Asthm Dignosis nd Obesity ORIGINAL ARTICLE Asthm Dignosis Is Not Associted With Obesity in Popultion of Adults From Mdrid P Brrnco, 1 F Grcí-Río, 2 J Olivres, 2 V López-Crrsco, 1 R Álvrez-Sl, 2 S Quirce 1,3 1 Allergy Deprtment, Hospitl L Pz, IdiPz, Mdrid, Spin 2 Pulmonology Deprtment, Hospitl L Pz, IdiPz, Mdrid, Spin 3 CIBER de Enfermeddes Respirtoris CIBERES Abstrct Bckground: Severl studies hve suggested reltionship between sthm nd obesity; however, this reltionship is uncler when obesity is compred with bronchil hyperresponsiveness to methcholine. Aim: To determine whether obesity is ssocited with dignosis of sthm. Methods: We conducted cross-sectionl study in popultion of Spnish dults in the north of Mdrid, Spin between 2003 nd 2007. The ptients included hd experienced sthm symptoms during the previous yer, but hd rtio of forced expirtory volume in the fi rst second of expirtion (FEV 1 ) to forced vitl cpcity (FVC) of >70%. Dignosis ws confi rmed by the presence of symptoms nd demonstrtion of bronchil hyperresponsiveness to methcholine. Obesity ws mesured by body mss index (BMI). Adjusted odd rtios (OR) were obtined by logistic regression. Results: Of totl of 1424 ptients included, 251 (17.6%) were dignosed with sthm. These ptients were younger (P<.001) nd hd lower BMI (P<.001) nd lung function prmeters (FEV 1 nd FEV1/FVC rtio) thn individuls without sthm (P<.001). After djusting the model for ge, gender, bseline FEV 1, nd FEV 1 /FVC rtio, ptients with overweight or obesity were not more frequently dignosed with sthm thn those with norml weight (OR, 0.848 [95% confi dence intervl (CI), 0.59-1.20]; nd OR, 0.616 [95% CI, 0.38-0.99], respectively). In ddition, obese mles were more frequently dignosed with sthm thn obese femles (P<.041). Conclusions: In this study, obesity nd overweight were not ssocited with dignosis of sthm bsed on the presence of consistent symptoms nd demonstrtion of irwy responsiveness to methcholine. Key words: Asthm. Obesity. Body mss index. Airwy hyperresponsiveness. Resumen Fundmento: Vrios estudios sugieren que l obesidd es un fctor de riesgo pr pdecer sm, lo que no siempre se confi rm cundo se compr l obesidd con l hiperrectividd bronquil (HRB) en pcientes con síntoms de sm. Objetivo: Determinr si l obesidd se soci con el dignóstico de sm, confi rmdo por presenci de síntoms e HRB metcolin. Pcientes y Métodos: Se relizó un estudio trnsversl en poblción dult del Áre Norte de Mdrid entre 2003 y 2007. Se incluyeron sujetos que hbín pdecido síntoms de sm en el último ño, con un FEV 1 /FVC>70% y que precisbn un prueb de metcolin pr confi rmr el dignóstico. L obesidd se defi nió según el índice de ms corporl (IMC). Se plicó un modelo de regresión logístic pr clculr odd rtios (OR) justds. Resultdos: Se estudiron 1.424 sujetos y se dignosticron de sm 251 sujetos (17,6%) que, comprdos con los 1.173 no dignosticdos de sm, ern más jóvenes y presentbn un IMC y prámetros de función pulmonr (FEV 1, FEV 1 /FVC) más bjos (p<0,001). Trs justr el modelo por edd, sexo, FEV 1 bsl y FEV 1 /FVC el dignóstico de sm no fue más prevlente en los sujetos obesos o con sobrepeso que en los sujetos con peso norml (OR 0,848, IC95% 0,59-1,20 y OR 0,616, IC95% 0,38-0,99, respectivmente). El dignóstico de sm fue más frecuente en hombres obesos que en mujeres obess (p=0,041). Conclusiones: L obesidd y el sobrepeso no se sociron con el dignóstico de sm estblecido por l presenci de síntoms e HRB metcolin. Plbrs clve: Asm. Obesidd. Índice de ms corporl. Hiperrectividd bronquil.
541 P Brrnco et l Introduction Asthm nd obesity re common disorders with n enormous impct on public helth. It hs been estimted tht up to 65% of the dult popultion of the United Sttes of Americ is obese or overweight [1], while in Spin bout 15% of the popultion is obese nd 39% is overweight [2]. These figures hve incresed progressively in recent yers. Although bronchil sthm ffects smller proportion of people, its prevlence hs lso incresed in the lst few decdes. According to the Centers for Disese Control nd Prevention, the prevlence of sthm in North Americn children incresed from 3.6% in 1980 to 5.8% in 2003 [3]. In Spin, the prevlence of sthm incresed by 0.26% per yer from 1991 to 2001 [4]. Epidemiologicl dt hve led some reserchers to suggest tht obesity is risk fctor for the development of new-onset sthm, with odds rtios (OR) of between 1.1 nd 3.0 when compring the highest body mss index (BMI) with the lowest BMI ctegories nd the effect is pprently stronger in women [5]. A met-nlysis investigting overweight nd obesity s risk fctors for incidentl sthm showed tht both conditions progressively incresed the odds of incident sthm nd tht the strength of this reltionship ws similr in men nd women [6]. The exct nture of this ssocition hs not been fully elucidted, nd methodologicl issues such s determining who hs sthm compred with who hs symptoms tht mimic sthm hmper mny studies [3]. However, mechnicl fctors or spects of systemic inflmmtion relted to obesity my contribute to the pthogenesis of sthm [2,7,8]. Simple obesity cn cuse n increse in irwy resistnce nd mild degree of irflow limittion [9]. Therefore, estblishing firm dignosis of sthm in obese ptients with or without irflow limittions would require confirmtion by n objective procedure, such s mesurement of irwy hyperresponsiveness. We report the results of crosssectionl study of popultion of dults from the north of Mdrid, Spin who were investigted for suspected sthm between 2003 nd 2007. The im of this study ws to determine whether obesity, mesured by BMI, is ssocited with dignosis of sthm, s estblished by the presence of symptoms nd demonstrtion of irwy responsiveness to methcholine. Methods Study Popultion Ptients were consecutively recruited from outptient sthm clinics t the Allergy nd Pulmonology Deprtments of L Pz Hospitl, Mdrid between 2003 nd 2007. All ptients were dults who, ccording to their llergist or pulmonologist, hd presented with symptoms suggestive of sthm (cough, shortness of breth, or wheezing) in the lst yer, with rtio of forced expirtory volume in the first second of expirtion (FEV 1 ) to forced vitl cpcity (FVC) of >70%, nd in whom it ws necessry to estblish the dignosis of sthm by mesuring irwy hyperresponsiveness (AHR) to methcholine. Ptients with contrindictions for methcholine chllenge testing s outlined in the Americn Thorcic Society (ATS) guidelines [10] were excluded. All ptients gve their written informed consent, nd the study ws pproved by the Ethics Subcommittee of the Reserch Committee of Hospitl Universitrio L Pz, Mdrid, Spin (code: HULP:PI-619). Vribles The vribles studied were ge, gender, smoking sttus, height (m), weight (kg), BMI, nd lung function (FVC, FEV 1, nd FEV 1 /FVC), which ws mesured immeditely before the methcholine chllenge test. The results of the methcholine chllenge test were considered positive or negtive. Definitions Asthm: Asthm ws defined s ctegoricl dichotomous vrible bsed on the presence of both consistent symptoms in the previous 12 months nd demonstrtion of AHR to methcholine. Obesity: The weight nd height of ech ptient were mesured in street clothes without shoes immeditely before performing the methcholine chllenge test. BMI (kg/m 2 ) ws clculted for ech ptient nd ctegorized s follows: norml weight, BMI <25 kg/m 2 ; overweight, BMI 25.0-29.9 kg/m 2 ; nd obese, BMI 30 kg/m 2. Spirometry nd Methcholine Chllenge Test Spirometry ws performed ccording to ATS recommendtions [11]. Methcholine chllenge tests were performed in both deprtments of the hospitl ccording to current guidelines [10], nd the spirometric reference vlues used were those reported by the Europen Community of Col nd Steel nd the Europen Respirtory Society in 1993 [12]. The methcholine chllenge test ws performed ccording to ATS recommendtions following the 5-breth dosimeter protocol [10]. In the Allergy Deprtment, testing ws conducted using n electronic dosimeter (Spir Elektro, Respirtory Cre Centre, Hmeelinn, Finlnd), with n output of 0.45 μl nd nebuliztion time of 0.6 seconds, nd the provoctive concentrtion cusing 20% drop in FEV 1 (PC 20 ) ws clculted. In the Pulmonology Deprtment, testing ws performed using bronchil erosol provoction system (APS, Jeger, Würzburg, Germny), with Medic-Aid SideStrem nebulizer (Medic-Aid Ltd, Bognor Regis, UK), nd the provoctive dose cusing 20% drop in FEV 1 (PD 20 ) ws clculted. This nebulizer ws clibrted to produce n output of 160 mg/ml with n irflow rte of 100 ml/s. A flow sensor in the expirtory port triggers solenoid tht exposes the nebulizer to compressed ir t 138 kp for bout 0.6 seconds to give clibrted output per puff of 9.0 μl. The nebulizer genertes heterodisperse droplets with medin erodynmic mss dimeter of 0.5 to 4 μm. AHR ws considered positive or present if there ws 20% fll in FEV 1 from bseline with PD 20 2.0 mg (9.9 μmol) of methcholine [13] or PC 20 (5-breth dosing) of 16 mg/ml of methcholine [10]. Sttisticl Anlysis Dt re expressed s men (SD) nd percentges. Univrite reltionships between dependent nd independent
Asthm Dignosis nd Obesity 542 vribles were explored using the t test. One-wy nlysis of vrince ws used to compre normlly distributed vribles, the Wilcoxon rnk sum test for skewed vribles, nd the χ 2 test for ctegoricl vribles. Univrite nd multivrite conditionl logistic regression models were constructed to determine the odds of hving sthm in different BMI ctegories fter djusting for the other vribles. For ll nlyses, 2-tiled P<.05 ws considered significnt. All nlyses were performed with the SAS sttisticl softwre pckge, version 9.1.3 (SAS Institute, Cry, North Crolin, USA). Results Study Popultion We included 1424 ptients, of whom 981 (86.9%) were from the Pulmonology Deprtment nd 443 (31.1%) were from the Allergy Deprtment. Men BMI ws 25.96 kg/m 2 (SD, 4.94). Norml weight ws recorded in 666 ptients (46.7%), overweight in 481 (33.8%), nd obesity in 277 (19.5%). Asthm ws dignosed in 251 ptients (17.6%). The results of univrite nlysis ccording to sthm dignosis re shown in Tble 1. Asthm ptients were younger nd hd Tble 1. Bseline Chrcteristics No. Asthm Asthm Totl P Vlue Ptients, n 1173 251 1424 Age, y, men (SD) 41.96 (16.94) 33.96 (14.67) 40.55 (16.83) <.001 BMI, kg/m 2, men (SD) 26.27 (5.01) 24.48 (4.27) 25.96 (4.94).001 Gender, n (%).549 b Mle 364 (81.4) 83 (18.6) 447 Femle 809 (82.8) 168 (17.2) 977 Smoking sttus, n (%).625 b Nonsmoker 810 (83.6) 159 (16.4) 969 Current smoker 184 (82.1) 40 (17.9) 224 Ex-smoker 139 (80.8) 33 (19.2) 172 FVC, L, men (SD) 3.800 (1.142) 4.229 (3.406) 3.875 (1.773).156 FEV 1, L, men (SD) 3.274 (.986) 3.321 (.850) 3.283 (.963).440 FEV 1, % predicted, men (SD) 86.48 (9.66) 82.88 (11.16) 85.84 (10.03) <.001 FEV 1/FVC, men (SD) 0.867 (.115) 0.829 (.111) 0.860 (.112) <.001 Abbrevitions: BMI, body mss index; FEV 1, forced expirtory volume in the fi rst second of expirtion; FVC, forced vitl cpcity. t test. b χ 2 test. Tble 2. Assocition Between Body Mss Index nd Asthm Dignosis (Symptoms nd Bronchil Hyperresponsiveness) BMI ctegory Asthm No sthm Totl OR Adjusted OR No. (%) No. (%) No. (%) (95% CI) (95% CI) b Norml weight, BMI<25 kg/m 2 125 515 666 (22.7%) (77.3%) (46.8%) Overweight, BMI 25-29.9 kg/m 2 72 409 481 0.6 0.848 (15%) (85%) (33.8%) (0.44-0.82) (0.59-1.20) Obese, BMI 30 kg/m 2 28 249 277 0.3841 0.616 (10.1%) (89.9%) (19.4%) (0.25-0.59) (0.38-0.99) All BMI ctegories 251 1173 1424 (17.6%) (82.4%) (100%) Abbrevitions: BMI, body mss index; CI, confi dence intervl; FEV 1, forced expirtory volume in the fi rst second of expirtion; FVC, forced vitl cpcity; OR, odds rtio; PC 20, provoctive concentrtion cusing 20% drop in FEV 1; PD 20, provoctive dose cusing 20% drop in FEV 1. Geometric men: PC 20, 3.58 mg/ml; PD 20, 0.77 mg. b Model djusted for ge, sex, FEV 1, nd FEV 1/FVC t bseline.
543 P Brrnco et l lower BMI thn those without sthm (P<.001). No significnt differences were observed in smoking sttus ccording to sthm dignosis. Lung function spirometric prmeters (FEV 1 s percent predicted nd FEV 1 /FVC rtio) were significntly lower in sthm ptients thn in those without sthm (Tble 1). Reltion of Asthm to Body Mss Index The distribution of ptients with confirmed sthm is shown in Tble 2. After djustment for ge, gender, bseline FEV 1, nd FEV 1 /FVC rtio, ptients with overweight or obesity were not more frequently dignosed with sthm thn those with norml weight (OR, 0.848 [95% confidence intervl (CI), 0.59-1.20]; nd OR, 0.616 [95% CI, 0.38-0.99], respectively). Effects of Other Vribles A multivrite nlysis of gender distribution (Tble 3) for ptients clssified ccording to BMI nd sthm showed tht obese mles were more frequently dignosed with sthm thn obese femles (P=.041). Smoking dt (Tble 4) reveled no significnt differences. Incresing BMI hd no significnt Tble 3. Gender Clssifi ed According to Body Mss Index nd Asthm BMI Ctegory Asthm No Asthm Totl P Vlue No. (%) No. (%) No. (%) Norml weight.176 Mle 34 (18.9%) 146 (81.1%) 180 (27%) Femle 117 (24.1%) 369 (75.9%) 486 (73%) Totl 151 515 666 Overweight.051 Mle 37 (19%) 158 (81%) 195 (40.5%) Femle 35 (12.2%) 251 (87.8%) 286 (59.5%) Totl 72 409 481 Obese.041 Mle 12 (17%) 60 (83%) 72 (26%) Femle 16 (7.8%) 189 (92.2%) 205 (74%) Totl 28 249 277 All ptients 251 1173 1424 χ 2 test. Tble 4. Smoking Sttus Clssifi ed According to Body Mss Index nd Asthm BMI Ctegory Asthm No Asthm Totl P Vlue No. (%) No. (%) No. (%) Norml weight.731 Nonsmoker 99 (22.6) 340 (77.4) 439 (69.5) Current smoker 26 (20.2) 103 (79.8) 129 (20.4) Ex-smoker 16 (25) 48 (75) 64 (10.1) Totl 141 (22.3) 491 (77.7) 632 Overweight.700 Nonsmoker 42 (13.5) 270 (86.5) 312 (67.7) Current smoker 10 (14.9) 57 (85.1) 67 (14.5) Ex-smoker 14 (17.1) 68 (82.9) 82 (17.8) Totl 66 (14.3) 395 (85.7) 461 Obese.530 Nonsmoker 18 (8.3) 200 (91.7) 218 (80.1) Current smoker 4 (14.3) 24 (85.7) 28 (10.3) Ex-smoker 3 (11.5%) 23 (88.5) 26 (9.6) Totl 25 (9.2) 247 (90.8) 272 All ptients 232 1133 1365 χ 2 test.
Asthm Dignosis nd Obesity 544 Tble 5. FEV 1, FEV 1, nd FEV 1/FVC Dt of Asthm Ptients Clssifi ed According to BMI Norml Weight Overweight Obese P Vlue b No. (%) No. (%) No. (%) FEV 1, L 3.33 (0.791) 3.38 (0.100) 3.10 (0.719).32 FEV 1, % predicted 83.7 (11) 81.01 (9.6) 83 (14.3).23 FEV 1/FVC 0.83 (0.11) 0.81 (0.96) 0.83 (14).23 Abbrevitions: BMI, body mss index; FEV 1, forced expirtory volume in the fi rst second of expirtion; FVC, forced vitl cpcity. Results expressed s men (SD). b Anlysis of vrince. effect on spirometric results (FEV 1, FEV 1 /FVC rtio) in sthm ptients (Tble 5). Discussion We found tht obesity nd overweight, defined s BMI of 30 kg/m 2 nd 25-29.9 kg/m 2, respectively, were not ssocited with higher prevlence of confirmed sthm dignosis in popultion of dults from Mdrid. Similr results were found in nother Spnish study [14]. The distribution of BMI in this smple ws similr to the distribution in the generl popultion of Spin [2]. Although obesity hs been ssocited with severe sthm [15], the results of the Severe Asthm Reserch Progrm [16], did not find obesity to be more prevlent in severe sthm thn in milder sthm; therefore, further studies re necessry in this re. The popultion we describe hd n FEV 1 /FVC rtio >70% nd similr chrcteristics to those of the popultion reported in the min rticles [17-19] on the ssocition between excess weight nd AHR in ptients with symptoms of sthm. In the Europen Community Respirtory Helth Survey, AHR incresed with BMI in men but not in women [17]. In cse-control study from prticipnts in the Normtive Aging Study, high initil BMI ws ssocited with the development of AHR to methcholine (OR, 10; 95% CI, 2-6-37.9) when ptients in the highest BMI quintile were compred with those in the middle quintile. There ws lso liner reltionship between incresing BMI during the study period nd subsequent development of AHR [18]. In contrst, Schchter et l [19] showed tht, in group of 1971 dults, BMI ws ssocited with sthm symptoms (dyspne nd wheezing) but not with irflow obstruction or AHR. Tntisir et l [20] showed similr results in peditric popultion. Chnges in ntomicl nd respirtory function could cuse incresed symptoms of cough, shortness of breth, nd wheezing without ltering irwy behvior. Sutherlnd et l [21] studied 30 obese nd nonobese dult women with sthm nd observed tht chnges in respirtory function, especilly dynmic hyperinfltion, were more pronounced in obese individuls with bronchoconstriction; however, BMI ws independently ssocited with chnges in lung volume nd AHR. In our study, no significnt effects of incresing BMI on spirometric results were observed in sthm ptients. Slome et l [22] studied the effect on brethlessness nd AHR to methcholine in 49 nonsthmtic ptients (23 obese nd 26 nonobese) ged between 18 nd 70 yers. The uthors found tht obesity reduced lung volume, but did not lter the sensitivity of or mximl response to methcholine. However, obese ptients hd n enhnced perception of dyspne ssocited with greter pprent stiffness of the respirtory system nd my therefore be t greter risk of symptoms. Similr results were encountered by Mchdo et l [23]. In ddition, simulted obesity-relted chnges in lung volume incresed irwy responsiveness in len nonsthmtic ptients [24]. Some prospective studies hve suggested tht the reltionship between obesity nd sthm is stronger in women [25]; however, the difference in estimtes of effect between men nd women is usully smll. In rndom-effects metnlysis of dt from 7 studies, similr increse in the odds of incident sthm due to overweight nd obesity ws observed in men (OR, 1.46; 95% CI, 1.05-2.02) nd women (OR, 1.68; 95% CI, 1.45-1-94) [6]. In the present study, dignosis of sthm ws more common in obese men thn obese women clssified ccording to BMI. The cuse of bronchil inflmmtion in obese ptients with sthm ppers to be different from tht of topy [8,24]. It is now well estblished tht obesity is chrcterized by stte of chronic low-grde systemic inflmmtion. Adipose tissue secretes importnt regultory dipokines such s leptin, proinflmmtory dipokine, nd diponectin, which hs ntiinflmmtory properties [8]. It hs been suggested tht leptin my contribute to the incresed prevlence of sthm observed mong obese persons [8]; however, recent studies indicte tht the ssocition between obesity nd sthm is unlikely to be due to direct effect of leptin on irwy smooth muscle [26]. In the present study, dignosis of sthm ws confirmed in 17.6% of ptients bsed on symptoms of cough, shortness of breth, or wheezing. Aron et l [27] found tht bout one-third of obese nd nonobese individuls with physicin-dignosed sthm did not hve sthm when objectively ssessed. Therefore, sthm my be overdignosed in developed countries. Moreover, if symptoms in this group re due to cuses unrelted to sthm, then sthm mediction would be unlikely to ffect their symptoms. In fct, symptoms lone do not pper to be good guide for the dignosis nd tretment of sthm. In conclusion, lthough our study is subject to the limittions of cross-sectionl studies, obesity ws not ssocited with sthm in popultion of dults from the north of Mdrid.
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Effect of obesity on brethlessness nd irwy responsiveness to methcholine in non-sthmtic subjects. Int J Obes (Lond). 2008;32:502-9. 23. Mchdo D, Tvres B, Loureiro G, Conde B, Cemlyn-Jones J, Cldo G, Sous N, Chieir C, Pereir C. Body mss index nd irwy hyper-responsiveness in individuls without respirtory disese. Eur Ann Allergy Clin Immunol. 2008;40:130-7. 24. Wng LY, Cerny FJ, Kufel TJ, Grnt BJB. Simulted obesity-relted chnges in lung volume increses irwy responsiveness in len, nonsthmtic subjects. Chest. 2006;130:834-40. 25. Chen Y, Dles R, Tng M, Krewski D. Obesity my increse the incidence of sthm in women but not in men: longitudinl observtions from the Cndin Ntionl Popultion Helth Surveys. Am J Epidemiol. 2002;155:191-7. 26. Nir PN, Rdford K, Fnt A, Jnssen LJ, Peters-Golden, Cox PG. The effects of leptin on irwy smooth muscle responses. Am J Respir Cell Mol Biol. 2008;39:475-81. 27. Aron SD, Vndemheen KL, Boulet LP, Mclvor RA, Fitzgerld JM, Hernndez P, Lemiere C, Shrm S, Field SK, Alvrez GG, Dles RE, Doucette S, Fergusson D; Cndin Respirtory Clinicl Reserch Consortium. Overdignosis of sthm in obese nd nonobese dults. CMAJ. 2008;179:1121-31. Mnuscript received December 28, 2010; ccepted for publiction My 5, 2011. Dr Pilr Brrnco Hospitl Universitrio L Pz Allergy Deprtment Pº de l Cstelln, 261 28046 Mdrid E-mil: pbrrnco.hulp@slud.mdrid.org