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.
Adolescent ; Asthma ; Bronchial Provocation Tests ; Child ; Humans ; Leukotriene D4 ; Methacholine Chloride ; Respiratory Hypersensitivity

PURPOSE: It is controversial whether indoor pet exposure is either a risk or protective factor developing sensitization to pet allergens or asthma. Therefore, we investigated whether indoor pet ownership entails a risk for the development of asthma and sensitization in childhood. METHODS: The Panel Study of Korean Children (PSKC) is a general-population-based birth cohort study that recruited 2,078 mother-baby dyads in Korea between April and July of 2008. Among 1,577 children who were followed up in 2015, 559 underwent skin prick tests, spirometry and bronchial provocation tests using Provocholine. Having a cat or a dog and the prevalence of asthma were evaluated by using self-reported questionnaires and physicians’ medical records. RESULTS: During infancy, the rate of dog ownership was 4.5% (71 of 1,574) and that of cat ownership was 0.5% (8 of 1,574). Of the subjects, 7.9% (n=109) currently had at least 1 dog and 2.5% (n=34) had at least 1 cat. Pet ownership during infancy was associated with sensitization to cats or dogs (adjusted odds ratio [aOR], 4.24; 95% confidence interval [CI], 1.29–13.98), wheezing within 12 months (aOR, 5.56; 95% CI, 1.65–18.75) and current asthma (wheezing episode in the last 12 months+diagnosed asthma by physicians) (aOR, 6.36; 95% CI, 1.54–26.28). In contrast, pet ownership during the last 12 months was not associated with sensitization to cats or dogs or current asthma. CONCLUSION: Indoor pet exposure during infancy can be critical for developing sensitization to cats or dogs and asthma in childhood. Avoidance of pet exposure in early life may reduce sensitization to cats or dogs and development of asthma.
Allergens ; Animals ; Asthma ; Bronchial Provocation Tests ; Cats ; Child ; Cohort Studies ; Dogs ; Humans ; Infant ; Korea ; Medical Records ; Methacholine Chloride ; Odds Ratio ; Ownership ; Parturition ; Pets ; Prevalence ; Protective Factors ; Respiratory Sounds ; Risk Factors ; Skin ; Spirometry

PURPOSE: Chronic cough in allergic rhinitis (AR) patients is common with multiple etiologies including cough variant asthma (CVA), non-asthmatic eosinophilic bronchitis (NAEB), gastroesophageal reflux-related cough (GERC), and upper airway cough syndrome (UACS). Practical indicators that distinguish these categories are lacking. We aimed to explore the diagnostic value of the fraction of exhaled nitric oxide (FeNO) and forced expiratory flow at 25% and 75% of pulmonary volume (FEF(25–75)) in specifically identifying CVA and NAEB in these patients. METHODS: Consecutive AR patients with chronic cough were screened and underwent induced sputum, FeNO, nasal nitric oxide, spirometry, and methacholine bronchial provocation testing. All patients also completed gastroesophageal reflux disease questionnaires. RESULTS: Among 1,680 AR patients, 324 (19.3%) were identified with chronic cough, of whom 316 (97.5%) underwent etiology analyses. Overall, 87 (27.5%) patients had chronic cough caused by NAEB, 78 (24.7%) by CVA, 16 (5.1%) by GERC, and 81 (25.6%) by UACS. Patients with either NAEB or CVA (n = 165, in total) were further assigned to a common group designated as CVA/NAEB, because they both responded to corticosteroid therapy. Receiver operating characteristic curves of FeNO revealed obvious differences among CVA, NAEB, and CVA/NAEB (area under the curve = 0.855, 0.699, and 0.923, respectively). The cutoff values of FeNO at 43.5 and 32.5 ppb were shown to best differentiate CVA and CVA/NAEB, respectively. FEF(25–75) was significantly lower in patients with CVA than in those with other causes. A FEF(25–75) value of 74.6% showed good sensitivity and specificity for identifying patients with CVA. CONCLUSIONS: NAEB, CVA, and UACS are common causes of chronic cough in patients with AR. FeNO can first be used to discriminate patients with CVA/NAEB, then FEF(25–75) (or combined with FeNO) can further discriminate patients with CVA from those with CVA/NAEB.
Asthma ; Bronchial Provocation Tests ; Bronchitis ; Cough ; Eosinophils ; Gastroesophageal Reflux ; Humans ; Methacholine Chloride ; Nitric Oxide ; Rhinitis, Allergic ; ROC Curve ; Sensitivity and Specificity ; Spirometry ; Sputum

Bronchial provocation tests are of value in the evaluation of airway hyperresponsiveness. Nonspecific bronchial challenge (methacholine, mannitol, exercise, etc.) is used when the symptoms, physical examination, and measurements of pulmonary function are unremarkable in the diagnosis of asthma, when a patient is suspected of having occupational asthma or exercise-induced bronchoconstriction (EIB), and when a screening test for asthma or EIB is required for some occupational groups in whom bronchospasm would pose an unacceptable hazard. Methacholine inhalation challenge is most widely used pharmacologic challenge and highly sensitive. For appropriate interpretation of the results of methacholine provocation, it is important to perform the test with the standardized protocol and to recognize that inhalation methods significantly influence the sensitivity of the procedure. Indirect challenges (e.g., mannitol and exercise) correlate with airway inflammation and are more specific but less sensitive for asthma. Indirect provocation tests are used to confirm asthma, to differentiate asthma from other airway diseases, and to evaluate EIB.
Asthma ; Asthma, Occupational ; Bronchial Provocation Tests ; Bronchial Spasm ; Bronchoconstriction ; Diagnosis ; Exercise Test ; Humans ; Inflammation ; Inhalation ; Mannitol ; Mass Screening ; Methacholine Chloride ; Occupational Groups ; Physical Examination

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.
Asthma* ; Blood Cell Count ; Body Mass Index ; Bronchial Provocation Tests* ; Diagnosis ; Eosinophils ; Forced Expiratory Volume ; Humans ; Immunoglobulin E ; Immunoglobulins ; Methacholine Chloride* ; Respiratory Hypersensitivity ; Smoke ; Smoking

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.
Asthma* ; Bronchial Provocation Tests ; Bronchoconstriction* ; Child* ; Dyspnea* ; Forced Expiratory Volume ; Humans ; Lung ; Methacholine Chloride* ; Retrospective Studies

BACKGROUND: A US Food and Drug Administration (FDA)-approved drug methacholine chloride (Provocholine®) was recently introduced to Korea where it is now widely used in clinical practice. We aimed to evaluate the prevalence, risk factors and cutoff value of bronchial hyperresponsiveness (BHR) to Provocholine in 7-year-old children. METHODS: Six hundred and thirty-three children from the Panel Study on Korean Children who visited 16 regional hospitals were evaluated. Skin prick tests, spirometry and bronchial provocation tests for Provocholine as well as a detailed history and physical examinations were performed. The bronchial provocation test was reliably performed on 559 of these children. RESULTS: The prevalence of ever-diagnosed asthma via medical records was 7.7%, and that of current asthma (wheezy episode in the last 12 months + diagnosed asthma by physicians) was 3.2%. The prevalence of BHR to Provocholine was 17.2% and 25.8%, respectively, for a PC20 < 8 and < 16 mg/mL. The risk factors for BHR (PC20 < 16 mg/mL) were atopic dermatitis diagnosis and current dog ownership, whereas those for current asthma were allergy rhinitis diagnosis, a history of bronchiolitis before the age of 3, recent use of analgesics/antipyretics and maternal history of asthma. The BHR prevalence trend showed an increase along with the increased immunoglobulin E (IgE) quartile. The cutoff value of PC20 for the diagnosis of current asthma in children at age 7 was 5.8 mg/mL (sensitivity: 47.1%, specificity: 87.4%). CONCLUSIONS: BHR to Provocholine (PC20 < 8 mg/mL) was observed in 17.2% of 7-year-olds children from the general population and the cutoff value of PC20 for the diagnosis of current asthma was 5.8 mg/mL in this age group. The risk factors for BHR and current asthma showed discrepancies suggesting different underlying mechanisms. Bronchial provocation testing with Provocholine will be a useful clinical tool in the future.
Animals ; Asthma ; Bronchial Hyperreactivity ; Bronchial Provocation Tests ; Bronchiolitis ; Child* ; Dermatitis, Atopic ; Diagnosis ; Dogs ; Humans ; Hypersensitivity ; Immunoglobulin E ; Immunoglobulins ; Korea ; Medical Records ; Methacholine Chloride* ; Ownership ; Physical Examination ; Prevalence* ; Rhinitis ; Risk Factors* ; ROC Curve ; Sensitivity and Specificity ; Skin ; Spirometry ; United States Food and Drug Administration

PURPOSE: We previously reported that the skin prick test was sensitive and the serum specific immunoglobulin E test was specific for predicting positive airway responses to house dust mites (HDMs) in patients with asthma. Because the nose and bronchus are one airway, the nasal provocation test would be more specific for predicting the bronchial responses to HDM than the skin test. METHODS: The allergy skin prick test and nasal and bronchial provocation tests using HDM (Dermatophagoides farinae) were performed in 41 young men (age, 19–28 years) who wanted military certification for asthma. The nasal responses to HDM was scored according to the severity of rhinorrhea, sneezing, and nose itching. RESULTS: The prevalence of a positive skin prick test to HDM did not significantly differ between patients with (n=24) and without (n=17) an early airway reaction (EAR; 79.2% vs 70.6%, P=0.534). However, the prevalence of a positive nasal test was significantly higher in the airway responders than in the others (37.5% vs 0%, P=0.005). The concordance of a positive response to the nasal test (κ=0.332, P=0.004) but not to the skin prick test (κ=0.091, P=0.529) was significant with an EAR. The diagnostic sensitivity of the nasal test (37.5%) was lower than that of the skin prick test (79.2%), but the specificity was higher (100% vs 29.4%). CONCLUSIONS: The skin prick test is more sensitive, whereas the nasal test is more specific and accurate, for predicting an EAR to HDM in patients with asthma.
Asthma* ; Bronchi ; Bronchial Provocation Tests ; Certification ; Dermatophagoides farinae ; Dust* ; Ear ; Humans ; Hypersensitivity ; Immunoglobulin E ; Immunoglobulins ; Male ; Military Personnel ; Nasal Provocation Tests ; Nose ; Prevalence ; Pruritus ; Pyroglyphidae* ; Sensitivity and Specificity ; Skin ; Skin Tests ; Sneezing

PURPOSE: Both atopy and bronchial hyperresponsiveness (BHR) are characteristic features of asthma. Several BHR studies comparing groups of atopic and nonatopic asthmatics have reported conflicting results. The aim of this study was to compare BHR to indirect stimuli, such as mannitol or exercise, between atopic and nonatopic asthmatics in children. METHODS: We performed a retrospective analysis of data from 110 children with asthma, aged 6–18 years using skin prick tests, and serum total and specific IgE levels. Atopy degree was measured using the sum of graded wheal size or the sum of the allergen-specific IgE. Bronchial provocation tests (BPTs) using methacholine were performed on all subjects. BPTs using indirect simuli, including exercise and mannitol, were also performed. RESULTS: Asthma cases were classified as atopic asthma (n=83) or nonatopic asthma (n=27) from skin prick or allergen-specific IgE test results. There was no significant difference in the prevalence of BHR to mannitol or exercise between atopic and nonatopic asthmatics. Atopic asthma had a significantly lower postexercise maximum decrease in % forced expiratory volume in 1 second (FEV1) (geometric mean [95% confidence interval]: 31.9 [22.9–40.9] vs. 14.0 [9.4–18.6], P=0.015) and a methacholine PC20 (provocative concentration of methacholine inducing a 20% fall in FEV1) than nonatopic asthmatics (geometric mean [95% confidence interval]: 1.24 [0.60–1.87] ng/mL vs. 4.97 [3.47–6.47]) ng/mL, P=0.001), whereas mannitol PD15 (cumulative provocative dose causing a 15% fall in FEV1) was not significantly different between the 2 groups. CONCLUSION: There was no significant difference in the prevalence of BHR to mannitol or exercise between atopic and nonatopic asthmatics in children.
Asthma ; Bronchial Provocation Tests ; Child* ; Forced Expiratory Volume ; Humans ; Immunoglobulin E ; Mannitol ; Methacholine Chloride ; Prevalence ; Retrospective Studies ; Skin

Bronchial asthma is a disease characterized by the condition of airway hyper-responsiveness, which serves to produce narrowing of the airway secondary to airway inflammation and/or various spasm-inducing stimulus. Nonspecific bronchoprovocation testing is an important method implemented for the purpose of diagnosing asthma; this test measures the actual degree of airway hyper-responsiveness and utilizes direct and indirect bronchoprovocation testing. Direct bronchoprovocation testing using methacholine or histamine may have superior sensitivity as these substances directly stimulate the airway smooth muscle cells. On the other hand, this method also engenders the specific disadvantage of relatively low specificity. Indirect bronchoprovocation testing using mannitol, exercise, hypertonic saline, adenosine and hyperventilation serves to produce reactions in the airway smooth muscle cells by liberating mediators with stimulation of airway inflammatory cells. Therefore, this method has the advantage of high specificity and also demonstrates relatively low sensitivity. Direct and indirect testing both call for very precise descriptions of very specific measurement conditions. In addition, it has become evident that challenge testing utilizing each of the various bronchoconstrictor stimuli requires distinct and specific protocols. It is therefore important that the clinician understand the mechanism by which the most commonly used bronchoprovocation testing works. It is important that the clinician understand the mechanism of action in the testing, whether direct stimuli (methacholine) or indirect stimuli (mannitol, exercise) is implemented, when the testing is performed and the results interpreted.
Adenosine ; Asthma ; Bronchial Provocation Tests ; Hand ; Histamine ; Hyperventilation ; Inflammation ; Mannitol ; Methacholine Chloride ; Methods ; Myocytes, Smooth Muscle ; Respiratory Hypersensitivity ; Sensitivity and Specificity