Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT03827538 |
| Other study ID # |
UModenaReggio 2 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
October 1, 2019 |
| Est. completion date |
December 31, 2024 |
Study information
| Verified date |
May 2023 |
| Source |
University of Modena and Reggio Emilia |
| Contact |
Marchioni Alessandro |
| Phone |
00390594225859 |
| Email |
marchioni.alessandro[@]unimore.it |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
This prospective study aims at evaluating diaphragmatic function before and after
endobronchial valves positioning in a COPD patients with lung hyperinflation.
Description:
Data obtained from clinical and bimolecular studies have showed that chronic obstructive
pulmonary disease (COPD) patients might present higher rates of diaphragm function impairment
when compared to age and sex matched healthy controls. The potential mechanisms of injury
have been found in regional stresses and strains due to disadvantageous muscle geometry,
increased workload during exertion, mechanical stress and metabolic factors (i.e., increased
protease activity, free radicals, oxidation). In particular emphysema, with the breakdown of
elastic alveolar tissue, leads to increased lung compliance and gas trapping. Lung
hyperinflation with amplified dynamic elastance and intrinsic positive end expiratory
pressure (PEEPi) limit the diaphragmatic excursion capacity. Moreover both end expiratory
lung volume (EELV) and residual volume (RV) increase, shifting tidal breathing (Vt) towards
the right side of the pressure-volume curve and imposing higher intra-thoracic pressures to
maintain an adequate Vt. Furthermore it has been showed that in COPD patients experiencing
frequent exacerbations the maximum pressure produced by diaphragm contraction seems
significantly lower as compared to non-COPD subjects, independently on the nature of the
tests used for assessment (both volitional - Pdi at Total Lung Capacity (TLC) or Pdi sniff-
or non volitional - phrenic nerve stimulation). Thus the reduction of diaphragm maximal
performances might be explained by muscle shortening and mechanical impairment following the
onset of progressive lung hyperinflation. Lung hyperinflation worsens with exercise leading
to breathlessness and is associated with reduced physical activity and reduced survival.
Inhaled bronchodilator medications have only modest impacts on symptoms and do not alter the
natural history of the disease. In selected patients with a heterogeneous pattern of
emphysema, surgical resection can be targeted at the worst affected areas of lung tissue,
which contribute disproportionately to gas trapping and hyperinflation, and so improve
respiratory mechanics. Lung volume reduction surgery in selected patients (LVRS) improves
symptoms and prolongs survival but can be associated with significant morbidity and a risk of
death, with a cost per quality adjusted life year (QALY) of at least $40 000.
A more recent approach has been to use endobronchial valves to occlude the airways supplying
the worst affected part of the lung. This is intended to cause atelectasis in the target
lobe, with a similar impact on the function of the rest of the lung as seen in LVRS. Several
trials have demonstrated that endobronchial valve treatment in patients with emphysema can
lead to improvements in symptoms, lung function and exercise capacity reductions in dynamic
hyperinflation and improvements in oxygen kinetics and chest wall synchrony. While studies on
surgical lung volume reduction have demonstrated improvement in diaphragmatic muscle function
no studies have investigated the effects of endobronchial valves positioning on diaphragm
performance in patients with lung hyperinflation.
Several methods have been used to evaluate diaphragmatic contractile activity. Among these,
the standard reference is represented by the measurement of trans-diaphragmatic (Pdi)
pressure expressed by the difference between pleural (or esophageal [Pes]) and abdominal (or
gastric [Pgas]) pressures through nasogastric probes equipped with pressure sensors. However,
such methods are still far from routine clinical practice, thus highlighting the need for
simple and accurate methods to assess diaphragmatic performance. In last years the ultrasound
(US) evaluation of the diaphragmatic function has been developing in the field of intensive
care as a tool to estimate patient's work of breathing during ventilation. In a recently
published study on 75 patients with AECOPD requiring mechanical ventilation, we showed a
complete correlation between US assessment and Pdi measurements at maximal inspiration in
evaluating diaphragm function. In particular we demonstrated that changes of the diaphragm
thickness (ΔTdi) < 20% during tidal volume has the same accuracy of transdiaphragmatic
pressure in identifying diaphragm impairment. Furthermore we investigated the US evaluation
of the diaphragm in patients with amyotrophic lateral sclerosis (ALS) through the ΔTmax index
(the ratio between diaphragm thickness at the end of Vt and after maximal inspiration up to
total lung capacity). We found that ΔTmax strongly correlates with respiratory functions
tests with high accuracy in identifying subjects with FVC <50% of predicted value. Moreover
in a recently published study, Bernardi and coworkers presented a non invasive technique to
measure PEEPi in COPD patients, through the US assessment of the time latency (msec) between
the onset of diaphragm contraction on US and the onset of inspiratory flow (28).
This prospective study aims at evaluating diaphragmatic function before and after
endobronchial valves positioning in a COPD patients with lung hyperinflation.
Materials and methods Study population and setting This prospective explorative observational
cohort study will be carried out in the Thoracic Endoscopic Unit (TEU) of the University
Hospital of Modena Italy over a 24-month period once approval from the local Ethics Committee
of Modena will be obtained. Written informed consent to participate to the study will be
obtained by all enrolled patients patient.
Patients will be eligible if admitted to the TEU for intervention of endobronchial valves
positioning due to documented lung hyperinflation.
Exclusion criteria will include previously documented diaphragmatic dysfunction, the presence
of neuromuscular diseases or other forms of myopathy.
All patients will be treated according to the best current clinical practice by the TEU
staff, which will be blinded to the purpose of the study.
General measures At enrollment respiratory clinical variables (age, sex, diagnosis and stage,
body mass index, smoke habits, comorbidities, previous treatment with systemic steroids) and
respiratory function test values will be recorded.
Study procedures A respiratory physician with high expertise in chest US will perform a US
assessment of the diaphragm before and after endobronchial valves placement. Motility of the
diaphragm is assessed with a B-mode US device (GE Vivid 7, Yorba Linda, CA, USA) connected to
a 7-12 MHz linear probe. Measurements are performed in supine position with an average
inclination of 45°. The position of the probe is set to obtain the best view of the zone of
apposition of the diaphragm, located between the mid-axillary and the posterior axillary
line. The diaphragm is identified as a three-layer structure consisting of one relatively
non-echogenic muscle layer coated in two echogenic lines determined by peritoneal serosa and
diaphragmatic pleura. Diaphragm thickness is measured bilaterally at end-inspiration and
end-expiration. The US images will be stored in electronic or paper format by an examiner
unaware of the purpose of the study.
In particular the following measurements will be performed:
- ΔTd: change in diaphragm thickness (Tdi) during inspiration starting from FRC to Vt =
[(end-inspiratory Tdi - end-expiratory Tdi) / end-expiratory Tdi] X 100)
- ΔTmax: ratio between Tdi at the end of Vt and Tdi after maximal inspiration up to TLC =
end-inspiratory Vt Tdi / end-inspiratory TLC Tdi.
- PEEPiecho: P0.1Mx(TLAT,US/100). TLAT = time latency (msec) between the onset of
diaphragm contraction on ultrasound and the onset of inspiratory flow; P0.1M = mouth
occlusion pressure at 100ms, an estimate of the effort a patient must make to generate
the inspiratory flow. It is measured using a unidirectional valve, occluded during
expiration so that the P0.1M is measured from functional residual capacity (FRC).
- US measurement of maximal diaphragmatic inspiratory excursion measured in right
subcostal window.
An assessment of maximal expiratory pressure (MEP) and maximal inspiratory pressure (MIP),
and sniff inspiratory nasal pressure (SNIP), will be performed before and after endobronchial
valves placement by a respiratory function technician unaware of the purpose of the study.
Each outcome measurements will be performed 24 hours, 48 hours, 7 days, 30 days, 60 days and
90 days after endobronchial valves placement.
Statistical analysis The statistical package GraphPad Prism 7.0 (GraphPad Software, Inc. La
Jolla, CA, USA) will be used for analysis. Descriptive statistics for continuous variables
will be presented as mean values ± standard deviation (SD) or associated to interquartile
range. The nonparametric Wilcoxon test (Mann-Whitney) and t student test will be used for
comparison of continuous variables.
