Mannitol Challenge Research Articles

Quantitative MRI of Gd-DOTA Accumulation in the Mouse Brain After Intraperitoneal Administration: Validation by Mass Spectrometry.

In mice, intraperitoneal (ip) contrast agent (CA) administration is convenient for mapping microvascular parameters over a long-time window. However, continuous quantitative MRI of CA accumulation in brain over hours is still missing. To validate a quantitative time-resolved MRI technique for mapping the CA kinetics in brain upon ip administration. Prospective, animal model. 25 C57Bl/6JRj mice underwent MRI. 7-T, gradient echo sequence. Gd-DOTA concentration was monitored by MRI (25 s/repetition) over 135 minutes with (N = 15) and without (N = 10) ip mannitol challenge (5 g/kg). After the final repetition, the brains were sampled to quantify gadolinium by mass spectrometry (MS). Upon manual brain segmentation, the average gadolinium concentration was compared with the MS quantification in transcardially perfused (N = 20) and unperfused (N = 5) mice. Precontrast T1-maps were acquired in 8 of 25 mice. One-tailed Spearman and Pearson correlation between gadolinium quantification by MRI and by MS, D'Agostino-Pearson test for normal distribution, Bland-Altman analysis to evaluate the agreement between MRI and MS. Significance was set at P-value <0.05. MRI showed that ip administered CA reached the blood compartment (>5 mM) within 10 minutes and accumulated continuously for 2 hours in cerebrospinal fluid (>1 mM) and in brain tissue. The MRI-derived concentration maps showed interindividual differences in CA accumulation (from 0.47 to 0.81 mM at 2 hours) with a consistent distribution resembling the pathways of the glymphatic system. The average in-vivo brain concentration 2 hours post-CA administration correlated significantly (r = 0.8206) with the brain gadolinium quantification by MS for N = 21 paired observations available. The presented experimental and imaging protocol may be convenient for monitoring the spatiotemporal pattern of CA uptake and clearance in the mouse brain over 2 hours. The quantification of the CA from the MRI signal in brain is corroborated by MS. N/A TECHNICAL EFFICACY: Stage 1.

Changes in exhaled volatile organic compounds following indirect bronchial challenge in suspected asthma

BackgroundInhaled mannitol provokes bronchoconstriction via mediators released during osmotic degranulation of inflammatory cells, and, hence represents a useful diagnostic test for asthma and model for acute attacks. We hypothesised that...

Mannitol Challenge to Assess Therapy Response in Asthmatic Children: An Interventional Cohort Study.

Bronchial provocation tests, such as the mannitol challenge, can be performed to identify and quantify the severity of bronchial hyperresponsiveness in asthmatic patients. Studies of the mannitol challenge as a monitoring tool in asthmatic children are limited. Our primary aim was to compare the bronchial hyperresponsiveness to mannitol in treatment-naive asthmatic children between baseline and three months after receiving the indicated asthma prophylaxis. Twenty-three asthmatic patients aged 4-16 years were analyzed in this prospective cohort study. All subjects underwent the mannitol challenge at baseline and after three months of treatment with budesonide ± formoterol. The difference in the provocative dose of mannitol to induce a 15% drop in FEV1 (PD15) between baseline and follow-up, as well as its association with the presence of exercise-induced or nocturnal asthma symptoms, were evaluated. The PD15 value increased significantly post-treatment (228.5 mg [4.50-458.15]; p = 0.04). Independently of the evaluation time point, the PD15 values were significantly lower in the presence of nocturnal asthma symptoms (490 mg [122-635] vs. 635 mg [635-635]; p = 0.03), whereas there was no association between the PD15 value and the presence of exercise-induced asthma (p = 0.73). These results suggest that bronchial hyperresponsiveness to mannitol may be a potential monitoring tool in the pediatric asthmatic population, reflecting therapy response in children receiving prophylactic treatment.

Evaluation of the Diagnostic Accuracy of Non-Specific Bronchial Provocation Tests in the Diagnosis of Asthma: A Randomized Cross-Over Study

IntroductionThe role of bronchial provocation tests in the diagnosis of asthma remains to be fully explored. We aimed to evaluate methacholine and mannitol challenge testing, and explore the factors associated with this broncoprovocation response. MethodsObservational, cross-over, randomized trial evaluating adult cases with suspected asthma, naïve to treatment, with normal pre-bronchodilator spirometry, and negative bronchodilator test. Patients were randomized to start with methacholine or mannitol. The diagnosis of bronchial asthma was confirmed if there was a good functional and clinical response to one month with twice daily formoterol/budesonide 9/320. The diagnostic profile and the concordance were calculated. Factors associated with a positive provocation test were entered into a multivariate binomial logistic regression analysis, and classification trees were created for both tests. ResultsThe study included 108 cases (50.0% diagnosed with asthma and 51.9% cases starting with methacholine). The percentage of cases positive to methacholine and mannitol were 30.6% and 25.0% respectively. Kappa values were 0.40 (p<0.001). The diagnostic profile for methacholine was sensitivity 59.3% and specificity 98.1%, while for mannitol it was sensitivity 48.1% and specificity 98.1%. Variables associated with a positive methacholine response included sex, atopy, FEV1, FEV1/FVC and FENO, whereas they were FEV1/FVC and FENO for mannitol. A FENO value>26ppb, FEV1≤103.3% and female sex correctly classified 78.7% of methacholine responders. FENO value>26ppb was enough to correctly classify 81.5% of mannitol responders. ConclusionsOur study confirms the diagnostic profile of methacholine and mannitol challenge tests and describes the variable associated to their positivity with new proposed cutoff values.

Laryngeal hypersensitivity and abnormal cough response during mannitol bronchoprovocation challenge.

Inhalational challenge with dry mannitol powder may potentially induce cough by two mechanisms: airway bronchoconstriction or laryngeal irritation. This prospective observational study investigated laryngeal and bronchial components of cough induced by mannitol challenge. We recruited consecutive patients referred for clinical mannitol challenge. The Newcastle Laryngeal Hypersensitivity Questionnaire (LHQ) was administered. Throughout testing, coughs were audio-recorded to derive a cough frequency index per time and dose of mannitol. Relationships between cough indices, laryngeal hypersensitivity and bronchial hyperresponsiveness (BHR) were examined. Participants were classified by cough characteristics with k-means cluster analysis. Of 90 patients who underwent challenge, 83 completed both the questionnaire and challenge. Cough frequency was greater in patients with abnormal laryngeal hypersensitivity (p=0.042), but not in those with BHR. There was a moderate negative correlation between coughs per minute and laryngeal hypersensitivity score (r=-0.315, p=0.004), with lower LHQ scores being abnormal. Cluster analysis identified an older, female-predominant cluster with higher cough frequency and laryngeal hypersensitivity, and a younger, gender-balanced cluster with lower cough frequency and normal laryngeal sensitivity. Cough frequency during mannitol challenge in our cohort reflected laryngeal hypersensitivity rather than BHR. Laryngeal hypersensitivity was more often present among older female patients. With the incorporation of cough indices, mannitol challenge may be useful to test for laryngeal hypersensitivity as well as BHR.

A retrospective cohort study to evaluate the relationship of airway hyperresponsiveness to type 2 biomarkers in persistent asthma

irway hyperresponsiveness (AHR) is a hallmark of persistent asthma measured using direct or indirect airway bronchial challenge testing. The purpose of this study is to investigate the putative relationships between type 2 inflammatory biomarkers, airway geometry (FEV1 and FEF25-75) and specific IgE (RAST or skin prick) to AHR. We performed a retrospective analysis of our database (n = 131) of patients with asthma. Of these subjects, 75 had a histamine challenge and 56 had a mannitol challenge. Fractional exhaled nitric oxide (FeNO) and specific immunoglobulin E (IgE) but not blood eosinophils were significantly higher in patients with AHR to either histamine or mannitol. FEV1 % and FEF25 - 75 % were significantly lower in patients with AHR. Elevated Type 2 biomarkers including FeNO and specific IgE but not blood eosinophils were associated with AHR. Highlights: FeNO and specific IgE but not blood eosinophils are raised in patients with airway hyperresponsiveness.

The impact of regular bisoprolol on the response to salbutamol in asthma: A double‐blind randomized placebo‐controlled crossover trial

Non-selective beta-blockers impair the bronchodilator response to beta2 -agonists. Cardio-selective beta1 -blockers are less likely to cause this effect, yet they remain relatively contraindicated in asthma. We investigated whether the response to salbutamol is impaired during cardio-selective beta1 -blocker treatment in people with asthma. A random-order, double-blind, placebo-controlled, non-inferiority, crossover study was conducted comparing up to 5 mg bisoprolol daily for 2 weeks with matching placebo, with an open-label extension of up to 10 mg bisoprolol daily. After each treatment period, mannitol was inhaled to induce bronchoconstriction with a 15% fall in forced expiratory volume in 1 s (FEV1 ). Immediately after mannitol challenge, salbutamol (100, 100 and 200 μg) was administered via spacer at 5-min intervals with repeated FEV1 measures. The FEV1 recovery with salbutamol was measured as an area under recovery curve (AUC). Based on earlier research, a clinically relevant non-inferiority limit of a 30% reduction in the AUC was set. A total of 19 adults with mild asthma and positive inhaled mannitol challenge completed the study. Adjusting for the FEV1 fall induced by mannitol and treatment sequence, the mean AUC response to salbutamol after bisoprolol was 5% lower than after placebo, with a one-sided 95% confidence interval (CI) of 26% lower. Thirteen participants completed the open-label extension up to 10 mg bisoprolol daily with mean AUC 11% higher after bisoprolol with a 95% CI of 5% lower. The bronchodilator response to rescue salbutamol after mannitol-induced bronchoconstriction is non-inferior during regular treatment with the cardio-selective beta1 -blocker, bisoprolol, compared to placebo. ACTRN12618000306213 at https://www.anzctr.org.au.

Cough-provocation tests with hypertonic aerosols.

Recent advances in cough research suggest a more widespread use of cough-provocation tests to demonstrate the hypersensitivity of the cough reflex arc. Cough-provocation tests with capsaicin or acidic aerosols have been used for decades in scientific studies. Several factors have hindered their use in everyday clinical work: i.e. lack of standardisation, the need for special equipment and the limited clinical importance of the response. Cough-provocation tests with hypertonic aerosols (CPTHAs) involve provocations with hypertonic saline, hypertonic histamine, mannitol and hyperpnoea. They probably act via different mechanisms than capsaicin and acidic aerosols. They are safe and well tolerated and the response is repeatable. CPTHAs can assess not only the sensitivity of the cough reflex arc but also the tendency of the airway smooth muscles to constrict (airway hyper-responsiveness). They can differentiate between subjects with asthma or chronic cough and healthy subjects. The responsiveness to CPTHAs correlates with the cough-related quality of life among asthmatic subjects. Furthermore, the responsiveness to them decreases during treatment of chronic cough. A severe response to CPTHAs may indicate poor long-term prognosis in chronic cough. The mannitol test has been stringently standardised, is easy to administer with simple equipment, and has regulatory approval for the assessment of airway hyper-responsiveness. Manual counting of coughs during a mannitol challenge would allow the measurement of the function of the cough reflex arc as a part of clinical routine.

Mannitol vs. methacholine in the evaluation of airway responsiveness in bakers' asthma.

Various indirect or direct airway challenge tests are used to measure nonspecific bronchial hyper-responsiveness (NSBHR). The evaluation of NSBHR in diagnosing occupational asthma (OA) is performed, e.g., to monitor the specific inhalation challenge test (SICT). The aim of this study was to preliminarily compare the results of methacholine and mannitol inhalation challenge tests in SICT monitoring in bakers with work-related airway symptoms. Four bakery workers with a suspicion of OA underwent single-blind placebo-controlled SICTs involving workplace allergens, accompanied by the evaluation of NSBHR with mannitol and methacholine, both before and after SICTs. Clinical examinations, spirometry tests, skin prick tests (SPTs) to common aeroallergens and occupational allergens, as well as tests to determine serum specific IgE antibodies to occupational aeroallergens were also performed. Positive SPTs results to occupational aeroallergens were found in all bakery workers, and specific IgE antibodies to flour were detected in 2 subjects. Three patients displayed positive SICT reactions. In all of these 3 patients, airway responsiveness to methacholine increased significantly. In 2 patients, airway reaction to mannitol was significant, whereas in 1 subject there was no increase in NSBHR after mannitol inhalation. The patient with a negative SICT result did not reveal any changes in NSBHR before and after the test, either to methacholine or mannitol. The data obtained by the authors show that there is no clear correlation between the methacholine and mannitol inhalation challenge tests in SICT monitoring. Preliminary results indicate the need for further investigations to evaluate the usefulness of the mannitol challenge test in the diagnostics of OA. Int J Occup Med Environ Health. 2020;33(2):235-9.

Assessment of fitness for recreational scuba diving in candidates with asthma: a pilot study

BackgroundAsthma may be regarded as a contraindication to scuba diving.PurposeA clinical algorithm to assess fitness to dive among individuals with asthma was developed and tested prospectively in clinical practice.Study designCohort...

The effect of deep inhalation on mannitol responsiveness.

Mannitol inhalation testing is specific for asthmatics with eosinophilic airway inflammation, a factor that has been negatively correlated with the development of deep inhalation bronchoprotection. To evaluate the effect of deep inhalations on responsiveness to inhaled mannitol in correlation with the degree of airway inflammation. Twenty participants with stable asthma completed this randomized, crossover study. A screening visit assessed responsiveness to methacholine and airway inflammation through fractional exhaled nitric oxide (FeNO) measures and sputum induction. Participants next completed two mannitol challenges, one with deep inhalations (standard method) and one with inhalations to half of total lung capacity, and two methacholine challenges, one with tidal breathing (standard method) and one with deep inhalations. Only the inhalation technique for dose administration differed between repeat mannitol or methacholine challenges. Deep inhalations did not significantly influence the provocative dose of mannitol causing a 15% fall in forced expiratory volume in 1second ((P=.73; n=7) or the mannitol dose-response slope (P=.26; n=20). Deep inhalations produced significant bronchoprotection against methacholine (P=.03; n=20). FeNO levels were significantly correlated to sputum eosinophilia (P=.02; n=15), responsiveness to deep inhalation methacholine (P=.005; n=20), the dose-response slopes from deep inhalation mannitol (P=.01; n=20), and the dose-response slope from non-deep inhalation mannitol (P=.005; n=20). Deep inhalations did not produce significant bronchoprotection against inhaled mannitol. This result is in agreement with past findings linking airway inflammation with loss of deep inhalation bronchoprotection. This study was prospectively registered on clinicaltrials.gov (NCT03505489).

Classification of asthma.

Asthma is a chronic inflammatory disorder of the airways that results, physiologically, in hyperreactivity and, clinically, in recurrent episodes of wheezing, chest tightness, or coughing. Airway inflammation, smooth-muscle contraction, epithelial sloughing, mucous hypersecretion, bronchial hyperresponsiveness, and mucosal edema contribute to the underlying pathophysiology of asthma. Diagnostic tests such as methacholine or mannitol challenges or spirometry (pre- and postbronchodilator responses) help to identify such underlying pathophysiology via assessments of bronchial hyperreactivity and lung mechanics but are imperfect and, ultimately, must be viewed in the context of a patient's clinical presentation, including response to pharmacotherapy. Asthma can be classified into either intermittent or persistent, and the latter is either mild, moderate, or severe. Some patients change, in either direction, from intermittent to persistent asthma. In addition, patients with asthma may be classified as allergic (immunoglobulin E mediated), nonallergic (often triggered by viral upper respiratory tract infections or no apparent cause), occupational, aspirin-exacerbated respiratory disease, potentially fatal, exercise-induced, and cough variant asthma. In the latter, the patients have a nonproductive cough that responds to treatment for asthma but not with antibiotics, expectorants, mucolytics, antitussives, or beta₂-adrenergic agonists, and to treatment for acid reflux and rhinosinusitis. Thus, cough variant asthma is in the differential diagnosis of chronic cough.

Usefulness of mannitol challenge testing for diagnosing asthma in everyday clinical practice

Background: The mannitol test is widely used for assessment of airway responsiveness in patients with possible asthma, but our knowledge of the value in everyday clinical practice is limited.Objective: To investigate the diagnostic value of the mannitol test in a clinical setting.Methods: All patients having a mannitol challenge test as part of their diagnostic work-up for asthma at the respiratory outpatient clinic, Hvidovre Hospital, over a 5-year period were included in the present analysis. Case history, including previous diagnoses, spirometry, exhaled nitric oxide (FENO) was obtained. The mannitol challenge was performed according to guidelines, i.e. increasing doses of mannitol (from 5 to 635 mg) until maximum dose or a 15% decline in FEV1 (PD15) was achieved (positive test defined as a PD15 < 635 mg).Results: Our cohort comprised 566 patients (210 men). Post-challenge, 247 patients were diagnosed with asthma by a specialist in respiratory medicine, of whom 138 (56%) had a positive mannitol test. A diagnosis of asthma was ruled out by the specialist in 319 individuals, of whom 18 (6%) had a positive mannitol test and 77 (24%) previous doctor-diagnosed asthma (but with no evidence of a confirmatory test). The specificity and sensitivity of the test was 94% and 56%, respectively. Female gender (p = 0.005), increasing BMI (p < 0.001), exercise-induced cough (p = 0.002), night-time respiratory symptoms (p = 0.002), low FEV1/FVC ratio (p = 0.008) and high FENO (p < 0.001) were determinants for a positive mannitol test.Conclusion: In everyday clinical work-up of patients with possible asthma, the sensitivity and specificity of the mannitol challenge test is comparable to previous controlled trials.

ERS technical standard on bronchial challenge testing: pathophysiology and methodology of indirect airway challengetesting.

Recently, this international task force reported the general considerations for bronchial challenge testing and the performance of the methacholine challenge test, a "direct" airway challenge test. Here, the task force provides an updated description of the pathophysiology and the methods to conduct indirect challenge tests. Because indirect challenge tests trigger airway narrowing through the activation of endogenous pathways that are involved in asthma, indirect challenge tests tend to be specific for asthma and reveal much about the biology of asthma, but may be less sensitive than direct tests for the detection of airway hyperresponsiveness. We provide recommendations for the conduct and interpretation of hyperpnoea challenge tests such as dry air exercise challenge and eucapnic voluntary hyperpnoea that provide a single strong stimulus for airway narrowing. This technical standard expands the recommendations to additional indirect tests such as hypertonic saline, mannitol and adenosine challenge that are incremental tests, but still retain characteristics of other indirect challenges. Assessment of airway hyperresponsiveness, with direct and indirect tests, are valuable tools to understand and to monitor airway function and to characterise the underlying asthma phenotype to guide therapy. The tests should be interpreted within the context of the clinical features of asthma.

Year in review 2017: Chronic obstructive pulmonary disease and asthma.

Year in review 2017: Chronic obstructive pulmonary disease and asthma.

The efficacy and safety of mannitol challenge in a workplace setting for assessing asthma prevalence

ABSTRACTObjective: There is no standard definition of asthma for epidemiological purposes; most surveys use symptoms and bronchial hyperresponsiveness. Few studies tested mannitol challenge test (MCT) in occupational settings. We sought to determine efficacy and safety of MCT in detecting subjects with asthma symptoms in the workplace. Methods: In this cross-sectional study we recruited 908 workers in 2 universities; they underwent a respiratory questionnaire, spirometry, skin prick tests, and MCT. Results: Eight hundred and eleven subjects completed the study; 11.1% had a positive MCT; 8.14% had asthma. MCT had low sensitivity (35.4–61.9%) but high specificity (90.2–94.9%) to detect symptomatic individuals. The most prevalent symptom was wheezing in the last 12 months. Twenty-four of those with a positive MCT (26.7%) had no positive replies to the questions on asthma symptoms. Among subjects with a positive MCT, 71.9% achieved 95% of baseline FEV1 after 15 minutes of salbutamol recovery treatment. Nine subjects (1.1%) had adverse events that prevented the test from being completed. Conclusions: MCT has high specificity but low sensitivity to detect symptomatic subjects in the workplace. It may detect subjects with hyperresponsiveness but no symptoms, who could be at risk of developing airway diseases. The test is safe and well tolerated.

Airway reactivity to mannitol is similarly increased in chronic cigarette and water pipe smokers.

BackgroundIn contrast to cigarette smoking, the association between water pipe smoking and airway hyperresponsiveness remains widely unexplored.MethodsA bronchoprovocation challenge with mannitol was performed in young adults recruited at the University of Basel, Switzerland. Subjects were categorized as acute water pipe smokers (single episode of water pipe smoking, no or <0.5 pack-years cigarette smoking); chronic water pipe smokers (weekly for ≥4 weeks, no or <0.5 pack-years cigarette smoking); cigarette smokers (no water pipe smokers); and never-smokers (no cigarette or water pipe smokers). Primary outcomes were airway reactivity as measured by the response-to-dose ratio (RDR) and airway responsiveness measured by the provocation dose to cause a 15% fall in forced expiratory volume in 1s (FEV1; PD15).ResultsSeventy-four subjects with a mean age of 22.5±2.5 years and FEV1 % predicted 90.1%±8.6% were included. Subgroups were matched in terms of age, gender, and spirometry results. RDR in chronic water pipe smokers and cigarette smokers was similar (0.013%/mg [0.010–0.015] vs 0.023%/mg [0.011–0.051], respectively; p=0.12) but significantly higher than in never-smokers (0.007%/mg [0.005–0.010], p<0.01). Neither a history of asthma (p=0.88) nor a positive skin prick test (p=0.69) was associated with increased airway reactivity to the mannitol challenge test. PD15 differed significantly between cigarette smokers and never-smokers (155 mg [115–395] vs 315 mg [155–475], respectively; p=0.04).ConclusionWeekly water pipe smoking may increase airway reactivity to a similar extent as cigarette smoking.

Asthma symptoms, mannitol reactivity and exercise-induced bronchoconstriction in adolescent swimmers versus tennis players

BackgroundStrenuous physical activity at an elite level is associated with an increased risk for asthma and, in some sports, also prevalence of allergies. The aim of this study was to investigate the prevalence of asthma and allergy among elite swimmers and tennis players and compare airway hyperreactivity to mannitol and exercise.Materials and methodsOne hundred and one adolescent swimmers and 86 tennis players answered a questionnaire about respiratory symptoms and allergy and performed mannitol challenge and sport-specific exercise challenge. Atopy was assessed and fractional exhaled nitric oxide was measured. Mannitol positivity was defined as drop in FEV1 ≥15% (ordinary criteria) and/or β2-reversibility (≥15%) after provocation (extended criteria). A positive exercise test was defined as a drop in FEV1 ≥10% (ordinary criteria) and/or β2-reversibility (≥15%) after provocation (extended criteria). Club cell protein (CC16) was measured in urine before and after the challenges.ResultsAsthma symptoms were common in both groups. More swimmers had exercise-induced symptoms (77% versus 50%) and current asthma symptoms (56% versus 38%), compared to the tennis players. More swimmers also had a positive mannitol challenge test both using ordinary (26% versus 6%) and extended criteria (43% versus 17%), while the number of positive exercise tests did not differ. After exercise (but not mannitol) challenge, CC16 level was increased in both groups, but to a higher extent in tennis players. There were no differences in atopy, rhinitis or fractional exhaled nitric oxide.ConclusionWe found a high prevalence of asthma among elite swimmers and tennis players and a higher frequency of current asthma and positive mannitol challenge tests among the swimmers. This indicates an unfavorable exercise environment.

Airway hyperresponsiveness to mannitol and methacholine and exhaled nitric oxide in children with asthma

ABSTRACTObjective: Asthma is characterized by airway hyperresponsiveness (AHR), inflammation, and obstruction. AHR to stimuli that indirectly cause bronchial smooth muscle (BSM) contractions via release of endogenous mediators is thought to better reflect airway inflammation than AHR to stimuli that act directly on BSM. Fractional exhaled nitric oxide (FeNO) is a useful parameter for noninvasive clinical airway inflammation assessments. Accordingly, this study aimed to examine the relationships of mannitol and methacholine challenge test outcomes with FeNO and the influence of inhaled corticosteroid treatment in children with asthma. Methods: One hundred thirty-four asthmatic children (89 males; ages: 5–17 years, median: 9 years) underwent spirometry, FeNO measurement, serum total/specific IgE testing, and blood eosinophil count. All subjects were challenged with mannitol dry powder (MDP; AridolH, Pharmaxis, Australia) and methacholine at 7-day intervals. Data of steroid-treated and steroid-naïve children were compared. Results: Positive responses to MDP and methacholine challenge tests were observed in 74.6% and 67.2% of total subject group, respectively, and 72 children had positive response to both challenge tests. The median FeNO level, response-dose ratio (RDR) of PC20 methacholine, and RDR of PD15 MDP were significantly higher in the steroid-treated group than in the steroid-naïve group (p < 0.001, 0.226, and 0.004, respectively). FeNO levels associated significantly with PD15 MDP and RDR PD15 MDP in total subject populations (p = 0.016 and 0.003, respectively); however, a significant correlation between FeNO and RDR PD15 MDP was observed only in the steroid-naïve group. Conclusions: Compared with AHR to methacholine, AHR to MDP more closely reflected the level of FeNO in steroid-naïve asthmatic children.

Comparison of diagnostic validity of mannitol and methacholine challenges and relationship to clinical status and airway inflammation in steroid-naïve asthmatic patients

ABSTRACTObjectives: The purpose of this study was to demonstrate and compare the diagnostic validity of two bronchial challenges and to investigate their correlation with patient clinical status, atopy and inflammation markers. Methods: Eighty-eight patients, 47 women and 41 men, mean age 38.56 ± 16.73 years who presented with asthma related symptoms and were not on any anti-asthma medication, were challenged with mannitol and methacholine on separate days. Medical history regarding asthmatic symptoms, physical examination, skin prick tests and FeNO levels were also assessed. The clinical diagnosis of asthma was based on bronchodilator reversibility test. Results: Sixty-seven patients were diagnosed with asthma and 21 without asthma. Both methacholine (P < 0.014) and mannitol (P < 0.000) challenges were significant in diagnosing asthma. The positive/negative predictive value was 93.33%/41.86% for methacholine, 97.72%/45.45% for mannitol and 97.05%/45.45%. for both methods assessed together. Worthy of note that 22% of asthmatics had both tests negative. There was a negative correlation between PC20 of methacholine and the FeNO level P < 0.001, and positive with the PD15 of mannitol P < 0.001 and the pre-test FEV1% pred P < 0.005, whereas PD15 of mannitol was negatively correlated with the FeNO level P < 0.001. Furthermore, dyspnea was the only asthmatic symptom associated with FeNO level P < 0.035 and the positivity of mannitol P < 0.014 and methacholine P < 0.04. Conclusions: Both challenge tests were equivalent in diagnosing asthma. Nevertheless, specificity appeared to be slightly higher in mannitol challenge.