During the 2000-2001 influenza immunization season in Canada, an increased number of vaccine recipients reported ocular and respiratory symptoms shortly after vaccination. These adverse events were later termed oculorespiratory syndrome (ORS) and defined by the presence of bilateral red eyes, facial edema, or any of the “ORS-defining respiratory symptoms,” which included coughing, wheezing, tightness of the chest, difficulty breathing, and sore throat. Analysis of the cases revealed that almost all (96 percent) followed vaccinations supplied from a single manufacturer. Electron microscopy of the vaccine preparation revealed large clumps of viral particles that had not been successfully split by the usual chemical processing of the vaccine. Federal Canadian regulators requested a reformulation of the problem vaccine using a different splitting agent and a controlled trial to demonstrate its safety. Scheifele and colleagues report on a randomized, double-blinded, crossover study of this revised vaccine product.

The trial recruited mostly health care workers and government office workers who were 30 to 59 years of age. Exclusion criteria included ever having ORS symptoms after receiving influenza vaccination, being allergic to any component of the vaccine, ever having a serious reaction to the influenza vaccine, or having preexisting ocular or respiratory conditions. Participants were randomly given influenza vaccine and placebo injections, at least five days apart. Telephone interviews were conducted 24 hours and six days after each vaccination to check for ORS or other adverse events.

Clinical symptoms consistent with ORS were reported in 39 patients (6.3 percent) after receiving influenza vaccinations and in 21 patients (3.4 percent) after receiving placebo; this was a statistically significant difference. The specific symptoms that were significantly increased after influenza shots were cough and hoarseness. The risk of ORS was not affected by gender, age, or the order in which the participants received the vaccine and the placebo. Patients receiving influenza vaccination for the first time were more likely to have ORS symptoms (5 percent) than those who had received previous flu shots (2.2 percent). No participants experienced a serious adverse event or anaphylaxis.

The authors conclude that even the reformulated influenza vaccination was associated with small increases in oculorespiratory symptoms, and speculated that this previously unrecognized phenomenon likely was associated with influenza vaccines in general.