Clinical Research Directory

Inspiratory Effort Assessed Through Nasal Pressure Measurement in Patients With Idiopathic Pulmonary Fibrosis

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.

HOXB7 and Linked Tissue and Blood Biomarkers in the Lungs of Patients With Pulmonary Fibrosis

This pilot, multicenter, interventional study investigates the expression of HOXB7 and its associated molecular pathway in lung tissue and blood-derived exosomes from patients with pulmonary fibrosis (PF), including idiopathic pulmonary fibrosis (IPF). Using RNA sequencing (RNA-Seq) and proteomic analysis via mass spectrometry (MS), the study aims to identify tissue and circulating biomarkers associated with fibrosis progression. The study compares different biopsy techniques (surgical vs. transbronchial cryobiopsy) and also includes a control group of patients undergoing lung resection for non-fibrotic conditions.

Rehabilitation Counselling for Patients with Interstitial Lung Disease

Idiopathic pulmonary fibrosis (IPF) is a rare chronic progressive disease of unknown etiology that affects physical and emotional well-being. It is characterized by irreversible loss of lung function due to fibrosis, which manifests itself with cough, dyspnea, and impaired quality of life. Lung transplantation is limited to a minority of patients and patients receive anti-fibrotic therapy in addition to supportive/palliative treatments. In light of the broad definition of pulmonary rehabilitation, and by virtue of the multidisciplinary nature of the process, the present study aims to observe the effects of the rehabilitation counseling offered to patients who attend the IPF clinic at the Pneumology Operating Unit of the IRCCS Company Bologna University Hospital, as part of the Intercompany PDTA (diagnostic therapeutic care path) for Pulmonary Fibrosis: the Intercompany PDTA for patients suffering from idiopathic pulmonary fibrosis involves a multidisciplinary approach which, also through therapeutic education/counselling, aims among others to "Offer the patient the opportunity to participate in clinical studies to increase knowledge about the disease and/or have access to innovative treatments". Primary objectives 1. Evaluate the effectiveness of the rehabilitation intervention contained in the PDTAI (Intercompany diagnostic therapeutic care path ) 2. Evaluate the improvement in functional capacity and cardiorespiratory endurance. Secondary objectives 3. Evaluate the progress and evolution of the pathology. 4. Evaluate the emotional burden of the caregiver in caring for the individual suffering from IPF 5. Evaluate the improvement in quality of life. 6. Evaluate the change in disability. 7. Evaluate the patient\'s fatigue and its evolution over the course of the disease. Fatigue is associated with dyspnea, impacts daily living activities and quality of life. 8. Evaluate the progress and evolution of dyspnea at rest and in relation to the performance of common daily activities. The study plans to enroll 40 patients newly diagnosed with IPF Inclusion criteria: * adulthood ≥18 years * Obtaining the patient\'s informed consent Exclusion criteria: * diagnosis of cancer in the active phase * Situations of clinical instability, of clinical worsening such as to deem the individual unsuitable for treatment because they are no longer able to go to follow up visits The included patients will receive the therapeutic education brochure from the physiotherapist and will be trained to perform the exercises during hospital visits. The physiotherapist will be able to evaluate and modify the retraining program based on the user\'s response according to the principles based on the individualized rehabilitation project. The direct comparison with the user allows to obtain a functional improvement adapted to the needs and performance of the person but at the same time, according to the principles of empowerment, helps the subject to become aware of their functional limits and address them with a more personalized. The sessions will be planned following the criteria of frequency, intensity, time and type of exercise: Frequency: one meeting/every fifteen days in the first month and one meeting every fifteen days (+/- five days) in the second and third months. Intensity: sixty minutes (with mBorg three dyspnea and minimum peripheral saturation 88%) Time: sixty minutes Type of treatment: exercises from the therapeutic education brochure. Endpoints measures: 1. % of patients participating in the physiotherapy session programme. It is expected that at least 80% of the total enrolled participants will participate in the proposed session cycle. 2. Six Minute Walking Test. This test is validated for multiple pathologies, including idiopathic pulmonary fibrosis. 3. % Survival of IPF patients. 4. Caregiver Strain Index. 5. EuroQoL scale. 6. Barthel Index Dyspnea. 7. Fatigue Assessment Scale. 8. Modified British Medical Research Council.

The Effect of Exercise Training on Quality of Life and Disease Progression in Fibrosing Interstitial Lung Patients

In this study, the progression of the disease and changes in quality of life will be examined over a 1-year follow-up period in groups of patients with Fibrosing Interstitial Lung Disease who either participated in or did not participate in a pulmonary rehabilitation program. After the initial evaluation, the patients will be randomized into two groups: one serving as the control group and the other as the pulmonary rehabilitation exercise group.