LAIV (Flumist®) Administration in CF Patients

Influenza (the "flu") is one of the most common respiratory viruses associated with respiratory deteriorations in children and adolescents with cystic fibrosis. These deteriorations usually mean antibiotics, hospitalizations, and worsening of pulmonary function tests. A new flu vaccine has been recently approved for use in Canada (Flumist®). What is particular about this flu vaccine is that it is a spray in the nose, which mimics how influenza usually infects us. This particular vaccine protects children and adolescents much better than the regular injectable flu shot.

This new vaccine has been given to \> 2,000 healthy children and to \>2,000 children with asthma and well tolerated. The investigators want to know if Flumist® is well tolerated in children with CF and does not cause worsening of respiratory symptoms. The investigators will conduct a study where all participants will receive Flumist® in the nose. This study is particularly important because its results will provide safety information on a vaccine that is more efficacious for a population who needs safe and easy to administer protection against the flu.

The literature demonstrates a significant impact of influenza on the disease course of children with cystic fibrosis (CF) and superior efficacy of live-attenuated influenza vaccine (LAIV - Flumist®) compared to trivalent inactivated vaccine (TIV) in healthy and asthmatic children and adolescents. LAIV has recently been approved for use in Canada in people aged 2-59 years. CF is described as a hyper-inflammatory disorder, with abnormal inflammatory signaling, excessive inflammatory response, and impairment in the resolution of inflammation that could be a risk for the development of adverse events after LAIV. Given the impact of influenza in CF patients, the likelihood of superior protection of LAIV, the hyper-inflammatory status of CF patients that could increase the risk of adverse events, and the scarcity of data on the safety of LAIV use in this population, the assessment of LAIV's safety profile in CF patients is necessary to determine whether the anticipated benefits associated with LAIV use will outweigh potential risks, mainly respiratory deterioration. Our study specifically aims to:

Aim 1: Explore the mucosal inflammatory response in participants exposed to LAIV: Using self-procured nasal swabs in 75 participants with CF (30 previously vaccinated and 45 LAIV naïve) and 45 healthy siblings, the investigators aim to explore: (a) the inflammatory response profiles in patients with and without CF before and after LAIV and (b) if participants' inflammatory profiles differ whether they report respiratory deteriorations after LAIV or not. As viral infections were shown to induce cytokines production (IL-1b IL-6, TNFa and CXCL-8 \[IL-8\]) in nasal secretions, the expression of these 4 inflammatory markers will be profiled using a multiplex cytokine detection kit after LAIV in participants with and without CF. The inflammatory signatures will be compared in patients with/without CF and with/without respiratory deteriorations.

Aim 2: Determine LAIV efficacy in preventing shedding of viral strains upon challenge: Using the same 75 participants with CF and 45 healthy siblings from aim 1, the investigators will compare the proportion of children shedding vaccine strains among the LAIV naïve and LAIV experienced. The clinical efficacy will be extrapolated from the efficacy in preventing shedding and derived as 1 - (% shedding in LAIV experienced/% shedding in LAIV naïve).

Aim 3: Assess LAIV safety in patients with CF: Compare the incidence of severe AEFI following LAIV in children with CF vaccinated with LAIV during the previous season (n = 70) compared to those without prior vaccination with LAIV (n = 45). Using a self-controlled case-series design, the investigators will compare the incidence of AEFI during the at-risk period (Day 1-28 post LAIV) and non at-risk period (Days 29-56). These incidence rate ratios will be compared in children with CF who are LAIV experienced and LAIV naïve.

Methods: The cohort of children with CF will be vaccinated with LAIV and followed for 56 days by phone for the development of severe adverse events following immunization (AEFI). Both periods (4 weeks) will be monitored using the same methodology: a diary for monitoring of symptoms and hospital charts. The cohort of children without CF will be vaccinated with LAIV and followed for 8 days by phone (one phone call on day 8) for the development of severe AEFIs.

A subgroup of participants with CF (30 LAIV experienced at MCH and 45 LAIV naïve in BC) and 45 participants without CF will be recruited to also provide self-procured nasal swabs on day 0 (before LAIV), and then on days 1,2, 4, and 7 for inflammatory markers and viral shedding.

Knowledge gained from this project will be used to determine LAIV safety in children with CF, a patient population in whom influenza has major health impacts and who could greatly benefit from a recommendation for LAIV preferential use. Moreover, the intranasal route of administration should make this vaccine more acceptable to patients that need yearly vaccination, thereby potentially increasing vaccination coverage. Patients with CF are also the population in whom the risk of adverse events with LAIV is the highest, given their baseline respiratory condition and inflammatory dysregulation. Therefore, if LAIV is well tolerated in this population, the investigators could generalize LAIV preferential use to other pediatric populations with chronic conditions.

Eligibility Criteria:
Inclusion Criteria:

* followed in one of the participating clinics
* considered in stable condition prior to enrollment as per their physician,

Exclusion Criteria:

* allergic to eggs or other vaccine components
* patients for whom LAIV is contraindicated (i.e. on oral steroids for an acute asthma exacerbation or with a medically-attended wheezing episode in the 7 days prior to immunization)
* participants with clinically significant nasal polyps
* have a significant febrile illness (oral temperature ≥ 380C) at day of vaccination
* pregnant women
* immunosuppressed subjects