The Italian Registry of Patients With Chronic Obstructive Pulmonary Disease (ICoRe)

The Italian COPD Registry. The DescribinG bUrden of COPD and Occurrence of mortaLity in a Cohort of Italian Patients

Chronic obstructive pulmonary disease (COPD) is a treatable but debilitating medical condition associated with persistent symptoms and chronic airflow obstruction. Despite the availability of multiple therapeutic options, COPD is the third leading cause of death worldwide and has a substantial socioeconomic impact.

The present real life study is aimed at describing the clinical and functional characteristics, treatment patterns, impact of exacerbations and comorbidities and their association with mortality in a large cohort of Italian patients with COPD.

Study Overview

• Status: Enrolling by invitation
• Conditions: Cardiovascular Diseases; Mortality; COPD; COPD Exacerbation Acute; Cardiovascular Events; COPD Prevalance; Comorbid Chronic Lung Disease on Heart Failure
• Intervention / Treatment: Other: Pharmacological treatment; Other: Pharmacological treatment

Detailed Description

The temporal relationship of observation period to time of participant enrollment will be both retrospective and prospective.

A digital dataset will be shared with the participating centers. The following variables, if available, will be collected.

Demographic and clinical variables:

• Age, sex, height, weight, BMI, waist circumference.
• Pneumonia episodes in the last 12 months and number of hospitalizations for pneumonia.
• Number of pulmonary rehabilitation cycles performed
• Vaccination status (Flu, SARS-CoV-2, pneumococcus, human respiratory syncytial virus, herpes zoster)

COPD characteristics:

• Date of COPD diagnosis.
• COPD exacerbations in the year before the index date (mild, moderate, severe exacerbations), hospitalizations and/or access to ICU.
• Type, dosages and duration of antibiotic and systemic corticosteroid treatments during exacerbations.
• Respiratory symptoms evaluated with mMRC and CAT
• Frequency and purulence of sputum, cough frequency
• Inhaled bronchodilator/corticosteroid therapy and type of device used, any treatment changes at index date or during follow up.
• Mucolytic agents (active molecules and dosage)
• Chronic use of azithromycin
• Therapy with roflumilast.
• Biological therapies (type of active molecules, duration, switch).
• Long-term oxygen therapy (FiO2, average flow), presence of tracheostomy and any invasive or non-invasive ventilatory support

Comorbidities:

• Concomitant respiratory diseases, history of exposure to risk factors, smoking history (active, former and non-smoker).
• Cardiovascular comorbidities and complications in the last 12 months before index date and during follow up
• Cardioactive pharmacological therapies
• Charlson score
• Other comorbidities

Biological and functional variables:

• Blood tests (RBC, Hb, hematocrit, MCV, PLT, WBC differential, CRP, glycemia, creatinine, uremia, NT-proBNP, cholesterol).
• Cardiopulmonary exercise test. The variables collected will include: VO2max, WR max, HRmax, VE max, VEmax, VE/VO2 ratio, PET CO2, O2 pulse, anaerobic threshold, A-a gradient. All values will be collected as absolute and as percentage of predicted values.
• Nocturnal oximetry: FiO2, T-90, mean SpO2, ODI.
• Polysomnography: type of support (e.g. CPAP or NIMV), FiO2, apnea-hypopnea index (AHI; obstructive, central, and mixed type), AI, oxygen desaturation index (ODI), T-90, Cheyne-Stokes respiration, snoring and body position during the exam.
• 6 minutes walking test: FiO2, distance walked in meters and predicted value, SpO2 at the beginning and end of the test, desaturation, if SpO2<90, modified Borg dyspnea score at the beginning and end of the test.
• Gas exchange: SpO2, FiO2, Blood Gas Analysis (pH, PaO2, PaCO2, HCO3-, A-a gradient, FiO2, PaO2/FiO2)
• Lung function test pre- and post-bronchodilator: FVC, FEV1, FEV1/FVC, FEF 25-75, VC, IC, FEV1/VC. All values will be collected as absolute values, ratio and percentage of predicted values.
• Body plethysmography pre- and post-bronchodilator: TGV, RV, TLC, RV/TLC, IC/TLC, sRAW. All values will be collected as absolute values, ratio and percentage of predicted values
• Diffusion capacity of the lung for carbon monoxide: DLCO, KCO, VA, TLC/VA
• Fractional exhaled nitric oxide
• Chest imaging: radiography or CT scan, presence of emphysema (panlobular or centrolobular), bronchiectasis or interstitial lung disease.
• Ecocardiography: ejection fraction, pathological signs, PAPs, left ventricular hypertrophy and left atrial, right ventricular or left ventricular enlargement.
• Coronary angiography: if pathological for stenosis and number of involved vessels, PTCA or CABG.

All these items will be also valued during the follow up period, with an emphasis on COPD exacerbations and date and cause of death.

• Study Type: Observational
• Enrollment (Estimated): 10000

Contacts and Locations

Study Locations

• Italy
  • Milan
    • Milan, Milan, Italy, 20157
      • Luigi Sacco University Hospital, Division of Department of Biomedical and Clinical Sciences, University of Milan

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

All patients with functionally confirmed COPD and a track medical record in the 12 months before enrollment

Description

Inclusion Criteria:

• established diagnosis of COPD (defined as age ≥ 40 years old, smoking history ≤ 20 pack years, postbronchodilator forced expiratory volume in one second to slow vital capacity ratio (FEV1/VC) ≤ the lower limit of normal (LLN) criteria.

Exclusion Criteria:

• Presence of current clinically significant asthma
• Diagnosis or clinically significant alternative respiratory diseases (such as interstitial lung disease or bronchiectasis)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

COPD patients; All patients with a functionally confirmed diagnosis of COPD

Other: Pharmacological treatment; Pharmacological and non pharmacological treatments will be assessed and monitored during the retrospective and prospective phase, and will include: bronchodilators, inhaled steroids and their combinations; mucolytics; biologic therapies for COPD; roflumilast; pulmonary rehabilitation; Other: Pharmacological treatment; All pharmacological and non pharmacological treatments for COPD will be assessed and monitored during the retrospective and prospective phase of the study, and will include: inhaled bronchodilators (long term beta-2 agonists and cholinergic antagonists), inhaled corticosteroids and their combinations; mucolytics; biologics for COPD (monoclonal antibodies); roflumilast; chronic oral azythromicin; pulmonary rehabilitation; oxygen therapy; non invasive/invasive ventilation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All cause mortality	Annual all-cause mortality rate	From index date (registry inclusion) until the date of death from any cause, assessed up to 120 months
Burden of moderate and severe COPD acute exacerbations	Incidence and annual rate of moderate and/or severe exacerbations	From index date (registry inclusion) until the date of first event of moderate or severe exacerbation, and any following event of moderate or severe exacerbation, or patient's death, whichever comes first, assessed up to 120 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular mortality	Annual death rate for cardiovascular events	From index date (registry inclusion) until the date of death provoked by a cardiovascular event, assessed up to 120 months
Cardiovascular comorbidities	prevalence of cardiovascular comorbidities and their relationship with lung function, respiratory symptoms, moderate and severe exacerbations, mortality	At index date (registry inclusion) comorbidities will be registered and updated at every new visit until patient's death
Cardiovascular events	Incidence and prevalence of cardiovascular events (overall and severe) and their relationship with COPD acute exacerbations	From index date (registry inclusion) until the date of any cardiovascular event or cardiovascular death, whichever comes first, assessed up to 120 months
Lung function decline	trend in lung function indexes (spirometric, plethysmographic, DLCO) over time	From index date (registry inclusion) until the date of the first lung function test, and any following available lung function assessment, or the date of patient's death, whichever comes first, assessed up to 120 months
Eosinophil count	Describe eosinophil count in absolute and % of leukocyte formula in the study population, its trend over time and its relationship with lung function, lung function decline, COPD exacerbations, cardiovascular events and mortality	From index date (registry inclusion) until the date of first available eosinophil count, and any following point in time with available eosinophil count updates, or patients' death, whichever comes first, assessed up to 120 months
Evaluation of the pharmacological treatment at baseline and treatment switches	Prevalence of type of inhaled therapy over time from index date until end of study	From index date (registry inclusion) until the date of first available inhaled treatment switch, and every point in time the patient changes inhaled treatment, or the patient's death from any cause, whichever comes first, assessed up to 120 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exacerbation etiology	Describe the frequency and type of viral or bacterial isolates during acute exacerbations, and their relationship with lung function, comorbidities and exacerbation severity	From index date (registry inclusion) until the date of the first available acute exacerbation of any severity, and any following event of modand any following exacerbation event date, or patient 's death, whichever comes first, assessed up to 120 months
Corticosteroid treatment during COPD exacerbation	Describe the frequency and dosage of systemic and oral corticosteroids, treatment duration and their relationship with COPD severity, comorbidities, exacerbation severity and exacerbation etiology	From index date (registry inclusion) until the date of first exacerbation of any severity, and any following event of moderate or severe exacerbation, or patient's death, whichever comes first, assessed up to 120 months.
Antibiotic treatments during acute COPD exacerbations	Describe the frequency and type of antibiotic treatments, treatment duration and their relationship with COPD severity, comorbidities, exacerbation severity and exacerbation etiology	From index date (registry inclusion) until the date of first exacerbation of any severity, and any following event of moderate or severe exacerbation, or patient's death, whichever comes first, assessed up to 120 months.
Gas exchange	Describe the prevalence of type I and II respiratory failure, trend over time in PaO2 and PaCo2 and their relationship with acute COPD exacerbations, cardiovascular comorbidities, cardiovascular events and mortality	From index date (registry inclusion) until the date of first outpatient visit with available data on gas exchange, and any following event (visit) with gas exchange information, or patient's death, whichever comes first, assessed up to 120 months.
Pneumonia events	incidence and annual pneumonia rate overall and divided by type of patient treatment	From index date (registry inclusion) until the date of first pneumonia event of any severity, and any following event of pneumonia, or patient's death, whichever comes first, assessed up to 120 months.
Cardiac function	Describe cardiac function in terms of heart ultrasound parameters at index date and its relationship with future events such as COPD exacerbations, cardiovascular events and mortality	From index date (registry inclusion) until the date of first available cardiac ultrasound, and the date of any following cardiac ultrasound assessment, or patient's death, whichever comes first, assessed up to 120 months.

Collaborators and Investigators

• Sponsor: University of Milan
• Collaborators: University of Palermo; Azienda Ospedaliera Universitaria Integrata Verona; University of Rome Tor Vergata; University of Pavia; University of Turin, Italy; University Hospital of Ferrara; University Magna Graecia; University of Genova; Università degli Studi di Sassari; University Hospital Verona, Italy; Societa Italiana di Pneumologia; Italian Association of Hospital Pneumologists

Publications and helpful links

General Publications

• Santus P, Di Marco F, Braido F, Contoli M, Corsico AG, Micheletto C, Pelaia G, Radovanovic D, Rogliani P, Saderi L, Scichilone N, Tanzi S, Vella M, Boarino S, Sotgiu G, Solidoro P. Exacerbation Burden in COPD and Occurrence of Mortality in a Cohort of Italian Patients: Results of the Gulp Study. Int J Chron Obstruct Pulmon Dis. 2024 Mar 1;19:607-618. doi: 10.2147/COPD.S446636. eCollection 2024.
• Radovanovic D, Contoli M, Marco FD, Sotgiu G, Pelaia G, Braido F, Corsico AG, Micheletto C, Rogliani P, Scichilone N, Saderi L, Santus P, Solidoro P. Clinical and Functional Characteristics of COPD Patients Across GOLD Classifications: Results of a Multicenter Observational Study. COPD. 2019 Aug;16(3-4):215-226. doi: 10.1080/15412555.2019.1659760. Epub 2019 Sep 9.

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2024
• Primary Completion (Estimated): December 31, 2035
• Study Completion (Estimated): December 31, 2035

Study Registration Dates

• First Submitted: September 3, 2024
• First Submitted That Met QC Criteria: October 21, 2024
• First Posted (Actual): October 22, 2024

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: lung function; COPD; AECOPD; heart failure; triple therapy; emphysema; chronic bronchitis; COPD prevalence; Bronchodilators; cardiovascular mortality; Mortality in AECOPD; COPD mortality risk factors; COPD hospitalization; COPD therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Chronic Disease; Disease Attributes; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchitis; Pathological Conditions, Signs and Symptoms; Heart Failure; Pulmonary Disease, Chronic Obstructive; Cardiovascular Diseases; Emphysema; Bronchitis, Chronic; Therapeutics; Drug Therapy
• Other Study ID Numbers: 20-27Sept2023

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No