Document rpJrgz14JYLzd2Q8Qgw8av7Kq

tUGUST 10, 1968 LETTERS TO THE EDITOR THE LANCET 351 Jl has been claimed ' cli.it disodiu'in cromoglycate makes it Pepys and his colleagues (July 20, p. 131), that it " promises possible to reduce the dose of long-term steroid therapy or even to be a valuable tool lor the study of immunological mechanisms a withdraw it completely. This may prove to he its most of respiratory allergic disease." tillable 1'ioperty. I louexer, any reduction of the maintenance awe of steroid should he attempted only il patients are closely wpctvised. with regular measurement of forced expired Kvspirjiory tnves(i|*jtiii Umi, Koval infirmary, C 4. !'. Moran J. D. H. Bankier (. Boyd, iolume ut one second, or peak expiratory tUnv. The subjective relief which disodiuin cromoglycate undoubtedly confers in siny patients may obscure the development of a potentially iingcrous situation in which the patient is deprived of symp toms which otherwise might give warning of an acute relapse WHAT'S IN P.V.C. ? it a time when he is especially vulnerable by reason of the Sir,--In your annotation (July 6, p. 34), discussing the lowered Jose of steroiJ. This seemed to be the only explanation need for standards specifications lor the use of plastics in ill recent case of very sudden death which occurred in a boy medicine, you mention that Parkhouse and I 1 drew attention of 14 who was under the care of the outpatient department of to this need several years ago. This seems an appropriate ' das hospital. time to amplify that suggestion. The criteria for selection of patients for treatment with There are two main approaches to the problem. One is to isodium cromoglycate are still far from clear. As your provide a detailed recipe for the manufacture of each plastic,- mnotation points out, the drug appears to inhibit the effects of and the other to define a scries of properties which those "certain antigen-antibody reactions " (type l). This suggests plastics which arc used in medicine should possess. It is at that in clinical use it should be most effective in allergic once apparent that to specify in detail the composition of nthma, its action being more of a prophylactic than a thora- acceptable plastics, and issue these in the form of a " white " peutic nature. My own experience of its use in a small number list, would hinder progress, and probably prevent the develop of carefully selected patients in both hospital and general ment of more suitable plastics for any particular purpose. ( practice confirms such a view. I have found it to be of great There is already evidence that preliminary attempts in this nlue in some patients, particularly children, who have chronic direction have failed to take into account the properties 'extrinsic " asthma, whereas I have not found any significant required for each specific use. A silicone sponge, for example, Senefic from its use in patients with non-allergicor " intrinsic " intended for use outside the body succeeded in reaching isthma. In the former group of patients its action appears to approval as a " medical " grade, and has since been used for x one of maintaining a state of remission rather than of implants. On the other hand a carefully purified and prepared suppressing active asthma. grade of silicone fluid, having been used in an obviously It seems likely that general practitioners will soon find unsuitable manner with adverse results, has been rejected. IAcmselves under increasing pressure to prescribe disodium So for more legitimate uses doctors are falling back on less aomoglycate. I hope that, much more information about its well purified grades never intended for the .purpose and I wion and use in clinical practice will bfc available before it therefore not subject to the ban. I ames to be prescribed widely and, possibly, indiscriminately. IBronpton Hoipitul, LonJon SAV.3. IAN GREGG. The need, therefore, is for specifications of the properties which plastics must have, whatever their composition. But the properties which arc specified need to be relevant to the problem. To take the example quoted by Dr. Duke and ] SlR,--We are grateful to Dr. Grant, who wrote last week < p. 282), for pointing out some obscurity in the description of jut trial * of disodium cromoglycate. However, we believe tn the situation is made clear three paragraphs later and ii in the tables; and, indeed, Dr. Grant has correctly inter preted the design of the trial. As we stated, our record card was of similar design to that i Smith and Dcvey,7 but it was not identical. The difference 3 unimportant. Wc expected that purulence of the sputum sight be important in assessing response and therefore gave ewer scores to purulent than to non-purulent sputum. This acreased the number of possible scores describing sputum production to seven. The average difference between mean scores for active frog and placebo included, of course, those patients who ihowed no response or even deterioration. The facts are that Ae differences described as significant are normally accepted b such, and that when all criteria were used 10 of the 21 patients showed much improvement and 5 more showed nine improvement on disodium cromoglycate. This is more iifl " an occasional case The discrepancy between the f.e.v., results and other indices iimprovement underlines the inadequacy of information both athc meaning of the f.e.v., in asthma and on the mode of xtion of disodium cromoglycate. We claim only that our Professor Vane (July 6, p. 21), the tubing found to be unsuit able for their purposes did comply to a Food Packaging regu lation which specifies the total weight of material which can be leached'out. For reactions with tissues this is meaningless. A comparatively large amount of a non-toxic material could be tolerated, but not a much smaller amount of toxic material. You rightly point out that all tests should be performed after the same sterilising procedure as that which will be used in practice. One might doubt, however, the statement that irradiation " can render p.v.c. toxic by the formation of hydrochloric acid". In practice, for the uses to which poly vinylchloride (p.v.c.) is normally put, abrasion from filler particle seems to be the cause of a number of effects reported as " toxic One grade of green tubing has produced chlorine during irradiation, but the manufacturers tell me this has now been withdrawn from production. These examples taken from The Lancet of July 6 illustrate the two essential points to be remembered in devising a standards specification. One is thac a particular plastic not only must be thought of as " suitable " or " not suitable " for general medical use, but also each plastic must be considered for the situation for which it is intended. The other is that the tests should be relevant. It can only induce a false sense of security if tests are adopted because " one ought to do some thing ". results suggest that disodium cromoglycate " will improve I would suggest that, as basic research reveals the pro ir general level of well-being of many patients with allergic perties that arc genuinely meaningful, then tests should be rronchial asthma", not that it should be regarded as "a devised to meet these situations as they arise. Thus with ajor advance We do, however, believe, with Professor biological testing, the tissue-culture methods using fibroblasts 1 Altounvan, R. E. C., Howell, J. B. L.. Proceedings of ih< 2nd Intemationjl Synp.isium on Tuberculosis, Climjic, Asihmj and Bronchitis, D\ov M.-Jna Thorax. |67 .in the press). Morrison Smith, ].. Dtvty, G. F. Or. nit-J. J. 190$, ii, 340. t Menu F., Bankier, J. D. H., Boyd, G. i.ancti, July 20, 1968, p. 137. '. Smith, J. M , Devey, G. F. Br. med.J. 1963, ii, 340. and chick-embryo cells devised by W. L. Guess and J. Autian give a reliable indication of the toxicity of the materials under test. But subcutaneous and intramuscular implantation tests suffer from the disadvantages that both toxic materials and ones 1. Little, K., Parkhouse, J. Lanctt, 1962, ii, 857. 20S48001 ffAj til ?VO 352 AUGUST 10, 196H LETTERS TO I I AUGUST 10, with unsuitable surfaces produce cell reactions, so that Che acute i.i-n:crs nv iti.iui'-ntisT inhalation on tulmonahv fukctm shape of the implant is important. Although they are invalu (7. UlANK.fS l-KOM VALUI-S IIHOKE DUST SHOWN IN I'ARENTUUU) able methods tor investigating the properties lor winch other tests must he Jevised, they are unsuitable lor routine testing, '('lie third type of biological test is tile long-term implant, in tlie ohiucu! situation required, to find out how the plastic itself withstands degradation by surrounding tissue iluids. Such Time Ucfure dust r.b.v., (J.) | 1 v.c. (Id i1 03 4 It r.K.v.,/ r.v e. (:,.) &n-1 r L.P.B. 6 53 vrrui 50", (r./Ms.j 1M tests need to be continued for periods up to 5 years, and there After Jim 2A-I , 1 on bin 5 HI 1 jis at present no saiistactury chemical method for obtaining Alter broil- { 1 j ( * l .'J (-113%) (-J12V the mhirm.ition. Attempts are being made to devise a formu Jiudil.iliir 1 2 V7 ' 111 67 0 6-72 2 34 lation such that so many hours exposure to a chemical brew ( 11 j ; 1 0 < 2 6'V.J {-4S\J will be equivalent to a number of months or years of implan 1l tation, but to Jo this there is a need to have plastics which have been in the body lor a number of years (either human or animal) for comparison. If any of your readers, removing Average results m |3 men in whom f.e.v., decreased more ihon 0-20 ktrp while exposed i,. Just, y.t v i and t V.C. H'LTtf measured during /><im CXpif.nionb mi ,lireei-rv;uliiii; NtHfumet CfS, !M`.F k. and vrnax ,il 30% were measured from maximum expiratory How-volume eurves (lev tijw*i plastic devices at either operation or necropsy, were to send them here for evaluation of the plastic, it would be most helpful. L'mied kumd.'m Atomic Kitcrpy Auihuriiy, YV.iiii.iju- Uese-ircli l..ib.*r..i,iry iAfKlb. Hok'hirv. < Is*- LITTLE# J this improvement, we believe that bronchial smooth-mutd contraction is the main cause of these changes. There is * evidence that any mechanism other than airway obstruct!* causes these changes in the men exposed to dust; yet thev changes yvouIJ presumably be described as " restrictive in nature if one adheres to the criteria to which Dr. Prime ud Professor Scudding object. Even if this airway obstructive RESTRICTIVE VERSUS OBSTRUCTIVE VENTILATORY IMPAIRMENT would result in pulmonary collapse, one would presumabl, have to consider the defect an obstructive one, although in oil view the definition then becomes a matter of semantic prefer Sin,--I3r. Prime and Professor Scadding 1 have aptly cnce. reminded us of the origin and definition of the terms " rcscric- The nature of the pulmonary-function change bccomr tivc " and " obstructive " ventilatory impairment. They morc dear if one measures maximum expiratory flow-ma, r discuss the development of a lung-function defect with different lung volumes, from maximum expiratory flo* decreased t-.F.v., (forced expiratory \olume in l second) and volume (.M.t.F.v.) curves. We recorded such curves i/u f.v.c. (.torced vital capacity), but with a relatively normal measured both peak expiratory flow-rate (P.E.F.R.) and nun f.e.v., f.v.c. ratio, us a hue consequence of obstructive lung mum expiratory flow-rate at u volume corresponding to loi. disease. \\*e wish to report data from a study on acute ven lung capacity minus 50",, of the control v.c. (vmax at 50 . tilatory changes in byssinosis which underline their comment, v.c.) (see accompanying figure). Total lung capacity (t.ix.. and which show that uch " pseudo-restrictive " patterns* may diJ not change significantly after dust, nor again after bronch. also be found in conditions of acutely induced broncho- dilator, in chese men. Therefore one may assume that thr constriction. measurement of vmax at 50",, v.c. yields a measurement i Hemp-dust inhalation causes dvspna?a and decreased maximum expiratory flow-rate at a constant degree of lutu ventilatory capacity in workers in the industry as yvcII as inflation. The liguie and the table show that these flow-rata healthy subjects.- The accompanying tabic shows average show more pronounced changes, both after dust and aftrr results of function tests in 2 healthy men and 11 hemp-workers bronchodilator, than flow-rates such as p.e.kr., which are maJc who were exposed to dust (.45 minutes to 4 hours). These are at volumes near t.l.C. The decrease of f.e.v., reflects the all experiments, from a larger series, in which f.e.v., decreased decrease of instantaneous maximum flow-rates through^, more than 0 2l> litres during dust exposure. Tests were done the first second of the forced expiration. The decrease of vi::l before and after exposure, and again 30 minutes after inhalation capacity reflects the fact that flow-rates arc proportional!* of an isopivnulme-phenylcphrine mixture (` Medihaler Duo '). more depressed at low lung volumes, so that residual volume The du*.t causes decreases of f.e.v., and F.v.c. in about the (i.c., the lung volume at which flow reaches zero) merest. same proportion, since the f.e.v., f.v.c. ratio changes little. Since in many of these men flow-rates are extremely low nut Since the Just effect is rapidly reversible by the bronchodilator residual volume, the end-point of the F.v.c. determination u treatment, jikI little or no sputum raised in association with often hard to deline, in particular from a Standard spirograph'; 1. I'rim.-. I:, J., ik-uUme, J. (.i. /..!>(if, l*#<>>, i, I 372. 2. Il.'ul-.uv-., A., il.irivi''. A.. I.inJetl, S-L , Koaelt, S. A., Schilling, record. The more time the subject is able and willing to spend, near residual volume, to expel the last bit of air, the larger the It. S. I'. .1 re/.-- ///;>,. 16ft7, 14. 533. measured F.v.c. will be.* A more complete report of our findings is in preparation. John 11. Pit-fee I-`.`UrHiari,>n laboratory an.1 Section of Chot l>iicjsc, Ocparrritenc of /nfermil Afttlicinc, Vale University Sehool of Medicine, Sew H.iven. ('.onnceiieut U6320. A. Bouhuys K. P. VAN DE WoBSTf/M. Average M.IT.F.V. curves before (' - ' , and after hemp- du>t exposure in 14 men. :\l'*.i'j (horacie e-is volume (in litres); ordinarc - maximum cxpir.in-ry lieu.rate on litres per sec.% Curves begin at T.t.c. " I 1 . ::cht-h.uid side of volume scale . vmax ru|iidlv increase* to pi.uk .jMi.r.K., hl.uk ih'i'i and decreases thereafter, vmax at su v.i* jihI re'iJu.il volume (2-7 ar.J 3 1 1.) both indicated by bl.uk .1.O'. BLOOD-GAS TENSIONS AND SPIROMETR1C FINDINGS Sir,--Dr. Grant and Dr. Harris (July 6, p. 45) suggest th* in our analysis of the changes in the forced expiratory spii>> gram and their relation to changes in arterial blooJ-ga tensions in patients with bronchial asthma 4 and chrrnk bronchitis,' partial rather than total correlation coefficients should have been calculated; they also ask for the " results-of i multiple correlation procedure " on our data. Accordingly at 3. I mil. I). I. , AU.iil. J. J.apft. I'hv'iAl. 1*67, 24, 221. I. Kilmer. k`. N\ V., Ift-imvnr, M. t.. l.an<te, 1VA*. /, VH. S. I'.iliiKr, K. N. V., Di.imcnf, M. L. ibid. p. 1233, PARTIAL fttitnis ul. ho. PiCO, hiuiitt uni A , - P*o. P4CO1 have calcul blood-gas 1. the perceni second (r.i The result the prevm. dear chat substantial Dr. Gr.. requiring i shown 1I1. correlated (F.v.c. and correlated nrtables (F.E.V., out requir Universe ESSIi" Sir, ' probj ipon(W_ uncritic totally d ment dn uticle, implied . Kids and Whi tions, 01 icid deli, intima) f| flcpharn record* reported W the slesion.' been no Secou 1 these 1insutlici. mother lesions i| re not media, of the 1 than w> As (j 'l. 2. Ur >. .Mi' 4. 13 1 I. Or. 6. blk BFG04334 20648002