Browsing by keyword "respiratory insufficiency"

Now showing items 1-2 of 2

    • AAV9 gene replacement therapy for respiratory insufficiency in very-long chain acyl-CoA dehydrogenase deficiency
      Zieger, Marina; Keeler, Allison M.; Flotte, Terence R.; ElMallah, Mai K. (2019-04-17)
      Very-long chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD) is an autosomal recessive disorder of fatty acid oxidation. Fatty acids are a major source of energy during catabolic stress, so the absence of VLCAD can result in a metabolic crises and respiratory insufficiency. The etiology of this respiratory insufficiency is unclear. Thus, our aims were: (1) to characterize respiratory pathophysiology in VLCADD mice (VLCAD(-/-) ), and (2) to determine if AAV9-mediated gene therapy improves respiratory function. For the first aim, VLCAD(-/-) and wild-type (WT) mice underwent an exercise/fast "stress protocol" and awake spontaneous breathing was evaluated using whole-body plethysmography (WBP) both at baseline and during a hypercapnic respiratory challenge (FiO2 : 0.21; FiCO2 : 0.07; nitrogen balance). During hypercapnia, VLCAD (-/-) mice had a significantly lower frequency, tidal volume, minute ventilation, and peak inspiratory and expiratory flow, all of which indicate respiratory insufficiency. Histologically, the cardiac and respiratory muscles of stressed VLCAD (-/-) animals had an accumulation of intramyocellular lipids. For the second aim, a single systemic injection of AAV9-VLCAD gene therapy improved this respiratory pathology by normalizing breathing frequency and enhancing peak inspiratory flow. In addition, following gene therapy, there was a moderate reduction of lipid accumulation in the respiratory muscles. Furthermore, VLCAD protein expression was robust in cardiac and respiratory muscle. This was confirmed by immuno-staining with anti-human VLCAD antibody. In summary, stress with exercise and fasting induces respiratory insufficiency in VLCAD(-/-) mice and a single injection with AAV9-VLCAD gene therapy ameliorates breathing.

    • Outcomes of Noninvasive and Invasive Ventilation in Patients Hospitalized with Asthma Exacerbation
      Stefan, Mihaela S.; Nathanson, Brian H.; Lagu, Tara; Priya, Aruna; Pekow, Penelope S.; Steingrub, Jay; Hill, Nicholas S.; Goldberg, Robert J.; Kent, David M.; Lindenauer, Peter K. (2016-07-01)
      RATIONALE: Little is known about the effectiveness of noninvasive ventilation for patients hospitalized with asthma exacerbation. OBJECTIVES: To assess clinical outcomes of noninvasive (NIV) and invasive mechanical ventilation (IMV) and examine predictors for NIV use in patients hospitalized with asthma. METHODS: This was a retrospective cohort study at 97 U.S. hospitals using an electronic medical record database. We developed a hierarchical regression model to identify factors associated with the choice of initial ventilation and used the Laboratory Acute Physiological Score to adjust for differences in the severity of illness. We assessed the outcomes of patients treated with initial NIV or IMV in a propensity-matched cohort. MEASUREMENTS AND MAIN RESULTS: Among 13,930 subjects, 73% were women and 54% were white. The median age was 53 years. Overall, 1,254 patients (9%) required ventilatory support (NIV or IMV). NIV was the initial ventilation method for 556 patients (4.0%) and IMV for 668 (5.0%). Twenty-six patients (4.7% of patients treated with NIV) had to be intubated (NIV failure). The in-hospital mortality was 0.2, 2.3, 14.5, and 15.4%, and the median length of stay was 2.9, 4.1, 6.7, and 10.9 days among those not ventilated, ventilated with NIV, ventilated with IMV, and with NIV failure, respectively. Older patients were more likely to receive NIV (odds ratio, 1.06 per 5 yr; 95% confidence interval [CI], 1.01-1.11), whereas those with higher acuity (Laboratory Acute Physiological Score per 5 units: odds ratio, 0.85; 95% CI, 0.82-0.88) and those with concomitant pneumonia were less likely to receive NIV. In a propensity-matched sample, NIV was associated with a lower inpatient risk of dying (risk ratio, 0.12; 95% CI, 0.03-0.51) and shorter lengths of stay (4.3 d less; 95% CI, 2.9-5.8) than IMV. CONCLUSIONS: Among patients hospitalized with asthma exacerbation and requiring ventilatory support (NIV or IMV), more than 40% received NIV. Although patients successfully treated with NIV appear to have better outcomes than those treated with IMV, the low rate of NIV failure suggests that NIV was being used selectively in a lower risk group. The increased risk of mortality for patients who fail NIV highlights the need for careful monitoring to avoid possible delay in intubation.