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Pneumologie (Stuttgart, Germany) Jun 2011This is an updated overview of indications, contraindications, performance and interpretation of bronchial challenge tests. As speciality, the diagnostic step by step... (Review)
Review
This is an updated overview of indications, contraindications, performance and interpretation of bronchial challenge tests. As speciality, the diagnostic step by step scheme comprises in addition to the clinical case history a detailed exposure (occupational) history, lung function testing, assessment of nonspecific bronchial hyperresponsiveness, allergological diagnostics (skin prick test, measurement of specific IgE antibodies), privation and reexposure test and as gold standard specific bronchial challenge tests. The last mentioned tests are of particular importance in the framework of a diagnostic backup with regard to specific therapeutic and preventive measures and insurance regulations (occupational disease?). Specific bronchial challenge tests and their variant, the workplace-related challenge test, serve to objectify or exclude the clinical relevance and the current state of a respiratory sensitization. They require a comprehensive experience of the physician performing the tests. The majority of diseases does not necessitate these tests, especially if case history, lung function testing, allergy tests, privation and reexposure test provide unanimously positive results. If allergic symptoms of conjunctiva or the upper respiratory tract are of prime importance the performance of a specific conjunctival or nasal challenge test is recommended.
Topics: Allergens; Alveolitis, Extrinsic Allergic; Asthma; Asthma, Occupational; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstrictor Agents; Contraindications; Humans; Isocyanates; Methacholine Chloride; Predictive Value of Tests; Respiratory Function Tests
PubMed: 21154201
DOI: 10.1055/s-0030-1255967 -
Experimental Biology and Medicine... May 2021Assessment of respiratory mechanics extends from basic research and animal modeling to clinical applications in humans. However, to employ the applications in human... (Review)
Review
Assessment of respiratory mechanics extends from basic research and animal modeling to clinical applications in humans. However, to employ the applications in human models, it is desirable and sometimes mandatory to study non-human animals first. To acquire further precise and controlled signals and parameters, the animals studied must be further distant from their spontaneous ventilation. The majority of respiratory mechanics studies use positive pressure ventilation to model the respiratory system. In this scenario, a few drug categories become relevant: anesthetics, muscle blockers, bronchoconstrictors, and bronchodilators. Hence, the main objective of this study is to briefly review and discuss each drug category, and the impact of a drug on the assessment of respiratory mechanics. Before and during the positive pressure ventilation, the experimental animal must be appropriately sedated and anesthetized. The sedation will lower the pain and distress of the studied animal and the plane of anesthesia will prevent the pain. With those drugs, a more controlled procedure is carried out; further, because many anesthetics depress the respiratory system activity, a minimum interference of the animal's respiration efforts are achieved. The latter phenomenon is related to muscle blockers, which aim to minimize respiratory artifacts that may interfere with forced oscillation techniques. Generally, the respiratory mechanics are studied under appropriate anesthesia and muscle blockage. The application of bronchoconstrictors is prevalent in respiratory mechanics studies. To verify the differences among studied groups, it is often necessary to challenge the respiratory system, for example, by pharmacologically inducing bronchoconstriction. However, the selected bronchoconstrictor, doses, and administration can affect the evaluation of respiratory mechanics. Although not prevalent, studies have applied bronchodilators to return (airway resistance) to the basal state after bronchoconstriction. The drug categories can influence the mathematical modeling of the respiratory system, systemic conditions, and respiratory mechanics outcomes.
Topics: Anesthetics; Animals; Bronchoconstrictor Agents; Bronchodilator Agents; Models, Animal; Neuromuscular Blocking Agents; Respiratory Mechanics
PubMed: 33601911
DOI: 10.1177/1535370221993095 -
Pulmonary Pharmacology & Therapeutics Apr 2018Inhaled airway challenges provoke bronchoconstriction in susceptible subjects and are a pivotal tool in the diagnosis and monitoring of obstructive lung diseases, both... (Review)
Review
Inhaled airway challenges provoke bronchoconstriction in susceptible subjects and are a pivotal tool in the diagnosis and monitoring of obstructive lung diseases, both in the clinic and in the development of new respiratory medicines. This article reviews the main challenge agents that are in use today (methacholine, mannitol, adenosine, allergens, endotoxin) and emphasises the importance of controlling how these agents are administered. There is a danger that the optimal value of these challenge agents may not be realised due to suboptimal inhaled delivery; thus considerations for effective and reproducible challenge delivery are provided. This article seeks to increase awareness of the importance of precise delivery of inhaled agents used to challenge the airways for diagnosis and research, and is intended as a stepping stone towards much-needed standardisation and harmonisation in the administration of inhaled airway challenge agents.
Topics: Administration, Inhalation; Bronchial Provocation Tests; Bronchoconstriction; Bronchoconstrictor Agents; Drug Delivery Systems; Humans; Lung; Lung Diseases, Obstructive; Reproducibility of Results; Tissue Distribution
PubMed: 29331645
DOI: 10.1016/j.pupt.2018.01.004 -
American Journal of Respiratory and... Oct 2005Basic and clinical research strategies used for many lung diseases have depended on volunteer subjects undergoing bronchoscopy to establish access to the airways to... (Review)
Review
RATIONALE
Basic and clinical research strategies used for many lung diseases have depended on volunteer subjects undergoing bronchoscopy to establish access to the airways to collect biological specimens and tissue, perhaps with added bronchoprovocation in asthma syndromes. These procedures have yielded a wealth of important scientific information. Since the last critical review more than a decade ago, some of the techniques and applications have changed, and untoward events have occurred, raising safety concerns and increasing institutional review scrutiny.
OBJECTIVES AND METHODS
To reappraise these investigational methods in the context of current knowledge, the National Heart, Lung, and Blood Institute and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health convened a working group to review these procedures used for airway disease research, emphasizing asthma and chronic obstructive pulmonary disease.
MAIN RESULTS
The group reaffirmed the scientific importance of investigative bronchoscopy and bronchoprovocation, even as less invasive technologies evolve. The group also considered the safety of bronchoscopy and bronchoprovocation with methacholine and antigen to be acceptable for volunteer subjects and patients, but stressed the need to monitor this closely and to emphasize proper training of participating medical research personnel. Issues were raised about vulnerable volunteers, especially children who need surrogates for informed consent.
CONCLUSION
This review of investigative bronchoscopy and bronchoprovocation could serve as the basis for future guidelines for the use of these procedures in the United States.
Topics: Asthma; Biopsy; Bronchi; Bronchial Provocation Tests; Bronchoalveolar Lavage; Bronchoconstrictor Agents; Bronchoscopy; Forced Expiratory Volume; Humans; Lung Diseases; Methacholine Chloride; Pulmonary Disease, Chronic Obstructive
PubMed: 16020805
DOI: 10.1164/rccm.200407-966WS -
American Journal of Physiology. Lung... Oct 2022The enzyme, nitric oxide-sensitive guanylyl cyclase (NO-GC), is activated by binding NO to its prosthetic heme group and catalyzes the formation of cGMP. The NO-GC is...
The enzyme, nitric oxide-sensitive guanylyl cyclase (NO-GC), is activated by binding NO to its prosthetic heme group and catalyzes the formation of cGMP. The NO-GC is primarily known to mediate vascular smooth muscle relaxation in the lung, and inhaled NO has been successfully used as a selective pulmonary vasodilator. In comparison, NO-GC's impact on the regulation of airway tone is less acknowledged and, most importantly, little is known about the issue that NO-GC signaling is accomplished by two isoforms: NO-GC1 and NO-GC2, implying the existence of distinct "cGMP pools." Herein, we investigated the functional role of the NO-GC isoforms in respiration by measuring lung function parameters of isoform-specific knockout (KO) mice using noninvasive and invasive techniques. Our data revealed the participation and ongoing influence of NO-GC1-derived cGMP in the regulation of airway tone by showing that respiratory resistance was enhanced in NO-GC1-KOs and increased more pronouncedly after the challenge with the bronchoconstrictor methacholine. The tissue resistance and stiffness of NO-GC1-KOs were also higher because of narrowed airways that cause tissue distortion. Contrariwise, NO-GC2-KOs displayed reduced tissue elasticity, elastic recoil, and airway reactivity to methacholine, which did not even increase in an ovalbumin model of asthma that induced hyperresponsiveness in NO-GC1-KOs. In addition, conscious NO-GC2-KOs showed a higher breathing rate with a shorter duration of inspiration and expiration time, which remained faster even in the presence of bronchoconstrictors that slow down breathing. Thus, we provide evidence of two distinct NO/cGMP pathways in airways, accomplished by either NO-GC1 or NO-GC2, adjusting differentially the airway reactivity.
Topics: Animals; Bronchoconstrictor Agents; Cyclic GMP; Guanylate Cyclase; Heme; Methacholine Chloride; Mice; Mice, Knockout; Nitric Oxide; Ovalbumin; Protein Isoforms; Soluble Guanylyl Cyclase; Vasodilator Agents
PubMed: 35972838
DOI: 10.1152/ajplung.00404.2021 -
American Journal of Physiology. Lung... Dec 2021Increased insulin is associated with obesity-related airway hyperreactivity and asthma. We tested whether the use of metformin, an antidiabetic drug used to reduce...
Increased insulin is associated with obesity-related airway hyperreactivity and asthma. We tested whether the use of metformin, an antidiabetic drug used to reduce insulin resistance, can reduce circulating insulin, thereby preventing airway hyperreactivity in rats with dietary obesity. Male and female rats were fed a high- or low-fat diet for 5 wk. Some male rats were simultaneously treated with metformin (100 mg/kg orally). In separate experiments, after 5 wk of a high-fat diet, some rats were switched to a low-fat diet, whereas others continued a high-fat diet for an additional 5 wk. Bronchoconstriction and bradycardia in response to bilateral electrical vagus nerve stimulation or to inhaled methacholine were measured in anesthetized and vagotomized rats. Body weight, body fat, caloric intake, fasting glucose, and insulin were measured. Vagally induced bronchoconstriction was potentiated only in male rats on a high-fat diet. Males gained more body weight, body fat, and had increased levels of fasting insulin compared with females. Metformin prevented development of vagally induced airway hyperreactivity in male rats on high-fat diet, in addition to inhibiting weight gain, fat gain, and increased insulin. In contrast, switching rats to a low-fat diet for 5 wk reduced body weight and body fat, but it did not reverse fasting glucose, fasting insulin, or potentiation of vagally induced airway hyperreactivity. These data suggest that medications that target insulin may be effective treatment for obesity-related asthma.
Topics: Animals; Asthma; Bronchial Hyperreactivity; Bronchoconstriction; Bronchoconstrictor Agents; Diet, High-Fat; Female; Glucose; Hyperinsulinism; Hypoglycemic Agents; Male; Metformin; Methacholine Chloride; Obesity; Rats; Rats, Sprague-Dawley; Vagus Nerve; Weight Gain
PubMed: 34668415
DOI: 10.1152/ajplung.00202.2021 -
Therapeutic Advances in Respiratory... Aug 2009Airway hyper-responsiveness (AHR) is a cardinal feature of asthma. Its absence has been considered useful in excluding asthma, whereas it may be present in other... (Review)
Review
Airway hyper-responsiveness (AHR) is a cardinal feature of asthma. Its absence has been considered useful in excluding asthma, whereas it may be present in other diseases such as atopic rhinitis and chronic obstructive pulmonary disease. AHR is often considered an epiphenomenon of airway inflammation. Actually, the response of airways to constrictor stimuli is modulated by a complex array of factors, some facilitating and others opposing airway narrowing. Thus, it has been suggested that AHR, and perhaps asthma, might be present even without or before the development of airway inflammation. We begin this review by highlighting some terminological and methodological issues concerning the measurement of AHR. Then we describe the neurohumoral mechanisms controlling airway tone. Finally, the pivotal role of airway smooth muscle and internal and external modulation of airway caliber in vivo are discussed in detail.
Topics: Animals; Asthma; Bronchi; Bronchial Hyperreactivity; Bronchoconstrictor Agents; Dose-Response Relationship, Drug; Humans; Muscle, Smooth; Respiratory Function Tests
PubMed: 19661157
DOI: 10.1177/1753465809343595 -
Respiratory Physiology & Neurobiology Mar 2020Nocturnal worsening of asthma may be due to reduced lung volumes and fewer sigh breaths, which have been shown to increase airway resistance and bronchoreactivity. We... (Clinical Trial)
Clinical Trial
Nocturnal worsening of asthma may be due to reduced lung volumes and fewer sigh breaths, which have been shown to increase airway resistance and bronchoreactivity. We hypothesized that mimicking deep inspiration using nocturnal mechanical support would improve symptoms in patients with asthma. Subjects with asthma underwent usual care and bilevel positive airway pressure (PAP) therapy for 4 weeks, separated by 4 weeks, and methacholine challenge (PC) and subjective assessments. 13 patients with asthma alone and 8 with asthma + OSA completed the protocol. Change in bronchoreactivity (ratio of Post/Pre PC) was not significantly different during usual care and bilevel PAP [0.86 (IQR 0.19, 1.82) vs 0.94 (IQR 0.56, 2.5), p = 0.88], nor was the change in Asthma Control Test different: 0.1 ± 2.2 vs. -0.2 ± 2.9, p = 0.79, respectively. Bilevel PAP therapy for four weeks did not improve subjective or objective measures of asthma severity in patients with asthma or those with asthma and OSA, although there was heterogeneity in response.
Topics: Adult; Asthma; Bronchial Provocation Tests; Bronchoconstrictor Agents; Continuous Positive Airway Pressure; Cross-Over Studies; Female; Humans; Lung Volume Measurements; Male; Methacholine Chloride; Middle Aged; Outcome Assessment, Health Care; Sleep Apnea, Obstructive
PubMed: 31805396
DOI: 10.1016/j.resp.2019.103355 -
The European Respiratory Journal Sep 2000Bronchial hyperresponsiveness (BHR), an abnormal increase in airflow limitation following the exposure to a stimulus, is an important pathophysiological characteristic... (Review)
Review
Bronchial hyperresponsiveness (BHR), an abnormal increase in airflow limitation following the exposure to a stimulus, is an important pathophysiological characteristic of bronchial asthma. Because of heterogeneity of the airway response to different stimuli, the latter have been divided into direct and indirect stimuli. Direct stimuli cause airflow limitation by a direct action on the effector cells involved in the airflow limitation, while indirect stimuli exert their action essentially on inflammatory and neuronal cells that act as an intermediary between the stimulus and the effector cells. This manuscript reviews the clinical and experimental studies on the mechanisms involved in indirect BHR in patients with asthma. Pharmacological stimuli (adenosine, tachykinins, bradykinin, sodium metabisulphite/sulphur dioxide, and propranolol) as well as physical stimuli (exercise, nonisotonic aerosols, and isocapnic hyperventilation) are discussed. The results of the different direct and indirect bronchial challenge tests are only weakly correlated and are therefore not mutually interchangeable. Limited available data (studies on the effects of allergen avoidance and inhaled corticosteroids) suggest that indirectly acting bronchial stimuli (especially adenosine) might better reflect the degree of airway inflammation than directly acting stimuli. It remains to be established whether monitoring of indirect BHR as a surrogate marker of inflammation (in addition to symptoms and lung function) is of clinical relevance to the long-term management of asthmatic patients. This seems to be the case for the direct stimulus methacholine. More work needs to be performed to find out whether, indirect stimuli are more suitable in asthma monitoring than direct ones. Recommendations on the application of indirect challenges in clinical practice and research will shortly be available from the European Respiratory Society Task Force.
Topics: Adenosine; Adenosine Monophosphate; Adrenergic beta-Antagonists; Aerosols; Asthma; Bradykinin; Bronchial Hyperreactivity; Bronchoconstrictor Agents; Exercise; Humans; Propranolol; Pulmonary Ventilation; Sulfites; Sulfur Dioxide; Tachykinins
PubMed: 11028670
DOI: 10.1034/j.1399-3003.2000.016003514.x -
Respiratory Physiology & Neurobiology Oct 2021Balb/c mice respiratory mechanics was studied in two intravenous methacholine (MCh) protocols: bolus and continuous infusion. The Constant Phase Model (CPM) was used in...
Balb/c mice respiratory mechanics was studied in two intravenous methacholine (MCh) protocols: bolus and continuous infusion. The Constant Phase Model (CPM) was used in this study. The harmonic distortion index (k) was used to assess the respiratory system nonlinearity. The analysis of variance showed difference between groups (OVA vs control) and among doses for both protocols. Bolus protocol posttest: there was a difference between OVA and control at 0.3 and 1 mg/kg doses (p<0.0001 and p<0.001) for R. Infusion: there was a difference between OVA and control at 192 μg.kg.min dose for R, G and H, (p<0.01; p<0.001; p<0.001). An increment was found in k values near to the observed peak values in bolus protocol. The bolus protocol could better differentiate inflamed and non-inflamed airway resistance, whereas the differences between OVA and control in continuous infusion protocol were associated to airway- and, mainly, parenchyma-related parameters. Moreover, the bolus protocol presented a higher nonlinear degree compared to the infusion protocol.
Topics: Animals; Asthma; Bronchoconstrictor Agents; Disease Models, Animal; Male; Methacholine Chloride; Mice; Mice, Inbred BALB C; Models, Theoretical; Respiratory Mechanics
PubMed: 34062282
DOI: 10.1016/j.resp.2021.103705