotective diet, rich with natural antioxidants, to physical activity as a part of a CR program, positively modifies not just classic risk factors and exercise capacity, but also diminishes chronic inflammation markers. These effects, and oxLDL decline were most prominent in nonsmoking patients.

Sarcoidosis treatment with antifungal medication: a follow-up.

INTRODUCTION: The aim of the study was to compare treatment of sarcoidosis with antifungal or corticosteroid medication. METHODS: In patients with sarcoidosis antifungal medication (n = 29), corticosteroids (n = 21) or a combination (n = 27) was given. Nine patients allotted to antifungal medication were later given corticosteroids because of the lack of regression of the disease. X-ray scores for the severity of granuloma infiltration were determined. Chitotriosidase and angiotensin converting enzyme were determined. The time in months till remission was observed as well as the number of recurrences.

Fungal exposure and low levels of IL-10 in patients with sarcoidosis.

BACKGROUND AND OBJECTIVES: Sarcoidosis is an inflammatory disease with increased levels of inflammatory cytokines. Previous studies have shown a relation between the degree of granuloma infiltration and serum cytokine levels, except for interleukin- (IL-) 10. The aim of the study was to further investigate the serum levels of IL-10 in patients with sarcoidosis and relate them to fungal exposure in terms of the amount of fungi in the air of their homes and ß-glucan in bronchoalveolar lavage (BAL) fluid. METHODS: Patients with sarcoidosis (n = 71) and healthy controls (n = 27) were enrolled. IL-10 was determined in serum. BAL was performed and the amount of ß-glucan was measured. Domestic exposure to fungi was determined by measuring airborne ß-N-acetylhexosaminidase (NAHA) in the bedrooms. RESULTS: At high levels of fungal exposure (domestic fungal exposure and ß-glucan in BAL), serum IL-10 values were lower than at low and intermediate exposure levels. CONCLUSION: The low serum IL-10 values at high fungal exposure suggest that fungal cell wall agents play a role in granuloma formation in sarcoidosis by inhibiting the secretion of the anti-inflammatory cytokine IL-10.

Serial chitotriosidase measurements in sarcoidosis--two to five year follow-up study.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The effect of short-term cardiac rehabilitation after acute myocardial infarction on high-sensitivity C-reactive protein.

BACKGROUND: High-sensitivity C-reactive protein (hsCRP) is an important biomarker of risk for coronary heart disease morbidity and mortality. We investigated the influence of short-term cardiac rehabilitation (CR) after acute myocardial infarction (AMI) on values of hsCRP and classical risk factors, including metabolic syndrome. METHODS: hsCRP and classical risk factors were measured before and after completed 2-week CR program in 30 men after AMI. The comparison group comprised 30 age-balanced healthy men, with no risk factors for coronary heart disease. RESULTS: As expected, in comparison to healthy individuals, patients had higher values of hsCRP; furthermore, smokers had significantly higher hsCRP values than nonsmokers. Patients had more expressed markers of metabolic syndrome and due to pharmacological therapy lower blood pressure, total cholesterol and low-density lipoprotein cholesterol (LDL-C). After CR was completed, a significant drop in hsCRP (P=0.006) and improvement of metabolic syndrome parameters (lower body mass index, blood pressure, LDL-C, triglycerides) was observed in nonsmokers, whereas no such changes occurred in smokers. CONCLUSIONS: Our study revealed that hsCRP and metabolic syndrome parameters can be substantially reduced by a 2-week CR program; however, this effect is present only in nonsmokers. Thus, all patients entering the CR program after AMI should be advised to quit smoking before entering the program to achieve optimal benefits.

Inflammatory markers and pulmonary granuloma infiltration in sarcoidosis.

BACKGROUND AND OBJECTIVE: Previous studies have demonstrated increases of inflammatory mediators in sarcoidosis while epidemiological studies have also demonstrated an association with increased fungi exposure. This study measured the level of ß-glucan in the lungs and of inflammatory mediators in serum, and correlated both with the extent of pulmonary granuloma infiltration. METHODS: This is a cross-sectional study of 98 patients with sarcoidosis and 26 controls. ß-glucan, a cell wall constituent of fungi, was measured in bronchoalveolar lavage. Inflammatory mediator levels were determined in serum. The extent of granuloma infiltration was estimated on the chest X-ray. Exposure to fungi at home was determined by taking air samples in bedrooms and analysing for the presence of ß-N-acetylhexosaminidase. RESULTS: Significantly, higher levels of ß-glucan were found in broncho-alveolar lavage in subjects with sarcoidosis as compared with controls. There were significant positive relationships between the extent of granuloma infiltration and the levels of the different inflammatory mediators, except for interleukin-10. Domestic fungal exposure was higher among subjects with sarcoidosis. CONCLUSIONS: This is the first time that a specific agent, previously suspected to be related to the risk of sarcoidosis, has been detected in the lung of subjects with sarcoidosis and related to the levels of inflammatory mediators and the degree of home exposure to fungi. The results suggest that exposure to fungi should be explored when investigating patients with sarcoidosis.

Influence of short-term cardiac rehabilitation on oxidative stress in men after myocardial infarction depends upon smoking status.

PURPOSE: Oxidative stress is an important nonclassical risk factor for myocardial infarction (MI), and thus, it seems extremely important to recognize factors that effectively reduce it. The aim of our study was to explore possible influences of short-term cardiac rehabilitation (CR) of only 2 weeks in duration on oxidative stress in men after MI. METHODS: Male patients (N = 21; aged 41-88 years, median 56 years), 6 to 8 weeks after acute MI, were included in our observational study using a pretest/posttest design. We investigated markers of oxidative stress and antioxidant enzymes before and after CR of only 2 weeks in duration and influence of smoking status on these differences. RESULTS: We found significant decrease in isoprostanes in urine in nonsmokers (n = 9) (P = .036) but not in smokers (n = 12) (not significant) during CR. After CR, nonsmokers had lower isoprostanes in urine (P = .039), lower non-transferrin-bound iron (P = .020), and higher erythrocyte catalase (P = .023) than smokers. Of classical risk factors, only low-density lipoprotein cholesterol was lower in nonsmokers before (P = .041) and after CR (P = .015) than in smokers. No other significant differences were seen at the beginning or at the end of CR. CONCLUSIONS: To our knowledge, the results of our study indicate for the first time that short-term CR of only 2 weeks in duration already has a positive effect on reduction of oxidative stress in the body. However, this positive effect is seen only in nonsmokers and not in smokers.

Antifungal medication is efficient in the treatment of sarcoidosis.

OBJECTIVES: Fungi have been suspected of contributing to the pathogenesis of sarcoidosis. A previous intervention study demonstrated an improvement in the clinical condition in 15 out of 18 patients with a long-term history of sarcoidosis when antifungal medication was added to corticosteroids. The present study was performed to compare the effects of antifungal treatment with corticosteroid treatment in sarcoidosis. METHODS: Patients with newly diagnosed sarcoidosis were recruited. Corticosteroids were given to 39 subjects, corticosteroid + antifungal to 31, and antifungal only to 22 subjects. The effects of the treatments were evaluated at 6 months. X-ray scores were measured before and after treatment together with pulmonary diffusion capacity and two markers of sarcoidosis activity, that is, angiotensin-converting enzyme in serum (sACE) and chitotriosidase (CTO). RESULTS: X-ray scores as well as sACE and CTO decreased significantly in all groups. The X-ray score decreased slightly more among subjects in the groups that received antifungal medication compared with corticosteroids only (p < 0.001). CONCLUSION: The results suggest that antifungal treatment is as efficient as corticosteroid treatment against the granulomatous and inflammatory manifestations of sarcoidosis. This is probably because this treatment is directed towards the causative agent. Additional studies are required to define the phenotype, where the antifungal treatment was not efficient (4/22) and to perform long-term follow up to determine the risk of recurrence.

Fungal cell wall agents suppress the innate inflammatory cytokine responses of human peripheral blood mononuclear cells challenged with lipopolysaccharide in vitro.

Exposure to high levels of fungi might lead to diseases, such as airway inflammation, hypersensitivity pneumonitis and allergy. To comprehend the mechanisms behind the exposure to fungi and a disease, we examined the in vitro innate inflammatory cytokine response of human peripheral blood mononuclear cells (PBMC) challenged by fungal cell wall agents (FCWAs), i.e., soluble and particulate (1→3)-ß-D-glucan-curdlan (BGS and BGP), zymosan (ZYM) and chitosan (CHT) in the absence or presence of lipopolysaccharide (LPS). We also studied FCWA effects on the mRNA expression of dectin-1, TLR2, TLR4 and mannose receptor (MR) by real-time RT-PCR. Our results demonstrated that BGP strongly induced the secretion of TNF-α, IL-6, IL-10 and IL-12; BGS, ZYM and CHT were weaker, but still significant cytokine inducers. We showed that BGS significantly augmented the LPS-induced in vitro secretion of TNF-α. On the other hand, BGP, ZYM and CHT suppressed the LPS-induced production of all cytokines. At the mRNA level, the dectin-1, TLR2 and TLR4 expressions were significantly reduced by all FCWAs in the absence of LPS and even more in the presence of LPS. While we demonstrated that the innate inflammatory cytokine response of PBMC induced by CHT was mediated by MR, the MR mRNA expression was significantly reduced by CHT. On the contrary, BGS significantly enhanced the MR mRNA expression. In conclusion, a long-term and massive exposure to LPS and FCWA (e.g., organic dust) may cause an important disruption of normal immune response and allow development and/or persistence of various immunopathological events.

Fungal exposure in homes of patients with sarcoidosis - an environmental exposure study.

BACKGROUND: There is increasing evidence that exposure to moulds (fungi) may influence the development of sarcoidosis. To assess the influence of the environmental exposure, a study was undertaken to determine the exposure to fungi in homes of subjects with sarcoidosis. METHODS: Subjects were patients with clinically established sarcoidosis recruited during the period September 2007 till June 2010. Of these 55 were newly diagnosed and currently under treatment for less than one year, 25 had been treated and had no recurrence and 27 had been treated but had recurrence of the disease. Controls were healthy subjects without any respiratory symptoms (n = 30). Samples of air (about 2.5 m3) were taken in the bedroom of the subjects using a portable pump and cellulose ester filters. The filters were analysed for the content of the enzyme N-acetylhexosaminidase (NAHA) as a marker of fungal cell biomass, using a specific substrate and a fluorescent technique and expressed as NAHA units (U)/m3. RESULTS: Compared to controls, subjects undergoing treatment of the disease (newly diagnosed or with recurrence) had significantly higher activities of NAHA in their homes than controls (33.6 and 39.9 vs 10.0 U/m3, p < 0.001 and <0.001). Among controls only 5 out of 30 subjects had levels of NAHA above the second quartile value (14 U/m3). In homes of subjects with newly diagnosed disease with treatment less than one year, values above 14 NAHA U/m3 were found among 35 out of 55 and among those with recurrent disease among 18 out of 27. CONCLUSIONS: The higher activities of NAHA enzyme found in homes of subjects with active and recurrent sarcoidosis suggest that exposure to fungi is related to the risk of sarcoidosis. Further environmental studies to assess the importance of this exposure for subjects with sarcoidosis are warranted. The results suggest that remedial actions in homes with high levels of fungi may be justified.

Fire-eater's lung complicated by an infectious abscess requiring surgical treatment.

We describe a case of fire-eater's pneumonia that was complicated by an infectious lung abscess with substantial haemoptysis. Conservative treatment was inadequate. Surgical resection was necessary and proved to be successful.

Chitotriosidase activity in sarcoidosis and some other pulmonary diseases.

BACKGROUND: Patients with sarcoidosis have elevated levels of several markers of inflammation. Particularly high levels have been reported for chitotriosidase. In this study, we evaluate whether determining chitotriosidase in serum would be useful in the diagnosis and clinical management of patients with sarcoidosis. METHODS: Patients with newly diagnosed sarcoidosis and patients with asthma, fibrosis, asbestosis, lung cancer or chronic obstructive pulmonary disease (n=190) were recruited from an outpatient department. Individuals with no disease (n=26) served as controls. An X-ray was taken, diffusion capacity was measured and blood samples were taken for analysis of chitotriosidase, soluble receptor for interleukin-2, tumour necrosis factor alpha and angiotensin converting enzyme. In most patients with sarcoidosis, the analyses were done before and after regular treatment with corticosteroids over 6 months. RESULTS: Some patients with sarcoidosis had markedly high activities of chitotriosidase, but activities above controls were also found among patients with asbestos, fibrosis and lung cancer. There were significant relationships between chitotriosidase and interleukin-2 receptor and angiotensin-converting enzyme. After treatment, chitotriosidase activity decreased in 52 of 69 patients. CONCLUSIONS: The results confirm that chitotriosidase activity is markedly increased in some cases of sarcoidosis. As increased activities are also found in other diseases, chitotriosidase cannot be considered a specific marker of sarcoidosis. In cases of sarcoidosis where high CTO activities are found, this enzyme could serve as a useful marker supporting the diagnosis of sarcoidosis when following the effects of treatment and in surveillance for recurrence of the disease.

DNA-based sputum cell image analysis for lung cancer in a clinical setting.

OBJECTIVE: To measure cell nuclei characteristics, previously reported to express probability for lung cancer, in subjects with different forms ofpulmonary disease and those without disease. STUDY DESIGN: Sputum and buccal cell samples were obtained from 846 patients without pulmonary disease, with nonmalignant disease, chronic obstructive pulmonary disease, asbestosis and lung cancer, stained for DNA, scanned by cytometer and scored. This was related to specificity and sensitivity for lung cancer. At score 4.5 sensitivity was 53.8% and specificity 70.9%. This score and higher were defined as high scores (HS) and used to compare groups with lung cancer and other pulmonary disease. RESULTS: Among subjects without disease, 21.1% had HS in sputum cells. Among those with nonmalignant pulmonary disease, 31.7% had HS, and among subjects with lung cancer, 53.8% had it. Repeated evaluations showed that about one third of those with HS on the first occasion were normal on repeat sampling. Among subjects without lung cancer, 33.8% of never-smokers had sputum cell HS compared to 22.7.2% among smokers. CONCLUSION: Results demonstrate that the DNA cellular characteristics on cytometry were more frequent among subjects with lung cancer but also among subjects with other pulmonary disease compared to subjects witbout pulmonary disease.