Clinical Trial Summary
Idiopathic Pulmonary Fibrosis (IPF) is a fibrosing progressive interstitial lung disease with
unknown etiology, with a median survival of 3 years since first diagnosis. The typical
radiologic pattern of the disease is usual interstitial pneumonia (UIP) defined by basal and
peripheral (subpleural) predominance and a typical cystic degeneration of lung parenchyma
(honeycombing), interstitial fibrotic thickening and traction bronchiectasis. Despite the
recent introduction of two antifibrotic treatments (Pirfenidone and Nintendanib) which proved
to be successful in slowing the decline of pulmonary function in patients with IPF, a benefit
of these therapies on average survival remains yet to be demonstrated.
A significant part of patients affected by IPF die due to progressive worsening of
respiratory failure, often accelerated by the insurgence of acute events, like acute
exacerbations. Processes leading to the development and progression of IPF are not yet
completely understood. We might hypothesize a regenerative deficit in the lungs of subjects
affected, due to a dysregulation of repair mechanism in response to repeated damage
(inflammatory, mechanics, infectious, chemical) to the alveolar and vascular epithelium.
Moreover, mechanism of damage caused by aging in tissues, with a dysfunction in resident stem
cell, might contribute to progression. Patients with IPF undergo mechanical alterations of
respiratory system due to progressive restrictive deficit caused by reduction in total lung
capacity. This functional alteration generates an ineffective and superficial ventilation due
to the waste of the majority inspiratory effort spent in ventilating dead anatomical space.
When physical effort occurs, the increased ventilatory necessity and the inability to
compensate due to functional impairment leads to increased inspiratory effort and subsequent
increase in negative intrathoracic pressure. Recent studies have demonstrated how exerting a
pressure (for example when the patient is mechanically ventilated) on lung tissue of subjects
with IPF and UIP pattern can generate damage due to unfavorable mechanism of
mechanotransduction caused by the pathological behavior of fibrotic lung (''squishy ball
lung''). Studies investigating inspiratory effort during spontaneous breathing and
respiratory failure highlighted how negative values of intrathoracic pressure might induce
self induced lung injury.
Respiratory effort can be quantified measuring esophageal pressure through a pressure
transducer inserted with a nasogastric tube in the inferior third part of the esophagus.
Measuring esophageal pressure is a precise and accurate way of quantifying inspiratory
effort, however its use in daily clinical practice is limited by invasiveness of the
maneuver, high cost and need for specific clinical training. Physiological studies show that
nasal pressure measured at the entrance of the nostril might correlate with esophageal
pressure and therefore estimate inspiratory effort of the patient in a noninvasive way.
The goal of our study is to evaluate the role of respiratory effort during spontaneous
breathing as a potential source of mechanical damage (hence favoring disease progression) in
subjects with IPF and UIP pattern. The study aims to identify patient with an unfavorable
mechanical phenotype defined by the simultaneous presence of UIP pattern and elevated
inspiratory effort after physical activity.
