BackgroundThere 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.MethodsSubjects 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.ResultsCompared 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.ConclusionsThe 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.
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.
We present a method for lung cancer detection exploiting reflectance spectra measured in vivo during endoscopic imaging of the lung. The measured reflectance spectra were analyzed using a specially developed light-transport model to obtain quantitative information about cancer-related, physiological, and morphologic changes in the superficial bronchial mucosa layers. The light-transport model allowed us to obtain the absorption coefficient ͑ a ͒ and further to derive the micro-vascular blood volume fraction in tissue and the tissue blood oxygen saturation. The model also allowed us to obtain the scattering coefficient ͑ s ͒ and the anisotropy coefficient ͑g͒ and further to derive the tissue scattering micro-particle volume fraction and size distribution. The specular component of the reflectance signal and the instrument response were accounted for during the analysis. The method was validated using 100 reflectance spectra measured in vivo in a noncontact fashion from 22 lung patients ͑50 normal tissue/benign lesion sites and 50 malignant lesion sites͒. The classification between normal tissue/benign lesions and malignant lesions was further investigated using the derived quantitative parameters and discriminant function analysis. The results demonstrated significant differences between the normal tissue/benign lesions and the malignant lesions in terms of tissue blood volume fraction, blood oxygen saturation, tissue scatterer volume fractions, and size distribution. The results also showed that the malignant lung lesions can be differentiated from normal tissue/benign lesions with both diagnostic sensitivity and specificity of better than 80%. © 2006 Society of Photo-Optical Instrumentation Engineers.
SummarySarcoidosis is an inflammatory disease. Epidemiological and treatment studies suggest that fungi play a part in the pathogenesis. The aim of this work was to study the effect of fungal cell wall agents (FCWA) on the in vitro secretion of cytokines from peripheral blood monocytes from subjects with sarcoidosis and relate the results to fungal exposure at home and clinical findings. Subjects with sarcoidosis (n = 22) and controls (n = 20) participated. Peripheral blood mononuclear cells were stimulated with soluble or particulate b-glucan (S-glucan, P-glucan), chitin or lipopolysaccharide (LPS), whereafter tumour necrosis factor (TNF)-a, interleukin (IL)-6, IL-10 and IL-12 were measured. The severity of sarcoidosis was determined using a chest X-raybased score. Serum cytokines (IL-2R, IL-6, IL-10 and IL-12) were determined. To measure domestic fungal exposure, air in the bedrooms was sampled on filters. N-acetylhexosaminidase (NAHA) on the filters was measured as a marker of fungal cell biomass. The induced secretion of cytokines was higher from peripheral blood mononuclear cells (PBMC) from subjects with sarcoidosis. P-glucan was more potent than S-glucan inducing a secretion. Chitin had a small effect. Among subjects with sarcoidosis there was a significant relation between the spontaneous PBMC production of IL-6, IL-10 and IL-12 and the NAHA levels at home. The P-glucan induced secretion of IL-12 was related to the duration of symptoms at the time of diagnosis. Their X-ray scores were related to an increased secretion of cytokines after stimulation with LPS or P-glucan. Subjects with sarcoidosis have a higher reactivity to FCWA in vitro and to home exposure. The influence of FCWA on inflammatory cells and their interference with the inflammatory defense mechanisms in terms of cytokine secretion could be important factors for the development of sarcoidosis.
Abstract: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 þ 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.
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