Endobronchial Valves Positioning Effects On Diaphragm Function In Patients With Lung Hyperinflation - EVELHYN

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.