Influenza A/H1N1 in patients with cystic fibrosis in Italy: a multicentre cohort study.

The clinical consequences of influenza are severe in cystic fibrosis (CF), but the impact of A/H1N1 virus infection remains poorly defined. 2 Pandemic influenza A/H1N1 started in Italy in September 2009 and CF patients were included among those at risk of complications and recommended to receive A/H1N1 vaccine. Better characterisation of the impact of influenza A/H1N1 in comparison with other flu-like illnesses in CF would provide a rational basis for antiviral treatment and vaccination strategies for the next flu season. Within the Italian Cystic Fibrosis Society, we sent a questionnaire to 30 centres to collect follow-up data for all patients with influenza-like symptoms consecutively seen between November 2009 and March 2010. Realtime RTPCR test was performed to define A/H1N1 status. Continuous variables are reported as medians, IQR (see online supplement for details of study methods). Nineteen centres reported data from 127 patients: 68 were ‘A/H1N1+ve’ and 59 were ‘A/H1N1eve’ for the RT-PCR test. Symptom onset peaked during calendar week 45 in A/H1N1+ve patients, similar to the general Italian population, whereas A/ H1N1eve patients showed a bimodal incidence peak at weeks 45 and 47 (online supplementary figure S1). A/H1N1+ve patients tended to be younger than A/H1N1eve patients (40% vs 58% aged $18 years; p1⁄40.051), with no other differences in clinical characteristics or symptoms leading to presentation to centres (online supplementary table S1). Oseltamivir (2e3 mg/kg/day as currently recommended) was administered to 82% A/ H1N1+ve and 12% A/H1N1eve patients. In the A/H1N1+ve group, treatment was started within 24e48 h from symptom onset upon virological confirmation. Oseltamivir was well tolerated and no treatment cessation was required. In one AH1N1+ve patient complications were associated with development of oseltamivir resistance. Clinical course and duration of disease are reported in table 1. In the entire CF patient population, shorter disease duration was seen in oseltamivir treated patients (5, 4e11 vs 10, 6e14 days; p1⁄40.008), a difference apparently limited to the A/H1N1eve subset. During illness, 68% A/H1N1+ve and 80% A/H1N1eve patients developed pulmonary exacerbations (p1⁄40.127). Disease course was uncomplicated in 85% and 88% patients, respectively (p1⁄40.639). Of note, immunosuppressive therapy for organ transplantation did not increase risk of complications in either group. Four patients with severe pulmonary disease (3 A/H1N1+ve, 1 A/H1N1eve) died of respiratory failure: none had been vaccinated and all had received antiviral therapy (online supplementary table S2). No significant FEV1 decline was observed in both groups after 1 and 6 months from symptom onset (online supplementary figure S2). In none of the cases, new isolation of Pseudomonas aeruginosa or Burkholderia cepacia complex was documented. In conclusion, in a cohort of patients who consecutively presented to Italian CF centres for flu-like symptoms during the 2009 pandemic period, accurate diagnostic testing did not identify clinical characteristics specifically associated with A/H1N1 infection, the only exception being younger age in A/H1N1+ve patients. The use of a reliable identification method allowed appropriate treatment to be initiated. Systematic collection of data at patient presentation and subsequent follow-up provided further information on A/H1N1 infection in CF, which will be useful to patients for the next influenza season. Influenza A/H1N1 has no major impact in CF, but patients with poor clinical conditions due to the disease are exposed to substantial risk of complications and unfavourable outcomes. Annual vaccination for seasonal influenza and A/H1N1 influenza is recommended in CF, with continuing efforts towards higher vaccination coverage levels especially in adult subjects.