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The prevalence of allergic airway diseases such as asthma and rhinitis has increased dramatically to epidemic proportions worldwide. Besides air pollution from industry derived emissions and motor vehicles, the rising trend can only be explained by gross changes in the environments where we live. The world economy has been transformed over the last 25 years with developing countries being at the core of these changes. Around the planet, in both developed and developing countries, environments are undergoing profound changes. Many of these changes are considered to have negative effects on respiratory health and to enhance the frequency and severity of respiratory diseases such as asthma in the general population.Increased concentrations of greenhouse gases, and especially carbon dioxide (CO2), in the atmosphere have already warmed the planet substantially, causing more severe and prolonged heat waves, variability in temperature, increased air pollution, forest fires, droughts, and floods – all of which can put the respiratory health of the public at risk. These changes in climate and air quality have a measurable impact not only on the morbidity but also the mortality of patients with asthma and other respiratory diseases. The massive increase in emissions of air pollutants due to economic and industrial growth in the last century has made air quality an environmental problem of the first order in a large number of regions of the world. A body of evidence suggests that major changes to our world are occurring and involve the atmosphere and its associated climate. These changes, including global warming induced by human activity, have an impact on the biosphere, biodiversity, and the human environment. Mitigating this huge health impact and reversing the effects of these changes are major challenges.This statement of the World Allergy Organization (WAO) raises the importance of this health hazard and highlights the facts on climate-related health impacts, including: deaths and acute morbidity due to heat waves and extreme meteorological events; increased frequency of acute cardio-respiratory events due to higher concentrations of ground level ozone; changes in the frequency of respiratory diseases due to trans-boundary particle pollution; altered spatial and temporal distribution of allergens (pollens, molds, and mites); and some infectious disease vectors. According to this report, these impacts will not only affect those with current asthma but also increase the incidence and prevalence of allergic respiratory conditions and of asthma. The effects of climate change on respiratory allergy are still not well defined, and more studies addressing this topic are needed. Global warming is expected to affect the start, duration, and intensity of the pollen season on the one hand, and the rate of asthma exacerbations due to air pollution, respiratory infections, and/or cold air inhalation, and other conditions on the other hand.

CYP2E1, a cytochrome P-450 that is well conserved across mammalian species, metabolizes ethanol and many low molecular weight toxins and cancer suspect agents. The cyp2e1 gene was isolated, and a mouse line that lacks expression of CYP2E1 was generated by homologous recombination in embryonic stem cells. Animals deficient in expression of the enzyme were fertile, developed normally, and exhibited no obvious phenotypic abnormalities, thus indicating that CYP2E1 has no critical role in mammalian development and physiology in the absence of external stimuli. When cyp2e1 knockout mice were challenged with the common analgesic acetaminophen, they were found to be considerably less sensitive to its hepatotoxic effects than wild-type animals, indicating that this P-450 is the principal enzyme responsible for the metabolic conversion of the drug to its active hepatotoxic metabolite.Cytochromes P-450 (P-450) 1 are a superfamily of hemoproteins that carry out oxidative metabolism of many endogenous and foreign chemicals (1). In mammals, P-450s can be functionally segregated into two groups, those that participate in biochemical pathways leading to the synthesis of steroid hormones and those that primarily metabolize foreign chemicals or xenobiotics such as drugs. The latter enzymes are included in the CYP1, CYP2, CYP3, and CYP4 families (2). Many of the hepatic xenobiotic-metabolizing P-450s also metabolize endogenous compounds, but the significance of these reactions is questionable. A clue to the lack of a critical role for many of the P-450s, particularly those in family 2, in development, reproduction, and longevity, is the marked species differences in their expression and catalytic activities (3). However, some of the xenobiotic-metabolizing P-450s are well conserved, including those in the CYP1 family and CYP2E1, suggesting that they may perform an important physiological function.CYP2E1 is the principal P-450 responsible for the metabolism of ethanol and is considered as a major component of the microsomal ethanol-oxidizing system (4, 5). Among xenobiotics metabolized by CYP2E1 are acetaldehyde, acetaminophen, acrylamide, aniline, benzene, butanol, carbon tetrachloride, diethylether, dimethyl sulfoxide, ethyl carbamate, ethylene chloride, halothane, glycerol, ethylene glycol, N-nitrosodimethylamine, 4-nitrophenol, pyrazole, pyridine, and vinyl chloride (6). Many of these chemicals are known toxins, established chemical carcinogens, or suspected carcinogens. CYP2E1-mediated oxidation of a variety of substrates is also believed to liberate a substantial amount of reactive oxygen that can lead to membrane lipid peroxidation and cell toxicity (7).CYP2E1 is also capable of metabolizing endogenous chemicals including acetone and acetol, which are key metabolites in the methylglyoxal and propanediol pathways of gluconeogenesis (8, 9). CYP2E1 can also carry out the metabolism of arachidonic acid, resulting in the production of several hydroxyeicosatetraenoic acids (10), some of which may have physiological and pharmacol...

CYP1B1-null mice, created by targeted gene disruption in embryonic stem cells, were born at the expected frequency from heterozygous matings with no observable phenotype, thus establishing that CYP1B1 is not required for mouse development. CYP1B1 was not detectable in cultured embryonic fibroblast (EF) or in different tissues, such as lung, of the CYP1B1-null mouse treated with the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin whereas the equivalent wild-type EF cells express basal and substantial inducible CYP1B1 and lung expresses inducible CYP1B1. CYP1A1 is induced to far higher levels than CYP1B1 in liver, kidney, and lung in wild-type mice and is induced to a similar extent in CYP1B1-null mice. 7,12-dimethylbenz[a]anthracene (DMBA) was toxic in wild-type EFs that express CYP1B1 but not CYP1A1. These cells effectively metabolized DMBA, consistent with CYP1B1 involvement in producing the procarcinogenic 3,4-dihydrodiol as a major metabolite, whereas CYP1B1-null EF showed no significant metabolism and were resistant to DMBA-mediated toxicity. When wild-type mice were administered high levels of DMBA intragastrically, 70% developed highly malignant lymphomas whereas only 7.5% of CYP1B1-null mice had lymphomas. Skin hyperplasia and tumors were also more frequent in wild-type mice. These results establish that CYP1B1, located exclusively at extrahepatic sites, mediates the carcinogenicity of DMBA. Surprisingly, CYP1A1, which has a high rate of DMBA metabolism in vitro, is not sufficient for this carcinogenesis, which demonstrates the importance of extrahepatic P450s in determining susceptibility to chemical carcinogens and validates the search for associations between P450 expression and cancer risk in humans.Cytochromes P450 (P450) are a superfamily of hemecontaining monooxygenases. A limited number of P450s participate in pathways of steroid hormone synthesis whereas the majority of these enzymes are involved in oxidative metabolism of drugs, other foreign compounds, and endogenous substrates, including steroids (1). These xenobioticmetabolizing P450s mostly fall within the CYP1, CYP2, and CYP3 families and exhibit broad and sometimes overlapping substrate specificity. A limited number of P450s within these families are responsible for the metabolic activation of chemical carcinogens. In the CYP1 family, CYP1A1 and CYP1B1 metabolically activate polycyclic aromatic hydrocarbons and CYP1A2 participates in the metabolic activation of arylamine, heterocylic amines, and aflatoxin B1. CYP2E1 activates a large number of low molecular weight carcinogens including benzene and N-nitrosodimethylamine. These carcinogenmetabolizing P450s are also among the most well conserved of the P450 superfamily and can be found in several mammalian species, including mouse and human (2). CYP1B1 is a conserved member of the P450 superfamily that was first identified and purified from mouse embryonic fibroblasts (EFs) (3) and rat adrenals (4). This form was characterized by its ability to metabolically act...