Diaphragm atrophy at the time of initiating mechanical ventilation (MV) after solid organ
transplantation and major surgery is associated with prolonged MV and higher hospital
mortality. The incidence of diaphragm dysfunction after LTx is estimated to be up to 30%;
post-transplant diaphragm dysfunction is associated with prolonged MV and hospitalization
after LTx.
The American Thoracic Society/European Respiratory Society (2013) guidelines recommend
further evaluation of inspiratory muscle training (IMT) combined with routine
rehabilitation prior to major surgery. Pre-operative IMT in patients with even normal
maximal inspiratory pressures (MIP) have been shown to decrease post-operative pulmonary
complications and shorten hospitalization after cardio-thoracic surgery. However,
pre-operative IMT is not commonly used for LTx candidates and its benefits are poorly
researched. IMT may prove to be a simple pre-transplant intervention to prevent
post-transplant morbidity and improve post-transplant functional status. The current
focus is to investigate the impact of IMT on early post-lung transplant results while
evaluating its effectiveness through a pilot multicenter randomized controlled trial.
Objectives: 1) To evaluate the feasibility of a multicenter randomized clinical trial of
IMT in LTx candidates in terms of recruitment rate, retention, program adherence, and
outcome ascertainment.
To establish the change in pre-transplant dyspnea perception, diaphragm structure and
function, health related quality of life (HRQoL) and post-transplant intensive care unit
(ICU), hospital and post-transplant 3-month outcomes with IMT relative to usual care
group.
To characterize the effect of pre-transplant IMT on peri-transplant diaphragm
myofibrillar cross-sectional area (CSA), oxidative capacity, inflammatory markers and
post-transplant diaphragm muscle thickness and function (UHN TGH site).
Hypotheses: 1) It will be feasible to recruit LTx candidates into an IMT program RCT with
a consent rate ≥ 30 %, enrolment rate of 2-3 patients per month at UHN and 1 patient per
month at each other participating site, adequate outcome ascertainment (≥ 80%), and
acceptable adherence (≥ 80% compliance with IMT sessions). 2) IMT will increase
respiratory muscle endurance by 20% and improve exertional dyspnea and HRQoL in
comparison to usual care over the pre-transplant period. IMT will be associated with
greater hospital free days at 90 days. 3) pre-transplant IMT increases diaphragm
myofibrillar CSA and post-LTx diaphragm thickness and maximal diaphragm thickening during
inspiration in comparison to usual care. The improved mitochondrial respiration will
occur concurrently with improvements in muscle fiber size, immune infiltration and
oxidative stress.
The IMT and exercise training group (IMT group) will perform two daily IMT sessions of 30
breaths (< 5 minutes/session) during the pre-LTx period. IMT will start at 30% of MIP
with a 5-10% weekly increase in training intensity guided by weekly MIP as tolerated
(median weekly Borg dyspnea score < 7 during IMT until reaching 70% of MIP) and continued
until LTx. In conjunction with their IMT program, IMT group participants will undergo
exercise training at least three times per week as part of their usual care. The control
group (exercise training group) will perform exercise training as part of their usual
care three times per week for the duration of the waitlist period. The exercise regimen
for both groups consists of aerobic, resistance, and flexibility training supervised by a
physiotherapist approximately three times a week. The training includes a combination of
in-person visits and home-based sessions. Both groups will also receive a respiratory
endurance device to evaluate respiratory endurance throughout the trial.
IMT can improve respiratory muscle strength and endurance, potentially helping those who
are candidates for LTx. In addition, studying patients undergoing LTx affords unique
opportunities to investigate the mechanistic effects of IMT on diaphragm structure and
function.
