- Email: [email protected]
MITES AND HOUSE-DUST ALLERGY
1270
mites detected, if these were the only source of the allergen. Voorhorst et al. (1967) suggest that secretory and excretory products of the mites may play a part. This may well be so, but it must also be remembered that the finest debris of fragmented mites are undetectable by our present methods of extraction, and it should also not be overlooked that house dust contains other allergenic material, and we believe, that these materials, varying in composition from house to house and from room to room, add to the potency of house dust. K. M. is indebted to the Asthma Research Council for a part-time grant to carry out this investigation. We thank Dr. R. Bruce Pearson, Prof. A. C. Cunliffe, Mr. M. E. Solomon for their support, Dr. D. A. Williams for helpful discussions and for providing us with dust samples from South Wales, and Miss D. M. Noakes who visited houses in London and collected samples. Requests for reprints should be addressed to K. M., Department of Bacteriology, King’s College Hospital, London S.E.1. REFERENCES
Berrens, L. (1967) J. Allergy, 40, 355. Cunnington, A. M. (1967) Acta allerg. 22, 415. Gregory, P. H. (1968) Nature, Lond. 217, 1271. Hughes, A. M. (1961) The Mites of Stored Food. H.M. Stationery Office. Maunsell, K. (1967) Acta allerg. 22, 413. Solomon, M. E. (1961) Sanitarian. (1962) in Proceedings of the Colloquium on Research Methods in Soil Zoology (Rothamsted, 1958) edited by P. W. Murphy; vol. I, p. 503. Cunnington, A. M. (1964) Acarologia, 6, suppl. p. 339. Spieksma, F. T. M. (1967a) M.D. thesis, University of Leiden. (1967b) Int. Rhinol. 5, 168. Storm van Leeuwen, W. (1922) in Oorzaken en Behandeling van Asthma bronchiale (edited by Wolters). Groningen. (1928) Allergische Krankheiten. Berlin. Bien, Z., Varekamp, H. (1925). Z. Immun. Forsch. exp. Ther. 43, —
—
—
—
—
—
490.
Varekamp, H., Spieksma, F. T. M., Leupen, M. J., Lyklema, A. W. (1966) in Proceedings of the 5th Interasma Congress; p. 256. Voorhorst, R. (1967) J. Allergy, 40, 355. Spieksma, F. T. M., Varekamp, H., Leupen, M. J., Lyklema, A. W. (1967) ibid. 39, 325. Spieksma-Boezeman, M. J. E., Spieksma, F. T. M. (1964) Allergie Asthma, 10, 329. Wraith, D. G. (1967) Acta allerg. 22, 414. Maunsell, K. (1967) Int. Congr. Allergy, 6, 60 (Excerpta med. no. 144). —
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-
J. PEPYS PROFESSOR OF CLINICAL IMMUNOLOGY
MOIRA CHAN Hong Kong, M.R.C.P., M.R.C.P.E.
RESEARCH ASSISTANT IN CLINICAL IMMUNOLOGY
F. E. HARGREAVE M.B. Leeds, M.R.C.P. LECTURER IN CLINICAL IMMUNOLOGY
Extracts of
of
the
culture of the acarine mite Dermatophagoides culinœ, which grows on dog meal, gave positive prick-test reactions in readily asthmatic subjects, which correlated well with a history of house-dust allergy and with asthmatic reactions to inhalation tests. The skin-test reactions were comparable to those of an extract of D. pteronyssinus, the " housedust mite," which grows more slowly on human dander, and is thus not so readily available as a test material.
Summary
Materials and Methods Test Materials Purified house-dust extract (Bencard, Brentford, Middlesex) was used for prick tests at 12 mg. per ml. and for inhalation tests at 1-2 and 12 mg. per ml. Extracts were made of dense cultures of D. culince, and house mite Glycyphagus domesticus, and the flour mite Acarus siro. The cultures, consisting of 1/2 to 3/4 mites, were heated at 50°C for several hours to kill the mites and were then defatted in ether and extracted for a week in 0-5% phenol/saline-solution. This extract was dialysed, Seitz-filtered and freeze-dried, being used for prick tests mainly at 10 mg. per ml. and for inhalation tests with D. culinae at 0’1, 1, and 10 mg. per ml. Similar control extracts were made of their culture media, namely wheat-germ flakes for A. siro, dried yeast for G. domesticus, and Gaine’s dog-meal, which consists of wheat, maize, soybean, bone and fish meal, meat byproducts, animal fats, and added vitamins, for D. culin6e. The mite cultures were provided by Mr. M. E. Solomon and Mr. A. M. CunningExtracts of cultures of D. pteronyssinus on human dander g. per 100 ml. extracting fluid) and of a similar control extract of the culture medium, were provided by Dr. Kate Maunsell. Inhalation Tests An aerosol of the test solution was made in a Wright’s nebuliser by oxygen at 8 litres per minute. The forced expiratory volume in one second (F.E.V.I.o) was recorded before, and at ten, twenty, and thirty minutes after the test and then twohourly. Control tests for five minutes were made with 0’5% phenol/saline-solution to exclude non-specific reactors and with the extract of the culture medium of D. culinv in patients giving positive reactions. One test was made daily, starting with the weakest concentration. A positive reaction was taken as asthma developing within a few minutes, accompanied by a fall in F.E.v.i.o of more than 15%. Results D. pteronyssinus, D. culinx, and House-dust Extracts in Asthmatic Patients
plus yeast (3
M.B. W’srand, F.R.C.P., F.R.C.P.E.
From the Department of Medicine, Institute of Diseases Chest, Brompton, London S.W.3
specimens from many countries contain common or allergens. Voorhorst et al. (1964), Spieksma and Voorhorst et al. (1967) claim that probably (1967), the major source of house-dust allergen is a little-known acarine mite, genus Dermatophagoides, and particularly D. pteronyssinus which grows best on human dander. Human dander itself is regarded as an important source of allergen (Voorhorst 1962); and Berrens et al. (1965) regard it as a major source of house-dust allergen. D. pteronyssinus has been found world-wide in house dust (Fain 1966, Spieksma 1967), including the U.K. (Cunnington 1967) where Wraith and Maunsell (1967) regard it as important in respiratory allergy, as did Oshima (1964) in Japan and Bachofen et al. (1967) in Switzerland. Since D. pteronyssinus grows slowly and on human dander, tests have been made in asthmatic patients with extracts of D. culinae, which grows more rapidly on a dog-meal medium. D. culinae is identical with, or closely related to, D. farinae which Ishizaki et al. (1967) found to be comparably allergenic to extracts of house dust. related
ton.
MITES AND HOUSE-DUST ALLERGY
M.B.
dusts vary widely in composition and allergenicity, though
a
Introduction
HOUSE dust has been recognised for more than forty years as probably the most important cause of allergic rhinitis and asthma (Kem 1921, Cooke 1922). House
We first compared the reactions in 22 asthmatic individuals to prick tests with the limited amount of extract of the culture of D. pteronyssinus (300 wB.) and with the freeze-dried extract of D. culinae culture at I and 10 mg. per ml. The extract of house dust was also used for testing. Positive and comparable reactions were obtained in 14 patients to the extracts of D. pteronyssinus (average weal diameter [A.w.D.], 4-2 mm.) and of D. culinae 10 mg. per ml. (A.W.D. 4-4 mm.). The extract of D. culinae
1271 1 mg. per ml. gave weaker reactions in 13 of the 14 (A.w.D. 2-2 mm.), the negative subject being the weakest reactor to the other extracts. The purified house-dust extract (12 mg. per ml.) gave positive reactions in 9 out of the 14 reactors (A.W.D. 0-7 mm.). The extract of D. culinae (10 mg. per ml.) was therefore used as the source of Dermatophagoides allergen in subsequent tests. The control extracts of human dander and of yeasts gave no reactions, and the extract of dog-meal gave weak reactions in 2 subjects. House-dust and D. culinae Extracts in Asthmatic and Individuals
We
Healthy
compared house-dust extract (12 mg. per ml.) extract (10 mg. per ml.). In 40 healthy subjects, positive prick-test reactions were given by house dust in 1 (25%), and to the D. culinae extract in 4 (10%). No reactions were given by the next
and D. culinae
control tests. In 100 asthmatic subjects, positive prick-test reactions were given by house-dust extract in 54 (A.w.D. 2 mm.) and by D. culinae extract in 73 (A.W.D. 6.4 mm.), 51 of these patients reacting to both extracts. The Gaine’s dog-meal gave positive reactions in 15 (A.W.D. 0-3 mm.) and the yeast extract in 9 (A.W.D. 0-4 mm.). Table i shows a statistically highly significant correlation (P < 0-0001) between the history of house-dust TABLE I-HOUSE-DUST
ALLERGY AND
PRICK-TEST
REACTIONS
IN
100
ASTHMATIC PATIENTS
allergy and the prick-test reaction to D. culina, and a slightly less significant correlation (P < 0-001) to the reaction to the house-dust extract. In 10 asthmatic subjects, positive prick-test reactions to the D. culinae extract were given by 6, and of these 5 gave immediate asthmatic reactions to the inhalation test, in 2 to the 1 mg. per ml., and in 3, who gave no reaction to 1 mg. per ml., reactions were given to the 10 mg. per ml. concentrations. Inhalation tests with the housedust extract in 4 of these asthmatic reactors gave an asthmatic reaction in 1 patient. The falls in F.E.V.1.o ranged from 22 to 50%. There were no late reactions. No reactions were obtained to the inhalation test with the D. culina extract in the 4 subjects giving negative pricktest reactions to it, nor in 3 of these who were tested with the house-dust extract. There were no reactions to the inhalation of the control extracts of the Gaine’s dog-meal
prick-test
TABLE II-PRICK-TEST REACTIONS IN TO PURIFIED HOUSE-DUST EXTRACT DRIED EXTRACTS
CULTURE MEDIA
(10
mg. PER
ml.)
27
SELECTED ASTHMATIC
(12
mg.
PER
ml.)
SUBJECTS
AND TO FREEZE-
OF THE MITE CULTURES AND THEIR
and of the yeast powder in the the D. culinae extract.
patients who reacted
to
A. siro and G. domesticus in Selected Positive Reactors A comparison was next made in 27 selected subjects,
who had reacted to D. culinae or to house dust, of the reactions to extracts of cultures of A. siro and G. domesticus. Table 11 shows that the house dust gave the fewest and the weakest reactions. The mites gave comparable numbers of reactions,with D. culinae at the head giving the largest reactions. These differences between the D. culinae and other reactions were highly statistically significant, ranging from p < 0-05 to p < 0-005. Discussion
This investigation shows that there is a good correlation, in asthmatic subjects, between a history of housedust allergy and prick-test and inhalation-test reactions to an extract of a culture of D. culince, which, as used here, was allergenically comparable with an extract of D. pteronyssinus, the " house dust mite" of Spieksma (1967) and Voorhorst et al. (1967). The allergenicity of housedust extracts was found, by the Dutch workers, to correlate well with the content of D. pteronyssinus. The more readily available D. culinae extracts seem to provide a suitable alternative for the scarcer D. pteronyssinus extracts for clinical purposes. The reactions to extracts of cultures of G. domesticus and A. siro in most of the patients reacting to the D. culinae extract suggest, though they were weaker, that these too may contain related allergens. More precise studies are needed in which the actual numbers of mites in cultures intended for extraction are known. G. domesticus and A. siro, were, however, found far less frequently in 150 house-dust samples examined by Spieksma (1967). The genus Dermatophagoides was found in all the house dusts, and made up 70% of the mites, of which 88% were D. pteronyssinus, whereas the genus Glycyphagus was found in 61 % of the house dusts and made up 9% of the mites, and the genus Acarus was found in 19 % of the house dusts and made up 1 % of the mite content. The role of the allergens of human dander in house-dust allergy and their relationship to the extracts of D. pteronyssinus cultured on human dander which were used by Voorhorst and his colleagues has been raised by Berrens (1967), who suggested that there are two distinct allergens in house dust, one of which is derived from human dander, and the other from the house dust itself, presumably of plant origin. He and his colleagues suggest that the reactions of the atopic subjects to both allergens may be explained by their having determinants in common (Berrens et al. 1965). Henocq et al. (1966) also report that human dander and house dust have two different allergens in spite of the parallelism of their reactions in patients with atopic aczema, and they found that the house-dust extract is 200 times stronger than that of the human dander. Voorhorst and Spieksma (1967) claim that the amount of human dander allergen in their test extract of D. pteronyssinus is far too low to give reactions. We found no reactions to prick-tests with control extracts of the human-dander medium for the culture of D. pteronyssinus, whereas extracts of the mite culture gave strong reactions. Reactions comparable to those of D. pteronyssinus were obtained by us with extracts of D. culinae, which was cultured on a medium without human dander. These findings suggest that these mites, or their products, are the source of the allergen, though the problem remains of
1272
whether the medium may be altered chemically by the growth of the mite so as to become more allergenic, or whether both mite and medium are sources of allergen. Varekamp (1925) in one of the earliest descriptions of allergy to mites in oats, found that the extract of the mites themselves gave weaker reactions than the residual culture medium. Spieksma (1967) has produced evidence suggesting that faecal pellets of the mite D. pteryonssinus are comparable, as sources of allergen, to the mites themselves. The method of skin testing is also important for the assessment of results. Bachofen et al. (1967) obtained positive reactions to intracutaneous tests with extracts of D. pteronyssinus in a half, and of house dust in all, of their healthy controls, none of whom gave reactions to inhalation tests. By contrast, we obtained in healthy subjects positive prick-test reactions in 2-5% to an extract of house dust and in 10% to an extract of D. also obtained positive culince. Bachofen et al. intracutaneous test reactions to both extracts in all of their 20 asthmatic subjects, of whom 8 gave asthmatic reactions to inhalation tests with D. pteronyssinus and 2 only to the house-dust extract. We, however, obtained prick-test reactions to D. culinae extract in 6 out of 10 asthmatic subjects, and 5 of these gave asthmatic reactions to the inhalation test; and no reactions were produced in those giving negative reactions to the prick test. Whilst some of the difficulties of intracutaneous tests can be overcome by tests with serial dilutions of extract to arrive at a threshold concentration, the reactions to the prick test are not only more relevant to the history and inhalation tests, but are simpler and more acceptable in clinical work. The presence of other allergens in house dust besides those of Dermatophagoides is shown by the inhalation-test reactions only to house dust which Bachofen et al. (1967) found in 2 cases and by the pricktest reactions to house dust and not to Dermatophagoides in 3% of asthmatics in the present study. It seems therefore, that the genus Dermatophagoides, and notably the " house dust mite " D. pteronyssinus, is at least closely associated with the allergenicity of house dust and it is not improbable that it is in itself a major source of house-dust allergen. The preparation of mitespecific allergen and its study in house-dust allergy are now needed for the next steps in this promising advance. We thank Mr. M. E. Solomon and Mr. A. M. Cunnington of the Agricultural Research Council Pest Infestation Laboratory and Dr. Kate Maunsell for their generous provision of materials for these investigations, and the clinicians of the Brompton Hospital for referring their patients for investigation. Requests for reprints should be addressed to J. P.
(1967)
*
REFERENCES
Bachofen, H., Scherrer, M., Träutlein, F., Wyss, F. (1967) Dt. med. Wschr. 92, 1597. Berrens, L. (1967) J. Allergy, 40, 355. Morris, J. H., Versie, R. (1965) Int. Archs Allergy, 27, 129. Cooke, R. A. (1922) J. Immun. 7, 147. Cunnington, A. M. (1967) Acta allerg., Copenh. 22, 415. Fain, A. (1966) Bull. Acad. R. méd. Beige, 6, 479. Hénocq, E., Bazin, J. C., Girard, J. (1966) Revue fr. Allergie, 6, 213. Ishizaki, T., Miyamoto, T., Oshima, S. (1967) Vlth int. Cong. Allergol. Excerpta med. Int. Congr. Ser. no. 144, p. 62. Kern, A. (1921) Med. Clins N. Am. 5, 751. Oshima, S. (1964) Jap. J. sanit. Zool. 15, 233. Spieksma, F. T. M. (1967) The House-dust Mite Dermatophagoides pteronyssinus (Trouessart 1897). Leiden. Varekamp, H. (1925) M.D. thesis, University of Leiden. Voorhorst, R. (1962) Basic Facts of Allergy, p. 232. Leiden. Spieksma, F. T. M. (1967) J. Allergy, 40, 357. Varekamp, H., Leupen, M. J., Lyklema, A. W. (1967) ibid. 39,
PROLONGED NASOTRACHEAL INTUBATION IN INFANTS AND CHILDREN DAVID
J.
HATCH
M.B. Lond., F.F.A. R.C.S. SENIOR ANÆSTHETIC REGISTRAR, THE HOSPITAL FOR SICK CHILDREN AND UNIVERSITY COLLEGE HOSPITAL, LONDON W.C.1
Prolonged intubation of the trachea has a useful place in the intensive care of infants and children, complementary to the use of tracheostomy, but it carries some mortality and morbidity. During a two-year period there were 5 deaths directly associated with anæsthesia in 134 patients, compared with 7 deaths associated with tracheostomy in over 500 patients over a nine-year period at the same hospital. If tubes are left in situ for long periods subglottic oedema and stenosis may present an extremely serious problem. This may be reduced by careful selection of tube size, by the use of polyvinyl-chloride tubes instead of red rubber ones, and by the avoidance of trauma during intubation. The problem may be more common in cases of laryngotracheobronchitis. Tube obstruction has proved fatal when using small tubes and can occur at any time after intubation. It can only be avoided by meticulous nursing care and attention to humidity. It is not possible to state a maximum time during which tubes may be safely left in the trachea. Tracheostomy is preferred in this hospital if an artificial airway is required for longer than forty-eight to seventy-two hours. Sum ary
Introduction
INTUBATION of the trachea has been recommended as an alternative to tracheostomy (Allen and Steven 1965, McDonald and Stocks 1965, Thomas et al. 1965, Brown et al. 1966, Cotev 1967). However, because of the risk of complications such as subglottic stenosis, some workers have suggested limiting intubation to short periods (Bush 1966, Markham et al. 1967) or even abandoning the technique (Fearon et al. 1966). This survey analyses the results of prolonged intubation at the Hospital for Sick Children from August, 1965, to August, 1967. Material and
Technique
In the two years of this survey 167 nasotracheal intubations were done on 134 patients aged between twelve hours and fifteen years. Of these patients 77 died, death being related usually to the primary disease (table i). The lowest mortality was in the group with congenital heart disease where 21 (34%) of the 59 patients died. Three-quarters of the patients in the first year and half in the second were under twelve months old; a third of the patients were under four weeks old (fig. 1). Repeated
—
TABLE I-PRIMARY DISEASE
—
—
—
325.
— Spieksma-Boezen, M. I. A., Spieksma, F. T. M. (1964) Allergie Asthma, 10, 329. Wraith, D. G., Maunsell, K. (1967) VIth Int. Cong. Allergy. Excerpta med. Int. Congr. Ser. no. 144, p. 60.
Figures
in
parentheses show
total
no.
of intubations.
mites detected, if these were the only source of the allergen. Voorhorst et al. (1967) suggest that secretory and excretory products of the mites may play a part. This may well be so, but it must also be remembered that the finest debris of fragmented mites are undetectable by our present methods of extraction, and it should also not be overlooked that house dust contains other allergenic material, and we believe, that these materials, varying in composition from house to house and from room to room, add to the potency of house dust. K. M. is indebted to the Asthma Research Council for a part-time grant to carry out this investigation. We thank Dr. R. Bruce Pearson, Prof. A. C. Cunliffe, Mr. M. E. Solomon for their support, Dr. D. A. Williams for helpful discussions and for providing us with dust samples from South Wales, and Miss D. M. Noakes who visited houses in London and collected samples. Requests for reprints should be addressed to K. M., Department of Bacteriology, King’s College Hospital, London S.E.1. REFERENCES
Berrens, L. (1967) J. Allergy, 40, 355. Cunnington, A. M. (1967) Acta allerg. 22, 415. Gregory, P. H. (1968) Nature, Lond. 217, 1271. Hughes, A. M. (1961) The Mites of Stored Food. H.M. Stationery Office. Maunsell, K. (1967) Acta allerg. 22, 413. Solomon, M. E. (1961) Sanitarian. (1962) in Proceedings of the Colloquium on Research Methods in Soil Zoology (Rothamsted, 1958) edited by P. W. Murphy; vol. I, p. 503. Cunnington, A. M. (1964) Acarologia, 6, suppl. p. 339. Spieksma, F. T. M. (1967a) M.D. thesis, University of Leiden. (1967b) Int. Rhinol. 5, 168. Storm van Leeuwen, W. (1922) in Oorzaken en Behandeling van Asthma bronchiale (edited by Wolters). Groningen. (1928) Allergische Krankheiten. Berlin. Bien, Z., Varekamp, H. (1925). Z. Immun. Forsch. exp. Ther. 43, —
—
—
—
—
—
490.
Varekamp, H., Spieksma, F. T. M., Leupen, M. J., Lyklema, A. W. (1966) in Proceedings of the 5th Interasma Congress; p. 256. Voorhorst, R. (1967) J. Allergy, 40, 355. Spieksma, F. T. M., Varekamp, H., Leupen, M. J., Lyklema, A. W. (1967) ibid. 39, 325. Spieksma-Boezeman, M. J. E., Spieksma, F. T. M. (1964) Allergie Asthma, 10, 329. Wraith, D. G. (1967) Acta allerg. 22, 414. Maunsell, K. (1967) Int. Congr. Allergy, 6, 60 (Excerpta med. no. 144). —
-
-
J. PEPYS PROFESSOR OF CLINICAL IMMUNOLOGY
MOIRA CHAN Hong Kong, M.R.C.P., M.R.C.P.E.
RESEARCH ASSISTANT IN CLINICAL IMMUNOLOGY
F. E. HARGREAVE M.B. Leeds, M.R.C.P. LECTURER IN CLINICAL IMMUNOLOGY
Extracts of
of
the
culture of the acarine mite Dermatophagoides culinœ, which grows on dog meal, gave positive prick-test reactions in readily asthmatic subjects, which correlated well with a history of house-dust allergy and with asthmatic reactions to inhalation tests. The skin-test reactions were comparable to those of an extract of D. pteronyssinus, the " housedust mite," which grows more slowly on human dander, and is thus not so readily available as a test material.
Summary
Materials and Methods Test Materials Purified house-dust extract (Bencard, Brentford, Middlesex) was used for prick tests at 12 mg. per ml. and for inhalation tests at 1-2 and 12 mg. per ml. Extracts were made of dense cultures of D. culince, and house mite Glycyphagus domesticus, and the flour mite Acarus siro. The cultures, consisting of 1/2 to 3/4 mites, were heated at 50°C for several hours to kill the mites and were then defatted in ether and extracted for a week in 0-5% phenol/saline-solution. This extract was dialysed, Seitz-filtered and freeze-dried, being used for prick tests mainly at 10 mg. per ml. and for inhalation tests with D. culinae at 0’1, 1, and 10 mg. per ml. Similar control extracts were made of their culture media, namely wheat-germ flakes for A. siro, dried yeast for G. domesticus, and Gaine’s dog-meal, which consists of wheat, maize, soybean, bone and fish meal, meat byproducts, animal fats, and added vitamins, for D. culin6e. The mite cultures were provided by Mr. M. E. Solomon and Mr. A. M. CunningExtracts of cultures of D. pteronyssinus on human dander g. per 100 ml. extracting fluid) and of a similar control extract of the culture medium, were provided by Dr. Kate Maunsell. Inhalation Tests An aerosol of the test solution was made in a Wright’s nebuliser by oxygen at 8 litres per minute. The forced expiratory volume in one second (F.E.V.I.o) was recorded before, and at ten, twenty, and thirty minutes after the test and then twohourly. Control tests for five minutes were made with 0’5% phenol/saline-solution to exclude non-specific reactors and with the extract of the culture medium of D. culinv in patients giving positive reactions. One test was made daily, starting with the weakest concentration. A positive reaction was taken as asthma developing within a few minutes, accompanied by a fall in F.E.v.i.o of more than 15%. Results D. pteronyssinus, D. culinx, and House-dust Extracts in Asthmatic Patients
plus yeast (3
M.B. W’srand, F.R.C.P., F.R.C.P.E.
From the Department of Medicine, Institute of Diseases Chest, Brompton, London S.W.3
specimens from many countries contain common or allergens. Voorhorst et al. (1964), Spieksma and Voorhorst et al. (1967) claim that probably (1967), the major source of house-dust allergen is a little-known acarine mite, genus Dermatophagoides, and particularly D. pteronyssinus which grows best on human dander. Human dander itself is regarded as an important source of allergen (Voorhorst 1962); and Berrens et al. (1965) regard it as a major source of house-dust allergen. D. pteronyssinus has been found world-wide in house dust (Fain 1966, Spieksma 1967), including the U.K. (Cunnington 1967) where Wraith and Maunsell (1967) regard it as important in respiratory allergy, as did Oshima (1964) in Japan and Bachofen et al. (1967) in Switzerland. Since D. pteronyssinus grows slowly and on human dander, tests have been made in asthmatic patients with extracts of D. culinae, which grows more rapidly on a dog-meal medium. D. culinae is identical with, or closely related to, D. farinae which Ishizaki et al. (1967) found to be comparably allergenic to extracts of house dust. related
ton.
MITES AND HOUSE-DUST ALLERGY
M.B.
dusts vary widely in composition and allergenicity, though
a
Introduction
HOUSE dust has been recognised for more than forty years as probably the most important cause of allergic rhinitis and asthma (Kem 1921, Cooke 1922). House
We first compared the reactions in 22 asthmatic individuals to prick tests with the limited amount of extract of the culture of D. pteronyssinus (300 wB.) and with the freeze-dried extract of D. culinae culture at I and 10 mg. per ml. The extract of house dust was also used for testing. Positive and comparable reactions were obtained in 14 patients to the extracts of D. pteronyssinus (average weal diameter [A.w.D.], 4-2 mm.) and of D. culinae 10 mg. per ml. (A.W.D. 4-4 mm.). The extract of D. culinae
1271 1 mg. per ml. gave weaker reactions in 13 of the 14 (A.w.D. 2-2 mm.), the negative subject being the weakest reactor to the other extracts. The purified house-dust extract (12 mg. per ml.) gave positive reactions in 9 out of the 14 reactors (A.W.D. 0-7 mm.). The extract of D. culinae (10 mg. per ml.) was therefore used as the source of Dermatophagoides allergen in subsequent tests. The control extracts of human dander and of yeasts gave no reactions, and the extract of dog-meal gave weak reactions in 2 subjects. House-dust and D. culinae Extracts in Asthmatic and Individuals
We
Healthy
compared house-dust extract (12 mg. per ml.) extract (10 mg. per ml.). In 40 healthy subjects, positive prick-test reactions were given by house dust in 1 (25%), and to the D. culinae extract in 4 (10%). No reactions were given by the next
and D. culinae
control tests. In 100 asthmatic subjects, positive prick-test reactions were given by house-dust extract in 54 (A.w.D. 2 mm.) and by D. culinae extract in 73 (A.W.D. 6.4 mm.), 51 of these patients reacting to both extracts. The Gaine’s dog-meal gave positive reactions in 15 (A.W.D. 0-3 mm.) and the yeast extract in 9 (A.W.D. 0-4 mm.). Table i shows a statistically highly significant correlation (P < 0-0001) between the history of house-dust TABLE I-HOUSE-DUST
ALLERGY AND
PRICK-TEST
REACTIONS
IN
100
ASTHMATIC PATIENTS
allergy and the prick-test reaction to D. culina, and a slightly less significant correlation (P < 0-001) to the reaction to the house-dust extract. In 10 asthmatic subjects, positive prick-test reactions to the D. culinae extract were given by 6, and of these 5 gave immediate asthmatic reactions to the inhalation test, in 2 to the 1 mg. per ml., and in 3, who gave no reaction to 1 mg. per ml., reactions were given to the 10 mg. per ml. concentrations. Inhalation tests with the housedust extract in 4 of these asthmatic reactors gave an asthmatic reaction in 1 patient. The falls in F.E.V.1.o ranged from 22 to 50%. There were no late reactions. No reactions were obtained to the inhalation test with the D. culina extract in the 4 subjects giving negative pricktest reactions to it, nor in 3 of these who were tested with the house-dust extract. There were no reactions to the inhalation of the control extracts of the Gaine’s dog-meal
prick-test
TABLE II-PRICK-TEST REACTIONS IN TO PURIFIED HOUSE-DUST EXTRACT DRIED EXTRACTS
CULTURE MEDIA
(10
mg. PER
ml.)
27
SELECTED ASTHMATIC
(12
mg.
PER
ml.)
SUBJECTS
AND TO FREEZE-
OF THE MITE CULTURES AND THEIR
and of the yeast powder in the the D. culinae extract.
patients who reacted
to
A. siro and G. domesticus in Selected Positive Reactors A comparison was next made in 27 selected subjects,
who had reacted to D. culinae or to house dust, of the reactions to extracts of cultures of A. siro and G. domesticus. Table 11 shows that the house dust gave the fewest and the weakest reactions. The mites gave comparable numbers of reactions,with D. culinae at the head giving the largest reactions. These differences between the D. culinae and other reactions were highly statistically significant, ranging from p < 0-05 to p < 0-005. Discussion
This investigation shows that there is a good correlation, in asthmatic subjects, between a history of housedust allergy and prick-test and inhalation-test reactions to an extract of a culture of D. culince, which, as used here, was allergenically comparable with an extract of D. pteronyssinus, the " house dust mite" of Spieksma (1967) and Voorhorst et al. (1967). The allergenicity of housedust extracts was found, by the Dutch workers, to correlate well with the content of D. pteronyssinus. The more readily available D. culinae extracts seem to provide a suitable alternative for the scarcer D. pteronyssinus extracts for clinical purposes. The reactions to extracts of cultures of G. domesticus and A. siro in most of the patients reacting to the D. culinae extract suggest, though they were weaker, that these too may contain related allergens. More precise studies are needed in which the actual numbers of mites in cultures intended for extraction are known. G. domesticus and A. siro, were, however, found far less frequently in 150 house-dust samples examined by Spieksma (1967). The genus Dermatophagoides was found in all the house dusts, and made up 70% of the mites, of which 88% were D. pteronyssinus, whereas the genus Glycyphagus was found in 61 % of the house dusts and made up 9% of the mites, and the genus Acarus was found in 19 % of the house dusts and made up 1 % of the mite content. The role of the allergens of human dander in house-dust allergy and their relationship to the extracts of D. pteronyssinus cultured on human dander which were used by Voorhorst and his colleagues has been raised by Berrens (1967), who suggested that there are two distinct allergens in house dust, one of which is derived from human dander, and the other from the house dust itself, presumably of plant origin. He and his colleagues suggest that the reactions of the atopic subjects to both allergens may be explained by their having determinants in common (Berrens et al. 1965). Henocq et al. (1966) also report that human dander and house dust have two different allergens in spite of the parallelism of their reactions in patients with atopic aczema, and they found that the house-dust extract is 200 times stronger than that of the human dander. Voorhorst and Spieksma (1967) claim that the amount of human dander allergen in their test extract of D. pteronyssinus is far too low to give reactions. We found no reactions to prick-tests with control extracts of the human-dander medium for the culture of D. pteronyssinus, whereas extracts of the mite culture gave strong reactions. Reactions comparable to those of D. pteronyssinus were obtained by us with extracts of D. culinae, which was cultured on a medium without human dander. These findings suggest that these mites, or their products, are the source of the allergen, though the problem remains of
1272
whether the medium may be altered chemically by the growth of the mite so as to become more allergenic, or whether both mite and medium are sources of allergen. Varekamp (1925) in one of the earliest descriptions of allergy to mites in oats, found that the extract of the mites themselves gave weaker reactions than the residual culture medium. Spieksma (1967) has produced evidence suggesting that faecal pellets of the mite D. pteryonssinus are comparable, as sources of allergen, to the mites themselves. The method of skin testing is also important for the assessment of results. Bachofen et al. (1967) obtained positive reactions to intracutaneous tests with extracts of D. pteronyssinus in a half, and of house dust in all, of their healthy controls, none of whom gave reactions to inhalation tests. By contrast, we obtained in healthy subjects positive prick-test reactions in 2-5% to an extract of house dust and in 10% to an extract of D. also obtained positive culince. Bachofen et al. intracutaneous test reactions to both extracts in all of their 20 asthmatic subjects, of whom 8 gave asthmatic reactions to inhalation tests with D. pteronyssinus and 2 only to the house-dust extract. We, however, obtained prick-test reactions to D. culinae extract in 6 out of 10 asthmatic subjects, and 5 of these gave asthmatic reactions to the inhalation test; and no reactions were produced in those giving negative reactions to the prick test. Whilst some of the difficulties of intracutaneous tests can be overcome by tests with serial dilutions of extract to arrive at a threshold concentration, the reactions to the prick test are not only more relevant to the history and inhalation tests, but are simpler and more acceptable in clinical work. The presence of other allergens in house dust besides those of Dermatophagoides is shown by the inhalation-test reactions only to house dust which Bachofen et al. (1967) found in 2 cases and by the pricktest reactions to house dust and not to Dermatophagoides in 3% of asthmatics in the present study. It seems therefore, that the genus Dermatophagoides, and notably the " house dust mite " D. pteronyssinus, is at least closely associated with the allergenicity of house dust and it is not improbable that it is in itself a major source of house-dust allergen. The preparation of mitespecific allergen and its study in house-dust allergy are now needed for the next steps in this promising advance. We thank Mr. M. E. Solomon and Mr. A. M. Cunnington of the Agricultural Research Council Pest Infestation Laboratory and Dr. Kate Maunsell for their generous provision of materials for these investigations, and the clinicians of the Brompton Hospital for referring their patients for investigation. Requests for reprints should be addressed to J. P.
(1967)
*
REFERENCES
Bachofen, H., Scherrer, M., Träutlein, F., Wyss, F. (1967) Dt. med. Wschr. 92, 1597. Berrens, L. (1967) J. Allergy, 40, 355. Morris, J. H., Versie, R. (1965) Int. Archs Allergy, 27, 129. Cooke, R. A. (1922) J. Immun. 7, 147. Cunnington, A. M. (1967) Acta allerg., Copenh. 22, 415. Fain, A. (1966) Bull. Acad. R. méd. Beige, 6, 479. Hénocq, E., Bazin, J. C., Girard, J. (1966) Revue fr. Allergie, 6, 213. Ishizaki, T., Miyamoto, T., Oshima, S. (1967) Vlth int. Cong. Allergol. Excerpta med. Int. Congr. Ser. no. 144, p. 62. Kern, A. (1921) Med. Clins N. Am. 5, 751. Oshima, S. (1964) Jap. J. sanit. Zool. 15, 233. Spieksma, F. T. M. (1967) The House-dust Mite Dermatophagoides pteronyssinus (Trouessart 1897). Leiden. Varekamp, H. (1925) M.D. thesis, University of Leiden. Voorhorst, R. (1962) Basic Facts of Allergy, p. 232. Leiden. Spieksma, F. T. M. (1967) J. Allergy, 40, 357. Varekamp, H., Leupen, M. J., Lyklema, A. W. (1967) ibid. 39,
PROLONGED NASOTRACHEAL INTUBATION IN INFANTS AND CHILDREN DAVID
J.
HATCH
M.B. Lond., F.F.A. R.C.S. SENIOR ANÆSTHETIC REGISTRAR, THE HOSPITAL FOR SICK CHILDREN AND UNIVERSITY COLLEGE HOSPITAL, LONDON W.C.1
Prolonged intubation of the trachea has a useful place in the intensive care of infants and children, complementary to the use of tracheostomy, but it carries some mortality and morbidity. During a two-year period there were 5 deaths directly associated with anæsthesia in 134 patients, compared with 7 deaths associated with tracheostomy in over 500 patients over a nine-year period at the same hospital. If tubes are left in situ for long periods subglottic oedema and stenosis may present an extremely serious problem. This may be reduced by careful selection of tube size, by the use of polyvinyl-chloride tubes instead of red rubber ones, and by the avoidance of trauma during intubation. The problem may be more common in cases of laryngotracheobronchitis. Tube obstruction has proved fatal when using small tubes and can occur at any time after intubation. It can only be avoided by meticulous nursing care and attention to humidity. It is not possible to state a maximum time during which tubes may be safely left in the trachea. Tracheostomy is preferred in this hospital if an artificial airway is required for longer than forty-eight to seventy-two hours. Sum ary
Introduction
INTUBATION of the trachea has been recommended as an alternative to tracheostomy (Allen and Steven 1965, McDonald and Stocks 1965, Thomas et al. 1965, Brown et al. 1966, Cotev 1967). However, because of the risk of complications such as subglottic stenosis, some workers have suggested limiting intubation to short periods (Bush 1966, Markham et al. 1967) or even abandoning the technique (Fearon et al. 1966). This survey analyses the results of prolonged intubation at the Hospital for Sick Children from August, 1965, to August, 1967. Material and
Technique
In the two years of this survey 167 nasotracheal intubations were done on 134 patients aged between twelve hours and fifteen years. Of these patients 77 died, death being related usually to the primary disease (table i). The lowest mortality was in the group with congenital heart disease where 21 (34%) of the 59 patients died. Three-quarters of the patients in the first year and half in the second were under twelve months old; a third of the patients were under four weeks old (fig. 1). Repeated
—
TABLE I-PRIMARY DISEASE
—
—
—
325.
— Spieksma-Boezen, M. I. A., Spieksma, F. T. M. (1964) Allergie Asthma, 10, 329. Wraith, D. G., Maunsell, K. (1967) VIth Int. Cong. Allergy. Excerpta med. Int. Congr. Ser. no. 144, p. 60.
Figures
in
parentheses show
total
no.
of intubations.