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Toxicological information

Epidemiological data

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Administrative data

epidemiological data
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
December 1987 through February 1988
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented study based on methods and results.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference Type:
Asthmatic Responses to Airborne Acid Aerosols
Bart D. Ostro, Michael J. Lipsett, Matthew B. Wiener, and John C. Selner
Bibliographic source:
American Journal of Public Health, Vol. 81, No. 6: 694-702.

Materials and methods

Study type:
case control study (retrospective)
Endpoint addressed:
respiratory irritation
Test guideline
no guideline available
Principles of method if other than guideline:
This study investigated whether acid aerosols were associated with respiratory symptoms in free-living asthmatics.
GLP compliance:

Test material

Constituent 1
Chemical structure
Reference substance name:
Nitric acid
EC Number:
EC Name:
Nitric acid
Cas Number:
Molecular formula:
nitric acid
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): nitric acid
- Molecular formula (if other than submission substance): N/A
- Molecular weight (if other than submission substance): N/A
- Smiles notation (if other than submission substance): N/A
- InChl (if other than submission substance): N/A
- Structural formula attached as image file (if other than submission substance): N/A
- Substance type: N/A
- Physical state: N/A
- Analytical purity: N/A
- Impurities (identity and concentrations): N/A
- Composition of test material, percentage of components: N/A
- Isomers composition: N/A
- Purity test date: N/A
- Lot/batch No.: N/A
- Expiration date of the lot/batch: N/A
- Radiochemical purity (if radiolabelling): N/A
- Specific activity (if radiolabelling): N/A
- Locations of the label (if radiolabelling): N/A
- Expiration date of radiochemical substance (if radiolabelling): N/A
- Stability under test conditions: N/A
- Storage condition of test material: N/A
- Other: N/A


Type of population:
other: individuals with asthma
Ethical approval:
confirmed, but no further information available
Details on study design:
HYPOTHESIS TESTED (if cohort or case control study): Controlled exposure studies suggest that asthmatics may be more sensitive to the bronchoconstrictive effects of acidic aerosols than individuals without asthma. This study investigates whether acidic aerosols and other air pollutants were associated with respiratory symptoms in free-living asthmatics.

- Type: Review of daily records kept by panelists.
- Details: The panel of asthmatic was asked to record, on a daily basis for several months, information about symptoms, medication use, utilization of medical services, indoor exposures, and other variables. A diary instrument was designed to provide daily information on asthma symptoms, including the presence and severity on a score of 0 to 4 (0=none, 1=mild, 2=moderate, 3=severe, 4=incapacitating) of cough, wheeze, shortness of breath, chest tightness, and sputum production, as well as physician and emergency room visits. In addition, information was obtained on frequency of mediation use, time spent outdoors, levels of exercise intensity and whether exercise occurred indoors or outside, indoor exposure to respiratory irritants (such as gas stove, fireplaces, and environmental tobacco smoke), and occupational exposures. Participants were told that this was an investigation of environmental factor affecting asthma, but not that the principal variables of interest were air pollutants.

STUDY PERIOD: December 1987 through February 1988

SETTING: Denver, Colorado

- Total population: There were 330 intake questionnaires (see below for description) distributed to potential panelists from November 15 to December 16, 1987. Of the initial group recruited, 256 returned the intake questionnaires and began participation in the study. Study subjects were contacted by clinic staff intermittently throughout the study period (December 1987 through February 1988) to enhance compliance and continued participation.
- Selection criteria: Study participants were recruited from patients attending the clinic of one of the co-authors of the publication (John C. Selner). Diagnosis of asthma was made in each case by history and signs of airway obstruction on physical examination, confirmed by spirometric demonstration of obstruction reversible with a B-agonist bronchodilator (>15 percent change in FEV1). Asthmatic patients were identified by clinic staff and were recruited for participation either during an office visit or by telephone and postcard contact. Denver residents between ages 18 and 70 were eligible to participate in the study if they had asthma currently managed with mediation. Individuals with any other chronic medical condition that would restrict their activity were excluded.
- Total number of subjects participating in study: Two hundred and seven patients returned their daily diaries.
- Sex/age/race: there were similar distribution of demographic variables and asthma severity in the initial study population and those who returned the daily diaries. The group under study was predominantly white, females, employed and well educated, with an average age of approximately 46. The mean subjective asthma rating of moderate to severe was supported by the relatively large proportion of individuals taking daily oral theophylline and steroid preparations.
- Smoker/nonsmoker: There percentages of current smokers in the total study population (n=256) and diary participants (n=207) are 3.1 and 3.0, respectively.
- Total number of subjects at end of study: Two hundred and seven patients completed the study and returned their diaries.
- Matching criteria: N/A
- Other: Participants were required to fill out an intake questionnaire providing background data on demographics (age, sex, race, level of education, employment status, and residential history), asthma severity and characteristic triggers and symptoms, medical history including medication use, smoking history, and previous environmental exposure.

- Type: N/A
- Details: N/A

- Disease(s): N/A
- ICD No.: N/A
- Year of ICD revision: N/A
- Diagnostic procedure: N/A
- Other health effects: respiratory symptoms in asthmatic patients

Exposure assessment:
Details on exposure:
The ambient air pollutants incorporated in the analysis were daily measures of sulfated, nitrate, PM2.5, nitric acid, hydrogen ion (H+) and sulfur dioxide. Two different pollutant averaging times were considered initially: the 24-hour average (ending at 4:00 pm on the reporting day) of pollutant readings from the monitor in downtown Denver, located about two miles from the clinic; and the daytime average (9:00 am to 4:00 pm) from the same monitor. Since these averaging times were highly correlated (usually r>0.90), only the daytime average was used in subsequent analysis. A second monitor located about seven miles away in the northwestern suburb of Arvada, also provided measurements of these pollutants. The mean value of nitric acid was 1.81 ug/m3. The study found no statistically significant relationship between any pollutant and with the number of the day of survey period or whether the reading was on a weekday or weekend and no significant time trend for either daily minimum temperature or daily humidity.
There was substantial covariation among some of the pollutants; the highest correlations were observed between PM2.5 and sulfates (r=.88), and between nitrates and nitric acid (r=0.78). Sulfates and H+ were both negatively correlated with maximum daily temperature. Of the pollutants measured on a daily basis, sulfates had the most complete data. Values for missing days of PM2.5 and nitrates were derived from stepwise regressions using all other pollutants. PM2.5 could be predicted well by concurrent values of sulfates and nitrates (r=0.97), and nitrates could be predicted by nighttime (4:00 pm to 9:00 am the following day) PM2.5 readings (r=0.86).
The data on H+ required additional attention. Because of problems in sample processing, the H+ data were available only for half of the study period. The first seven days of H+ readings were extremely high, with a mean of 288 nanoequivalents per cubic meter (neq/m3) versus a mean of 10.1 for the following 28 days. The hydrogen ion concentrations during the first seven days were also unrelated to any other pollutant or meteorologic variables, while during the next 28 days there was a correlation, as expected between H+ and sulfates (r=0.66). Consequently, the first seven days were dropped from the subsequent analysis. For H+, missing values for the entire survey period were predicted using regression results with concurrent sulfate as the explanatory variable. With these substitutions, the daytime mean of H+ was 8.15 neq/m3 or approximately 0.4 ug/m3 measured as sulfuric acid, with the highest daily average of 44 neq/m3. All subsequent analysis of H+ combined actual and imputed values. The one-hour peak may be three to four times higher than this longer-term average. These levels were typical of urban areas. Analysis of the two monitors recording H+ indicated that the concentrations of airborne acidity were fairly evenly distributed throughout the Denver area; the daily correlation of the readings was 0.88. Thus, the one downtown monitor was used to represent daily levels of H+. Ozone concentration, which frequently are highly correlated with sulfates and acids in the summer, were essentially at background levels through the winter in Denver (i.e. the maximum one-hour concentration was 0.042 ppm) and do not correlate with H+ concentrations.
Previous research suggested that incorporating information on exercise and time spent outdoors would improve the estimate of exposure. Therefore, the study developed a measure of exposure that involved the product of the ambient pollution level, the duration of exposure, the time spent indoors and outdoors, and the ventilation rates based on exercise level (i.e. ventilation rates of 7, 10, 25 and 40 liters per minute for resting, mild, moderate, or strenuous exercise, respectively). Since the actual time and duration of exercise was not recorded in the diary, it was assumed to occur during the day and to last for one hour. Hours outdoors and exercise levels were taken directly from the daily diary, while the penetration ratio of indoor to outdoor levels of H+ of 0.3 was derived from the published literature. This adjustment for exposure was crude but represented an improvement over simply using outdoor levels of air pollution. The extent of the reduction in measurement error (and improvement in exposure assessment) was specifically tested in the subsequent analysis.
All data from questionnaires, daily diaries, air quality and meteorologic monitoring were recorded and edited in a SAS format for analysis.
Statistical methods:
See "any other information on materials and methods" section below.

Results and discussion

- Number of measurements: N/A
- Average concentrations: N/A
- Arithmetic mean: N/A
- Geometric mean: N/A
- Median: N/A
- 95-Percentile: N/A
- Standard deviation: N/A
- Date(s) of measurement(s): N/A
- Other: N/A

FINDINGS: Nitric acid was not associated with moderate cough, asthma, or shortness of breath. The results did not change when exposure-adjusted measures were used.

- Incidence/ Number of cases for each disease / parameter under consideration: N/A
- Other: N/A

- SMR (Standard mortality ratio): N/A
- RR (Relative risk): N/A
- OR (Odds ratio): N/A
- Other: N/A

Confounding factors:
Strengths and weaknesses:

Any other information on results incl. tables


Applicant's summary and conclusion

This study investigated whether acidic aerosols and other air pollutants are associated with respiratory symptoms in free-living asthmatics. Nitric acid was not associated with moderate cough, asthma, or shortness of breath. The results did not change when exposure-adjusted measures were used.
Executive summary: