Do clinicians understand the size of treatment effects? A randomized survey across 8 countries Double-blind crossover study comparing sodium cromoglycate, reproterol, reproterol plus sodium cromoglycate, and placebo in exercise-induced asthma. Duration of the common cold and similar continuous outcomes should be analyzed on the relative scale: a case study of two zinc lozenge trials Combination drug therapy for the prevention of exercise-induced bronchoconstriction in children. Prevention of exercise induced asthma by inhaled salmeterol xinafoate. Tolerance to the bronchoprotective effect of salmeterol in adolescents with exercise-induced asthma using concurrent inhaled glucocorticoid treatment. Inhaled formoterol in the prevention of exercise-induced bronchoconstriction in asthmatic children. Effects of inhaled budesonide alone and in combination with low-dose terbutaline in children with exercise-induced asthma. An Evaluation of Levalbuterol HFA in the Prevention of Exercise-Induced Bronchospasm Salmeterol in exercise-induced bronchoconstriction in asthmatic children: comparison of two doses. Laboratory protocol for exercise asthma to evaluate salbutamol given by two devices. Dichotomizing continuous predictors in multiple regression: a bad idea. Does single dose salmeterol affect exercise capacity in asthmatic men? Bitolterol mesylate in exercise-induced asthma. The attenuation of exercise-induced bronchospasm by ascorbic acid. Inhaled Terbutaline Administered via a Spacer Fully Prevents Exercise-Induced Asthma in Young Asthmatic Subjects: A Double-Blind, Randomized, Placebo-Controlled Study Protective effect and duration of action of inhaled formoterol and salbutamol on exercise-induced asthma in children. Inhaled and oral salbutamol in exercise-induced asthma. Statistical considerations in studies of exercise-induced bronchospasm.
Background : Meta-analyses of continuous outcomes typically provide enough information for decision-makers to evaluate the extent to which chance can explain apparent differences between interventions . The interpretation of the magnitude of these differences — from trivial to large — can , however , be challenging . We investigated clinicians ’ underst and ing and perceptions of usefulness of 6 statistical formats for presenting continuous outcomes from meta-analyses ( st and ardized mean difference , minimal important difference units , mean difference in natural units , ratio of means , relative risk and risk difference ) . Methods : We invited 610 staff and trainees in internal medicine and family medicine programs in 8 countries to participate . Paper-based , self-administered question naires presented summary estimates of hypothetical interventions versus placebo for chronic pain . The estimates showed either a small or a large effect for each of the 6 statistical formats for presenting continuous outcomes . Questions addressed participants ’ underst and ing of the magnitude of treatment effects and their perception of the usefulness of the presentation format . We r and omly assigned participants 1 of 4 versions of the question naire , each with a different effect size ( large or small ) and presentation order for the 6 formats ( 1 to 6 , or 6 to 1 ) . Results : Overall , 531 ( 87.0 % ) of the clinicians responded . Respondents best understood risk difference , followed by relative risk and ratio of means . Similarly , they perceived the dichotomous presentation of continuous outcomes ( relative risk and risk difference ) to be most useful . Presenting results as a st and ardized mean difference , the longest st and ing and most widely used approach , was poorly understood and perceived as least useful . Interpretation : None of the presentation formats were well understood or perceived as extremely useful . Clinicians best understood the dichotomous presentations of continuous outcomes and perceived them to be the most useful . Further initiatives to help clinicians better grasp the magnitude of the treatment effect are needed Sixteen patients were included in the analysis of this double-blind crossover study comparing the effect of sodium cromoglycate , reproterol , sodium cromoglycate plus reproterol , and placebo in exercise-induced asthma . Both the sodium cromoglycate and the reproterol-containing treatment significantly inhibited  exercise-induced asthma .  The best protection is effected by the combination of sodium cromoglycate and reproterol . A synergistic effect of both medications could not be confirmed statistically so that their combined effect is simply additive Background The relative scale has been used for decades in analysing binary data in epidemiology . In contrast , there has been a long tradition of carrying out meta-analyses of continuous outcomes on the absolute , original measurement , scale . The biological rationale for using the relative scale in the analysis of binary outcomes is that it adjusts for baseline variations ; however , similar baseline variations can occur in continuous outcomes and relative effect scale may therefore be often useful also for continuous outcomes . The aim of this study was to determine whether the relative scale is more consistent with empirical data on treating the common cold than the absolute scale . Methods Individual patient data was available for 2 r and omized trials on zinc lozenges for the treatment of the common cold . Mossad ( Ann Intern Med 125:81–8 , 1996 ) found 4.0 days and 43 % reduction , and Petrus ( Curr Ther Res 59:595–607 , 1998 ) found 1.77 days and 25 % reduction , in the duration of colds . In both trials , variance in the placebo group was significantly greater than in the zinc lozenge group . The effect estimates were applied to the common cold distributions of the placebo groups , and the result ing distributions were compared with the actual zinc lozenge group distributions . Results When the absolute effect estimates , 4.0 and 1.77 days , were applied to the placebo group common cold distributions , negative and zero ( i.e. , impossible ) cold duration s were predicted , and the high level variance remained . In contrast , when the relative effect estimates , 43 and 25 % , were applied , impossible common cold duration s were not predicted in the placebo groups , and the cold distributions became similar to those of the zinc lozenge groups . Conclusions For some continuous outcomes , such as the duration of illness and the duration of hospital stay , the relative scale leads to a more informative statistical analysis and more effective communication of the study findings . The transformation of continuous data to the relative scale is simple with a spreadsheet program , after which the relative scale data can be analysed using st and ard meta- analysis software . The option for the analysis of relative effects of continuous outcomes directly from the original data should be implemented in st and ard meta- analysis programs BACKGROUND Sequential administration of a beta-agonist and cromolyn or nedocromil before exercise is recommended for patients whose symptoms are not controlled by beta-agonists alone ; however , this practice reduces compliance . OBJECTIVE To evaluate the effectiveness of a new pre-combined aerosol formulation ( salbutamol and nedocromil ) in preventing exercise-induced bronchoconstriction and to compare it to salbutamol alone . METHODS Twelve children with asthma were studied in a double-blind , double-dummy , r and omized , crossover , placebo-controlled design to compare the protective effect of salbutamol and a new pre-combined salbutamol/nedocromil formulation against exercise-induced bronchoconstriction . The drugs were delivered by a metered-dose inhaler ( salbutamol , 200 microg ; salbutamol/nedocromil , 200 microg/4 mg ; placebo , 2 puffs ) 20 minutes before exercise . RESULTS Both active drugs were significantly more protective than placebo but there was no difference between them . Complete protection was obtained in 12/12 , 10/12 , and 1/12 subjects for the salbutamol/nedocromil combination , salbutamol alone and placebo , respectively . CONCLUSIONS Although inhaled beta-agonists alone are highly efficacious in preventing exercise-induced bronchoconstriction , a minority of patients exists for whom a combined treatment with salbutamol and nedocromil is advantageous . This group may represent a sub population of subjects who release more , or different , mediators in response to exercise The effect of inhaled salmeterol xinafoate , a long acting beta 2 agonist , on  exercise induced asthma  was studied in a double blind , crossover , and placebo controlled trial . Thirteen asthmatic children with a fall of at least 15 % in their forced expiratory volume in one second ( FEV1 ) after a st and ard exercise test on a motorised treadmill , on separate days performed the same test 1 , 5 , and 9 hours after a single dose of 50 micrograms salmeterol or placebo .  FEV1 was measured before treatment , and before and for 30 minutes after each exercise test . After placebo the number of children with exercise induced asthma was : 10 at 1 hour , 11 at 5 hours , and 12 at 9 hours . Salmeterol prevented exercise induced asthma in all 13 children studied , at 1 , 5 , and 9 hours . Mean maximum falls in FEV1 after exercise were at 1 hour : salmeterol 2.7 % and placebo 24.6 % , 5 hours : salmeterol 5.3 % and placebo 22.7 % ; and 9 hours : salmeterol 3.4 % and placebo 26.6 % . After salmeterol the mean increase in FEV1 was 17.8 % at 1 hour , 19.6 % at 5 hours , and 19.2 % at 9 hours . Inhaled salmeterol prevents exercise induced asthma and produces significant bronchodilatation for at least 9 hours OBJECTIVES The long-acting beta2-adrenergic agonist salmeterol prevents exercise-induced asthma , but tolerance may develop to its bronchoprotective effect . We wanted to ascertain if the development of tolerance could be prevented by using a low-dose treatment regimen of 50 microg once daily , instead of the usual dose of 50 microg twice daily , in adolescents receiving regular glucocorticoid inhalations . Methods . In a r and omized , double-blind , 2x28-day crossover study , we administered salmeterol ( 50 microg ) or placebo once daily via a metered-dose inhaler and Nebulizer Chronolog device to monitor compliance . Exercise challenge tests were performed 1 and 9 hours after salmeterol or placebo inhalation on the 1st and 28th day of each treatment period . The primary outcome variable was the maximum decrease in percent predicted FEV1 postexercise . RESULTS Fourteen subjects with a mean age of 13.1 years completed the study . The first dose of salmeterol had an excellent bronchoprotective effect against exercise-induced asthma at 1 and 9 hours . After the 28th consecutive daily dose of salmeterol , the bronchoprotective effect was significantly greater than that of placebo at 1 hour , but not at 9 hours . CONCLUSIONS We conclude that a single 50-microg dose of salmeterol has an excellent protective effect against exercise-induced asthma for at least 9 hours , but that this effect may wane during regular once-daily salmeterol treatment , despite the reduced frequency of dosing and despite concomitant use of inhaled glucocorticoids The duration and magnitude of the effect of inhaled formoterol ( 12 micrograms ) against exercise-induced bronchoconstriction ( EIB ) was compared with that of inhaled salbutamol ( 200 micrograms ) and that of placebo in 15 children with asthma and EIB in a double-blind , double-dummy , within-patient , placebo-controlled study . The treatments were given by metered dose aerosol on three different days . The exercise test was performed at the 3rd and the 12th hour after dosing . The magnitude of the blocking effect was assessed both by evaluating the lowest FEV1 reading obtained within an hour after each exercise test and by considering the percent decrease below the baseline FEV1 measured before drug administration . Comparison of the lowest values obtained during the hour after each exercise test shows that formoterol was significantly better than both salbutamol ( p = 0.022 ) , and placebo ( p = 0.001 ) in limiting exercise-induced bronchoconstriction after the first exercise test ( 3 h after dosing ) , while no difference was observed between salbutamol and placebo ( p = 0.198 ) . After the second exercise test ( 12 h after dosing ) , formoterol again proved to be more effective than both salbutamol ( p = 0.008 ) and placebo ( p = 0.001 ) , and no significant difference was observed between salbutamol and placebo ( p = 0.391 ) . The evaluation of the mean percentage decrease in FEV1 confirmed the results in favor of formoterol in both the exercise tests . No adverse effects were reported in any treatment group . The protection against EIB is significantly more prolonged after formoterol than after salbutamol , and persists for 12 h after dosing The effect of aerosolized terbutaline in a dose of 32.5 micrograms and its placebo , administered in a double-blind fashion , was studied in 14 children with exercise-induced asthma ( EIA ) before and during a 4-wk treatment period with aerosolized steroid ( budesonide , 400 micrograms/day ) . Effects were assessed from the changes in peak expiratory flow ( PEF ) , forced expiratory volume in one second ( FEV1 ) , and forced expiratory flow ( FEF25 - 75 ) before and after treadmill exercise challenge . Compared with placebo there was a significant improvement in pulmonary function after terbutaline . During budesonide therapy , pulmonary function improved further , but there was no enhancement of the response to terbutaline . Terbutaline alone , budesonide plus placebo , and budesonide plus terbutaline reduced the exercise-induced fall in FEV1 by 30 , 51 , and 84 % , respectively . The effect of budesonide on EIA was delayed during the 4 wk of treatment as compared with the improvement in resting pulmonary function . The present results suggest that 1 to 4 wk of therapy with inhaled corticosteroids decreases the severity of EIA . Further , the combined effect of inhaled corticosteroid and beta-2 agonist on pulmonary function appears to be additive Background . Exercise-induced bronchospasm ( EIB ) affects up to 90 % of all patients with asthma . Objective . This study evaluated the ability of levalbuterol hydrofluoroalkane ( HFA ) 90 μg ( two actuations of 45 μg ) administered via metered dose inhaler ( MDI ) to protect against EIB in mild-to-moderate asthmatics . Methods . This was a r and omized , double-blind , placebo-controlled , two-way cross-over study . Patients with asthma ( n = 15 ) were ≥18 years , had a ≥6-month history of EIB , ≥ 70 % baseline predicted forced expiratory volume in 1 second ( FEV1 ) , and a 20 % to 50 % decrease in FEV1 after treadmill exercise challenge using single-blind  placebo MDI . Levalbuterol or placebo was self-administered 30 minutes before exercise . Treatment sequences were separated by a 3-to 7-day washout period . Spirometry was performed predose , 20 minutes postdose/pre-exercise , and 5 , 10 , 15 , 30 , and 60 minutes post-exercise . The primary endpoint was the maximum percent decrease in FEV1 from baseline ( postdose/pre-exercise ) . The percentage of protected ( ≤ 20 % decrease in post-exercise FEV1 ) patients was also assessed . Results . Levalbuterol had significantly smaller maximum percent post-exercise decrease in FEV1 compared with placebo ( LS mean ± SE ; −4.8 % ± 2.8 % versus −22.5 % ± 2.8 % , respectively ) . For levalbuterol , 14/15 ( 93.3 % ) patients had < 20 % decrease in post-exercise FEV1 compared with 8/15 ( 53.3 % ) for placebo ( p = 0.0143 ) . Treatment was well tolerated . Conclusion . Levalbuterol HFA MDI ( 90 μg ) administered 30 minutes before exercise was significantly more effective than placebo in protecting against EIB after a single exercise challenge and was well tolerated . Clinical Implication s. Levalbuterol HFA MDI when administered before exercise was effective in protecting adults with asthma from EIB Since the optimal dose of salmeterol in asthmatic children has not yet been clearly defined , we compared the efficacy and duration of the protective effect of two doses of salmeterol ( 25 and 50 micrograms ) against exercise-induced bronchoconstriction . Twelve children ( aged 7 - 14 yrs ) with asthma were studied in a double-blind , cross-over , placebo-controlled design . On three separate days , exercise tests were performed 1 h and 12 h after administration of the drug . Pulmonary function measurements were performed before drug inhalation , before every exercise test and 1 , 5 , 10 , 15 and 30 min after the end of exercise . The response was expressed as maximal decrease in forced expiratory volume in one second ( FEV1 ) . Both doses of salmeterol provided significant bronchodilation for up to 12 h , with no difference between them . Maximal exercise-induced decrease in FEV1 ( % fall ) 1 h after pretreatment was ( mean + /- SD ) 35 + /- 16 , 10 + /- 10 and 4 + /- 3 % for placebo , 25 and 50 micrograms salmeterol , respectively . At 12 h after pretreatment these values were 31 + /- 14 , 19 + /- 12 and 15 + /- 13 % , respectively . Individual protection against exercise-induced bronchoconstriction at 1 and 12 h did not vary between the dosages ( p < 0.05 ) , even though the protection obtained by 25 micrograms at 12 h was no longer significant versus placebo . We conclude that 25 micrograms of inhaled salmeterol provides equally effective long-lasting bronchodilation and acute protection against exercise-induced bronchoconstriction as 50 micrograms , and may be a suitable dose for most asthmatic children PURPOSE As new delivery devices and formulations are being introduced for drugs given by inhalation , there is a need to evaluate their equivalence with old preparations . One way to do this is to investigate their equivalence in protecting from exercise-induced asthma ( EIA ) . METHODS We used a protocol for EIA to compare the protective effect of salbutamol delivered by the pressurised metered dose inhaler ( pMDI ) and the new Diskus dry powder device .  Twenty-seven asthmatic subjects with moderately severe EIA completed an exercise test on four separate days at two study centers . Exercise was performed by cycling for 8 min while inhaling dry air ( 0 % RH , 20 - 24 degrees C ) . The target workload in W was predicted as ( 53.76 x predicted FEV1 ) - 11.07 and 95 % of this target was achieved at 4 min of exercise . This target was chosen in order to achieve ventilation between 50 and 60 % of predicted maximum in the last 4 min . RESULTS There was no significant difference in the workload , ventilation , or heart rate achieved on the study days . The severity of EIA was measured as the % fall in FEV1 . EIA severity was similar on the placebo and control day and the coefficient of variation was 19.4 % . The mean + /- SD % fall on the control , placebo , salbutamol by Diskus , and pMDI were 42.0 % + /- 15 , 39.4 % + /-17.6 , 13.4 % + /- 13.2 , and 8.5 % + /- 13.8 , respectively . Salbutamol significantly inhibited the % fall in FEV1 after exercise , and there was no difference between the preparations . CONCLUSION The protocol described here is suitable for evaluating equivalence of salbutamol preparations in protecting against EIA and could be used to evaluate the protective effect of other medications In medical research , continuous variables are often converted into categorical variables by grouping values into two or more categories . We consider in detail issues pertaining to creating just two groups , a common approach in clinical research . We argue that the simplicity achieved is gained at a cost ; dichotomization may create rather than avoid problems , notably a considerable loss of power and residual confounding . In addition , the use of a data -derived ' optimal ' cutpoint leads to serious bias . We illustrate the impact of dichotomization of continuous predictor variables using as a detailed case study a r and omized trial in primary biliary cirrhosis . Dichotomization of continuous data is unnecessary for statistical analysis and in particular should not be applied to explanatory variables in regression models The aim of this study was to investigate whether the long-acting beta-agonist salmeterol affects athletic performance in patients with asthma . The effect of 50 micrograms salmeterol on the cardiorespiratory responses to a progressive maximal cycle exercise test and on endurance capacity ( defined as the exercise duration at 70 % maximum oxygen uptake ) , was compared with 200 micrograms salbutamol and a matched placebo in eight asthmatic men . Both salmeterol and salbutamol improved pre- and postexercise forced expiratory volume in one second ( FEV1 ) for maximal and endurance exercise . Following active treatment , patients exercised from a significantly high baseline FEV1 , with both salmeterol ( 3.58(1.16)l ) ( mean ( SD ) ) and salbutamol ( 3.55(1.24)l ) compared with placebo ( 3.29(1.35)l ) . Similar improvements preceded endurance exercise . Cardiorespiratory , haemodynamic or subjective responses to the progressive maximum exercise tests were not different with salmeterol , salbutamol or placebo , nor did endurance capacity change with any treatment modality . Blood lactate levels , after 15 min exercise , were significantly higher with salbutamol ( 3.64 ( 1.83 ) mM ) , but not with salmeterol ( 3.03 ( 1.64 ) mM ) , compared with placebo ( 2.95 ( 1.69 ) mM ) . These results demonstrate the absence of significant cardiorespiratory or metabolic effects during exercise after a single dose of salmeterol , together with a lack-of ergogenic effect , as measured by maximal or endurance exercise performance , in patients with asthma Exercise-induced asthma is a useful model for evaluating the activity and duration of action of pharmacologic agents of asthma . The main objective of this double-blind , crossover study was to determine the effect of the aerosolized beta-adrenergic agent , bitolterol mesylate , on exercise-induced asthma while its efficacy was being compared with isoproterenol and placebo .  Twelve subjects with exercise-induced asthma performed cycloergometer exercise 45 minutes after three inhalations of bitolterol mesylate aerosol ( 1050 micrograms ) , or isoproterenol ( 255 micrograms ) , or placebo in r and om sequence . Bitolterol mesylate aerosol was very effective in protecting against exercise-induced asthma . The mean percent maximal decrease of FEV1 after exercise was 5.0 % for bitolterol , 22.2 % for isoproterenol , and 23.2 % for placebo . Subjects experienced skeletal muscle tremor with both bitolterol mesylate ( four subjects ) and isoproterenol ( three subjects ) , but not with placebo . No other side effects were noted In order to study the potential benefit of ascorbic acid in asthma we investigated its role in exercise-induced bronchospasm ( EIB ) . Twelve asthmatic subjects were recruited on the basis of findings compatible with EIB . On two subsequent days the subjects ingested 500 mg . of ascorbic acid or a placebo . The study was performed in a double-blind r and omized fashion . Partial and maximal expiratory flow volume ( PEFV and MEFV ) curves were used to determine pulmonary function changes . Pretreatment with ascorbic acid led to a significant attenuation of the bronchospasm seen five minutes after exercise compared to placebo , as measured by FVC ( 0.23 + /- 0.08 L decrease after ascorbic acid , 0.48 + /- 0.14 L decrease after placebo ) and by FEV1 ( 0.24 + /- 0.06 decrease after ascorbic acid , 0.44 + /- 0.14 decrease after placebo ) Mean + /- SE ) . These results suggest a mild antibronchospastic action of ascorbic acid in subjects with EIB The effects of inhaled terbutaline , a β2-adrenergic agonist , administered via a 750-ml spacer device were studied in young asthmatic subjects with exercise-induced asthma . A double-blind , r and omized , placebo-controlled study of the effects of inhaled 0.5 mg terbutaline and placebo was conducted in 10 asthmatic children ( age range 6–16 years ) with documented exercise-induced asthma . Forced expiratory volume in 1 s ( FEV1 ) was measured at baseline , 15 min after inhaling terbutaline or placebo , and at intervals up to 60 min after exercising . Subjects exercised using a cycle ergometer for 5 min at a submaximal , constant work-load while breathing dry air at room temperature . Terbutaline induced bronchodilation at rest in all subject and fully prevented exercise-induced asthma in nine out of the 10 subjects ; the exercise-induced fall in FEV1 was markedly reduced in the remaining subject . It is concluded that exercise-induced asthma can be inhibited by pretreatment with inhaled terbutaline , administered via a spacer , in a majority of young asthmatics The magnitude and duration of protection against exercise-induced asthma ( EIA ) afforded by salbutamol and the new , long-acting beta 2-agonist , formoterol , were compared in a double-blind , placebo-controlled crossover study . Twelve children with asthma and EIA ( greater than 25 % fall from baseline at a pretrial exercise test ) were studied on 3 different days receiving , in r and om order , either formoterol , 12 micrograms , salbutamol , 200 micrograms , or placebo by inhalation . The effect on EIA was evaluated by st and ardized treadmill-exercise tests repeated at the following times after medication : 1/2 hour ( test 1 ) , 3 hours ( test 2 ) , and , if the trial drug still demonstrated an effect , 5 1/2 hours ( test 3 ) and 8 hours ( test 4 ) . The mean ( SD ) maximum percent fall in FEV1 at the pretrial test was 45 % ( 14 % ) . Placebo treatment had no effect on EIA . The mean ( SD ) maximum percent fall in FEV1 was 44 % ( 14 % ) ( test 1 ) and 39 % ( 13 % ) ( test 2 ) ( not significant ) . Salbutamol offered good protection against EIA after 1/2 hour ( percent fall in FEV1 , 18 % [ 18 % ] ; p less than 0.02 ) but was not significantly different from that of placebo after 3 hours , 39 % ( 13 % ) fall in FEV1 . Formoterol blocked EIA in all the children and demonstrated a significant effect in most children for at least 8 hours . The percent fall in FEV1 after the various tests were 8 % ( 16 % ) ( test 1 ) , 10 % ( 9 % ) ( test 2 ) , 18 % ( 15 % ) ( test 3 ) , and 18 % ( 7 % ) ( test 4 ; N = 9 ) ( all tests , p less than 0.001 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Twenty-one asthmatic patients participated in a single blind , crossover study comparing the effects of aerosol and oral salbutamol ( a beta-adrenergic bronchodilator ) , on exercise-induced bronchospasm . By both routes of administration , salbutamol ( albuterol ) produced significant bronchodilatation at rest , but only the aerosol effectively prevented post-exercise bronchospasm in most patients . Because exercise-induced bronchospasm is a common problem in children and adults with asthma , these observations are relevant to the drug therapy of these patients . The existence of separate mechanisms for bronchodilatation and the prevention of exercise-induced asthma is postulated . It is possible that differing tissue concentrations of salbutamol are responsible for the observed differences between the 2 routes of administration The clinical evaluation of drugs used in the treatment of asthmatics can be very difficult and timeconsuming . Prior to a careful evaluation of long-term dosing , many investigators have used bronchoprovocation testing with exercise-induced bronchospasm ( EIB ) , one of the tests used most often , to screen potential asthma drugs . This article will present some of the statistical considerations that can increase the effectiveness of EIB testing . Many of my recommendations are based upon my experience as a biostatistician in analyzing data obtained from bronchoprovocation trials and are not intended to imply a rigidness in study design or analysis of EIB trials
Background The relative scale adjusts for baseline variability and therefore may lead to findings that can be generalized more widely .
It is routinely used for the analysis of binary outcomes but only rarely for continuous outcomes .
Our objective was to compare relative vs absolute scale pooled outcomes using data from a recently published Cochrane systematic review that reported only absolute effects of inhaled β2-agonists on exercise-induced decline in forced-expiratory volumes in 1 s ( FEV1 ) .