Document k1wB40ED0Zv2q9oEJBbp9X8B

786 PostScript . Thorax 2002;57 :186-188 NOT!C~':-f`~iS h"~AiCfttAl h' .4Y iE F`" <1 .^;>"F?,t~;Fi?L4'e^! (s1-1.F 17 PROTECTED U.S . CODs) LE7TER5 TO THE EDITOR BMD and airways disease the papers recently published in Thorax by 78ctersfield n al' and Welsh n aY offer important information about the possible adverse affects of corricoste+otds on bone mineral density (BMD). 7atcer5fie10 and her colleagues reported no change in BMD with inhaled wrumseeroids tot mild asthma, while Welsh of al found a dose related Increase in the Incidence of fractures in those taking oral corticostemids. %t would like to report Our study of BMD in patients with airways disease, which reinforces these findings and highlights menas being particularly ai risk . We prospectively studied 100 consecutive outpatients (44 mm) with steroid responsive airways diuase. The formulation and cumulative dose of cortimsferaid was recorded in each individual, together with all prescribed prophylasis (or osteoporosis . Bone mineral density was measured in the non-dominant forearm . We found no relationship between inhaled mrGCOStemid dose and BMD. Mean BMD was significantly reduced in those on oral as If you hove a biming desire to respond so 7b.i~hod in Thorax, why not rapid response' option? log on b our websile (www.ihoroxjnl .com), find the pope' 11ad interests you, and sand your response via email by clicking on the eLetteri option in the box at the top right hand comer. Providing it isn't libellous or obscene, ii will be potted within seven days . You can retrieve it by disking on 'read eLaBers' on our homepope. The edits will decide as before whether so also publish it In a future paper issue . asthma in population studies. However, they hoax endorsed airway hyperresponsiveness (AHRI while neatly sidestepping the issue of whoa test they a discussing . Inhaled prow cation tests used in epidemiological work have included histamine, methachuline, hypertoMc cline, mid air, and adenosine. Exercise provocation tests have also been Authors' reply Primhakand Poweli make thevalid point that the essence of airway hyperrespunsivrness (AHR) Is nut an absolute attribute, Abnormal AHR represmis ant end of a continuum of responsiveness . Furthermore, the distribution of that continuum varies according to the nature of thedirect or indirect stimulus that is applied . In our studies. referred to in The m" im, we ham defined abnormal airway responsiveness as a decline of more than 20% in tarred expiratory whims N 1 second (FEV,) after inhalation of a cumulative dose of histamine of 53 .9 ymol . Using this criterion, the presence of AHR is a useful marker of airway abnormality consistent with asthma in epldcmioloRLad studies' and is also predictive of the subsequent course of the disease .' We acknowledge that usher attach for the presentt of AHR have not been evaluated as extensively in epidemiological studies. However, there is evidence that at least some indirttt agonises, such as nun-isDTonic aerosols and exercise, also have a high level of specificity but only moderate sensitivity as markers of asthma symptoms ." opposed to inhaled steroids. In men the MUD Z scores for those on inhaled and oral curdm" steroids were 0.1 and -0.b, respectively used. Peat et of have prmiouqly shown trial exercise and histamine challenges may define different groups of children,' and we have 1 K Pact, B G Toe110, G B Marks, C M Mellis (p=0.U7f, while women had mean Z scores of 0.5 and -03 for inhaled and oral mnicrn steroids, respectively jp=0.010. Our patient shown that longer term repeatability of a free running exercise provocation test is poor within a childhood population! In adults Im1iNk of Respirolo~yMMdidne . University of Sydney, Box M77. Mhsenden Rood P O, Comperdown, NSW 2050, Aushalio numbers was insufficient m confirm a dose response . The surprising resuL was shat men were mare likely m meet the WHO criteria for osteoporosis than women (25% v 13 .5%1 . This result is explained at least in pan by the use of quite considerable within Subject variability in PD m methacboline has been observed during a 1 year period,' and a childhood population study found that methacholine PD, varied by >4 doubling doses within the References 1 Twlla BG, Peon JN, Sobme CM, et of. Toward e definition of aNhmo far epidemiebgy . Am Rev Raspb Dis 1992;146 :633-7 . pmphyluiswhich was proscribed w 21 women course of a year in 33% of the subjects .' 2 Peat J, Toelle B, Salem C, of ol. Predictive but to only two turn. Of those on regular oral steroids, only 5.4%. or men received prophylaxis compared with 62 .5% of women. Similar results have been reported in otherchronic dlscasa, with a greater reduction in SMD being reported in men with cystic fibrosis .' Unfortunately it appears m have been assumed that men are protected from osieo- we would suggest that more cars should be taken to define the precise measure of nHR used before comments can be made about Its sensitivity and speBficity in an epidemVologi~ cal survey. The medium term temporal variation In AHR seen by a number of researchers is another measure which may make n difficult to make useful comparisons baween nrawtpuirrea.b1rybrsonycmhpimalmsrupinoraoiorvreonye'sas"acnadtions sh+dyof Sydney uhookhildrm . fu, Fenpirl 1993 ;6 :662-9 . 3 Smith C, Anderwn 5. Inhalolion prwxofen tots using roniadonic aeroml sJ Allergy Clin Hnmund 1989;89 :781-90 . d Noby M, Veal l, MOM C, al al. An acetic cholleige forepidemiological studies of Erorosis by virtue of their gender. When populations. chiklhoed .,! validity amd+apeabbiliN . chronic disease is treated with oral corticu- R A Primhak hr ReTpirals1h495 ;8 :749-36 . steraids, both men and women aye equally at Sheffield Children's Haspiml, Wmlern Bank, risk of osteoporosis and all should be considered for prophylazts. Sheffield SIO 27H, UK One fibre or many; what causes C 4 E Powell mesolheliomp? C Elmer, P Barlhelemew, A Wpworlh, P Turner, C Kelly Department of Medicine, Oueen Elizabeth Hasphrol, Gateshead NE965%, UK Deponmenh e! Emngincy Modkine and General PardiaMies, Royal Childieo'e Hospital. Potkvilk, Victoria 3052 end University d Melbourne, Victoria, Australia Referenees In a rxent use (DO?I.Q/1284) in the Queen's Bench Division of the High Court in England, a widow sued on behalf 0f her husband who had died at the age of 60 of mesolhclfoma . References I Tollarsfiuld AE, Town GI, Johnell O, et of. 1 Peel J, Talk B, Marks G. .1 J. Cemla .ig the debate o6au1 mensuring asthma in Unusually for such cases, Mr Justice Curus found for [hr defendants. sod the grounds for BeoanAemaminrearnadlomdimsseidytoinnawubilmecslms with with mild Inhaled pwpeWlion ~ludies. Thwax 2001 ;56 :d06-11 . 2 Ho6y M, Anderson 5, Peat l . of al. M his judgement wars sufficiently curious to be of general interest and worthy o! debate. cohlcosRroids a nw~coficoporoid 7eolmenl !or two years, ihorox?001 ;54272-8 . 2WoIthU.Wmg CA,OhemeJ,alol. A~lvurse eHsct of aal conlm,laroids in relation b dose in Patients with lung disease. epidemidogiwlsWdies of asthma in children : comparison, with histomine challenge. Eur RnpirJ 19V49A3-9 . 3 Powall t, Whik R, Primhak R. langiNdinel it was not dispaicd that the doomed had been exposed to substantial quantities of asUestos during two periods of employment, nor that there had been a breach of statutory 7.h 2001 ;56:279$4 . ewdydheervnnin exercisechollerige : deny by his employers at that time .-Thejudgc- 3 Conway SP, Morron AM, ddroyd 6 . vial. reproducibiliy. Ave Da Child ment was based, however, on the expert and Osteoporosis and asleopenlo in oduHe end 1996;74:126-30 . agreed opinion of "two mast highly qualified adolauenls in rysfic fibrosis ; prevalence and uuodakd factor, ihaaR 2000;55:798004 . AHR in asthma Peat er W' have contributed a helpful review to 4 Trigg C, Tooley M, D'Souzo M, M of. Factors oNccfino the longkrm variability of bronchiol responsiveness in an adult genoml practice populofion . Eur Respw J 1994 ;7:703-9 . 5 Clough J, 7dilliom, 1, Hdgaw 5. Profile of 6roncbiol rcspoiuiveneu In children with respimroy symptoms . Arch Drs Child medico' men" . In their joint report and oral evidence, the judge believed these doctors to have stated that mesotbelioma is the consequencc of malignant transformation in a single cell, the result of a hit by either one or srveral fibres. This led the judge to reason than, the debate on techniques for measuring 1992 ;67:57e-9. although a fibre or fibres instated during one wwwtl~orm~j~ .com Postscript 187 I or other period of employmrnt may well have led to the fatal cellular transformation. h was not possible to say which, aid hr was therefore unable to find richer responsible . natural mechanisms eliminated- I( this is whereby such true, and it is cells arc certainly more plausible than the one fibre theory, Then mesoehelioma is caused 6y the access of large M Muers Respiratory 11,11. The General infirmary Leeds L51 al Lend', 3EX, UK ; omondo .jonesQkadsth.nha .uk In mining m his Judgement. Mr Justice Curtis made a distinction between causation numbers of fibres Since is a dose to the related mesothdial tissue . disease, it may 6e Statement on malignant I 7 I and risk favors- In his words "the only relevance of The number of fibres is in connection with the risk at convicting the disease" . He was thus dissuaded from being influenced by any evidence that might have shown a relationship between risk of mesocheltama and dose of asbestos,although there is much such evidence from studies both of humanlungs and of animals. 7 haw heard the view exprascd before chat one fibre causes mesotheUoma . It depends what you mean by "cnusC' .lt is in one sense argued that all ocposures to asbestos before a critical time would be expecd to have contributed is the causation of the disease . Thus, attribution of blame should be on the basis of relative intensity and duration of exposure in different aides. The moral of this story is that lawyers are clever people and part of their business is the meaning of words. The word "more" is me that requires a bit of thought. My Shorter Oxford Dictionary dcwtcs a column to I[ . mesorhelioma in the UK Nor would like a provide the following additional material to Appendix ) "Sources of information and help available for patients and uwrers"which appeared on pages 163-9of the S75 statement on malignant meso[hiHama in the UK published recently in Thorax.' The following Asbestos Support Groups are the majar practical sources of information In the uX for purple with asbestos related diseases. Most provide a drop in and tele- obvious nonsense . we all haw millions of A Section phone service. giving confidential free advice asbestos fibres in our lungs and the likelihood of us developing mesothelloma depends on how many millions This means that the disease is dose related . The problem in this Depoelmenl of Envirenmenbl and Oceupnlional Medicine, Abortion . Utwrsy Medical School, Foreatsrhill, A6erdwn A825 7ZP, UK; a.seabnlabdn .oc.uk and support to patients and families . They also haw particular expertise in the field or Industrial injury benefits and government and civil compensation claims . Although most case arose from confusing the disease mewihr- of the groups arc in the north of England. lioma with transformation in a cell, which may Mesotheliomabe a factor in the development of the disease. telephone queries from any pivot Great Britain are acceptable to [hem . Take the case of the butterfly flapping its We write as the three medical witnesses who Manchester lie] : 0161 953 4037/ wings in the Amazon rain forest . It may be provided evidence (all in writing. two orally to Sheffield lie) : 0114 282 3212 or 01709 513 possible for an Ingenious QC to prove that the the Court in the eau referred m by Professor 587) hurricane that hit the coast of west Africa was Season . Essentially we agree with his analysis . Liverpool (ml: 0151 236 1895) caused by [hat Insect's acrton. 6w the ether The medical evidence pressured to the Court Bradford (leC 01274 393 949 side mold surely point to other risk factors that, Taken with the action of the butterfly, contributed significantly W the disaster. is it molly possible to say that the only and necessary cause of roewthclloma is translorv mauon i++ a cell? Arewe sure that the milieu in which shat cell lives and divides is not inlluenual? Are we awe that inflammation to the N.s sue involved is not an, important precoaditim [or the development of thediscau?Are we sure that the action of asbestos on other cells does rat interim with the names] defences [hat would otherwise eliminate the transformed cell? Arc we, sure that genetic factors and viruses do no( also determine whether Elie Transformation occurs or succeeds In overcoming the body ., defences? Or looked at another way, experimentally, how many rats would have to be used to produce one mesorbellorm after injection oione fibreintothe peritoneum? Of mutts, no onehasever shown shat one (bra causes mesothelioma. All that has been mnjec" Lured is that the malignant cells that form part of the tumour may be the gaietfc offspring of one mundfortricd cell The judge appears in this case to have been persuaded co accept a naive view of causation-that disease has one ultimate cause. Most who hew studied the CauSauon of disease would argue that the likelihood of made it dear drat the risk of meso[helioma increase., in relation to the dose ofasbcstos and that i1 i5 not possible to identify the particular fibre or fibres involved in du genesis of a particular mesodielioma . From an epidemiclogical standpoint it is therefore appropriate To, regard all sources of significant exposure as hamming contributed m causation of the disease. in the same way that all cigarettes smoked would be considered m have mnnibuted m causation of a lung cancer. Mr Justice Curtis, however, accepted the invitation of Leading Counsel for one of the defendants to adopt a strictly mechanistic approach m causation. He decided that, 6ecause the claimant mind not show whetherthe fibre or fibres actually involved in the genesis of the tumwr were derived from either or both of two sources of exposure, causation mind me be established against either of two defendants. Mare recently, a different view has been taken In a similar case by Mr Justice Mitring (Queen's Bench Division C20D10111) He considered chat chars was "no substantial differc= between saying that what the defendant did materially increased the risk of injury to the claimant and saying that what the defendant did made a material contribution to his Injury". It would be "wholly artificial to West 7brks (gel: 0113 243 99791 Cheshire (tel :01928 576611) Nottingham (tel: 0115 927 5108) In Scotland ; Clydaide Action on Asbestos (gel : OIAI 551 8852) Clydebank Asbestos Group pal: 0141 vsl 1008) Other important sources of help and information ate: The Macmillan Mesolhelioma information line (ml: 0113 206 6466 ; email: mavisro@Wth.nort4y.nhs.uk) and the Occupational and envuonmenwl Diseases Acwciation (OEDA),both of which were mentioned in the original statement. M Robinson Memtheliamo Inlormalion Serviu, Coektidge Hospital, Leeds L516 6OB, UK ; mavisrcQullh .nenhy .nAs .uk J Wi99inc Deparlment of C,nnal Medicine, WeRlwm Pork Hospital, Slough, Berkshire 512 aHL, UK Reference I British Thoracic Society Standards of Cam comrrrilan. Slokmem on mollgiwnl mesoilelioma in the Untied K.ingdom Thorax 2001 ;56250-65. disease occurring in any individual is influ- require a claimant w prove which fibre or rnccd by multiple factors, the outcome of inherited and acquired susceptibility and environmental precipitants. In the case of mesmhellome, a very heavily asbestos ex- fibres, inhaled in whose employment in precisely what circumstances, caused or set off or contributed [o the process by which one or more meso[helial cells become malisnant" . Asymptomotic pulmonary involvement in RA Dewson ei al' fount HRCT evidence of ftbros- posed individual mayhave ame in 10 lifetime disk of the disease . Most of us,with very small incidental exposures, have about a one in 1 million annual risk . The risk varies with the He concluded that breach of duty on the pan of both defendants caused the mesalhe{ioma . Both cans err soon to be considered by the Goun of Appeal and the outcome will ing alvcoll[Is CFA) in 19% of 150 outpatients with rheumatoid arthritis (RA) .The presence of FA did nut relate to previously described predisposing factors such as male sex, nodular length and Intensity of exposure, as assessed . by the individual's occupational history. we know Gum animal5wdksthat asbestos fibres do indeed cause mesothelioma, w this evidence of a dose edited association strongly suggests [hat factors other then Transformdon of one cell are alto. and critically,responsiblc (m the disease. Among these is likely to be inflammation in thepleura initiated by the determine whether the many mewtheliuma violins who happen to haw derived their asEesms exposure from mwe than one source am to be left without redress. R Rudd Medical Ontology Si lkxriit .lmew's Hwpibl, London EC1A 7BE, UK; R.M ..0uddOqmul.7c.uk and/or eztraarucular disease, disease duration and s.everity Moreover, the authors did not find any relation with respiratory symp " toms such as dyspmra or cough, chest radio. graphic appearance of FA, or restrictive pattern at pulmonary function tesizihe only features significantly associated with FA on the HRGT scam were the presence of bibasal trickles and the reduction in carbon monox~ presence of many fibres . Such inflammation J Moore-Gillon ids Transfer factor (Tucol . These findings err may not only result in malignant transforma- Respiratory Medicine Delimited, 5t Bonholonew's mare difficult to explain, especially consider . tion, of many ills, bin may also inhibit the Hospital, London EG1A 76E, UK log that PA was defined as an HRCT pattern wynv .lFwraKJrd .wm