Comorbidities in end-stage lung disease.
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Humans↗
Biomedical subjects
S Kesten
Publications and source records attributed to S Kesten.
Comparison of hallway and treadmill six-minute walk tests.
The 6-min walk test (SMWT) performed in the hallway (HW) is used as a clinical indicator of functional capacity in patients with lung disease. A 6-min walk test utilizing a treadmill (TM) is easier to perform and allows easier patient monitoring. Therefore, we formulated a standardized TM SMWT protocol and compared the results with those of a HW SMWT. All patients were enrolled in a pulmonary rehabilitation program. Patients with current infection, recent change in inhaled medications or oral steroid use, and significant cardiovascular disease were excluded. Each subject performed three HW SMWTs and three TM SMWTs assigned randomly on subsequent days. There was a 30-min rest between each walk and at least a 48-h rest between each test day. All patients completed both HW and TM SMWT within 7 d. Supplemental oxygen was utilized or increased if the saturation fell below 88%. The best of the three tests was used for data analysis. Twenty-one subjects completed the protocol. The mean age was 65 +/- 10.9 yr (range, 35 to 79 yr). Ten subjects were receiving supplemental oxygen. The mean FEV(1) was 1.07 +/- 0.53 L. The mean HW SMWT distance was 1,228 +/- 255 ft (range, 612 to 1,679 ft) and the mean TM SMWT distance was 1,060 +/- 389 ft (range, 475 to 1,819 ft), which were statistically different (p = 0.01). The mean difference was 168 +/- 280 ft (range, -326 to 743 ft). Oxygen saturation and supplemental oxygen requirements did not differ significantly. The intra-test variability of the three HW SMWTs was similar to the three TM SMWTs and no significant difference in the coefficient of variation was found. A standardized TM SMWT is feasible and allows easier patient monitoring, but there is a statistically significant difference between the HW and TM SMWT distance and therefore they are not interchangeable. However, the intratest reproducibility of the TM and HW SMWTs are similar when three walks are performed in a single test session. The role of the TM SMWT in pulmonary rehabilitation requires further exploration.
Adult↗
Bronchial hyperreactivity after lung transplantation predicts early bronchiolitis obliterans.
Nonspecific bronchial hyperreactivity (NSBHR) has been observed in patients who have undergone lung transplantation, but studies have provided conflicting reports as to the incidence and significance of this finding. To delineate more clearly the natural history of NSBHR after lung transplantation, data from 111 consecutive patients undergoing double lung transplantation between February 1988 and May 1994 were reviewed. Methacholine challenge testing was requested in conjunction with regular postoperative follow-up. Among 60 patients tested at 3 mo, 18 (30%) had a positive methacholine challenge; at 6 mo, the incidence was 14 of 59 (24%). Of 21 patients for whom complete testing was performed for 12 mo or longer, 13 (62%) had exclusively negative challenges. Patients with a positive challenge at 3 mo were significantly more likely to develop bronchiolitis obliterans syndrome (BOS) (p < 0.006). Mean time to development of BOS was 16.9 mo in the group with positive challenges versus 43.9 mo for those with negative challenges. We conclude that increased NSBHR is a common, but by no means universal, finding after lung transplantation. Furthermore, early positive methacholine challenges are associated with development of BOS. We hypothesize that NSBHR may represent an early marker of chronic rejection in these patients.
Adult↗
Mycobacterial infections in lung transplant recipients.
BACKGROUND: Immunosuppression and chronic lung disease are known risk factors for mycobacterial infection and might be expected to develop with an increased frequency in lung transplant recipients. We therefore sought to document the incidence and type of mycobacterial infections in a large lung transplant program. METHODS: A retrospective review of 219 transplant procedures (60 single lung transplants and 159 double lung transplants) in 210 patients was conducted. All patients had scheduled surveillance bronchoscopies at 3, 6, 9, 12, 18, and 24 months, and yearly thereafter. BAL samples were processed routinely for mycobacterium. RESULTS: Eight patients (3.8%) had evidence of infection (5 men, 3 women; age range, 26 to 63 years). The reasons for transplant were obstructive lung disease (six), cystic fibrosis (one), and pulmonary fibrosis (one). Five recipients had infection in their native lungs; two of five cultured mycobacterium from BAL following transplantation. At least four of five patients had nontuberculous mycobacterium (one showed acid fast bacilli and granuloma on a biopsy specimen that was not sent for culture). None of the five developed disease (mean follow-up = 22 months; range, 3 to 30 months). The organisms were Mycobacterium avium complex (three), Mycobacterium xenopi (one), and unidentified (one). Of the three remaining patients who developed infection after transplantation, one grew Mycobacterium chelonae and the others grew Mycobacterium tuberculosis (both received double lung transplants and had no evidence of mycobacterium in their native lungs). The only definite symptomatic disease occurred in the patients with M tuberculosis, one of whom had evidence of dissemination. The patients with M tuberculosis responded to standard treatment. There have been no deaths due to mycobacterium. CONCLUSION: Mycobacterial disease rarely occurs following lung transplantation. Cultures for mycobacterium in surveillance BALs in the absence of symptoms are likely unnecessary.
Adult↗
Development of nonspecific interstitial pneumonitis associated with long-term treatment of primary pulmonary hypertension with prostacyclin.
A young woman with primary pulmonary hypertension presented with interstitial lung disease approximately 5 years after successful treatment with IV prostacyclin. The pathology was consistent with nonspecific interstitial pneumonitis and was unresponsive to steroids and immunosuppressive medications. We speculate that further cases of this syndrome may be reported as more patients are living beyond 5 years with prostacyclin.
Adult↗
Conversion from standard cyclosporine to Neoral in lung transplant recipients.
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Administration, Oral↗
Exhaled nitric oxide in human lung transplantation. A noninvasive marker of acute rejection.
Acute allograft rejection in animals and humans has been associated with increased nitric oxide production in the graft. Exhaled nitric oxide (ENO) measurement is a noninvasive method of assessing inflammation in airway diseases, e.g., asthma, which might be applicable to lung transplant recipients. Over 12 months, ENO of lower respiratory origin was measured in 108 lung transplant recipients with a mean time after transplant of 1,083 d. ENO (mean +/- SEM; ppb) in stable patients (19.5 +/- 1.1; p < 0.001) was not different from that of healthy controls (23.8 +/- 3.2). ENO was significantly higher in episodes of clinical acute rejection (51.1 +/- 6.3) compared with stable patients but not elevated in bronchiolitis obliterans syndrome (18.6 +/- 1.5) or pulmonary infection (25.9 +/- 4.0). A retrospective analysis of bronchoscopy findings and concurrent ENO (n = 99) showed that ENO did not vary according to histological findings (normal, acute rejection grade I, nonspecific inflammatory change) or with a positive BAL culture. ENO was not correlated with differential lymphocyte and neutrophil counts. ENO appears to be a valid marker of clinical acute rejection in human lung transplantation as distinct from infection or bronchiolitis obliterans. Furthermore, bronchoscopic findings in the absence of a clinical illness were not associated with a rise in ENO.
Adult↗
The acute effects of nasal positive pressure ventilation in patients with advanced cystic fibrosis.
OBJECTIVE: To evaluate the acute effects of noninvasive positive pressure ventilation (NPPV) in patients with stable chronic respiratory failure secondary to cystic fibrosis. PATIENTS: Eight patients (29+/-5 years of age) with severe airflow limitation (mean FEV1, 24+/-3% predicted) and chronic respiratory failure (PaO2=67+/-15 mm Hg and PaCO2=50+/-4 mm Hg) were evaluated. METHODS: Tidal volume, respiratory rate, minute ventilation, oxygen saturation, and transcutaneous CO2 (TcCO2) measurements were made over a 20-min period before and after the application of NPPV (inspiratory pressure of 10 to 12 cm H2O and expiratory pressure of 4 to 6 cm H2O). RESULTS: NPPV increased saturation from 88+/-2% to 90+/-1% (p<0.05) and decreased TcCO2 from 51+/-3 mm Hg to 50+/-2 mm Hg (p<0.05). Tidal volume increased from 219+/-20 mL to 256+/-37 mL (p=not significant [NS]) and respiratory rate decreased from 24+/-2 to 18+/-1 (p<0.01). Minute ventilation decreased from 5.3+/-0.8 L/min to 4.6+/-0.6 L/min (p=0.08). There was no change in duty cycle (32+/-5% to 34+/-5%, p=NS). In two patients, esophageal pressure measurements were also recorded. There was a decrease in pressure from -21+/-1 cm H2O to -11+/-2 cm H2O and -14+/-1 cm H2O to -7+/-1 cm H2O. CONCLUSIONS: In patients with stable, severe cystic fibrosis, NPPV (1) acutely improves gas exchange, (2) decreases minute ventilation, suggesting either a reduction in CO2 production or an increase in alveolar ventilation, and (3) reduces work of breathing.
Adult↗
Lung volume reduction surgery: an analysis of hospital costs.
OBJECTIVE: Lung volume reduction surgery (LVRS) represents a potential breakthrough in the management of advanced emphysema, although questions remain about clinical and economic implications of widespread application of LVRS. In this report, we describe hospital costs, excluding physicians' fees, for LVRS. DESIGN: Hospital charges were obtained from billing records and converted to costs by applying multiple cost-to-charge ratios. SETTING: A large, urban academic medical center. PATIENTS: Fifty-two consecutive patients who received bilateral LVRS through a median sternotomy between April 1995 and August 1996. RESULTS: Median hospital stay was 10 days (mean= 14.8+/-12.8 days; range=3 to 48 days), including 2 days (mean=6+/-9.2 days; range=1 to 35 days) in the ICU. One hospital death occurred. Hospital costs per case ranged from $11,712 to $121,829, with mean costs of $30,976 and median costs of $19,771. Costs were related significantly to duration of ICU stay and length of hospitalization. Patients who accrued the highest costs were significantly older than the remainder of the sample (69.3 years vs 62.4 years). CONCLUSIONS: Hospital costs of LVRS vary significantly but are related directly to hospital stay. Identification of factors associated with prolonged stays can be used in assessing benefits and risks of LVRS against utilization of health-care dollars.
Academic Medical Centers↗
Cytomegalovirus viremia in lung transplant recipients receiving ganciclovir and immune globulin.
BACKGROUND: Cytomegalovirus (CMV) disease is an important cause of organ transplant-related morbidity and mortality. During the last 5 years at our institution, prophylactic ganciclovir and hyperimmune globulin have been routinely administered to lung transplant recipients whenever the donor or the recipient was CMV antibody-positive. We sought to assess the efficacy of prophylaxis on viremia, CMV disease, and bronchiolitis obliterans syndrome (BOS). METHODS: A retrospective chart review of 61 consecutive lung transplants performed between recipients between January 1993 and August 1995 was performed. Fifty-six patients who survived at least 1 month were analyzed. Patients were considered at risk for CMV disease whenever pretransplant donor or recipient serology was positive. RESULTS: Fourteen of the 39 patients at risk (36%) had viremia while on prophylaxis. The rate of CMV disease was 13% during the first 6 months following transplantation. A donor whose CMV serology was positive appeared to increase the risk of BOS in a Cox regression model (relative risk=2.4; 95% confidence interval=0.86-6.74; p=0.0957). Neither age, CMV infection (viremia or a positive specimen from BAL), recipient's serology at the time of transplantation, or CMV disease was associated with BOS. None of these variables was associated with mortality on Cox regression analysis or univariate analysis. CONCLUSIONS: Administration of combination ganciclovir and hyperimmune globulin prophylactic therapy to lung transplant recipients at risk for CMV infection and disease is associated with a relatively low incidence of disease, which appears only after prophylaxis treatment with ganciclovir is completed. Ganciclovir prophylaxis does not prevent CMV viremia; however, viremia while on prophylaxis is not predictive of disease.
Adult↗
Bronchiolitis obliterans after lung transplantation: a review.
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Animals↗
Return to work after lung transplantation.
The social rehabilitation of lung transplant recipients becomes increasingly important as the results of lung transplantation improve. Although return-to-work (RTW) rates have been published for recipients of other organ transplants, no such data are available after lung transplantation. The purpose of this study was to determine what factors influence RTW after lung transplantation. Of 99 lung transplant recipients (43 single, 56 bilateral) surveyed from Denver, Colorado, (n = 49) and Toronto, Ontario, Canada (n = 50), 22% (n = 22) were employed, 38% (n = 38) were unemployed but medically able to work, 29% (n = 29) were medically disabled, and 10% (n = 10) had retired. The RTW rate for those medically able to work was 37% (22/60), and it was identical at each center (n = 11). Only Canadian lung transplant recipients (36%, 4/11) secured new jobs, whereas all Colorado lung transplant recipients returned to their previous employment (100%, 11/11). A stepwise discriminant analysis revealed that (1) pretransplantation employment, (2) a diagnosis of emphysema, cystic fibrosis, or primary pulmonary hypertension, (3) a self-report of being physically able to work, (4) greater functional improvement as measured by post-lung transplantation percent predicted forced vital capacity, and (5) post-lung transplantation 6-minute walk > 550 m positively influenced RTW. This analysis accurately profiled 82% of the employed and 76% of the unemployed recipients for an overall effectiveness of 79%. The findings of this study are that (1) a 37% employment rate for those physically able was comparable to other types of organ transplant recipients, (2) employment was not determined by the type of lung transplantation procedure (single or bilateral), and (3) social factors remain employment barriers for some recipients, but their absence did not guarantee a better employment rate.
Adult↗
Mass media and transplantation.
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Humans↗
Quality of life in female lung transplant candidates and recipients.
OBJECTIVE: Quality of life (QOL) studies of lung transplant recipients indicate that there are improvements following transplantation. More recently, there has been some suggestion that certain QOL issues are different for men and women. The purpose of the present study was to examine changes in QOL, body satisfaction, and sexual functioning in women lung transplant recipients. STUDY POPULATION: Seven prelung transplant (PRE) and 34 postlung transplant (POST) women. MAIN OUTCOME MEASURES: The RAND-36 Health Survey, Body Cathexis Scale, Derogatis Sexual Functioning Inventory, Hospital Depression and Anxiety Scale, Rosenberg Self-Esteem Scale, and an open-ended questionnaire. RESULTS: Higher scores were found in the POST group with respect to general health and role limitations due to physical health. We were unable to detect significant differences between the groups with respect to emotional well-being, role limitations due to emotional health, and social functioning. There were significant differences between the PRE and the POST body satisfaction scores. Although there was no significant difference in overall sexual functioning, recipients in the PRE group reported higher sex drive. Eleven of the POST recipients (52%) scored below the 10th percentile in overall sexual functioning. CONCLUSIONS: Overall QOL improves following lung transplantation; however, the lack of differences in many domains of QOL raises the concern that women lung transplant recipients may continue to have significant impairments, including those regarding sexuality and body satisfaction.
Adult↗
Lymphocytic airway infiltration as a precursor to fibrous obliteration in a rat model of bronchiolitis obliterans.
BACKGROUND: Bronchiolitis obliterans is the most significant complication adversely affecting prolonged survival of lung allograft recipients. The evolution from the initial insult to the final pathologic entity is largely unknown. The aim of this study was to characterize the evolution of transplant-induced fibrous airway obliteration in a rat tracheal transplant model of bronchiolitis obliterans. METHODS: Tracheal segments were transplanted from Brown Norway rats to Brown Norway rats (isografts) or to Lewis rats (allografts). Grafts were implanted into a subcutaneous pouch and an abdominal omental wrap. They were harvested at 14 different time points (from 1 day to 1 year after transplantation) and assessed histologically. RESULTS: The fibrous airway obliteration developed only in allografts showing a triphasic time course: an initial ischemic phase (observed in both isografts and allografts) was followed by a marked lymphocytic infiltrative phase with complete epithelial loss (observed only in allografts, P<0.01), and finally by an obliterative phase with fibrous obliteration of the allograft airway lumen (P<0.01). CONCLUSIONS: This animal model shows a distinct and reproducible triphasic time course in the development of obliterative airway lesions in allografts. It confirms that the mechanism leading to airway obliteration is immune mediated as only allografts showed this lesion and that lymphocytic infiltration is a precursor of the lesion in this model. The insights into the different phases demonstrated may lead to novel approaches regarding the type and timing of therapeutic interventions.
Animals↗
Pulmonary rehabilitation and surgery for end-stage lung disease.
Pulmonary rehabilitation is a multidisciplinary approach to the comprehensive management of patients with end-stage lung disease. Components of the pulmonary rehabilitation program include education, exercise, nutrition, and psychosocial support. Most of the information published on pulmonary rehabilitation has been from patients with COPD. There are some data on patients with cystic fibrosis but, unfortunately, there is a lack of information on other causes of end-stage lung disease. Published data almost invariably show improvements in functional capacity (i.e., walk distance) and quality of life. There are no objective physiologic changes in lung function. Because patients who attend programs regularly are a carefully selected subpopulation, conclusions from published reports may not apply to all patients with end-stage lung disease. The recommendation for pulmonary rehabilitation prior to lung volume reduction surgery or lung transplantation is based on assumptions that may not necessarily be true. No data exist that conclusively show that preoperative rehabilitation alters outcome. Nevertheless, given the relatively benign nature of pulmonary rehabilitation and the documented benefits, it is reasonable to recommend such a program to patients who are awaiting surgical intervention. Further research is required to define the role, nature, duration, intensity, and frequency of exercise training in the management of patients who are to undergo surgical treatment for advanced lung disease.
Activities of Daily Living↗
Infections in lung transplant recipients.
Advances in surgical technique and better knowledge of the physiologic and immunologic changes in the transplant population, combined with improved diagnostic tools and treatment strategies, have decreased the likelihood of early and, possibly, late mortality caused by a primary infection. Nevertheless, infection continues to be an important cause of death in both the early and late post-transplant periods. Risk of death attributable to infection after prolonged survival, however, is greatest in the setting of chronic rejection. The most significant advances in antimicrobial management have been in the area of prophylaxis. The effectiveness of prophylaxis against P carinii has virtually eliminated that organism as a cause of significant morbidity. Ganciclovir prophylaxis protocols require refinement but have been proved effective against CMV, although that virus continues to be a major pathogen in lung transplant recipients. Ultimately, a careful monitoring protocol and a high index of suspicion for infection requiring investigation and treatment are necessary in the ongoing care of lung transplant recipients. The approach to infections should be guided by the knowledge of the various factors that increase susceptibility to microorganisms and any previous culture and sensitivity results. As transplant physicians try to increase the donor pool through the use of donors who previously might have been rejected and through the potential of xeno-transplantation, vigilance and research must be maintained.
Anti-Bacterial Agents↗