Lung transplantation outcomes in underweight recipients: A single center experience

Abstract

Background

Current guidelines recommend a body mass index (BMI) of 16 kg/m² as the minimum threshold for lung transplantation, despite mixed evidence on outcomes in underweight patients. The current study aimed to describe survival outcomes of underweight patients who underwent lung transplantation at a single center.

Methods

This retrospective observational study included adult lung transplant recipients who underwent transplantation for the first time between March 2010 and March 2022 at King Faisal Specialist Hospital and Research Center and excluded patients with obesity. We defined an underweight status as a BMI <17 kg/m².

Results

Forty-eight of the 202 lung transplant recipients were underweight at the time of surgery. The underweight patients had similar lengths of hospital (p = 0.53) and intensive care unit (p = 0.81) stays compared to other patients. Thirty-three percent of underweight patients had died within 5-year follow-up, compared to 34% of patients who were not underweight. There was no significant difference in mortality risk between underweight patients and patients with normal BMIs in our multivariable Cox regression model (adjusted HR 1.57, 95%CI: 0.77–3.20, p = 0.21). Exploratory analyses revealed that a pre-transplant BMI <13 kg/m² was associated with a trend towards increased 5-year mortality (adjusted HR 4.00, 95%CI: 0.87–18.35, p = 0.07).

Conclusions

Our findings suggest that patients with BMIs of 13–17 kg/m² may be candidates for lung transplantation. Large multi-center cohort studies are needed to confirm the lower BMI limit for safely transplanting patients.

1. Introduction

Since 1992, at least 67,000 lung transplants have been reported in the International Society for Heart and Lung Transplantation (ISHLT) registry [1]. The accumulated data have been used to identify factors portending a poor prognosis after transplantation and to refine the inclusion and exclusion criteria for transplantation. The selection of transplant recipients is a major ethical issue in transplant medicine; on an individual level, the benefit of transplantation should outweigh the risks of the primary disease. There is also a societal obligation to maximize the benefits from an already limited organ pool, as an inappropriately transplanted organ deprives other patients of the opportunity to benefit from it.

End-stage lung disease is a risk factor for poor nutritional status, which is associated with waitlist and post-transplant mortality [[2], [3], [4]]. Body mass index (BMI) has historically been associated with lung function, morbidity, and mortality following transplantation [5,6]. Previous studies described a positive association between high BMI and 1-year mortality after transplant, which prompted the ISHLT to recommend excluding candidates with BMIs >35 kg/m² from transplant surgery [7]. Later studies suggested that the relationship between BMI and mortality is J-shaped rather than linear, with underweight patients also being at increased risk of mortality [8,9]. As a result, in its latest consensus from 2021, the ISHLT specified that a BMI <16 kg/m² is high risk for lung transplantation and that a BMI of 16–17 kg/m² still poses considerable risk [10].

The evidence for poor survival outcomes in underweight patients is mixed [9,[11], [12], [13], [14], [15]]. Patients' underlying lung disease may modify the effect of a low BMI on post-transplant mortality. In patients with cystic fibrosis, an underweight status generally does not increase the risk of mortality [13,[16], [17], [18]], and being slightly underweight may be advantageous [19]. In other diseases, being underweight is more strongly associated with mortality in patients with chronic obstructive pulmonary disease (COPD) than in those with interstitial lung disease (ILD) [8,9]. Studies often use a single BMI cut-off to define underweight groups without exploring whether the degree of underweight also affects post-transplant risk. Survival rates appear to differ in patients with cystic fibrosis who have a BMI <17 kg/m² and in those with a BMI of 17–18.5 kg/m², supporting the need to delineate the risk at different strata [15,19,20]. Such sub-analyses, however, have rarely been performed [19].

Based on the current recommendations by the ISHLT, underweight patients are generally excluded from lung transplantation; a recent survey focusing on recipients with cystic fibrosis found that 54–69% of transplant centers in the US had not operated on any patient whose BMI was <17 kg/m² [18]. Multiple considerations challenge these guidelines. The greatest benefit from transplantation is achieved in lower-weight patients, and their exclusion based on BMI may preclude this benefit [21]. Furthermore, the disease-specific associations between BMI and transplant outcomes suggest that other patient-related factors should also be considered during evaluation, and BMI cut-off values should not be used as the sole exclusion criterion. For example, patients with cystic fibrosis who are underweight have better survival outcomes than patients with COPD who have normal weight [18]. Thus, basing exclusion on BMI values alone may not necessarily translate into a low-risk allocation of organs. Finally, the lack of data on outcomes in underweight patients at varying levels of BMI necessitates a discussion on whether some patients with low BMIs can undergo transplantation safely and whether the current thresholds should be revisited.

We aimed to describe the effect of BMI on lung transplant outcomes at our institution with a focus on underweight recipients. As of current, select cases with BMIs below the conventional range undergo lung transplantation at King Faisal Specialist Hospital & Research Center (KFSH&RC).

2. Materials and methods

2.1. Study population

The lung transplant program at KFSH&RC was established in 1998. This retrospective study included data from all adult patients (age 18 years and above) who underwent lung transplantation for the first time at our center between March 2010 and March 2022. We excluded patients who underwent re-transplantation, patients who received more than one organ, and patients with obesity.

2.2. Variables

Baseline patient and donor characteristics, surgery details, and survival statuses at the latest follow-up were extracted from the lung transplant registry at KFSH&RC. The most recent laboratory parameters, pulmonary function indices, and anthropometric measurements were recorded as baseline values before the transplant surgery. Two physicians determined the patients' underlying lung diseases through a review of referral letters, physician documentation, and laboratory and radiological test results. The presence of diabetes at baseline was established if the diagnosis was documented, the patient received anti-diabetic medications, or if laboratory evidence of diabetes was present. Donor characteristics and surgery details, including ischemia times and the use of intra-operative extracorporeal membrane oxygenation (ECMO), are routinely recorded. Clinical status before surgery, operative details, and postoperative hospital course details were obtained from patients' medical records.

2.3. BMI categorization

We classified patients as underweight if their pre-transplant BMI was <17 kg/m². We chose this cutoff, since BMIs in the range of 17–18.5 kg/m² are generally accepted for transplantation among international centers. Normal weight was defined as a BMI between 17 and 24.9 kg/m², overweight as a BMI of 25–29.9 kg/m² and obesity as a BMI of 30 kg/m² or higher.

2.4. Statistical analysis

The Kolmogorov-Smirnov test was used to assess the normality of variables. The appropriate statistical tests were then used to compare baseline characteristics and post-operative outcomes between underweight patients and the remaining cohort (normal and overweight patients). Kaplan–Meier curves were used to estimate survival after transplant surgery, and differences in survival rates between BMI categories were compared using log-rank testing. Patients with follow-up beyond 5 years were censored. We also generated Kaplan–Meier curves for the following disease groups: ILD, cystic fibrosis, and non-cystic fibrosis bronchiectasis. A multivariable Cox regression analysis was performed to determine the hazard ratio (HR) for mortality in underweight patients. Based on our experiences and previously reported prognostic factors in lung transplantation [1], we adjusted for the following confounding variables: recipient age, sex, underlying lung disease (cystic fibrosis versus others), diabetes, total bilirubin, cytomegalovirus (CMV) IgG serology status, the use of pre-transplant ECMO and mechanical ventilation, type of transplant (single-lung versus double-lung transplant), and donor age. Potential confounding variables with a high proportion of missing data (>5%) were not included in our final model.

Exploratory analyses were performed to determine the optimal lower BMI cut-off values for predicting mortality. We used the previously described multivariable Cox regression model (including the same covariates) and sequentially tested BMI cut-off values between 13 and 16 kg/m² against a reference group (patients with BMIs 17–29.9 kg/m²).

A post-hoc power analysis was performed for our multivariable Cox regression model [22]. Given the current sample size of 202 patients and 76.47% of all deaths occurring in the reference group (normal and overweight patients), our model had a 73% statistical power to detect an HR of at least 1.57 among underweight recipients (at a 1-sided alpha level of 0.05).

All statistical analyses were carried out using the Stata software version 17.0 (College Station, Tx, USA) and the R software version 4.1.2 (R Foundation for Statistical Computing).

Ethical approval

The study was approved by the Institutional Review Board at KFSH&RC (study number 2221091) with a waiver of consent as data collection was retrospective.

3. Results

3.1. Baseline characteristics

The baseline characteristics of the 202 patients meeting the study’s inclusion criteria are presented in Table 1, Table 2. Forty-eight patients (24% of our sample) were underweight at baseline, including 13% of patients with ILD, 54% with cystic fibrosis, and 39% with non-cystic fibrosis bronchiectasis. There was no significant difference in the presence of pre-transplant diabetes between underweight and other patients (p = 0.36). Underweight patients were almost twice as likely to have hypoalbuminemia compared to other patients (31% vs. 14%, p = 0.01). They had similar hospital and intensive care unit lengths of stays compared to other patients (p = 0.53 and p = 0.81, respectively) as well as similar numbers of ventilator days and need for tracheostomy (p = 0.82 and p = 0.39, respectively).

Table 1.

Baseline characteristics of 202 patients who underwent lung transplantation for the first time. King Faisal Specialist Hospital and Research Center 2010 to 2022.

Characteristics/*(%missing)/median [min-max]	Underweight (n = 48)	Not underweight (n = 154)	p-valuea
Age at transplant (years)	27 [18–59]	46.5 [20–73]	<0.000
Height (cm)	160.5 [142−176]	164 [138−185]	0.15
Weight (kg)	38.6 [25.3–52]	60 [37–97.6]	<0.000
BMI (kg/m2)	15.1 [11.7–16.9]	22.2 [17–29.8]	<0.000
Six-minute walk distance (meters)*(62.8)	276 [46−506]	230 [38−483]	0.124
Characteristics/*(%missing)/n(%)			p-valueb
Male sex	30 (62.50%)	101 (65.58%)	0.731
BMI values			<0.000
<17 kg/m2	48 (100%)	–
17-24.9 kg/m2	–	103 (66.8%)
25-29.9 kg/m2	–	51 (33.12%)
Underlying lung disease			<0.000
Cystic fibrosis	14 (29.17%)	12 (7.79%)
Non-cystic fibrosis bronchiectasis	17 (35.42%)	27 (16.88%)
Interstitial lung disease/pulmonary fibrosis	15 (31.25%)	98 (63.64%)
Group 1 pulmonary arterial hypertension	0	2 (1.30%)
Chronic obstructive pulmonary disease	1 (2.08%)	4 (2.60%)
Others	1 (2.08%)	12 (7.79%)
Diabetes	11 (22.92%)	47 (30.52%)	0.364
Albumin <35 g/L	15 (31.25%)	22 (14.29%)	0.01
Positive CMV IgG*(1.4)	45 (95.74%)	149 (98.03%)	0.33
Pre-transplant mechanical ventilation	3 (6.25%)	9 (5.84%)	1.00
Pre-transplant ECMO	2 (4.17%)	2 (1.30%)	0.24

^aWilcoxon rank-sum test.

^bFisher’s exact test.

Table 2.

Donor characteristics and operative details of 202 patients who underwent lung transplantation for the first time. King Faisal Specialist Hospital and Research Center 2010 to 2022.

Donor characteristics/*(%missing)/median [min-max]	Underweight (n = 48)	Not underweight (n = 154)	p-valuea
Donor age (years)	40 [9−60]	41 [13–61]	0.626
Donor characteristics/*(%missing)/n(%)			p-valueb
Donor male sex	37 (77.08%)	122 (79.22%)	0.84
Height (cm)*(22.7)	165 [120−180]	165 [120−183]	0.15
Weight (kg)*(21.2)	65.5 [20–90]	70 [35–95]	0.12
BMI (kg/m2)*(22.7)	24.36 [10.8–35.16]	24.91 [14.8–39.6]	0.16
Positive donor CMV IgG*(13.8)	44 (100%)	128 (98.46%)	1.00
Operative details/*(%missing)/n(%)			p-valueb
Double lung transplant	48 (100%)	131 (85.06%)	0.003
Transplant side (for single lung transplants)
Left	–	11 (47.83%)	–
Right	–	12 (52.17%)
Operative details/*(%missing)/median [min-max]			p-valuea
Total cold ischemia time*(7.9)
Single lung transplant	–	270 [180−480]	–
Double lung transplant	652.5 [360–1110]	680 [360–1350]	0.752
Cold ischemia time* (7.8)
Double left	340.5 [210−630]	355 [150−708]	0.771
Double right	320 [150−600]	322 [135−660]	0.869
Cold ischemia time*(8.7)
Single left	–	257.5 [180−355]	–
Single right	–	270 [240−480]	–
Post-operative course/*(%missing)/median [min-max]			p-valuea
Hospital length of stay (days)	38.5 [14−121]	319.5 [135−660]	0.533
ICU length of stay (days)	12.5 [2−59]	33 [0–480]	0.811
Time on mechanical ventilation (days)*(5.4)	5 [0−55]	12 [0−1131]	0.821
Time on ECMOc (days)	5 [3–31]	6.5 [0–142]	0.85
Post-operative course/*(%missing)/n(%)			p-valueb
ECMO after transplant	9 (18.75%)	36 (23.38%)	0.557
Type of ECMOc*(2.2)
VV ECMO	5 (62.50%)	23 (63.89%)	1.00
VA ECMO	3 (37.50%)	13 (36.11%)
Tracheostomy	20 (41.67%)	53 (34.42%)	0.392

^aWilcoxon rank-sum test.

^bFisher’s exact test.

^cAmong those who received ECMO after transplant n = 45.

3.2. Survival analysis

Sixty-eight deaths occurred (33.6% of the total sample) during the study period, including 16 deaths (33.3%) in underweight patients and 52 deaths (33.7%) in other patients. The median follow-up time for our sample was 2.9 years (interquartile range, 0.8–4.5 years). Kaplan–Meier survival estimates were similar between underweight, normal-weight, and overweight patients (Fig. 1), and BMI groups did not significantly vary in mortality risk compared to normal weight in our multivariable Cox regression model (Table 3).

Fig. 1.

Kaplan–Meier 5-year survival estimates according to the body mass index (BMI) category for patients who underwent lung transplantation.

Table 3.

Multivariable Cox proportional hazards regression of factors associated with 5-year mortality in lung transplant recipients.

Variables	Adjusted Hazard ratio	95% CI	p-value
BMI
Normal	reference	–	–
Underweight	1.57	[0.77–3.20]	0.21
Overweight	1.03	[0.56–1.92]	0.92
Age (years)	1.03	[1–1.06]	0.07
Sex
Male	reference	–	–
Female	1.23	[0.73–2.09]	0.44
Underlying lung disease
Cystic fibrosis	reference	–	–
Other disease	0.69	[0.29–1.62]	0.39
Diabetes	1.38	[0.80–2.36]	0.25
Total bilirubin	0.99	[0.96–1.01]	0.32
Recipient CMV IgG
Negative	reference	–	–
Positive	0.45	[0.10–1.98]	0.29
Donor age (years)	1.01	[0.99–1.98]	0.48
Pre-transplant ECMO	3.76	[0.63–22.56]	0.15
Pre-transplant mechanical ventilation	0.35	[0.06–1.99]	0.24
Transplant type
Single lung transplant	reference	–	–
Double lung transplant	0.34	[0.17–0.69]	0.003
CI confidence interval

The supplementary figures (Figures S2–S4) illustrate the survival curves of patients with ILD, cystic fibrosis, and non-cystic fibrosis bronchiectasis. Within each disease group, there was no significant difference in survival between underweight, normal, and overweight patients.

3.3. Exploration of lower BMI cut-off values

Table 4 details the multivariable models that were used to explore the effect of varying the lower BMI limit. Compared to the reference group (BMI 17–29.9 kg/m²), there was a trend towards increased mortality risk when the pre-transplant BMI fell below 13 kg/m² (adjusted HR: 4.00, p = 0.07). Figure S1 illustrates the survival curves of patients with BMIs in the ranges of <13 kg/m², 13–17 kg/m², and 17–29.9 kg/m².

Table 4.

Hazard ratios of mortality within a 5 year follow-up at different underweight cut-off values.

BMI cut-off	n	aHR1	95% CI	p-value	Model likelihood ratio
BMI 17–29.9 kg/m2 (reference)	152	–	–	–	–
BMI <17 kg/m2	47	1.57	[0.77–3.18]	0.21	27.33
BMI <16 kg/m2	35	1.34	[0.60–2.97]	0.47	28.39
BMI 16–16.9 kg/m2	12	2.35	[0.87–6.40]	0.09
BMI <15 kg/m2	22	1.30	[0.53–3.21]	0.57	27.83
BMI 15–16.9 kg/m2	25	1.88	[0.81–4.38]	0.14
BMI <14 kg/m2	13	2.11	[0.76–5.89]	0.15	27.86
BMI 14–16.9 kg/m2	34	1.40	[0.64–3.07]	0.41
BMI <13 kg/m2	4	4.00	[0.87–18.35]	0.07	28.69
BMI 13–16.9 kg/m2	43	1.43	[0.69–2.98]	0.33

aHR; adjusted hazard ratio, CI; confidence interval.

¹Model covariates: age, sex, cystic fibrosis versus other lung disease, diabetes, total bilirubin, recipient CMV IgG, donor age, pre-transplant ECMO, pre-transplant mechanical ventilation, transplant type.

4. Discussion

The risk of mortality in underweight patients who undergo lung transplantation is not consistently described. Moreover, underweight status has not been shown to negate the quality of life gains from transplantation [23,24]. To contribute to the discussion in the literature, we investigated differences in mortality risk among our lung transplant patients according to their BMI categories. In the current study, underweight patients with a BMI of 13–17 kg/m² showed survival rates compared to normal- and overweight patients. Underweight candidates are already at a high risk of waitlist mortality and are more likely to be clinically unstable before transplantation [16]. Consequently, our data may have implications for expediting transplantation in these patients versus deferring surgery to meet nutritional goals. Nutritional interventions prior to transplantation do not necessarily result in weight gain [25] or improved outcomes [26]. In fact, underweight patients often regain lean mass after transplant surgery [25,[27], [28], [29]], even when their caloric intake remains unchanged [30]. This highlights the role of the primary lung disease in inducing malnutrition, which lung transplantation may reverse [31].

Our study population largely consisted of patients with ILD, cystic fibrosis, and non-cystic fibrosis bronchiectasis. We found a higher proportion of underweight patients for each disease group compared to other cohorts: 13% and 54% of the patients with ILD and cystic fibrosis, respectively, who underwent lung transplantation had BMIs <17 kg/m² compared to 0.5% and 16% of patients reported by the United Network for Organ Sharing (UNOS) [18].

Komatsu et al. showed that a BMI <17 kg/m² significantly increased the mortality risk among 93 patients who underwent lung transplantation in Japan, while our study indicated that transplant patients with BMIs within the range of 13–17 kg/m² showed satisfactory survival outcomes [15]. The underweight population in the previous study was limited to patients with underlying bronchiolitis obliterans syndrome, hematopoietic stem cell transplantation-related disease, and bronchiectasis, which emphasizes the potential influence of primary lung diseases on BMI-associated mortality. Three European studies found no association between patients with BMIs <18.5 kg/m² and mortality, but they mainly comprised patients with COPD or emphysema [12,13,32]. Madill et al.’s [11] Canadian transplant population had a different composition of etiologies (cystic fibrosis, emphysema, and interstitial pulmonary fibrosis). The study showed a 3.7-fold increased risk of death at the 90-days when the BMI was <17 kg/m², but this was not statistically significant. Chaikriangkrai et al.’s [14] study in Houston reported that underweight patients had increased mortality over a median follow-up of 2.3 years; most of the patients had restrictive lung disease. Other American studies have shown that underweight status increases mortality risk; however, in the UNOS population, this risk was only observed until 1-year follow-up [9,33].

In our exploratory analyses, we found that patients with a BMI <13 kg/m² had a trend towards increased mortality risk compared to our reference range of 17–29.9 kg/m². Studies that have graphically modeled the relationship between BMI and mortality have shown an increased risk of death with each unit of decrement in BMI below 25 kg/m² [8,17]. Because few patients with very low BMIs undergo transplantation, this observation is usually accompanied by large confidence intervals, precluding definite conclusion [8]. Our data suggest that lowering the threshold for transplantation to 13 kg/m² may be associated with comparable survival outcomes to normal- and overweight patients, however we emphasize that the analyses is limited by our small sample size.

In patients with cystic fibrosis, a slightly underweight status (BMI 17–18.5 kg/m²) may be optimal for undergoing transplantation [19,34], while overweight status is associated with mortality [16,34]. Most studies in the US and Europe have failed to demonstrate an adverse effect of being underweight on survival in patients with cystic fibrosis [13,[16], [17], [18]]. One recent study of pooled data from the US and Canada showed a significant mortality risk in transplantation when BMIs were <18.5 kg/m² [35]. Lederer’s study in the pre-lung allocation score era showed an increased mortality risk but only after the first year of transplant [8]. Another study conducted by Ramos et al. reported shorter survival times among patients with cystic fibrosis who were underweight (mean survival of 7 years compared to 8.2 years in those with a BMI >17 kg/m²), however, this effect was confounded by transplant year and center and became non-significant after accounting for these variables [18].

BMI appears to affect outcomes in other diseases differently. Singer’s analysis of 1-year mortality rates suggests that being underweight has a greater effect on mortality risk in patients with obstructive lung disease than in patients with restrictive lung disease (adjusted HR of 1.8 versus 1.3) [9]. Older UNOS data similarly show that underweight patients with COPD have higher 1-year mortality rates than normal-weight patients, while a low BMI does not predict mortality in patients with diffuse parenchymal lung disease [8]. Patients with ILD who have undergone transplantation tend to have higher thoracic muscle mass, which may explain the weaker association between BMI and mortality in these patients [36]. An alternative explanation is that the effect of mismatching lung sizes (in particular undersized donor lungs) may be less pronounced among patients with ILD [37] although this was not examined in the current study. Size matching by height and weight is an important determinant of post-transplant survival across all disease groups except ILD; patients with ILD who receive undersized lungs have similar survival to recipients of normal sized lungs [38]. The evidence for transplant outcomes in underweight patients with ILD is limited in previous studies as their numbers are usually small [8,14,16,18]. We did not identify any difference in mortality risk by BMI category within different disease groups; however, our study was limited due to the small sample size. The present study is one of few reporting outcomes of underweight patients with non-cystic fibrosis bronchiectasis [15]. The patients showed survival outcomes comparable to those of patients with normal BMIs.

We found that underweight patients spent a similar number of days on mechanical ventilation and had similar tracheostomy rates compared to other patients. De la Torre et al. also reported similar ventilation times across BMI categories, except for patients with obesity who required a longer intubation time [39]. Weig et al. observed that decreases in psoas muscle masses were associated with longer ventilation times and increased tracheostomy rates [40]. Schwebel et al.’s [41] study suggests that ventilator dependence is more strongly linked to low lean mass than to adiposity, although a combination of both is the most adverse. Other studies have found a low weight status to be associated with longer hospital lengths of stay, although we could not demonstrate this in our study [34,41].

Low BMI is thought to signify sarcopenia in patients with chronic lung disease, a sequela of poor oral intake, and a higher basal metabolism arising from systemic inflammation and increased work of breathing [42]. Multiple measures of muscle mass, strength, and function have been used to evaluate the relationship between sarcopenia and transplant outcomes [36,43]. While muscle mass is inconsistently linked to mortality after lung transplantation, muscle strength and function may be predictive [36,44,45]. Lower limb strength, in particular, has been shown to correlate with the overall functional status after transplantation [46]. The pattern of sarcopenia may vary according to disease group; patients with cystic fibrosis may have decreased muscle masses compared to other lung diseases, those with ILD may be more likely to demonstrate reduced strength, and those with COPD may be more likely to have respiratory muscle impairments [36,43].

The rising incidence of older patients undergoing transplantation has generated interest in evaluating frailty among lung transplant candidates and studying its association with transplant outcomes [47,48]. Our sample of transplant recipients contained relatively young patients, with only 11 patients aged 65 years or older, compared to the US, where older patients formed 38% of recipients in 2020 [49]. Nevertheless, frailty is not necessarily an age-dependent phenomenon in patients with chronic lung disease [43]. In the context of nutritional status, muscle mass measures may linearly correlate with frailty; however, conventional sarcopenic ranges and BMI categories have not been shown to predict frailty in the lung transplant population [43,[50], [51], [52]].

BMI is an easy, non-invasive means of assessing nutritional status and is universally available in hospital records. Most studies categorize BMI groups using the WHO classification; however, their use to predict outcomes in the lung transplant population is debatable. Fernandez et al. sequentially tested BMI values among transplant recipients and found that the optimum BMI for survival was approximately between 25 and 26 kg/m², with significant adverse outcomes occurring at cut-offs of 20 and 28 kg/m², respectively [17]. Furthermore, BMI as a measure may not accurately reflect undernourishment or adiposity. While a BMI cut-off of <18.5 kg/m² may identify most patients with a low lean mass, a normal BMI does not exclude malnourishment [25]. Likewise, individuals with significant adiposity do not necessarily have obese BMIs [9]. The serum leptin level may be a more accurate marker of adiposity that correlates with post-transplant mortality but may be redundant when BMIs exceed 25 kg/m² [9]. Female patients have higher body fat compositions than male patients; therefore, using the same BMI cut-offs for both may not accurately reflect their nutritional states [9]. Nevertheless, BMI has been informative in uncovering general epidemiological trends within the lung transplant population and is superior to other proxy markers, such as ideal body weight and albumin levels, for predicting mortality [41,53].

4.1. Limitations

The study’s reference group (patients with BMI 17–29.9 kg/m²) included patients that would be considered underweight according to the WHO classification (<18.5 kg/m²) as well as overweight patients, which may lead to a slightly skewed risk of death among the reference and may limit comparability to other studies that have used 18.5–25 kg/m² as a control. Our sensitivity analyses may have limited power due to the inclusion of a small number of patients within each disease group. Different selection practices among centers and their varying experiences in operating on underweight patients caution the direct generalizability of our findings [18,35].

5. Conclusion

Current guidelines cite a BMI <16 kg/m² as a relative contraindication to lung transplantation [10]. Our study demonstrated that patients with BMIs of 13–17 kg/m² had survival rates comparable to those with BMIs within the range of 17–29.9 kg/m², suggesting that they may be candidates for lung transplantation– a life-saving procedure. Large multi-center cohort studies are needed to confirm the lower BMI limit for safely transplanting patients.

Author contribution statement

RA Conceived and designed the experiments; analyzed and interpreted the data; wrote the paper.

RS Conceived and designed the experiments, analyzed and interpreted the data, and wrote the paper.

ED Analyzed and interpreted the data, and wrote the paper.

HA Analyzed and interpreted the data, and wrote the paper.

WS Contributed reagents, materials, analysis tools or data.

MH Contributed reagents, materials, analysis tools or data.

EA Contributed reagents, materials, analysis tools or data.

GA Conceived and designed the experiments and contributed reagents, materials, analysis tools or data.

MK Analyzed and interpreted the data.

EA Conceived and designed the experiments and analyzed and interpreted the data.

Data availability statement

Data will be made available on request.

Declaration of interest's statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Funding

None.

Abbreviations

BMI

body mass index

CMV

cytomegalovirus

COPD

chronic obstructive pulmonary disease

ECMO

extracorporeal membrane oxygenation

HR

hazard ratio

ILD

interstitial lung disease

ISHLT

International Society for Heart and Lung Transplantation

KFSH&RC

King Faisal Specialist Hospital and Research Center

UNOS

United Network for Organ Sharing

WHO

World Health Organization

Appendix A. Supplementary data

The following is the Supplementary data to this article: