Discussion on Reactive Airways Dysfunction Syndrome (RADS):

Chronic and recurrent asthma-like respiratory symptoms resulting from toxic inhalation
exposures have been recognized for many years. In 1985, this characteristic post-chemical injury
asthma-like syndrome was formally recognized in clinical observations by Brooks and
colleagues, who coined the term “Reactive Airways Dysfunction Syndrome (RADS).” Brooks
and associates described 10 patients who developed an asthma-like condition that persisted
beyond the usual recovery period.

This condition developed after a single inhalational exposure to high levels of a toxic

The exposures were either brief (lasting just a few minutes) or as long as 12 hours, and there was
a short time interval between exposure and the onset of symptoms – ranging from several
minutes to several hours. In almost all instances, the asthma-like symptoms developed as a result of accidental exposure or as a result of a high level of exposure in a poorly ventilated setting. Most important, asthmatic symptoms were persistent, that is, defined as lasting at least three months and averaging three years in duration from the time of initial exposure to the irritant.

RADS is the most common and best characterized form of irritant-induced asthma, but it has also
been reported to occur following repeated moderate to high level exposure to an inciting agent.
Several salient points regarding RADS should be emphasized. First, RADS results from a high
level of inhalation exposure to a toxic substance. Generally, the intensity of the exposure is such
that the affected individual seeks immediate medical attention.

Second, the asthma-like condition originates with the exposure. Individuals with preexisting
asthma (and therefore preexisting bronchial hyperresponsiveness) may develop pronounced
symptoms of cough, wheezing, and SOB induced by a nonspecific irritant exposure. This is not
RADS, but a temporary exacerbation of a preexisting condition.

Third, RADS is associated with persistent symptoms. In patients with RADS, respiratory
symptoms and nonspecific bronchial hyperresponsiveness, by definition, persist for at least three
months and commonly for years following an exposure. The available clinical, physiologic, and
histologic evidence strongly suggests that RADS represents the persistent and severe end of the
spectrum of irritant responses in the airways.

Finally, once RADS is established, because of the induced nonspecific bronchial
hyperresponsiveness, the patient is then subject to bronchospastic responses from many and
varied environmental stimuli, including cigarette smoke, cold air, traffic fumes, and common
household chemicals, such as hairsprays, perfumes, and bleaches.

The diagnosis of RADS is based on the clinical history and the demonstration of persistent
nonspecific bronchial hyperresponsiveness. The latter may be implied by a significant spirometry
response to an inhaled bronchodilator or documented by a positive nonspecific
bronchoprovocation challenge test (e.g., methacholine challenge testing).

Clinical Manifestations
The onset of symptoms in RADS is usually so abrupt that subjects are able to date their
occurrence precisely, although a few patients report respiratory symptoms developing up to
seven days after the exposure. Patients with multiple exposures to high concentrations of
products such as chlorine may be able to identify the timing, nature, and frequency of most

Patients with the not-so-sudden onset may not be aware of multiple low level irritant exposures
and may report episodic symptoms that are not precisely linked to known exposures.
After an acute exposure to gas, smoke, fumes, or vapors with irritant properties, some subjects
with no history of respiratory complaints report a burning sensation in the throat and nose
referred to as respiratory upper airways distress syndrome (RUDS), in addition to cough,
dyspnea, wheeze, and chest pain. These symptoms typically develop within 24 hours of the
exposure and are severe enough that approximately 78 percent seek emergency room treatment.

There is no single objective test or “gold standard” to confirm the diagnosis of RADS. For
example, these patients do not develop recurrence of symptoms after re-exposure to a low level
of the substance that initiated the problem as might be expected with other forms of occupational
asthma. Therefore, confirmation of the diagnosis by objective means, such as a fall in lung
function on returning to work or improvement when away from work, is not possible.
Specific bronchoprovocation challenge tests utilizing low-level exposures would be expected to
be negative. Therefore, accurate diagnosis depends on history.

Baseline spirometry is obtained in all patients suspected of having RADS; bronchodilator
reversibility is assessed if airflow limitation is present. In a series of 19 patients seen after
chlorine exposure, 10 had airflow limitation when assessed soon after the exposure; many
showed reversal of obstruction with time [Brooks et al, 1998]. In a separate study of 10 subjects
with RADS due to high level exposures to a variety of agents, four had airflow obstruction with a
forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio <70 percent
[Brooks et al., 1985].

Following baseline spirometry, bronchodilator reversibility is assessed by inhalation of a shortacting beta agonist. In general, reversibility is defined as an increase in FEV1 of 12 percent or
more, accompanied by an absolute increase in FEV1 of at least 200 mL in adults. Airway
obstruction is generally less responsive to a bronchodilator in RADS than in asthma, although
some degree of reversibility may be present. A comparison of 30 subjects with immunologic
occupational asthma and 15 subjects with RADS found a mean improvement in FEV1 after
bronchodilator of close to 20 percent in the subjects with immunologic occupational asthma,
nearly double the response seen among those with RADS. However, significant heterogeneity was seen among the RADS group: 6 of the 15 subjects had a postbronchodilator improvement in
FEV1 of more than 15 percent [Gautrin et al., 1995].

In a minority of patients, a restrictive defect is noted on pulmonary function testing, although an
obstructive pattern is much more common. Nonspecific bronchoprovocation challenge (methacholine challenge) — If baseline spirometry shows absent or minimal airflow limitation and no significant bronchodilator reversibility, nonspecific (or nonallergic) bronchial challenge (e.g., methacholine) is performed to assess for non-specific bronchial hyperresponsiveness. Among various case reports, a positive bronchoprovocation challenge was present at initial evaluation in virtually all patients who were
able to perform the testing.

Etiological agents
Cases of inhalation accidents, reported to Surveillance of Work Related and Occupational
Respiratory Disease (SWORD) and the Open Public Records Act (OPRA) between 1992 and
2001, classified the offending agents into five categories. The most frequently reported agents
were irritant gases (42%) [including hydrogen sulfide] followed by solvent vapors (18%),
metallic fumes (11%), acid mists (9%), and other (18%). The originally reported causative agents
of RADS include uranium hexafluoride gas, floor sealant, spray paint containing significant
concentrations of ammonia, heated acid, 35-percent hydrazine, fumigating fog, metal coating
remover, and smoke.

The management of the patient with established RADS or irritant-induced asthma is no different
from that of any other asthmatic. In addition to relieving symptoms with bronchodilators,
treatment should be directed at reducing the level of nonspecific bronchial hyperresponsiveness
(i.e., corticosteroids, cromolyn sodium, and nedocromil sodium). Because patients with RADS
are no more susceptible upon re-exposure to the causative agent than are other asthmatics, the
worker may return to the workplace if measures are taken to limit subsequent exposures to less
than the provocative threshold for that individual.

The long-term expected outcome for patients with RADS has not been well documented.
Individuals with RADS generally continue to report bronchial irritability symptoms and
demonstrate nonspecific bronchial hyperresponsiveness for years after the inciting event. Tarlo
and coworkers reported that if symptoms of irritant-induced asthma do not clear within six
months, they are likely to persist for several years. It is not yet possible to predict which patients
will have persistent symptoms and permanent hyperresponsiveness on the basis of the agent or
the circumstances of exposure.

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