How Nocturnal Hypoventilation Predicts Long-term Response to Non-invasive Ventilation in Hypercapnic COPD Patients (HYPONIV)

Role of Nocturnal Hypoventilation in Predicting the Long-Term Ventilatory Response in Hypercapnic COPD Patients Treated With Non-Invasive Ventilation: A Prospective Observational Study With Clinical, Functional, and Radiological Assessment

The study is an observational, single-center, prospective cohort study aiming to evaluate respiratory mechanics data, as well as clinical and functional parameters commonly used in clinical practice in patients with COPD and hypercapnic respiratory failure. The study population consists of patients with COPD and hypercapnia requiring NIV. The primary objective of the study is to evaluate the association between the reduction in partial pressure of carbon dioxide in arterial blood (PaCO₂) levels at 6 and 12 months after initiating non-invasive ventilation (NIV) and the presence of nocturnal hypoventilation detected at baseline in patients with COPD and chronic hypercapnia. Secondary objectives of this study are the evaluation of the following parameters measured at baseline and/or after 6 and 12 months of NIV treatment in patients with COPD and chronic hypercapnia:

• Magnitude of esophageal pressure swing during nocturnal monitoring.
• Diaphragm thickness and diaphragmatic thickening fraction assessed by thoracic ultrasound.
• Presence of overlap syndrome (COPD + OSA).
• Radiological classification of COPD subtypes to assess the association between radiological findings, functional profile, severity of nocturnal hypoventilation, and patterns of chronic hypercapnia.
• Respiratory functional parameters, including FEV₁, FVC, FEV₁/FVC ratio, carbon monoxide diffusion capacity (DLCO), and airway resistance (R5 and R20).
• Frequency of severe exacerbations and subsequent rehospitalizations during follow-up.
• Rate of compliance with respiratory treatment.

Study Overview

• Status: Recruiting
• Conditions: COPD; Hypercapnia; COPD (Chronic Obstructive Pulmonary Disease); Hypercapnic Respiratory Failure, COPD

Detailed Description

To date, the pathophysiological mechanisms underlying the development of persistent hypercapnia in patients with COPD are not completely understood. Likewise, reliable predictive markers capable of identifying both patients at risk of developing this condition and those who may derive the greatest benefit from long-term non-invasive ventilation (NIV) are still lacking. Early identification of a patient phenotype more responsive to this type of intervention could substantially reduce exacerbations, emergency department visits, hospitalizations, and associated healthcare costs, thereby improving the overall efficiency of the local healthcare system. The aim of this study is therefore to identify more accurate and earlier criteria to recognize patients with COPD and hypercapnic respiratory failure who may benefit from long-term non-invasive ventilatory support, through an integrated analysis of respiratory mechanics data and clinical and functional parameters commonly used in routine clinical practice.

The study population consists of patients with COPD and hypercapnic respiratory failure who require NIV and who are evaluated in the outpatient clinic and/or inpatient unit of the Respiratory and Critical Care Unit of the IRCCS AOU of Bologna. For these patients clinical, functional, and respiratory mechanics data will be collected. Data will be collected at the baseline visit-corresponding to the first visit at the OSAS Ventilated outpatient clinic or the first day of hospitalization in the Pneumology and Respiratory Intensive Care Unit-and during follow-up visits, scheduled according to routine clinical practice at 6 and 12 months after initiation of NIV treatment.

The total duration of the study will be 30 months, including 12 months for patient enrollment, 12 months of follow-up, and 6 months for data analysis.

A total of 25 patients will be included.

• Study Type: Observational
• Enrollment (Estimated): 25

Contacts and Locations

• Study Contact: Name: Lara Pisani, PhD; Phone Number: 0512143253; Email: lara.pisani@unibo.it

Study Locations

• Italy
  • Bologna, Italy, 40138
    • Recruiting
    • IRCCS Azienda Ospedaliero-Universitaria di Bologna
    • Contact: Lara Pisani, PhD; Phone Number: 0512143253; Email: lara.pisani@unibo.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of patients with COPD and hypercapnic respiratory failure who require NIV and who are evaluated in the outpatient clinic and/or inpatient unit of the Respiratory and Critical Care Unit of the IRCCS AOU of Bologna.

Description

Inclusion Criteria:

• Age ≥ 18 years
• Patients with COPD and hypercapnia, defined as PaCO₂ > 50 mmHg either chronically or 4 weeks after an acute exacerbation requiring invasive or non-invasive mechanical ventilation
• Provision of informed consent

Exclusion Criteria:

• Progressive neurodegenerative diseases
• Diaphragmatic disorders
• Severe hemodynamic instability (>1 vasoactive agent for at least 24 hours)
• Acute coronary syndrome (unstable angina / myocardial infarction)
• Severe arrhythmias
• Presence of contraindications to NIV
• Cognitive impairment interfering with treatment adherence
• Active and unstable coronary artery disease
• Malignancies undergoing active treatment
• Patients already receiving home non-invasive mechanical ventilation

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The association between the reduction in PaCO₂ levels and the presence of nocturnal hypoventilation	The primary outcome is measured through arterial blood gas analysis (ABG) to determine PaCO₂ levels, and through transcutaneous monitoring of oxygen saturation and carbon dioxide (SpO₂ and TcCO₂) to assess the presence of nocturnal hypoventilation. Nocturnal hypoventilation is defined as an increase in PaCO₂ during sleep (TcCO₂ >10 mmHg above daytime PaCO₂ with TcCO₂ >50 mmHg for at least 10 minutes, or TcCO₂ >55 mmHg for ≥25% of total sleep time).	PaCO₂ (mmHg), measured by ABG - baseline, 3, 6, and 12 months TcCO₂ (mmHg), measured by transcutaneous monitoring - baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Magnitude of esophageal pressure swing during nocturnal monitoring	Placement of a nasogastric respiratory mechanics catheter equipped with an esophageal balloon, and measurement of maximal inspiratory pressure swing (ΔPES).	Baseline
Diaphragm thickness and diaphragmatic thickening fraction	Assessment of diaphragm thickness variation (TDi-exp, measured from pleural to peritoneal line at end-expiration; normal <1.5 mm suggesting diaphragmatic weakness). Unit of measure: mm	Baseline
Diaphragmatic thickening fraction	Thickening fraction will be measured with the following formula: TFdi = (inspiratory thickness - expiratory thickness) / expiratory thickness × 100). This outcome will be measure via thoracic ultrasound using a linear probe positioned sagittally along the axillary line at the 8th-9th intercostal space.	Baseline
Presence of overlap syndrome (COPD + OSA)	Overnight cardiorespiratory monitoring	Baseline
Radiological classification of COPD subtypes	Data collection from High-resolution computed tomography (HRCT) for morphological evaluation and structural phenotyping (presence or absence of: emphysema, airway-wall thickening, bronchiectasis, air trapping).	Baseline
Respiratory functional parameters	FEV₁, FVC, FEV₁/FVC ratio measured by spirometry. Unity of measure: L	Baseline, 6 and 12 months
Respiratory functional parameters	DLCO	Baseline, 6 and 12 months
Respiratory functional parameters	Resistance at 5 Hz (R5) and Resistance at 20 Hz (R20)	Baseline, 6 and 12 months
Respiratory functional parameters	6 Minutes Walking Test (6MWT)	Baseline, 6 and 12 months
Frequency of severe exacerbations	number of hospital admissions, ICU admissions, high-dependency unit admissions, and episodes of acute hypercapnic respiratory failure (AHRF) throughout the study period.	baseline, 6 and 12 months
Compliance with respiratory treatment	number of nights where the respiratory support has been used for at least 4 hours/night divided by the total number of nights during treatment.	baseline, 6 and 12 months

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna

Publications and helpful links

General Publications

• Murray I, Paterson E, Thain G, Currie GP. Outcomes following non-invasive ventilation for hypercapnic exacerbations of chronic obstructive pulmonary disease. Thorax. 2011 Sep;66(9):825-6. doi: 10.1136/thx.2010.152264. Epub 2010 Dec 9. PMID: 21148571.

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: December 12, 2025
• First Submitted That Met QC Criteria: February 10, 2026
• First Posted (Actual): February 17, 2026

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Lung Diseases, Obstructive; Signs and Symptoms, Respiratory; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pulmonary Disease, Chronic Obstructive; Respiratory Insufficiency; Hypercapnia
• Other Study ID Numbers: HYPONIV; 2023.0267 (Other Grant/Funding Number: Fondazione Cassa di Risparmio Bologna)

Drug and device information, study documents

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