O ccupational asthma

Occupational asthma Conf. Dr.Brandusa Constantin

Definition • The OCCUPATIONAL ASTHMA is a syndrome characterized by a reversible bronchospasm with wheezing that is initially caused by occupational exposure to the substances present in the workplace. • A recent definition (1999) is: asthma is a respiratory disease characterized by airways obstruction, partially or complete reversible (spontaneously or after therapy), inflammation of the respiratory ways and high reactivity to many stimuli.

Etiology • A large range of agents/factors at the workplace that may act like allergens or irritant agents of the bronchial mucosa. The etiological factors of occupational asthma • Animal and vegetal organic powders Animal products: • feathers, mites, avian proteins (serum and dejections); • animal hair, furs, epidermis desquamation, human hair;

insects and mites: • grain moth, grain mites, • bees’ toxins, chitin powder; • silkworms (hair, butterflies, sericin); • daphnia, moths. • fish gelatin; • animal extracts: ACTH, retrohypophysis, peptone powder, tripsine; • moulds, spores; • enzymes of subtilis bacillus: subtilysins, subtilpeptidasis.

Vegetal products Powders of: • FLOUR, grain and other cereals dust;

Wood dust: oak, fir, pine, beach, walnut, mahogany, red cedar,ebony,Brazilianrosewood,teak,whitecedar,samba

Coffee beans, tobacco leaves

Vegetal powders of: • cotton, flax, hemp, jute; • paper; • seeds of caster-oil plant, soy, hop; • medicinal herbs; • spices; • pollens.

Organic and inorganic (chemical substances) Inorganic substances: • Chrome • Cobalt • Nickel sulphate

Welding gases

Foundry

Vanadium penta oxide • Tungsten • Complex salts of platinum (tetrachloroplatinate of ammonium, hexachloroplatinate) • Chlorine • Ammonia • Lime • Cement

Organic substancesisocyanates: toluendiisocyanate (TDI), phenilmethan-diisocyanate (MDI), naphtalendiisocyanate (NDI), hexamethilendiisocyanates (HDI)

antibiotics: penicillin, ampicillin, streptomycin, spiramicin etc.

drugs: aspirin, quinine, amydopyrin, ipecacuanha, rhubarb, codein, cocaine, novocaine, sulphamids etc. • organophosphorous esthers, pyretru

anhydride: phtalic, trimelithic, hexahydrophtalic, tetrachlorophtalic • formaldehyde, polyurethanes • colophony, propylene glycol, organic resins • organic solvents: diluter, acetone, petroxin etc. • fibers of polyesters.

cosmetics: hairs permanent solution, ethylene diamine, sulphchloramide, phenol, chloramines, tanic acid

Etiopathogenesis classification • Allergic asthma; • Irritant-induced asthma; • Mixed asthma. • The allergic and irritant-induced asthma may be associated with exercise-induced asthma.

Pathogenesis • The non-specific bronchial hyperreactivity as the usual abnormality for all the etiopathogenic aspects of asthma. • It is an exacerbated bronchoconstriction to stimuli well tolerated by some persons (10-100 times more sensitive to Ach and histamine, 100 times more sensitive to PgF2 action).

The non-specific bronchial hyperreactivity mechanism • abnormality of the smooth bronchial muscles: hyperplasia, hypertrophy, hyper-contractility, excessive localization in submucosa; • abnormality of the bronchial muscles: • thickening, • inflammation, • permeability disorders, • mast cells presence in bronchial epithelium; • nervous disorders: • vagalhypertonia: • abnormal reactivity of the irritation receptors, • cortical-bulbar disorder, • hyperreactivityof the bronchial muscles to acetylcholine; • hypertonia • decrease of -adrenergic sensitivity.

Mechanisms of producing the asthma attack 1. allergens inhalation: allergen + IgE  degranulated mast cells in submucosa  mediators release  histamine Histamine: • raises the vascular permeability; • the contraction of the bronchial muscles stimulates the parasympathetic receptors;

A long period of action: • leukotrienes release: LTC4, LTD4, LTE4 – the inflammation accelerates the bronchial constriction, attracts the polymorphonuclear cells an eosinophils; • release of the platelet activating factor; • release of the chemotactic factors for PMN; 2. Irritants inhalation:-direct action on irritant receptors  bronchoconstriction - blockade of -bronchial receptors - hapten mechanism:isocyanates, anhydrides AFTAL, trimellitic anhydride, some platinum, dyes, formaldehyde, organic solvents etc.; 3. In exercise-induced asthma: • reflex involving of parasympathetic system; • release of mediators from mast cells.

Diagnosis criteria in occupational asthma Occupational anamnesis: • crisis occurrence at the workplace: beginning, middle and the end of shift, during the way to home; • absence of the attacks in days off work: holiday, week-end; • attack re-occurrence at the work restart; • double crisis occurrence: at work and at home; • long exposure to an allergic/irritant factor.

Non-occupational history: • family history of asthma; • starts after a “cold”; • rhinitis that precedes the asthma with a few years ago; • crisis described like a “stifle”; • wheezing described like “whistling”, “violin sound”, “peeping”, “mew” etc. • cough with pearl expectoration; • ocular, nasal and pharyngeal burning pain; • tearing, rhinorhea, cough.

Making evident the bronchial hyperreactivity: • Non-specific bronchial provocation test; • Specific inhalation challenge test; Bronchial provoking test: Commune conditions to do these tests: • asymptomatique patient, • without rattles, • without medicines for at least 2 days, • initial VEMS recording (VEMS over 1500 ml), • test making.

The NON-SPECIFIC BRONCHIAL PROVOCATION TEST with histamine, acethylcoline, metilcholine, serotonine establishES the asthma diagnosis: • it lastS 3 minutes; • it is positive when the pharmaceutical index (VEMS I –VEMS II/VEMS I) x 100 decreased over 20%; • for the persons with hyperreactivity, the asthma attack may occur in the first minute.

THE SPECIFIC INHALATION CHALLENGE TEST with the incriminated etiologic agents = establishes the occupational asthma: • it lasts 30 minutes; • it takes place in a special and closed room; • the patient manipulates flour, hemp, cement, dyes, glue, mixes solvents for 30 minutes ; • the test is positive when the pharmaceutical index is over 10%

! The crisis may occur: • in the first 10-15 minutes; • after 30 minutes; • Lately, after 1-2-6-10 h. • The patient needs medical surveillance. THE WORKPLACE TEST: • clinical and spirometric surveillance (every each hour) of the patient (non-symptomatic) at the workplace, made by the company’s doctor).

Diagnosis criteria in occupational asthma A. The asthma crisis - clinical confirming of a physician or bronchial hyperreactivity proved by tests; B. The asthma symptoms preceded by an occupational exposure; C. Association between the asthmatic symptoms and occupational environment;

D. The exposure or the physiological test of asthma and occupational environment relationship. • workplace exposure to a recognized etiologic factor; • VEMS or PEF work-related changes; • work-related changes of the serial tests of non-specific bronchial reactivity; • positive specific inhalation challenge test; • asthma occurrence clear related to a symptomatic exposure to a irritative agent inhalator at the workplace • Occupational asthma diagnosis requires A and C criteria and one criterium from D1 to D5.

In order to differentiate occupational asthma by an asthma aggravated by the workplace, the American College of Chest Physicians recommends the next diagnosis criteria for the asthma aggravated by work: • A and C criteria presence; • pre-existent asthma or previous symptoms of asthma (with disorder in the latest year in a certain workplace and before the first exposure). • net worsening of symptoms or increased need for medical treatment or to highlight the changes in their work in terms of PEF or FEV made after the date of employment or after the first exposure occurred.

Evolution 1. Removal from occupational environment will stop asthma attacks. 2. Return in occupational environment = = crisis recurrence= aggravation= corticosteroid dependency = frequent crisis= continue dyspnea= progression to chronic pulmonary heart disease and respiratory failure 3. Themultisensitisation usually is associated  asthma loses its character of professionality/occupationality

Treatment • etiological, • pathogenic, • symptomatic. Etiological therapy • Removal from exposure to etiologic agent is the most efficient method of treatment. It is obtained by changing of workplace - out of the environment with the incriminated substances. • The typical hypo-sensitiveness is a method with good results if the patient is cooperative. • The sea and saline cures are efficient especially in pure allergic asthma. The cases must be carefully chosen.

Pathogenic therapy • Simpato-mimetics: 2-selective: Salbutamol, Terbutaline, Phenoterol, Reproterol, Clenbuterol, Serevent • Anticholinergic drugs: atropine, ipratropiumbromid (Atrovent) • Pphosphodiesterasis inhibitors: methylxantine (ampulla, tablets) • –receptors blocking: phentolamine • Mast cells degranulation inhibitors: sodium chromoglicat, Ketotiphen, Zaditen.

Leukotrienes antagonists (blocking of the type I receptors and anti-inflammatory effect): Montelucast (Singulair-Merck) • Corticosteroid-therapy: Hydrocortisone hemisuccinate (i.v.), drugs with local action (inhalation way)- Beclometazone spray, Prednison - tablets in a short cure, retard drugs (Diprophos, Volon, Kelanog). Nowadays, a very large range of drugs are available. These drugs associate a –stimulant with an anticholinergic or a –stimulant with sodium chromonoglicat or –stimulant with a corticoid.

Symptomatic treatment • Generally, it is considered that asthma aggravation is caused by a supra-infection, thus an antibiotic is prescribed in ambulatory for asthma attack. • For the most cases, the supra-infection is not present, but a high level of exposure to sensitive or irritant agents, and the antibiotic is not necessary. • For the cases with 2-4 crisis/24 h it is recommended HHC perfusion (600-1000 mg/first day).

If the dose is well chosen, the results are seen from the next day, crisis disappearing completely, or only one remains, the crisis disappear in the fourth, fifth or seventh day of HHC therapy. • If after 7 days of therapy cu HHC the crisis persists, this means supra-infection and antibiotics are required.

Prophylaxis • Knowledge of the workplaces with a high risk of sensitisation and avoid employment of persons with atopy and persons with asthma or rhinitis. • Limiting the number of people exposed by isolating operations or jobs at high risk;

Monitoring of workplaces with risk and taking measures to reduce discharges into the air of irritants and sensitizing substances. • Early detection of rhinitis and asthma symptoms, early diagnosis of occupational asthma and indication of job change or professional reorientation.

Attention • In recent cases, diagnosed shortly after onset, removal from occupational environment is followed by crisis disappearance and long calm periods (for years). • Any doctor in the position to confirm asthma first has to eliminate the possibility of any occupational etiology. • Ignoring occupational causative factor aggravates asthma and leads to disability.

In cases diagnosed late, removal from exposure can lead to an improvement which installs slower, with disappearance of crisis only after 1-2 years. • In occupational asthma, the evolution may be aggravated by polisensitisation of the patient or the combination of irritant-induced asthma by exposure to the new job or home.

O ccupational asthma