TINO: T Cells in the Nose of Older Adults

NCT06039527 | Recruiting

• 2 other identifiers: P21.066NL77841.058.21
• Study Type: observational
• Target: 170
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: Individuals with advanced age are at a progressively increasing risk of acquiring lower respiratory tract infections. Besides calendar age, the degree of frailty also associates with increased susceptibility to pneumonia requiring hospitalization. How alterations in the mucosal immune system with advanced age predispose to infections remains unclear as access to relevant tissue samples is limited. With minimally-invasive nasal sampling methods, it was recently observed that in vital older adults, both CD4+ T cells and CD8+ T cells are selectively lost from the nasal mucosa. However, the exact phenotype, underlying mechanisms, key molecules and consequences of this have not yet been investigated. Objective: Elucidate the mechanisms underlying the loss of nasal T cells and characterize in depth the differences of T cells in young and older adults and associate this loss with susceptibility to infections. Study design: Prospective cohort study Study population: Participants will be recruited from 3 groups:

• healthy young adults (18-30 years, n=50)
• vital older adults (\>65 years, n=60)
• frail elderly (\>65 years, n=60). This group includes individuals without a history of recurrent respiratory infections or with \>2 self-reported episodes of respiratory infection in the past year. Main study parameters/endpoints: Frequency of nasal CD8+ T cells in young adults and frail older adults. Secondary study parameters/endpoints:
• Phenotype (subsets, activation status), functionality, transcriptomic state, clonality and frequency of nasal and blood T cell populations
• Stability of T cells and other immune parameters, as described for main study parameter, during a second sample after 3 months.
• Analysis of other immune populations as for main study parameter
• Concentration of nasal and systemic factors (e.g. cytokines and metabolites) and their association with T cells and other immune populations
• Respiratory tract microbiota profiles and presence of asymptomatic viral infections and their association with T cells and other immune parameters
• Chronological and biological age, sex, and other immunologically relevant parameters with T cell populations and other immune parameters
• Alteration of T cell phenotype, during and following respiratory tract infections. Levels of antigen-specific T cells and other immune parameters in nose and blood post infection.

Conditions

Respiratory Tract Infections; Aging

Outcome Measures

Primary Outcomes (1)

• Frequency of nasal CD8+ T cells in young adults and frail older adults.

  CD8 T cells relative to nasal epithelial cells (ratio)

  baseline sample or month 3 sample

Secondary Outcomes (16)

• Phenotype of nasal and blood T cell populations in young adults, healthy older adults and frail older adults that suffer from recurrent respiratory tract infections or not.

  baseline sample or month 3 sample

• Functionality of nasal and blood T cell populations in young adults, healthy older adults and frail older adults that suffer from recurrent respiratory tract infections or not.

  baseline sample or month 3 sample

• Transcriptomic cluster composition of nasal and blood T cell populations in young adults, healthy older adults and frail older adults that suffer from recurrent respiratory tract infections or not, as frequency of T cell subsets.

  baseline sample or month 3 sample

• Clonality of nasal and blood T cell populations in young adults, healthy older adults and frail older adults that suffer from recurrent respiratory tract infections or not.

  baseline sample or month 3 sample

• Stability of nasal T cells, as described for main study parameter, during a second sample after 3 months.

  baseline sample versus month 3 sample

Study Arms (3)

Young adults

N=50 of this group No intervention. Sampling at timepoint 0 and for 50% of the group another sample at 3 months If respiratory symptoms develop in the 3 months after timepoint 0, participants are invited to provide a NPS/OPS to identify causative agent, and if one is established, individuals are sampled 3 more times at months 1, 3 and 5 post symptom onset

Vital elderly

N=60 of this group No intervention. Sampling at timepoint 0 and for 50% of the group another sample at 3 months If respiratory symptoms develop in the 3 months after timepoint 0, participants are invited to provide a NPS/OPS to identify causative agent, and if one is established, individuals are sampled 3 more times at months 1, 3 and 5 post symptom onset

Frail elderly

N=60 of this group. Half with recurring respiratory infections, and half without No intervention. Sampling at timepoint 0 and for 50% of the group another sample at 3 months If respiratory symptoms develop in the 3 months after timepoint 0, participants are invited to provide a NPS/OPS to identify causative agent, and if one is established, individuals are sampled 3 more times at months 1, 3 and 5 post symptom onset

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Study population: Investigators will recruit participants from 3 groups: * healthy young adults (18-30 years, n=50) * vital older adults (\>65 years, n=60) * frail elderly (\>65 years, n=60). These will be consist of individuals without a history of recurrent respiratory infections or with \>2 self-reported episodes of respiratory infection in the past year. Frailty will be determined by a clinical frailty score. The Clinical Frailty Scale (CFS) is a scale that caretakers can use to identify level of frailty in older patients from 1 (very fit) through 9 (terminally ill). For the present study, "vital older patients" are defined as those with a CFS of 1-3 and "older patients living with frailty with a CFS of 4 or higher".

You may qualify if:

• Adults able and willing to provide informed consent.
• Young adults aged 18-30 years old
• Healthy elderly aged \>65 years old
• Frail elderly \>65 years old
• Clinical Frailty score healthy elderly 1-3
• Clinical Frailty score frail elderly \>3
• Self-reported respiratory tract infection in previous year healthy elderly 0-1
• Self-reported respiratory tract infection in previous year frail elderly 0-1 or \>1

You may not qualify if:

• Incompetence to provide informed consent prior or during study
• Current smoker or \>40 pack year history
• History of severe nose bleedings
• Diagnosed with asthma, COPD or chronic rhinosinusitis
• Use of inhalation corticosteroids or antibiotics in the past 6 weeks
• Current use of anti-coagulants (to prevent nosebleeds). Platelet inhibitors like acetylsalicylzuur (Ascal) are allowed.
• Respiratory tract infection or common cold in the past 2 weeks
• Immunocompromised individuals (with primary immune deficiency or secondary immune deficiency)
• Life expectancy \<28 days in the opinion of study physician
• Vaccination in the 2 months prior to study start. A potential subject that is only excluded from participation based on a recent vaccination will be asked to re-participate 2 months post vaccination.

Sponsors & Collaborators

• Leiden University Medical Center: lead

Study Sites (1)

Leiden University Medical Center

Leiden, South Holland, 2333ZA, Netherlands

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Investigators will collect the following samples: * peripheral blood * nasopharyngeal swab * oropharyngeal swab * nasal curettes * nasosorption

MeSH Terms

Conditions

Respiratory Tract Infections

Condition Hierarchy (Ancestors)

Infections; Respiratory Tract Diseases

Study Officials

• Simon P Jochems, PhD

  LUMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Simon P Jochems, PhD

CONTACT

+31715261328; s.p.jochems@lumc.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant professor

Study Record Dates

• First Submitted: September 1, 2023
• First Posted: September 15, 2023
• Study Start: January 24, 2021
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: September 9, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)