Home-Based Spirometry Telemonitoring After Allogeneic Hematopoietic Cell Transplantation: Mixed Methods Evaluation of Acceptability and Usability.

BACKGROUND: Home-based spirometry (HS) allows for the early detection of lung complications in recipients of an allogeneic hematopoietic cell transplant (AHCT). Although the usability and acceptability of HS are critical for adherence, patient-reported outcomes of HS use remain poorly understood in this setting. OBJECTIVE: The aim of this study is to design a longitudinal, mixed methods study to understand the usability and acceptability of HS among recipients of AHCT. METHODS: Study participants performed HS using a Bluetooth-capable spirometer that transmitted spirometry data to the study team in real time. In addition, participants completed usability questionnaires and in-depth interviews and reported their experiences with HS. Analysis of interview data was guided by the constructs of performance expectancy, effort expectancy, and social influence from the Unified Theory of Acceptance and Use of Technology model. RESULTS: Recipients of AHCT found HS to be highly acceptable despite modest technological barriers. On average, participants believed that the HS was helpful in managing symptoms related to AHCT (scores ranging from 2.22 to 2.68 on a scale of 0-4) and for early detection of health-related problems (score range: 2.88-3.12). Participants viewed HS favorably and were generally supportive of continued use. No significant barriers to implementation were identified from the patient's perspective. Age and gender were not associated with the patient perception of HS. CONCLUSIONS: Study participants found HS acceptable and easy to use. Some modifiable technical barriers to performing HS were identified; however, wider implementation of pulmonary screening is feasible from the patient's perspective.

Severity of Hypoxemia and Effect of High-Frequency Oscillatory Ventilation in Acute Respiratory Distress Syndrome.

RATIONALE: High-frequency oscillatory ventilation (HFOV) is theoretically beneficial for lung protection, but the results of clinical trials are inconsistent, with study-level meta-analyses suggesting no significant effect on mortality. OBJECTIVES: The aim of this individual patient data meta-analysis was to identify acute respiratory distress syndrome (ARDS) patient subgroups with differential outcomes from HFOV. METHODS: After a comprehensive search for trials, two reviewers independently identified randomized trials comparing HFOV with conventional ventilation for adults with ARDS. Prespecified effect modifiers were tested using multivariable hierarchical logistic regression models, adjusting for important prognostic factors and clustering effects. MEASUREMENTS AND MAIN RESULTS: Data from 1,552 patients in four trials were analyzed, applying uniform definitions for study variables and outcomes. Patients had a mean baseline PaO2/FiO2 of 114 ± 39 mm Hg; 40% had severe ARDS (PaO2/FiO2 <100 mm Hg). Mortality at 30 days was 321 of 785 (40.9%) for HFOV patients versus 288 of 767 (37.6%) for control subjects (adjusted odds ratio, 1.17; 95% confidence interval, 0.94-1.46; P = 0.16). This treatment effect varied, however, depending on baseline severity of hypoxemia (P = 0.0003), with harm increasing with PaO2/FiO2 among patients with mild-moderate ARDS, and the possibility of decreased mortality in patients with very severe ARDS. Compliance and body mass index did not modify the treatment effect. HFOV increased barotrauma risk compared with conventional ventilation (adjusted odds ratio, 1.75; 95% confidence interval, 1.04-2.96; P = 0.04). CONCLUSIONS: HFOV increases mortality for most patients with ARDS but may improve survival among patients with severe hypoxemia on conventional mechanical ventilation.

Effects of inhaled CO administration on acute lung injury in baboons with pneumococcal pneumonia.

Inhaled carbon monoxide (CO) gas has therapeutic potential for patients with acute respiratory distress syndrome if a safe, evidence-based dosing strategy and a ventilator-compatible CO delivery system can be developed. In this study, we used a clinically relevant baboon model of Streptococcus pneumoniae pneumonia to 1) test a novel, ventilator-compatible CO delivery system; 2) establish a safe and effective CO dosing regimen; and 3) investigate the local and systemic effects of CO therapy on inflammation and acute lung injury (ALI). Animals were inoculated with S. pneumoniae (10(8)-10(9) CFU) (n = 14) or saline vehicle (n = 5); in a subset with pneumonia (n = 5), we administered low-dose, inhaled CO gas (100-300 ppm × 60-90 min) at 0, 6, 24, and/or 48 h postinoculation and serially measured blood carboxyhemoglobin (COHb) levels. We found that CO inhalation at 200 ppm for 60 min is well tolerated and achieves a COHb of 6-8% with ambient CO levels ≤ 1 ppm. The COHb level measured at 20 min predicted the 60-min COHb level by the Coburn-Forster-Kane equation with high accuracy. Animals given inhaled CO + antibiotics displayed significantly less ALI at 8 days postinoculation compared with antibiotics alone. Inhaled CO was associated with activation of mitochondrial biogenesis in the lung and with augmentation of renal antioxidative programs. These data support the feasibility of safely delivering inhaled CO gas during mechanical ventilation and provide preliminary evidence that CO may accelerate the resolution of ALI in a clinically relevant nonhuman primate pneumonia model.

Physiologic effects of an ambulatory ventilation system in chronic obstructive pulmonary disease.

RATIONALE: Exercise intolerance limits the ability of patients with chronic obstructive pulmonary disease (COPD) to perform daily living activities. Noninvasive ventilation reduces dyspnea and improves exercise performance, but current systems are unsuitable for ambulatory use. OBJECTIVES: In patients with COPD experiencing exercise-induced desaturation, we evaluated improvements in exercise tolerance facilitated by a wearable, 1-lb, noninvasive open ventilation (NIOV) system featuring a nasal pillow interface during constant work rate (CWR) cycle ergometer exercise and associated effects on dyspnea, respiratory muscle activation, and pulmonary gas exchange efficiency. METHODS: Fifteen men with COPD (FEV1 = 32.2 ± 12.0% predicted; FEV1/FVC = 31.6 ± 7.1%; exercise oxygen saturation as measured by pulse oximetry [Spo2] = 86.5 ± 2.9%) participated. After incremental testing establishing peak work rate, subjects completed three visits in which they performed CWR exercise to tolerance at 80% peak work rate: (1) unencumbered breathing room air, (2) using NIOV+compressed air, (3) using NIOV+compressed O2, or (4) using O2 via nasal cannula. Assessments included exercise duration, surface inspiratory muscle EMG, Spo2, transcutaneous Pco2, and Borg dyspnea scores. MEASUREMENTS AND MAIN RESULTS: Exercise endurance was 17.6 ± 5.7 minutes using NIOV+O2, greatly prolonged compared with unencumbered (5.6 ± 1.9 min), nasal O2 (11.4 ± 6.8 min), and NIOV+Air (6.3 ± 4.1 min). Isotime Spo2 was higher and intercostal, scalene, and diaphragmatic EMG activity was reduced using NIOV+O2 compared with unencumbered, nasal O2, and NIOV+Air, signifying respiratory muscle unloading. Isotime dyspnea reduction correlated with isotime EMG reduction (r = 0.42, P = 0.0053). There were no significant differences in isotime VD/VT or transcutaneous Pco2 among treatments. CONCLUSIONS: NIOV+O2 yielded substantial exercise endurance improvements accompanied by respiratory muscle unloading and dyspnea reductions in patients with severe hypoxemic COPD.

Gaseous nitric oxide bactericidal activity retained during intermittent high-dose short duration exposure.

Previously, we have shown that gaseous Nitric oxide (gNO) has great potential as an effective topical anti-infective agent for non-healing wounds due to its non-specific antimicrobial properties. These same antimicrobial attributes may be useful for pulmonary infections. However, gNO would have limited usefulness as an inhaled antimicrobial agent as continuous exposure to the concentration required for a bactericidal effect (160-200 ppm) leads to methemoglobinemia. To overcome this problem, we investigated whether a thirty minute exposure of 160 ppm every four hours would retain the same antimicrobial effect as continuous delivery. In vitro, exposure of clinical multi-drug resistant Staphylococcus aureus and Escherichia coli strains isolated from the lungs of nosocomial pneumonia patients and a lethal antibiotic-resistant strain of Pseudomonas aeruginosa, isolated from a deceased cystic fibrosis patient resulted in over a 5 log(10) reduction in bacterial load after multiple thirty minute treatments (4 cycles) every four hours to 160 ppm gNO. The intermittent regimen required 320 (SD=0)ppm h for 100% lethality whereas the continuous exposure required 800 (SD=160)ppm h. We have also shown that selection for a gNO resistant phenotype did not lead to decrease sensitivity to gNO therapy (p>0.05). In addition, no host cellular toxicity was observed in human THP-1 monocytes and macrophages following intermittent delivery of a high concentration of gNO, and the proliferation and migration of pulmonary epithelial cells was not adversely affected by the administration of intermittent high-dose gNO. These results justify further studies that should focus on whether intermittent delivery of 160 ppm of gNO every four hours can technically be administered while keeping inhaled NO(2) levels less than 2 ppm and methemoglobin saturation less than 2.5 percent.