ORIGINAL RESEARCH Open Access Montelukast for the high ...

journalCapriles Hulett et al World Allergy Organization Journal 2014 720httpwwwwaojournalorgcontent7120

ORIGINAL RESEARCH Open Access

Montelukast for the high impact of asthmaexacerbations in Venezuela a practical and validapproach for Latin AmericaArnaldo Capriles Hulett1 Maria Gonzalez Yibirin2 Amaris Garcia3 and Dollys Hurtado4

Abstract

Background Asthma affects mainly Venezuelarsquos urban and poor majority Exacerbations bring about a highdemand in health services thus becoming a significant public health problem In general asthma control programs(GINA) with use of inhaled steroid medications have proven effective although their implementation in real liferemains cumbersome Montelukast could be a useful and practical tool for these deprived socioeconomic sectors

Methods This real-life pilot study was conducted in a prospective double blinded placebo-controlled mannerwith randomized and parallel groups Asthmatics that had never used leukotriene modifiers were recruited andfollowed-up every three months The main outcome was the number of exacerbations meriting use of nebulizedbronchodilators administered by the health care system

Results Eighty-eight asthmatic patients were enrolled between children and adults Groups were comparable indemographic data previous use of other medications ACT scores pulmonary functions (Wright Peak Flow meter)allergy status (Skin Prick Test) as well as adherence to the prescribed Montelukast treatment By an intention to treat(ITT) a total of 64 patients were included for analysis For the three and six months time points the differencebetween placebo and Montelukast was found to be significant (p lt 003 and p lt 004 respectively) Such trendscontinued for the rest of the year but without statistical significance due to patient attrition

Conclusions This real-life pilot study shows that a simplified strategy with oral Montelukast was practical andeffective in controlling exacerbations in an asthmatic population of a vulnerable community from Caracas Such anapproach reinforces the role of primary care in asthma treatment

Keywords Asthma Asthma exacerbations Asthma control Montelukast Practical approach Deprived urbanmajorities Venezuela Latin America

IntroductionAsthma in Venezuela is a public health problem derivedfrom its high prevalence and significant impact due torecurrent exacerbations [1-5] About one third of asth-matics share severe asthma characteristics [6] Venezuelarsquospopulation is predominantly urban (90) and approxi-mately half of it [7] lives under variable conditions of pov-erty (Graffar Scalersquosa D and E) Asthma prevails in suchdeprived socioeconomic sectors [8] and a recent study of a

Correspondence arnaldocaprilesgmailcom1Centro Meacutedico de Caracas Centro Meacutedico Docente La Trinidad y Programade Medicina Comunitaria Allergology Unit Hospital San Juan de DiosCaracas VenezuelaFull list of author information is available at the end of the article

copy 2014 Capriles Hulett et al licensee BioMedCreative Commons Attribution License (httpdistribution and reproduction in any mediumDomain Dedication waiver (httpcreativecomarticle unless otherwise stated

vulnerable population in Caracas reflecting its urban andpoor majority supports such findings [9]The increase in exacerbation rates for the past 20 to

25 years represent asthmarsquos major impact one millionacute episodesyear for 28 million inhabitants [2] iscompelling evidence (data from the Ministry of Health -MoH - ambulatory network caring for 80 or more ofthe population) Furthermore in such settings asthmaexacerbations are often found second only to the febrilesyndrome and rarely overtaken by consultations fordiarrheas [2]An existing National Asthma Control Program [12]

patterned after the Global Initiative for Asthma (GINA)guidelines was last revised in 1998 but weakly

Central Ltd This is an Open Access article distributed under the terms of thecreativecommonsorglicensesby20) which permits unrestricted use provided the original work is properly credited The Creative Commons Publicmonsorgpublicdomainzero10) applies to the data made available in this

Capriles Hulett et al World Allergy Organization Journal 2014 720 Page 2 of 6httpwwwwaojournalorgcontent7120

implemented over the years Inconveniences related tothe use of inhaled medications [10] make among otherconsiderations a simplified asthma approach worth pur-suing [11] In analogy to oral rehydration therapies inthird world countries [12] use of an oral and for themost part innocuous medication (Montelukast MLK )seems particularly attractive for Venezuelarsquos urban andpoor majority context [8911]To address the impact from exacerbations a real-life

pilot project with Montelukast was carried-out in adouble blinded placebo-controlled manner for six monthsto be further prolonged over a year-long period Adher-ence [10] educational needs tobacco smoke exposure[13] and sustainability in time were among the many is-sues considered Inaction is not an option regarding thesocial determinants of asthma [1014]

Materials and methodsThis real-life pilot study was registered and auditedunder number 090267 by the clinical trials departmentof the Instituto Nacional de Higiene Rafael Rangel anofficial organization of the Venezuelan MoH The Insti-tutional Review Board of ldquoCentro Meacutedico de Caracasrdquoalso approved this study Funding was obtained fromLETI laboratories in Caracas Venezuela The study wasdouble blinded randomized and run in parallel groupsPatients including children with their representativessigned a consent form regarding the scope of the studyand the use of placebos The ldquoLos Erasosrdquo slum waschosen (see Figure 1) because it possessed [9] the livingconditions of 50 of the inhabitants of Caracas the capitalcity of Venezuela and is located near the private medicalcenter In addition this community demonstrated in aprevious evaluative survey the relationship betweenasthma and poverty A high prevalence of physician di-agnosed asthma (15) was found among its inhabi-tants with 23 of these patients in a non - controlstatus as determined by the ACT for both children andadults [9]Asthma diagnosis also carried a recent history of fre-

quent extra-domiciliary nebulizations for acute symp-toms relief The existing health care system [2] providesroutine rescue treatments dispensed with nebulizationsof a FenoterolIpatropium bromide inhalation solution(025 mgs05 mgs) at an age adjusted dosing (10 gttschildren - 20 gtts adults) diluted in 2ndash3 cc of 09saline No patients were admitted at any stage of preg-nancy nursing or having had previous use of leukotrienemodifiers however any other therapy was allowed andrecorded If during the course of the study a patient wasto become pregnant she would have to be withdrawnimmediately Patients and their families attended volun-tarily and were invited to participate in the study bymeans of information from slum community leaders and

word of mouth from neighbors Eagerly concerned fam-ilies made for children numbers come close to half ofthe participants along with very few adult asthmaticsmokersThe main variable was the number of exacerbations

(primary endpoint) needing rescue nebulizations with aFenoterolIpatropium combination administered at thehealth care system patients in need of assistance afterevening hours had to attend local hospitals nearby butoutside the community Close monitoring of the primaryoutcome was carried by monthly phone calls and de-tailed questioning during regular visits This project wasoriginally conceived for execution at the ambulatoryhealth facility (MoH) located within the communityhowever due to security concerns for the researchers itwas carried out in a private medical office (ACH) acrossthe street imposing limits on logistics particularly re-garding number of participantsA total of 88 known asthmatic patients (roughly 12

were children) were recruited The patients were between5 and 44 years of age and were either smokers or non-smokers Those patients who had not smoked cigarettesin the last 6 months were considered as non-smokers Thedaily consumption rate and the years of smoking were re-corded for those who reported tobacco use Asthmaticsbetween the ages of 5 and 12 were referred to as childrenwhile those 13 and up to 44 years of age were defined asadults in conformity with the ACT age ranges These ageconsiderations helped avoiding confusion with other re-spiratory syndromes such as early ages viral wheezing andchronic obstructive pulmonary disease in the elderly Thisdoes not imply however the existence of asthma outsideof these age rangesAsthmatics underwent a detailed clinical history and

physical examination (with an emphasis on co-morbiditiessuch as allergic rhinitis and flexural atopic dermatitis)Weight height body mass index pulse and blood pres-sure together with prick skin tests (Lancetters Hollister-Stier) for inhalant allergens (Greer Labs ALK-Abello)were recorded during the examination The best of threestanding Wright Peak Flow Meter measurements in Lmin(Ferraris Medical Holland New York USA) not varyingby more than 5 and performed before and 20 minutesafter 400 mcg of albuterol were obtained Patients wereadministered the ACT test according to age and receivedminimal oral information and a simple written one-pageeducational pictorial documentChildren received a 5 mg dosage of Montelukast daily

while adults received a 10 mg daily dosage Montelukastand placebo treatments were supplied in aluminum blisterpacks (chewable tablets for those 4ndash15 years of age 10 mgstablets for those 15ndash44 years of age) to be taken at nightprior to going to bed The counting of empty blister packsallowed for the estimation of adherence on return visits

Figure 1 The first photo taken from the nearby private medical facility Centro Meacutedico de Caracas portrays living conditions of thestudied community The second an aerial photo (below) provides a better insight into these aspects of Caracas


Visits were scheduled every 3 months and patients re-ceived a monthly phone call During those calls theywere reminded to take the prescribed medication and tofollow recommendations on environmental controlLikewise emphasis was placed on the date of the nexthearing and on returning the blister aluminum packs forproper evaluation of adherence Furthermore and mostimportantly they were urged to take note of exacerba-tions that merited medical care (extra domiciliary) fromthe local health care systemThis information was requested on every visit and

collated with the data obtained from the monthly

phone calls Patients were allowed to take any othersuitable medications to treat their asthma (except leu-kotriene modifiers) in an attempt to reflect a real lifesituation no further recommendations were givenDuring follow-up visits patients were questioned as towhether their rhinitis had improved had remained thesame or had worsened as an indirect means of evaluat-ing adherence

StatisticsThe sample size was calculated using as a reference astudy [15] of Infliximab vs placebo (Erin EM Leaker


BR Nicholson GC et al The effects of a monoclonalantibody directed against tumor necrosis factor-alphain asthma American Journal Respiratory Critical CareMedicine 2006 174 (7) 753ndash762) This study com-pared the number of exacerbations (primary endpoint)in asthmatic patients resulting in 72 of exacerbationsfor the placebo group vs 29 for the Infliximab groupWe needed at least 30 patients per group to show a dif-ference between the placebo and the Montelukasttreated group for a power of 80 The percentage ofpatients with acute exacerbations (primary end point)was evaluated by the Chi square test Alpha error levelfor all variables was 5

ResultsFrom the onset the groups were comparable with regardsto the use of asthma medication ACT test scores WPFMmeasurements and demographic data (age sex weightheight BMI blood pressure and pulse) No patient hadpreviously used MLK forty-six asthmatics comprised themedication and forty-two the placebo group (Table 1)During the intended first six months the number of

patients allowed for significant statistical analysis if childrenand adults were grouped together The loss of patientswhereby only 19 of the initial 88 recruited patients com-pleted the extended year-long treatment did not permitthisApproximately 57 of the asthmatic patients had a

positive (gt than 3 mm papule over negative control andread at 10 min) prick skin test to a mixture of mites(Dermatophagoides pteronyssinusDermatophagoides fari-nae) as well as to Blomia tropicalis which was in agree-ment with what had previously been reported in VenezuelaAs well lower rates of sensitization to other inhalant aller-gens did not reveal (epithelia molds grasses cockroachrodents) any significant difference between the groupsIn regards to the co-morbidities (average rhinitis diagno-

sis of 70 and flexural atopic dermatitis 8) in patients andthe functional aspects for the diagnosis of asthma (revers-ibility) no difference was observed among the groupsIn the case of children however a better response to

Table 1 Demographics

Montelukast Placebo p

Patients Ndeg 46 42

Age 1827+-1414 1688+-1381 069

Sex FM 1817 2715 093

Weight 4716+-2511 4596+-2849 O91

BMI 2148+-645 2130+_813 099

Mite allergy 5652 4762 074

Allergic Rhinitis 7826 6308 071

t studentChi2

bronchodilatadors (gt20 reversibility) was shown (80)There was a trend for improvement in the MLK group forthe WPFM and ACT scores though no significant differ-ences between the groups were detected during the year-long studyFollowing analysis allowed detecting during the first

6 months a significant difference between the groups inthe number of exacerbations needing assistance fromthe health care system (Figure 2) Although there wasnot a statistically significant difference in the second halfof the study a continued tendency for fewer exacerbationswith the use of MLK was observed We believe this wasdue to the small number of patientsAdherence to the medication was between 80 and

90 for the three and six months time points respectivelywith no significant differences observed between thegroups By adherence we meant a return of 70 or more ofconsumed tablets from the blister aluminum pack Pa-tients who received the active drug reported a significantldquoimprovementrdquo in their rhinitis symptoms (yesno) incomparison with the placebo group Three adverse effectsfrom the use of this medication were reported Two oc-curred in adults and were mild and unrelated to the treat-ment (one patient had a slight foot pain and the other hadan urticarial reaction that was medicated with Loratadine)One child had diarrhea but did not require suspension ofthe treatment An episode of diarrhea in an adult showedup in the placebo group which required suspension of thetreatment

DiscussionAsthma in Venezuela is an important public healthproblem [125] as evidenced by its high prevalence andsignificant impact due to exacerbations We attemptedto show that for Venezuelanrsquos urban and poor majoritycontext a reduction in the number of exacerbationsby regular use of Montelukast is an attainable goalVenezuelarsquos public health care system however persistson the view that asthma is mainly an acute problem [9]

1610 9

4246

43

25

50

0

10

20

30

40

50

60

3 6 9 12

Percentage

Montelukast Placebo

P =003P =004

Figure 2 Percentage of all patients with acute exacerbations inneed of rescue nebulizations at the local health system attendedby the group studied


Venezuela has approximately 28 million inhabitantswith 90 living [7] in low socio-economic urban areaswhich according to a WHO operational classificationcan be considered as ldquoslumsrdquo [16] In addition close to50 of the population is classified under Graffarrsquos D andE scale [717] where the greatest prevalence of asthma isfound [89] Furthermore asthma is a social disease [18]demanding approaches that should not discard the variedcultural elements surrounding itThe number of asthma exacerbations has increased

significantly over the past 20 years [29] coming closeto a million acute asthma episodesyear This surpassesthe number of exacerbationsyear [19] in the USA (apopulation ten times higher) by more than five timesThese asthma exacerbations occur primarily duringevening hours when these MoH outpatient health fa-cilities [29] are closed and increased security issuesbecome more apparent The significant absenteeismfrom school and work whereby 90 of childrensuffering from acute asthma do not attend school and50 of adults do not attend work rounds up asthmarsquosimpact [9]Venezuelarsquos National Asthma Control Program based on

the GINA guidelines (inhaled Beclomethasone) has beenonly weakly implemented and not revised since 1998 [12]Moreover data from a non-profit organization (PROVEA2006) points clearly for asthma to be underfunded [820]Since 2004 there has been a parallel health care systemrun by Cubans [21] which addresses a portion of theurban and poor majorities however no financial or clin-ical information is availableSuccessful asthma control strategies under the GINA

guidelines have been carried out in some areas of LatinAmerica [22] Inconveniences around the use of steroidinhaled medications [10] make for mitigating asthma ex-acerbations with simpler yet effective strategies [2324]For these vulnerable urban and poor majorities and inanalogy to oral rehydration therapies [12] for diarrheasand dehydration a paradigm for asthma is found wantingthis study is conceived within these limits Incidentallysimplifying asthma treatments has been a cornerstone ofsome of our previous efforts [2526]An important aspect of this real-life pilot study was the

double-blinded placebo-controlled design with monthlytelephone calls for main outcome monitoring (asthmaexacerbations meriting the use of nebulized FenoterolIpatropium Bromide bronchodilators in the health caresystem) nearly all urban households in Venezuela havea cell phone-line [27] Similar techniques have provenuseful in clinical settings [28] by increasing the degreeof reliability of predetermined outcomes Patient groupsat entry were comparable in their demographics ACTscores atopy (positive skin prick test to mites) and co-morbidities

An unexpected drawback however was the high attri-tion rate of patients as the study progressed through thefinal six months It was acknowledged from the begin-ning that this slum population was a hard one to studynot discarding cultural elements for the high dropoutrate The same was not carried out inside the commu-nity boundaries to attend the doctorrsquos office patientshad to climb a series of long staircases an elementwhich may have contributed to the high attrition rateOne of the lessons learned and an issue that must beseriously considered for future similar projects in urbanand poor settings is the need to maintain a high motiv-ation level among local community leaders patients andfamilies alike Most importantly any such program mustbe conducted physically within the host community anddealt ldquoin siturdquo with any issues that may arise These as-pects were not given the weight they deserved given theconcerns pertaining to the researchersrsquo securityThe opportunity offered during an exacerbation to ver-

bally educate and succinctly reinforce concepts with pic-torially written material should be taken advantage ofThis may be the only contact an asthmatic in Venezuelahas with the health care system A simple rule of tworsquos(2primes) might serve [29] to discern which patients are inneed of asthma control treatments Focus on primarycare remains pivotal when a simple approach as this isused Adherence issues as with any asthma interven-tions around the world need to be dealt with local andcultural factors Sustainability in relation to cost issues isan important consideration the recent expiration of theMLK patent [30] comes in rather conveniently if bulkquantities are to be needed for large scale programs AnIMS Health report for Venezuela [31] reveals a particu-lar and interesting reality a combination of a brandname FluticasoneSalmeterol 50050 Diskus for a onemonth treatment is 3 times more expensive than awhole month of Montelukast 10 mgs tablets such as theone employed in this study (US$ 16 vs US$ 5 respect-ively) As a comparison one pack of 20 cigarettes of acommon local brand costs US$ 13 and the minimummonthly wage is set at US$ 825 (April 2014)To conclude we believe that simplifying the treatment

of asthma by aiming to reduce exacerbations can beachieved with the administration of the oral medicationMontelukast If these results are reproduced they maygive a boost and allow for significant changes in theNational Asthma Control Programs and thus lessen theimpact that asthma exacerbations impose on the qualityof life of patients and families Given the contributoryrole that rhinitis [32] plays in the lack of control of asthmasymptoms the recent availability in the Venezuelanpharmaceutical market of a Desloratadine - Montelukastcombination [33] in one tablet (Desler Mreg) promptsfuture research in this area Though acknowledging the


need for further study we think these efforts point intothe right direction

EndnoteaGraffar Scale is a widely applied index that divides

population in five descending layers (A through E) accord-ing to a score of socioeconomic features [17]

Competing interestsThe authors declare that they have no competing interests

Authorsrsquo contributionsACH participated in study design and patient care MGY participated inlogistics support study design and statistical analysis AG participated inpatient care DH participated in study design and performed needed socialwork with the community All authors read and approved the finalmanuscript

AcknowledgementsTo the community and leaders of ldquoLos Erasosrdquo in particular to LimeyiMachado for liaison endeavors To Jhon Jimenez and Gustavo Latorraca MDMoH Distrito 1 Zona Metropolitana Caracas To the Medical Society andBoard of Directors Hospital Privado Centro Medico de Caracas To CarolinaReina Urdaneta Benitez certified public translator for her tireless extensivegrammatical review of the manuscript and helpful suggestions

Author details1Centro Meacutedico de Caracas Centro Meacutedico Docente La Trinidad y Programade Medicina Comunitaria Allergology Unit Hospital San Juan de DiosCaracas Venezuela 2LETI Laboratories Caracas Venezuela 3GeneralPractitioner ambulatory health care facility ldquoLos Erasosrdquo Health District 1Ministry of Health Caracas Venezuela 4Programa de Medicina ComunitariaCentro Meacutedico Docente La Trinidad Venezuela

Received 10 September 2013 Accepted 10 July 2014Published 4 September 2014

References1 Istuacuteriz G Guilarte A Meacutendez R Espantildea M Norma Oficial Venezolana del

Programa Nacional Integrado de Control del Asma Publicacioacuten del MSASDivisioacuten de Tuberculosis y Enfermedades Pulmonares patrocinado por elPrograma de las Naciones Unidas para el Desarrollo 1998

2 Capriles Hulett A Carvallo C Sanchez A Alfonzo I Kondracki ERevisioacuten sobre el estado del asma infantil en Venezuela y unapropuesta para su manejo Revista de la Sociedad Venezolana deAlergia Asma e Inmunologia 2004 VI(1)25ndash35

3 Aldrey O De Stefano M Capriles-Hulett A Prevalencia del asma infantilen Caracas ISAAC 2003 Revista de la Sociedad Venezolana de AlergiaAsma e Inmunologiacutea 2003 V(No 2)33ndash40

4 Mallol J Sole D Baeza-Bacab M Aguirre-Camposano V Soto-Quiros MBaena-Cagnani C Regional variation in asthma symptom prevalence inLatin American children LatinAmerica ISAAC group J of Asthma 201047(6)644ndash650

5 Villamizar I Garcia Lamogglia M Meza J Romero J Generalidades El asmacomo problema de salud publica Definicion Factores de riesgoFenotipos Arch Venez Pueric Pediatr 2010 73(2)48ndash54

6 Lai CKW Beasley R Crane J Foliaki S Shah J Weiland S Global variation inthe prevalence and severity of asthma symptoms Phase III of ISAACThorax 2009 64476ndash483

7 Espantildea LP 10 antildeos detraacutes de la pobreza Publicaciones UCAB 20108 Sanchez-Borges M Capriles-Hulett A Caballero-Fonseca F Asthma care in

resource - poor settings WAO J 2011 4(4)68ndash729 Hulett AC Yibirin MG Barreto RB Garcia A Hurtado D Perez PA Home

social environment and asthma profiles in a vulnerable community fromCaracas lessons for urban Venezuela J Asthma 2013 50(1)14ndash24

10 Price D Bosnic-Anticevivh BA Chrystin H Rand C Scheuch G Bousquet JThe inhaler error steering committee Inhaler competence in asthmacommon errors barriers to use and recommended solutionsRespir Med 2013 10737ndash46

11 Capriles A Gonzalez M Hurtado D Symposium ldquoPitfalls of Allergic Diseases inLatin Americardquo Slum Asthma in Latin America a Novel Approach LondonHandouts 29th Congress of EAACI 2010 June 6th

12 Oral rehydration salts Production of the new ORD accesed febraury 2013at whqlibdocwhoinf

13 Price D Popov TA Bjermer L Lu S Petrovic R Vandormael K Mehta A Strus JDPolos PG Phillip G Effect of Montelukast for treatment of asthma incigarette smokers Allergy Clin Immunol 2013 Feb 1 Epub ahead of print

14 Cruz AA Bateman ED Bousquet J The social determinants of asthmaEur Resp J 2010 35239ndash242

15 Erin EM Leaker BR Nicholson GC Tan AJ Green LM Neighbour HZachariasiewicz AS Turener J Barnathan ES Kon OM Barnes PJ Hansel TTThe effects of a monoclonal antibody directed against tumor necrosisfactor - alpha in asthma Am J Res Crit Care Med 2006 174(7)753ndash762

16 Unger A Childrenrsquos health in slums settings Arch Dis Child 2013 98799ndash80517 Graffar M Une methode de classification sociale drsquoenchantillons de

population Courier 1956 6(L)8 Septiembre 195618 Wright R Suglia S Levy J Fortum K Shields A Subramaniam SV Wright R

Transdisciplinary research strategies for understanding socially patterneddisease the Asthma Coalition on Community Environment and Social Stress(ACCESSS) project as a case study Cien Saude Colet 2008 13(6)1729ndash174

19 Jackson D Sykes A Mallia P Johnston S Asthma exacerbations origineffect and prevention J Allerg Clin Immunol 2011 128(6)1165ndash1174

20 PROVEA 2006 Informe anual http wwwderechosorgvepwattachment_id=1771 Derecho a la salud accesed July 2014

21 Hoyer and Clarembaux Barrio adentro historias de una misioacuten Coleccion Librosde EL NACIONAL 2009 ISBN9789803884673

22 Souza-Machado C Souza-Machado A Franco R Ponte EV Barreto MCRodrigues LC Bousquet J Cruz AA Rapid reduction in hospitalizationsafter an intervention to manage severe asthma Eur Resp J 201035(3)515ndash521

23 Price D Musgrave SD Shepstone L Hillyer EN Sims EJ Guilbert RF Juniper EFAyres JG Kemp L Blyth A Wilson EC Wolfe S Freeman D Mugford HMMurdoch J Harvey I Leukotrienes antagonists as first - line or add - onasthma controller therapy N Engl J Med 2011 364(18)1695ndash1707

24 Ducharme F Noya FI Allen-Rammey FC Maisese EM Gingres J Blais LClinical effectiveness of inhaled corticosteroids versus montelukast inchildren with asthma prescription patterns and patient adherence askey factors Curr Med Research Opinion 2012 28(1)111ndash119

25 Rodriguez E Vera V Perez-Puigbo A Capriles-Hulett A Ferro S Manrique JAbate J A single dose of nebulized formoterol powder is as effective asthree doses of albuterol in childrenrsquos acute asthma Allergol Immunopathol(madr) 2008 36(4)196ndash200

26 Capriles E Do Campo A Verde O Pluchino S Capriles HA Childrenrsquosasthma and the third world an approach J Investig Allergol Clin Immunol2006 16(1)11ndash18

27 For information regarding phone services in Venezuela 2013 wwwconatelgobve telefonia movil estadisticas accesed July 2014

28 Petrie KJ Perry K Broadbent E Weinman J A text message programmedesigned to modify patientrsquos illness and treatment beliefs improvesself-reported adherence to asthma preventer medication Br J HealthPsycholo 2012 1774ndash84

29 Rule of tworsquos accessed at wwwdcasthmaorgrules_of_two_posterpdf Is afederally registered trademark of Baylor Health Care system

30 Summary of Merck and Co Inc yahoo finance Accessed March 2013 bizyahoocomehellipmlk10-qhtml

31 IMSrsquo XPLORA Here the Reader can Find Data Regarding Actual Prices ofMedications in Venezuela Gaceta Oficial 2014 Estimations in text weremade according to the official rate of exchange (xls Sicad II Banco Centralde Venezuela at wwwbcvorgvec5sicadc9tme01asp Informationconcerning miacutenimum monthly wage can be found at wwweluniversalcomeconomia140518Venezuela-entre-los-paises-con-retraso-del-salariio-minimo

32 Ponte EV Franco R Nascimento HF Souza-Machado A Cunha S Barreto LNaspitz C Cruz AA Lack of control of severe asthma is associated withco-existence of moderate-to severe rhinitis Allergy 2008 63564

33 Desler Mreg 10 mgs tablets httpwwwlaboratorioslasantecom

doi1011861939-4551-7-20Cite this article as Capriles Hulett et al Montelukast for the high impactof asthma exacerbations in Venezuela a practical and valid approachfor Latin America World Allergy Organization Journal 2014 720

Abstract

Background

Methods

Results

Conclusions

Introduction

Materials and methods

Statistics

Results

Discussion

Endnote

Competing interests

Authorsrsquo contributions

Acknowledgements

Author details

References

Capriles Hulett et al World Allergy Organization Journal 2014 720 of 6httpwwwwaojournalorgcontent7120

implemented over the years Inconveniences related tothe use of inhaled medications [10] make among otherconsiderations a simplified asthma approach worth pur-suing [11] In analogy to oral rehydration therapies inthird world countries [12] use of an oral and for themost part innocuous medication (Montelukast MLK )seems particularly attractive for Venezuelarsquos urban andpoor majority context [8911]To address the impact from exacerbations a real-life

pilot project with Montelukast was carried-out in adouble blinded placebo-controlled manner for six monthsto be further prolonged over a year-long period Adher-ence [10] educational needs tobacco smoke exposure[13] and sustainability in time were among the many is-sues considered Inaction is not an option regarding thesocial determinants of asthma [1014]

Materials and methodsThis real-life pilot study was registered and auditedunder number 090267 by the clinical trials departmentof the Instituto Nacional de Higiene Rafael Rangel anofficial organization of the Venezuelan MoH The Insti-tutional Review Board of ldquoCentro Meacutedico de Caracasrdquoalso approved this study Funding was obtained fromLETI laboratories in Caracas Venezuela The study wasdouble blinded randomized and run in parallel groupsPatients including children with their representativessigned a consent form regarding the scope of the studyand the use of placebos The ldquoLos Erasosrdquo slum waschosen (see Figure 1) because it possessed [9] the livingconditions of 50 of the inhabitants of Caracas the capitalcity of Venezuela and is located near the private medicalcenter In addition this community demonstrated in aprevious evaluative survey the relationship betweenasthma and poverty A high prevalence of physician di-agnosed asthma (15) was found among its inhabi-tants with 23 of these patients in a non - controlstatus as determined by the ACT for both children andadults [9]Asthma diagnosis also carried a recent history of fre-

quent extra-domiciliary nebulizations for acute symp-toms relief The existing health care system [2] providesroutine rescue treatments dispensed with nebulizationsof a FenoterolIpatropium bromide inhalation solution(025 mgs05 mgs) at an age adjusted dosing (10 gttschildren - 20 gtts adults) diluted in 2ndash3 cc of 09saline No patients were admitted at any stage of preg-nancy nursing or having had previous use of leukotrienemodifiers however any other therapy was allowed andrecorded If during the course of the study a patient wasto become pregnant she would have to be withdrawnimmediately Patients and their families attended volun-tarily and were invited to participate in the study bymeans of information from slum community leaders and

word of mouth from neighbors Eagerly concerned fam-ilies made for children numbers come close to half ofthe participants along with very few adult asthmaticsmokersThe main variable was the number of exacerbations

(primary endpoint) needing rescue nebulizations with aFenoterolIpatropium combination administered at thehealth care system patients in need of assistance afterevening hours had to attend local hospitals nearby butoutside the community Close monitoring of the primaryoutcome was carried by monthly phone calls and de-tailed questioning during regular visits This project wasoriginally conceived for execution at the ambulatoryhealth facility (MoH) located within the communityhowever due to security concerns for the researchers itwas carried out in a private medical office (ACH) acrossthe street imposing limits on logistics particularly re-garding number of participantsA total of 88 known asthmatic patients (roughly 12

were children) were recruited The patients were between5 and 44 years of age and were either smokers or non-smokers Those patients who had not smoked cigarettesin the last 6 months were considered as non-smokers Thedaily consumption rate and the years of smoking were re-corded for those who reported tobacco use Asthmaticsbetween the ages of 5 and 12 were referred to as childrenwhile those 13 and up to 44 years of age were defined asadults in conformity with the ACT age ranges These ageconsiderations helped avoiding confusion with other re-spiratory syndromes such as early ages viral wheezing andchronic obstructive pulmonary disease in the elderly Thisdoes not imply however the existence of asthma outsideof these age rangesAsthmatics underwent a detailed clinical history and

physical examination (with an emphasis on co-morbiditiessuch as allergic rhinitis and flexural atopic dermatitis)Weight height body mass index pulse and blood pres-sure together with prick skin tests (Lancetters Hollister-Stier) for inhalant allergens (Greer Labs ALK-Abello)were recorded during the examination The best of threestanding Wright Peak Flow Meter measurements in Lmin(Ferraris Medical Holland New York USA) not varyingby more than 5 and performed before and 20 minutesafter 400 mcg of albuterol were obtained Patients wereadministered the ACT test according to age and receivedminimal oral information and a simple written one-pageeducational pictorial documentChildren received a 5 mg dosage of Montelukast daily

while adults received a 10 mg daily dosage Montelukastand placebo treatments were supplied in aluminum blisterpacks (chewable tablets for those 4ndash15 years of age 10 mgstablets for those 15ndash44 years of age) to be taken at nightprior to going to bed The counting of empty blister packsallowed for the estimation of adherence on return visits















Patients Ndeg 46 42

Age 1827+-1414 1688+-1381 069

Sex FM 1817 2715 093

Weight 4716+-2511 4596+-2849 O91

BMI 2148+-645 2130+_813 099



t studentChi2





1610 9

4246

43

25

50

0

10

20

30

40

50

60

3 6 9 12

Percentage

Montelukast Placebo

P =003P =004























































Abstract

Background

Methods

Results

Conclusions

Introduction


Statistics

Results

Discussion

Endnote

Competing interests


Acknowledgements

Author details

References















Patients Ndeg 46 42

Age 1827+-1414 1688+-1381 069

Sex FM 1817 2715 093

Weight 4716+-2511 4596+-2849 O91

BMI 2148+-645 2130+_813 099



t studentChi2





1610 9

4246

43

25

50

0

10

20

30

40

50

60

3 6 9 12

Percentage

Montelukast Placebo

P =003P =004























































Abstract

Background

Methods

Results

Conclusions

Introduction


Statistics

Results

Discussion

Endnote

Competing interests


Acknowledgements

Author details

References






















































Abstract

Background

Methods

Results

Conclusions

Introduction


Statistics

Results

Discussion

Endnote

Competing interests


Acknowledgements

Author details

References

ORIGINAL RESEARCH Open Access Montelukast for the high ...

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