American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Oct 2024
ReviewPathogenesis of Post-Tuberculosis Lung Disease: Defining Knowledge Gaps and Research Priorities at the 2nd International Post-Tuberculosis Symposium.
Post-tuberculosis (post-TB) lung disease is increasingly recognized as a major contributor to the global burden of chronic lung disease, with recent estimates indicating that over half of TB survivors have impaired lung function after successful completion of TB treatment. However, the pathologic mechanisms that contribute to post-TB lung disease are not well understood, thus limiting the development of therapeutic interventions to improve long-term outcomes after TB. ⋯ The committee first identified six areas with high translational potential: 1) tissue matrix destruction, including the role of matrix metalloproteinase dysregulation and neutrophil activity; 2) fibroblasts and profibrotic activity; 3) granuloma fate and cell death pathways; 4) mycobacterial factors, including pathogen burden; 5) animal models; and 6) the impact of key clinical risk factors, including HIV, diabetes, smoking, malnutrition, and alcohol. We share the key findings from a literature review of those areas, highlighting knowledge gaps and areas where further research is needed.
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Am. J. Respir. Crit. Care Med. · Oct 2024
Multicenter StudyOutcomes in Critically Ill Allogeneic Hematopoietic Stem-Cell Transplantation Recipients.
Rationale: Allogeneic hematopoietic stem-cell transplantation (Allo-HSCT) recipients are still believed to be poor candidates for ICU management. Methods: We investigated outcomes and determinants of mortality in a large multicenter retrospective cohort of Allo-HSCT patients admitted between January 1, 2015, and December 31, 2020, to 14 French ICUs. The primary endpoint was 90-day mortality. ⋯ In patients requiring mechanical ventilation, mortality rates ranged from 39% (no other risk factors for mortality) to 100% (four associated risk factors for mortality). Conclusions: Most critically ill Allo-HSCT recipients survive their ICU stays, including those requiring mechanical ventilation, with an overall 90-day survival rate reaching 51.8%. A careful assessment of goals of care is required in patients with two or more risk factors for mortality.
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Am. J. Respir. Crit. Care Med. · Oct 2024
High-Dimensional Mass Cytometry Reveals Emphysema-associated Changes in the Pulmonary Immune System.
Rationale: Chronic inflammation plays an important role in alveolar tissue damage in emphysema, but the underlying immune alterations and cellular interactions are incompletely understood. Objectives: To explore disease-specific pulmonary immune cell alterations and cellular interactions in emphysema. Methods: We used single-cell mass cytometry (CyTOF) to compare the immune compartment in alveolar tissue from 15 patients with severe emphysema and 5 control subjects. ⋯ Conclusions: Using CyTOF, we characterized the alterations of the immune cell signature in alveolar tissue from patients with chronic obstructive pulmonary disease stage III or IV emphysema versus control lung tissue. These data contribute to a better understanding of the pathogenesis of emphysema and highlight the feasibility of interrogating the immune cell signature using CyTOF and IMC in human lung tissue. Clinical trial registered with www.clinicaltrials.gov (NCT04918706).