Flu Vaccine - wheeze now or sick later?

The prestigious New England Journal of Medicine just published a paper claiming to demonstrate a superiority of attenuated live flu vaccine over the conventional, dead flu vaccine for young children. About half as many kids in the attenuated vaccine group went on to contract flu (figure). USA Today and other publications trumpeted the results with headlines such as "FluMist spray protects kids better than flu shots". They downplayed the concern raised by independent scientists that the live vaccine "comes with a significant risk for medically important wheezing".
This story illustrates some of the problems with reporting such clinical trials. First, it was "sponsored" (paid for) by MedImmune, the producer of the live vaccine. Sponsors have been known to not publish disappointing results, producing a publication bias. Although we can welcome these results, the arrangement raises questions about the "spin". How should parents and pediatricians balance the decrease in disease (from 9% to 4%) with the increase in wheezing (from 3% to 6%)? Second, the description of the trial is misleading. The Methods section begins "children ... were randomly assigned ...to receive either ... live attenuated influenza vaccine ... or inactivated vaccine in a double-blind manner" (emphasis added). This use of the term "double-blind" is nonsensical because random is completely "blind". The wording seems intended to make the reader think the trial was double-blind. Double-blind is the gold standard for trials because it reduces bias by keeping the both the doctor and patient ignorant of which treatment they are assigned. In this trial, however, the treatments could not be "blinded" because one involves a shot and the other involves sniffing the virus, treatments that are clearly distinguishable even by a patient. Finally, journals and journalists like to report positive, exciting news. These results merit a more sober discussion.
N Engl J Med. 2007 Feb 15;356(7):685-96. "Live attenuated versus inactivated influenza vaccine in infants and young children." Belshe RB, Edwards KM, Vesikari T, Black SV, Walker RE, Hultquist M, Kemble G, Connor EM

Biology of the 1918 Flu

Gnome writes "The 1918 flu caused an unusually high death rate among healthy young adults (ages 15-34). Genomic RNA was recovered several years ago from autopsy material and victims buried in the Alaskan permafrost. The 1918 flu had unique hemagglutinin and neuraminidase proteins on its surface (H1N1). However, they did not cause its pathogenicity because later viruses with this combination are not particularly deadly (e.g., Texas/91). Now, Tumpey and colleagues have reconstructed the entire 1918 virus and tested it. Unlike current flu viruses, the 1918 virus does not require an exogenous protease to infect cells in culture. Moreover, all 13 mice infected through the nose by the 1918 virus developed severe lung inflammation and died within 7 days, while none infected with the Texas/91 strain died. Surprisingly, recombinants between 1918 flu and Texas/91 suggest that the viral polymerase acts in concert with the other 7 proteins to increase virulence. On the bright side, existing antiviral drugs and a novel siRNA therapy were previously shown to protect mice against certain 1918 recombinant viruses.
Tumpey et al., "Characterization of the Reconstructed 1918 Spanish Influenza Pandemic Virus" Science. 2005 Oct 7;310(5745):77-80.