Steroid-Induced Reduction of Histamine Release Does Not Alter the Clinical Nasal Response to Cold, Dry Air (CDA)

The following information is provided by: Fisher & Paykel Healthcare

By Dr. Vanessa MB Jordan Ph.D., Research Scientist, Fisher & Paykel Healthcare

A.A. Cruz, A.G. Togias, L.M. Lichtenstein, A. Kagey-Sobotka, D. Proud, and R.M. Naclerio
American Review of Respiratory Disease 1991; 143: 761-765

Key Points

• Pre-treating nasal membranes with a nasal steroid for one week prior to a CDA challenge did not alter the nasal membrane response.
• Symptom scores, as indicated by test subjects, were similar in response to a CDA challenge regardless of whether the subject had been pre-treated with a nasal steroid or a placebo.
• Although pre-treating nasal membranes with beclomethasone decreased the histamine response to a CDA challenge, it did not alter any of the other parameters measured.

Aim

To determine if topical application of the steroid, beclomethasone dipropionate nasal aqueous solution, will reduce the effects of a cold, dry air challenge on nasal membranes.
To acquire information on the role of mast cell activation and histamine release in the pathogenesis of the nasal reaction to CDA.

Method

The authors conducted a double blind randomised placebo controlled trial to study the effects of CDA on the nasal mucosa.

16 subjects were enrolled in the study (10 male, 6 female). Age range covered 20-52 yrs. All had a history of nasal reaction when exposed to CDA. Some participants had a history of an allergy-induced rhinitis but none of these were currently symptomatic and none were currently on medication. (Three subjects were excluded from the final analysis as no reaction to the CDA challenge was detected).

Initially subjects were given a solution to administer twice daily in each nostril for one week. The solution was either an 84mg solution of beclomethasone dipropionate or a placebo. Which treatment the subjects initially received was decided by random allocation. Following the week of treatments, patients were given a CDA nasal challenge. The subjects were then given at least a one week break and subsequently were given the alternate treatment to use for a another week terminating with another CDA challenge.

The CDA challenge involved inhaling air through the nose, which was between -3 and -10oC, and less than 10% relative humidity. Nasal lavages, to collect nasal secretions, were performed seven times at one minute intervals prior to the challenge and then twice, at ten and twenty minutes, post the CDA challenge.

Subjects were also asked to fill in symptom scores using a visual analog scale with zero equalling no symptoms and ten being the worst it has ever been.

Investigators measured histamine levels, TAME-esterase activity and albumin concentrations and fluid osmolality.

Results

Significant elevations in TAME-esterase activity, albumin and total symptom scores in subjects following the CDA challenge were shown regardless of whether they had been pre-treated with beclomethasone or with the placebo.

The only difference between pre-treatment with the active drug and the placebo following a CDA challenge, was the level of histamine. Following treatment with beclomethasone there was no significant increase above the baseline recording for the concentration of histamine. This was in contrast to the placebo treatment, which showed a significant increase above baseline.

The osmolality of the nasal fluid following the CDA challenge also showed a significant increase above the baseline recording. This effect was not altered by pre-treatment with steroids.

There were no significant differences between those volunteers who had previously suffered form allergies comparative to those who had not.

Conclusions

Results suggest that one-week of nasal pre-treatment with topical beclomethasone dipropionate will decrease histamine release, but did not significantly effect other parameters assessed during early nasal reaction including symptom scores.

The significant reduction of histamine release by nasal steroids points towards an effect of these agents on the source of histamine, the mast cells. However, as the beclomethasone did not effect the symptoms induced by the CDA challenge the authors suggest that water loss leading to increased osmolality may trigger the observed nasal reaction to CDA.