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Respiratory Care Aug 2021The spirometric response to fast-acting bronchodilator is used clinically to diagnose asthma and in clinical research to verify its presence. However, bronchodilator...
BACKGROUND
The spirometric response to fast-acting bronchodilator is used clinically to diagnose asthma and in clinical research to verify its presence. However, bronchodilator responsiveness does not correlate with airway hyper-responsiveness measured with the direct-acting stimulus of methacholine, demonstrating that bronchodilator responsiveness is a problematic method for diagnosing asthma. The relationship between bronchodilator responsiveness and airway hyper-responsiveness assessed with indirect-acting stimuli is not known.
METHODS
Retrospectively, the spirometric responses to inhaled bronchodilator and a eucapnic voluntary hyperpnea challenge (EVH) were compared in 39 non-smoking adult subjects with asthma (26 male, 13 female; mean ± SD age 26.9 ± 7.8 y; mean ± SD body mass index 26.3 ± 4.7 kg/m). All subjects met one or both of 2 criteria: ≥ 12% and 200 mL increase in FEV after inhaled bronchodilator, and ≥ 10% decrease in FEV after an EVH challenge.
RESULTS
Overall, FEV increased by 9.9 ± 7.9% after bronchodilator (3.93 ± 0.97 to 4.28 ± 0.91 L, < .001) and decreased by 23.9 ± 15.0% after the EVH challenge (3.89 ± 0.89 to 2.96 ± 0.88 L, < .001). However, the change in FEV after bronchodilator did not correlate with the change after EVH challenge (r = 0.062, = .71). Significant bronchodilator responsiveness predicted a positive response to EVH challenge in 9 of 33 subjects (sensitivity 27%). Following EVH, the change in FEV strongly correlated with the change in FVC (FEV percent change vs FVC percent change, r = 0.831, < .001; FEV ΔL vs FVC ΔL, r = 0.799, < .001).
CONCLUSIONS
These results extend previous findings that demonstrate a lack of association between bronchodilator responsiveness and methacholine responsiveness. Given the poor concordance between the spirometric response to fast-acting bronchodilator and the EVH challenge, these findings suggest that the airway response to inhaled β-agonist must be interpreted with caution and in the context of its determinants and limitations.
Topics: Adult; Asthma; Bronchial Provocation Tests; Bronchodilator Agents; Female; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Retrospective Studies; Young Adult
PubMed: 34006592
DOI: 10.4187/respcare.08421 -
Journal of Korean Medical Science May 2021Most epidemiological studies depend on the subjects' response to asthma symptom questionnaires. Questionnaire-based study for childhood asthma prevalence may...
BACKGROUND
Most epidemiological studies depend on the subjects' response to asthma symptom questionnaires. Questionnaire-based study for childhood asthma prevalence may overestimate the true prevalence. The aim of this study was to investigate the prevalence of "Current asthma" using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and methacholine challenge test in Korean children.
METHODS
Our survey on allergic disease included 4,791 children (age 7-12 years) from 2010 to 2014 in Korean elementary schools. Bronchial hyperresponsiveness (BHR) was defined as provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20) ≤ 16 mg/mL. "Current asthma symptoms" was defined as positive response to "Wheezing, current," "Treatment, current," or "Exercise, current." "Current asthma" was defined when the subjects with "Current asthma symptoms" showed BHR on the methacholine challenge test or had less than 70% of predicted FEV1 value.
RESULTS
The prevalence of "Wheezing, ever," "Wheezing, current," "Diagnosis, ever," "Treatment, current," "Exercise, current," and "Current asthma symptoms" was 19.6%, 6.9%, 10.0%, 3.3%, 3.5%, and 9.6%, respectively, in our cross-sectional study of Korean elementary school students. The prevalence of BHR in elementary school students was 14.5%. The prevalence of BHR in children with "Wheezing, ever," "Wheezing, current," "Diagnosis, ever," "Treatment, current," and "Exercise, current" was 22.3%, 30.5%, 22.4%, 28.8%, and 29.9%, respectively. BHR was 26.1% in those with "Current asthma symptoms." The prevalence of "Current asthma" was 2.7%.
CONCLUSIONS
Our large-scale study provides 2.7% prevalence of current asthma in Korean elementary school children. Since approximately one third of the children who have "Current asthma symptoms" present BHR, both subjective and objective methods are required to accurately predict asthma in subjects with asthma symptoms.
Topics: Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstrictor Agents; Child; Cross-Sectional Studies; Female; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Prevalence; Republic of Korea; Respiratory Sounds; Surveys and Questionnaires
PubMed: 34002550
DOI: 10.3346/jkms.2021.36.e130 -
BMC Pulmonary Medicine May 2021Methacholine challenge tests (MCTs) are used to diagnose airway hyperresponsiveness (AHR) in patients with suspected asthma where previous diagnostic testing has been...
BACKGROUND
Methacholine challenge tests (MCTs) are used to diagnose airway hyperresponsiveness (AHR) in patients with suspected asthma where previous diagnostic testing has been inconclusive. The test is time consuming and usually requires referral to specialized centers. Simple methods to predict AHR could help determine which patients should be referred to MCTs, thus avoiding unnecessary testing. Here we investigated the potential use of baseline spirometry variables as surrogate markers for AHR in adults with suspected asthma.
METHODS
Baseline spirometry and MCTs performed between 2013 and 2019 in a large tertiary center were retrospectively evaluated. Receiver-operating characteristic curves for the maximal expiratory flow-volume curve indices (angle β, FEV1, FVC, FEV1/FVC, FEF, FEF) were constructed to assess their overall accuracy in predicting AHR and optimal cutoff values were identified.
RESULTS
A total of 2983 tests were analyzed in adults aged 18-40 years. In total, 14% of all MCTs were positive (PC20 ≤ 16 mg/ml). All baseline spirometry parameters were significantly lower in the positive group (p < 0.001). FEF showed the best overall accuracy (AUC = 0.688) and proved to be useful as a negative predictor when applying FEF ≥ 110% as a cutoff level.
CONCLUSIONS
This study highlights the role of FEF in predicting AHR in patients with suspected asthma. A value of ≥ 110% for baseline FEF could be used to exclude AHR and would lead to a substantial decrease in MCT referrals.
Topics: Adult; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstrictor Agents; Cross-Sectional Studies; Female; Forced Expiratory Volume; Humans; Israel; Logistic Models; Male; Methacholine Chloride; Predictive Value of Tests; ROC Curve; Retrospective Studies; Spirometry; Vital Capacity; Young Adult
PubMed: 33957916
DOI: 10.1186/s12890-021-01506-6 -
Tuberkuloz Ve Toraks Mar 2021Airway hyper-responsiveness (AHR) is a characteristic feature of asthma. The aim of this study was to compare the impulse oscillometry (IOS) and spirometry to... (Comparative Study)
Comparative Study
INTRODUCTION
Airway hyper-responsiveness (AHR) is a characteristic feature of asthma. The aim of this study was to compare the impulse oscillometry (IOS) and spirometry to methacholine for AHR detection among individuals with clinically hyper-reactive airway disease suggestive of bronchial asthma and baseline spirometry were normal.
MATERIALS AND METHODS
Adults with symptoms suggestive of AHR and normal baseline spirometry test were selected. The short protocol of methacholine challenge test (MCT) was performed for all subjects using IOS and spirometry simultaneously. The primary endpoint was to compare the methacholine dosage causing a 20% drop in forced expiratory volume in one second (FEV1), with methacholine dosage that causing 40% increasing the baseline respiratory resistance at 5 hertz (R5), as measured by IOS.
RESULT
A total of 235 participants were analyzed, 184 (78.2%) had positive test results with R5, while 81 (34.4%) had positive MCT results with FEV1.The sensitivity and specificity of MCT with R5were 87.3%, 64.6%, and MCT with FEV1 were 39.1%, 85.4%, respectively. The area under the receiver operating characteristic (ROC) curve was greater at lower doses of MCT at R5, (AUROC: 0.653; p= 0.01).
CONCLUSIONS
The results showed higher sensitivity, negative predictive value, and earlier response of the short protocol of MCT with IOS, compared to MCT with spirometry. Our study suggested the utility of IOS in addition to conventional spirometry as a method of choice in MCT for detection of AHR.
Topics: Adult; Airway Obstruction; Airway Resistance; Asthma; Bronchial Provocation Tests; Female; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Oscillometry; ROC Curve; Respiratory Function Tests; Respiratory Hypersensitivity; Sensitivity and Specificity; Spirometry
PubMed: 33853300
DOI: 10.5578/tt.20219901 -
The European Respiratory Journal Jun 2021
Topics: Bronchial Provocation Tests; Forced Expiratory Volume; Humans; Lymphangioleiomyomatosis; Methacholine Chloride; Vascular Endothelial Growth Factor D
PubMed: 33653809
DOI: 10.1183/13993003.04270-2020 -
Journal of Cellular Physiology Sep 2021Bitter taste receptors (TAS2Rs) and their signaling elements are detected throughout the body, and bitter tastants induce a wide variety of biological responses in...
Bitter taste receptors (TAS2Rs) and their signaling elements are detected throughout the body, and bitter tastants induce a wide variety of biological responses in tissues and organs outside the mouth. However, the roles of TAS2Rs in these responses remain to be tested and established genetically. Here, we employed the CRISPR/Cas9 gene-editing technique to delete three bitter taste receptors-Tas2r143/Tas2r135/Tas2r126 (i.e., Tas2r triple knockout [TKO]) in mice. The fidelity and effectiveness of the Tas2r deletions were validated genetically at DNA and messenger RNA levels and functionally based on the tasting of TAS2R135 and TAS2R126 agonists. Bitter tastants are known to relax airways completely. However, TAS2R135 or TAS2R126 agonists either failed to induce relaxation of pre-contracted airways in wild-type mice and Tas2r TKO mice or relaxed them dose-dependently, but to the same extent in both types of mice. These results indicate that TAS2Rs are not required for bitter tastant-induced bronchodilation. The Tas2r TKO mice also provide a valuable model to resolve whether TAS2Rs mediate bitter tastant-induced responses in many other extraoral tissues.
Topics: Animals; Base Sequence; Gene Deletion; Gene Expression Profiling; Ligands; Methacholine Chloride; Mice, Knockout; Muscle Contraction; Muscle Relaxation; Muscle, Smooth; Receptors, G-Protein-Coupled; Respiratory System; Taste; Tongue; Mice
PubMed: 33559206
DOI: 10.1002/jcp.30315 -
BMC Pulmonary Medicine Feb 2021Cough variant asthma (CVA) is one of the special populations of asthma. The aim of the study was to compare small airways, the degree of bronchial hyperresponsiveness...
BACKGROUND
Cough variant asthma (CVA) is one of the special populations of asthma. The aim of the study was to compare small airways, the degree of bronchial hyperresponsiveness (BHR) and airway inflammatory subtypes between CVA and classic asthma (CA), and investigate the relationship between these markers to determine the accuracy as indicators of CVA.
METHODS
A total of 825 asthmatic patients participated in the study and 614 were included. 614 patients underwent spirometry and a bronchial challenge with methacholine and 459 patients performed induction sputum cell test.
RESULTS
The number of CVA patients showed less small airway dysfunction than those of CA patients (p < 0.005). The degree of small airways dysfunction was higher in the CA group compared with the CVA group (p < 0.001). Small airways dysfunction was severer in the eosinophilic airway inflammatory subtype compared with other subtypes (p < 0.05).The area under curve of MMEF, FEF and FEF (% predicted) was 0.615, 0.621, 0.606, respectively. 0.17mcg of PD and 4.7% of sputum eosinophils was the best diagnostic value for CVA with an AUC of 0.582 and 0.575 (p = 0.001 and p = 0.005, respectively).
CONCLUSIONS
The eosinophilic airway inflammatory subtype may be increased small airway dysfunction. The value of small airways, BHR and induction sputum cells in CVA prediction, which reflected significant, but not enough to be clinically useful.
Topics: Adult; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstrictor Agents; Cough; Dose-Response Relationship, Drug; Eosinophil Cationic Protein; Eosinophils; Female; Forced Expiratory Volume; Humans; Leukocyte Count; Male; Methacholine Chloride; Middle Aged; Multivariate Analysis; Retrospective Studies; Sputum
PubMed: 33536015
DOI: 10.1186/s12890-021-01419-4 -
American Journal of Physiology. Lung... Apr 2021Obesity increases incidence and severity of asthma but the molecular mechanisms are not completely understood. Hyperinsulinemia potentiates vagally induced...
Obesity increases incidence and severity of asthma but the molecular mechanisms are not completely understood. Hyperinsulinemia potentiates vagally induced bronchoconstriction in obese rats. Since bronchoconstriction results from airway smooth muscle contraction, we tested whether insulin changed agonist-induced airway smooth muscle contraction. Obesity-prone and resistant rats were fed a low-fat diet for 5 wk and treated with insulin (Lantus, 3 units/rat sc) 16 h before vagally induced bronchoconstriction was measured. Ex vivo, contractile responses to methacholine were measured in isolated rat tracheal rings and human airway smooth muscle strips before and after incubation (0.5-2 h) with 100 nM insulin or 13.1 nM insulin like growth factor-1 (IGF-1). M and M muscarinic receptor mRNA expression was quantified by qRT-PCR and changes in intracellular calcium were measured in response to methacholine or serotonin in isolated rat tracheal smooth muscle cells treated with 1 µM insulin. Insulin, administered to animals 16 h prior, potentiated vagally induced bronchoconstriction in both obese-prone and resistant rats. Insulin, not IGF-1, significantly increased methacholine-induced contraction of rat and human isolated airway smooth muscle. In cultured rat tracheal smooth muscle cells, insulin significantly increased M, not M mRNA expression and enhanced methacholine- and serotonin-induced increase in intracellular calcium. Insulin alone did not cause an immediate increase in intracellular calcium. Thus, insulin acutely potentiated agonist-induced increase in intracellular calcium and airway smooth muscle contraction. These findings may explain why obese individuals with hyperinsulinemia are prone to airway hyperreactivity and give insights into future targets for asthma treatment.
Topics: Animals; Bronchial Hyperreactivity; Bronchoconstriction; Calcium; Humans; Hyperinsulinism; Hypoglycemic Agents; Insulin; Male; Methacholine Chloride; Muscarinic Agonists; Muscle Contraction; Muscle, Smooth; Obesity; Rats; Rats, Sprague-Dawley; Receptors, Muscarinic; Trachea; Vagus Nerve
PubMed: 33501891
DOI: 10.1152/ajplung.00232.2020 -
Medical Journal, Armed Forces India Jan 2021Bronchial hyper-responsiveness (BHR) is the hallmark of bronchial asthma, characterized by clinical features of cough, wheeze, breathlessness and chest tightness which...
BACKGROUND
Bronchial hyper-responsiveness (BHR) is the hallmark of bronchial asthma, characterized by clinical features of cough, wheeze, breathlessness and chest tightness which are confirmed by spirometry showing obstructive pattern and reversibility to bronchodilators. In individuals having features of bronchial asthma but normal spirometry, demonstration of BHR with bronchial challenge test (direct or indirect) confirms/ rules out the diagnosis. The aim of this study was to assess BHR in patients (methacholine challenge) with a history suggestive of bronchial asthma but normal spirometry and its role in diagnosis of bronchial asthma.
METHODS
This study was conducted at tertiary care respiratory center. Patients having clinical features of bronchial asthma but spirometry not confirming obstructive disorder and or reversibility were included in the study. After written consent, methacholine challenge test with methacholine chloride and exercise spirometry was done in all patients as per the American Thoracic Society protocol.
RESULTS
A total of 50 (n) patients were included in the study. Among them, 42 patients had clinical features suggestive of bronchial asthma but having normal spirometry and eight patients were diagnosed as they had bronchial asthma in the past but asymptomatic and off drugs were included in the study. At PC20 4mg/ml 32 (64%) patients had a positive test, 28(66%) symptomatic patients and four (50%) asymptomatic asthmatics. There were no significant side effects with methacholine test.
CONCLUSION
Airway hyper-responsiveness is an important aspect of bronchial asthma and its demonstration with bronchial challenge (direct and indirect) test is an important diagnostic tool. Methacholine challenge test is a safe procedure to perform under supervision.
PubMed: 33487871
DOI: 10.1016/j.mjafi.2020.05.007 -
Biomedicine & Pharmacotherapy =... Feb 2021Asthma is a chronic airway inflammatory disease and acupuncture is frequently used in patients suffering from asthma in clinic. However, the regulatory mechanism of...
TMT-based quantitative proteomics reveals suppression of SLC3A2 and ATP1A3 expression contributes to the inhibitory role of acupuncture on airway inflammation in an OVA-induced mouse asthma model.
Asthma is a chronic airway inflammatory disease and acupuncture is frequently used in patients suffering from asthma in clinic. However, the regulatory mechanism of acupuncture treatment in asthma is not fully elucidated. We sought to investigate the effectiveness of acupuncture on asthma and the associated regulatory mechanism. An ovalbumin (OVA)-induced mouse asthma model was established and the effect of acupuncture on airway hyperresponsiveness (AHR), mucus hypersecretion and inflammation was assessed. Tandem mass tag (TMT)-based quantitative proteomics analysis of lung tissue and bioinformatics analysis were performed. Our results revealed that the OVA-induced mouse asthma model was successfully established with the significantly elevated AHR to methacholine (Mch), and acupuncture was effective in attenuation of AHR to Mch, peribronchial and perivascular inflammation and mucus production. The inflammatory cells around the airways, mucous secretion as well as levels of IgE, CCL5, CCL11, IL-17A in bronchoalveolar lavage fluid (BALF) and IL-4, IL-5 and IL-13 levels in serum were siginificantly inhibited by acupuncture. TMT-based quantitative proteomics analysis found that a total of 6078 quantifiable proteins were identified, and 564 (334 up-regulated and 230 down regulated) differentially expressed proteins (DEPs) were identified in OVA-induced asthma model group (A) versus normal control group (NC). Acupuncture treatment resulted in 667 DEPs (416 up-regulated and 251 down regulated) compared with A group, and 86 overlapping DEPs were identified in NC, A and AA groups. Among the 86 overlapping DEPs, we identified 41 DEPs regulated by acupuncture. Based on the above data, we performed a systematic bioinformatics analysis of the 41 DEPs, and results showed that these 41 DEPs were predominantly related to 4 KEGG pathways including SNARE interactions in vesicular transport, ferroptosis, endocrine and other factor-regulated calcium reabsorption, and protein digestion and absorption. DEPs of SLC3A2 and ATP1A3 expression levels were verified by immumohistochemical staining. Mice in OVA-induced asthma model group had elevated SLC3A2 and ATP1A3 expression and acupuncture had the ability to downregulate SLC3A2 and ATP1A3 protein expression. Furthermore, acupuncture reduced the MDA level and increased the GSH and SOD levels in the lung tissue. Taken together, our data suggested that acupuncture was effective in treating asthma by attenuation of AHR, mucus secretion and airway inflammation, and the mechanism was associated with regulation of ferroptosis, SLC3A2 and ATP1A3 protein expression as well as oxidative stress. Results from our experiments revealed the anti-inflammatory effect of acupuncture in OVA-induced mouse asthma model, leading to a more effective approach to be chosen by patients in clinic.
Topics: Acupuncture Therapy; Animals; Asthma; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Female; Fusion Regulatory Protein 1, Heavy Chain; Inflammation; Lung; Methacholine Chloride; Mice; Mice, Inbred BALB C; Mucus; Ovalbumin; Proteomics; Respiratory Hypersensitivity; Sodium-Potassium-Exchanging ATPase
PubMed: 33341053
DOI: 10.1016/j.biopha.2020.111001