Impact of Seasonal Influenza in Patients With CF
Early studies suggested that seasonal influenza viruses play a role in worsening the lung function of CF patients and disease progression. However, although the development of more sensitive methods have now overcome the difficulty of detecting viruses in viscous sputum specimens, recent studies have not found any evidence that influenza is more common in CF patients than healthy subjects, or that influenza is responsible for their increased lower respiratory tract morbidity. In a 4-year cohort study of 8625 adults and 12,881 children with CF, Ortiz et al. found that there was an estimated annual excess of 147.6 cases per 10,000 person-months and that an excess of 2.1% of all exacerbations occurring during the influenza season can reasonably be attributed to influenza. In another study of 38 young adults with CF hospitalized for respiratory exacerbations, Punch et al. found that 22.6% (12 out of 53) of their sputum samples were positive for a respiratory virus (four for influenza B, three for parainfluenza 1, three for influenza A and two for respiratory syncytial virus) when tested using a multiplex reverse transcriptase PCR assay combined with an enzyme-linked amplicon hybridization assay, and there was no statistical relationship between viral status and the rates of isolation of P. aeruginosa, Staphylococcus aureus or Aspergillus fumigatus. Wat et al. used nucleic acid sequence-based amplification and detected a high rate of viruses (46%) in nasal swabs and sputum samples taken from 71 children with CF during respiratory exacerbations. Influenza A (8%), influenza B (7.2%) and rhinovirus (15.9%) were the main viruses detected but, unlike previous studies, they found that symptomatic viral infections did not seem to increase the likelihood of bacterial exacerbations. In another study, Olesen et al. found 97 viral and 21 atypical bacterial infections in 76 children with CF followed for 12 months with regular outpatient clinic visits. The viral detection rate was 16%, with rhinovirus in 87% and influenza A in 3% of the sputum/laryngeal aspiration samples. No influenza B infection was detected. The authors also found a significant decrease in lung function during viral infection (forced expiratory volume in 1 s: -12.5%; p = 0.048) except in the case of rhinovirus infection, but failed to find any positive correlation between respiratory viruses and bacterial infections or changes in colonization.
Finally, two very recent studies have confirmed the limited role of influenza in respiratory exacerbations. In the first study, Burns et al. rarely detected influenza viruses during the respiratory exacerbations of children with CF, whereas rhinovirus was relatively frequent in both upper airway and sputum samples. The second study found that 24 out of 63 children with CF (60.5%) were positive for at least one virus during pulmonary exacerbations with coxsackie/echovirus being detected most frequently in mid-turbinate swabs, throat swabs or sputum samples; no influenza viruses were detected.
A number of methodological aspects of these studies of the impact of seasonal influenza on patients with CF need to be addressed. First, most of them had a small sample size and no healthy control subjects. Second, none described the clinical status of the patients and it is likely that the true impact of influenza on CF may be underestimated in children with pulmonary deterioration. Third, there were no data concerning the patients' influenza vaccination status. Finally, the relatively low frequency of influenza infection even during the epidemic period and the mild course of the disease might be influenced by vaccination coverage.