Ethical Issues in Clinical Research in Occupational Bronchial Asthma Patients
L.Ivanova, O.Rumyantseva
RAMS Institute of Occupational Health, Moscow, Russia
To determine the role of occupational fraction in the development of bronchi and pulmonary pathologies, altogether 30 workers (28 men and 2 women) were examined in the
Clinic of the RAMS Institute of Occupational Health.
The group was composed of workers of the Kolchugino Metallurgic Enterprise who worked in rolling and casting shops as thermal operators, polishers, vacuum and centrifugal casters, founders. The main dangerous factor at work was non-ferrous aerosols including metals –allergens such as chromium, nickel and cobalt in concentration not more than the
MAC (maximum allowable concentration) value. The number of workers subject to dangerous work conditions was from 70% to 80% with length of service more than 10 years.
Examined workers aged from 40 to 49 (17 men), over 50 (13 men).
To determine the role of occupational fraction in the development of bronchi pulmonary pathologies in the examined patients test of natural migration of leukocytes inhibition (TNMLI) in vivo was used in the Clinic.
The method is based on a change of directed leukocyte migration to the section where allergens were accumulated (mucous of cavity mouth) due to allergic response.
Allergens are diluted in 1:100 ratio by physiological salt solution and mouth rinsing is performed by 10 ml of physiologic salt solution, 10-ml antigen solution, then again by 10-ml salt solution (sample portions). Sediment of washed out water from 1, 3 and 4 glass are to be analyzed by microscopy. Migration index (MI) is calculated by formulae: MI=NL – LS
100%, where:
NL is the number of leukocytes of the portion in control (1 glass);
LS is the number of leukocytes of the sample portions (4 glass). The results are positive if leukocyte migration is more than 60% increased, or if leukocyte migration is more than 30% oppressed in comparison with the primary values after gapten exposition.
Taking into account the fact that this study is done in vivo on men applying allergen solution, a number of ethical questions is confronting a researcher and it becomes clear that
Commission of Ethics of the RAMS Institute of Occupational Health should approve the research as well as written informed consent of a volunteer. The following documents go to the Commission on Ethics:
1.
Application for a research to be done;
2.
Protocol of a research;
3.
Written informed consents of a patient-participant;
4.
Information on research methods to be applied;
5.
Information of likely adverse responses during the research.
Protocol of Clinical TNMLI Study
Purpose: to reveal sensitivity to industrial allergens in workers exposed to nonferrous aerosols.
Sample dosage: nickel sulfide (5%-water solution), cobalt sulfide (5%-water solution), and Potassium bichromate (0.5%-spiritus solution).
Pathology: diseases of bronchi pulmonary system due to exposure to non-ferrous aerosols.
Diagnoses: bronchial asthma (15 subjects), chronic obstructive bronchitis (12 subjects), and hypersensitive pneumonite (3 subjects).

2
Criteria of patients selection:
1.
Subjects with long length of service are to be examined who work in contact with non-ferrous aerosols and suffer from chronic bronchi and pulmonary
2.
pathologies.
Inflammation of bronchi pulmonary process is a contraindication for other studies necessary to confirm occupational genesis of bronchi pulmonary pathology (provocative inhalation sample with some allergen).
3.
4.
Patients not treated glucostyroids and with no complicate allergic history.
Anamnesis is analyzed together with retrospective data of outpatient medical history of a patient before the study and hygienic parameters of working conditions are described, work places enlisted, allergy history given, clinical
5.
manifestations described, acute inflammatory respiratory pathologies are examined and attempted to be connected with expiratory asphyxia attacks.
To specify obstruction mechanisms pickfluometry is conducted if manifestations are not clear. Indices of morning and evening expiration per 1 second are performed.
The study is stopped if:

Undesirable side responses appear;

A patient refuses from participation;

Conditions come that require urgent therapeutic measures.
Study lasts for 68 minutes
Results and discussion : adverse side effects have been noticed in two patients out of 30 examined subjects. One patient showed face skin reddening accompanied with itching. These symptoms were removed in 15 minutes after antihistamine substance was taken in. The next patient showed nettle rash on the face and neck accompanied with itching and burning, which were stopped by administration of S.Suprastini 1.0 in 24 minutes.
23 positive results were found: 14 patients showed the test positive due to increased leukocyte emigration (which corresponded to allergic hypersensitivity response of immediate type (I easy reacting type) , 10 patients showed the test positive due to oppressed leukocyte migration (which corresponded to allergic hypersensitivity responses of immediate type (III immune complex type) and delayed type (IV cell type); 4 subjects showed test-negative results, 2 showed dubious results.
In 23 cases correlation of bronchi pulmonary pathologies with occupation was clear, no correlation was found in 4 subjects of an occupational fraction for asthma, 3 subjects who have dubious TNMLI results diagnosis was not put. The latter group of patients will be tested provocative sampling in industrial conditions (in other words it is an exposure test, or putting of a patient into the former work conditions and in contact with former occupational hazards till appearance of clinically manifested pathology). This diagnosis technique requires the same set of ethical documents as the ones needed for TNMLI such as informed written consent, research protocols and others.