J. Parmar

Profound adrenal suppression secondary to treatment with low dose inhaled steroids and itraconazole in allergic bronchopulmonary aspergillosis in cystic fibrosis.

The case history is presented of a patient with cystic fibrosis in whom the treatment of allergic bronchopulmonary aspergillosis with itraconazole produced an initial response but was complicated by profound adrenal shutdown and impairment of inhaled steroid clearance resulting in paradoxical Cushing’s syndrome. The authors conclude that, while it is laudable to attempt to reduce the steroid burden in any patient, it is imperative that due vigilance is exercised when using a combination of agents which interact. If such a combination therapy is embarked upon, regular assessment of the pituitary adrenal axis is advisable.

Ex vivo lung perfusion: a comprehensive review of the development and exploration of future trends.

There is a critical mismatch between the number of donor lungs available and the demand for lungs for transplantation. This has created unacceptably high waiting-list mortality for lung transplant recipients. Currently (2012) in the United Kingdom, there are 216 patients on the lung transplant waiting list and 17 on heart and lung transplant list. The waiting times for suitable lungs average 412 days, with an increasing mortality and morbidity among the patients on the lung transplant list. Ex vivo lung perfusion (EVLP) has emerged as a technique for the assessment, resuscitation, and potential repair of suboptimal donor lungs. This is a rapidly developing field with significant clinical implications. In this review article, we critically appraise the background developments that have led to our current clinical practice. In particular, we focus on the human and animal experience, the different perfusion-ventilation strategies, and the impact of different perfusates and leukocyte filters. Finally, we examine EVLP as a potential research tool. This will provide insight into EVLP and its future development in the field of clinical lung transplantation.

Comparison of Outcomes From Smoking and Nonsmoking Donors: Thirteen-Year Experience

BACKGROUND Lung transplantation remains the best treatment option for a variety of end-stage lung diseases. Pressure on the limited donor pool has led to the use of extended criteria donors. One aspect of this has been the liberalization of the use of smoking donors (SmD). METHODS This study is a retrospective review of lung transplants performed between April 1995 and August 2008 at a single institute. We examined the impact of donor smoking on short-term and long-term survival in relationship to recipient and donor demographics such as ischemic time, cytomegalovirus status, rates of rejection and infection, ventilation, and intensive care stay. Endpoints were survival, infection, and rejection. RESULTS During this 13-year period, 454 lung transplants were performed. Smoking history was available on 424 (93.4%) of these (SmD, n = 184; NSmD, n = 240). Seventy-one patients died within 3 months of transplant leaving 353 alive at 3 months posttransplant. Fatalities within the first 3 months were significantly higher in the SmD group (21% vs 13%, odds ratio 1.9, hazard ratio 3.3, p = 0.04). No significant difference in rejection and infection rates between recipients of lungs from SmD and NSmD at 3 months and at 1 year posttransplantation (p = 0.51 and 0.09) was found. Although recipients of lungs from SmD had higher odds of ventilation for more than 10 hours, the odds were only increased by 20%, which was not statistically significant. Recipients from SmD had significantly longer stays in the intensive care (odds ratio 1.9, p = 0.002). There was little evidence for an effect of SmD on the development of bronchiolitis obliterans. CONCLUSIONS In this large cohort of patients, donor smoking history has an effect on early survival but no effect on long-term survival. The cause of this early mortality is independent of infection and rejection. However, these data suggest that overall outcomes from the use of donor lungs from smokers are acceptable, particularly in the current era with limited donor organs.

Original articleGeneral thoracicComparison of Outcomes From Smoking and Nonsmoking Donors: Thirteen-Year Experience

BACKGROUND Lung transplantation remains the best treatment option for a variety of end-stage lung diseases. Pressure on the limited donor pool has led to the use of extended criteria donors. One aspect of this has been the liberalization of the use of smoking donors (SmD). METHODS This study is a retrospective review of lung transplants performed between April 1995 and August 2008 at a single institute. We examined the impact of donor smoking on short-term and long-term survival in relationship to recipient and donor demographics such as ischemic time, cytomegalovirus status, rates of rejection and infection, ventilation, and intensive care stay. Endpoints were survival, infection, and rejection. RESULTS During this 13-year period, 454 lung transplants were performed. Smoking history was available on 424 (93.4%) of these (SmD, n = 184; NSmD, n = 240). Seventy-one patients died within 3 months of transplant leaving 353 alive at 3 months posttransplant. Fatalities within the first 3 months were significantly higher in the SmD group (21% vs 13%, odds ratio 1.9, hazard ratio 3.3, p = 0.04). No significant difference in rejection and infection rates between recipients of lungs from SmD and NSmD at 3 months and at 1 year posttransplantation (p = 0.51 and 0.09) was found. Although recipients of lungs from SmD had higher odds of ventilation for more than 10 hours, the odds were only increased by 20%, which was not statistically significant. Recipients from SmD had significantly longer stays in the intensive care (odds ratio 1.9, p = 0.002). There was little evidence for an effect of SmD on the development of bronchiolitis obliterans. CONCLUSIONS In this large cohort of patients, donor smoking history has an effect on early survival but no effect on long-term survival. The cause of this early mortality is independent of infection and rejection. However, these data suggest that overall outcomes from the use of donor lungs from smokers are acceptable, particularly in the current era with limited donor organs.

Comparison between cellular and acellular perfusates for ex vivo lung perfusion in a porcine model

BACKGROUND Ex vivo lung perfusion with acellular solutions is an established technique for assessing marginal donor lungs. We evaluated the utility of a blood-based lung preservation fluid as an alternative perfusate. METHODS Donor lungs from 50-kg donation after cardiac death pigs (n = 24) were randomized into 3 groups: acellular, commercial blood-based, and Papworth-Blood. Physiologic function was evaluated using conventional markers of pulmonary vascular resistance, pulmonary compliance, lactate excretion, partial pressure of oxygen/fraction of inspired oxygen, and wet-to-dry ratios. The immunologic profile was assessed by fluorescence-activated cell sorting analysis of bronchoalveolar lavage and cells entrapped in the leucocyte filter. Cytokines were quantified using a commercial platform. RESULTS No significant difference was noted in pulmonary vascular resistance (p = 0.26), compliance (p = 0.12), partial pressure of oxygen/fraction of inspired oxygen (p = 0.06) and wet-to-dry ratios (p = 0.26) between groups. There was no difference between the percentages of lymphocytes (p = 0.51), macrophages (p = 0.87), monocytes (p = 0.68), and dendritic cells (p = 0.65) in the leukocyte filters. Interleukin (IL)-1β (p = 0.36), IL-6 (p = 0.08), IL-8 (p = 0.64), and IL-18 (p = 0.14) were elevated in all groups. In bronchoalveolar lavage, IL-8 was significantly higher in the acellular group (p = 0.04). Electron microscopy cell characteristics were similar among the groups. CONCLUSIONS This study demonstrated no significant difference in the physiologic, immunologic, or ultrastructural parameters between lungs perfused with cellular or acellular solutions. The Papworth-Blood solution is a potential alternative perfusate for ex vivo lung perfusion.

Size matching in lung transplantation: an evidence-based review.

The evidence base for size matching between donors and recipients in lung transplantation has not recently been reviewed in a comprehensive manner. Our aim in this study was to assimilate published studies that have addressed size matching of donors to recipients and to establish a pragmatic understanding of the range of lung sizes that may be used for lung transplantation. A comprehensive literature search was performed using Medline and PubMed up to and including September 2012, to identify scientific articles that relate to size matching between donors and lung transplant recipients. Seventy-two articles were identified, of which 21 had addressed the question of the impact of size mismatching on outcomes in lung transplantation. No study has specifically tested the consequences of intentionally mismatching above or below the hypothetical limits for double lung transplantation of a predicted total lung capacity for the donor of between 75% and 125% of the recipient predicted total lung capacity as set out in the ISHLT consensus report on lung donor acceptability criteria. Research is lacking that has robustly defined limits for size mismatch for single lung transplantation and for recipients with restrictive lung pathologies such as pulmonary fibrosis. Published research on the impact of size mismatching between lung transplant donors and recipients is limited by study design and size. It is centered on addressing the issue of mismatch in double lung transplantation in cohorts with a diagnostically heterogeneous make-up and in single lung transplant patients with chronic obstructive pulmonary disease.

Cavitatory lung disease in thoracic transplant recipients receiving sirolimus

Sirolimus is a potent immunosuppressant agent that has utility in solid-organ transplantation (SOT), particularly for its renal-sparing effects. However, lung toxicity can be a significant issue and a variety of different lung injury patterns have been described. We report an unrecognized association of sirolimus with lung cavitation in patients who have undergone cardiothoracic transplantation. Between 1996 and 2010, lung and heart transplant patients received sirolimus-based immunosuppression as a second-line agent after initial therapy with calcineurin inhibitors. All cases of sirolimus-induced lung cavities were recorded and a retrospective review of the case notes of these patients was undertaken. A total of 9 patients were identified. Clinical symptoms, time to first cavity and mean levels were variable. Some patients showed complete resolution, whereas others had persistent cavitatory lung lesions. Patients who developed persistent lung cavities had a worse outcome than those who did not have cavitation.

Percutaneous dilatation of right inferior pulmonary vein stenosis following single-lung transplant

We present a 62-year old male who underwent right single-lung transplantation. An autologous pericardial rim was constructed at implantation, as there was insufficient donor atrial cuff. The patient was discharged home but deteriorated over 12 months resulting in oxygen dependency. Computed tomography scan showed stenosis of the right inferior pulmonary vein. The patient underwent pulmonary vein angioplasty under general anaesthesia in September 2007, which was successful and resulted in significant improvement in clinical status. However, his symptoms recurred 2 months later and a second attempt at angioplasty failed. He died 6 weeks later.

Patient outcomes from time of listing for lung transplantation in the UK: Are there disease-specific differences?

Background The demand for lung transplantation vastly exceeds the availability of donor organs. This translates into long waiting times and high waiting list mortality. We set out to examine factors influencing patient outcomes from the time of listing for lung transplantation in the UK, examining for differences by patient characteristics, lung disease category and transplant centre. Methods Data were obtained from the UK Transplant Registry held by NHS Blood and Transplant for adult lung-only registrations between 1January 2004 and 31 March 2014. Pretransplant and post-transplant outcomes were evaluated against lung disease category, blood group and height. Results Of the 2213 patient registrations, COPD comprised 28.4%, pulmonary fibrosis (PF) 26.2%, cystic fibrosis (CF) 25.4% and other lung pathologies 20.1%. The chance of transplantation after listing differed by the combined effect of disease category and centre (p<0.001). At 3 years postregistration, 78% of patients with COPD were transplanted followed by 61% of patients with CF, 59% of other lung pathology patients and 48% of patients with PF, who also had the highest waiting list mortality (37%). The chance of transplantation also differed by height with taller patients having a greater chance of transplant (HR: 1.03, 95% CI: 1.02 to 1.04, p<0.001). Patients with blood group O had the highest waiting mortality at 3 years postregistration compared with all other blood groups (27% vs 20%, p<0.001). Conclusions The way donor lungs were allocated in the UK resulted in discrepancies between the risk profile and probability of lung transplantation. A new donor lung allocation scheme was introduced in 2017 to try to address these shortcomings.

Lung donation after circulatory determined death: a single-centre experience†

OBJECTIVES Donor organ utilization and shortage remain the major limitations to the opportunity of a lung transplantation (LTx). Donation after circulatory determined death (DCD) has been adopted as a source of additional organs worldwide. However, concerns about organ quality and ischaemia-reperfusion injury have limited its application. The aim of this study was to retrospectively analyse a single-centre experience in the DCD LTx and compare early and mid-term outcomes with those from a standard donation after brain death (DBD). METHODS During the 6-year study period, 186 LTxs were performed: 147 bilateral LTxs (79%) and 39 single LTxs (21%). Of these, 23 recipients received organs retrieved from DCD donors (12.4%). RESULTS No differences were found between the 2 groups of recipients except for age and cystic fibrosis as an underlying disease. No differences in terms of duration of mechanical ventilation, incidence of postoperative extracorporeal membrane oxygenation support, intensive care unit stay, hospital length of stay, airway anastomotic complications, incidence and grade of rejection and freedom from bronchiolitis obliterans syndrome were demonstrated. There was a non-statistically significant trend towards older age in the DCD group. Actuarial survival in the subgroup of bilateral LTx at 1 year and 5 years was 75% and 51% for the DCD group and 82% and 61% for the DBD group, respectively (P = 0.12). CONCLUSIONS Short- and medium-term outcomes after the DCD LTx are comparable with those achieved after transplantation from the DBD donors, despite a tendency to use DCD lungs for older recipients. Therefore, the DCD LTx is a clinical option that can be used with favourable results to expand the lung donor pool.