Oxidative Stress Index ( OSI ) Condensed Questionnaire

Elevated oxidative stress (OS) is well known to be a direct cause of disease [Kelly, 2003; Zeliger 2016; Riggs, et al., 2020] and the oxidative stress index (OSI) has been shown to be an indicator of the likelihood of noncommunicable disease onset [Zeliger, 2017]. The OSI can also be used in multiple other applications, including predicting disease causing parameters for Alzheimer’s disease and other diseases [Zeliger, 2019], as a public health survey instrument [Zeliger, 2019a], predicting adverse drug reactions [Zeliger, 2019a] and as a health prescreening tool and for health screening in areas with limited medical facilities and personnel [Zeliger, 2017]. The detailed OSI is based upon responses to a detailed questionnaire that address all contributory items to a person’s OS level. In addition to being a valuable predictor of disease onset likelihood, it is also an indicator of lifestyle changes that can be made to lower OS and thereby help prevent disease. The OSI addresses genetics, age, weight, illnesses, conditions that are exacerbated by increased OS, medical symptoms, clinical laboratory results, prescription medications regularly taken, lifestyle and emotional stress. The length of the detailed OSI questionnaire (containing more than 400 items), however, does not readily lend itself to regular use in clinical settings. Presented here and shown in table 1 is a condensed form of the OSI questionnaire, containing only eight parts, which can be readily used as a screening device to indicate the OSI level. Analysis has shown that OSI values obtained from the condensed OSI form produce scores that are nearly identical to those obtained from the original detailed OSI form. Accordingly, the condensed form can serve as a preliminary screening device to flag potential problems. Those with elevated OSIs in the condensed form can then use the detailed form to help identify specific causes of elevated OS. This can lead to clinically relevant follow up and preventive measures. The modified, currently used, detailed OSI form is shown in Table 2.


I. INTRODUCTION
Elevated oxidative stress (OS) is well known to be a direct cause of disease [Kelly, 2003;Zeliger 2016;Riggs, et al., 2020] and the oxidative stress index (OSI) has been shown to be an indicator of the likelihood of noncommunicable disease onset [Zeliger, 2017]. The OSI can also be used in multiple other applications, including predicting disease causing parameters for Alzheimer's disease and other diseases , as a public health survey instrument [Zeliger, 2019a], predicting adverse drug reactions [Zeliger, 2019a] and as a health prescreening tool and for health screening in areas with limited medical facilities and personnel [Zeliger, 2017].
The detailed OSI is based upon responses to a detailed questionnaire that address all contributory items to a person's OS level. In addition to being a valuable predictor of disease onset likelihood, it is also an indicator of lifestyle changes that can be made to lower OS and thereby help prevent disease. The OSI addresses genetics, age, weight, illnesses, conditions that are exacerbated by increased OS, medical symptoms, clinical laboratory results, prescription medications regularly taken, lifestyle and emotional stress.
The length of the detailed OSI questionnaire (containing more than 400 items), however, does not readily lend itself to regular use in clinical settings. Presented here and shown in table 1 is a condensed form of the OSI questionnaire, containing only eight parts, which can be readily used as a screening device to indicate the OSI level. Analysis has shown that OSI values obtained from the condensed OSI form produce scores that are nearly identical to those obtained from the original detailed OSI form. Accordingly, the condensed form can serve as a preliminary screening device to flag potential problems. Those with elevated OSIs in the condensed form can then use the detailed form to help identify specific causes of elevated OS. This can lead to clinically relevant follow up and preventive measures. The modified, currently used, detailed OSI form is shown in Table 2. The eight items in the condensed form are; age, personal information, prevalent diseases, medications taken, genetics, education level, place of residence and psychological stress. As discussed below, these include all major sources of OS elevation and produce OSI values that are within 90 percent of those obtained using the detailed OSI questionnaire.

II. METHODS
The OSI condensed form is based upon health impacts of the various parameters as reported in the literature. The scoring assignments for the individual parameters in the condensed form are based upon experience with the detailed OSI form. The point values assigned to each parameter are based upon those obtained via the detailed OSI questionnaire.

A. Age
Aging is accompanied by an increase in OS, generally starting around age 40 and continuing throughout life [Epel, et al., 2004;Hou, et al., 2015]. Accordingly, one OSI point is scored for each decade. For one aged 40-49, one OSI point is added to his or her total, 2 points are added for those aged 50-59, etc. [Zeliger, 2017].

B. Personal
Being overweight is associated with elevated OS and the onset of numerous diseases. Excessive weight is a worldwide health issue that continues to grow. In the United States, more than 70 percent of adults are overweight, more than half of whom are obese [CDC, 2018]. Diseases associated with excess weight include, but are not limited to; hypertension, dyslipidemia, type 2 diabetes, coronary heart disease, stroke, gallbladder disease, osteoarthritis, sleep apnea, breathing difficulties, anxiety, depression and several cancers (endometrial, breast, colon, kidney, liver and gallbladder [CDC, 2015]. Gender, height and weight information enables one to determine if the person is of normal weight, is heavy, or obese. The original detailed OSI addresses weight impact by number of pounds a person is overweight [Zeliger, 2017. The condenses OSI categorizes weight into three categories; normal, overweight and obese. Normal weight is assigned a value of zero. Heavy individuals are assigned a score of 1 and obese people are assigned a score of 2.

C. Chronic Prevalent Diseases
The number of prevalent diseases at the time of OSI measurement is a critical indicator of OS. It is well established that disease increases total OS and hence the OSI [Zeliger, 2016;Zeliger 2017]. All diseases have symptoms associated with them. These are individually addressed in the detailed OSI. The OSI condensed form does not probe individual symptoms. Rather, it has been found that assigning five points for each prevalent disease adequately incorporates elevations in OS associated with the prevalent diseases. Respondents are asked to list all diseases they currently have been diagnosed with. Multiplying the number of prevalent diseases by five yields the disease number in the condensed OSI.

D. Medications
Essentially all pharmaceutical medications raise OS [Zeliger, 2017] and all have adverse drug reactions associated with them [Zeliger, 2019b]. The detailed OSI form addresses these individually. In the condensed form, one OSI point is assigned for each medication taken.

E. Genetics
Genetics is well known to be a factor in most noncommunicable diseases [Dato, et al., 2013;Jiang, et al., 2013;Guillaumet-Adkins, et al., 2017]. Indeed, many diseases such including Alzheimer's disease, Parkinson's disease and cancers, just to name and few, "run in families." Recently, epigenetics, as well, has been shown to lead to heritable diseases [Cencioni, et al., 2013;Guillaumet-Adkins, et al., 2017]. Though all non-communicable diseases are more prevalent in those whose ancestors have suffered from those diseases, parental disease is most closely associated with the likelihood of disease onset in an individual [Awdeh, et al., 2006]. Both genetic traits and epigenetic effects raise OS [Cencioni, et al., 2013;Dato, et al., 2013;Jiang, et al., 2013;Guillaumet-Adkins, et al., 2017]. In the condensed OSI form, respondents are asked to check which of their prevalent diseases were also prevalent in their parents and each genetic limk is assigned a value of one OSI point.

F. Education
Socioeconomic status (SES) is well established as an indicator of detrimental lifestyle choices that raise OS [Mielck, et al., 2014]. These lifestyle choices include diets high in fats, sugar, salt or processed foods, tobacco, alcohol and recreational drug abuse, radiation exposure and the need to reside or work in a toxic environment Zeliger, 2016]. SES is also associated with an increased likelihood of having undiagnosed diseases [Bein, et al., 2012;Mielck, et al., 2014;Shaw, et al., 2016].
The detailed OSI lists numerous items that address these points. In the condensed form, all of these are factored into SES as indicated by highest educational level achieved. Educational achievement has been shown to be a valid indicator of SES, with lower SES individuals more likely more likely to lead unhealthy, OS raising life styles and to have undiagnosed diseases [Yin, et al., 2017]. In the condensed OSI form, 5 education levels are identified: some high school, high school graduate, some college, college graduate and graduate degree. These are assigned 5,4,3,2 and 1 OSI point respectively.
SES can also be obtained from annual income information, but asking income information can be considered being nosy and discourage some people from completing the questionnaire. Hence, income is not used in the condensed OSI questionnaire.

G. Residence
In the 21 st century, 90 percent of the world's people, regardless of SES, are exposed to air pollution, as air quality is the same on both sides of the tracks [Combes and Franchineau, 2019;World Health Organization, 2018]. All air pollutants are toxic, raise OS in a dose response relationship, impact the OSI, and are responsible for the onset of numerous diseases including respiratory diseases, cardiovascular diseases, several cancers and Alzheimer's disease [Combes and Franchineau, 2019;Zhou, et al., 2019;Xia, et al., 2019;Kilian J and Kitazawa M, 2018].
Recently, a method to quantify air pollution impact on disease onset, termed the Air Quality Toxicity Index (AQTI) has been reported . This method, based upon the dose response relationship between toxic exposure and OS elevation [Zeliger, 2016 and the numerous references contained therein], enables the classification of air quality for individual locations to be calculated and reported as cumulative annual values.
In America, the United States Environmental Protection Agency (EPA) measures air quality in multiple locations on a daily basis and reports the data on-line daily as the Air Quality Index (AQI) [EPA, 2019]. Worldwide, the World Air Quality Project similarly reports air quality data for hundreds of cities. [World Air Quality Index Project, 2019]. On an annual basis, these indices identify the number of days in which the air quality in a given locale is classified as either good, moderate, unhealthy for sensitive groups, unhealthy, very unhealthy or hazardous. Hazard numbers ranging from 1 -6 have been assigned to the six air quality classifications, as follows .

Air Quality Classification
Hazard The air pollution impact on OSI is obtained by multiplying the number of days per year for each of the six EPA classifications at the residence of the responder by the hazard number for that classification and adding the these up to yield the AQTI total as shown in table 3. Also shown in table 3. are the OSI air pollution severities (OSI -AP). These are assigned number values from 0-5, and entered into the OSI condensed form. It should also be noted that EPA publishes daily and annual air quality data for cities and counties in all U.S. states [EPA, 2019].

H. Chronic Psychological Stress
Psychological stress, anxiety and depression are associated with most diseases and are more pronounced as illnesses progress [Sahle, et al., 2020]. Psychological stress, anxiety and depression raise OS via the release of hormones that elevate OS. Chronic activation of this stress response system results in disease and triggers numerous health problems [Mayo Clinic, 2019], including: Anxiety Depression Memory and concentration issues Digestive problems Headaches Heart disease Sleep problems Weight gain Respondents are asked to check if they often feel stressed, anxious or depressed. One point is assigned for each positive response.
The relevance of the OSI to predicting disease onset probability as well as for other applications uses has been previously established [Zeliger, 2017[Zeliger, , 2019a[Zeliger, , 2019b[Zeliger, , 2019c. When the OSI condensed form values are used as presented here an excellent correlation between standard form and condensed form OSI values obtains, with condensed form values showing less than a 10% variation from standard form values.
To sum up, the point values assigned to each of the parameters contained in the OSI condensed questionnaire are as follows: Age 1 for each decade of age starting at age 40. Personal 0,1, or 2, depending upon weight status Diseases 5 per prevalent disease Medications 1 per prescribed or over-the-counter medication regularly taken Genetics 1 per each item checked Education 5,4,3,2 or 1, depending upon highest education level achieved Residence 0,1,2,3,4, or 5, depending upon air pollution level at residence Stress 0,1,2 or 3, depending upon chronic psychological status The OSI score has been shown to be related to the likelihood of further disease onset as follows [Zeliger, 2017] Though the OSI can predict the likelihood of disease onset, it cannot predict which disease(s) are likely to strike.
The condensed OSI form has multiple uses, including the following: -Part of routine medical examinations to alert clinicians to potential illnesses in seemingly healthy people. -Use as a screening aid in areas with limited medical personnel and facilities. -Serving to identify lifestyle changes that will lower OS and likelihood of disease onset. -Taking of public health surveys to identify disease clusters arising from exposures to chronic exposures to toxic chemicals. -Making community medical need projections including estimating clinical staffing and resource needs.
-Serving as an indicator of the need to have a person fill out the detailed OSI form which can alert clinicians to specific potential problems. -Researching sequences of disease onset in those with multiple diseases. -Predicting numbers of people likely to ail with noncommunicative diseases in different geographic areas. The detailed OSI questionnaire has been modified since it was first introduced. The form currently in use to build a data base has the condensed form questions embedded in it, thus facilitating a comparison of the two forms.
The OSI condensed form does have limitations. It does not probe as yet undiagnosed diseases, conditions and symptoms that are addressed in the detailed form. Also, to date the number of OSI questionnaire responders evaluated is not yet large enough to yield statistically significant data. Work in this area is ongoing, with the understanding that the point values of the condensed form OSI can be adjusted, if necessary, and that additional parameters could be added to the eight reported here, if indicated. Despite the limitations just noted, preliminary results indicate that the condensed OSI form produces values that are 90 percent or more in agreement with that from the detailed OSI form.

IV. CONCLUSIONS
The premise of this paper is that a questionnaire consisting of eight parameters can be used to determine the OSI and that these are representative of all sources of oxidative stress elevation.
The eight parameters used to calculate the condensed form OSI all raise OS levels in dose response relationships [Zeliger, 2016]. These have all been shown to be additive in predicting disease onset likelihood, demonstrating that multiple causes of the same disease are probable, and that no single cause need be the sole one .
The condensed form of the OSI is a simplified version of the detailed OSI and that like the detailed OSI, can be used to predict the likelihood of disease onset.