Lesion-Specific Immune Response in Granulomas of Patients with Pulmonary Tuberculosis: A Pilot Study.

The formation and maintenance of granulomas is central to the host response to Mycobacterium tuberculosis (Mtb) infection. It is widely accepted that the lungs of patients with tuberculosis (TB) usually contain multiple infection foci, and that the granulomas evolve and differentiate independently, resulting in considerable heterogeneity. Although gene expression profiles of human blood cells have been proposed as biomarkers of Mtb infection and/or active disease, the immune profiles of discrete lesion types has not been studied extensively. Using histology, immunopathology and genome-wide transcriptome analysis, we explored the immunological profile of human lung TB granulomas. We show that although the different granulomas share core similarities in their immunological/inflammatory characteristics, they also exhibit significant divergence. Despite similar numbers of CD68+ macrophages in the different lesions, the extent of immune reactivity, as determined by the density of CD3+ T cells in the macrophage rich areas, and the extent of fibrosis, shows considerable variation. Both quantitative and qualitative differences among significantly differentially expressed genes (SDEG) were noted in each of the lesion types studied. Further, network/pathway analysis of SDEG revealed differential regulation of inflammatory response, immune cell trafficking, and cell mediated immune response in the different lesions. Our data highlight the formidable challenges facing ongoing efforts to identify peripheral blood biomarkers due to the diversity of lesion types and complexity of local immune responses in the lung.

Approach to a solid solitary pulmonary nodule in two different settings-"Common is common, rare is rare".

A new solid solitary pulmonary nodule (SPN) is a common feature in the daily practice of physicians, pulmonologists and thoracic surgeons. The etiology and consequently the diagnostic approach is very different in various parts of the world. Identification of malignant nodules is the universal goal to proceed to a potential curable therapy. In countries with a low incidence of inflammatory disease and a high incidence of lung cancer the diagnostic work up includes a positron emission tomography (PET) scan or PET-computer tomography (CT) as a main pillar. In countries with a high incidence of inflammatory and infectious disease and a low incidence in lung cancer this diagnostic work up needs to be adapted. In these settings a PET scan has a limited role and tissue diagnosis, whether with a trans-thoracic, trans-bronchial biopsy or a video-assisted wedge resection is the most targeted approach to determine or exclude malignancy. The evaluation of a solid SPN in the two different situations is outlined in our algorithm. Recommendations stress the value of clinical judgement in different settings, determination of probabilities of malignancy, cost-effective use of diagnostic tools and evaluation of various management alternatives according to the risk profile and the patients preferences.