The placebo effect is nothing to sneeze at

The placebo effect is nothing Sheldon

L. Spector,

MD Los Angeles, Calif.

In the late 1970s we compared the steroid aerosol tlunisolide with placebo in patients with perennial allergic rhinitis.’ The placebo was the vehicle, propylene and polyethylene glycol. Although one would expect that approximately 30% of placebo-treated patients would show benefit, we found a substantially higher rate of improvement as measured by objective parameters such as nasal peak flow and blockage index as well as eosinophil counts from a nasal smear. Other investigators’ a year earlier had also been impressed by the “high placebo effect” in their study of flunisolide versus placebo. Because we were unsure if there was something special about the propylene and polyethylene glycol per se, we designed a second study to comp’are this vehicle with saline solution, with the

TABLE I. Comparison of baseline of patients with rhinitis

biopsy

specimens

hope of placing the previously mentioned, unexpectedly high placebo response into perspective. 3Eighteen patients were followed during a 2-week baseline period and subsequently during 4 weeks of active treatment with either saline solution or propylene and polyethylene glycol in a double-blind, randomized study. After 2 and 4 weeks there was significant improvement in nasal function compared with baseline with no difference between the two treatments. Patients had less sneezing at 2 and 4 weeks and less stuffiness at 4 weeks. This study confirmed that wetting agents per se can offer both subjective and objective improvements in the treatment of perennial rhinitis and merited consideration before the introduction of other agents with known systemic side effects. Interestingly,

of normal

Baseline

Patient No.

1

Mucosa

co1 sq co1 co1 co1 co1 co1 co1 sq co1 co1

to sneeze at

BM*

biopsy

with baseline

of normal

patients

Edemat

Plasma cells per high-power field

O-l

0

0

1-2

o-1 o-1

0 10-15 o-3 l-2

3-5

O-l

o-1

2-3

3-5 1-2

1-2 3-5

l-2 2-5

3-6 3-5 o-1 0

8-12 0 2-4 0

o-1 1 1-2

o-1

2-4

co1

I

o-1 0 0

co1

I

4-6

Modified from Spector SL, et al. Clin Allergy 1982;12:193, by permission of Blackwell Scientific Publications *Basement membrane: I = intact; A = attenuated; Th = thickened; Ab = absent. ‘Edema: 0 = none; 1 = mild; 2 = moderate; 3-4 = marked.

1042

specimens

Mast cells per high-power field

sq, squamous; col, columnar.

l/O/42380

biopsy

Eosinophils per high-power field

2

Slightly A I

patients

VOLUME NUMBER

90 6 PART 2

Placebo effect is nothIng 10 sn+m- at

DeWeese and Saunders4 specifically mention the installation of moisturizing agents as beneficial treatment in their 1973 textbook. Thus the so-called vehicle may actually be an active medication in certain patients. To help clarify the responding group, biopsy studies were done on so-called control subjects who had no symptoms as well as in the group with rhinitis (Table Ii. A certain amount of inflammation was present in many of the “normal” biopsy specimens. As would be expected, those patients with allergic rhinitis who had more abnormal biopsy specimens, that is, with more edema and eosinophils, mast cells, and/or plasma cells. were the ones who could best respond to the treatment. We were impressed by the heterogeneity of our so-called normal population as well as our patients with rhinitis. Because the biopsy procedure is cumbersome. inconvenient, and sometimes painful, we do not expect that it will become a useful

3043

clinical parameter to follow to help predict the rcsponder versus the nonresponder groups. For this reason, other objective means to quantitative nasal rcsponse will be discussed in this supplement, Nevertheless, the heterogeneity of patients c”wn wirh the same clinical diagnosis should be kept i-1 rrrmd with review of the data presented. REFERENCES I. Jones LM, Spector SL. English GM, Tayior-Dawsc~~ I(. Treatment of perennial rhinitls with flunisohde cortrc~~~rcroid spray. Ann Allergy 1979:42: 139-44. 2. Schultz JI. Johnson JD. Freedman SO. Double blind rrral comparing Hunisolide and placebo for the treatrnenf o: perennrnl rhinitis. Clin Allergy 1978;8:313. 3. Spector SL, Toshener D, Gay I, Rosenman k. Beneirciai effect5 of propylene and polyethylene glycol and salrneIU the trt’atment of perennial rhmitis. Clin Allergy 1982; 12: 1X7-%. 4. DeWeese DE, Saunders WH. The nasal \eptui!l: rhmoplasty; maxillary and nasal fractures. In: Textbook of o~niarynpology St. Loui\. The 0’ Moshy Co. lQ73:11~

.--.__- ,__I--___ Baseline

Mucosa

Sq

sq

Col and Sq Sy and Cal

sq co1 Cal

and and and and

Col Col Col Cal

Edemat

I

0 0

A and I

sq

Sq Sq Sq Sq

BM*

biopsy

of patients

with

Eosinophils

rhinitis

Mast cells

O-2 0

l-2 0-l

I

0

0

O-4

A and Th I and Th

2 1

20 O-2

7 0

I and A I and Th I and Th I, A, and Th 1. Ab, and Th Th Th and 1

0 2 0 2 0 2 I

0 0 0

0 0 3-4

6) .;

O-l

O-I

(I- ]

0 I0 0

IO-20 o- I 4-6

:J I’ I ii