A Comparison of Measurements of Change in Respiratory Status in Spontaneously Breathing Volunteers by the ExSpiron Noninvasive Respiratory Volume Monitor Versus the Capnostream Capnometer.

BACKGROUND: Current respiratory monitoring technologies such as pulse oximetry and capnography have been insufficient to identify early signs of respiratory compromise in nonintubated patients. Pulse oximetry, when used appropriately, will alert the caregiver to an episode of dangerous hypoxemia. However, desaturation lags significantly behind hypoventilation and alarm fatigue due to false alarms poses an additional problem. Capnography, which measures end-tidal CO2 (EtCO2) and respiratory rate (RR), has not been universally used for nonintubated patients for multiple reasons, including the inability to reliably relate EtCO2 to the level of impending respiratory compromise and lack of patient compliance. Serious complications related to respiratory compromise continue to occur as evidenced by the Anesthesiology 2015 Closed Claims Report. The Anesthesia Patient Safety Foundation has stressed the need to improve monitoring modalities so that "no patient will be harmed by opioid-induced respiratory depression." A recently available, Food and Drug Administration-approved noninvasive respiratory volume monitor (RVM) can continuously and accurately monitor actual ventilation metrics: tidal volume, RR, and minute ventilation (MV). We designed this study to compare the capabilities of capnography versus the RVM to detect changes in respiratory metrics. METHODS: Forty-eight volunteer subjects completed the study. RVM measurements (MV and RR) were collected simultaneously with capnography (EtCO2 and RR) using 2 sampling methods (nasal scoop cannula and snorkel mouthpiece with in-line EtCO2 sensor). For each sampling method, each subject performed 6 breathing trials at 3 different prescribed RRs (slow [5 min], normal [12.6 ± 0.6 min], and fast [25 min]). All data are presented as mean ± SEM unless otherwise indicated. RESULTS: Following transitions in prescribed RRs, the RVM reached a new steady state value of MV in 37.7 ± 1.4 seconds while EtCO2 changes were notably slower, often failing to reach a new asymptote before a 2.5-minute threshold. RRs as measured by RVM and capnography during steady breathing were strongly correlated (R = 0.98 ± 0.01, bias = Capnograph-based RR - RVM-based RR = 0.21 ± 1.24 [SD] min). As expected, changes in MV were negatively correlated with changes in EtCO2. However, large changes in MV following transitions in prescribed RR resulted in relatively small changes in EtCO2 (instrument sensitivity = ΔEtCO2/ΔMV = -0.71 ± 0.11 and -0.55 ± 0.11 mm Hg per 1 L/min for nasal and in-line sampling, respectively). Nasal cannula EtCO2 measurements were on average 4 mm Hg lower than in-line measurements. CONCLUSIONS: RVM measurements of MV change more rapidly and by a greater degree than capnography in response to respiratory changes in nonintubated patients. Earlier detection could enable earlier intervention that could potentially reduce frequency and severity of complications due to respiratory depression.

Genome Editing Therapy for the Blood: Ex Vivo Success and In Vivo Prospects.

Hematopoietic stem cells (HSCs) provide the body with a continuous supply of healthy, functional blood cells. In patients with hematopoietic malignancies, immunodeficiencies, lysosomal storage disorders, and hemoglobinopathies, therapeutic genome editing offers hope for corrective intervention, with even modest editing efficiencies likely to provide clinical benefit. Engineered white blood cells, such as T cells, can be applied therapeutically to address monogenic disorders of the immune system, HIV infection, or cancer. The versatility of CRISPR-based tools allows countless new medical interventions for diseases of the blood, and rapid ex vivo success has been demonstrated in hemoglobinopathies via transplantation of the patient's HSCs following genome editing in a laboratory setting. Here we review recent advances in therapeutic genome editing of HSCs and T cells, focusing on the progress in ex vivo contexts, the promise of improved access via in vivo delivery, as well as the ongoing preclinical efforts that may enable the transition from ex vivo to in vivo administration. We discuss the challenges, limitations, and future prospects of this rapidly developing field, which may one day establish CRISPR as the standard of care for some diseases affecting the blood.