Coronavirus disease 2019 (COVID-19) pandemic has led to considerable morbidity and mortality across the world. Lung transplant is a viable option for a few with COVID-19-related lung disease. Whom and when to transplant has been the major question impacting the transplant community given the novelty of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We describe a pitfall of presumed prolonged shedding of SARS-CoV-2 in a patient with COVID-19 associated acute respiratory distress syndrome leading to COVID-19 pneumonia after lung transplant. This raises concerns that replication-competent SARS-CoV-2 virus can persist for months post-infection and can lead to re-infection of grafts in the future.

Respiratory syncytial virus (RSV) is the most common cause of viral bronchiolitis among children worldwide, yet there is no vaccine for RSV disease. This study investigates the potential of cube and sphere-shaped cerium oxide nanoparticles (CNP) to modulate reactive oxygen (ROS) and nitrogen (RNS) species and immune cell phenotypes in the presence of RSV infection in vitro and in vivo. Cube and sphere-shaped CNP were synthesized by hydrothermal and ultrasonication methods, respectively. Physico-chemical characterization confirmed the shape of sphere and cube CNP and effect of various parameters on their particle size distribution and zeta potential. In vitro results revealed that sphere and cube CNP differentially modulated ROS and RNS levels in J774 macrophages. Specifically, cube CNP significantly reduced RSV-induced ROS levels without affecting RNS levels while sphere CNP increased RSV-induced RNS levels with minimal effect on ROS levels. Cube CNP drove an M1 phenotype in RSV-infected macrophages in vitro by increasing macrophage surface expression of CD80 and CD86 with a concomitant increase in TNFα and IL-12p70, while simultaneously decreasing M2 CD206 expression. Intranasal administration of sphere and cube-CNP were well-tolerated with no observed toxicity in BALB/c mice. Notably, cube CNP preferentially accumulated in murine alveolar macrophages and induced their activation, avoiding enhanced uptake and activation of other inflammatory cells such as neutrophils, which are associated with RSV-mediated inflammation. In conclusion, we report that sphere and cube CNP modulate macrophage polarization and innate cellular responses during RSV infection.

Measurement of the levels of serum immunoglobulin A antibody against glycopeptidolipid (GPL) core antigen, a cell surface antigen found in Mycobacterium avium complex (MAC), has been reported to be useful in the diagnosis and management of pulmonary MAC infection. However, evidence on its utility in hypersensitivity pneumonitis (HP) associated with MAC (i.e., \"hot-tub lung\") is limited. We herein report a case of HP associated with MAC in which the GPL core antibody levels were serially measured from diagnosis to treatment and thereafter. A 61-year-old man was suspected to have non-fibrotic HP based on the clinical course, laboratory findings, imaging pattern, bronchoalveolar lavage (BAL) lymphocytosis, and histopathological findings. Based on the history of whirlpool bath use, inhalation of aerosolized MAC was suspected as the cause of HP. The GPL core antibody level, measured using an enzyme-linked immunosorbent assay kit, was elevated, suggesting an immunological sensitization to MAC. A provocation test using the patient\'s whirlpool bath was positive. An identical MAC strain was isolated from the BAL fluid and bathtub. Accordingly, the patient was diagnosed with HP caused by the inhalation of aerosolized MAC from the whirlpool bath. The patient recovered after steroid treatment and discontinuation of the whirlpool bath. The GPL core antibody levels decreased with disease improvement. In conclusion, GPL core antibody levels could be elevated in HP associated with MAC and decrease with disease improvement. Thus, measurement of the GPL core antibody level may be useful for the diagnosis and management of HP associated with MAC.

An 80-year-old woman with myelofibrosis sought evaluation for progressive dyspnea. Her past medical history included essential thrombocytosis, which transformed to myelofibrosis. Inspiratory computed tomography of chest showed diffuse mosaic attenuation with lymphadenopathy. Flexible bronchoscopy with lymph node and pulmonary parenchymal cryo biopsy revealed nodular deposits of extramedullary hematopoiesis in lung parenchyma and moderate to severe vascular medial and intimal thickening of pulmonary vasculature consistent with pulmonary parenchymal extramedullary hematopoiesis associated with pulmonary hypertension (a rare compensatory mechanism in myeloproliferative disorders). In this report, we explore the manifestations, pathogenesis, treatment, and prognosis of pulmonary extramedullary hematopoiesis reported in the literature.

Pulmonary alveolar proteinosis (PAP) is a diffuse lung disease characterized by the accumulation of alveolar surfactants due to dysfunction of granulocyte-macrophage colony-stimulating factor-dependent cholesterol clearance. Whole-lung lavage is the current standard of care for PAP, but it can lead to the exacerbation of hypoxia. A medication targeting cholesterol homeostasis is a promising therapy for refractory PAP. We present a case of autoimmune PAP with severe hypoxia that was successfully treated with segmental lung lavage (SLL). Following SLL for disease relapse, statin treatment for dyslipidemia was started. After initiating statin treatment, the patient did not require bronchoalveolar lavage for 10 months.

Neutrophil extracellular traps (NETs) contribute to inflammatory pathogenesis in numerous conditions, including infectious and cardiovascular diseases, and have attracted attention as potential therapeutic targets. H2 acts as an antioxidant and has been clinically and experimentally proven to ameliorate inflammation. This study was performed to investigate whether H2 could inhibit NET formation and excessive neutrophil activation. Neutrophils isolated from the blood of healthy volunteers were stimulated with phorbol-12-myristate-13-acetate (PMA) or the calcium ionophore A23187 in H2-exposed or control media. Compared with control neutrophils, PMA- or A23187-stimulated human neutrophils exposed to H2 exhibited reduced neutrophil aggregation, citrullination of histones, membrane disruption by chromatin complexes, and release of NET components. CXCR4high neutrophils are highly prone to NETs, and H2 suppressed Ser-139 phosphorylation in H2AX, a marker of DNA damage, thereby suppressing the induction of CXCR4 expression. H2 suppressed both myeloperoxidase chlorination activity and production of reactive oxygen species to the same degree as N-acetylcysteine and ascorbic acid, while showing a more potent ability to inhibit NET formation than these antioxidants do in PMA-stimulated neutrophils. Although A23187 formed NETs in a reactive oxygen species-independent manner, H2 inhibited A23187-induced NET formation, probably via direct inhibition of peptidyl arginine deiminase 4-mediated histone citrullination. Inhalation of H2 inhibited the formation and release of NET components in the blood and bronchoalveolar lavage fluid in animal models of lipopolysaccharide-induced sepsis (mice and aged mini pigs). Thus, H2 therapy can be a novel therapeutic strategy for NETs associated with excessive neutrophil activation.

UNASSIGNED: Coronavirus disease 2019 is characterized by the elevation of a broad spectrum of inflammatory mediators associated with poor disease outcomes. We aimed at an in-silico analysis of regulatory microRNA and their transcription factors (TF) for these inflammatory genes that may help to devise potential therapeutic strategies in the future.
UNASSIGNED: The cytokine regulating immune-expressed genes (CRIEG) were sorted from literature and the GEO microarray dataset. Their co-differentially expressed miRNA and transcription factors were predicted from publicly available databases. Enrichment analysis was done through mienturnet, MiEAA, Gene Ontology, and pathways predicted by KEGG and Reactome pathways. Finally, the functional and regulatory features were analyzed and visualized through Cytoscape.
UNASSIGNED: Sixteen CRIEG were observed to have a significant protein-protein interaction network. The ontological analysis revealed significantly enriched pathways for biological processes, molecular functions, and cellular components. The search performed in the miRNA database yielded ten miRNAs that are significantly involved in regulating these genes and their transcription factors.
UNASSIGNED: An in-silico representation of a network involving miRNAs, CRIEGs, and TF, which take part in the inflammatory response in COVID-19, has been elucidated. Thus, these regulatory factors may have potentially critical roles in the inflammatory response in COVID-19 and may be explored further to develop targeted therapeutic strategies and mechanistic validation.

We present a case of sarcoidosis presenting as unilateral forearm swelling. A 65-year-old male with a long history of asthma presented with unexplained left forearm and hand swelling. Over many years, chest imaging had been devoid of adenopathy or parenchymal findings suspicious for sarcoid, until after the extremity findings emerged. The patient was diagnosed based on subcutaneous, dermal and mediastinal lymph node histopathology. Sarcoid presenting with isolated extremity findings prior to more typical pulmonary manifestations is rare even for cutaneous or soft tissue sarcoid, highlighting the need to maintain a high index of suspicion for sarcoidosis.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare but fatal cancer-related disease. Owing to its non-specific findings, aggressive course, and lack of established treatment guidelines, only a few cases of antemortem diagnosis in long-term survivors have been reported. We aimed to report a case of uterine cervical cancer induced PTTM that was suspected based on pulmonary hypertension and successfully treated using combination chemotherapy despite of delayed diagnose. It is important to be aware that PTTM should be suspected when respiratory failure occurs in patients with unexplained pulmonary hypertension. Multidisciplinary treatments including molecular targeted therapies might be effective treatment options.

A 73-year-old woman who visited our hospital complaining of dry cough for three months was refractory to antimicrobial therapy. Chest computed tomography revealed subpleural consolidation. Specimens obtained from surgical lung biopsy revealed subpleural perilobular airspace organization and fibrosis. After the biopsy, mechanic\'s hand and Gottron\'s papules appeared, and anti-melanoma differentiation-associated gene 5 (MDA5) antibody was found to be positive. Subsequently, anti-MDA5 antibody measured in cryopreserved serum from her first admission proved to be positive. It is difficult to suspect the presence of anti-MDA-5 antibody in patients with interstitial lung disease without typical dermatomyositis symptoms or slow disease progression.