Reactive Airways Dysfunction Syndrome (RADS)

Occupational medicine

Article by Adam L. Seidner, MD - Fellow, UCONN Health Center, Division of Occupational and Environmental Medicine, Farmington, CT
published in "Occupational Airways", Vol. 3. No. 1 May 1997, newsletter of Connecticut Department of Public Health May 1997

REACTIVE AIRWAYS DYSFUNCTION SYNDROME (RADS)

Over two hundred agents have been identified as causes of work-related asthma. It is estimated that two to fifteen percent of adult asthma cases are caused by some chemical irritant or immunogen in the work environment.

Occupational asthma is recognized as a result of the development of an immune response to a variety of agents such as animal proteins and isocyanates. It has also been reported to develop after a single inhalation exposure to high levels of irritant gases, fumes or vapors, eliciting a nonimmunological response. This condition was coined Reactive Airways Dysfunction Syndrome (RADS) by Brooks and colleagues in 1985.

RADS has been seen in exposure at home and in the workplace to various chemicals such as ammonia, chlorine, toluene diisocyanate (TDI) and glacial acetic acid. Table 1 lists other agents that have been known to cause RADS.

Table 1
Selected Occupational Exposures Which Cause RADS

Acetone
Ammonia
Bleaching Agents
Chlorine
Cleaning Agents
Cutting Oils
Detergents
Disinfectants
Floor Sealants
Formaldehyde (high
concentration)
Glacial Acetic Acid
Hydrochloric Acid
Hydrogen Sulfide
MDI (methylene bisphenyl isocyanate)
Perchloroethylene
Pesticides
Rust Inhibitors
Smoke
Sodium Hydroxide
Solvents
Sulfur Dioxide
Sulfuric Acid
TDI (toluene diisocyanate)
Trichloroethylene
Welding fumes

Clinical manifestations of RADS are considered similar to those of immunogenic asthma, and include inflammation, airway hyperresponsiveness and reversibility of bronchial constriction. However, the most fundamental difference between the two types of asthma lies in the absence of asthma attacks after exposure to small amounts of the causative agent(s) a few weeks after onset. Therefore, standard diagnostic immunogenic procedures for asthma caused by immunogic agents cannot be utilized for RADS.

Accurate diagnosis of RADS relies on patient history and demonstration of persistent nonspecific hyperresponsiveness. Brooks and colleagues outlined a diagnostic criteria for RADS as follows:

· Documented absence of previous respiratory complaints, no atopic predisposition
· Onset of symptoms after a single specific exposure incident or accident
· Exposure to a gas, smoke, fume or vapor that was present in very high concentrations and had irritant qualities
· Onset of symptoms occurring within 24 hours after the exposure and persisting for more than three months
· Immediate medical attention required
· Symptoms simulating asthma, with cough, wheezing, and dyspnea predominating
· Airflow obstruction possibly shown on pulmonary function tests
· Bronchial biopsy specimen with mucosal damage and inflammation without eosinophilia
· Positive methacholine challenge testing
· Other types of pulmonary diseases ruled out

Atopy has not been found to be a risk factor for RADS. Patients with pre-existing asthma may develop symptoms after exposure to a nonspecific irritant. However, this is not considered RADS, but a temporary exacerbation of a pre-existing condition.

Once RADS has been diagnosed, because of the nonspecific bronchial hyperresponsiveness, the patient is subject to respond to other environmental stimuli, such as cigarette smoke, cold air, vehicle emissions, and common household chemicals (hairsprays, perfumes, cleaners, bleaches).

Pathophysiology:

The basic pulmonary reactions to toxic agents may include bronchoconstriction, vasoconstriction, increased vascular permeability, and inflammation.

These events are mediated or modulated by biogenic amines, peptides, enzymes and acidic lipids. The prostaglandins, prostaglandin endoperoxides, thromboxanes, bradykinin, spasmogenic lung peptide, and proteases may all play a role in the development of irritant-induced pulmonary disease.

An irritant receptor has been proposed for the bronchoconstriction seen in patients with irritant asthma. Stimulation of irritant cough receptors by inhaled material and mediation by the vagus nerve is prominent among those pathogenic processes producing airways obstruction in asthmatics.

In persons with immune mediated asthma, the pathomorphologic biopsies taken from bronchi usually show neutrophilic and lymphocytic infiltrations as well as frequent and severe destruction of the bronchial epithelium. The pathologic findings in patients with RADS has been conflicting. Research has indicated that patients with RADS do not have these eosinophilic infiltrations or basement membrane thickening. However, other research has demonstrated an increased number of cells with a predominance of lymphocytes, and biopsy specimens have shown increased basement membrane thickness. If a common pathway exists for irritant or nonimmune asthma and asthma with an immune basis, then pathologic changes common to both would be expected.

Discussion:

Occupational asthma is not a single entity even when a single specific causal factor can be identified in the workplace. There continues to be controversy as to whether RADS is a “real clinical entity” and whether it is a form of occupational asthma, although the majority of data show that it is a distinct clinical entity. Therefore, the physician must be aware of the patient's entire medical history, the precise occupational exposures, and be able to demonstrate a cause-and-effect relationship before making a definitive diagnosis of work-related asthma.

When a causal relationship between the occupational agent and asthma has been established, the most important part of the treatment is protection from the exposure. This can be accomplished through substitution of materials, ventilation, personal protective equipment, or change in job. These industrial exposures can cause permanent impairment. Individuals with RADS are treated in the same manner as other asthmatics. The use of beta 2-adrenergic drugs, steroids, inhaled cromolyn and ipratropium can be helpful. Prevention of RADS requires plans for reducing or eliminating accidents and spills, plans for engineering controls and proper and effective local exhaust ventilation, and plans for emergency response if spills or releases occur. There is still much research needed to understand RADS, its pathogenesis and appropriate forms of treatment.

REFERENCES
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