Influenza Vaccination in Children With Cystic Fibrosis

Abstract and Introduction

Abstract

Cystic fibrosis (CF) is an inherited autosomal recessive disease characterized by progressive pulmonary damage and respiratory failure. It is known that bacterial infections play a critical role in the development of significant lung damage, whereas the role of respiratory viruses in CF pulmonary exacerbations and the relationship between viral infections and the progression of lung damage are uncertain. Health authorities throughout the world recommend influenza vaccination for CF patients. The aim of this review is to analyze the impact of seasonal and pandemic influenza on CF patients and data concerning influenza vaccination in order to assess the current situation and identify areas for future study. As data are limited, further well-constructed clinical studies of the effectiveness of influenza vaccination on the main clinical outcome measures of pulmonary function and nutritional status in patients with CF are required.

Introduction

Cystic fibrosis (CF) is characterized by progressive pulmonary damage and respiratory failure, which is the cause of death in the majority of the patients. It is an inherited autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, and its clinical phenotypes are directly related to ion channel liquid volume regulation attributable to CFTR mutations.^[1–3] At the extremes, there are young patients diagnosed at birth after neonatal screening with perfect pulmonary function and older patients listed for lung transplantation. It is known that bacterial infections play a critical factor in the development of significant lung damage,^[4–6] whereas the role of respiratory viruses in CF pulmonary exacerbations and the relationship between viral infections and the progression of lung damage is uncertain. However, previous studies might have underestimated the prevalence of viral infections as it is only recently that molecular-based techniques have improved the detection of respiratory viruses. In a 17-month prospective study of 165 CF patients aged <18 years, upper respiratory symptoms significantly correlated with positive respiratory viral detection (p < 0.05);^[7] alongside this the authors of a 6-month winter period prospective study concluded that acute respiratory illnesses were similarly frequent in 20 children with CF and 18 age-matched, healthy control subjects (3.8 ± 1.0 and 4.2 ± 1.7 episodes, respectively), with similar seasonal occurrences and a similar distribution of respiratory viruses.^[8] However, the upper respiratory tract symptom scores of the CF patients were associated with significantly greater increases in lower respiratory tract symptom scores.^[8] Moreover, a recent cross-sectional study found that 26 out of 43 children with CF (60.5%) were positive for at least one respiratory virus during a pulmonary exacerbation, and that viral-related exacerbations were associated with more severe disease and poorer quality of life scores than nonviral exacerbations, although pulmonary inflammation was similar.^[9]

Respiratory viruses might also have a considerable impact on respiratory exacerbations in CF patients because of their diminished specific antiviral defenses. Some studies have found that their airway epithelial cells have impaired nitric oxide synthesis (a regulator of innate antiviral defenses), and CF cells show less interferon-related antiviral gene induction and increased production of proinflammatory cytokines.^[10,11] Furthermore, a profound impairment of the antiviral early innate response in CF airway epithelial cells has recently been identified and is thought to explain the increased susceptibility of patients with CF to rhinovirus infections, suggesting a potential use of interferons in the treatment of rhinovirus-induced CF exacerbations.^[12] The role of interferons and proinflammatory cytokines in immune responses to vaccines, as well as in vaccine-related adverse events, is unknown.

Finally, respiratory viruses may also contribute to the pathogenesis of bacterial exacerbations, and it has been suggested that respiratory viral infections facilitate Pseudomonas aeruginosa acquisition and colonization, thus affecting the host's pulmonary defenses.^[13,14]

Health authorities throughout the world recommend influenza vaccination for all patients with CF regardless of their nutritional, respiratory or immunologic status.^[15] The aim of this review is to analyze the impact of seasonal and pandemic influenza on CF patients and data concerning influenza vaccination in order to assess the current situation and identify areas for future studies.