Clinical and Experimental Allergy, 1992, Volume 22, pages 867-868
Correspondence Can asthma be cured? Sirs, I was impressed by the article 'Can Asthma Be Cured?' published by Professor Margaret Turner-Warwick [1] in Clinical and Experimental Allergy, Volume 21 Supplement 1, January 1991. In particular, the hypothesis of the theory of a dynamic balance in asthma is most interesting, and may lead to new approaches to the treatment of bronchial asthma. On the basis of studies of childhood asthma, the Author emphasizes the spontaneous cure in 30-70% of patients when they are in their teens, and she suggests the possible intervention of some mechanisms which control asthma response: some of which promote airway narrowing and others prevent or normalize such narrowing. I would like to add that the spontaneous remission of asthma without any treatment has been observed in other circumstances, not only during pregnancy in one third of cases, but also in some specific pathological conditions (jaundice, fever, pneumonia [2,3]). The onset of any one of these diseases causes asthma to disappear. In other terms, a 'negative correlation' may exist between some diseases and bronchial asthma.
We studied this problem many years ago and described five cases of asthma patients in whom clinical manifestations promptly disappeared with the onset of hepatitis and were absent for the duration of the disease. It is interesting to note that a decrease in blood eosinophiis during the asthma-free period of jaundice was also recorded in one of these patients. Commenting on these cases, we wrote that 'the organism possesses the capacity of favourably modifying asthma, probably by means of mechanisms rendered efficient by the hepatitis itself. We also studied the therapeutic effect of provoked fever on asthma and observed both remission of symptomatology and a marked decrease of blood eosinophiis and lymphocytes, and an increase in blood neutrophils [3,4]. Moreover, the injection ofhistamine (1 mg) produced an asthma crisis and an increase of blood histamine, whereas after provoked fever no asthma crisis or increase in blood histamine was observed. The spontaneous remission of asthma in children (and less frequently in adults) and in some physiopathological conditions led us to consider with particular attention the existence of these biological control mechanisms [5].
Table 1. Regulation of bronchial calibre Bronchoconstricting factors
Inhibiting factors (controllers)
Neurotransmitters and neuropeptides
Alpha adrenergics Cholinergics Substance P (SP) Neurokinin A Calcitonin gene-related peptide (CGRP)
Beta adrenergics Vasoactive intestinal peptide (VIP) Peptide histidine methionine (PHM)
Mast cell and other cell derived mediators
Histamine PAF HRFs
Arachidonic acid derivatives
Leukotrienes
Lipocortin-like peptides
PGD2, PGFja
PGE2
PAF acetylhydrolase HRFs inhibitor
Thromboxane Cytokines
IL-4*, IL-5, GM-CSF
IFN-gamma and alphaf
Epithelium derivatives
Endothelins Epithelium-derived relaxing factor(s) deficit Neutral endopeptidase deficit
Epithelium-derived relaxing factor(s) Neutral endopeptidase
* As inducer IgE synthesis in allergic bronchial asthma. t As inhibitory of IgE synthesis in allergic bronchial asthma. 867
868
Correspondence
If we accept the existence in normal individuals of a balance between those factors promoting bronchial inflammation and constriction and the other inhibiting factors or controllers, it seems evident that an imbalance towards the former exists in asthmatics. During the above mentioned remission from asthma, it is likely that the inhibitory factors controlling bronchoconstriction prevail. In Table 1 we have attempted to put together some of the known elements which should be considered bronchoconstricting (favouring) or inhibiting (controllers) factors. Recently, several techniques became available for the measurement of bronchoconstricting and inhibiting factors. This should prompt us to study their balance in childhood asthma when remission occurs in the teens, and in subsets of asthmatics whose symptomatology disappears during certain physiopathological conditions. For instance, some recent data show that during acute and chronic infections numerous T-lymphocytes are produced capable of releasing IFN-gamma and IL-2. This considerable rise in IFN-gamma brings about a fall in those T-cells which produce IL-4 and IL-5. The identification of the factors, possibly faulty in
asthmatics [6], which produce inhibitory effects on the airways inflammatory process, may lead to a new approach to the treatment of this disease. U. SERAFINI
University 'La Sapienza', Rome, Italy References 1 Turner-Warwick M. Can asthma be cured? Clin Exp Allergy 1991;21(Suppl. l):105-10. 2 Serafini U, Di Nardo U. Sulla remissione dei sintomi asmatici nel corso di sindromi itteriche. Gaz Intern Med Chir 1950; 54:338-44. 3 Serafini U, De Sanctis C, Fabiani F. Alcune modificazioni ematiche ed emochimiche negli asmatici durante la febbre provocata. Clin Nuova 1964; 2:43-8. 4 Serafini U. Studies on histamine and histamine antagonists. J Allergy 1948; 19:256-70. 5 Serafini U. Attualita in tema di terapia delle sindromi allergiche respiratorie. In: Atti XX Congresso Soc It Allergol Immunol Clin. J.J.C. Medical Press, Florence, 1991:3. 6 Barnes PJ. Inflammatory mediators and airway function. In: Olivieri D, Bianco S (eds). Airway obstruction and inflammation. Prog Resp Res. Basel: Karger, 1990; 24:68-77.
Correspondence Can asthma be cured? Sirs, I was impressed by the article 'Can Asthma Be Cured?' published by Professor Margaret Turner-Warwick [1] in Clinical and Experimental Allergy, Volume 21 Supplement 1, January 1991. In particular, the hypothesis of the theory of a dynamic balance in asthma is most interesting, and may lead to new approaches to the treatment of bronchial asthma. On the basis of studies of childhood asthma, the Author emphasizes the spontaneous cure in 30-70% of patients when they are in their teens, and she suggests the possible intervention of some mechanisms which control asthma response: some of which promote airway narrowing and others prevent or normalize such narrowing. I would like to add that the spontaneous remission of asthma without any treatment has been observed in other circumstances, not only during pregnancy in one third of cases, but also in some specific pathological conditions (jaundice, fever, pneumonia [2,3]). The onset of any one of these diseases causes asthma to disappear. In other terms, a 'negative correlation' may exist between some diseases and bronchial asthma.
We studied this problem many years ago and described five cases of asthma patients in whom clinical manifestations promptly disappeared with the onset of hepatitis and were absent for the duration of the disease. It is interesting to note that a decrease in blood eosinophiis during the asthma-free period of jaundice was also recorded in one of these patients. Commenting on these cases, we wrote that 'the organism possesses the capacity of favourably modifying asthma, probably by means of mechanisms rendered efficient by the hepatitis itself. We also studied the therapeutic effect of provoked fever on asthma and observed both remission of symptomatology and a marked decrease of blood eosinophiis and lymphocytes, and an increase in blood neutrophils [3,4]. Moreover, the injection ofhistamine (1 mg) produced an asthma crisis and an increase of blood histamine, whereas after provoked fever no asthma crisis or increase in blood histamine was observed. The spontaneous remission of asthma in children (and less frequently in adults) and in some physiopathological conditions led us to consider with particular attention the existence of these biological control mechanisms [5].
Table 1. Regulation of bronchial calibre Bronchoconstricting factors
Inhibiting factors (controllers)
Neurotransmitters and neuropeptides
Alpha adrenergics Cholinergics Substance P (SP) Neurokinin A Calcitonin gene-related peptide (CGRP)
Beta adrenergics Vasoactive intestinal peptide (VIP) Peptide histidine methionine (PHM)
Mast cell and other cell derived mediators
Histamine PAF HRFs
Arachidonic acid derivatives
Leukotrienes
Lipocortin-like peptides
PGD2, PGFja
PGE2
PAF acetylhydrolase HRFs inhibitor
Thromboxane Cytokines
IL-4*, IL-5, GM-CSF
IFN-gamma and alphaf
Epithelium derivatives
Endothelins Epithelium-derived relaxing factor(s) deficit Neutral endopeptidase deficit
Epithelium-derived relaxing factor(s) Neutral endopeptidase
* As inducer IgE synthesis in allergic bronchial asthma. t As inhibitory of IgE synthesis in allergic bronchial asthma. 867
868
Correspondence
If we accept the existence in normal individuals of a balance between those factors promoting bronchial inflammation and constriction and the other inhibiting factors or controllers, it seems evident that an imbalance towards the former exists in asthmatics. During the above mentioned remission from asthma, it is likely that the inhibitory factors controlling bronchoconstriction prevail. In Table 1 we have attempted to put together some of the known elements which should be considered bronchoconstricting (favouring) or inhibiting (controllers) factors. Recently, several techniques became available for the measurement of bronchoconstricting and inhibiting factors. This should prompt us to study their balance in childhood asthma when remission occurs in the teens, and in subsets of asthmatics whose symptomatology disappears during certain physiopathological conditions. For instance, some recent data show that during acute and chronic infections numerous T-lymphocytes are produced capable of releasing IFN-gamma and IL-2. This considerable rise in IFN-gamma brings about a fall in those T-cells which produce IL-4 and IL-5. The identification of the factors, possibly faulty in
asthmatics [6], which produce inhibitory effects on the airways inflammatory process, may lead to a new approach to the treatment of this disease. U. SERAFINI
University 'La Sapienza', Rome, Italy References 1 Turner-Warwick M. Can asthma be cured? Clin Exp Allergy 1991;21(Suppl. l):105-10. 2 Serafini U, Di Nardo U. Sulla remissione dei sintomi asmatici nel corso di sindromi itteriche. Gaz Intern Med Chir 1950; 54:338-44. 3 Serafini U, De Sanctis C, Fabiani F. Alcune modificazioni ematiche ed emochimiche negli asmatici durante la febbre provocata. Clin Nuova 1964; 2:43-8. 4 Serafini U. Studies on histamine and histamine antagonists. J Allergy 1948; 19:256-70. 5 Serafini U. Attualita in tema di terapia delle sindromi allergiche respiratorie. In: Atti XX Congresso Soc It Allergol Immunol Clin. J.J.C. Medical Press, Florence, 1991:3. 6 Barnes PJ. Inflammatory mediators and airway function. In: Olivieri D, Bianco S (eds). Airway obstruction and inflammation. Prog Resp Res. Basel: Karger, 1990; 24:68-77.
