Received date: June 29, 2012; Accepted date: August 20, 2012; Published date: August 21, 2012
Citation: Ohyama M, Takenaka N, Bandow H (2012) Possible Link between Nitrous Acid and Asthma Induced by Fine Particles. J Clinic Toxicol 2:e107. doi: 10.4172/2161-0495.1000e107
Copyright: © 2012 Ohyama M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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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 PM2.5 (PMnumber denotes particulate matter with aerodynamic diameters of <number). This reported link is significantly stronger than the comparable links between asthma and either coarse particles PM2.5–10, or respirable suspended particles PM10 [5,6]. PM2.5 consists mainly of sulfate, nitrate, ammonium, elemental carbon, and organic carbon . Interestingly, the coarser PM2.5–10, which is not so strongly associated with asthma, contains the same components. Therefore, it is difficult to explain the relationship between PM2.5 and asthma by the major components.
How, other than in particle size, does PM2.5 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 PM2.5 these are secondary aerosols and vehicle exhaust, whereas for PM 2.5-10 they are marine and mineral aerosols .The secondary aerosols in PM2.5 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 . 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 PM2.5. 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 . 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 . 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 . A few epidemiological studies have assessed the relationship between HONO, and respiratory symptoms and lung function. Jarvis et al.  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 . 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 . 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 ; reaction of NO2 and particle surface (soot, soil particles (Humic acid), etc.): NO2 + surface (+H2O) → HONO ; reaction of NO and hydroxyl radical, NO + OH·→ HONO ; a primary product of material combustion . Therefore, HONO can be produced spontaneously with NO2 or NO in the atmosphere. Moreover, when NO2 comes in contact with PM2.5, 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 PM2.5 is HONO. We suspect that NO2 must be present on PM2.5 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 PM2.5? 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.