Journal of Asthma Research
ISSN: 0021-9134 (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/ijas19
Effect of triiodothyronine on bronchial asthma. II Ahmed A. Ismail, Ernest Shalaby & Ibrahim Gadalla To cite this article: Ahmed A. Ismail, Ernest Shalaby & Ibrahim Gadalla (1977) Effect of triiodothyronine on bronchial asthma. II, Journal of Asthma Research, 14:3, 111-118, DOI: 10.3109/02770907709104182 To link to this article: http://dx.doi.org/10.3109/02770907709104182
Published online: 02 Jul 2009.
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Date: 18 July 2016, At: 08:36
The Journal of Asthma Research. Vol. 14, No. 3, April, 1977
Effect of Triiodothyronine on Bronchial Asthma. 11.
Downloaded by [RMIT University Library] at 08:36 18 July 2016
AHMEDA. ISMAIL, ERNEST SHALABY, AND IBRAHIM GADALLA* In a previous communicationYwe reported that triiodothyronine (T:J administration ameliorates the condition in cases of chronic bronchial asthma (CBA) particularly as regards acute exacerbations. It was also noticed to improve allergy of the nose.22 In this communication we would like to report on the effect of T, on CBA when administered for a longer period than that in our previous communication. Work Done Twelve patients, clinically euthyroid and complaining of CBA for a period of at least 5 years, were selected from those regularly attending the outpatient department of Cairo University Hospital. All were males below the age of 35, free of chronic suppurative disease and not subject to frequent acute chest infections. None of them was on steroid therapy or chromoglycate. The patients were requested to continue on their usual medical line of treatment and to try reduction of the doses of the drugs they needed if possible. The patients had a physical examination before the drug administration and at the end of two months. Each patient had an E.C.G. and an expiratory peak flow (P.F.) measurement with each medical examination. Estimation of the P.F. was carried out by a standard flow meter (Air Med). The P.F. for the patient was considered as the best of three satisfactory efforts. All medications, except for T:], were withheld for 12 hours before P.F. testing. T, was given daily for 60 days as 20 p tablets morning and evening before meals. The drug was dispensed by us and the patients did not know the nature of the drug given. The results are seen in Tables 1-111 and Figs. 1 & 2.
Analysis of Result As seen from the results, none of the patients had a significant change in the pulse rate, morning body temperature, respiratory rate, blood pressure or body weight. In two patients, the resting respiratory rate fell from 28 and 30/minute to 20 and 22/minute respectively. Both cases reported a feeling of marked improvement. One of them was able to dispense with adrenaline injections altogether. One patient complained of mild insomnia and another of feeling tense and anxious. Three patients reported marked improvement of their asthmatic condition,
* Department of Medicine, Faculty of Medicine, 111
Cairo University, Cairo, Egypt.
112
A. ISMAIL, E. SHALABY, AND I. GADALLA
TABLE I Environmental Conditions, Occupational Hazards and Incidence of Smoking in the Patients Studied Home Conditions Ser. No.
Age
Age at Onset
occup. Hazard
Duration in Years Dust
Downloaded by [RMIT University Library] at 08:36 18 July 2016
1 2
3 4 5 6 7 8 9 10 11 12
35 27 28 28
34 33 31
25 22
10 5
13
15 11 12 15 4 12 11 10 12 10
17 22
18 27
26
14
31 37
20 27
27
15
30
20
+ +
+ + + + + -
+ + -
Sun -
+ + + + + + ~
+ +
Crowd
+ + + + + + + -
+ + + -
+
Cigaret. Smoking Duration Y
Number Id
10
-
15 4 12
-
-
+
-
15 -
7 7
5 15
-
-
-
+
-
-
10
20
20
-
-
-
-
10
10
Other habits
xx -
-
-
xx -
Crowdedness: + = More than 2 persons per room. xx = Patients number 1 & 10 admitted irregular consumption of (moasel), sometimes with cannabis.
two patients felt better and two felt “slightly better.” The remaining five reported no improvement, though one of these did not need adrenaline injections all through the period of drug administration whereas he used to need two injections twice a day to relieve his distress. The P.F. for the group averaged 246.7 Llm 2 48.43 S.D. as compared to an expected peak flow for normals of 491.3 +- 11.654 L/m, as suggested by manufacturer. The difference between the P.F. as expected in normals and that of the group of patients chosen is statistically valid to P < 0.001. At the end of two months of drug administration the peak flow averaged 308.3 L & 71.712 by an average increase of 22.4% which is statistically valid (P < 0.001). The difference between the P.F. before and after the drug is valid to P < 0.05. There was no direct relation between the degree of improvement as felt by the patient and the amount of increase in the P.F. (Fig. 2). Some cases that had improvement of 27-31% in their P.F. reported that they did not feel any more comfortable than before, while a patient who had an increase in the P.F. of 15% reported that he felt markedly better. There was also no correlation between the amount of increase in P.F., the subjective feeling of improvement, or the degree of incapacity of the patient before the test.
Discussion There is a general agreement that the P.F. is a reliable method to test the degree of asthma, especially as regards It is also easier to perform in the outpatient than the timed vital capacity. In a previous communication, we presented evidence that T, administration for a period of up to one month induced an increase in the P.F.9 In this
37.0 37.0 36.4
74 76 90
88 82 72 82 80 70
86
79.4
70 84 82
78 100 68 76 96 76
94
82
3 4 5
6 7 8 9 10 I1
12
36.89
37.0
36.6 37.1 36.9 37.0 36.9 36.8
36.8 37.1
81 72
74 86
1
2
Before
~
~
36.92
37.1
37.0 36.8 36.9 36.8 36.8 36.8
'37.2 37.2 36.6
37 36.9
After
Temp.
After
Pulse
gFi
Ser. No.
23.5
21.5
23
17 20 24 22 22 20
21 22 19 26 20 24
18
18 20 22
25 26
24 28 30
28 22
EFL After 140175 130/65
After
131/73
120/60
130/65 135/75 120/70 145/70 145/85 130/80
133/73
125/65
115/65 135/75 130/70 130/75 145180 135/75
125/70 135/75 135/80 . 130/80 125/80 140/80
140180 120/65
Before
-
ft -
+
-
+
-
Appetite
71.3
76.5
69.4 68.5 58.3 77 73 66.5
68.2 71 82
76.1 68.5
Before
Psychological Changes Reported by the Patient
71.3
76.0
-
? Tense and anxious
67.5
74
-
69.8 68.5 58.4 77.5
68.0 ? Sleep decreased 70 81.3
76.4 68.4
After
gm)
Slight
Moderate No improvement Marked No improvement Moderate No improvement
Slight Marked Marked
No improvement No improvement
provement Reported by the Patient
TABLE II Subiective and Objective Clinical Observations in the Patients Studied Weight (K Resp. Rate B1. Pressure Subjective Im-
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Now using l/z the previous doses
Significant reduction
-
Stopped adrenaline injection
-
Stopped adrenaline injection
-
Effect on Antiasthmatic Drugs Used
1:
0
0
114
A . ISMAIL, E . SHALABY, AND I . GADALLA
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TABLE 111 Changes in the P.F., Subjective Feeling and Usual Treatment after Two Months on T , Ser. Nr.
Age
Height c.m.
1 2 3 4 5 6 7 8 9 10 11 12
35 27 28 28 34 33 31 26 31 37 27 30
171 162 165 170 177 160 164 162 169 160 172 168
Range Average
S.D.
''*'Start at the
P.F. 2 Months Later
483 498 497 500 490 482 485 500 492 471 503 495
225 295 3 10 200 225 190 270 215 180 305 335 210
280 375 405 230 36P 210 345 275 200 340 415 265
+19.6% +27.1% +30.6% +15.0% +33.3% +10.6% +31.5% +27.9% +11.1% +11.5% +23.9% +26.2%
(471-503)
(180-335)
(200-415)
(+10.6-33.3)
491.3
246.7
308.3
+24.6%
2 11.654
248.43
k71.712
k8.48
% Change
of P.F.
communication, T:, was administered for two months. We avoided the type of cases that had shown a poor response or complications in our first communication. The average age in this communication was younger, and none of the cases had an active pyogenic infection or repeated attacks of bronchitis. As seen from our results, there was no correlation between the report of the patient and the improvement in P.F. whichever way it is considered, i.e. whether considered in absolute figures or percentage, etc. However, most cases that had a marked reduction in the rate of respiration reported an obvious improvement in their condition and vice versa. As mentioned before, the patients were allowed to continue their previous line of treatment. A number of cases reported a reduction of the amount of bronchodilators they needed. It is the practice in our hospital to resort to subcutaneous adrenaline injection if the patient is not relieved by his usual drugs. Dispensing with adrenaline thus denotes that the patient is having less acute exacerbations. Again, this did not correlate with the subjective feeling of being better. In all, about half of the patients felt better and two patients requested to continue treatment at the end of the experiment. All patients showed an improvement in their P.F. It averaged 24.6% k 8.48 and ranged between 10.6%and 33.3%. This response is better than the one we obtained in our previous communication. This might be due to the more strict selection of the cases and the longer period of treatment. The fact that all cases happened to be males is unlikely to be the cause of this observation, since no sex difference was observed in our previous communication. The mode of action of T, in asthma is still not clear. It is possible, as we mentioned in our first communication, that it acts through affecting the immune body forming mechanism.2*4, 5 , l5
EFFECT OF l'RIIODOTHYRONINE ON BRONCHIAL ASTHMA
115
/
//
400.
350. a, c 3
c_
E
\
c
Downloaded by [RMIT University Library] at 08:36 18 July 2016
J
LL
300
Y
m
a,
a
250
200 -
Time in Days
60
FIG.1 -Peak flow at the start and at the end of administration of 40 F/day triiodothyronine orally for 60 days.
It is also possible that thyroid hormones potentiate the action of sympathicomimics. In fact an interrelation between the thyroid hormones and catecholamines has been established for a long lo, We have, however, failed to find such an effect in the case of asthma. C-AMP plays an important role in the beta receptors. It is possibly the mediator for bronchodilatation.20Its deficiency could thus aggravate asthma and reduce the effect of drugs and vice versa. C-AMP excretion was found to be deficient in asthmatics,19* 20 and lymphocytes from asthmatics in exacerbations contain less C-AMP than n0rma1s.l~ Its amount increases in remission. It was also found that the lymphocytes of asthmatics are less able to excrete C-AMP than normal ones6 and that asthmatics who did not receive steroids fail to respond to isoproterenol in a normal way.18 It is possible thus that the reduced beta receptor function in
116
A . ISMAIL, E . SHALABY, AND I . GADALLA
+
30%
-
.
a 0
0
Downloaded by [RMIT University Library] at 08:36 18 July 2016
+
20%-
. 0
. 0
FIG.2-Graph showing the relation between the degree of change in peak flow and the subjective improvement at the end of administration of triiodothyronine orally for 60 days.
asthma reflects a failure of counter-regulatory mechanism due to reduction in C-AMP.I4One might note here that disodium chromoglycate, h useful drug in asthma, possibly acts by inhibiting the mast cell phosphodiesterase which activates C-AMP and in this way protects the mast cells from C-AMP exhaustion.*?One might also note that C-AMP plays a n important role in immune globulin formationI8in addition to its role in response to brochodilators.20 There is accumulating evidence that thyroxine improves C-AMP concentration in hypothyroids. Hardman et al. (1966)*demonstrated that depressed urinary C-AMP concentration found in thyroparathyroidectomized rats can be restored with thyroxine administration. Levy et al. (1969)". l 2 demonstrated that thyroxine might primarily alter C-AMP generation. Lin et al. (1973) and Guttler et al. (1975)7proved that hypothyroids have both a low CAMP level and response to epinephrine infusion and that an opposite state is present in hyperthyroidism. They have come out with the conclusion that thyroid hormones induce a significant alteration in C-AMP generation system. According to these observations and others confirming the same results, one can postulate that it is possible that T, beneficial effects in asthmatics might be through improvement of C-AMP synthesis, a condition that seems to be deficient in asthmatics. As pointed out before, an improvement in C-
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EFFECT OF TRIIODOTHYRONINE O N BRONCHIAL ASTHMA
117
AMP level would reflect an improved response to sympathomimetic drug, immune body formation, and very possibly to internal sympathicomimics. The fact that the beneficial effect of T, does not show fully before the lapse of some timey can be explained according to the above mentioned hypothesis, by which replenishment of the C-AMP would naturally need some time to occur. It is unfortunate that we did not estimate the free T, and C-AMP level in our cases before and after the Ti3administration. Such a step might have helped in this discussion. though beneficial, has to be given One would like to point out here that T:%, with due caution. It would be advisable to avoid patients past 35, those who are the subject of repeated acute chest infections, and those who are particularly excitable. The patient should be warned of the possible development of a state of hyperreactability to sympathicomimic drugs. Accordingly, one can conclude that T, administration to clinically euthyroid chronic asthmatic patients induces a beneficial effect. The effect takes some time to appear and is not necessarily combined with an equal degree of subjective improvement. Based on these results, we believe it would be advisable to give T, particularly to young patients who cannot be maintained in active life without the administration of steroids. We believe T, in the doses used in this communication is safer than steroids and devoid of side effects.
Summary Triiodothyronine (T,) administration to patients suffering from chronic bronchial asthma or patients suffering from nasopharyngeal allergy was reported to ameliorate the attacks. Twelve patients aged less than 35 years suffering from chronic bronchial asthma for more than 5 years, who were maintained on usual anti-asthmatic drugs with the exception of steroids and chromoglycate and who were not the subject of repeated attacks of bronchitis were chosen for the study. Each patient was given T, orally as 40 piday divided into two doses, for a period of 60 days. The drug increased the peak flow in all cases. The increase averaged 24.6% 8.48 (P < 0.001). Three cases reported marked improvement and four were able to reduce the dose of anti-asthmatic drugs. There was no significant change in the pulse rate, ECG, body weight, blood pressure, or appetite. One patient complained of insomnia and another of increased anxiety. It is possible that T, exerts its beneficial effect through correcting the level of C-AMP, which is known to be low in asthmatics, through improvement of body mechanism for antibody formation, or through other unidentified mechanisms.
*
References 1. ARVIDSSON, E. AND DANO,G. Evaluation of the peak expiratory flow rate, Scand. J . Clin. Lab. Invest. 32:279-284. 1973. 2. BRODY, J. AND GREENE~~W+ J. Lymphocyte dysfunction in thyrotoxicosis, J . CIzn. Endocrino1 Met. 35:574. 1972.
Downloaded by [RMIT University Library] at 08:36 18 July 2016
118
A . ISMAIL, E . SHALABY, AND I . GADALLA
3. D’LORIO,A. AND MAVRIDES, C. Actions of the thyroid hormones and analogues in vitro on catechol-0-methyltransferase, Biochemical pharmacology 12: 1307-1313, 1963. 4. ~ ~ R N S T RU. OM AND , LARSSON, B. Thymic & thoracic duct contribution to blood lymphocytes in normal and thyroxine treated guinea pigs, Actu Physiol. Scand. 66:189, 1966. 5. FABRIS, N. Immunodepression in thyroid-deprived animals, Clin. Expt. Zmmunol. 15:601611, 1973. 6. GILLESPIE,E., VALENTINE, M. D. AND LICHTENSTEIN, L. M. Cyclic AMP metabolism in asthma: Studies with leukocytes and lymphocytes, J . Allergy Clin. Immunology 5311.2733, 1974. 7. GUTTLER,R. B., SHOW,J. N- , OTIS, C. L. AND NICOLOFF,J . T. Epinephrine-induced alterations in urinary cyclic AMP in hyper- and hypothyroidism, J . Clin. Endocrinol Met. 41:707-711, 1975. 8. HARDMAN, J. Measurement of guanosine 3 ’ 4 ’ monophosphate and other cyclic nucleotides, J . Biol. Chemist. 241:4832-4815, 1966. E. AND GADALLA, I. Effect of triiodothyronine on bronchial 9. ISMAIL,A. A,, SHALABY, asthma, J . Egypt. Med. Ass. 57:415-423, 1974. 10. LEE, W. C., LEE, C. Y. AND Yoo, C. S. Effects of treatment with thyroxine on the noradrenaline content of the rabbit heart, Brit. J . Phurmacol. 25:651-657, 1965. 11. LEVEY, F. S., SKELTON, C. L. AND EPSTEIN,S. E. Influence ofhyperthyroidism on the effects of norepinephrine on myocardial adenyl cyclase activity and contractile state, Endocrinology 85:1004-1009, 1969. 12. LIN,T., KOPP,L. E. AND TUCCI,R. Urinary excretion of cyclic -3’, 5’ adenosine monophosphate in hyperthyroidism, J . Clin. Endocrinol. Met. 36: 1033-1036, 1973. 13. PARKER, C. W. AND SMITH,J. W. Alterations i n cyclic adenosine monophosphate metabolism in human bronchial asthma, J . Clin. Znues. 52:48-59, 1973. 14. PATEL,K . R., ALSTON, W. C. AND KERR,J. W. The relationship of leucocyte adenyl cyclase activity and airways response to beta blockade and allergen challenge in extrinsic asthma, Clin. Allergy 4/3:311-322, 1974. 15. PIERPAOLI, W. et al. Hormones and thelmmune Response. Edited by Wolstenholm, E. W. & Knight, J. Churchill, London, 1970. 16. RITCHIE,B. A comparison of forced expiratory volume and peak flow in clinical practice, Lancet 2:271-273, 1962. 17. SCHERRER, M. Disodium cromoglicate in management of bronchial asthma, Therumsch 31 I 11:823-828, 1974. 18. SHERMAN, N. A., SMITH,R. S. AND MIDDLETON, E. JR.Comparison of immunoglobulin formation in vitro by leukocytes of normal donors and steroid and nonsteroid treated asthmatics, J . Allergy Clin. lmmunol. 54/2:77-85, 1974. 19. SMITH,J . W., AND PARKER,C. W. The responsiveness of leukocytes cyclic adenosine monophosphate to adrenergic agents in patients with asthma, J . Lab. Clin. Med. 76:993, 1970. 20. TAYEAU, F. AMP cyclique e t Asthme, Le Poumon et le coeur31:271-275,1975, and Bordeaux Med. 7:2853-2859, 1974. 21. WALDSTEIN, S. S. Thyroid catecholamine interrelations, Ann. Rev. Med. 17:123-132, 1966. 22. WILHERS,B. T. Hypometabolism in allergy, Laryngoscope 84:43-52, 1974.
ISSN: 0021-9134 (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/ijas19
Effect of triiodothyronine on bronchial asthma. II Ahmed A. Ismail, Ernest Shalaby & Ibrahim Gadalla To cite this article: Ahmed A. Ismail, Ernest Shalaby & Ibrahim Gadalla (1977) Effect of triiodothyronine on bronchial asthma. II, Journal of Asthma Research, 14:3, 111-118, DOI: 10.3109/02770907709104182 To link to this article: http://dx.doi.org/10.3109/02770907709104182
Published online: 02 Jul 2009.
Submit your article to this journal
Article views: 4
View related articles
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ijas19 Download by: [RMIT University Library]
Date: 18 July 2016, At: 08:36
The Journal of Asthma Research. Vol. 14, No. 3, April, 1977
Effect of Triiodothyronine on Bronchial Asthma. 11.
Downloaded by [RMIT University Library] at 08:36 18 July 2016
AHMEDA. ISMAIL, ERNEST SHALABY, AND IBRAHIM GADALLA* In a previous communicationYwe reported that triiodothyronine (T:J administration ameliorates the condition in cases of chronic bronchial asthma (CBA) particularly as regards acute exacerbations. It was also noticed to improve allergy of the nose.22 In this communication we would like to report on the effect of T, on CBA when administered for a longer period than that in our previous communication. Work Done Twelve patients, clinically euthyroid and complaining of CBA for a period of at least 5 years, were selected from those regularly attending the outpatient department of Cairo University Hospital. All were males below the age of 35, free of chronic suppurative disease and not subject to frequent acute chest infections. None of them was on steroid therapy or chromoglycate. The patients were requested to continue on their usual medical line of treatment and to try reduction of the doses of the drugs they needed if possible. The patients had a physical examination before the drug administration and at the end of two months. Each patient had an E.C.G. and an expiratory peak flow (P.F.) measurement with each medical examination. Estimation of the P.F. was carried out by a standard flow meter (Air Med). The P.F. for the patient was considered as the best of three satisfactory efforts. All medications, except for T:], were withheld for 12 hours before P.F. testing. T, was given daily for 60 days as 20 p tablets morning and evening before meals. The drug was dispensed by us and the patients did not know the nature of the drug given. The results are seen in Tables 1-111 and Figs. 1 & 2.
Analysis of Result As seen from the results, none of the patients had a significant change in the pulse rate, morning body temperature, respiratory rate, blood pressure or body weight. In two patients, the resting respiratory rate fell from 28 and 30/minute to 20 and 22/minute respectively. Both cases reported a feeling of marked improvement. One of them was able to dispense with adrenaline injections altogether. One patient complained of mild insomnia and another of feeling tense and anxious. Three patients reported marked improvement of their asthmatic condition,
* Department of Medicine, Faculty of Medicine, 111
Cairo University, Cairo, Egypt.
112
A. ISMAIL, E. SHALABY, AND I. GADALLA
TABLE I Environmental Conditions, Occupational Hazards and Incidence of Smoking in the Patients Studied Home Conditions Ser. No.
Age
Age at Onset
occup. Hazard
Duration in Years Dust
Downloaded by [RMIT University Library] at 08:36 18 July 2016
1 2
3 4 5 6 7 8 9 10 11 12
35 27 28 28
34 33 31
25 22
10 5
13
15 11 12 15 4 12 11 10 12 10
17 22
18 27
26
14
31 37
20 27
27
15
30
20
+ +
+ + + + + -
+ + -
Sun -
+ + + + + + ~
+ +
Crowd
+ + + + + + + -
+ + + -
+
Cigaret. Smoking Duration Y
Number Id
10
-
15 4 12
-
-
+
-
15 -
7 7
5 15
-
-
-
+
-
-
10
20
20
-
-
-
-
10
10
Other habits
xx -
-
-
xx -
Crowdedness: + = More than 2 persons per room. xx = Patients number 1 & 10 admitted irregular consumption of (moasel), sometimes with cannabis.
two patients felt better and two felt “slightly better.” The remaining five reported no improvement, though one of these did not need adrenaline injections all through the period of drug administration whereas he used to need two injections twice a day to relieve his distress. The P.F. for the group averaged 246.7 Llm 2 48.43 S.D. as compared to an expected peak flow for normals of 491.3 +- 11.654 L/m, as suggested by manufacturer. The difference between the P.F. as expected in normals and that of the group of patients chosen is statistically valid to P < 0.001. At the end of two months of drug administration the peak flow averaged 308.3 L & 71.712 by an average increase of 22.4% which is statistically valid (P < 0.001). The difference between the P.F. before and after the drug is valid to P < 0.05. There was no direct relation between the degree of improvement as felt by the patient and the amount of increase in the P.F. (Fig. 2). Some cases that had improvement of 27-31% in their P.F. reported that they did not feel any more comfortable than before, while a patient who had an increase in the P.F. of 15% reported that he felt markedly better. There was also no correlation between the amount of increase in P.F., the subjective feeling of improvement, or the degree of incapacity of the patient before the test.
Discussion There is a general agreement that the P.F. is a reliable method to test the degree of asthma, especially as regards It is also easier to perform in the outpatient than the timed vital capacity. In a previous communication, we presented evidence that T, administration for a period of up to one month induced an increase in the P.F.9 In this
37.0 37.0 36.4
74 76 90
88 82 72 82 80 70
86
79.4
70 84 82
78 100 68 76 96 76
94
82
3 4 5
6 7 8 9 10 I1
12
36.89
37.0
36.6 37.1 36.9 37.0 36.9 36.8
36.8 37.1
81 72
74 86
1
2
Before
~
~
36.92
37.1
37.0 36.8 36.9 36.8 36.8 36.8
'37.2 37.2 36.6
37 36.9
After
Temp.
After
Pulse
gFi
Ser. No.
23.5
21.5
23
17 20 24 22 22 20
21 22 19 26 20 24
18
18 20 22
25 26
24 28 30
28 22
EFL After 140175 130/65
After
131/73
120/60
130/65 135/75 120/70 145/70 145/85 130/80
133/73
125/65
115/65 135/75 130/70 130/75 145180 135/75
125/70 135/75 135/80 . 130/80 125/80 140/80
140180 120/65
Before
-
ft -
+
-
+
-
Appetite
71.3
76.5
69.4 68.5 58.3 77 73 66.5
68.2 71 82
76.1 68.5
Before
Psychological Changes Reported by the Patient
71.3
76.0
-
? Tense and anxious
67.5
74
-
69.8 68.5 58.4 77.5
68.0 ? Sleep decreased 70 81.3
76.4 68.4
After
gm)
Slight
Moderate No improvement Marked No improvement Moderate No improvement
Slight Marked Marked
No improvement No improvement
provement Reported by the Patient
TABLE II Subiective and Objective Clinical Observations in the Patients Studied Weight (K Resp. Rate B1. Pressure Subjective Im-
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Now using l/z the previous doses
Significant reduction
-
Stopped adrenaline injection
-
Stopped adrenaline injection
-
Effect on Antiasthmatic Drugs Used
1:
0
0
114
A . ISMAIL, E . SHALABY, AND I . GADALLA
Downloaded by [RMIT University Library] at 08:36 18 July 2016
TABLE 111 Changes in the P.F., Subjective Feeling and Usual Treatment after Two Months on T , Ser. Nr.
Age
Height c.m.
1 2 3 4 5 6 7 8 9 10 11 12
35 27 28 28 34 33 31 26 31 37 27 30
171 162 165 170 177 160 164 162 169 160 172 168
Range Average
S.D.
''*'Start at the
P.F. 2 Months Later
483 498 497 500 490 482 485 500 492 471 503 495
225 295 3 10 200 225 190 270 215 180 305 335 210
280 375 405 230 36P 210 345 275 200 340 415 265
+19.6% +27.1% +30.6% +15.0% +33.3% +10.6% +31.5% +27.9% +11.1% +11.5% +23.9% +26.2%
(471-503)
(180-335)
(200-415)
(+10.6-33.3)
491.3
246.7
308.3
+24.6%
2 11.654
248.43
k71.712
k8.48
% Change
of P.F.
communication, T:, was administered for two months. We avoided the type of cases that had shown a poor response or complications in our first communication. The average age in this communication was younger, and none of the cases had an active pyogenic infection or repeated attacks of bronchitis. As seen from our results, there was no correlation between the report of the patient and the improvement in P.F. whichever way it is considered, i.e. whether considered in absolute figures or percentage, etc. However, most cases that had a marked reduction in the rate of respiration reported an obvious improvement in their condition and vice versa. As mentioned before, the patients were allowed to continue their previous line of treatment. A number of cases reported a reduction of the amount of bronchodilators they needed. It is the practice in our hospital to resort to subcutaneous adrenaline injection if the patient is not relieved by his usual drugs. Dispensing with adrenaline thus denotes that the patient is having less acute exacerbations. Again, this did not correlate with the subjective feeling of being better. In all, about half of the patients felt better and two patients requested to continue treatment at the end of the experiment. All patients showed an improvement in their P.F. It averaged 24.6% k 8.48 and ranged between 10.6%and 33.3%. This response is better than the one we obtained in our previous communication. This might be due to the more strict selection of the cases and the longer period of treatment. The fact that all cases happened to be males is unlikely to be the cause of this observation, since no sex difference was observed in our previous communication. The mode of action of T, in asthma is still not clear. It is possible, as we mentioned in our first communication, that it acts through affecting the immune body forming mechanism.2*4, 5 , l5
EFFECT OF l'RIIODOTHYRONINE ON BRONCHIAL ASTHMA
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/
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Y
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FIG.1 -Peak flow at the start and at the end of administration of 40 F/day triiodothyronine orally for 60 days.
It is also possible that thyroid hormones potentiate the action of sympathicomimics. In fact an interrelation between the thyroid hormones and catecholamines has been established for a long lo, We have, however, failed to find such an effect in the case of asthma. C-AMP plays an important role in the beta receptors. It is possibly the mediator for bronchodilatation.20Its deficiency could thus aggravate asthma and reduce the effect of drugs and vice versa. C-AMP excretion was found to be deficient in asthmatics,19* 20 and lymphocytes from asthmatics in exacerbations contain less C-AMP than n0rma1s.l~ Its amount increases in remission. It was also found that the lymphocytes of asthmatics are less able to excrete C-AMP than normal ones6 and that asthmatics who did not receive steroids fail to respond to isoproterenol in a normal way.18 It is possible thus that the reduced beta receptor function in
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+
30%
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.
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. 0
. 0
FIG.2-Graph showing the relation between the degree of change in peak flow and the subjective improvement at the end of administration of triiodothyronine orally for 60 days.
asthma reflects a failure of counter-regulatory mechanism due to reduction in C-AMP.I4One might note here that disodium chromoglycate, h useful drug in asthma, possibly acts by inhibiting the mast cell phosphodiesterase which activates C-AMP and in this way protects the mast cells from C-AMP exhaustion.*?One might also note that C-AMP plays a n important role in immune globulin formationI8in addition to its role in response to brochodilators.20 There is accumulating evidence that thyroxine improves C-AMP concentration in hypothyroids. Hardman et al. (1966)*demonstrated that depressed urinary C-AMP concentration found in thyroparathyroidectomized rats can be restored with thyroxine administration. Levy et al. (1969)". l 2 demonstrated that thyroxine might primarily alter C-AMP generation. Lin et al. (1973) and Guttler et al. (1975)7proved that hypothyroids have both a low CAMP level and response to epinephrine infusion and that an opposite state is present in hyperthyroidism. They have come out with the conclusion that thyroid hormones induce a significant alteration in C-AMP generation system. According to these observations and others confirming the same results, one can postulate that it is possible that T, beneficial effects in asthmatics might be through improvement of C-AMP synthesis, a condition that seems to be deficient in asthmatics. As pointed out before, an improvement in C-
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AMP level would reflect an improved response to sympathomimetic drug, immune body formation, and very possibly to internal sympathicomimics. The fact that the beneficial effect of T, does not show fully before the lapse of some timey can be explained according to the above mentioned hypothesis, by which replenishment of the C-AMP would naturally need some time to occur. It is unfortunate that we did not estimate the free T, and C-AMP level in our cases before and after the Ti3administration. Such a step might have helped in this discussion. though beneficial, has to be given One would like to point out here that T:%, with due caution. It would be advisable to avoid patients past 35, those who are the subject of repeated acute chest infections, and those who are particularly excitable. The patient should be warned of the possible development of a state of hyperreactability to sympathicomimic drugs. Accordingly, one can conclude that T, administration to clinically euthyroid chronic asthmatic patients induces a beneficial effect. The effect takes some time to appear and is not necessarily combined with an equal degree of subjective improvement. Based on these results, we believe it would be advisable to give T, particularly to young patients who cannot be maintained in active life without the administration of steroids. We believe T, in the doses used in this communication is safer than steroids and devoid of side effects.
Summary Triiodothyronine (T,) administration to patients suffering from chronic bronchial asthma or patients suffering from nasopharyngeal allergy was reported to ameliorate the attacks. Twelve patients aged less than 35 years suffering from chronic bronchial asthma for more than 5 years, who were maintained on usual anti-asthmatic drugs with the exception of steroids and chromoglycate and who were not the subject of repeated attacks of bronchitis were chosen for the study. Each patient was given T, orally as 40 piday divided into two doses, for a period of 60 days. The drug increased the peak flow in all cases. The increase averaged 24.6% 8.48 (P < 0.001). Three cases reported marked improvement and four were able to reduce the dose of anti-asthmatic drugs. There was no significant change in the pulse rate, ECG, body weight, blood pressure, or appetite. One patient complained of insomnia and another of increased anxiety. It is possible that T, exerts its beneficial effect through correcting the level of C-AMP, which is known to be low in asthmatics, through improvement of body mechanism for antibody formation, or through other unidentified mechanisms.
*
References 1. ARVIDSSON, E. AND DANO,G. Evaluation of the peak expiratory flow rate, Scand. J . Clin. Lab. Invest. 32:279-284. 1973. 2. BRODY, J. AND GREENE~~W+ J. Lymphocyte dysfunction in thyrotoxicosis, J . CIzn. Endocrino1 Met. 35:574. 1972.
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3. D’LORIO,A. AND MAVRIDES, C. Actions of the thyroid hormones and analogues in vitro on catechol-0-methyltransferase, Biochemical pharmacology 12: 1307-1313, 1963. 4. ~ ~ R N S T RU. OM AND , LARSSON, B. Thymic & thoracic duct contribution to blood lymphocytes in normal and thyroxine treated guinea pigs, Actu Physiol. Scand. 66:189, 1966. 5. FABRIS, N. Immunodepression in thyroid-deprived animals, Clin. Expt. Zmmunol. 15:601611, 1973. 6. GILLESPIE,E., VALENTINE, M. D. AND LICHTENSTEIN, L. M. Cyclic AMP metabolism in asthma: Studies with leukocytes and lymphocytes, J . Allergy Clin. Immunology 5311.2733, 1974. 7. GUTTLER,R. B., SHOW,J. N- , OTIS, C. L. AND NICOLOFF,J . T. Epinephrine-induced alterations in urinary cyclic AMP in hyper- and hypothyroidism, J . Clin. Endocrinol Met. 41:707-711, 1975. 8. HARDMAN, J. Measurement of guanosine 3 ’ 4 ’ monophosphate and other cyclic nucleotides, J . Biol. Chemist. 241:4832-4815, 1966. E. AND GADALLA, I. Effect of triiodothyronine on bronchial 9. ISMAIL,A. A,, SHALABY, asthma, J . Egypt. Med. Ass. 57:415-423, 1974. 10. LEE, W. C., LEE, C. Y. AND Yoo, C. S. Effects of treatment with thyroxine on the noradrenaline content of the rabbit heart, Brit. J . Phurmacol. 25:651-657, 1965. 11. LEVEY, F. S., SKELTON, C. L. AND EPSTEIN,S. E. Influence ofhyperthyroidism on the effects of norepinephrine on myocardial adenyl cyclase activity and contractile state, Endocrinology 85:1004-1009, 1969. 12. LIN,T., KOPP,L. E. AND TUCCI,R. Urinary excretion of cyclic -3’, 5’ adenosine monophosphate in hyperthyroidism, J . Clin. Endocrinol. Met. 36: 1033-1036, 1973. 13. PARKER, C. W. AND SMITH,J. W. Alterations i n cyclic adenosine monophosphate metabolism in human bronchial asthma, J . Clin. Znues. 52:48-59, 1973. 14. PATEL,K . R., ALSTON, W. C. AND KERR,J. W. The relationship of leucocyte adenyl cyclase activity and airways response to beta blockade and allergen challenge in extrinsic asthma, Clin. Allergy 4/3:311-322, 1974. 15. PIERPAOLI, W. et al. Hormones and thelmmune Response. Edited by Wolstenholm, E. W. & Knight, J. Churchill, London, 1970. 16. RITCHIE,B. A comparison of forced expiratory volume and peak flow in clinical practice, Lancet 2:271-273, 1962. 17. SCHERRER, M. Disodium cromoglicate in management of bronchial asthma, Therumsch 31 I 11:823-828, 1974. 18. SHERMAN, N. A., SMITH,R. S. AND MIDDLETON, E. JR.Comparison of immunoglobulin formation in vitro by leukocytes of normal donors and steroid and nonsteroid treated asthmatics, J . Allergy Clin. lmmunol. 54/2:77-85, 1974. 19. SMITH,J . W., AND PARKER,C. W. The responsiveness of leukocytes cyclic adenosine monophosphate to adrenergic agents in patients with asthma, J . Lab. Clin. Med. 76:993, 1970. 20. TAYEAU, F. AMP cyclique e t Asthme, Le Poumon et le coeur31:271-275,1975, and Bordeaux Med. 7:2853-2859, 1974. 21. WALDSTEIN, S. S. Thyroid catecholamine interrelations, Ann. Rev. Med. 17:123-132, 1966. 22. WILHERS,B. T. Hypometabolism in allergy, Laryngoscope 84:43-52, 1974.
