The Fractional exhaled Nitric Oxide (FeNO)- test as add-on test in the diagnostic work-up of asthma: a study protocol.

BACKGROUND: Asthma is a common disease characterized by chronic inflammation of the lower airways, bronchial hyperactivity, and (reversible) airway obstruction. The Global Initiative of Asthma Guideline recommends a flowchart to diagnose asthma with first-step spirometry with reversibility and a bronchial challenge test (BPT) with histamine or methacholine as a second step [1]. The BPT is considered burdensome, time-consuming for patients and staff, can cause side effects, and is expensive. In addition, this test strongly encumbers lung function capacity. Elevated Nitric Oxide (NO) is associated with airway eosinophilic inflammation in asthma patients and can be measured in exhaled air with the Fractional exhaled (Fe) NO-test. This low-burden FeNO-test could be used as an 'add-on' test in asthma diagnostics [2, 3]. METHODS AND ANALYSIS: This multi-center prospective study (Trial number: NCT06230458) compares the 'standard asthma diagnostic work-up' (spirometry with reversibility and BPT) to the 'new asthma diagnostics work-up' (FeNO-test as an intermediate step between the spirometry with reversibility and the BPT), intending to determine the impact of the FeNO-based strategy, in terms of the number of avoided BPTs, cost-effectiveness and reduced burden to the patient and health care. The cost reduction of incorporating the FeNO-test in the new diagnostic algorithm will be established by the number of theoretically avoided BPT. The decrease in burden will be studied by calculating differences in the Visual Analogue Scale (VAS) -score and Asthma Quality of Life Questionnaire (AQLQ) -score after the BPT and FeNO-test with an independent T-test. The accuracy of the FeNO-test will be calculated by comparing the FeNO-test outcomes to the (gold standard) BPTs outcomes in terms of sensitivity and specificity. The intention is to include 171 patients. ETHICS AND DISSEMINATION: The local medical ethics committee approved the proposed study and is considered a low-burden and risk-low study. The local medical ethics committee registration number: R23.005. STRENGTHS AND LIMITATIONS OF THIS STUDY: Strengths: This is the first study that investigates the value of the FeNO-test (cut off ≥ 50 ppb) as an add-on test, to determine the impact of the FeNO-based strategy, in terms of the number of avoided BPTs, cost-effectiveness, and reduced burden on the patient and health care. LIMITATIONS: High FeNO levels may also be observed in other diseases such as eosinophilic chronic bronchitis and allergic rhinitis. The FeNO-test can be used to rule in a diagnosis of asthma with confidence, however, due to the poor sensitivity it is not suitable to rule out asthma.

Impact of the pulmonary ventilation function on the prognosis of suspected asthma patients: a retrospective observational study.

OBJECTIVE: Asthma is a common chronic respiratory diseases, and the relationship between pulmonary ventilation function and the prognosis of patients with suspected asthma is not well understood. This study aims to explore the impact of pulmonary ventilation functions on the prognosis of patients with suspected asthma. METHODS: This retrospective observational study included patients with suspected asthma who were diagnosed and treated at the Guangdong Provincial Hospital of Traditional Chinese Medicine between August 2015 and January 2020. The primary outcome of interest was improvement in asthma symptoms, as measured by bronchial provocation test (BPT) results within one year after diagnosis. The impact of pulmonary ventilation functions on prognosis was explored by multivariable logistic regression analysis. RESULTS: Seventy-two patients were included in the study. Patients with normal (OR = 0.123, p = .004) or generally normal (OR = 0.075, p = .039) pulmonary ventilation function were more likely to achieve improvement in asthma symptoms compared with patients with mild obstruction. There were no significant differences between the improvement and non-improvement groups in baseline characteristics. CONCLUSION: These results suggest that suspected asthma patients with normal or generally normal pulmonary ventilation function are more likely to achieve improvement in asthma symptoms within one year compared to patients with mild obstruction.

Novel Artificial Intelligence-Based Technology to Diagnose Asthma Using Methacholine Challenge Tests.

PURPOSE: The methacholine challenge test (MCT) has high sensitivity but relatively low specificity for asthma diagnosis. This study aimed to develop and validate machine learning (ML) models to improve the diagnostic performance of MCT for asthma. METHODS: Data from 1,501 patients with asthma symptoms who underwent MCT between 2015 and 2020 were analyzed. The patients were grouped as either the training (80%, n = 1,265) and test sets (20%, n = 236) depending on the time of referral. The conventional model (provocative concentration that causes a 20% decrease in forced expiratory volume in one second [FEV1]; PC20 ≤ 16 mg/mL) was compared with the prediction models derived from five ML methods: logistic regression, support vector machine, random forest, extreme gradient boosting, and artificial neural network. The area under the receiver operator characteristic curves (AUROC) and area under the precision-recall curves (AUPRC) of each model were compared. The prediction models were further analyzed using different input combinations of FEV1, forced vital capacity (FVC), and forced expiratory flow at 25%-75% of forced vital capacity (FEF25%-75%) values obtained during MCT. RESULTS: In total, 545 patients (36.3%) were diagnosed with asthma. The AUROC of the conventional model was 0.856 (95% confidence interval [CI], 0.852-0.861), and the AUPRC was 0.759 (95% CI, 0.751-0.766). All the five ML prediction models had higher AUROC and AUPRC values than those of the conventional model, and random forest showed both highest AUROC (0.950; 95% CI, 0.948-0.952) and AUROC (0.909; 95% CI, 0.905-0.914) when FEV1, FVC, and FEF25%-75% were included as inputs. CONCLUSIONS: Artificial intelligence-based models showed excellent performance in asthma prediction compared to using PC20 ≤ 16 mg/mL. The novel technology could be used to enhance the clinical diagnosis of asthma.

Beyond forced exhalation: impulse oscillometry as a promising tool for bronchial hyperresponsiveness evaluation.

Introduction: The multiple forced expiratory maneuvers that must be performed during methacholine test require a high degree of collaboration and can lead to fatigue. However, impulse oscillometry (IOS) is a noninvasive test, quick and easy to perform, that does not require effort-dependent maneuvers.Objectives: The primary endpoint was to evaluate the relationship between IOS and spirometry during the methacholine test. The secondary endpoint was to study the predictive value of baseline IOS in the development of bronchial hyperreactivity.Methods: Observational, prospective, cross-sectional study, with recruitment of consecutive patients from the pulmonology department with clinical suspicion of bronchial asthma with negative bronchodilator test and normal FeNO.Results: Twenty-five patients were included, with a mean age of 49 ± 18 years. Thirteen patients (52%) had a positive methacholine test. The correlation between IOS indices and FEV1 was significant (p < 0.05) in all cases. The indices with the highest predictive power were R5-20 and AX. The optimal cutoff points were an increase of greater than 32.96% in R5, greater than 120.83% for X5, an increase of 30.30 [kPa l-1s-1] in R5-20, and an increase of 1.01 [kPa l-1] for AX. Baseline oscillometry demonstrated a strong predictive value in the development of bronchial hyperreactivity, with a sensitivity of 61.5% and a specificity of 91.7%, using the cut-off point of 160.0% for R5.Conclusions: IOS may be a valuable alternative to forced spirometry in detecting bronchial hyperreactivity during the methacholine test, showing a good correlation between both tests.

Based on what parameters is safe to discontinuate inhaled corticosteroids in children with asthma?

OBJECTIVE: Remission of childhood asthma has not been widely studied. Patients in clinical remission continue to have some degree of bronchial hyperresponsiveness (BHR). The aim of this study was to investigate whether clinical parameters and lung function test are good parameters for discontinuation of inhaled corticosteroids (ICS) in asthmatic children, including patients with persistent BHR, as measured by the methacholine challenge test (MCT). METHODS: One year after discontinuation of inhaled corticosteroids (ICS), MCT was performed in a group of 40 asthmatic children to confirm or exclude BHR. In all patients, ICS treatment was discontinued based on the same parameters: symptoms, spirometry, daily PEF, and negative bronchodilator test. After achieving complete asthma control for at least 6 to 12 months, ICS treatment was stepped down and discontinued. Clinical course and spirometry were followed up after ICS discontinuation. RESULTS: Positive MCT was found in 50% of the patients. There was no statistically significant difference between the positive and negative MCT groups in age at initiation and discontinuation of ICS therapy, duration of ICS therapy, duration of stepping down period, FEV1, and PEF at the time of withdrawal of ICS and one year later. ICS treatment had to be restarted in two patients from the positive MCT group, due to recurrence of asthma symptoms. CONCLUSION: Clinical parameters, normal spirometry, daily PEF values, and a negative bronchodilator test are good parameters for discontinuing ICS treatment in asthmatic children, even in patients with persistent BHR. Children should continue to be monitored, as symptoms may recur.

Diagnostic value of fractional exhaled nitric oxide combined with small airway function test for chronic cough / 中国基层医药

Objective:To investigate the value of fractional exhaled nitric oxide (FeNO) combined with small airway function test to replace bronchial provocation test and induced sputum test in differentiating cough variant asthma (CVA) from eosinophilic bronchitis (EB).Methods:The clinical data of 105 patients with chronic cough admitted to The Third People's Hospital of Hubei, Jianghan University from January 2018 to December 2021 were retrospectively analyzed. These patients consisted of 40 patients with CVA (CVA group), 25 patients with EB (EB group), and 40 patients with other chronic coughs (other chronic cough group). FeNO and lung function were compared between groups. The value of FeNO, small airway function, and their combination in differentiating CVA from EB were analyzed using the receiver operating characteristic curves.Results:FeNO level was the highest in the CVA group [33.0 (30.0, 37.8) ppb], followed by the EB group [28.0 (25.5, 32.0) ppb], and the lowest in other chronic cough group [13.0 (11.0, 15.0) ppb]. There was significant difference in FeNO level between groups ( H value = 79.00, P < 0.05). There were no significant differences in forced vital capacity (FVC), forced expiratory volume in 1 second (FEV 1), FEV 1/FVC, peak expiratory flow (PEF) between groups (all P > 0.05). Maximal mid-expiratory flow (MMEF) [74 (66.0, 77.4) in the CVA group, 80 (79.0, 83.3) in the EB group, 88.0 (86.4, 90.0) in other chronic coughs group], FEF25 (%) [70.0 (60.3, 75.1) in the CVA group, 78.0 (74.1, 85.0) in the EB group, 81.7 (78.9, 86.3) in other chronic coughs group], FEF50 (%) [75.2 (67.1, 80.8) in the CVA group, 80.6 (75.7, 85.9) in the EB group, 89.4 (87.0, 90.5) in other chronic coughs group], FEF75 (%) [76.4 (68.7, 85.8) in the CVA group, 80.9 (77.4, 89.7) in the EB group, 90.8 (87.2, 94.2) in other chronic coughs group] were significantly lower in the CVA group than those in other chronic coughs group. With the exception of FEF25 (%), MMEF (%), FEF50 (%), and FEF75 (%) were significantly lower in the EB group compared with other chronic coughs group. MMEF (%) and FEF25 (%) in the CVA group were significantly lower compared with the EB group. There were significant differences in MMEF (%), FEF50 (%), and FEF75 (%) between groups ( H = 62.82, 47.04, 47.41, 49.11, all P < 0.01). There were significant differences in FEF50 (%) and FEF75 (%) between CVA and EB groups (both P > 0.05). In binary logistic regression equation, FeNO and MMEF (%) were important indexes to distinguish CVA from EB ( P < 0.05). Bronchial provocation test and induced sputum test were used as the gold standard to distinguish CVA from EB. When FeNO and MMEF (%) were used separately to distinguish CVA from EB, the optimal threshold value was 30.0 ppb and 77.7 respectively, the area under the receiver operating characteristic curve was 0.77 and 0.82 respectively, the diagnostic sensitivity was 70% and 77.5% respectively, and the diagnostic specificity was 72% and 88% respectively. When FeNO and MMEF (%) were used in combination to distinguish CVA from EB, the area under the receiver operating characteristic curve was 0.89, and the diagnostic sensitivity and specificity was 75% and 96% respectively. Conclusion:FeNO and MMEF (%) can be used to distinguish CVA from EB. FeNO combined with MMEF (%) has a higher value in distinguishing CVA from EB than FeNO and MMEF alone.

Allergic sensitization pattern as a marker of bronchial hyperresponsiveness in allergic rhinitis patients living in temperate continental climate zone.

BACKGROUND: Bronchial hyperresponsiveness (BHR) is a key feature of asthma, but it may also appear in allergic rhinitis. The type of allergen, as well as regional characteristics, play an important role in the development of BHR. The aim of our study was to analyze allergen sensitization patterns and the factors that affect BHR in allergic rhinitis patients living in temperate continental climate zone. METHODS: This study retrospectively analyzed allergic rhinitis patients from Eastern Slovakia who underwent skin-prick tests to aeroallergens, spirometry, histamine and methacholine bronchial provocation tests for evaluation of lower airway symptoms. We analyzed the associations between BHR and the pattern of aeroallergen sensitization, lung function parameters, and the total IgE and eosinophil levels. RESULTS: Out of 365 allergic rhinitis patients (age range 16-64 years), 114 showed BHR. Sensitization to house dust mites (HDMs) and grass were the most common. BHR was significantly associated with sensitization to dogs (odds ratio, OR = 2.15, 95% confidence interval, CI: 1.13-4.11) and Alternaria (OR = 2.15, 95% CI: 1.06-4.35); however, BHR did not show a relationship with HDMs sensitization. The levels of total IgE and eosinophils were higher in the BHR-positive group. Sensitization to more than six allergens significantly increased the probability of BHR (p < 0.01). CONCLUSION: Dogs and Alternaria, but not HDMs, were the sensitizing agents most closely associated with BHR. High-grade sensitization and increased total IgE and eosinophil levels were characteristic clinical signs in BHR-positive allergic rhinitis patients in the temperate continental climatic zone.

Allergic sensitisation did not affect bronchial hyper-responsiveness in children without respiratory tract symptoms.

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.

Diagnostic value of the hypertonic saline bronchial provocation test in children with asthma using the high-power aerosol provocation system.

Objective: This study aimed to evaluate the diagnostic value of the modified hypertonic saline bronchial provocation test (HS-BPT) for children with asthma by using the high-power Aerosol Provocation System (APS).Methods: A total of 330 children suspected of having asthma and receiving HS-BPT-APS were included in this prospective survey conducted in Guangzhou, China from February 2017 to September 2018. The positive rate of HS-BPT-APS and the volume and types of adverse reactions were observed. There was also a retrospective cohort of 123 children with suspected asthma who underwent a methacholine BPT from 2015 to 2017. Using the method of nearest neighbor matching, a comparison was made of the positive rate and adverse reaction between the methacholine BPT group and HS-BPT-APS group.Results: The total positive rate of HS-BPT-APS was 43.9%. Common adverse reactions included cough, wheezing and chest tightness. There were no serious adverse reactions. Results of nearest neighbor matching showed a difference in the positive rate between the methacholine BPT group and HS-BPT-APS group (8.1% vs 18.2%, p = 0.026), but there was no statistically significant difference between the age groups in patients who received the methacholine BPT or HS-BPT-APS. There was a similar adverse reaction rate in the two groups (p = 0.609).Conclusions: HS-BPT-APS is simple, safe, and time-saving, with few adverse reactions. The positive rate of HS-BPT-APS was higher than that of methacholine BPT in children with asthma. HS-BPT-APS may be a valuable tool in the diagnosis of children with asthma, and further study is required.

[Leukotriene D4 bronchial provocation test for detection of airway hyper-responsiveness in children].

OBJECTIVE: To explore the value of leukotriene D4 (LTD4) bronchial provocation test (BPT) in detection of airway hyper-responsiveness (AHR) in children. METHODS: A total of 151 children aged 6 to 14 years, including 86 in remission of asthma and 65 with acute bronchitis, who were followed up in our respiratory clinic between November, 2017 and August, 2018. The children were randomly divided into LTD4 group (78 cases) and methacholine (MCH) group (73 cases). In LTD4 group, the 78 children underwent LTD4-BPT, including 46 with asthma and 32 children having re-examination for previous episodes of acute bronchitis; in MCH group, the 73 children underwent MCH-BPT, including 40 with asthma and 33 with acute bronchitis. MCH-BPT was also performed in the asthmatic children in the LTD4 group who had negative responses to LTD4 after an elution period. The major adverse reactions of the children to the two BPT were recorded. The diagnostic values of the two BPT were evaluated using receiver-operating characteristic (ROC) curve. RESULTS: There was no significant difference in the results of basic lung function tests between LTD4 group and MCH group (P>0.05). The positive rate of BPT in asthmatic children in the LTD4 group was significantly lower than that in the MCH group (26.1% vs 72.5%; P < 0.05). The positive rate of BPT in children with previous acute bronchitis in the LTD4 group was lower than that in the MCH group (3.1% vs 15.2%). The positive rate of MCH-BPT in asthmatic children had negative BPT results in LTD4 group was 58.8%, and their asthma was mostly mild. The sensitivity was lower in LTD4 group than in MCH group (0.2609 vs 0.725), but the specificity was slightly higher in LTD4 group (0.9688 vs 0.8485).The area under ROC curvein LTD4 group was lower than that in MCH group (0.635 vs 0.787). In children with asthma in the LTD4 group, the main adverse reactions in BPT included cough (34.8%), shortness of breath (19.6%), chest tightness (15.2%), and wheezing (10.9%). The incidence of these adverse reactions was significantly lower in LTD4 group than in MCH group (P < 0.05). Serious adverse reactions occurred in neither of the two groups. CONCLUSIONS: LTD4-BPT had high safety in clinical application of children and was similar to the specificity of MCH-BPT. However, it had low sensitivity, low diagnostic value, and limited application value in children's AHR detection.

Bronchial Provocation Testing for the Identification of Exercise-Induced Bronchoconstriction.

Exercise-induced bronchoconstriction (EIB) occurs in patients with asthma, children, and otherwise healthy athletes. Poor diagnostic accuracy of respiratory symptoms during exercise requires objective assessment of EIB. The standardized tests currently available are based on the assumption that the provoking stimulus to EIB is dehydration of the airway surface fluid due to conditioning large volumes of inhaled air. "Indirect" bronchial provocation tests that use stimuli to cause endogenous release of bronchoconstricting mediators from airway inflammatory cells include dry air hyperpnea (eg, exercise and eucapnic voluntary hyperpnea) and osmotic aerosols (eg, inhaled mannitol). The airway response to different indirect tests is generally similar in patients with asthma and healthy athletes with EIB. Furthermore, the airway sensitivity to these tests is modified by the same pharmacotherapy used to treat asthma. In contrast, pharmacological agents such as methacholine, given by inhalation, act directly on smooth muscle to cause contraction. These "direct" tests have been used traditionally to identify airway hyperresponsiveness in clinical asthma but are less useful to diagnose EIB. The mechanistic differences between indirect and direct tests have helped to elucidate the events leading to airway narrowing in patients with asthma and elite athletes, while improving the clinical utility of these tests to diagnose and manage EIB.

Leukotriene D4 bronchial provocation test for detection of airway hyper-responsiveness in children / 南方医科大学学报

OBJECTIVE@#To explore the value of leukotriene D4 (LTD4) bronchial provocation test (BPT) in detection of airway hyper-responsiveness (AHR) in children.@*METHODS@#A total of 151 children aged 6 to 14 years, including 86 in remission of asthma and 65 with acute bronchitis, who were followed up in our respiratory clinic between November, 2017 and August, 2018. The children were randomly divided into LTD4 group (78 cases) and methacholine (MCH) group (73 cases). In LTD4 group, the 78 children underwent LTD4-BPT, including 46 with asthma and 32 children having re-examination for previous episodes of acute bronchitis; in MCH group, the 73 children underwent MCH-BPT, including 40 with asthma and 33 with acute bronchitis. MCH-BPT was also performed in the asthmatic children in the LTD4 group who had negative responses to LTD4 after an elution period. The major adverse reactions of the children to the two BPT were recorded. The diagnostic values of the two BPT were evaluated using receiver-operating characteristic (ROC) curve.@*RESULTS@#There was no significant difference in the results of basic lung function tests between LTD4 group and MCH group (>0.05). The positive rate of BPT in asthmatic children in the LTD4 group was significantly lower than that in the MCH group (26.1% 72.5%; < 0.05). The positive rate of BPT in children with previous acute bronchitis in the LTD4 group was lower than that in the MCH group (3.1% 15.2%). The positive rate of MCH-BPT in asthmatic children had negative BPT results in LTD4 group was 58.8%, and their asthma was mostly mild. The sensitivity was lower in LTD4 group than in MCH group (0.2609 0.725), but the specificity was slightly higher in LTD4 group (0.9688 vs 0.8485).The area under ROC curvein LTD4 group was lower than that in MCH group (0.635 0.787). In children with asthma in the LTD4 group, the main adverse reactions in BPT included cough (34.8%), shortness of breath (19.6%), chest tightness (15.2%), and wheezing (10.9%). The incidence of these adverse reactions was significantly lower in LTD4 group than in MCH group ( < 0.05). Serious adverse reactions occurred in neither of the two groups.@*CONCLUSIONS@#LTD4-BPT had high safety in clinical application of children and was similar to the specificity of MCH-BPT. However, it had low sensitivity, low diagnostic value, and limited application value in children's AHR detection.

Actualización de la prueba de provocación bronquial con ejercicio (PPBE) / Update of the bronchial provocation test with exercise

The bronchial challenge test with exercise aims to demonstrate the presence of exercise-induced bronchial hyperreactivity, characteristic of bronchial asthma. Its realization is well standardized, requiring special environmental conditions, preparation and submaximum effort of the patient. The response is measured by spirometry, and it is considered a positive exercise test a drop in the expired volume at the first second (FEV1) of 10%. This article describes the elements necessary to facilitate this exam, according to national and international standards and guidelines.

La prueba de provocación bronquial con ejercicio tiene como objetivo demostrar la presencia de hiperreactividad bronquial inducida por ejercicio, característica del asma bronquial. Su realización está bien estandarizada, requiriendo de condiciones ambientales especiales, preparación y esfuerzo submáximo del paciente. La respuesta se mide mediante espirometría, y se considera una prueba de provocación con ejercicio positivo, a una caída del volumen espirado al primer segundo (VEF1) del 10%. En este artículo se describen los elementos necesarios para facilitar la realización de este examen, acorde a normas y guías nacionales e internacionales.

Methacholine bronchial provocation test for assessment of bronchial hyperresponsiveness in preschool children.

BACKGROUND: Bronchial hyperresponsiveness (BHR) has not been extensively performed in preschool children, possibly because of the difficulty in cooperating with the tests. We sought to determine the usefulness and safety of methacholine bronchial provocation test (MCh-BPT) for BHR assessment in preschool children. METHODS: We recruited 252 preschool children (190 healthy and 62 with wheezing) who underwent MCh-BPT at baseline. MCh-BPT was re-scheduled in case initial attempts failed. Forced expiratory volumes in 0.5 (FEV0.5), 0.75 (FEV0.75) and one second (FEV1) were measured. We recorded the provocative dose causing 15% (PD15) or 20% reduction (PD20) in FEV0.5, FEV0.75 and FEV1, thus allowing for comparison of the diagnostic value of PD15 and PD20. RESULTS: A total of 209 children [156 (82.1%) healthy, 53 (85.5%) with wheezing] successfully completed MCh-BPT. Compared with healthy children, a significantly greater proportion of children with wheezing had measurable PD15FEV0.5, PD15FEV0.75 and PD15FEV1 (P<0.01), and PD20FEV0.5, PD20FEV0.75 and PD20FEV1 (P<0.05). The sensitivity was 92.5% and 94.3% for PD20FEV1, and PD15FEV1 and the specificity was 93.6% and 93.6% respectively, for discriminating asthmatic from healthy children. CONCLUSIONS: Most preschool children successfully and safely complete MCh-BPT, with higher success rate in larger age group. PD20FEV0.5 and PD20FEV0.75 can be surrogates of PD20FEV1 among children whose expiration lasted for less than one second. PD15 has a good diagnostic value as PD20 for diagnosing of BHR in preschool children, which are also more suitable for children five years old or elder.

Effects of bronchial provocation test and bronchial dilation test for the diagnosis of lung diseases.

AIM: Present study was performed to explore the effects of bronchial provocation test (BPT) and bronchial dilation test (BDT) for the diagnosis of lung diseases. METHODS: BPT and BDT results were respectively detected by methacholine and albuterol in patients with different lung diseases and non-lung diseases. BPT and BDT indexes including exhaled nitric oxide (ENO), forced expiratory volume of first minute (FEV1), forced vital capacity (FVC), diffusion of carbon monoxide in the lungs (DLCO) and eosinophilia (EOS) were compared by t-test between different groups. RESULTS: Positive and negative BPT indexes were significantly different in lung diseases, similar results of BDT results were also discovered in patients with lung diseases (p < .001). Obvious differences of ENO, FEV1/FVC and EOS levels were discovered in different BPT degrees (p < .05). FEV1, FVC and FEV1/FVC levels were distinctly higher in I BDT degree than II and III BDT degrees (p < .05) in lung diseases. Significant differences of BPT and BDT indexes were discovered between different lung diseases (p < .05). CONCLUSION: BPT and BDT may be employed as the tools for diagnosis of lung diseases. Moreover, the patients with different lung diseases show significantly different BPT and BDT indexes.

Identification of Pen m 4 as a potential cause of occupational asthma to Gammarus shrimp.

We present the case of a 34-year-old male patient employed for 8 years in a company manufacturing and packaging animal feed. The patient developed occupational asthma to dry Gammarus powder. The diagnosis was confirmed by specific bronchial provocation test. The determination of specific IgE antibodies was positive for Pen m 4, a sarcoplasmic calcium binding protein, with a level of 6.7 ISU-E. The sensitization to Pen m 4 described here may identify a new allergen causing occupational asthma in these workers.

Exhaled nitric oxide and mannitol test to predict exercise-induced bronchoconstriction.

BACKGROUND: Exercise-induced bronchoconstriction (EIB) is diagnosed via exercise challenge on a treadmill, but such testing requires complex equipment and sufficient health-care resources. The fraction of exhaled nitric oxide (FeNO) test and mannitol bronchial provocation test (BPT) may serve as a surrogate for exercise testing. METHODS: We compared the diagnostic utilities of the FeNO test and mannitol BPT in predicting EIB in asthmatic children. We retrospectively analyzed data from 60 asthmatic children aged 6-16 years. We compared the exercise BPT results, FeNO levels, and mannitol BPT data. RESULTS: All subjects were divided into exercise-positive (n = 41) or -negative (n = 19) BPT groups. Of the 41 exercise-positive patients, 32 were mannitol BPT positive and nine were mannitol BPT negative. Of the 19 exercise-negative patients, nine and 10, respectively, were mannitol BPT positive and BPT negative. The maximum % forced expiratory volume in 1 s (FEV1 ) decrease after exercise was positively correlated with FeNO (r = 0.556, P < 0.001), and with mannitol response-dose ratio (RDR; r = 0.416, P = 0.001). The receiver operating characteristic (ROC) curve for FeNO to discriminate between asthmatic subjects with and without EIB had an area under the curve (AUC) of 0.771 (95%CI: 0.643-0.870). The discriminatory ROC curve for mannitol RDR had an AUC of 0.763 (95%CI: 0.633-0.864). The AUC of FeNO and mannitol RDR did not differ significantly. CONCLUSIONS: EIB significantly correlated with both FeNO and mannitol BPT data. Given that both methods similarly predicted EIB in asthmatic children, the simpler and safer FeNO test alone may be a clinically useful diagnostic tool.

Dyspnea Perception During Induced Bronchoconstriction Is Complicated by the Inhaled Methacholine in Children With Clinical Asthma.

PURPOSE: Dyspnea is not widely utilized as an indicator of asthma provocation despite its universal presentation. We hypothesized that dyspnea severity was proportionate with the lung function decline, methacholine dose-step, and the degree of bronchial hyperresponsiveness (BHR). METHODS: We retrospectively analyzed 73 children's bronchial provocation test data with an assessment of dyspnea at every dose-step. Dyspnea severity was scored using a modified Borg (mBorg) scale. A linear mixed effect analysis was performed to evaluate the relationship between the mBorg scale, the percentage fall in the forced expiratory volume in 1 second (FEV1) (ΔFEV1%), the methacholine dose-step, and the degree of BHR (BHR grade). RESULTS: Subjects were divided into 5 BHR groups based on their last methacholine dose-steps. The mBorg scores did not differ significantly among BHR groups (P=0.596, Kruskal-Wallis test). The linear mixed effect analysis showed that ΔFEV1% was affected by the methacholine dose-step (P<0.001) and BHR grade (P<0.001). The mBorg score was affected by the dose-step (P<0.001) and BHR grade (P=0.019). We developed a model to predict the mBorg score and found that it was affected by the methacholine dose-step and ΔFEV1%, elevating it by a score of 0.039 (χ² [1]=21.06, P<0.001) and 0.327 (χ² [1]=47.45, P<0.001), respectively. A significant interaction was observed between the methacholine dose-step and ΔFEV1% (χ² [1]=16.20, P<0.001). CONCLUSIONS: In asthmatic children, inhaled methacholine, as well as the degree of BHR and lung function decline, may affect dyspnea perception during the bronchial provocation test. If we wish to draw meaningful information from dyspnea perception, we have to consider various complicating factors underlying it.

Specific airway resistance is a better outcome parameter in bronchial provocation testing compared to FEV1 in patients with bronchial asthma.

OBJECTIVES: Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR). A bronchial provocation test (BPT) is used to test for AHR. However forced expiratory volume in one second (FEV1), used as outcome parameter is effort-related, in contrast to specific airway resistance (sRaw). This research was conducted to provide insight in the usefulness of sRaw as an outcome parameter in BPT. METHODS: A total of 85 patients performing a BPT were included in the study. Bronchial reactivity was defined as the provocative dosage or provocative concentration causing a 20% decrease in FEV1 (PC-20) or a 100% increase in sRaw (PC+100). RESULTS: No significant response in either FEV1 or sRaw was found in 20 patients (24%). Twenty-nine patients (34%) only had a positive response for sRaw; 24 out of these 29 patients recognized their symptoms. 36 patients (42%) showed a positive response for both PC-20 and PC + 100. CONCLUSIONS: Twenty-nine patients (34%) showed a significant increase in sRaw without a fall in FEV1. As performing sRaw is not a routine investigation, these patients are at risk of being excluded from a diagnosis of asthma. We suggest performing sRaw for patients without a fall in FEV1 during BPT when they report recognizable symptoms.

Methacholine bronchial provocation test in patients with asthma: serial measurements and clinical significance.

Background/Aims: The methacholine bronchial provocation test (MBPT) is used to detect and quantify airway hyper-responsiveness (AHR). Since improvements in the severity of asthma are associated with improvements in AHR, clinical studies of asthma therapies routinely use the change of airway responsiveness as an objective outcome. The aim of this study was to assess the relationship between serial MBPT and clinical profiles in patients with asthma. METHODS: A total of 323 asthma patients were included in this study. The MBPT was performed on all patients beginning at their initial diagnosis until asthma was considered controlled based on the Global Initiative for Asthma guidelines. A responder was defined by a decrease in AHR while all other patients were considered non-responders. RESULTS: A total of 213 patients (66%) were responders, while 110 patients (34%) were non-responders. The responder group had a lower initial PC20 (provocative concentration of methacholine required to decrease the forced expiratory volume in 1 second by 20%) and longer duration compared to the non-responder group. Members of the responder group also had superior qualities of life, compared to members of the non-responder group. Whole blood cell counts were not related to differences in PC20; however, eosinophil concentration was. No differences in sex, age, body mass index, smoking history, serum immunoglobulin E, or frequency of acute exacerbation were observed between responders and non-responders. Conclusions: The initial PC20, the duration of asthma, eosinophil concentrations, and quality-of-life may be useful variables to identify improvements in AHR in asthma patients.