Numerous animal studies have demonstrated that adult marrow-derived cells can contribute to the cellular component of the lung. Lung injury is a major variable in this process; however, the mechanism remains unknown. We hypothesize that injured lung is capable of inducing epigenetic modifications of marrow cells, influencing them to assume phenotypic characteristics of lung cells. We report that under certain conditions, radiation-injured lung induced expression of pulmonary epithelial cell-specific genes and prosurfactant B protein in cocultured whole bone marrow cells separated by a cell-impermeable membrane. Lung-conditioned media had a similar effect on cocultured whole bone marrow cells and was found to contain pulmonary epithelial cell-specific RNA-filled microvesicles that entered whole bone marrow cells in culture. Also, whole bone marrow cells cocultured with lung had a greater propensity to produce type II pneumocytes after transplantation into irradiated mice. These findings demonstrate alterations of marrow cell phenotype by lung-derived microvesicles and suggest a novel mechanism for marrow cell-directed repair of injured tissue.

Objective-Previous studies have demonstrated the production of various types of lung cells from marrow cells under diverse experimental conditions. Our aim was to identify some of the variables that influence conversion in the lung. Methods-In separate experiments, mice received various doses of total-body irradiation followed by transplantation with whole bone marrow or various subpopulations of marrow cells (Lin −/+ , ckit −/+ , Sca-1 −/+ ) from GFP + (C57BL/6-TgN[ACTbEGFP]1Osb) mice. Some were given intramuscular cardiotoxin and/or mobilized with granulocyte colony-stimulating factor (G-CSF).Results-The production of pulmonary epithelial cells from engrafted bone marrow was established utilizing green fluorescent protein (GFP) antibody labeling to rule out autofluorescence and deconvolution microscopy to establish the colocaliztion of GFP and cytokeratin and the absence of CD45 in lung samples after transplantation. More donor-derived lung cells (GFP + /CD45 − ) were seen with increasing doses of radiation (5.43% of all lung cells, 1200 cGy). In the 900-cGy group, 61.43% of GFP + /CD45 − cells were also cytokeratin + . Mobilization further increased GFP + / CD45 − cells to 7.88% in radiation-injured mice. Up to 1.67% of lung cells were GFP + /CD45 − in radiation-injured mice transplanted with Lin − , c-kit + , or Sca-1 + marrow cells. Lin + , c-kit − , and Sca-1 − subpopulations did not significantly engraft the lung. Conclusions-We have established that marrow cells are capable of producing pulmonary epithelial cells and identified radiation dose and G-CSF mobilization as variables influencing the production of lung cells from marrow cells. Furthermore, the putative lung cell-producing marrow cell has the phenotype of a hematopoietic stem cell.

Study Objective: To validate the ApneaLINK (AL) as an accurate tool for determining the presence of obstructive sleep apnea (OSA) in an at-risk sleep clinic population in a home test environment. Methods: Consecutive participants referred with the suspicion of OSA were evaluated in the home with the AL portable monitor (AL Home), followed by simultaneous data collection with diagnostic polysomnography (PSG) and AL in the sleep laboratory (AL Lab). Prevalence, sensitivity, specifi city, and ROC curves were calculated for PSG vs. AL Lab, PSG vs. AL Home, and AL Lab vs. AL Home test. Pearson correlations and Bland-Altman plots were constructed. Results: Fifty-three (55% female) participants completed the entire study. The mean age of the population was 45.1 ± 11.3 years, and body mass index was 35.9 ± 9.1 kg/m 2 . The prevalence of an apnea hypopnea index (AHI) ≥ 15 in the cohort was 35.9%. The results demonstrated a high sensitivity and specificity of the AL respiratory disturbance index (RDI-AL) compared with the AHI from the PSG. The AL Lab had the highest sensitivity and specificity at RDI-AL values ≥ 20 events/h (sensitivity 100%, specificity 92.5%). The AL Home was most sensitive and specific at an RDI-AL ≥ 20 events/h (sensitivity 76.9%, specificity 92.5%). The Pearson correlations for PSG vs. AL Lab and PSG vs. AL Home were ρ = 0.88 and ρ = 0.82, respectively. The BlandAltman Plots demonstrated good agreement between the methodologies. Conclusion: The AL home test is an accurate alternative to PSG in sleep clinic populations at risk for moderate and severe OSA. Trial Registration: clinicaltrials.gov ID: NCT00354614. Keywords: Obstructive sleep apnea, portable monitoring, diagnosis Citation: Oktay B; Rice TB; Atwood CW; Passero M; Gupta N; Givelber R; Drumheller OJ; Houck P; Gordon N; Strollo PJ. Evaluation of a single-channel portable monitor for the diagnosis of obstructive sleep apnea.