Beyond the clot: perfusion imaging of the pulmonary vasculature after COVID-19.

A compelling body of evidence points to pulmonary thrombosis and thromboembolism as a key feature of COVID-19. As the pandemic spread across the globe over the past few months, a timely call to arms was issued by a team of clinicians to consider the prospect of long-lasting pulmonary fibrotic damage and plan for structured follow-up. However, the component of post-thrombotic sequelae has been less widely considered. Although the long-term outcomes of COVID-19 are not known, should pulmonary vascular sequelae prove to be clinically significant, these have the potential to become a public health problem. In this Personal View, we propose a proactive follow-up strategy to evaluate residual clot burden, small vessel injury, and potential haemodynamic sequelae. A nuanced and physiological approach to follow-up imaging that looks beyond the clot, at the state of perfusion of lung tissue, is proposed as a key triage tool, with the potential to inform therapeutic strategies.

Pulmonary Langerhans cell histiocytosis (PLCH): a new UK register.

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare interstitial lung disease of unknown aetiology. We aimed to characterise a UK-wide cohort of patients with PLCH and compare diagnostic and management methods in specialist and non-specialist centres. 106 cases (53 hospitals) identified. Complete data received in 67 cases (53.7% female, age 37.1±14.4 years). 96% current or ex-smokers. Treatment; smoking cessation (79%), corticosteroids (30.6%), cytotoxic therapy (26.9%) and lung transplant (6%). Patients at specialist centres received cytotoxic drugs more often (p=0.0001) and survival appeared higher. This dataset indicates a more even gender distribution than previously documented. It suggests variation in clinical management and outcomes achieved dependent on clinical experience.

PET scanning of macrophages in patients with scleroderma fibrosing alveolitis.

RATIONALE: Assessment of disease activity in fibrosing alveolitis due to systemic sclerosis (FASSc) is difficult without using invasive investigation. A repeatable noninvasive method of assessing disease at a cellular level such as with positron emission tomography (PET) could be of great value in evaluating high-resolution changes in the pathological process. OBJECTIVES: To investigate whether the level of inflammatory cell traffic and lung density in FASSc, imaged in vivo by PET, is different to controls and whether they are associated with changes in pulmonary function indices. METHODS: We used PET to measure lung density and tissue uptake of (11)C-[R]-PK11195, a ligand that binds to receptors found in abundance in macrophages. Fifteen patients with FASSc were compared to seven controls. RESULTS: A trend of reduced uptake of (11)C-[R]-PK11195 was observed in FASSc patients (P=.09) and correlated inversely with lung density (r=-.62; P<.05), which was significantly elevated in FASSc [0.35+/-0.02 vs. 0.23+/-0.02 g/cc (mean+/-S.E.M.); P<.005]. CONCLUSION: These results demonstrate that inflammatory cell traffic and lung density can be imaged in vivo in FASSc using PET, and that this approach might be of potential value in understanding, in situ, components of pathogenesis that may have value for prognosis.

Peripheral-type benzodiazepine receptors in bronchoalveolar lavage cells of patients with interstitial lung disease.

INTRODUCTION: PK11195 is a ligand with high affinity for peripheral benzodiazepine receptors (PBRs), which are present in large numbers in macrophages. PBRs play a role in antioxidant pathways and apoptosis, key factors in control of lung health. Intrapulmonary PBRs, assessed in vivo by positron emission tomography (PET), are decreased in interstitial lung disease (ILD) despite increased macrophage numbers. We wished to ascertain whether the observed decrease in in vivo expression of PBRs in the PET scans could be accounted for by a reduction in PBRs per cell by saturation-binding assays of R-PK11195 in cells obtained by bronchoalveolar lavage (BAL). METHODS: We performed receptor saturation-binding assays with [(3)H]-R-PK11195 on a mixed population of cells recovered by BAL to quantify the number of R-PK11195 binding sites per macrophage in 10 subjects with ILD and 10 normal subjects. RESULTS: Receptor affinity [dissociation constant (Kd)] was similar in ILD patients and controls. However, R-PK11195 binding sites per cell [(maximal binding sites available (B(max))] were decreased in macrophages obtained by BAL from subjects with ILD compared to normal (P<.0005). Microautoradiography confirmed localization of R-PK11195 to macrophages in a mixed inflammatory cell population obtained by BAL. CONCLUSION: These results demonstrate that in vitro PBR expression per cell on macrophages obtained by BAL is reduced in patients with ILD indicating a potentially functionally different macrophage phenotype. As PBRs are involved in the orchestration of lung inflammatory responses, this finding offers further insight into the role of macrophages in the pathogenesis of ILDs and offers a potential avenue for pharmacological strategy.