Methacholine Provocation Test Research Articles

Nasal allergen and methacholine provocation tests influence co‑expression patterns of TGF‑β/SMAD and MAPK signaling pathway genes in patients with asthma.

Asthma is characterized by chronic bronchial inflammation and is a highly heterogeneous disease strongly influenced by both specific and non-specific exogenous factors. The present study was performed to assess the effect of nasal allergen provocation tests and methacholine provocation tests on the mRNA co-expression patterns of genes (SMAD1/3/6/7, MPK1/3 and TGFB1/3) involved in SMAD and non-SMAD TGF-β signaling pathways in patients with asthma. Reverse transcription-quantitative PCR was performed on blood samples taken pre-provocation and 1 h post-provocation to assess gene expression changes. Of the 59 patients studied, allergen provocations were administered to 27 patients and methacholine provocations to 32 patients. Correlations between expression levels of studied genes were found to be influenced markedly by the challenge administered, challenge test result and time elapsed since challenge. Importantly, increases in expression levels for four gene pairs (MAPK1-SMAD3, MAPK3-SMAD3, SMAD1-SMAD3 and SMAD3-TGFB1) were found to correlate significantly with asthma occurrence in the allergen provocation cohort, but not in the methacholine provocation cohort. The present study allows us to draw the conclusion that both intranasal allergen and bronchial methacholine challenges influence mRNA co-expression patterns of the SMAD1/3/6/7, MPK1/3 and TGFB1/3 genes.

Bronchial reactivity and asthma at school age after early-life metapneumovirus infection.

The association between early-life lower respiratory tract infection (LRTI) and asthma is well established. Knowledge about bronchial hyperresponsiveness (BHR) and asthma after metapneumovirus (MPV) LRTI is scarce. The aim of this study was to assess BHR and current asthma in school-aged children after hospital admission for early-life LRTI with MPV, and to compare with more well-known viruses, rhinovirus (RV) and respiratory syncytial virus (RSV), and with controls. A cohort consisting of children admitted for LRTI and controls was followed-up at school age with a clinical research assessment and lung function tests, including a methacholine provocation test. Current asthma was defined based on objective variable airway obstruction and clinical symptoms. BHR and asthma were compared according to viral groups. 135 children (median age 9.3 years) were included (16 MPV, 34 RV, 51 RSV, 13 mixed infections and 21 controls). Compared with controls there was increased BHR after MPV and RV LRTI (provocative dose causing a 20% fall in forced expiratory volume in 1 s and dose-response slope; p<0.05). Using Kaplan-Meier statistics, BHR was increased for MPV compared with both controls and RSV (p=0.02 and p=0.01). The proportion of children with current asthma at follow-up was higher in the LRTI children compared with the controls (46% versus 24%; p=0.06). Among children who had undergone MPV and RV infection, 50% fulfilled the asthma criteria compared with 43% in the RSV group (p=0.37). We found increased BHR and a high prevalence of asthma in school-aged children after early-life MPV infection, and findings were similar to RV, and less to RSV, compared with controls.

Severe bronchial hyperresponsiveness along with house dust mite allergy indicates persistence of asthma in young children.

Significant risk factors for persistence of asthma later in life are family history of allergies, early allergic sensitization and bronchial hyperresponsiveness (BHR). The evolution of BHR in young children without allergic sensitization and with house dust mite allergy (HDM) was investigated. In this retrospective analysis, electronic charts of 4850 young children with asthma and wheezy bronchitis between 2005 and 2018 were reviewed in order to study all patients ≤6 years with BHR assessed by methacholine provocation tests (MCT) at least once (n = 1175). Patients with more than two follow-up measurements were divided in group 1 (no allergic sensitization; n = 110) and group 2 (HDM allergy; n = 88). Additionally, skin prick test, exhaled nitrite oxide (eNO), and asthma treatment were analyzed. Forty-seven patients of group 1 aged median 4.3 years and 48 patients of group 2 aged median 4.7 years showed initially severe BHR <0.1 mg. At follow-up, patients with HDM were more likely to show persistence of severe BHR than non-sensitized patients (severe BHR group 1: n = 5 (10.6%) vs. group 2: n = 21 (43.8%), p < .001). In addition, 89.4% of group 1 had mild to moderate or no BHR, compared to only 56.2% of group 2. There was a significant difference in eN0 (median group 1: 9 ppb vs. group 2: 26 ppb, p < .001), at last follow-up. Age, sex, and asthma therapy had no effect on BHR. In young children without sensitization BHR normalizes, whereas HDM allergy indicates a persistence of asthma beyond infancy.

Is asthma over-diagnosed in Cyprus? A clinical study at the outpatient’s primary care level

Background: Although asthma is a common disease accurate diagnosis is missing and it has been reported that often it is over or under-diagnosed. Aim: To investigate if a physician’s diagnosis of asthma in Cyprus is correct by using a structured algorithm at the outpatient primary care level. Subjects and Methods: Sixty adults with a self-reported physician diagnosis of asthma, mean age of 47,8 years (29 males and 31 females) were included in the study. Medical history and physical examination, pre-post bronchodilation spirometry and methacholine bronchial challenge test was used to confirm or rule out the diagnosis as well as a three months follow-up. In addition, the cost of treatment was estimated. Results: Sixteen subjects (27%) had a positive pre-post bronchodilation spirometric test and were considered asthmatics. In 9 out of the 44 remaining subjects a positive Methacholine provocation test confirmed the diagnosis of asthma. The rest of the subjects (n = 35) went into a 3 months observational period during which only 2 showed asthmatic symptoms and were considered asthmatics by a second methacholine test that confirmed the diagnosis. Therefore, a correct asthma diagnosis was established in only 27(45%) of subjects. The annual average cost of medication for asthma confirmed the group was 313 euro/patient (171-454, 95% CI) and the average 2-year unnecessary (asthma ruled-out group) cost of treatment was approximately 297 euro/patient. (179-415, 95% CI). Conclusions: Physician-diagnosed asthma overestimates the actual prevalence of disease in adults in Cyprus since it was shown that more than half of the participants did not have Asthma. These individuals consume unneeded medications at a significant cost. Thus, the correct diagnosis of Asthma should be made by using more specific tests starting at the primary care level.

Reduced forced expiratory flow between 25% and 75% of vital capacity in children with allergic rhinitis without asthmatic symptoms

ABSTRACT Introduction: Allergic rhinitis (AR) and asthma are closely associated in children. Reduced FEF25%-75% which reflects small airway airflow limitation is frequently observed in asthma. This study aimed to examine the proportion of small airway dysfunction in children with AR and to determine its associated factors. Methods: The medical records of 144 aged 6-18-year children with AR without overt asthmatic symptoms were retrospectively reviewed. Subjects were divided into 2 groups according to the FEF25%-75% values; normal FEF25%-75% group (n = 129) and reduced FEF25%-75% group (n = 15). Clinical data, allergen sensitization profile, exhaled nitric oxide, spirometry, and methacholine provocation test results were compared between the two groups. Results: The mean FEV1 and FEF25%-75% values in the reduced FEF25%-75% group (73.5 ± 9.4%pred and 56.0 ± 7.7%pred, respectively) were significantly lower than in the normal FEF25%-75% group (87.0 ± 12.5%pred and 99.1 ± 21.4%pred, respectively). The mean disease duration was significantly longer in the reduced FEF25%-75% group than in the normal FEF25%-75% group (5.39 ± 1.85 y vs 3.14 ± 1.80 y, p < 0.001). Subjects with positive bronchial hyperresponsiveness (MChPC20<16 mg/mL) were more frequently detected in the reduced FEF25%-75% group than in the normal FEF25%-75% group (26.7% vs 8.52%, p = 0.013). Long disease duration and severity of AR were significantly associated with impaired FEF25%-75% values. Conclusions: Subjects with AR alone may have impaired FEF25%-75% values which is considered as a marker of early bronchial involvement. Longer disease duration and severity of AR are important risk factors for progressive declines in small airway function. Physicians should be aware of need for the measurement of FEF25%-75% values for early detection of small airway dysfunction, particularly in children with severe long-lasting allergic rhinitis.

Differences in lung function, bronchial hyperresponsiveness and respiratory health between elite athletes competing in different sports

ABSTRACT 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 (FENO), spirometry, methacholine provocation (PD20met) and skin prick test. Three cut-off levels defined BHR; i.e. PD20met ≤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 (FEV1) 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 (FEF25-75), and/or FEV1/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%). Highlights Swimmers and ball game athletes had higher mean FVC and FEV1 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 FEF25-75 and/or FEV1/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.

Application of a Cold Dry Air Provocation Test in Pediatric Patients with Asthma.

Asthma is a chronic inflammatory airway disease characterized by reversible airway obstruction and airway hyperreactivity. We proposed a cold dry air (CDA) provocation test and investigated its application in pediatric patients with asthma. We enrolled 72 children and adolescents older than 5 years who presented to our hospital with chronic cough, shortness of breath, and wheezing. We analyzed the results of allergy, pulmonary function, methacholine provocation, and CDA provocation tests. The FEV1 change 5 min after the provocation was recorded as CDA5 dFEV1; that after 15 min was recorded as CDA15 dFEV1. PT10 was the provocation time causing a 10% decrease in FEV1; a decrease of >10% in dFEV1 was considered a positive CDA test. Among the 72 subjects, 51 were diagnosed with asthma. A positive CDA test in patients with asthma correlated with non-eosinophilic asthma. In patients with asthma, sputum eosinophils and eosinophil cationic protein (ECP) levels of the patients with a positive CDA test were significantly lower than those of patients with a negative test. CDA5 dFEV1 correlated with PC20 and total immunoglobulin E. CDA15 dFEV1 correlated with PC20, sputum eosinophils, and ECP. PT10 became shorter as the peripheral blood eosinophil, FVC, FEV1, FEV1/FVC, and FEF25-75 decreased. The CDA provocation test showed airway hyperreactivity to non-specific stimuli, a high correlation with non-eosinophilic asthma, and the possibility of assessing asthma severity via PT10.

Asthma predictive index as a useful diagnostic tool in preschool children: a cross-sectional study in Korea.

BackgroundIt is challenging to diagnose asthma in preschool children. The asthma predictive index (API) has been used to predict asthma and decide whether to initiate treatment in preschool children.PurposeThis study aimed to investigate the association between questionnaire-based current asthma with API, pulmonary function, airway hyperreactivity (AHR), fractional expiratory nitric oxide (FeNO), and atopic sensitization in preschool children.MethodsWe performed a population-based cross-sectional study in 916 preschool children aged 4–6 years. We defined current asthma as the presence of both physician-diagnosed asthma and at least one wheezing episode within the previous 12 months using a modified International Study of Asthma and Allergies in Childhood questionnaire. Clinical and laboratory parameters were compared between groups according to the presence of current asthma.ResultsThe prevalence of current asthma was 3.9% in the study population. Children with current asthma showed a higher rate of positive bronchodilator response and loose and stringent API scores than children without current asthma. The stringent API was associated with current asthma with 72.2% sensitivity and 82.0% specificity. The diagnostic accuracy of the stringent API for current asthma was 0.771. However, no intergroup differences in spirometry results, methacholine provocation test results, FeNO level, or atopic sensitization rate were observed.ConclusionThe questionnaire-based diagnosis of current asthma is associated with API, but not with spirometry, AHR, FeNO, or atopic sensitization in preschool children.

Lung function and bronchial hyper-reactivity from 11 to 18years in children with bronchiolitis in infancy.

Various trajectories for lung function and bronchial hyper-reactivity (BHR) from early childhood to adulthood are described, including puberty as a period with excessive lung growth. Bronchiolitis in infancy may be associated with increased risk of developing chronic obstructive pulmonary disease, but the development of respiratory patterns during puberty is poorly characterized for these children. We aimed to study the development and trajectories of lung function and BHR from 11 to 18years of age in children hospitalized for bronchiolitis in infancy. Infants hospitalized for bronchiolitis at the University Hospitals in Stavanger and Bergen, Norway, during 1997-1998, and an age-matched control group, were included in a longitudinal follow-up study and examined at 11 and 18years of age with spirometry and methacholine provocation test (MPT). The MPT data were managed as dose-response slope (DRS) in the statistical analyses. Changes in lung function and DRS from 11 to 18years of age were analyzed by generalized estimating equations, including interaction terms. z-scores for forced vital capacity (FVC), forced expiratory volume in first second (FEV1 ), FEV1 /FVC ratio, and DRS were not different from 11 to 18years of age in both the post-bronchiolitis and the control group. The trajectories from 11 to 18years did not differ between the two groups. BHR at age 11 was independently associated with asthma at age 18. Children hospitalized for bronchiolitis had stable predicted lung function and BHR from 11 to 18years of age. The lung function trajectories were not different from controls.

Diagnostic Value of Astograph Airway Responsiveness Measurement in Chest Suffocation Variant Asthma

Objective To investigate the diagnostic value of Astograph methacholine provocation test in patients with chest tightness variant asthma(CTVA). Methods From January 2011 to February 2017, 156 patients with CTVA in outpatient or inpatient department of respiratory medicine of Kailuan General Hospital affiliated to North China University of Science and Technology were selected as case group (chest tightness variant asthma group). The control group were 361 non-asthmatic patients including interstitial lung disease(23 cases), coronary disease (157 cases), hypertensive cardiopathy(22 cases), myocardiosis (16 cases), congenital heart disease (3 cases), rheumatic valvular heart disease (6 cases), central airway disease (3 cases), thyromegaly (10 cases), mediastinal tumor (5 cases), thoracic or spinal deformity (8 cases), phrenoparalysis (2 cases) and vegetative nerve functional disturbance (106 cases). All participants received pulmonay ventilation test, average daily and nightly variation rate of PEF(Peak expiratory flow) or PEF weekly variability, Astograph methacholine provocation test (forced expirataory volume in one second≥70% expectation), and other relevant examinations.The diagnostic value of Astograph methacholine provocation test on CTVA was assessed by analyzing the sensitivity, specificity, positive predictive value, negative predictive value, and Yunden index of Astograph methacholine airway. Results Compared with the control group((1.18±0.44)%), theforced expiratory flow from 75% of Forced vital capcacity (FEF75)index of CTVA group((1.29±0.50)%) had significant difference(, t=2.96, P=0.006). The sensitivity, specificity, positive predictive value, negative predictive value, Yunden index, and diagnostic accuracy of Astograph methacholine provocation test on CTVA were 0.814, 0.695, 0.536, 0.305, 0.509 and 0.731, respectively. Conclusion The sensitivity, negative predictive value, Yunden index and diagnostic accuracy of Astograph methacholine provocation test on CTVA were higher, whereas the specificity and positive predictive value were relatively lower, suggesting that Astograph methacholine provocation test had a reliable diagnostic value on CTVA, with lower false negative and higher false positive. Key words: Astograph method; Chest tightness variant asthma; Diagnosis

Longitudinal analysis to better characterize Asthma-COPD overlap syndrome: Findings from an adult asthma cohort in Korea (COREA).

Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS), which has received much attention, has not been unanimously defined. In this study, we tried to demonstrate that longitudinally defined ACOS is more useful in the real world than blending patients with asthma and COPD. The study patients had undergone two consecutive pulmonary function tests measured at least 3months apart (n=1889). We selected the patients who had positive bronchodilator response or methacholine provocation tests (n=959). Next, we defined ACOS as a patient with a persistent airflow obstruction [forced expiratory volume in 1second (FEV1)/forced vital capacity <0.7] that was identified twice consecutively by an interval of at least 3months (n=228). The proportions of patients who were older, male and smokers were significantly higher, and baseline lung function was lower in patients with ACOS. In the longitudinal analysis, the mean change in lung function was high, and a greater decline in FEV1 was observed in patients with ACOS. In addition, we compared ACOS and severe asthma, and we also performed a cluster analysis and compared the results with our definition of ACOS. According to our definition, ACOS is an independent subtype with distinctive characteristics. Finally, a genome-wide association study (GWAS) was performed to identify genetic variations associated with ACOS, but no significant single nucleotide polymorphisms were identified. Our findings suggest that ACOS should be defined longitudinally and considered as an independent subgroup distinguished by inherited environmental factors rather than as a genetically distinct independent group.

Physiotherapy improves symptoms of exercise-induced laryngeal obstruction in young elite athletes: a case series

ObjectiveA constricted, upper chest breathing pattern and postural dealignments habitually accompany exercise-induced laryngeal obstruction (EILO), but there are few effective treatments for athletes presenting with EILO. This case series was...

Phenotypic analysis of asthma in Japanese athletes

BackgroundAsthma in athlete populations such as Olympic athletes has various pathogeneses. However, few reports are available on the features of asthma in the athlete population in clinical practice. In this study, we focused on classifying asthma in Japanese athlete population. MethodsWe performed a cluster analysis of data from pulmonary function tests and clinical biomarkers before administering inhaled corticosteroids (ICS) therapy in athlete population of individuals diagnosed with asthma (n = 104; male, 76.9%; median age, 16.0 years), based on respiratory symptoms and positive data on methacholine provocation tests. We also compared backgrounds, sports types, and treatments between clusters. ResultsThree clusters were identified. Cluster 1 (32%) comprised athletes with a less atopic phenotype and normal pulmonary function. Cluster 2 (44%) comprised athletes with a less atopic phenotype and lower percent predicted forced expiratory volume in 1 s (%FEV1) values, despite less symptomatic state. Cluster 3 (24%) comprised athletes with a strong atopic phenotype such as high eosinophil count in the blood and total serum immunoglobulin E level. After treatment with ICS or ICS plus long-acting β-adrenergic receptor agonist for 6–12 months, %FEV1 values were significantly improved in Cluster 2 athletes, whereas Cluster 3 athletes had a significant decrease in the fraction of exhaled nitric oxide compared to pretreatment values. ConclusionsThese data suggest three clusters exist in Japanese athlete population with asthma. Between the clusters, the characteristics differed with regard to symptoms, atopic features, and lower %FEV1 values. The pathogeneses between clusters may vary depending on the inflammation type and airway hyperresponsiveness.

Comparison on the profiles of a modified Borg scale and the pediatric dyspnea scale during an induced bronchoconstriction in children with clinical asthma

Purpose: Dyspnea is the cardinal symptom of asthma, but it is difficult to quantify clinically. Although modified Borg (mBorg) scale has been successfully used in adult, but there has been some difficulties to apply in children. Recently, Pediatric Dyspnea Scale (PDS) was adequately designed and has been widely used. The aim of this study is to compare 2 evaluating scales of dyspnea provoked by induced-bronchoconstriction in childhood asthma. Methods: Seventy-three clinically suspected children with asthma were enrolled in this study. Each ‘fractional exhaled nitric oxide (FeNO)’ was documented. Forced expiratory volume in 1 second (FEV1), mBorg score and PDS score were recorded during metha-choline provocation test. Results: Mapping using canonical plot demonstrated global similarity between 2 scales with some distinctive features. Whereas mBorg score showed more diverse categories in low level of dyspnea, PDS score did in medium level of it. A distribution of dyspnea perception score at a 20% decrease in FEV1 relative to baseline (PS20), a perception score of dyspnea at 20% fall in FEV1 of 2 scales represented similar wide, biphasic feature. Statistical relevance was verified with spearman correlation (Rs=0.903, P<0.001) and Bland-Altman analysis. PS20 of both scores and FeNO had no statistical relationship. While relationship between PS20 by mBorg score and the concentration of methacholine at 20% fall in FEV1 (PC20) was not significant (Rs=0.224, P=0.154), that between PS20 by PDS and PC20 was weak positive (Rs=0.29, P=0.063). Conclusion: PDS had similar pattern to assess the dyspnea with the mBorg scale suggesting adequacy of PDS in evaluating pediat-ric clinical asthma. We expect these scales to help clinical practice in complementary ways. (Allergy Asthma Respir Dis 2017;5:262-268)

Bronchial provocation testing does not detect exercise-induced laryngeal obstruction

ABSTRACTIntroduction: Exercise-induced laryngeal obstruction (EILO) is a key differential diagnosis for asthma in the presence of exertional respiratory symptoms. Continuous laryngoscopy during exercise (CLE), the current gold standard diagnostic test for EILO, has practical limitations. We aimed to establish if inspiratory flow data obtained during standard bronchoprovocation testing, to establish the presence of extra-thoracic hyper-responsiveness, may prove diagnostic for EILO and thus preclude requirement for CLE testing. Methods: We consecutively evaluated 37 adult subjects with exertional dyspnea and possible asthma referred over 6 months. All subjects received comprehensive assessment including a detailed clinical evaluation; pulmonary function testing, indirect and direct bronchial provocation testing, and CLE testing. Results: Out of 37 subjects, moderate or severe EILO was diagnosed in 8 subjects (22%, all female) while 5 (14%) had both asthma and EILO. There was no correlation between degree of EILO during CLE and mean decrease in forced inspiratory flow (%FIF50) obtained during neither the Methacholine (r = −0.15; p = 0.38) nor Mannitol (r = 0.04; p = 0.84) provocation tests. Conclusion: Inspiratory flow parameters obtained during bronchoprovocation tests did not reliably detect EILO. It remains that CLE is an important and key investigation modality in establishing a secure diagnosis of EILO.

Persistence of respiratory and inflammatory responses after dermal sensitization to persulfate salts in a mouse model of non-atopic asthma.

BackgroundExposure to ammonium persulfate (AP) has been reported to be the main cause of occupational asthma in hairdressers. The aim of this study is to assess how long the asthmatic response to AP can be induced after dermal sensitization in a mouse model.MethodsBALB/c mice received dermal applications of AP or dimethylsulfoxide (DMSO) (control) on days 1 and 8. They then received a single nasal instillation (challenge) of AP or saline on days 15, 22, 29, 36, 45, 60 and 90. Respiratory responsiveness to methacholine was measured 24 h after the challenge using a non-specific methacholine provocation test. Pulmonary inflammation was analysed in bronchoalveolar lavage (BAL), and total serum immunoglobulin (Ig) E, IgG1 and IgG2a were measured in serum samples. Histological analysis of lung slides was performed.ResultsMice dermally sensitized and intranasally challenged with AP showed respiratory responsiveness to methacholine as long as 45 days after initial sensitization, as well as increased percentage of neutrophils in BAL compared with the control group. At day 60, dermally sensitized mice still presented bronchial hyperresponsiveness, while the percentage of neutrophils returned to baseline levels similar to those of controls. Total serum IgE increased significantly on day 22 after dermal sensitization. Total serum IgG1 and IgG2a increased from 45 days after dermal sensitization and remained high at 90 days.ConclusionsBoth respiratory responsiveness to methacholine and airway inflammation responses decrease with increasing time between sensitization and challenge. Respiratory responsiveness to methacholine tends to persist longer than inflammation.

Predictive risk factors for relapse after cessation of inhaled corticosteroids in well-controlled childhood asthma.

There is limited data for predicting the risk of exacerbations following the cessation of inhaled corticosteroids (ICS) in well controlled childhood asthma. In current study, clinical, functional and inflammatory parameters at the time of ICS withdrawal were investigated in that respect. Forty children asymptomatic for at least 3 months on low dose ICS's were enrolled and ICS were discontinued in summer. At enrolment symptom/medication diary, pulmonary function parameters, methacholine provocation testing, peripheral blood eosinophilia, serum total and allergen-specific IgE levels and skin prick testing were performed. In a subgroup of patients, phytohemaglutinin induced secretion of IL-5, IL-13, IFN-γ and IL-10 from blood mononuclear cells were measured. Patients were assessed with symptom/medication diary and pulmonary function test every 2 months for 6 months. Eighteen of 37 patients experienced recurrence of acute asthma symptoms. In patients with acute attack (group I), changes in rhinitis symptom scores at 2nd month vs. baseline were statistically higher. In addition, group I had significantly higher rhinitis symptom scores compared to group II at fourth-month visit. Patients with acute exacerbation revealed a significant decrease in FEV1% at 2nd month compared to baseline. Moreover, group I showed significantly lower FEF 25-75% compared to group II at 2nd month. Baseline bronchial hyper-responsiveness with methacholine was found to be an independent risk factor for asthma exacerbation. The findings of this study identified baseline bronchial hyperreactivity, higher rhinitis symptom scores and gradual decrease in pulmonary function parameters during follow-up as risk factors for subsequent exacerbation of asthma.

Elite Swimmers Have Larger Lung Volumes But More Severe Bronchial Hyperresponsiveness Than Elite Cross Country Skiers

A few previous reports have shown that lung volumes, diffusion capacity as well as bronchial hyperresponsiveness (BHR) are increased in well trained swimmers as compared to other athletes and controls. It is unknown if this can be applied to elite athletes and if this is due to genetic or environmental factors such as the specificity of the swim training and the exposure to chlorine derivatives in the swimming pools. PURPOSE: To compare lung function, BHR and respiratory symptoms in elite swimmers and cross country skiers. METHODS: In a cross sectional study, 29 elite swimmers (17♂/12♀) aged 16–28 years and 30 elite cross-country skiers (20♂/10♀) aged 20–37 years, all competing at high international level, measured lung function by maximal expiratory flow volume loops, forced expiratory flow the first second (FEV1), forced vital capacity (FVC), forced expiratory flow at 50 % of FVC (FEF50) and bronchial hyperresponsiveness was measured by methacholine provocation test, provocation dose at 20 % reduction in FEV1 (PD20meth). Training time per week, symptoms and use of antiasthmatic medication were recorded with the AQUA-questionnaire and by a clinical examination. Antiasthmatic medication was withheld according to ERS guidelines. RESULTS: The elite swimmers had a significant higher FEV1, as compared to the cross country skiers, 4.73L (4.39, 5.07) mean (95 % confidence interval) vs 4.31L (4.06, 4.57) (p=0.05) respectively, FEV1 (% predicted), 114.7 % (110.2, 119.2) vs 103.0 % (99.2, 106.7) (p<0.001) respectively and FVC (% predicted), 122.4 % (116.9, 127.8) vs112.2 % (108.4, 115.9) (p=0.002) respectively. Twenty-three swimmers had a PD20meth ≤ 4 umol as compared to six cross country skiers. Mean training time per week was significant higher in swimmers, 23.8 hours (23.1, 24.4) vs 17.1 hours (16.6, 17.6) (p< 0.001). 27.6 % of the swimmers and 70 % of the skiers had an asthma diagnosis and 37.9 % of the swimmers and 83.3 % of the skiers used daily antiasthmatic medication. No differences were found in the other lung function variables or in self-reported symptoms. CONCLUSION: Elite swimmers have larger lung volumes and FEV1 than elite cross country skiers, but it seems that swimmers are more likely to develop severe BHR due to exposure to chlorine derivatives during their prolonged daily training sessions.

Effect of Prenatal Maternal Trait Anxiety on Atopic Dermatitis and Immunoglobulin E Level: Cocoa Study

U E S D A Y 855 Phenotypes of Atopic Dermatitis in School Children Eun Lee, Si Hyeon Lee, Ji-Won Kwon, Song I. Yang, MD, Young Ho Jung, MD, Hyung-Young Kim, Ju-Hee Seo, MD, Byoung-Ju Kim, MD, PhD, Hyo-Bin Kim, MD, PhD, So Yeon Lee, MD, PhD, HoJang Kwon, MD PhD, Soo-Jong Hong, MD, PhD; Department of Pediatrics, Childhood Asthma Atopy Center, Research Center for Standardization of Allergic Diseases, Asan Medical Center, University of Ulsan College of Medicine, Asan Institute for Life Sciences, University of ulsan College of Medicine, Department of Pediatrics, Bundang CHA Medical Center, CHA University College of Medicine, Childhood Asthma Atopy Center, Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea, Department of Pediatrics, Pusan National University Yangsan Hospital, Yangsan, Department of Pediatrics, Korea Cancer Center Hospital, Seoul, South Korea, Department of Pediatrics, Hae-undae Paik Hospital, Inje University College of Medicine, Busan, South Korea, Department of Pediatrics,Inje University Sanggye Paik Hospital, Seoul, South Korea, Department of Pediatrics, Hallym University College of Medicine, Seoul, South Korea, Dankook University, Cheonan. RATIONALE: Atopic dermatitis (AD) develops from a complex interplay between environmental and immunologic factors incomplete understanding of its pathophysiology. AD is characterized by heterogeneous features in its onset and severity. The aim was to define the distinct phenotypes of AD children aged 6 to 13 years. METHODS: 242 children diagnosed with AD ever and AD symptoms during the last 12 months were included from the first survey of Children’s Health and Environmental Research survey (n52491). Variables such as personal characteristics, age at onset of AD, treatment during the last 12 months, number of positive skin prick tests (SPTs), total serum IgE levels and eosinophil were included. After 4 years, lung function tests, methacholine provocation tests, and blood test including IgE and eosinophil were performed. RESULTS: We identified 4 AD phenotypes. Class types were characterized as ‘‘early onset with low atopy’’ (26.4% of sample, Group 1), ‘‘early onset with high atopy’’ (48.3%, Group 2), ‘‘late onset with low atopy’’ (9.9%, Group 3), ‘‘intermediate onset with high atopy’’ (15.3%, Group 4). At 4 year follow-up, although group 2 and 4 showed persistently elevated IgE levels, only group 2 showed persistently elevated eosinophil level, increased prevalence of new onset of bronchial hyper-responsiveness (BHR) (13.5%) and new diagnosis of asthma (8.5%), and higher positive SPTs, compared to group 4. CONCLUSIONS: The LCA revealed four distinct AD phenotypes in school children. Cluster analysis of ADmay lead to a better understanding of the pathophysiology of AD, a better prediction of the prognosis, and furthermore, an ideal application of personalized therapy in future.

Fractional exhaled nitric oxide: comparison between portable devices and correlation with sputum eosinophils.

This study was performed to compare the 2 different portable devices measuring fractional exhaled nitric oxide (FeNO) and to see the correlation between FeNO and induced sputum eosinophil count (ISE). Forty consecutive subjects clinically suspected to have asthma underwent FeNO measurement by NIOX-MINO® and NObreath® concurrently. All also had induced sputum analysis, methacholine provocation test or bronchodilator response test, and spin prick test. Agreement between the 2 devices was evaluated. The correlation between FeNO and ISE was assessed, as well as the cut-off level of FeNO to identify ISE ≥3%. The intraclass correlation coefficient (ICC) between FeNO levels measured by NIOX-MINO® (FeNONIOX-MINO) and NObreath® (FeNONObreath) was 0.972 with 95% confidence interval of 0.948-0.985. The 95% limits of agreement were -28.9 to 19.9 ppb. The correlation coefficient between ISE and FeNONIOX-MINO was 0.733 (P<0.001), and 0.751 between ISE and FeNONObreath (P<0.001). The ROC curve found that the FeNONIOXMINO of 37.5 ppb and the FeNONObreath of 36.5 ppb identified ISE ≥3% with 90% sensitivity and 81% specificity. Age, sex, body mass index, smoking history, atopy, and the presence of asthma did not affect the FeNO level and its correlation with ISE. The NIOX-MINO ® and NObreath® agree with each other to a high degree. Both devices showed close correlation with ISE with similar cut-off value in identifying ISE ≥3%.