Inflammatory and immune dysregulation associated lung disease

National Heart, Lung, And Blood Institute

Investigators

Linked publications, trials & patents

Abstract

The pulmonary involvement in disorders of immune or inflammatory regulation can range from a primary manifestation such as with sarcoidosis or a relatively minor manifestations such as seen with the Mendelian Susceptibility to Mycobacterial Disease immune deficiencies. While both of these can be associated with granulomatous inflammation in the lung, the clinical pulmonary manifestations are quite different as are the management strategies. The Laboratory of Chronic Airway Infection (LCAI) has sought to capitalize on the close collaboration with the Laboratory of Clinical Immunology and Microbiology (LCIM) and other branches within the NIAID and NIAMS focused on these disorders to describe the pulmonary manifestations of known and emerging immune and inflammatory diseases. Over the past year we have continued collaboration with investigators in the NIAID/LCIM to characterize and describe the lung manifestations of GATA2 deficiency. GATA2 deficiency is a genetic disorder of hematopoiesis, lymphatics, and immunity caused by autosomal dominant or sporadic mutations in GATA2. The disease has a broad phenotype encompassing immunodeficiency, myelodysplasia, leukemia, and vascular or lymphatic dysfunction as well as prominent pulmonary manifestations. We conducted a retrospective review of 124 patients (95 probands and 29 ascertained) with lung disease in 56%. Chronic nontuberculous mycobacterial infection was the most common, but pulmonary alveolar proteinosis and pulmonary hypertension were seen in 9% and 7%, respectively. Clinical presentations within families were variable. GATA2 deficiency has characteristic clinical and radiographic manifestations and hematopoietic stem cell transplantation can reverse the major pulmonary manifestations of the disease (Marciano 2021). The use of bronchoscopic sampling can be important in the evaluation of inflammatory and immune dysregulation lung diseases. Biopsies obtained bronchoscopically are often limited by and inability to direct instruments to the correct location of abnormalities seen on static CT images. Novel navigational imaging utilizing cone-beam computed tomography (CT)-based augmented fluoroscopy (AF) for endobronchial navigation to peripheral lung targets offers potential for more accurate lung tissue sampling. Prototypic endobronchial navigation AF software that superimposed segmented airways, targets, and pathways based on cone-beam CT onto fluoroscopy images was evaluated ex vivo in fixed swine lungs and in vivo in healthy swine (n = 4) without a bronchoscope. First-pass success was 100% (10/10) ex vivo and 19/24 (79%) and 11/15 (73%) for in vivo phases 1 and 2, respectively. Phase 2 second-pass success was 4/4 (100%). AF can guide endobronchial navigation with endovascular catheters and steerable guiding sheaths to peripheral lung targets, potentially overcoming limitations associated with bronchoscopy. (AF can guide endobronchial navigation with endovascular catheters and steerable guiding sheaths to peripheral lung targets, potentially overcoming limitations associated with bronchoscopy.AF can guide endobronchial navigation with endovascular catheters and steerable guiding sheaths to peripheral lung targets, potentially overcoming limitations associated with bronchoscopy. (de Ruiter, 2020)