J Int Med Res (1978) 6, 50
Clinical Trial with Lunerin" Mixture and Lunerln" Mite in Children with Secretory Otitis Media Carsten Saunte,· MD, ENT Department, Namdal Hospital, Namsos, Norway Sten-Ake Johansson, M Pharm Sci, Medical Department, AB Draco, Lund, Sweden
A double-blind comparison between a combined antihistaminic and vasoconstricting preparation (Lunerin® Mixture, Lunerin® Mite) and placebo was performed in children with secretory otitis media. It was shown that the children given the active drug reacted more favourably on every investigated parameter (hearing threshold, appearance and mobility of the ear drum, number of myringotomies and observation time) than the patients who were given placebo. The incidence of side-effects was low.
Introduction Opinions of different authors vary considerably on the aetiology of secretory otitis media in children. In view of the many factors involved, there could be different reasons for secretory otitis media with occlusion of the eustachian tube, accumulation of fluid in the middle ear, and conductive hearing loss. Some authors regard ' ... the majority of cases of chronic secretory otitis ... due to a definite allergy to house-dust or to a food' (Derlacki 1952). In 1949, Jordan reported one hundred and twenty-three cases of secretory otitis media, ninety-one being caused by allergy (74%). This diagnosis of allergy was based on findings of eosinophils in nasal smears, positive skin tests, and response to anti-allergic therapy.
·Address requests for reprints to: Carsten Saunte, MD, ENT Department Regionsykehuset in Trondheim, N7000, Trondheim, Norway.
Senturia (1960) states that ' ... the largest percentage of middle ear effusions are not allergic but inflammatory in origin,' and that the examinations ' ... provide additional support for the earlier conclusion that most effusions in humans are of inflammatory origin'. In recent years, investigators have been working on studies suggesting that the middle ear maintains a local immunological defence system (Mogi et aI1974). The highest frequency of secretory otitis media in children has been observed to coincide with the age of maximum adenoid hypertrophy and with the peak age of allergy onset (Friedman 1974). Irrespective of the cause of secretory otitis media, the therapy is aimed at obtaining a ventilated middle ear and, with that, normal hearing. This can be done either by the Politzer Method, or by myringotomy, with or without the insertion of a tube. Adenotomy is also carried out in a large number of cases, but mostly as a treatment of last resort.
Downloaded from imr.sagepub.com at UNIV OF TOKYO on May 19, 2015
C Saunte and s-l Johansson Antihistamines and vasoconstrictors are also frequently used, both perorally and as nose-drops. In recent years, both have been used in combination, one such preparation being Lunerin" (AB Draco)]. However, there is a lack of controlled studies on the effects of this preparation in secretory otitis media. This study evaluated the effects and sideeffects of a combined antihistaminic vasoconstricting product, in comparison with placebo, in children with secretory otitis media. Lunerin mixture contains 0·4 mg of brompheniramine maleate (with antihistaminic effect) and 1·7 mg of phenylpropanolamine hydrochloride (sympathomimetic effect) per ml. Lunerin Mite is a tablet with prolonged duration of action and with the same technical properties as Lunerin (Lindberg & Persson 1972). Lunerin Mite contains half the amount of Lunerin per tablet, i.e, 6 mg of brompheniramine maleate and 25 mg phenylpropanolamine hydrochloride. Mercke & Wihl (l973), among others, have investigated the clinical properties of Lunerin. Kjellman (l975) investigated the effectiveness of Lunerin Mite in children with allergic rhinitis. So far, there are no published studies on Lunerin mixture.
Material and Methods Children suffering from secretory otitis media are included. When the children came to the ENT department, a thorough anamnesis was taken and only children who fulfilled the following criteria were included: (a) The patient, or the patient's parents, had recognized a reduced hearing ability for at least fourteen days. (b) When measured audiometric ally, the hearing ability was reduced to, or below, 20 dB. (c) A reduced mobility of the ear drum was found by otoscopy.
t A subsidiary of Astra Pharmaceuticals AB, Sodertalje, Sweden.
51 (d) If the secretory otitis media was preceded by an acute otitis, the acute otitis must be regarded as cured and the patient without symptoms for at least two weeks before he or she enters the study. (e) The child should be known to have had a normal hearing ability before the secretory otitis media. The patients (or their parents) were asked about earlier troubles of the same kind and about allergic heredity. The ear drum was inspected and investigated for mobility and transudate. The prevalence of adenoids and sinusitis was also investigated. Patients with adenoids, where an adenotomy was decided, were omitted from the study. The patients were also asked about subjective complaints, such as nasal secretion, obstruction, and decreased hearing acuity. If there was a need for myringotomy this was performed and repeated if necessary. In some children myringotomy was done for social reasons (difficulties in following school work) and in others because of increased pressure. The same doctor (CS) investigated all patients. Audiograms were taken at 500, 1000, and 2000 Hz. All these measurements were made by the same, specially trained, assistant. To be included in the audiologic material, the minimum hearing threshold, at the starting visit, had to be 20 dB. The above-mentioned investigation procedure was repeated at each visit, and the patients (parents) were asked whether they had noticed any side-effects. The patients visited the ENT clinic every two weeks until they could be described as symptom-free or as treatment failures. Observation time was recorded, i.e. the number of days that elapsed from the visit when the patient entered the trial to the visit when the patient was found either to have recovered or to be a treatment failure were counted. The trial was double-blind. The drugs (active or placebo) used were of the same appearance and taste and allocated at random to a consecutive series of numbers. This was done by the manufacturer. The children selected were numbered consecutively as they entered the trial and were thus allocated to active drug or placebo. There was a free choice for the child (parents) to use either the tablet with sustained action, or the mixture.
>
Downloaded from imr.sagepub.com at UNIV OF TOKYO on May 19, 2015
52
The Journal ofInternational Medical Research
The mixture doses were age-dependent. Children of 3-4 years were given 7·5 mI, 6-10 years 10 ml, and > 11 years 15 mI, three times a day. The patients using tablets took one in the morning and one in the afternoon. The children were not allowed to use other decongestants, antihistamines, or nose-drops during the trial. Statistical evaluations used were Student's ttest and chi-square test. Thirty-one children entered the study. Five were later excluded because of adenotomy and five failed to follow the trial regimen. Twentyone were left: ten in the placebo group, mean age 5·8 years (range 1-12), and eleven in the Lunerin group, mean age 6·3 years (range 3-10). Atopic heredity to allergic rhinitis to a moderate degree was present in four children in the Lunerin group and in five in the placebo group. Eight out of eleven children in the Lunerin group and nine out of ten in the placebo group had had infectious otitis media at least once before. In the Lunerin group, three of the children used tablets; the others used mixture. All patients were treated ambulantly and
were asked to return a fortnight later to undergo the same examination as at the first visit. Results The average time between the first and second visit to the ENT Department was 17·4 days (range 14-28) for the Lunerin group and 15·3 days (range 8-29) for the placebo group. A. Audiometry There was a statistically significant decrease of the hearing thresholds in all investigated frequencies with Lunerin (500 Hz-p < 0·001; 1000 Hz-p < 0·01; 2000 Hz-p < 0·05), but not at any frequency with placebo. However, the difference between the decreases in hearing thresholds observed with Lunerin and placebo was not significant (Table 1 and Figure 1). B. Eardrum There was a statistically significant difference between Lunerin and placebo in favour of Lunerin, regarding thickness (p < 0·001), mobility (p < 0·01), and total symptoms (p < 0·001) (thickness, mobility, transudate, vascularity) (Table 2).
Table 1 Hearing threshold at commencement of trial and change after two weeks treatment
Number ofears
Before treatment dB
SEM
Placebo
10
36·0
4·2
Lunerin
14
27·5
Placebo
12
Lunerin
Drug
Change after 2 weeks treatment dB
SEM
to
-3·0
5·3
0·57
1·6
-8·9
2·0
4·52***
35·0
3·3
-1·7
5·4
0·31
14
27·1
2·2
-9·3
2·2
4·19**
Placebo
10
33·5
3·4
-6·0
3·2
1·86
Lunerin
7
29·3
3·7
-12·9
4·9
2·64*
500Hz
t diff
1·05
1000 Hz
1·30
2000 Hz
1·18
* = p < 0·05 **=p
Clinical Trial with Lunerin" Mixture and Lunerln" Mite in Children with Secretory Otitis Media Carsten Saunte,· MD, ENT Department, Namdal Hospital, Namsos, Norway Sten-Ake Johansson, M Pharm Sci, Medical Department, AB Draco, Lund, Sweden
A double-blind comparison between a combined antihistaminic and vasoconstricting preparation (Lunerin® Mixture, Lunerin® Mite) and placebo was performed in children with secretory otitis media. It was shown that the children given the active drug reacted more favourably on every investigated parameter (hearing threshold, appearance and mobility of the ear drum, number of myringotomies and observation time) than the patients who were given placebo. The incidence of side-effects was low.
Introduction Opinions of different authors vary considerably on the aetiology of secretory otitis media in children. In view of the many factors involved, there could be different reasons for secretory otitis media with occlusion of the eustachian tube, accumulation of fluid in the middle ear, and conductive hearing loss. Some authors regard ' ... the majority of cases of chronic secretory otitis ... due to a definite allergy to house-dust or to a food' (Derlacki 1952). In 1949, Jordan reported one hundred and twenty-three cases of secretory otitis media, ninety-one being caused by allergy (74%). This diagnosis of allergy was based on findings of eosinophils in nasal smears, positive skin tests, and response to anti-allergic therapy.
·Address requests for reprints to: Carsten Saunte, MD, ENT Department Regionsykehuset in Trondheim, N7000, Trondheim, Norway.
Senturia (1960) states that ' ... the largest percentage of middle ear effusions are not allergic but inflammatory in origin,' and that the examinations ' ... provide additional support for the earlier conclusion that most effusions in humans are of inflammatory origin'. In recent years, investigators have been working on studies suggesting that the middle ear maintains a local immunological defence system (Mogi et aI1974). The highest frequency of secretory otitis media in children has been observed to coincide with the age of maximum adenoid hypertrophy and with the peak age of allergy onset (Friedman 1974). Irrespective of the cause of secretory otitis media, the therapy is aimed at obtaining a ventilated middle ear and, with that, normal hearing. This can be done either by the Politzer Method, or by myringotomy, with or without the insertion of a tube. Adenotomy is also carried out in a large number of cases, but mostly as a treatment of last resort.
Downloaded from imr.sagepub.com at UNIV OF TOKYO on May 19, 2015
C Saunte and s-l Johansson Antihistamines and vasoconstrictors are also frequently used, both perorally and as nose-drops. In recent years, both have been used in combination, one such preparation being Lunerin" (AB Draco)]. However, there is a lack of controlled studies on the effects of this preparation in secretory otitis media. This study evaluated the effects and sideeffects of a combined antihistaminic vasoconstricting product, in comparison with placebo, in children with secretory otitis media. Lunerin mixture contains 0·4 mg of brompheniramine maleate (with antihistaminic effect) and 1·7 mg of phenylpropanolamine hydrochloride (sympathomimetic effect) per ml. Lunerin Mite is a tablet with prolonged duration of action and with the same technical properties as Lunerin (Lindberg & Persson 1972). Lunerin Mite contains half the amount of Lunerin per tablet, i.e, 6 mg of brompheniramine maleate and 25 mg phenylpropanolamine hydrochloride. Mercke & Wihl (l973), among others, have investigated the clinical properties of Lunerin. Kjellman (l975) investigated the effectiveness of Lunerin Mite in children with allergic rhinitis. So far, there are no published studies on Lunerin mixture.
Material and Methods Children suffering from secretory otitis media are included. When the children came to the ENT department, a thorough anamnesis was taken and only children who fulfilled the following criteria were included: (a) The patient, or the patient's parents, had recognized a reduced hearing ability for at least fourteen days. (b) When measured audiometric ally, the hearing ability was reduced to, or below, 20 dB. (c) A reduced mobility of the ear drum was found by otoscopy.
t A subsidiary of Astra Pharmaceuticals AB, Sodertalje, Sweden.
51 (d) If the secretory otitis media was preceded by an acute otitis, the acute otitis must be regarded as cured and the patient without symptoms for at least two weeks before he or she enters the study. (e) The child should be known to have had a normal hearing ability before the secretory otitis media. The patients (or their parents) were asked about earlier troubles of the same kind and about allergic heredity. The ear drum was inspected and investigated for mobility and transudate. The prevalence of adenoids and sinusitis was also investigated. Patients with adenoids, where an adenotomy was decided, were omitted from the study. The patients were also asked about subjective complaints, such as nasal secretion, obstruction, and decreased hearing acuity. If there was a need for myringotomy this was performed and repeated if necessary. In some children myringotomy was done for social reasons (difficulties in following school work) and in others because of increased pressure. The same doctor (CS) investigated all patients. Audiograms were taken at 500, 1000, and 2000 Hz. All these measurements were made by the same, specially trained, assistant. To be included in the audiologic material, the minimum hearing threshold, at the starting visit, had to be 20 dB. The above-mentioned investigation procedure was repeated at each visit, and the patients (parents) were asked whether they had noticed any side-effects. The patients visited the ENT clinic every two weeks until they could be described as symptom-free or as treatment failures. Observation time was recorded, i.e. the number of days that elapsed from the visit when the patient entered the trial to the visit when the patient was found either to have recovered or to be a treatment failure were counted. The trial was double-blind. The drugs (active or placebo) used were of the same appearance and taste and allocated at random to a consecutive series of numbers. This was done by the manufacturer. The children selected were numbered consecutively as they entered the trial and were thus allocated to active drug or placebo. There was a free choice for the child (parents) to use either the tablet with sustained action, or the mixture.
>
Downloaded from imr.sagepub.com at UNIV OF TOKYO on May 19, 2015
52
The Journal ofInternational Medical Research
The mixture doses were age-dependent. Children of 3-4 years were given 7·5 mI, 6-10 years 10 ml, and > 11 years 15 mI, three times a day. The patients using tablets took one in the morning and one in the afternoon. The children were not allowed to use other decongestants, antihistamines, or nose-drops during the trial. Statistical evaluations used were Student's ttest and chi-square test. Thirty-one children entered the study. Five were later excluded because of adenotomy and five failed to follow the trial regimen. Twentyone were left: ten in the placebo group, mean age 5·8 years (range 1-12), and eleven in the Lunerin group, mean age 6·3 years (range 3-10). Atopic heredity to allergic rhinitis to a moderate degree was present in four children in the Lunerin group and in five in the placebo group. Eight out of eleven children in the Lunerin group and nine out of ten in the placebo group had had infectious otitis media at least once before. In the Lunerin group, three of the children used tablets; the others used mixture. All patients were treated ambulantly and
were asked to return a fortnight later to undergo the same examination as at the first visit. Results The average time between the first and second visit to the ENT Department was 17·4 days (range 14-28) for the Lunerin group and 15·3 days (range 8-29) for the placebo group. A. Audiometry There was a statistically significant decrease of the hearing thresholds in all investigated frequencies with Lunerin (500 Hz-p < 0·001; 1000 Hz-p < 0·01; 2000 Hz-p < 0·05), but not at any frequency with placebo. However, the difference between the decreases in hearing thresholds observed with Lunerin and placebo was not significant (Table 1 and Figure 1). B. Eardrum There was a statistically significant difference between Lunerin and placebo in favour of Lunerin, regarding thickness (p < 0·001), mobility (p < 0·01), and total symptoms (p < 0·001) (thickness, mobility, transudate, vascularity) (Table 2).
Table 1 Hearing threshold at commencement of trial and change after two weeks treatment
Number ofears
Before treatment dB
SEM
Placebo
10
36·0
4·2
Lunerin
14
27·5
Placebo
12
Lunerin
Drug
Change after 2 weeks treatment dB
SEM
to
-3·0
5·3
0·57
1·6
-8·9
2·0
4·52***
35·0
3·3
-1·7
5·4
0·31
14
27·1
2·2
-9·3
2·2
4·19**
Placebo
10
33·5
3·4
-6·0
3·2
1·86
Lunerin
7
29·3
3·7
-12·9
4·9
2·64*
500Hz
t diff
1·05
1000 Hz
1·30
2000 Hz
1·18
* = p < 0·05 **=p
