Pulmonary and Critical Care Associates

Anti-Mi-2 Dermatomyositis in Skin of ColorAuthors:Albert Holler, MD MPH - Department of Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA Salem Hernandez, MD - Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine, New Haven, CT, USACorresponding Author:Albert Holler, MD MPH 600 N Wolfe St, Baltimore, MD 21287, USA Email: albertholleriv@gmail.comPhone: 630-795-9529Funding Source(s):None.Conflict of Interest Statement:The authors declare no conflicts of interest.

FOXP3+ natural regulatory T cells (nTregs) promote resolution of inflammation and repair of epithelial damage following viral pneumonia–induced lung injury, thus representing a cellular therapy for patients with severe viral pneumonia and the acute respiratory distress syndrome. Whether in vitro–induced Tregs (iTregs), which can be rapidly generated in substantial numbers from conventional T cells, also promote lung recovery is unknown. nTregs require specific DNA methylation patterns maintained by the epigenetic regulator ubiquitin-like with PHD and RING finger domains 1 (UHRF1). Here, we tested whether iTregs promote recovery following viral pneumonia and whether iTregs require UHRF1 for their pro-recovery function. We found that adoptive transfer of iTregs to mice with influenza virus pneumonia promotes lung recovery and that loss of UHRF1-mediated maintenance DNA methylation in iTregs leads to reduced engraftment and a delayed repair response. Transcriptional and DNA methylation profiling of adoptively transferred UHRF1-deficient iTregs that had trafficked to influenza-injured lungs demonstrated transcriptional instability with gain of transcription factors that define effector T cell lineage. Strategies to promote the stability of iTregs could be leveraged to further augment their pro-recovery function during viral pneumonia and other causes of severe lung injury.

Inhalation of methanol vapor is a rare but potentially life-threatening occupational hazard, particularly in environments with inadequate ventilation and safety controls. We report the case of an 18-year-old male shrimp processing worker who developed acute respiratory failure following accidental inhalation of methanol vapors mislabeled as kerosene. The patient presented with severe dyspnea, hypoxemia, metabolic acidosis, and radiographic findings of diffuse pulmonary infiltrates. He required mechanical ventilation, corticosteroids, antibiotics, and intensive supportive care. Bronchoscopy revealed erythematous bronchial mucosa with hemorrhagic stippling and was followed by bronchoalveolar lavage (BAL). Based on imaging findings, therapeutic segmental pulmonary lavage (TSPL) was performed, targeting the most affected lower lobe segments. The procedure involved instillation and aspiration of small saline aliquots to remove inflammatory debris. Following TSPL, the patient exhibited marked clinical improvement, with normalization of inflammatory markers and successful extubation within 48 hours. This case illustrates the potential value of TSPL as an adjunctive therapy in methanol-induced chemical pneumonitis. Unlike standard BAL, TSPL enables targeted clearance of toxic exudates from specific lung segments, potentially accelerating recovery in patients with localized airway injury. Given the rarity of inhalational methanol poisoning and the absence of established respiratory interventions beyond supportive care, TSPL may offer a novel approach to managing severe pulmonary complications. This experience highlights the need for heightened clinical awareness of inhalational toxic exposures and further research into therapeutic lavage techniques. Our findings suggest that TSPL could be considered in selected cases of toxic inhalation injury when conventional measures fail to produce timely improvement.

Pulmonary fibrosis (PF) has been called a fibroproliferative disease, yet the functional importance of proliferating fibroblasts to PF has not been systematically examined. In response to alveolar injury, quiescent alveolar fibroblasts differentiate into fibrotic fibroblasts that express high amounts of collagens. However, what role, if any, proliferation plays in the accumulation of fibrotic fibroblasts has remained unclear. Using 5-ethynyl-2′-deoxyuridine (EdU) incorporation, genetic lineage tracing, and single-cell RNA-Seq, we delineated the proliferation dynamics of lung fibroblasts during post-injury fibrogenesis. We found substantial DNA replication in progeny of alveolar fibroblasts in 2 independent models of PF. Lineage labeling revealed clonal expansion of these fibroblast descendants principally in regions of fibrotic remodeling. The transcriptome of proliferating fibroblasts closely resembled that of fibrotic fibroblasts, suggesting that fibroblasts can first differentiate into fibrotic fibroblasts and then proliferate. Genetic ablation of proliferating fibroblasts and selective inhibition of cytokinesis in alveolar fibroblast descendants significantly mitigated PF and rescued lung function. Furthermore, fibroblasts in precision-cut lung slices from human fibrotic lungs exhibited higher proliferation rates than did those in nondiseased lungs. Together, this work establishes fibroblast proliferation as a critical driver of PF and suggests that specifically targeting fibroblast proliferation could be a new therapeutic strategy for fibrotic diseases.

Rationale: Persistent critical illness (PerCI) is costly, increasing in incidence, and not reliably predicted with existing risk-prediction tools. Objective: To assess whether attending intensivists can identify patients at heightened risk of developing PerCI. Methods: We conducted a prospective longitudinal assessment from August 2020 to January 2023. Intensivists were assessed on each patient within 24 hours of admission to the medical intensive care unit (ICU) and on ICU Day 3. We measured intensivists' prognostication of within-ICU events (late-onset shock and/or acute hypoxic respiratory failure [AHRF] and PerCI) and self-rated confidence in prognostications. Test characteristics were calculated for both outcomes at each time point and stratified by self-rated confidence. Results: A total of 1,295 assessments were completed (response rate, 87.9%), assessing 875 ICU admissions by 18 intensivists. Late-onset shock/AHRF and PerCI occurred in 7.3% and 16.0% of ICU admissions, respectively. C-statistics for intensivist prognostication of late-onset shock/AHRF were 0.5 (95% confidence interval [CI], 0.5-0.6) and 0.6 (95% CI, 0.5-0.6) on admission and Day 3, respectively. C-statistics for PerCI were 0.7 (95% CI, 0.7-0.7) and 0.7 (95% CI, 0.7-0.8), respectively. C-statistics for late-onset shock/AHRF were no different for confident versus unconfident assessments. C-statistics for PerCI were higher for confident versus unconfident assessments (0.8 vs. 0.6; P < 0.01) on admission, but not different on Day 3 (0.7 vs. 0.7; P = 0.20). Conclusions: Intensivist prognostications have poor discriminatory accuracy for the development of late-onset shock/AHRF and moderate accuracy for development of PerCI. Further research is needed to understand what factors influence intensivists' prognostications of within-ICU deterioration and how this information is conveyed to patients and families.