Nasal Mucosal Immune Responses to Live Attenuated Influenza Virus (LAIV) in Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Phenotypes

21-0254

This study will determine the functional status of the nasal immune environment with LAIV exposure in COPD persons with frequent exacerbations (defined as individuals with two or more episodes of worsening in COPD symptoms requiring treatment with antibiotics and/or steroids in the prior 12 months) and COPD persons without frequent exacerbations to determine acute exacerbation of COPD (AECOPD)-associated dysfunction in a) cytokines and immune effector cells of the nasal mucosa and b) viral replication. The investigators hypothesize that: 1) COPD frequent exacerbators, compared to COPD infrequent exacerbators, will demonstrate altered mucosal immune responses to LAIV exposure, and 2) COPD frequent exacerbators, compared to COPD infrequent exacerbators, will demonstrate increased markers of influenza viral replication after LAIV exposure.

2022-10-03

2025-03-01

2025-03-01

Recruiting

Early phase I

40

Inclusion Criteria: In order to be eligible to participate in this study, an individual in the COPD group must meet all of the following criteria: * Age\>40 years old * Physician diagnosis of COPD confirmed by post-bronchodilator testing (defined as forced expiratory volume in one second (FEV1)/forced vital capacity (FVC)\< lower limit of normal and FEV1/FVC\<0.70) and FEV1\>30% predicted at screening * Free of acute exacerbation of COPD for prior four weeks at time of recruitment * Resting oxygen saturation \>94 percent * Blood pressure systolic values between 90-160 mm Hg and diastolic between 55-90 mm Hg * No nasal symptoms based on questionnaire * Willingness and ability to participate in study procedures * Completion of informed consent In order to be eligible to participate in this study, an individual in the healthy control group must meet all of the following criteria: * Age\>40 years old * Spirometry testing showing normal lung function (defined as pre and post--bronchodilator FEV1/FVC\>=lower limit of normal and FEV1\>80 percent predicted) at screening * Resting oxygen saturation \>94 percent * Blood pressure systolic values between 90-160 mm Hg and diastolic between 55-90 mm Hg * No nasal symptoms based on questionnaire * Willingness and ability to participate in study procedures * Completion of informed consent Exclusion Criteria: * Inability or unwillingness to consent * Active tobacco or e-cigarette use (within last six months) * Active diagnosis of asthma * Any regular suppressive antibiotics (i.e., azithromycin) * Daily oral prednisone use * Any supplemental oxygen use beyond nocturnal oxygen therapy * Use of intranasal corticosteroids in the 30 days prior to screening visit * Chronic illness associated with immunosuppression (i.e., HIV, malignancy) * History of documented or self-reported positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection requiring hospitalization * Receipt of SARS-CoV-2 vaccine within 14 days prior to study screening visit or plan to receive SARS-CoV-2 vaccine from screening visit to 14 days after completion of all study procedures * History of epistaxis, prior nasal surgery or anatomical abnormalities * Current use of blood thinner beyond full dose aspirin \[e.g., warfarin (coumadin), clopidogrel (Plavix), dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis)\] * Self-reported history of easy bruising or bleeding gums * Serological evidence of HIV infection at screening (Positive HIV antibody test) * Relative leukopenia (WBC\<4000), neutropenia (Absolute neutrophil count\<2000) or lymphopenia (absolute lymphocyte count\<1500) on screening CBC * Respiratory infection (cough, sore throat, sinusitis, fever) within prior 4 weeks * Active wheezing at day 0 visit * Pregnancy or nursing or women who are currently trying to become pregnant. (All female subjects, except those who have had a hysterectomy with oophorectomy, will undergo urine pregnancy testing on the morning of the screening visit and again on the on Day 0 at the time of arrival to the lab and prior to LAIV administration. A positive pregnancy test will exclude the subject) * Use of chronic immunosuppression in the 30 days prior to screening visit * History of hypersensitivity, especially anaphylactic reactions, to egg proteins, gentamicin, gelatin, or arginine, or with a reaction to previous influenza vaccination at a severity level precluding the subject's participation as judged by the study physician * History of Guillain-Barre syndrome * Subjects who will be unable to avoid contact with immunocompromised individuals for 3 weeks after receiving LAIV vaccine * Receipt of the LAIV during the current or prior flu vaccine season * Physician diagnosed influenza, a positive test for influenza or suspicion of influenza illness in the 18 months prior to enrollment. Suspicion of influenza will be based on the CDC's influenza-like illness case definition ("fever\>100 °F AND cough/sore throat in the absence of a known cause other than influenza. Temperature can be measured in the office or at the home") * Any condition that, in the opinion of the study investigator, would compromise the subject's ability to participate in the study

{'studyType': 'INTERVENTIONAL', 'phases': ['EARLY_PHASE1'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'This study is an early Phase 1, single-center, parallel-group unmasked exposure study of nasal immune responses after controlled exposure to LAIV.', 'primaryPurpose': 'BASIC_SCIENCE', 'maskingInfo': {'masking': 'NONE', 'maskingDescription': 'This is an open label exposure study.'}}, 'enrollmentInfo': {'count': 40, 'type': 'ESTIMATED'}}

2024-04-12