Longitudinal assessment of interstitial lung disease in single lung transplant recipients with scleroderma.

OBJECTIVE: To investigate the natural history of fibrotic lung disease in recipients of a single lung transplant for scleroderma-associated interstitial lung disease (ILD). METHODS: Global ILD (including ground glass, nodular opacities and fibrosis) was categorized into severity quintiles on first and last post-transplant CT scans, and percent fibrosis by manual contouring was also determined, in nine single lung transplant recipients. Quantitative mean lung densities and volumes for the native and allograft lungs were also acquired. RESULTS: In the native lung, global ILD severity quintile worsened in two cases and percent fibrosis worsened in four cases (range 5-28%). In the lung allograft, one case each developed mild, moderate and severe ILD; of these, new fibrotic ILD (involving <10% of lung) occurred in two cases and acute cellular rejection occurred in one. The average change in native lung density over time was +2.2 Hounsfield Units per year and lung volume +1.4 ml per year, whereas the allograft lung density changed by -5.5 Hounsfield Units per year and total volume +27 ml per year (P = 0.011 and P = 0.039 for native vs allograft density and volume comparisons, respectively). CONCLUSIONS: While the course of ILD in the native and transplanted lungs varied in this series, these cases illustrate that disease progression is common in the native lung, suggesting that either the immune process continues to target autoantigens or ongoing fibrotic pathways are active in the native lung. Mild lung disease may occur in the allograft after several years due to either allograft rejection or recurrent mild ILD.

Effect of broader geographic sharing of donor lungs on lung transplant waitlist outcomes.

BACKGROUND: The United States lung allocation system prioritizes allocation based on medical urgency and benefit but does not address a federal mandate for broader geographic organ sharing. It is unknown whether broader geographic sharing of donor lungs would improve lung transplant waitlist outcomes. METHODS: A discrete event microsimulation model simulated donor lung allocation according to different geographic lung-sharing policies, including the historic local donor service area (DSA)-based policy and hypothetical policies that prioritize candidates to donors within 500-mile or 1,000-mile geographic radii. Candidate waitlist mortality, number of transplants, and 1-year survival were compared across organ allocation policies. Waitlist mortality rates were further stratified by diagnosis, Lung Allocation Score (LAS) threshold, ABO blood type, and region. RESULTS: Under broader geographic lung sharing, the proportion of chronic obstructive pulmonary disease transplant recipients decreased, whereas the proportion of pulmonary fibrosis recipients increased. Waitlist mortality decreased with broader geographic lung sharing with a 21.3% decrease in waitlist mortality with 500-mile lung sharing and a 31.8% decrease in waitlist mortality with 1,000-mile lung sharing. The decrease in waitlist deaths occured across all U.S. geographic regions and was greatest in candidates with pulmonary fibrosis and/or high medical urgency. CONCLUSIONS: Broader geographic sharing of donor lungs could reduce waitlist mortality, particularly among pulmonary fibrosis and high-medical-urgency candidates.

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.

Patient factors associated with lung transplant referral and waitlist for patients with cystic fibrosis and pulmonary fibrosis.

BACKGROUND: Since 2005, the Lung Allocation Score (LAS) has prioritized patient benefit and post-transplant survival, reducing waitlist to transplant time to <200 days and decreasing mortality on the waitlist. A current challenge is the wait for the waitlist-the time between the patient's transplant-eligible diagnosis and waitlist registration. METHODS: We investigated whether sociodemographic (age, sex, race, insurance, marital status, median household income) and clinical (forced expiratory volume in 1 second [FEV1] percent of predicted, body mass index, depression/anxiety, alcohol/substance misuse, absolute/relative contraindications) factors influenced referral and waitlist registration. We conducted a retrospective cohort study through chart review of hospitalized patients on the University of Chicago general medicine service from 2006 to 2014 who met transplant-eligible criteria and ICD-9 billing codes for cystic fibrosis (CF) and pulmonary fibrosis (PF). We analyzed the times from transplant eligibility to referral, work-up and waitlisting using Kaplan-Meier curves and log-rank tests. RESULTS: Overall, the referral rate for transplant-eligible patients was 64%. Of those referred, approximately 36% reach the lung transplant waitlist. Referred CF patients were significantly more likely to reach the transplant waitlist than PF patients (CF 60% vs PF 22%, p < 0.05). In addition, CF patients had a shorter wait from transplant eligibility to waitlist than PF patients (329 vs 2,369 days, respectively [25th percentile], p < 0.05). Patients with PF and CF both faced delays from eligibility to referral and waitlist. CONCLUSIONS: Quality improvement efforts are needed to better identify and refer appropriate patients for lung transplant evaluation. Targeted interventions may facilitate more efficient evaluation completion and waitlist appearance.

Analysis of access to hypertensive and diabetic drugs in the Family Health Strategy, State of Pernambuco, Brazil / Análise do acesso ao tratamento medicamentoso para hipertensão e diabetes na Estratégia de Saúde da Família no Estado de Pernambuco, Brasil

To evaluate the access to drugs for hypertension and diabetes and the direct cost of buying them among users of the Family Health Strategy (FHS) in the state of Pernambuco, Brazil.

Avaliar o acesso a medicamentos para hipertensão e diabetes e o gasto direto relacionado à aquisição destes insumos entre os usuários da Estratégia Saúde da Família (ESF), no estado de Pernambuco.

Quality of life assessment in two consecutive years of patients in a waiting list for lung transplantation.

BACKGROUND: Patients on a waiting list for lung transplantation (LT) have physical and emotional setbacks due to limiting symptoms such as dyspnea and cough. Time on a waiting list may worsen the conditions of these patients and affect their quality of life (QoL). OBJECTIVE: Our objective was to evaluate QoL components in patients in 2 consecutive years who were waiting for transplantation. MATERIAL AND METHODS: We studied patients who remained on a waiting list for transplantation in the first 2 years after inclusion on the list. Evaluation was performed using the Short-Form-36 (SF-36) Questionnaire and the Saint George's Respiratory Questionnaire (SGRQ). RESULTS: Fifty-six patients were included (38.5 ± 15 years), 33 women (59%) and 23 men (41%). Of these, 18 had bronchiectasis, 14 had cystic fibrosis, 9 had lung fibrosis, 8 had lung emphysema, and 7 had other diseases. The domains with greater involvement in the first and second year were Functional Capacity and Physical Aspects. In the second year there was a significant worsening in Physical Aspects (2.5-0 points; P = .032). The domains related to the emotional component did not have significant changes. CONCLUSION: The progression of the disease and progressive worsening of symptoms of patients on a transplantation waiting list led to less physical exercise, worsening the effects of inactivity. After 1 year on a waiting list for LT, patients had a significant loss of functionality, which had an impact on QoL.

[Results of lung transplantation]. / Résultats de la transplantation pulmonaire.

INTRODUCTION: Lung transplantation has experienced an increasing expansion with a significant improvement in results with the passage of time. Evaluation of these results consists of several domains: survival, function, quality of life and cost-effectiveness. BACKGROUND: The success of lung transplantation is confirmed by a median survival that currently exceeds 5 years. Cystic fibrosis is the disease associated with the best results with, in France, a survival of 76% at 1 year, 56% at 5 years and 47% at 10 years and a median survival of 8 years. According to French data the 5-year survival is 46% for PAHT, 42% for COPD and 36% for pulmonary fibrosis. Studies have shown a survival benefit for cystic fibrosis and interstitial lung disease but definitive conclusions cannot be drawn for patients with COPD. Lung transplantation brings similar benefits in terms of quality of life and cost-effectiveness. VIEWPOINTS: New statistical methods would allow a better estimate in terms of years of survival and quality of life to be made for each candidate on an individual basis. CONCLUSIONS: Lung transplantation improves survival and quality of life compared to medical treatment, at an acceptable cost. These outcomes should be assessed at both an individual and social level to justify the resources involved.

Lung allocation score predicts survival in lung transplantation patients with pulmonary fibrosis.

BACKGROUND: Since 2005, the Organ Procurement and Transplantation Network has used the lung allocation score (LAS) to assign organ allocation priority in lung transplantation. This study was designed to determine whether LAS predicts short-term survival for patients with pulmonary fibrosis. METHODS: Organ Procurement and Transplantation Network data was retrospectively reviewed to identify 1,256 first-time adult lung transplantation recipients with pulmonary fibrosis since initiation of the LAS (May 2005 to December 2007). Patients were stratified by quartiles of LAS. Multivariable Cox proportional hazards regression predicted the risk of 30-day, 90-day, and 1-year mortality. RESULTS: Lung allocation scores ranged from 31.1 to 94.1. Lung allocation score quartiles (Q) were as follows: Q1, 29.8 to 37.8, n = 315; Q2, 37.9 to 42.5, n = 313; Q3, 42.6 to 51.9, n = 314; and Q4, 52.0 to 94.1, n = 314. Lung allocation score correlated strongly with cumulative survival at 90 days and 1 year after lung transplantation. Patients in the highest LAS quartile (LAS Q4, 52.0 to 94.1) had a 10% lower cumulative survival at 1 year after transplantation when compared with patients in the lowest LAS quartile (p = 0.04). On Cox proportional hazards regression, patients in the highest LAS quartile (those above 52.0) had a significant increase in the risk of mortality at both 90 days and 1 year after transplantation (relative to reference Q1: hazard ratio, 2.09; 95% confidence interval, 1.16 to 3.80; p = 0.01 for 90 days; and hazard ratio, 1.59; 95% confidence interval, 1.04 to 2.44; p = 0.03 for 1 year). CONCLUSIONS: An initial examination of survival for pulmonary fibrosis lung transplantation recipients in the post-LAS era was performed. Lung allocation score predicts short-term mortality in this cohort.

Lung transplantation in the United States, 1998-2007.

This article highlights trends and changes in lung and heart-lung transplantation in the United States from 1998 to 2007. The most significant change over the last decade was implementation of the Lung Allocation Score (LAS) allocation system in May 2005. Subsequently, the number of active wait-listed lung candidates declined 54% from pre-LAS (2004) levels to the end of 2007; there was also a reduction in median waiting time, from 792 days in 2004 to 141 days in 2007. The number of lung transplants performed yearly increased through the decade to a peak of 1 465 in 2007; the greatest single year increase occurred in 2005. Despite candidates with increasingly higher LAS scores being transplanted in the LAS era, recipient death rates have remained relatively stable since 2003 and better than in previous years. Idiopathic pulmonary fibrosis became the most common diagnosis group to receive a lung transplant in 2007 while emphysema was the most common diagnosis in previous years. The number of retransplants and transplants in those aged > or =65 performed yearly have increased significantly since 1998, up 295% and 643%, respectively. A decreasing percentage of lung transplant recipients are children (3.5% in 2007, n = 51). With LAS refinement ongoing, monitoring of future impact is warranted.

Single versus double lung transplantation in pulmonary fibrosis: a debated topic.

Idiopathic pulmonary fibrosis (IPF) represents the second most frequent indication for lung transplantation after chronic obstructive pulmonary disease. Survival rate after transplantation is poorer compared with other lung diseases for reasons that are not completely clear. Medical therapy with anti-inflammatory drugs may improve symptoms and quality of life, but it does not influence the survival rate. Lung transplantation is the best therapy for end-stage IPF. The debate regarding the superiority of double lung transplantation (DLT) compared with single lung transplantation (SLT) is still ongoing. Until some years ago, SLT was almost uniformly utilized for this indication. In the most recent years, a larger application of DLT has been observed worldwide, probably related to higher 1-year and 5-year survivals. The unanswered question is whether it is ethical to use two lungs for the same patient, considering the donor shortage, when a single lung would suffice. Many reports have demonstrated that SLT offers acceptable pulmonary function and satisfactory early and intermediate survival. Probably DLT should be reserved for younger recipients, for those with concomitant or possible chronic infection of the contralateral lung, or cases of marginal donors. Further studies will be needed to formulate recommendations regarding the preferred surgical approach in IPF.

Effects of lung allocation score on waiting list rankings and transplant procedures.

The effect of the new lung allocation score on ranking of patients on the waiting list and the number of transplants performed is not known. We assessed this effect on our lung transplant program and conducted a simulation of lung transplants for the first few months of the new system, using the old waiting lists. Patients with idiopathic pulmonary fibrosis had improved rankings and patients with emphysema had worse rankings, but the number of transplants for each disease category did not change significantly compared with the simulated transplants.

Outcomes of patients with interstitial lung disease referred for lung transplant assessment.

BACKGROUND: Patients with interstitial lung disease (ILD) very frequently die before the opportunity to receive lung transplantation (LTx). This retrospective study describes the clinical course of 86 patients with ILD referred for LTx assessment between January 1999 and December 2002. AIMS: (i) To describe the outcomes, (ii) to identify reasons of delay to transplantation, (iii) to describe the causes of death/complications and (iv) to assess the pathological diagnosis and concordance with explanted lung pathology. METHODS: Data were collected from the case notes of all patients with ILD referred to the Alfred Hospital over a 4-year period. RESULTS: Twenty women and 66 men, mean age of 55 +/- 8 years, were referred for LTx assessment. Forty-five patients were deemed not suitable for LTx and 41 were listed. Twenty-two patients underwent transplantation, 16 died on the waiting list and 7 are still on the waiting list. Complications were frequent (e.g. pulmonary embolism, malignancy and infection) and carried high mortality. Patients dying on the waiting list appeared generally to be in accelerated decline, dying shortly after listing, with no evidence in their lung function test assessment predicting them as a poor prognosis group. CONCLUSIONS: Serious complications and death on the waiting list of patients with idiopathic pulmonary fibrosis are high, not apparently because of delayed referral but usually in patients undergoing very rapid decline.

Quality of life during one-year observation of patients with idiopathic pulmonary fibrosis awaiting lung transplantation.

The aim of the study was to evaluate the quality of life and its changes in patients with idiopathic pulmonary fibrosis (IPF), waiting for lung transplantation. Sixteen IPF patients, who qualified for lung transplantation, and 14 chronic obstructive pulmonary disease (COPD) patients on long term oxygen therapy, taken as a reference group, were assessed. The quality of life was estimated twice, using an SF-36-questionnaire, at the time of qualification for lung transplantation and 12 months later. The IPF and reference patients had similarly profound disturbances in lung function and arterial blood gas content. The IPF patients had a statistically greater score in their physical functioning (PF; 45 vs. 18), the role of limitations due to physical problems (RP; 43 vs. 11), social functioning (SF; 58 vs. 30), and the role of emotional limitations in everyday life (RE; 65 vs. 12) than the reference ones. After a year's observation, there were no differences in SF-36 questionnaire results, except for the role of limitations due to physical problems (RP). A correlation was noted between spirometry and blood gas results and SF-36 questionnaire results in IPF patients qualified for lung transplantation. There was a positive correlation between the partial pressure of oxygen (PaO(2)), on one side, and mental and general health, on the other. There also were positive correlations between FEV1 and SF and FEV1 and the level of bodily pain (BP). We conclude that the SF-36 questionnaire is a sensitive tool to assess the quality of life in IPF patients qualified for lung transplantation. The information gained can help assess the severity of the disease, clinical symptoms, and functional impairment in these patients.

[Visual assessment of functional lungs parenchyma on HRCT and (3)He-MRI in patients after single lung transplantation: comparison with quantitative volumetric results]. / Visuelle Abschätzung der funktionellen Lungenanteile in der HRCT und (3)He-MRT bei Patienten nach Einzel-Lungentransplantation: Vergleich mit der absoluten Volumetrie.

PURPOSE: Visual assessment of the ventilation using HRCT and (3)He-MRI in patients after single lung transplantation (SLTX). Analysis of specific ventilation defects found with (3)He-MRI and morphological changes found with HRCT. MATERIALS AND METHODS: We evaluated 8male patients (54 +/- 6 years) suffering from emphysema and six patients (3males and 3 females, 58 +/- 9.5 years) suffering from idiopathic pulmonary fibrosis (IPF) after SLTX. The morphological changes at HRCT were classified and localized. In (3)He-MRI (2D FLASH), 10 to 14 slices (slice thickness 10 mm, gap 5 mm) were acquired in coronal orientation to cover the whole lung. Ventilation defects were localized and characterized. The visually estimated ventilation was recorded on a 5-point scoring system. A double threshold technique was applied to volumetric quantification in (3)He-MRI to serve as internal reference. RESULTS: We found no correlation between morphological changes in HRCT and ventilation defects in (3)He-MRI. The visual assessment of ventilation in (3)He-MRI was sufficient in patients with emphysema, but this was not confirmed in patients with IPF. The visual assessment in HRCT did not correlate with the volumetric evaluation in both conditions. CONCLUSION: The various ventilation defects were not linked to specific morphological changes. For the visually assessed ventilation in patients with emphysema, (3)He-MRI is superior to HRCT.

Indications, patient selection and timing of referral for lung transplantation.

Lung transplantation (LTx) is now generally accepted as a useful modality of care for patients with severe life-threatening respiratory diseases that are refractory to other medical or surgical therapies. With the huge development of LTx over the last 15 yrs, the disparity between the number of potential recipients and the number of donor organs available has become a major constraint, with many patients dying on the waiting lists. Therefore, it is of primary importance to control and optimise the use of this limited organ resource by weighting the risks and benefits of transplantation in individual patients, and to identify those patients who have a better chance of having a favourable outcome with transplantation. This article discusses the selection process of potential candidates and the currently accepted absolute and relative contraindications, and proposes general and disease-specific recommendations for optimising the timing of referral. Early referral for consideration of lung transplantation is highly desirable as it enhances the patient's chance of surviving to transplant and allows the transplant team to actively manage identified comorbidities during the waiting period.

Limitations of radionuclide angiographic assessment of left ventricular systolic function before lung transplantation.

To evaluate the influence of increased right ventricular afterload on radionuclide assessment of the left ventricular ejection fraction (LVEF), we compared the preoperative and postoperative value of isotopic LVEF in 11 patients who underwent lung transplantation and had a preoperative LVEF value below 55% (normal value: 68 +/- 8%). The underlying disease conditions were obstructive lung disease (n = 7) and pulmonary fibrosis (n = 4). The transplantation procedure was unilateral in 10 patients and bilateral in one. The mean value of isotopic LVEF prior to transplantation was 51 +/- 3% (range: 49% to 55%). At 42 +/- 13 mo postoperatively, isotopic LVEF increased significantly, to 65 +/- 10% (p = 0.001), suggesting that intrinsic left ventricular systolic function was in fact normal in these patients. We hypothesize that the low preoperative isotopic LEVF was not related to intrinsic dysfunction of the left ventricle, but rather to right ventricular pressure overload, leading to bulging of the interventricular septum into the left ventricle and to subsequent geometric distortion of the left ventricle. We conclude that isotopic LVEF may underestimate intrinsic left-ventricular systolic function in patients with severe chronic lung disease. Candidates for lung transplantation should not be rejected on the basis of a low isotopic LVEF, provided echocardiographic examination does show apparently normal left ventricular contraction.

Selective assessment of single-lung graft function with 133Xe radiospirometry in acute rejection and infection.

In single-lung transplant recipients, the usefulness of spirometric indexes in detecting acute events involving the lung graft is limited due to the bias caused by the native lung. Selective functional monitoring is needed for the proper evaluation of complications after transplantation, but thus far, to our knowledge, no clinically feasible methods for selective graft-function assessment have been presented. In ten single-lung recipients, of whom six had a parenchymal lung disease and four had pulmonary hypertension, the relative ventilation (Vtx), perfusion (Qtx), and ventilation/perfusion ratio of the transplanted lung (V/Qtx) were determined with multidetector 133Xe radiospirometry. Additionally, the fractions of FEV1, FVC, and diffusing capacity for carbon monoxide (Dco) of the transplant (FEV1tx, FVCtx, Dcotx, respectively) were determined by using corresponding radiospirometric parameters for the calculation of their distribution between the lungs. The analysis included seven episodes of acute rejection and nine episodes of infection. The Qtx decreased during acute rejection but did not change during infection (p=0.001). Compared with the figures during infection, the V/Qtx increased during acute rejection significantly (p<0.05) in patients with underlying fibrosis or emphysema, but not in those with pulmonary hypertension. In detection of acute events, the sensitivity of the selective parameters, ie, FEV1tx (86%) and FVCtx (73%), was higher than that of the sum-function parameters, FEV1 (66%) and FVC (40%). Moreover, the sensitivity of Dcotx (80%) was higher than that of Dco (60%) in detecting acute rejection. The findings indicate that, in single-lung recipients with a parenchymal lung disease, the assessment of Qtx, V/Qtx, and Dcotx with a radioactive tracer can help to distinguish acute rejection from infection. The graft-selective parameters, ie, FEV1tx, FVCtx, and Dcotx, tended to be more sensitive than the corresponding sum-function parameters in detecting acute events, thus providing a more accurate functional profile of the single-lung graft.