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Clinical Investigations: THE PULMONARY LAB |

Variable Extrathoracic Airflow Obstruction and Chronic Laryngotracheitis in Gulf War Veterans* FREE TO VIEW

Arvind K. Das, MD; Lawrence D. Davanzo, DO; George J. Poiani, MD; Peter G. Zazzali, MD; Anthony T. Scardella, MD; Martha L. Warnock, MD; Norman H. Edelman, MD
Author and Funding Information

*From the Medical Service of VA New Jersey Healthcare System, Lyons Campus, and the Department of Medicine, Division of Pulmonary and Critical Care Medicine (Drs. Das, Davanzo, Poiani, Zazzali, Scardella, and Edelman), UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ; and the Department of Pathology (Dr. Warnock), University of California, San Francisco, CA.



Chest. 1999;115(1):97-101. doi:10.1378/chest.115.1.97
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Study objectives: To study the flow-volume loop for evidence of variable extrathoracic airflow obstruction in Persian Gulf War veterans.

Design: Retrospective case-control, single-center study.

Setting: The pulmonary division of an academic health-care center.

Subjects: A convenience sample of the Persian Gulf Registry.

Measurements and interventions: (1) Midvital capacity ratio (ratio of maximum forced midexpiratory to maximum forced midinspiratory flow). This ratio is the criterion standard for the diagnosis of variable extrathoracic airflow obstruction. (2) Evaluation of the anatomy and function of the extrathoracic airway by fiberoptic bronchoscopy. (3) Further investigation into the airway abnormality by histologic evaluation of tracheal biopsy samples in Gulf War veterans only.

Results: Midvital capacity was >1.0 in 32 of 37 Gulf War veterans compared with only 11 of 38 control subjects. The mean (± SD) value was 1.37 ± 0.4 among Gulf War veterans and 0.88 ± 0.3 among control subjects (p = 0.0000005). FVC and its ratio to FEV1 were normal in all these subjects. Bronchoscopy showed inflamed larynx and trachea in all (n = 17) Gulf War veterans. Histologic study showed chronic inflammation of the trachea in everyone (n = 12) who had an adequate biopsy sample.

Conclusion: Physicians should be made aware of the presence of chronic inflammation of the upper airways and inspiratory airflow limitation in a number of Gulf War veterans.

Abbreviations: mid-VC ratio = ratio of maximum forced expiratory to maximum forced inspiratory flow at midvital capacity; PFT = pulmonary function tests; VA = Veterans Affairs; VC = vital capacity

Figures in this Article

A number of Persian Gulf War veterans complain of chronic cough, shortness of breath on exertion, and sleep disturbances among other nonspecific symptoms. Many have been evaluated medically, but clear diagnoses have not emerged. In 1994, we noticed that a pattern of variable extrathoracic airflow obstruction was present in the results of pulmonary function tests (PFTs) of all the five Gulf War veterans who had been referred to our laboratory to that date.

We subsequently had the opportunity to study 48 Gulf War veterans drawn from the Persian Gulf Registry, 17 of whom also had bronchoscopy. We report the finding of an upper airway abnormality.

Subject Selection

The Department of Veterans Affairs (VA) created the Persian Gulf Registry Program in 1992 for Gulf War veterans with health concerns, inviting them to come to the VA facilities for a free examination and tests, whether or not the veteran is ill. We sent letters to all the 86 veterans enrolled in the Persian Gulf Registry at the VA New Jersey Healthcare System, Lyons Campus, if they had not already been tested. Our letter offered them a “breathing test” without questioning them about symptoms. Thirty-eight Gulf War veterans came to be tested in response to our letters and during this time, five more with respiratory complaints were referred to this laboratory by their VA physicians. We did not study five women because the control population consists of men. We eliminated six from analysis because of poor effort, which was defined as FVC of < 80% of predicted in the absence of any evidence of obstructive or restrictive lung disease. For comparison, 46 normal, asymptomatic, men were recruited from among the hospital employees and the local community. Eight were excluded because of poor effort. Of the remaining 38 control subjects, 29 were nonveterans and 9 were veterans of other wars. Bronchoscopy with tracheal biopsy was recommended to those veterans with physiologic evidence of upper airway obstruction. Seventeen underwent the procedure following consent. Bronchoscopy and tracheal biopsy were not recommended to physiologically normal subjects.

Testing

PFTs were done (Collins GS/Plus System; Braintree, MA). Prior to the test, subjects were asked to fill out a brief questionnaire about their smoking history and presence or absence of respiratory symptoms. Flow-volume loop was obtained by performing a forced expiratory vital capacity (VC) followed by a forced inspiratory VC maneuver. Three such maneuvers were performed and the best effort, based on the FVC and the FEV1, was selected by the computer. The flow-volume loop of this best FVC maneuver was used to obtain the mid-VC ratio. A ratio of> 1 was used to diagnose variable extrathoracic airflow obstruction.1,,2,,3 Lung volumes were measured by helium dilution method. The standards of Crapo et al4,,5 were used for normal values. Bronchoscopies to the main tracheal carina were done with a fiberoptic videobronchoscope (Olympus; Melville, NY) under lidocaine topical anesthesia. Still pictures were taken and video recording was made of the entire procedure. During the procedure, we paid special attention to the position and movements of vocal cords during quiet and forced respiration and during phonation. Collapsibility of tracheal wall was also assessed during quiet and forced respiration. The mucosal appearance was called inflamed if it met the bronchoscopic criteria of Stradling6 of inflammation, which includes increased redness of the epithelium, increased number and engorgement of the mucosal vessels, longitudinal corrugations, and obscuring of landmarks due to edema. Two mucosal biopsy specimens were obtained from the upper third of the trachea in each case. Five-micrometer-thick sections were cut and stained with hematoxylin-eosin. Biopsy specimens were reviewed by one of us (M.L.W.) who was unaware of the PFT findings and the visual findings of bronchoscopies. The following criteria were used for histologic diagnosis of inflammation: epithelial inflammation; infiltration of the subepithelial tissue with inflammatory cells; edema of the subepithelial tissue; and subepithelial collagenosis, referred to here as thickening of the basement membrane. Each of these features was noted as present or absent. The thickness of the basement membrane was measured on a videomicroscope by superimposing a micrometer scale, at× 2,000 magnification. Measurements were made at five different points in each specimen in areas of well-oriented epithelium, and the mean of these five measurements was used for further analysis. A mean thickness of > 5 μm signified basement membrane thickening.

Statistical Analysis

Ninety-five percent confidence intervals were calculated for the mean mid-VC ratios of Gulf War veterans and control subjects. A priori contrast was conducted comparing registry-recruited veterans with the referred veterans and when found not different, the same test was performed comparing the combined population of Gulf War veterans with the normal control subjects. One-way analysis of variance was performed to compare the mid-VC ratios of the subgroups (based on their source of entry and smoking status) of Gulf veterans and the normal control subjects, followed by a Student-Newman Keuls multiple comparison test. We also compared the 14 smokers within the Gulf veterans group with the 19 nonsmokers using Student’s t test.

Table 1 shows the demographic characteristics and the PFT data of the Gulf War veterans (n = 37) and the control subjects (n = 38). Twenty-seven (73%) of the Gulf War veterans were recruited by us from the registry. The other 10 had presented themselves for evaluation of their medical symptoms. Fifteen (40%) of the Gulf War veterans and 9 (23%) of the control subjects were smokers. Thirty-two of the 37 Gulf War veterans reported at least one of the three respiratory symptoms of cough, dyspnea, and wheezing on the questionnaire.

The outstanding functional abnormality was in the flow-volume loops. Many Gulf War veterans had the characteristic “flattening” of the inspiratory portion on the flow axis (Fig 1). The means of FVC and FEV1/FVC ratio were not significantly different among the Gulf War veterans and control subjects. The mean mid-VC ratio for Gulf War veterans was 1.37 ± 0.4, with a 95% confidence interval of 1.23 to 1.51. This is significantly greater than the mean mid-VC ratio (0.88 ± 0.3) of control subjects (95% confidence interval, 0.78 to 0.98) with a p value of 0.0000005 (Fig 2). The mean mid-VC ratio of Registry-recruited veterans (1.40 ± 0.49) was not different from that of the referred veterans (1.34 ± 0.3), and each of these subgroups was individually different from the control group. Among the control subjects, the mean mid-VC ratio of the nine veterans was not different from that of the nonveterans (p = 0.9). Thirty two of the 37 Gulf War veterans (86.5%) had a mid-VC ratio of > 1 and were diagnosed as having variable extrathoracic airflow obstruction.1,,2,,3 Among the Gulf War veterans, the mean mid-VC ratio of smokers (1.19 ± 0.26) was less than that of nonsmokers (1.52 ± 0.51) (p = 0.03), which is consistent with expiratory flow limitation, due to the effect of smoking on intrathoracic airways. Gulf War veterans had a mean maximum voluntary ventilation of 78.4 ± 16% of predicted, mean total lung capacity of 99.7 ± 12% of predicted, mean residual volume of 125 ± 37% of predicted, and mean diffusing capacity of 77.4 ± 13% of predicted.

Bronchoscopy revealed mucosal inflammation of the larynx and trachea in every Gulf War veteran. Dynamic inspiratory collapse of the posterior membrane of trachea was seen in only two and this did not correlate with the severity of laryngeal inflammation. No gross dysfunction of the vocal cords was noted during the procedure. Chronic inflammation was histologically confirmed in all of the 12 (100%) subjects from whom a biopsy sample containing sufficient subepithelial tissue was obtained (Table 2). Nine of the 12 specimens met all four histologic criteria of inflammation. The other three specimens met only three criteria. The cells infiltrating the subepithelial tissue were predominantly mononuclear, including lymphocytes and plasma cells. The mean thickness of the basement membrane in the Gulf War veterans was 5.41 ± 1.69μ m (Fig 2). Two specimens showed squamous metaplasia; one of these two Gulf War veterans had never smoked.

Extrathoracic airway obstruction reduces inspiratory and expiratory flow. It is called variable when inspiratory flow is limited more than the corresponding expiratory flow. In such cases, a dynamic narrowing of the extrathoracic airway lumen develops under the increasing negative intraluminal pressure of forced inspiration, thus limiting the maximum inspiratory flow. Several criteria for diagnosis of this condition have been examined in the past. The one that has been found most useful on a consistent basis is the mid-VC ratio.1,,2,,3,,7,,8,,9 Other measurements that have been used suffer either from greater variability due to effort dependence or lesser ability to distinguish intrathoracic from extrathoracic obstruction.2,,8,,10,,11 The criteria proposed by Sackner,12 a combination of increased airway resistance with a normal distribution of ventilation, requires special tests, not commonly performed clinically. The normal range of mid-VC ratio previously reported is similar to that in our control subjects.1,,8 Variable extrathoracic airflow obstruction is caused by a variety of upper airway lesions, including vocal cord paralysis, goiter, neoplasm, etc. It was also seen in burn patients suspected of having thermal or smoke-related injury to their upper airways.3

The chronic inflammatory changes found in the upper airways of these Gulf War veterans cannot be attributed to smoking or allergies. We found these changes equally among smoking and nonsmoking Gulf War veterans. Thickening of the basement membrane is seen routinely in asthmatics (5 to 10 μm), and commonly, although to a lesser degree, in nonasthmatic atopic individuals (3.6 to 7.7 μm) as compared with normal humans (2.2 to 6.0 μm).13,,14 Thickening of the basement membrane rarely occurs in those with chronic bronchitis.15 While none of our Gulf veterans was suffering from asthma, the average thickness of their basement membranes was 5.41 ± 1.69 μm. Moreover, infiltration of the epithelium and the subepithelial tissue with exclusively mononuclear cells, seen in our Gulf War veterans, is distinct from the usual findings associated with asthma and atopy.

The cause of variable extrathoracic airflow obstruction in our subjects is not clear. However, a coexistent chronic inflammation raises the possibility of a cause and effect relationship. Conceivably, inflammation of the vocal cords themselves or inflammation involving the posterior cricoarytenoid muscles and joints with resultant dysfunction or fibrosis can result in this type of airflow limitation. Edema and inflammation of the tracheal wall could also cause sufficient narrowing of the lumen so that a dynamic collapse occurs under the high-flow state of a forced inspiratory maneuver. Indeed we were limited by the inability of our subjects to perform a forced inspiratory VC maneuver under bronchoscopy. We saw such inspiratory collapse occurring in only two subjects. In a study of the upper airway function of burn patients with thermal airway injury, Haponik et al3 reported abnormal mid-VC ratios in 18 (43%) of their 42 patients. When fiberoptic examination was done, they found that 29 (70%) of these subjects had only minimal injury to their upper airways; 8 of these (27.6%) showed variable extrathoracic airflow obstruction. They concluded that abnormality of airflow was a more sensitive indicator of injury to the upper airways than, and sometimes antedated, the visible mucosal changes in such patients. As in our study, narrowing of the upper airways was not apparent, and significant edema or restricted movement of vocal cords was only rarely obvious.

The findings of variable extrathoracic airflow obstruction in 86.5%, and of histologically confirmed but uncontrolled, chronic inflammation in all of the studied Gulf War veterans seems quite substantial. Although this was not a random sample, the Gulf War veterans with the abnormality constitute more than one third of all the veterans on the Persian Gulf Registry of that facility at that time. While a great majority of them reported at least one respiratory symptom on the questionnaire, most did not seek medical attention on their own.

During the Gulf War, veterans were exposed to a variety of known and unknown hazardous materials, such as noxious and irritant fumes and gases from the Kuwaiti oil fires. Approximately 600 oil wells were on fire in March 1991, and over the next 9 months, approximately 900 million barrels of oil were burned or spilled. Preliminary reports of the wartime air sampling data from the region show that the levels of a variety of pollutants were below Environmental Protection Agency standards but the level of PM-10 (fine particulate) was, on an average, sevenfold to eightfold higher than the set Environmental Protection Agency standards.16,,17,,18,,19,,20 Based on these preliminary data, the Office of Technology Assessment concluded that the risk to health from exposure to the smoke and background air contaminants in the Persian Gulf is likely to be extremely small.21However the possibility of long-term health effects has not been ruled out. We believe that a consequence of such exposures could be a prolonged inflammatory process involving the upper airways. Although the borderline abnormalities in the sample means of VC and residual volume raise the possibility of disease of the smaller airways as well, the present evidence suggests that the upper airways were primarily affected. This would be expected in airway injury due to smoke inhalation. An analog to prolonged smoke exposure would be found in firefighters. To our knowledge, there has been no published study evaluating the long-term effects of smoke inhalation on upper airways of animals or humans. The longitudinal studies of pulmonary function in firefighters do not contain information on their inspiratory airflow or upper airway abnormalities.22,,23,,24,,25,,26,,27

Physicians should be made aware of the presence of variable extrathoracic airflow obstruction and a chronic inflammation of larynx and trachea in Gulf War veterans. The exact prevalence and clinical significance of this finding remain to be established.

Correspondence to: Arvind K. Das, MD, Assistant Professor of Clinical Medicine, Division of Pulmonary and Critical Care Medicine, UMDNJ-Robert Wood Johnson Medical School, One Robert Wood Johnson Place, CN-19, New Brunswick, NJ 08903-0019

Table Graphic Jump Location
Table 1. Demographic and Spirometric Findings in Gulf War Veterans and Control Subjects
* 

NS = not significant.

Figure Jump LinkFigure 1.  Flow-volume loops of a Gulf War veteran (left) and a control subject (right). Lung volume in liters is plotted on x-axis, and flow in liters/seconds is plotted on y-axis. Note the characteristic flattening of the inspiratory portion (below the baseline) of the loop in the Gulf War veteran.Grahic Jump Location
Figure Jump LinkFigure 2.  Tracheal biopsy specimen from a nonsmoking Gulf veteran showing thickened basement membrane and infiltration of the subepithelial tissue with mononuclear inflammatory cells (hematoxylin-eosin, original magnification ×1,000).Grahic Jump Location
Table Graphic Jump Location
Table 2. Histologic Findings in Tracheal Biopsy Specimens of Gulf War Veterans

We would like to express our thanks to Jin Choe, MD, chief pathologist at Lyons VAMC, Ronald Cody, EdD, for statistical support, Jean Fiori, CRTT, for technical assistance, and Nita Sinha Das for computer assistance and data analysis.

Miller, RD, Hyatt, RE (1969) Obstructing lesions of larynx and trachea: clinical and pathological characteristics.Mayo Clin Proc44,145-161. [PubMed]
 
Miller, RD, Hyatt, RE Evaluation of obstructing lesions of the trachea and larynx by flow-volume loops.Am Rev Respir Dis1973;108,475-481. [PubMed]
 
Haponik, EF, Munster, AM, Wise, RA, et al Upper airway function in burn patients.Am Rev Respir Dis1984;129,251-257. [PubMed]
 
Crapo, RO, Morris, AH, Gardner, RM Reference spirometric values using techniques and equipment that meet ATS recommendations.Am Rev Respir Dis1981;123,659-664. [PubMed]
 
Crapo, RO, Morris, AH, Clayton, PD, et al Lung volumes in healthy nonsmoking adults.Bull Eur Physiopathol Respir1982;18,419-425. [PubMed]
 
Stradling, P Inflammatory and associated changes.Diagnostic bronchoscopy1991,69-94 Churchill Livingstone. London, UK:
 
Shim, C, Corpo, P, Park, SS, et al Pulmonary function studies in patients with upper airway obstruction.Am Rev Respir Dis1972;106,233-238. [PubMed]
 
Jordanoglou, J, Pride, NB A comparison of maximum inspiratory and expiratory flow in health and in lung disease.Thorax1968;23,38-45. [PubMed] [CrossRef]
 
Rotman, HH, Liss, HP, Weg, JG Diagnosis of upper airway obstruction by pulmonary function testing.Chest1975;68,796-799. [PubMed]
 
Kryger, M, Bode, F, Antic, R, et al Diagnosis of obstruction of upper and central airways.Am J Med1976;61,85-90. [PubMed]
 
Jordanoglou, J, Pride, NB Factors determining maximum inspiratory and maximum expiratory flow of the lung.Thorax1968;23,33-37. [PubMed]
 
Sackner, MA Physiologic features of upper airway obstruction.Chest1972;62,414-417. [PubMed]
 
Djukanovic, R, Lai, LKW, Wilson, JW, et al Bronchial mucosal manifestations of atopy: a comparison of markers of inflammation between atopic asthmatics, atopic nonasthmatics and healthy controls.Eur Respir J1992;5,538-544. [PubMed]
 
Roche, WR, Beasley, R, Williams, JH, et al Subepithelial fibrosis in bronchi of asthmatics.Lancet1989;1,520-524. [PubMed]
 
Salvato, G Some histologic changes in chronic bronchitis and asthma.Thorax1968;23,168-172. [PubMed]
 
Environmental crisis in the Gulf. The US response. Available from, National Technical Information Service. Springfield, VA; accession No. PB92–226182.
 
Chemical and physical properties of emission from Kuwaiti oil fires. Available from, National Technical Information Service. Springfield, VA; accession No. PB92–206481.
 
Air quality monitoring in Kuwait. First National Institute for Luftforskning mission, 5–12 June 1991. Available from, National Technical Information Service. Springfield, VA; accession No. DE92715793.
 
Dispersion of smoke plumes from oil fires in Kuwait. NCAR/TN-402+STR. Available from, National Technical Information Service. Springfield, VA; accession No. PB94–164555.
 
Report to Congress. United States Gulf Environment Technical Assistance. January 27–July 31, 1991. Under Public Law 102-27, section 309. Available from, National Technical Information Service. Springfield, VA; accession No. PB93–157634.
 
The Department of Defense, Kuwait oil fire health risk assessment (The Persian Gulf Veterans’ Registry). An Office of Technology Assessment Review presented to the US Congress. Available from the US General Accounting Office; reference No. DS 79.744.H4 D46; October 1994.
 
Loke, J, Farmer, W, Matthay, RA, et al Acute and chronic effects of fire fighting on pulmonary function.Chest1980;77,369-373. [PubMed]
 
Liu, D, Tager, IB, Balmes, JR, et al The effect of smoke inhalation on lung function and airway responsiveness in wildland fire fighters.Am Rev Respir Dis1992;146,1469-1473. [PubMed]
 
Musk, AW, Peters, JM, Bernstein, L, et al Pulmonary function in fire fighters: a 6-year follow-up in Boston fire department.Am J Ind Med1982;3,3-9. [PubMed]
 
Peters, JM, Theriault, GP, Fine, LJ, et al Chronic effects of fire fighting on pulmonary function.N Engl J Med1974;291,1320-1322. [PubMed]
 
Sparrow, D, Bosse, R, Rosner, B, et al The effects of occupational exposure on pulmonary function.Am Rev Respir Dis1982;125,319-322. [PubMed]
 
Tepper, A, Comstock, GW, Levine, M A longitudinal study of pulmonary function in fire fighters.Am J Ind Med1991;20,307-316. [PubMed]
 

Figures

Figure Jump LinkFigure 1.  Flow-volume loops of a Gulf War veteran (left) and a control subject (right). Lung volume in liters is plotted on x-axis, and flow in liters/seconds is plotted on y-axis. Note the characteristic flattening of the inspiratory portion (below the baseline) of the loop in the Gulf War veteran.Grahic Jump Location
Figure Jump LinkFigure 2.  Tracheal biopsy specimen from a nonsmoking Gulf veteran showing thickened basement membrane and infiltration of the subepithelial tissue with mononuclear inflammatory cells (hematoxylin-eosin, original magnification ×1,000).Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. Demographic and Spirometric Findings in Gulf War Veterans and Control Subjects
* 

NS = not significant.

Table Graphic Jump Location
Table 2. Histologic Findings in Tracheal Biopsy Specimens of Gulf War Veterans

References

Miller, RD, Hyatt, RE (1969) Obstructing lesions of larynx and trachea: clinical and pathological characteristics.Mayo Clin Proc44,145-161. [PubMed]
 
Miller, RD, Hyatt, RE Evaluation of obstructing lesions of the trachea and larynx by flow-volume loops.Am Rev Respir Dis1973;108,475-481. [PubMed]
 
Haponik, EF, Munster, AM, Wise, RA, et al Upper airway function in burn patients.Am Rev Respir Dis1984;129,251-257. [PubMed]
 
Crapo, RO, Morris, AH, Gardner, RM Reference spirometric values using techniques and equipment that meet ATS recommendations.Am Rev Respir Dis1981;123,659-664. [PubMed]
 
Crapo, RO, Morris, AH, Clayton, PD, et al Lung volumes in healthy nonsmoking adults.Bull Eur Physiopathol Respir1982;18,419-425. [PubMed]
 
Stradling, P Inflammatory and associated changes.Diagnostic bronchoscopy1991,69-94 Churchill Livingstone. London, UK:
 
Shim, C, Corpo, P, Park, SS, et al Pulmonary function studies in patients with upper airway obstruction.Am Rev Respir Dis1972;106,233-238. [PubMed]
 
Jordanoglou, J, Pride, NB A comparison of maximum inspiratory and expiratory flow in health and in lung disease.Thorax1968;23,38-45. [PubMed] [CrossRef]
 
Rotman, HH, Liss, HP, Weg, JG Diagnosis of upper airway obstruction by pulmonary function testing.Chest1975;68,796-799. [PubMed]
 
Kryger, M, Bode, F, Antic, R, et al Diagnosis of obstruction of upper and central airways.Am J Med1976;61,85-90. [PubMed]
 
Jordanoglou, J, Pride, NB Factors determining maximum inspiratory and maximum expiratory flow of the lung.Thorax1968;23,33-37. [PubMed]
 
Sackner, MA Physiologic features of upper airway obstruction.Chest1972;62,414-417. [PubMed]
 
Djukanovic, R, Lai, LKW, Wilson, JW, et al Bronchial mucosal manifestations of atopy: a comparison of markers of inflammation between atopic asthmatics, atopic nonasthmatics and healthy controls.Eur Respir J1992;5,538-544. [PubMed]
 
Roche, WR, Beasley, R, Williams, JH, et al Subepithelial fibrosis in bronchi of asthmatics.Lancet1989;1,520-524. [PubMed]
 
Salvato, G Some histologic changes in chronic bronchitis and asthma.Thorax1968;23,168-172. [PubMed]
 
Environmental crisis in the Gulf. The US response. Available from, National Technical Information Service. Springfield, VA; accession No. PB92–226182.
 
Chemical and physical properties of emission from Kuwaiti oil fires. Available from, National Technical Information Service. Springfield, VA; accession No. PB92–206481.
 
Air quality monitoring in Kuwait. First National Institute for Luftforskning mission, 5–12 June 1991. Available from, National Technical Information Service. Springfield, VA; accession No. DE92715793.
 
Dispersion of smoke plumes from oil fires in Kuwait. NCAR/TN-402+STR. Available from, National Technical Information Service. Springfield, VA; accession No. PB94–164555.
 
Report to Congress. United States Gulf Environment Technical Assistance. January 27–July 31, 1991. Under Public Law 102-27, section 309. Available from, National Technical Information Service. Springfield, VA; accession No. PB93–157634.
 
The Department of Defense, Kuwait oil fire health risk assessment (The Persian Gulf Veterans’ Registry). An Office of Technology Assessment Review presented to the US Congress. Available from the US General Accounting Office; reference No. DS 79.744.H4 D46; October 1994.
 
Loke, J, Farmer, W, Matthay, RA, et al Acute and chronic effects of fire fighting on pulmonary function.Chest1980;77,369-373. [PubMed]
 
Liu, D, Tager, IB, Balmes, JR, et al The effect of smoke inhalation on lung function and airway responsiveness in wildland fire fighters.Am Rev Respir Dis1992;146,1469-1473. [PubMed]
 
Musk, AW, Peters, JM, Bernstein, L, et al Pulmonary function in fire fighters: a 6-year follow-up in Boston fire department.Am J Ind Med1982;3,3-9. [PubMed]
 
Peters, JM, Theriault, GP, Fine, LJ, et al Chronic effects of fire fighting on pulmonary function.N Engl J Med1974;291,1320-1322. [PubMed]
 
Sparrow, D, Bosse, R, Rosner, B, et al The effects of occupational exposure on pulmonary function.Am Rev Respir Dis1982;125,319-322. [PubMed]
 
Tepper, A, Comstock, GW, Levine, M A longitudinal study of pulmonary function in fire fighters.Am J Ind Med1991;20,307-316. [PubMed]
 
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