Investigation of the Effects of Oxidized Antigens on the T-Cell Response and the Epigenetic Reprogramming of Neutrophils in Lung Diseases - OXIGENE - (OXIGENE)

The OXIGENE study is a research project that aims to better understand how the immune system behaves in people with lung diseases such as asthma, COPD, pneumonia, tuberculosis, and viral lung infections. By analyzing a single blood sample, the study examines how certain immune cells react during inflammation and infection, and whether lasting changes in these cells influence how strongly the body responds to disease. Although participants do not receive direct medical benefit, the results may help improve future diagnosis and treatment of lung diseases by providing deeper insight into immune responses.

Study Overview

• Status: Not yet recruiting
• Conditions: Asthma; Tuberculosis; COPD; Bacterial Pneumonia; Viral Pneumonia
• Intervention / Treatment: Other: Characterization of the neutrophil granulocyte epigenome; Other: Characterization of the T-cell immune response to to various oxidatively modified mycobacterial antigens

Detailed Description

The OXIGENE study is an observational research project that explores how the human immune system responds in different lung diseases, including asthma, COPD, pneumonia, tuberculosis, and viral lung infections such as COVID-19 or influenza. The study focuses on two key components of the immune system: neutrophils, which are among the first immune cells to respond to inflammation, and T cells, which play an important role in longer-term immune defense. Researchers investigate whether neutrophils show lasting changes in their behavior during lung disease and how these changes may differ depending on the type of illness or individual patient characteristics. In people with tuberculosis, the study also examines whether chemical changes to bacterial proteins caused by inflammation influence how strongly T cells are activated.

Participation in the study involves a single blood draw, similar to a routine blood test, with no medications, interventions, or follow-up visits required. The study does not provide direct medical benefit to participants, but the risks are minimal and limited to those associated with blood sampling. By improving the understanding of how immune responses are altered in lung diseases, the OXIGENE study aims to generate knowledge that could support the development of better diagnostic tools and more targeted treatments for future patients.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Niklas Koehler, Dr. med.; Phone Number: +49 4537 188 8080; Email: studienzentrum@fz-borstel.de
• Study Contact Backup: Name: Tobias Dallenga, Dr. rer. nat.; Phone Number: +49 4537 188 5561; Email: tdallenga@fz-borstel.de

Study Locations

• Germany
  • Schleswig-Holstein
    • Borstel, Schleswig-Holstein, Germany, 23845
      • Medical Service Center MVZ, Research Center Borstel, Leibniz Lung Center
      • Contact: Niklas Koehler, Dr. med.; Phone Number: +49 4537 188 8080; Email: studienzentrum@fz-borstel.de
      • Contact: Barbara Kalsdorf, PD Dr. med.; Phone Number: +49 4537 188 3510; Email: lungenpraxis@fz-borstel.de
    • Kiel, Schleswig-Holstein, Germany, 24105
      • Department of Pulmonology, University Hospital Schleswig-Holstein
      • Contact: Jan Heyckendorf, Prof. Dr. med.; Phone Number: +49 431 500-22223; Email: Jan.Heyckendorf@uksh.de
      • Principal Investigator: Jan Heyckendorf, Prof. Dr. med.

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

The study population includes only adult patients (≥18 years) with lung diseases who are capable of providing informed consent and are medically fit for a single venous blood draw. Minors, healthy volunteers, and adults lacking the capacity to consent are not included, as consent by legal representatives is not provided for, and the study involves no interventions beyond blood sampling. Women of childbearing potential may participate regardless of contraceptive use, as study participation poses no additional risk. Patients with insufficient German language proficiency may also be included; in such cases, study information is provided orally in a language the participant fully understands by a qualified translator, with the translation process documented, and written consent is given using the German-language consent form once full understanding has been ensured, allowing all participants to make an informed and voluntary decision.

Description

Inclusion Criteria:

• Diagnosis of an acute or chronic inflammatory lung disease, infectious or non-infectious, including asthma, COPD, pneumonia, tuberculosis, or viral pulmonary infection (e.g., COVID-19, influenza).
• Age ≥ 18 years at the time of informed consent.
• Ability to provide informed consent and consent to the collection and processing of clinical and laboratory data, as well as to the analysis of blood samples as part of study participation.
• Sufficient physical condition to undergo a single venous blood draw (approximately 50 mL), as assessed by the treating physician.

Exclusion Criteria:

• Active malignant disease or ongoing cancer therapy (e.g., chemotherapy or immunotherapy), due to potential immunological confounding.
• Immunosuppressive therapy or known severe immunodeficiency that could interfere with the interpretation of cellular immune responses.
• Pregnancy or breastfeeding, for general research-ethical reasons and to protect vulnerable populations.
• Acute unstable clinical condition that, in the opinion of the treating physician, makes study participation unreasonable.
• Known intolerance to blood sampling or relevant hematological disorders that could compromise the safety or feasibility of venipuncture.
• Lack of capacity to provide informed consent or insufficient understanding of the study content despite supportive explanation.

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Asthma; Patients with Asthma	Other: Characterization of the neutrophil granulocyte epigenome; Characterization of epigenomic differences in neutrophils from patients with different lung diseases (asthma, COPD, pneumonia, tuberculosis, and viral pulmonary infections such as COVID-19 and influenza) by identifying disease-specific epigenetic and functional signatures
COPD; Patients with chronic obstructive pulmonary disease	Other: Characterization of the neutrophil granulocyte epigenome; Characterization of epigenomic differences in neutrophils from patients with different lung diseases (asthma, COPD, pneumonia, tuberculosis, and viral pulmonary infections such as COVID-19 and influenza) by identifying disease-specific epigenetic and functional signatures
Viral pneumonia; Patients suffering from viral pneumonia, e.g. COVID-19 or Influenza	Other: Characterization of the neutrophil granulocyte epigenome; Characterization of epigenomic differences in neutrophils from patients with different lung diseases (asthma, COPD, pneumonia, tuberculosis, and viral pulmonary infections such as COVID-19 and influenza) by identifying disease-specific epigenetic and functional signatures
Bacterial pneumonia; Patients suffering from bacterial pneumonia	Other: Characterization of the neutrophil granulocyte epigenome; Characterization of epigenomic differences in neutrophils from patients with different lung diseases (asthma, COPD, pneumonia, tuberculosis, and viral pulmonary infections such as COVID-19 and influenza) by identifying disease-specific epigenetic and functional signatures
Tuberculosis; Patients treated for tuberculosis	Other: Characterization of the neutrophil granulocyte epigenome; Characterization of epigenomic differences in neutrophils from patients with different lung diseases (asthma, COPD, pneumonia, tuberculosis, and viral pulmonary infections such as COVID-19 and influenza) by identifying disease-specific epigenetic and functional signatures; Other: Characterization of the T-cell immune response to to various oxidatively modified mycobacterial antigens; Investigation of the response (activation/stimulation) of antigen-specific T cells from patients with tuberculosis to various oxidatively modified mycobacterial antigens, with the aim of determining whether changes in the redox status of these antigens measurably influence the adaptive immune response.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of the neutrophil granulocyte epigenome	Stratification of patients with different lung diseases based on epigenetic signatures of neutrophils: Epigenetics: identification of disease-specific differences in DNA methylation patterns and transcriptional profiles (RNA sequencing).	2030
Characterization of functional signatures	Stratification of patients with different lung diseases based on functional signatures of neutrophils: Functional reactivity: quantitative assessment of reactive oxygen species production (oxidative burst) and cellular cell death (e.g., Sytox Green, Annexin V/PI) following stimulation with defined stimuli (e.g., PMA, LPS, Gram-positive/Gram-negative bacteria, BCG, Mycobacterium tuberculosis).	2030

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Influence of demographic and clinical variables	Correlation of demographic and clinical variables (age, sex, disease severity, medication, comorbidities) with epigenetic and functional parameters	2030
Identification of subgroups within diseases	Exploratory identification of subgroups with characteristic or divergent profiles within the studied patient cohorts	2030

Collaborators and Investigators

• Sponsor: Research Center Borstel
• Investigators: Principal Investigator: Jan Heyckendorf, Prof. Dr. med., University Hospital Schleswig-Holstein

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: January 27, 2026
• First Submitted That Met QC Criteria: January 27, 2026
• First Posted (Actual): February 4, 2026

Study Record Updates

• Last Update Posted (Actual): February 4, 2026
• Last Update Submitted That Met QC Criteria: January 27, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: epigenome; oxidation; antigens; neutrophil granulocytes
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Immune System Diseases; Respiratory Tract Infections; Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Pneumonia; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Mycobacterium Infections; Pathological Conditions, Signs and Symptoms; Pulmonary Disease, Chronic Obstructive; Asthma; Tuberculosis; Pneumonia, Bacterial; Pneumonia, Viral
• Other Study ID Numbers: OXIGENE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will be shared upon reasonable request. Please contact the prinicpal investigator.

Drug and device information, study documents

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