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The Cochrane Database of Systematic... 2000Exercise-induced asthma causes cough, dyspnea, wheeze and chest tightness. Management of focuses on prevention through pharmaco-therapy and alternate strategies. Single... (Review)
Review
BACKGROUND
Exercise-induced asthma causes cough, dyspnea, wheeze and chest tightness. Management of focuses on prevention through pharmaco-therapy and alternate strategies. Single use, pre-exercise beta2-agonists and non-steroidal anti-inflammatory agents such as the cromones are the most common treatments.
OBJECTIVES
The objective of this review was to assess the effects of a single dose of nedocromil sodium to prevent exercise-induced bronchoconstriction.
SEARCH STRATEGY
We searched the Cochrane Airways Group trials register, the Cochrane Controlled Trials Register, Current Contents, review articles, textbooks and reference lists of articles. We also contacted the drug manufacturer and primary authors for additional citations.
SELECTION CRITERIA
Randomised trials comparing a single dose of nedocromil sodium with placebo to prevent exercise-induced bronchoconstriction in people over six years of age.
DATA COLLECTION AND ANALYSIS
Trial quality assessment and data extraction were conducted independently by two reviewers. Study authors were contacted for confirmation of data.
MAIN RESULTS
Twenty randomised controlled trials involving 280 participants were identified. 15-60 min following inhalation of 4 mg nedocromil, the maximum fall in forced expiratory volume in one second due to exercise was improved by 15.6%, (95% CI:13.2 to 18.1) compared to the placebo response. The maximum percentage fall in peak expiratory flow rate was of the same magnitude (weighted mean difference 15.0%; 95% CI 8.3 to 21.6). Nedocromil shortened the time to recover lung normal function from more than 30 minutes with placebo to less than 10 minutes with the drug. The relative magnitude of its effect was greatest in patients with more severe exercise-induced bronchoconstriction (defined as an exercise-induced fall in lung function > 30% from baseline). There were no significant adverse effects reported.
REVIEWER'S CONCLUSIONS
Nedocromil sodium used before exercise appears to reduce the severity and duration of exercise-induced bronchoconstriction. This effect appears to be more pronounced in people with severe exercise-induced bronchoconstriction.
Topics: Adolescent; Adult; Aged; Asthma, Exercise-Induced; Bronchoconstriction; Humans; Middle Aged; Nedocromil
PubMed: 10796616
DOI: 10.1002/14651858.CD001183 -
Respiratory Medicine Feb 2003A high prevalence of asthma has been reported in athletes. However, studies in this population usually show an even higher prevalence of airway hyperresponsiveness (AHR)... (Review)
Review
A high prevalence of asthma has been reported in athletes. However, studies in this population usually show an even higher prevalence of airway hyperresponsiveness (AHR) and exercise-induced bronchoconstriction (EIB). This report compares studies on self-reported or physician-diagnosed asthma in athletes with those using objective measures of airflow limitation or airway responsiveness. The higher prevalence of AHR (or EIB) measured in athletes, when compared with the prevalence of self-reported or physician-diagnosed asthma, suggests that abnormal airway responses are common in athletes, although they are infrequently associated with troublesome respiratory symptoms. This may indicate underdiagnosis of asthma in athletes, possibly due to an underreporting of respiratory symptoms or a reduction in perception of nociceptive sensations with repeated exercise over time, or it may simply mean that high-level training is associated with asymptomatic AHR. In athletes, as in the general population, the use of subjective methods such as surveys and questionnaires results in an underestimation ofthe prevalence of airway dysfunction when compared with objective measurements. The significance of these observations is unknown, and there is a need to determine their long-term consequences for athletes.
Topics: Asthma, Exercise-Induced; Bronchial Hyperreactivity; Bronchoconstriction; Diagnostic Errors; Forced Expiratory Volume; Humans; Prevalence; Sports
PubMed: 12587959
DOI: 10.1053/rmed.2003.1451 -
Proceedings of the American Thoracic... 2005It is now clear that the beta2-adrenergic receptor continuously oscillates between various conformations in the basal state, and that agonists act to stabilize one or... (Review)
Review
It is now clear that the beta2-adrenergic receptor continuously oscillates between various conformations in the basal state, and that agonists act to stabilize one or more conformations. It is conceivable that synthetic agonists might be engineered to preferentially confine the receptor to certain conformations deemed clinically important while having a less stabilizing effect on unwanted conformations. In addition, studies of genetically engineered mice have revealed previously unrecognized cross-talk between the beta2-receptor and phospholipase C, such that removal of the primary dilating pathway results in downregulation of constrictive pathways and overactivity of the dilating pathway increases the contractile response. These results indicate a dynamic interaction between beta2-receptor activity and Gq-coupled receptors that constrict the airway. Potentially, then, during chronic beta-agonist therapy, expression of phospholipase C is increased, the functions of Gq-coupled constrictive receptors are enhanced, and there may be an increased tendency for clinical decompensation due to asthma and chronic obstructive pulmonary disease triggers. Antagonists to these receptors might be able to act synergistically with chronic beta-agonists to block the effect of phospholipase C. Alternatively, perhaps novel phospholipase C antagonists would provide the most efficacious approach to blocking the physiologic sequelae of cross-talk between the beta2-receptor and phospholipase C.
Topics: Adrenergic beta-2 Receptor Agonists; Animals; Asthma; Bronchoconstriction; Humans; Mice; Pulmonary Disease, Chronic Obstructive; Receptor Cross-Talk; Receptors, Adrenergic, beta-2; Signal Transduction; Type C Phospholipases
PubMed: 16267351
DOI: 10.1513/pats.200504-027SR -
Sports Medicine (Auckland, N.Z.) Aug 2016In athletes, a secure diagnos is of exercise-induced bronchoconstriction (EIB) is dependent on objective testing. Evaluating spirometric indices of airflow before and... (Review)
Review
In athletes, a secure diagnos is of exercise-induced bronchoconstriction (EIB) is dependent on objective testing. Evaluating spirometric indices of airflow before and following an exercise bout is intuitively the optimal means for the diagnosis; however, this approach is recognized as having several key limitations. Accordingly, alternative indirect bronchoprovocation tests have been recommended as surrogate means for obtaining a diagnosis of EIB. Of these tests, it is often argued that the eucapnic voluntary hyperpnea (EVH) challenge represents the 'gold standard'. This article provides a state-of-the-art review of EVH, including an overview of the test methodology and its interpretation. We also address the performance of EVH against the other functional and clinical approaches commonly adopted for the diagnosis of EIB. The published evidence supports a key role for EVH in the diagnostic algorithm for EIB testing in athletes. However, its wide sensitivity and specificity and poor repeatability preclude EVH from being termed a 'gold standard' test for EIB.
Topics: Asthma, Exercise-Induced; Bronchoconstriction; Exercise; Forced Expiratory Volume; Humans; Hyperventilation
PubMed: 27007599
DOI: 10.1007/s40279-016-0491-3 -
The novel TRPA1 antagonist BI01305834 inhibits ovalbumin-induced bronchoconstriction in guinea pigs.Respiratory Research Feb 2021Asthma is a chronic respiratory disease in which the nervous system plays a central role. Sensory nerve activation, amongst others via Transient Receptor Potential...
BACKGROUND
Asthma is a chronic respiratory disease in which the nervous system plays a central role. Sensory nerve activation, amongst others via Transient Receptor Potential Ankyrin 1 (TRPA1) channels, contributes to asthma characteristics including cough, bronchoconstriction, mucus secretion, airway hyperresponsiveness (AHR) and inflammation. In the current study, we evaluated the efficacy of the novel TRPA1 antagonist BI01305834 against AHR and inflammation in guinea-pig models of asthma.
METHODS
First, a pilot study was performed in a guinea-pig model of allergic asthma to find the optimal dose of BI01305834. Next, the effect of BI01305834 on (1) AHR to inhaled histamine after the early and late asthmatic reaction (EAR and LAR), (2) magnitude of EAR and LAR and (3) airway inflammation was assessed. Precision-cut lung slices and trachea strips were used to investigate the bronchoprotective and bronchodilating-effect of BI01305834. Statistical evaluation of differences of in vivo data was performed using a Mann-Whitney U test or One-way nonparametric Kruskal-Wallis ANOVA, for ex vivo data One- or Two-way ANOVA was used, all with Dunnett's post-hoc test where appropriate.
RESULTS
A dose of 1 mg/kg BI01305834 was selected based on AHR and exposure data in blood samples from the pilot study. In the subsequent study, 1 mg/kg BI01305834 inhibited AHR after the EAR, and the development of EAR and LAR elicited by ovalbumin in ovalbumin-sensitized guinea pigs. BI01305834 did not inhibit allergen-induced total and differential cells in the lavage fluid and interleukin-13 gene expression in lung homogenates. Furthermore, BI01305834 was able to inhibit allergen and histamine-induced airway narrowing in guinea-pig lung slices, without affecting histamine release, and reverse allergen-induced bronchoconstriction in guinea-pig trachea strips.
CONCLUSIONS
TRPA1 inhibition protects against AHR and the EAR and LAR in vivo and allergen and histamine-induced airway narrowing ex vivo, and reverses allergen-induced bronchoconstriction independently of inflammation. This effect was partially dependent upon histamine, suggesting a neuronal and possible non-neuronal role for TRPA1 in allergen-induced bronchoconstriction.
Topics: Administration, Inhalation; Animals; Asthma; Bronchoconstriction; Bronchodilator Agents; Dose-Response Relationship, Drug; Guinea Pigs; Humans; Lung; Male; Organ Culture Techniques; Ovalbumin; Pilot Projects; TRPA1 Cation Channel
PubMed: 33557843
DOI: 10.1186/s12931-021-01638-7 -
The British Journal of Nutrition May 2017Although high dose n-3 PUFA supplementation reduces exercise- and hyperpnoea-induced bronchoconstriction (EIB/HIB), there are concurrent issues with cost, compliance and...
Comparable reductions in hyperpnoea-induced bronchoconstriction and markers of airway inflammation after supplementation with 6·2 and 3·1 g/d of long-chain n-3 PUFA in adults with asthma.
Although high dose n-3 PUFA supplementation reduces exercise- and hyperpnoea-induced bronchoconstriction (EIB/HIB), there are concurrent issues with cost, compliance and gastrointestinal discomfort. It is thus pertinent to establish the efficacy of lower n-3 PUFA doses. Eight male adults with asthma and HIB and eight controls without asthma were randomly supplemented with two n-3 PUFA doses (6·2 g/d (3·7 g EPA and 2·5 g DHA) and 3·1 g/d (1·8 g EPA and 1·3 g DHA)) and a placebo, each for 21 d followed by 14 d washout. A eucapnic voluntary hyperpnoea (EVH) challenge was performed before and after treatments. Outcome measures remained unchanged in the control group. In the HIB group, the peak fall in forced expiratory volume in 1 s (FEV1) after EVH at day 0 (-1005 (sd 520) ml, -30 (sd 18) %) was unchanged after placebo. The peak fall in FEV1 was similarly reduced from day 0 to day 21 of 6·2 g/d n-3 PUFA (-1000 (sd 460) ml, -29 (sd 17) % v. -690 (sd 460) ml, -20 (sd 15) %) and 3·1 g/d n-3 PUFA (-970 (sd 480) ml, -28 (sd 18) % v. -700 (sd 420) ml, -21 (sd 15) %) (P<0·001). Baseline fraction of exhaled nitric oxide was reduced by 24 % (P=0·020) and 31 % (P=0·018) after 6·2 and 3·1 g/d n-3 PUFA, respectively. Peak increases in 9α, 11β PGF2 after EVH were reduced by 65 % (P=0·009) and 56 % (P=0·041) after 6·2 and 3·1 g/d n-3 PUFA, respectively. In conclusion, 3·1 g/d n-3 PUFA supplementation attenuated HIB and markers of airway inflammation to a similar extent as a higher dose. Lower doses of n-3 PUFA thus represent a potentially beneficial adjunct treatment for adults with asthma and EIB.
Topics: Adult; Asthma; Biomarkers; Bronchoconstriction; Dietary Supplements; Dose-Response Relationship, Drug; Fatty Acids, Omega-3; Humans; Inflammation; Male; Phospholipids; Young Adult
PubMed: 28606216
DOI: 10.1017/S0007114517001246 -
Journal of Investigational Allergology... 2011A 13-year-old elite swimmer presented with wheezing after indoor swimming training. On the basis of her clinical history and the tests performed, exercise-induced asthma...
A 13-year-old elite swimmer presented with wheezing after indoor swimming training. On the basis of her clinical history and the tests performed, exercise-induced asthma and mold-induced asthma were ruled out and a diagnosis of chlorine-induced asthma was made.
Topics: Adolescent; Asthma, Exercise-Induced; Bronchoconstriction; Chlorine; Female; Humans; Skin Tests; Swimming; Swimming Pools
PubMed: 21548454
DOI: No ID Found -
The European Respiratory Journal Jun 2006beta(2)-Adrenoceptor agonists evoke rapid bronchodilatation and are the mainstay of the treatment of asthma symptoms worldwide. The mechanism of action of this class of... (Review)
Review
beta(2)-Adrenoceptor agonists evoke rapid bronchodilatation and are the mainstay of the treatment of asthma symptoms worldwide. The mechanism of action of this class of compounds is believed to involve the stimulation of adenylyl cyclase and subsequent activation of the cyclic adenosine monosphosphate (cAMP)/cAMP-dependent protein kinase cascade. This classical model of beta(2)-adrenoceptor-mediated signal transduction is deeply entrenched, but there is compelling evidence that agonism of beta(2)-adrenoceptors can lead to the activation of multiple effector pathways, which now compels researchers in academia and the pharmaceutical industry alike to think beyond the traditional dogma. Therefore, the regulation by beta(2)-adrenoceptor agonists of responses, including airways smooth muscle tone and the secretory capacity of the epithelium and pro-inflammatory/immune cells, may be highly complex, involving both cAMP-dependent and -independent mechanisms that, in many cases, may act in concert. In this article, the current status of beta(2)-adrenoceptor-mediated signalling in the airways is reviewed in the context of understanding mechanisms that may underlie both the beneficial and detrimental effects of these drugs in asthma symptom management.
Topics: Adrenergic beta-Agonists; Airway Resistance; Asthma; Bronchoconstriction; Cyclic AMP; Humans; Immunity, Cellular; Inflammation; Lung; Muscle, Smooth; Receptors, Adrenergic, beta-2; Signal Transduction
PubMed: 16772391
DOI: 10.1183/09031936.06.00112605 -
Prostaglandins & Other Lipid Mediators Oct 2023Exercise-induced bronchoconstriction (EIB) is thought to be triggered by increased osmolarity at the airway epithelium. The aim of this study was to define the... (Review)
Review
Exercise-induced bronchoconstriction (EIB) is thought to be triggered by increased osmolarity at the airway epithelium. The aim of this study was to define the contractile prostanoid component of EIB, using an ex vivo model where intact segments of bronchi (inner diameter 0.5-2 mm) isolated from human lung tissue and subjected to mannitol. Exposure of bronchial segments to hyperosmolar mannitol evoked a contraction (64.3 ± 3.5 %) which could be prevented either by elimination of mast cells (15.8 ± 4.3 %) or a combination of cysteinyl leukotriene (cysLT), histamine (H) and thromboxane (TP) receptor antagonists (11.2 ± 2.3 %). Likewise, when antagonism of TP receptor was exchanged for inhibition of either cyclooxygenase-1 (8 ± 2.5 %), hematopoietic prostaglandin (PG)D synthase (20.7 ± 5.6 %), TXA synthase (14.8 ± 4.9 %), or the combination of the latter two (12.2 ± 4.6 %), the mannitol-induced contraction was prevented, suggesting that the TP-mediated component is induced by PGD and TXA generated by COX-1 and their respective synthases.
Topics: Humans; Bronchoconstriction; Prostaglandins; Lung; Bronchi; Mannitol
PubMed: 37336434
DOI: 10.1016/j.prostaglandins.2023.106761 -
Effects of posture and bronchoconstriction on low-frequency input and transfer impedances in humans.Journal of Applied Physiology... Jul 2004We simultaneously evaluated the mechanical response of the total respiratory system, lung, and chest wall to changes in posture and to bronchoconstriction. We... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
We simultaneously evaluated the mechanical response of the total respiratory system, lung, and chest wall to changes in posture and to bronchoconstriction. We synthesized the optimal ventilation waveform (OVW) approach, which simultaneously provides ventilation and multifrequency forcing, with optoelectronic plethysmography (OEP) to measure chest wall flow globally and locally. We applied an OVW containing six frequencies from 0.156 to 4.6 Hz to the mouth of six healthy men in the seated and supine positions, before and after methacholine challenge. We measured mouth, esophageal, and transpulmonary pressures, airway flow by pneumotachometry, and total chest wall, pulmonary rib cage, and abdominal volumes by OEP. We computed total respiratory, lung, and chest wall input impedances and the total and regional transfer impedances (Ztr). These data were appropriately sensitive to changes in posture, showing added resistance in supine vs. seated position. The Ztr were also highly sensitive to lung constriction, more so than input impedance, as the former is minimally distorted by shunting of flow into alveolar gas compression and airway walls. Local impedances show that, during bronchoconstriction and at typical breathing frequencies, the contribution of the abdomen becomes amplified relative to the rib cage. A similar redistribution occurs when passing from seated to supine. These data suggest that the OEP-OVW approach for measuring Ztr could noninvasively track important lung and respiratory conditions, even in subjects who cannot cooperate. Applications might range from routine evaluation of airway hyperreactivity in asthmatic subjects to critical conditions in the supine position during mechanical ventilation.
Topics: Adult; Airway Resistance; Biomechanical Phenomena; Bronchoconstriction; Elasticity; Functional Residual Capacity; Humans; Lung; Male; Oxygen; Posture; Respiratory Mechanics; Supine Position; Thoracic Wall
PubMed: 14966017
DOI: 10.1152/japplphysiol.00721.2003