DRUG THERAPY OF UPPER RESPIRATORY TRACT INFECTIONS
EASINESS IN DOWNS: A SURVEY ON 328 PERSONS
Renato
COCCHI MD, neurologist and medical psychologist
Abstract
This is a retrospective study of a
consecutive series of 328 home reared Down Ss treated by drug therapy. Sample
data: 188 M and 140 F; M/F ratio = 134.29; chromosomal diagnosis: standard
trisomy 21 = 90.85%; mosaicisms = 3.66%; translocations = 3.66%; only clinical
diagnosis: 1.83%; Average age at first consultation; 77.70 +/- 61.64 months;
average age at last checkups; 116.60 +/-67.86 months; average therapy length:
48.04 +/- 43.58 months.
The reduction of upper respiratory tract
infections (URTI) easiness after at least 1 year drug therapy had its score by
the same 0-4 points scale scored during the first consultation.
The sample, as representative of the
Italian population of Down Ss, had two age stratifications by two-years
subsamples till 16 years inclusive, and one subsample for the age 16;1 and more
years. The first stratification is for scores at first consultation, and the
second one for scoring at last checkups.
This URTI easiness decreases up to 71.88%
disappearance in the 4 subsamples from 2;1 to 10 years of age (.02 - .0009)
till 16 years inclusive (80.77% disappearance), but it does not reach any
significant level due to the superimposed age reduction effect (see: Cocchi,
It. J. Intellect. Impair. 1997: 10: 143-149). More severe URTI forms, which in
non-treated Downs Ss disappeared since 14;1-16 years, had a null rate since
8;1-10 years. Also the subsample of infants up to 2 years inclusive had a
significant reduction of that easiness (.047), but scoring was made after
average six-months therapy. A list of drugs in use at last checkups was
provided with their daily doses.
Key words: Down's syndrome; Upper
Respiratory Tract Infections; Easiness; Drug therapy.
Down's syndrome
Mental retardation
Immunity
Drug modulation of stress reactions
Home Page
In my previous research (Cocchi, 1997) I
investigated the time-course of easiness to Upper Respiratory Tract Infections
(URTI) in 510 non drug treated Downs, as reported at first consultation. Part
of them followed drug therapies for different time length, so I can evaluate
global therapy results on URTI easiness. The time-course of that easiness will
have the comparison with non treated subjects.
Materials and methods
This second survey deals with the
clinical records related to all subjects who took the prescribed drug therapy
and had at least one checkup after the first visit. This makes a casual
consecutive series of Downs that has its selection criterion on the fact that
those Downs came back for checkups. As home reared and home living Downs they
came from all parts of Italy to outpatients' consultations, between January
1979 and April 1997.
During their 1st consultation all these
Ss had their easiness to URTI evaluated and recorded by severity, along with
other signs and symptoms. This easiness was appraised with reference to the
past 12 months (or, in children aged less than one year, with reference to past
months) by recording according to a severity scale as follows:
(0) = as in a healthy child;
(1) = nasal catarrh usually present;
(2) = 1 + susceptibility to cough and
cold with few feverish episodes;
(3) = 1 + 2 + easiness to tonsillitis,
pharyngitis, bronchitis with moderate fever and limited need of antibiotics (up
to four regimens per year);
(4) = 1 + 2 + 3 + high temperatures,
occasional otitis and bronchial pneumonia, and frequent use of antibiotics
(more than four regimens per year).
I used the same scoring's way during the first checkup or following
checkups. From these checkups I collected the scores recorded during the last
ones, but some cases came back only
once for checkup.
The records about autistic or PDD DS Ss
were discarded because we saw that this second heavier pathology can modify the
URTI easiness (Cocchi and Bonaduce, 1988).
From the remaining records I collected:
sex; chromosomal diagnosis; age at 1st consultation; age at last consultation;
length of the drug therapy; scoring of URTI easiness at 1st consultation; the
same at last checkup; drugs in use at the last checkup and their daily doses. I
processed data by age intervals' statistics and I applied Chi Square Test, when
suitable.
Results
Only 328 cards out of 510 fitted the
criteria of this survey. They refer to home reared Downs coming from all Italy.
Table 1 summarizes epidemiological data of these subjects, table 2 shows drugs
in use at last checkups, and tables 3-11 present the URTI easiness scoring
according to age intervals.
In graphics 1-5 I showed the time-course
of URTI easiness and of each grade of severity, as recorded during the 1st
consultation and the last checkup.
Table 1: Epidemiological and clinical data of the sample
|
|
||
|
No. of Ss |
328 |
100.00% |
|
M |
188 |
57.31% |
|
F |
140 |
42.31% |
|
M/F ratio |
134.29 |
|
|
|
|
|
|
Chromosomal diagnosis |
|
|
|
Standard trisomy 21 |
298 |
90.85% |
|
Mosaicisms |
12 |
3.66% |
|
Translocations |
12 |
3.66% |
|
Unknown, only clinical diag. |
6 |
1.83% |
|
|
|
|
|
Age at 1st consult.: range (months) |
4-410 |
|
|
Average +/- SD |
67.70 +/-61.64 |
|
|
Age at last checkup: range |
7-417 |
|
|
Average +/- SD |
116.60 +/-67.88 |
|
|
|
|
|
|
Length of drug therapy: range |
2-169 |
|
|
Average +/- SD |
48.04 +/-43.58 |
|
As we can see in Table 1 the M/F ratio
closely overlaps what we know for live born Italian infants. The distribution
of the chromosomal diagnoses stays within the variance limits for Italian and
International samples. For that we can maintain the sample here surveyed as a
representative sample at least of the Italian population of Downs.
Table 2: Drugs in use at the
last checkup
|
|
|||||
|
Drug in use |
mg/die (*) |
no. of Ss |
% |
||
|
Pyridoxine |
75-150 |
267 |
81.40 |
||
|
Diazepam |
1-2.5 |
237 |
72.26 |
||
|
S-adenosil-l-methionine |
100 |
190 |
72.26 |
||
|
A polyvitaminc compound (BEROCCA)TM |
1 cp x sett |
189 |
57.93 |
||
|
L-glutamine |
125-250 |
187 |
45.12 |
||
|
Folates |
7.5 |
143 |
43.60 |
||
|
Pyritinol |
50-100 |
139 |
42.38 |
||
|
Alpha-tocopherole |
50 |
74 |
22.56 |
||
|
Vit. B1+B6+B12 |
125+125+500mcg |
63 |
19.21 |
||
|
Bromazepam |
0.5-1.5 |
59 |
17.99 |
||
|
Biotin |
2.5-5 |
59 |
17.99 |
||
|
5-hydroxytriptofan |
25-50 |
43 |
13.11 |
||
|
Arginine pidolas |
250 |
42 |
12.80 |
||
|
L-glutamine + pemoline |
45+5 - 90+10 |
41 |
12.50 |
||
|
Glycine(in BIOTASSINA)TM |
200 |
34 |
10.37 |
||
|
Carnitine |
500 |
34 |
10.37 |
||
|
Viloxazine |
50-100 |
22 |
6.71 |
||
|
Delorazepam |
0.5 |
18 |
5.59 |
||
|
Alpha-ketoglutarato of pyridoxine |
300 |
18 |
4.00 |
||
|
Deanol |
320 |
10 |
3.05 |
||
|
Oxazepam |
7.5-15 |
9 |
2.74 |
||
|
Piracetam |
800 |
7 |
2.13 |
||
|
Pantotenate |
150 |
7 |
2.13 |
||
|
Amitriptyline+ perphenazine |
10 + 2 |
6 |
1.83 |
||
|
Acetyl-carnitine |
250 |
5 |
1.52 |
||
|
Clobazam |
10 |
5 |
1.52 |
||
|
Taurine |
500 |
3 |
0.91 |
||
|
Total |
|
1802 |
|
||
(*) In many cases the
drug was prescribed every second day, so the daily dose reports it as it was
prescribed every day.
The average prescription summed up 5.49
drugs per person. Pyridoxine, alone or in combination with thiamine and
cyanocobalamine, and a low dose benzodiazepine were always in it.
Tab. 3: Global comparison between initial and final scores
|
|
||||
|
URTI easiness graduation |
initial scores |
final scores |
||
|
|
No.of Ss |
% |
No. of Ss |
% |
|
Not present (0) |
99 |
30.19 |
221 |
67.37 |
|
Present, mild (1) |
37 |
11.28 |
35 |
10.67 |
|
moderatea (2) |
49 |
14.94 |
30 |
9.15 |
|
severe (3) |
97 |
29.57 |
32 |
9.76 |
|
profound (4) |
46 |
14.02 |
10 |
3.05 |
|
Totals |
328 |
100.00 |
328 |
100.00 |
Chi Square = 107.032
with 4 df and p < .0009
As a global survey, 69% of the sample
presented URTI easiness at 1st consultation, with increased severity (grades
3-4) in 40% of them. At final scoring only about 33% of the same sample went
along to present URTI easiness, but increased severity went down to less than
13% of them.
Tab. 4: Comparison between initial and final scores of
age interval
up to 24 months (Average length of
therapy: 5.94 months.)
|
|
||||
|
URTI easiness graduation |
initial scores |
final scores |
||
|
|
No. of Ss |
% |
No. of Ss |
% |
|
|
|
|
|
|
|
Not present (0) |
24 |
24.49 |
10 |
58.83 |
|
Present, mild (1) |
14 |
14.28 |
2 |
11.76 |
|
moderate (2) |
17 |
17.35 |
1 |
5.88 |
|
severe (3) |
26 |
26.53 |
1 |
5.88 |
|
profound (4) |
17 |
17.35 |
3 |
17.65 |
|
|
|
|
|
|
|
Totals |
98 |
100.00 |
17 |
100.00 |
Chi Square = 9.690 with
4 df and p < .047
The results on infants up to 24 months
with average 6-month therapy, although significant, need caution. Nearly all of
them went back to checkups nearly before one-year of therapy.
Tab. 5: Comparison between initial and final scores of
age interval
from 25 to 48 months (Average length of
therapy: 16.70 months.)
|
|
||||
|
URTI easiness graduation |
initial scores |
final scores |
||
|
|
No.of Ss |
% |
No.of Ss |
% |
|
|
|
|
|
|
|
Not present (0) |
9 |
14.75 |
18 |
40.92 |
|
Present, mild (1) |
5 |
8.20 |
6 |
13.63 |
|
moderate (2) |
8 |
13.11 |
5 |
11.36 |
|
severe(3) |
24 |
39.35 |
12 |
27.27 |
|
profound (4) |
15 |
24.59 |
3 |
6.82 |
|
|
|
|
|
|
|
Totals |
61 |
100.00 |
44 |
100.00 |
Chi Square = 13.302
with 4 df and p < .011
In this age interval no URTI easiness
turned out from 15% to nearly 41% and increased severity went down from about
64% to a while more than 34%.
Tab. 6: Comparison between initial and final scores of
age interval
from 49 to 72 months (Average length of
therapy: 28.86 months.)
|
|
||||
|
URTI easiness graduation |
initial scores |
final scores |
||
|
|
No. of Ss |
% |
No.of Ss |
% |
|
|
|
|
|
|
|
Not present (0) |
8 |
16.33 |
18 |
48.65 |
|
Present, mild (1) |
7 |
14.28 |
4 |
10.81 |
|
moderate (2) |
4 |
8.16 |
9 |
24.32 |
|
severe (3) |
21 |
42.86 |
9 |
24.32 |
|
profound (4) |
9 |
18.37 |
3 |
6.11 |
|
|
|
|
|
|
|
Totals |
49 |
100.00 |
37 |
100.00 |
Chi Square = 21.838
with 4 df and p < .0009
In this age interval no URTI easiness
turned out from about 16% to nearly 49%, while increased severity went down
from about 61% to about 14%.
Tab. 7: Comparison between initial and final scores of
age interval
from 73 to 96 months (Average length of
therapy: 35.90 months.)
|
|
||||
|
URTI esasiness graduation |
initial scores |
final scores |
||
|
|
No. of Ss |
% |
No. of Ss |
% |
|
|
|
|
|
|
|
Not present (0) |
10 |
38.45 |
30 |
71.43 |
|
Present, mild (1) |
4 |
15.38 |
7 |
16.67 |
|
moderate (2) |
3 |
11.54 |
3 |
7.14 |
|
severe (3) |
8 |
30.76 |
1 |
2.38 |
|
profound (4) |
1 |
3.85 |
1 |
2.38 |
|
|
|
|
|
|
|
Totals |
26 |
100.00 |
42 |
100.00 |
Chi Square = 13.230 with 4 df and p <
.011
In these children no URTI easiness
turned out from about 38% to more than 71%, while more severe forms decreased
from nearly 35% to less than 5%.
Tab. 8: Comparison between initial and final scores of
age interval
from 97 to 120 months (Average length of
therapy: 47.69 months.)
|
|
||||
|
URTI easiness graduation |
initial scores |
final scores |
||
|
|
No. of Ss |
% |
No. of Ss |
% |
|
|
|
|
|
|
|
Not present (0) |
16 |
43.25 |
28 |
71.80 |
|
Present, mild (1) |
1 |
2.70 |
4 |
10.25 |
|
moderate (2) |
8 |
21.62 |
4 |
10.25 |
|
severe (3) |
9 |
24.32 |
3 |
7.70 |
|
profound (4) |
2 |
5.41 |
0 |
0.00 |
|
|
|
|
|
|
|
Totals |
26 |
100.00 |
42 |
100.00 |
Chi Square = 11.304
with 4 df and p < .024
No URTI easiness got up from 43% to
nearly 72%. More severe forms went down from 30% to less than 8%.
Tab. 9: Comparison between initial and final scores of
age interval
from 121 to 144 months (Average length
of therapy: 58.6 months.)
|
|
||||
|
URTI easiness graduation |
initial scores |
final scores |
||
|
|
No. of Ss |
% |
No.of Ss |
% |
|
|
|
|
|
|
|
Not present (0) |
16 |
55.18 |
29 |
72.50 |
|
Present, mild (1) |
3 |
10.34 |
6 |
15.00 |
|
moderate (2) |
6 |
20.69 |
2 |
5.00 |
|
severe (3) |
3 |
10.34 |
3 |
7.50 |
|
profound (4) |
1 |
3.45 |
0 |
0.00 |
|
|
|
|
|
|
|
Totals |
29 |
100.00 |
40 |
100.00 |
Chi Square = 6.158 with
4 ds and p < .189 NS
No URTI easiness increases from about
55% to 72.5%, while its grades 3-4 decrease from 14% to 7.5%. The variable of
age starts having its weight so Chi Square does not reach the minimal
significant level.
Tab. 10: Comparison between initial and final scores of
age interval
from 145 to 168 months (Average length
of therapy: 76.55 months.)
|
|
||||||
|
URTI easiness graduation |
initial scores |
final scores |
||||
|
|
No.of Ss |
% |
No.of Ss |
% |
||
|
|
|
|
|
|
||
|
Not present (0) |
4 |
57.16 |
35 |
79.55 |
||
|
Present, mild (1) |
1 |
14.28 |
3 |
6.82 |
||
|
moderate (2) |
1 |
14.28 |
1 |
2.27 |
||
|
severe (3) |
0 |
0.00 |
5 |
11.36 |
||
|
profound (4) |
1 |
14.28 |
0 |
0.00 |
||
|
|
|
|
|
|
||
|
Totals |
7 |
100.00 |
44 |
100.00 |
||
Chi Square = 10.129 with 4 df and p <
.039
No URTI easiness goes from about 57% to
nearly 80%, while its grades 3-4 go down from about 14% to 11.36%
Tab. 11: Comparison between initial and final scores of
age interval
from 169 to 192 months (Average length
of therapy: 79.81 months.)
|
|
||||||
|
URTI easiness graduation |
initial scores |
final scores |
||||
|
|
No.of Ss |
% |
No.of Ss |
% |
||
|
|
|
|
|
|
||
|
Not present (0) |
6 |
54.55 |
21 |
80.77 |
||
|
Present, mild (1) |
1 |
9.09 |
2 |
7.69 |
||
|
moderate (2) |
1 |
9.09 |
1 |
3.85 |
||
|
severe (3) |
3 |
27.27 |
2 |
7.69 |
||
|
profound (4) |
0 |
0.00 |
0 |
0.00 |
||
|
|
|
|
|
|
||
|
Totals |
11 |
100.00 |
26 |
100.00 |
||
Chi Square = 3.333 with
3 df and p < .465 NS
No URTI easiness goes from more than 54%
to about 81%, while its severe grades go down from 27% to less than 8%.
Tab. 12: Comparison between initial and final scores of
age interval
from 193 and more months (Average length
of therapy: 69.15 months.)
|
|
||||||
|
URTI easines graduation |
initial scores |
final scores |
||||
|
|
No.of Ss |
% |
No.of Ss |
% |
||
|
|
|
|
|
|
||
|
Not present (0) |
6 |
60.00 |
32 |
82.05 |
||
|
Present, mild (1) |
1 |
10.00 |
1 |
2.56 |
||
|
moderate (2) |
1 |
10.00 |
4 |
10.26 |
||
|
severe (3) |
2 |
20.00 |
2 |
5.13 |
||
|
profound (4) |
0 |
0.00 |
0 |
0.00 |
||
|
|
|
|
|
|
||
|
Totals |
10 |
100.00 |
39 |
100.00 |
||
Chi Square = 3.734 with
3 df and p < .394 NS
In this age group no URTI easiness
turned out from 60% to more than 82%, while more severe forms turned down from
20% to a while more than 5%.
Initial
and final data as a function of age have summaries in graphic 1 (time-course of
no URTI easiness) and in graphics 2-5 (time-course of each grade of severity).
As you can see, drug treated persons
have always a higher rate of no URTI easiness.
The graphic 2 shows that drug treated
subjects have low rates of grade 1 URTI easiness since their 12-14 years of
age.
As we can see, since 8 years of age
drug treated Downs have a lower rate of grade 2 URTI easiness than non treated
Downs.The final peak seems only a statistical artifact.
The graphic 4 shows that drug treated
Downs had always lesser grade 3 URTI easiness rate than non treated Downs. The
null rate in 14 years non treated Downs comes from a statistical artifact.
From the graphic 5 it clearly appears
that drug treated Downs do not catch the more severe form of URTI easiness
since their 10 years. The same fact happens only since 16 years in non treated
Downs.
Discussion
This research is the first one on drug therapies
for URTI easiness in Down's syndrome that takes into account the age as a
favourable factor. The graduation of the scale used for scoring URTI easiness
is the same I used in previous research (Cocchi, 1987, Cocchi and Bonaduce,
1988; Cocchi, 1990, Cocchi, 1997). The examined sample represents at least the
Italian population of 21 trisomics. This is so for its extent, the coming from
all Italy and the M/F ratio overlapping what already found in live births of
Italian Downs (Camera and Mastroiacovo, 1984). The distribution of chromosomal
diagnoses too, is not far from what usually found either in Italy and foreign
countries (Camera and Mastroiacovo, 1984, Hook, 1981). Being present 6 Ss with
only a clinical diagnosis, it does not spoil the distribution congruence of
sample chromosomal anomalies.
The average drug therapy lasted four years.
The drugs in use at last checkups, as reported in Tab. 2, have a basis on a
benzodiazepine and pyridoxine as prescribed alone or together with thiamine and
cyanocobalamine. I made the choice of drugs according to signs, symptoms and
behaviours of each child, considering both age and the length of the therapy up
to now. If I collected the therapies prescribed at first consultations, I had a
lesser amount of different drugs. So the presence of l-glutamine, alone or in a
compound with pemoline, should have been more significant.
The whole sample had double age
stratification in two ways, both for URTI easiness at the age of 1st
consultation and URTI easiness at the last checkup. Except infants' age up to
24 months, already debatable because the last checkup happened after average 6
months therapy, subjects compared into the same age interval are nearly all
different. This double stratification let to cutting off the variable of the
age, so pointing out the effects of the therapies.
In this survey we can already note a surely
positive effect of drug therapies per se till 10 years of age. This is
confirmed by the early disappearance of more severe forms since 8-10 years, a fact
noted only since 16 years in non treated Downs (Cocchi, 1997).
How the probands could get out at such a cut
off, I send back to my previous papers as for a whole explanation of action
mechanisms, with a wide references support (Cocchi, 1981 e 1987). By shortly
summarizing, l-glutamine, pyridoxine and the benzodiazepine as antistress drugs
reduce the immune suppressive action of the cortisol. On the other hand
l-glutamine acts as a sole supplier of a carbon atom for the production of
cells' nuclei. This is of value for the leukocytes nuclei that are the basis of
the non specific immunity. I always need to remind that this result, again
found in Downs, is not peculiar of them. My first clinical research on this
topic dealt with 61 depressed children among which I treated my first Down
patient (Cocchi, 1981)
Conclusions
This new retrospective study on narrowing
down of URTI easiness in drug treated Downs bears out the previous one (Cocchi,
1987). The result does not depend on the favouring variable of age and it is
significant, at least till 10 years of age. After this time the favouring
effect of age overlaps the effect of drugs, thus avoiding a clear distinction.
This comes out according the type of detection of this study, where I thought
out the scoring of the last checkup. Since this is an early and quite firm
effect, I have to plan a future research where scoring it at a fixed distance
from first consultation. Although I reached now positive results, I think that
fixed times of 1 and 2 years would offer more information.
References
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225-230
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Gerald P.S. (eds): Trisomy 21 (Down Syndrome) research perspectives. University
Park Press, Baltimore, 1981.
Printed on It. J. Intellect. Impair. 1998, 11: 9-17.
Author's address: Renato COCCHI MD, via Rabbeno, 3
42100 Reggio Emilia (Italy)
renatococchi@libero.it
Down's syndrome
Mental retardation
Immunity
Drug modulation of stress reactions
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