Methacholine Challenge Research Articles

Standard technical specifications for methacholine chloride (Methacholine) bronchial challenge test (2023)

Standard technical specifications for methacholine chloride (Methacholine) bronchial challenge test (2023)

Pets, furry animal allergen components, and asthma in childhood

AbstractBackgroundThe use of component‐resolved allergy diagnostics has provided a clearer understanding of the species‐specific sensitization and severity of potential allergic reactions. This cross‐sectional study aimed to determine whether sensitization to allergen components in furry animals is indicative of blood eosinophilia, a positive fractional exhaled nitric oxide (FeNO) test, abnormal lung function, and asthma symptoms in children. Additionally, we investigated whether having pets during childhood affects the development of asthma or allergic sensitization to furry animals.MethodsWe recruited 203 children aged 4–17 years with asthma diagnosis based on abnormal lung function and 33 controls. IgE‐sensitization to allergen components for dogs, cats, and horses was analyzed using a multiplex microarray. Children were tested with FeNO, impulse oscillometry, spirometry, methacholine challenge, and skin prick test. A questionnaire was used to investigate pet ownership and symptom profile.ResultsFeNO results and blood eosinophilia revealed a correlation with sensitization to all furry animal allergens, particularly lipocalins (r = 0.203–0.560 and 0.206–0.560, respectively). Can f 3 was found to correlate with baseline R5 (r = 0.298). No association between methacholine challenge results and sensitization to furry animal allergens was found. Children with asthma who were sensitized to Can f 1, Can f 6, or both frequently reported asthma symptoms. Dog ownership was associated with a lower level of IgE‐sensitization to lipocalins, fewer asthma symptoms, and less blood eosinophilia.ConclusionFurry animal allergen component IgE‐sensitization is a risk factor for type 2‐inflammation and asthma symptoms.

Antenatal Endotoxin Induces Dysanapsis in Experimental Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, is characterized by impaired lung development with sustained functional abnormalities due to alterations of airways and the distal lung. Although clinical studies have shown striking associations between antenatal stress and BPD, little is known about the underlying pathogenetic mechanisms. Whether dysanapsis, the concept of discordant growth of the airways and parenchyma, contributes to late respiratory disease as a result of antenatal stress is unknown. We hypothesized that antenatal endotoxin (ETX) impairs juvenile lung function as a result of altered central airway and distal lung structure, suggesting the presence of dysanapsis in this preclinical BPD model. Fetal rats were exposed to intraamniotic ETX (10 μg) or saline solution (control) 2 days before term. We performed extensive structural and functional evaluation of the proximal airways and distal lung in 2-week-old rats. Distal lung structure was quantified by stereology. Conducting airway diameters were measured using micro-computed tomography. Lung function was assessed during invasive ventilation to quantify baseline mechanics, response to methacholine challenge, and spirometry. ETX-exposed pups exhibited distal lung simplification, decreased alveolar surface area, and decreased parenchyma-airway attachments. ETX-exposed pups exhibited decreased tracheal and second- and third-generation airway diameters. ETX increased respiratory system resistance and decreased lung compliance at baseline. Only Newtonian resistance, specific to large airways, exhibited increased methacholine reactivity in ETX-exposed pups compared with controls. ETX-exposed pups had a decreased ratio of FEV in 0.1 second to FVC and a normal FEV in 0.1 second, paralleling the clinical definition of dysanapsis. Antenatal ETX causes abnormalities of the central airways and distal lung growth, suggesting that dysanapsis contributes to abnormal lung function in juvenile rats.

Novel Artificial Intelligence-Based Technology to Diagnose Asthma Using Methacholine Challenge Tests.

The methacholine challenge test (MCT) has high sensitivity but relatively low specificity for asthma diagnosis. This study aimed to develop and validate machine learning (ML) models to improve the diagnostic performance of MCT for asthma. Data from 1,501 patients with asthma symptoms who underwent MCT between 2015 and 2020 were analyzed. The patients were grouped as either the training (80%, n = 1,265) and test sets (20%, n = 236) depending on the time of referral. The conventional model (provocative concentration that causes a 20% decrease in forced expiratory volume in one second [FEV1]; PC20 ≤ 16 mg/mL) was compared with the prediction models derived from five ML methods: logistic regression, support vector machine, random forest, extreme gradient boosting, and artificial neural network. The area under the receiver operator characteristic curves (AUROC) and area under the precision-recall curves (AUPRC) of each model were compared. The prediction models were further analyzed using different input combinations of FEV1, forced vital capacity (FVC), and forced expiratory flow at 25%-75% of forced vital capacity (FEF25%-75%) values obtained during MCT. In total, 545 patients (36.3%) were diagnosed with asthma. The AUROC of the conventional model was 0.856 (95% confidence interval [CI], 0.852-0.861), and the AUPRC was 0.759 (95% CI, 0.751-0.766). All the five ML prediction models had higher AUROC and AUPRC values than those of the conventional model, and random forest showed both highest AUROC (0.950; 95% CI, 0.948-0.952) and AUROC (0.909; 95% CI, 0.905-0.914) when FEV1, FVC, and FEF25%-75% were included as inputs. Artificial intelligence-based models showed excellent performance in asthma prediction compared to using PC20 ≤ 16 mg/mL. The novel technology could be used to enhance the clinical diagnosis of asthma.

Clinical relevance of cluster analysis in phenotyping allergic rhinitis in the paediatric population of the Kuyavian-Pomeranian voivodeship, Poland.

Allergic rhinitis (AR) is the most common allergic disease in the world, and additionally, its prevalence is successively increasing. Children with AR constitute a heterogeneous group of patients differing both in the course of AR and in the frequency of asthma coexistence. It is possible to identify children with AR at risk of a more severe course of the disease by analysing the potential family, environmental and clinical factors related to the development of the disease; the findings will help identify patients with a higher risk of developing asthma in the future, and who will benefit the most from early allergen-specific immunotherapy. Evaluation of clinical relevance of cluster analysis in phenotyping AR based on an analysis of selected clinical and environmental factors. The study sample was 80 children (7-17 y.o.) with AR, including 28 children with associated asthma. The effects of AR symptoms on the patients daily functioning, skin prick tests (Allergopharma), allergen-specific IgE for airborne allergens (Biocheck GmbH), total cholesterol, cholesterol high-density lipoprotein (HDL), cholesterol low-density lipoprotein (LDL), triglyceride levels in the blood (ARCHITECTcSystem), FeNO and nNO concentrations (HypAir FeNO Medisoft) and results of methacholine challenge test (Lungtest 1000Ispa) were analysed. Four clusters of patients with AR were extracted, differing in the incidence and severity of AR symptoms and the coincidence of asthma. Most of the children from cluster 1 (n = 24; 85.71%) and cluster 2 (n = 15; 78.95%) had persistent AR, while most of the children from cluster 3 (n = 11; 73.33%) and cluster 4 (n = 14; 77.78%) had intermittent AR. The co-occurrence of asthma was significantly higher in cluster 1 than in other clusters (p = 0.0002). Children in clusters 3 and 4 reported a lower impact of AR symptoms on daily functioning (p = 0.0153). Children in cluster 1 had significantly more often an abnormally high total cholesterol level (p = 0.033) and in cluster 4 significantly more often abnormally high triglyceride levels (p = 0.009) were observed. Patients in cluster 2 were significantly less likely to have abnormal high LDL levels (p = 0.015). Children with AR from the Kuyavian-Pomeranian voivodeship differing in the course of AR, the frequency of coexistence of asthma, and occurrence of lipid parameter abnormalities.

Pulmonary Function Tests in Thunderstorm-associated Respiratory Symptoms: A Cross-sectional Study.

Epidemic thunderstorm asthma is an observed increase in cases of acute bronchospasm following thunderstorms. This study aimed to compare the frequency of obstructive airway disease or bronchial hyperresponsiveness in subjects with thunderstorm-associated respiratory symptoms with subjects with similar symptoms presented at other times. A cross-sectional study from June to November of 2013 was conducted on subjects with thunderstorm-associated respiratory symptoms living in Ahvaz City, Iran. Thunderstorm-associated subjects were presented with asthmatic symptoms in thunderstorms, and other patients presented with similar symptoms at other times. Baseline spirometry was performed on patients to examine the presence of obstructive airway disease. In all patients with normal spirometry, a provocation test was applied. A comparison of qualitative and quantitative variables was made using the Chi-square and independent t test, respectively. All analyses were carried out using SPSS Statistics Version 22. A P value less than 0.05 was considered statistically significant. Out of 584 subjects, 300 and 284 participants were in thunderstorm-associated and non-thunderstorm-associated groups, respectively. After the final analysis, 87 (30.6%) and 89 (33.3%) of the thunderstorm-associated subjects and non-thunderstorm-associated group, respectively, had pieces of evidence of airflow limitation (P=0.27). Among the patients with normal spirometry, 161 (81.72%) of the thunderstorm-associated patients and 100 (56.17%) patients of the non-thunderstorm-associated symptoms group had a positive methacholine challenge test result (P<0.001). Most of the patients with thunderstorm-associated respiratory symptoms had no obvious evidence of airflow limitation in spirometry.

Force adaptation through the intravenous route in naïve mice

Aim of the study: Force adaptation is a process whereby the contractile capacity of the airway smooth muscle increases during a sustained contraction (aka tone). Tone also increases the response to a nebulized challenge with methacholine in vivo, presumably through force adaptation. Yet, due to its patchy pattern of deposition, nebulized methacholine often spurs small airway narrowing heterogeneity and closure, two important enhancers of the methacholine response. This raises the possibility that the potentiating effect of tone on the methacholine response is not due to force adaptation but by furthering heterogeneity and closure. Herein, methacholine was delivered homogenously through the intravenous (i.v.) route. Materials and Methods: Female and male BALB/c mice were subjected to one of two i.v. methacholine challenges, each of the same cumulative dose but starting by a 20-min period either with or without tone induced by serial i.v. boluses. Changes in respiratory mechanics were monitored throughout by oscillometry, and the response after the final dose was compared between the two challenges to assess the effect of tone. Results: For the elastance of the respiratory system (Ers), tone potentiated the methacholine response by 64 and 405% in females (37.4 ± 10.7 vs. 61.5 ± 15.1 cmH2O/mL; p = 0.01) and males (33.0 ± 14.3 vs. 166.7 ± 60.6 cmH2O/mL; p = 0.0004), respectively. For the resistance of the respiratory system (Rrs), tone potentiated the methacholine response by 129 and 225% in females (9.7 ± 3.5 vs. 22.2 ± 4.3 cmH2O·s/mL; p = 0.0003) and males (10.7 ± 3.1 vs. 34.7 ± 7.9 cmH2O·s/mL; p < 0.0001), respectively. Conclusions: As previously reported with nebulized challenges, tone increases the response to i.v. methacholine in both sexes; albeit sexual dimorphisms were obvious regarding the relative resistive versus elastic nature of this potentiation. This represents further support that tone increases the lung response to methacholine through force adaptation.

Usefulness of functional tests in the diagnosis of allergic asthma

Respiratory function tests are of crucial importance in the diagnosis, assessment and management of asthma. Asthma, a chronic respiratory condition characterized by inflammation and airway obstruction, affects millions of people globally. Respiratory function tests, such as spirometry and bronchial challenge tests, are vital tools in determining the severity and type of asthma, providing objective data on lung function. This article highlights how these tests help in personalizing treatment, allowing doctors to adjust medication regimens and monitor their effectiveness. It also discusses the role of the tests in identifying patients’ responses to various triggers and in the management of asthma exacerbations. Through the regular and strategic use of respiratory function tests, better asthma control can be achieved, significantly improving the patients’ quality of life.

A new tidal breathing measurement device detects bronchial obstruction during methacholine challenge test

PurposeBronchial hyperresponsiveness (BHR), a hallmark of bronchial asthma, is typically diagnosed through a methacholine inhalation test followed by spirometry, known as the methacholine challenge test (MCT). While spirometry relies on proper patients' cooperation and precise execution of forced breathing maneuvers, we conducted a comparative analysis with the portable nanomaterial-based sensing device, SenseGuard™, to non-intrusively assess tidal breathing parameters. Materials and methodsIn this prospective study, 37 adult participants with suspected asthma underwent sequential spirometry and SenseGuard™ measurements after inhaling increasing methacholine doses. ResultsAmong the 37 participants, 18 were MCT responders, 17 were non-responders and 2 were excluded due to uninterpretable data. The MCT responders exhibited a significant lung function difference when comparing the change from baseline to maximum response. This was evident through a notable decrease in forced expiratory volume in 1 ​s (FEV1) levels in spirometry, as well as in prominent changes in tidal breathing parameters as assessed by SenseGuard™, including the expiratory pause time (Trest) to total breath time (Ttot) ratio, and the expiratory time (Tex) to Ttot ratio. Notably, the ratios Trest/Ttot (∗p ​= ​0.02), Tex/Ttot (∗p ​= ​0.002), and inspiratory time (Tin) to Tex (∗p ​= ​0.04) identified MCT responders distinctly, corresponding to spirometry (∗p ​< ​0.0001). ConclusionsThis study demonstrates that tidal breathing assessment using SenseGuard™ device reliably detects clinically relevant changes of respiratory parameter during the MCT. It effectively distinguishes between responders and non-responders, with strong agreement to conventional spirometry-measured FEV1. This technology holds promise for monitoring clinical respiratory changes in bronchial asthma patients pending further studies.

Anticipating undiagnosed asthma in symptomatic adults with normal pre- and post-bronchodilator spirometry: a decision tool for bronchial challenge testing

BackgroundSome patients with asthma demonstrate normal spirometry and remain undiagnosed without further testing.ObjectiveTo determine clinical predictors of asthma in symptomatic adults with normal spirometry, and to generate a tool to help clinicians decide who should undergo bronchial challenge testing (BCT).MethodsUsing random-digit dialling and population-based case-finding, we recruited adults from the community with respiratory symptoms and no previous history of diagnosed lung disease. Participants with normal pre- and post-bronchodilator spirometry subsequently underwent BCT. Asthma was diagnosed in those with symptoms and a methacholine provocative concentration (PC20) of < 8 mg/ml. Sputum and blood eosinophils, and exhaled nitric oxide were measured. Univariate analyses identified potentially predictive variables, which were then used to construct a multivariable logistic regression model to predict asthma. Model sensitivity, specificity, and area under the receiver operating curve (AUC) were calculated.ResultsOf 132 symptomatic individuals with normal spirometry, 34 (26%) had asthma. Of those ultimately diagnosed with asthma, 33 (97%) answered ‘yes’ to a question asking whether they experienced cough, chest tightness or wheezing provoked by exercise or cold air. Other univariate predictors of asthma included female sex, pre-bronchodilator FEV1 percentage predicted, and percent positive change in FEV1 post bronchodilator. A multivariable model containing these predictive variables yielded an AUC of 0.82 (95% CI: 0.72–0.91), a sensitivity of 82%, and a specificity of 66%. The model was used to construct a nomogram to advise clinicians which patients should be prioritized for BCT.ConclusionsFour readily available patient characteristics demonstrated a high sensitivity and AUC for predicting undiagnosed asthma in symptomatic adults with normal pre- and post-bronchodilator spirometry. These characteristics can potentially help clinicians to decide which individuals with normal spirometry should be investigated with bronchial challenge testing. However, further prospective validation of our decision tool is required.

Presence of variable extrathoracic airflow limitation in patients with a negative methacholine challenge test

PurposeDetermine whether variable extrathoracic airflow limitation (VEAL) is observed in patients with negative methacholine challenge tests (MCT).MethodsElectronic medical records of patients undergoing MCT at Jesse Brown VA Medical Center between January 2017 and December 2019 were reviewed. Only patients with negative MCT were selected. Pertinent demographic, clinical, and pulmonary function tests (PFT) and MCT data were abstracted from each record. Spirometric flow-volume loops recorded during each test were inspected by one co-author to determine the first inhaled methacholine concentration at which FEF50/FIF50 was either > 1 or further increased if baseline FEF50/FIF50 after nebulized saline (vehicle) already exceeded 1. Student’s t-test was used for statistical analysis. P < 0.05 was considered statistically significant.ResultsOne hundred and twenty-seven consecutive patients with normal baseline PFT and negative MCT were identified. Thirteen patients (10.2%) had negative MCT and FEF50/FIF50 > 1 after testing. They were predominately obese (BMI, 31.3 ± 6.6), non-smoking (10), White (8) males (9) aged 51.3 ± 14.1 years (mean ± SD) referred for symptoms suggestive of asthma (n = 7) or for chronic cough (n = 6). Five had obstructive sleep apnea, three gastroesophageal reflux disease, and two chronic rhinosinusitis. FEF50/FIF50 increased significantly from 0.72 ± 0.21 after nebulized saline (vehicle) to 1.21 ± 0.13 after inhaled methacholine (p < 0.001). Median inhaled methacholine concentration eliciting these responses was 1.0 mg/mL (range, 0.25–16 mg/mL).ConclusionsVEAL is observed in a subset of patients with a negative MCT. This phenomenon should be recognized and reported to the referring healthcare providers and its clinical significance addressed as indicated.

Correlation of Impulse Oscillometry with Spirometry in Deployed Military Personnel with Airway Obstruction.

Evaluation of chronic respiratory symptoms in deployed military personnel has been conducted at Brooke Army Medical Center as part of the Study of Active Duty Military for Pulmonary Disease Related to Environmental Deployment Exposures III study. Although asthma and airway hyperreactivity have been the most common diagnoses, the clinical findings in these patients may be multifactorial. This study aims to evaluate the utility of impulse oscillometry (IOS) in diagnosing airway obstruction in patients undergoing multiple pulmonary function testing (PFT) studies. Military personnel referred for deployed-related pulmonary symptoms underwent a standardized evaluation at Brooke Army Medical Center and Walter Reed National Military Medical Center over a 5-year span. Initial studies included laboratory tests, high-resolution computed tomography imaging, cardiac evaluation with electrocardiogram, and echocardiography. PFT consisted of full PFTs, forced inspiratory/expiratory pressures, post-spirometry bronchodilator testing, IOS, exhaled nitric oxide, and methacholine challenge testing. A total of 360 patients have completed an evaluation to date. In this cohort, 108 patients (30.0%) have evidence of obstruction by spirometry, whereas 74 (20.6%) had IOS values of both an R5 > 150% and X5 < -1.5. Only 32 (8.9%) had evidence of obstruction by both spirometry and IOS, whereas 210 (57.3%) had neither. A comparison among R5 (resistance at 5 Hz), R20 (resistance at 20 Hz), and X5 (reactance at 5 Hz) was performed in those individuals with and without spirometric obstruction. R5 (% predicted) was 156.2 ± 57.4% (obstruction) vs. 129.1 ± 39.6% (no obstruction) (P < .001); R20 (% predicted) was 138.1 ± 37.7% (obstruction) vs. 125.3 ± 31.2% (no obstruction) (P = .007); and X5 (cmH2O/L/s) was -1.62 ± 1.28 (obstruction) vs. -1.25 ± 0.55 (no obstruction) (P < .001). Impulse oscillometry has been advocated as a supplemental pulmonary function test to aid in the diagnosis of airway obstruction. The use of IOS has been primarily used in pediatrics and elderly populations as a validated tool to establish a diagnosis of airway obstruction but is limited in the adult population because of a well-validated set of reference values. Prior studies in adults have most often demonstrated a correlation with an elevated R5 > 150%, elevated resonant frequency, and a negative X5 < -1.5 or a decrease of 30 to 35% in R5 post-bronchodilator. Impulse oscillometry may serve as an adjunct to diagnosis but likely cannot replace a standard spirometric evaluation. Our study highlights the future utility for diagnosing early obstructive disease in the symptomatic individual.

Airway-associated adipose tissue accumulation is increased in a kisspeptin receptor knockout mouse model.

Airway-associated adipose tissue increases with body mass index and is a local source of pro-inflammatory adipokines that may contribute to airway pathology in asthma co-existing with obesity. Genetic susceptibility to airway adiposity was considered in the present study through kisspeptin/kisspeptin receptor signalling, known to modulate systemic adiposity and potentially drive airway remodelling. Therefore, the aim of the study was to determine the effects of kisspeptin/kisspeptin receptor signalling in the lung, focusing on airway-associated adipose tissue deposition and impact on airway structure-function. Wild-type, heterozygous and kisspeptin receptor knockout mice were studied at 6 or 8 weeks of age. Lung mechanics were assessed before and after methacholine challenge and were subsequently fixed for airway morphometry. A separate group of mice underwent glucose tolerance testing and bronchoalveolar lavage. At 6 weeks of age, kisspeptin/kisspeptin receptor signalling did not affect body adiposity, airway inflammation, wall structure or function. Despite no differences in body adiposity, there was a greater accumulation of airway-associated adipose tissue in knockout mice. By 8 weeks of age, female knockout mice displayed a non-diabetic phenotype with increased body adiposity but not males. Airway-associated adipose tissue area was also increased in both knockout females and males at 8 weeks of age, but again no other respiratory abnormality was apparent. In summary, airway-associated adipose tissue is decoupled from body adiposity in prepubescent mice which supports a genetic susceptibility to fatty deposits localised to the airway wall. There was no evidence that airway-associated adipose tissue drives pathology or respiratory impairment in the absence of other environmental exposures.

Comparison of the respiratory effects of commonly utilized general anaesthesia regimes in male Sprague-Dawley rats.

Background: Respiratory parameters in experimental animals are often characterised under general anaesthesia. However, anaesthesia regimes may alter the functional and mechanical properties of the respiratory system. While most anaesthesia regimes have been shown to affect the respiratory system, the effects of general anaesthesia protocols commonly used in animal models on lung function have not been systematically compared. Methods: The present study comprised 40 male Sprague-Dawley rats divided into five groups (N = 8 in each) according to anaesthesia regime applied: intravenous (iv) Na-pentobarbital, intraperitoneal (ip) ketamine-xylazine, iv propofol-fentanyl, inhaled sevoflurane, and ip urethane. All drugs were administered at commonly used doses. End-expiratory lung volume (EELV), airway resistance (Raw) and tissue mechanics were measured in addition to arterial blood gas parameters during mechanical ventilation while maintaining positive end-expiratory pressure (PEEP) values of 0, 3, and 6cm H2O. Respiratory mechanics were also measured during iv methacholine (MCh) challenges to assess bronchial responsiveness. Results: While PEEP influenced baseline respiratory mechanics, EELV and blood gas parameters (p < 0.001), no between-group differences were observed (p > 0.10). Conversely, significantly lower doses of MCh were required to achieve the same elevation in Raw under ketamine-xylazine anaesthesia compared to the other groups. Conclusion: In the most frequent rodent model of respiratory disorders, no differences in baseline respiratory mechanics or function were observed between commonly used anaesthesia regimes. Bronchial hyperresponsiveness in response to ketamine-xylazine anaesthesia should be considered when designing experiments using this regime. The findings of the present study indicate commonly used anaesthetic regimes allow fair comparison of respiratory mechanics in experimental animals undergoing any of the examined anaesthesia protocols.

Association between the Consumption of Ultra-Processed Foods and Asthma in Adults from Ribeirão Preto, São Paulo, Brazil.

Ultra-processed Food (UPF) consumption can play a role in the pathogenesis and progression of asthma. The aim of this study was to evaluate the association between the consumption of UPF and asthma. This cross-sectional study included 1857 adults aged 23-25 years from the Ribeirão Preto-SP birth cohort (1978/1979). The exposure variable was the consumption of UPF (expressed as their percentage contribution to energy intake-% total caloric value [%TCV] and their percentage contribution to the amount of food ingested-%grams), which was assessed with a food frequency questionnaire. Asthma was the outcome and was defined based on a positive methacholine challenge test and the presence of wheezing, chest tightness, or shortness of breath over the last 12 months. Poisson regression with robust variance was used to estimate the association between these variables. Unadjusted analyses and analyses adjusted for sex, age, household income, smoking, and physical activity level were performed. The prevalence of asthma in the sample was 13.2%. The mean total consumption of UPF was 37.9 ± 11.2% TCV (corresponding to 35.1 ± 15.1% grams). There was no association between the consumption of UPF and asthma in adults. This study provides no evidence for an association between the consumption of UPF and asthma in young adults.

Disposition of Work-Related Asthma in a Spanish Asthma Cohort: Comparison of Asthma Severity Between Employed and Retired Workers

Exposure to certain agents in the workplace can trigger occupational asthma or work-exacerbated asthma, both of which come under the heading of work-related asthma (WRA). Understanding the burden that WRA represents can help in the management of these patients. To assess the influence of occupation on asthma in real life and analyze the characteristics of patients with WRA included in an asthma cohort. This was a prospective multicenter study of a cohort of consecutive patients with asthma. A standardized clinical history was completed. Patients were classified as having WRA or non-WRA. All patients underwent respiratory function tests, FeNO test, and methacholine challenge (methacholine concentration that causes a 20% drop in FEV1) at the beginning of the study. They were classified into two groups, depending on their employment status: employed (group 1) or unemployed (group 2). Of the 480 patients included in the cohort, 82 (17%) received the diagnosis of WRA. Fifty-seven patients (70%) were still working. Mean age (SD) was 46 (10.69) years in group 1 and 57 (9.91) years in group 2 (P < .0001). Significant differences were observed in adherence to treatment (64.9% in group 1 vs 88% in group 2; P= .0354) and in severe asthma exacerbations (35.7% in group 1 vs 0% in group 2; P= .0172). No significant differences were observed in the rest of the variables analyzed. The burden of WRA in specialized asthma units is not negligible. The absence of differences in the severity of asthma, the treatment administered, alterations in lung function, and the number of exacerbations in those working versus not working may support the idea that advice regarding changing jobs should be customized for individual patients.

Desert particulate matter from Afghanistan increases airway obstruction in human distal lungs exposed to type 2 cytokine IL-13.

Deployment related asthma-like symptoms including distal airway obstruction have been described in U.S. military personnel who served in Iraq and Afghanistan. The mechanisms responsible for the development of distal airway obstruction in deployers exposed to desert particulate matter (PM) is not well understood. We sought to determine if respiratory exposure to PM from Afghanistan (PMa) increases human distal airway hyperresponsiveness (AHR) with or without exposures to IL-13, a type 2 cytokine. We further tested whether mitochondrial dysfunction, such as ATP signaling and oxidative stress, may contribute to PMa- mediated AHR. Precision-cut lung slices from donors without a history of lung disease, tobacco smoking, or vaping were pre-treated with IL-13 for 24 h. This was followed by exposure to PMa or PM from California (PMc, control for PMa) for up to 72 h. The role of hydrogen peroxide and ATP in AHR was assessed using the antioxidant enzyme catalase or an ATP receptor P2Y13 antagonist MRS2211. AHR in response to methacholine challenges as well as cytokine IL-8 production were measured. PMa alone, but not PMc alone, trended to increase AHR. Importantly, the combination of PMa and IL-13 significantly amplified AHR compared to control or PMc+IL-13. PMa alone and in combination with IL-13 increased IL-8 as compared to the control. PMa increased H2O2 and ATP. MRS211 and catalase reduced AHR in PCLS exposed to both PMa and IL-13. Our data suggests that PMa in a type 2 inflammation-high lung increased AHR in part through oxidative stress and ATP signaling.

Based on what parameters is safe to discontinuate inhaled corticosteroids in children with asthma?

Objective Remission of childhood asthma has not been widely studied. Patients in clinical remission continue to have some degree of bronchial hyperresponsiveness (BHR). The aim of this study was to investigate whether clinical parameters and lung function test are good parameters for discontinuation of inhaled corticosteroids (ICS) in asthmatic children, including patients with persistent BHR, as measured by the methacholine challenge test (MCT). Methods One year after discontinuation of inhaled corticosteroids (ICS), MCT was performed in a group of 40 asthmatic children to confirm or exclude BHR. In all patients, ICS treatment was discontinued based on the same parameters: symptoms, spirometry, daily PEF, and negative bronchodilator test. After achieving complete asthma control for at least 6 to 12 months, ICS treatment was stepped down and discontinued. Clinical course and spirometry were followed up after ICS discontinuation. Results Positive MCT was found in 50% of the patients. There was no statistically significant difference between the positive and negative MCT groups in age at initiation and discontinuation of ICS therapy, duration of ICS therapy, duration of stepping down period, FEV1, and PEF at the time of withdrawal of ICS and one year later. ICS treatment had to be restarted in two patients from the positive MCT group, due to recurrence of asthma symptoms. Conclusion Clinical parameters, normal spirometry, daily PEF values, and a negative bronchodilator test are good parameters for discontinuing ICS treatment in asthmatic children, even in patients with persistent BHR. Children should continue to be monitored, as symptoms may recur.

Provocative dose determination for methacholine challenge test aerosols through in vitro – in silico methods

Inhaled aerosols have wide-ranging applications in the treatment and diagnosis of respiratory diseases. Methacholine challenge testing (MCT) is a diagnostic test frequently used to evaluate airway hyper-reactivity. We hypothesize that a significant fraction of the inhaled dose of methacholine is exhaled during treatment, given the small droplet sizes produced by nebulizers traditionally used for MCT. Here, an in vitro – in silico approach was developed to predict respiratory tract deposition achieved with various nebulizers proposed for use with MCT.Emitted doses, particle sizes, and the temperature and humidity of the nebulized airstream were experimentally measured for three nebulizers (RX160, Roxon Meditech; Hudson RCI Micro Mist [HRCI], Teleflex; AirLife Misty Max 10 [MM10], CareFusion) at methacholine chloride concentrations of 0.0625, 1, and 16 mg/mL in 0.9% saline solutions. Emitted doses at a concentration of 1 mg/mL were measured to be 42.0 (SD 5.1) μg from the RX160 over 120 s, 96.3 (SD 33.7) μg from the HRCI over 60 s, and 162.3 (SD 38.4) μg from the MM10 over 60 s. For a typical adult tidal inhalation, the inhaled dose was found to be half of the emitted dose. Our hygroscopic lung deposition model predicted considerable condensational growth within the respiratory tract for aerosols used with MCT. For the 1 mg/mL methacholine chloride solution, the fraction of the inhaled dose predicted to deposit in the lungs was 0.40 (8.3 μg) for the RX160, 0.62 (29.6 μg) for the HRCI, and 0.60 (48.7 μg) for the MM10. Predicted exhaled dose fractions were greatest with the RX160 (0.60) and similar for the HCRI (0.34) and MM10 (0.36). Hygroscopic modeling thus suggests that the exhaled dose obtained during methacholine challenge testing is considerable, with the characteristics of the nebulizer influencing the relative proportion of the dose that is exhaled.

Use of methacoline challenge test to detect bronchial hyperresponsiveness in children with persistent rhinitis

Purpose: The incidence of persistent rhinitis in childhood is increasing day by day. Since bronchial hyperreactivity (BHR) and asthma can also be seen in a significant proportion of patients with persistent rhinitis, the use of markers that may indicate the risk of developing asthma in these patients is very important in clinical follow-up. In this study, it was aimed to demonstrate the relationship between persistent rhinitis and asthma in childhood using the bronchial methacoline challenge test (BMCT) and to investigate other factors associated with the risk of developing asthma in patients with persistent rhinitis.&#x0D; Materials and Methods: Patients aged 6-18 years who presented with findings of persistent rhinitis were evaluated with a detailed history, physical examination, and spirometry. Patients with normal examination findings and spirometry findings, and patients whose examination findings and nasal inflammation findings were compatible with moderate-to-severe rhinitis were included in the study, and their atopy status was evaluated by skin prick test, and their BHR was evaluated by BMCT.&#x0D; Results: Seventy-three patients were included in the study. The mean age was 9±2.7years, 45.2% of the patients were male. 63% of the patients were allergic and family history of allergy was present in 45.2% of the patients. 82.2% of the patients had BHR detected with BMCT. The median blood eosinophil count (BEC) was 320/mm3 and the IgE level was 160kU/L. Patients with atopy had statistically significantly higher IgE and BEC values compared with non-allergic patients. Patients with BHR were found to be younger, and had higher median BEC values. In multivariant analysis, it was observed that the patient's age300/mm3, and IgE levels&gt;250IU/L increased the probability of detecting BHR with BMCT. &#x0D; Conclusion: Care should be taken for every patient with persistent rhinitis because of the risk of BHR and asthma. Atopy examinations should be performed, but the possibility of developing BHR and asthma should not be overlooked even in the patients who are non- allergic.