Bronchial reactivity in experimental infections with influenza virus

In an attempt to develop an objective, quantitative test to assess the reactogenicity of candidates for attenuated influenza virus vaccines, the clinical responses and bronchial reactivity to methacholine were assessed in 36 normal volunteers lacking antibody to both hemagglutinin and neuraminidase (doubly seronegative) who were inoculated with either wild-type or temperature-sensitive attenuated influenza A (H1N1) virus by intranasal droplets. Five of six volunteers infected with wild-type virus developed systemic and/or febrile illness that lasted for a mean of five days. Nineteen of 30 persons who received attenuated virus developed infection without febrile or systemic illness. In the six recipients of wild-type virus, bronchial reactivity appeared to increase after inoculation and persist for four weeks. This trend was not observed in infected or noninfected vaccinees. Analysis of variance provided suggestive (but not significant) evidence that the different trends in bronchial reactivity manifested by the wild-type virus and vaccine groups were distinct (P = 0.075).