Lung transplantation for high-risk patients with idiopathic pulmonary fibrosis.

BACKGROUND: Survival for patients with idiopathic pulmonary fibrosis (IPF) and high lung allocation score (LAS) values may be significantly reduced in comparison to those with lower LAS values. OBJECTIVES: To evaluate outcomes for high-risk IPF patients as defined by LAS values ≥46 (N=42) versus recipients with LAS values <46 (N=89). METHODS: We retrospectively reviewed records of 131 consecutive patients with IPF who received lung transplants at our institution between 1999 and 2013. RESULTS: The mean LAS was significantly higher (59.5, interquartile range 43.9-75.9 vs. 39.3, interquartile range 37.7-44.3; p<0.01) for the high-risk cohort. The higher LAS cohort had significantly lower percent predicted forced vital capacity (FVC) versus recipients with LAS <46 (41.3±14.1% vs. 53.2±16.2%; p<0.01) and required more supplemental oxygen (7±5 vs. 4±2 L/min, p<0.01) prior to transplant versus recipients with LAS <46. Although the incidence of early post-LTX pulmonary complications was increased for the higher LAS group versus recipients with LAS <46, 30-day mortality and actuarial survival did not differ between the two cohorts. CONCLUSIONS: Although lung transplantation in patients with IPF and high LAS values is associated with increased risk of early post-transplant complications, long-term post-transplant survival for our high-LAS cohort was equivalent to that for the lower LAS recipients.

Timing and Frequency of Unplanned Readmissions After Lung Transplantation Impact Long-Term Survival.

BACKGROUND: Adverse events that require hospital readmission frequently occur long after lung transplantation (LT) that has been successfully performed. We sought to identify the causes and rate of unplanned readmissions after LT and to determine whether unplanned readmissions have a significant impact on post-LT survival. METHODS: We retrospectively reviewed the outcomes in 174 LT recipients who underwent LT at our center from June 2005 to May 2014. The median follow-up period was 38 months (range, 17 to 72 months). RESULTS: One hundred sixty (92%) of the 174 recipients were readmitted 854 times (5.3 times per patient). The median time to first readmission was 71 days (interquartile range [IQR], 28 to 240 days), and the median hospital length of stay at readmission was 3 days (IQR, 2 to 6 days). Freedom from first readmission was observed for 65% of patients at 1 month, 48% at 3 months, 43% at 6 months, and 26% at 12 months. Gender, lung allocation score, body surface area, year of transplantation, air leak longer than 5 days after operation, and allograft function were risk factors for readmission. The causes of readmission included infections (33%), respiratory adverse events (18%), rejection (15%), gastrointestinal events (15%), renal dysfunction (5%), and cardiac events (4%). Patients who died were found to have had early readmissions (p = 0.04) and more frequent readmissions (p = 0.001). CONCLUSIONS: The first year after LT remains a high-risk period for unplanned readmissions regardless of pretransplantation diagnosis. Readmissions soon after discharge at index hospitalization and multiple readmissions are associated with an increased risk of mortality.

Restless Legs Syndrome Following Lung Transplantation: Prevalence and Relationship With Tacrolimus Exposure.

CONTEXT: Complications following lung transplantation are common and significantly reduce quality of life, and increase morbidity and mortality. Increasing evidence suggests sleep disorders are prevalent following lung transplantation, but factors associated with their development are not known. OBJECTIVES: We sought to evaluate the prevalence of restless legs syndrome (RLS) in a lung transplant population and determine if a relationship exists between RLS and exposure to immunosuppressant medications. DESIGN, SETTING, AND PARTICIPANTS: Subjects were recruited through the University of Wisconsin Hospital and Clinics Lung Transplant Clinic (N = 125). Participants (N = 81) completed sleep questionnaires, including the four RLS diagnostic criteria, insomnia severity index, and Sheehan disability scale. Cumulative tacrolimus exposure was determined in 62 subjects by calculating an area under the curve (AUC) to assess for a relationship with restless legs syndrome. RESULTS: Prevalence of RLS was 35 percent. Cumulative mean ± SEM tacrolimus exposure was similar in patients with RLS versus those without RLS (17446 ± 1855 ng days/mL vs. 15303 ± 1643 ng days/mL, respectively; p = 0.42). Insomnia severity index scores (12.5 ± 1.0 vs 6.8 ± 0.7, p < 0.0001) and Sheehan disability scores (7.8 ± 1.3 vs 3.6 ± 0.6, p = 0.003) were significantly higher in those with vs those without RLS symptoms, respectively. CONCLUSIONS: Our data confirms increased prevalence of RLS following lung transplantation reported by previous studies. RLS symptoms were not related to estimated tacrolimus exposure. Predictors of RLS following lung transplantation need to be further investigated to better identify and control RLS symptoms and reduce associated insomnia and disability.

Safety of and cellular response to segmental bronchoprovocation in allergic asthma.

RATIONALE: Despite its incorporation into research studies, the safety aspects of segmental allergen bronchoprovocation and differences in cellular response among different allergens have received limited consideration. METHODS: We performed 87 segmental challenges in 77 allergic asthma subjects. Allergen dose was based on each subject's response to whole lung allergen challenge. Bronchoalveolar lavage was performed at 0 and 48 hours. Safety indicators included spirometry, oxygen saturation, heart rate, and symptoms. RESULTS: Among subjects challenged with ragweed, cat dander, or house dust mite, there were no differences in safety indicators. Subjects demonstrated a modest oxygen desaturation and tachycardia during the procedure that returned to normal prior to discharge. We observed a modest reduction in forced vital capacity and forced expiratory volume in one second following bronchoscopy. The most common symptoms following the procedure were cough, sore throat and fatigue. Total bronchoalveolar lavage fluid cell numbers increased from 13±4 to 106±108×10(4) per milliliter and eosinophils increased from 1±2 to 44±20 percent, with no significant differences among the three allergens. CONCLUSIONS: In mild allergic asthma, segmental allergen bronchoprovocation, using individualized doses of aeroallergens, was safe and yielded similar cellular responses.

Lung transplant for interstitial lung disease: outcomes before and after implementation of the united network for organ sharing lung allocation scoring system.

OBJECTIVES: This study was undertaken to evaluate whether the adoption of the united network for organ sharing lung allocation score (LAS) was associated with significant changes in lung transplantation (LTX) outcomes for patients with interstitial lung disease (ILD) who underwent LTX at the University of Wisconsin Hospital and Clinics. METHODS: Outcomes for 107 consecutive patients with various forms of ILD who underwent LTX between January 1993 and March 2009 were examined. Patients transplanted following the implementation of the LAS system (LAS, n = 56) were compared with those transplanted prior to LAS implementation (pre-LAS, n = 51) for whom LAS scores were calculated. RESULTS: Patients with idiopathic pulmonary fibrosis (IPF) comprised the majority of patients with ILD. Recipients transplanted after the implementation of the LAS were significantly older (pre-LAS: 50.4 vs. LAS: 56.7 years, P < 0.01), required more supplemental oxygen (3 vs. 5 l/min, P < 0.01) and displayed lower cardiac index values (3.1 vs. 2.6 l/m(2), P < 0.01). The estimated LAS was significantly increased from 38.3 (pre-LAS) to 43.3 (LAS), P < 0.01. However, waiting time decreased from 266 to 78 days (P < 0.01). The rate of bilateral vs. single LTX was lower (35 vs. 16%, P = 0.02) for the post-LAS group. Cold ischaemic time was shorter in the post-LAS group (434 vs. 299 min, P < 0.01), and the length of hospital stay decreased from 24 to 11 days (P < 0.01). Hospital mortality (11 vs. 7%, P = 0.51) and post-transplant survival did not differ between the groups. CONCLUSIONS: Post-transplant outcomes for patients with ILD or the subset of recipients with IPF were not adversely affected by the implementation of the LAS.

Lung transplant for interstitial lung disease: outcomes for single versus bilateral lung transplantation.

This study was undertaken to evaluate outcomes for single (SLT) vs. bilateral lung transplantation (BLT) in patients with interstitial lung disease (ILD). One hundred and eleven patients with ILD who underwent lung transplantation between January 1993 and March 2009 were evaluated. Recipients with BLT were younger (43 ± 12 vs. 57 ± 7 years), and significantly more patients with non-idiopathic pulmonary fibrosis (IPF) received BLT (50%) vs. patients with IPF (18%). BLT recipients had a significantly longer mean waitlist time (240 vs. 125 days), significantly higher systolic (51 ± 18 vs. 40 ± 11 mmHg) pulmonary artery pressures, were placed on cardiopulmonary bypass more frequently (67 vs. 31%), had a higher incidence of primary graft dysfunction (63 vs. 17%), more frequently were given prolonged peri-operative inhaled nitric oxide and more frequently required prolonged post-operative mechanical ventilatory support (6.0 vs. 1.7 days). Additionally, BLT recipients had a significantly longer intensive care unit (8 vs. 4 days) and hospital (24 vs. 15 days) length of stay. We did not detect a difference in survival (Kaplan-Meier) for SLT vs. BLT. Our findings suggest that outcomes for SLT for patients with ILD are comparable or somewhat superior to those for BLT, and short- and long-term survival are not significantly different for the two procedures.

Colon cancer in lung transplant recipients with CF: increased risk and results of screening.

OBJECTIVE: To determine the incidence of colon cancer in lung transplant recipients with cystic fibrosis (CF) and review screening colonoscopic findings in other recipients with CF. METHODS: A retrospective chart review was performed for all patients with CF transplanted at the University of Wisconsin Hospital and Clinics (January 1994 through December 2010). RESULTS: Four of 70 transplant recipients with CF developed fatal colon carcinoma following transplantation, and the cancer was advanced in all 4 recipients (age 31, 44, 44, 64) at the time of diagnosis. In contrast, only one of 287 recipients transplanted for non-CF indications developed colon cancer. Of all recipients with CF who did not develop colon cancer, 20 recipients underwent screening colonoscopy at 1 to 12 years following transplantation. Seven (35%) of the screened transplant recipients (ages 36, 38, 40, 41, 43, 49, 51) had colonic polyps in locations ranging from cecum to sigmoid colon and up to 3 cm in diameter. CONCLUSIONS: In contrast to non-CF recipients, patients with CF displayed a significant incidence of colon cancer (4 of 70 recipients; 5.7%) with onset ranging from 246 days to 9.3 years post-transplant, which may be due to a combination of their underlying genetic disorder plus intense, sustained immunosuppression following lung transplantation. Colonoscopic screening may identify patients with pre-malignant colonic lesions and prevent progression to colonic malignancy.

The impact of the lung allocation scoring system at the single national Veterans Affairs Hospital lung transplantation program.

OBJECTIVE: The lung allocation score (LAS) has changed the distribution of donor lungs for transplantation. This study was undertaken to evaluate the impact of the LAS on a unique patient population undergoing lung transplantation (LTX) at the single national Veterans Affairs (VA) LT center. METHODS: One hundred and ten consecutive VA patients underwent LTX between 1994 and 2007. Patients transplanted using the LAS (LAS, n=26) were compared to patients transplanted prior to introduction of the LAS (pre-LAS, n=84). RESULTS: Waiting time decreased from 353.8+/-254.7 (pre-LAS) to 238.0+/-306.6 (LAS) days (p<0.01). Recipient diagnoses have changed with an increase in idiopathic pulmonary fibrosis [11% (9/84) pre-LAS vs 46% (12/26) LAS, p<0.01] and a decrease in emphysema [57% (48/84) pre-LAS vs 35% (9/26) LAS, p<0.01]. Mean LAS calculation was 33.1+/-2.9 for pre-LAS versus 41.9+/-9.8 for the LAS (p<0.01). Postoperative complications did not differ between the groups. Length of hospital stay decreased from 44.3+/-42.9 (pre-LAS) to 18.1+/-12.3 (LAS) days (p<0.01). Hospital mortality and 1-year survival did not differ between the pre-LAS and LAS groups (7% vs 8%; p=0.72 and 92% [95% confidence interval (CI) 86-98] vs 92% [CI 82-100]; p=0.23, respectively). CONCLUSIONS: The LAS appears to be achieving its objectives by reducing waitlist time and altering the distribution of lung disease being transplanted on the basis of medical necessity in the U.S. VA population. In addition, the LAS does not appear to have adversely affected short-term post-transplant outcomes in our recipient cohort.

Redo lung transplantation for acute and chronic lung allograft failure: long-term follow-up in a single center.

OBJECTIVE: This study was undertaken to evaluate outcomes of redo lung transplantation (LT) for acute and chronic graft failure. METHODS: Between 1988 and 2007, 388 LT procedures were performed on 369 patients. From those, 17 (4.6%) patients had redo LT once and 2 patients had redo LT twice. Patient survival and recurrence of bronchiolitis obliterans syndrome (BOS) after redo LT were reviewed. RESULTS: The overall survival rates of the 17 redo LT recipients at 1, 2 and 5 years were 59+/-23%, 59+/-23% and 42+/-25%, respectively. For the chronic graft failure group (n=12), survival rates at 1, 2 and 5 years were 67+/-26%, 67+/-26% and 44+/-30%, respectively. These survival rates were significantly lower than the survival rates observed in our experience after primary LT (n=352, 1-, 2- and 5-year survival rates of 88+/-4%, 80+/-4% and 65+/-5%, respectively. For the acute graft failure group (n=5), the 1-year survival rate was 40%; two patients remain free from BOS. Two patients had a second redo LT, one died from multi-organ failure on postoperative day 86 and the other died from pulmonary aspergillosis on postoperative day 214. CONCLUSIONS: Redo LT is a valid therapeutic option for selected patients with BOS and might be an option for highly selected patients with acute lung graft failure. Outcomes from a second redo LT are poor, and a second lung retransplantation must be used very cautiously, if at all.

Quantitative and qualitative analysis of rhinovirus infection in bronchial tissues.

Although rhinovirus (RV) infections can cause asthma exacerbations and alter lower airway inflammation and physiology, it is unclear how important bronchial infection is to these processes. To study the kinetics, location, and frequency of RV appearance in lower airway tissues during an acute infection, immunohistochemistry and quantitative polymerase chain reaction analysis were used to analyze the presence of virus in cells from nasal lavage, sputum, bronchoalveolar lavage, bronchial brushings, and biopsy specimens from 19 subjects with an experimental RV serotype 16 (RV16) cold. RV was detected by polymerase chain reaction analysis on cells from nasal lavage and induced sputum samples from all subjects after RV16 inoculation, as well as in 5 of 19 bronchoalveolar lavage cell samples and in 5 of 18 bronchial biopsy specimens taken 4 days after virus inoculation. Immunohistochemistry detected RV16 in 39 and 36% of all biopsy and brushing samples taken 4 and 15 days, respectively, after inoculation. Infected cells were primarily distributed in discrete patches on the epithelium. These results confirm that infection of lower airway tissues is a frequent finding during a cold and further demonstrate a patchy distribution of infected cells, a pattern similar to that reported in upper airway tissues.

Aspergillus infection in lung transplant recipients with cystic fibrosis: risk factors and outcomes comparison to other types of transplant recipients.

STUDY OBJECTIVES: To characterize Aspergillus infections in lung transplant recipients with cystic fibrosis (CF). DESIGN: A retrospective analysis of 32 consecutive lung transplant recipients with CF who underwent bilateral lung transplant at the University of Wisconsin from 1994 to 2000 to determine the incidence, risk factors, and consequences of Aspergillus infection. The findings were compared to 101 non-CF recipients of lung transplants (93) and heart-lung transplants (8) for other transplant indications. SETTING: A university hospital. PATIENTS OR PARTICIPANTS: Lung transplant recipients with CF or other indications for transplantation. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Seventeen of 32 CF recipients (53%) had Aspergillus fumigatus isolated from their respiratory secretions prior to undergoing transplantation. Ten of these 17 (59%) recipients had A fumigatus persistently found in their respiratory secretions posttransplant vs 6 of 15 CF patients (40%) who had not been colonized pretransplant and 28 of 101 of the non-CF recipients (28%). Four of the preoperatively colonized CF recipients developed tracheobronchial aspergillosis (TBA) just distal to the bronchial anastomoses, and one recipient had dehiscence of the involved anastomosis. None of the CF recipients developed disseminated aspergillosis or pneumonia. Prophylactic antifungal therapy did not prevent TBA, and IV amphotericin B therapy was required to clear the infection in all four patients, with endobronchial debridement of necrotic tissue required in two of them. In contrast, 10 of the non-CF (10%) recipients developed Aspergillus infections posttransplant (TBA, 4 recipients; pneumonitis, 6 recipients), and only 3 patients had successful treatment and long-term survival (TBA, 2 patients; pneumonia, 1 patient). Donor lung ischemia time, cytomegalovirus infection or pneumonia, or pretransplant mechanical ventilation did not increase the risk of developing TBA in CF recipients. CONCLUSIONS: The risk of TBA for patients receiving lung transplants for CF warrants early surveillance bronchoscopy to detect TBA, particularly in recipients with pretransplant colonization.