Aging, Respiratory Tract Infections
Conditions
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.
Interventions
None listed
Sponsors
Leiden University Medical Center
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
•Adults able and willing to provide informed consent. Specific inclusion criteria per group: * 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
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of nasal CD8+ T cells in young adults and frail older adults. | baseline sample or month 3 sample | CD8 T cells relative to nasal epithelial cells (ratio) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | percentage of T cells and T cell subsets |
| 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 | percentage of T cells responding to in vitro stimulations |
| 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 | T cell clusters based on gene expression patterns |
| 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 | Number and proportion of TCR clones |
| Stability of nasal T cells, as described for main study parameter, during a second sample after 3 months. | baseline sample versus month 3 sample | CD8 T cells relative to nasal epithelial cells (ratio) |
| Stability of nasal immune populations, during a second sample after 3 months. | baseline sample versus month 3 sample | immune cell populations relative to nasal epithelial cells (ratio) |
| Comparison of nasal immune cell populations between young adults, vital and frail elderly | baseline sample or month 3 sample | ratio to epithelial cells |
| Comparison of peripheral immune cell populations between young adults, vital and frail elderly | baseline sample or month 3 sample | percentage of total CD45+ cells |
| Concentration of nasal and systemic cytokines | baseline sample or month 3 sample | concentrations |
| Concentration of nasal and systemic metabolitesother immune populations | baseline sample or month 3 sample | concentrations |
| Respiratory tract microbiota profiles and their association with T cells and other immune parameters | baseline sample or month 3 sample | microbiota abundance (total sum scaling) |
| Presence of asymptomatic viral infections and their association with T cells and other immune parameters | baseline sample or month 3 sample | viral of loads (Ct) |
| Effect of sex on aging effects of nasal immune populations | baseline sample or month 3 sample | ratio to nasal epithelial cells |
| Effect of sex on aging effects of blood immune populations | baseline sample or month 3 sample | percentage of CD45+ cells |
| Frequencies of antigen-specific T cells in nose post infection. | symptom onset and 1, 3 and 5 months later | antigen-specific T cells as percentage of T cells |
| Frequencies of antigen-specific T cells in blood post infection. | symptom onset and 1, 3 and 5 months later | antigen-specific T cells as percentage of T cells |
Countries
Netherlands
Contacts
PRINCIPAL_INVESTIGATORSimon P Jochems, PhD
LUMC
Outcome results
None listed