Influenza vaccination: changes in exhaled nitric oxide levels and sputum cytology

Influenza vaccination is routinely recommended for patients with chronic lung disease, but has been reported to cause a small increase in airway reactivity. The use of simple, non-invasive methods of assessing changes in airway inflammation could potentially allow improved understanding of the cellular mechanisms underlying such changes.

We studied a group of 44 hospital workers before and after routine influenza vaccination, using spirometry, and exhaled nitric oxide (eNO) as a marker of pulmonary inflammation (Group A). In addition, methacholine challenge and sputum induction were also performed in a subgroup (subgroup B, n = 7) at baseline and at 7 days after vaccination.

Spirometry did not change in either group. In Group A there was a small but significant rise in mean peak eNO from 47.32 +/- 4.5 (mean NO p.p.b. +/- SEM) to 53.2 +/- 4.9 between days 0 and 7 (P < 0.05). A non-significant rise in eNO was seen in subgroup B. In subgroup B, when the differential cell counts in induced sputum were compared between baseline and sampling 1 week later, there was a significant rise in the percentage of lymphocytes, from 3.9 (1.8-9.8: median %total (range)) to 11.9 (6.0-18.5, P < 0.02) and a non-significant increase in shed respiratory epithelial cells from 3.1 (0.6-5.8) to 13.0 (1-30.3, P=0.06). There was a corresponding significant fall in the percentage of macrophages. Methacholine challenge in subgroup B showed no change in reactivity in these normal subjects.

Influenza vaccination causes a small increase in exhaled NO, and is accompanied by increased sputum lymphocytosis and respiratory epithelial shedding. An influx of inflammatory cells may help to explain the induction of increased airway reactivity that has been described in other studies.