OBJECTIVE: To compare the performance of various diagnostic bronchoprovocation tests (BPT) in the assessment of lower airway dysfunction (LAD) in athletes and inform best clinical practice.
METHODS: Systematic review with sensitivity and specificity meta-analyses.
METHODS: PubMed, EBSCOhost and Web of Science (1 January 1990-31 December 2021).
METHODS: Original full-text studies, including athletes/physically active individuals (15-65 years) who underwent assessment for LAD by symptom-based questionnaires/history and/or direct and/or indirect BPTs.
RESULTS: In 26 studies containing data for quantitative meta-analyses on BPT diagnostic performance (n=2624 participants; 33% female); 22% had physician diagnosed asthma and 51% reported LAD symptoms. In athletes with symptoms of LAD, eucapnic voluntary hyperpnoea (EVH) and exercise challenge tests (ECTs) confirmed the diagnosis with a 46% sensitivity and 74% specificity, and 51% sensitivity and 84% specificity, respectively, while methacholine BPTs were 55% sensitive and 56% specific. If EVH was the reference standard, the presence of LAD symptoms was 78% sensitive and 45% specific for a positive EVH, while ECTs were 42% sensitive and 82% specific. If ECTs were the reference standard, the presence of LAD symptoms was 80% sensitive and 56% specific for a positive ECT, while EVH demonstrated 65% sensitivity and 65% specificity for a positive ECT.
CONCLUSIONS: In the assessment of LAD in athletes, EVH and field-based ECTs offer similar and moderate diagnostic test performance. In contrast, methacholine BPTs have lower overall test performance.
UNASSIGNED: CRD42020170915.

Exercise-induced bronchoconstriction (EIB) is the most common chronic disease among elite athletes and when left untreated, can impact both respiratory health and sports performance. In recent years, there has been an increase in the awareness and detection of EIB in elite athletes. This narrative review aims to evaluate the risk, prevention, diagnosis, medication, and anti-doping policies of EIB in elite athletes, and to provide more references for athletes with EIB. The results showed that athletes of endurance, winter, and water sports generally have a higher prevalence of EIB than athletes of other sports. Adaptive warm-up before formal exercise and using heat exchange masks at low temperatures are effective ways for athletes to prevent EIB. For physicians, the exercise challenge test and eucapnic voluntary hyperpnea are the recommended diagnostic methods for EIB in athletes. The treatment of athletes with EIB is medication-based, such as inhaled corticosteroids and beta-2 agonists, but current anti-doping policies should be considered when used.

Activation of various isoforms of NADPH oxidase contributes to the pathogenesis of asthma at multiple levels: promoting hypercontractility, hypertrophy, and proliferation of airway smooth muscle; enabling lung influx of eosinophils via VCAM-1; and mediating allergen-induced mast cell activation. Free bilirubin, which functions physiologically within cells as a feedback inhibitor of NADPH oxidase complexes, has been shown to have a favorable impact on each of these phases of asthma pathogenesis. The spirulina chromophore phycocyanobilin (PhyCB), a homolog of bilirubin\'s precursor biliverdin, can mimic the inhibitory impact of biliverdin/bilirubin on NADPH oxidase activity, and spirulina\'s versatile and profound anti-inflammatory activity in rodent studies suggests that PhyCB may have potential as a clinical inhibitor of NADPH oxidase. Hence, spirulina or PhyCB-enriched spirulina extracts merit clinical evaluation in asthma. Promoting biosynthesis of glutathione and increasing the expression and activity of various antioxidant enzymes - as by supplementing with N-acetylcysteine, Phase 2 inducers (eg, lipoic acid), selenium, and zinc - may also blunt the contribution of oxidative stress to asthma pathogenesis. Nitric oxide (NO) and hydrogen sulfide (H2S) work in various ways to oppose pathogenic mechanisms in asthma; supplemental citrulline and high-dose folate may aid NO synthesis, high-dose biotin may mimic and possibly potentiate NO\'s activating impact on soluble guanylate cyclase, and NAC and taurine may boost H2S synthesis. The amino acid glycine has a hyperpolarizing effect on airway smooth muscle that is bronchodilatory. Insuring optimal intracellular levels of magnesium may modestly blunt the stimulatory impact of intracellular free calcium on bronchoconstriction. Nutraceutical regimens or functional foods incorporating at least several of these agents may have utility as nutraceutical adjuvants to standard clinical management of asthma.

Exercise-induced bronchoconstriction (EIB) is a common complication of athletes and individuals who exercise regularly. It is estimated that about 90% of patients with underlying asthma (a sexually dimorphic disease) experience EIB; however, sex differences in EIB have not been studied extensively. With the goal of better understanding the prevalence of EIB in males and females, and because atopy has been reported to occur at higher rates in athletes, in this study, we investigated sex differences in EIB and atopy in athletes. A systematic literature review identified 60 studies evaluating EIB and/or atopy in post-pubertal adult athletes (n = 7501). Collectively, these studies reported: (1) a 23% prevalence of EIB in athletes; (2) a higher prevalence of atopy in male vs. female athletes; (3) a higher prevalence of atopy in athletes with EIB; (4) a significantly higher rate of atopic EIB in male vs. female athletes. Our analysis indicates that the physiological changes that occur during exercise may differentially affect male and female athletes, and suggest an interaction between male sex, exercise, and atopic status in the course of EIB. Understanding these sex differences is important to provide personalized management plans to athletes with underlying asthma and/or atopy.

Chronic airway inflammatory diseases remain a major problem worldwide, such that there is a need for additional therapeutic targets and novel drugs. Transient receptor potential (TRP) channels are a group of non-selective cation channels expressed throughout the body that are regulated by various stimuli. TRP channels have been identified in numerous cell types in the respiratory tract, including sensory neurons, airway epithelial cells, airway smooth muscle cells, and fibroblasts. Different types of TRP channels induce cough in sensory neurons via the vagus nerve. Permeability and cytokine production are also regulated by TRP channels in airway epithelial cells, and these channels also contribute to the modulation of bronchoconstriction. TRP channels may cooperate with other TRP channels, or act in concert with calcium-dependent potassium channels and calcium-activated chloride channel. Hence, TRP channels could be the potential therapeutic targets for chronic airway inflammatory diseases. In this review, we aim to discuss the expression profiles and physiological functions of TRP channels in the airway, and the roles they play in chronic airway inflammatory diseases.

Psychological stress has long been suspected to have a deleterious effect on asthma, with acute psychological stress being associated with physiological responses in asthma patients.
The purpose of this systematic review was to provide a narrative synthesis of the impact of acute laboratory psychological stress on physiological responses among asthma patients.
An extensive search was conducted by two independent authors using Pubmed, PsycINFO, PsyArticles and the Cochrane Library electronic databases (up to September 2016). English and French articles which assessed physiological responses during or post-stress and compare them to baseline or pre-stress values were included.
Thirty-two studies met the inclusion criteria. Studies indicated that exposure to active stressors (e.g., arithmetic tasks) was associated with an increase in sympathetic nervous system (SNS) responses, cortisol, and inflammatory responses, but had little effect on the caliber of the bronchi. Exposure to passive stressors (e.g., watching stressful movies or pictures) was also associated with an increase in SNS responses and with mild bronchoconstriction. However, a paucity of data for passive stressors limited conclusions on other measures.
In patients with asthma, both active and passive stressors seem to be associated with an increased activation of the SNS. Passive stressors seem to have a more immediate, deleterious impact on the airways than active stressors, but the latter may be associated with delayed inflammatory driven an asthma exacerbation. Further studies are needed to understand the impact of acute stressors on the physiological mechanisms associated with asthma, particularly HPA and immune markers. Systematic review registration number: CRD42015026431.

Bronchial thermoplasty is a device-based therapy for treatment of severe refractory asthma that uses radiofrequency energy to reduce airway smooth muscle and decrease bronchoconstriction. BT improves quality of life and decreases the rate of severe exacerbations with no known major long-term complications. The effectiveness of bronchial thermoplasty persists at least 5 years after the treatment is completed. Further investigation is needed to better define the specific subpopulation of patients with severe asthma who would best benefit from this treatment.

BACKGROUND: Although yoga is frequently used by patients with asthma, its efficacy in alleviating asthma remains unclear.
OBJECTIVE: To systematically assess and meta-analyze the available data on efficacy and safety of yoga in alleviating asthma.
METHODS: MEDLINE/PubMed, Scopus, the Cochrane Central Register of Controlled Trials, PsycINFO, CAM-Quest, CAMbase, and IndMED were searched through January 2014. Randomized controlled trials of yoga for patients with asthma were included if they assessed asthma control, symptoms, quality of life, and/or pulmonary function. For each outcome, standardized mean differences (SMDs) or risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. Risk of bias was assessed using the Cochrane tool.
RESULTS: Fourteen randomized controlled trials with 824 patients were included. Evidence for effects of yoga compared with usual care was found for asthma control (RR, 10.64; 95% CI, 1.98 to 57.19; P = .006), asthma symptoms (SMD, -0.37; 95% CI, -0.55 to -0.19; P < .001), quality of life (SMD, 0.86; 95% CI, 0.39 to 1.33; P < .001), peak expiratory flow rate (SMD, 0.49; 95% CI, 0.32 to 0.67; P < .001), and ratio of forced expiratory volume in 1 second to forced vital capacity (SMD, 0.50; 95% CI, 0.24 to 0.75; P < .001); evidence for effects of yoga compared with psychological interventions was found for quality of life (SMD, 0.61; 95% CI, 0.22 to 0.99; P = .002) and peak expiratory flow rate (SMD, 2.87; 95% CI, 0.14 to 5.60; P = .04). No evidence for effects of yoga compared with sham yoga or breathing exercises was revealed. No effect was robust against all potential sources of bias. Yoga was not associated with serious adverse events.
CONCLUSIONS: Yoga cannot be considered a routine intervention for asthmatic patients at this point. It can be considered an ancillary intervention or an alternative to breathing exercises for asthma patients interested in complementary interventions.

Asthma affects millions of individuals worldwide. Exercise-induced bronchoconstriction is common in patients diagnosed with asthma, but may also occur in patients without chronic asthma. Patients with isolated exercise-induced bronchoconstriction may require pretreatment with inhaled short-acting β-agonists prior to exercise. Patients diagnosed with asthma can achieve good control of the symptoms of exercise-induced bronchoconstriction with appropriate treatment of underlying chronic asthma. Current guidelines suggest staging patients with asthma based on severity of symptoms and initiating therapy according to their stage. Pharmacotherapy for asthma management consists of both quick-relief medications (short-acting β-agonists) as well as maintenance, or long-term control, medications (inhaled corticosteroids, long-acting β-agonists, leukotriene receptor antagonists, cromolyn, and theophylline).

BACKGROUND: Although physical exercise is recommended for asthmatics, evidence on the effects of exercise on clinical key factors is still missing.
OBJECTIVE: We performed a systematic review and meta-analysis to determine the effect of exercise training (EXT) on quality of life (QoL), bronchial hyperresponsiveness (BHR), exercise-induced bronchoconstriction (EIB), lung function and exercise capacity, plus the factors affecting changes in QoL and exercise capacity in asthmatics after a period of EXT.
METHODS: A computerized search was conducted in MEDLINE, EMBASE, and CINAHL (last search on 15 November 2012), without language restriction, and references of original studies and reviews were searched for further relevant studies.
METHODS: Two independent investigators screened full-text studies with asthmatic subjects undertaking EXT (defined as training for ≥7 days, ≥2 times per week, ≥5 training sessions in total) that assessed at least one of the following outcomes: QoL, airway hyperreactivity, forced expiratory volume in one second (FEV₁), peak expiratory flow (PEF), inflammatory parameters, exercise capacity, or exercise endurance. Potentially relevant studies were excluded if only respiratory muscle training, breathing exercises or yoga was performed, if asthmatic subjects with co-morbidities were investigated, if only data of mixed patient groups without separate results for asthmatics were presented, if training regimens were not sufficiently specified, if no numerical outcome data were presented, and if new long-term medication was introduced in addition to physical training. Of 500 potentially relevant articles, 13.4 % (67 studies including 2,059 subjects) met the eligibility criteria and were included for further analyses.
METHODS: Data extraction and risk of bias assessment was performed according to the Cochrane Handbook for Systematic Reviews of Interventions. A meta-analysis of all randomized controlled trials (RCTs) was performed to determine the effect of EXT on asthma symptoms, BHR, EIB, FEV₁, exercise capacity and exercise endurance compared with control training. In addition, relative pre/post changes were analysed in all RCTs and controlled trials. Finally, multiple linear regression models were used to identify effects of relative changes in airway hyperreactivity (BHR or EIB), lung function (FEV₁ or PEF) and training hours on QoL and exercise performance.
RESULTS: In a total of 17 studies including 599 subjects, meta-analyses showed a significant improvement in days without asthma symptoms, FEV1 and exercise capacity while BHR only tended to improve. The analysis of relative within-group changes after EXT showed, however, significant improvements in QoL (17 %), BHR (53 %), EIB (9 %), and FEV1 (3 %) compared with control conditions. Multiple linear regression models revealed that changes in airway hyperreactivity and lung function significantly contributed to the change in QoL, while mainly the changes in airway hyperreactivity contributed to the change in exercise capacity.
CONCLUSIONS: EXT was shown to improve asthma symptoms, QoL, exercise capacity, BHR, EIB, and FEV1 in asthmatics and improvements in BHR explained part of the improvement in QoL and exercise capacity. Thus, physical activity should be recommended as a supplementary therapy to medication. However, more well controlled studies should be performed assessing the relationship of physical activity, QoL, airway hyperreactivity, lung function and especially airway inflammation as well as medication intake.