Right Ventricular Assist Device with an Oxygenator for the Management of Combined Right Ventricular and Respiratory Failure: A Systematic Review.

BACKGROUND: Severe lung disease frequently presents with both refractory hypoxemia and right ventricular (RV) failure. OxyRVAD is an extra-corporeal membrane oxygenation (ECMO) configuration of RV bypass that also supplements gas exchange. This systematic review summarizes the available literature regarding the use of OxyRVAD in the setting of severe lung disease with associated RV failure. METHODS: PubMed, Embase, and Google Scholar were queried on September 27th, 2023, for articles describing the use of an OxyRVAD configuration. The main outcome of interest was survival to ICU discharge. Data on the duration of OxyRVAD support and device-related complications were also recorded. RESULTS: Of 475 identified articles, 33 were retained for analysis. Twenty-one articles were case reports and 12 were case series representing a total of 103 patients. No article provided a comparison group. Most patients (76.4%) were transitioned to OxyRVAD from another type of mechanical support. OxyRVAD was used as a bridge to transplant or curative surgery in 37.4% and as a bridge to recovery or decision in 62.6%. Thirty-one patients (30.1%) were managed with the dedicated single-access dual-lumen ProtekDuo cannula. Median time on OxyRVAD was twelve days (IQR 8-23) and survival to ICU discharge was 63.9%. Device-related complications were infrequently reported. CONCLUSION: OxyRVAD support is a promising alternative for RV support when gas exchange is compromised with good ICU survival in selected cases. Comparative analyses in patients with RV failure with and without severe lung disease are needed.

Virtual Physical Prehabilitation in Lung Transplant Candidates: A Proof-of-Concept Study.

This study aimed to preliminary test the effectiveness of 12-week virtual physical prehabilitation program followed by a maintenance phase. The main objective was to estimate the extent to which it affects exercise capacity, frailty, lower limb strength and health-related quality of life (HRQOL) in lung transplant candidates. The program offered supervised strengthening exercises, independent aerobic exercises and weekly phone calls (maintenance phase). Primary outcome was the six-minute walk distance (6MWD). Secondary outcomes: the Short Physical Performance Battery (SPPB), five-times sit-to-stand test (5STS), the St George's Respiratory Questionnaire (SGRQ) for HRQOL. Twenty patients were included (mean age 57.9; 6 women/14 men); fourteen completed the prehabilitation program and 5 completed the maintenance phase. There was no statistically significant improvement in 6MWD, SPPB or SGRQ after the 12-week program. Most patients either maintained or improved the 6MWT and SPPB scores. There was a significant improvement in the 5STS. After the maintenance phase, most patients either improved or maintained their scores in all outcomes except for the sub-score of symptoms in the SGRQ. A 12-week virtual physical prehabilitation program with a 12-week maintenance phase can help lung transplant candidates improve or maintain their physical function while waiting for transplantation.

Post-transplant outcomes among cystic fibrosis patients undergoing lung transplantation colonized by Burkholderia: A single center cohort study.

BACKGROUND: Prior infection with Burkholderia cepacia complex (BCC) has been associated with poorer outcomes after lung transplantation, posing an important dilemma for cystic fibrosis (CF). Although current guidelines consider BCC infection to be a relative contraindication, some centers continue to offer lung transplantation to BCC-infected CF patients. METHODS: We conducted a retrospective cohort study which included all consecutive CF-LTR between 2000 and 2019 to compare the postoperative survival of BCC-infected CF lung transplant recipients (CF-LTR) to BCC-uninfected patients. We used a Kaplan-Meier analysis to compare survival of BCC-infected to BCC-uninfected CF-LTR and fitted a multivariable Cox model, adjusted for age, sex, BMI and year of transplantation as potential confounders. As an exploratory analysis, Kaplan-Meier curves were also stratified by the presence of BCC and urgency of transplantation. RESULTS: A total of 205 patients were included with a mean age of 30.5 years. Seventeen patients (8%) were infected with BCC prior to LT. Patients were infected with the following species: B. multivorans5, B. vietnamiensis3, combined B. multivorans and B. vietnamiensis3 and others4. None of the patients were infected with B. cenocepacia. Three patients were infected with B. gladioli. One-year survival was 91.7% (188/205) for the entire cohort, 82.4% (14/17) among BCC-infected CF-LTR, and 92.5% (173/188) among BCC uninfected CF-LTR (crude HR = 2.19; 95%CI 0.99-4.85; p = 0.05). In the multivariable model, presence of BCC was not significantly associated with worse survival (adjusted HR 1.89; 95%CI 0.85-4.24; p = 0.12). In the stratified analysis for both presence of BCC and urgency of transplantation, urgency of transplantation among BCC-infected CF-LTR appeared to be associated with poorer outcome (p = 0.003 across the 4 subgroups). CONCLUSION: Our results suggest that non-cenocepacia BCC-infected CF-LTR have comparable survival rate to BCC-uninfected CF-LTR.

Long-term bone mineral density changes and fractures in lung transplant recipients with cystic fibrosis.

BACKGROUND: Little is known about long-term bone mineral density (BMD) changes and fractures in lung transplant recipients with cystic fibrosis (CF). We examined femur and lumbar spine (LS) BMD changes in men and women with CF up to 10 years post-transplant and documented post-transplant fracture prevalence. METHODS: Retrospective study of individuals who had undergone a lung transplant (2000-2015) and had a pre-transplant and at least one BMD measurement after transplant. Vertebral fractures were assessed on chest computed tomography scans and other fractures abstracted from medical records. RESULTS: The cohort consisted of 131 individuals; 53% males, median age: 28 years [interquartile range: 24-35] and 31% having pre-transplant low bone mass. Most recipients were given bisphosphonates after transplant with proportion reaching 94% at 10 years. Up to 10 years post-transplant, men experienced positive or little change in LS BMD, indicating minimal loss from pre-transplant values. In contrast, women displayed negative changes in BMD up to 5 years post-transplant before recovering pre-transplant BMD values by 10 years. Similar patterns were observed at the femur BMD where men demonstrated a lower bone loss and faster recovery towards pre-transplant values than women. After transplant, 88% of recipients maintained their pre-transplant bone status, 3% experienced an improvement, mostly progressing from low bone mass to normal status whereas 9% had a deterioration of their pre-transplant bone status. Twenty-seven recipients suffered fractures in the post-transplant period. CONCLUSIONS: These findings underline that lung recipients with CF remain at risk of skeletal fragility despite prompt initiation of post-transplant anti-osteoporosis therapy.

Large pH oscillations promote host defense against human airways infection.

The airway mucosal microenvironment is crucial for host defense against inhaled pathogens but remains poorly understood. We report here that the airway surface normally undergoes surprisingly large excursions in pH during breathing that can reach pH 9.0 during inhalation, making it the most alkaline fluid in the body. Transient alkalinization requires luminal bicarbonate and membrane-bound carbonic anhydrase 12 (CA12) and is antimicrobial. Luminal bicarbonate concentration and CA12 expression are both reduced in cystic fibrosis (CF), and mucus accumulation both buffers the pH and obstructs airflow, further suppressing the oscillations and bacterial-killing efficacy. Defective pH oscillations may compromise airway host defense in other respiratory diseases and explain CF-like airway infections in people with CA12 mutations.

Changes in 6-minute walking distance in lung transplant candidates while participating in a home-based pre-habilitation program-A retrospective chart review.

Home-based exercise programs may offer a less costly alternative to providing exercise pre-transplant to a large number of patients. We describe the changes in 6-minute walk distance (6MWD) in lung transplant candidates who participated in a home-based exercise program and their relationship to post-transplant outcomes. Retrospectively, we investigated 159 individuals while awaiting transplantation who performed the surgery between 2011 and 2015. Primary outcome was 6MWD at time of assessment for transplant, last test prior to transplant and one-month post-transplant. 6MWD decreased by 28 ± 93.9 m between the time of assessment and the last 6MWD prior to transplantation (P < .001). Forty-one patients (25.8%) increased their 6MWD (mean + 85.8 ± 42.8 m); 72 patients (45.3%) decreased their 6MWD (mean -109.8 ± 71.2 m); and 46 patients (28.9%) had no change in 6MWD (-1.5 ± 15.7 m). There was a moderate correlation (r = .528; P < .001) between the last 6MWD prior to transplant and 6MWD post-transplant. Change in 6MWD prior to transplant weakly correlated with length of time on mechanical ventilation (r = -.185; P = .034). When adjusted for covariates, change in 6MWD prior to transplant was not associated with length of time on mechanical ventilation, total hospital LOS, or intensive care unit LOS. The majority of the patients were able to either increase or maintain their 6MWD while participating in a home-based pre-habilitation program during the waiting list period. Prospective research is needed to evaluate the effects of home-based pre-habilitation program for lung candidates.

Double lung transplantation in an HIV-positive patient with Mycobacterium kansasii infection.

Good outcomes with kidney and liver transplantation in HIV-positive patients have led clinicians to recommend lung transplantation in HIV-positive patients based on extrapolated data. Pre-transplant mycobacterial infection is associated with an increased risk of developing new infection or aggravating existing infection, though it does not contraindicate transplantation in non-HIV-infected patients. However, no data exists regarding the outcome of HIV-positive patients with pre-transplant mycobacterial infection. We report a case of double lung transplantation in a 50-year-old HIV-positive patient with alpha-1 antitrypsin deficiency. Prior to transplantation, Mycobacterium kansasii was isolated in one sputum culture and the patient was considered merely colonized as no clinical evidence of pulmonary or disseminated disease was present. The patient successfully underwent a double lung transplantation. Nontuberculous mycobacterial infection was diagnosed histologically on examination of native lungs. Surveillance and watchful waiting were chosen over treatment of the infection. HIV remained under control post-transplantation with no AIDS-defining illnesses throughout the follow-up. A minimal acute rejection that responded to increased corticosteroids was reported. At 12 months post-transplant, a bronchiolitis obliterans syndrome was diagnosed after a drop in FEV1. No evidence of isolation nor recurrence of nontuberculous mycobacteria was reported post-transplantation. At 15 months post-transplant, the patient remained stable with an FEV1 of 30%. The presence of pre-transplant nontuberculous mycobacterial infection did not translate into recurrence of nontuberculous mycobacterial infection post-transplant. Whether it contributed to bronchiolitis obliterans syndrome remains unknown.

Postoperative imaging after lung transplantation.

Lung transplantation (LT) is an established procedure for chronic end-stage lung diseases. Complications are frequent and diverse and are the consequence of the complex surgical technique, the severity of the initial pathology, and the deep state of posttransplantation immunosuppression. Complications following LT include primary graft dysfunction, rejection (hyperacute, acute, and chronic), infections, posttransplantation lymphoproliferative disease, pleural and airway complications, native lung complications, and recurrence of primary disease. An understanding of these complications, their temporal evolution, and the role of radiology and other diagnostic methods in their diagnosis and management will help reduce the morbidity and mortality associated with LT.

Development of a decision aid for adult cystic fibrosis patients considering referral for lung transplantation.

CONTEXT: Most adults with cystic fibrosis are eventually required to make a decision about referral for lung transplantation. OBJECTIVE: To identify the decisional needs of these patients and to develop a decision aid to address these needs. METHODS: A comprehensive review of the literature, a review of Canadian transplant statistics from 2002 to 2006, and a self-assessment survey of patients who had already made a decision about referral were performed to identify the decisional needs of patients. A decision aid was then developed and evaluated by an expert panel of health care professionals and patients. RESULTS: Transplant referral patterns vary widely among Canadian cystic fibrosis clinics. Canadian patients with cystic fibrosis who were not residing in transplant centers between 2002 and 2006 were significantly less likely to undergo lung transplants (P < .001). Decisional needs identified by patients included wanting more information on (1) relocation to the transplant center, (2) the benefits and risks of surgery, and (3) how to cope with anxiety and depression when making the decision. In response to these identified needs, a decision aid for lung transplantation was developed. A panel of health care professionals and patients reviewed the decision aid and agreed that the content was appropriate, easy to understand, and unbiased. CONCLUSION: The decisional needs of patients with cystic fibrosis who are considering lung transplantation are not being addressed in Canadian cystic fibrosis clinics, especially in clinics outside of transplant centers. An evidence-based decision aid could serve as a useful tool to help address these needs.

Late retrograde perfusion of donor lungs does not decrease the severity of primary graft dysfunction.

BACKGROUND: The ideal preservation strategy has yet to be established in lung transplantation. This clinical study compares primary graft dysfunction using antegrade and retrograde perfusion of donor lungs. METHODS: Over a 6-year period, 153 consecutive patients underwent lung transplantation in our institution. Group I consists of 65 patients who received lungs preserved with an antegrade flush of modified Euro-Collins solution. Group II includes 65 patients who received lungs preserved with an antegrade flush of low-potassium dextran (LPD) solution. Group III consists of 23 patients who received lungs preserved with an antegrade and a preimplantation retrograde flush of LPD solution. Endpoints evaluated were the following: acute lung injury (ALI) score, time to achieve a fraction of inspired oxygen (Fio2) of 40% and a positive end-expiratory pressure (PEEP) of 5, length of ventilation, length of intensive care unit (ICU) stay, 90-day operative mortality, and patient survival rates. RESULTS: The patient demographic data, underlying diagnosis, number of single and double lung transplants, use of cardiopulmonary bypass, and mean ischemic times were similar in all 3 groups. The mean ALI score (6.2, 5.8, and 6.0) and the median length of ventilation (23.5, 24.0, and 27.0 hours) in groups I, II, and III, respectively, were not significantly different. The length of ICU stay, the 90-day operative mortality, and the survival rates were not significantly different in the 3 groups. CONCLUSIONS: Our results suggest that late retrograde perfusion of donor lungs does not decrease the severity of primary graft dysfunction when compared with standard antegrade techniques.

Cyp3A4, Cyp3A5, and MDR-1 genetic influences on tacrolimus pharmacokinetics in renal transplant recipients.

OBJECTIVE: The immunosuppressive drug tacrolimus requires strict therapeutic monitoring due to its narrow therapeutic index and great inter-individual variability. Cytochrome P450 3A4 (Cyp3A4) and Cyp3A5 are the most important contributors to tacrolimus metabolism while the P-glycoprotein pump (MDR-1) modulates its bioavailability. The objective was to investigate the association between Cyp3A4, Cyp3A5, and MDR-1 polymorphisms and tacrolimus pharmacokinetics in the early period after renal transplantation. METHODS: Forty-four renal transplant recipients were genotyped for 8 Cyp3A4, 7 Cyp3A5, and 5 MDR-1 genetic variants affecting the proteins' expression and/or function. Dose-adjusted tacrolimus though levels were determined during the first week after transplantation and correlated with corresponding genotype. RESULTS: We found no correlation between Cyp3A4 polymorphism and tacrolimus pharmacokinetics. Patients who do not carry both Cyp3A5*3 alleles achieved lower mean dose-adjusted tacrolimus blood concentrations (p<0.001) and needed a longer time to reach the target concentration (10-12 ng/ml; p<0.001) compared to Cyp3A5*3 homozygotes. Patients with less than three copies of MDR-1 (T-129C, C3435T and G2677T) polymorphisms, associated with reduced expression of P-glycoprotein, had also lower dose-adjusted tacrolimus blood concentrations compared to patients having equal to or greater than three copies of MDR-1 genetic variants (P=0.003). There was no difference in the rate of biopsy-confirmed acute rejection among groups during the first 3 months after transplantation. CONCLUSION: The complete absence of Cyp3A5*3 allele and the accumulation of less than three copies of MDR-1 (T-129C, C3435T and G2677T) polymorphisms are associated with lower tacrolimus blood levels identifying these genotypes as markers for patients requiring higher tacrolimus doses.

A cost-effectiveness and cost-utility study of lung transplantation.

BACKGROUND: Life-threatening complications and expensive posttransplantation medical care raises the issue whether lung transplantation (L-Tx) is cost effective. We studied, from a health care system perspective, the cost effectiveness (C/E) and cost utility (C/U) of L-Tx in a Canadian setting. METHODS: An incremental C/E and C/U analysis of L-Tx, compared with the waiting list (WL), was carried out on 124 patients accepted into the Quebec L-Tx WL (1997-2001). Survival was presented in mean life-years (LYs). Utility, assessed with the standard gamble, was used in computing the quality-adjusted life-years (QALY). Different person-time experiences were simulated. Costs (95% confidence interval), in US dollars, were discounted at 5%. RESULTS: The mean LYs and QALYs gained were 0.57 (0.36-0.78) and 0.62 (0.36-0.78), respectively. The cost per patient without Tx was 1102 dollars (856 dollars-1348 dollars) per month. The L-Tx program induced a screening cost of 6208 dollars per patient. The cost of the L-Tx procedure (n = 91) was 31,815 dollars (25,301 dollars-44,816 dollars). The post-Tx cost per month in the first, second, third, and fourth year was 1809 dollars dollars (1187 dollars-2446 dollars), 1060 dollars (703 dollars-1478 dollars), 1128 dollars (519 dollars-1735 dollars), and 626 dollars (495 dollars-758 dollars), respectively. The projected C/E and C/U of the L-Tx program, assessed on the basis of pre- and post-Tx extrapolations, reached 40,048 dollars and 46,631 dollars, respectively. CONCLUSIONS: L-Tx in this Canadian setting yielded a benefit in mean LYs and QALYs gained. Although the program is expensive, the C/E and C/U ratios for some patient groups prove to be an acceptable cost for the benefits observed.

Acute postoperative pain in lung transplant recipients.

BACKGROUND: This retrospective study was designed to assess the quality of postoperative pain control and the facility of transition from epidural to oral analgesia in lung transplant recipients. METHODS: After institutional review board approval, data were collected from the charts of all patients who underwent lung transplantation at our institution between 1998 and 2002. The study group consisted of the patients for whom an epidural was the first postoperative pain management modality. To serve as a control group we reviewed the charts of 30 patients, randomly selected over the same period, who underwent a thoracotomy for indications other than transplantation and who received postoperative epidural analgesia. RESULTS: Eighty-three patients were available for analysis. Unilateral and bilateral lung transplant recipients had equivalent quality of pain control. However, lung transplant recipients had a lower incidence of adequate pain relief than patients undergoing thoracotomy for other indications (73% vs 87%, p < 0.05). Lung transplant recipients also had a higher incidence of epidural to oral analgesia transition failure (47% vs 20%, p < 0.01). CONCLUSIONS: This is the first study to assess the quality of postoperative pain control and success of transition from epidural to oral analgesia in lung transplant recipients. Prospective studies are needed to assess the impact of our findings on patients' outcome.