Histamine Challenge Test

Written by Dr J Vermeulen

Histamine challenge tests are performed using the protocol of Yan et al (Ref. 1). After baseline spirometric function, normal saline is delivered via a De Vilbiss No. 40 hand held nebuliser to the subject, to practice the inhalation technique and to ensure that there is no reaction to the test solution. Following this, increasing doses of the histamine are inhaled, starting with the lowest dose. After one minute the spirometric function is repeated. If no change in FEV1 has occurred the next dose will be given. This procedure is continued until the FEV1 falls by 20%, at which point the PC20 will be noted i.e. the concentration of histamine that induces a reduction in FEV1 of 20%. These dosage schedules for histamine acid phosphatase are shown in the table below.

Chart of histamine doses

Dose	Cumulative Dose (umoles)	Histamine Concentration	No. of Inhalations
1 2 3 4 5 6 7 8 9	0.03 0.06 0.12 0.24 0.48 0.96 1.80 3.91 7.8	0.3% 0.3% 0.6% 0.6% 2.5% 2.5% 2.5% 5.0% 5.0%	1 1 1 2 2 2 4 4 8

 

The assessment of airway responsiveness to a pharmacologic inhalational agent that provokes broncho-constriction in a susceptible individual is expressed as the concentration or dose of the agonsits causing a required change in pulmonary. Most commonly used agonists are metacholine and histamine.

 

Indications for Bronchial Challenges

1. Pharmacologic

1. Suspicion of hyper-sensitive or hyper-active airways.
2. Atypical asthma.
3. Identification subjects at risk of developing occupational asthma (?)
4. Research

2. Conditions when inhalation challenges are usually not necessary or should be performed with caution

1. Well-documented asthma
2. Broncho-spastic response to diluent
3. Demonstrated reversibility of broncho-spasm by bronchodilators
4. Patients with impaired pulmonary functions

3. Factors Affecting Response to Bronchial Inhalation Challenges

A. Factors Influencing Aerosol Delivery and Penetration

1. Physical Factors
   • Nebulizers
   • Delivery Systems
2. Physiologic Factors
3. State of Airway

B. Pre-challenge Period

The following factors either increase or decrease bronchial responsiveness:

i. Increase

Upper and lower respiratory infection	6 weeks
Vaccination with influenza vaccine	3-6 weeks
Treatment with Clonidine or beta blockers
Allergen exposure with late response	1-3 weeks
Occupational sensitizers	months
Cigarette smoke	2-4 hours
Air pollution (ozone, NO2,SO2)	days-week

 

ii. Decrease

Calcium channel blockers	8 hours
Beta-2 agonists	4-12 hours
Antihistamines	48 hours
Anticholinergics	18 hours
Disodium cromoglycate	(see below)
Theophylline plain	12 hours
Theophylline sustained	48 hours
Steroids	(see below)
Morphine sulfate

iii. On the Challenge Day

Airway calibre (decreased lumen gives increased BR) Time of the day (increased BR in the evening and night)

Interpretation of Results

PC20 FEV1: Is the provocative concentration of agonist causing a 20% decrease in forced expiratory volume in one second and is used with the continuous inhalational method and expressed in mg/ml.

PD20 FEV1: Is the provocative dose of agonist causing a 20% decrease in forced expiratory volume in one second. Used when inhalation is given by an intermittent technique, and expressed in dose units or milligram or micromoles delivered to the month.

Non-asthmatic subjects are relatively resistant to the bronchospastic effects of histamine challenge. Generally a lower PD20 FEV1 value indicates greater reactivity of the airways.

References

1. Yan K, Salone C, Woolcock AJ, Act Rapid method for measurement of bronchial responsiveness Thorax 1983; 38: 7 60-5.
2. The Clinical Value of Pharmacologic Broncho Provication Challenge Medical Clinic of North America Volume 74 no. 3 May 1990 page. 767-778.
3. Measurement of Bronchial Responsiveness Ceilia J Wintriche and Robert J Davies. Clinical Reviews in Allergy Vol. 7 in 1989 page. 279-301.