Airway hyperreactivity and peripheral airway dysfunction in influenza A infection

Am Rev Respir Dis. 1978 Aug;118(2):295-303. doi: 10.1164/arrd.1978.118.2.295.


We studied 39 consecutive college students with documented nonpneumonitic influenza A/Victoria/3/75/H3N2 infection to examine alterations in pulmonary mechanics and airway reactivity to cholinergic challenge, and to assess the effect of the antiviral agent amantadine on these changes. Thirty-six of the 39 subjects (92 per cent) demonstrated diminished forced flow rates and decreased density-dependent forced flow rates while breathing a helium-O2 mixture as compared to an air mixture. On initial evaluation, there was no significant difference in forced flow rates or density dependence between a group of 18 subjects treated with amantadine and 21 subjects given a placebo. However, the placebo group demonstrated further decreases in density dependence 7 days after initial presentation, whereas the amantadine group demonstrated a significant increase in density dependence (P less than 0.05), which suggested an accelerated improvement in peripheral airway dysfunction in the treated group. After inhalation of carbachol aerosol, 25 subjects showed a significant (P less than 0.05) increase in total respiratory resistance that was prolonged and independent of hay fever history. Airway hyperreactivity gradually diminished during a 7-week period in both groups. There was no significant difference in the initial degree of hyperreactivity or in the rate of improvement between groups. These data suggest that nonpneumonitic influenza infection may be associated with both an inflammatory response predominantly in the peripheral airways and transient bronchial hyperreactivity. By means of its antiviral effect, amantadine may arrest the proliferation of virus and associated inflammatory response in peripheral airways, but airway hyperreactivity presumably related to initially damaged airway depithelium is not attenuated by inhibition of viral replication after infection has been established.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aerosols
  • Air
  • Airway Resistance*
  • Amantadine / therapeutic use
  • Carbachol / pharmacology
  • Clinical Trials as Topic
  • Drug Interactions
  • Female
  • Helium / pharmacology
  • Humans
  • Influenza A virus
  • Influenza, Human / drug therapy
  • Influenza, Human / physiopathology*
  • Male
  • Maximal Expiratory Flow-Volume Curves
  • Oxygen / pharmacology
  • Placebos
  • Research Design
  • Vital Capacity / drug effects


  • Aerosols
  • Placebos
  • Helium
  • Carbachol
  • Amantadine
  • Oxygen