Clinical Scholar, Medicine - Pulmonary, Allergy & Critical Care Medicine
Molecular and cellular biology of the distal lung
High altitude medicine
The distal lung is a honeycomb-like collection of delicate gas exchange sacs called alveoli lined by two interspersed epithelial cell types: the cuboidal, surfactant-producing alveolar type II (AT2) and the flat, gas-exchanging alveolar type I (AT1) cell. During aging, a subset of AT2 cells expressing the canonical Wnt target gene, Axin2, function as stem cells, renewing themselves while generating new AT1 and AT2 cells. Wnt activity endows AT2 cells with proliferative competency, enabling them to respond to activating cues, and simultaneously blocks AT2 to AT1 cell transdifferentiation. Acute alveolar injury rapidly expands the AT2 stem cell pool by transiently inducing Wnt signaling activity in "bulk" AT2 cells, facilitating rapid epithelial repair. AT2 cell "stemness" is thus tightly regulated by access to Wnts, supplied by a specialized single-cell fibroblast niche during maintenance and by AT2 cells themselves during injury repair. Two non-AT2 "reserve" cell populations residing in the distal airways also contribute to alveolar repair, but only after widespread epithelial injury, when they rapidly proliferate, migrate, and differentiate into airway and alveolar lineages. Here, we review alveolar renewal and repair with a focus on the niches, rather than the stem cells, highlighting what is known about the cellular and molecular mechanisms by which they control stem cell activity in vivo.
View details for DOI 10.1101/cshperspect.a035717
View details for PubMedID 32179507
Alsup, Carl, Grant S. Lipman, David Pomeranz, Rwo-Wen Huang, Patrick Burns, Nicholas Juul, Caleb Phillips, Carrie Jurkiewicz, Mary Cheffers, Christina Evans, Anirudh Saraswathula, Peter Baumeister, Lucinda Lai, Jessica Rainey, and Viveta Lobo. Interstitial pulmonary edema assessed by lung ultrasound on ascent to high altitude and slight association with acute mountain sickness: A prospective observational study. High Alt Med Biol. 00:000-000, 2019. Background: Acute mountain sickness (AMS) is a common disease that may have a pulmonary component, as suggested by interstitial pulmonary edema quantified by the B-line score (BLS) on ultrasound (US). This subclinical pulmonary edema has been shown to increase with ascent to high altitude and AMS severity, but has not been prospectively associated with AMS incidence in a large prospective study. Materials and Methods: This prospective observational study was part of a randomized controlled trial enrolling healthy adults over four weekends ascending White Mountain, California. Subjects were assessed by lung US and the Lake Louise Questionnaire at 4110?ft (1240?m), upon ascent to 12,500?ft (3810?m), and the next morning at 12,500?ft (3810?m). Results: Three hundred five USs in total were completed on 103 participants, with 73% total incidence of AMS. The mean (±standard deviation) BLS increased from baseline (1.15?±?1.80) to high altitude (2.56?±?2.86), a difference of 1.37 (±2.48) (p?=?0.04). Overall BLS was found, on average, to be higher among those diagnosed with AMS than without (2.97 vs. 2.0, p?=?0.04, 95% confidence interval [CI] -? to -0.04). The change in BLS (?BLS) from low altitude baseline was significantly associated with AMS (0.88 vs. 1.72, r2?=?0.023, 95% CI -? to -0.01, p?=?0.048). Conclusions: Interstitial subclinical pulmonary edema by lung US was found to have a small but significant association with AMS.
View details for PubMedID 31045443