Methacholine Bronchoprovocation Research Articles

Airway Hyperresponsiveness, but Not Bronchoalveolar Inflammatory Cytokines Profiles, Is Modified at the Subclinical Onset of Severe Equine Asthma.

Airway hyperresponsiveness (AHR) and inflammation are both observed in human and equine asthma. The aim of this study was to assess the timeline and relationship of both features at the subclinical onset of severe equine asthma (SEA). First, the repeatability of the pulmonary function test (PFT) using impulse oscillometry system, and the methacholine bronchoprovocation test (BPT) were assessed at a 1-day interval on six SEA horses in clinical remission and six control horses. Then, clinical and ancillary tests were performed before and after a 1-week low-dust environmental challenge, including weighted clinical score, respiratory endoscopy, bronchoalveolar fluid cytology, PFT, and BPT. Both PFT and BPT showed acceptable repeatability. No test allowed SEA horses in clinical remission to be distinguished from control, unlike in human patients. Because of the low-dust environment, no significant difference was observed in the results of clinical and conventional ancillary examinations after the challenge. However, SEA horses showed increased AHR after the environmental challenge. At that stage, no signs of inflammation or changes in pro-inflammatory cytokines profiles (quantification and gene expression) were observed, suggesting AHR is present at an earlier stage of equine asthma than airway inflammation. This feature indicates SEA could present in a different disease pathway than neutrophilic human asthma.

Longitudinal follow-up of the asthma status in a French–Canadian cohort

Asthma affects 340 million people worldwide and varies in time. Twenty years ago, in Canada, the Saguenay–Lac-Saint-Jean asthma family cohort was created to study the genetic and environmental components of asthma. This study is a follow-up of 125 participants of this cohort to explore the appearance, persistence, and progression of asthma over 10–20 years. Participants answered a clinical standardized questionnaire. Lung function was assessed (forced expiratory volume in 1 s, forced vital capacity, bronchial reversibility, and methacholine bronchoprovocation), skin allergy testing was performed, blood samples were obtained (immunoglobulin E, white blood cell counts) and phenotypes were compared between recruitment and follow-up. From the participants without asthma at recruitment, 12% developed a phenotype of adult-onset asthma with the presence of risk factors, such as atopy, high body mass index, and exposure to smoking. A decrease of PC20 values in this group was observed and a decrease in the FEV1/FVC ratio in all groups. Also, 7% of individuals with asthma at recruitment developed chronic obstructive pulmonary disease, presenting risk factors at recruitment, such as moderate-to-severe bronchial hyperresponsiveness, exposure to smoking, and asthma. This study allowed a better interpretation of the evolution of asthma. Fine phenotypic characterization is the first step for meaningful genetic and epigenetic studies.

Aerosol Generation and Mitigation During Methacholine Bronchoprovocation Testing: Infection Control Implications in the Era of COVID-19.

Methacholine bronchoprovocation or challenge testing (MCT) is commonly performed to assess airway hyper-responsiveness in the setting of suspected asthma. Nebulization is an aerosol-generating procedure, but little is known about the risks of MCT in the context of the ongoing coronavirus disease 2019 (COVID-19) pandemic. We aimed to quantify and characterize aerosol generation during MCT by using different delivery methods and to assess the impact of adding a viral filter. Seven healthy subjects performed simulated MCT in a near particle-free laboratory space with 4 different nebulizers and with a dosimeter. Two devices continuously sampled the ambient air during the procedure, which detected ultrafine particles, from 0.02-1 μm, and particles of sizes 0.3, 0.5, 1.0, 2.0, 5.0, and 10 µm, respectively. Particle generation was compared among all the devices, with and without viral filter placement. Ultrafine-particle generation during simulated MCT was significant across all the devices. Ultrafine-particle (0.02-1 μm) concentrations decreased 77%-91% with the addition of a viral filter and varied significantly between unfiltered (P < .001) and filtered devices (P < .001). Ultrafine-particle generation was lowest when using the dosimeter with filtered Hudson nebulizer (1,258 ± 1,644 particle/mL). Ultrafine-particle concentrations with the filtered nebulizer devices using a compressor were higher than particle concentrations detected when using the dosimeter: Monaghan (3,472 ± 1,794 particles/mL), PARI (4,403 ± 2,948), Hudson (6,320 ± 1,787) and AirLife (9,523 ± 5,098). The high particle concentrations generated during MCT pose significant infection control concerns during the COVID-19 pandemic. Particle generation during MCT was significantly reduced by using breath-actuated delivery and a viral filter, which offers an effective mitigation strategy.

Lung function trajectories and bronchial hyperresponsiveness during childhood following severe RSV bronchiolitis in infancy.

Children with severe respiratory syncytial virus (RSV) bronchiolitis in infancy have increased risks of asthma and reduced lung function in later life. There are limited studies on the longitudinal changes of lung function and bronchial hyperreactivity from early to late childhood in infants hospitalized for RSV bronchiolitis. In a prospective cohort of 206 children with their first episode of RSV-confirmed bronchiolitis in the first year of life, 122 had spirometry performed at least twice between 5-16years of age. Methacholine bronchoprovocation was available in 127 and 79 children at 7 and 12years of age, respectively. Longitudinal changes in FEV1 , FVC, and FEV1 /FVC z-scores and methacholine PC20 were analyzed. 55% of the study cohort (N=122) were male, and 55% were Caucasian. During follow-up, longitudinal changes in z-scores for pre- and post-bronchodilator FEV1 (P<.0001) FVC (P<.0001) and FEV1 /FVC (P<.0001 for pre- and 0.007 for post-bronchodilator) from age 5 to 10-16years were observed. Declined lung function in late childhood was significantly associated with gender, physician diagnosis of asthma, and allergic sensitization. PC20 geometric mean increased from 0.28mg/mL at 7years to 0.53mg/mL at 12years of age, and the frequency of abnormal bronchial hyperreactivity decreased from 96% to 78% (P=.0003). Following severe RSV bronchiolitis, there appear to be significant longitudinal changes in pre- and post-bronchodilator lung function during childhood. The study has several limitations including significant dropouts and the lack of a control group and post-bronchodilator measurements. Bronchial hyperreactivity is common in children following severe RSV bronchiolitis; however, it appears to decrease as they enter late childhood.

Health Services Utilization Is Increased in Poor Perceivers of Bronchoconstriction and Hyperinflation in Asthma

Impaired symptom perception is often listed as a risk factor for life-threatening asthma, but there is limited evidence to support this. We aimed to determine whether impaired perception of bronchoconstriction (BC) and/or dynamic hyperinflation (DH) are risk factors for severe asthma exacerbations. In this prospective cohort study, individuals with asthma underwent high-dose methacholine challenge testing. Changes in forced expiratory volume in 1 second (FEV1) (% predicted) and inspiratory capacity (IC) (% predicted) were measured to assess the degree of BC and DH, respectively, during high-dose methacholine bronchoprovocation. Participants rated dyspnea intensity during testing and were categorized as poor, normal, and over perceivers of BC and DH based on perception scores at standardized changes (20%, 30%, and 40%) in FEV1 (% predicted) and IC (% predicted). We compared the rates of severe asthma exacerbations (defined as one of emergency department [ED] visit or hospitalization) between groups, using Ontario's administrative health databases. Poor perceivers had higher rates of ED visits and hospitalizations as compared with normal perceivers at 4 of 6 threshold decreases in FEV1 and IC studied. Poor perceivers of severe DH had a 6-fold increase in asthma exacerbations (odds ratio, 5.7; 95% confidence interval, 1.31-25.03). Health services utilization is increased in individuals with asthma who have poor perception of BC andDH. Poor perceivers of severe DH appear to be at the highest risk of exacerbations.

Athletes Do Not Condition Inspired Air More Effectively than Nonathletes during Hyperpnea.

Twenty-three endurance athletes from various sports, 12 with airway hyperresponsiveness (AHR) and/or exercise-induced bronchoconstriction (EIB) (A+), 11 without AHR and/or EIB (A-), 12 nonathletes with AHR and/or EIB (C+), and 11 nonathletes without AHR and/or EIB (C-) were recruited. All subjects attended the laboratory on three occasions, twice for baseline characterization, including questionnaires, pulmonary function, methacholine bronchoprovocation, allergy skin prick tests, exhaled nitric oxide measurement, and a standard EVH, and once to perform a modified EVH to assess ΔT. Inspired and expired air temperatures were measured with a high-precision probe during EVH and at regular intervals until 30 min after the end of the test. The global ΔT during the EVH was +5.8°C ± 1.5°C and +4.7°C ± 1.5°C during the 30 min after the EVH. No difference was found between groups for either the ΔT or the slope of ΔT, during and after the EVH. This study shows no evidence of improved capacity to condition inspired air in endurance athletes, which could have suggested an increased bronchial blood flow or another adaptive mechanism. The absence of an adaptive mechanism could therefore contribute to airway damage observed in athletes in allowing colder but mainly dryer air to penetrate deeper in the lung.

Variability of methacholine bronchoprovocation and the effect of inhaled corticosteroids in mild asthma

BackgroundThe methacholine challenge test quantifies airway hyper-responsiveness, which is measured by the provocative concentration of methacholine causing a 20% decrease in forced expiration volume in 1 second (PC20). The dose–response effect of inhaled corticosteroids (ICS) on PC20 has been inconsistent and within-patient variability of PC20 is not well established. ObjectiveTo determine the effect of high- vs low-dose ICS on PC20 and within-patient variability in those with repeated measurements of PC20. MethodsA randomized, double-masked, crossover trial was conducted in patients with asthma on controller medications with PC20 of 8 mg/mL or lower (n = 64) to evaluate the effect of high-dose (1,000 μg/d) vs low-dose (250 μg/d) fluticasone for 4 weeks on PC20. In addition, the variability of PC20 was assessed in participants who underwent 2 or 3 PC20 measurements on the same dose of ICS (n = 27) over a 4-week interval. ResultsBecause there was a significant period effect, dose comparison of the change in PC20 was assessed in the first treatment period. There was no significant difference in the change in PC20 for high- vs low-dose ICS (39% vs 30% increase, respectively; P = .87). The within- and between-participant variances for log PC20 were 0.84 and 0.96, respectively, with an intra-class correlation of 0.53, and 37% of participants had more than 2 doubling dose changes in PC20 in those with repeated measurements. ConclusionThe effect of ICS on PC20 is not dose dependent at fluticasone levels of 250 and 1,000 μg/d. Interpersonal variability for PC20 is large. A lack of precise measurements should be taken into account when interpreting any change in PC20.

Perception of Bronchoconstriction: A Complementary Disease Marker in Children with Asthma

Introduction. Asthma guidelines use symptoms as the most important aspect of asthma control. Symptom perception varies widely between individuals. Over-perception as well as underperception of bronchoconstriction could have a negative effect on asthma management. We hypothesized that perception of bronchoconstriction in childhood asthma is not related to common measures of disease control. For that reason, we examined the clinical determinants of the perception of bronchoconstriction and the repeatability of perception measurements. Patients and methods. In school-age children with moderately severe atopic asthma, we measured the perception of bronchoconstriction (decrease in forced expiratory volume in 1 second (FEV1)) during methacholine bronchoprovocation challenges. The perception of bronchoconstriction was assessed as the slope of the relation between FEV1 and Borg score, and as the Borg score at a 20% decrease in FEV1 from baseline during the provocation test (PS20). Data from subjects who had a 20% or more decrease in FEV1 (n = 112) were used for the analysis. Fifty-four children repeated the test after 3 months. Symptoms, use of rescue medication, and peak expiratory flows were scored in diaries during the 2 weeks before testing. Results. Symptom perception was significantly better in children without (PD20 > 1570 μg, n = 28) than in children with airway hyperresponsiveness (PD20 ≤ 1570 μg, n = 112), slope 0.22 versus 0.13 respectively (p < .001). Borg scores correlated with PD20 (p = .01), baseline FEV1 (only for slope, p = .04), and use of rescue beta agonist (p = .01), but not with other aspects of asthma control. Repeatability of Borg scores was good (slope: R = 0.59, PS20: R = 0.52). Conclusion. Poorer symptom perception in asthmatic children correlated with hyperresponsiveness, and was associated with lower baseline FEV1 and less use of rescue bronchodilators. This suggests that the measurement of symptom perception should be taken into account in individual management plans for children with asthma.CATO Study Group Members: Department of Pediatric Respiratory Medicine, Haga Hospital/Juliana Children’s Hospital, The Hague (M. Nuijsink, M.D., J. M. Kouwenberg, M.D.). Department of Epidemiology and Biostatistics, Erasmus University Medical Center, Rotterdam (W. C. J. Hop, Ph.D.). Department of Respiratory Medicine, Academic Medical Centre, University, Amsterdam (Prof. P. J. Sterk, Ph.D.). Leiden University Medical Center, Leiden (E. R. V. M. Rikkers-Mutsaerts, M.D.). Department of Pediatric Respiratory Diseases, University Medical Center Groningen (Prof. E. J. Duiverman, M.D., Ph.D.). Department of Pediatric Respiratory Medicine, Erasmus University Medical Center/Sophia Children’s Hospital, Rotterdam (Prof. J. C. de Jongste, M.D., Ph.D.). Asthma Center Heideheuvel, Hilversum (O. H. van der Baan-Slootweg, M.D., E. E. M. van Essen-Zandvliet, M.D., Ph.D.). Flevo Hospital, Almere (N. J. van den Berg, M.D., Ph.D.). Prof. Dr. J. M. Boogaard, Ph.D. Isala Klinieken, Zwolle (P. L. P. Brand, M.D. Ph.D., Ph.D., A. W. A. Kamps, M.D., Ph.D.). Medical Center, Alkmaar (G. Brinkhorst, M.D.). VU Medical Center, Amsterdam (J. E. Dankert-Roelse, M.D. Ph.D., A. F. Nagelkerke M.D.). Maxima Medical Center, Veldhoven (R. van Gent, M.D., Ph.D.). Maasland Hospital, Sittard (J. W. C. M. Heijnens, M.D.). University Hospital Maastricht (J. J. E. Hendriks, M.D., Ph.D., Q. Jöbsis, M.D., Ph.D.). University Medical Center/Wilhelmina Children’s Hospital, Utrecht (J. van der Laag, M.D., H. J. L. Brackel, M.D., Ph.D.). Academic Medical Center, Amsterdam (J. C. van Nierop, M.D.). Amphia Hospital, Breda (A. A. P. H. Vaessen-Verberne, M.D., Ph.D.) all from The Netherlands.

The Arg16Gly Polymorphism in the B2-Adrenergic Receptor Gene is Associated with Bronchial Hyperresponsiveness and Allergic Rhinitis in the Bulgarian Population

ABSTRACTBronchial Hyperresponsiveness (BHR) is a risk factor for asthma but it can be observed in allergic rhinitis (AR) and healthy subjects, too. The mechanisms of genetic susceptibility to BHR are unknown. In general, it is thought to result from both genetic and environmental factors. Some studies have demonstrated that nonspecific airway hyperresponsiveness is associated with a specific β2-adrenergic receptor (β2-AR) genotype in asymptomatic healthy subjects. The present study was performed to determine the impact of single nucleotide polymorphism (SNP) on allergic rhinitis patients with evidence for bronchial hyperresponsiveness. One hundred allergic rhinitis patients analyzed for BHR and forty healthy controls were genotyped for polymorphism of the β2-AR gene. Nonspecific airway hyperesponsiveness was measured using the methacholine bronchoprovocation (BPT) test. Polymerase chain reaction (PCR) was used to identify (Arg16/Gly) polymorphism at codon 16 in the β2-AR gene. It was observed that allergic rhinitis patients who are homozygous for the Gly16 allele are more responsive to methacholine than patients who carry the Arg16 allele.

Relationships between Fraction of Nitric Oxide, Airway Hyperresponsiveness, Blood Eoshinophil Counts and Serum Eosinophil Cationic Protein in Asthmatic Children

Purpose:The measurement of fraction of nitric oxide (FeNO) is a noticeable tool that reflects airway inflammation in asthmatic patients. We wanted to find out the relationship between pulmonary function, bronchial hyperresponsiveness (AHR), blood eosinophilic inflammatory markers and FeNO level before and after methacholine bronchoprovocation test in asthmatic patients. Methods:Fifty-five children, who visited the Allergy Clinic of Korea University Anam Hospital from March 2011 to February 2012, due to asthmatic symptoms, such as history of episodic wheezing or dyspnea during the previous year and resolved after using bronchodilators, were enrolled. We performed the baseline pulmonary function and methacholine bronchoprovocation test in the enrolled patients. Blood eosinophil counts and blood eosinophil cationic protein (ECP) were measured. FeNO levels were measured before and after the methacholine bronchoprovocation test. Results:The mean FeNO levels (36.3 ppb) fell after methacholine bronchoprovocation test (25.7 ppb). Forced expiratory volume in one second (FEV1) %pred inversely correlated both with FeNO level before (R 2 =0.07, P=0.029) and after (R 2 =0.059, P=0.01) methacholine bronchoprovocation test. The provocative concentration, causing a 20% decrease in FEV1 to methacholine (methacholine PC20) inversely correlated both with FeNO levels before (R 2 =0.086, P=0.001) and after (R 2 =0.141, P=0.001) the challenge. FeNO level measured at bronchoconstriction state significantly correlated with blood eosinophil counts (R 2 =0.112, P=0.028). Serum ECP levels correlated FeNO level, neither before nor after bronchoprovocation. Conclusion:The baseline FeNO levels were higher in asthmatic children. However, FeNO levels rather decreased after methacholine induced bronchoconstriction. Repeated spirometry maneuver was considered to have an effect on reducing FeNO levels. FeNO correlated with pulmonary function, airway AHR and blood eosinophil counts. (Pediatr Allergy Respir Dis(Korea) 2012;22:282-291)

Asthma diagnosis and treatment: Filling in the information gaps

Current approaches to the diagnosis and management of asthma are based on guideline recommendations, which have provided a framework for the efforts. Asthma, however, is emerging as a heterogeneous disease, and these features need to be considered in both the diagnosis and management of this disease in individual patients. These diverse or phenotypic features add complexity to the diagnosis of asthma, as well as attempts to achieve control with treatment. Although the diagnosis of asthma is often based on clinical information, it is important to pursue objective criteria as well, including an evaluation for reversibility of airflow obstruction and bronchial hyperresponsiveness, an area with new diagnostic approaches. Furthermore, there exist a number of treatment gaps (ie, exacerbations, step-down care, use of antibiotics, and severe disease) in which new direction is needed to improve care. Amajor morbidity in asthmatic patients occurs with exacerbations and in patients with severe disease. Novel approaches to treatment for these conditions will be an important advance to reduce the morbidity associated with asthma.

Rising prevalence of asthma is sex-specific in a US farming population

Asthma prevalence is increasing worldwide in most populations, likely due to a combination of heritable factors and environmental changes. Curiously, however, some European farming populations are protected from asthma, which has been attributed to their traditional lifestyles and farming practices. We conducted population-based studies of asthma and atopy in the Hutterites of South Dakota, a communal farming population, to assess temporal trends in asthma and atopy prevalence and describe the risk factors for asthma. We studied 1325 Hutterites (ages 6-91 years) at 2 time points from 1996 to 1997 and from 2006 to 2009 by using asthma questionnaires, pulmonary function and methacholine bronchoprovocation tests, and measures of atopy. The overall prevalence of asthma increased over the 10- to 13-year study period (7.5%-11.1%, P= .049), whereas the overall prevalence of atopy did not change (45.0%-44.8%, P= .95). Surprisingly, the rise in asthma was only among females (5.8%-11.2%, P= .02); the prevalence among males remained largely unchanged (9.4%-10.9%, P= .57). Atopy, which was not associated with asthma risk in 1996 to 1997, was the strongest risk factor for asthma among Hutterites studied in 2006 to 2009 (P=.003). Asthma has increased over a 10- to 13-year period among Hutterite females and atopy has become a significant risk factor for asthma, suggesting a change in environmental exposures that are either sex limited or that elicit a sex-specific response.

Negative methacholine challenge tests in subjects who report physician-diagnosed asthma

The frequency of adults reporting a history of asthma is rising. However, it is unclear whether this increased prevalence accurately demonstrates a rising trend or if it reflects an overall increase in asthma awareness. To determine the frequency of negative methacholine bronchoprovocation tests in adults who report physician-diagnosed asthma and to explore the clinical characteristics of subjects with negative tests. Data from methacholine challenge, spirometry, and physician assessment were analysed from 304 adults who reported physician-diagnosed asthma and responded to community-based advertising for asthma research studies. The clinical characteristics of methacholine-positive and -negative subjects were compared and a predictive model was tested to identify those characteristics associated with a negative test. Of the 304 subjects tested, 83 (27%) had a negative methacholine test. A negative test was positively associated with an adult-onset of symptoms (P<0.001), normal forced expiratory volume in 1 s (P<0.001), and having no history of exacerbation requiring oral steroids (P=0.03). Over half (60%) of those with a negative test reported weekly asthma-like symptoms (cough, dyspnoea, chest tightness, or wheeze), while 39% reported emergency department visits for asthma-like symptoms. A sizeable percentage of subjects who report physician-diagnosed asthma have a negative methacholine challenge test. These subjects are characterized by diagnosis of asthma as an adult and by normal or near normal spirometry. Caution should be exercised in the assessment and diagnosis of adults presenting with asthma-like symptoms, because they may not have asthma. Further diagnostic studies, including bronchoprovocation testing, are warranted in this patient group, especially if their spirometry is normal.

Bronchial Hyper‐Reactivity in Migraine Without Aura: Is It a New Clue for Inflammation?

We attempted to investigate the relationship between migraine without aura (MwoA) and bronchial hyper-reactivity to postulate inflammation as an underlying mechanism in migraine. Comorbidity of migraine and atopic diseases such as asthma has been an argument for suspected immune system dysfunction in migraineurs. Twenty patients with MwoA and 5 control subjects without history of atophy and asthma were included in study. Subjects with abnormal physical examination and chest radiographs were excluded. After a normal spirometry, methacholine bronchoprovocation test was performed in all subjects and controls according to 5 breath dosimeter methods. Sixteen of 20 patients and 2 of 5 control subjects were women. Mean ages were 37.5 (19-56) and 33.8 (26-43) years, respectively. Methacholine bronchoprovocation test was positive in 3 patients (15%) but was normal in all controls (0%). The relationship between MwoA and bronchial hyper-reactivity may help to postulate the inflammation in migraine as an underlying mechanism.

Nasal Polyps: An Independent Risk Factor for Bronchial Hyperresponsiveness in Patients with Allergic Rhinitis

Many studies were conducted to figure out the relationship between allergic rhinitis (AR) and lower airway diseases. This study was designed to elucidate the clinical parameters that could predict the coexistence of bronchial hyperresponsiveness (BHR) in AR and suggest a guideline for lower airway evaluation in these patients. One hundred seventy-three patients newly diagnosed with AR were evaluated for the lower airway with the methacholine bronchoprovocation test. BHR was more prevalent in patients with nasal polyps (p = 0.01), in patients complaining of moderate to severe symptoms (p = 0.023), with higher serum total IgE levels (p = 0.001), and with blood eosinophil count (p = 0.008). No statistically significant difference was observed between intermittent and persistent AR patients (p = 0.364). Blood eosinophil count that could predict BHR was calculated as 320 cells/μL (p = 0.004). Instead of a routine lower airway evaluation for all AR patients, we recommend lower airway evaluation for the selected patients with nasal polyps, moderate to severe symptoms, and high blood eosinophil count.

Effects of extra‐fine inhaled beclomethasone/formoterol on both large and small airways in asthma

Airway inflammation in asthma involves both large and small airways, and the combination of inhaled corticosteroids (ICS) and long acting beta-2 agonists (LABA) is the mainstay of therapy. Available inhaled combinations differ in terms of drug delivery to the lung and the ability to reach small airways. To evaluate whether treatment with an extra-fine inhaled combination provides additional effects vs a nonextra-fine combination on airway function. After a 1- to 4-week run-in period, patients with asthma were randomized to a double blind, double dummy, 12-week treatment with either extra-fine beclomethasone/formoterol (BDP/F) 400/24 microg daily or fluticasone propionate/salmeterol (FP/S) 500/100 microg daily. Methacholine (Mch) bronchoprovocation challenge and single breath nitrogen (sbN2) test were performed. Thirty patients with asthma (15 men), mean age 43, mean forced expiratory volume in the first second (FEV(1)) 71.4% of predicted, were included. A significant increase (P < 0.01) versus baseline was observed in predose FEV(1) in both BDP/F and FP/S groups (0.37 +/- 0.13 l and 0.36 +/- 0.12 l, respectively). PD(20)FEV(1) Mch improved significantly from 90.42 (+/-30.08) microg to 432.41 (+/-122.71) microg in the BDP/F group (P = 0.01) but not in the FP/S group. A trend toward improvement vs baseline was observed for BDP/F in closing capacity (CC), whereas no differences were recorded in other sbN(2) test parameters. The findings of this pilot study suggest that an extra-fine inhaled combination for the treatment of asthma has beneficial effects on both large and small airways function as expressed by Mch and sbN(2) tests.

Preventive effects of mycobacteria and their culture supernatants against asthma development in BALB/c mice

PurposeLive Mycobacterium bovis Bacille Calmette-Guérin (BCG) has a suppressive effect on asthma, but its use in clinical practice may be limited due to adverse reactions. To develop a product that is effective for suppressing asthma with minimal adverse reactions, we investigated whether the heat-killed body or culture supernatants of mycobacteria could also prevent asthma development.MethodsFemale BALB/c mice were treated with live BCG, the heat-killed body, or culture supernatants of BCG or Mycobacterium tuberculosis intraperitoneally, while sensitizing and provoking with ovalbumin. Then they underwent a methacholine bronchoprovocation test, and the peribronchial inflammatory cell numbers and cytokine levels in splenocyte culture supernatants were assessed.ResultsThe airway sensitivity to methacholine decreased significantly after treatment with not only live BCG (30.8 versus 10.0 mg/mL, P<0.001) but also with the culture supernatant (BCG, 23.0 mg/mL, P<0.05; M. tuberculosis, 20.5 mg/mL, P<0.05). In contrast, heat-killed mycobacteria did not effectively decrease airway sensitivity. The peribronchial eosinophil counts and the goblet cell proportions in total epithelial cells decreased significantly in most of the groups. The interferon-γ/interleukin-5 ratios increased significantly in most of the treatment groups except for the heat-killed groups, and were significantly related to airway sensitivity (r=0.312, P<0.01) and peribronchial eosinophil counts (r=-0.416, P<0.001). Interleukin-17A level was inversely related to airway sensitivity (r=-0.212, P<0.05) and was significantly lower in the live BCG group than in the control (137±20 versus 308±57 pg/mL, P<0.05).ConclusionsBCG and mycobacteria culture supernatants may effectively prevent the development of asthma associated with altered Th1/Th2 cytokines and interleukin-17A levels.

Effects of Obesity on Perceptual and Mechanical Responses to Bronchoconstriction in Asthma

The influence of obesity on the perception of respiratory discomfort during acute bronchoconstriction in asthma is unknown. We hypothesized that the respiratory impairment associated with an increased body mass index (BMI) would predispose to greater perceived symptom intensity during acute airway narrowing. We therefore compared relationships between induced changes in dyspnea intensity and lung function during methacholine (MCh) bronchoprovocation in obese (OBA) and normal-weight (NWA) individuals with asthma of mild to moderate severity. High-dose MCh challenge tests to a maximum 50% decrease in FEV(1) were conducted in 51 NWA (BMI, 18.5-24.9 kg/m(2); 29% male) and 45 OBA (BMI, 30.1-51.4 kg/m(2); 33% male) between 20 and 60 years of age. Serial spirometry, inspiratory capacity (IC), plethysmographic end-expiratory lung volume (EELV) and dyspnea intensity using the Borg scale were measured throughout bronchoprovocation. Spirometry and airway sensitivity were similar in both groups; baseline EELV was lower (P < 0.0005) and IC was higher (P = 0.007) in OBA compared with NWA. From baseline to PC(20), EELV increased more in OBA (20% predicted) than NWA (13% predicted) (P = 0.008) with concomitant greater reductions in IC (P < 0.0005). Dyspnea ratings were not different for a given FEV(1) or IC across groups. By mixed effects regression analysis, relationships between induced dyspnea and changes in lung function parameters were not influenced by BMI, sex, or their interaction. Perceptual responses to MCh-induced bronchoconstriction and lung hyperinflation were similar in obese and normal-weight individuals with asthma despite significant group differences in baseline lung volumes.

Subclassification of Leukotriene‐Based Asthmatics

Previously we identified the idea of four subtypes of asthmatics, three of which were cytokine‐based asthmatics and another larger leukotriene‐based family. Previous studies identified that the leukotriene specific subtype is n‐3 PUFA responsive. It was our intent to determine if a leukotriene‐specific family of asthmatics could be further subclassified into families of asthmatics or not.Twenty‐two asthmatics went through a methacholine bronchoprovocation challenge on two occasions separated by one month. Saliva for one half hour, a blood sample four hours post‐bronchoprovocation, and 24 urine samples were collected. Saliva and urine were analyzed by reverse‐phase high‐pressure liquid chromatography (RP‐HPLC) coupled with a diode array‐UV detector at 280 nm and a flow rate of 1.0 mL/min for analysis of cysteinyl leukotrienes on a Schimadzu HPLC.Ten individuals were identified as being non‐LT based asthmatics while twelve were identified as being LT‐based asthmatics. Based on saliva LT production, three individuals were identified as being overlapping LT asthmatics: a C4/D4, a B4/C4/D4, and a B4/C4 based asthmatic. However, the remaining asthmatics separated almost evenly into each subfamily of LTB4, LTC4, LTD4 and LTE4 based asthmatics. While this is a small study, these data indicate differing types of LT based asthmatics at the mechanistic level.

Predictors of bronchial hyperresponsiveness in chronic rhinosinusitis with nasal polyp

Chronic rhinosinusitis with nasal polyposis (CRSNP) and asthma are inflammatory lesions of the respiratory epithelium. This study was conducted to evaluate predictive factors of bronchial hyperresponsiveness (BHR) in patients with CRSNP. BHR was evaluated using a methacholine bronchoprovocation test (MBPT) in 122 consecutive patients newly diagnosed with CRSNP at Seoul National University Hospital from January 2004 to June 2006. The following parameters were analyzed and compared between the BHR and non-BHR groups: symptoms, atopic status, current smoking, disease severity of CRSNP based on the Lund-Mackay scoring system of sinus CT, and counts of eosinophils in the serum and nasal tissues. Thirty-five percent of the patients were found to have BHR, and BHR was found to occur more frequently in patients that were currently suffering from sneezing (P = 0.007). In addition, the mean eosinophil counts of the serum and nasal tissues were higher in the BHR group than in the non-BHR group (P = 0.001 for the serum, P = 0.045 for the nasal tissues), and the eosinophil counts of the serum correlated to those of the nasal tissues (r = 0.334, P = 0.013). The disease severity, as determined by the Lund-Mackay scoring system, was not different between the two groups (P > 0.05). The best cutoff serum eosinophil count for predicting BHR in CRSNP patients was determined to be 300 cells/microl (sensitivity 70%, specificity 70%). Taken together, these results indicate that moderate to severe sneezing and a serum eosinophil count > or = 300 cells/microl may be predictive factors for BHR in patients with CRSNP.