Evaluation of Bone Mineral Density in Lung Transplant Recipients by Chest Computed Tomography.

INTRODUCTION: Lung transplantation (LT) recipients are at risk of bone mineral density (BMD) loss. Pre- and post-LT BMD loss has been reported in some cross-sectional studies; however, there are limited studies regarding the serial BMD change in LT recipients. The aim of this study was to investigate the serial BMD changes and the clinical characteristics associated with BMD decline. METHODS: This was a single-center, retrospective observational study. BMD was serially measured in thoracic vertebral bodies (Th4, 7, 10) using computed tomography (CT) before and 3 and 12 months after LT. The frequency of osteoporosis and factors associated with pre-LT osteoporosis and post-LT BMD loss were evaluated. The frequency of post-LT compression fracture and its associated factors were also analyzed. RESULTS: This study included 128 adult LT recipients. LT recipients had decreased BMD (151.8 ± 42.2 mg/mL) before LT compared with age-, sex-, and smoking index-matched controls (176.2 ± 35.7 mg/mL). The diagnosis of COPD was associated with pre-LT osteoporosis. LT recipients experience further BMD decline after transplantation, and the percentage of recipients classified as exhibiting osteoporosis increased from 20% at baseline to 43% at 12 months. Recipients who had been taking no or small doses of glucocorticoids before LT had rapid BMD loss after LT. Early bisphosphonate use (within 3 months) after LT attenuated BMD loss and decreased new-onset compression fracture. CONCLUSION: LT recipients are at high risk for BMD loss and compression fracture after LT. Early bisphosphonate use may decrease BMD loss and compression fracture.

Perioperative changes in radiographic density in erector spinae muscle and mortality after lung transplantation.

RATIONALE: The radiographic density of the erector spinae muscle (ESM) is often decreased early after lung transplantation (LTx). The prognostic impact of this change has not been elucidated. OBJECTIVE: To investigate whether the decrease in the radiographic density of ESMs early after LTx is associated with a poor prognosis. METHODS: This study is a single center retrospective cohort study. Routine follow-up chest computed tomography scan data just before and 12 weeks after LTx were retrospectively retrieved for adult patients who underwent primary LTx at Kyoto University Hospital. The radiographic density of ESM was quantitatively evaluated as the mean attenuation of the ESM (ESMct), and the impact of the decreased ESMct during the 12 weeks after LTx on overall survival (OS) was examined by Cox proportional hazard regression. RESULTS: A total of 151 recipients (94 cadaveric LTx, 57 living-donor lobar LTx) were included in this study. The median duration of postoperative observation was 4.4 years, during which time 39 recipients (26%) died. Decreased postoperative ESMct was significantly associated with poor OS (HR, 1.64; 95% CI, 1.14-2.35, P = 0.008 per 1 Z score decrease) in the multivariate model adjusted for age, sex, episodes of acute rejection, and preoperative ESMct. Similar results were obtained when the subjects were limited to those with cadaveric LTx. CONCLUSION: A decreased perioperative ESMct was strongly associated with a poor prognosis after LTx in addition to low preoperative ESMct. Maintaining postoperative muscle radiographic density, which reflects muscle quality, may be important for a better prognosis after LTx.

Physical activity measurements in individuals with interstitial lung disease: a systematic review and meta-analysis.

BACKGROUND: Physical activity (PA) measurements are becoming common in interstitial lung disease (ILD); however, standardisation has not been achieved. We aimed to systematically review PA measurement methods, present PA levels and provide practical recommendations on PA measurement in ILD. METHODS: We searched four databases up to November 2022 for studies assessing PA in ILD. We collected information about the studies and participants, the methods used to measure PA, and the PA metrics. Studies were scored using 12 items regarding PA measurements to evaluate the reporting quality of activity monitor use. RESULTS: In 40 of the included studies, PA was measured using various devices or questionnaires with numerous metrics. Of the 33 studies that utilised activity monitors, a median of five out of 12 items were not reported, with the definition of nonwear time being the most frequently omitted. The meta-analyses showed that the pooled means (95% CI) of steps, time spent in moderate to vigorous PA, total energy expenditure and sedentary time were 5215 (4640-5791) steps·day-1, 82 (58-106) min·day-1, 2130 (1847-2412) kcal·day-1 and 605 (323-887) min·day-1, respectively, with considerable heterogeneity. CONCLUSION: The use of activity monitors and questionnaires in ILD lacks consistency. Improvement is required in the reporting quality of PA measurement methods using activity monitors.

Efficacy of personalized exercise program on physical function in elderly patients with rheumatoid arthritis at high risk for sarcopenia: study protocol for a randomized controlled trial.

BACKGROUND: Patients with rheumatoid arthritis (RA) are prone to muscle atrophy due to inflammatory cytokines and corticosteroid use and immobility due to joint pain and deformity. Although resistance training is effective and safe in reversing muscle atrophy in RA, some patients are unable to perform a conventional high-load exercise program due to disease-related limitations. This study aims to examine the efficacy of individualized exercise therapy on physical function in elderly patients with RA who are at a high risk for sarcopenia. METHODS: This study is a single-center, parallel-group, two-arm, healthcare provider- and outcome assessor-blinded, superiority randomized controlled trial with a 1:1 allocation ratio. A total of 160 participants with RA between 60 and 85 years of age with a positive screening test for sarcopenia will be included. The intervention group will receive nutritional guidance and a four-month individualized exercise program in addition to the usual treatment. The control group will receive nutritional guidance in addition to the usual care. The primary endpoint will be physical function assessed using the Short Physical Performance Battery (SPPB) at 4 months. The data on outcome measures will be collected at baseline and at the two- and four-month follow-ups. Linear mixed-effects models for repeated measures will be conducted using the modified intention-to-treat analysis population. DISCUSSION: This study will provide evidence on whether a personalized exercise program can improve physical function and quality of life in elderly patients with RA. Some limitations include limited generalizability due to the single-center study and lack of blinding of the patients to the intervention assignment because of the nature of the exercise. Physical therapists may use this knowledge in their daily practice to improve RA treatment. Tailored exercise may enhance the health outcomes of the RA population and contribute to a reduction in healthcare costs. TRIAL REGISTRATION: The study protocol was retrospectively registered at the University hospital Medical Information Network-Clinical Trial Repository (UMIN-CTR) (registration number: UMIN000044930, https://www.umin.ac.jp/ctr/index-j.htm ) on January 4, 2022.

Management of sarcopenia in patients with rheumatoid arthritis.

This review summarizes the evidence for the management of sarcopenia in patients with rheumatoid arthritis (RA) in terms of drugs, exercise, and nutrition. Sarcopenia is a decrease in skeletal muscle mass and muscle strength or physical function. The prevalence of sarcopenia in patients with RA is higher than that in the general population. The treatment and management of sarcopenia in patients with RA are clinically important for long-term prognosis. One of the mechanisms of muscle metabolism is the pro-inflammatory cytokine pathway, which involves tumour necrosis factor α and interleukin-6, and is a common pathway in the pathogenesis of RA. Thus, tumour necrosis factor α and interleukin-6 inhibitors may play a potential role in controlling sarcopenia. In exercise therapy, a combination of moderate resistance and aerobic exercise may be effective in improving muscle strength, muscle mass, and physical function; however, intense exercise may exacerbate the inflammatory response in RA. Regarding nutrition, protein intake is generally considered beneficial, but other nutrients such as vitamin D and carotenoids have also been studied. Overall, there remains a lack of concrete evidence on sarcopenia treatment and management in patients with RA from any perspective; more longitudinal and intervention studies are needed in the future.

Factors associated with early postoperative exercise tolerance after living-donor liver transplantation.

BACKGROUND: Physical dysfunction, including exercise intolerance, is a major factor for delayed societal reintegration for patients who underwent living-donor liver transplantation (LDLT). However, what may contribute to early postoperative physical function is not well known. The purpose of this study is to elucidate the perioperative factors affecting early posttransplant exercise intolerance. METHODS: 103 consecutive patients who underwent LDLT were enrolled, and 68 patients were retrospectively analyzed. We examined the relationship between postoperative exercise tolerance evaluated by a 6-minute walking distance (6MWD) at discharge after surgery and demographic data, surgical information, preoperative physical function, clinical course, and the postoperative decline in physical function with univariate and multivariate analyses. RESULTS: Almost all patients were discharged within 3 months after surgery. The postoperative 6MWD was 408 ± 94 m (68 [61-84]% of the predicted value), and patients who had a low %6MWD at discharge had significantly lower preoperative physical function than patients who had a high %6MWD at discharge (grip strength: 29.8 ± 8.9 kgf vs. 23.0 ± 8.8 kgf, P < .01, knee extensor strength: 138.9 ± 59.4 Nm vs. 95.2 ± 42.1 Nm, P < .01). Multivariate analysis revealed that preoperative knee extensor strength (standardized ß = 0.35, P < .01) and first postoperative walking day (standardized ß = -0.22, P = .04) were independently associated with the postoperative %6MWD. CONCLUSION: These results suggest that maintaining preoperative muscle strength and allowing for early postoperative mobilization might help to enhance the recovery of physical function and facilitate the patient's social reintegration after LDLT.

Comparison of international and Japanese predictive equations for maximal respiratory mouth pressures.

Respiratory muscle weakness has attracted attention because sarcopenia and respiratory muscle dysfunction may play a key role in the development of respiratory failure. To evaluate respiratory muscle strength appropriately, individual factors such as sex, age, body size, and ethnicity should be considered. This study aimed to compare equations available in Japan and other countries for predicting respiratory muscle strength. We tested 21 equations for maximal inspiratory pressure (MIP) and 17 for maximal expiratory pressure (MEP) for each sex (76 equations in total) in 159 normal, healthy subjects. We observed wide variations in the overall agreement among the MIP and MEP equations. Some equations showed a proper normal distribution, with median values of almost 100%, and the Japanese equations released in 1997 generally showed the best distributions of both %MIP and %MEP. We can conclude that it is better to use Japanese equations when evaluating respiratory muscle strength in Japanese subjects.

Impact of inspiratory muscle strength on exercise capacity after lung transplantation.

BACKGROUND AND PURPOSE: Though inspiratory muscle strength is essential for patients with respiratory disease, it is unclear whether the recovery of inspiratory muscle strength contributes to an exemplary achievement of exercise tolerance after lung transplantation (LTx). We aimed to elucidate the inspiratory muscle strength affects the recovery of exercise capacity after LTx. METHODS: Recipients who underwent LTx between June 2017 and September 2018 were enrolled, and 6-min walking distance (6MWD), quadriceps force, inspiratory muscle strength (maximal inspiratory pressure [MIP]), and spirometry were evaluated at 3, 6, and 12 months after LTx. The relationships between inspiratory muscle strength and changes in physical performance were analyzed. RESULTS: Nineteen recipients (mean age: 44.8 years, male: 32%) who completed all follow-ups were analyzed. At 3 months after LTx, mean MIP (88.4% predicted) and vital capacity (60.9% predicted), quadriceps force (QF; 2.1 N*m/kg), and 6MWD (504 m) were lower than normal values. After LTx, 6MWD significantly improved up to 12 months. From 3 to 6 months after LTx, changes in MIP were significantly associated with increases in 6MWD by univariate (r = 0.55, p = 0.02) and multivariate (ß = 0.59, p = 0.01) regression analyses, whereas changes of QF in place of MIP were significantly associated with the recoveries of 6MWD from 6 to 12 months. DISCUSSION: Improvements in MIP may impact the recovery of exercise capacity in the early phase after LTx. Factors that determine the improvement in exercise capacity following LTx may vary with postoperative time.

Changes in the health-related quality of life and social reintegration status after lung transplantation following hematopoietic stem cell transplantation.

PURPOSE: Late-onset non-infectious pulmonary complications (LONIPCs) after allogeneic hematopoietic stem cell transplantation are fatal; however, lung transplantation might achieve good survival. Nevertheless, improving the health-related quality of life (HRQoL) is still a major concern. This study aimed to investigate, in detail, the recovery in HRQoL and social reintegration status after lung transplantation in patients with LONIPC after allo-HSCT. METHODS: This prospective cohort study involving 18 patients examined changes in the health and social reintegration status after lung transplantation following LONIPC. RESULTS: Physical function and HRQoL were lowest before lung transplantation. Two years after lung transplantation, the dyspnea scores and performance status improved. Most patients had made a successful return to society, and patients who achieved social reintegration were significantly younger and had a good performance status. However, their Physical Functioning score and Physical Component Summary did not show significant improvement after lung transplantation. Moreover, recipients who were unemployed before lung transplantation were likely to remain unemployed and continued to show poor HRQoL. CONCLUSIONS: These results showed poor recovery of HRQoL, especially in terms of physical function, and the likelihood of failure to reintegrate into society within 2 years after lung transplantation. It is necessary to consider long-term follow-up and physical training to improve social reintegration and HRQoL.

Erector spinae muscle radiographic density is associated with survival after lung transplantation.

OBJECTIVE: The study objective was to verify whether low preoperative radiographic density of erector spinae muscles is associated with poor prognosis after lung transplantation. METHODS: Preoperative chest computed tomography scans for patients who underwent deceased-donor lung transplantation between 2013 and 2019 at Kyoto University Hospital were retrospectively retrieved. The radiographic density of erector spinae muscles was quantitatively evaluated as the mean attenuation of erector spinae muscles, and low mean radiographic density of the erector spinae muscles was defined as a mean radiographic density of the erector spinae muscles value below the median value for all patients. Overall survival and chronic lung allograft dysfunction-free survival with high and low mean radiographic density of the erector spinae muscles were estimated using the Kaplan-Meier method and evaluated by the log-rank test, as well as by univariate and multivariate Cox proportional hazard analyses. RESULTS: Of the 107 adult patients who underwent primary transplantation, 96 underwent at least 1 chest computed tomography scan within 24 hours before lung transplantation. The median mean radiographic density of the erector spinae muscles in these 96 patients was 49.2 Hounsfield units. A low mean radiographic density of the erector spinae muscles value was significantly associated with decreased overall survival (hazard ratio, 4.50; P = .030) and chronic lung allograft dysfunction-free survival (hazard ratio, 3.18; P = .028) in the multivariate analysis. Additionally, patients with preoperative steroid use and a low mean radiographic density of the erector spinae muscles value had a worse overall survival (P < .001) and chronic lung allograft dysfunction-free survival (P < .001) than patients with preoperative steroid use and a high mean radiographic density of the erector spinae muscles value and those without preoperative steroid use. CONCLUSIONS: Low mean radiographic density of the erector spinae muscles was closely associated with a poor prognosis after lung transplantation. The prognosis was particularly poor in patients with preoperative steroid use and a low mean radiographic density of the erector spinae muscles. These results may be useful when considering the indications for lung transplantation or preoperative interventions. VIDEO ABSTRACT.

Physical function after lung transplantation for late-onset noninfectious pulmonary complications after allogeneic hematopoietic stem cell transplantation.

PURPOSE: Late-onset noninfectious pulmonary complications (LONIPCs) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are fatal, and lung transplantation is the only curative treatment. Although lung transplantation for LONIPCs may confer good survival rates, it is unclear whether or how impaired physical functioning is restored. Thus, this study aimed to investigate the long-term course and associated changes in physical functions after lung transplantation in patients with LONIPCs after allo-HSCT. METHODS: This prospective cohort study enrolled 15 patients who received lung transplantation for LONIPCs after allo-HSCT between 2012 and 2018. Dyspnea scores, performance status, physical function, and exercise tolerance were assessed before lung transplantation and up to 2 years after transplantation. RESULTS: Two years after lung transplantation, the dyspnea scores and performance status improved, but did not recover completely. Physical function was assessed using the knee extensor strength (KES) and 6-min walk test (6MWT); the results were poor until 3 months after transplantation but improved over 2 years. The 6MWT distance showed improvement to a nearly healthy level (562.7 m). Recovery of exercise tolerance was associated with recovery in % vital capacity (%VC; r=0.5) and KES (r=0.4) from 3 months to 2 years after lung transplantation. Furthermore, a flat thorax, which is a characteristic of patients with LONIPCs, affected the %VC at 2 years after transplantation (r=0.8). CONCLUSION: Lung transplantation for LONIPCs may restore impaired physical function. A multifaceted rehabilitation program should be considered, especially to improve muscle weakness and pulmonary function.

Quantity and quality of antigravity muscles in patients undergoing living-donor lobar lung transplantation: 1-year longitudinal analysis using chest computed tomography images.

BACKGROUND: Skeletal muscle dysfunction is a common feature in patients with severe lung diseases. Although lung transplantation aims to save these patients, the surgical procedure and disuse may cause additional deterioration and prolonged functional disability. We investigated the postoperative course of antigravity muscle condition in terms of quantity and quality using chest computed tomography. METHODS: 35 consecutive patients were investigated for 12 months after living-donor lobar lung transplantation (LDLLT). The erector spinae muscles (ESMs), which are antigravity muscles, were evaluated, and the cross-sectional area (ESMCSA) and mean attenuation (ESMCT) were analysed to determine the quantity and quality of ESMs. Functional capacity was evaluated by the 6-min walk distance (6MWD). Age-matched living donors with lower lobectomy were evaluated as controls. RESULTS: Recipient and donor ESMCSA values temporarily decreased at 3 months and recovered by 12 months post-operatively. The ESMCSA of recipients, but not that of donors, surpassed baseline values by 12 months post-operatively. Increased ESMCSA (ratio to baseline ≥1) may occur at 12 months in patients with a high baseline ESMCT. Although the recipient ESMCT may continuously decrease for 12 months, the ESMCT is a major determinant, in addition to lung function, of the postoperative 6MWD at both 3 and 12 months. CONCLUSION: The quantity of ESMs may increase within 12 months after LDLLT in recipients with better muscle quality at baseline. The quality of ESMs is also important for physical performance; therefore, further approaches to prevent deterioration in muscle quality are required.

Nutrition-related factors associated with waiting list mortality in patients with interstitial lung disease: A retrospective cohort study.

Japanese patients with interstitial lung disease (ILD) sometimes die waiting for lung transplantation (LTx) because it takes about 2 years to receive it in Japan. We evaluated nutrition-related factors associated with waiting list mortality. Seventy-six ILD patients were hospitalized in Kyoto University Hospital at registration for LTx from 2013 to 2015. Among them, 40 patients were included and analyzed. Patient background was as follows: female, 30%; age, 50.3 ± 6.9 years; body mass index, 21.1 ± 4.0 kg/m2 ; 6-minute walk distance (6MWD), 356 ± 172 m; serum albumin, 3.8 ± 0.4 g/dL; serum transthyretin (TTR), 25.3 ± 7.5 mg/dL; and C-reactive protein, 0.5 ± 0.5 mg/dL. Median observational period was 497 (range 97-1015) days, and median survival time was 550 (95% CI 414-686) days. Survival rate was 47.5%, and mortality rate was 38.7/100 person-years. Cox analyses showed that TTR (HR 0.791, 95% CI 0.633-0.988) and 6MWD (HR 0.795, 95% CI 0.674-0.938) were independently correlated with mortality and were influenced by body fat mass and leg skeletal muscle mass, respectively. It is suggested that nutritional markers and exercise capacity are important prognostic markers in waitlisted patients, but further study is needed to determine whether nutritional intervention or exercise can change outcomes.

Clinical significance of radiological pleuroparenchymal fibroelastosis pattern in interstitial lung disease patients registered for lung transplantation: a retrospective cohort study.

BACKGROUND: Radiological pleuroparenchymal fibroelastosis (PPFE) lesion is characterized by pleural thickening with associated signs of subpleural fibrosis on high-resolution computed tomography (HRCT). This study evaluated the clinical significance of radiological PPFE as an isolated finding or associated with other interstitial lung diseases (ILDs) in patients having fibrotic ILDs and registered for cadaveric lung transplantation (LT). METHODS: This retrospective study included 118 fibrotic ILD patients registered for LT. Radiological PPFE on HRCT was assessed. The impact of radiological PPFE on clinical features and transplantation-censored survival were evaluated. RESULTS: Radiological PPFE was observed in 30/118 cases (25%): definite PPFE (PPFE concentrated in the upper lobes, with involvement of lower lobes being less marked) in 12 (10%) and consistent PPFE (PPFE not concentrated in the upper lobes, or PPFE with features of coexistent disease present elsewhere) in 18 (15%). Of these, 12 had late-onset non-infectious pulmonary complications after hematopoietic stem-cell transplantation and/or chemotherapy (LONIPCs), 9 idiopathic PPFE, and 9 other fibrotic ILDs (idiopathic pulmonary fibrosis, IPF; other idiopathic interstitial pneumonias, other IIPs; connective tissue disease-associated ILD, CTD-ILD, and hypersensitivity pneumonia, HP). Radiological PPFE was associated with previous history of pneumothorax, lower body mass index, lower percentage of predicted forced vital capacity (%FVC), higher percentage of predicted diffusion capacity of carbon monoxide, less desaturation on six-minute walk test, and hypercapnia. The median survival time of all study cases was 449 days. Thirty-seven (28%) received LTs: cadaveric in 31 and living-donor lobar in six. Of 93 patients who did not receive LT, 66 (71%) died. Radiological PPFE was marginally associated with better survival after adjustment for age, sex, %FVC, and six-minute walk distance < 250 m (hazard ratio 0.51 [0.25-1.05], p = 0.07). After adjustment for covariates, idiopathic PPFE and LONIPC with radiological PPFE was associated with better survival than fibrotic ILDs without radiological PPFE (hazard ratio 0.38 [0.16-0.90], p = 0.03), and marginally better survival than other fibrotic ILDs with radiological PPFE (hazard ratio, 0.20 [0.04-1.11], p = 0.07). CONCLUSIONS: idiopathic PPFE and LONIPC with radiological PPFE has better survival on the wait list for LT than fibrotic ILDs without radiological PPFE, after adjustment for age, sex, %FVC, and six-minute walk distance.

Pulmonary Function and Exercise Capacity in Patients With Flat Chests After Lung Transplantation.

BACKGROUND: Severe chest wall deformation is generally a contraindication for lung transplantation; however, it is not known whether patients with flat chests have reduced postoperative exercise capacity and pulmonary function. This study's purpose was to investigate the relationship between preoperative thoracic shape and postoperative exercise capacity and pulmonary function in patients undergoing lung transplantation. METHODS: Twenty recipients who underwent successful bilateral living-donor lobar lung transplantation were evaluated. To analyze postoperative graft function in relation to preoperative thoracic shape, 40 donor grafts implanted into 20 recipients were divided into two groups: flat chest group and normal chest group. Flat chest is diagnosed when the thoracic anteroposterior diameter to transverse diameter ratio is 1:3 or less. RESULTS: The ratio of the postoperative forced vital capacity to the preoperatively estimated forced vital capacity was significantly lower in the flat chest group than in the normal chest group 1 year after lung transplantation (p = 0.002). However, there were no significant differences in postoperative 6-minute walk distances between the two groups. Furthermore, the thoracic anteroposterior diameter to transverse diameter ratio in the flat chest group significantly increased after lung transplantation (p = 0.02). CONCLUSIONS: Although postoperative pulmonary function was significantly poorer for patients with flat chests than for patients with normal chests, their postoperative exercise capacity was equivalent. We also found that flat chest severity significantly improved after lung transplantation. Our study, the first investigating postoperative functional status in patients with flat chests, clearly shows that it is possible to perform lung transplantation in such patients with acceptable outcomes.