Isocyanate-Induced Asthma

Isocyanate induced asthma is occupational asthma caused by sensitisation to diisocyanates such as toluene diisocyanate, methylene diphenyl diisocyanate and hexamethylene diisocyanate. It is among the commonest causes of chemical induced occupational asthma.

Exposure. Spray painting with two pack polyurethane paints, foam and insulation manufacture, vehicle repair, foundry core making, adhesives and varnishes, and spray on foam.

Epidemiology. A proportion of exposed workers develop asthma, with risk related to exposure level and, in some cohorts, to atopy and genetic factors.

Latency. Weeks to years after first exposure.

Prognosis. Early removal gives the best outcome. A substantial proportion still have asthma years after removal, particularly after longer symptomatic exposure and with lower baseline FEV1.

Pathophysiology.

Isocyanates are reactive chemicals that bind airway proteins and form haptens. Specific IgE is found in a minority, so non-IgE immune mechanisms, neurogenic signalling and cytokine driven airway inflammation are involved.

Persistent inflammation produces bronchial hyperresponsiveness, with airway remodelling when exposure continues.

• Cough, wheeze, chest tightness and dyspnoea, often worse at work or during the evening or night after work, and improved on days off or holidays.
• Rhinitis and conjunctivitis may accompany it.
• Delayed reactions can occur hours after exposure.

Red flags.

• Severe attacks needing urgent care.
• Rapid decline in lung function or persistent symptoms despite treatment.

• Detailed work history, tasks, ventilation, protection and co-worker symptoms.
• Confirm asthma by spirometry with reversibility of 12% and 200 mL, peak flow variability, FeNO, or methacholine challenge (PC20 under 8 mg/mL suggests asthma).
• Confirm work relatedness with serial peak flow at least 4 times daily over at least 2 weeks at work and 2 weeks away, analysed by a validated method.
• Compare methacholine reactivity at work and away from work.
• Specific inhalation challenge in a specialist centre is the reference test. A fall in FEV1 of 20% or more after exposure indicates sensitisation.
• Specific IgE to isocyanate protein conjugates has high specificity but low sensitivity; skin prick testing is not reliable.

Differential diagnosis. Work exacerbated asthma, irritant induced asthma, chronic obstructive pulmonary disease, vocal cord dysfunction, hypersensitivity pneumonitis, eosinophilic bronchitis, rhinitis.

• Remove from exposure promptly, ideally in the first 1 to 2 years of symptoms; engineering controls and enclosed spraying for those who remain.
• Budesonide with formoterol 200/6 micrograms inhaled, 1 inhalation twice daily as maintenance plus 1 inhalation as needed (adults and adolescents 12 and over). Usual maximum 8 inhalations in 24 hours, up to 12 for a short period. Monitor symptoms, spirometry, exacerbations and oral candidiasis; rinse mouth after use. No renal adjustment; step up or down by control.
• Exacerbation: salbutamol 100 microgram metered dose through a spacer, 4 to 10 puffs, repeated every 20 minutes for the first hour, then every 4 hours as needed. Maximum 10 puffs each dose. Monitor heart rate, potassium and oxygen saturation. Caution in arrhythmia and hyperthyroidism.
• Exacerbation: prednisolone 40 to 50 mg orally once daily for 5 days, with no taper. Maximum 50 mg daily. Monitor glucose and blood pressure. Caution in diabetes and peptic ulcer; acceptable in pregnancy when needed; no renal adjustment.
• Avoid re-exposure even to low levels; sensitised workers should not return to isocyanate work.

Monitoring. Review every 3 months initially with spirometry and symptom control; serial peak flow if exposure continues.

Referral and escalation. Respiratory and occupational physician; workplace assessment and health surveillance for co-workers; urgent care for severe attacks; notification and compensation where required.

Special groups. Pregnancy: continue inhaled corticosteroid and avoid exposure. Workers with prior asthma may need exposure restriction.