Kubbara, Aahd

Abstract RATIONALE: Mesenchymal progenitor cells (MPCs) in the lungs of individuals with Idiopathic Pulmonary Fibrosis (IPF) show intrinsic fibrogenic properties, possessing a distinct transcriptomic profile and maintaining fibrogenic activity, which contributes to the fibroblast population in IPF. We hypothesize that IPF MPCs are distinguished from control MPCs by a unique gene interaction network. METHODS: We analyzed bulk RNA-seq data, available on the Gene Expression Omnibus (GEO) under accession numbers GSE97038 and GSE276568. In these experiments, CD44hi MPCs were isolated through flow cytometry from mesenchymal cell lines derived from IPF patients (explanted lungs from live IPF patients after lung transplant) and control subjects (lobectomy for clinical reasons) using antibodies against CD44 and SSEA4. The pooled dataset comprises nine IPF and nine control MPC lines. We identified differentially expressed genes (DEGs) in IPF MPCs compared to controls using DESeq and performed pathway enrichment analysis on DEGs using Gene Ontology (GO). We also conducted Gene Set Enrichment Analysis (GSEA) with gene sets related to stemness, pluripotency, and self-renewal. Weighted gene co-expression network analysis (WGCNA) identified functional modules specifically associated with IPF MPCs. RESULTS: Applying an adjusted p-value threshold of 0.05, we identified 134 DEGs in IPF MPCs compared to controls. GO analysis showed significant enrichment in pathways associated with leukocyte migration, extracellular matrix organization, and cell differentiation and growth. GSEA highlighted significant enrichment in two gene sets related to stemness, with adjusted p-values of 0.002 and 0.048. Using WGCNA, we identified 16 functional modules, one of which reached significance based on an adjusted p-value threshold of 0.05 and a correlation coefficient cutoff of 0.45. This significant module demonstrated a positive correlation with IPF status (correlation coefficient of 0.69, adjusted p-value 0.0085). CONCLUSION: This study is the first to characterize a distinct gene expression profile in IPF MPCs compared to controls, highlighting enriched biological processes relevant to IPF pathogenesis. GSEA results further support the hypothesis that IPF MPCs display stem cell-like gene expression patterns, including genes associated with pluripotency and self-renewal. Additionally, we identified functional gene modules that significantly correlate with the fibrogenic properties of IPF MPCs, including hub genes that may play critical roles in promoting fibrosis in IPF. These findings deepen our understanding of IPF MPC biology and identify potential targets for future research. We plan to expand this approach by increasing the sample size to enhance statistical power, aiming to identify more robust functional modules and their highly connected hub genes.

The detection of antibodies against Histoplasma capsulatum remains a frequently relied-on approach to diagnose histoplasmosis. We retrospectively assessed the performances of complement fixation (CF) and immunodiffusion (ID) assays for anti- Histoplasma antibody detection in patients with culture-confirmed histoplasmosis at Mayo Clinic (Rochester, MN) over a 10-year period (2011 to 2020).

Abstract Background: Although psoriasis is considered a systemic disease, no clear association has been established between psoriasis and lung diseases. This study aims to detect and describe subclinical pulmonary involvement in psoriasis patients with various degrees of cutaneous manifestations.Methods: Adult psoriasis patients with no known active pulmonary disease or respiratory symptoms were screened for subclinical pulmonary manifestations and possible parenchymal changes using high-resolution computed tomography (HRCT) scan of the chest. Patients were classified according to the severity of skin manifestations. The clinical characteristics and radiographic findings of these patients were evaluated.Results: Fifty-nine patients with psoriasis were included, among which 47 (79.7%) had abnormal HRCT scan features. Micronodules were the most common detected lung lesions (66.1%), followed by nonspecific interstitial changes (32.2%), including pleuro-parenchymal band/atelectasis, scarring, and focal ground-glass opacities. Other HRCT findings included emphysematous changes and calcified granulomas. Abnormal HRCT findings correlated with older age and duration of psoriasis but not with the severity of skin manifestations.Conclusions: Micronodules and minor focal nonspecific interstitial changes were the most detected lung alterations in patients with psoriasis. These findings of the pilot study highlight a possible pulmonary involvement in patients with psoriasis. Larger multicenter studies are needed to clarify these findings further.

We present a case of a woman who had progressive shortness of breath and wheezing with a mild restrictive pulmonary function pattern. She was initially diagnosed with eosinophilic granulomatosis with polyangiitis on the basis of peripheral eosinophilia, bronchoalveolar lavage eosinophilia (47%) and surgical lung biopsy findings. Six months following her diagnosis, the patient returned because of persistent symptoms, and a second review of the lung biopsy revealed thrombotic lesions in the pulmonary vessels with polarisable foreign body materials, associated giant cell reactions and numerous eosinophil infiltrates, consistent with intravenous drug abuse. Further investigation showed that she had a history of intravenous heroin overdose, and the diagnosis of excipient lung disease was made. This case highlights the importance of expert pathological, radiological and clinical review of complex presentations and the need for a thorough medication and drug use history review.

Abstract Background: Although psoriasis is considered a systemic disease, no clear association has been established between psoriasis and lung diseases. Methods: Adult psoriasis patients with no known active pulmonary disease or respiratory symptoms were screened for subclinical pulmonary manifestations and possible parenchymal changes using high-resolution computed tomography (HRCT) scan of the chest. Patients were classified according to the severity of skin manifestations. The clinical characteristics and radiographic findings of these patients were evaluated.Results: A total of 59 patients with psoriasis were included, among which 47 (79.7%) had abnormal HRCT scan features. Micronodules were the most common detected lung lesions (66.1%), followed by interlobular septal thickening (23.7%), fibrosis (11.9%), and ground-glass opacity (6.8%). Other HRCT findings included emphysematous changes and calcified granulomas. Abnormal HRCT findings correlated with older age and duration of psoriasis but not with the severity of skin manifestations.Conclusions: Micronodules and interlobular septal thickening were the most detected lung lesions in patients with psoriasis. These findings of the pilot study highlight the possible pulmonary involvement in patients with psoriasis. Larger multicenter studies are needed to further clarify these findings.

AbstractInflammatory processes, such as an infection or drug reaction, can cause antineutrophil cytoplasmic autoantibody (ANCA)‐associated vasculitis (AAV). Although quite rare, AAV may occur with SARS‐coronavirus disease 2019 (COVID‐19) antigenic exposure, either from infection or immunization. We present two cases of AAV: one that developed after COVID‐19 infection presenting as diffuse alveolar haemorrhage and another that developed shortly after vaccination, presenting as granulomatous pulmonary nodules. Both patients improved with supportive care and immunosuppressive therapies. This adverse event appears to be a very rare complication of COVID‐19 infection or vaccination. Early diagnosis of AAV is important because immunosuppressive therapy may improve patient outcomes.

Diffuse alveolar haemorrhage (DAH) is known to occur from several infectious and non-infectious aetiologies. Among the infectious aetiologies, Haemophilus influenzae , an organism known to cause community-acquired pneumonia, has not been reported in association with DAH prior to this case. On the other hand, vaping, an evolving epidemic concern, has been linked to various types of lung injury, including DAH. However, DAH related to vaping is only limited to several case reports. Our case describes H. influenzae pneumonia with DAH in a patient known to have vaped until the night prior to elective lobectomy for lung cancer and developed DAH within 24 hours of hospitalisation. He subsequently recovered with treatment. DAH requires immediate recognition, and healthcare providers need to be aware that neither haemoptysis nor decrease in haemoglobin level is necessarily associated. Prior to diagnosis, empirical treatment with intravenous steroids and antibiotics can be life-saving.