Respiratory, Limb Muscle Properties, and Physical Performance in Adult Lung Transplant Recipients

Overview

The goal of this observational study is to evaluate respiratory and limb muscle properties in adults awaiting lung transplantation and determine how these measures relate to physical performance, symptoms, and recovery after transplantation. Respiratory and limb muscle weakness may contribute to impaired mobility, frailty, and delayed postoperative recovery, but their specific role in lung transplant candidates is not well understood. Participants will undergo muscle ultrasound imaging at weekly basis, respiratory and limb strength testing, physical performance assessments, and symptom questionnaires once before and after transplantation. Researchers will also collect information from medical records regarding intensive care unit stay, hospital length of stay, rehabilitation participation, and postoperative recovery outcomes.

Detailed description

Respiratory and peripheral muscle dysfunction are common in individuals with advanced lung disease awaiting lung transplantation. Muscle weakness, atrophy, and impaired contractile function may contribute to reduced physical performance, frailty, symptom burden, and delayed recovery after transplantation. Although physical function tests provide an overall assessment of performance, they provide limited information regarding specifics of respiratory and limb muscle impairments. Ultrasound imaging is a noninvasive and reliable method to evaluate muscle structure, quality, and contractile function and has been associated with clinical outcomes in several critically ill populations, including prolonged mechanical ventilation, longer intensive care unit (ICU) and hospital stays, and increased morbidity.

The purpose of this study is to characterize respiratory and limb muscle properties before and after lung transplantation and determine how these measures relate to physical performance, patient-reported outcomes, and postoperative recovery. Respiratory muscle function will be assessed using maximal respiratory pressure testing and ultrasound evaluation of the diaphragm and abdominal muscles. Limb muscle function will be assessed using ultrasound imaging and strength testing of the quadriceps muscles. Physical performance, frailty, dyspnea, pain, fatigue, anxiety, and ICU/hospital-related outcomes will also be evaluated.

The central hypothesis of this study is that respiratory and limb muscle weakness, atrophy, and impaired contractile function are associated with poorer physical performance, greater symptom burden, and delayed postoperative recovery after lung transplantation. To test this hypothesis, a prospective observational study of adult lung transplant candidates will be conducted from their hospital admission to their post-operative day 14. Participants will undergo serial ultrasound imaging assessments before transplantation and during the early postoperative period along with symptom questionnaires; while respiratory and limb strength testing, functional assessments, symptom questionnaires will be collected on the first and last day of research visit. Collection of ICU and hospital outcomes will occur from the electronic medical record. The central hypothesis will be evaluated through the following aims:

Aim 1: Evaluate relationships between respiratory strength and ultrasound measurements of contractile dysfunction in candidates awaiting lung transplant.

Aim 2: Characterize the associations between respiratory and limb muscle properties (atrophy, strength), physical performance, and patient-centered outcomes (dyspnea, frailty, pain, fatigue, and anxiety) in pre-lung transplant candidates.

Aim 3: Identify the influence of preoperative respiratory and quadriceps contractile function on the early postoperative mobility progression in lung transplant recipients Aim 4: Determine relationships between postoperative diaphragm dysfunction and functional status at hospital discharge

Interventions

• Diagnostic test Respiratory and Limb Muscle Assessment
  Participants undergo serial assessments of respiratory and limb muscle structure and function before and after lung transplantation. Assessments include ultrasound imaging of the diaphragm, rectus abdominis, and quadriceps muscles; respiratory muscle strength testing; handgrip strength testing; knee extension strength testing; physical performance measures; and patient-reported outcome questionnaires.

Primary outcome measures

• Diaphragm structure [Time frame: Weekly from baseline through postoperative day 14 (±2 days)]
• Respiratory Muscle Strength [Time frame: Baseline and at postoperative day 14 (±2 days)]
• Abdominal muscle structure [Time frame: Baseline through postoperative day 14 (±2 days)]
• Limb muscle strength [Time frame: At the first baseline visit and postoperative day 14 (±2 days)]
• Rectus femoris thickness [Time frame: Baseline through postoperative day 14 (±2 days)]

Secondary outcome measures (5)

• Five-Repetition Sit-to-Stand Test [Time frame: Baseline and hospital discharge]
• Frailty Status [Time frame: Baseline and at postoperative day 14 (±2 days)]
• patient-reported symptoms [Time frame: Baseline and at postoperative day 14 (±2 days)]
• Six-Minute Walk Distance [Time frame: Baseline and at hospital discharge, an average of 3 weeks after surgery.]
• Anxiety [Time frame: Baseline and at hospital discharge, up to an average of 3 weeks after surgery.]

Eligibility criteria

Inclusion criteria

• 18 years or older.
• Hospitalized as potential candidates for single- or bilateral-lung transplant surgery.
• Hemodynamically stable for out-of-bed mobilization

Exclusion criteria

• Baseline cognitive impairment
• History of previous solid organ transplantation or thoracic surgery
• Existing phrenic nerve lesion
• Lower limb amputation or fracture
• External fixators or open wounds of the lower extremities
• Diagnosed neuromuscular disorder.
• Morbid obesity (body mass index >45 kg/m²).
• Any other medical condition that, in the opinion of the investigators, would make participation unsuitable.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United States · 1 center

• UF Health Shands Medical Center — Gainesville

Publications

• Maury G, Langer D, Verleden G, Dupont L, Gosselink R, Decramer M, Troosters T. Skeletal muscle force and functional exercise tolerance before and after lung transplantation: a cohort study. Am J Transplant. 2008 Jun;8(6):1275-81. doi: 10.1111/j.1600-6143.2008.02209.x. Epub 2008 Apr 29. PMID 18444941
• Parry SM, El-Ansary D, Cartwright MS, Sarwal A, Berney S, Koopman R, Annoni R, Puthucheary Z, Gordon IR, Morris PE, Denehy L. Ultrasonography in the intensive care setting can be used to detect changes in the quality and quantity of muscle and is related to muscle strength and function. J Crit Care. 2015 Oct;30(5):1151.e9-14. doi: 10.1016/j.jcrc.2015.05.024. Epub 2015 Jun 3. PMID 26211979
• Huh S, Cho WH, Kim D, Son BS, Yeo HJ. Clinical impact of preoperative diaphragm dysfunction on early outcomes and ventilation function in lung transplant: a single-center retrospective study. J Intensive Care. 2022 May 15;10(1):23. doi: 10.1186/s40560-022-00614-7. PMID 35570300
• LoMauro A, Righi I, Privitera E, Vergari M, Nigro M, Aliverti A, Frykholm P, Tarsia P, Morlacchi L, Nosotti M, Palleschi A. The impaired diaphragmatic function after bilateral lung transplantation: A multifactorial longitudinal study. J Heart Lung Transplant. 2020 Aug;39(8):795-804. doi: 10.1016/j.healun.2020.04.010. Epub 2020 Apr 21. PMID 32362476
• Kelm DJ, Bonnes SL, Jensen MD, Eiken PW, Hathcock MA, Kremers WK, Kennedy CC. Pre-transplant wasting (as measured by muscle index) is a novel prognostic indicator in lung transplantation. Clin Transplant. 2016 Mar;30(3):247-55. doi: 10.1111/ctr.12683. Epub 2016 Feb 11. PMID 26701203
• Rozenberg D, Wickerson L, Singer LG, Mathur S. Sarcopenia in lung transplantation: a systematic review. J Heart Lung Transplant. 2014 Dec;33(12):1203-12. doi: 10.1016/j.healun.2014.06.003. Epub 2014 Jun 9. PMID 25044057

Identifiers

NCT: NCT07747337 · IRB202501059

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗