Inflammatory and immune dysregulation associated lung disease

National Heart, Lung, And Blood Institute

Investigators

Linked publications & trials

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. One of these disorders, Autoimmune Polyendocrinopathy, Candidiasis and Ectodermal Dysplasia (APECED) can have particularly bad pulmonary manifestations. We described a case requiring extensive surgical, interventional pulmonary and medical treatment of for extensive pulmonary and pleural space infection (Kubala. Respir Med Case Rep,2021). Whole exome and genome sequencing has led to a remarkable increase in diagnosis and characterization of patients with complex immune phenotypes, many of whom have lung manifestations. A report of the first 1000 families evaluated in a centralized sequencing program describes progress toward comprehensive genomic evaluations (Similuk. J Allergy Clin Immunol, 2022). Sarcoidosis is a poorly understood multisystem disease that often affects the lung as well as other organs such as the heart. Members of the lab with an interest in sarcoidosis participated in a collaborative effort to optimize screening procedures for cardiac sarcoidosis (Holtzclaw. Respir Med, 2021). Finally, COVID19 has had overlapping interests of lab members in recent past. Investigations of novel therapeutics using the longstanding close collaboration with the Advanced Lung Disease Program at Inova Fairfax involved the clinical trial of the syk inhibitor, fostamatanib, as a treatment for COVID19 which showed some benefit (Strich. Clin Infect Dis, 2021). An ongoing longitudinal study of COVID19 sequelae and immune responses involves investigation of lung disease status over time and is producing very timely information about vaccine effectiveness, treatment response and long term effects of this disease (Sneller. Ann Intern Med, 2022) 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)