Differential Diagnosis Of Asthma Research Articles

An integrated metabo-lipidomics profile of induced sputum for the identification of novel biomarkers in the differential diagnosis of asthma and COPD

BackgroundDue to their complexity and to the presence of common clinical features, differentiation between asthma and chronic obstructive pulmonary disease (COPD) can be a challenging task, complicated in such cases also by asthma–COPD overlap syndrome. The distinct immune/inflammatory and structural substrates of COPD and asthma are responsible for significant differences in the responses to standard pharmacologic treatments. Therefore, an accurate diagnosis is of central relevance to assure the appropriate therapeutic intervention in order to achieve safe and effective patient care. Induced sputum (IS) accurately mirrors inflammation in the airways, providing a more direct picture of lung cell metabolism in comparison to those specimen that reflect analytes in the systemic circulation.MethodsAn integrated untargeted metabolomics and lipidomics analysis was performed in IS of asthmatic (n = 15) and COPD (n = 22) patients based on Ultra-High-Pressure Liquid Chromatography-Mass Spectrometry (UHPLC-MS) and UHPLC–tandem MS (UHPLC-MS/MS). Partial Least Squares-Discriminant Analysis (PLS-DA) was applied to resulting dataset. The analysis of main enriched metabolic pathways and the association of the preliminary metabolites/lipids pattern identified to clinical parameters of asthma/COPD differentiation were explored. Multivariate ROC analysis was performed in order to determine the discriminatory power and the reliability of the putative biomarkers for diagnosis between COPD and asthma.ResultsPLS-DA indicated a clear separation between COPD and asthmatic patients. Among the 15 selected candidate biomarkers based on Variable Importance in Projection scores, putrescine showed the highest score. A differential IS bio-signature of 22 metabolites and lipids was found, which showed statistically significant variations between asthma and COPD. Of these 22 compounds, 18 were decreased and 4 increased in COPD compared to asthmatic patients. The IS levels of Phosphatidylethanolamine (PE) (34:1), Phosphatidylglycerol (PG) (18:1;18:2) and spermine were significantly higher in asthmatic subjects compared to COPD.ConclusionsThis is the first pilot study to analyse the IS metabolomics/lipidomics signatures relevant in discriminating asthma vs COPD. The role of polyamines, of 6-Hydroxykynurenic acid and of d-rhamnose as well as of other important players related to the alteration of glycerophospholipid, aminoacid/biotin and energy metabolism provided the construction of a diagnostic model that, if validated on a larger prospective cohort, might be used to rapidly and accurately discriminate asthma from COPD.Graphical

Diagnostic Performance of a Machine Learning Algorithm (Asthma/Chronic Obstructive Pulmonary Disease [COPD] Differentiation Classification) Tool Versus Primary Care Physicians and Pulmonologists in Asthma, COPD, and Asthma/COPD Overlap

The differential diagnosis of asthma and chronic obstructive pulmonary disease (COPD) poses a challenge in clinical practice and its misdiagnosis results in inappropriate treatment, increased exacerbations, and potentially death. To investigate the diagnostic accuracy of the Asthma/COPD Differentiation Classification (AC/DC) tool compared with primary care physicians and pulmonologists in asthma, COPD, and asthma-COPD overlap. The AC/DC machine learning-based diagnostic tool was developed using 12 parameters from electronic health records of more than 400,000 patients aged 35 years and older. An expert panel of three pulmonologists and four general practitioners from five countries evaluated 119 patient cases from a prospective observational study and provided a confirmed diagnosis (n= 116) of asthma (n= 53), COPD (n= 43), asthma-COPD overlap (n= 7), or other (n= 13). Cases were then reviewed by 180 primary care physicians and 180 pulmonologists from nine countries and by the AC/DC tool, and diagnostic accuracies were compared with reference to the expert panel diagnoses. Average diagnostic accuracy of the AC/DC tool was superior to that of primary care physicians (median difference, 24%; 95% posterior credible interval: 17% to 29%; P < .0001) and was noninferior and superior (median difference, 12%; 95% posterior credible interval: 6% to 17%; P < .0001 for noninferiority and P= .0006 for superiority) to that of pulmonologists. Average diagnostic accuracies were 73%, 50%, and 61% by AC/DC tool, primary care physicians, and pulmonologists versus expert panel diagnosis, respectively. The AC/DC tool demonstrated superior diagnostic accuracy compared with primary care physicians and pulmonologists in the diagnosis of asthma and COPD in patients aged 35 years and greater and has the potential to support physicians in the diagnosis of these conditions in clinical practice.

Differential diagnosis of asthma and dysfunctional breathing and vocal cord dysfunction

The clinical manifestations of bronchial asthma are complex and variable, which can easily be confused with other diseases. So misdiagnosis and missed diagnosis of asthma are common. In the differential diagnosis of asthma, organic diseases such as left ventricular dysfunction, chronic obstructive pulmonary disease, and upper airway obstruction are most often considered, but the understanding of functional disease is insufficient. In fact, GINA guidelines suggested that the differential diagnosis in adult patients with suspected asthma needed to prioritize functional diseases such as dysfunctional breathing (DB)/hyperventilation syndrome (HVS) and vocal cord dysfunction (VCD), rather than organic disease. Here we review the concepts of DB and VCD and their differentiation from asthma.

Association between YKL-40 and asthma: a systematic meta-analysis.

Many studies have shown that chitinase-3-like protein 1 (CHI3L1), also known as YKL-40, is associated with asthma. The purpose of this meta-analysis was to evaluate the role of serum YKL-40 in the diagnosis and differential diagnosis of asthma, severity grading, and determination of disease state. The PubMed, Ovid, and Cochrane databases were searched. A total of 17 articles involving 5696 subjects were included in this meta-analysis. The results showed that the level of YKL-40 was significantly higher in asthmatic patients than in the normal group regardless of age and residential location, and increased with severity and acute exacerbation (p < 0.05). YKL-40 levels were significantly different between chronic obstructive pulmonary disease (COPD) and asthma, and also between asthma-COPD overlap syndrome (ACO) and asthma (p < 0.05). YKL-40 may act as a potential serological marker for the diagnosis of asthma, assessment of severity, indicator of the disease state, and differential diagnosis of COPD, ACO, and asthma.

High Prevalence of Exercise-induced Laryngeal Obstruction in a Cohort of Elite Cross-country Skiers.

ABSTRACTIntroductionExercise-induced laryngeal obstruction (EILO) is a differential diagnosis for asthma and prevalent in athletes referred for exercise-induced dyspnea. The aim of this study was to estimate the prevalence of EILO in elite cross-country skiers, known for a high prevalence of asthma.MethodElite cross-country skiers were invited for screening of EILO. Screening consisted of clinical assessment, questionnaires, skin prick test, spirometry, eucapnic voluntary hyperventilation test, and continuous laryngoscopy during exercise test. Current asthma was defined as physician-diagnosed asthma and use of asthma medication during the last 12 months. EILO was defined as ≥2 points at the supraglottic or glottic level during exercise at maximal effort, using a visual grade score system.ResultA total of 89 (51% female) cross-country skiers completed the study. EILO was identified in 27% of the skiers, 83% of whom were female. All skiers with EILO had supraglottic EILO, and there was no glottic EILO. Current asthma was present in 34 (38%) of the skiers, 10 (29%) of whom had concomitant EILO. In the skiers with EILO, a higher proportion reported wheeze or shortness of breath after exercise, compared with skiers without EILO. In skiers with EILO and current asthma, compared with skiers with asthma only, a higher proportion reported wheeze or shortness of breath after exercise. Asthma medication usage did not differ between these groups.ConclusionEILO is common in elite cross-country skiers, especially females. Asthma and EILO may coexist, and the prevalence of respiratory symptoms is higher in skiers with both. Testing for EILO should be considered in cross-country skiers with respiratory symptoms.

Differential diagnosis of asthma and restrictive respiratory diseases by combining forced oscillation measurements, machine learning and neuro-fuzzy classifiers.

To design machine learning classifiers to facilitate the clinical use and increase the accuracy of the forced oscillation technique (FOT) in the differential diagnosis of patients with asthma and restrictive respiratory diseases. FOT and spirometric exams were performed in 97 individuals, including controls (n = 20), asthmatic patients (n = 38), and restrictive (n = 39) patients. The first experiment of this study showed that the best FOT parameter was the resonance frequency, providing moderate accuracy (AUC = 0.87). In the second experiment, a neuro-fuzzy classifier and different supervised machine learning techniques were investigated, including k-nearest neighbors, random forests, AdaBoost with decision trees, and support vector machines with a radial basis kernel. All classifiers achieved high accuracy (AUC ≥ 0.9) in the differentiation between patient groups. In the third and fourth experiments, the use of different feature selection techniques allowed us to achieve high accuracy with only three FOT parameters. In addition, the neuro-fuzzy classifier also provided rules to explain the classification. Neuro-fuzzy and machine learning classifiers can aid in the differential diagnosis of patients with asthma and restrictive respiratory diseases. They can assist clinicians as a support system providing accurate diagnostic options.

The Diagnosis and Differential Diagnosis of Asthma in Adolescents and Adults

The Diagnosis and Differential Diagnosis of Asthma in Adolescents and Adults

2) Differential Diagnosis of Asthma in the Elderly and COPD Including ACO

2) Differential Diagnosis of Asthma in the Elderly and COPD Including ACO

The Use of Fractional Exhaled Nitric Oxide in COPD: The Relationship to Pulmonary Function Tests and Its Importance in Differential Diagnosis

SESSION TITLE: COPD 2 SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, November 1, 2017 at 01:30 PM - 02:30 PM PURPOSE: To study the values of FENO in COPD exacerbation, the relationship with disease stage and pulmonary function test and the use of FENO in differential diagnosis of COPD exacerbation and bronchial asthma METHODS: This was a prospective study. FFNO has been measured in 112 patients with COPD exacerbation, 98 male and 14 female, mean age 63 (±11.1) years and 122 patients with bronchial asthma. FENO was measured by an electrochemical nitric oxide analyzer (NIOX MINO; Aerocrine AB, Solna, Sweden), consistent with the ATS guidelines published in 2005. We used t test and ANOVA. Significance was defined as a p value of < 0.05. RESULTS: The mean of FENO in asthma and COPD was 41.4 ± 36,7 SD and 11.9 ppb ± 7.6 SD respectively. This difference is statistically significant (p <0.01). Among the 112 subjects with COPD the FENO values according to the severity of bronchial obstruction are: Small airways 13,8 ± 9,3 SD, Mild 11,8 ±6,1 SD, Moderate 11.5 ± 8 SD, Severe 11 ± 5,8 SD, Very severe 11,6 ± 7,7SD. CONCLUSIONS: There was no significant change between the mean of FENO to the degrees of bronchial obstruction of COPD exacerbation. There is no correlation between FENO values with the values of FEV1, FVC, FEV1/FVC, TLC, RV, RV/TLC, Raw, MEF 25, MEF 50, MEF 75 in COPD patients.On future it is important to know which are the FENO values after the treatment of COPD exacerbations. CLINICAL IMPLICATIONS: FENO is important biomarker in differential diagnosis of asthma with COPD exacerbation. DISCLOSURE: The following authors have nothing to disclose: Eugerta Dilka, Artan Simaku, Eritjan Tashi, Esmeralda Nushi, Dafina Todri, Alma Teferici, Oltion Sina, Serxho Golgota, Jetmira Shehu, Jeta Beli, Roland Kore, Perlat Kapisyzi No Product/Research Disclosure Information

Airway Evaluation with Multidetector Computed Tomography Post-Processing Methods in Asthmatic Patients.

Asthma is a chronic inflammatory obstructive airways disease. The disease occurs regardless of age and manifests with cough, attacks of breathlessness, and tightness in the chest. The pathophysiology of asthma is complex and still not fully understood. It is essential to find answers concerning the role of each part of the bronchial tree in asthma, especially the role of small bronchioles. With the development of newer generations of multidetector computed tomography (MDCT) and advanced post-processing methods it is possible to obtain more detailed images and gain insight into further aspects of asthma. MDCT post-processing methods can be divided into two-dimensional (2D) and three-dimensional (3D). In 2D projections, visualized hypodense regions correspond to the airway flow limitations. With the more advanced methods, such as multi planar reconstructions (MPR), images in different planes (axial, coronal, or sagittal) can be created. In the MPR technique only the voxels which are adjacent to each other in the predetermined plane can be extracted from the data set. Using the minimal/maximal intensity projections and shaded surface display, the volume of interest (VOI) can be extracted. High resolution CT scans can be used to create a more advanced imaging tool - the virtual bronchoscopy (VB). Using the VB makes it possible to visualize regions of obturation in the bronchi of up to the 5-8th generation. The MDCT with advanced post-processing methods is likely to assume an important role in the differential diagnosis of asthma, particularly when the diagnosis is dubious or hard to settle due to accompanying other lung diseases.

The role ofTc‐99mDTPAaerosol scintigraphy in the differential diagnosis ofCOPDand asthma

Chronic obstructive lung disease (COPD) and asthma are characterized as similar to each other in causing airway obstruction and being an inflammatory process. The purpose of this study was to investigate whether technetium-99m diethylenetriaminepentaacetic acid ((99m) Tc-DTPA) aerosol scintigraphy could be used in the differential diagnosis of asthma and COPD. Eighty-four patients (male/female: 32/52; mean age 50.2 ± 12.7 years) with obstructive lung disease and 30 healthy volunteers as the control group were enrolled in the study. The patients were divided into two groups as COPD and asthma and also smoking subgroups. Alveolar clearance study was performed using a radiolabeled aerosol of (99m) Tc-DTPA. Mucociliary clearance was evaluated with T½ , cap value and penetration index parameters. All patient underwent pulmonary function tests and Forced expiratory volume (FEV1 ), forced vital capacity (FVC) and FEV1 /FVC parameters were obtained. The mean of T½ values of (99m) Tc-DTPA aerosol and FEV1 /FVC value among spirometric tests of the nonsmoking COPD patients were significantly lower than nonsmoking asthma patients (46.1 ± 14.3, 62.3 ± 18.7, P = 0.02; 65.2 ± 10.8, 81.4 ± 16.5, P = 0.04, respectively). The cap value was significantly higher in nonsmoking COPD patients (1.21 ± 0.49, 0.76 ± 0.22, P = 0.03). While there were no statistically and significantly different between control and asthmatic groups at the scintigraphic parameters and spirometric parameters, the mean of T½ values, cap value and spirometric parameters were statistically different between control and COPD groups (P < 0.05). We showed that assessment of mucociliary permeability with (99m) Tc-DTPA aerosol scintigraphy was a useful, easy to apply and a noninvasive technique to use in the differential diagnosis of nonsmoker COPD and asthma.

Combination therapy versus monotherapy for gastroesophageal reflux in children with difficult-to-treat bronchial asthma

Gastroesophageal reflux (GER) is a common disorder in children with bronchial asthma. It has been identified as a potential trigger, complication and even differential diagnosis for asthma. Our aim was to find out the efficacy of the combined use of both the proton pump inhibitor esomeprazole and the antidopaminergic prokinetic domperidone versus the sole use of esomeprazole in improving asthma severity in children with difficult to treat asthma. Patients and methodsAmong 178 children with difficult-to-treat asthma, GER was assessed using upper GIT endoscopy. Those who had GER were randomly divided into 2 equal subgroups the first was treated with esomeprazole for 12weeks while the other was treated with esomeprazole and domperidone for the same period (beside the usual treatment for asthma in both groups). Childhood-asthma control test (C-ACT), forced expiratory volume in 1st second (FEV1) [% of predicted], peak expiratory flow (PEF) variability, induced sputum substance P (SP) and endoscopic reflux score (ERS) were recorded before and after the treatment. ResultsGastro-esophageal reflux (GER) was observed in about 45% of children with difficult-to-treat asthma. The C-ACT, induced sputum SP, ERS and FEV1 showed significant improvement while PEF variability showed no significant changes when comparing combination therapy subgroup (esomeprazole and domperidone) with esomeprazole only subgroup. ConclusionsCombination of domperidone and esomeprazole was more effective in improving the endoscopic reflux score, childhood-asthma control test (C-ACT) and FEV1 (% of predicted) and significantly reduced the sputum SP than the use of esomeprazole only in children with difficult-to-treat asthma.

Right sided arcus aorta as a cause of dyspnea and chronic cough

BackgroundRight sided arcus aorta (RSAA) is a rare condition that is usually asymptomatic. Patients may present with exertional dyspnea and chronic cough. A recent article suggested that RSAA should be included in the differential diagnosis of asthma, especially in patients with intractable exertional dyspnea. We aimed to present the clinical, radiologic and spirometric features of thirteen patients with RSAA observed in four years at the Rize Education and Research Hospital and Samsun Chest Diseases and Thoracic Surgery Hospital.MethodsThe characteristics of patients with RSAA, including age, gender, symptoms, radiologic and spirometric findings, were retrospectively evaluated.ResultsA total of thirteen patients were diagnosed with RSAA. Their ages ranged from 17 to 86 years and the male to female ratio was 11:2. Seven of the patients (54%) were symptomatic. The most common symptoms were exertional dyspnea, dysphagia and chronic cough. Five patients had received treatment for asthma with bronchodilators. Spirometry showed intrathoracic tracheal obstruction in five patients.ConclusionsThe RSAA anomaly occurs more frequently than might be estimated from the number of patients who are detected. Patients with intractable exertional dyspnea and chronic cough should be evaluated for the RSAA anomaly by thoracic CT.

Right sided arcus aorta as a cause of dyspnea and chronic cough

Background: Right sided arcus aorta (RSAA) is a rare condition that is usually asymptomatic. Patients may present with exertional dyspnea and chronic cough. A recent article suggested that RSAA should be included in the differential diagnosis of asthma, especially in patients with intractable exertional dyspnea. We aimed to present the clinical, radiologic and spirometric features of thirteen patients with RSAA observed in four years at the Rize Education and Research Hospital and Samsun Chest Diseases and Thoracic Surgery Hospital. Methods: The characteristics of patients with RSAA, including age, gender, symptoms, radiologic and spirometric findings, were retrospectively evaluated. Results: A total of thirteen patients were diagnosed with RSAA. Their ages ranged from 17 to 86 years and the male to female ratio was 11:2. Seven of the patients (54%) were symptomatic. The most common symptoms were exertional dyspnea, dysphagia and chronic cough. Five patients had received treatment for asthma with bronchodilators. Spirometry showed intrathoracic tracheal obstruction in five patients. Conclusions: The RSAA anomaly occurs more frequently than might be estimated from the number of patients who are detected. Patients with intractable exertional dyspnea and chronic cough should be evaluated for the RSAA anomaly by thoracic CT.

Reversibility of Airway Obstruction vs Bronchodilatation: Do We Speak the Same Language?

Airway reversibility test (or bronchodilatation test) is performed routinely in the diagnosis of obstructive lung diseases. The results of this test may be helpful in the diagnosis and differential diagnosis of asthma and chronic obstructive pulmonary disease (COPD), but sometimes bring confusion. Unfortunately, the nomenclature used for test result is not uniform, which also leads to confusion. Next the reader will find an attempt to order the state of affairs and the introduction of a uniform nomenclature, which would be consistent with the logic and allow for unambiguous classification of reversibility test results to facilitate future decisions based on the differential diagnosis.

Utility of cough response during hypertonic histamine challenge in diagnosing asthma

Airway responses to bronchial provocation tests are traditionally assessed with spirometry which necessitates considerable patient co-operation. It has been shown that coughing during bronchial provocation tests is related to the degree of bronchoconstriction which, in turn, is independent of patient co-operation. The aim of the present study was to evaluate the utility of coughing induced by the hypertonic histamine challenge in the differential diagnosis of asthma in a clinically relevant patient population. The study population consisted of 25 healthy volunteers, 30 asthmatics, and 82 non-asthmatic subjects with respiratory symptoms due to other diseases. Hypertonic histamine solution was administered with ultrasonic nebuliser with the challenges being videotaped. The cough response was expressed as the cumulative number of coughs divided by the final histamine concentration administered (CCR). The geometric mean (95% CI) of CCR for asthmatics was 302 (166-562) coughs per mg/ml, for the symptomatic controls 29.5 (20.0-43.7) coughs per mg/ml (p<0.001) and for the healthy controls 6.61 (3.02-14.5) (p<0.001) coughs per mg/ml. According to the ROC curve, the optimal cut-off point for logCCR was 2.22, with the specificity and sensitivity to detect asthma among symptomatic subjects being 86% and 70%. Cough response to hyperosmolar challenge may be useful in the differential diagnosis of airway diseases.

The Diagnostic Differences of Asthma in the Elderly

Asthma is a common disease among elderly persons. The prevalence of asthma in subjects aged over 65 years is 6.5-17%. The diagnosis of asthma is based on typical symptoms with confirmatory information gained from physical examination and laboratory studies. Respiratory symptoms are less specific in older people. Additionally the clinical manifestations of asthma is complicated by co-morbidities, polypragmasy, underreporting of symptoms, cognitive impairment. Moreover, elderly patients are sometimes unable to perform pulmonary function tests. Consequently, discriminating asthma from chronic obstructive pulmonary disease is difficult in this group of patients. The difficulties in differential diagnosis of asthma in older adults entails that disease in the elderly is often underdiagnosed and inadequately treated.

Asthma in the elderly

A population aged 65 and over has been increasing in the developed countries. The prevalence of asthma in elderly patients is estimated between 6.5 and 17%. Asthma is an important cause of morbidity and mortality in the elderly. Moreover, death due to asthma occurs mostly in elderly patients. Only a few studies have reported the characteristics of asthma in the elderly patients. Two distinct clinical presentations of asthma have been described in the elderly. There are differences both in the pathophysiology and the clinical manifestation of asthma between elderly patients with a long-standing disease and those with late-onset disease. Additionally, aging of the respiratory system influences the asthma presentation. Asthma has been presented for many years may lead to persistent obstructive ventilatory defect and can mimic chronic obstructive pulmonary disease. Irreversible obstruction is commonly observed in elderly patients with asthma. The differential diagnosis of asthma is difficult in older adults and asthma is underrecognized and undertreated in the older population. Undertreatment is common in elderly asthmatics which largely is related to diagnostic issues.

Trudności interpretacyjne w ocenie rozmazów komórkowych BAL i plwociny indukowanej

The role of quantitative methods in the cytological diagnosis of pulmonary diseases increases in recent years. Bronchoalveolar lavage (BAL) and induced sputum (IS) belong to these methods. Bronchoalveolar lavage plays an important role in the diagnosis of interstitial lung diseases, IS - in the differential diagnosis of asthma, chronic obstructive lung disease, persistent cough. Both methods are valuable in the evaluation of pathogenesis of lung diseases. The aim of this presentation is to show the main similarities and differences in the morphology of cells in the BAL and IS and difficulties in the interpretation of results of these examinations (on the basis of 1000 BAL and 200 IS smears). The preparation of cell smears according to the obligatory standards plays the most important role in the quality of BAL and IS. If the fluid is bloody or epithelial cells are numerous it can not be qualified as diagnostic. A very good knowledge of the cell morphology is necessary in the quantitative analysis. Epithelial cells, macrophages, lymphocytes, neutrophils and eosinophils are routinely identified. Alveolar macrophages are very numerous heterogeneous cell population in the BAL. IS macrophages are less numerous, are smaller in size, have more condensed cytoplasm, contain less cigarette smoke particles, have higher expression of activation markers than BAL cells. Neutrophils are larger and eosinophils more often degranulated in the IS than in the BALF. Interpretation of squamous epithelial cells needs caution because of the phagocytary function of these cells. This study details differences significant in quantitative and qualitative analysis of BAL and IS in routine and immunocytochemical tests.

Utility of hypertonic histamine challenge in distinguishing difficult‐to‐diagnose asthma

Although classical asthma is associated with airway hyperresponsiveness (AHR), this condition is also present in many cardiopulmonary disorders undermining the rational basis of its measurement in the differential diagnosis of asthma. We have recently introduced a new method to investigate AHR, the hypertonic histamine challenge (HHC). The aim of this study was to evaluate the differential diagnostic power of HHC in a clinically representative sample of 138 patients. Fifty-seven patients from the outpatient clinic of the authors' hospital with symptoms indicative of asthma were consecutively recruited. Asthma was confirmed in 31 subjects. The remaining 26 subjects formed the control group, in conjunction with seven patients with COPD, 15 patients with interstitial lung disease, 21 patients with rhinitis, 13 patients with heart failure and 25 healthy controls. Hypertonic histamine solution was administered with an ultrasonic nebuliser. Only the PC(20) values of asthmatic subjects differed statistically significantly from those of the healthy group (P < 0.0001). The receiver operator characteristic curve indicated that a PC(20) value of 0.83 mg/mL would be the optimal cut-off point of HHC to separate the asthmatics from the symptomatic controls with a sensitivity of 81% and specificity of 70%. With the PC(20) values of 0.1 and 4.0 mg/mL, the sensitivities were 42% and 100%, and the specificities were 96% and 40%, respectively. In these limits, HHC either confirmed or excluded asthma in 64 out of 138 patients (46%). The authors' attempt to improve the accuracy of the airway challenge test by combining direct and indirect challenges did not overcome the diagnostic limitations of previously utilised airway challenges.