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The European Respiratory Journal Dec 2019There are few data on the usefulness of different tests to diagnose asthma in children.
INTRODUCTION
There are few data on the usefulness of different tests to diagnose asthma in children.
AIM
We assessed the contribution of a detailed history and a variety of diagnostic tests for diagnosing asthma in children.
METHODS
We studied children aged 6-16 years referred consecutively for evaluation of suspected asthma to two pulmonary outpatient clinics. Symptoms were assessed by parental questionnaire. The clinical evaluation included skin-prick tests, measurement of exhaled nitric oxide fraction ( ), spirometry, bronchodilator reversibility and bronchial provocation tests (BPT) by exercise, methacholine and mannitol. Asthma was diagnosed by the physicians at the end of the visit. We assessed diagnostic accuracy of symptoms and tests by calculating sensitivity, specificity, positive and negative predictive values and area under the curve (AUC).
RESULTS
Of the 111 participants, 80 (72%) were diagnosed with asthma. The combined sensitivity and specificity was highest for reported frequent wheeze (more than three attacks per year) (sensitivity 0.44, specificity 0.90), awakening due to wheeze (0.41, 0.90) and wheeze triggered by pollen (0.46, 0.83) or by pets (0.29, 0.99). Of the diagnostic tests, the AUC was highest for measurement (0.80) and BPT by methacholine (0.81) or exercise (0.74), and lowest for forced expiratory volume in 1 s (FEV) (0.62) and FEV/forced vital capacity ratio (0.66), assessed by spirometry.
CONCLUSION
This study suggests that specific questions about triggers and severity of wheeze, measurement of and BPT by methacholine or exercise contribute more to the diagnosis of asthma in school-aged children than spirometry, bronchodilator reversibility and skin-prick tests.
Topics: Adolescent; Asthma; Bronchial Provocation Tests; Bronchodilator Agents; Child; Exhalation; Female; Forced Expiratory Volume; Humans; Male; Mannitol; Medical History Taking; Methacholine Chloride; Nitric Oxide; Pollen; Respiratory Sounds; Skin Tests; Spirometry; Vital Capacity
PubMed: 31515409
DOI: 10.1183/13993003.01326-2019 -
Chest Aug 2020In patients with a history suggestive of asthma, diagnosis is usually confirmed by spirometry with bronchodilator response (BDR) or confirmatory methacholine challenge...
BACKGROUND
In patients with a history suggestive of asthma, diagnosis is usually confirmed by spirometry with bronchodilator response (BDR) or confirmatory methacholine challenge testing (MCT).
RESEARCH QUESTION
We examined the proportion of participants with negative BDR testing who had a positive MCT (and its predictors) result and characteristics of MCT, including effects of controller medication tapering and temporal variability (and predictors of MCT result change), and concordance between MCT and pulmonologist asthma diagnosis.
STUDY DESIGN AND METHODS
Adults with self-reported physician-diagnosed asthma were recruited by random-digit dialing across Canada. Subjects performed spirometry with BDR testing and returned for MCT if testing was nondiagnostic for asthma. Subjects on controllers underwent medication tapering with serial MCTs over 3 to 6 weeks. Subjects with a negative MCT (the provocative concentration of methacholine that results in a 20% drop in FEV [PC] > 8 mg/mL) off medications were examined by a pulmonologist and had serial MCTs after 6 and 12 months.
RESULTS
Of 500 subjects (50.5 ± 16.6 years old, 68.0% female) with a negative BDR test for asthma, 215 (43.0%) had a positive MCT. Subjects with prebronchodilator airflow limitation were more likely to have a positive MCT (OR, 1.90; 95% CI, 1.17-3.04). MCT converted from negative to positive, with medication tapering in 18 of 94 (19.1%) participants, and spontaneously over time in 25 of 165 (15.2%) participants. Of 231 subjects with negative MCT, 28 (12.1%) subsequently received an asthma diagnosis from a pulmonologist.
INTERPRETATION
In subjects with a self-reported physician diagnosis of asthma, absence of bronchodilator reversibility had a negative predictive value of only 57% to exclude asthma. A finding of spirometric airflow limitation significantly increased chances of asthma. MCT results varied with medication taper and over time, and pulmonologists were sometimes prepared to give a clinical diagnosis of asthma despite negative MCT. Correspondingly, in patients for whom a high clinical suspicion of asthma exists, repeat testing appears to be warranted.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asthma; Bronchial Provocation Tests; Bronchodilator Agents; Cohort Studies; Female; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Middle Aged; Predictive Value of Tests; Spirometry; Young Adult
PubMed: 32298731
DOI: 10.1016/j.chest.2020.03.052 -
American Journal of Physiology. Lung... May 2020Transient receptor potential ankyrin-1 (TRPA1) is a ligand-gated cation channel that responds to endogenous and exogenous irritants. TRPA1 is expressed on multiple cell...
Transient receptor potential ankyrin-1 (TRPA1) is a ligand-gated cation channel that responds to endogenous and exogenous irritants. TRPA1 is expressed on multiple cell types throughout the lungs, but previous studies have primarily focused on TRPA1 stimulation of airway sensory nerves. We sought to understand the integrated physiological airway response to TRPA1 stimulation. The TRPA1 agonists allyl isothiocyanate (AITC) and cinnamaldehyde (CINN) were tested in sedated, mechanically ventilated guinea pigs in vivo. Reproducible bronchoconstrictions were induced by electrical stimulation of the vagus nerves. Animals were then treated with intravenous AITC or CINN. AITC and CINN were also tested on isolated guinea pig and mouse tracheas and postmortem human trachealis muscle strips in an organ bath. Tissues were contracted with methacholine, histamine, or potassium chloride and then treated with AITC or CINN. Some airways were pretreated with TRPA1 antagonists, the cyclooxygenase inhibitor indomethacin, the EP receptor antagonist PF 04418948, or tetrodotoxin. AITC and CINN blocked vagally mediated bronchoconstriction in guinea pigs. Pretreatment with indomethacin completely abolished the airway response to TRPA1 agonists. Similarly, AITC and CINN dose-dependently relaxed precontracted guinea pig, mouse, and human airways in the organ bath. AITC- and CINN-induced airway relaxation required TRPA1, prostaglandins, and PGE receptor activation. TRPA1-induced airway relaxation did not require epithelium or tetrodotoxin-sensitive nerves. Finally, AITC blocked airway hyperreactivity in two animal models of allergic asthma. These data demonstrate that stimulation of TRPA1 causes bronchodilation of intact airways and suggest that the TRPA1 pathway is a potential pharmacological target for bronchodilation.
Topics: Acrolein; Animals; Bronchoconstriction; Dinoprostone; Electric Stimulation; Gene Expression Regulation; Guinea Pigs; Histamine; Humans; Indomethacin; Isothiocyanates; Male; Methacholine Chloride; Mice; Muscle, Smooth; Organ Culture Techniques; Potassium Chloride; Prostaglandin-Endoperoxide Synthases; Respiration, Artificial; Signal Transduction; TRPA1 Cation Channel; Tetrodotoxin; Trachea; Vagus Nerve
PubMed: 32233794
DOI: 10.1152/ajplung.00277.2019 -
Pediatric Research Jun 2020Supplemental oxygen exposure administered to premature infants is associated with chronic lung disease and abnormal pulmonary function. This study used mild (40%),...
BACKGROUND
Supplemental oxygen exposure administered to premature infants is associated with chronic lung disease and abnormal pulmonary function. This study used mild (40%), moderate (60%), and severe (80%) oxygen to determine how hyperoxia-induced changes in lung structure impact pulmonary mechanics in mice.
METHODS
C57BL/6J mice were exposed to room air or hyperoxia from birth through postnatal day 8. Baseline pulmonary function and methacholine challenge was assessed at 4 and 8 weeks of age, accompanied by immunohistochemical assessments of both airway (smooth muscle, tethering) and alveolar (simplification, elastin deposition) structure.
RESULTS
Mild/moderate hyperoxia increased baseline airway resistance (40% only) and airway hyperreactivity (40 and 60%) at 4 weeks accompanied by increased airway smooth muscle deposition, which resolved at 8 weeks. Severe hyperoxia increased baseline compliance, baseline resistance, and total elastin/surface area ratio without increasing airway hyperreactivity, and was accompanied by increased alveolar simplification, decreased airway tethering, and changes in elastin distribution at both time points.
CONCLUSIONS
Mild to moderate hyperoxia causes changes in airway function and airway hyperreactivity with minimal parenchymal response. Severe hyperoxia drives its functional changes through alveolar simplification, airway tethering, and elastin redistribution. These differential responses can be leveraged to further develop hyperoxia mouse models.
Topics: Animals; Animals, Newborn; Dose-Response Relationship, Drug; Female; Hyperoxia; Lung; Lung Compliance; Male; Methacholine Chloride; Mice; Mice, Inbred C57BL; Muscarinic Agonists; Muscle, Smooth; Pulmonary Alveoli; Respiratory Function Tests; Respiratory Mechanics; Sex Factors
PubMed: 31835269
DOI: 10.1038/s41390-019-0723-y -
European Journal of Sport Science Aug 2023The aim of this study was to examine lung function, bronchial hyperresponsiveness (BHR) and exercise-induced respiratory symptoms in elite athletes performing different...
The aim of this study was to examine lung function, bronchial hyperresponsiveness (BHR) and exercise-induced respiratory symptoms in elite athletes performing different sports. Norwegian national-team athletes (30 swimmers, 32 cross-country skiers, 16 speed-skaters, 11 rowers/paddlers, 17 handball players and 23 soccer players) completed a validated questionnaire, measured exhaled nitric oxide (FE), spirometry, methacholine provocation (PD) and skin prick test. Three cut-off levels defined BHR; i.e. PD ≤2 µmol, ≤4 µmol and ≤8 µmol. Mean forced vital capacity (FVC) was highest in swimmers (Mean z-score[95%CI] = 1.16 [0.80, 1.51]), and close to or higher than reference values according to the Global Lung Initiative equation, across all sports. Mean forced expiratory volume in 1 s (FEV) was higher than reference values in swimmers (0.48 [0.13, 0.84]), and ball game athletes (0.69 [0.41, 0.97]). Mean forced expiratory flow between 25 and 75% of FVC (FEF), and/or FEV/FVC were lower than reference values in all endurance groups. BHR defined by ≤2 and ≤8 µmol methacholine was observed in respectively 50%-87% of swimmers, 25%-47% of cross-country skiers, 20%-53% of speed-skaters, 18%-36% of rowers/paddlers, and 0%-17% of the ball game athletes. Exercise-induced symptoms were common in all groups, most frequent in cross-country skiers (88%), swimmers (83%) and speed-skaters (81%).Swimmers and ball game athletes had higher mean FVC and FEV when compared to the reference values predicted by the Global Lung Initiative (GLI) reference equation. Contrasting this, across all sports except ball game athletes, mean FEF and/or FEV/FVC were lower than reference values.The prevalence of bronchial hyperresponsiveness (BHR) was high among elite athletes competing in swimming, cross-country skiing, speed skating and rowing/paddling, with swimmers being most affected.The majority of the elite athletes reported exercise-induced respiratory symptoms independent of lung function or BHR.
Topics: Humans; Methacholine Chloride; Bronchial Provocation Tests; Bronchial Hyperreactivity; Athletes; Swimming; Lung
PubMed: 35975407
DOI: 10.1080/17461391.2022.2113144 -
The European Respiratory Journal Feb 2021Oxidised phosphatidylcholines (OxPCs) are produced under conditions of elevated oxidative stress and can contribute to human disease pathobiology. However, their role in...
Oxidised phosphatidylcholines (OxPCs) are produced under conditions of elevated oxidative stress and can contribute to human disease pathobiology. However, their role in allergic asthma is unexplored. The aim of this study was to characterise the OxPC profile in the airways after allergen challenge of people with airway hyperresponsiveness (AHR) or mild asthma. The capacity of OxPCs to contribute to pathobiology associated with asthma was also to be determined.Using bronchoalveolar lavage fluid from two human cohorts, OxPC species were quantified using ultra-high performance liquid chromatography-tandem mass spectrometry. Murine thin-cut lung slices were used to measure airway narrowing caused by OxPCs. Human airway smooth muscle (HASM) cells were exposed to OxPCs to assess concentration-associated changes in inflammatory phenotype and activation of signalling networks.OxPC profiles in the airways were different between people with and without AHR and correlated with methacholine responsiveness. Exposing patients with mild asthma to allergens produced unique OxPC signatures that associated with the severity of the late asthma response. OxPCs dose-dependently induced 15% airway narrowing in murine thin-cut lung slices. In HASM cells, OxPCs dose-dependently increased the biosynthesis of cyclooxygenase-2, interleukin (IL)-6, IL-8, granulocyte-macrophage colony-stimulating factor and the production of oxylipins protein kinase C-dependent pathways.Data from human cohorts and primary HASM cell culture show that OxPCs are present in the airways, increase after allergen challenge and correlate with metrics of airway dysfunction. Furthermore, OxPCs may contribute to asthma pathobiology by promoting airway narrowing and inducing a pro-inflammatory phenotype and contraction of airway smooth muscle. OxPCs represent a potential novel target for treating oxidative stress-associated pathobiology in asthma.
Topics: Administration, Inhalation; Allergens; Animals; Asthma; Humans; Methacholine Chloride; Mice; Phosphatidylcholines
PubMed: 32883680
DOI: 10.1183/13993003.00839-2020 -
Pulmonary Pharmacology & Therapeutics Oct 2020Cough variant asthma (CVA) is the most common cause of chronic cough and responds well to bronchodilator therapy. Previous studies on methacholine -induced cough have...
BACKGROUND
Cough variant asthma (CVA) is the most common cause of chronic cough and responds well to bronchodilator therapy. Previous studies on methacholine -induced cough have shown that heightened cough response due to bronchoconstriction is a feature of CVA. The aim of this study was to assess Mch-induced cough as an indicator of bronchodilator-responsive cough (BRC).
METHODS
This was a single-center retrospective study of prolonged/chronic cough cases who underwent evaluation via spirometry, FeNO and bronchial challenge testing using Mch and capsaicin (C5). Resultant bronchoconstriction after Mch challenge was assessed by flow-volume curves measuring the expiratory flow of the partial flow-volume curve 40% above residual volume (PEF) and FEV. BRC was defined as a decrease in cough with bronchodilator therapy by 30% or more on a visual analog scoring scale.
RESULTS
Of the 100 patients evaluated, 63 were diagnosed with BRC. Mch-induced cough at a decrease in PEF of 35% (PC-PEF) was predictive of BRC on AUROC analysis with an AUC of 0.82 (95% CI 0.73-0.90) and cut-off of 24. The AUC for C5, FeNO and PC-FEV were 0.65, 0.47, and 0.58, respectively.
CONCLUSION
Compared to C5, FeNO and PC-FEV, Mch-induced cough better supports a diagnosis of BRC.
Topics: Bronchial Provocation Tests; Bronchodilator Agents; Cough; Forced Expiratory Volume; Humans; Methacholine Chloride; Retrospective Studies
PubMed: 33039668
DOI: 10.1016/j.pupt.2020.101962 -
Respiratory Care Mar 2021A 20% reduction in the FEV is routinely used as an end point for methacholine challenge testing (MCT). Measurement of FEV is effort dependent, and some patients are not...
BACKGROUND
A 20% reduction in the FEV is routinely used as an end point for methacholine challenge testing (MCT). Measurement of FEV is effort dependent, and some patients are not able to perform acceptable and repeatable forced expiration maneuvers. The goal of the present study was to investigate the diagnostic value of airway resistance measurement by forced oscillation technique (FOT), body plethysmography, and interrupter technique compared with the traditionally accepted standard FEV measurement in evaluating the responsiveness to methacholine during MCT.
METHODS
We included in the study adult subjects referred for MCT because of asthma-like symptoms and with normal baseline spirometry. We modified routine MCT protocol by adding the assessment of airway resistance to the measurement of FEV at each step of MCT.
RESULTS
We observed, in the subjects with airway hyper-responsiveness versus those with normal airway responsiveness, a significantly greater percentage change in median (interquartile range) FOT resistance at 10 Hz (25.9% [13.7%-35.4%] vs 16% [15.7%-27.2%]), plethysmographic resistance (70.2% [39.5%-116.3%] vs 37.1% [23.9%-81.9%]), and mean ± SD conductance (-41.3 ± 15.4% vs -29.6 ± 15.9%); and a significantly greater change in mean ± SD FOT reactance at 10 Hz (-0.41 ± 0.48 cm HO/L/s vs -0.09 ± 0.32 cm HO/L/s) and at 15 Hz (-0.29 ± 0.2 cm HO/L/s vs -0.1 ± 0.19 cm HO/L/s). We also recorded significant differences in airway resistance parameters (FOT resistance at 10 Hz, FOT reactance at 15 Hz, plethysmographic airway resistance, and conductance indices as well as interrupter resistance) in FEV non-responders at the onset of respiratory symptoms during MCT compared with baseline.
CONCLUSIONS
Measurements of airway resistance could possibly be used as an alternative method to spirometry in airway challenge. Significant changes in airway mechanics during MCT are detectable by airway resistance measurement in FEV non-responders with methacholine-induced asthma-like symptoms. (ClinicalTrials.gov registration NCT02343419.).
Topics: Adult; Airway Resistance; Bronchial Provocation Tests; Forced Expiratory Volume; Humans; Methacholine Chloride; Spirometry
PubMed: 33203723
DOI: 10.4187/respcare.08331 -
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 -
Acta Paediatrica (Oslo, Norway : 1992) Feb 2022The potential for immunotherapy to prevent asthma development has become a hot topic. This prompted us to revisit data from an early study that examined allergic...
AIM
The potential for immunotherapy to prevent asthma development has become a hot topic. This prompted us to revisit data from an early study that examined allergic sensitisation on bronchial hyperresponsiveness (BHR) in children with and without respiratory symptoms. Unlike previous studies, it used both indirect and direct test methods.
METHODS
The study was conducted in Kuopio, Finland, in 1994 and 247 children (55.1% boys) with a mean age 10.5 ± 1.7 years were recruited using a school survey: 165 with lower respiratory symptoms and 82 healthy controls. Each child underwent a 6-min free-running test and a methacholine test with a cumulative dose of 4900 µg. All participants underwent skin-prick tests: 127were sensitised and 120 were non-sensitised.
RESULTS
There were no significant differences in lung function between the sensitised and non-sensitised children. However, sensitisation was associated with BHR which was measured by both the methacholine test (2400 µg versus >4900 µg, p < 0.001) and the free-running test (-3.5% versus -2.6%, p = 0.042). No such differences were observed among the healthy controls. Sensitisation was a predictor of allergic diseases, and only multisensitisation to a minimum of four allergens increased the incidence of asthma.
CONCLUSION
Allergic sensitisation did not affect BHR in children without respiratory symptoms.
Topics: Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Child; Female; Humans; Male; Methacholine Chloride; Respiratory System; Skin Tests
PubMed: 34586680
DOI: 10.1111/apa.16129