Peak Cough Flow Fails to Detect Upper Airway Collapse During Negative Pressure Titration for Cough-Assist.

OBJECTIVE: To study the ability of peak cough flow (PCF) and effective cough volume, defined as the volume exsufflated >3 L/s, to detect upper airway collapse during mechanical insufflation-exsufflation (MI-E) titration in neuromuscular patients. DESIGN: Prospective observational study. SETTING: Rehabilitation hospital. PARTICIPANTS: Patients (N=27) with neuromuscular disease causing significant impairment of chest wall and/or diaphragmatic movement. INTERVENTIONS: The lowest insufflation pressure producing the highest inspiratory capacity was used. Exsufflation pressure was decreased from -20 cm H2O to -60/-70 cm H2O, in 10-cm H2O decrements, until upper airway collapse was detected using the reference standard of flow-volume curve analysis (after PCF, abrupt flattening or flow decrease vs previous less negative exsufflation pressure). MAIN OUTCOME MEASURES: PCF and effective cough volume profiles during expiration with MI-E. RESULTS: Upper airway collapse occurred in 10 patients during titration. Effective cough volume increased with decreasing expiratory pressure then decreased upon upper airway collapse occurrence. PCF continued to increase after upper airway collapse occurrence. In 5 other patients, upper airway collapse occurred at the initial -20 cm H2O exsufflation pressure, and during titration, PCF increased and effective cough volume remained unchanged at <200 mL. PCF had 0% sensitivity for upper airway collapse, whereas effective cough volume had 100% sensitivity and specificity. CONCLUSION: Of 27 patients, 15 experienced upper airway collapse during MI-E titration. Upper airway collapse was associated with an effective cough volume decrease or plateau and with increasing PCF. Accordingly, effective cough volume, but not PCF, can detect upper airway collapse.

Macrophage-derived oncostatin M contributes to human and mouse neurogenic heterotopic ossifications.

Neurogenic heterotopic ossification (NHO) is the formation of ectopic bone generally in muscles surrounding joints following spinal cord or brain injury. We investigated the mechanisms of NHO formation in 64 patients and a mouse model of spinal cord injury-induced NHO. We show that marrow from human NHOs contains hematopoietic stem cell (HSC) niches, in which mesenchymal stromal cells (MSCs) and endothelial cells provide an environment supporting HSC maintenance, proliferation, and differentiation. The transcriptomic signature of MSCs from NHOs shows a neuronal imprinting associated with a molecular network required for HSC support. We demonstrate that oncostatin M (OSM) produced by activated macrophages promotes osteoblastic differentiation and mineralization of human muscle-derived stromal cells surrounding NHOs. The key role of OSM was confirmed using an experimental model of NHO in mice defective for the OSM receptor (OSMR). Our results provide strong evidence that macrophages contribute to NHO formation through the osteogenic action of OSM on muscle cells within an inflammatory context and suggest that OSM/OSMR could be a suitable therapeutic target. Altogether, the evidence of HSCs in ectopic bones growing at the expense of soft tissue in spinal cord/brain-injured patients indicates that inflammation and muscle contribute to HSC regulation by the brain-bone-blood triad.