Asthma is a particularly serious detrimental outcome of exposure to air pollutants. Numerous epidemiological studies show a link between asthma and exposure to pollutants such as nitrogen dioxide (NO₂) and airborne dust [1-4]. Specifically, some of these studies report a link between asthma and fine particles (with aerodynamic diameter of <2.5 μm), denoted PM_2.5 (PM_number denotes particulate matter with aerodynamic diameters of <number). This reported link is significantly stronger than the comparable links between asthma and either coarse particles PM_2.5–10, or respirable suspended particles PM₁₀ [5,6]. PM_2.5 consists mainly of sulfate, nitrate, ammonium, elemental carbon, and organic carbon [7]. Interestingly, the coarser PM_2.5–10, which is not so strongly associated with asthma, contains the same components. Therefore, it is difficult to explain the relationship between PM_2.5 and asthma by the major components.

How, other than in particle size, does PM_2.5 differ from PM _2.5-10, if not in identity of its major particles? Our most promising lead is that it differs in the nature of its major aerosol mass contributors: for PM_2.5 these are secondary aerosols and vehicle exhaust, whereas for PM _2.5-10 they are marine and mineral aerosols [8].The secondary aerosols in PM_2.5 are mainly ammonium and nitrate, whose concentrations are related to the transfer timescale between gas and particle phase, which is a function of ambient temperature, relative humidity, and gas phase constituent concentration in the atmosphere [9]. Furthermore, NO₂ and NO are main components of nitrogen oxide in the atmosphere. It is known that nitrogen oxide finally changes to nitrate. Therefore, it is considered that NO₂ and NO play a pivotal role in the production of nitrate of the secondary aerosol components of PM_2.5. However, various changes occur during the reactions of nitrogen oxide; some unsolved reactions also exist.

What mechanism of NO₂ induces asthma? Numerous epidemiological studies have long linked the presence of NO₂ to asthma. However, we know now that NO₂ exerts its effects on asthma by increasing the severity of exacerbations, and its main contributor is Nitrous Acid (HONO) [10-13]. HONO exists as an atmospheric gas [14]. Conventional NO₂ assay methods such as those using the Saltzman reagent method, or NOx analyzers, also detect HONO and include it in the reported NO₂ level: they do not separate it out [15]. Therefore, previous studies on the respiratory effects of NO₂ may have unconsciously included data on exposure to HONO as well, without independent measurement of exposure to and the effects of HONO [16]. A few epidemiological studies have assessed the relationship between HONO, and respiratory symptoms and lung function. Jarvis et al. [13] observed that indoor HONO levels are associated with decreased lung function and possibly with more respiratory symptoms, and that the association between NO₂ and lung function is explained by HONO [13]. Moreover, in animal-exposure experiments using guinea pigs, we have demonstrated that exposure (24 h/day for four weeks) to 3.6 ppm HONO induces alterations that resemble pulmonary emphysema in the alveolar-duct centriacinar regions, distortion of the alveolar-duct centriacinar regions with extension of the bronchial epithelial cells and smooth muscle cells, and expansion of bronchial lumens [12]. In addition, we have shown that the exposure to 0.1 ppm HONO for the same duration induces alterations that resemble pulmonary emphysema (unpublished data).

Where does HONO come from? A variety of reactions are known to produce HONO. Here are just a few: reaction of NO₂ and water, 2 NO₂ + H₂O → HONO + HNO₃ [17]; reaction of NO₂ and particle surface (soot, soil particles (Humic acid), etc.): NO₂ + surface (+H₂O) → HONO [18]; reaction of NO and hydroxyl radical, NO + OH·→ HONO [17]; a primary product of material combustion [19]. Therefore, HONO can be produced spontaneously with NO₂ or NO in the atmosphere. Moreover, when NO₂ comes in contact with PM_2.5, reactions between NO₂ and water as well as NO₂ and particle surface takes place, which in turn produce HONO. Therefore, we propose that a major contributor to the asthma effect of PM_2.5 is HONO. We suspect that NO₂ must be present on PM_2.5 as the strongest stimulator to induce the asthma effect. In support of these ideas, numerous epidemiological studies report that asthma symptoms are related to the presence of airborne dust and NO₂ [20-22].

Why is the asthma effect less for PM _2.5-10 than that for PM_2.5? We suggest that PM _2.5-10 is less capable of producing HONO, probably because it has less surface area, as determined in comparisons per weight. The strong likelihood that a link exists between HONO and asthma prompts us to recommend that future epidemiological studies of the asthma effects of air pollutants should include measurements of HONO levels.