Single-Cell Profiling of Cells in the Lung of a Patient with Chronic Hypersensitivity Pneumonitis Reveals Inflammatory Niche with Abundant CD39+ T Cells with Functional ATPase Phenotype: A Case Study.

This study investigated immune cell characteristics in chronic hypersensitivity pneumonitis (HP), focusing on CD39-expressing cells' impact on inflammation and tissue remodelling. Lung tissue from an HP patient was analysed using single-cell transcriptomics, flow cytometry, and gene expression profiling. The tissue revealed diverse cell types like macrophages, T cells, fibroblasts, and regulatory T cells (Tregs). CD39-expressing Tregs exhibited heightened ATP hydrolysis capacity and regulatory gene expression. CD39hi cells displayed markers of both Tregs and proinflammatory Th17 cells, suggesting transitional properties. Communication networks involving molecules like SPP1, collagen, CSF1, and IL-1ß were identified, hinting at interactions between cell types in HP pathogenesis. This research provides insights into the immune response and cell interactions in chronic HP. CD39-expressing cells dual nature as Tregs and Th17 cells suggests a role in modulating lung inflammation, potentially affecting disease progression. These findings lay the groundwork for further research, underscoring CD39-expressing cells as potential therapeutic targets in HP.

Inferior outcomes in lung transplant recipients with serum Pseudomonas aeruginosa specific cloaking antibodies.

BACKGROUND: Chronic Lung Allograft Dysfunction (CLAD) limits long-term survival following lung transplantation. Colonization of the allograft by Pseudomonas aeruginosa is associated with an increased risk of CLAD and inferior overall survival. Recent experimental data suggests that 'cloaking' antibodies targeting the O-antigen of the P. aeruginosa lipopolysaccharide cell wall (cAbs) attenuate complement-mediated bacteriolysis in suppurative lung disease. METHODS: In this retrospective cohort analysis of 123 lung transplant recipients, we evaluated the prevalence, risk factors and clinical impact of serum cAbs following transplantation. RESULTS: cAbs were detected in the sera of 40.7% of lung transplant recipients. Cystic fibrosis and younger age were associated with increased risk of serum cAbs (CF diagnosis, OR 6.62, 95% CI 2.83-15.46, p < .001; age at transplant, OR 0.69, 95% CI 0.59-0.81, p < .001). Serum cAbs and CMV mismatch were both independently associated with increased risk of CLAD (cAb, HR 4.34, 95% CI 1.91-9.83, p < .001; CMV mismatch (D+/R-), HR 5.40, 95% CI 2.36-12.32, p < .001) and all-cause mortality (cAb, HR 2.75, 95% CI 1.27-5.95, p = .010, CMV mismatch, HR 3.53, 95% CI 1.62-7.70, p = .002) in multivariable regression analyses. CONCLUSIONS: Taken together, these findings suggest a potential role for 'cloaking' antibodies targeting P. aeruginosa LPS O-antigen in the immunopathogenesis of CLAD.

Pulmonary alveolar proteinosis after lung transplantation.

We report the case of a 69-year-old man five-month post double lung transplant for idiopathic pulmonary fibrosis (IPF) who presented with progressive breathlessness, loss of lung function, and diffuse ground glass shadowing on the chest computed tomography. Transbronchial lung biopsy revealed foamy macrophages, hyperplasia of type II pneumocytes, and eosinophilic material in the alveolar space. Video thoracic lung biopsy was performed, and histology confirmed pulmonary alveolar proteinosis. Anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies were negative. Bilateral sequential whole lung lavage (WLL) was performed. Lavage fluid recovered during WLL was notably dark brown in colour and upon analysis was shown to contain heavily oxidized protein (lipofuscin), giant lipofuscin-engorged macrophages, and a highly pro-inflammatory gene expression profile. Following WLL, the patient's symptoms, lung function, and radiology appearance improved. His repeat bronchoalveolar lavage (BAL) fluid analysis showed reduced lipofuscin and normalized macrophage size and gene expression.

Long-term Outcomes of Lung Transplant With Ex Vivo Lung Perfusion.

Importance: The mortality rate for individuals on the wait list for lung transplant is 15% to 25%, and still only 20% of lungs from multiorgan donors are used for lung transplant. The lung donor pool may be increased by assessing and reconditioning high-risk extended criteria donor lungs with ex vivo lung perfusion (EVLP), with similar short-term outcomes. Objective: To assess the long-term outcomes of transplant recipients of donor lungs treated with EVLP. Design, Setting, and Participants: This retrospective cohort single-center study was conducted from August 1, 2008, to February 28, 2017, among 706 recipients of donor lungs not undergoing EVLP and 230 recipients of donor lungs undergoing EVLP. Exposure: Donor lungs undergoing EVLP. Main Outcomes and Measures: The incidence of chronic lung allograft dysfunction and allograft survival during the 10-year EVLP era were the primary outcome measures. Secondary outcomes included donor characteristics, maximum predicted percentage of forced expiratory volume in 1 second, acute cellular rejection, and de novo donor-specific antibody development. Results: This study included 706 patients (311 women and 395 men; median age, 50 years [interquartile range, 34-61 years]) in the non-EVLP group and 230 patients (85 women and 145 men; median age, 46 years [interquartile range, 32-55 years]) in the EVLP group. The EVLP group donors had a significantly lower mean (SD) Pao2:fraction of inspired oxygen ratio than the non-EVLP group donors (348 [108] vs 422 [88] mm Hg; P < .001), higher prevalence of abnormal chest radiography results (135 of 230 [58.7%] vs 349 of 706 [49.4%]; P = .02), and higher proportion of smoking history (125 of 204 [61.3%] vs 322 of 650 [49.5%]; P = .007). More recipients in the EVLP group received single-lung transplants (62 of 230 [27.0%] vs 100 of 706 [14.2%]; P < .001). There was no significant difference in time to chronic lung allograft dysfunction between the EVLP and non-EVLP group (70% vs 72% at 3 years; 56% vs 56% at 5 years; and 53% vs 36% at 9 years; log-rank P = .68) or allograft survival between the EVLP and non-EVLP groups (73% vs 72% at 3 years; 62% vs 58% at 5 years; and 50% vs 44% at 9 years; log-rank P = .97) between the 2 groups. All secondary outcomes were similar between the 2 groups. Conclusions and Relevance: Since 2008, 230 of 936 lung transplants (24.6%) in the Toronto Lung Transplant Program were performed after EVLP assessment and treatment. Use of EVLP-treated lungs led to an increase in the number of patients undergoing transplantation, with comparable long-term outcomes.

Successful treatment of cytomegalovirus associated hemophagocytic lymphohistiocytosis with the interleukin 1 inhibitor - anakinra.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, frequently under-recognized condition associated with multi-organ failure and very high mortality. A 44-year-old woman was admitted with a 4-day history of fever, headache, delirium, and dyspnea. She progressed rapidly to type 1 respiratory failure and required intubation and mechanical ventilation. Laboratory tests showed pancytopenia, abnormal liver enzyme levels, elevated triglyceride level, and elevated ferritin level. Bone marrow biopsy showed features of HLH. Computed tomography scan showed bilateral consolidation. Bronchoalveolar lavage was positive for cytomegalovirus. She was treated with ganciclovir, methylprednisolone, broad spectrum antibiotics, and cytomegalovirus hyperimmunoglobulin without clinical response. Given the poor prognosis and reports of success in pediatric HLH, anakinra 100 µg subcutaneously daily was commenced. There was rapid defervescence, resolution of delirium, and improvement in gas exchange, leading to complete recovery. This case illustrates successful treatment of HLH associated with cytomegalovirus pneumonitis with the interleukin 1 inhibitor anakinra.

Pregnancy after lung transplant: Case Report.

Improved survival now means that more women with lung transplants than ever before may be able to consider #pregnancy http://ow.ly/Ute17.