Ling Ling Chiang

Effects of Physical Training on Functional Status in Patients With Prolonged Mechanical Ventilation

Background and Purpose. Patients requiring prolonged mechanical ventilation (PMV) are frequently deconditioned because of respiratory failure precipitated by the underlying disease, the adverse effects of medications, and a period of prolonged immobilization. The effects of 6 weeks of physical training on the strength of respiratory and limb muscles, on ventilator-free time, and on functional status in patients requiring PMV were examined. Subjects. Thirty-nine patients with PMV were initially enrolled in the study and were assigned to either a treatment group (n=20) or a control group (n=19). Three subjects in the treatment group and 4 subjects in the control group died during the 6-week intervention period and thus their data were excluded from the final analysis. Methods. Subjects in the treatment group received physical training 5 days a week for 6 weeks. Strength of respiratory and limb muscles, ventilator-free time, and functional status, which was measured by the Barthel Index of Activities of Daily Living (BI) and Functional Independence Measure (FIM), were examined at baseline and at the third and sixth weeks of the study period. Results. Respiratory and limb muscle strength improved significantly at the third and sixth weeks in the treatment group compared with baseline measurements. Total BI and FIM scores increased significantly in the treatment group and remained unchanged in the control group. Effect sizes of the BI and FIM scores were 2.02 and 1.93, respectively, at the sixth week. Discussion and Conclusion. The results show that a 6-week physical training program may improve limb muscle strength and ventilator-free time and thus improve functional outcomes in patients requiring PMV.

Preventive Use of Noninvasive Ventilation After Extubation: A Prospective, Multicenter Randomized Controlled Trial

BACKGROUND: The effectiveness of noninvasive ventilation (NIV) after extubation in preventing post-extubation respiratory failure is still controversial. METHODS: We conducted a prospective, multicenter randomized controlled study involving patients on mechanical ventilation for > 48 hours who tolerated a 2-hour spontaneous breathing trial and were subsequently extubated. The patients were randomized to NIV or standard medical therapy. Re-intubation rate within 72 hours was the primary outcome measure. Multivariable logistic regression analysis was used to determine predictors for extubation failure. RESULTS: We randomized 406 patients to either NIV (no. = 202) or standard medical therapy (no. = 204). The 2 groups had similar baseline clinical characteristics. There were no differences in extubation failure (13.2% in control and 14.9% in NIV), intensive care unit or hospital mortality. Cardiac failure was a more common cause of extubation failure in control than in NIV. There was no difference in rapid shallow breathing index (RSBI) in extubation failure patients between control (80) and NIV (73). When using data from all patients, we found Acute Physiology and Chronic Health Evaluation (APACHE II) scores (odds ratio [OR] 1.13, 95% CI 1.07–1.20, P < .001), maximal inspiratory pressure (OR 1.04, 95% CI 1.00–1.08, P = .03), and RSBI (OR 1.03, 95% CI 1.02–1.05, P < .001) to be predictors of extubation failure. Abundant secretions were the most common reason (35.1%) for extubation failure identified by attending physicians. CONCLUSIONS: Preventive use of NIV after extubation in patients who passed spontaneous breathing trial did not show benefits in decreasing extubation failure rate or the mortality rate.

Physical training is beneficial to functional status and survival in patients with prolonged mechanical ventilation

BACKGROUND/PURPOSE Early physical training is necessary for severely deconditioned patients undergoing prolonged mechanical ventilation (PMV), because survivors often experience prolonged recovery. Long-term outcomes after physical training have not been measured; therefore, we investigated outcome during a 1-year period after physical training for the PMV patients. METHODS We conducted a prospective randomized control trial in a respiratory care center. Thirty-four patients were randomly assigned to the rehabilitation group (n = 18) and the control group (n = 16). The rehabilitation group participated in supervised physical therapy training for 6 weeks, and continued in an unsupervised maintenance program for 6 more weeks. The functional independence measurement (FIM) was used to assess functional status. Survival status during the year after enrollment, the number of survivors discharged, and the number free from ventilator support were collected. These outcome parameters were assessed at entry, immediately after the 6 weeks physical therapy training period, after 6 weeks unsupervised maintenance exercise program, and 6 months and 12 months after study entry. RESULTS The scores of total FIM, motor domain, cognitive domain, and some sub-items, except for the walking/wheelchair sub-item, increased significantly in the rehabilitation group at 6 months postenrollment, but remained unchanged for the control group. The eating, comprehension, expression, and social interaction subscales reached the 7-point complete independence level at 6 months in the rehabilitation group, but not in the control group. The 1-year survival rate for the rehabilitation group was 70%, which was significantly higher than that for the control group (25%), although the proportion of patients discharged and who were ventilator-free in the rehabilitation and control groups did not differ significantly. CONCLUSION Six weeks physical therapy training plus 6 weeks unsupervised maintenance exercise enhanced functional levels and increased survival for the PMV patients compared with those with no such intervention. Early physical therapy interventions are needed for the PMV patients in respiratory care centers.

Domiciliary Positive Expiratory Pressure Improves Pulmonary Function and Exercise Capacity in Patients with Chronic Obstructive Pulmonary Disease

BACKGROUND/PURPOSE This study assessed how positive expiratory pressure (PEP) affected pulmonary function, functional capacity, and subjective cough difficulty in individuals with chronic obstructive pulmonary diseases (COPD). METHODS This was a prospective, randomized, controlled study. Subjects were recruited from an outpatient department at a university hospital. Thirty-two patients with COPD were allocated to either PEP + FET (forced expiratory technique) group (n = 16) or FET only group (n = 16). Subjects in PEP + FET and FET groups were in a clinically stable condition before and during the study. Subjects in the PEP + FET group received PEP breathing using a mouth adjunct to FET, and the FET group was administered FET for 4 weeks only. Patients received weekly follow-up during the study period. Pulmonary function, 6-minute walk tests, and subjective cough difficulty scores were measured before and after the 4-week interventions. RESULTS Subjects in the PEP + FET group had a significantly increased diffusing capacity (DLCO) compared to preintervention (p < 0.05) and after intervention in the FET group (p < 0.05). DLCO significantly increased in the PEP + FET group from 18.0 +/- 7.3 to 20.1 +/- 7.2 mL/min/mmHg. The 6-minute walking distance (6MWD) also increased significantly from 516.8 +/- 94.1 to 570.6 +/- 60.4 m in the PEP + FET group (p < 0.001) after intervention, compared to that for the FET group (p < 0.05). Additionally, the PEP + FET group had significantly lower cough difficulty scores compared to those at baseline and in the FET group. CONCLUSION Four-week PEP therapy as an adjunct to FET further enhanced DLCO and 6MWD, and reduced cough difficulty compared to FET only in COPD patients with mucus hypersecretion.

Six-month nocturnal nasal positive pressure ventilation improves respiratory muscle capacity and exercise endurance in patients with chronic hypercapnic respiratory failure

BACKGROUND/PURPOSE This study was designed to investigate the effects of 6 months of nocturnal nasal positive pressure ventilation (NNPPV) on respiratory muscle function and exercise capacity in patients with chronic respiratory failure. METHODS A prospective, randomized, controlled design was used. Twenty-nine patients with chronic respiratory failure were enrolled and allocated to either the NNPPV (n = 14) or control group (n = 15). Patients in the NNPPV group received bi-level positive pressure ventilation via nasal mask for 6 consecutive months. Arterial blood gas, respiratory muscle assessment and 6-minute walk test (6MWT) were performed before and after the 6-month NNPPV intervention. Respiratory muscle function was assessed using the variables of maximal inspiratory pressure (Pimax), maximal expiratory pressure (Pemax), and maximum voluntary ventilation (MVV). RESULTS Subjects in the NNPPV group showed a significant improvement in blood gas exchange and increased 6-minute walk distance (6MWD) compared to baseline and the control group. The 6MWD was significantly increased from 257.1 +/- 114.1 to 345.2 +/- 109.9 m (34.3%) in the NNPPV group. NNPPV also significantly improved MVV and Pimax relative to baseline. MVV was significantly increased from 19.2 +/- 6.5 to 22.3 +/- 7.1 L/min (16.1%) in the NNPPV group (p < 0.05). Furthermore, there was a significant correlation between the magnitude of MVV improvement and 6MWD change. CONCLUSION The 6-month NNPPV treatment significantly decreased the partial pressure of carbon dioxide and improved daytime respiratory muscle function, thus contributing to exercise-capacity increase in patients with chronic respiratory failure.

Comparison of domiciliary oxygen using liquid oxygen and concentrator in northern Taiwan

BACKGROUND/PURPOSE Long-term oxygen therapy has become standard treatment for patients with chronic respiratory insufficiency. However, patterns of long-term home oxygen therapy have not been well studied in Taiwan. Oxygen concentrator systems are commonly used in Taiwan, but liquid oxygen delivery systems are portable and may provide advantages over the concentrator system. This study compared oxygen usage between patients from a liquid oxygen group (LOG) and an oxygen concentrator group (OCG). The authors also assessed the physiologic responses of patients with chronic obstructive pulmonary disease (COPD) to ambulatory oxygen use at home. METHODS The study used a retrospective, cross-sectional, observational survey design. The LOG comprised 42 patients, and the OCG comprised 102 patients. We recruited participants in northern Taiwan from July 2009 to April 2010. The questionnaire instruments that were used to collect data consisted of three parts: demographic characteristics, devices used in respiratory care, and activity status with portable oxygen. Two-minute walking tests were performed on COPD patients in their homes. RESULTS COPD was the most common diagnosis in our study, with more than 50% of patients who received oxygen long term in both groups having received this diagnosis. The LOG used oxygen for an average of 21.7 hours per day, whereas OCG averaged 15.2 hours per day (p<0.001). In the OCG, 92.2% of patients used a concentrator alone, whereas 23.8% of the LOG used liquid oxygen alone (p<0.001). The LOG patients were involved in significantly more outdoors activities (p=0.002) and reported traveling with oxygen more often (p<0.001) than the OCG patients. For patients with the same dyspnea level of COPD severity, those using liquid oxygen had a lower increase in pulse rate after the walking test, in comparison with the concentrator users. CONCLUSION Patients in the LOG used oxygen for longer hours, went on more outings, and were more likely to travel with oxygen than patients in the OCG. Being ambulatory with liquid oxygen might enable patients with COPD to walk more effectively.

Amelioration of superoxide dismutase on ventilator-induced lung injury by suppressing leukocyte in the lungs and systemic circulation.

Superoxide dismutase (SOD) is a free radical scavenger and a broad-spectrum antioxidant. Its anti-inflammatory and immunomodulatory effects have recently been noted. We studied the effects of this antioxidant on lung damage, oxidative stress, and inflammation in a model of ventilator-induced lung injury (VILI), using 8- to 12-wk-old Sprange-Dawley rats (n = 40). Animals were randomized and evenly divided into two experimental groups, low tidal volume (V(T)) ventilation (V(T) = 9 ml/kg) and high V(T) ventilation (V(T) = 28 ml/kg). Each group was evenly divided into two subgroups: ten animals were treated with superoxide dismutase (SOD; 10,000 U/kg i.v., 2 h prior to the ventilation) and the rests were treated with vehicle. Lung injury was evaluated by histological examination, and cells counts of red blood cells (RBC) and white blood cells (WBC) in the alveoli and the septal wall thickness in lung tissues and serum lactate dehydrogenase (LDH). The lung permeability was assessed by the wet-to-dry weight ratio (W/D), lung weight to body weight ratio (LW/BW) and protein concentration in broncholavage fluid (BALF). Levels of oxidative stress and lipid peroxidation in the lungs were evaluated by tissue malondialdehyde (MDA) and methylguanidine (MG) in BALF, respectively. SOD pretreatment significantly decreased WBC counts in systemic circulation and in alveoli, and effectively attenuated high V(T) ventilation induced lung injury by reducing hyaline membrane development, septal wall thickness, lung W/D and LW/BW and serum LDH in relation to those of the control. In addition, lung tissues MDA and MG in BALF were also notably reduced.

Apoptosis-dependent and -independent mechanisms mediate the phagocytic recognition/clearance of the HL60-A1 transfectants with prolonged survival

Abstract.Objective:The phagocytic recognition and clearance of the recruited inflammatory cells with prolonged survival play a pivotal role in relieving tissue inflammation and maintaining tissue homeostasis. Transgenic mice expressing Bcl-2 in mature neutrophils demonstrated that Bcl-2 attenuated neutrophil apoptosis, while the homeostasis of the neutrophil population was essentially unaffected. This result suggests that clearance of neutrophils with prolonged survival operates independently from apoptosis. Owing to the constitutive and inducible expression of Bcl-2 homologue, A1 in human neutrophils and the intolerance of preparation for the isolated human neutrophils with prolonged survival, the human promyelocytic HL60-A1 transfectants were established to study the mechanism of phagocytic recognition/clearance of the cells with prolonged survival.Materials and Methods:The non-apoptotic cells with prolonged survival were enriched by serum withdrawal for five days and negatively isolated by annexin V-binding beads. Then, the cells were labeled with a fluorogenic marker. Monocyte-derived macrophages (MDM) were co-cultured to perform the phagocytosis assay, and flow cytometry was employed to determine the phagocytic index.Results:In the serum-free condition, the phagocytic index of HL60-A1 transfectants was little different from that of the HL60-EGFP control, despite showing a significantly lower degree of apoptosis. While the phagocytic index of HL60-EGFP control was significantly correlated with the degree of apoptosis, the index of the HL60-A1 transfectants was less relevant to it. The phagocytic index for the annexin V-positive cells did not distinguish the two cell types. However, the phagocytic index for the annexin V-negative cells from the HL60-A1 transfectants was increased with age in days. Preincubation of MDM with the scavenger receptor inhibitor, Oxi-LDL, and the inhibitory antibodies against αvβ3, CD14 and CD36 surface molecules could attenuate the phagocytic recognition of the annexin V-positive HL60 cells but not the annexin V-negative A1 transfectants with prolonged survival.Conclusions:This study thus suggests that a mechanism unrelated to apoptosis exists, which mediates the phagocytic clearance of the non-apoptotic cells with prolonged survival and may be associated with A1 function in the myeloid cells.

Cyclosporine, an Immunosuppressant, Attenuates Phorbol-Induced Lung Injury in Rats

OBJECTIVE White cell activation in the lung plays a critical role to induce lung injury and lymphocytes in the thoracic duct system may also participate. We evaluated the effect of cyclosporine on phorbol myristate acetate (PMA)-induced lung injury. MATERIALS AND METHODS We used an in situ isolated, blood perfused rat lung model to measure pulmonary arterial pressure (PAP) and lung weight gain (LWG; g) for 50 minutes after a bolus injection of PMA (0.05 microg/mL). Oxygen radical release was estimated by an LKB 1251 luminometer and by nitric oxide (NO) release as measured by an ENO-20 NO analyzer. RESULTS In the group exposed to PMA alone, the mean PAP increased from 16.53 +/- 1.28 to 43.33 +/- 3.40 mm Hg (P < .001), and lung weight increased by 4.35 +/- 0.67 g during the 50-minute perfusion after PMA challenge (P < .001). In vitro measurement showed that PMA induced a significant increase in oxygen radical release (P < .001). PMA attenuated NO release (P < .001) into the perfusion system. Pretreatment with cyclosporine (3 mg/kg) for 3 days prevented the increases in both PAP (P < .01) and LWG (P < .001). NO release was maintained in cyclosporine-pretreated rats. Cyclosporine also showed dose-dependent attenuation of oxygen radical release by PMA-activated white blood cells. CONCLUSION The mechanisms responsible for the protective effect of cyclosporine on the lung injury induced by phorbol may be related to an attenuation of oxygen radical production with maintenance of NO release.

RE: Noninvasive mechanical ventilation for prevention of post- extubation respiratory failure

In their prospective multicenter randomized controlled trial, Su et al report that noninvasive mechanical ventilation (NIV) used in all patients after extubation did not reduce re-intubation rate, when compared to standard oxygen therapy.[1][1] Nevertheless, we believe that the concept of “