Clinical trial NCT05826613: Respiratory Registry for Lung Health: a Prospective, Observational Study on Adult Patients With Asthma or COPD
Official title: Respiratory Registry for Lung Health: a Prospective, Observational Study on Adult Patients With Asthma or COPD for the Identification of Genetic Biomarkers Related to the Chronic Obstructive Lung Diseases
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Chronic Obstructive Pulmonary Disease
Asthma
Lead sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Sponsor class: OTHER
First posted: 2023-04-24
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Male or Female aged \> 18 years with clinical Diagnosis of either COPD or Asthma.

Asthma and COPD will be defined according to the latest international guidelines (https://goldcopd.org and https://ginasthma.org/2018-gina-report-global-strategy-for-asthmamanagement-and-prevention/)

Brief summary: The database will contain a wide range of demographic, clinical, radiological, laboratory, functional, microbiological, treatment, and clinical outcomes data on adults with chronic obstructive pulmonary disease (COPD) and asthma enrolled during stable state with annual follow-up (either one or two-year follow up).

Primary Objective: To collect clinical (including quality of life measurements), laboratory (including non-invasive measurement of biomarkers), microbiological, radiological, functional, treatment variables and clinical outcomes, in adult patients with either asthma or COPD during stable state.

Secondary Objectives: To identify genetic and other omics patterns to develop phenotype handprints for adults with either asthma or COPD. To characterize the airways microbiome in stable patients with either asthma or COPD and identify correlation with clinical phenotypes and/or endotypes.

Detailed description: Currently, the World Health Organization estimates that chronic obstructive pulmonary disease (COPD) affects 65 million individuals worldwide and asthma affects 235 million. (World Health Organization. Chronic respiratory diseases. URL: http://www.who.int/respiratory/en/). In 2015, mortality from COPD exceeded 3 million deaths, while mortality from asthma included approximately 400 000 deaths (1). Unquestionably, COPD and asthma pose a significant global burden to which many of our healthcare resources are devoted.

COPD pathology is thought to be primarily due to inflammation. However, Eapen et al.(2) found a reduction in total cellularity in both large (endobronchial biopsies) and small airways (resected lung tissues) with a corresponding reduction in key innate inflammatory cell populations in mild-moderate COPD patients. Colonizing microbes were also found to contribute to pathogenesis, with a possible mechanism through perpetuation of negative immune responses over time (3).

Although cigarette smoking is the most significant risk factor, only a fraction of smokers develops COPD, so genetic associations should also be considered when assessing potential risk factors. The knowledge of the pathogenic mechanisms and genetic bases of respiratory diseases is fundamental for the correct setting of pharmacological and non-pharmacological management. If we consider the main respiratory diseases (COPD, asthma, idiopathic pulmonary fibrosis) but also the so-called rare diseases (e.g. cystic fibrosis), it is evident that both the expression of the disease and the response to treatment are very different among patients. Recent evidences have shown that these responses are related to different genetic models. Decision-making in medical care for decades has often relied on a "one-size-fits-all" approach that applies mean-effect-size results from studies to individual patients. The goal of precision medicine, in contrast, is to allow for more accurate treatment and prevention, decisions based on matching a patient's exposure, lifestyle and biological profile to that of similar patients with measured outcomes. It could be reasonable to hypothesize that mutations in genes which are involved in other respiratory diseases (such as primary ciliary dyskinesia or cystic fibrosis) might be present also in patients with either asthma or COPD. These mutations might alter the function of specific proteins (such as the cystic fibrosis transmembrane conductance regulator protein) and, thus, contribute to the pathophysiology of asthma or COPD. The goal of many "-omics" studies thus far has been to build a knowledgebase of omic variation using single-technology approaches that will help enable precision medicine by providing reference data to identify groups of individuals who share various attributes. In addition to collecting omics data, the application of sophisticated algorithms and use of extensive computational resources to integrate datasets are required to fully characterize diverse patients. The Respiratory Registry project aims to describe the epidemiology of chronic respiratory diseases, including COPD and Asthma, in the cities of Milan, Bergamo and Rome, to define different clinical phenotypes of these diseases, the relative genetic models and the endotypic expression, and then propose new therapeutic approaches, through the implementation of a clinical registry and an enlarged genetic study.

A database of respiratory diseases would have many important functions including but not limited to: 1) Analysis and evaluation of current standard operating procedures in different centres in Milan, Bergamo and Rome in order to compare them with recommendations of the international guidelines and with those used in other countries; 2) Analysis and assessment of differences in the management of adult patients by various professionals in the different centres in order to identify any area of improvement and/or the need to perform further clinical or translation studies; 3) Analysis and evaluation of several factors of disease severity (e.g., recurrence, hospitalization, mortality) that require large amounts of data not obtainable from monocentric studies.

The database will contain a wide range of demographic, clinical, radiological, laboratory, functional, microbiological, treatment, and clinical outcomes data on adults with COPD and asthma enrolled during stable state with annual follow-up (either one or two-year follow up). The database will be developed at the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano and managed by the University Pneumology Unit of this hospital (Promoter of the study). Other University Pneumology Units will be involved, including those from the ASST Santi Paolo e Carlo Hospital in Milan, the ASST Fatebenefratelli-Sacco Hospital in Milan, the IRCCS Policlinico San Donato Hospital in San Donato, Milan, the Papa Giovanni XXIII Hospital in Bergamo and the Respiratory Unit of the Policlinico Gemelli in Rome. Data will be recorded using a case report form (CRF), incorporating all the variables related to the obstructive respiratory diseases identified as relevant for the purpose of this study: COPD and asthma. Study participants will also enter patient follow-up data on an annual basis to provide longitudinal data regarding clinical and therapeutic changes, as well as clinical outcomes. The total study duration will be 3 years, including 2 years for enrollment and at least 1 year of follow-up.

The study will be conducted in accordance with the principles of Good Clinical Practice (GCP). A favourable ethical opinion will be obtained first (as coordinating centre) by the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico in Milan and then by each partner site from the appropriate research ethics committee. Furthermore, any other necessary approval required by partner site will be obtained prior to the commencement of the study at that site. All patients must provide written consent to participate in the registry. It is the responsibility of the investigator at each centre to obtain the appropriate local approvals. This prospective observational study will provide important data for the personalised management of obstructive lung diseases. No risk for the patient is foreseen. Informed consent for participation in the study, sample collection and omic analyses will be mandatory.

Eligibility criteria: Inclusion Criteria:

* Provision of informed consent prior to any study specific procedures.
* Male or Female aged \> 18 years.
* Clinical Diagnosis of either COPD or Asthma

Exclusion Criteria:

* No specific exclusion criteria will be applied to the registry in order to be as adherent as possible to the real-life population

Primary outcomes:
measure: Auscultation of the chest
timeFrame: 1 year
measure: Presence of dyspnoea (mMRC scale)
timeFrame: 1 year
measure: Forced vital capacity (FVC)
timeFrame: 1 year
measure: Forced Expiratory Volume in the 1st second (FEV1)
timeFrame: 1 year
measure: Peak expiratory flow (PEF)
timeFrame: 1 year
measure: Vital capacity (VC)
timeFrame: 1 year
measure: Total Lung Capacity (TLC)
timeFrame: 1 year
measure: Residual Volume (RV)
timeFrame: 1 year
measure: specific airway resistance (SRaw)
timeFrame: 1 year
measure: specific airway conductance (SGaw)
timeFrame: 1 year
measure: Diffusing Capacity Of The Lungs For Carbon Monoxide (DLCO)
timeFrame: 1 year
measure: fraction of exhaled NO (FENO)
timeFrame: 1 year
measure: Blood pulse
timeFrame: 1 year
measure: Blood pressure
timeFrame: 1 year
measure: body temperature
timeFrame: 1 year
measure: respiratory rate
timeFrame: 1 year
measure: St. George Respiratory Questionnaire
timeFrame: 1 year
measure: Asthma control test (ACT)
timeFrame: 1 year
measure: COPD assessment test (CAT)
timeFrame: 1 year
Secondary outcomes:
measure: Collection of biological samples
timeFrame: 1 year
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
state: MI
city: Bergamo
country: Italy
facility: Ospedale Papa Giovanni XXIII
city: Milano
country: Italy
facility: Ospedale Luigi Sacco, Milano
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
Study officials:
affiliation: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
name: Francesco Blasi, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: GBD 2015 Chronic Respiratory Disease Collaborators. Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Respir Med. 2017 Sep;5(9):691-706. doi: 10.1016/S2213-2600(17)30293-X. Epub 2017 Aug 16.
citation: Eapen MS, McAlinden K, Tan D, Weston S, Ward C, Muller HK, Walters EH, Sohal SS. Profiling cellular and inflammatory changes in the airway wall of mild to moderate COPD. Respirology. 2017 Aug;22(6):1125-1132. doi: 10.1111/resp.13021. Epub 2017 Mar 22.
citation: Leung JM, Tiew PY, Mac Aogain M, Budden KF, Yong VF, Thomas SS, Pethe K, Hansbro PM, Chotirmall SH. The role of acute and chronic respiratory colonization and infections in the pathogenesis of COPD. Respirology. 2017 May;22(4):634-650. doi: 10.1111/resp.13032. Epub 2017 Mar 25.