Adenosine Monophosphate Challenge Research Articles

Diagnostic value of bronchoprovocation challenge with adenosine monophosphate versus exercise testing in early diagnosis of asthma

BackgroundAirway hyperresponsiveness (AHR) is a characteristic feature of bronchial asthma and is diagnosed using direct and indirect bronchoprovocation tests. The diagnosis of AHR is a challenge in symptomatic patients with a normal baseline prebronchodilator spirometry and postbronchodilator spirometry. Exercise-induced asthma or exercise-induced bronchoconstriction (EIB) is a distinct form of AHR. There is no single test that is sufficient to exclude AHR in symptomatic military personnel with normal spirometry. This study was conducted to compare the diagnostic value of indirect bronchoprovocation test using inhaled adenosine monophosphate (AMP) and exercise challenge test (ECT) in the diagnosis of EIB. MethodsA crossover study was conducted with consecutive sampling of patients presenting with symptoms suggestive of asthma and with normal spirometry results who were subjected to both ECT and bronchoprovocation test using inhaled AMP on separate days. ResultsForty participants were recruited (the mean age: 25 yrs, 100% male). The commonest presentation was breathlessness on exercise (55%). With exercise alone, 40% tested positive for AHR, while with AMP alone, the positivity increased to 53%, and the difference was statistically significant (p= 0.03). Exercise alone failed to detect 8 cases that tested positive for AHR by inhaled AMP challenge. ConclusionIndirect bronchoprovocation test using inhaled AMP may be used to diagnose AHR in conditions in which exercise challenge testing is not available or the patient is unable to complete ECT.

Factors Associated with Positive Adenosine Challenge Test in Young Children with Suspected Asthma.

Background: To investigate the predictive factors associated with positive adenosine monophosphate challenge using the auscultation method (AMP-PCW) test results. Methods: This is a prospective study of young children with suspected asthma who underwent AMP-PCW test. Patients with a positive AMP-PCW test were compared with those with a negative AMP-PCW. A multivariate logistic regression model was performed to identify the independent determinants of positive AMP-PCW. Results: A total of 159 patients completed the AMP-PCW test. The median age was 53 months. In total, 54.0% of patients had a positive AMP-PCW. The prevalence of atopic dermatitis and family history of asthma and allergy were significantly higher among the positive AMP-PCW group (P = 0.04, P = 0.02, and P = 0.007, respectively), as were the prevalences of elevated immunoglobulin E (IgE), peripheral blood eosinophils percentage (P = 0.003, P < 0.001, respectively), and number of emergency department (ED) visits/hospitalizations before AMP-PCW test (P = 0.006). A significant inverse correlation exists between peripheral blood eosinophils percentage and serum IgE levels with the AMP end-point concentrations (r = -0.302, P = 0.001, and r = -0.312, P = 0.001, respectively). In multivariate logistic regression model, peripheral blood eosinophils percentage, IgE levels, and the number of ED visits/hospitalizations before the AMP-PCW test were found as independent predictors for positive AMP-PCW test result. Conclusions: Our results suggest that bronchial responsiveness to AMP-PCW is related to proxy markers of airway inflammation (elevated eosinophils and IgE levels) and clinical exacerbation of asthma before the test. This may support the role of AMP-PCW in detecting inflammatory changes and monitoring their trend among young children with suspected asthma.

The correlation of adenosine challenge test results with subsequent clinical course among young children with suspected asthma: a retrospective cohort study

Our aim was to evaluate the correlation of Adenosine monophosphate challenge test (AMP-PCW) results with the patients' subsequent clinical course. We performed a 6-year retrospective cohort study of young children with suspected asthma who underwent AMP-PCW test. Fifty four children were included in the study (median age, 50.5 months; range, 26-90). AMP-PCW was positive in 35 (65%) children. During the 3-year follow-up period, among 22 of 35 patients in the positive AMP-PCW group and among 17 of 19 in the negative AMP-PCW group-prophylactic therapy was not changed. Prophylactic therapy was initiated or its dose was escalated in 12 of 13 (92.3%) of the children with a positive AMP-PCW test compared to none of the children with a negative challenge test (P < 0.001). Prophylactic therapy was discontinued in only one (7.6%) of the children with a positive test as compared to two (100%) of the children with a negative test (P < 0.001). There were significantly fewer severe asthma exacerbations during a 3-year follow-up period after the challenge test as compared to the preceding 3-year period both in children with a positive (from 34 to 9 total events, P = 0.01) or a negative challenge test (from 16 to 0 events P = 0.01). The severity of airway hyper responsiveness was found to associate with the number of severe asthma exacerbations (P = 0.04) and with a diagnosis of asthma during the following 3 years (P = 0.02). AMP-PCW test results correlates with the subsequent clinical course of young children with suspected asthma performing the test.

Effects of low- versus high-dose fluticasone propionate/formoterol fumarate combination therapy on AMP challenge in asthmatic patients: A double-blind, randomised clinical trial

BackgroundThe dose-response relationship between two dose levels of fluticasone/formoterol (flutiform®, 100/10 μg and 500/20 μg) was evaluated in asthmatic patients. Non-invasive inflammatory markers were used including adenosine monophosphate (AMP) challenge (primary endpoint), and sputum eosinophils and fractional exhaled nitric oxide (FeNO) (secondary endpoints). MethodsPatients aged ≥18 years with forced expiratory volume in 1 s (FEV1) ≥60% predicted and who required a dose of <60 mg AMP to elicit a 20% drop in FEV1 (AMP PD20) were randomised in this incomplete block, crossover study to receive 2 of 3 treatments b.i.d.: fluticasone/formoterol 500/20 μg (high dose), 100/10 μg (low dose) or placebo, during 2 periods of 28 ± 3 days each, separated by 2–3 weeks. AMP challenges were performed pre-dose and 12 h after last dose at the end of each treatment period. A series of post hoc analyses were performed only in patients allocated to both fluticasone/formoterol doses, who completed the study and had evaluable AMP PD20 data for both treatments (“fluticasone/formoterol subgroup”). Changes in AMP PD20 FEV1, percentage sputum eosinophils and FeNO levels (Day 1 vs Day 28) between treatments were compared by an analysis of covariance (ANCOVA). ResultsSixty-two patients were randomised and 46 completed the study. Fifteen patients received both high- and low-dose fluticasone/formoterol (post hoc subgroup). The difference in AMP PD20 for the overall population was not statistically significant between high- and low-dose fluticasone/formoterol (LS mean fold difference: 1.3; p = 0.489), although both dose levels were superior to placebo: high-dose vs placebo LS mean fold difference: 4.4, p < 0.001; low-dose vs placebo LS mean fold difference: 3.5, p < 0.001. In the post hoc subgroup, the difference in AMP PD20 between the doses was statistically significant in favour of the high-dose (LS mean fold difference: 2.4, p = 0.012). Other inflammatory parameters (sputum eosinophil counts and FeNO) showed small differences and statistically non-significant changes between high- and low-dose fluticasone/formoterol. ConclusionsA significant dose-response was found between low- and high-dose fluticasone/formoterol in the post hoc subgroup (patients who received both doses), but not in the overall population, with the higher dose demonstrating a greater reduction in airway responsiveness to AMP.

Comparison between exhaled nitric oxide and bronchial challenge with methacholine or adenosine-5'-monophosphate in the diagnosis of childhood asthma

Purpose: Asthma is a chronic airway inflammatory disease characterized by bronchial hyperresponsiveness and reversible airway obstruction. Bronchial challenge with methacholine or adenosine-5`-monophosphate (AMP) has been used to diagnose asthma. Recently, measurement of exhaled nitric oxide (eNO) can also be used for the diagnosis of asthma. The aim of this study was to compare the diagnostic value for asthma between challenge with methacholine or AMP and eNO in children with chronic nonspecific respiratory symptoms. Methods: One hundred thirty-three children who have chronic nonspecific respiratory symptoms were enrolled. Bronchial challenge with methacholin and AMP were performed, and eNO was measured in all subjects. Subjects were defined as asthma based on the clinical symptoms and bronchodilator response during follow-up of at least 3 months after test. Results: Thirty-three subjects (34%) were finally diagnosed as asthma among 97 patients after 3-month follow-up. The area under the receiver operating characteristic curves for the diagnosis of asthma were 0.903 (95% confidence interval [CI], 0.838-0.969; P<0.001) for methacholline challenge, 0.867 (95% CI, 0.783-0.950; P<0.001) for AMP challenge, and 0.588 (95% CI, 0.467-0.709, P=0.156) for eNO measurement. The cutoff values of these tests were methacholine PC20 (provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second) 12.0 mg/mL (sensitivity, 87.9%; specificity, 82.8%), AMP PC20 566.2 mg/mL (sensitivity, 84.8%; specificity, 85.9%), and eNO 18.5 ppb (sensitivity, 45.5%; specificity, 71.9%). Conclusion: Measurement of eNO may be inferior to challenge with methacholine and AMP for the diagnosis of asthma in children. (Allergy Asthma Respir Dis 2016;4:100-106)

Axial distribution of nitric oxide airway production in asthma patients

In healthy subjects, axial distribution of nitric oxide (NO) airway production is likely heterogeneous: notably a distal peak of production in terminal bronchioles and a quasi-nil NO production in the most of the conducting airways. In asthma, few information exists about the contributions of the proximal and distal airways to NO overproduction. In 18 asthma patients, sites of constriction after methacholine and adenosine 5′-monophosphate (AMP) challenges were assessed by ventilation distribution tests with He and SF6. The resulting decreases in fractional exhaled NO (FENO) were measured. Changes in He and SF6 slopes indicated a pre-acinar bronchoconstriction due to AMP and a more proximal action for methacholine. FENO decreased by 38.7% and 20.2% (p<0.001) after AMP and methacholine challenges, respectively. Significant FENO decreases after AMP and methacholine implies substantial pre-acinar but also, contrary to healthy subjects, more proximal airway production. In conclusion, nitric oxide overproduction in asthma patients appears to involve the most part of the conducting airways.

Bronchodilator Responses after Methacholine and Adenosine 5′-Monophosphate (AMP) Challenges in Children with Asthma: Their Relationships with Eosinophil Markers

Background. Bronchodilator responsiveness (BDR) and eosinophilic inflammation are characteristic features of asthma. Objective. The aim of this study was to compare the relationships of BDR after methacholine challenge or adenosine 5′-monophosphate (AMP) challenge to blood eosinophil markers in children with asthma. Methods. Methacholine and AMP challenges were performed on 69 children with mild intermittent to moderate persistent asthma. BDR was calculated as the change in forced expiratory volume in 1 second, expressed as percentage change of the value immediately after the each challenge and the value after inhalation of salbutamol. Serum total IgE levels, blood eosinophil counts, and serum eosinophil cationic protein (ECP) levels were determined for each subject. Results. A positive relationship between serum total IgE levels and BDR was found only after the AMP challenge (R2 = 0.345, p = .001) rather than after the methacholine challenge (R2 = 0.007, p = .495). Peripheral blood eosinophil counts correlated more significantly with BDR after AMP challenge (R2 = 0.212, p = .001) than BDR after methacholine challenge (R2 = 0.002, p = .724). Both BDR after methacholine challenge (R2 = 0.063, p = .038) and BDR after AMP challenge (R2 = 0.192, p = .001) were significantly correlated with serum ECP levels. Conclusion. BDR after AMP challenge may be more closely related to eosinophilic inflammation, compared with that after methacholine challenge.

Predictive Value of Adenosine 5′-Monophosphate Challenge in Preschool Children for the Diagnosis of Asthma 5 Years Later

We evaluated the predictive values of preschool bronchial challenge with nebulized adenosine 5'-monophosphate (AMP) using the auscultation method for having asthma 5 years later. Preschool AMP challenge had a high negative (90%) and a moderate positive (67%) predictive value for asthma 5 years later. Positive predictive value increased with the age at which the challenge was performed. The degree of preschool response to AMP was associated with the severity of asthma at school age.

Association Between The STIP1 Polymorphism And The Response To Inhaled Steroid In Children With Asthma

Bronchial hyperresponsiveness is usually measured by bronchial challenges using direct stimuli by methacholine or indirect stimuli by adenosine 5’-monophosphate (AMP). Airway inflammation is more closely reflected by AMP challenge test. The stress-induced-phosphoprotein 1 (STIP1) is one of the genes in steroid pathway. And polymorphisms in STIP1 are correlated with lung function after corticosteroid treatment in white subjects. We investigated whether polymorphism (rs4980524) of the STIP1 was associated with clinical phenotypes and responsiveness to inhaled steroid in Korean asthmatic children.

Bronchial Hyperresponsiveness to Methacholine and AMP in Children With Atopic Asthma

PurposeBronchial hyperresponsiveness (BHR) is typically measured by bronchial challenge tests that employ direct stimulation by methacholine or indirect stimulation by adenosine 5'-monophosphate (AMP). Some studies have shown that the AMP challenge test provides a better reflection of airway inflammation, but few studies have examined the relationship between the AMP and methacholine challenge tests in children with asthma. We investigated the relationship between AMP and methacholine testing in children and adolescents with atopic asthma.MethodsThe medical records of 130 children with atopic asthma (mean age, 10.63 years) were reviewed retrospectively. Methacholine and AMP test results, spirometry, skin prick test results, and blood tests for inflammatory markers (total IgE, eosinophils [total count, percent of white blood cells]) were analyzed.ResultsThe concentration of AMP that induces a 20% decline in forced expiratory volume in 1 second [FEV1] (PC20) of methacholine correlated with the PC20 of AMP (r2=0.189, P<0.001). No significant differences were observed in the levels of inflammatory markers (total eosinophil count, eosinophil percentage, and total IgE) between groups that were positive and negative for BHR to methacholine. However, significant differences in inflammatory markers were observed in groups that were positive and negative for BHR to AMP (log total eosinophil count, P=0.023; log total IgE, P=0.020, eosinophil percentage, P<0.001). In contrast, body mass index (BMI) was significantly different in the methacholine positive and negative groups (P=0.027), but not in the AMP positive and negative groups (P=0.62). The PC20 of methacholine correlated with FEV1, FEV1/forced vital capacity (FVC), and maximum mid-expiratory flow (MMEF) (P=0.001, 0.011, 0.001, respectively), and the PC20 of AMP correlated with FEV1, FEV1/FVC, and MMEF (P=0.008, 0.046, 0.001, respectively).ConclusionsOur results suggest that the AMP and methacholine challenge test results correlated well with respect to determining BHR. The BHR to AMP more likely implicated airway inflammation in children with atopic asthma. In contrast, the BHR to methacholine was related to BMI.

Rapid effects of extrafine beclomethasone dipropionate/formoterol fixed combination inhaler on airway inflammation and bronchoconstriction in asthma: a randomised controlled trial

BackgroundThe dose-dependent anti-inflammatory effects of a recent fixed combination of extrafine beclomethasone dipropionate/formoterol (BDP/F) were investigated using non-invasive markers of inflammation, exhaled nitric oxide (NO) and adenosine monophosphate (AMP) provocative challenge. The aim was to assess the onset of the anti-inflammatory action of low and high doses and evaluate the suitability of non-invasive assessments to demonstrate dose response.MethodsSteroid naïve adult out-patients with mild asthma, sensitive to AMP with baseline exhaled NO > 25 parts per billion entered a double-blind, placebo-controlled, 3-way, cross-over study. Patients were randomised to low dose (1 actuation) or high dose (4 actuations) extrafine BDP/F 100/6 μg, or placebo administered twice daily on Days 1 and 2 and once in the morning on Day 3 of each period. Exhaled NO was measured pre-dose on Day 1, then 2 and 4 hours post-administration on Day 3. The AMP challenge was performed 4 hours post-administration on Day 3 and forced expiratory volume in 1 second (FEV1, L) was measured from 0 to 4 hours post-dose on Day 1. Endpoints were NO at 2 and 4 hours, AMP challenge at 4 hours after the fifth dose on Day 3 and FEV1 area under the curve from 0 to 4 h post-dose on Day 1. Analysis of covariance was performed for NO and FEV1 and analysis of variance for AMP challenge.ResultsEighteen patients were randomised and completed the study. Exhaled NO was significantly lower for both doses of extrafine BDP/F versus placebo at 2 and 4 hours (high dose LS mean difference: -22.5 ppb, p < 0.0001 and -20.5 ppb, p < 0.0001; low dose: -14.1 ppb, p = 0.0006 and -12.1 ppb, p = 0.0043) with a significant dose response (p = 0.0342 and p = 0.0423). Likewise, AMP challenge revealed statistically significant differences between both doses of extrafine BDP/F and placebo (high dose LS mean difference: 4.8 mg/mL, p < 0.0001; low dose: 3.7 mg/mL, p < 0.0001), and a significant dose response (p = 0.0185). FEV1 was significantly improved versus placebo for both doses (high dose LS mean difference: 0.2 L, p = 0.0001; low dose: 0.2 L p = 0.0001), but without a significant dose response.ConclusionsThe fixed combination inhaler of extrafine BDP/F has early dose-dependent anti-inflammatory effects with a rapid onset of bronchodilatation in mild asthmatic patients.Trial RegistrationClinicalTrials.gov: NCT01343745

Is it really time to look at distal airways to improve asthma phenotyping and treatment?

In 2011, severe asthma and/or insufficient control of disease remain major challenges for the pulmonologist [1]. Small airway involvement has been demonstrated by a number of studies, particularly in fatal, severe or poorly controlled asthma, and may be a potential target to improve treatment and asthma outcomes [2–5]. Although inhaled corticosteroids (ICSs) remain the cornerstone of asthma treatment, there is a continuing debate on the potential benefit of small-particle formulations. In this context, the recent study by Cohen et al. [6] clearly adds new data to this controversial topic. It is the first to compare airway hyperresponsiveness (AHR) to small-particle adenosine monophosphate (AMP) with large and standard particles in a reasonable sample of mild-to-moderate asthmatics. In addition, the impact of small- (ciclesonide) versus large-particle (fluticasone) ICS formulations was compared at 4 weeks using the same original AMP challenges, exhaled NO and spirometry. Unfortunately, asthma control was not assessed. The results clearly indicate that small-particle ICSs may improve corresponding AHR, but other functional outcomes were surprisingly not correlated with this benefit. Such an approach targeting evaluation and treatment of small airways raises a series of questions. AHR is a complex phenomenon in asthma and the contribution of small airways to this hyperresponsiveness is poorly characterised, particularly regarding its variable inflammatory component. Distal airway inflammation has been demonstrated by a number of histopathological studies using lung resection specimens or transbronchial biopsies [2]. Taken together, these data suggest an important role for distal airway inflammation in severe asthma. Consistent with these histopathological findings, direct measurement of distal airway resistance showed that they accounted for up to 50–90% of total airflow resistance in asthma [7], implying that distal airways were the main site of airflow obstruction. Early experimental and theoretical models …

Effects of intranasal salmeterol and fluticasone given alone and in combination in persistent allergic rhinitis

Backgroundβ2-Agonists have previously been shown to be effective inhibitors of mediator release from airway mucosal mast cells. ObjectiveTo evaluate the effects of intranasal salmeterol and fluticasone propionate alone and in combination on the response to nasal adenosine monophosphate (AMP) challenge to assess mast cell activation. MethodsTwenty-three patients with persistent allergic rhinitis completed a randomized, double-blind, placebo-controlled, 4-way crossover trial. They received once daily treatment with placebo, salmeterol, 50 μg, fluticasone propionate, 500 μg, or fluticasone propionate and salmeterol combination, 500/50 μg, delivered via an antistatic spacer with nasal adapter for 1 week each, with trough measurements being made 12 hours after the first and last dose. The primary outcome was the maximum percentage decrease in peak nasal inspiratory flow after nasal AMP challenge. ResultsFor the primary outcome there was significant protection after single and long-term dosing with fluticasone alone and fluticasone-salmeterol combination, whereas salmeterol alone only afforded protection after the first dose. Fluticasone-salmeterol combination and fluticasone but not salmeterol conferred significant chronic dosing effects on secondary outcomes of nasal symptoms and disease-specific quality of life. There was no potentiation of the response to fluticasone by salmeterol on any outcomes when given in combination. ConclusionChronic dosing with fluticasone but not salmeterol confers anti-inflammatory activity against nasal AMP challenge, but there was no potentiation of fluticasone when given in combination with salmeterol. Thus, salmeterol may not be an effective treatment for use in allergic rhinitis. Trial Registrationclinicaltrials.gov Identifier: NCT01388595.

Relationships of Methacholine and Adenosine 5′-Monophosphate (AMP) Responsiveness to the Postbronchodilator FEV1/FVC Ratio in Children with Asthma

Background. Airway remodeling has been assumed to cause bronchial hyperresponsiveness (BHR). A low postbronchodilator FEV1/FVC ratio has been suggested to be a functional surrogate marker of airway remodeling in asthma. BHR is commonly assessed by bronchial challenges using direct or indirect stimuli. Objective. The aim of this study was to compare BHR to methacholine and adenosine 5′-monophosphate (AMP) with regard to their relationship with a marker of airway remodeling in children with asthma. Methods. Methacholine and AMP challenge tests were performed in 129 children with asthma, aged 12 years, and a provocative concentration causing a 20% fall in FEV1 (PC20) was calculated for each challenge. All subjects also underwent pre- and postbronchodilator spirometry. A postbronchodilator FEV1/FVC ratio below the lower limits of normal was used as a marker of airway remodeling. Results. A low postbronchodilator FEV1/FVC ratio was found in 17 subjects (13.2%). These subjects had a significantly lower methacholine PC20 (geometric mean: 0.63 mg/mL, range of 1 SD: 0.17–2.29) than those (n = 112) with a normal postbronchodilator FEV1/FVC ratio (2.42 mg/mL, 0.57–10.32, p = .000), whereas AMP PC20 was similar between the two groups (22.1 mg/mL, 3.9–125.9 vs. 27.7 mg/mL, 4.2–183.5, p = .231). In the whole group of subjects, methacholine PC20, but not AMP PC20, correlated significantly with the postbronchodilator FEV1/FVC ratio (r = 0.340, p = .000, and r = 0.056, p = .526, respectively). Conclusions. Our results provide evidence, though indirect, that BHR to methacholine is related to airway remodeling in children with asthma and suggest that BHR to methacholine may be a better marker of airway remodeling than BHR to AMP.

Adenosine 5′-monophosphate challenge elicits a more peripheral airway response than methacholine challenge

Adenosine 5'-monophosphate (AMP) and methacholine are commonly used to assess airway hyperreactivity. However, it is not fully known whether the site of airway constriction primarily involved during challenges with either agent is similar. Using a ventilation distribution test, we investigated whether the constriction induced by each agent involves the lung periphery in a similar fashion. Ventilation distribution was evaluated by the phase III slope (S) of the single-breath washout, using gases with different diffusivities like helium (He) and hexafluorosulfur (SF(6)). A greater postchallenge increase in S(He) reflects alterations at the level of terminal and respiratory bronchioles, while a greater increase in S(SF6) reflects alterations in alveolar ducts, increases to an equal extent reflecting alterations in more proximal airways where gas transport is still convective for both gases. S(SF6) and S(He) were measured in 15 asthma patients before and after airway challenges (20% forced expired volume in 1-s fall) with AMP and methacholine. S(He) increased to a greater extent than S(SF6) after AMP challenge (5.7 vs. 3.7%/l; P = 0.002), with both slopes increasing to an equal extent after methacholine challenge (3.1%/l; P = 0.959). The larger increase in S(He) following AMP challenge suggests distal ventilation impairment up to the level of terminal and respiratory bronchioles. With methacholine, the similar increases in S(He) and S(SF6) suggest a less distal impairment. AMP, therefore, seems to affect more extensively the very peripheral airways, whereas methacholine seems to have an effect on less distal airways.

Comparison of Bronchodilator Responsiveness After Methacholine-induced and AMP-induced Bronchoconstriciton in Asthmatic Children

RATIONALE: Airway Hyperresponsivness (AHR) and airway obstruction, relieved by bronchodilators are one of the main characteristics of asthma. We aimed to evaluate bronchodilator responsiveness (BDR) by applying a short-acting β-agonist (SABA) after methacholine- and adenosine 5'-monophosphate (AMP)-induced bronchoconstriction, respectively.METHODS: Methacholine and AMP challenges were performed with 3 days of interval in 69 children with mild persistent to moderate asthma. They were followed up at the Allergy Clinic of Korea University Anam Hospital. Each provocation test was terminated when the FEV1 decreased by more than 20% of its baseline value. Fifteen minutes after SABA inhalation in the state of bronchoconstriction, BDR was evaluated by measuring the FEV1. Each subject was evaluated by serum total IgE, blood eosinophil counts and serum eosinophil cationic protein (ECP).RESULTS: BDR after methacholine challenge (30.7±18.0%) and AMP challenge (35.2±24.0%) showed no significant differences. BDR after AMP challenge showed a significant correlation with the serum total IgE, and blood eosinophil counts, and serum ECP, but not in the methacholine challenge.CONCLUSIONS: In asthmatic children, BDR after each methacholine and AMP provocation tests showed no differences. However, BDR after AMP challenge test showed a significant correlation with total IgE and blood eosinophilic inflammatory markers, compared to BDR after methacholine challenge test. RATIONALE: Airway Hyperresponsivness (AHR) and airway obstruction, relieved by bronchodilators are one of the main characteristics of asthma. We aimed to evaluate bronchodilator responsiveness (BDR) by applying a short-acting β-agonist (SABA) after methacholine- and adenosine 5'-monophosphate (AMP)-induced bronchoconstriction, respectively. METHODS: Methacholine and AMP challenges were performed with 3 days of interval in 69 children with mild persistent to moderate asthma. They were followed up at the Allergy Clinic of Korea University Anam Hospital. Each provocation test was terminated when the FEV1 decreased by more than 20% of its baseline value. Fifteen minutes after SABA inhalation in the state of bronchoconstriction, BDR was evaluated by measuring the FEV1. Each subject was evaluated by serum total IgE, blood eosinophil counts and serum eosinophil cationic protein (ECP). RESULTS: BDR after methacholine challenge (30.7±18.0%) and AMP challenge (35.2±24.0%) showed no significant differences. BDR after AMP challenge showed a significant correlation with the serum total IgE, and blood eosinophil counts, and serum ECP, but not in the methacholine challenge. CONCLUSIONS: In asthmatic children, BDR after each methacholine and AMP provocation tests showed no differences. However, BDR after AMP challenge test showed a significant correlation with total IgE and blood eosinophilic inflammatory markers, compared to BDR after methacholine challenge test.

When to perform a bronchial challenge with mannitol?

When to perform a bronchial challenge with mannitol?

Bronchial hyperresponsiveness to methacholine and adenosine monophosphate and the degree of atopy in children with allergic rhinitis

nonasthmatic patients with allergic rhinitis often have bronchial hyperresponsiveness (BHR). Not only the presence but also the degree of atopy are important factors in BHR of patients with asthma. BHR is commonly evaluated by bronchial challenges using direct or indirect stimuli. to assess BHR to methacholine (direct) and to adenosine monophosphate (AMP) (indirect) in children with allergic rhinitis and to compare their relationships with the degree of atopy. methacholine and AMP challenges were performed in 88 children with allergic rhinitis, and a provocative concentration causing a 20% decrease in forced expiratory volume in 1 second (PC(20)) was calculated for each challenge. The degree of atopy was measured using serum total IgE levels, number of positive skin prick test results, and atopic scores (sum of graded wheal size). BHR to methacholine (PC(20) <8 mg/mL) and to AMP (PC(20) <200 mg/mL) was observed in 22 (25%) and 30 (34%) patients, respectively. No association was found between BHR to methacholine and any atopy parameter. In contrast, serum total IgE levels and atopic scores were higher in the group with BHR to AMP than in the group without BHR to AMP. Furthermore, a significant association was found between the degree of these 2 parameters and BHR to AMP (score for trend, P < .001 and P = .03, respectively). both BHR to methacholine and BHR to AMP were detected in a significant proportion of children with allergic rhinitis. The degree of atopy seems to be an important factor in BHR to AMP but not in BHR to methacholine.

Proof of concept study to evaluate step‐down therapy with inhaled corticosteroid alone or additive therapy on surrogate inflammatory markers in asthma

Much of the focus of inflammatory surrogates and airway challenges in asthma has been directed towards success of therapy and diagnosis. Few have considered them in the context of guiding dose reduction once sufficient control has been achieved. Adenosine monophosphate (AMP) as an indirect bronchial airway challenge, together with non invasive inflammatory surrogate measures were not found to be clinically useful when guiding therapy in a group of asthmatic patients through step 3-4 in British Thoracic Society asthma guidelines. However, they may still play a role in predicting failure of individual step-down. The aim of the study was to evaluate the usefulness of inflammatory surrogates in determining step-down therapy in asthma. AMP challenge, serum eosinophil cationic protein (ECP), exhaled nitric oxide (eNO) and pulmonary function tests were recorded. Subjects were divided into two groups following high dose inhaled corticosteroids (ICS): Group A fixed dose ICS vs. Group B ICS alone and in combination with add on therapies. No differences were seen in inflammatory measures between fixed dose ICS and reduced dose ICS alone or with combination therapies. AMP challenge conferred no additional benefit in guiding step-down therapy. The role of inflammatory surrogates may still play a role in predicting failed step-down on an individual basis.

Prolonged protection of the new inhaled corticosteroid fluticasone furoate against AMP hyperresponsiveness in patients with asthma

Single-dose inhaled corticosteroids (ICS) induce direct anti-inflammatory effects in asthma thereby improving airway hyperresponsiveness (AHR). A novel enhanced-affinity ICS, fluticasone furoate (FF), demonstrated a prolonged duration of action in vitro. The aim of this study was to evaluate the efficacy and duration of action of a single dose of FF by studying protection against AHR to adenosine 5'-monophosphate (AMP) and effects on exhaled nitric oxide (eNO). A randomized, double-blind, placebo-controlled, 6-way crossover study (FFA10026) was performed in 24 patients with allergic asthma (mean age 32.8 years, FEV(1) ≥ 70% predicted and PC(20) AMP ≤ 50 mg/ml). Each subject received a single dose of FF 1000 μg, fluticasone proprionate (FP) 1000 μg, or placebo at 2 (FF only), 14 or 26 h prior to AMP challenge and eNO measurement. FF significantly improved PC(20) AMP compared to placebo, the difference in doubling concentrations being 2.18 (95% confidence interval: 1.13-3.23), 1.54 (0.48-2.59), and 1.30 (0.26-2.34) at 2, 14 and 26 h. FP improved PC(20) AMP significantly at 14 h compared to placebo, but not at the 26-hour time point, the difference in doubling concentrations being 1.72 (0.70-2.75) and 0.33 (-0.69-1.34). There was no significant effect on eNO after either FF or FP at all time points. FF was well tolerated and there were no serious adverse events. The new inhaled corticosteroid FF, but not FP, demonstrates prolonged protection up to 26 h against AHR to AMP in asthma patients.