REVERSIBILITY OF AIRFLOW OBSTRUCTION IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE SECONDARY TO SULFUR MUSTARD GAS INJURY

K. Hosseini MD,* S. Alavi MD ,** A.R. Abedi MSc**

* Division of Respiratory Diseases, Department of Internal Medicine, Shiraz University of Medical Sciences, **The Fars Center for Chemical Warfare Victims, Shiraz, Iran

  • Abstract

    Background-Acute heavy exposure to sulfur mustard gas during Iran-Iraq war has resulted in various chronic pulmonary diseases among Iranian veterans, which tend to be irreversible to a large extent.
    Objective-This study was conducted to determine the rate of reversibility of airflow obstruction in patients with mustard-gas-induced chronic obstructive pulmonary disease (COPD).
    Methods-Baseline and post-bronchodilator spirometric studies were performed in 45 patients who had developed COPD following mustard gas exposure. Patients were selected randomly from the documented cases of mustard gas injury who were attending the Special Clinic for Chemical Gas Victims in Shiraz. The criteria for selection were the presence of COPD with a forced expiratory volume in first second (FEV1) of <75% of predicted, and the FEV1/FVC of <75%.
    Results-17 patients (37.7%) showed an increase in FEV1 of >15% of baseline.
    Conclusion-These patients, who can be categorized as chronic asthmatic bronchitis, constitute a significant proportion of chemical victims with COPD. Detection of this group of patients may lead to a more appropriate treatment using the asthma protocols.

    Keywords · Chronic obstructive pulmonary disease (COPD) · chronic asthmatic bronchitis · mustard gas · chemical injury.

    •

    Introduction

    Chronic respiratory diseases are the most prevalent late sequelae of sulfur mustard gas injury observed among Iranian veterans who have been acutely exposed to this chemical warfare in the battle fields of Iran-Iraq war.1-3 It was observed that a subset of these patients with COPD presented with signs and symptoms similar to asthma and could be reversed by bronchodilators. This study was conducted to determine the prevalence of these individuals among our patient group.

    Patients and Methods

    Forty-five Iranian veterans with sulfur mustard gas-induced chronic bronchitis and chronic airflow obstruction were randomly selected from patients who were under regular follow-up at the Special Clinics for Chemical Gas Victims in Shiraz, South of Iran. All of them had a documented history of an acute episode of heavy exposure to mustard gas between 1984 and 1987, in the battle fields of Iran-Iraq war. In all of them, respiratory symptoms had begun after the exposure. None of the patients had any personal or family history of allergic disorders(including asthma, allergic rhinitis and eczema). None of them were smokers either before or after the injury.

    The inclusion criteria were: 1) fulfillment of the definition of chronic bronchitis, and COPD, 2) baseline FEV1<75% of the predicted, and a ratio of FEV1/FVC <75%, 3) lack of history of smoking, 4) lack of any acute respiratory disorder at the time of the study. The patients were asked not to take any inhaled or oral bronchodilator (ß2-agonists, theophylline, and ipratropium bromide) for 24 hours before the study commenced. Baseline spirometric studies were performed for each patient, using a Pneumoscope version 2 (Jaeger, Co, Germany), and the best results from 3 consecutive trials were selected for further data processing. Each patient was then given 3 puffs of salbutamol (100 µg/puff) at one-minute intervals, via a metered-dose inhaler (MDI). Proper use of MDI was assured by one of the authors who supervised the procedure. A second spirometric study was performed 15 minutes after the administration of inhaled salbutamol.4,5

    Results

    The meanąSD age of the patients was 37ą12.09 years (range: 27 to 76 years). The mean baseline and post-bronchodilator values for the measured FEV1 and FVC in our patients are shown in Table 1.Seventeen patients (37.7%) showed an increase in FEV1 of >15% compared to the baseline and, thus, by definition, can be labeled as having chronic asthmatic bronchitis.

    Discussion

    In general, acute heavy exposure to sulfur mustard gas results in various chronic pulmonary diseases which tend to be irreversible in most cases.6,7 Some patients however present with reversible disease components upon use of bronchodilators. The present study shows that a significant portion of mustard gas victims (37.7%) who have chronic bronchitis with airflow obstruction ((COPD), show >15% increase in their FEV1 (considered as significant reversibility)8,9 after inhalation of salbutamol. By definition, these patients can be labeled as asthmatics,10,11 however, since differentiating these patients is difficult from those with pure asthma, such patients are often referred to as asthmatic bronchitis or the asthmatic form of COPD.4The basis for this presentation might be due to development of mustard-gas-induced airway hyperresponsiveness.12 Induction of airway hyperresponsiveness by sulfur mustard has been demonstrated in animal models. Guinea pigs exposed to mustard gas have shown bronchial hyperresponsiveness to substance P and histamine two weeks after exposure. Hyperresponsiveness to substance P, has been attributed to reduction of the enzyme Neural Endopeptidase (NEP) in the airway epithelium, which appears following severe damage and atrophy of the epithelium. Decreased NEP also helps indirectly in the development of hyperresponsiveness to histamine.13 It should be emphasized that although our study shows some degrees of reversibility in airflow obstruction in a group of patients with mustard induced COPD, it could not be documented in all cases in whom the reversibility were expected. This may be in part due to the fact that at the time of the study a number of patients

    were receiving inhaled corticosteroids, and occasionally low-dose oral corticosteroids, thus affecting their bronchial hyperresponsiveness and airflow obstruction. This in turn, might have blunted the acute response to inhaled bronchodilator in some cases, and/or have resulted in a lesser degree of response in others

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