Quality of life following lung transplantation

INTRODUCTION — While most lung transplant referral guidelines are based on expected survival benefit, hope of improved quality of life (QOL) is a major driving force for patients who seek lung transplantation.

The effect of lung transplantation on health-related quality of life (HRQOL) will be presented here. Other outcome measures, such as survival and physiologic function, are discussed separately. (See "Lung transplantation: An overview" and "Physiologic changes following lung transplantation".)

DEFINING HRQOL — Health-related quality of life (HRQOL) can be formally defined as "the extent to which one’s usual or expected physical, emotional, and social well-being are affected by a medical condition or its treatment" [1] and focuses upon the patient's perception of the impact of illness before, during, and after treatment. HRQOL is by nature subjective and must be measured from the individual’s viewpoint rather than that of outside observers (ie, caregivers or health care professionals). (See "Evaluation of health-related quality of life (HRQL) in patients with a serious life-threatening illness".)

HRQOL is also multidimensional, encompassing a broad range of domains:

●Physical health (eg, pain, fatigue, sleep)

●Psychological (eg, body image, mood, memory, concentration)

●Level of independence/function (eg, mobility, activities of daily living, work capacity)

●Social (eg, work, personal relationships, sexuality)

●Environment (eg, financial resources, transportation resources)

●Spirituality/religion/personal beliefs

ASSESSMENT OF QUALITY OF LIFE — Patients often cite QOL as a prime motivation for undergoing lung transplantation. Several transplant programs routinely assess QOL in their follow-up of lung transplant recipients. However, QOL is much more difficult to measure and report than survival or lung function.

Some of the challenges surrounding interpretation of the QOL literature include variability in the instruments used to measure health-related QOL (HRQOL), lack of consensus on the most important and useful QOL instruments, the small number of longitudinal studies, and small study size. Most studies have been too small to allow for extensive multivariate analysis; therefore, bias and confounding are important limitations to the literature.

Measuring HRQOL — QOL instruments have been developed to assess important patient outcomes. They can broadly assess HRQOL, as with the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36), or focus more specifically on lung disease, as with the St. George's Respiratory Questionnaire (SGRQ). The Lung Transplant Quality of Life Survey (LT-QOL) was developed and validated as an HRQOL instrument specifically for use in lung transplant recipients [2]. The LT-QOL contains 10 scales that measure symptoms, health perceptions, functioning, and well-being.

Effects of lung transplant on quality of life — Generic and respiratory disease-specific instruments have demonstrated major improvements in HRQOL among lung transplant recipients in both cross-sectional and longitudinal studies [3-11]. Improvements are noted across most HRQOL domains.

For example, a one-year study of 131 adult, first-time lung transplant recipients showed a significant increase from baseline in the physical component score (PCS) of the SF-36, a generic HRQOL index, with the greatest increase occurring in the first three months after transplant [11]. While the mental component score of the SF-36 did not increase significantly from baseline, scores in the domains of social function and role-emotional did improve.

In other studies, lung transplant recipients reported significant improvements in all domains of the SGRQ, a respiratory disease-specific index; component and total scores improved from baseline by more than 50 units after lung transplant (on a scale of 0 to 100; minimal clinically important difference [MCID]: 4 units) [7,9].

The magnitude of the impact of lung transplantation on QOL is huge. Two separate studies found lung transplant-associated improvements in most HRQOL measures that reached several times their MCID [12,13]. Lung transplant has a greater impact on HRQOL compared with other treatments for end-stage lung disease. For example, the improvement in total SGRQ scores after lung volume reduction surgery [14] and pulmonary rehabilitation [15,16] is approximately 11 units and 7 units, respectively, which is substantially less than an observed mean change of 47 units after lung transplantation [13]. Some studies have demonstrated that HRQOL among lung transplant recipients approximates that of the general population [10,11].

Changes in quality of life over time — Both cross-sectional and longitudinal studies suggest that HRQOL benefits are preserved for at least a few years after transplantation [4,6,13,17-21] but tend to decline over time [6,13,17,18,20-22], although one cross-sectional study (90 lung and heart-lung recipients) found that HRQOL was highest among lung transplant recipients six to eight years after transplant [17]. A longitudinal study of 326 patients who provided both pretransplant and posttransplant data found that after the initial large increase in HRQOL by three months posttransplant, the subsequent HRQOL decline was gradual and at a much lower rate than that experienced pretransplant [13]. However, even five-year survivors with some decrement in HRQOL reported better HRQOL than lung transplant candidates on the wait list [6]. A small study of 10-year survivors showed that their scores across most SF-36 domains were significantly lower compared with normative and chronic disease data, except for mental health and bodily pain [22]. The limited available data suggest that post-lung transplant HRQOL remains stable unless chronic lung allograft dysfunction (CLAD) or severe extrapulmonary complications intervene.

DETERMINANTS OF QUALITY OF LIFE AFTER LUNG TRANSPLANTATION

Pretransplant diagnosis and type of transplant operation — At most transplant programs, the type of lung disease dictates, to some extent, the type of transplant operation performed. Bilateral lung transplant is mandatory for suppurative lung disease, and significant cardiac dysfunction requires heart-lung transplantation, but most programs prefer either single or bilateral lung transplantation for diseases where either procedure is acceptable. Many programs preferentially allocate bilateral transplants to recipients who are perceived to have a better prognosis due to explicit (eg, age, functional capacity) or implicit (eg, motivation, comorbidity burden, social determinants of health) factors. This makes it extremely difficult to separate the effects of pretransplant diagnosis and transplant operation type on posttransplant QOL. Consequently, the few studies in this area have usually chosen to look at one of these two factors.

Pretransplant diagnosis does appear to influence both the absolute health-related QOL (HRQOL) posttransplant and the posttransplant gain in HRQOL, but studies are limited. Some studies have reported better HRQOL in recipients with cystic fibrosis (CF) and bronchiectasis [6,11-13,23]. It should also be noted that CF patients have higher HRQOL scores than other diagnostic groups prior to transplantation [19]. Patients with pulmonary fibrosis or chronic obstructive pulmonary disease (COPD) experience similar improvements in HRQOL, and patients with pulmonary hypertension may experience the smallest improvement [12,13]. However, patients with any diagnosis clearly experience significant HRQOL gains after lung transplantation.

Effects of the lung transplant operation type (single, bilateral, or heart-lung) are contradictory. Some cross-sectional studies found that single-lung transplant recipients reported lower HRQOL (as measured by EuroQol-5D [EQ-5D] and standard gamble [SG] utility) than other recipients [4,17]. One study showed that while bilateral lung transplant recipients did report higher Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) physical component scores (PCS) than single-lung transplant recipients throughout the first posttransplant year, the advantage was not statistically significant after accounting for native lung disease [11]. However, another study that included both age and diagnosis in a multivariate model found that bilateral lung transplantation was associated with lower SF-36 scores across several domains [6]. The existing literature is insufficient to consider QOL when selecting the lung transplant operation type.

Chronic lung allograft dysfunction — Chronic lung allograft dysfunction (CLAD), formerly known exclusively as bronchiolitis obliterans syndrome (BOS) before the recognition of a restrictive phenotype, is by far the most important determinant of HRQOL after lung transplantation. (See "Chronic lung allograft dysfunction: Bronchiolitis obliterans syndrome" and "Chronic lung allograft dysfunction: Restrictive allograft syndrome".)

In a landmark study, the development of BOS was associated with significant reductions in the physical mobility and energy domains of the Nottingham Health Profile [18], and a follow-up study of the same cohort showed that HRQOL deteriorated over the 18 months after the development of BOS [24]. Several cross-sectional studies have since corroborated this negative association using a variety of HRQOL measures [17,25-28]. One multivariate analysis showed that BOS was associated with a substantial (0.27 unit) reduction in SG utility scores on average [17]. SG utility scores reflect the value the patient places on their current health state and range from 0 (death) to 1 (perfect health). A longitudinal study of 328 patients followed for an average of four years posttransplant reported mean SG utility scores and visual analog scale scores of 0.88 and 0.77, respectively, among patients without CLAD, and 0.77 and 0.57, respectively, among patients with CLAD [29]. CLAD is most detrimental to HRQOL domains related to physical functioning, energy, and mobility, but mental health is also affected. The negative impact of CLAD increases with severity [25].

Age — Data on the impact of age on HRQOL gains after lung transplantation are conflicting. For example, in one age-stratified analysis, lung transplant recipients aged 65 years and older reported substantially smaller improvements in generic HRQOL scores and smaller but not significantly different improvements in respiratory-specific HRQOL scores than younger lung transplant recipients, after adjusting for diagnosis and other factors [12]. However, another analysis found that recipient age had minimal effect on the HRQOL benefits of lung transplantation [13].

HRQOL data among pediatric lung transplant recipients are very limited. A study of 10 pediatric lung transplant recipients reported that HRQOL significantly improved after transplant, as measured by a generic HRQOL measure validated in children and adolescents [30].

Other determinants of quality of life — Other determinants of HRQOL after lung transplant have also been examined, although with conflicting results and limited data.

●Sex – An association between sex and HRQOL benefit after lung transplantation has been variably reported in studies, with females sometimes having greater improvement in HRQOL than males [5,6,11,17].

●Preoperative severity of illness – Preoperative severity of illness likely does not impact posttransplant HRQOL; the degree of improvement in HRQOL after lung transplant among recipients who were bridged to transplant using extracorporeal life support and those who were not was comparable [31,32].

●Frailty – Patients who were defined as frail prior to transplant had a larger adjusted improvement in the total St. George's Respiratory Questionnaire (SGRQ) score after transplant than nonfrail patients [33]. However, persistent or emergent frailty after lung transplant, as measured by the Short Physical Performance Battery (SPPB), was associated with lower HRQOL in a mixed effects model [34]. Improvements in frailty after transplant was associated with improved HRQOL, independent of changes in lung function, among patients with CF [35].

●Kidney dysfunction – Kidney dysfunction is likely modestly associated with post-lung transplant HRQOL; each 25 mL/minute reduction in creatinine clearance was associated with a 0.1 reduction in SG utility scores in a cross-sectional analysis [17].

●Nutritional factors – Pretransplant body mass index had a negative impact on posttransplant SF-36 physical functioning scale scores in a multivariable analysis [36]. The negative effects of being overweight and obese prior to transplant were comparable. Neither pretransplant diabetes mellitus nor decreased bone density were significantly associated with posttransplant HRQOL [36].

●Primary graft dysfunction – Primary graft dysfunction (PGD), a common complication of ischemia-reperfusion injury within 72 hours of lung transplant, appears to impact HRQOL. In a study of 251 lung transplant recipients, those who developed the most severe form of PGD (grade 3) experienced a lower magnitude of improvement in HRQOL at three and six months after transplant compared with other recipients [37].

INTERVENTIONS TO IMPROVE QUALITY OF LIFE — Very few trials of interventions to improve health-related quality of life (HRQOL) have been reported in lung transplant recipients. Given the major impact of chronic lung allograft dysfunction (CLAD) on HRQOL, it would be essential to include HRQOL as an outcome measure in any trial of therapy to prevent or improve CLAD.

●Pulmonary rehabilitation – Pulmonary rehabilitation and exercise training following lung transplant likely improve HRQOL [38]. In an uncontrolled study of 36 lung transplant recipients who participated in supervised exercise training three times per week for three months, all Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) domains improved; however, physical function and social function scores continued to improve up until the end of the study period, whereas other domains likely more related to the transplant itself tended to improve less significantly after the first posttransplant month [39]. In a small randomized, controlled trial of uncomplicated post-lung transplant patients, three months of supervised exercise training immediately after hospital discharge was associated with significantly higher scores in two physical functioning domains of the SF-36, but not other domains, at one year after discharge [40].

●Hand-held device to promote and record self-care – The use of a handheld device for patients to record health data, review data trends, and report changes to their transplant team was associated with significantly higher SF-36 physical component scores (PCS) in a small randomized, controlled trial of lung transplant recipients within the first two posttransplant months [41].

●Psychosocial intervention – A telephone-based psychosocial intervention was shown to improve HRQOL in lung transplant candidates on the waiting list [42,43].

●Pet ownership – Pet ownership has been associated with higher life satisfaction, optimism, and perceived social support in lung transplant recipients without any untoward medical consequences, despite the traditional advice for transplant recipients to avoid pets due to the potential risks of infection [44].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Lung transplantation".)

SUMMARY AND RECOMMENDATIONS

●Definition – Health-related quality of life (HRQOL) focuses upon the patient's perception of the impact of illness before, during, and after treatment and is by nature subjective. (See 'Defining HRQOL' above.)

●Overall substantial improvement in HRQOL – Despite many challenges, most transplant recipients achieve excellent physiologic function, and this is accompanied by life-altering changes in HRQOL. (See 'Effects of lung transplant on quality of life' above.)

●Effect of pretransplant diagnosis – The pretransplant diagnosis appears to influence both the absolute HRQOL posttransplant and the posttransplant gain in HRQOL; patients with cystic fibrosis (CF) and bronchiectasis tend to have better HRQOL than patients with pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), or pulmonary hypertension. It is difficult to know how much this observation is affected by the transplant procedure (single lung, bilateral lung, or heart-lung). (See 'Pretransplant diagnosis and type of transplant operation' above.)

●Effect of chronic lung allograft dysfunction (CLAD) – CLAD, which includes bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), is the most important determinant of HRQOL after lung transplant. CLAD is most detrimental to HRQOL domains related to physical functioning, energy, and mobility, but mental health is also affected. (See 'Chronic lung allograft dysfunction' above.)

●Impact of age – The impact of age on increases in HRQOL after lung transplant is unclear. It is possible that transplant recipients of age 65 years or older experience less of an improvement in HRQOL compared with younger recipients, but variable results have been reported. (See 'Age' above.)

●Other determinants of HRQOL – Sex, severity of illness prior to transplant, frailty, kidney dysfunction, and nutrition have a variable or modest effect on HRQOL. Severe primary lung graft dysfunction within the first 72 hours of transplant adversely affects HRQOL in the first six months after transplant. (See 'Other determinants of quality of life' above.)

●Interventions to improve HRQOL – Preliminary studies suggest that certain posttransplant interventions may improve QOL, such as pulmonary rehabilitation, use of self-monitoring devices, psychosocial interventions, and pet ownership. (See 'Interventions to improve quality of life' above.)