Lung

OPTN/SRTR 2017 Annual Data Report: Lung

Abstract

Each year since 2012, the number of lung transplants has increased, reflecting an increase in the number of donors, improved use of recovered organs, and more candidates being listed for transplant. However, the need for organs continues to outpace available donors. Despite an increase of 126 donors in 2017, 1360 candidates remained on the waiting list at the end of the year, and 326 patients died or became too sick to undergo transplant. Approximately 14,000 individuals were living with a lung transplant in 2017; 9492 were aged 50 years or older, 4075 were aged 18-49 years, and 408 were aged younger than 18 years.

Introduction

In 2017, 2478 lung transplants were performed in the US, the highest number to date (Figure LU 43). Each year since 2012, the number of lung transplants has increased, reflecting an increase in the number of donors (Figure LU 35), improved use of recovered organs (Figure LU 40), and more candidates being listed for transplant (Figure LU 1). However, the need for organs continues to outpace available donors. Despite an increase of 126 donors in 2017, 1360 candidates remained on the waiting list at the end of the year (Figure LU 1), and 326 patients died or became too sick to undergo transplant (Table LU 5).

The Organ Procurement and Transplantation Network (OPTN) continuously monitors and adjusts the US organ allocation system to ensure improved access for candidates at highest risk for mortality while awaiting transplant. Candidates aged 12 years or older access lung transplant based on calculated lung allocation score (LAS), age, geography, blood type (ABO) compatibility, and, if necessary, waiting time. Candidates aged younger than 12 years access transplant based on illness-based priority status, age, geography, blood type (ABO) compatibility, and waiting time. The LAS primarily considers the risk of waitlist mortality, while giving some consideration to posttransplant survival to minimize allocation of lungs to candidates with poor likelihood of posttransplant survival. In calculating the LAS, pulmonary diseases are categorized into four main groups based on similar survival probability and disease pathophysiology. These are group A, obstructive lung disease; group B, pulmonary vascular disease; group C, cystic fibrosis and immunodeficiency disorders; and group D, restrictive lung disease.

Some noted trends may reflect recent changes to the US allocation system. After implementation of the LAS in 2005, the proportion of waitlisted candidates with LAS values in the lowest range predominated; however, this trend has been declining since 2006 (Figure LU 8). A revision of the LAS system that occurred in February 2015, reflecting a more updated cohort and adding new variables to more accurately reflect disease severity for candidates in group B. Due to the change in LAS calculation, scores before and after 2015 may not be directly comparable. Another change in policy occurred in March 2017, when the OPTN implemented policies for broader geographic sharing of organs for child (age 0-11 years) and adolescent (age 12-17 years) candidates. Adolescents also receive preference for adult donor lungs through the LAS system. These efforts may partly explain why waitlist mortality for adolescents has decreased in the past year (Figure LU 23). Finally, an important policy change occurred in November 2017 regarding the role geography plays in allocation of lungs for transplant; donation service area was removed as the first unit of allocation for donor lungs and replaced by a 250-nautical-mile circle from the donor hospital. The OPTN/SRTR is currently studying this policy.

In this report, all lung transplant candidates and recipients aged 12 years or older are included under Adult Lung Transplant, and those aged 0-11 years are included under Lung Transplant in Children. Heart-lung patients are included in all tabulations.

Waiting List

Characteristics of US candidates waiting for a lung transplant

In 2017, 2901 candidates were added to the lung transplant waiting list, continuing a trend toward increased use of lung transplant as a treatment for end-stage lung disease (Figure LU 1). At the same time, more lung transplants are being performed in the US than ever (Figure LU 43), resulting in fewer candidates remaining on the waiting list at each year’s end (Figure LU 2). Characteristics of US lung transplant candidates remain largely unchanged, although candidates are increasingly older and have interstitial lung disease (diagnosis group D).

Candidates aged 65 years or older comprised 30.1% of the waiting list in 2017, compared with only 22.1% 5 years prior (Figure LU 3). Since 2014, the proportion of candidates in each diagnosis group remained relatively stable: 51.6%, group D; 30.9%, group A; 10.8%, group C; and 6.7%, group B (Figure LU 6). Candidates with low LAS have made up a smaller proportion of the waiting list. In 2006, 56.8% of candidates had LAS < 35, and by 2017 that group declined to 37.6% of candidates. Those with LAS ≥ 50 grew from 7.3% of candidates in 2006 to 15.0% in 2017 (Figure LU 8). In 2017, the proportion of candidate with LAS values were: < 30, 0.7%; 30-<35, 36.9%; 35-<40, 28.2%; 40-<50, 19.3%; and 50-100, 15.0% (Figure LU 8).

Outcome of US candidates listed for lung transplant

Lung transplant rates in the US have increased consistently every year; the 2017 rate was 173.2 per 100 waitlist-years, compared with 106.6 per 100 waitlist-years in 2012 (Figure LU 13). This is primarily due to increasing numbers of adult deceased donors (Figure LU 35), but also to increased use of lungs recovered for transplant (Figure LU 40). Candidates spend less time on the waiting list; 30.3% wait less than 1 month and 81.9% less than 1 year (Figure LU 7). The median waiting time for transplant recipients was 2.5 months, varied by diagnosis as follows: group D, 1.9 months; group C, 2.1 months; group A, 4.0 months; and group B, 5.1 months (Figure LU 19). Corresponding transplant rates were: group D, 236.9; group C, 194.1; group A, 118.7; and group B, 99.1 per 100 waitlist-years (Figure LU 13). Transplant rates were highest among candidates aged 12-17 years, followed by candidates aged 65 years or older, with rates of 235.7 and 226.0 per 100 waitlist-years, respectively (Figure LU 11).

Mortality rates in 2016-2017 were slightly lower overall and for most subgroups examined, to an overall rate of 17.2 per 100 waitlist-years (Figure LU 24). Pretransplant mortality rates decreased for adolescents, from 38.9 per 100 waitlist years in 2014-2015 to 19.4 in 2016-2017 (Figure LU 23), and decreased slightly among adults aged 18 years or older (Figure LU 23). Mortality rates varied by diagnosis; waitlist mortality was highest for patients in group D, a trend that has been consistent in lung transplantation irrespective of the allocation system, followed by groups B, A, and C, respectively (Figure LU 26). Mortality by LAS decreased for all candidates with LAS ≥ 35, but most dramatically for candidates with LAS ≥50, an expected outcome of increasing transplant rates in an acuity-based allocation system such as the LAS (Figure LU 27). Despite these substantial gains in transplant rates and decreasing mortality rates, 326 patients died while waiting or became too sick to undergo transplant in 2017 (Table LU 5).

Transplant

Characteristics of US lung transplant recipients

In 2017, 2478 lung transplants were performed, an increase of 133 from the previous year and the most lung transplants performed in a single year in the US (Figure LU 43). Of these, 1860 were bilateral and 618 were single transplants, reflecting the trend toward increased use of bilateral lung transplants (Figure LU 43). Candidates aged 50-64 years undergo the most transplants; however, numbers of transplants have increased each year in candidates aged >65 years (Figure LU 44). Candidates in diagnosis group D underwent 1416 transplants in 2017, as did 669 in group A, 266 in group C, and 127 in group B (Figure LU 47). In 2017, 96.8% of candidates underwent primary lung transplant and 3.2% re-transplant (Table LU 8).

For transplant recipients, the median LAS at transplant was 40.3 in 2017, virtually unchanged from 2016 (Figure LU 50). Median LAS at transplant by diagnosis group was: 44.1, group B; 43.8, group D; 43.5, group C; and 33.5, group A (Figure LU 51). Despite changes in LAS calculation in 2015, LAS distribution at transplant remained largely stable between 2012 and 2017, 30-50 at transplant for almost all candidates. Most candidates were not hospitalized prior to transplant; only 9.5% required hospitalization outside intensive care, and 12.0% required care in the intensive care unit in 2017, trends similar to trends in 2012 (Table LU 7). Proportions of candidates requiring support with mechanical ventilation (vent) were 3.0%, extracorporeal membrane oxygenation (ECMO) 2.2%, and vent + ECMO 3.0% (Table LU 7). Although use of ECMO alone rose from 17 (1.0%) in 2012 to 53 (2.2%) in 2017, it is not a prominent mode of support for transplant candidates (Table LU 7).

In 2017, there were 65 centers in the US that performed transplants in adults. The median number of transplants performed was 26 per program in 2017 (Figure LU 56). The annual lung transplant program volume of 17 transplants represented the 25th percentile and 54 transplants the 75th percentile of transplant volume activity (Figure LU 56). Three programs performed >100 transplants in 2017, accounting for 15.1% of transplants in the US. Nineteen programs performed 41-100 transplants, accounting for 50.6%; 35 programs performed 11-40 transplants, accounting for 32.5%; and 8 programs performing <10 transplants annually accounted for 1.9% (Figure LU 57).

Outcomes of US lung transplant recipients

Approximately 14,000 individuals were living with a lung transplant in 2017; 9492 were aged 50 years or older, 4075 were aged 18-49 years, and 408 were aged younger than 18 years (Figure LU 67). Short-term survival seemed to improve, but the pattern for longer-term survival is unclear. By 2017, 3-year mortality had increased slightly and 5-year mortality had declined some; however, 10-year mortality had clearly increased (Figure LU 66). Among recipients 2010-2012, 1-year survival was 85.8%; 68.8% of transplant recipients surviving to 3 years and 56.1% to 5 years (Figure LU 58). Age remained an important factor in posttransplant survival, which was worse for recipients aged 12-17 and 65 years or older and best for those aged 35-49 years (Figure LU 58). Survival differed by LAS, and was slightly lower for recipients in the highest LAS range of 60-100 at all time points compared with recipients with lower LAS values (Figure LU 60). Survival differed by diagnosis, and was highest for recipients in groups C and A and lowest for recipients in groups B and D (Figure LU 62). Early survival was similar for recipients of single and bilateral lung transplant, but began to diverge by 6 months posttransplant and was higher for recipients of bilateral transplant, a finding that may be confounded by unadjusted comorbid conditions (Figure LU 63).

Most lung transplant recipients (79.3%) received induction therapy; 70.5% received induction with interleukin-2 receptor antagonist (Figure LU 53). Tacrolimus, mycophenolate mofetil (MMF), and steroids were the most common immunosuppression regimens, used in 83.2% of recipients (Figure LU 54). Use of induction did not seem to make a difference in incidence of acute rejection by 1 year (Figure LU 69). In the first year posttransplant, infectious causes accounted for the highest percentage of deaths (Figure LU 72). Infection remains an important cause of death, but is surpassed by graft failure and respiratory causes by year 3 (Figure LU 73).

Lung Transplant in Children

Waiting List

In 2017, 30 new child (ages 0-11 years) candidates were added to the lung transplant waiting list; 5 were inactive at the time of listing (Figure LU 74). The number of prevalent child candidates (i.e., on the waiting list on December 31 of a given year) steadily decreased from a peak of 111 in 2006 to 25 in 2017 (Figure LU 75). The largest age group of child candidates on the waiting list in 2017 was 6-11 years; these candidates made up 59.1% of the waiting list, followed by candidates aged 1-5 years, 22.7%, and younger than 1 year, 18.2% (Figure LU 76). Most child lung transplant candidates were white (56.8%), with increasing proportions of Hispanic (20.5%), black (11.4%), and Asian (6.8%) candidates (Figure LU 77). Of child candidates in 2017, 63.7% were on the waiting list for less than 6 months, 11.4% for 6 months to less than 1 year, 15.9% for 1 to less than 2 years, and 9.1% for 2 or more years (Figure LU 79). In 2017, 100% of candidates were listed for lung-only transplant, compared with 85.7% in 2007 (Table LU 13).

Of 27 candidates removed from the waiting list in 2017, 16 (59.3%) were removed due to undergoing transplant, 8 (29.6%) due to death, 2 (7.4%) due to improved condition, and 1 (3.6%) due to becoming too sick to undergo transplant (Table LU 14, Table LU 15). Regarding 3-year outcomes for child lung transplant candidates listed in 2014, 58.3% underwent deceased donor transplant, 22.2% died waiting, and 19.4% were removed from the list for reasons other than transplant or death (Figure LU 80). The overall child lung transplant rate rose dramatically in 2013, at 68.7 per 100 waitlist-years compared with 27.0 in 2012, and has remained relatively stable since, with a rate of 68.3 per 100 waitlist-years in 2017 (Figure LU 81). Pretransplant mortality decreased for the most recent cohort in 2016-2017 to 10.8 deaths per 100 waitlist-years for all candidates aged 0-11 years (Figure LU 83). Rates were higher for candidates aged younger than 6 years than for those aged 6-11 years, 24.3 versus 6.3 per 100 waitlist-years.

Transplant

In 2017, a total of 13 lung transplants were performed in recipients aged 0-11 years, 3 in recipients aged younger than 1 year, 4 in recipients aged 1-5 years, and 6 in recipients aged 6-11 years (Figure LU 85). Seven out of 70 programs were characterized as pediatric programs in 2017, compared with 56 adult-only programs (Figure LU 86). In 2015-2017, the proportion of child lung transplant recipients aged 6-11 years was larger than in 2005-2007, and more recipients were Hispanic (Table LU 16). In 2015-2017, lung-only transplants increased to 97.8% from 86.4% in 2005-2007 (Table LU 18).

Pediatric Immunosuppression and Outcomes

Induction therapy has changed over time, with an increase in use of T-cell-depleting agents to 55.2% of patients in 2016-2017 and a continued decrease in the use of interleukin-2 receptor antagonists to 31.0% (Figure LU 87). The most common initial immunosuppression agent regimen was tacrolimus, MMF, and steroids, in 86.7% of recipients (Figure LU 88). The incidence of posttransplant lymphoproliferative disorder among Epstein-Barr virus (EBV)-negative recipients who underwent transplant in 2005-2015 was 6.7% at 5 years posttransplant, compared with 1.1% among EBV-positive recipients (Figure LU 90). Incidence of death was 24.3% at 6 months and 33.6% at 1 year for transplants in 2015-2016, 31.3% at 3 years for transplants in 2013-2014, 22.0% at 5 years for transplants in 2011-2012, and 51.7% at 10 years for transplants in 2005-2006 (Figure LU 91). For children who underwent transplant in 2005-2012, overall 1-, 3-, and 5-year patient survival was 83.2%, 66.4%, and 59.7%, respectively (Figure LU 92). By age, patient survival rates were highest for recipients aged 6-11 years at all time points. Among children, the diagnosis of cystic fibrosis was associated with higher survival rates compared with the diagnosis of pulmonary hypertension and other diagnoses (Figure LU 93). Leading causes of death were infection at 1 year posttransplant (3.8%, Figure LU 94) and graft failure at 5 years (9.7%), followed by respiratory (5.8%), infection (3.8%), and cerebro/cardiovascular causes (2.9%) (Figure LU 95).

Among child lung transplant recipients in 2013-2017, the combination of a cytomegalovirus (CMV)-positive donor and CMV-negative recipient occurred in 25.8% of transplants; this combination for EBV occurred in 37.6% of transplants (Table LU 19).

Complication rates in child lung transplant recipients increased with time posttransplant, including bronchiolitis obliterans syndrome (4.8% at 1 year and 34.8% at 5 years) (Table LU 20). For most surviving child lung transplant recipients (91.3%), functional status was reported as fully active at 5 years posttransplant.

Figure List

Waiting list

Deceased donation

Figure LU 35. Deceased lung donor count by age
Figure LU 36. Distribution of deceased lung donors by age
Figure LU 37. Distribution of deceased lung donors by race
Figure LU 38. Percent of pediatric lung donors allocated to adult recipients
Figure LU 39. Rates of lungs recovered for transplant and not transplanted by donor age
Figure LU 40. Rates of lungs recovered for transplant and not transplanted, by donor risk of disease transmission
Figure LU 41. Lung donors with a smoking history of 20 pack-years or more
Figure LU 42. Cause of death among deceased lung donors

Transplant

Figure LU 43. Total lung transplants
Figure LU 44. Total lung transplants by age
Figure LU 45. Total lung transplants by sex
Figure LU 46. Total lung transplants by race
Figure LU 47. Total lung transplants by diagnosis group
Figure LU 48. Total lung transplants by LAS
Figure LU 49. Total lung transplants by CPRA
Figure LU 50. Median LAS at transplant
Figure LU 51. Median LAS at transplant by diagnosis group
Figure LU 52. Bilateral transplants among lung recipients aged 12 years or older by diagnosis
Figure LU 53. Induction agent use in lung transplant recipients aged 12 years or older
Figure LU 54. Immunosuppression regimen use in transplant recipients aged 12 years or older
Figure LU 55. Total HLA A, B, and DR mismatches among deceased donor lung transplant recipients aged 12 years or older, 2013-2017
Figure LU 56. Annual adult lung transplant center volumes, by percentile
Figure LU 57. Distribution of adult lung transplants by annual center volume

Outcomes

Pediatric transplant

Table List