Exploring the role of cold air in airway hyperresponsiveness and asthma diagnostic testing: a systematic review and meta-analysis

Asthma diagnosis and treatment: Filling in the information gaps

Asthma is a heterogeneous disease. One of the non-allergic phenotypes is exercise-induced asthma, which can aggravate the course of asthma, requiring enhanced therapy. Diagnosis of exercise-induced asthma is difficult due to underestimation of symptoms - wheezing appears only during physical exertion. A promising direction in the diagnostics of exercise-induced asthma is dynamic electronic auscultation of wheezing during bronchoprovocation tests. Objective of the study: to evaluate the capabilities of dynamic electronic auscultation in real time in the diagnosis of exercise-induced asthma in patients with an established diagnosis of asthma during a test with physical exertion. Material and methods. The prospective, observational experimental clinical study included 42 outpatients with suspected exercise-induced asthma (32 mild and 10 moderate BA). Computer spirometry was performed using a Vitalograph ALPHA spirometer (England). Dynamic electronic auscultation of the lungs was performed using our own developed technique during and after physical activity. The resulting audio files were subjected to computer analysis. Results. Registration of respiratory sounds during physical activity and after the test was successfully performed in all 42 patients. Wheezing rales were recorded during physical activity in 11 patients, of which wheezing resumed in 7 patients at 8-14 minutes of the recovery period - 9,8 (7,1; 13,2) min. In 5 patients, the dynamics of the auscultatory picture corresponded to bronchoobstruction - a decrease in FEV1 by 17% or more, in 2 patients, despite the appearance of dry wheezing during physical exertion, clinically significant dynamics of external respiration function were not noted - a decrease in FEV1 by 0.16 0.04 l (by 3.4 0.25%). In 5 patients, there were no wheezing during physical exertion, but in the recovery period at 5-8 minutes - 6,3 (5,3; 7,7) min. Wheezing with a corresponding decrease in FEV1 by 17% or more was recorded. Exercise-induced asthma was diagnosed in 12 of 42 asthma patients (28%). A direct strong correlation was observed between the occurrence of wheezing and obstructive changes in the function of external respiration (r= 0.76, p˂0.05). Conclusion. Dynamic electronic auscultation in real time has proven to be a highly sensitive method that allows reliable recording of the occurrence of wheezing both during the exercise test and in the recovery period in patients with bronchial asthma. This method allows specifying the time intervals of occurrence and disappearance of wheezing and can be used remotely.

Beyond our pages

As the 2008 Summer Olympics in Beijing approach, both the general public and health care professionals are gaining interest in the potential health implications of sport. When asthma and allergy are present in athletes, this may affect their performance and achievements and justify the special attention of health care professionals who specialize in taking care of top athletes. However, the impact of allergy and asthma on sport and exercise goes further than just top athletes. The Editors of Allergy decided that in this issue they would focus the attention of allergy and asthma specialists by presenting a series of articles on the relationship between sport, asthma and allergy in the hope that an increased awareness of these problems would be highlighted not only for sports medicine doctors but also for all practicing allergists. Exercise-induced asthma (EIA) is a general concern for growing children and adolescents. In most international guidelines, one of the main objectives of treating asthma during childhood is for the child to be able to master EIA. Also among athletes, and especially elite athletes, EIA and bronchial hyperresponsiveness (BHR) have become major problems with regard to the correct diagnosis and to treatment. EIA is increasingly common among the top athletes of several different types of sport. Traditionally this has been reported mainly in athletes competing in endurance sports in cold climates, especially among cross-country skiers (1, 2) and swimmers (3, 4), but also among endurance athletes in summer sports (5). A surprisingly high prevalence of asthma (56%) diagnosed by the reversibility of lung function to inhaled ß2-agonists (56%) was reported among professional Canadian football players (6). The prevalence of EIA among top athletes has increased over the past decades. Weiler et al. reported 11% prevalence of EIA among American athletes participating in the 1984 Summer Olympic Games (7) and an increase to a prevalence of more than 20% was noticed among American participants in the 1996 Summer Olympic Games in Atlanta (8). Treating asthma and EIA in top athletes might seem a trivial matter and perhaps a luxury, given that athletes usually master physical performance better than most of us. However, even athletes need an optimal diagnosis and treatment for their asthma. This has been demonstrated by Becker et al. who reported deaths linked to athletic performance over a 7-year period in the USA (9). Out of 263 deaths, 61 were asthma related. Among those occurring in competitive athletes, 51% occurred while participating in organized sports. Only one of the 61 athletes used inhaled steroids (9). Thus, optimal asthma treatment is a must among competitive athletes. Two hypotheses attempt to explain the relationship between physical activity and EIA. One relates to cooling of the airways because of increased ventilation during exercise, the other because of an increased loss of water from the respiratory tract, also caused by increased ventilation during exercise. Airway cooling because of respiratory heat loss during the increased ventilation in exercise is thought to cause vasoconstriction in bronchial vessels followed by a secondary reactive hyperemia with resulting edema and airways narrowing (10). Secondly, there is substantial evidence that EIA is effected through the release of mediators from mast cells and other inflammatory cells of the airways. This is thought to be caused by the high ventilation rates of top athletes (up to >280 l/min) during exercise with a considerable water loss due to the saturation of inhaled air with water. The cause of mediator release is the change in osmolarity of the periciliary fluid lining the respiratory mucosal membranes (11). The effectiveness of inhaled mannitol as a tool to diagnose BHR further confirms this hypothesis (12). The first observation that high intensive exercise may cause an increase in BHR was made in Norwegian competitive swimmers in whom the BHR increased after a swimming exercise of 3000 m (3) and then in young skiing athletes during the competitive season (13). Heavy endurance training, especially when performed in an unfavorable environment, presents stress to the mucosal membrane of the airways. This was shown by Sue Chu et al. in bronchial biopsies from highly-trained young skiers without asthma but with increased airways responsiveness to cold air (14, 15). They described an increased airways inflammation with lymphoid aggregates and an increased tenascin expression (as measured through the thickness of the tenascin-specific immunoreactivity band in the basement membrane) in the skiers (14, 15). Similar findings were recently described experimentally comparing exercising and sedentary mice (16). Furthermore, inflammatory changes in induced sputum were reported among competitive swimmers (4). Thus, intense and repeated physical endurance training over prolonged periods of time in combination with nonoptimal environmental conditions may contribute to the development of asthma and BHR among top athletes. Endurance training and competition in unfortunate environmental conditions are thought to contribute to the development of BHR among top athletes. Examples are the development of BHR and EIA among cross-country skiers (1, 2) and among competitive swimmers (4). Larsson showed that cold air inhalation increased the number of inflammatory cells in broncho alveaveolar lavage (17). In children, Bernard et al. found a relationship between the time spent in swimming pools during early childhood and the development of asthma as well as signs of lung involvement by increased serum levels of surfactant proteins (18) and reduced levels of Clara cell protein (19). Also, respiratory tract infections increase bronchial responsiveness in actively training athletes (20). Thus, the combination of intense and repeated exercise with unfavorable environmental conditions is probably important for the development of asthma among top athletes. Despite epidemiological evidence regarding the increased prevalence of EIA and BHR among top athletes, frequent use of asthma drugs leads to concern about the possible improvement in performance by asthma drugs and especially by inhaled β2-agonists. Thus, already in 1993, the Medical Commission of the International Olympic Committee (IOC-MC) set restrictions for the use of asthma drugs in sports. Among the β2-agonists, salbutamol and terbutaline were permitted, and only by the inhaled route. Athletes with a confirmed diagnosis of asthma were allowed to use these drugs. Later, these regulations were changed several times. Shortly before the Salt Lake City Winter Olympic Games in 2002, the IOC-MC introduced new rules for the use of inhaled β2-agonists and inhaled steroids during the Games (21). Applications had to be determined beforehand and the results of laboratory tests such as exercise tests, bronchial provocation tests with metacholine, eucapnic hyper ventilation tests or documented reversibility to inhaled β2-agonists had to be submitted (21). Several allergologists and pulmonologists felt that these rules were too strict as they focused upon the specificity of the asthma diagnosis and not upon the sensitivity (22). As a result, a joint Task Force was set up by the European Respiratory Society (ERS) and the European Academy of Allergology and Clinical Immunology (EAACI). This task force has worked on several articles related to asthma and sport, which were published as a European Respiratory Monograph (23). The report of the Task Force reviewed the problem of asthma among athletes as well as the pathogenetic mechanisms and provided recommendations related to the diagnosis of asthma and BHR and to asthma treatment among athletes. The Task Force report is published in two parts in Allergy. The first part, published in this issue, discusses epidemiology, pathogenetic mechanisms and the diagnosis of asthma among athletes, whereas the second part will provide recommendations related to treatment and will discuss questions regarding doping. As the regulations for the use of asthma drugs among athletes have been repeatedly changed, physicians treating asthmatic athletes and children and adolescents with asthma should keep themselves updated on the current regulations. This may be done by consulting the World Antidoping Association website (http://www.wada-ama.org/en/t1.asp; accessed 22 January 2008) or, with regard to the Olympic games, the IOC website (http://www.olympic.org/uk/utilities/reports/level2_uk.asp?HEAD2=1&HEAD1=1; accessed 22 January 2008). The work initiated by the Task Force has been continued by the Global Asthma and Allergy European Network (GA2LEN), the European network of centers of excellence in allergy. The work package within this network related to asthma, allergy and sports has decided to carry out a European study related to the prevalence and diagnosis of asthma among athletes. Several European countries will participate in this project, which is a co-operation between GA2LEN and the National Olympic Committees of the participating countries. In addition to asthma (which is not always allergic), other allergic disorders like allergic rhinitis or atopic eczema have been observed as common among elite athletes. In Australian Olympic athletes, 29% suffered from allergic rhinoconjunctivitis and 41% had positive skin tests to at least one aeroallergen (24). Allergic athletes experience symptoms of upper and lower airway disease on exposure to both outdoor and indoor aeroallergens, which may significantly decrease their physical performance (25). Furthermore, athletes with hay fever have significantly more exercise-related airway symptoms. Sensitization to alleroallergens may be particularly important during the Olympic Games, which usually take place during the peak of the pollen season. As demonstrated during the Olympic Games in Athens, pollen monitoring may help allergic athletes to achieve peak performance under prophylactic measures (http://www.aeroallergen.gr). The presence of atopic sensitization seems to be a risk factor for the development of bronchial hyperreactivity and asthma among athletes (26). From a practical point of view, these observations strongly suggest that WHO-ARIA recommendations to investigate all asthmatic subjects for rhinitis and patients with rhinitis for asthma should also be applied to elite athletes. Another phenomenon, which is not yet well explored, is the association of physical exercise with the development of allergic sensitization. Competitive swimmers had a higher incidence of allergic diseases and subclinical sensitization to common allergens (27). Moreover, chlorinated pool attendance by children was associated with an increased risk of the development of bronchial asthma but also of hay fever (28). On the other hand, the physical activity of children may be a protective factor for the development of asthma (29). The combination of these observations should prompt further studies on the relationship between various forms of physical activity and allergic sensitization. Starting with this issue, Allergy will publish a series of articles aiming to review the relationship between asthma, allergy and sport and to help solve problems related to these interactions. As already mentioned, the ERS/EAACI Task Force Report will be published in two parts, and other articles, either review articles or systematic reviews, will take on questions such as the prevalence of asthma and EIA among athletes, diagnostic procedures and questions related to the use of asthma drugs and athletic performance. This is an important series as problems related to sport will be of interest to most allergists/pulmonologists and their patients. The issue is also of significance because asthma drugs should not be considered as doping, and young people should not stop using their asthma drugs because of questions related to doping.

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 randomized, 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 Implications. Levalbuterol HFA MDI when administered before exercise was effective in protecting adults with asthma from EIB.

Risk of Rupture and All Cause Mortality of Abdominal Aortic Ectasia: A Systematic Review and Meta-Analysis

This study aimed to comprehensively evaluate the efficacy of music intervention as a non-pharmacological approach for improving physiological and psychological outcomes in patients with hypertension through a systematic review and meta-analysis of randomized controlled trials (RCTs). We systematically searched PubMed, Embase, The Cochrane Library, Web of Science Core Collection, Wanfang Data, and CNKI for RCTs investigating the effects of music therapy on blood pressure, heart rate (HR), anxiety, and depression in hypertensive adults. Data were pooled using random-effects models, and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated. The robustness of findings was assessed via sensitivity analysis, and publication bias was evaluated using Egger's and Begg's tests. Twenty-one RCTs involving 1436 participants were included. Meta-analysis revealed that music intervention significantly reduced systolic blood pressure (SBP) (WMD = -8.26mmHg, 95% CI: -10.56 to -5.96), diastolic blood pressure (DBP) (WMD = -5.91mmHg, 95% CI: -8.03 to -3.79), HR (WMD = -4.17, 95% CI: -7.22 to -1.12), anxiety levels (measured by Self-Rating Anxiety Scale, SAS) (WMD = -5.22, 95% CI: -7.03 to -3.40), and depression levels (measured by Self-Rating Depression Scale, SDS) (WMD = -7.12, 95% CI: -10.27 to -3.98). Sensitivity analyses confirmed the stability of these findings, and statistical tests showed no significant publication bias for primary outcomes. Music therapy is an effective complementary intervention for reducing blood pressure, HR, anxiety, and depression in hypertensive patients. Personalized music selections and longer intervention sessions may enhance efficacy. Future research should focus on standardizing intervention protocols, clarifying underlying mechanisms, and exploring long-term efficacy.

Aim: To assess the progression of bronchial reactivity (BR) and incidence of bronchial hyperreactivity (BH), exercise-induced bronchoconstriction (EIB) and asthma in triathletes over 2 years. Methods: Subjects were seven athletes...

Standard technical specifications for methacholine chloride (Methacholine) bronchial challenge test (2023)

Nedocromil sodium and sodium cromoglycate inhaled shortly before exercise appear to reduce the severity of exercise-induced bronchoconstriction. There is some debate over which drug may be more effective. The objective of this review was to compare the effects on post-exercise lung function between prophylactic doses of nedocromil sodium (NSG) and sodium cromoglycate (SCG) in persons diagnosed with exercise-induced bronchoconstriction. Randomized controlled trials were identified from the Cochrane Airways Review Group Asthma Register which compiles searches of CINAHL, EMBASE, MEDLINE and CENTRAL, plus hand searches for trials in 20 journals. Bibliographies of relevant studies and review articles were searched and primary authors, content experts and manufacturers of drugs were contacted for additional relevant studies. No language restrictions were applied. Randomized controlled trials comparing NCS to SCG in prophylactic treatment of exercise-induced bronchoconstriction were eligible. Studies were included if: the participants, aged 6 or over, had a confirmed diagnosis of asthma with exercise-induced bronchoconstriction, were subjected to an exercise challenge sufficient to trigger bronchoconstriction, and the measures of lung function were reported as either changes in forced expiratory volume in one second or peak expiratory flow rate. Data extraction and methodological quality assessments were conducted independently by two reviewers using standard forms and validated assessment criteria. In some cases results were extrapolated from graphs. Results from similar studies were pooled and reported as the weighted mean difference (WMD) or odds ratio (OR) with 95% confidence intervals (CI) using the random effects model. Of the 92 citations retrieved from the original search, a total of 8 studies were included in this review (117 participants). No significant difference was noted between NCS and SCG with respect to the maximum percent decrease in FEV1 (WMD = -0.88; 95% CI: -4.50, 2.74), complete protection (i.e. maximum % fall FEV1 still =>10%); OR = 0.95; 95% CI: 0.50 to 1.8, clinical protection (i.e. < 50% improvement over placebo); OR = 0.71; 95% CI: 0.36 to 1.39; unpleasant taste (OR = 6.85; 95% CI: 0.77, 60.73), or sore throat (OR = 3.46; 95% CI: 0.32, 37.48). For these pooled comparisons, no statistically significant heterogeneity was identified. Subgroup analyses based on age, dosage of medications and timing of exercise post-inhalation were consistent with the overall pooled analyses. No significant differences were evident between the effect of NCS and SCG during the immediate post-exercise period in adults and children with EIB with regards to pulmonary function - specifically maximum percent decrease in FEV1, complete protection, clinical protection, or side effects.

Inositol and its derivatives may help mitigate risks associated with cardiovascular diseases; however, existing evidence remains inconsistent. The primary aim of this systematic review and meta-analysis of RCTs was to quantify the effects of inositol and its stereoisomers on anthropometric, and cardiometabolic measures. A systematic review and meta-analysis of RCTs was conducted to clarify this. Searches in PubMed and Scopus, along with hand-searching references, identified RCTs on inositol supplementation lasting ≥ 4-week. Using random-effects models, the analysis determined mean effect sizes as weighted mean differences (WMD) with 95% CIs. Heterogeneity was assessed via the Cochrane Chi-squared test and Galbraith plots, while the ROBI tool evaluated bias risk. The strength of the evidence was assessed using the GRADE framework. Eighteen RCTs (n = 898) were totally included in this meta-analysis. Significant reductions in BMI (WMD (95%CIs):-0.57kg/m²(-1.10, -0.03), I²=88.6), waist-to-hip ratio(WMD (95%CI):-0.02(-0.04, -0.001), I²=84.1), and waist circumference (WMD (95%CI):-2.36cm(-4.39, -0.33) I²=55.0) were noted with high heterogeneity and low to very low certainty evidence. Inositol significantly decreased glucose levels (WMD (95%CI):-7.25mg/dL(-10.98, -3.52), I²=90.7), insulin (WMD (95%CI):-4.74µU/mL(-6.16, -3.32), I²=90.6) and HOMA-IR (WMD (95%CI):-1.21(-1.58, -0.85), I²=85.0), both with moderate evidence certainty and high heterogeneity. Notable reductions in triglycerides (WMD (95%CI):-29.80mg/dL(-48.16, -11.44), I²=96.0) and total-cholesterol (WMD (95%CI):-18.26mg/dL(-30.75, -5.77), I² = 95.8) were observed, with high and low evidence certainty, respectively, and high heterogeneity. LDL-C and HDL-C improved with moderate certainty (WMDs (95%CIs):-5.15mg/dL(-8.89, -1.42), I²= 0.0; and 2.76mg/dL(1.16, 4.36), I²=52.9). Additionally, inositol significantly lowered systolic (WMD (95%CI):-5.34mmHg(-6.91, -3.78), I²=38.0) and diastolic blood pressure (WMD (95%CI):-6.12mmHg(-8.44, -3.80), I²=69.7) with low, and very low evidence certainty. Overall, inositol may offer modest cardiometabolic benefits, with moderate-to-high certainty for improvements in insulin resistance and lipid profiles. However, existing studies show a high risk of bias and low certainty of evidence, particularly for anthropometric outcomes, creating cautious interpretation. Future research should involve large-scale, rigorous trials with standardized protocols, longer follow-up, and diverse populations.

Relative to a control intervention, but not to a variety of alternative treatments, CT is probably associated with small to moderate positive effects on global cognition and verbal semantic fluency at end of treatment, and these benefits appear to be maintained in the medium term. Our certainty in relation to many of these findings is low or very low. Future studies should take stronger measures to mitigate well-established risks of bias, and should provide long-term follow-up to improve our understanding of the extent to which observed gains are retained. Future trials should also focus on direct comparison of CT versus alternative treatments rather than passive or active control conditions.

Disturbance of inflammatory/oxidative status of the body is an important player in chronic disease pathophysiology. Ginger (Zingiber officinale Roscoe, Zingiberaceae) supplementation has been vastly investigated in this regard. The present dose-response meta-analysis is aimed at summing up the findings of existing literature. Online databases of PubMed, Scopus, Web of Science Core Collection, and Google Scholar were searched for eligible randomised controlled trials (RCTs) on ginger supplementation. Outcome variables included: C-reactive protein (CRP), tumour necrosis factor α (TNF-α), interleukin-6 (IL-6), total antioxidant capacity (TAC), malondialdehyde (MDA), and superoxide dismutase (SOD). Findings were reported as weighted mean differences (WMDs). Subgroup analysis was conducted. Linear and non-linear associations between dosage/duration of intervention and the observed effects were assessed. Protocol registered in PROSPERO (CRD420251011148(. Twenty-nine RCTs were included. Our findings show that ginger supplementation improves all inflammation/anti-oxidant biomarkers, as follows: CRP (WMD = -0.86mg/L; 95% CI = -1.10, -0.62), TNF-α (WMD = -1.90pg/mL; 95% CI = -2.61, -1.18), IL-6 (WMD = -1.15pg/mL; 95% CI = -1.90, -0.41), TAC (WMD = 0.22mmol/L; 95% CI = 0.06, 0.38), MDA (WMD = -0.76 mcmol/L; 95% CI = -1.19, -0.33), and SOD (WMD = 48.12u/L; 95% CI = 30.57, 65.58). The effect of ginger on IL-6 seems to associate with the dosage and duration of intervention in a non-linear fashion. Ginger supplementation may improve inflammatory and antioxidant biomarkers, particularly in individuals with underlying health conditions. Given the high heterogeneity among studies, findings should be interpreted cautiously.

Exercise-induced bronchoconstriction (or asthma) following strenuous physical exertion is common and can cause sub-optimal performance, symptoms such as cough, dyspnea, wheeze, chest tightness, and can lead people to avoid physical activity. Management focuses on prevention with pre-exercise treatment using various pharmacologic agents. Mast cell stabilizing agents are effective in attenuating exercise-induced bronchoconstriction but their effectiveness compared to bronchodilator agents is unclear. To quantitatively compare the effects of inhaling a single dose of either mast cell stabiliser - nedocromil sodium or sodium cromoglycate - to a single dose of short acting beta-agonists or anti-cholinergic agents - atropine or ipratropium bromide - prior to a strenuous exercise challenge in participants with asthma who are at least 6 years of age and suffer from reproducible exercise-induced bronchoconstriction. The review also compares the effects between a short acting beta-agonist alone to a combination of a short acting beta-agonist + mast cell stabiliser. We searched the Cochrane Airways Group ASTHMA and WHEEZ* trials register, Cochrane CENTRAL, Current Contents, review articles, textbooks and reference lists of articles. We also contacted the drug manufacturer and primary authors for additional citations. Randomised trials comparing a single prophylactic dose of a mast cell stabiliser to a short acting beta-agonist, anti-cholinergic agent, or a short acting beta-agonist alone to a combination of short acting beta-agonist plus a mast cell stabiliser to prevent exercise-induced bronchoconstriction in asthmatics over six years old. The exercise challenge had to conform to acceptable standards and pulmonary function (PFT) reported as percent decrease from baseline of FEV1 or peak flow. Complete protection (maximum % fall PFT <15% post-exercise) and clinical protection (50% improvement over placebo effect) measures were included. Trial inclusion and quality assessments were conducted independently by two reviewers using standardised forms. A second reviewer confirmed data extraction and calculations. Attempts were made to contact study authors. The pooled estimate involving continuous pulmonary function measures are reported as a weighted mean difference (WMD), dichotomous data as an odds ratio (OR), both with 95% confidence intervals (95%CI) using a random effects model. Heterogeneity tests for pooled results were performed. Twenty-four trials (518 participants) conducted in 13 countries between 1976 and 1998 were included. All drugs were effective at attenuating the exercise-induced bronchoconstriction response but to varying degrees even within the same individual. Compared to anti-cholinergic agents, mast cell stabilisers were somewhat more effective at attenuating bronchoconstriction. On average the maximum fall on MCS was reduced to 7.1% compared to 13.8% on AC ( WMD = 6.7%; 95% CI: 3.3 to 10.0), provided more individuals with complete protection (73% vs 56%; OR = 2.2; 95% CI: 1.3 to 3.7) and clinical protection (73% vs 52%; OR = 2.7; 95% CI: 1.1 to 6.4). There were no subgroup differences based on age, severity, or study quality, and no adverse effects were reported for either agent group. When compared to short acting beta-agonists mast cell stabilisers were not as effective at preventing deterioration. On average the maximum fall on MCS was 11.2% compared to 4.3% on beta agonists ( WMD = 6.8%; 95% CI: 4.5 to 9.2). MCS provided fewer individuals with complete protection (66% vs 85%; OR = 0.3; 95% CI: 0.2 to 0.5) or clinical protection (55% vs 77%; OR = 0.4; 95% CI: 0.2 to 0.8). There were no significant subgroup differences based on age, severity, drug, delivery, or study quality. A non-significant difference in side effects was demonstrated with 11% of short acting beta-agonist patients experiencing side effects compared to 3% of those receiving mast cell stabilisers (OR = 0.2; 95% CI: 0.0 to 8.2). Combining masta-agonist patients experiencing side effects compared to 3% of those receiving mast cell stabilisers (OR = 0.2; 95% CI: 0.0 to 8.2). Combining mast cell stabilisers with a short acting beta-agonist did not produce significant advantages to pulmonary function over short acting beta-agonists alone. On average the maximum fall on SABA only was reduced to 5.3% compared to 3.5% on the combination ( WMD = 1.8%; 95% CI: -1.1 to 4.6). Beta-agonists alone provided fewer individuals with complete protection (68% vs 80%; OR = 0.5; 95% CI: 0.2 to 1.4) or clinical protection (70% vs 86%; OR=0.4; 95% CI: 0.1 to 1.2) but the difference did not reach significance (p=0.17). There were no subgroup differences. In a population of stable asthmatics short acting beta-agonists, mast cell stabilisers, or anticholinergics will provide a significant protective effect against exercise-induced bronchoconstriction with few adverse effects. On average, SABAs resulted in more effective attenuation than mast cell stabilisers, while mast cell stabilisers were more effective than anti-cholinergic agents. Combining SABA and mast cell stabilisers may be appropriate in selected cases. The variability in the individual degree of response to these drugs in multi arm trials suggests clinicians and patients work together to identify the most effective prophylactic therapy.

Onset and duration of protection against exercise-induced bronchoconstriction by a single oral dose of montelukast