Subtherapeutic ganciclovir (GCV) levels and GCV-resistant cytomegalovirus in lung transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) infection results in significant morbidity and mortality in lung transplant recipients. Ganciclovir (GCV) has dramatically reduced complications caused by CMV infections. Unfortunately, GCV resistance is identified in 5-10% of CMV-infected patients. Mismatched CMV status and ongoing replication due to immunosuppression are risk factors for drug resistance. Whether subtherapeutic GCV levels contribute to resistance remains unknown. METHODS: A retrospective review was conducted in all 51 patients who underwent lung transplantation between March 2007 and June 2008 at Loyola University Medical Center. GCV resistance and outcome data of CMV-infected patients were analyzed to identify variables that may contribute to suboptimal response to CMV infection. RESULTS: During the 16-month period, CMV infection was identified in 21 of 51 lung transplant recipients. Ten of 21 patients (47.6%) had CMV infection with early response to GCV, and 11 patients (52.4%) had CMV infection with suboptimal response to GCV. GCV levels were obtained in the 11 CMV-infected patients with suboptimal response. In 6 patients, GCV levels were therapeutic; all 6 had delayed response to GCV. In 5 patients, GCV levels were subtherapeutic; each had persistent suboptimal response to GCV. Genotyping documented GCV-resistant (GCV-R) CMV in all 5 patients. Cystic fibrosis as the diagnosis requiring lung transplantation was associated with GCV-R CMV infection (P = 0.01). CONCLUSION: In our lung transplant recipient cohort, GCV levels were subtherapeutic in all patients with persistent suboptimal response to GCV, each of whom had GCV-R CMV infection. In contrast, GCV levels were therapeutic in CMV-infected patients with delayed GCV response.

Extending ventilator circuit change interval beyond 2 days reduces the likelihood of ventilator-associated pneumonia.

OBJECTIVE: To determine the risk of acquiring ventilator-associated pneumonia (VAP) and the impact on costs when extending ventilator circuit change intervals beyond 2 days to 7 and 30 days. DESIGN: Prospective 4-year review of mechanically ventilated patients. SETTING: The respiratory and medical ICUs of an 800-bed tertiary teaching Veterans Affairs hospital. PATIENTS: All adult patients receiving mechanical ventilation from January 1991 through December 1994. INTERVENTIONS: Ventilator circuits with active heated water humidifiers were changed at 2-day intervals during a 2-year control period, followed by 7-day and 30-day intervals (for 1 year each). Heated wire circuits were adopted with the 30-day interval. The rate of VAP per 1,000 ventilator days was calculated for each circuit change interval group. Survival analysis was used to model VAP with ventilator circuit change to determine risk. RESULTS: During the study period, 637 patients received mechanical ventilation. During the 2 years with 2-day change intervals, the VAP per 1,000 ventilator days was 11.88 (n=343), compared with 3.34 (n=137) and 6.28 (n=157) for 7-day and 30-day change intervals, respectively. The risk of acquiring a VAP for those with a circuit change every 2 days was significantly greater (relative risk, 3.1; p=0.0004; 95% confidence interval, 1.662, 5.812) than those with the 7- and 30-day circuit changes. Extending circuit change intervals reduced supply and labor costs averaging $4,231/yr for each ventilator in use. CONCLUSIONS: Circuit change intervals of 7 and 30 days have lower risks for VAP than the 2-day intervals, yielding substantial reductions in morbidity as well labor and supply costs.

Discontinuous incremental threshold loading test: measure of respiratory muscle endurance in patients with COPD.

STUDY OBJECTIVE: To assess the discontinuous incremental threshold loading (DC-ITL) test as a measure of respiratory muscle endurance for patients with COPD in terms of perceived breathing difficulty, reliability, and validity. DESIGN: The DC-ITL test was repeated three times at weekly intervals under identical test conditions. SETTING: Clinical research laboratory. PATIENTS: Forty-eight patients with moderate to severe COPD. MEASUREMENTS AND RESULTS: Rating of perceived breathing difficulty (RPBD) was measured at the end of each stage of the DC-ITL test with a Borg category-ratio scale. The maximal inspiratory pressure (PImax) was measured before and after the DC-ITL test. Breathing patterns were measured during the DC-ITL test. The mean (+/-SD) for RPBD at the maximal load was 6.3 (3.1), 6.6 (2.8), and 6.7 (2.7) for visits one, two, and three, respectively (not significant). The mean relative maximal load for the DC-ITL test (peak mouth pressure as a percent of PImax) at the last completed stage was 59+/-23%, 62+/-20%, and 63+/-19% for visits one, two, and three, respectively (not significant). Test-retest reliability was r1,2=0.82 and r2,3=0.69 for relative maximal load and r1,2=0.90 and r2,3=0.90 for absolute maximal load (peak mouth pressure). Tidal volume decreased (p < 0.01) and respiratory rate increased (p < 0.01) from the next-to-the-last to the last completed stage. PImax decreased after the DC-ITL test (p < 0.01). CONCLUSIONS: Moderate breathing difficulty was experienced during the DC-ITL test. The test was reliable and the results of this study support its validity as a measure of respiratory muscle endurance.

Maximal inspiratory pressure. Learning effect and test-retest reliability in patients with chronic obstructive pulmonary disease.

Reliability of the maximal inspiratory pressure (Pimax) was examined by measuring Pimax once a week for 4 weeks in 91 patients with chronic obstructive pulmonary disease using an aneroid pressure gauge. Five Pimax trials were conducted at each test. From the first to the fourth test, the Pimax increased by a mean of 9 cm H2O (SD = 10). From the third to the fourth test, Pimax increased by a mean of 2 cm H2O and performance appeared to be plateauing. The test-retest reliability coefficient was r = 0.97 for Pimax measured at the third and fourth test session. The 95 percent confidence interval for the absolute difference in Pimax at the third and fourth test was 3 to 5 cm H2O. We conclude that performance of Pimax improves with practice in naive COPD patients and Pimax is reliable when measured with an aneroid gauge by experienced data collectors if patients are given sufficient practice.

Changes in end-expiratory lung volume during sleep in patients with occlusive apnea.

Eight patients with occlusive sleep apnea were monitored during non-rapid-eye-movement (NREM) sleep to study the factors that contribute to negative inspiratory pressure generation and thus upper airway occlusion. End-expiratory lung volume assessed by respiratory inductive plethysmography [sum of end-expiratory levels (SUM EEL)] increased early and decreased late during the ventilatory phases (P less than 0.0001, one-way analysis of variance). Inspiratory change in esophageal pressure (Pes) and peak inspiratory diaphragmatic and genioglossal electromyograms (EMGdi and EMGge) decreased while the inspiratory pressure generated for a given diaphragmatic activity (Pes/EMGdi) increased during the preapneic phase (P less than 0.0001, for all). Multiple regression analysis with Pes/EMGdi as the dependent variable (R2 = 0.90) indicated that both the changes in SUM EEL and EMGge significantly contributed to the model (P less than 0.008 and 0.004, respectively). These results indicate that end-expiratory lung volume fluctuates during NREM sleep in patients with occlusive apnea and suggest that these changes along with the changes in upper airway muscle activity contribute to the generation of negative inspiratory pressure, leading to the passive collapse of the upper airways.

Effects of continuous positive airway pressure on upper airway and respiratory muscle activity.

To study the effects of continuous positive airway pressure (CPAP) on lung volume, and upper airway and respiratory muscle activity, we quantitated the CPAP-induced changes in diaphragmatic and genioglossal electromyograms, esophageal and transdiaphragmatic pressures (Pes and Pdi), and functional residual capacity (FRC) in six normal awake subjects in the supine position. CPAP resulted in increased FRC, increased peak and rate of rise of diaphragmatic activity (EMGdi and EMGdi/TI), decreased peak genioglossal activity (EMGge), decreased inspiratory time and inspiratory duty cycle (P less than 0.001 for all comparisons). Inspiratory changes in Pes and Pdi, as well as Pes/EMGdi and Pdi/EMGdi also decreased (P less than 0.001 for all comparisons), but mean inspiratory airflow for a given Pes increased (P less than 0.001) on CPAP. The increase in mean inspiratory airflow for a given Pes despite the decrease in upper airway muscle activity suggests that CPAP mechanically splints the upper airway. The changes in EMGge and EMGdi after CPAP application most likely reflect the effects of CPAP and the associated changes in respiratory system mechanics on the afferent input from receptors distributed throughout the intact respiratory system.

Upper airway occlusion during sleep in patients with Cheyne-Stokes respiration.

Sleep-induced periodic breathing has been suggested to lead to the development of occlusive apneas in patients with sleep apnea syndrome. If this were true, patients with Cheyne-Stokes respiration should also develop upper airway occlusion during sleep. To study this hypothesis, 6 nonobese patients with Cheyne-Stokes respiration lacking evidence for sleep apnea syndrome and anatomic upper airway abnormalities underwent polysomnography during daytime naps. A total of 463 apneas were analyzed in the 6 patients studied. In 1 patient, no evidence of upper airway occlusion was observed. In the remaining 5 patients, a varying frequency of upper airway occlusion resembling the pattern of mixed apnea was seen in 3 to 97% of the total apneas analyzed. The mean number (+/- 1 SD) of occluded inspiratory efforts per mixed apnea in these 5 patients was 1.69 +/- 0.59. These results show that patients with Cheyne-Stokes respiration may develop upper airway occlusion during sleep and are consistent with the contention that sleep-induced periodic breathing in patients with sleep apnea syndrome is primary to the development of occlusive apneas.

Test-retest reliability of symptom-limited cycle ergometer tests in patients with chronic obstructive pulmonary disease.

BACKGROUND: Symptom-limited exercise tests are widely used to evaluate the effects of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD), but the reliability of these tests is not well established in COPD patients. OBJECTIVES: We compared test-retest reliability of two repeated symptom-limited exercise tests between COPD patients and healthy elderly subjects and between male and female patients. METHOD: Fifty-six COPD patients (40 men, 16 women) and 16 healthy subjects (6 men, 10 women) performed two symptom-limited exercise tests approximately 2 weeks apart. Measures of oxygen uptake (VO2), minute ventilation (VE), heart rate, and ratings of breathlessness and leg fatigue were obtained at peak exercise at each symptom-limited exercise test. RESULTS: Repeated measures of peak exercise responses were stable for patients and healthy subjects and for male and female patients. Although mean percent error (absolute difference/mean) for peak exercise responses was low, some individuals' values exceeded 10%. There was no difference in the percent error between COPD patients and healthy subjects or between men and women with COPD. Test-retest reliability was lower for breathlessness ratings than for other peak exercise responses for all groups. CONCLUSIONS: Repeated symptom-limited exercise tests are reliable in COPD patients and healthy subjects. However, some individuals are less reliable, and these patients may require more than one exercise test to establish reliable performance.

Inspiratory muscle training in patients with chronic obstructive pulmonary disease.

The effects of 6 months of muscle training with an inspiratory pressure load equal to 30% of the maximal inspiratory pressure (PImax) was compared with sham training with a light inspiratory pressure load. In this double-blind randomly assigned study, 67 patients with chronic obstructive pulmonary disease were followed for 6 months. Both groups demonstrated improvements in performance of PImax, respiratory muscle endurance time for breathing against an inspiratory pressure load equal to 66% of PImax, 12-minute distance walk, and dyspnea. The treatment group did not demonstrate significant effects beyond those observed in the control group. Improvements in performance were related to improved coordination of the inspiratory muscles and desensitization to dyspnea.

Reliability and validity of the 12-minute distance walk in patients with chronic obstructive pulmonary disease.

Validity and test-retest liability of the 12-minute distance (12MD) walk, a measure of functional status, were examined in patients with chronic obstructive pulmonary disease. Four tests were administered at weekly intervals. Performance increased (p < .01) over the first three tests. Test-retest reliability was r34 = .98 (df = 46) for tests 3 and 4. The 12MD walk correlated with the Sickness Impact Profile, Physical Dimension (r = -.45); forced expiratory volume in 1 second % predicted ( r = .40); maximal inspiratory pressure (PImax) (r = .52); and exercise-related breathlessness (r = -.49). Exercise-related breathlessness and PImax accounted for 42% of the variance. The validity and reliability of the 12MD walk were supported.

Cycle ergometer and inspiratory muscle training in chronic obstructive pulmonary disease.

In patients with chronic obstructive pulmonary disease (COPD) the intensity of aerobic training is limited by dyspnea. Improving strength of the inspiratory muscles could enhance aerobic exercise training by reducing exercise-related dyspnea. We examined effects of home-based inspiratory muscle training (IMT) and cycle ergometry training (CET) in 53 patients with moderate to severe COPD (FEV(1)% pred, 50 +/- 17 [mean +/- SD]). Patients were randomly assigned to 4 mo of training in one of four groups: IMT, CET, CET + IMT, or health education (ED). Patients were encouraged to train to the limits of their dyspnea. Inspiratory muscle strength and endurance increased in IMT and CET + IMT groups compared with CET and ED groups (p < 0. 01). Peak oxygen uptake increased and heart rate, minute ventilation, dyspnea, and leg fatigue decreased at submaximal work rates in the CET and CET + IMT groups compared with the IMT and ED groups (p < 0. 01). There were no differences between the CET and CET + IMT groups. Home-based CET produced a physiological training effect and reduced exercise-related symptoms while IMT increased respiratory muscle strength and endurance. The combination of CET and IMT did not produce additional benefits in exercise performance and exercise-related symptoms. This is the first study to demonstrate a physiological training effect with home-based exercise training.

High-intensity inspiratory muscle training in patients with chronic obstructive pulmonary disease and severely reduced function.

PURPOSE: This study examined the effects of inspiratory muscle training (IMT) with high-intensity inspiratory pressure loads on respiratory muscle performance and exertional dyspnea. METHODS: This was a randomized single-blind clinical trial. Twenty-seven patients with chronic obstructive pulmonary disease (18 men, 9 women) with severe to very severe airflow obstruction and severely limited functional performance were assigned randomly to an IMT group (n = 12) or an educational control group (n = 15). The IMT group trained with a threshold loaded device for 30 minutes a day for 16 weeks using interval training techniques. Training was initiated with inspiratory pressure loads equal to 30% of maximal inspiratory pressure (Plmax) and increased as tolerated to 60% of Plmax. Dependent variables were measured before and after 4 months of IMT: inspiratory muscle strength (Plmax), respiratory muscle endurance (discontinuous incremental threshold loading test [DC-ITL]), dyspnea (Chronic Respiratory Disease Questionnaire [CRQ]), and the Borg Category-Ratio Scale ratings of perceived breathing difficulty (RPBD) at equal loads during the DC-ITL. RESULTS: In the IMT group, Plmax increased from 64 +/- 15 to 75 +/- 17 cm H2O (P < .05), performance on the DC-ITL test increased from a maximal load of 37 +/- 12 to 53 +/- 13 cm H2O (P < .05), RPBD decreased from 5.5 +/- 2.5 to 3.8 +/- 2.6 for equal loads on the DC-ITL (P < .05) and the CRQ Dyspnea Scale improved from 18.1 +/- 5.1 to 22.4 +/- 5.2 (P < .05). CONCLUSIONS: Inspiratory muscle training at high-intensity loads significantly improved inspiratory muscle strength, respiratory muscle endurance, and respiratory symptoms during daily activities and respiratory exertion.

Diaphragm pacing with a quadripolar phrenic nerve electrode: an international study.

We sought to determine the international experience with the quadripolar diaphragm pacer system and to test two hypotheses: the incidence of pacer complications would be (1) increased among pediatric as compared to adult patients; and (2) highest among active pediatric patients with idiopathic congenital central hypoventilation syndrome (CCHS). Data were collected via a questionnaire coupled with the Atrotech Registry data for a total of 64 patients (35 children and 29 adults) from 14 countries. Thoracic implantation of electrodes and bilateral pacer use each occurred in 94% of all subjects. Tetraplegic (vs pediatric CCHS) patients were more typically paced 24 hours/day (P = 0.001). Pacing duration averaged 2.0 +/- 1.0 years among children and 2.2 +/- 1.1 years among adults. Infections occurred among 2.9% of surgical procedures, all in pediatric CCHS patients (vs pediatric tetraplegic patients, P = 0.01). The incidence of mechanical trauma was 3.8%, without significant differences among patient groups. The incidence of presumed electrode and receiver failure were 3.1% and 5.9%, respectively, with internal component failure greater among pediatric CCHS than pediatric tetraplegic patients (P < 0.01). Intermittent or absent function of 0-4 electrode combinations occurred among 19% of all patients, with increased frequency among pediatric CCHS than pediatric tetraplegic patients (P < 0.03). Complication-free successful pacing occurred in 60% of pediatric and 52% of adult patients. In all, 94% of the pediatric and 86% of the adult patients paced successfully after the necessary intervention. Although pacer complications were not increased among pediatric as compared to adult patients, the incidence of complications was highest among the active pediatric patients with CCHS. Longitudinal study of these patients will provide invaluable information for modification and improvement of the quadripolar system.