GBZ 57-2019Diagnosis of occupational asthma (English PDF)

3.1 Occupational asthma

Chronic inflammatory disease of the airway involving a variety of cells including

eosinophils, mast cells, T lymphocytes, neutrophils, smooth muscle cells,

airway epithelial cells, and other cellular components, which is caused by

contact with certain chemical substances in occupational activities. It is

accompanied by variable airflow limitation and airway hyperresponsiveness.

Occupational asthma in this Standard includes occupational sensitizer-induced

asthma and occupational reactive airway dysfunction syndrome.

3.2 Occupational sensitizer-induced asthma

Chronic inflammatory disease of the airway characterized by intermittent attack

of wheezing, shortness of breath, chest tightness, or cough, etc. caused by

inhalation of sensitizers in occupational activities, with a period of incubation.

3.3 Occupational reactive airway dysfunction syndrome

Chronic airway neurogenic inflammatory disease with cough, wheezing, and

5.1.7 If 5.1.1+5.1.2+5.1.3 or 5.1.2+5.1.3+5.1.4 or 5.1.1+5.1.2+5.1.5 or

5.1.1+5.1.2+5.1.6 are met, occupational sensitizer-induced asthma can be

diagnosed.

5.2 Occupational reactive airway dysfunction syndrome

The following conditions shall be met at the same time:

a) There is an exact occupational inhalation history of large doses of irritant

chemicals in a short period of time;

b) After contact, mucosal irritation symptoms such as shedding tears,

pharyngalgia, cough, etc. appear immediately;

c) Within 24 h after inhalation, bronchial asthma symptoms appear. The

duration of the symptoms is longer than 3 months;

d) Pulmonary function test shows reversible obstructive ventilation function

disturbance or non-specific airway hyperresponsiveness;

e) There is no history of diseases of respiratory system such as chronic

bronchitis and chronic obstructive pulmonary disease.

6.1 Therapeutic principles

6.1.1 After the diagnosis of occupational asthma is established, the patient shall

be removed from the original occupational activity environment as soon as

possible, to avoid and prevent the relapse of asthma.

6.1.2 Patients with acute asthma attacks shall be relieved for symptoms as soon

as possible, relieved for airflow limitation and hypoxemia. The main

pharmacotherapy methods are repeated inhalation of fast-acting beta2 receptor

agonists, oral or intravenous glucocorticoids, inhalation of anticholinergic drugs,

and intravenous aminophylline, etc. Patients with severe asthma attacks and

acute respiratory failure, if necessary, shall be treated with mechanical

ventilation.

6.1.3 For long-term therapy of asthma, according to the severity of the disease,

an appropriate therapeutic regimen shall be selected. The goal is to achieve

and maintain symptom control, maintain normal activity level, and maintain

normal pulmonary function as much as possible.

6.2 Other treatment

Appendix A

(Informative)

Instructions for the correct use of this Standard

A.1 Occupational sensitizer or irritant chemical is one of the pathogenic factors

of bronchial asthma. Compared with common asthma, occupational sensitizer-

induced asthma has no difference in pathological changes, clinical

manifestations, pulmonary function changes, therapy, etc. The pathogenesis is

mainly sensitizer-induced mechanism, but other mechanisms are often mixed.

Respiratory inhalation is the main contact route for occupational sensitizer-

induced asthma and the starting position for stimulating the immune response.

A.2 Case data show that individual chemicals can, through skin contact, cause

occupational sensitizer-induced asthma, such as occupational sensitizer-

induced asthma caused by skin contact with latex. If epidemiological

investigations, toxicological studies indicate that other chemicals can also

cause sensitizer-induced asthma by skin contact, occupational asthma can be

diagnosed.

A.3 Case data show that occupational sensitizer-induced asthma often occurs

in the 6 months to 10 years of contact with sensitizers. The shortest is 2 months.

A.4 Patients with occupational sensitizer-induced asthma, before the onset of

the disease, may develop allergic rhinitis symptoms such as running nose,

nasal itching, nasal congestion, and sneezing. Therefore, when there are

frequent attacks of nasal congestion, nasal itching, thin nasal discharge,

continuous sneezing, and other symptoms, the possibility of occupational

asthma shall be tracked.

A.5 In the early and middle stages of occupational sensitizer-induced asthma,

the occurrence and development of asthma symptoms are closely related to

sensitizer exposure. Typical occupational asthma patients often develop

asthma attacks during work or a few hours after work. The symptoms are more

pronounced on the first day of the workday. On weekends, holidays, or after

leaving the workplace, asthma symptoms can be alleviated. If the worker,

during work or a few hours after work, develops repeated attack of wheezing,

shortness of breath, cough, and other symptoms, and has medical records; or

there are two or more workmates (same type of work or same post) proof

materials proving that the patients often develop cough, chest tightness,

asthma symptoms during work or a few hours after work and develop repeated

attacks, it can be considered that occupational contact is associated with

Appendix B

(Normative)

Laboratory sensitizer bronchial provocation test and job-site bronchial

provocation test

B.1 Laboratory sensitizer bronchial provocation test

B.1.1 Conditions and requirements for subjects

B.1.1.1 During the test, asthma symptoms have been alleviated. There is no

wheezing in the auscultation of the lungs.

B.1.1.2 Before the test, subjects have a FEV1>=70 % of the predicted value.

Under close observation, some patients may be relaxed to FEV1 >60 % of the

predicted value.

B.1.1.3 Subjects with cardiac and (or) pulmonary insufficiency, aortic aneurysm,

recent myocardial infarction or cerebrovascular accident, uncontrolled

hypertension, hyperthyroidism, pregnancy, and recent upper respiratory tract

infection (< 2 weeks), etc. are not suitable for the test. Subjects who are allergic

to certain strong sensitizers (such as penicillin, etc.) or have had a history of

hypersensitivity (such as anaphylactic shock) are also not suitable for the test.

B.1.1.4 Drugs to be discontinued

a) Discontinuation of inhaled short-acting beta2-receptor agonist or

anticholinergic drugs for 6h, oral short-acting beta2-receptor agonist or

theophylline drugs for 12h, long-acting or sustained-release dosage form

drugs for 24 h;

b) Discontinuation of inhaled glucocorticoids for 12 h, oral glucocorticoids for

48 h;

c) Discontinuation of antihistamines for 48h;

d) Other drugs, such as beta-receptor blockers, barbiturates, benzodiazepines,

etc., can reduce the tolerance to the activator; and shall be discontinued

48h before the measurement.

B.1.1.5 6h before the measurement, it shall avoid drinking coffee, strong tea,

and alcoholic beverages. 2h before the measurement, it shall avoid vigorous

exercise or cold air inhalation.

B.1.3.2 If there are obvious symptoms and signs after the provocation, such as

chest tightness, shortness of breath, sharp cough, lung wheezing, etc., the

upper value shall be relaxed. If FEV1 drops by more than 10%, it can be judged

as positive.

B.1.4 Matters needing attention

B.1.4.1 There is still a potential danger in the process of provocation test. The

sensitizer inhalation concentration should not be too high, so as to avoid the

irritative reaction. At the same time, the indications and contraindications shall

be strictly controlled. The operation specification shall be strictly followed. The

technician who performs the operation must be proficient in the operation

procedures. The examination room shall be provided with bronchodilator,

oxygen, and other first-aid medicines.

B.1.4.2 In view of the fact that this test requires certain equipment and technical

conditions, during the test, individual cases may be overreacted, so this test

shall be carried out in a hospital with conditions.

B.1.4.3 It is not advisable to give hints before or during the test that the subject

should not be too nervous.

B.2 Job-site bronchial provocation test

B.2.1 Pre-test preparation and basic conditions

Same as B.1.1.

B.2.2 Method

B.2.2.1 Before the test, the value of the basic Fractional exhaled nitric oxide

(FeNO) is measured. Within the 1st hour after entering the job site, every 15

min, the ventilation function (FEV1) is measured once. The 2nd hour, every 0.5

h, the ventilation function is measured once. According to the situation, it is

possible to stay at the site for 1 h~2 h.

B.2.2.2 After disengagement, every 1 h, the pulmonary function is measured

once. The clinical symptoms and signs shall be paid attention to and recorded.

Continuous observation for at least 8 h. 24 h, it shall be measured again. FeNO

after the test shall also be measured.

B.2.2.3 If pulmonary function indices are significantly reduced, and there are

respiratory symptoms and signs, the provocation test can be terminated; the

bronchodilator can be inhaled. The recovery of pulmonary function indices shall

be observed.

Appendix C

(Informative)

Sensitizer-specific IgE antibody detection-enzyme-linked

immunosorbent assay (ELISA)

C.1 Principle

The basis of enzyme-linked immunosorbent assay is the immobilization of

antigen or antibody and the enzyme labelling of antigen or antibody. The

antigen or antibody bound to the surface of solid phase support retains its

immunological activity. The enzyme-labelled antigen or antibody retains both its

immunological activity and the activity of the enzyme. In the measurement, the

known specific antigen is first immobilized on the surface of solid phase support

to form a solid phase antigen. The sample to be tested is added. Then the

enzyme-labelled antibody is added, so that an antigen-antibody to be tested-

labelled antibody complex is formed on the solid phase support. After adding

enzyme substrate and chromogen, color is generated. The degree of color

generation is expressed by the absorbance (A) value. The measured A value is

correlated with the level of the sensitizer to be tested.

C.2 Equipment

Porous polystyrene board (universal 96-pore board, 12×8 pores), micropipette,

enzyme-labelled immunoassay instrument, PH test paper, thermostat,

refrigerator, wash bottle, wet box, common glassware, etc.

C.3 Reagents

C.3.1 Currently, various ELISA tests have commercialized special kits, including

reaction plates coated with goat anti-human IgE, serial standards (0 U/mL, 10

U/mL, 100 U/mL, 500 U/mL), and quality control serum; enzyme (HRP) labelled

anti-human IgE monoclonal antibody; buffer solution, stop buffer, etc.

C.3.2 Dedicated labelling enzyme: Horse-radish peroxidase (HRP) is most

commonly used to label various antibodies.

C.3.3 Commonly-used enzyme substrates and chromogens: HRP substrate is

H2O2 (or urea peroxide), which requires hydrogen donor to participate in the

catalysis. The latter is mostly a reductive dye, which reacts to form a dark or

fluorescent oxidative dye. There are many chromogens (hydrogen donors)

available for HRP. Commonly used are o-phenylenediamine (OPD), 3,3',5,5'-

Appendix D

(Informative)

Specific sensitizer skin test

D.1 Intracutaneous test

D.1.1 Selection of skin test solution

D.1.1.1 Sensitizer skin test solution: SELECT a standardized skin test solution.

D.1.1.2 Skin test control solution and purpose: In order to obtain an accurate

skin test result, a skin test is performed with both positive and negative controls.

The positive control solution is histamine dihydrochloride at a concentration of

0.017mg/mL or histamine diphosphate at a concentration of 0.028 mg/mL,

which is equivalent to a 0.01 mg/mL histamine substrate.

The purpose of using a positive control solution:

a) JUDGE the positive degree of sensitizer skin test: USE positive control

solution caused papule as the standard "scale" to determine the positive

degree of sensitizer skin test.

b) Determine the level of skin reactivity of the subjects: Due to age, physical

condition, and region, the skin's reactivity is not the same. For example,

the skin reactivity of the elderly is poor; and the reaction of the positive

control is also weak.

c) Observe the inhibitory effect of drugs: When the positive control solution

shows negative reaction, it indicates that the skin test result is likely to be

inhibited by certain drugs, such as antihistamines, thus the skin test result

is invalid. Only when the positive control solution shows positive reaction,

it indicates that the skin test is not affected by drug inhibition or other

factors, and the skin test result is valid. The negative control solution is

usually normal saline or sensitizer diluted preservation solution. The

negative control solution shows negative reaction. If the patient is highly

sensitive, a false positive reaction may appear. At this time, the skin test

positive reaction produced by the sensitizer is not clinically significant.

D.1.2 Operation procedures

D.1.2.1 The skin of the subject's forearm palmaris is disinfected using 75%

alcohol. When disinfecting, do not apply it repeatedly. Do not use iodine tincture

b) People with obvious dermatographism should not be skin tested;

c) Before the test, STOP taking the antihistamine drugs. When the conditions

permit, it shall stop taking adrenal glucocorticoid;

d) The antigen used shall be sterile and of appropriate concentration;

e) The test operation shall be accurate. Do not be bleeding;

f) After injection, do not press and rub the wheal;

g) Attention shall be paid to systemic reaction. First-aid medicines shall be

provided.

D.2 Prick test

D.2.1 Selection of skin test solution

D.2.1.1 Sensitizer skin test solution: same as D.1.1.1.

D.2.1.2 Skin test control solution and purpose: The concentration of histamine

dihydrochloride or histamine diphosphate used in the positive control solution

is 100 times that of the intracutaneous test, which is equivalent to 1mg/mL

histamine substrate. The purpose of using the control solution is the same as

D.1.1.2.

D.2.2 Operation procedures

D.2.2.1 The test area disinfection is the same as that of intracutaneous test.

D.2.2.2 Apply a drop of sensitizer skin test solution or control solution to the skin

test site. USE a pricking needle to prick in the center of the skin where the skin

test solution is dripped. The method of pricking is: USE a pricking needle to

vertically and gently press down on the skin for 1s; and quickly LIFT the needle;

2min~3min, WIPE the skin test solution. If multiple sensitizer pricks are

performed at the same time, each pricking site shall be separated by more than

3cm.

D.2.3 Observation and judgment

D.2.3.1 About 15 min after pricking, the reaction results are observed. Observe

whether there is a papule at the pricking site and the papule size. In the next

10min~15min, it is observed several times. If the papule increases, RECORD

the latter reaction. If it is reduced, RECORD the previous reaction.

D.2.3.2 Observation method: same as D.1.3.2.

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