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
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|
No. of Ss |
328 |
100.00% |
|
M |
188 |
57.31% |
|
F |
140 |
42.31% |
|
M/F ratio |
134.29 |
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|
|
|
|
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 |
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|
Average +/- SD |
67.70 +/-61.64 |
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|
Age at last checkup: range |
7-417 |
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|
Average +/- SD |
116.60 +/-67.88 |
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Length of drug therapy: range |
2-169 |
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|
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
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|
Drug in use |
mg/die (*) |
no. of Ss |
% |
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|
Pyridoxine |
75-150 |
267 |
81.40 |
||
|
Diazepam |
1-2.5 |
237 |
72.26 |
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|
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 |
||
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Total |
|
1802 |
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||
(*) 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
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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.)
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|
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.)
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|
||||
|
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.)
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|
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.)
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|
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.)
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|
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|
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.)
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|
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|
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.)
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|
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.)
|
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|
URTI easines graduation |
initial scores |
final scores |
||||
|
|
No.of Ss |
% |
No.of Ss |
% |
||
|
|
|
|
|
|
||
|
Not present (0) |
6 |
60.00 |
32 < | |||