Nasal Mucosal Immune Responses to Live Attenuated Influenza Virus (LAIV) in Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Phenotypes
概览
- 阶段
- 早期 1 期
- 干预措施
- LAIV
- 疾病 / 适应症
- COPD
- 发起方
- University of North Carolina, Chapel Hill
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Difference in mucosal immune response between COPD frequent exacerbators and COPD infrequent exacerbators
- 状态
- 已完成
- 最后更新
- 2个月前
概览
简要总结
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.
详细描述
This study is an early Phase 1, single-center, single-group unmasked exposure study of nasal immune responses after controlled exposure to LAIV. This trial will test the differences in the nasal immune responses to the nasal flu vaccine in two diseased groups of individuals along with healthy controls: 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 (defined as individuals with less than two episodes of worsening in COPD symptoms requiring treatment with antibiotics and/or steroids in the prior 12 months). A healthy control cohort will also be recruited, defined as individuals with spirometry-confirmed normal lung function and no asthma history. A total of 15 COPD frequent exacerbators, 15 infrequent exacerbators and 10 healthy controls will be enrolled for this trial. Investigators will balance the sex of participant as closely as possible to 50% male and 50% female. At screening visit, after obtaining informed consent and authorization to obtain medical records, all potential individuals will be screened for specific inclusion and exclusion criteria to ensure suitability and safety to receive the influenza nasal vaccine. A baseline assessment will be done including reviewing medical history and verifying eligibility, a physical exam by a study investigator, spirometry testing before and after bronchodilator, laboratory testing to screen for immunocompromised state \[Human Immunodeficiency Virus (HIV) antibody testing, compete blood count (CBC) with differential\], an assessment of symptoms, and pregnancy testing if pre-menopausal. Women who are pregnant, nursing, or women who are currently trying to become pregnant are not eligible for this study. Participants who meet eligibility after screening will be brought back for an enrollment visit where they will undergo a baseline assessment of their nasal inflammatory state. This includes sampling of the nose in three different ways. First, investigators will gently place a small strip of absorbent paper inside the lower part of the nose, and a nose clip will be applied for two minutes (ELF collection). Next, investigators will wash the inside of the nose with a small amount of sterile salt water to collect samples (NLF collection). Finally, investigators will take a small plastic device and gently scrape the inside of the nose to collect nasal cells (scraping collection). Investigators will also collect blood samples for inflammatory phenotyping. Within two weeks of enrollment visit, all enrolled individuals will receive the nasal influenza vaccine (there is no placebo component to the study). On days one, two, three, and seven after vaccine administration, participants will return to the study site to undergo nasal sampling including the nasal paper strip and washing, as well as blood collection. On Day 3, a nasal scraping will also be obtained. On Day 21 (optional visit), investigators will obtain nasal washing and blood collection. Investigators will collect patient reported outcomes using a validated influenza severity score to assess for unbiased correlations with biological measures.
研究者
入排标准
入选标准
- •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 based on spirometry testing available in the prior year or completed at screening (if no historical testing available)
- •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:
排除标准
- •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
研究组 & 干预措施
COPD Frequent Exacerbators
Individuals with two or more episodes of worsening in COPD symptoms requiring treatment with antibiotics and/or steroids in the prior 12 months
干预措施: LAIV
COPD Infrequent Exacerbators
Individuals with less than two episodes of worsening in COPD symptoms requiring treatment with antibiotics and/or steroids in the prior 12 months
干预措施: LAIV
Healthy Control
Individuals with spirometry-confirmed normal lung function and no asthma history
干预措施: LAIV
结局指标
主要结局
Difference in mucosal immune response between COPD frequent exacerbators and COPD infrequent exacerbators
时间窗: Baseline, Day 3
Epithelial lining fluid interferon-gamma (INF-ɣ) area under the curve (AUC) from day 0 (baseline) to day 3 (pg/mL x days)
次要结局
- Difference in viral clearance between COPD frequent exacerbators and COPD infrequent exacerbators(Baseline, Day 3)