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(Postlethwait and Bidani 1990; Postlethwait, I-angford et al. 1990). This is increased with
alkalosis and hyperthermia @ostlethwait, Langford et al. 1991; Postlethwait and Bidani
1994). A number of studies have been conducted to determine the acute effects of NOz
exposure at levels seen in air pollution on airway lining (usually the nose), lavage fluid, lung
function and airway reactivity in normal and asthmatic adult subjects. The exposures have
ranged from two to six hours at levels from 200 to 800ppb, aild were to NOz alone or
combined with either ozone or SOz @evalia, Rusznak et al. 1996; Devalia, Bayram et al.
1997; Jenkins, Devalia et al. 1999). These exposures resulted in disruption of the airway
epithelia, resulting in an increase of inflammatory cells with eosinophil 'priming', and a
release of inflammatory cytokines such as TNFo and IL8. Increased airway hyper-reactivity
in normal (Utell, Frampton et al. l99l) as well as asthmatic subjects was also demonstrated
@evalia, Rusznak et al. 1996; Devalia, Rusznak et al. 1996; Jenkins, Devalia et al. 1999).
Cilia were also disrupted and, after exposure to NOz at 2ppm for 4 hours, ultra-structurally
altered cilia with excess matrix and multiple ciliary ru(enomes were seen (Carson, Collier et
al. L993). Intermittent NOz exposure over a period of weeks in rats also resulted in
emphysematous like destruction of alveolar septa with reduction in the ventilatory surface
@vans, Stephens et al. 1972; Freeman, Crane et al. 1972; Mercer, Costa et al. 1995). There
was also hyperplasia of the respiratory epithelium with squamous metaplasia (Maejima,
Suzuki et al. 1992), disturbed surfactant (Muller, Barth et al. 1992) and aldehyde release
(Robison, Forman et al. 1995). Prolonged inhalation of 2ppm NOz is associated with terminal
bronchial epithelial hypertrophy and alveolar cell hyperplasia (Sherwin, Dibble et al. t972).
Gas mixtures of NOz and NO, each in concentrations of less than lppm, have been shown to
reduce peak expiratory flows and diffusion capacity in beagles (Bloch, kwis et al. 1972).ln
studies using lower concentrations (similar to pollution values) the damage in the airway was
related to duration of exposure (Maejima, Suzuki et al. 1992), but when exposed to high doses
the dose was more damaging than the duration of exposure (Lehnert, Archuleta et al. 1994).
NOz of l75ppm has been used in rats to create severe lung damage but avoiding death to
develop an ARDS model for study (Meulenbelt, Dormans et al. 1992). NOz has been
recognised as the product of grain fermentation responsible for the syndrome of pulmonary
oedema and haemorrhagic bronchiolitis obliterans known as silo fillers disease (Ramirez and
Dowell l97l; Horvath, doPico et al. 1978; Leavey, Dubin et d. 2004).
The Occupational Safety and Health Administration guidelines (NIOSH 2005) recommend
that the safety limit of mixed nitrogen oxides is below 25ppm. Inhalation at this concentration
may cause immediate pulmonary irritation and higher doses may cause haemorrhagic
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