Risk of Misdiagnosis, Health-Related Quality of Life, and BMI in Patients Who Are Overweight With Doctor-Diagnosed Asthma

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1 CHEST Originl Reserch Risk of Misdignosis, Helth-Relted Qulity of Life, nd BMI in Ptients Who Are Overweight With Doctor-Dignosed Asthm Stephen Scott, MB; Jcqueline Currie ; Pul Albert, MBBS ; Peter Clverley, MBBS ; nd John P. H. Wilding, DM ASTHMA Bckground: Obesity nd sthm both cuse brethlessness, nd there is risk of misdignosis of sthm in ptients who re obese. Impired helth-relted qulity of life (HRQoL) nd incresed BMI increse physicin ttendnce rtes, incresing this risk. We explored the possibility of misdignosis nd the reltionship between BMI, HRQoL, nd other trditionl mesures of sthm severity in subjects who were obese with doctor s dignosis of sthm. Methods: Dt were obtined from subjects who were overweight with physicin-dignosed sthm screened s prt of nother study, including bronchil provoctive concentrtion of methcholine to produce 20% fll in (PC 20 ) or reversibility to bronchodiltors, HRQoL mesured using generic (Short Form-36 [SF-36]) nd disese-specific (St. George Respirtory Questionnire nd Impct of Weight on Qulity of Life-Lite) questionnires. The frction of exhled nitric oxide (F ENO ), height, weight, nd topic sttus were lso recorded. Results: Of 91 subjects (men BMI, 38 kg/m 2 ; men %, 85.8%; men /FVC, 70.0%; men F ENO, 25.1 prts per billion tking men chlorofluorocrbon-beclomethsone-equivlent dose of 1,273.5 m g/d), 36.3% hd no bronchil hyperresponsiveness (possible misclssifiction of sthm dignosis.) The BMI nd HRQoL were significntly relted: The St. George Respirtory Questionnire totl ( r , P,.001), SF-36 physicl helth subtotl ( r , P,.001), SF-36 mentl helth subtotl ( r , P,.001), nd Impct of Weight on Qulity of Life-Lite totl ( r , P,.001) showed no reltionship to irwys inflmmtion nd bronchil rectivity. There ws no significnt difference in qulity-of-life scores in subjects with or without bronchil hyperrectivity. Conclusions: We found evidence of misdignosis of sthm in subjects who were obese. The BMI in subjects who were obese nd hd sthm negtively correltes with the HRQoL, which my relte to the dignostic uncertinty nd requires further explortion. Tril registry: ISRCTN Register; No.: ; URL: CHEST 2012; 141(3): Abbrevitions: ATS 5 Americn Thorcic Society; F eno 5 frction of exhled nitric oxide; HRQoL 5 helth-relted qulity of life; IQR 5 interqurtile rnge; IWQoL-Lite 5 Impct of Weight on Qulity of Life-Lite; PC 20 5 provoctive concentrtion of methcholine to produce 20% fll in ; SF-36 5 Short Form-36; SGRQ 5 St. George Respirtory Questionnire Asthm is chrcterized by vrible irflow limittion together with bronchil hyperresponsiveness to stimuli, resulting in irwy nrrowing nd symptoms of wheeze nd brethlessness. 1,2 The prevlence of physicin-dignosed sthm is incresing, in prt becuse of link between sthm nd obesity. 3 Severl mechnisms led to sthm-like symptoms in ptients who re obese, 4,5 including the mechnicl effects of incresed BMI on lung volumes, incresed work of brething, nd incresed relese of dipokines from dipose tissue, lthough whether these mechnisms re ssocited with objectively demonstrted bronchil hyperresponsiveness is less certin. 6 A s brethlessness is common symptom of both sthm nd obesity, there is risk of dignostic misclssifiction of sthm, view supported by Cndin study tht found one-third of subjects with prior physicin dignosis of sthm hd no evidence of sthm s judged by symptoms, lung function, nd bronchil chllenge testing Originl Reserch

2 Obesity, like sthm, ffects helth-relted qulity of life (HRQoL), 8,9 nd incresed BMI hs been relted to incresed generl prctitioner ttendnce rtes. 10 Since HRQoL nd sthm control re relted, 11 it is esy to see how helth impirments rising from obesity could be ttributed to sthm, further incresing the likelihood of misdignosis. We hypothesized tht ptients who re obese with physicin-dignosed sthm re t risk for misdignosis of sthm nd would hve significntly impired HRQoL. Also, BMI my correlte more strongly with HRQoL thn trditionl mrkers of sthm severity. To test this hypothesis, we used dt from n interventionl study investigting weight loss in ptients with sthm who were obese (ISRCTN ), in which we recruited subjects with dignosis of sthm receiving respirtory therpy with BMI 30. At the screening visit, we collected dt bout bronchil hyperresponsiveness nd helth sttus, both generic nd disese-specific, to estblish which spects of their bseline condition relted best to their helth problems. Additionlly, the reltionship of exhled nitric oxide ( mrker of irwys inflmmtion in sthm 12 ) nd bronchil responsiveness to HRQoL were secondry outcome mesures. Mterils nd Methods Ptient Selection Subjects were recruited from clinics t University Hospitl Aintree or by poster dvertisement, with self-reported BMI 30 kg/m2, ged 18 to 65 yers, either nonsmokers or ex-smokers of. 2 yers, nd tking sthm mediction. Individuls receiving long-term orl corticosteroid therpy, those with other significnt comorbidities, or those reporting n excerbtion within the previous 2 weeks were excluded. Four subjects hd BMI, 30 kg/m 2. In these, the BMI ws 28 kg/m2 nd inclusion did not significntly ffect the outcome, so they were included in the intention to recruit nlysis. The study ws pproved by the Sefton Locl Ethics Committee Institutionl Review Bord (04/Q1508/51), nd ll subjects gve written informed consent. Before their visit, subjects withheld mediction s per Americn Thorcic Society (ATS) guidelines for chllenge testing. 13 Demogrphic dt, including mediction history nd physicl exmintion, were recorded. Weight nd height were mesured using clibrted scles nd stdiometer, respectively, nd BMI (kg/m 2 ) ws clculted. Venous blood ws drwn to exclude significnt Mnuscript received April 26, 2011; revision ccepted August 1, Affilitions : From the Clinicl Science Centre, University Hospitl Aintree, Liverpool University, Liverpool, Englnd. Funding /Support: This work ws supported by project grnt from Asthm UK. Correspondence to: Stephen Scott, MB, Deprtment of Respirtory Medicine, Countess of Chester Hospitl, Liverpool Rd, Chester, CH2 1UL, Englnd; e-mil: stephenscott2@nhs.net 2012 Americn College of Chest Physicins. Reproduction of this rticle is prohibited without written permission from the Americn College of Chest Physicins ( site/misc/reprints.xhtml ). DOI: /chest nemi, hypothyroidism, hyperthyroidism, dibetes, or other biochemicl bnormlities tht might dversely ffect helth sttus. Questionnires Prticipnts completed the St. George Respirtory Questionnire (SGRQ), 14 Short Form-36 (SF-36), 15 nd Impct of Weight on Qulity of Life-Lite (IWQoL-Lite) 16 questionnires. These questionnires re vlidted to ssess the effect of respirtory disese, generic fctors, nd weight, respectively, on qulity of life. Atopy Atopic sttus ws determined using skin prick testing with bttery of common erollergens. A positive result ws defined s t lest one response with whel dimeter 3 mm or lrger thn control response fter 15 min. Exhled Mrkers of Inflmmtion Prticipnts bstined from cffeinted drinks nd food for 12 h before testing. The frction of exhled nitric oxide (F eno ), mesured in prts per billion, ws mesured using chemiluminescence nlyzer (NIOX; Aerocrine) t flow rte of 50 ml/s, s per Europen Respirtory Society nd ATS guidelines. 17 Bronchil Responsiveness Methcholine inhltion testing ws performed using the fivebreth dosimeter method, s per ATS guidelines. 13 Airwys responsiveness to methcholine ws expressed s the provoctive concentrtion of methcholine to produce 20% fll in (PC 20 ). Subjects unble to undergo methcholine testing due to n 50% predicted underwent spirometry with bronchodiltor response to nebulized slbutmol. Bronchil hyperresponsiveness ws defined by 20% drop in with 8 mg/ml methcholine or n increse 15% nd 200 ml in from bseline following nebulized slbutmol. Sttisticl Methods This ws n observtionl study with the smple size determined by the number of subjects recruited for n interventionl tril powered for subjects who were obese nd hd sthm with bronchil hyperresponsiveness. Ctegoricl vribles re expressed s percentges of totl subjects nd compred using x 2 test. Continuous vribles re expressed using men SD nd compred using the Student unpired t test if normlly distributed. Nonnorml distributions determined by Shpiro-Wilk testing re expressed using medin nd interqurtile rnge (IQR). Correltions were performed between normlly distributed vribles using Person correltions two-tiled tests, nd between nonnormlly distributed vribles using Spermn tests. PC 20 nd F eno were log trnsformed to provide norml distributions before correltions were clculted using Person tests. A wek correltion ws defined s r , moderte correltion s r , nd strong correltion s r The SPSS softwre, version 16 for Windows (SPSS Inc) ws used for clcultion. Significnce ws determined if P,.05. Significnce of comprisons of multiple vribles ws djusted using the Bonferroni correction. Results Subject Recruitment In totl, 397 subjects underwent telephone screening, s outlined in Figure 1. Of these, 91 subjects were retined in the nlysis. CHEST / 141 / 3 / MARCH,

3 Subject Chrcteristics: All Subjects Dt on the demogrphic chrcteristics, pulmonry function, nd Feno of the study prticipnts re summrized in Tble 1. Subjects were obese with reltively well-preserved lung function. Five subjects were tking inhled steroid mediction but did not know their inhled dose, while four were not using inhled steroid. Short-cting b gonists were prescribed for ll. Fifty-five subjects (60.4%) used longcting b gonists. One subject refused skin-prick testing. The dose of inhled steroid (chlorofluorocrbonbeclomethsone-equivlent) wekly relted to % predicted ( r , P 5.007) nd /FVC ( r , P 5.017), but not PC 20. There ws no significnt difference in PC 20 (P 5.630), presence of bronchil hyperresponsiveness ( P 5.673), % predicted ( P 5.055), or /FVC ( P 5.179) between those tking nd those not tking long-cting b gonists. The BMI wekly correlted with the PC 20 ( r 50.29, P 5.033) nd F eno (r , P 5.025). Questionnires SF-36 dt were not vilble in one subject due to completion error. Questionnire scores for the whole group re shown in Tble 2. The men (SD) Tble 1 Demogrphics, Medicl Chrcteristics, Pulmonry Function, nd Bronchil Responsiveness to Methcholine nd FENO for All Subjects Vribles Dt Age, y 49.2 (9.6) Femle sex 60/91 (65.9) Ex-smokers 32/91 (35.2) Pck-yer (ex-smokers) 17.2 (19.3) BMI, kg/m 2 38 (7) Weight, kg (22.6) Subjects with topy 61/90 (67.8%) Dose of inhled steroids, mg/d 1,273.5 (937.1), % predicted 85.8 (19.8) FVC, % predicted (17.2) /FVC, % 70 (10.6) PC 20, mg/ml (6.71) F eno, ppb 25.1 (21.5) Numbers expressed s men (SD) or No. cses/no. in group (%). F eno 5 frction of exhled nitric oxide; PC 20 5 provoctive concentrtion of methcholine to produce 20% fll in ; ppb 5 prts per billion. totl scores were: SGRQ, 44.4 (17.0); SF-36 (mentl helth subtotl), 56.9 (21.2); SF-36 (physicl helth subtotl), 52.0 (22.9); nd IWQoL-Lite, 39.1 (21.6), with good correltions between them ( P,.001) (Fig. 2). HRQoL, Pulmonry Function, Bronchil Responsiveness, BMI, nd Airwys Inflmmtion The influence of pulmonry function, irwys responsiveness, BMI, nd irwys inflmmtion on HRQoL re shown in Tble 3. Airwys Inflmmtion nd HRQoL There were no significnt correltions with F eno nd SGRQ domins or SF-36 domins following Bonferroni correction. There were sttisticlly significnt wek correltions found with F eno nd IWQoL- Lite physicl functioning ( r , P 5.004), public distress ( r , P 5.008), nd totl ( r , P 5.003) domins. BMI nd HRQoL St. George Respirtory Questionnire: The BMI correlted modertely with the Activity domin of the SGRQ ( r , P,.001) nd wekly with the SGRQ totl domin ( r , P,.001), but not symptoms. Figure 1. Consort digrm shows study orgniztion. Short Form-36: There were moderte negtive correltions between the BMI, physicl function ( r , P,.001), nd physicl helth subtotls ( r , P,.001), nd wek negtive correltions with the body pin ( r , P,.001), generl helth ( r , P 5.005), role emotionl ( r , P 5.004), mentl helth ( r , P 5.033), nd mentl helth subtotls ( r , P,.001). (Note 618 Originl Reserch

4 Tble 2 Questionnire Scores for All Subjects for SGRQ, SF-36, nd IWQoL-Lite Domin Score, Men (SD) SGRQ domin Symptoms 61.1 (18.4) Activity 54.7 (22.2) Impcts 33.2 (17.6) Totl 44.4 (17.0) SF-36 domin Role, physicl 53.3 (43.3) Body pin 62.5 (25.8) Generl helth 50.0 (22.3) Vitlity 43.5 (23.3) Socil functioning 65.3 (26.2) Role, emotionl 61.1 (42.6) Mentl helth 64.4 (19.3) Mentl helth, totl 56.9 (21.2) Physicl helth, totl 52.0 (22.9) IWQoL-Lite domin Physicl function 42.8 (25.5) Self-esteem 50.6 (28.0) Sexul life 31.3 (56.2) Public distress 25.0 (30.0) Work 18.8 (37.5) Totl 39.1 (21.6) IWQoL-Lite 5 Impct of Weight on Qulity of Life-Lite; SF-36 5 Short Form-36; SGRQ 5 St. George Respirtory Questionnire. Distribution nonnorml. tht lower score indictes worse HRQoL for SF-36). Impct of Weight on Qulity of Life-Lite: There were moderte correltions between the BMI, physicl function ( r , P,.001), public distress ( r , P,.001), nd totl domins ( r , P,.001), with wek correltion between the BMI nd work domins ( r , P,.001). FEV 1 % Predicted, FVC % Predicted, nd HRQoL There were no significnt correltions between ny mesures of qulity of life nd % predicted or FVC % predicted. Bronchil Hyperresponsiveness s n Explntory Vrible Subjects with bronchil hyperresponsiveness (n 558, 63.7%) were compred with those without (n 533, 36.3%), nd subject chrcteristics for ech group re summrized in Tble 4. Those with bronchil hyperresponsiveness (medin PC 20, 1.64 [IQR 3.48] mg/ml) were younger (47.6 [9.7] yers vs 52.0 [9.0] yers, P,.05), hd lower % predicted (81.3% [21.3%] vs 93.7% [13.7%], P,.05), nd lower /FVC (67% [11.3%] vs 75% [6.3%], P,.05). There ws no significnt difference in FVC % predicted. The F eno (medin [IQR]) ws significntly greter (19.1 [22.8] ppb vs 15 [16.2] ppb, P.05), nd the percentge with topy ws greter in the bronchil hyperresponsive group (78.9% vs 48.5%, P,.05), s were ex-smokers (43.1% vs 21.2%, P.05). Between groups there ws no significnt difference in femle sex, BMI, dose of inhled steroids, or those tking b gonists. There were no significnt differences in ny domin or totl scores for the SGRQ, SF-36 subtotls, or IWQoL-Lite ( Tble 5 ) between those with nd without bronchil hyperresponsiveness. There were no significnt correltions between PC 20 nd ny HRQoL domins. Discussion In group of subjects who were obese (men BMI 38.0 kg/m 2 ) with prior dignosis of sthm using inhled mediction, 36.3% did not demonstrte bronchil hyperresponsiveness. Although this does not exclude sthm, it hs high negtive predictive vlue 13 nd suggests misclssifiction of dignosis supported by lower F eno, 12 higher /FVC percentge, nd less topy in the unrective ptients. These ptients hd significnt helth impirment despite reltively well-preserved lung function, the disese nd weight-specific qulity of life being worse thn in previous published helthy popultions, There ws good correltion between the totl scores of ll questionnires, suggesting they were mesuring similr outcomes. The vrible tht correlted strongest with the degree of helth impirment ws BMI rther thn other trditionl mrkers of sthm severity, 1 tht is, irwys responsiveness (PC 20 ), lung function ( % predicted nd FVC % predicted), or irwys inflmmtion (F eno ). There ws no significnt difference in HRQoL between those with nd without bronchil hyperresponsiveness, gin suggesting less influence thn BMI. Our study supports the results of Aron et l, 7 who showed tht one-third of subjects with prior physicin dignosis of sthm hd no evidence of sthm s judged by symptoms, lung function, nd bronchil chllenge testing, nd it lso extends the observtions from more rigidly prespecified popultion, where it might be expected tht the incidence of hyperresponsiveness in ptients who re obese would be higher. 22 We hve shown consistent negtive correltion of incresing BMI with HRQoL s mesured by both generic nd disese-specific instruments. This effect ws much greter thn ny ssocitions with the degree of irwys inflmmtion s ssessed by F eno, which might hve been expected to trck sthm severity. 12,23 The presence of bronchil hyperresponsiveness itself ws not good discrimintor of impired helth sttus, while mediction use, specificlly long-cting bronchodiltors in ddition to inhled corticosteroids, ws CHEST / 141 / 3 / MARCH,

5 Figure 2. Sctterplots show the correltion of totl scores for the SGRQ nd IWQoL-Lite questionnires nd subtotls for mentl helth nd physicl helth scores for the SF-36 questionnire. IWQoL-Lite 5 Impct of Weight on Qulity of Life-Lite; SF-36 5 Short Form-36; SGRQ 5 St. George Respirtory Questionnire. neither different in the rective nd nonrective groups nor predictive of differences in helth sttus. As might be expected, rective individuls tended to hve mrginlly worse lung function, more obstruction, nd more topy, but none of these fctors would be relible discrimintor. A reduced qulity of life ssocited with obesity is relted to incresed ttendnce rtes to primry 620 Originl Reserch

6 Tble 3 Correltions (r Vlues Shown) Between Mesures of Pulmonry Function, Airwy Responsiveness, BMI, nd Airwy Inflmmtion Domin, % predicted FVC % predicted Log10 PC 20 BMI Log10 F eno SGRQ domin Symptoms Activity Impcts Totl SF-36 domin Physicl function Role, physicl Body pin Generl helth Vitlity Socil functioning Role, emotionl Mentl helth Physicl helth, subtotl Mentl helth, subtotl IWQoL-Lite domin Physicl function Self-esteem Sexul life Public distress Work Totl See Tble 1 nd Tble 2 legends for expnsion of the bbrevitions. P,.05 Bonferroni djusted. cre,10 where ptients hve the opportunity to report respirtory symptoms nd ech visit cn potentilly led to misclssifiction of sthm dignosis. Incresed physicin interction my explin some of the ssocition of sthm with obesity, nd cre must be tken when interpreting studies of sthm nd obesity bsed on self-reporting of sthm dignosis. It is likely tht the negtive correltion of body mss with HRQoL is due to generic effect, 9 s there were correltions cross ll questionnires nd we did not find significnt correltion between BMI nd the symptoms domin of the SGRQ, which includes questions on the frequency of cough, sputum, brethlessness, wheeze, nd excerbtions. Tble 4 Demogrphics, Medicl Chrcteristics, Pulmonry Function, Bronchil Responsiveness to Methcholine, nd FENO between Subjects With Bronchil Hyperresponsiveness, Defined s PC 20 Methcholine 8 mg/ml, nd Those Without Vribles Subjects With Bronchil Hyperresponsiveness (n 5 58) Subjects Without Bronchil Hyperresponsiveness (n 5 33) P Vlue Age, y 47.7 (9.7) 52.0 (9.0),.05 Femle sex 38/58 (65.5) 22/33 (66.7).911 Ex-smokers 25/58 (43.1) 7/33 (21.2),.05 Pck-yer (ex-smokers) 17.4 (20.7) 16.1 (14.1).882 BMI, kg/m (6.5) 38.5 (7.9).560 Weight, kg (21.6) (22.1).895 Subjects with topy 45/57 (78.9) 16/33 (48.5),.05 Dose of inhled steroids (chlorofluorocrbonbeclomethsone-equivlent), 1,370.9 (1033.5) 1,082.1 (688.0).186 mg/d, % predicted 81.3 (21.3) 93.7 (13.7),.05 FVC, % predicted (19) (13.5).498 /FVC, % 67 (11.3) 75.3 (6.3),.05 F eno, ppb 19.1 (22.8) 15.0 (16.2),.05 Tking SABA, % 57/58 (98.3) 32/33 (97).683 Tking LABA, % 36/58 (62.1) 19/33 (57.6).673 Numbers expressed s men (SD) or No. cses/no. in group (%). LABA 5 long-cting b gonist; SABA 5 short-cting b gonist. See Tble 1 legend for expnsion of other bbrevitions. Distribution nonnorml, therefore medin/iqr quoted. CHEST / 141 / 3 / MARCH,

7 Tble 5 Comprison of Questionnire Scores for SGRQ, SF-36, nd IWQoL-Lite Between Subjects With nd Without Bronchil Hyperresponsiveness Domin Subjects With Bronchil Hyperresponsiveness (n 5 58) Subjects Without Bronchil Hyperresponsiveness (n 5 33) P Vlue SGRQ domin Symptoms 63.0 (19.5) 57.7 (16.0).194 Activity 53.0 (21.4) 57.7 (23.7).332 Impcts 32.7 (15.8) 34.2 (26.6).710 Totl 43.9 (15.7) 45.2 (19.3).721 SF-36 domin Physicl functioning 51.5 (25.8) 57.2 (23.5).297 Role, physicl 41.7 (42.7) 59.9 (42.7).054 Body pin 55.4 (28.2) 66.5 (23.6).060 Generl helth 50.5 (24.1) 49.7 (21.3).870 Vitlity 45.6 (23.1) 42.3 (23.5).521 Socil functioning 60.5 (27.3) 68.1 (25.4).194 Role, emotionl 56.5 (42.1) 63.8 (43.0).435 Mentl helth 63.2 (21.5) 65.0 (18.1).673 Physicl helth, subtotl 48.9 (24.0) 53.7 (22.2).349 Mentl helth, subtotl 55.2 (22.8) 57.8 (20.4).585 IWQol-Lite domin Physicl function 47.3 (27.9) 40.2 (23.8).223 Self-esteem 51.8 (29.5) 49.9 (27.3).773 Sexul life 37.5 (65.6) 21.9 (50.0).080 Public distress 25.0 (42.5) 22.5 (30.0).304 Work 25.0 (46.9) 15.6 (37.5).123 Totl 43.3 (23.8) 36.7 (20.1).182 Numbers expressed s men (SD). Distribution nonnorml, therefore medin/iqr quoted. Mnn Whitney U test s test of significnce. Our study hs some limittions due to its observtionl nture nd use of dt from screening subjects for n interventionl study. Subject numbers were not eqully mtched between groups, but groups were well mtched for ge, weight, nd BMI. Although there were more ex-smokers in the bronchil hyperresponsiveness group, excluding ex-smokers from nl ysis did not lter outcomes. Our study entry criteri precluded the inclusion of ptients with norml BMI, nd so our dt re confined to ptients who were obese. There is no universlly ccepted definition of sthm, 1 nd ptients cn hve sthm without demonstrble bronchil hyperresponsiveness. Mny studies require the presence of bronchil responsiveness defined s PC 20 clculted by liner interpoltion of the log concentrtion to methcholine to cuse 20% fll in of, 8 mg/ml or reversibility of to inhled bronchodiltors of 15%. 13 We, therefore, used these criteri towrd mking our dignosis of sthm, which is supported by the evidence of less irwy inflmmtion, less irwy obstruction, nd less topy in those who did not show bronchil hyperresponsiveness. It is possible tht the use of inhled steroids resulted in improvement in bronchil responsiveness. 11 However, there ws no difference in the men dose of inhled steroid between those with nd without incresed bronchil responsiveness. The screening protocol ws not designed to mesure sttic lung volumes, nd therefore we re unble to show reltionship between HRQoL nd functionl residul cpcity or expirtory reserve volume, which re reduced in obesity 27,28 nd possibly linked to bronchil hyperresponsiveness. 22 We did however mesure FVC, which cn give n ide of lung volume, nd there ws no difference in FVC between those with nd without bronchil hyperresponsiveness nd no correltion between FVC nd PC 20 or HRQoL. The SGRQ is not specific for sthm but is vlidted s tool for sthm reserch, 29 with similr bility to discriminte mong groups of ptients bsed on sthm severity nd control compred with the sthm qulity-of-life questionnire. 30 Obesity increses the risk of other comorbidities, which my influence HRQoL. 31 We excluded these through screening. Previous studies of the impct of sthm on HRQOL exist, 32 nd the effect is multifctoril, including disese severity, pulmonry function, symptoms, nd other mesures, lthough little is known bout the impct of weight on this complex reltionship. 8 There re similr reltionships between the effect of BMI on HRQOL, 9 nd further work is required to explore these complex reltionships. We found significnt number of ptients with potentil misclssifiction of dignosis of sthm in popultion tht is obese. The strongest correltions with either generic or disese-specific HRQoL were 622 Originl Reserch

8 found with BMI. This hs some clinicl implictions. Much of modern sthm tretment is focused on symptom reduction, either by incresing the intensity of mintennce tretment (Gining Optiml Asthm Control [GOAL] 33 ) or djusting the dily tretment regimen (Single Inhler for Mintennce nd Reliever Therpy [SMART] 34 ). Applying such pproches to ptients who remin s symptomtic s our ptients, who were nonrective nd obese, might be hrmful. The rective nd nonrective groups reported similr degrees of symptom intensity nd used similr mounts of sthm tretment. Future studies should consider whether therpy cn be withdrwn effectively in these ptients who re obese nd receiving more therpy. Certinly more robust initil dignostic pproch might sve time nd money over the long term by identifying ptients whose sthm corresponds to more conventionl dignostic criteri. These dt emphsize the complex problems of identifying respirtory disese ccurtely in subjects who re obese. Future work is needed to study the impct of weight loss in this ptient group nd its impct on HRQoL. Acknowledgments Author contributions: Dr Scott is the gurntor nd tkes responsibility for the integrity of the work. Dr Scott: collected nd nlyzed the dt, undertook the sttisticl nlysis, nd wrote the initil nd finl drfts of the mnuscript. Ms Currie: helped to collect the dt nd reviewed the mnuscript. Dr Albert: helped to collect the dt nd reviewed the mnuscript. Dr Clverley: helped to conceive of the study nd ssisted with writing the mnuscript nd the revision. Dr Wilding: conceived of the study nd ssisted with writing the mnuscript nd the revision. Finncil/ nonfinncil disclosures: The uthors hve reported to CHEST the following conflicts of interest: Dr Albert hs received speker fees for meetings on COPD nd sthm (GlxoSmithKline, Astr-Zenec, nd Pfizer). Dr Wilding hs received grnt support, lecture fees, nd consultncy fees from phrmceuticl nd device compnies in reltion to reserch into obesity, dibetes, nd sleep pne, but none in reltion to obesity nd sthm (Astr-Zenec, Astells, Boehringer Ingleheim, Bristol Myers Squibb, Johnson&Johnson, Lilly, Novo Nordisk, Snofi, Prosidion, Resmed). Drs Scott nd Clverley nd Ms Currie hve reported tht no potentil conflicts of interest exist with ny compnies/orgniztions whose products or services my be discussed in this rticle. Role of sponsors : The sponsor hd no role in the design of the study, the collection nd nlysis of the dt, or in the preprtion of the mnuscript. Other contributions: This work ws performed t the Clinicl Science Centre, University Hospitl Aintree, Liverpool University, Liverpool, Englnd. Other contributions: We re grteful for the help of ll the stff in the Respirtory Lbortory t University Hospitl Aintree, to Ms Jcqueline Currie for her help in the conduct of the study, nd especilly to our ptients for giving up their time to prticipte. References 1. British Thorcic Society Stndrds of Cre Committee. BTS sttement on criteri for specilist referrl, dmission, dischrge nd follow-up for dults with respirtory disese. Thorx ;63(suppl 1 ):i1-i Btemn ED, Hurd SS, Brnes PJ, et l. Globl strtegy for sthm mngement nd prevention: GINA executive summry. Eur Respir J ;31 (1 ): Rönmrk E, Andersson C, Nyström L, Forsberg B, Järvholm B, Lundbäck B. Obesity increses the risk of incident sthm mong dults. Eur Respir J ;25 (2 ): Shore SA. Obesity nd sthm: cuse for concern. Curr Opin Phrmcol ;6 (3 ): Beuther DA, Weiss ST, Sutherlnd ER. Obesity nd sthm. Am J Respir Crit Cre Med ;174 (2 ): Schchter LM, Slome CM, Pet JK, Woolcock AJ. 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