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Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

5
RESPIRATORY OUTCOMES

This chapter focuses on several long-term respiratory conditions: asthma, chronic bronchitis, emphysema, and chronic obstructive pulmonary disease (COPD). The nature of respiratory symptoms and the reversibility of airway obstruction distinguish asthma from the other respiratory conditions listed above.

Asthma is marked by reversible airway obstruction and airway inflammation. People with asthma manifest symptoms—such as wheezing, coughing, and exertional dyspnea—that are accompanied by increased airflow obstruction. Chronic bronchitis is characterized by chronic cough and sputum production. Pulmonary emphysema (commonly referred to as emphysema) is a pathologic process involving air-space enlargement distal to the terminal bronchioles, accompanied by destruction of the bronchiolar walls. COPD includes chronic bronchitis and emphysema. The diagnosis of COPD requires objective evidence of airflow obstruction with spirometry according to GOLD1 criteria (Pauwels et al. 2001).

The epidemiologic literature covering environmental agents and respiratory conditions has used varying definitions as knowledge has evolved. Summaries of key studies used by the committee in drawing its conclusions include details of how respiratory conditions were defined. Because of the impracticality of spirometry for large-scale epidemiologic studies, researchers often asked respondents about “physician-diagnosed” respiratory conditions or about respiratory symptoms. The hallmark symptom of asthma is wheezing, and that of chronic bronchitis is persistent cough and phlegm production (usually lasting 3 months/year for more than 2 years). For the last half-century, epidemiologic studies have used standard questions about cough and phlegm or sputum to define chronic bronchitis. Definitive diagnosis of emphysema requires pathologic examination of lung tissue or high-resolution thoracic computed tomography, although it can be inferred from characteristic physiologic changes, such as reduction in diffusion capacity.

The present report focuses on induction rather than exacerbation of disease, so this chapter emphasizes incident cases rather than exacerbation of pre-existing disease (for example, Eisner et al. 2002; Hong et al. 1994). Studies of prevalent disease are also included because they cover both new cases and exacerbation of preexisting conditions. The committee excluded the numerous time-series studies as they examine episodes of daily morbidity or mortality. Time-

1  

World Health Organization Global Initiative for Chronic Obstructive Lung Disease (GOLD).

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

series studies do not consider pre-existing conditions and report on acute outcomes rather than long-term health effects. For relevance to Gulf War veterans, the committee focused on long-term respiratory effects that persist after exposure ceases (see Chapter 2).

The first section of this chapter will discuss respiratory outcomes related to exposure to fuels, and the next section will discuss outcomes related to exposure to combustion products. The section on combustion products has the benefit of several large epidemiologic studies of Gulf War veterans who had objectively confirmed exposure to smoke from oil-well fires.

FUELS AND RESPIRATORY OUTCOMES

Most studies of fuel exposure reviewed by the committee were cohort-mortality studies. They included Australian petroleum-industry workers (Christie et al. 1987), Chevron petroleum-refinery workers (Dagg et al. 1992), Exxon refinery and chemical-plant workers (Hanis et al. 1985), US petroleum-refinery workers (Kaplan 1986), UK oil-refinery workers (Rushton and Alderson 1981), and petroleum-refinery workers in Beaumont, Texas (Wong et al. 2001a) and Torrance, California (Wong et al. 2001b). The occupational-cohort studies, which had multiple outcomes apart from respiratory disease, are described briefly in Appendix D.

All the occupational studies examined mortality due to noncancer respiratory outcomes among petroleum workers. Generally, the studies failed to indicate specific respiratory outcomes, although some do examine asthma, bronchitis, emphysema, and pneumonia or influenza separately. Most studies group all respiratory outcomes under the broad heading of “diseases of the respiratory system or tract” or “non-malignant respiratory disease”.

Nonmalignant Respiratory Disease

The studies that examined nonmalignant respiratory disease (Christie et al. 1987; Dagg et al. 1992; Hanis et al. 1985; Kaplan 1986; Wong et al. 2001a, 2001b) included all respiratory disorders, such as acute infections, diseases of the upper respiratory tract, pneumonia and influenza, asthma, bronchitis, emphysema, COPD, pneumoconiosis and other diseases due to external agents (such as asbestos), and other respiratory diseases. In all of those studies, the standardized mortality ratios (SMRs) were below 1.0 when compared with the general population or those not employed in the petroleum industry; this indicates that persons involved in the petroleum industry are not at greater risk for dying from respiratory diseases than the general population. However, selection bias is a limitation of the studies cited above because of the “healthy-worker” effect.

In addition to the retrospective mortality studies identified above, the committee reviewed a cross-sectional study of Norwegian cable-plant workers exposed to oil mist or kerosene vapors (Skyberg et al. 1986). Seven cases of pulmonary fibrosis were found in 25 workers compared with one case in the control group. In a followup study of those workers (Skyberg et al. 1992), the authors examined whether the progression of pulmonary fibrosis continued after exposure to oil mist and vapors ceased and found that 10 of the 25 workers had pulmonary fibrosis compared with one in the control group. Smoking and exposure to asbestos were possible confounders in both studies.

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

Asthma

Occupational factors are estimated to account for about 15% of the total burden of adult asthma (Balmes et al. 2003). Asthma is the most commonly reported occupational lung disease in most industrialized countries, and trends from long-standing surveillance in Finland and the UK show little change in incidence of occupational asthma over the last 10 years (Meyer et al. 2001; Reijula et al. 1996).

Four cohort studies of refinery workers (Kaplan 1986); Rushton and Alderson 1981; Wong et al. 2001a, 2001b) did not find an increased risk of asthma compared with that in the general population, however, that may be due to the “healthy worker” effect which might involve self-selection against having asthma specifically. All the SMRs were below 1.0.

The committee reviewed two case reports of asthma due to prolonged exposure to kerosene vapor from accidental domestic oil storage-tank spills (Todd and Buick 2000) and exposure to aviation fuel in an aircraft-engine mechanic (Makker and Ayres 1999). Six adults and three children were exposed to kerosene vapor, and one adult and the three children developed asthma that persisted for 3 years after the incident.

A 42-year-old aircraft-engine mechanic reported being exposed to both high concentrations of aviation-fuel vapors and jet-stream emissions from aircraft engines. He developed symptoms almost immediately on beginning his job and was diagnosed with asthma within 4 years. The man reported that his symptoms improved when he was away from work for periods of at least 2 or 3 days.

A review article by Rodriguez de 1a Vega et al. (1990) cites a study (Rodriguez de 1a Vega et al. 1981) in which 286 asthmatic patients who used kerosene for cooking were followed for 5 years. The authors found that 43.9% of those whose asthma did not improve continued to use kerosene as fuel for cooking; this suggests a relationship between exposure to kerosene and asthma.

Chronic Bronchitis and Emphysema

Rushton and Alderson (1981) and Wong et al. (2001a, 2001b) examined rates of bronchitis among refinery workers. Two of the three studies found no increased risk, however, one study found an SMR of 1.32, with a 95% confidence interval (CI) of 0.27–3.84 (Wong et al. 2001b).

Three studies (Kaplan 1986; Wong et al. 2001a, 2001b) examined at emphysema and found SMRs of 1.0 or less, indicating no increased risk among refinery workers compared with the general population. The healthy-worker effect probably contributed to the results.

Summary and Conclusion

A fairly extensive literature describes results of cohort studies designed to examine mortality in workers in the petroleum industry (Table 5.1). Generally, those studies did not provide information about specific respiratory disease outcomes but rather provided SMRs for broad categories of diseases that are designated as “diseases of the respiratory system or tract” or “non-malignant respiratory disease.” The studies generally did not report exposure assessment, so it is difficult to reach a conclusion as to a relationship between respiratory disease outcomes and exposure to fuels. Most of the studies indicate a healthy-worker effect, which complicates interpretation of their results.

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

The committee concludes, from its assessment of the epidemiologic literature, that there is inadequate/insufficient evidence to determine whether an association exists between exposure to fuels and any specific, nonmalignant respiratory outcomes including asthma, bronchitis, and emphysema.

COMBUSTION PRODUCTS AND RESPIRATORY OUTCOMES

The committee divided the epidemiologic literature of respiratory effects and exposure to combustion products into four general types: studies of Gulf War veterans exposed to oil-well fires, community air pollution studies, occupational studies, and studies of biomass fuel, which is burned for heating or cooking primarily in developing countries. Each part of this section begins with the most robust primary studies (that is, studies with strong methods and exposure information), and continues with mortality studies and support studies that add weight to the primary evidence but are not as methodologically robust. Key primary studies used to draw conclusions are also depicted in tables (Tables 5.1 to 5.5). Most studies reported on more than one respiratory condition.

TABLE 5.1 Selected Epidemiologic Studies—Fuel Exposure and Respiratory Outcomes

Reference

Population

Exposed Cases

Estimated Relative Risk (95% CI)

Nonmalignant Respiratory Disease

Cohort Studies—Mortality

Christie et al. 1987

Australian petroleum workers (range of ICD-9 codes used)

0

0.00 (0.00–0.44)

Dagg et al. 1992

Chevron petroleum-refinery workers (range of ICD-8 codes used)

 

 

 

Richmond Plant

118

0.69 (0.57–0.82)

El Segundo Plant

59

0.59 (0.45–0.76)

Total

177

0.65 (0.56–0.75)

Hanis et al. 1985

Exxon refinery and chemical-plant workers (range of ICD-8 codes used)

 

 

 

Total

164

0.64 (0.55–0.75)

Active employees

16

0.27 (0.15–0.44)a

Employees hired before 1956

162

0.65 (0.55–0.75)a

White men

150

0.64 (0.54–0.75)a

Black men

14

0.82 (0.45–1.37)a

Baton Rouge plant

66

0.71 (0.55–0.91)

Baytown plant

48

0.70 (0.52–0.93)

Bayway/Bayonne plant

50

0.54 (0.40–0.71)

Kaplan 1986

US petroleum-refinery workers (range of ICD-8 codes used)

167

0.64 (0.54–0.74)

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

Reference

Population

Exposed Cases

Estimated Relative Risk (95% CI)

Wong et al. 2001a

Beaumont, Texas, refinery workers (range of ICD-8 codes used)

 

 

 

Entire cohort

155

0.62 (0.52–0.72) (p<0.01)

Female employees

1

0.16 (0.004–0.86)

Male employees

154

0.63 (0.53–0.73) (p<0.01)

Length of employment, <10 years

14

0.56 (p<0.05)

Length of employment, 10–29 years

51

0.74 (p<0.05)

Length of employment, 30+ years

89

0.59 (p<0.01)

Time since employment, <20 years

4

0.33 (p<0.05)

Time since employment, 20–39 years

51

0.74 (p<0.05)

Time since employment, 40+ years

99

0.60 (p<0.01)

Wong et al. 2001b

Torrance, California, refinery workers (range of ICD-8 codes used)

 

 

 

Entire cohort

55

0.79 (0.60–1.03)

Length of employment, <10 years

8

0.77

Length of employment, 10–29 years

34

0.79

Length of employment, 30+ years

13

0.86

Time since employment, <20 years

2

0.35

Time since employment, 20–39 years

21

0.77

Time since employment, 40+ years

32

0.90

Cohort Study—Incidence

Tsai et al. 1992

Shell Deer Park refinery and petroleum workers (range of ICD-9 codes used)

725

1.05 (0.98–1.13)

 

Production employees, 1981–1988

646

1.08 (1.00–1.17)

 

Staff employees, 1981–1988

79

0.88 (0.69–1.09)

Asthma

Cohort Studies—Mortality

Kaplan 1986

US petroleum-refinery workers (range of ICD-8 codes used)

5

0.79 (0.26–1.85)

Rushton and Alderson 1981

UK oil-refinery workers (range of ICD-8 codes used)

15

0.80 (0.45–1.32)a

Wong et al. 2001a

Beaumont, Texas, refinery workers (range of ICD-8 codes used)

 

 

 

Entire cohort

3

0.78 (0.16–2.28)

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

Reference

Population

Exposed Cases

Estimated Relative Risk (95% CI)

Bronchitis

Cohort Studies—Mortality

Rushton and Alderson 1981

UK oil refinery-workers (range of ICD-8 codes used)

253

0.64 (0.57–0.73)a

Wong et al. 2001a

Beaumont, Texas, refinery workers (range of ICD-8 codes used)

 

 

 

Entire cohort

3

0.34 (0.07–0.99)

Wong et al. 2001b

Torrance, California, refinery workers (range of ICD-8 codes used)

 

 

 

Entire cohort

3

1.32 (0.27–3.84)

Emphysema

Cohort Studies—Mortality

Kaplan 1986

US petroleum-refinery workers (range of ICD-8 codes used)

46

0.63 (0.46–0.84)

Wong et al. 2001a

Beaumont, Texas, refinery workers (range of ICD-8 codes used)

 

 

 

Entire cohort

42

1.03 (0.74–1.40)

Wong et al. 2001b

Torrance, California, refinery workers (range of ICD-8 codes used)

 

 

 

Entire cohort

9

0.82 (0.38–1.56)

Pneumonia and Influenza

Cohort Studies—Mortality

Kaplan 1986

US petroleum-refinery workers—pneumonia (range of ICD-8 codes used)

45

0.51 (0.37–0.68)

Rushton and Alderson 1981

UK oil-refinery workers (range of ICD-8 codes used)

 

 

 

Pneumonia

157

0.86 (0.73–1.00)a

 

Influenza

11

0.40 (0.20–0.72)a

Wong et al. 2001a

Beaumont, Texas, refinery workers (range of ICD-8 codes used)

 

 

 

Entire cohort

60

0.58 (0.44–0.75)

Female employees

1

0.39 (0.01–2.18)

Male employees

59

0.59 (0.45–0.76)

Length of employment, <10 years

4

0.44

Length of employment, 10–29 years

16

0.54

Length of employment, 30+ years

39

0.63

Time since employment, <20 years

2

0.36

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

Reference

Population

Exposed Cases

Estimated Relative Risk (95% CI)

 

Time since employment, 20–39 years

10

0.40

Time since employment, 40+ years

47

0.68

Wong et al. 2001b

Torrance, California, refinery workers (range of ICD-8 codes used)

 

 

 

Entire cohort

15

0.59 (0.33–0.98)

Length of employment, <10 years

0

0.00 (p<0.05)

Length of employment, 10–29 years

12

0.75

Length of employment, 30+ years

3

0.59

Time since employment, <20 years

0

0.00

Time since employment, 20–39 years

5

0.59

Time since employment, 40+ years

10

0.71

Cohort Study—Incidence

Tsai et al. 1992

Shell Deer Park refinery and petroleum workers (range of ICD-9 codes used)

 

 

 

Production employees

168

0.97 (0.83–1.13)

 

Staff employees

28

0.74 (0.49–1.08)

NOTE: ICD, International Classification of Diseases.

a95% CI calculated by committee with standard methods from observed and expected numbers presented in original study.

Gulf War Studies

In February 1991, retreating Iraqi forces set fire to more than 600 oil wells. Fires burned over a 10-month period, until November 1991, exposing thousands of US troops to combustion products. Several studies of US Gulf War veterans exposed to oil-well fires stand out from most other Gulf War studies by virtue of their focus on a narrow set of respiratory health outcomes and on a single type of exposure (smoke from oil-well fires) and their exposure validation on the basis of models of troop unit movements in relation to air-monitoring data. The vast majority of Gulf War health studies focused on multiple health outcomes, multiple exposures, and self-reporting of exposures without validation. The studies summarized below examined long-term respiratory effects as veterans were surveyed after their deployment to the Persian Gulf. The first indication of possible long-term effects was from an uncontrolled study conducted in Germany, four weeks after deployment, which found that Army veterans that had been stationed near the fires reported coughing more frequently than before the war (Petruccelli et al. 1999). All studies discussed below are summarized in Table 5.2.

Cowan et al. (2002) conducted a case-control study to identify prevalent cases of physician-diagnosed asthma in the Department of Defense (DOD) registry (n=873) and controls without asthma (n=2,464). The DOD registry was established for active-duty Gulf War military who wished to receive a comprehensive physical examination. Cases of asthma were defined by physical examination conducted by military physicians (ICD-9-CM [Clinical Modification] codes 493 and 493.91). Exposure to smoke from oil-well fires was estimated by linking troop

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

locations with modeled oil-fire smoke exposure. National Oceanic and Atmospheric Administration (NOAA) researchers modeled exposure on the basis of meteorologic and ground-station air-monitoring data (Draxler et al. 1994; McQueen and Draxler 1994). DOD personnel records were used to ascertain each study subject’s unit and dates of service. Only Army personnel were included in the study because their location data were more precise. Two exposure measures were used: cumulative smoke exposure (the sum of the estimated concentration on all days when each subject was in the Gulf War theater) in milligrams per cubic meter per day (mg/m3 per day), with referent exposure less than 1.0 mg/m3 per day; and number of days when the subject was exposed at μg/m3 or higher.

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

TABLE 5.2 Gulf War Veteran Health Studies of Oil-Well Fire Smoke

Reference

Type of Study and Population

Exposure Determination

Health Outcome and How Measured

Results

Adjusted OR (95% CI or p)

Limitations

Lange et al. 2002

Population-based cohort study of 1,560 Iowa veterans

Self-reported exposure to “smoke from oil well fires” (5 years after war), duration 1–5, 6–30, or >30 days; exposure modeling via troop positions and air-monitoring data

Self-reported symptoms of bronchitis and asthma (wheezing and coughing) vs control symptoms of major depression and injury

Small correlation between self-reported and modeled exposures (r=0.40–0.48, p<0.05); no association between modeled exposure and symptoms of any type (ORs near 1.0, range 0.77–1.26); association found between self-reported exposure and asthma or bronchitis

For modeled exposure, adjusted ORs for symptom groups, including control symptoms, near 1.0, range 0.77–1.26; for self-reported exposure, asthma, OR 1.77–2.83, bronchitis OR 2.14–4.78

Symptom-based case definitions of asthma and bronchitis

Cowan et al. 2002

Case-control study of 873 cases of asthma vs 2,464 controls; DOD registry Army personnel only

Exposure modeling via troop positions and air monitoring data: Cumulative exposure and number of days at high concentration (≥65 μg/m3)

Physician-diagnosed asthma 3–6 years after war

Asthma associated with both estimates of exposure, dose-response

Cumulative exposure: OR 1.24 (95% CI 1.00–1.55) for intermediate exposure; 1.40 (95% CI 1.11–1.75) for high exposure; number of days at high levels: OR 1.22 (95% CI 0.99–1.51) for 1–5 days; 1.41 (95% CI 1.12–1.77) for 6–30 days

Self-selected population, pre-exposure asthma status unknown, active-duty military (Army only)

Smith et al. 2002

405,142 active-duty US military deployed to Gulf War

Exposure modeling via troop positions and air-monitoring data used to create seven exposure levels based on average, daily exposure and length of exposure: no exposure; 1–260 μg/m3 for: 1–25 days, 26–50 days, >50 days; >260 μg/m3 for 1–25 days, 26–50 days, >50 days

Hospitalizations (1991–1999) for any cause, major ICD-9-CM diagnoses and specific diagnoses related to oil-well fires (such as asthma, ischemic heart disease, and emphysema)

With Cox modeling, three of 25 models showed increase in adjusted risk of hospitalization, but no dose-response relationship; when nonexposed and exposed, were compared, none of the adjusted risk ratio for postwar hospitalization

 

Limited to DOD hospitals, exposures unknown except for oil-well smoke, outpatient data not available

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

Reference

Type of Study and Population

Exposure Determination

Health Outcome and How Measured

Results

Adjusted OR (95% CI or p)

Limitations

 

due to diagnosis related to respiratory system was significant. The seven categories were collapsed into two (exposed and nonexposed) because of relatively small numbers

 

NOTE: CI=confidence interval; DOD=Department of Defense; ICD-9-CM=International Classification of Diseases, 9th Edition, Clinical Modification; OR=odds ratio.

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

Self-reported oil-well fire smoke exposure was associated with a higher risk of asthma (OR [odds ratio] 1.56, 95% CI 1.23–1.97). In addition, modeled cumulative smoke exposure was related to a greater risk of asthma (OR 1.21, 95% CI 0.97–1.51 for the intermediate-exposure group; OR 1.40, 95% CI 1.12–1.76 for the high-exposure group) after controlling for sex, age, race or ethnicity, rank, smoking history, and self-reported exposure. When exposure was classified as number of days with exposure over 65 μg/m3, the risk of asthma also increased. For both exposure metrics, there was evidence of a linear exposure-response trend. Smoking appeared to modify the effect—the effect of oil-well fire smoke exposure was observed among never and former smokers but not among current smokers. Study strengths include the objective exposure assessment and use of physician-diagnosed asthma on the basis of clinical evaluations. Limitations include the self-selection into the DOD registry, which could have introduced selection bias; for example, if the cohort was enriched in persons who both experienced exposure and have respiratory conditions, the risk estimate could be biased upward. Moreover, the study examined prevalent-asthma cases, so a higher incidence of asthma cannot be distinguished from exacerbation or recrudescence of pre-existing disease. The study did not ask about chronic bronchitis or other respiratory effects.

In contrast, the population-based Iowa cohort of 1,560 Gulf War veterans found no association between oil-well fire exposure and the risk of asthma (Lange et al. 2002). Five years after the war, veterans were asked about their exposures and current symptoms. Exposure was modeled with an approach similar to that of Cowan et al. Each veteran’s exposure was modeled the basis of the identified unit and its location during the period of oil-well fires (February–October 1991). Cases of asthma were defined by questions assessing wheezing and chest tightness. Cases of bronchitis were assessed by self-reported cough and phlegm production. Both questions pertained to symptoms in the preceding month, so it is not possible to determine whether symptoms were chronic. Self-reported exposure to oil-well fires was associated with a greater risk of asthma and bronchitis. There was no statistical association, however, between modeled exposure and the risk of asthma or bronchitis, when sex, age, race, military rank, smoking history, military service, and level of preparedness for war were controlled for. The three higher exposure quartiles were associated with a similar risk of asthma and bronchitis compared with the lowest-exposure quartile (all ORs near 1.0 with a range of 0.77–1.26). The correlation between self-reported exposure and modeled exposure was moderate (range of 0.40–0.48, p<0.05). The authors ascribed the different results for self-reported vs objective exposure measurement to recall bias. Study strengths include the population-based sampling: findings probably can be generalized to all military personnel in the Persian Gulf; however, the study speaks to the outcome of asthma symptoms rather than an asthma diagnosis. Chronic bronchitis also was not defined with the standard epidemiologic definition, so it was impossible to distinguish between acute and chronic symptoms.

Gray et al. (2000) conducted a study of hospitalizations (1991–1994) at DOD, Department of Veterans Affairs (VA), and used data from the California Office of Statewide Health Planning and Development. Because of the absence of denominator data, the authors compared proportional morbidity ratios (PMRs) of hospitalization discharge diagnoses (14 diagnostic categories from ICD-9) in Gulf War vs nondeployed veterans. PMRs of most disease categories were not increased; however, those of respiratory diseases were increased in veterans (PMR 1.19, 95% CI 1.10–1.29) but not in active-duty military or California residents. Among respiratory diseases, the authors reported increases in asthma, but no data were shown. The study was of hospitalizations, so no data were collected on individual self-reported exposures. The

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

study is reported here because it was antecedent to a more detailed study of respiratory hospitalizations by Smith et al. (2002).

In a historical cohort study of 405,142 active-duty Gulf War veterans, Smith et al. (2002) examined the effect of oil-well fire exposure on the risk of postwar hospitalization. Exposure was estimated by using troop location data and estimated smoke (that is, PM) concentrations based on NOAA modeling (Draxler et al. 1994; McQueen and Draxler 1994). Six exposure categories were created by using average daily exposure and length-of-exposure data (Table 5.3). Hospitalizations were examined for the period 1991–1999, including admissions for any cause, major ICD-9-CM diagnoses, and nine specific diagnoses presumed to be related to oil-well fires. If a subject was hospitalized before the war with one of the specific diagnoses, the subject was excluded from further analysis. The study examined hospitalizations only in DOD hospitals because of the availability of data. Active-duty personnel are rarely hospitalized outside the DOD medical system whereas veterans and National Guard and reserve personnel often use other hospitals. There was no association between exposure to oil-well fires and the risk of hospitalization for asthma (RR [relative risk] 0.90, 95% CI 0.74–1.10), acute bronchitis (RR 1.09, 95% CI 0.62–1.90), or chronic bronchitis (RR 0.78, 95% CI 0.38–1.57). Because most adults who have asthma or chronic bronchitis are never hospitalized for the condition, the study would not be expected to have captured most cases. No information was available on smoking or other exposures that may be related to respiratory symptoms, and although there was an increase in the RR between smoke from oil-well fires and emphysema, the CI included the null value (RR 1.36, 95% CI 0.62–2.98).

TABLE 5.3 Exposure in Smith et al. 2002

Exposure to Smoke from Oil-Well Fires

% of Subjects (n=405,142) Active-Duty Military During Gulf War

% Hospitalized After War (Feb–Jan 1999) in DOD Hospitals

Not exposed

16.8

19.1

1–260 μg/m3 for 1–25 days

33.7

20.0

1–260 μg/m3 for 26–50 days

5.73

19.2

1–260 μg/m3 for >50 days

0.9

19.3

>260 μg/m3 for 1–25 days

16.8

20.2

>260 μg/m3 for 26–50 days

17.0

17.9

>260 μg/m3 for >50 days

9.0

19.4

NOTE: DOD=Department of Defense.

Several other studies of smoke from oil-well fires in the Persian Gulf were less methodologically robust. A cohort study of Gulf War veterans evaluated self-reported combustion exposure but examined pulmonary symptoms only as a broad class; asthma and bronchitis were not specifically evaluated (Proctor et al. 1998). A prospective study of 125 British Royal Engineer bomb-disposal unit members stationed in Kuwait City found no change in pulmonary function after the oil-well fires were set—forced expiratory flow 25–75% (FEF25–75), the average forced expiratory flow rate over the middle 50% of the forced vital capacity (FVC)—but asthma and bronchitis were not specifically evaluated (Coombe and Drysdale 1993). Finally, an ecologic study of Kuwaiti residents found no increase in the rate of asthma hospitalization after the Gulf War (Al-Khalaf 1998).

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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Outdoor Air Pollution

Community air-pollution studies typically evaluate the health effects of routinely measured air pollutants, such as nitrogen oxides (NOx), sulfur dioxides, particles of various sizes (for example, PM10, PM2.5)2 or concentrations (TSP), and in some cases atmospheric transformation products, such as ozone. Some of the studies used single-location measures (or community averages) of air pollutants to characterize exposures of residents of each study community, and a few estimated exposure of individual residents on the basis of interpolation of ambient monitoring data.

Prospective Studies

The Adventist Health Smog study, a prospective cohort study, began in 1976 by following a cohort of 6,000 Seventh-Day Adventists (SDAs) in areas of California with varied air-pollution magnitudes. SDAs are a unique cohort because they are non-smokers (35% of men and 14% of women were smokers before joining the church). The church’s prohibition of smoking reduced the confounding effect of current smoking for studying health effects of air pollution.

The following studies of incidence of respiratory outcomes were based on the SDA cohort. Each study used similar methods and confounding and bias controls. Study subjects were over 25 years old, baptized members of the SDA church, non-Hispanic and white, had lived within 5 miles of their permanent residence for more than 10 years, and resided in San Francisco, the Los Angeles Basin, or San Diego. Participants were studied for respiratory and other health outcomes. Respiratory outcomes were studied in a subcohort of nearly 4,000 people. Three respiratory outcomes were analyzed according to responses to a 21-item symptom questionnaire: asthma, chronic bronchitis, and overall airway obstructive disease (AOD). AOD included asthma, chronic bronchitis, and emphysema (there were so few cases of emphysema that it was not analyzed separately). Each subject’s symptoms were classified as none, possible, and definite3 for each respiratory outcome. Exposure to air pollutants was determined for each participant on the basis of ambient monitoring sites in 1977–1987 by interpolating residential ZIP codes and work-location history. The precision of interpolating concentrations was verified. In 1976, each study participant completed a detailed demographic and lifestyle questionnaire about smoking, occupation, hours spent in driving on highways, and other topics. In 1977 and 1987, each participant completed standardized respiratory-symptoms questionnaires (American Thoracic Society, ATS) to ascertain self-reported symptoms of chronic respiratory disease. Most analyses controlled for age, sex, previous smoking, occupational exposure to tobacco smoke, AOD before the age of 16 years, and education. Overall, study findings are informative, particularly because they focus on incident, rather than prevalent, respiratory disease. Study limitations include self-reporting of respiratory symptoms, varying specificity in measures of exposure, and coexposures to ozone and photochemical oxidants. The following paragraphs summarize a series of four reports about the incidence of respiratory outcomes covering various

2  

PM10 and PM2.5 are notations for participate matter of less than 10 microns in diameter and less than 2.5 microns in diameter, respectively.

3  

Criteria for definite chronic bronchitis required symptoms of cough or sputum on most days for at least 3 months/year, for 2 years or more. Criteria for definite asthma required a history of wheezing and a physician’s diagnosis of asthma. Asthma self-reporting was validated with information from medical charts.

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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individual pollutants, exposure groupings (for example, mean concentrations or exceedance frequencies), and time frames.

Abbey et al. (1993b) reported on the 10-year incidence (1977–1987) of chronic respiratory disease in relation to long-term ambient concentrations of air pollutants (TSPs), ozone, and sulfur dioxide (SO2). Symptom incidence was determined for 1977–1987 by questionnaire (NHLBI). Confounding variables included in the analysis were education, sex, possible symptoms in 1977, and years worked with a smoker. The mortality results in the SDAs are summarized in a later section on air-pollution mortality findings. For TSPs, exposure was grouped into several magnitudes (average hours exposed to TSP at over 60, 100, 150, and 200 μg/m3). Self-reported respiratory symptoms, as noted above, were grouped into asthma, chronic bronchitis, and AOD (any of asthma, chronic bronchitis, and emphysema). The outcome of the study noted increases in the incidence of definite symptoms of AOD and chronic bronchitis with hours exposed to TSP at over 100, 150, and 200 μg/m3 and asthma above of 150 and 200 μg/m3 (AOD, RR 1.36, 95% CI 1.11–1.66 for 1,000 hours above 200 μg/m3 TSP; chronic bronchitis, RR 1.33, 95% CI 1.07–1.65 for 1,000 hours above 200 μg/m3; and asthma, RR 1.74, 95% CI 1.11–2.72 for 1,000 hours above 200 μg/m3).

In the same report, mean concentration and average annual exceedance frequencies of 100, 120, 150, and 200 parts per billion (ppb) were not associated with new cases of any respiratory outcomes, although a possible association between ozone and exceedances of 100 ppb and new cases of asthma (point estimate RR 1.40, 95% CI 0.99–2.34) was noted for 500 hours of average annual increment. An elevated risk in men (not women) was associated with ozone and exceedances of 100 ppb and new cases of asthma (point estimate RR 1.95, 95% CI 1.0–3.94) for 500 hours of annual increment. Because of multicollinearity, the analyses were unable to show whether TSP or ozone was more strongly associated with new cases of asthma (ozone and TSP correlation 0.74). There was no association between SO2 and respiratory symptoms; however, the average ambient concentrations were low. There also was no association between nitrogen dioxide (NO2) and each of the respiratory outcomes (Abbey et al. 1993a).

Another report by Abbey et al. (1993c) analyzed the 10-year incidence (1977–1987) of chronic respiratory disease associated with long-term ambient concentrations of sulfate (SO4) particles. The 10-year cumulative exposure to SO4 particles was determined for each participant in 1977–1987. Multivariate analysis was conducted for AOD, chronic bronchitis, and asthma for new cases of disease, persistent prevalence (that is, symptoms in both 1977 and 1987), and change in severity of symptoms (from 1977 to 1987). The 10-year mean ambient concentration of SO4 particles was strongly associated with the development of definite asthma (RR 2.87, 95% CI 1.03–7.55 per increment of 7 μg/m3) but not with AOD and chronic bronchitis. Working with a smoker and having AOD before the age of 16 years were strongly associated with asthma.

Finally, Abbey et al. (1995) examined respiratory outcomes in a subset of the cohort (n=1,868) in relation to estimated long-term ambient concentrations of PM2.5 and other air pollutants. Exposure to PM2.5 was estimated with regression of site- and season-specific regression equations from paired PM2.5 and visibility observations (1979–1986) and applied to visibility data at nine airports in California. The subset of the cohort was selected on the basis of having lived at least 80% of months (1966–1986) close to the airports. Long-term means of each subject’s estimated monthly PM2.5 mean concentrations and exceedance frequencies were cumulated over 1966–1977 according to ZIP code by monthly residence. A 45 μg/m3 increase in mean PM2.5 exposure was associated with a greater risk of incident chronic bronchitis (RR 1.81,

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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95% CI 0.98 to 3.25). (When a larger subset of the cohort with less stringent residency criteria is included, this association is stronger, p<0.05.) There was no association with onset of asthma and AOD for PM2.5 (means or exceedance frequencies). Mean PM2.5 was associated with a change in severity score for AOD, chronic bronchitis, and asthma. Meaningful regression coefficients applied for AOD at all levels of PM2.5, for chronic bronchitis at PM2.5 levels above 20 μg/m3, and for asthma at levels above 40 μg/m3.

Cross-Sectional or Case-Control Studies of Air Pollution

While the majority of epidemiologic studies of morbidity and mortality associated with community air pollution are time series (ecologic) design, the committee focused on cross-sectional or case-control studies of air pollution. The time series studies examine daily mortality or morbidity, while the focus for the committee is on long-term health effects.

A population-based study in France examined the relationship between SO2 concentration and asthma (Baldi et al. 1999). A random sample of adults 25–59 years old who resided for at least 3 years during 1974–1976 in 24 areas of seven French towns were selected. Air pollution was measured over the same 3 year period by pollution-monitoring stations (subjects lived within 500 meters of a station). There was an ecologic correlation between mean annual regional SO2 concentration and the prevalence of asthma (r=0.45, p=0.01), defined as responding affirmatively to the question “Have you ever had asthma?” In individual-level, cross-sectional analysis, higher mean annual SO2 was associated with a greater risk of self-reported asthma (OR 1.24 for each 50 μg/m3 increment, 95% CI 1.08–1.44), when age, educational attainment, and smoking history were controlled for. Geographic clustering of data was taken into account by using random effects. Limitations include the cross-sectional design and the use of self-reported asthma; strengths include the population-based sampling and direct air-pollution monitoring.

Karakatsani et al. (2003) conducted a nested case-control study of Greeks enrolled in a population-based cohort study, the European Prospective Study into Cancer and Nutrition. Residents of greater Athens completed a questionnaire, which was used to recruit 168 participants who reported a history of COPD, chronic bronchitis, emphysema, or respiratory symptoms (including chronic productive cough for 3 months per year for 2 years). The same number of age- and sex-matched controls without respiratory conditions or symptoms was selected. A thoracic-disease specialist visited, interviewed, and measured with spirometry each subject (n=84) at home to confirm the diagnosis of COPD. Air pollution was ascertained retrospectively on the basis of average long-term concentrations of black smoke and NO2 recorded at 14 monitoring stations for the decade 1987–1997. Boroughs were classified into quintiles of NO2 concentration. Residential and employment histories were used to calculate time-weighted averages for each subject. Subjects who resided in rural areas or other cities were assigned to categories based on their presumed pollution exposure. Conditional logistic regression revealed an association between the highest quartile of estimated exposure during the preceding 5 years and the risk of COPD (OR 1.89, 95% CI 0.83–4.31). Exposure during the preceding 20 years was not associated with COPD (OR 1.31, 95% CI 0.52–3.28). Study strengths include the population-based recruitment of cases and controls, the attempt to confirm the diagnosis of COPD with physician examination, the objective exposure assessment, and statistical control for sociodemographic and smoking variables. The study had several limitations: There was a lack of uniform criteria for diagnosing COPD; although exposure was objectively ascertained, the lack of monitoring data on subjects who lived outside greater Athens

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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reduced the accuracy of exposure classification; and the wide confidence intervals, reflecting low precision of the effect estimates, limit interpretation of the data.

In a population-based sample of adults aged 40 years or older, investigators studied the relation between regional SO2 concentration in the Osaka prefecture in Japan and the prevalence of self-reported chronic bronchitis (Tsunetoshi et al. 1971). Average SO2 concentrations for a 3-year period before the study began were noted. The researchers found a moderate relationship between chronic-bronchitis prevalence and regional average SO2 when they controlled for age and smoking (mean prevalence increased 1.94 for each SO2 increment of 1 mg/100 cm2 per day). There was no relationship between regional SO2 and the prevalence of reduced 1-second forced respiratory volume (FEV1). Limitations include the use of an exposure measurement based on averaging SO2 over a long time (3 years) before the study and the lack of control for socioeconomic status (SES) or other exposures.

A population-based, cross-sectional study of 18,873 people 20–44 years old evaluated the relationship between regional mean annual NO2 concentration and asthma prevalence across Italy (De Marco et al. 2002). Mean annual outdoor NO2 was measured with fixed monitoring stations near the study subjects’ residences; concentrations were measured for the period 1996–1999 (surveys took place in 1998–2000). Asthma prevalence was measured with a question asking whether the respondent had had an attack of asthma during the preceding 12 months. Higher ambient NO2 was associated with a greater risk of asthma attacks, when climate, age, sex, smoking, social class, season, and type of contact (telephone vs mail) were controlled for (OR per standard-deviation increment in NO2 1.13, 95% CI 0.98–1.32). The confidence interval did not exclude absence of an association. Study strengths include the population-based sampling and objective exposure measurement. A limitation of the study, for the committee in interpreting the data for purposes of its charge, is the use of “asthma attacks” as a study outcome, which probably overrepresents exacerbation of previously established asthma, rather than incident asthma cases; the cross-sectional design; and the lack of information about distance between monitoring stations and subjects’ residences.

A population-based study in western Australia compared 255 cases of asthma that required hospitalization with 903 population-based controls (Hunt and Holman 1987). Residential SO2 was estimated with a validated model based on meteorologic data and industry emissions data. There was no relation between mean residential SO2 and risk of asthma hospitalization (OR 0.8–1.1). There was also no association between frequent high peak exposure (hours of exposure at over 486 μg/m3 per year) and risk of hospitalization. A major limitation for the committee in interpreting the data for purposes of its charge is that asthma hospitalizations could reflect either incident disease or exacerbation of pre-existing disease. In addition, most asthma patients are never hospitalized for the disease, so hospitalization is a poor measure of disease causation.

Air-Pollution Mortality Studies

Mortality studies of respiratory outcomes are, for purposes of this report, often difficult to interpret and inconclusive. One reason is that many mortality studies use composite ICD codes instead of minor groupings or individual codes, which would have greater specificity. A second is that because asthma and chronic bronchitis are rarely fatal, mortality studies tend to be insensitive to any relationship between an environmental or occupational exposure and long-term respiratory effects. Finally, although emphysema is the respiratory effect that is the exception because it can be fatal, most emphysema deaths are related to cigarette-smoking. Further

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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complicating matters, emphysema deaths are often caused by pneumonia or cardiovascular disease, so ascertainment of emphysema deaths is not robust.

Respiratory mortality findings in several large-scale cohorts have been reported: American Cancer Society (ACS) (Pope et al. 1995, 2002), Six-Cities (Dockery et al. 1993), SDAs (Abbey et al. 1999), and Netherlands Cohort Study on Diet and Cancer (Hoek et al. 2002). Those studies, however, examined outcomes that are too broad to draw conclusions from, considering that they group composite ICD codes (for example, 460–519) under the broad labels “cardiopulmonary diseases”, “respiratory diseases”, and “non-malignant respiratory diseases.” A recent analysis of the ACS cohort (Pope et al. 2004) performed somewhat more diagnosis-specific analyses with the same methods as Pope et al. (2002). The RR of “COPD and allied conditions” (ICD codes 490–496) in relation to air-pollution exposure was not increased after adjusting for former and current smoking.

Air Pollution: Other Support Studies

Garshick et al. (2003) studied US male veterans in Massachusetts (n=2,628) who resided near major roadways; such residence is an indicator of motor vehicle exhaust exposure. Veterans who lived within 50 meters of a major roadway were compared with those who lived more than 400 meters away. By virtue of their age (mean age 60.6 years), the veterans were not likely to be Gulf War veterans. They were drawn from the general population of southeastern Massachusetts, and they had not been treated in a VA medical center in the year before being surveyed. Estimates of individual exposure were based on current residential address (without information on residential history) linked to road type and traffic-count data in a geographic information system. Living near a major roadway appeared to be associated with increased reporting of persistent wheeze (OR 1.31, 95% CI 1.00–1.71), as did living near a major roadway with high traffic volume (over 10,000 vehicles per 24 hours) (OR 1.7, 95% CI 1.2–2.4), compared with living near a roadway with lower traffic volume. Self-reports of physician-diagnosed asthma or COPD (defined as chronic bronchitis or emphysema) were analyzed as confounders and effect modifiers. Associations were adjusted for cigarette-smoking, age, and occupational exposure to dust. The authors noted that limitations of the study include lack of information on duration of residence at each address and information about home exposure to NOx from cooking or heating. Information is lacking about the health effects of the nonresponders, because the study had a response rate of 58%.

Zhang et al. (1999) studied the effects of air pollution on respiratory health of adults in three Chinese cities. A study of parents of schoolchildren was performed on 4,108 adults who resided in four school districts of three major cities.4 Questionnaires adapted from the American Thoracic Society (ATS) Epidemiologic Standardization project were used to collect information on health status, occupation, level of education, smoking history, indoor air pollution in the home (coal use and smoking), history of respiratory illnesses, and symptoms. The self-reported symptoms ascertained were cough, phlegm, wheeze, and persistent cough and phlegm (PCP, an indicator of chronic bronchitis). Self-reported respiratory illnesses “ever diagnosed by a physician” were asthma and bronchitis, but the latter could have included acute or chronic bronchitis. Exposure to air pollution was determined on the basis of ambient air pollution data from monitoring stations in each district. Four-year average concentrations of TSP, SO2, and

4  

A separate report covered findings on schoolchildren, but this young population is not relevant to Gulf War veterans.

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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NOx were assessed to estimate long-term exposure to outdoor air pollution. The trend for TSP was Lanzhou>Wuhan-urban>Guangzhou>Wuhan-suburban. The differences for SO2 and NOx were less pronounced. Crude prevalences of each respiratory symptom in both mothers and fathers were Lanzhou>Wuhan urban+suburban>Guangzhou. The ORs and 95% CIs compared with Guangzhou, were determined with a logistic-regression model, which adjusted for age, years of residence, occupation, education, smoking status, home coal use, and use of ventilation device use (chimney, exhaust hood, and exhaust fan). For both mothers and fathers, the ORs (with Guangzhou as a reference) for each respiratory symptom were Lanzhou>Wuhan urban+suburban. The findings suggest that increased TSP concentration is associated with increased symptoms. The ORs for the only symptom indicative of chronic bronchitis (PCP) ranged from 0.86 to 12.62, and all demonstrated an association except for the ORs of the mothers who lived in Wuhan-suburban. Physician-diagnosed asthma and bronchitis showed inconsistent trends. For bronchitis (acute or chronic), ORs for mothers followed the same trend as respiratory symptoms (Lanzhou OR 9.69, 95% CI 5.50–17.06). In a comparison of urban with suburban Wuhan, only the asthma OR for the father was increased (OR 3.59, 95% CI 1.36–9.49). A limitation of the study is that it did not associate air-pollution concentrations themselves with health outcomes; it only associated residence in some regions with health outcomes. The authors cautioned that nonmeasured between-city factors may have been responsible for the associations.

In an ecologic study in Sweden (Bjornsson et al. 1994), the risk of chronic-bronchitis symptoms was higher in Gotborg than Uppsala (OR 1.2.95% CI 1.02–1.4). There was no difference in the prevalence of self-reported asthma. Although Gotborg was more polluted, there were also differences in climate and SES that could have accounted for the findings.

An ecologic study evaluated the relation between short-term SO2 peaks and emergency-department visits for asthma in low income neighborhoods in New York City in 1968–1972 (Goldstein and Weinstein 1986). No association was observed between days of “high” SO2 (defined according to three threshold values) and days with high numbers of emergency-department visits for asthma. Limitations include the lack of control for confounding factors, such as smoking and sociodemographic characteristics, and the likelihood that emergency-department visits reflected exacerbation of pre-existing asthma rather than incident asthma cases.

Two other studies compared the prevalence of asthma or chronic bronchitis among geographic regions that had different air-pollution magnitudes. The geographic areas probably differ in other important ways, such as sociodemographic characteristics of the inhabitants, smoking prevalence, and allergen exposure. Because there were no specific measurements of air pollution, it is difficult to draw any inferences from the studies (Papageorgiou et al. 1997; Woods et al. 2000). The Woods et al. study was a large population-based cross-sectional survey of people 20–44 years old. Self-reported “air-pollution annoyance” was associated with a greater risk of self-reported physician-diagnosed asthma (OR 1.11, 95% CI 1.09–1.14) and chronic bronchitis symptoms (OR 1.14, 95% CI 1.11–1.17). The self-reported-exposure measure is suspect, however, in that persons who have respiratory disease may be more likely to remember and report perceived air-pollution annoyance.

An ecologic study in Brisbane, Australia, examined the association between weekly smoke density (coefficient of haze) and admissions to the casualty department of the Royal Brisbane Hospital at night (Derrick 1970). There was no noteworthy correlation between smoke density and weekly number of asthma admissions (r=−0.04 to −0.05).

Hastings and Jardine (2002) evaluated the association between measured particulate air pollution and upper respiratory disease rates in soldiers deployed to Bosnia in 1997–1998. The

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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study used a composite upper respiratory disease definition that included upper and lower respiratory tract diseases. No specific information on asthma, chronic bronchitis, or COPD was presented.

Zelikoff et al. (2002) has conducted a review of the toxicology of inhaled wood. Additionally, several studies (for example, Aditama 2000; Kunii et al. 2002; Sastry 2002) have conducted studies of mortality and morbidity (primarily through the examination of lung function) of wood smoke.

Domestic gas-stove use releases NO2, a potential respiratory irritant, into the indoor environment (Samet et al. 1987). Many epidemiologic studies examining the effects of gas-stove use have focused on healthy members of the adult population (Dow et al. 1999; Jarvis et al. 1996, 1998; Ng et al. 1993; Ostro et al. 1993; Samet et al. 1987; Viegi et al. 1992, 1991). In those studies, the effect of gas stove exposure on the development of respiratory symptoms, including asthma symptoms and pulmonary function impairment has been inconclusive.

Hydrogen Sulfide and Respiratory Diseases

The city of Rotorua, New Zealand, is above a geothermally active area with substantial hydrogen sulfide (H2S) exposure. About one-fourth of the population of 40,000 is regularly exposed to H2S over 200 μ/m3 (143 ppb). A series of studies by Bates et al. investigated morbidity and mortality from the full range of diseases, including respiratory diseases (Bates et al. 1997; Bates et al. 1998, 2002). The impetus for the studies was a 1981 World Health Organization report that recommended research in Rotorua to take advantage of the natural conditions to study the health effects of H2S.

Bates et al. (1997), using census data, compared deaths in Rotorua with those in the rest of New Zealand (1981–1990). First examining the composite category respiratory diseases (ICD codes 460–519), they found the SMR to be higher in Rotorua (SMR 1.18, 95% CI 1.08–1.29, p<0.001). They also found an elevated SMR for chronic obstructive respiratory disease (CORD), ICD-9 codes 490–496, which include asthma, bronchitis, COPD, and allied conditions (SMR 1.20, 95% CI 1.06–1.35, p<0.004). Rotorua has a higher density of Maori residents than other areas of New Zealand. The authors noted the potential for underreporting of Maori mortality statistics because ethnicity on death certificates is based on funeral directors’ impressions.

In a subsequent report, Bates (2002) used hospital-discharge data over a 3-year period (1993–1996) to calculate standardized incidence ratios (SIRs) for respiratory and other diseases (and subgroupings) in Rotorua residents. Exposure was designated as high, medium, and low on the basis of area of residence where H2S was mapped outdoors with passive sampling. Exposure-response trends were found for diseases of the respiratory system (p for trend was <0.0001), and for CORD and allied conditions, codes 490–496; p for trend was <0.0001. The authors had no information on smoking and SES as potential confounders.

In a third report, Bates et al. (1998) used hospital-discharge data over a decade (1981–1990) to calculate SIRs for respiratory and other diseases (and subgroupings) in Rotorua residents. No exposure groups were designated. The SIRs for respiratory diseases (ICD codes 460–519) were not increased (SIR 1.01, 95% CI 0.99–1.04). CORD was not increased. A major limitation of the series of Bates studies for purposes of the present report is the grouping of respiratory diseases without specifying whether they were asthma, bronchitis, COPD, or individual conditions. Additionally, the Bates studies were the only epidemiologic studies of H2S found by the committee that examined long-term health outcomes. Due to the paucity of literature, the committee did not make a separate conclusion on H2S.

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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Occupational Studies

Osterman et al. (1989a) studied a cohort of 145 male silicon carbide production workers in Quebec, Canada. Individual exposures were to respirable dust and to SO2 at relatively low concentrations (less than 1.5 ppm). Exposures were estimated based on the basis of job-specific measurements and linkage to worker-specific job titles and employment duration. Average duration of employment was 14 years. The estimates included a measure of cumulative exposure, average exposure, and most recent exposure. It is notable that the plant had been closed in the 6 months preceding the study, so the evaluation of outcome probably occurred after an exposure-free interval. Respiratory symptoms were ascertained with a translated version of the ATS respiratory-disease questionnaire. Lung function was also measured and reported separately (Osterman et al. 1989b). Although all symptoms occurred more frequently in current smokers (53.8% of the study population), analyses adjusting for age and current smoking indicated a dose-dependent association between chronic phlegm and both average and cumulative exposure to SO2. For cumulative SO2 exposure, the highest exposure (over 3 ppm-years) had OR 11.8, 95% CI 2.58–52.9; moderate exposure (>1.0–3.0) OR 2.94, 95% CI 0.84–10.3; and lowest exposure (>0.25–1.0) OR 1.43, 95% CI 0.42–4.83, with the referent being 0–0.25 ppm-years. The strong SO2-symptom associations persisted and were almost identical with those obtained from regression models that did not include a dust variable. There was no evidence of a dust-SO2 interaction. The association was more closely related to exposure concentration rather than to duration. A similar dose-dependent association was observed between SO2 exposure and chronic wheeze. The associations with respirable dust were generally negative. Because the study measured symptoms only 6 months after cessation of exposure, it is not known whether they were reduced or eliminated after a longer exposure-free period.

In a companion article, Osterman et al. (1989b) performed pulmonary-function testing—FEV1 and forced vital capacity (FVC)—on the same group of 145 former silicon carbide production workers. The cohort experienced reductions in FEV1 and FVC values, but they were unrelated to cumulative and average SO2 exposures. No effects of a dust-SO2 interaction were seen.

Mortality Studies

Studies of respiratory-system mortality in particular occupations are often difficult to interpret. They tend to examine composite or poorly defined outcomes (for example, “respiratory diseases” as a group of ICD codes) or to provide scanty information about exposure (for example, studies of professional drivers (Borgia et al. 1994; Rafnsson and Gunaarsdottir 1991) and highway workers (Maizlish et al. 1988). Other studies examine occupations that entail exposure to chemicals of uncertain relevance to Gulf War veterans, including studies of urban firefighters (Aronson et al. 1994; Baris et al. 2001; Beaumont et al. 1991; Feuer and Rosenman 1986). Although most mortality studies had negative results, three found higher mortality from emphysema (Maizlish et al. 1988) or from a composite category of nonmalignant respiratory diseases (Aronson et al. 1994; Feuer and Rosenman 1986); the design of the three studies, however, precluded adjustment for the effects of smoking, a major risk factor for death from emphysema. A separate analysis of the ACS prospective study found that emphysema mortality was not meaningfully increased among workers exposed to diesel exhaust, after adjustment for the effects of smoking (Boffetta et al. 1988). A large study of firefighters in 27 states (over 5,700

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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deaths), which included a mix of urban and rural firefighting jurisdictions, did not find higher mortality from COPD (Burnett et al. 1994).

Support Studies

The effects of occupational exposure to engine exhaust were studied in 116 Copenhagen street-cleaners in comparison with a similar number of cemetery workers (Raaschou-Nielsen et al. 1995). Environmental monitoring confirmed that street cleaners had higher average exposures to air pollutants (except ozone) than did cemetery workers, but similar wages and similar exertion. Cemetery workers were younger and less likely to smoke cigarettes. The study did not indicate whether the symptom questionnaire was sent after an exposure-free interval, but the likelihood is that there was no interval, inasmuch as this was a study of current workers. The study found, after adjustment for age and smoking, that street-cleaners were at higher risk for chronic bronchitis (OR 2.5, 95% CI 1.2–5.1) and asthma (OR 2.3, 95% CI 1.0–5.1). Asthma and chronic bronchitis were defined on the basis of responses to the standard questionnaire by the British Medical Research Council. The average duration of employment was 5–9 years. A limitation of the study is the potential for nonmeasured differences between the two types of workers that could confound the exposure-outcome relationships.

Occupational exposure to diesel-exhaust emissions was associated with increased self-reported symptoms of cough and sputum and with lower pulmonary function in coal miners vs matched controls (Reger et al. 1982). When disparities in various health characteristics between workers in or at diesel-using mines and their matched controls were related to an index of diesel exposure, they showed no noteworthy trends. Although a pattern consistent with early airway disease was shown, factors other than diesel may be responsible inasmuch as exposure duration and concentrations were low.

The respiratory health of 259 workers at five salt mines was evaluated with a questionnaire and spirometry (Gamble and Jones 1983); no direct exposure measurements were available. Comparisons within the study population showed a dose-related association of phlegm and diesel-exhaust exposure, no noteworthy trend for cough and dyspnea, and no association with spirometry was seen.

Residence near a factory that produced plastic-coated wallpaper, which emitted combustion products of paraffin oil, was associated with a 24% increase in asthma prevalence defined by computerized medication-dispensing patterns (95% CI 4%–44%) (Dunn et al. 1995). The factory also emitted azodicarbonamide, which has been associated with occupational asthma.

Investigators evaluated clerical and industrial workers (in four engineering factories) in Brisbane, Australia (Smithurst and Williams 1976). Although cough and phlegm were more common among industrial than clerical workers, there was no specific evaluation of exposure to combustion products. There also was no statistical control for potentially confounding variables, such as SES.

A study of 1,933 men 22–54 years old living in Norway found that self-reported occupational exposure to SO2 was associated with a greater decline in FEV1 from initial examination (1965–1970) to followup (1988–1990). Investigators demonstrated a decline in FEV1 after occupational diesel-exhaust exposure, but the decline normalized after an exposure-free period of 3 days (Ulfvarson et al. 1987).

Several other morbidity studies assessed occupational exposures but were limited by lack of exposure information or other features. One study (Fleming and Charlton 2001) found that

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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transport workers have an increased risk of physician-diagnosed asthma (PR 116, 95% CI 101–131), but no measurements of exposure were available. Occupational exposure to engine exhaust was not associated with adult asthma in a study in Sweden (Toren et al. 1999). Other studies are limited in that they did not provide specific estimates of exposure to combustion products but rather studied exposures to a composite category (for example, vapors, gas, dust, or fumes) (Flodin et al. 1996; Kogevinas et al. 1999; Xu and Christiani 1993; Zock et al. 2001).

Some studies have assessed the effect of forest firefighting on various intermediate measures or indexes of pulmonary function rather than on respiratory diseases themselves. Forest firefighters’ exposures might be more relevant to Gulf War veterans’ exposures than to urban firefighters’ exposures, which include combustion products of synthetic materials (Burgess et al. 1999). Most forest-firefighter studies, however, did not examine effects on lung function after an exposure-free period. An exposure-free period is important for distinguishing between reversible, short-term outcomes and long-term outcomes. In one study that had an exposure-free period of 2.5 months after a fire, firefighters were noted to have decreased indexes of expiratory function (FEV1, and FEF25–75) (Betchley et al. 1997).

Liu et al. (1992) studied 63 members of the US Department of Agriculture Forest Service hotshot crews in northern Montana before and after the forest-fire season. Crews worked full-time in May–November. Spirometric measures indicated declines in FVC, FEV1, and FEF25–75, and results of methacholine challenge indicated an increase in airway responsiveness. Findings were independent of smoking. The duration of the exposure-free interval between fire exposure and testing appears to have been at most 2 weeks, so it is difficult to determine whether effects are short-term effects, which may reverse, or long-term effects.

A prospective study of 1,768 urban firefighters in 1970–1976 found no exposure-related decline in pulmonary function. The mean FEV1 and FVC were not reduced by more than 3% over the 6 years (Musk et al. 1979). A study of retirees from the same urban fire department did not find appreciably reduced respiratory function that was unrelated to smoking (Musk et al. 1982). Urban-firefighter studies, however, are probably less relevant to Gulf War veterans (see above) than are studies of rural firefighters, because of the nature of the materials in urban fires.

Biomass-Fuel Combustion

Several studies evaluated the effects of exposure to products of biomass fuel combustion for heating or cooking, which includes combustion of wood, dung, and agricultural residue. The homes in question often do not have a separate kitchen or a way to vent fumes. The studies assessed exposure by self-reporting of duration of cooking-fuel use and, in some cases, by measurement of air quality at the time of the survey.

Population-based Studies

A study in India used data from the population-based National Family Health Survey (n=38,595) to examine people 60 years old or older (Mishra 2003). On the basis of survey items about 10 cooking fuels, the author classified cooking-smoke exposure as high (only biomass fuels), medium (a mix of biomass and cleaner fuels, such as kerosene, petroleum gas, biogas, or electricity), and low (only cleaner fuels). Asthma was reported by the head of the household (the respondent) for each member of the household in response to the question “Does anyone [in the household] suffer from asthma?” When sociodemographic factors and smoking history were controlled for, biomass-fuel use was associated with a greater risk of asthma than the use of

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

clean fuels (OR 1.59, 95% CI 1.30–1.94). The risk was also increased for the medium group (mixed fuels) vs clean fuels (OR 1.24, 95% CI 1.04–1.49). The asthma results were stronger for women (OR 1.83, 95% CI 1.32–2.53) than men (OR 1.46, 95% CI 1.14–1.88). The strengths of the study are its population-based design, thorough ascertainment of fuel use, and control for confounding. Limitations include the cross-sectional design and the use of a self-reported definition of asthma that did not require symptoms or a physician diagnosis. No information is available on duration of exposure.

Albalak et al. (1999) studied all 241 adults in two rural Bolivian villages. The villages were similar, except that one used indoor cooking and the other outdoor cooking. They were given a Spanish translation of the British Medical Research Council questionnaire for chronic bronchitis. Measured kitchen PM10 was substantially higher in the indoor-cooking village; total daily integrated PM10 exposure based on a time-budget analysis was also much higher. The outdoor-cooking village had a lower risk of chronic bronchitis, after adjustment for age, sex, and exclusion of smokers (OR 0.4, 95% CI 0.2–0.8). The villages were similar in a variety of socioeconomic indicators. The validation of exposure with direct ambient-air monitoring (specifically PM10) is a strength of the study. Although duration of residence was not reported, air monitoring was carried out over a 10-month period, and a case of chronic bronchitis was identified by uninterrupted cough for at least 3 months over 2 years.

Other Biomass Studies

A case-control study from Mexico City recruited 127 women who had chronic bronchitis or chronic airway obstruction (FEV1 less than 75% predicted) from a tertiary referral hospital (Perez-Padilla et al. 1996). They had reported a range of 2.5–25 years of cooking with a woodstove. There were four different groups: people who had tuberculosis, interstitial lung disease, or ear nose and throat (ENT) conditions (sinusitis, otitis media, or deviated nasal septum) and healthy visitors of hospitalized patients with no respiratory symptoms or pulmonary function impairment. The primary exposure was to wood smoke while cooking. The selection of controls that had tuberculosis or interstitial lung disease is suspect because such subjects may differ from persons who have chronic airway disease in a variety of important ways. In analyses that used the other control groups, wood-smoke exposure was associated with a greater risk of chronic bronchitis without chronic airway obstruction than in ENT controls (OR 3.6, 95% CI 1.7–8) or healthy visitor controls (OR 8.1, 95% CI 3.4–14). The analysis controlled for age, cigarette-smoking, region of origin, income, education, and place of residence. Wood-smoke exposure was not associated with the risk of chronic airway obstruction without chronic bronchitis. Wood-smoke exposure was associated with a greater risk of chronic airway obstruction plus chronic bronchitis compared with ENT controls (OR 5.2, 95% CI 1.9–15) and healthy controls (OR 15, 95% CI 4–55). Cumulative lifetime exposure (the product of average hours per day of exposure and years of exposure) was also linearly related to a greater risk of chronic bronchitis only than in the ENT or visitor controls. Findings in the tuberculosis and interstitial-lung-disease control groups are difficult to interpret, because these conditions could be related to wood-smoke exposure; alternatively, the conditions, because they are severe diseases, might reduce the likelihood of cooking and consequent exposure. In addition, wood-smoke exposure could be a cause of the ENT conditions and result in a bias toward the null value in the analyses. The small sample resulted in imprecise estimates with wide confidence intervals.

A study in the hill region of Nepal evaluated 1,375 people (Pandey 1984). They reported exposure to domestic smoke produced by burning firewood, straw, and other biomass fuels, and

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

their homes were likely to have been poorly ventilated. The cross-sectional prevalence of chronic bronchitis increased with hours spent near the fireplace. In women, chronic bronchitis was observed among smokers, ex-smokers, and never smokers. In men, it was observed in all groups except nonsmokers. However, the study did not control for SES.

Quereshi (1994) randomly selected two villages in Kashmir. In Gujjar, inhabitants live in single-room hutments and burn firewood in a mud hearth for cooking and heating. In Wahidpora, living conditions are better; kerosene stoves, gas stoves, and electric heaters are more commonly used. The SES was lower in Gujjar, and the prevalence of cigarette-smoking was also lower. The prevalence of chronic bronchitis was higher in Gujjar (10.1%) than in Wahidpora (5.1%). Among Gujjar residents, the prevalence of chronic bronchitis increased with average hours spent near the fireplace (no statistical testing was performed). In a pooled analysis of both villages, the prevalence of chronic bronchitis among women but not men varied with hours spent near the fireplace. A major limitation of the study is the lack of control for confounding variables, such as cigarette-smoking and SES, both within and between villages.

A case-control study in Saudi Arabia recruited 50 people who had COPD defined by airflow obstruction with pulmonary-function testing and 71 healthy controls (Dossing et al. 1994). Exposure to indoor fire during childhood was associated with a greater risk of COPD among women (96% of COPD cases vs 29% of controls) and men (78% vs 39%) (p<0.01 and p <0.05, respectively). Among women, the likelihood of long-term exposure (to indoor fire over 20 years) was higher in the COPD group than in controls (67% vs 5%) (p<0.01). A serious limitation of the study is the lack of control for smoking, age, SES, and other factors.

A case-control study in Bogotá, Columbia, recruited 104 people who had obstructive airways disease (defined with pulmonary-function testing among pulmonary outpatients and medical-ward patients that showed below 70% of predicted FEV1/FVC and FEV1) and 104 age-matched controls (surgical or gynecology inpatients or general-medicine outpatients) in three community hospitals (Dennis et al. 1996a, 1996b). Cases and controls averaged more than 15 years of wood use, usually beginning in childhood or adolescence. Use of wood as a cooking fuel was associated with a greater risk of obstructive airways disease (OR 3.92, 95% CI 1.7 to 9.1), when smoking, passive smoke exposure, age, hospital, and gasoline use were controlled for. A study strength is the use of pulmonary-function testing to define cases. Limitations include the lack of control for SES and the limited evaluation of wood-smoke exposure in multivariate analysis (for example, no exposure-response relationship was examined). In addition, the recruitment process in a variety of inpatient and outpatient settings did not clearly result in controls that were comparable with cases.

Investigators examined the use of planchas (wood-burning chimney stoves) compared with open wood fires by 340 women in the rural highlands of Guatemala (Bruce et al. 1998). Although cough and phlegm production were less common among those using planchas, the risk of chronic bronchitis was similar (OR 0.57, 95% CI 0.22–1.46) after adjustment for age. The risk was increased after further adjustment for other indicators of SES (OR 0.72, 95% CI 0.26–1.98). The investigators noted that use of planchas was related to other indicators of higher SES, such as radio ownership, spousal employment in business and trade, and cement or tile floors (as opposed to dirt floors). The authors commented on the potential for strong confounding in studies that use fuel type as an exposure measure.

A population-based study in India evaluated 3,608 nonsmoking women in their homes in villages of Chandigarh in northern India (Behera and Jindal 1991). Cooking with a chulla—which uses dung, crop residues, and agricultural wastes—was associated with a higher

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

prevalence of chronic bronchitis than using a kerosene stove, liquefied petroleum gas, or mixed fuel (2.9% vs 1.3%, 2.5%, and 1.2%, respectively; p<0.05). There was no statistical difference in the prevalence of asthma, but there were very few cases. A major limitation of the study is the lack of control for confounding factors apart from sex and smoking, such as SES.

Investigators in Finland conducted a mail-based survey of Finnish university students to examine the effect of wood-stove heating during childhood (age 0–6 years) on the development of asthma and allergic conditions in young adulthood (age 18–25 years) (Kilpelainen et al. 2001). There was no association between wood-stove exposure during childhood and ever having a self-reported physician diagnosis of asthma (OR 0.99, 95% CI 0.65–1.53) or other atopic conditions when sex, SES, parental atopy, number of older siblings, residential environment at the age of 0–6 years (farm, nonfarm rural, and urban), passive smoking during childhood, furred pets in the home during childhood, and history of day care were controlled for. Study limitations include the cross-sectional survey design and the lack of control for cigarette-smoking.

Additional studies have linked biomass-smoke exposure to impaired pulmonary function with spirometry (Pandey et al. 1985; Peters et al. 1999) and symptom questionnaire (Behera 1997), to increased bronchial hyperresponsiveness with methacholine bronchoprovocation (Jindal et al. 1996), and to increased mortality and morbidity (Smith 2000).

The committee excluded some reports because they contained no specific information about asthma, chronic bronchitis, or COPD (Amoli 1998; Perez-Padilla et al. 2001). Another study was excluded because the statistical analysis could not be clearly interpreted (Golshan et al. 2002): a population-based study in Isfahan, Iran, examined the relation between cooking-fuel use and self-reported respiratory conditions, but the multivariate analysis could not be clearly interpreted, in that both wood and kerosene fuel were included in the same analysis and the referent group was not clearly defined.

Conclusions

Asthma

The series of related studies of Seventh-Day Adventists comprise the only high quality study of asthma incidence related to outdoor air pollution in adults. The studies found that new cases of asthma were associated with combustion-product exposure in air pollutants (Abbey et al. 1993b, 1993c, 1995) The study of Gulf War veterans of Cowan et al. (2002), which used an objective exposure-measurement method, found an association between oil-well fire smoke and asthma in Gulf War veterans, but it could not distinguish between new cases arising after the war and exacerbation of pre-existing conditions. Although the other key Gulf War study based on the Iowa cohort (Lange et al. 2002), which had the advantage of avoiding the potential selection bias of the Cowan et al. study, found no relationship between exposure and asthma, its definition of asthma was inadequate. The study of Mishra (2003) also supports an association between biomass combustion and prevalent asthma. Other studies of biomass-fuel combustion and outdoor air pollution support a relationship between combustion exposure and asthma (Baldi et al. 1999; Garshick et al. 2003; Raaschou-Nielsen et al. 1995) (Table 5.4).

The committee concludes, from its assessment of the epidemiologic literature, that there is limited/suggestive evidence of an association between exposure to combustion products and incident asthma.

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

TABLE 5.4 Key Studies of Asthma

Reference

Type of Study and Population

Exposure Determination

Health Outcome and How Measured

Results

Adjusted OR (95% CI or p)

Limitations

Abbey et al. 1993b,c

Prospective cohort, n=3,914, 1977–1987

TSP, ozone, sulfates

AOD, asthma, chronic bronchitis incidence via symptom questionnaire

TSP and asthma

TSP>200 μg/m3 associated with new cases asthma (RR 1.74, CI 1.11–2.72) with increase in average annual exceedance frequency of 1,000 hr/yr; TSP>150 μg/m3 associated with new cases of asthma (RR 1.23, p<0.05) with increase in average annual exceedance frequency of 1,000 hr/yr

Symptom questionnaire, varying specificity in measures of exposure

Exceedance frequencies expressed as average, hours exceeding TSP thresholds of 60, 75, 100, 150, 175, 200 μg/m3

Abbey et al. 1993a

Prospective cohort, n=3,914, 1977–1987

Sulfates (10-yr mean ambient concentrations)

Same as above

10-yr mean ambient concentrations of SO4 associated only with asthma

Asthma RR 2.87, CI 1.03–7.55 per increment of 7 μg/m3

Same as above

Cowan et al. 2002

Case-control study, 873 cases of asthma vs 2,464 controls

Exposure modeling via troop positions and air-monitoring data; cumulative exposure and number of days at high concentrations (defined as ≥65 μg/m3)

Physician-diagnosed asthma 3–6 years after war

Asthma associated with both estimates of exposure, dose-response

Cumulative exposure: OR 1.24 (CI 1.00–1.55) for intermediate exposure, 1.40 (CI 1.1 1–1.75) for high exposure

Self-selected population, pre-exposure asthma status unknown, active-duty military (Army only)

US DOD registry, Army personnel only

 

No. days at high concentrations: OR 1.22 (CI 0.99–1.51) for 1–5 days, 1.41 (CI 1.12–1.77) for 6–30 days

 

Mishra 2003

Population-based National Family

Self-reported exposure to cooking smoke from biomass

Affirmative response to question “Does

Asthma associated with biomass-fuel

OR 1.59, CI 1.30–1.94 for biomass vs clean fuel

Prevalent cases, limited nature of

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

Reference

Type of Study and Population

Exposure Determination

Health Outcome and How Measured

Results

Adjusted OR (95% CI or p)

Limitations

 

Health Survey (n=38,595), adults 60 years old or older

fuels, cleaner fuels, or mix

anyone [in the household] suffer from asthma?”

use

OR 1.24, CI 1.04–1.49 for mixed fuel vs clean fuel

question

NOTE: AOD=airway obstructive disease; CI=confidence interval; DOD=Department of Defense; OR=odds ratio; RR=relative risk; TSP=total suspended particles.

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×
Chronic Bronchitis

Chronic bronchitis is defined by symptoms of chronic cough and sputum production. A major prospective study of outdoor air pollution with more than a decade of exposure (Abbey et al. 1993b, 1995) and a cross-sectional study of biomass-fuel combustion (Albalak et al. 1999) revealed associations between long-term exposure to combustion products and chronic bronchitis (Table 5.5). Supporting findings were reported by five other studies (Dennis et al. 1996b; Garshick et al. 2003; Osterman et al. 1989a; Perez-Padilla et al. 1996; Raaschou-Nielsen et al. 1995). The study of Gulf War veterans in Iowa of Lange (2002) showed no relationship between exposure to oil-well fires and chronic bronchitis, but the standard epidemiologic definition of chronic bronchitis was not used, so acute and chronic bronchitis could not be distinguished. Although the studies reviewed by the committee indicate a probable relationship between long-term (over 1 year) exposure to combustion products and chronic bronchitis, a key unresolved issue is whether shorter-term exposures (less than 1 year) can cause the condition. The committee found inadequate published data that address the effect of shorter-term combustion-product exposures (less than 1 year) on the risk of developing chronic bronchitis.

A related issue is the exposure-free period after combustion-product exposure. Will chronic bronchitis remit after exposure cessation? If so, how long does it take for symptoms to remit? Only one of the studies in this chapter examined people after an exposure-free period. Osterman et al. (1989a) examined silicon carbide workers with SO2 and dust exposure 6 months after cessation of exposure. They found strong symptom-SO2 associations after adjusting for the effects of dust exposure. The study suggests that chronic-bronchitis symptoms can persist for at least 6 months after cessation of combustion-product exposure, but there are no data from this study or others to indicate whether chronic-bronchitis symptoms might abate thereafter. It is instructive to examine the influence of smoking on the natural history of chronic bronchitis. Smoking is the dominant risk factor for chronic bronchitis. It is well known that chronic bronchitis, when defined as mucous hypersecretion, usually remits after smoking cessation (Fletcher 1976; Kanner et al. 1999; Willemse et al. 2004). In the Lung Health Study, most of the people who had COPD (defined by airway obstruction) and chronic cough had resolution of the cough by a year after sustained smoking cessation (Kanner et al. 1999). At 5-year followup, remission of symptoms persisted among the sustained quitters. Similarly, Fletcher (1976) showed that the most people who had chronic bronchitis had resolution of their symptoms after smoking cessation.

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

TABLE 5.5 Key Studies of Chronic Bronchitis

Reference

Type of Study and Population

Exposure Determination

Health Outcome and How Measured

Results

Adjusted OR (95% CI or p)

Limitations

Abbey et al. 1993b,c

Prospective cohort n=3,310, 1977–1987

TSP, ozone, sulfates

AOD, asthma, chronic bronchitis incidence via symptom questionnaire

TSP and AOD, chronic bronchitis

TSP>200 μg/m3 associated with new cases AOD (RR 1.36, CI 1.11–1.66), chronic bronchitis (RR 1.33, CI 1.07–1.65) with increase in average annual exceedance frequency of 1000 hr/yr

Symptom questionnaire, varying specificity in measures of exposure

Exceedance frequencies were expressed as average, hours exceeding TSP thresholds of 60, 75, 100, 150, 200 μg/m3

Abbey et al. 1995

Prospective cohort n=1,631, 1987

PM2.5 exposure estimated by regression of site, season-specific regression equations from paired PM2.5-visibility observations (1979–1986) and visibility data at nine airports throughout California; long-term averages of each subject’s estimated monthly PM2.5 mean concentrations and exceedance frequencies cumulated 1966–1977 according to ZIP code by monthly residence

Same as above

Onset of AOD and chronic bronchitis related to PM2.5 exposure, onset of asthma not noteworthy for increasing cutoffs of PM2.5, increased magnitudes of regression coefficients of AOD significant at all cutoffs, chronic bronchitis significant >20 μg/m3

Onset of chronic bronchitis RR 1.81 (0.98–3.25) per 45-μg/m3 increase in mean concentration

Same as above

Albalak 1999

Two villages in Bolivia (n=241), one with outdoor kitchens, other with indoor kitchens

PM10 for kitchen and total daily integrated

Chronic bronchitis via British Medical Research Council questionnaire

Outdoor-kitchen village associated with lower risk of chronic bronchitis than indoor-kitchen village

OR 0.4 (95% CI 0.2–0.8) with adjustment for age and sex and excluding smokers

 

NOTE: AOD=airway obstructive disease; CI=confidence interval; DOD=Department of Defense; OR=odds ratio; PM=particulate matter; RR=relative risk; TSP=total suspended particles.

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

Consequently, even if it could be shown that long-term exposure to combustion products caused chronic bronchitis, it might be expected to remit after exposure cessation without long-term health consequences. The committee found inadequate published data to evaluate the natural history of chronic bronchitis after cessation of exposure to combustion products.

The committee concludes, from its assessment of the epidemiologic literature, that there is inadequate/insufficient evidence of an association between short-term exposure (less than 1 year) to combustion products and chronic bronchitis.

Emphysema

Emphysema is a pathologic process involving air-space enlargement distal to the terminal bronchioles accompanied by destruction of the bronchiolar walls. Its major risk factor is cigarette-smoking. The ACS prospective study found that emphysema mortality was not considerably increased among workers exposed to diesel exhaust after adjustment for the effects of smoking (Boffetta et al. 1988). A study of veterans exposed to oil-well fires did not find a relationship with emphysema (Smith et al. 2002). Other studies that included emphysema in the analysis were methodologically inadequate.

The committee concludes, from its assessment of the epidemiologic literature, that there is inadequate/insufficient evidence of an association between exposure to combustion products and the development of emphysema.

Chronic Obstructive Pulmonary Disease (COPD)

The committee did not identify any high-quality studies that evaluated the effect of exposure to combustion products on the risk of COPD, as defined by objective evidence of irreversible airflow obstruction with spirometry, for example, GOLD criteria (Pauwels et al. 2001). The study of Karakatsani (2003) used a clinical definition of COPD, but the 95% CI for FEV1 percent predicted among COPD cases ranged from 86 to 95%, which did not include values less than 80% of the predicted value. That range indicates that most subjects would not meet the GOLD criteria for airway obstruction, which require an FEV1 of less than 80% of predicted values (Pauwels et al. 2001). Several studies of biomass-smoke exposure used measures of airflow obstruction but had methodologic limitations that precluded clear conclusions about the connection between combustion exposure and COPD (Dennis et al. 1996a, 1996b; Dossing et al. 1994; Perez-Padilla et al. 1996).

The committee concludes, from its assessment of the epidemiologic literature, that there is inadequate/insufficient evidence of an association between exposure to combustion products and the development of COPD as defined by irreversible airflow obstruction.

Although some toxicologic studies do provide mechanistic insight as to how inhaled combustion products might act to bring about symptoms associated with asthma or COPD (for example, reviewed in Barnes 1995; Ichinose et al. 1998; MacNee and Donaldson 2003; Takano et al. 1998), the published toxicologic literature has a number of shortcomings that diminish its usefulness for extrapolation to either the human exposure scenario in general or the Gulf War experience specifically. Most controlled-exposure studies either are of short duration, fail to examine long-term residual effects, or use compromised animal models. In addition, the

Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×

endpoints selected for examination in those studies cannot be specifically linked to the pathogenesis of any particular respiratory disease.

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Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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Page 274
Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
×
Page 275
Suggested Citation:"5 Respiratory Outcomes." Institute of Medicine. 2005. Gulf War and Health: Volume 3: Fuels, Combustion Products, and Propellants. Washington, DC: The National Academies Press. doi: 10.17226/11180.
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Page 276
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The third in a series of congressionally mandated reports on Gulf War veterans’ health, this volume evaluates the long-term, human health effects associated with exposure to selected environmental agents, pollutants, and synthetic chemical compounds believed to have been present during the Gulf War. The committee specifically evaluated the literature on hydrogen sulfide, combustion products, hydrazine and red fuming nitric acid. Both the epidemiologic and toxicologic literature were reviewed.

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