Comparison between the use of adsorbed and aqueous immunotherapy material in dermatophagoides pteronyssinus sensitive asthmatic children

Comparison between the use of adsorbed and aqueous immunotherapy material in dermatophagoides pteronyssinus sensitive asthmatic children

D. U. Altžntas*, N. Akmanlar*, S. K. Güneser*, R. Burgut**, M. Yžlmaz*, R. Bugdaycž** and P. Aksungur***

*Deparment of Pediatric Allergy and Immunology. **Biostatistics. ***Central Laboratory. Çukurova University Medical Faculty. Adana. Turkey.

Correspondence:

Derya Ufuk Altžntas,, MD

Mücahitler cad. 134/17

01140 Adana

Turkey

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SUMMARY

Background: dermatophagoides pteronyssinus (Der PI) is the major allergen which causes allergic asthma and perennial rhinitis. The extracts of Der PI may be used in treatment of patients who are unresponsive to pharmacological treatment and avoidance of allergens. The success of immunotherapy (IT) depends on the selection of appropriate patients and allergens as well as a regular follow up.

Objective: three different groups of IT materials and a placebo were tested on 34 patients with Der PI sensitive asthma. Clinical evaluations of allergen challenge and in vitro immunologic tests were made on the patients before, on the 6^th month and at the end of the second year of IT. The results were compared to the placebo treated group.

Results: there were no significant differences among the groups in regard to age, sex and duration of illness. The time required for reaching the maintenance dose for group I (Alutard^®), II (APSI retard Ca^®) and III (Greer ^®) was 15.40 ± 0.69, 18.2 ± 4.0 and 108 ± 33 weeks, respectively. Even though there was some significant difference between those receiving aqueous IT and the placebo (p < 0.05), there was a greater significant difference between those receiving adsorbed IT and placebo (p < 0.00001). Also there was a significant difference between the I and II groups receiving adsorbed IT. There was no significant difference in the maximum tolerated doses between group I and II (p > 0.05), but significant differences was found between group III and the other two groups (p < 0.05). Specific IgE levels were not changed by IT. There were no differences in the side effects scores among the groups (p < 0.05). The maximum tolerated dose of the diluted skin prick test (DSPT) solution increased significantly after 6 months and two years treatment as compared to the dose before specific immunotheraphy (SIT). Significant differences were found between group III and group I or group II as well as between the groups under treatment and that group given a placebo (p < 0.05). The maximum tolerated dose with the bronchial provocation test (BPT) increased significantly after IT (p < 0.05). The differences between the groups under treatment and that given a placebo were significant (p < 0.05). A significant increase was detected in the levels of the Der PI specific IgG4 after IT (p < 0.01). The difference between the treatment groups and the placebo group was significant. There was a significant difference between group I and the other groups (p < 0.05) but differences between group II and III was not significant (p > 0.05). No significant correlation was found between (1) spIgE and the symptom medication score (SMS) (2) sp IgE and spIgG4 (3), DSPT and BPT. A significant positive correlation was found between the maximum tolerated dose with DSPT and increase in spIgG4 (r = 0.33, p = 0.046). A negative correlation was found between SMS and spIgG4 (p = 0.012, r = ­0.42) after IT.

Conclusion: SIT with Der PI is an effective and reliable treatment in allergic asthmatic children. Adsorbed extracts may be preferable to in childhood because of effectively, safety, tolerability and, fewer numbers of injection. The best IgG4 response and velocity of maintenance doses achieved was found in group I. Easy, cheap and safe parameters such a SMS and DSPT can be useful for a follow-up of SIT. Further investigation is required to determine which one of the products is the best.

Key words: Immunotherapy. Asthmatic children. Allergic asthma. Perennial rhinitis.

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INTRODUCTION

Specific immunotherapy (SIT) with allergens has been widely used for more than 80 years but is considered to be a controversial treatment of allergic asthma. Although the clinical efficacy has been documented in controlled studies particularly with new high quality extracts, most allergic patients do not receive SIT because of uncertainty as to the clinical efficacy, long-term effect mechanisms of action, and the risk of inducing systemic side effects (1, 2). In Europe, it is practiced only in certain areas of different countries. There has been considerable progress every year in the preparation of allergen extracts and standardization of new methods, and the use of new products has been suggested (3). House dust mites of the species Dermatophagoides pteronyssinus (Der PI) represent one of the major allergens inducing asthma. It has been suggested that SIT with house dust mite extracts is more effective in children than adults (4, 5). However, specific IT with classic aqueous products has some technical difficulties such as injections every week for a long time and side effects. The aim of this study was to compare the efficacy of two products, aluminium and calcium adsorbed extracts, with traditional aqueous extracts. The comparision was done using different parameters such as symptom medication scores, the level of diluted skin prick test, bronchial provocation test, specific IgE and IgG4, first on the 6^th month and at the end of the second year of IT.

PATIENTS AND METHODS

This study was carried out prospectively between December 1994 and January 1997 in the Division of Pediatric Allergic and Immunology of the Çukurova University Faculty of Medicine. Thirty-four patients whose ages ranged between 4-18 were selected according to the following criteria (a) having mild or moderate asthma [FEV₁ > 80% of the predicted value (5)] (b) poor symptom control during the previous year despite regular environmental control and treatment (c) positive skin prick test result with Der PI (wheal diameter greater than histamine) and/or positive radio allergo sorbent test (RAST) with Der PI (d) positive bronchial provocation test with Der PI (e) patients were excluded if they gave an appreciable clinical history of other allergens, a history of SIT in previous years or a history of other medical and immunological diseases.

Study design

The study was performed after written verbal permission by the parents. Thirty-four patients were randomly divided into four groups. Group I (n = 10) received immunotherapy (IT) with allergen extracts adsorbed to aluminium hydroxide (Alutard SQ:ALK Laboratories, Denmark). Group II (n = 10) received IT with allergen extracts adsorbed to calcium phosphate (Stallergenes Laboratories, France). Group III (n = 9) received aqueous IT (Greeer Laboratory) and the group IV (n = 5) received a placebo.

Skin prick test

Skin prick-tests (SPT) using standard panel allergens of ALK (Soluprick SQ:ALK Laboratories, Denmark) were performed on all the asthma patients coming to the out-patient clinic. Glycerinated normal saline and histamine HCL 10 mg/ml were used as controls. Those giving a positive reaction with Der PI were selected for this study.

Diluted skin prick test

The diluted skin prick est (DSPT) was performed with different concentrations of standardized Der PI extract on those selected. The concentrations of the Der PI solution used were 1000, 3000, 10000, 30000, 100000 SQ/ml. After 15 minutes, the wheal were marked with a soft, fine-tip pen, and transparent adhesive tape was placed over the wheals. Then, the tape was transferred to a record sheet and the area of the wheals was measured. The dilution which produced a wheal as great as histamine was accepted as the cutaneous tolerance index.

Specific IgE and IgG4

Patient sera were collecte before initiating therapy, at the end of the 6^th month and at the end of the second year of the study. The samples were stored at ­40° C. These samples were tested for specific IgE and G4 in duplicate in one session. We performed DSPT, BPT, spIgE and, spIgG4 only at the end of the 24^th month in group III and IV since the ideal maintenance dose had not been achieved by group III. If the analyses had been made on the 6^th month, we would have found very little significant difference. So we analyzed only at the end of the 24^th month. Standard tests provided by the manufacturers were employed. Specific IgE levels, expressed in Kua/L were quantified in undiluted serum samples by a flourimetric enzyme immunoassay (CAP System, Pharmacia, Upspsala, Sweden). Allergen specific IgG4 antibodies were detected by fluorimetric enzyme immunoassay (CAP System, Pharmacia, Uppsala, Sweden) of serum diluted 1:50. Results were expressed as a percent of the reference response by comparing the mean absorbency of each samples to the mean absorbency of the reference serum.

Symptom medication scores

The symptom-medication scores (SMS) were modified according to Bousquet (6) (table I). Most of the patients used the peak-flow-metre morning and evening. SMS were made by same specialist who did not know which IT material had been used. SMS were performed upon the onset of IT, on 6 th month, and at the end of the 2^th year.

 

Table I Asthma symptom medication score
Medication			Sympton
No medication		0	None	0
Inhaled salbutamol	200 µg	1	Wheezing at expiration	1
Inhaled salbutamol	600 µg	2	Wheezing at inspiration and expiration	2
Inhaled cromolyn or nedocromil or ofral ketotifen		3	High pitched wheezing also at rest	3
Inhaled steroid		4
Inhaled steroid + oral aminophylline		5
Oral steroid < 20 mg		6
Oral steroid > 20 mg		7

Immunotherapy

In group I and II, these extracts are supplied as four biologically standardized allergen concentrations of 100, 1000, 10000, 100000 SQ/ML (standard quality unit) for ALK and 0.01, 0.1, 1, 10 IR (index of reactivity, 0.01 IR = 1/1.000.000 w/v) for Stallergen, These materials were administered in increasing doses, weekly, for 3-4 months until a maximum tolerated dose (50000-100000 SQ/mL), was reached and then they were given at monthly intervals. In group III, extract 5000 Au/mL (Allergy unit) (Greer Lab^®) was used, was diluted before use, and was given at weekly intervals. The dose increment is shown in table II and III. SIT was usually administered by the supervisor of the study or occasionally by other investigators. The patients were observed for 30 minutes following the allergen injection. Before every injection, information was taken about side effects and symptoms. Side effects were recorded according to reaction score scale (table IV).

 

Table II The schedule of adsorbed vaccine dose increase
Bottle	Week	Dose	Concentration *for group I **for group II	Total volume (mL)	Frequency
	0	1	100 SQ/mL*	0.20	Weekly
1	1	2	0,01 IR or	0.40
	2	3	1/1.000.000w/v**
	3	4	1.000 SQ/mL*	0.20	Weekly
2	4	5	0.1 IR or	0.40
	5	6	1/100.000 w/v**	0.80
	6	7	10.000 SQ/mL*	0.20	Weekly
3	7	8	1 IR or	0.40
	8	9	1/10.000 w/v**	0.80
	9	10	100.000 SQ/mL	0.1	Weekly
	10	11	10 IR or	0.2
	11	12	1/1.000 w/v**	0.3
4	12	13		0.4 week
	13	14		0.6 or 0.8
	14	15		1.0	***
***IT was given once a month after reaching the maximum tolerated dose.

 

Table III The schedule of aqueous IT material dose increase
Week	Concentration	Bottle and formula	Volume (mL)	Frequency
1	1 Au/mL	1 (0.2 cc + 5.8 cc diluent)	0.1
2			0.2
3			0.3	Weekly
4			0.4
5			0.5*
16	1 Au/mL	2 (0.4 cc + 5.6 cc diluent)	0.1
17			0.2
18			0.3	Weekly
19			0.4
*			0.5*
*
48	10 Au/mL	4 (0.2 cc + 5.8 cc diluent)	0.1
*			*
*			*
192	5000 Au/mL	16		Weekly
*This volume was continued until completion fo the study.

 

Table IVReaction score scale
Local
Enduration and/or erythema < 3 cm	0
Enduration and/or erythema > 3 cm	1
Systemic
Generalized urticaria	2
Generalized pruritus and sneezing,
nasal congestion	3
Wheezing, tachypnea, decrease of FEV1 and PEF	4
Anaphylaxis, hypotension, sever wheezing,
laryngeal edema	5
Cardiopulmonary arrest	6

Bronchial provocation test

Bronchial provocation test (BPT) was performed on patients with a basal value of FEV₁ above the predicted value of 80% mg. Der PI extracts (Aqugen, ALK) were inhaled from a nebulizer (Pari inhaler, West Germany). The concentrations of extract were increased as follows; 1000, 3000, 10000, 30000, 60000, 100000 SQ/mL. Forced expiratory maneuvers were performed 3 and 10 minutes after inhalation of each allergen solution. Whenever FEV₁ was less than 20% of the predicted value, the test was discontinued and salbutamol was inhaled by the patient immediately.

Statistics

Nonparametric statistical methods were used for calculations. Statistical analyses were performed using the SPSS-PC and BMDP+package. For differences between the groups, the Kruskal-Wallas test, one-way analysis of variant (ANOVA), and repeated measures of analyses of variant were used. The spearman correlation test was used for correlation analyses. The chi-square test of indepedence was used for testing the influence of one variable upon another. The statistics of IgE, SPT, BPT, spIgG4 levels and graphics were evaluated by geometric means.

RESULTS

Of the 35 patients initially selected, 34 (22 males, 12 females) completed the study. One patient did not complete the study because she had moved from Adana. The ages of the thirty-four patients who were included in the study ranged between 5 to 18 years (mean age ± SD, 10.64 ± 3.4). In group I, ten patients (10.8 ± 3.72) received IT with allergen extracts adsorbed on aluminum hydroxide. In group II, ten patients (10.0 ± 3.62) received IT with allergen extracts adsorbed on calcium phosphate. In group III, nine patients (10.8 ± 3.72) received IT with an aqueous extract. Five patients (group IV) (11.0 ± 3.10) received only placebos. The characteristics of patients, protocols, maintenance doses, the time of the achievement of maintenance dose and, intervals have been given in table V.

 

Table V Characteristics of the patients and manufacture of material
No	Name	Age (year)	Sex	IT Group	Time of MD (week)	Maintenance dose	Interval of MD
1	T.D	8	Male	Alutard	16	100.000 SQ/ml	Monthly
2	S.B	9	Male	Alutard	15	100.000 SQ/ml	Monthly
3	A.p	14	Male	Alutard	14	100.000 SQ/ml	Monthly
4	C.A	16	Boy	Alutard	16	100.000 SQ/ml	Monthly
5	K.A	7	Girl	Alutard	15	100.000 SQ/ml	Monthly
6	B.E	7	Boy	Alutard	15	100.000 SQ/ml	Monthly
7	Ç.K	16	Girl	Alutard	15	100.000 SQ/ml	Monthly
8	E.C	9	Boy	Alutard	16	100.000 SQ/ml	Monthly
9	O.G	14	Boy	Alutard	16	100.000 SQ/ml	Monthly
10	U.C	8	Boy	Alutard	16	60.000 SQ/ml	Twice a month
11	Y''.B	9	Boy	APSI-Ca	16	10 IR*	Monthly
12	O.Y	13	Boy	APSI-Ca	14	10 IR	Monthly
13	T.H	10	Girl	APSI-Ca	20	10 IR	Monthly
14	D.K	7	Girl	APSI-Ca	20	8 IR	Monthly
15	p.U	8	Girl	APSI-Ca	20	10 IR	Monthly
16	F.A	15	Boy	APSI-Ca	26	6 IR	Monthly
17	C.Ö	10	Girl	APSI-Ca	15	8 IR	Monthly
18	M.K	16	Boy	APSI-Ca	22	6 IR	Monthly
19	D.E	7	Boy	APSI-Ca	15	10 IR	Monthly
20	M.K	5	Boy	APSI-Ca	14	8 IR	Monthly
21	M.Ö	7	Boy	Greer	104	1000 au/ml	Weekly
22	A.K	12	Girl	Greer	104	1000 au/ml	Weekly
23	G.D	7	Girls	Greer	104	1000 au/ml	Weekly
24	Z.T	18	Girl	Greer	78	1000 au/ml	Weekly
25	Ü.E	8	Boy	Greer	120	1000 au/ml	Weekly
26	H.C	9	Boy	Greer	104	1000 au/ml	Weekly
27	D.Y''	12	Girl	Greer	120	1000 au/ml	Weekly
28	Y''.B	10	Boy	Greer	104	1000 au/ml	Weekly
29	Ö.G	15	Boy	Greer	104	1000 au/ml	Weekly
30	O.D	6	Boy	Placebo			Weekly
31	T.T	12	Girl	Placebo			Weekly
32	M.A	14	Boy	Placebo			Weekly
33	N.B	13	Girl	Placebo			Weekly
34	O.Y	11	Boy	Placebo			Weekly
*10 IR = 1/1000 w/v.

The mean time that the maintenance dose was given as 15.40 ± 0.69 weeks for group I, 18.2 ± 4.0 weeks for group II, and 108 ± 33 weeks for group III. There was a significant difference in the time required to obtain the maintenance dose between group I and II (p < 0.05). The most significant difference was found between group III and group I and II (p < 0.00001).

The maintenance dose was the maximal tolerated amount of allergen individually for each individual case. The ideal maintenance doses were different for each IT material because of different units. For this reason, analysis were made separately. The mean of the IT side-effect score was 0.5 ± 1.3. These values were found to be 0.8 ± 1.5, 0.7 ± 1.2, 0.5 ± 1.3, 0.0 ± 0 for the groups I, II, III, and IV, respectively. There was no significant difference among the groups (p > 0.05). IT was well tolerated by all patients, and the incidence of side-effects was low. Treatment resulted in significant reduction in specific cutaneous reactivity, increased bronchial tolerance and IgG4 blocking antibodies. Parameters involved in the efficacy of IT, are as follows: the SMS was significantly reduced after IT period (p < 0.05). The most significant improvement occurred in group I and the least improvement, in group IV with no significant difference among the IT group (p > 0.05).

Skin sensitivity was determined according to the cutaneous tolerance concentration in DSPT. The mean cutaneous tolerance concentration was significantly increased in all of the groups after IT (p < 0.05) (tabla VI). The increase in groups I and II was significantly higher than in group III and IV (p < 0.05). The changes in results of BPT are shown in table VI. While the geometric mean of the tolerated dose was 4.786 SQ, on the 6^th and 24^th months, the concentrations were 22.389 SQ and, 36.307 SQ in group I and II, respectively. There was no significant difference among groups given treatment (p > 0.05), but there was between these groups and the group given placebos (p < 0.05).

 

Table VI Evolution of clinic and laboratory parameters of the patients before after IT
	Mean of the IT groups	Group I	Group II	Group III	Group IV
SMS
Before IT	51.1 ± 3.3	6.2 ± 2.1	5.1 ± 2.4	4.6 ± 2.9	4.0 ± 1.9
At 6^th month	3.1 ± 2.3	3.2 ± 2.2	3.1 ± 2.1	3.1 ± 2.3	3.4 ± 3.1
At 2^nd year	1.7 ± 1.8	0.7 ± 1.0	2.4 ± 2.5	1.4 ± 1.7	3.2 ± 1.6
Side effect score	0.5 ± 1.3	0.8 ± 1.5	0.7 ± 1.2	0.5 ± 1.3	0.0 ± 0
Diluted SPT*
Before IT	3235.93	2511.8	3890	2570	2790
At 6 ^th month	10000	26915	7943	ND**	ND
At 2^nd year	27542	34673	43651	10000	2520
BPT*
Before IT	4786	7244	4786	2137	4786
At 6^th month	22387	38904	14125	ND	ND
At 2^nd year	36307	31622	39810	31153	7100
SpIgE*
Before IT	5.4 ± 1.2	5.0 ± 1.8	5.6 ± 1.2	5.7 ± 0.6	5.4 ± 0.4
At 6^th month	5.3 ± 0.9	5.2 ± 0.9	5.5 ± 0.7	ND	ND
At 2 nd year	5.5 ± 0.9	5.3 ± 0.9	5.6 ± 1.0	5.5 ± 1.0	6.0 ± 0
SpigG4
Before IT	6.3 ± 1.5	6.3 ± 1.6	5.0 ± 2.6	10 ± 1.7	7.0 ± 2.2
At 6^th month	22.5 ± 2.5	22.5 ± 2.5	3.7 ± 1.2	ND	ND
At 2^nd year	19.0 ± 2.5	50.1 ± 1.9	14.4 ± 1.6	8.9 ± 2.3	5.4 ± 1.2
SMS: symptom medication score; SPT: skin prick test; BPT: bronch provocation test. *Geometric mean. **Not done.

The mean of Der PI specific IgE level did not change significantly after IT (table VI). The geometric mean of spIgG4 was 6.3 ± 1.5% ref before IT. Ont he 6^th month and at the end of the 2^nd year, these values were 22.5 ± 2.5% ref and 19.0 ± 2.5% ref in groups I and II, respectively.

The level of spIgG4 increased significantly in the treated groups in comparison to group IV (p < 0.01). There were also significant differences among the other groups (p < 0.01). The greatest increase was found in group I (p < 0.05) as compared to group II and III. There was no significant difference between group II and III (p > 0.05).

Correlation between clinical and immunologic changes

The improvement in the SMS was not correlated to changes in spIgE (r = 0.35-0.99, p > 0.05), but was correlated to changes in spIgG4 (r = ­0.42, p = 0.012). Changes in the levels of spIgG4 were correlated to cutaneous sensitivity (diluted skin prick test) (r = 0.33, p = 0.046). It seems that the decrease in cutaneous sensitivity was related to improvement in respiratory tolerance to the allergen, but this was not statistically significant (p > 0.05). No significant correlation was seen in changes in spIgE and spIgG4 as compared to DSPT and BPT.

Tolerance and adjustment

The IT was generally well tolerated. In group I, the dose of 100.000 SQ, previously shown to be effective in mite allergy, was reached by eight patients. Two patients developed local swellings larger than 3 cm, making it necessary to decrease the doses as much as 60.000 and 80.000 SQ. When one of the patients was treated with a maintenance dose fo 60.000 SQ monthly, his SMS increased. For this reason, IT was done with at interval of two weeks. The SMS of this patient improved.

In group II, 4 patients could not achieve an ideal maintenance dose (10 IR). Three of these patients could not tolerate monthly injections and were given the injections every two weeks because of the reason mentioned above. In group III, IT was usually tolerated very well.

Second and/or 3^rd BPT was not performed on seven patients. Four of seven patients discontinued medication. The remaining three patients suffered from late asthmatic symptoms with BPT. These patients were hospitalized and treated. All of these patients with late asthmatic symptoms were approximately seven years old. The tests were performed in the spring.

Four patients (one of them in group I, three of them in group II) developed a local swelling, which was greater than 3 cm when the concentration was increased during up-dosing. No reaction occurred during the updating and maintenance phase in group III and IV.

DISCUSSION

The efficacy of IT with standardized Der PI extracts was confirmed by several studies, but the selection of patients should follow the same criteria and only Der PI allergic individuals should be treated. Although all patients may benefit from IT, several studies showed that children more significantly improved than did adults and that IT was only effective in patietns with normal or subnormal FEV₁ (1, 4-7).

In this study, 34 children with asthma who were monosensitized to Der PI were evaluated prospectively. Groups of children receiving three different IT materials were compared to those receiving a placebo.

We have been using aqueous extracts for 20 years. Severe systemic reactions have not been seen during this time. Our major problem is the number of injections which have to be given to children for approximately 5 years. Furthermore, since a longer time before the maintenance dose is achieved with weekly injections, the clinical response is delayed.

Our study showed that, SIT with all of the standardized Der PI extracts was effective after two years of treatment. Clinical improvement was accompanied by a decreased reactivity of the target organ (bronchi), skin sensitivity and changes of spIgG4 levels except in the group given placebos.

The objective assessments of efficacy and/or the results from the patients'' cards used for recording their PEF, indicated a significant improvement in symptoms and reduction in the use of medication. The immunologic changes of IT was demonstrated by its ability to modulate spIgG4 and spIgE responses (4, 5).

The scores of IT side-effect was similar in all of the groups. No clinically subcutaneous fat necrosis occurred with the use of adsorbed aluminum extract.

There was an association between successful IT and reductions in the magnitude of late-phase responses inthe skin (8). The coetaneous tolerance concentration was significantly increased by adsorbed extracts in comparison to the aqueous extract. This may be explained by the fact that the ideal maintenance dose was achieved in less time. There was no difference in the effects produced by the two adsorbed extracts.

We found an increase in the tolerated concentration of BPT with IT in contrast to the placebo. The increase in this group I was rather rapid until the 6^th month, then, leveled off. The increase in this group II began after the 6^th month. In group III, the increase was showed a systematic acceleration until the 24^th month. However, there was no significant difference among the groups at the end of the 24^th month. Picher showed a decrease in bronchial hyperactivity (BHR) with mite IT by the 18-24 month (8). This reduction of BHR may be important for the well-being of the allergic patient, since it is often the main complaint of patients with mite asthma. Aas (11, 12), repored a correlation between BPT and FEV₁. We also found a correlation between the improvement in SMS and an increase in tolerance of BPT concentration.

As has been previously reported, specific IgE did not change at the end of the 2^nd year in our study (2, 7, 8). The spIgG4 level increased in all of the IT groups except for the placebo group. But the pattern of increase was different in each group. The greatest increase was in group I. The increase in group II and III was similar. SpIgG4 is one of the most important parameters (2, 4, 13).

Although it has been reported that there is a correlation between clinical improvement and an increase in the IgG4 levels (2, 8, 9), no report was found which showed a relationship with antigen standardization. We found an important correlation between changes in SMS, DSPT and increase in the IgG4 level. For a follow-up of the efficacy of IT, cheaper and simpler techniques such as SMS and DSPT may be substituted for spIgG4.

According to these results, adsorbed extracts are more advantageous than aqueous extracts, because of 1) they achieve a maintenance dose more rapidly and as a result, increase coetaneous tolerance and 2) there is a decrease in the number of injections. In group I, given aluminum adsorbed extract, the level of sp IgG4 and the number of patients who achieved the maintenance dose were higher than that in the group given calcium adsorbed extract. But it might be misleading to suppose that the aluminum adsorbed extract is more efficient than the others, because of the small size of the study groups.

These conclusions can be obtained from this study.

1. IT with Der PI is effective in monosensitizied children who had FEV₁ > 80%.

2. In children, BPT is unsafe. It is undesirable to use it as a routine test. SMS and DSPT may be substituted for spIgG4 and BPT in clinical practice.

3. Adsorbed extracts are safe and efficient in children. A decreased number of injections and earlier achievement of the maintenance dose show its superiority to the aqueous extract.

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RESUMEN

Antecedentes: dermatophagoides pteronyssinus (Der PI) es el principal alergeno que causa asma alérgica y rinitis perenne. Los extractos de Der PI pueden utilizarse en el tratamiento de los pacientes que no responden al tratamiento farmacológico y a la evitación de los alergenos. El éxito de la inmunoterapia (IT) depende de la selección de los pacientes y de los alergenos apropiados, así como de un seguimiento regular.

Objetivos: se ensayaron tres grupos diferentes de materiales de IT y un placebo en 34 pacientes con asma sensible a Der PI. Las evaluaciones clínicas de la provocación con alergeno y las pruebas inmunológicas in vitro se realizaron en los pacientes antes de la IT, al sexto mes y al final del segundo año de IT. Los resultados se compararon con el grupo tratado con placebo.

Resultados: no hubo diferencias significativas entre los grupos con respecto a la edad, el sexo y la duración de la enfermedad. El tiempo necesario para alcanzar la dosis de mantenimiento para el grupo I (Alutard^®), el grupo II (APSI retard CA^®) y el grupo III (Greer^®) fue de 15,40 ± 0,69; 18,2 ± 4,0 y 108 ± 33 semanas, respectivamente. Aun cuando hubo alguna diferencia significativa entre los que recibieron IT acuosa y los que recibieron placebo (p < 0,05), hubo una diferencia significativa mayor entre los que recibieron IT adsorbida y los que recibieron placebo (p < 0,00001). Hubo también una diferencia significativa entre los grupos I y II, que recibieron IT adsorbida. No hubo diferencia significativa en cuanto a las dosis máximas toleradas entre el grupo I y el grupo II (p > 0,05), pero se encontraron diferencias significativas entre el grupo III y los otros dos grupos (p < 0,05). La IT no modificó los niveles de IgE específica. No hubo diferencia en las puntuaciones de efectos colaterales entre los grupos (p < 0,05). La dosis tolerada máxima de la solución diluida utilizada en el prick-test (DSPT) aumentó de manera significativa después de seis meses y dos años de tratamiento, en comparación con la dosis antes de inmunoterapia específica (ITS). Se encontraron diferencias significativas entre el grupo III y el grupo I o el grupo II, así como entre los grupos sometidos a tratamiento y el grupo que recibió placebo (p < 0,05). La dosis tolerada máxima con la prueba de provocación bronquial (PPB) aumentó de manera significativa después de la IT (p < 0,05). Las diferencias entre los grupos sometidos a tratamiento y el grupo que recibió placebo fueron significativas (p < 0,05). Se detectó un aumento significativo en los niveles de IgG4 específica contra el Der PI después de la IT (p < 0,01). La diferencia entre los grupos de tratamiento y el grupo placebo fue significativa. Hubo una diferencia significativa entre el grupo I y los otros grupos (p < 0,05), pero las diferencias entre el grupo II y el III no fueron significativas (p > 0,05). No se encontró correlación significativa entre (1) la IgE específica y la puntuación de medicación sintomática (PMS) (2), la IgE específica y la IgG4 específica, y (3) la DSPT y la PPB. Se encontró una significativa correlación positiva entre la dosis tolerada máxima con la DSPT y un aumento de la IgG4 específica (r = 0,33, p = 0,046). Se encontró una correlación negativa entre la PMS y la IgG4 específica (p = 0,012, r = ­0,42) después de la IT.

Conclusión: la ITS con Der PI es un tratamiento eficaz y fiable para los niños con asma alérgica. En la infancia, puede ser preferible la adsorción de extractos, debido a su eficacia, seguridad, tolerabilidad y menor número de inyecciones necesarias. La mejor respuesta de la IgG4 y de velocidad hasta alcanzar la dosis de mantenimiento se encontró en el grupo I. Parámetros fáciles, baratos y seguros como el PMS y la DSPT pueden ser útiles para el seguimiento de la ITS. Es necesario realizar más investigaciones para determinar cuál de los productos es el mejor.

Palabras clave: Inmunoterapia. Niños asmáticos. Asma alérgica. Rinitis perenne.

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