The Impact of Alemtuzumab and Basiliximab Induction on Patient Survival and Time to Bronchiolitis Obliterans Syndrome in Double Lung Transplantation Recipients.

We examined the effect of alemtuzumab and basiliximab induction therapy on patient survival and freedom from bronchiolitis obliterans syndrome (BOS) in double lung transplantation. The United Network for Organ Sharing database was reviewed for adult double lung transplant recipients from 2006 to 2013. The primary outcome was risk-adjusted all-cause mortality. Secondary outcomes included time to BOS. There were 6117 patients were identified, of whom 738 received alemtuzumab, 2804 received basiliximab, and 2575 received no induction. Alemtuzumab recipients had higher lung allocation scores compared with basiliximab and no-induction recipients (41.4 versus 37.9 versus 40.7, p < 0.001) and were more likely to require mechanical ventilation before to transplantation (21.7% versus 6.5% versus 6.2%, p < 0.001). Median survival was longer for alemtuzumab and basiliximab recipients compared with patients who received no induction (2321 versus 2352 versus 1967 days, p = 0.001). Alemtuzumab (hazard ratio 0.80, 95% confidence interval 0.67-0.95, p = 0.009) and basiliximab induction (0.88, 0.80-0.98, p = 0.015) were independently associated with survival on multivariate analysis. At 5 years, alemtuzumab recipients had a lower incidence of BOS (22.7% versus 55.4 versus 55.9%), and its use was independently associated with lower risk of developing BOS on multivariate analysis. While both induction therapies were associated with improved survival, patients who received alemtuzumab had greater median freedom from BOS.

Blunted expression of miR-199a-5p in regulatory T cells of patients with chronic obstructive pulmonary disease compared to unaffected smokers.

Chronic obstructive pulmonary disease (COPD) is characterized by an abnormal regulatory T cell (T(reg)) response and increases in T helper type 1 (Th1) and Th17 cell responses. It is unclear if dysregulation of microRNAs (miRNA) within T(reg) cells contributes to the abnormal inflammatory response in COPD. In this study, we aimed to compare the miRNA profile of COPD T(reg) cells with that of healthy controls and to explore the function of differentially expressed miRNAs. We first obtained T(reg) and T effector cells (Teff ) from peripheral blood of non-smokers, unaffected current smokers and COPD current smokers. Then, we assessed their miRNA expression by microarray analysis followed by real-time reverse transcription-polymerase chain reaction (RT-PCR) validation of particular miRNAs. Six and 96 miRNAs were expressed differentially in COPD T(reg) cells versus T(reg) cells of healthy non-smokers and healthy smokers, whereas no differences were found in miRNA expression in T(eff) cells. We found that miR-199a-5p was repressed by approximately fourfold in T(reg) cells of COPD patients compared to healthy smokers (P < 0·05). In addition, miR-199a-5p was over-expressed in T(reg) cells compared to Teff cells (P < 0·001) and had significant over-representation of its target genes in the T(reg) transcriptome, being associated with the transforming growth factor (TGF)-ß activation pathway (P < 0·01). We also confirmed the function of miR-199a5p in an in-vitro loss-of-function cell model running TaqMan® arrays of the human TGF-ß pathway. These findings suggest that the abnormal repression of miR-199a-5p in patients with COPD compared to unaffected smokers may be involved in modulating the adaptive immune balance in favour of a Th1 and Th17 response.

Biologic lung volume reduction therapy for advanced homogeneous emphysema.

This report summarises phase 2 trial results of biologic lung volume reduction (BioLVR) for treatment of advanced homogeneous emphysema. BioLVR therapy was administered bronchoscopically to 25 patients with homogeneous emphysema in an open-labelled study. Eight patients received low dose (LD) treatment with 10 mL per site at eight subsegments; 17 received high dose (HD) treatment with 20 mL per site at eight subsegments. Safety was assessed in terms of medical complications during 6-month follow-up. Efficacy was assessed in terms of change from baseline in gas trapping, spirometry, diffusing capacity, exercise capacity, dyspnoea and health-related quality of life. There were no deaths or serious medical complications during the study. A statistically significant reduction in gas trapping was observed at 3-month follow-up among HD patients, but not LD patients. At 6 months, changes from baseline in forced expiratory volume in 1 s (-8.0+/-13.93% versus +13.8+/-20.26%), forced vital capacity (-3.9+/-9.41% versus +9.0+/-13.01%), residual volume/total lung capacity ratio (-1.4+/-13.82% versus -5.4+/-12.14%), dyspnoea scores (-0.4+/-1.27 versus -0.8+/-0.73 units) and St George's Respiratory Questionnaire total domain scores (-4.9+/-8.3 U versus -12.2+/-12.38 units) were better with HD than with LD therapy. BioLVR therapy with 20 mL per site at eight subsegmental sites may be a safe and effective therapy in patients with advanced homogeneous emphysema.

Prevalence and clinical correlates of bronchoreversibility in severe emphysema.

Chronic obstructive pulmonary disease (COPD) exhibits airflow obstruction that is not fully reversible. The importance of bronchoreversibility remains controversial. We hypothesised that an emphysematous phenotype of COPD would be associated with decreased bronchoreversibility. 544 patients randomised to the medical arm of the National Emphysema Treatment Trial formed the study group. Participants underwent multiple measurements of bronchoreversibility on a mean of four sessions over 1.91 yrs. They were also characterised by measures of symptoms, quality of life and quantitative measures of emphysema by computed tomography. Mean baseline forced expiratory volume in 1 s (FEV(1)) in this patient population is 24% predicted. 22.2% of patients demonstrated bronchoreversibility on one or more occasions using American Thoracic Society/European Respiratory Society criteria. Few patients (0.37%) had bronchoreversibility on all completed tests. Patients who demonstrated bronchoreversibility were more likely to be male, and have better lung function and less emphysema. 64% of patients demonstrated large (> or =400 mL) changes in forced vital capacity (FVC). In a severe emphysema population, bronchoreversibility as defined by change in FEV(1) is infrequent, varies over time, and is more common in males and those with less severe emphysema. Improvements in FVC, however, were demonstrated in the majority of patients.

The GOLD Summit on chronic obstructive pulmonary disease in low- and middle-income countries.

Chronic obstructive pulmonary disease (COPD) is one of the top three causes of death worldwide, but governments and non-governmental organisations have not given its prevention and treatment the priority it requires. This is particularly true in low- and middle-income countries, where most of the people suffering from this disease live. The United Nations (UN) has targeted a reduction of premature deaths from non-communicable diseases (NCDs) by a third by 2030; however, a coordinated UN/World Health Organization (WHO) strategy to address the burden of COPD (one of the most important NCDs) is still lacking. To explore the extent of the problem and inform the development of policies to improve the situation, the Board of Directors of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) held a 1-day Summit. The key themes that emerged were the need to ensure accurate data on prevalence, raise awareness of the disease among the public, healthcare professionals and governments, including the fact that COPD aetiology goes beyond smoking (and other inhaled pollutants) and includes poor lung development in early life, and ensure that spirometry and both pharmacological and non-pharmacological therapies are available and affordable. Here, we present the actions that must be taken to address the impact of COPD. We believe that the WHO is particularly well-positioned to co-ordinate an attack on COPD, and GOLD will do all it can to help and rally support.

Swallowing dysfunction in patients receiving prolonged mechanical ventilation.

Several studies have suggested that swallowing dysfunction and pulmonary aspiration occur in patients receiving prolonged ventilation. However, the incidence of swallowing dysfunction, its rate of resolution, and the sensitivity of tests used to characterize swallowing abnormalities are not well defined. The goals of our study were to evaluate swallowing function in this group of patients by (1) defining the specific swallowing abnormalities that occur in this patient population, (2) comparing the sensitivity of bedside evaluations to modified barium swallow with videofluoroscopy (MBS/VF), (3) performing endoscopic evaluation of the upper airway to characterize glottic function during swallowing, (4) evaluating the relationship between swallowing dysfunction and neuromuscular disorders, and (5) studying the temporal resolution of swallowing abnormalities. Swallowing function was evaluated in 35 patients receiving prolonged ventilation (ie, > or = 3 weeks) admitted to a specialized rehabilitation unit dedicated to the care of patients requiring prolonged ventilation. The average age of the 35 patients was 61 +/- 15 years. The total duration of intubation at the time of the initial swallowing evaluation was 29 +/- 34 days via a cuffed tracheostomy tube and 15 +/- 9 days via an endotracheal tube. Neuromuscular disorders were present in 16 patients (45%). Thirty-four percent of the patients had at least one swallowing abnormality detected by bedside examination. Results of bedside swallowing examination were abnormal in 31% of patients with a neuromuscular disorder and 37% of patients without a neuromuscular disorder. MBS/VF was abnormal in 83% of patients (85% in patients with and 80% in patients without a neuromuscular disorder). Results of early (< 1 month) repeated MBS/VF examinations usually remained unchanged; however, in a small group of patients, later studies (> or = 1 month) revealed significant improvement. In 50% of patients who underwent direct laryngoscopy, important abnormalities were found that contributed to swallowing dysfunction. Our data show that patients requiring prolonged mechanical ventilation have a high incidence of swallowing abnormalities, regardless of the presence or absence of neuromuscular disorders. MBS/VF and direct laryngoscopy can provide useful information about laryngeal action and swallowing dysfunction, and can facilitate the implementation of corrective actions to prevent respiratory complications.

Recovery from cryptococcemia and the adult respiratory distress syndrome in the acquired immunodeficiency syndrome.

We describe a patient who presented with cryptococcosis and the adult respiratory distress syndrome (ARDS) as the initial manifestation of the acquired immunodeficiency syndrome. This patient represents the first reported recovery from ARDS secondary to widespread cryptococcosis. He is currently doing well as an outpatient on maintenance therapy with amphotericin B and azidothymidine.

Diffuse alveolar hemorrhage temporally related to cocaine smoking.

Previous reports of respiratory complications from cocaine abuse have focused on pulmonary barotrauma or a reduction in carbon monoxide diffusing capacity. We report a patient who developed life-threatening alveolar hemorrhage following repeated inhalation of alkaloid cocaine.

Pattern of non-ICU inpatient supplemental oxygen utilization in a university hospital.

Random assessments of SaO2 were performed via pulse oximetry in 274 hospitalized non-ICU patients prescribed supplemental O2 in a large tertiary care university hospital. In 507 assessments performed in patients inspiring the prescribed O2, 426 were receiving excessive amounts of O2 to maintain a SaO2 > or = 92 percent. In 233 of these assessments, SaO2 was > or = 92 percent while breathing ambient air. In an additional 193 assessments, the concentration of inspired supplemental O2 was excessive to maintain a SaO2 > or = 92 percent. However, in 81 assessments performed in patients inspiring O2, the prescribed amount was insufficient to maintain SaO2 > or = 92 percent. These results indicate that O2 prescription in hospitalized non-ICU patients is excessive or not required in the majority of cases. Furthermore, routine use of pulse oximetry in hospitalized patients prescribed O2 may be useful in determining the continued need for supplemental O2 and adjusting the proper concentration needed to avoid hypoxemia.

Sleep in the intensive care unit.

The most critically ill patients in the hospital are located in the ICU. Due to intensive individualized care and monitoring, these patients often suffer from severe sleep deprivation. The amount and continuity of sleep as well as normal sleep architecture are all affected. Moreover, by impairing protein synthesis, cell division, and cellular immunity, sleep deprivation can affect the healing process and thus contribute to an increased morbidity and mortality. Reasons for sleep deprivation appear to be multifactorial and include the following: the patient's chronic underlying illness, an acute superimposed illness or surgical procedure, medications used in treatment of the primary illness, and the ICU environment itself. Therapeutic interventions need to address each of these potential causes, with an emphasis placed on providing an environment that is both diurnal and focused on the importance of uninterrupted sleep.

Efficacy and compliance with noninvasive positive pressure ventilation in patients with chronic respiratory failure.

STUDY OBJECTIVES: Previous studies have shown the acute effects of noninvasive positive pressure ventilation (NPPV) in chronic respiratory failure; however, information on the chronic effects of NPPV is limited. We examined the acute and chronic effects of NPPV on gas exchange, functional status, and respiratory mechanics in patients with chronic respiratory failure related to restrictive ventilatory disorders or COPD. DESIGN: Descriptive analysis of prospectively collected clinical data. SETTING: Inpatient noninvasive respiratory care unit and outpatient clinic of university hospital. PATIENTS: Forty patients with chronic respiratory failure (20 with severe COPD and 20 with restrictive ventilatory disorders). INTERVENTIONS AND MEASUREMENTS: All patients were admitted to a noninvasive respiratory care unit for 20 +/- 3 days for inpatient evaluation consisting of medical treatment, rehabilitation, and NPPV evaluation and instruction. NPPV was titrated via a ventilatory support system (BiPAP; Respironics Inc; Monroeville, PA) or a portable volume ventilator (PLV 102; Lifecare, Inc; Boulder, CO) to achieve a > or = 20% increase in baseline minute ventilation while monitoring gas exchange, expired volume, and clinical evidence of a decrease in the patient's work of breathing. RESULTS: The patients' mean age (+/- SD) was 65 +/- 9.7 years, and there was a 3:1 female:male predominance. In the noninvasive respiratory care unit, 36 patients used NPPV for 7.31 +/- 0.26 h/night. Four patients (three with COPD, one with restrictive disorder) withdrew from the study during the 3-week inpatient stay because they could not tolerate NPPV. Six patients (5 with COPD, 1 with restrictive disorder) used a portable volume ventilator and 34 patients used BiPAP (15 with COPD, 19 with restrictive disorders). At discharge, compared with at admission, daytime PaO2/fraction of inspired oxygen (FIO2) increased (327 +/- 10 vs 283 +/- 13 mm Hg; p = 0.01), PaCO2 was reduced (52 +/- 2 vs 67 +/- 3 mm Hg; p = 0.0001), and functional score increased (4.76 +/- 1.16 vs 2.7 +/- 1.64 arbitrary units (AUs); p < 0.01). Six months after discharge, improvements in PaO2/FIO2 (317 +/- 10 vs 283 +/- 13; p = 0.05), PaCO2 (52 +/- 2 vs 67 +/- 3 mm Hg; p = 0.0001), and functional score (5.66 +/- 0.41 vs 2.7 +/- 0.3 AUs; p < 0.001) were maintained compared with admission values. FVC, FEV1, and maximum inspired and expired mouth pressures were unchanged before and after long-term NPPV. Ten patients (7 with COPD, 3 with restrictive disorders) discontinued NPPV at 6 months, and 3 progressed to tracheostomy. The remaining 26 patients continued to use NPPV at the 6-month follow-up. They claimed to use NPPV for 7.23 +/- 0.24 h/night, but logged metered use was 4.5 +/- 0.58 h/night. Problems that required adjustment in either the mask (36%) or ventilator source (36%) included mask leaks (43%), skin irritation (22%), rhinitis (13%), aerophagia (13%), and discomfort from mask headgear (7%). CONCLUSION: NPPV acutely and chronically improves gas exchange and functional status in patients with chronic respiratory failure, but a significant number of patients do not tolerate NPPV on a chronic basis. Comprehensive follow-up is required to correct problems with NPPV and ensure optimal patient compliance.

Stability of improvements in exercise performance and quality of life following bilateral lung volume reduction surgery in severe COPD.

STUDY OBJECTIVE: To evaluate the long-term stability of improvements in exercise capacity and quality of life (QOL) after lung volume reduction surgery (LVRS). DESIGN: Case-series analysis. SETTING: University hospital. PATIENTS: Twenty-six patients with severe airflow obstruction (mean FEV1 of 0.67+/-0.18 L) and moderate to severe hyperinflation (mean total lung capacity of 7.30+/-1.90 L). INTERVENTION AND MEASUREMENTS: All patients underwent bilateral LVRS via median sternotomy. Serial measurement of lung function, symptom-limited cardiopulmonary exercise tests, 6-min walk distances (6MWD), and sickness impact profile (SIP) scores were done before, and at 3, 6, 12, and 18 months after surgery. RESULTS: FEV1 (0.93+/-0.29 vs 0.68+/-0.19 L, p<0.001) increased while residual volume (3.47+/-1.2 vs 4.77+/-1.5 L, p<0.001) decreased significantly at 3 months post-LVRS compared to baseline, and these changes were maintained at 12 to 18 months follow-up. Similarly, the increase in 6MWD at 3 months post-LVRS (340+/-84 vs 251+/-114 m, p<0.001) was sustained at all follow-up times. On cardiopulmonary exercise testing, total exercise time (9.0+/-1.8 vs 6.1+/-1.9 min, p<0.001), oxygen uptake at peak exercise (VO2 peak) (14.9+/-4 vs 11.9+/-3 mL/kg/min, p<0.001), maximum oxygen pulse (7.43+/-2.37 vs 5.85+/-1.96 mL/beat, p<0.005), and maximum minute ventilation (VEmax) (30.3+/-10 vs 23.5+/-7.1 L/min, p<0.001) increased significantly at 3 months post-LVRS. On serial study following LVRS, total exercise time remained significantly greater at 6 (8.5+/-1.38 min) and 12 months (8.71+/-2.0 min) post-LVRS compared to baseline (5.81+/-1.9 min, p<0.05). VO2 peak tended to be higher at all follow-up periods (3 months, 16.1+/-4.3; 6 months, 14.5+/-2.6; 12 months, 14.1+/-3.5 mL/kg) compared to baseline (12.6+/-3.9 mL/kg, p=0.08). Similarly, maximum O2 pulse tended to be higher in all follow-up studies (3 months, 8.45+/-2.7; 6 months, 7.6+/-1.7; 12 months, 7.42+/-2.1 mL/beat) compared to baseline (6.39+/-2.5 mL/beat, p=0.06). Higher VEmax continued to be observed at 6 (30+/-10 L/min) and 12 months (28+/-10 L/min) post-LVRS, compared to baseline (23+/-7 L/min, p=0.02). VEmax post-LVRS was significantly higher at 3 and 6 months compared to baseline on post-hoc analysis (p<0.05). Overall SIP scores were lower at 3 months (7 vs 18, p<0.0002) post-LVRS and were sustained in long-term follow-up. CONCLUSION: We conclude that bilateral LVRS via median sternotomy in selected patients with severe, diffuse emphysema improves exercise performance and QOL at 3 months following LVRS and these improvements are maintained for at least 12 to 18 months in follow-up.

Surveillance bronchoscopy in lung transplant recipients.

STUDY OBJECTIVES: To establish whether a consensus exists among active transplant centers regarding the use and interpretation of information obtained by surveillance bronchoscopic lung biopsy (SBLB). DESIGN: Prospective standardized questionnaire answered via mail and telephone communications. PARTICIPANTS: A five page, 18-question survey was sent to all lung transplant programs listed by the United Network of Organ Sharing in North America, as well as eight selected international programs. Ninety-one surveys were sent to 83 North American and eight international programs. Seventy-four programs (81%) responded. Seventeen programs (19%) were excluded secondary to inactivity. The remaining 57 programs (63%) were included in final data analysis. INTERVENTIONS: None. RESULTS: Sixty-eight percent (39/57) of the responding programs perform SBLBs. Ninety-two percent of the programs performing SBLBs do so within the first month, and 69% continue to do so on a regular basis. Sixty-nine percent (27/39) of programs performing SBLBs continue to do so after 1 year. Eighty-six percent (32/37) of respondents believe that SBLB impacts on patient management at least 10% of the time. Technically, 90% (35/39) take biopsy specimens from more than one lobe per SBLB session. Fifty-nine percent (23/39) took 6 to 10 biopsy specimens per session, 33% (13/39) took three to five biopsy specimens, and 7% (4/39) took > 10 biopsy specimens per session. Eighty-six percent (32/37) of the responding centers reported treating asymptomatic rejection at grade 2A, while 14% (5/37) waited until histologic grade 3A before beginning treatment. Complications from SBLB were minimal with < 5% rates of pneumothorax, requirement for chest tube placements, or significant bleeding during SBLB reported by > 95% of the programs performing SBLB. CONCLUSIONS: Most active lung transplant centers perform SBLBs and do so on a regular basis. However, a wide range of opinion exists over the utility and technique of SBLB and the impact of its results influencing outcome in the lung transplant recipient. To answer these questions, a randomized multicentered trial or registry to determine the effect of SBLB on lung transplant recipient morbidity and mortality is required.

Effects of noninvasive positive pressure ventilation on gas exchange and sleep in COPD patients.

STUDY OBJECTIVE: The role of nocturnal noninvasive positive pressure ventilation (NPPV) in the treatment of patients with hypercapnic COPD remains controversial. Beneficial effects reported after prolonged use have included an improvement in gas exchange. The purpose of this study was to examine the short-term effects of NPPV on gas exchange and sleep characteristics in patients with hypercapnic COPD and to determine if similar acute changes in gas exchange are associated with improved sleep quality. DESIGN: Prospective, randomized, controlled trial. SETTING: Sleep laboratory of a university hospital. PATIENTS: Six patients with severe but stable hypercapnic COPD (PaCO2=58+/-4 [SE] mm Hg). Mean age was 63+/-6 (SD) with an FEV1=0.58+/-0.09 L. INTERVENTIONS AND MEASUREMENTS: Patients were studied in the sleep laboratory for a total of three nights. On nights 2 and 3, arterial catheters were placed prior to the study. Following an acquaintance night, patients were randomized to either a control-sham night on 5 cm H2O nasal continuous positive airway pressure (CPAP) or an NPPV night using a ventilatory support system (BiPAP; Respironics Inc; Murrysville, Pa) at previously determined optimal settings. The third night consisted of the opposite for each patient, either a control-sham or an NPPV night. On the second and third nights, three arterial blood gas readings were obtained: (1) baseline wakefulness; (2) non-rapid eye movement (NREM) sleep; and (3) rapid eye movement (REM) sleep. RESULTS: During NREM sleep, NPPV in comparison to the control-sham night on low level CPAP caused no significant change in PaCO2 (60+/-4 to 59+/-3 mm Hg [p=0.6]) and a decrease in PaO2 (96+/-9 to 72+/-5 mm Hg [p=0.04]). During REM sleep, NPPV in comparison to the control-sham night on low level CPAP caused no significant change in either PaCO2 (63+/-7 to 57+/-2 mm Hg [p=0.46]) or PaO2 (67+/-7 to 75+/-8 mm Hg [p=0.51]). Sleep efficiency and total sleep time (TST) increased significantly with NPPV in comparison to the control-sham night on low level CPAP: from 63+/-7% to 81+/-4% (p<0.05) and from 205+/-32 to 262+/-28 min (p<0.05), respectively. Sleep architecture, expressed as a percentage of TST, was unchanged on the NPPV night compared to the control-sham night on low level CPAP. The number of arousals during the night was also unchanged with NPPV in comparison to the control-sham night on low level CPAP (45+/-11 to 42+/-9 [p=not significant]). CONCLUSIONS: NPPV acutely improved sleep efficiency and TST in patients with hypercapnic COPD without significantly improving gas exchange. Other sleep parameters, including sleep architecture and the number of arousals during the night, remained unchanged during NPPV. These data suggest that the beneficial effects of NPPV in patients with hypercapnic respiratory failure are not solely due to an improvement in gas exchange but may be more complex with other factors potentially having contributing roles.

Improvements in lung function, exercise, and quality of life in hypercapnic COPD patients after lung volume reduction surgery.

STUDY OBJECTIVE: To determine the impact of preoperative resting hypercapnia on patient outcome after bilateral lung volume reduction surgery (LVRS). METHODS: We prospectively examined morbidity, mortality, quality of life (QOL), and physiologic outcome, including spirometry, gas exchange, and exercise performance in 15 patients with severe emphysema and a resting PaCO2 of > 45 mm Hg (group 1), and compared the results with those from 31 patients with a PaCO2 of < 45 mm Hg (group 2). RESULTS: All preoperative physiologic and QOL indices were more impaired in the hypercapnic patients than in the eucapnic patients. The hypercapnic patients exhibited a lower preoperative FEV1, a lower diffusing capacity of the lung for carbon monoxide, a lower ratio of PaO2 to the fraction of inspired oxygen, a lower 6-min walk distance, and higher oxygen requirements. However, after surgery both groups exhibited improvements in FVC (group 1, p < 0.01; group 2, p < 0.001), FEV1 (group 1, p=0.04; group 2, p < 0.001), total lung capacity (TLC; group 1, p=0.02; group 2, p < 0.001), residual volume (RV; group 1, p=0.002; group 2, p < 0.001), RV/TLC ratio (group 1, p=0.03; group 2, p < 0.001), PaCO2 (group 1, p=0.002; group 2, p=0.02), 6-min walk distance (group 1, p=0.005; group 2, p < 0.001), oxygen consumption at peak exercise (group 1, p=0.02; group 2, p=0.02), total exercise time (group 1, p=0.02; group 2, p=0.02), and the perceived overall QOL scores (group 1, p=0.001; group 2, p < 0.001). However, because the magnitude of improvement was similar in both groups, and the hypercapnic group was more impaired, the spirometry, lung volumes, and 6-min walk distance remained significantly lower post-LVRS in the hypercapnic patients. There was no difference in mortality between the groups (p=0.9). CONCLUSIONS: Patients with moderate to severe resting hypercapnia exhibit significant improvements in spirometry, gas exchange, perceived QOL, and exercise performance after bilateral LVRS. The maximal achievable improvements in postoperative lung function are related to preoperative level of function; however, the magnitude of improvement can be expected to be similar to patients with lower resting PaCO2 levels. Patients should not be excluded from LVRS based solely on the presence of resting hypercapnia. The long-term benefit of LVRS in hypercapnic patient remains to be determined.

Bilateral apical vs nonapical stapling resection during lung volume reduction surgery.

STUDY OBJECTIVES: To determine whether biapical stapling resection alone or resection of diseased, nonapical areas of emphysematous lung provides comparable physiologic outcomes or alters morbidity and mortality after lung volume reduction surgery (LVRS). DESIGN: Consecutive case-series analysis. SETTING: Urban university hospital. PATIENTS: Forty-seven patients ([mean +/- SD] aged 58+/-8 years; 18 men) with severe emphysema (FEV1, 0.7+/-0.2 L; total lung capacity [TLC], 139+/-23% predicted). INTERVENTIONS: Thirty-two patients underwent biapical LVRS, 27 by median sternotomy (MS) and 5 by video-assisted thoracoscopic surgery (VATS), and 15 underwent nonapical resection, 9 by MS and 6 by VATS. Patients were assessed for postoperative complications (respiratory tract infections, air leak duration, and death), length of stay, and physiologic parameters, which included a 6-min walk distance, spirometry, lung volume, gas exchange, diaphragm strength, and quality-of-life measures. MEASUREMENTS AND RESULTS: Patients were studied at baseline and at 3 months postoperatively. At the preoperative baseline, both groups had similar ages (57 vs 60 years; p = 0.2), 6-min walk distance (294 vs 263 m; p = 0.3), FEV1 (28% vs 29% predicted; p = 0.6), degree of hyperinflation (TLC, 138% vs 141% predicted; p = 0.8), gas exchange (PaO2/fraction of inspired oxygen, 344 vs 313, p = 0.1; PaCO2 46 vs 48 mm Hg, p = 0.4), and diaphragm strength (maximal transdiaphragmatic pressure sniff, 54 vs 46 cm H2O, p = 0.4). Resected tissue weight was similar in both groups (94 vs 93 g, p = 0.9). There were no differences in the mean percentage of change from baseline for these physiologic parameters or for quality-of-life measures between the two groups. The 6-min walk distances increased by 20% and 33%, FEV1 increased by 37% and 38%, the degrees of hyperinflation (residual volume/TLC) decreased by 16% and 15%, and the quality-of-life scores improved by 51% and 41%, respectively, in the groups that underwent biapical and nonapical resections at 3 months post-LVRS. The length of stay in the hospital for LVRS (18 vs 23 days; p = 0.4) and the duration of air leak (10 vs 15 days; p = 0.4) were also similar. Complications between the two groups (biapical vs nonapical) were similar (respiratory tract infection, 47% vs 60%, p = 0.2; reintubation, 34% vs 33%, p = 0.2; reoperation, 9% vs 20%, p = 0.4; and death, 9% vs 7%, p = 0.2). CONCLUSIONS: LVRS, by biapical or nonapical resection, produces similar improvements in lung function, exercise, diaphragm strength, and quality of life, with comparable morbidity and mortality.

Effect of lung volume reduction surgery on bony thorax configuration in severe COPD.

STUDY OBJECTIVES: Hyperinflation in patients with severe COPD is associated with an increased anteroposterior (AP) rib cage diameter. We sought to determine whether bilateral lung volume reduction surgery (LVRS) affects bony thorax configuration. DESIGN: Prospective of clinical data collection before and after LVRS. SETTING: Tertiary-care university medical center. PATIENTS: We measured multiple AP and transverse thoracic diameters, by using plain chest roentgenograms (CXRs) in 25 patients (11 men, 14 women), and thoracic CT scans in 14 patients (7 men, 7 women), preoperatively and 3 months postoperatively. A subgroup of 7 patients (reference data) also had CXR thoracic diameter measurements made, using films obtained previously within a year of their presurgical evaluation. Another subgroup of 10 patients had CT scan measurements also made 12 months postoperatively. MEASUREMENTS AND RESULTS: CXR dimensions were taken at the level of the manubrium sterni (M) and thoracic T7 and T11 levels. CT dimensions were taken at T4, T6, T8, and T10 levels. At each level, left (L), midsagittal (C), and right (R) AP and maximal transverse diameters were measured. The sum of the three AP diameters (Total) was used for calculations. Patients also underwent tests such as spirometry, lung volumes, diffusing capacity of the lung for carbon monoxide, 6-min walk distance (6MWD), and transdiaphragmatic pressures during maximum static inspiratory efforts (Pdimax sniff) measured before and 3 months after LVRS. Patients were (mean +/- SD) 58+/-8 years old, with severe COPD and hyperinflation (FEV1, 0.68+/-0.23 L; FVC, 2.56+/-7.3 L; and total lung capacity [TLC], 143+/-22% predicted). After LVRS, AP diameters were reduced at thoracic level T7 (from 24.2+/-2.0 cm to 23.3+/-2.2 cm, p = 0.0002), and transverse diameters were reduced at T7 (from 26.8+/-1.9 cm to 26.4+/-1.7 cm, p = 0.001) and T11 (from 29.9+/-2.2 cm to 29.5+/-2.2 cm, p = 0.03), as measured using the CXR. In contrast, thoracic diameters were similar in subjects with CXRs before LVRS and within 1 year before evaluation. CT-measured AP diameters were significantly reduced 3 months after LVRS at T6, (from 48.8+/-6.0 cm to 46.7+/-5.4 cm, p = 0.02), T8 (from 54.2+/-7.0 cm to 52.3+/-6.5 cm, p = 0.004), and T10 (from 53.8+/-7.5 cm to 51.2+/-8.0 cm, p = 0.001), but not at T4. These AP diameter reductions directly correlated with the postoperative reductions in TLC and residual volume, and also with the increases in Pdimax sniff and 6MWD after LVRS. The reduction in AP diameters at thoracic levels T8 and T10 seen 3 months after LVRS remained stable at 12-month follow-up, whereas those measured at T6 lost statistical significance. CT-measured transverse diameters were unchanged at all levels after LVRS. CONCLUSIONS: We conclude that LVRS decreases mid-to-lower AP rib cage diameter as assessed by CXR and thoracic CT. Although transverse diameters were reduced on CXR, the magnitude was small and was not confirmed with CT. After LVRS, AP diameter reductions are most likely the result of reduction in lung volume, and they are associated with improvements in diaphragm strength and exercise endurance.

Financial implications of noninvasive positive pressure ventilation (NPPV).

Noninvasive positive pressure ventilation (NPPV) is effective in the treatment of acute and chronic respiratory failure. However, the costs and financial balance between costs and diagnosis-related group (DRG) reimbursement for patients with moderate to severe respiratory failure treated with NPPV are unknown. We examined the costs and DRG reimbursement for 27 patients receiving Medicare referred with moderately severe respiratory failure for NPPV to the ventilator rehabilitation unit (VRU) at Temple University Hospital. This unit is one of four Health Care Financing Administration chronic ventilator-dependent demonstration sites that evaluates patients for NPPV, instructs them in home NPPV use, emphasizes rehabilitation, and uses strict cost accounting methods. Nineteen patients were treated with NPPV in the ICU and then referred to the VRU, and 8 patients were directly admitted for NPPV to the VRU. Patients were (mean +/- SE) 69 +/- 9 years age, 14 had severe COPD, and 13 had various restrictive disorders. All were hypercapneic at the time of hospital admission (restrictive 60 +/- 15; obstructive 67 +/- 3 mm Hg, PaCO2) with impaired lung mechanics and limited functional status. Patients averaged 8 +/- 15 days in the ICU, or 8 +/- 4.7 days on the medical floor prior to VRU transfer. The VRU length of stay averaged 20 +/- 18 days, for a total length of stay of 29 +/- 21 days. After implementation of NPPV, all patients had an improvement in gas exchange while spontaneously breathing and functional status that was maintained in follow-up. At 1 and 2 years of follow-up, 74% and 63% of patients were alive, respectively. Eleven patients were admitted with DRG 475 (respiratory system diagnosis with ventilator support); however, 16 of 27 patients were admitted across five different non-475 DRG codes with reimbursement rates ranging from $2,673 to $4,215. After DRG and outlier reimbursement, a total deficit of $261,948 remained (average deficit $9,701 per patient). However, individual patient deficits ranged from $1,113 to $32,892. Eighty-two percent of patients treated with NPPV incurred substantial financial losses that were underreimbursed across all assigned DRGs, including DRG 475, the highest-weighted DRG. We conclude that patients with moderate to severe respiratory failure receiving NPPV demonstrate an improvement in functional status and gas exchange that is maintained in follow-up. In addition, patients treated with NPPV incur high costs that are currently underreimbursed by the present DRG system. Newer DRG payment scales that recognize NPPV as specific treatment should be implemented.

Correlation of changes in quality of life after lung volume reduction surgery with changes in lung function, exercise, and gas exchange.

STUDY OBJECTIVES: To evaluate correlations between improvement in quality of life (QOL) in patients with severe COPD before and after they undergo lung volume reduction surgery (LVRS) with changes in pulmonary function tests, gas exchange, exercise performance, and alterations in medical management. DESIGN: Case-series analysis. SETTING: University hospital. PATIENTS: Forty-two patients (mean [+/- SD] age, 56+/-8 years; 53% women) with severe airflow obstruction (FEV(1), 0.62+/-0.2 L), and moderate to severe hyperinflation (total lung capacity [TLC], 6.9+/-1.7 L). INTERVENTION AND MEASUREMENTS: All patients underwent bilateral LVRS via median sternotomy. Measurements of lung function, symptom-limited cardiopulmonary exercise testing, the total distance the patient was able to walk in 6 min in a corridor, and sickness impact profile (SIP) scores were made before and 3 months after LVRS. SIP scores are inversely proportional to the level of function and QOL. RESULTS: Compared to baseline, FEV(1) increased (0.87+/-0.3 vs. 0.62+/-0.2 L, respectively; p<0.01) while residual volume significantly decreased (3.2+/-1.8 vs. 6.3+/-1.2 L, respectively; p<0.004) at 3 months post-LVRS. On cardiopulmonary exercise testing, values increased from baseline to post-LVRS for total exercise time (9.0+/-2.2 vs. 6.0+/-1.5 min, respectively; p = 0.045), maximum oxygen uptake (VO(2)) (16+/-3 vs. 11+/-2 mL/kg/min, respectively; p = 0.01), and maximum minute ventilation (VE) (33+/-9 vs. 28+/-5 L/min, respectively; p = 0.03). The percentage change in the oxygen cost of breathing (VO2/VE ratio) from low to high workloads during exercise was significantly lower after LVRS (p = 0.002). There was no significant change in oxygenation after LVRS (PaO(2)/fraction of inspired oxygen, 331+/-27 vs. 337+/-39, respectively; p = 0.76), but PaCO(2) tended to be lower (41+/-9 vs. 48+/-6 mm Hg, respectively; p = 0.07). Overall SIP scores were significantly lower after LVRS than before (8+/-4 vs. 15+/-2, respectively; p = 0.002). Changes in SIP scores correlated with the change in VO2/VE ratio from low to high workloads, with patients having the smallest changes in VO2/VE ratio having the smallest changes in SIP scores after LVRS (r = 0.6; p = 0.01). Improved or lower SIP scores also tended to correlate with a reduction in residual volume/TLC ratio (r = 0.45; p = 0.09), and there was a linear correlation with a statistically significant Pearson r value with decreased steroid requirements (r = 0.7; p = 0.001). Moreover, changes in psychological SIP subscore tended to correlate with diminished oxygen requirements post-LVRS (r = 0.45; p = 0.09). However, there was no significant correlation between changes in SIP scores and routine measurements of lung function, exercise performance, or gas exchange. CONCLUSION: There is an association between an improvement in QOL and reduced hyperinflation after LVRS. Reduced hyperinflation may lead to more efficient work of breathing during exercise and, therefore, to an increased ability to perform daily activities. Changes in QOL scores correlate best with behaviorally based variables that directly affect the patient's well-being, such as systemic steroid administration.

Efficacy of a new full face mask for noninvasive positive pressure ventilation.

Previous studies have shown that noninvasive positive pressure ventilation (NPPV) improves gas exchange in acute and chronic respiratory failure. However, some patients are unable to tolerate NPPV due to air leaks around the mask, facial discomfort, and claustrophobia. A new mask that covers the entire face (Total, Respironics, Monroeville, Pa), attempts to overcome these obstacles. We studied the efficacy of NPPV via the Total face mask (TFM) in nine patients with chronic respiratory failure. In three patients, respiratory failure was due to chronic obstructive lung disease, and in six patients, it was secondary to restrictive disorders. None of the patients were previously able to tolerate NPPV via nasal (N) or nasal-oral (NO) masks. At baseline, all patients had impaired gas exchange with low PaO2/FIO2 (241 +/- 14), elevated PaCO2 (79 +/- 5 mm Hg), and poor functional status (1.89 +/- 1.45, on a scale of 1 to 7). After NPPV in the hospital for 7.1 +/- 1.5 h per night for 22 +/- 26 days, the PaCO2 fell to 59 +/- 3 mm Hg, and the PaO2/FIO2 rose to 304 +/- 27. Following nocturnal NPPV via the TFM for 6.7 +/- 1.5 h a night 6 +/- 5 weeks after hospital discharge, sustained improvements in PaCO2 (58 +/- 3 mm Hg, p < 0.05), PaO2/FIO2 (304 +/- 18), and functional status (5.38 +/- 1.06, p < 0.05) were observed. In four patients, measurements of respiratory rate, tidal volume, minute ventilation, dyspnea, discomfort with the face mask, and mask and mouth leaks were made during 30-min sessions of NPPV applied at constant levels via all three masks (N, NO, TFM). Discomfort with the face mask (0.38 +/- 0.18 vs 1.44 +/- 0.34 vs 2.38 +/- 0.32, p < 0.05) and mask leaks (0.44 +/- 0.18 vs 1.89 +/- 0.39 vs 1.89 +/- 0.35, p < 0.05) were least during NPPV via TFM compared with the N or NO masks, respectively. Moreover, expired tidal volume was highest (804 +/- 10 vs 498 +/- 9 vs 537 +/- 13 ml, p < 0.05) and PaCO2 lowest (51 +/- 2 vs 57 +/- 2 vs 58 +/- 3, p < 0.05) during NPPV via the TFM compared with N or NO masks. We conclude that NPPV delivered via a Total mask ensures a comfortable, stable patient-mask interface and improves gas exchange in selected patients intolerant of more conventional N or NO masks.