Bronchial Provocation Test Research Articles

Report on the methacholine bronchial provocation test protocol: An updated statement of Korean Academy of Asthma, Allergy and Clinical Immunology

Report on the methacholine bronchial provocation test protocol: An updated statement of Korean Academy of Asthma, Allergy and Clinical Immunology

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.

Study on the Relationship Between Bronchoalveolar Lavage Fluid Cell Count, Th1/Th2 Cytokines and Pulmonary Function in Patients with Cough Variant Asthma

This study aimed to compare lung function and airway inflammation among cough variant asthma (CVA), chronic cough and classical asthma (CA) and investigate the relationship between these indicators and their possible mechanisms of action in the progression of CVA to CA. 36 patients with chronic cough, 39 patients with CA, and 57 patients with CVA were included in this study. Pulmonary function tests, bronchial provocation tests and FeNO tests were performed. The patients' bronchoalveolar lavage fluid (BALF) was collected, the cells in BALF were counted, and the levels of Th1 and Th2 cytokines were detected. The neutrophils, lymphocytes, and eosinophils in BALF in the CA and CVA groups were significantly higher than those in the chronic cough group. Also, they were negatively correlated with FEV1, FVC, and FEV1/FVC and positively correlated with IgE and FeNO. The expression of Th2-related cytokines was increased in CVA and CA patients, and it was positively correlated with FEV1, FVC and FEV1/FVC and negatively correlated with IgE and FeNO, while the results of Th1-related cytokines were the opposite of those for Th2-related cytokines. CVA differs from asthma and chronic cough in terms of Th1/Th2 cytokines and lung function and provides a reference for understanding the disease mechanism of early clinical progression of CVA to CA.

Allergic sensitization pattern as amarker of bronchial hyperresponsiveness in allergic rhinitis patients living in temperate continental climate zone.

Bronchial hyperresponsiveness (BHR) is akey feature of asthma, but it may also appear in allergic rhinitis. The type of allergen, as well as regional characteristics, play an important role in the development of BHR. The aim of our study was to analyze allergen sensitization patterns and the factors that affect BHR in allergic rhinitis patients living in temperate continental climate zone. This study retrospectively analyzed allergic rhinitis patients from Eastern Slovakia who underwent skin-prick tests to aeroallergens, spirometry, histamine and methacholine bronchial provocation tests for evaluation of lower airway symptoms. We analyzed the associations between BHR and the pattern of aeroallergen sensitization, lung function parameters, and the total IgE and eosinophil levels. Out of 365 allergic rhinitis patients (age range 16-64years), 114 showed BHR. Sensitization to house dust mites (HDMs) and grass were the most common. BHR was significantly associated with sensitization to dogs (odds ratio, OR = 2.15, 95% confidence interval, CI: 1.13-4.11) and Alternaria (OR = 2.15, 95% CI: 1.06-4.35); however, BHR did not show arelationship with HDMs sensitization. The levels of total IgE and eosinophils were higher in the BHR-positive group. Sensitization to more than six allergens significantly increased the probability of BHR (p < 0.01). Dogs and Alternaria, but not HDMs, were the sensitizing agents most closely associated with BHR. High-grade sensitization and increased total IgE and eosinophil levels were characteristic clinical signs in BHR-positive allergic rhinitis patients in the temperate continental climatic zone.

Daily Inhaled Corticosteroids Treatment Abolishes Airway Hyperresponsiveness to Mannitol in Defence and Police Recruits.

BackgroundAirway hyperresponsiveness (AHR) is a key pathophysiological feature of asthma and causes exercise-induced bronchoconstriction (EIB). Indirect bronchial provocation tests (BPTs) (e.g., exercise, mannitol) aid to diagnose asthma and identify EIB. Daily inhaled corticosteroids (ICS) can abolish AHR caused by indirect stimuli. Where strenuous physical exertion is integral to an occupation, identification of those at risk of EIB is important and documentation of inhibition of AHR with ICS is required before recruitment.Methods/ObjectivesA retrospective analysis was performed on 155 potential recruits with AHR to mannitol who underwent follow-up assessment after daily ICS treatment to determine the proportion that can abolish AHR using ICS and to determine any predictors of the persistence of AHR.ResultsAirway hyperresponsiveness was abolished in the majority (84%, n = 130) over the treatment period (mean ± SD 143 ± 72days), and it was defined as the provoking dose of mannitol to cause a 15% fall in FEV1 (cumulative inhaled dose of mannitol to cause 15% fall in FEV1, PD15) improved from (GeoMean) 183 to 521 mg. Compared with recruits in whom AHR was abolished with daily ICS (i.e., no 15% fall in FEV1 to the maximum cumulative dose of mannitol of 635 mg), in those where AHR remained (16%, n = 25), baseline AHR was more severe (PD15: 85 mg vs. 213 mg, P < 0.001), baseline FEV1% was lower (89 vs. 96%; 95%CI:2–12, P=0.004), and they had a longer follow-up duration (180 vs. 136 days; 13–74, P = 0.006). Baseline FEV1% (adjusted odds ratio 0.85; 95%CI:0.77–0.93), FEV1/FVC (0.78; 0.67–0.90), FEF25−75% (1.15; 1.06–1.25), and airway reactivity to mannitol (%Fall/cumulative dose of mannitol multiplied by 100) (1.07; 1.03–1.11) predicted AHR remaining after daily ICS.ConclusionAirway hyperresponsiveness to mannitol can be abolished after 20 weeks of daily treatment with ICS. Inhibition of AHR is likely due to attenuation of airway inflammation in response to ICS treatment. Increased airway reactivity and lower spirometry variables predicted the persistence of AHR. Thus, those with a slower response to daily ICS on AHR can potentially be identified at the commencement of monitoring ICS using inhaled mannitol.

A preliminary study on assessment of lead exposure in competitive biathletes: and its effects on respiratory health

Aim: In this preliminary study, we aimed to assess the blood lead level (BLL) in biathletes compared to cross-country skiers, and to look at the effects on airway function, responsiveness, allergic sensitization and the report of training-induced respiratory symptoms. Methods: Eleven biathletes (19 ± 2 years old, sex: 6M:4F) and 12 cross-country skiers (18 ± 3 years old, sex: 4M:8F) had a blood sample, spirometry, bronchial provocation test to Methacholine, skin prick tests, and induced sputum. Biathletes performed the tests within 3 h after a 90 to 120 min shooting session (150 ± 45 bullets fired). Results: Lung function, airway responsiveness, sensitization to common airborne allergens, and the report of training-induced respiratory symptoms were not different between both groups of winter sport athlete. BLL was significantly higher in biathletes vs. cross-country skiers (geometric mean [95%CI]: 2.15 [1.37–2.94] μg/dL vs. 0.85 [0.81–0.89] μg/dL, respectively, p &lt; 0.001, Cohen’s d = 1.25). One biathlete had a BLL greater than the recommended threshold (&gt; 5 μg/dL). Significant correlations were observed in biathletes only between BLL and FEV1 and FVC in absolute value (r = 0.69, p = 0.02 and r = 0.69, p = 0.02, respectively). Conclusion: Despite higher BLL in biathletes, no difference in atopy, respiratory function or symptoms was observed with cross-country skiers in our experimental conditions.

A historical overview of childhood asthma in southern Africa: Are we there yet?

Background The prevalence of asthma, the most common respiratory disease in children, has increased in many low- and middle-income countries (LMICs), particularly in Africa. Despite poor infrastructure and limited resources, researchers in southern Africa have sought to determine the prevalence of childhood asthma, with variable results reflecting actual differences as much as methodological limitations and biases. Objectives To collate and report findings from studies on the epidemiology of childhood asthma in southern Africa. Methods A review of the literature was undertaken. Results The prevalence of childhood asthma in southern Africa is variable but has increased over the last four decades, particularly in South Africa (3.17% to 21.29%). Methods used to assess the burden of asthma have been in the form of questionnaires, bronchial hypersensitivity provocation tests, lung function measurement and fractional exhaled nitric oxide (FENO). Conclusion The prevalence of childhood asthma is increasing in rural and urban areas in southern Africa. Research collaboration driven by a better understanding of the heterogeneous nature of asthma can improve challenges faced in evaluating the burden of asthma in African countries.

Prevalence and impact of airway diseases on clinical outcomes in idiopathic pulmonary fibrosis.

Background/AimsThe prevalence and effects of airway diseases, including asthma, eosinophilic bronchitis (EB), chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO) have not been thoroughly studied in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to evaluate the prevalence of airway diseases in patients with IPF and to identify the differences in symptoms based on the presence of airway diseases.MethodsThis single-institution prospective cohort study was conducted from June 2017 to September 2018, at the Seoul National University Hospital. Spirometry with bronchodilator, methacholine bronchial provocation test, induced sputum with eosinophil stain, and exhaled nitric oxide were performed to confirm the presence of airway disease. The modified Medical Research Council (mMRC) dyspnea scale, COPD assessment test (CAT), St. George’s Respiratory Questionnaire (SGRQ), EuroQol-5 dimension (EQ-5D) index, and cough-specific quality of life questionnaire (CQLQ) data were collected to assess symptom severity.ResultsTotal 147 patients with IPF were screened, and 70 patients were analyzed. The prevalence of airway diseases in the participants was as follows: 5.0% had COPD, 1.7% had asthma, 3.3% had ACO, and 1.7% had EB. The mMRC, CAT, SGRQ, EQ-5D, and CQLQ scores did not differ regardless of combined airway disease. After 3 months, the SGRQ (p = 0.028) and CQLQ (p = 0.030) scores were significantly higher in patients with airway disease than in those without.ConclusionsThe prevalence of airway diseases in patients with IPF is low, but when airway diseases are accompanied by IPF, symptom severity and quality of life may worsen rapidly.

Clinical implications of concentration of alveolar nitric oxide in asthmatic and non-asthmatic subacute cough

Asthma is an important cause of subacute cough. The concentration of alveolar nitric oxide (CANO) is a sensitive inflammatory indicator in peripheral airways, and it has received much less attention than the fraction of exhaled nitric oxide (FeNO50). The main objective of this study was to explore the correlation between CANO and clinical parameters in asthmatic and non-asthmatic subacute cough, which might promote understanding of the clinical utility of CANO in these special patient populations. 155 patients with subacute cough were included consecutively, of which 25 were diagnosed as asthmatic. Data for demographic characteristics, FeNO50, CANO, baseline spirometry, bronchial provocation test (or bronchodilation test) and response dose ratio (RDR) were collected. Differences between the asthmatic and non-asthmatic groups were analyzed. Spearman’s correlation coefficient (ρ) was used to evaluate the correlation between FeNO50, CANO and other clinical parameters. In patients with subacute cough, baseline CANO values did not differ between asthmatic and non-asthmatic patients (4.4(1.3, 11.4) versus 4.0(2.1, 6.8) ppb, P > 0.05). Besides, CANO exhibited a stronger association with pulmonary function parameters when compared with FeNO50. For asthmatic subacute cough, CANO was inversely correlated with FEV1/FVC (ρ = −0.69, P < 0.01) and small airway parameters including MEF25 (ρ = −0.47, P < 0.05) and MMEF (ρ = −0.45, P < 0.05). For non-asthmatic subacute cough, CANO was inversely correlated with MEF25 (ρ = −0.19, P < 0.05) and RDR (ρ = −0.21, P < 0.05). In subacute cough, asthmatic and non-asthmatic patients had similar values of baseline CANO. In both asthmatic and non-asthmatic subacute cough, CANO exhibited a stronger association with pulmonary function parameters when compared with FeNO50. A low CANO value in non-asthmatic subacute cough corresponded to a higher value of RDR, which implied a stronger tendency towards airway responsiveness.

Beware of Dog: Practical Consideration in Asthmatic Patients with Poor Perception of Respiratory Symptoms

Symptoms are often difficult to quantify, represent and depict for the patients and sometime also for the attending physicians. Anyway their role is crucial in influencing the relationship patient/physician in many ways. Respiratory symptoms (cough, thoracic pain, dispnoea) are not free of this challenging drawback. In asthmatic patients the subjective awareness of their disease condition, expecially their insight in the quality of breathing pattern, is critical to assess severity and control of their disease: under-perception of respiratory symptoms make this task problematic for patients and physicians. To estimate the magnitude of problem two set of reports have been examined: one on “real life” patients with chronic stable asthma and secondly studies evaluating the level of perception in selected asthmatic patients in a laboratory setting using bronchial provocation tests tool. Cumulatively a rough percentage of 20% asthmatic patients showed a reduced ability to be aware of their low level of pulmonary function. This impaired ability to perceive and report symptoms could also be a harbinger of undesirable and sometimes dangerous consequences. These data show that poor perception in asthma is a challenging problem affecting a large proportion of patients, with the potential of severe outcomes that need to be accurately addressed.

Le syndrome de Brooks : à propos de 15 cas colligés au service de médecine du travail et de pathologies professionnelles au CHU Farhat Hached de Sousse

BackgroundReactive airways dysfunction syndrome or Brook's syndrome is a distinct entity of non-immunologic asthma with specific diagnostic criteria. The emergence of chemical irritants at workplace had short-, medium- and long-term repercussions on the respiratory system and negatives consequences on occupational life. ObjectivesTo describe the socio-demographic, professional, clinical and paraclinical profile of patients with Brooks syndrome. Material and MethodsWe carried out a descriptive epidemiological study from January 2010 to December 2019 at the Department of Occupational Medicine in Farhat Hached Teaching Hospital-Tunisia including patients diagnosed with Brooks syndrome. ResultsA total of 15 patients was enrolled in the study with a mean age of 43.13±8 years. The average job tenure was 17.27±9 years. Healthcare sector and Textile and clothing industry were the most represented sectors. Agents incriminated in RADS were, detergents (dominated by chlorine found in bleach), solvents (paint and glue), pesticides, disinfectants (formaldehyde), strong acids. A major improvement in RADS symptoms within 3 months was noticed in 6 patients. A recurrence of symptoms after every exposure to irritant agent was notified in 13 patients. In most cases, spirometry showed an obstructive reversible syndrome. The non-specific methacholine bronchial provocation test was applied to only 2 patients. Only 4 patients needed to receive long-term treatment. Six cases of RADS were recorded as a work-related accident. ConclusionIt is necessary to highlight the importance of early detection of inhalation injuries and identification of agents in cause in order to establish adequate preventives measures at workplace.

STAT3 and IL-6 Contribute to Corticosteroid Resistance in an OVA and Ozone-induced Asthma Model with Neutrophil Infiltration.

Exposure to high levels of ozone contributes to insensitivity to glucocorticoids in asthma treatment, but the underlying mechanisms are not known. We built two asthma models: a “T2-high” asthma model was established by ovalbumin (OVA) sensitization/challenge and OVA sensitization/challenge combined with ozone exposure (OVA + ozone) was used to induce airway inflammation with increased numbers of neutrophils to simulate “T2-low” asthma. The expression of T-helper (Th)1/2/17-related cytokines was measured by cytokine antibody arrays. Bronchial provocation tests were carried out to evaluate the lung resistance of mice. Hematoxylin and eosin staining, periodic acid-Schiff staining, and immunohistochemical (IHC) analyses of alpha-smooth muscle actin were undertaken to observe morphology changes in lungs. The expression of glucocorticoid receptors (GRs) and phosphorylated-GR (p-GR) was measured by western blotting. Nr3c1 mRNA was quantified by RT-qPCR. Protein expression of proinflammatory cytokines, signal transducer and activator of transcription 3 (STAT3), suppressor of cytokine signaling 3 (SOCS3), and CXCL1 was measured through ELISAs, western blotting, or IHC analyses. Resected lung tissue from seven asthma patients and 10 healthy controls undergoing thoracotomy for pulmonary nodules was evaluated by IHC analyses and ELISAs. In both asthma models, mucus hypersecretion, as well as inflammation, hyperresponsiveness, and remodeling of the airways, was present compared with the control group, whereas the OVA + ozone group showed severe neutrophil infiltration. The expression of Th17-related cytokines (interleukin (IL)-6, IL-17A, IL-21), GR protein, and CXCL1 increased in the OVA + ozone group, whereas the expression of p-GR decreased. Dexamethasone (Dex) could not totally reverse the expression of p-GR and histone deacetylase-2 in the OVA + ozone group. STAT3 expression increased in the OVA + ozone group and could not be completely reversed by Dex, and nor could IL-6 expression. A positive correlation between IL-6 or IL-17A and STAT3 and negative correlation between SOCS3 and STAT3 were shown, suggesting that the IL-6/STAT3 pathway may be involved in OVA + ozone–induced corticosteroid-resistant airway inflammation. In clinical samples, IL-17A expression in lung tissue was positively correlated with percent STAT3-positive area and negatively correlated with SOCS3 expression. The IL-6/STAT3 pathway may contribute to corticosteroid insensitivity in OVA + ozone–induced neutrophilic airway inflammation through regulation of Th17 cells and could provide new targets for individual treatment of corticosteroid resistance in asthma.

Hypersensitivity may be involved in severe COVID-19.

BackgroundDeaths attributed to Coronavirus Disease 2019 (COVID‐19) are mainly due to severe hypoxemic respiratory failure. Although the inflammatory storm has been considered the main pathogenesis of severe COVID‐19, hypersensitivity may be another important mechanism involved in severe cases, which have a perfect response to corticosteroids (CS).MethodWe detected the serum level of anti‐SARS‐CoV‐2–spike S1 protein‐specific IgE (SP‐IgE) and anti‐SARS‐CoV‐2 nucleocapsid protein‐specific IgE (NP‐IgE) in COVID‐19. Correlation of levels of specific IgE and clinical severity were analysed. Pulmonary function test and bronchial provocation test were conducted in early convalescence of COVID‐19. We also obtained histological samples via endoscopy to detect the evidence of mast cell activation.ResultThe levels of serum SP‐IgE and NP‐IgE were significantly higher in severe cases, and were correlated with the total lung severity scores (TLSS) and the PaO2/FiO2 ratio. Nucleocapsid protein could be detected in both airway and intestinal tissues, which was stained positive together with activated mast cells, binded with IgE. Airway hyperresponsiveness (AHR) exists in the early convalescence of COVID‐19. After the application of CS in severe COVID‐19, SP‐IgE and NP‐IgE decreased, but maintained at a high level.ConclusionHypersensitivity may be involved in severe COVID‐19.

Diagnosis and management of cough-variant asthma

Abstract Cough is a natural defence mechanism of the lungs to prevent aspiration and to keep the airway clean. Cough, wheezing and shortness of breath are common symptoms of asthma. Cough-variant asthma is one of the phenotypes of asthma with the main symptom of cough without shortness of breath and wheezing. Cough-variant asthma is largely observed in patients with bronchial hyperresponsiveness who experience cough due to innocuous stimuli, and it is associated with a family history and seasonal allergy. In the present study, in patients with cough-variant asthma, no abnormalities were found during the lung function test, particularly forced expiratory flow in the first second (FEV1) or peak expiratory flow (PEF), although these values were lower than those in normal individuals. A bronchial provocation test using methacholine is needed to assess airway hyperresponsiveness, and depending on the outcome of the test, an assessment can be made as to the probability of the patient requiring a diagnosis of cough-variant asthma. Administration of inhalation therapy with bronchodilators and corticosteroids is the mainstay of management in patients with cough-variant asthma presenting with the symptom of persistent cough. Until now, there have been no specific guidelines for drug selection, dose and duration of inhaled corticosteroid use in cough-variant asthma. If symptoms do not resolve with inhaled corticosteroid monotherapy, consideration may be given to increase the inhalation dose or to add other drugs such as long-acting B2 agonists, slow-release theophylline or leukotriene receptor antagonist (LTRA).

Bronchial provocation test measured by using the forced oscillation technique to assess airway responsiveness.

Background: The bronchial provocation test (BPT) performed by using the forced oscillation technique (FOT) is cooperated without forced expiratory effort. However, a comparison of the application value and safety of BPTs measured by using the FOT and the standardized dosimeter method is lacking, which limits its clinical practice. Objective: We aimed to analyze the diagnostic value and safety of the BPT as measured by the FOT in patients with asthma and in healthy subjects. Methods: This was a randomized cross-over clinical study. Airway responsiveness was measured by using the FOT and the aerosol provocation system (APS) dosimeter method in all the participants. The between-test interval was 24 hours. The diagnostic value and safety of the two tests were analyzed. Results: Asthma control status was assessed based on ACT scores, and patients with asthma (including 27 uncontrolled, 34 partially controlled, and 32 controlled) were collected, and 69 healthy subjects were recruited. Receiver operating characteristic curves revealed slightly superior screening capability of cumulative dose of methacholine causing a 20% decrease (PD20)-forced expiratory volume in the first second of expiration when measured by using the APS-dosimeter method (area under the curve [AUC] 0.981 [95% confidence interval {CI}, 0.952-1.000]) over that of cumulative dose of inhaled methacholine at the inflection point when respiratory resistance began to increase continuously (Dmin) by using the FOT (AUC 0.959 [95% CI, 0.924-0.994]). The sensitivity and specificity were 98.9% and 98.6%, respectively, with the APS-dosimeter method, and 100% and 87.0%, respectively, with the FOT. It took an average of 9.0 minutes (range, 6.0-11.0 minutes) when using the FOT and an average of 17.0 minutes (range, 14.0-25.0 minutes) when using APS-dosimeter method (p < 0.01) in all the participants. The measurement time for the FOT was reduced by 47.1% than the APS-dosimeter. The incidence rate of the adverse events with the FOT was slightly higher than that with the APS-dosimeter method (p < 0.05). Both tests were well tolerated. No serious adverse event was found. Conclusion: The FOT, characterized as being simple, safe, and time saving, could be used to assess airway hyperresponsiveness in patients with asthma and worthy of clinical application.

Can Fractional Exhaled Nitric Oxide with Blood Eosinophil Count Have a Place in the Diagnostic Algorithm for Asthma?

Objective: Guidelines suggest using bronchial provocation testing (BPT), which is hard to attain, in patients with asthma-like symptoms presenting with nondiagnostic spirometric tests. To eliminate the risk of over/underdiagnosing asthma, we aimed to evaluate the predictive value of not only fractional exhaled nitric oxide (FeNO) but also other easily accessible clinical indices for ruling in/out asthma. Materials and Methods: This retrospective study included adults presenting to our clinic with respiratory symptoms suggestive of asthma but with normal spirometric values and negative reversibility test, who underwent FeNO and methacholine BPT (MchBPT). Medical records were used to obtain descriptive characteristics, clinical history, allergy screening, eosinophils in peripheral blood, and spirometry. Results: Among 51 patients, 19 were diagnosed with asthma. Body mass index and blood eosinophils were significantly higher in patients with positive MchBPT (p=0.042 and p=0.037, respectively). No significant difference was found in other indices, including FeNO (p=0.293). Receiver operating characteristic curve analysis revealed the best diagnostic cutoff level for FeNO as 14 ppb and blood eosinophil as 150/μl for the prediction of positive MchBPT (with 63.16%-62.5% and 80%-61% sensitivity-specificity, respectively). These two indices were the only independent predictors of positive BHR, and the model of FeNO>14ppb combined with eos>150/μl showed 100% specificity with a 100% negative predictive value. Conclusion: Our results suggest using the combination of FeNO with blood eosinophil count as a rule-out test, adding a new step in the algorithmic diagnosis of asthma. This might avoid an unnecessary BPT procedure, reduce the risk of over/under-diagnosis of asthma, and hasten the correct diagnosis.

Diagnostic Value of Fractional Exhaled Nitric Oxide and Small Airway Function in Differentiating Cough-Variant Asthma from Typical Asthma.

Purpose To explore the diagnostic value of fractional exhaled nitric oxide (FeNO), small airway function, and a combined of both in differentiating cough-variant asthma (CVA) from typical asthma (TA). Methods A total of 206 asthma subjects, including 104 CVA and 102 TA, were tested for pulmonary function, bronchial provocation test and FeNO. The correlation between FeNO, small airway function and other pulmonary indicators was analyzed by single correlation and multiple regression analysis. The receiver operating characteristic (ROC) curve was established to evaluate the diagnostic efficiency of FeNO, small airway function, and their combination and to predict the optimal cut-off point. Results All the respiratory function parameters and small airway function indicators in TA group were significantly different from those in CVA group, and FeNO value was significantly higher than that in CVA group. In addition, the area under the ROC curve (AUC) was estimated to be 0.660 for FeNO, 0.895 for MMEF75%/25%, 0.873 for FEF50%, 0.898 for FEF25%, 0.695 for Fres, 0.650 for R5-R20, and 0.645 for X5. The optimal cut-off points of FeNO, MMEF75%/25%, FEF50%, FEF25%, Fres, R5-R20 and X5, were 48.50 ppb, 60.02%, 63.46%, 45.26%, 16.63 Hz, 0.38 kPa·L−1·s−1, and −1.32, respectively. And the AUC of FeNO combined with small airway function indexes FEF25%, Fres, R5-R20, and X5 were prior than single indicators. Conclusion FeNO and small airway function indexes might have great diagnostic value for differentiating CVA from TA. The combination of FeNO and FEF25%, Fres, R5-R20, and X5 provided a significantly better prediction than either alone.

Diagnostic possibility of the combination of exhaled nitric oxide and blood eosinophil count for eosinophilic asthma

BackgroundTests to identify reversible airflow limitation are important in asthma diagnosis, but they are time-consuming and it may be difficult for patients to cooperate. We aimed to evaluate whether the combination of fractional exhaled nitric oxide (FeNO) and blood eosinophil (B-Eos) can be used to distinguish some asthma patients who could avoid objective tests.MethodsWe conducted a retrospective cohort study on 7463 suspected asthma cases between January 2014 and December 2019 in Chongqing, China, and identified 2349 patients with complete FeNO, B-Eos count, and spirometry data. Asthma was diagnosed by clinicians by the criteria of recurrent respiratory symptoms and a positive bronchial-provocation or bronchodilation test (BPT, BPD). We evaluated the diagnostic accuracy of FeNO or B-Eos alone or both in combination for asthma using receiver operating characteristic (ROC) curve analysis.ResultsIn this study, 824 patients were diagnosed with asthma. When FeNO and B-Eos counts were used in combination, the area under the ROC curve (AUC) for diagnosing asthma increased slightly (0.768 vs. 0.745 [FeNO] or 0.728 [B-Eos]; both P < 0.001). The odds ratio for having asthma increased progressively with a gradual increase in FeNO or B-Eos count (both P < 0.001; assessed using the Cochran–Armitage trend test). Further analysis of in-series combinations of different threshold values for these biomarkers indicated that moderately elevated biomarker levels (FeNO > 40 ppb and B-Eos > 300 cells/μl) support a diagnosis of asthma because diagnostic specificity was > 95% and the positive likelihood ratio (PLR) was > 10. This conclusion was verified when selecting the 2017–2019 data as the internal validation dataset.ConclusionFeNO or B-Eos count alone is insufficient to accurately diagnose asthma. Patients with moderately elevated biomarkers (FeNO > 40 ppb and B-Eos > 300 cells/μl) could be diagnosed with asthma and avoid objective tests when such tests are not feasible.

Predictive Markers of Bronchial Hyperreactivity in a Large Cohort of Young Adults With Cough Variant Asthma

Cough variant asthma (CVA), a common asthma phenotype characterized by nonproductive cough and bronchial hyperreactivity (BHR), is usually detected by bronchial provocation tests (BPTs) which are time-consuming, expensive, and unsafe. The primary study objective was to provide proof of concept for the use of fractional exhaled nitric oxide (FENO), eosinophil count percentage in induced sputum (sEOS%), forced expiratory flow between 25 and 75% of forced vital capacity (FEF25–75%) % predicted value, and FEF25–75% z-scores as surrogate markers predicting BHR in young adults with suspected CVA; the secondary objective was to compare the diagnostic performance of the various techniques. Three hundred and ten subjects (median age 24 years) were included in a cross-sectional study. Subjects were characterized as BHR positive (POS) (n = 147) or BHR negative (NEG) (n = 163) according to methacholine BPT. Classification accuracies were expressed as areas under the receiver operator characteristic curves (AUC). Compared with BHR NEG, FEF25–75% % predicted value and FEF25–75% z-scores were lower in the BHR POS group (p < 0.001), whereas FENO (p < 0.001) and sEOS% were higher (p < 0.001). AUC values for detecting BHR were as follows: FENO, 0.98 (SD = 0.02); sEOS%, 0.98 (SD = 0.02); FEF25–75% % pred, 0.93 (SD = 0.05); FEF25–75% z scores, 0.92 (SD = 0.05). Optimal cutoff values (OCV) for BHR prediction were as follows: FENO, 32.7 ppb (sensitivity = 0.93, specificity = 0.96), sEOS%, 3.80% (sensitivity = 0.94, specificity = 0.94), FEF25–75% % predicted value, 80.0% (sensitivity = 0.90, specificity = 0.87), and FEF25–75% z-score, −0.87 (sensitivity = 0.89, specificity = 0.87). Non-invasive/semi-invasive airway inflammatory or small airway functional measures might be used as surrogate markers predicting BHR in young adults with suspected CVA.

Perioperative airway management of nasal endoscopic surgery

Objective:To evaluate the perioperative airway management process of nasal endoscopic surgery, and find clinical evidence for accelerating recovery and reducing respiratory complications. Methods:The perioperative airway management process for nasal endoscopic surgery was developed according to the patient's preoperative risk factors and preoperative pulmonary function. 512 patients who entered the airway management process from March 2019 to May 2020 were included. The improvement of pulmonary function and the occurrence of adverse respiratory events during the perioperative period were analyzed. Results:265 of 512 patients showed abnormal pulmonary function, including 203 cases with ventilatory dysfunction; 103 cases with positive bronchial provocation test; 59 cases with positive bronchodilation test. Patients with abnormal lung function were treated with aerosol inhalation for 3 to 5 days before surgery, the pulmonary function indicators were greatly improved（P<0.01）. After individualized airway management, patients were then treated with surgery, and there was no perioperative dyspnea event. Conclusion:Perioperative airway management can improve pulmonary function and reduce the risk of nasal endoscopic surgery.