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Exercise-induced bronchoconstriction (EIB) is a common condition in athletes, both with and without asthma. It involves the narrowing of the airways during intense exercise and is prevalent among elite athletes. Identifying and monitoring EIB is crucial for determining the best treatment. Inhaled corticosteroids (ICS) can effectively control EIB when taken daily for at least three months. Achieving remission in athletes with severe asthma through targeted treatments that inhibit eosinophils and mast cells is discussed, with the loss of airway hyperresponsiveness to mannitol proposed as a marker for documenting remission. Preventing and managing EIB in athletes, especially during the Olympics, is emphasized, and the use of inhaled corticosteroids is suggested as a potential treatment to reduce the risk of EIB. [Extracted from the article]

Background: 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. Methods: 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. Results: 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). Conclusion: Most of the patients with thunderstorm-associated respiratory symptoms had no obvious evidence of airflow limitation in spirometry. [ABSTRACT FROM AUTHOR]

A 22-year-old male ice hockey player reported days of worsening bilateral upper-extremity weakness, hand tremors, and difficulty grasping his stick. Subjective information included sleeping in a "curled-up" position due to lack of heat in their residence. Provocation tests and imagining studies were positive for thoracic outlet syndrome. Primary treatment focused on decreasing stress on the anterior chest wall while secondary treatment focused on strengthening the posterior thorax to improve posture. Emphasis is given to core stability and scapular mobility. Removal from sport never occurred, but symptom alleviation occurred after 3 weeks. Thoracic outlet syndrome can be resolved quickly if proper recognition and adequate treatment are utilized. Athletic trainers fill a sociomedical role for their patients and should perform patient-centered care rather than tunnel vision on the pathology. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine lung function, bronchial hyperresponsiveness (BHR) and exercise-induced respiratory symptoms in elite athletes performing different sports. Norwegian national-team athletes (30 swimmers, 32 cross-country skiers, 16 speed-skaters, 11 rowers/paddlers, 17 handball players and 23 soccer players) completed a validated questionnaire, measured exhaled nitric oxide (FENO), spirometry, methacholine provocation (PD20met) and skin prick test. Three cut-off levels defined BHR; i.e. PD20met ≤2 µmol, ≤4 µmol and ≤8 µmol. Mean forced vital capacity (FVC) was highest in swimmers (Mean z-score[95%CI] = 1.16 [0.80, 1.51]), and close to or higher than reference values according to the Global Lung Initiative equation, across all sports. Mean forced expiratory volume in 1 s (FEV1) was higher than reference values in swimmers (0.48 [0.13, 0.84]), and ball game athletes (0.69 [0.41, 0.97]). Mean forced expiratory flow between 25 and 75% of FVC (FEF25-75), and/or FEV1/FVC were lower than reference values in all endurance groups. BHR defined by ≤2 and ≤8 µmol methacholine was observed in respectively 50%–87% of swimmers, 25%–47% of cross-country skiers, 20%–53% of speed-skaters, 18%–36% of rowers/paddlers, and 0%–17% of the ball game athletes. Exercise-induced symptoms were common in all groups, most frequent in cross-country skiers (88%), swimmers (83%) and speed-skaters (81%). Highlights Swimmers and ball game athletes had higher mean FVC and FEV1 when compared to the reference values predicted by the Global Lung Initiative (GLI) reference equation. Contrasting this, across all sports except ball game athletes, mean FEF25-75 and/or FEV1/FVC were lower than reference values. The prevalence of bronchial hyperresponsiveness (BHR) was high among elite athletes competing in swimming, cross-country skiing, speed skating and rowing/paddling, with swimmers being most affected. The majority of the elite athletes reported exercise-induced respiratory symptoms independent of lung function or BHR. [ABSTRACT FROM AUTHOR]

Occupational asthma triggered by inhaling fish-derived aerosols is estimated to affect 2–8% of exposed individuals. This primarily affects workers in the fish processing industry. Fishmongers, rarely experience this issue, as recent research found no significant difference in asthma rates compared to a control group. We report the case of a fishmonger who presented with a 1-year history of rhinoconjunctivitis and asthma. The patient attributed these symptoms to his occupational exposure within the fish market environment, which worsened in the cold storage warehouse. Symptoms improved during holidays. Diagnosis involved skin-prick tests, sIgE (ImmunoCAP-specific IgE) measurements, and bronchial challenge tests, confirming occupational asthma from fish bioaerosol exposure. Parvalbumins, common fish proteins, share structural similarities, leading to cross-reactivity in fish allergy sufferers. In this case, sensitivity to rGad c1 (cod parvalbumin) was identified as the primary trigger for the patient's asthma, and responsible for sensitizations observed across various tested fish species. [ABSTRACT FROM AUTHOR]

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

Nocturnal worsening of asthma may be due to reduced lung volumes and fewer sigh breaths, which have been shown to increase airway resistance and bronchoreactivity. We hypothesized that mimicking deep inspiration using nocturnal mechanical support would improve symptoms in patients with asthma. Subjects with asthma underwent usual care and bilevel positive airway pressure (PAP) therapy for 4 weeks, separated by 4 weeks, and methacholine challenge (PC20) and subjective assessments. 13 patients with asthma alone and 8 with asthma + OSA completed the protocol. Change in bronchoreactivity (ratio of Post/Pre PC20) was not significantly different during usual care and bilevel PAP [0.86 (IQR 0.19, 1.82) vs 0.94 (IQR 0.56, 2.5), p = 0.88], nor was the change in Asthma Control Test different: 0.1 ± 2.2 vs. -0.2 ± 2.9, p = 0.79, respectively. Bilevel PAP therapy for four weeks did not improve subjective or objective measures of asthma severity in patients with asthma or those with asthma and OSA, although there was heterogeneity in response.

Background: Published guidelines on spirometry interpretation suggest an elevated FVC and FEV1 > 100% of predicted with an obstructive ratio may represent a physiological variant. Further evidence is needed on whether this finding indicates symptomatic airways obstruction and what additional evaluation should be done.Methods: Participants were prospectively enrolled to undergo additional testing for a technically adequate spirometry study with an FEV1 > 90% of predicted, and FEV1/FVC below the lower limit of normal, based on 95th percentile confidence intervals. Further testing consisted of full pulmonary function testing, impulse oscillometry (IOS), post-bronchodilator testing, fractional exhaled nitric oxide (FeNO), and methacholine challenge testing (MCT).Results: A total of 49 patients meeting entry criteria enrolled and completed testing. Thirty-three were considered symptomatic based on clinical indications for initial testing and 16 were considered asymptomatic. Baseline pulmonary function test values were not different between groups while IOS R5 values (% predicted) were higher in the symptomatic group (126.5 ± 0.37 vs 107.1 ± 0.31). Bronchodilator responsiveness on PFT or IOS was infrequent in both groups. There was a 29% positivity rate for MCT in the symptomatic group compared to one borderline study in asymptomatic participants. FeNO was similar for symptomatic, 26.17 ± 31.3 ppb, compared to asymptomatic, 22.8 ± 13.5 ppb (p = 0.93). The dysanapsis ratio was higher in the symptomatic (0.15 ± 0.03) compared to the asymptomatic (0.13 ± 0.02) (p < 0.05).Conclusion: Normal FEV1 > 90% of predicted and obstructive indices may not represent a normal physiological variant in all patients. In symptomatic patients, a positive MCT and elevated baseline IOS values were more common than in asymptomatic patients with similar PFT characteristics. These findings suggest that clinicians should still evaluate for airway hyperresponsiveness in patients with exertional dyspnea with airway obstruction and FEV1 > 90% of predicted and consider alternative diagnoses to include a normal physiologic variant if non-reactive. [ABSTRACT FROM AUTHOR]

Background: Assessment of IgE-mediated sensitization to flour allergens is widely used to investigate flour-induced occupational asthma. The diagnostic efficiency of detecting specific IgE antibodies (sIgEs) against wheat and rye flour, however, has not been thoroughly compared with other diagnostic procedures., Objective: We sought to evaluate the diagnostic accuracy of sIgE against wheat and rye compared with specific inhalation challenge (SIC) with flour as the reference standard., Methods: This retrospective multicenter study included 264 subjects who completed an SIC with flour in eight tertiary centers, of whom 205 subjects showed a positive SIC result., Results: Compared with SIC, sIgE levels of 0.35 kU A /L or greater against wheat and rye provided similar sensitivities (84% to 85%, respectively), specificities (71% to 78%), positive predictive values (91% to 93%), and negative predictive values (56% to 61%). Increasing the threshold sIgE value to 5.10 kU A /L for wheat and to 6.20 kU A /L for rye provided a specificity of 95% or greater and further enhanced the positive predictive value to 98%. Among subjects with a positive SIC, those who failed to demonstrate sIgE against wheat and rye (n = 26) had significantly lower total serum IgE level and blood and sputum eosinophil counts and a lesser increase in postchallenge FeNO compared with subjects with a detectable sIgE., Conclusion: High levels of sIgE against wheat and/or rye flour strongly support a diagnosis of flour-induced occupational asthma without the need to perform an SIC. The absence of detectable sIgE against wheat and rye in subjects with a positive SIC seems to be associated with lower levels of T H 2 biomarkers., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is often characterized by a severe course of chronic rhinosinusitis with nasal polyps (CRSwNP), comorbid asthma, and NSAID hypersensitivity. The gold standard for N-ERD diagnosis is challenge with acetylsalicylic acid (ASA). In expert recommendations, the diagnosis of N-ERD is established based on a plausible positive history of NSAID hypersensitivity and CRSwNP with asthma., Objective: The following review describes the performance of ASA challenges and their sensitivity and specificity. It also examines the extent to which a positive history of NSAID hypersensitivity correlates with ASA challenge results in clinical trials and when ASA challenges should be performed., Results and Conclusion: ASA challenges have high sensitivity and specificity. In clinical ASA challenge studies, there is a high concordance between a positive history of NSAID hypersensitivity obtained by rhinologists and the measured data of ASA challenge in patients with CRSwNP and comorbid asthma. Therefore, ASA challenge is primarily indicated in patients with an unclear history of NSAID hypersensitivity., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Inhalant allergens provide a source of environmental factors that contribute to the development of clinical symptoms in patients with atopic dermatitis (AD)., Objective: To review the relationship between inhalant allergens and AD., Methods: A literature review was conducted using three databases: PubMed/MEDLINE, ClinicalKey, and Web of Science. Search terms, including "atopic dermatitis," "atopic eczema," and "eczema," were used in combination with "inhalant allergen," "inhaled allergen," and "aeroallergen" to identify relevant published manuscripts that highlight the relationship between AD and exposures to inhalant allergens., Results: Fifteen articles were suitable for review. The studies included in the review investigated the effect of inhalant allergens on the clinical manifestations of AD through bronchial provocation, direct skin contact, and allergen sensitization., Conclusion: There is a significant relationship between exposures to inhalant allergens and AD. Inhalant allergens may aggravate AD symptoms by either bronchial provocation or direct skin contact. Sensitization of inhalant allergens, mainly house dust mites, follows a specific age-related pattern., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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

Asthma is a chronic inflammatory airway disease characterized by reversible airway obstruction and airway hyperreactivity. We proposed a cold dry air (CDA) provocation test and investigated its application in pediatric patients with asthma. We enrolled 72 children and adolescents older than 5 years who presented to our hospital with chronic cough, shortness of breath, and wheezing. We analyzed the results of allergy, pulmonary function, methacholine provocation, and CDA provocation tests. The FEV1 change 5 min after the provocation was recorded as CDA5 dFEV1; that after 15 min was recorded as CDA15 dFEV1. PT10 was the provocation time causing a 10% decrease in FEV1; a decrease of >10% in dFEV1 was considered a positive CDA test. Among the 72 subjects, 51 were diagnosed with asthma. A positive CDA test in patients with asthma correlated with non-eosinophilic asthma. In patients with asthma, sputum eosinophils and eosinophil cationic protein (ECP) levels of the patients with a positive CDA test were significantly lower than those of patients with a negative test. CDA5 dFEV1 correlated with PC20 and total immunoglobulin E. CDA15 dFEV1 correlated with PC20, sputum eosinophils, and ECP. PT10 became shorter as the peripheral blood eosinophil, FVC, FEV1, FEV1/FVC, and FEF25-75 decreased. The CDA provocation test showed airway hyperreactivity to non-specific stimuli, a high correlation with non-eosinophilic asthma, and the possibility of assessing asthma severity via PT10. [ABSTRACT FROM AUTHOR]

Background: The reversibility of bronchial obstruction is needed to diagnose asthma. Bronchodilation (BD) testing is, therefore, used in asthma work-up. This study explored the benefit of performing BD testing in asthmatic children without bronchial obstruction. Methods: The study included 60 subjects with asthma and normal lung function, 13 (21.7%) females and 47 (78.3%) males; the mean age was 11.5 years, 26 were adolescents, and 34 were children. Lung function, symptoms, use of asthma medications, type 2 inflammation, and asthma control were assessed in all subjects. Results: Eleven (18%) subjects positively responded to BD testing. Fifty-five percent of subjects were uncontrolled based on Global Initiative for Asthma (GINA) criteria. The multivariate analysis identified 2 factors associated with a positive response to BD testing: FEV1 [odds ratio (OR) = 0.91) and ACT (OR = 0.79). Conclusions: This study showed that BD testing could give additional helpful information in clinical practice. In addition, uncontrolled asthma, based on GINA criteria, was prevalent in children with normal lung function. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether skin tests are suitable to predict the allergy reactions induced by Chinese herbal injections (CHIs). Methods: The skin tests including skin prick tests (SPT), intradermal tests (IDT) and provocation tests including subcutaneous tests and intravenous tests were administered to 249 healthy subjects and 180 allergic patients for 3 CHIs, including ginkgolide injection, diterpene ginkgolide meglumine injection and Salvianolate lyophilized injection. The results of the provocation tests were used as the "gold standard" to determine the sensitivity and specificity of the skin tests. Results: The results did not show any significant differences between the healthy and allergy groups in both skin tests and provocation tests (P>0.05). The specificities of SPT and IDT were 0.976 and 0.797, respectively, and the sensitivities of both SPT and IDT were 0. Conclusion: Skin tests are insufficient to predict the likelihood of allergic reactions resulting from CHIs. (ChiCTR-CPC-15006921) [ABSTRACT FROM AUTHOR]

BACKGROUND: Methacholine bronchoprovocation or challenge testing (MCT) is commonly performed to assess airway hyper-responsiveness in the setting of suspected asthma. Nebulization is an aerosol-generating procedure, but little is known about the risks of MCT in the context of the ongoing coronavirus disease 2019 (COVID-19) pandemic. We aimed to quantify and characterize aerosol generation during MCT by using different delivery methods and to assess the impact of adding a viral filter. METHODS: Seven healthy subjects performed simulated MCT in a near particle-free laboratory space with 4 different nebulizers and with a dosimeter. Two devices continuously sampled the ambient air during the procedure, which detected ultrafine particles, from 0.02--1 μm, and particles of sizes 0.3, 0.5, 1.0, 2.0, 5.0, and 10 µm, respectively. Particle generation was compared among all the devices, with and without viral filter placement. RESULTS: Ultrafine-particle generation during simulated MCT was significant across all the devices. Ultrafine-particle (0.02--1 μm) concentrations decreased 77%--91% with the addition of a viral filter and varied significantly between unfiltered (P < .001) and filtered devices (P < .001). Ultrafine-particle generation was lowest when using the dosimeter with filtered Hudson nebulizer (1,258 ± 1,644 particle/mL). Ultrafine-particle concentrations with the filtered nebulizer devices using a compressor were higher than particle concentrations detected when using the dosimeter: Monaghan (3,472 ± 1,794 particles/mL), PARI (4,403 ± 2,948), Hudson (6,320 ± 1,787) and AirLife (9,523 ± 5,098). CONCLUSIONS: The high particle concentrations generated during MCT pose significant infection control concerns during the COVID-19 pandemic. Particle generation during MCT was significantly reduced by using breath-actuated delivery and a viral filter, which offers an effective mitigation strategy. [ABSTRACT FROM AUTHOR]

Background: Although mucus plugging is a well-reported feature of asthma, whether asthma and type 2 inflammation affect mucociliary clearance (MCC) is unknown.Research Question: Does type 2 inflammation influence mucus clearance rates in patients with mild asthma who are not receiving corticosteroids?Study Design and Methods: The clearance rates of inhaled radiolabeled particles were compared between patients with mild asthma with low (n = 17) and high (n = 18) levels of T2 inflammation. Fraction exhaled nitric oxide (Feno) was used to prospectively segregate subjects into T2 Lo (Feno < 25 ppb) and T2 Hi (Feno > 35 ppb) cohorts. Bronchial brush samples were collected with fiber-optic bronchoscopy, and quantitative polymerase chain reaction was performed to measure expression of genes associated with T2 asthma. MCC rate comparisons were also made with a historical group of healthy control subjects (HCs, n = 12).Results: The T2 Lo cohort demonstrated increased MCC when compared with both T2 Hi and historic HCs. MCC within the T2 Hi group varied significantly, with some subjects having low or zero clearance. MCC decreased with increasing expression of several markers of T2 airway inflammation (CCL26, NOS2, and POSTN) and with Feno. MUC5AC and FOXJ1 expression was similar between the T2Lo and T2Hi cohorts.Interpretation: Increasing T2 inflammation was associated with decreasing MCC. High rates of MCC in T2 Lo subjects may indicate a compensatory mechanism present in mild disease but lost with high levels of inflammation. Future studies are required to better understand mechanisms and whether impairments in MCC in more severe asthma drive worse clinical outcomes. [ABSTRACT FROM AUTHOR]

Context: Kosovo is a region in the Western Balkans that is rich in minerals and coal, so pollution is a serious public health problem there. Workers in the heavy and precious metal smeltery in Zveqan, Kosovo, were studied with regard to the roles that vapor from the smelting of metals (Pb, Zn, Au, Ag, P, and Cu) and particulate matter play in causing bronchial hyperreactivity. Objectives: The purpose of the article was to measure the parameters of lung function as determined by body plethysmography, diagnosis of respiratory diseases, and assessment of respiratory function using a histamine bronchoprovocation test. Settings and Design: The present study was conducted in two groups of participants: A control group, which included 25 healthy persons, and a smeltery worker group, which included 45 mine workers (15 smokers and 30 nonsmokers) holding permanent jobs in the mineral foundry of Zvecan, Kosovo. Subjects and Methods: Pulmonary function parameters (specific airway resistance [Raw] and intrathoracic gas volume) were measured and used to calculate the specific resistance (SRaw) and specific conductance (SGaw) of the airways, and a histamine bronchoprovocation test was conducted. Statistical Analysis Used: The data were entered and analyzed using the Microsoft Excel and INSTAT 3 software. Results: Airway specific resistance (SRaw) was significantly higher in the smeltery worker group (P < 0.01) as compared to the control group (P > 0.1). Conclusion: These results suggest that occupational exposure to vapors during the metal refining process poses a risk to the workers' health and can cause bronchial hyperreactivity, bronchial asthma, or chronic obstructive pulmonary disease. [ABSTRACT FROM AUTHOR]

Objective: In this research, we aimed to elucidate the effect of obstructive sleep apnea syndrome (OSAS) and obesity on pulmonary volumes and bronchial hyperreactivity, and particularly the effect of supine position on pulmonary volume and functions., Patients and Methods: This was a prospective, cross-sectional study with a total of 96 patients (age range, 20-65 years). Based on the body mass index (BMI) and Apnea-Hypopnea Index (AHI) scores, the patients were divided into four groups: Group 1: AHI≥15/h, BMI≥30 kg/m2 (n=24), Group 2: AHI≥15/h, BMI<30 kg/m2 (n=24), Group 3: AHI<15/h, BMI≥30 kg/m2 (n=24), and Group 4: AHI<15/h, BMI<30 kg/m2 (n=24). All patients first had static and dynamic pulmonary function tests and carbon monoxide diffusion tests (TLco and Kco) in the sitting and supine positions. A bronchial provocation test with methacholine was applied to all patients in the sitting position one day later. Analysis of variance (ANOVA) and multivariate linear regression was used in the statistical analysis., Results: Airway responsiveness was observed in 4 of the patients included in the study, and there was no statistically significant difference between the groups. A statistically significant decrease was observed in forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), total lung capacity (TLC) and functional residual capacity (FRC), especially in  Group 1 in sitting position compared to Group 4 (p=0.001, p=0.001, p=0.025, p=0.043, and p=0.001, respectively). Changes in pulmonary functions in the transition from sitting to a supine position did not show any significant difference in the study groups (p<0.05). We observed no difference in the diffusion capacity in the sitting and supine positions among the groups (p<0.05)., Conclusions: The severity of AHI and BMI particularly affect the lower airway, but changes in the position did not show any significant difference in the study groups.

Spirometry plays a crucial role in the diagnosis of asthma. The hallmark spirometry finding of expiratory airflow variability can be demonstrated in several ways including peak airflow and bronchodilator and bronchoprovocation testing. Challenges of overdiagnosis and underdiagnosis underscore the need to consider clinical context while interpreting these tests. A meticulous and multifaceted approach prioritizing objective testing is imperative while diagnosing asthma., Competing Interests: Disclosure This work was supported by NIH (P30027482-14 and 1K08HL1 to GMS)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Bronchial hyperresponsiveness (BHR) is a representative feature of asthma. Although methacholine and mannitol are commonly used for bronchial challenge tests, the optimal roles of the two agents for assessing BHR remain unclear. We compared the diagnostic performance of methacholine and mannitol in bronchial challenge tests. A systematic literature search was performed using MEDLINE, EMBASE, and the Cochrane Central Register. The sensitivity, specificity, diagnostic odds ratio (DOR), and a hierarchical summary of the receiver-operating characteristic curve (HSROC) of the two agents for detecting BHR in asthma were pooled using meta-analysis. A meta-regression analysis was used to identify potential sources of heterogeneity within the selected studies. We identified six studies comprising 565 patients. The pooled sensitivity, specificity, and DOR of methacholine were 0.61 (95%CI, 0.44-0.76), 0.93 (95%CI, 0.70–0.99), and 23.47 (95% CI, 2.51–219.89), respectively. The pooled sensitivity, specificity, and diagnostic odds ratio of mannitol were 0.50 (95%CI, 0.28–0.73), 0.97 (95% CI, 0.94–0.99), and 35.22 (95% CI, 8.82–140.62), respectively. The area under the HSROC for mannitol was higher than that for methacholine (0.97 vs. 0.81, p < 0.01). Considerable between-study heterogeneity was present for sensitivity and specificity in studies of both index tests. Univariate meta-regression analysis revealed that age and sex of the study participants were probable sources of heterogeneity for specificity in studies of methacholine. Although mannitol showed better diagnostic performance than methacholine for identifying BHR in asthma, substantial between-study heterogeneity necessitates caution when interpreting the data. [ABSTRACT FROM AUTHOR]

Work-related asthma (WRA) is highly prevalent in the adult population. WRA includes occupational asthma (OA), which is asthma caused by workplace exposures, and work-exacerbated asthma (WEA), also known as work-aggravated asthma, which is preexisting or concurrent asthma worsened by workplace conditions. In adults, the estimated prevalence of OA is 16.0%, whereas that of WEA is 21.5%. An increasing number of chemicals used in industrial production, households, and services are associated with the incidence of adult-onset asthma attributable to exposure to chemicals. This review article summarizes the different types of WRA and describes diagnostic procedures, treatment, prevention, and approaches to patient management. It is not always easy to distinguish between OA and WEA. It is important to establish a diagnosis (of sensitizer-/ irritant-induced OA or WEA) in order to prevent worsening of symptoms, as well as to prevent other workers from being exposed, by providing early treatment and counseling on social security and work-related issues. [ABSTRACT FROM AUTHOR]

ABSTRACT Work-related asthma (WRA) is highly prevalent in the adult population. WRA includes occupational asthma (OA), which is asthma caused by workplace exposures, and work-exacerbated asthma (WEA), also known as work-aggravated asthma, which is preexisting or concurrent asthma worsened by workplace conditions. In adults, the estimated prevalence of OA is 16.0%, whereas that of WEA is 21.5%. An increasing number of chemicals used in industrial production, households, and services are associated with the incidence of adult-onset asthma attributable to exposure to chemicals. This review article summarizes the different types of WRA and describes diagnostic procedures, treatment, prevention, and approaches to patient management. It is not always easy to distinguish between OA and WEA. It is important to establish a diagnosis (of sensitizer-/irritant-induced OA or WEA) in order to prevent worsening of symptoms, as well as to prevent other workers from being exposed, by providing early treatment and counseling on social security and work-related issues.

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.

Background: Capnography waveform contains essential information regarding physiological characteristics of the airway and thus indicative of the level of airway obstruction. Our aim was to develop a capnography-based, point-of-care tool that can estimate the level of obstruction in patients with asthma and COPD.Methods: Two prospective observational studies conducted between September 2016 and May 2018 at Rabin Medical Center, Israel, included healthy, asthma and COPD patient groups. Each patient underwent spirometry test and continuous capnography, as part of, either methacholine challenge test for asthma diagnosis or bronchodilator reversibility test for asthma and COPD routine evaluation. Continuous capnography signal, divided into single breaths waveforms, were analyzed to identify waveform features, to create a predictive model for FEV1 using an artificial neural network. The gold standard for comparison was FEV1 measured with spirometry.Measurements and Main Results: Overall 160 patients analyzed. Model prediction included 32/88 waveform features and three demographic features (age, gender and height). The model showed excellent correlation with FEV1 (R = 0.84), R2 achieved was 0.7 with mean square error of 0.13.Conclusion: In this study we have developed a model to evaluate FEV1 in asthma and COPD patients. Using this model, as a point-of-care tool, we can evaluate the airway obstruction level without reliance on patient cooperation. Moreover, continuous FEV1 monitoring can identify disease fluctuations, response to treatment and guide therapy.Trial Registration: clinical trials.gov, NCT02805114. Registered 17 June 2016, https://clinicaltrials.gov/ct2/show/NCT02805114. [ABSTRACT FROM AUTHOR]

Background: Methacholine challenge tests (MCTs) are used to diagnose airway hyperresponsiveness (AHR) in patients with suspected asthma where previous diagnostic testing has been inconclusive. The test is time consuming and usually requires referral to specialized centers. Simple methods to predict AHR could help determine which patients should be referred to MCTs, thus avoiding unnecessary testing. Here we investigated the potential use of baseline spirometry variables as surrogate markers for AHR in adults with suspected asthma.Methods: Baseline spirometry and MCTs performed between 2013 and 2019 in a large tertiary center were retrospectively evaluated. Receiver-operating characteristic curves for the maximal expiratory flow-volume curve indices (angle β, FEV1, FVC, FEV1/FVC, FEF50%, FEF25-75%) were constructed to assess their overall accuracy in predicting AHR and optimal cutoff values were identified.Results: A total of 2983 tests were analyzed in adults aged 18-40 years. In total, 14% of all MCTs were positive (PC20 ≤ 16 mg/ml). All baseline spirometry parameters were significantly lower in the positive group (p < 0.001). FEF50% showed the best overall accuracy (AUC = 0.688) and proved to be useful as a negative predictor when applying FEF50% ≥ 110% as a cutoff level.Conclusions: This study highlights the role of FEF50% in predicting AHR in patients with suspected asthma. A value of ≥ 110% for baseline FEF50% could be used to exclude AHR and would lead to a substantial decrease in MCT referrals. [ABSTRACT FROM AUTHOR]

Occupational and environmental lung diseases are on the rise because of the widespread use of various toxic agents in industry. Asthma etiopathogenesis is unclear because of exposure to high and low molecular agents in workplaces. Approximately 15-25% of asthma in adults is reported to be related to occupational exposure. The prevalence of occupational asthma (OA) is predicted to be high. The difficulties in diagnosing OA results in inadequate treatment, permanent airway damage, and medicolegal and social problems. As with other occupational diseases, it is necessary to demonstrate a direct causal relationship between the suspected agent and OA. Spirometry, peak expiratory flow rate, and/or non-specific bronchial hyperresponsiveness are frequently used to show airway hyperresponsiveness at the workplace and away from work. However, there are some controversies about the specificity and sensitivity of these test methods. Furthermore, these tests do not identify the exposure agent, which could be the causative agent. Specific inhalation challenge (SIC) tests that demonstrate the direct causal relationship are currently the gold standard. However, their positive and negative predictive values have not yet been established; therefore, many low molecular weight agents could cause late or atypical reactions. Therefore, a negative SIC test cannot exclude the disease. This review describes the procedures for the SIC test and discusses the importance of using the combined test methods with the SIC test. [ABSTRACT FROM AUTHOR]

Background: Cough variant asthma (CVA) is one of the special populations of asthma. The aim of the study was to compare small airways, the degree of bronchial hyperresponsiveness (BHR) and airway inflammatory subtypes between CVA and classic asthma (CA), and investigate the relationship between these markers to determine the accuracy as indicators of CVA.Methods: A total of 825 asthmatic patients participated in the study and 614 were included. 614 patients underwent spirometry and a bronchial challenge with methacholine and 459 patients performed induction sputum cell test.Results: The number of CVA patients showed less small airway dysfunction than those of CA patients (p < 0.005). The degree of small airways dysfunction was higher in the CA group compared with the CVA group (p < 0.001). Small airways dysfunction was severer in the eosinophilic airway inflammatory subtype compared with other subtypes (p < 0.05).The area under curve of MMEF, FEF50 and FEF75 (% predicted) was 0.615, 0.621, 0.606, respectively. 0.17mcg of PD20 and 4.7% of sputum eosinophils was the best diagnostic value for CVA with an AUC of 0.582 and 0.575 (p = 0.001 and p = 0.005, respectively).Conclusions: The eosinophilic airway inflammatory subtype may be increased small airway dysfunction. The value of small airways, BHR and induction sputum cells in CVA prediction, which reflected significant, but not enough to be clinically useful. [ABSTRACT FROM AUTHOR]

Behavioral inhibition reflects a disposition to react warily to novel situations, and has been associated with atopic diseases such as asthma. Retrospective work established the relationship between behavioral inhibition in rhesus monkeys (Macaca mulatta) and airway hyperresponsiveness, but not atopy, and the suggestion was made that behavioral inhibition might index components of asthma that are not immune-related. In the present study, we prospectively examined the relationship between behavioral inhibition and airway hyperresponsiveness, and whether hormonal and immune measures often associated with asthma were associated with behavioral inhibition and/or airway hyperresponsiveness. In a sample of 49 yearling rhesus monkeys (mean=1.25 years, n=24 behaviorally inhibited animals), we measured in vitro cytokine levels (IL-4, IL-10, IL-12, IFN-γ) in response to stimulation, as well as peripheral blood cell percentages, cortisol levels, and percentage of regulatory T-cells (CD3+CD4+CD25+FOXP3+). Airway reactivity was assessed using an inhaled methacholine challenge. Bronchoalveolar lavage was performed and the proportion of immune cells was determined. Behaviorally inhibited monkeys had airway hyperresponsiveness as indicated by the methacholine challenge (p=0.031), confirming our earlier retrospective result. Airway hyperresponsiveness was also associated with lower lymphocyte percentages in lavage fluid and marginally lower plasma cortisol concentrations. However, none of the tested measures was significantly related to both behavioral inhibition and airway hyperresponsiveness, and so could not mediate their relationship. Airway hyperresponsiveness is common to atopic and non-atopic asthma and behavioral inhibition has been related to altered autonomic activity in other studies. Our results suggest that behavioral inhibition might index an autonomically mediated reactive airway phenotype, and that a variety of stimuli (including inflammation within lung tissue that is not specifically associated with behavioral inhibition) may trigger the airways response.

Decrease in forced expiratory volume in one second (FEV 1 ) of 10% or 15% in exercise challenge test is considered diagnostic for asthma, but a decrease of 15% in peak expiratory flow (PEF) is recommended as an alternative. Our aim was to assess the accuracy of different PEF cut-off points in comparison to FEV 1 . We retrospectively studied 326 free running exercise challenge tests with spirometry in children 6-16 years old. FEV 1 and PEF were measured before and 2, 5, 10 and 15 min after exercise. Receiver operating characteristics (ROC) analysis, sensitivity, specificity, positive and negative predictive values (PPV and NPV) and ϰ-coefficient were used to analyse how decrease in PEF predicts decrease of 10% or 15% in FEV 1 . In the ROC analysis, areas under the curve were 0.851 (p < 0.001) and 0.921 (p < 0.001) for PEF decrease to predict a 10% and 15% decrease in FEV 1 , respectively. The agreement between changes in PEF and FEV 1 varied from slight to substantial (ϰ values of 0.199-0.680) depending on the cut-points. Lower cut-off for decrease in PEF had higher sensitivity and NPV, while higher cut-off values had better specificity and PPV. Decrease of 20% and 25% in PEF seemed to be the best cut-offs for detecting 10% and 15% decrease in FEV 1 , respectively. Still, a fifth of the positive findings based on PEF were false. Change in PEF is not a precise predictor of change in FEV 1 in exercise test. The currently recommended cut-point of 15% decrease in PEF seems to be too low and leads to high false positive rate., (© 2023 The Authors. Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Background: Chest tightness-variant asthma (CTVA) is a novel atypical asthma characterized by chest tightness as the sole or primary symptom., Objectives: To investigate the value of bronchial provocation testing combined with fractional exhaled nitric oxide (FeNO) in the diagnosis of CTVA in children., Methods: This study included 95 children aged 6-14 years with chest tightness as the sole symptom, with a duration of symptoms exceeding 4 weeks. All subjects underwent FeNO measurement, pulmonary function testing, and bronchial provocation testing using the Astograph method. Subjects with positive bronchial provocation testing were classified as the CTVA group, while those with negative results served as the non-CTVA control group., Results: The lung function of children in both groups was normal. The FeNO level in the CTVA group was (22.35 ± 9.91) ppb, significantly higher than the control group (14.85 ± 5.63) ppb, with a statistically significant difference (P < 0.05). The value of FeNO in diagnosing CTVA was analyzed using an ROC curve, with an area under the curve of 0.073 (P < 0.05). The optimal cutoff point for diagnosing CTVA using FeNO was determined to be 18.5 ppb, with a sensitivity of 60.3 % and specificity of 77.8 %. There was a negative correlation between FeNO and Dmin as well as PD15 (P = 0.006)., Conclusion: FeNO can serve as an adjunctive diagnostic tool for CTVA, with the optimal cutoff point for diagnosing CTVA being 18.5 ppb. However, FeNO is not a specific diagnostic marker for CTVA and should be used in conjunction with bronchial provocation testing to enhance its diagnostic value., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Asthma is characterized by airway hyperresponsiveness due to chronic inflammation in the airways. One of the main cells involved in airway inflammation is eosinophils. In the current study, a bronchial provocation test (BPT) was performed to demonstrate airway hyperresponsiveness. We investigated the relationship between BPT and blood eosinophil count and the cut-off value of blood eosinophil count., Patients and Methods: In this study, we retrospectively evaluated the data of 246 patients who visited our immunology and allergy clinic, a tertiary reference center, with asthma symptoms between May 2017 and March 2020 and underwent BPT with methacholine for the diagnosis of asthma. The cases were grouped according to the level of BPT positivity and negativity., Results: Of 246 patients, BPT was positive in 90 (36.6%) and negative in 156 (63.4%). The blood eosinophil measurement of the BPT-positive cases was found to be statistically significantly higher than that of the BPT-negative cases (135 vs. 119 cells/µl, respectively, p=0.029). When BPT is grouped according to positivity levels, there was no statistically significant difference in blood eosinophil measurements between subgroups (p=0.174). As a result of the evaluations, the cut-off point obtained for the blood eosinophil count was determined as ≥226 cells/µl. For the blood eosinophil count, for the cut-off value of ≥226 cells/µl, sensitivity was 30.0%, specificity 87.7%, positive predictive value 58.7%, and negative predictive value 68.3%., Conclusions: This study shows that BPT positivity is associated with blood eosinophil count. The cut-off value (≥226 cells/µl) determined for blood eosinophil count may be helpful when planning BPT and evaluating the diagnosis of asthma.

Objective: This retrospective observational cohort study aimed to assess the real-life application of bronchial challenge test (BCT) in the management of preschool children presenting with atypical recurrent respiratory symptoms (ARRS)., Methods: We included children aged 0.5-6 years referred to a pediatric-pulmonology clinic who underwent BCT using methacholine or adenosine between 2012 and 2018 due to ARRS. BCT was considered positive based on spirometry results and/or wheezing, desaturation, and tachypnea reactions. We collected data on demographics, BCT results, pre-BCT and post-BCT treatment changes, and 3-6 months post-BCT compliance and symptom control. The primary outcome measure was the change in treatment post-BCT (step-up or step-down)., Results: A total of 228 children (55% males) with a mean age of 4.2 ± 0.6 years underwent BCT (52% adenosine-BCT, 48% methacholine-BCT). Children referred for methacholine were significantly younger compared with adenosine (3.6 ± 1.2 vs. 4.2 ± 1.2 years, p < .01). Methacholine and adenosine BCTs were positive in 95% and 61%, respectively. Overall, changes in management were observed in 122 (53.5%) children following BCT, with 83 (36.4%) being stepped up and 37 (17%) being stepped down. Significantly more children in the methacholine group were stepped up compared with the adenosine group (46% vs. 28%, p = .004). During the follow-up assessment, we observed a clinical improvement in 119/162 (73.4%) of the children, with nearly 87% being compliant., Conclusion: This study demonstrates the importance of BCT in the management of preschool children presenting to pediatric pulmonary units with ARRS. The change in treatment and subsequent clinical improvement observed highlight the added value of BCT to the pulmonologist., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

A high proportion of house dust mite (HDM)-allergic asthmatics suffer from both an early asthmatic reaction (EAR) and a late asthmatic reaction (LAR) which follows it. In these patients, allergic inflammation is more relevant. MiRNAs have been shown to play an important role in the regulation of asthma's pathology. The aim of this study was to analyze the miRNA profile in patients with mild asthma and an HDM allergy after bronchial allergen provocation (BAP). Seventeen patients with EAR/no LAR and 17 patients with EAR plus LAR, determined by a significant fall in FEV1 after BAP, were differentially analyzed. As expected, patients with EAR plus LAR showed a more pronounced allergic inflammation and FEV1 delta drop after 24 h. NGS-miRNA analysis identified the down-regulation of miR-15a-5p, miR-15b-5p, and miR-374a-5p after BAP with the highest significance in patients with EAR plus LAR, which were negatively correlated with eNO and the maximum decrease in FEV1. These miRNAs have shared targets like CCND1 , VEGFA , and GSK3B , which are known to be involved in airway remodeling, basement membrane thickening, and Extracellular Matrix deposition. NGS-profiling identified miRNAs involved in the inflammatory response after BAP with HDM extract, which might be useful to predict a LAR.

Purpose: This retrospective study investigates the influence of overweight and obesity status on pulmonary function, airway inflammatory markers, and airway responsiveness in elderly asthma patients. Methods: Patients with asthma older than 65 years old who completed a bronchial provocation test (BPT) or bronchial dilation test (BDT) and a fractional exhaled nitric oxide (FeNO) test between December 2015 and June 2020 were identified retrospectively for this study. All of the patients were categorized into overweight/obesity and non-obesity groups based on their BMI. Pulmonary function test (PFT) and FeNO measurements were accomplished according to the 2014 recommendations of the Chinese National Guidelines of Pulmonary Function Test and American Thoracic Society/European Respiratory Society recommendations, respectively. Results: A total of 136 patients with an average age of 71.2 ± 5.40 years were identified. The average BMI was 23.8 ± 3.63, while the value of FeNO was 42.3 ± 38.4 parts per billion (ppb). In contrast to the non-obesity group, which had a value of 48.8 ± 43.1 ppb for FeNO, the overweight/obesity group had a significant lower value of 35.4 ± 31.4 ppb. There was no significant difference in the proportion of individuals with high airway hyperresponsiveness between the overweight/obesity and non-obesity groups (96 patients in total). Multiple linear regression analysis established an inverse correlation between FeNO and Provocation concentration causing a 20% fall in FEV 1 (PC20) but excluded significant relationships with age and BMI. The model's R is 0.289, and its p value is 0.045. Conclusion: The elderly Chinese Han asthmatics with overweight/obesity had lower FeNO levels than those with non-obese according to our findings. In addition, the FeNO level was inversely correlated between FeNO levels and PC20 in elderly asthmatics., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The role of early airway hyperresponsiveness (AHR) in the lung function of school-age children is currently unclear., Objective: To conduct a prospective follow-up study of lung function in schoolchildren with a history of lower airway symptoms and AHR to methacholine in early childhood and to compare the findings to schoolchildren with no previous or current lung diseases. We also explored symptoms and markers of type 2 inflammation., Methods: In 2004 to 2011, data on atopic markers, lung function, and AHR to methacholine were obtained from 193 symptomatic children under 3 years old. In 2016 to 2018, a follow-up sample of 84 children (median age, 11 years; IQR, 11-12) underwent measurements of atopic parameters, lung function, and AHR to methacholine. Moreover, in 2017 to 2018, 40 controls (median age, 11 years; IQR, 9-12) participated in the study., Results: Schoolchildren with early childhood lower airway symptoms and increased AHR had more frequent blood eosinophilia than their peers without increased AHR and lower prebronchodilator forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity Z-scores than those without increased AHR and controls. Post-bronchodilator values were not significantly different between the two AHR groups. Atopy in early childhood (defined as atopic eczema and at least 1 positive skin prick test result) was associated with subsequent lung function and atopic markers, but not AHR., Conclusion: In symptomatic young children, increased AHR was associated with subsequent obstructive lung function, which appeared reversible by bronchodilation, and blood eosinophilia, indicative of type 2 inflammation., Competing Interests: Disclosures The authors have no conflicts of interest to report., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: 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., Methods: 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., Results: 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)., Conclusion: Most of the patients with thunderstorm-associated respiratory symptoms had no obvious evidence of airflow limitation in spirometry., Competing Interests: None declared., (Copyright: © Iranian Journal of Medical Sciences.)

Rationale: Group 2 innate lymphoid cells (ILC2s) are critical for type 2 inflammation. In murine models of asthma, some ILC2s remain activated in the absence of epithelial cell-derived cytokine signaling, implicating alternate stimulatory pathways. DR3 (death receptor 3), a member of the tumor necrosis factor receptor superfamily, is expressed on ILC2s. Genome-wide association studies report an association between DR3 ligand, TL1A (tumor necrosis factor-like protein 1A), and chronic inflammatory conditions.Objectives: We investigated the TL1A/DR3 axis in airway ILC2 biology in eosinophilic asthma.Methods: Stable subjects with mild asthma were subject to allergen inhalation challenge, and DR3 expression on sputum cells was assessed. We investigated cytokine regulation of DR3 expression on ILC2s and steroid sensitivity. Airway TL1A was assessed in sputum from subjects with mild asthma and subjects with prednisone-dependent severe eosinophilic asthma.Measurements and Main Results: There was a significant increase in sputum DR3+ ILC2s 24 hours after allergen challenge, and DR3 expression on ILC2s was upregulated by IL-2, IL-33, or TSLP in vitro. Stimulation with TL1A significantly increased IL-5 expression by ILC2s and was attenuated by dexamethasone, an effect that was negated in the presence of TSLP. Airway TL1A levels were increased 24 hours after allergen challenge in subjects with mild asthma but were significantly greater in those with severe eosinophilic asthma. The highest levels were detected in subjects with severe asthma with airway autoimmune responses. C1q+ immune complexes from the sputa of subjects with severe asthma with high autoantibody levels stimulated TL1A production by monocytes.Conclusions: The TL1A/DR3 axis is a costimulator of ILC2s in asthma, particularly in the airways of patients with a predisposition to autoimmune responses. [ABSTRACT FROM AUTHOR]

Background: In patients with a history suggestive of asthma, diagnosis is usually confirmed by spirometry with bronchodilator response (BDR) or confirmatory methacholine challenge testing (MCT).Research Question: We examined the proportion of participants with negative BDR testing who had a positive MCT (and its predictors) result and characteristics of MCT, including effects of controller medication tapering and temporal variability (and predictors of MCT result change), and concordance between MCT and pulmonologist asthma diagnosis.Study Design and Methods: Adults with self-reported physician-diagnosed asthma were recruited by random-digit dialing across Canada. Subjects performed spirometry with BDR testing and returned for MCT if testing was nondiagnostic for asthma. Subjects on controllers underwent medication tapering with serial MCTs over 3 to 6 weeks. Subjects with a negative MCT (the provocative concentration of methacholine that results in a 20% drop in FEV1 [PC20] > 8 mg/mL) off medications were examined by a pulmonologist and had serial MCTs after 6 and 12 months.Results: Of 500 subjects (50.5 ± 16.6 years old, 68.0% female) with a negative BDR test for asthma, 215 (43.0%) had a positive MCT. Subjects with prebronchodilator airflow limitation were more likely to have a positive MCT (OR, 1.90; 95% CI, 1.17-3.04). MCT converted from negative to positive, with medication tapering in 18 of 94 (19.1%) participants, and spontaneously over time in 25 of 165 (15.2%) participants. Of 231 subjects with negative MCT, 28 (12.1%) subsequently received an asthma diagnosis from a pulmonologist.Interpretation: In subjects with a self-reported physician diagnosis of asthma, absence of bronchodilator reversibility had a negative predictive value of only 57% to exclude asthma. A finding of spirometric airflow limitation significantly increased chances of asthma. MCT results varied with medication taper and over time, and pulmonologists were sometimes prepared to give a clinical diagnosis of asthma despite negative MCT. Correspondingly, in patients for whom a high clinical suspicion of asthma exists, repeat testing appears to be warranted. [ABSTRACT FROM AUTHOR]

Background. Efficacy of allergen immunotherapy (AIT) in local allergic rhinitis (LAR) is a new subject of research. The presence of asthmatic symptoms in patients with LAR in the context of AIT is unexplored. Objective. The efficacy and safety of AIT in patients with LAR towards birch pollen were investigated. The possibility of concomitant local allergic asthma in studied patients and the impact of AIT on it were examined. Methods. 36 patients with LAR towards birch were included in three years of AIT in a double-blind, placebo-control study. Primary outcome measurement was the mean changes in the combined symptom and medication scores (CSMSs) after AIT, and the second is the changes in the quality of life (QoL). Skin prick tests, serum, nasal allergen-specific IgE to birch, nasal and bronchial provocation challenge tests with birch allergen, methacholine tests, and spirometry were carried out at baseline and after AIT. Results. Mean CSMSs of three years of AIT were significantly decreased in the active group from 5.88 (range: 4.11-9.01) to 1.98 (range: 1.22-4.51; p < 0.05). After three years of AIT, there was a significant increase of toleration for birch allergen from the mean concentration of 6250 ± 1200 SQ-U/ml up to 45000 ± 2500 SQ-U/ml (p = 0.02) during repeated nasal challenges. 16 patients with LAR had the positive results of methacholine tests, and 11 of them had a positive bronchial challenge to birch allergen. After AIT, the significant decrease of bronchial responsiveness to birch allergen in 5 from 7 patients was confirmed (p = 0.03). QoL assessed by the use of the RQLQ score was improved after AIT from 1.84 (95% CI: 1.53-1.97) to 1.45 (95% CI: 1.32-1.62) score in the active group after three years of AIT therapy (p = 0.03). Conclusion. AIT to birch can be useful and safe in a patient with local allergic rhinitis and also with concomitant asthmatic symptoms. Further studies are needed. [ABSTRACT FROM AUTHOR]

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

Clinical testing of bronchial hyperreactivity (BHR) provides valuable information in asthma diagnostics. Nevertheless, the test results depend to a great extent on the testing procedure: test substance, apparatus and protocol. In Nordic countries, three protocols predominate in the testing field: Per Malmberg, Nieminen and Sovijärvi methods. However, knowledge of their equivalence is limited. We aimed to find equivalent provocative doses (PD) to obtain similar bronchoconstrictive responses for the three protocols. We recruited 31 patients with suspected asthma and health care workers and performed BHR testing with methacholine according to Malmberg and Nieminen methods, and with histamine according to Sovijärvi. We obtained the individual response-dose slopes for each method and predicted equivalent PD values. Applying a mixed-model, we found significant differences in the mean (standard error of mean) response-dose (forced expiratory volume in one second (FEV1)%/mg): Sovijärvi 7.2 (1.5), Nieminen 13.8 (4.2) and Malmberg 26 (7.3). We found that the earlier reported cut-point values for moderate BHR and marked BHR between the Sovijärvi (PD15) and Nieminen (PD20) methods were similar, but with the Malmberg method a significant bronchoconstrictive reaction was measured with lower PD20 values. We obtained a relationship between slope values and PD (mg) between different methods, useful in epidemiological research and clinical practice. [ABSTRACT FROM AUTHOR]

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

Background: The respiratory duty cycle (Ti/Ttot) can influence bronchoprovocation test results and nebulized drug delivery. The Ti/Ttot has not yet been examined in individuals with airway hyperresponsiveness (AHR) in typical bronchoprovocation test conditions. This study investigated the mean Ti/Ttot in participants with and without AHR and whether the Ti/Ttot changes with increasing bronchoconstriction.Methods: Fifteen participants with AHR and fifteen participants without AHR completed this randomized crossover study. An ultrasonic spirometer was used for continuous measurement of the Ti/Ttot as participants inhaled room air or aerosolized solution. Each participant completed two methacholine challenges, one using a continuous-output vibrating mesh nebulizer/ultrasonic spirometer and one with the nebulizer only. Prior to each methacholine challenge, participants inhaled room air and aerosolized saline through the nebulizer/spirometer setup to record baseline Ti/Ttot data.Results: The mean Ti/Ttot findings [95% CIs] during room air inhalation were 0.392 [0.378-0.406] and 0.447 [0.426-0.468] in participants with and without AHR, respectively (P < .001). The mean Ti/Ttot during saline inhalation were 0.389 [0.373-0.405] and 0.424 [0.398-0.450] in participants with and without AHR (P = .040). The Ti/Ttot showed a nonsignificant downward trend with progressive methacholine-induced bronchoconstriction.Conclusions: The mean Ti/Ttot in participants with AHR closely resembles the assumed Ti/Ttot of 0.40 recommended for standard use when calculating methacholine challenge results. Since the Ti/Ttot did not change significantly over the course of a methacholine challenge, the same Ti/Ttot can be used to calculate the dose of methacholine inhaled, regardless of the level of bronchoconstriction.Trial Registry: ClinicalTrials.gov; No.: NCT03505489; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Background: Various trajectories for lung function and bronchial hyper‐reactivity (BHR) from early childhood to adulthood are described, including puberty as a period with excessive lung growth. Bronchiolitis in infancy may be associated with increased risk of developing chronic obstructive pulmonary disease, but the development of respiratory patterns during puberty is poorly characterized for these children. We aimed to study the development and trajectories of lung function and BHR from 11 to 18 years of age in children hospitalized for bronchiolitis in infancy. Methods: Infants hospitalized for bronchiolitis at the University Hospitals in Stavanger and Bergen, Norway, during 1997‐1998, and an age‐matched control group, were included in a longitudinal follow‐up study and examined at 11 and 18 years of age with spirometry and methacholine provocation test (MPT). The MPT data were managed as dose‐response slope (DRS) in the statistical analyses. Changes in lung function and DRS from 11 to 18 years of age were analyzed by generalized estimating equations, including interaction terms. Results: z‐scores for forced vital capacity (FVC), forced expiratory volume in first second (FEV1), FEV1/FVC ratio, and DRS were not different from 11 to 18 years of age in both the post‐bronchiolitis and the control group. The trajectories from 11 to 18 years did not differ between the two groups. BHR at age 11 was independently associated with asthma at age 18. Conclusion: Children hospitalized for bronchiolitis had stable predicted lung function and BHR from 11 to 18 years of age. The lung function trajectories were not different from controls. [ABSTRACT FROM AUTHOR]

Aim: To examine the pathogenesis and clinical presentation of sports-related femoroacetabular impingement (SRFAI) in a large consecutive series of symptomatic athletes. Methods: Between January 2009 and February 2017 prospectively collected data from competitive athletes within the Gaelic Athletic Association (GAA), and who subsequently underwent arthroscopic treatment for symptomatic FAI, were analysed. Data was collected using internationally validated health questionnaires (Harris Hip Score, UCLA, SF-36, WOMAC) and recognised clinical (ROM, symptom presentation, provocation tests) and radiological (AP pelvis, Dunn, False profile) indicators/measures of FAI. Results: A total of 1021 consecutive cases (mean 26.6 ± 6.2 years) were included. In every case, conservative treatment failed to resolve symptoms with athletes attending an average of 2.4 ± 1.1 health care professionals prior to referral. Symptoms developed gradually (78%) and consisted primarily of groin pain (76.1%) and hip stiffness (76.5%) following activity. An acetabular rim deformity (pincer) was present in all cases; a cam deformity in 72.1%. The prevalence and degree of cam deformity increased with progressing age groups (p < 0.001); mean lateral centre-edge angle remained static (p = 0.456). Increasing CEA, alpha angle and presence of rim fracture was associated with a reduction in all ranges of hip movement (p < 0.001). Conclusion: Symptomatic SRFAI presented in this large series of GAA athletes failed to resolve with non-operative treatment. Increasing hip deformity resulted in poorer ROM. Abnormal acetabular morphology remains static with increasing athletic age while cam deformity is progressive and most likely a secondary pathology. [ABSTRACT FROM AUTHOR]

Background: Fractional exhaled nitric oxide (FeNO) is a non-invasive biomarker for airway eosinophilic inflammation. However, the clinical value of ultrahigh FeNO (≥100 parts per billion (ppb)) in predicting asthma is never explored. We aimed to investigate the value of ultrahigh FeNO as a predictor of bronchial hyperresponsiveness (BHR), an important index for asthma diagnosis.Methods: A retrospective cohort study was conducted on 259 patients with suspected asthma who received the examination of FeNO, spirometry, bronchial provocation test (BPT) and differential cell count of induced sputum. Patients were stratified by FeNO value: ultrahigh (group A:≥100 ppb), high (group B: 50-99 ppb), intermediate (group C: 26-49 ppb) and normal (group D:≤25 ppb). The positive rates of BPT and sputum eosinophils percentage (Eos%) were compared among four cohorts. The correlations between FeNO and sputum Eos% were measured.Results: A significant higher positive rate of BPT was observed in group A (90.91%) than all others (B: 51.43%, C: 31.43%, D: 28.13%, all p<0.01). Referring to group D, the ORs of positive BPT in groups A, B and C were 26.84, 2.84 and 1.05. Sputum Eos% in group A (19.75 (7.00, 46.25)) is higher than that in others (B: 3.50 (1.00, 12.75), C: 1.13 (0.06,3.50), D: 0.50 (0.00, 2.13)). FeNO correlates with sputum Eos% in groups A and B, but not group C or D.Conclusions: Ultrahigh FeNO correlates with BHR and could serve as a practical alternative to methacholine challenge to support an asthma diagnosis in patients with suspected asthma in primary care. [ABSTRACT FROM AUTHOR]

BackgroundThe pulmonary surfactant protein (SP)-A has potent immunomodulatory activities but its role and regulation during allergic airway inflammation is unknown.MethodsWe studied changes in SP-A expression in the bronchoalveolar lavage (BAL) using a murine model of single Aspergillus fumigatus (Af) challenge of sensitized animals.ResultsSP-A protein levels in the BAL fluid showed a rapid, transient decline that reached the lowest values (25% of controls) 12 h after intranasal Af provocation of sensitized mice. Decrease of SP-A was associated with influx of inflammatory cells and increase of IL-4 and IL-5 mRNA and protein levels. Since levels of SP-A showed a significant negative correlation with these BAL cytokines (but not with IFN-gamma), we hypothesized that SP-A exerts an inhibitory effect on Th2-type immune responses. To study this hypothesis, we used an in vitro Af-rechallenge model. Af-induced lymphocyte proliferation of cells isolated from sensitized mice was inhibited in a dose-dependent manner by addition of purified human SP-A (0.1-10 microg/ml). Flow cytometric studies on Af-stimulated lymphocytes indicated that the numbers of CD4+ (but not CD8+) T cells were significantly increased in the parental population and decreased in the third and fourth generation in the presence of SP-A. Further, addition of SP-A to the tissue culture inhibited Af-induced IL-4 and IL-5 production suggesting that SP-A directly suppressed allergen-stimulated CD4+ T cell function.ConclusionWe speculate that a transient lack of this lung collectin following allergen exposure of the airways may significantly contribute to the development of a T-cell dependent allergic immune response.

Background/Aim. Impulse oscillometry (IOS) is a technique valid for measuring the lung function in obstructive lung diseases and bronchial provocation tests. However, no consensus exists for its use. The aim of the study was to assess impulse oscillometry sensitivity for detection of early airways changes during bronchial provocation testing and to compare with changes obtained with spirometry and bodyplethysmography in male army recruits. Methods. Male military recruits were submitted to bronchial provocation test with histamine by the aerosol provocation system. Out of 52 male military recruits subjected to attempts to make the diagnosis of asthma the study included 31 subjects with fall of forced expiratory volume in one second (FEV1) above 20%. The changes of impulse oscillometry were measured one step before and after provocation dose (PD) of histamine and compared with the changes of bodyplethysmography and spirometry. Results. The average age of male army recruits was 23.3 year. After bronchoprovocation there was an average increase of the total resistance at 5 Hz (R5) by 66.6%, resonant frequency (Fres) by 102.2%, Goldman index (AX) by 912.1%, the arway resistance (Raw) by 121.5%, and a decrease in reactance at 5 Hz (X5) by 132.1% and FEV1 by 25.6%. One step before the last inhaled of PD20 there was an average increase of 26.7% in R5, 24.1% in Fres, 85.3% in AX, 11.9% in Raw and a decrease in X5 by 26.9% and FEV1 by 4.3%. A correlation between impulse oscillometry and bodyplethysmography parameters was obtained. Conclusion. This paper demonstrates a sufficient sensitivity of impulse oscillometry to detect changes in airways, so it may play a complementary role in the diagnosis of asthma in male military recruits.

Objectives Chronic rhinosinusitis (CRS) is common disease in otorhinolaryngology and will lead to lower airway abnormality. However, the only lung function in CRS patients and associated factors have not been much studied. Methods One hundred patients with CRS with nasal polyps (CRSwNP group), 40 patients with CRS without nasal polyps (CRSsNP group), and 100 patients without CRS were enrolled. The difference in lung function was compared. Meanwhile, CRSwNP and CRSsNP group were required to undergo a bronchial provocation or dilation test. Additionally, subjective and objective outcomes were measured by the visual analogue scale (VAS), 20-item Sino-Nasal Outcome Test (SNOT-20), Lund-Mackay score, Lund-Kennedy endoscopic score. The correlation and regression methods were used to analyze the relationship between their lung function and the above parameters. Results The forced expiratory volume in 1 second (FEV1) and forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75) of CRSwNP group were significantly lower than other groups (P