Inspiratory Effort and Respiratory Mechanics in Spontaneously Breathing Patients With Acute Exacerbation of Idiopathic Pulmonary Fibrosis: a Matched Control Study (IERATIC)

Idiopathic pulmonary fibrosis is a life-threatening lung disease characterized by progressive deterioration of lung function and a median survival time of 3-5 years from diagnosis. The onset of an acute deterioration (AE) of respiratory function, the so called acute exacerbation of IPF (AE-IPF), may lead to severe hypoxemia, further worsening prognosis. During these events, the typical usual interstitial pneumonia pattern (UIP) - the radiologic and histologic hallmark of IPF- is overlapped with diffuse alveolar damage (DAD), sharing similarities with the acute respiratory distress syndrome (ARDS) and often requiring respiratory assistance. Several studies show that the need for mechanical ventilation (MV) is associated with high mortality in IPF patients, probably due to the pathophysiological properties of UIP-like fibrotic lung (i.e. collapse induration areas, elevated lung elastance, high inhomogeneity) that make it more susceptible to ventilatory-induced lung injury (VILI). It has been theorized that the application of PEEP on a UIP-like lung pattern can determine the protrusion of the most distensible areas through a dense anelastic fibrotic tissue circles, causing increased rigidity, worsening compliance, and thus enabling tissue breakdown. In this scenario, non-invasive mechanical ventilation (NIV) may therefore represent an alternative option to assist these patients, although no specific recommendations have been made so far. In patients with ARDS, the efficacy of NIV in reducing the patient's inspiratory effort early after its application has been related to a favorable clinical outcome. Indeed, the mitigation of respiratory drive might have resulted in a lower risk for the self-inflicted lung injury (SILI) during spontaneous breathing, whose onset is very likely to worse outcomes of patients undergoing acute respiratory failure (ARF).

To date no data available on the inspiratory effort and the lung mechanics in patients with AE-IPF either during unassisted of assisted spontaneous breathing. Aim of this study was then to compare respiratory mechanics, at baseline and 2-h following NIV application, in AE-IPF and ARDS patients matched for severity.

Study Overview

• Status: Active, not recruiting
• Conditions: Idiopathic Pulmonary Fibrosis

• Study Type: Observational
• Enrollment (Actual): 20

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patients with IPF developing AE consecutively admitted to the Respiratory Intensive Care Unit and the Intensive Care Unit of the University Hospital of Modena over the period August 1st, 2016 to January 1th, 2022 were prospectively considered eligible for enrollment.

Description

Inclusion Criteria:

previously established diagnosis of IPF; occurring acute exacerbation of IPF as defined by an acute, clinically significant respiratory deterioration characterized by evidence of new widespread alveolar abnormality on chest CT scan (12); age >18 years; presence of ARF with PaO2/FiO2 ratio <200 mmHg despite HFNC (set with at least 60 L/min and FiO2 higher than 0.6); suitability for a NIV trial according to the attending staff; consent to measure esophageal pressure.

Exclusion Criteria:

• acute cardiogenic pulmonary edema,
• concomitant hypercapnic respiratory failure (PaCO2 >45 mmHg) of any etiology,
• neuromuscular disease or chest wall deformities,
• home long-term oxygen therapy,
• intolerance or contraindication to NIV, such as the need for immediate endotracheal intubation

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
IPF patients with UIP pattern requiring NIV
ARDS patients requiring NIV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inspiratory effort in IPF patients	Assessment of esophageal pressure swing in IPF patients during acute exacerbation of disease as compared to ARDS	On respiratory intensive care unit admission

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory mechanics change after NIV application in IPF patients acute exacerbation	Respiratory mechanics change after NIV application in IPF patients acute exacerbation as compared to ARDS	2 hours

Collaborators and Investigators

• Sponsor: Roberto Tonelli

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Actual): April 1, 2022
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: March 28, 2022
• First Submitted That Met QC Criteria: March 28, 2022
• First Posted (Actual): April 6, 2022

Study Record Updates

• Last Update Posted (Actual): April 25, 2025
• Last Update Submitted That Met QC Criteria: April 24, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Esophageal manometry; Non-invasive mechanical ventilation; Inspiratory effort
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Lung Diseases, Interstitial; Respiratory Aspiration; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis
• Other Study ID Numbers: UModenaReggio21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No