Antigen-specific multifunctional T-cells in sarcoidosis patients with Lofgren's syndrome

Sarcoidosis is a granulomatous disease of unknown aetiology, mainly affecting the lungs. Recently, T-cell responses towards a specific mycobacterial protein, catalase-peroxidase (mKatG), were observed in sarcoidosis patients. Bronchoalveolar lavage (BAL) fluid and peripheral blood were obtained from a total of 23 sarcoidosis patients, of whom 13 had L?fgren's syndrome and lung accumulations of T-cell receptor AV2S3+ T-cells. Using six-colour flow cytometry in combination with intracellular cytokine staining, T-cell subsets were studied with regard to interferon (IFN)-γ, tumour necrosis factor (TNF) and interleukin-2 production, after stimulation with mKatG or Mycobacterium tuberculosis purified protein derivate (PPD). Stimulation with mKatG resulted in higher simultaneous IFN-γ and TNF production, but less single IFN-γ production, from total BAL fluid CD4+ T-cells of L?fgren's syndrome patients, when compared with non-L?fgren's patients. In contrast, PPD stimulation gave rise to largely similar cytokine responses in both patient subgroups. Furthermore, mKatG stimulated higher IFN-γ production in BAL fluid and blood AV2S3+ T-cells than AV2S3- T-cells, whereas the opposite was seen in BAL fluid with PPD stimulation. Our finding that patients with L?fgren's syndrome exhibited a more pronounced multifunctional cytokine profile (simultaneous IFN-γ and TNF production) towards the mycobacterial protein mKatG may help to explain the distinct disease presentation in this patient subgroup.     

Respiratory health and endotoxin: associations and modification by CD14/-260 genotype

Exposure to endotoxin has been associated with increased respiratory symptoms and decrements in lung function in occupational settings but little is known about the health effects of domestic exposure in adults. Here, we describe the association of respiratory disease, immunoglobulin (Ig)E sensitisation, bronchial reactivity and lung function with mattress endotoxin levels in adults, and determine whether these associations are modified by polymorphisms in CD14. Endotoxin levels in mattress dust from a population-based sample of 972 adults were measured. Associations were examined using generalised linear mixed models, adjusting for individual and household confounders. Effect modification of these associations by CD14/-260 (rs2569190) was assessed. Mattress endotoxin levels varied from 0.1 to 402.6 EU · mg(-1). Although there was no overall association of lung function with endotoxin exposure, there was evidence that the association of forced expiratory volume in 1 s and forced vital capacity with endotoxin was modified by CD14/-260 genotype (p-value for interaction 0.005 and 0.013, respectively). There was no evidence that symptoms, IgE sensitisation or bronchial reactivity were associated with mattress endotoxin levels. In this large epidemiological study of adults, there was no evidence that mattress endotoxin level was associated with respiratory symptoms or IgE sensitisation but the association of lung function with endotoxin levels may be modified by CD14 genotype.     

Forceps biopsy and suction catheter for sampling in pulmonary nodules and infiltrates

Transbronchial lung biopsy with forceps is a standard procedure in bronchoscopic tissue sampling. Suction catheter aspiration is another technique, but it is not widely known and almost no data exist regarding its diagnostic efficiency. 272 patients were included in a prospective and randomised study between February 2007 and October 2009. All were referred for bronchoscopic evaluation of pulmonary nodules/masses or infiltrates. We compared the diagnostic yield of forceps biopsy and suction catheter aspiration for a definite diagnosis and looked at whether such a diagnosis depends on the underlying pulmonary change. All patients underwent bronchoscopy with forceps biopsy and catheter aspiration. A definitive diagnosis was reached in a total of 183 (67.3%) patients, with catheter aspiration in 140 (51.5%) patients and with forceps biopsy in 136 (50.0%) patients. In 90 (33.1%) patients, a definite diagnosis could only be reached with the combination of both techniques. The diagnostic yield of forceps biopsy was better than catheter aspiration in infiltrates (p = 0.027), but was no different in nodules or masses (p = 0.09). Suction catheter aspiration is a useful technique of bronchoscopic tissue sampling. The combination of catheter aspiration and forceps biopsy results in a higher diagnostic yield than either method used alone.