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Background: Some studies have suggested that the forced expiratory flow between 25 and 75% of vital capacity (FEF25-75) can be used as an early marker of bronchial hyperresponsiveness (BHR) in asthma and allergic rhinitis (AR), but is highly variable. Here, we aimed to assess whether the FEF25-75 can be used to diagnose BHR in patients with asthma-like symptoms and AR. Methods: PubMed, EMBASE, Web of Science, Wiley Online Library, Cochrane Library, SinoMed, CNKI, and Wanfang Data were searched to acquire eligible studies. Articles published before 30 Sep 2023 were included. Quality Assessment of Diagnostic Accuracy Studies 2 was used to evaluate the risk of bias and application concern of the included articles. Data were pooled using random-effects models. The univariable meta-regression and subgroup analyses were used to explore the sources of heterogeneity. Results: Twenty-five studies were included, describing 12,310 patients with asthma-like symptoms and AR. In terms of the FEF25-75, the pooled sensitivity and specificity were 0.56(95% CI 0.47–0.65) and 0.86 (95% CI 0.80–0.90), respectively. In addition, the pooled diagnostic odds ratio (DOR) was 8.00 (95% CI 6–10) and the area under the curve (AUC) was 0.80 (95% CI 0.76–0.83). Furthermore, we performed the univariable meta-regression and subgroup analyses, indicating that the disease types and ethnicity may be the sources of heterogeneity. Conclusion: This meta-analysis showed that if BPT cannot be performed a value of FEF25-75 < 65% of predicted may suggest the presence of BHR in patients with suspected asthma and /or AR. [ABSTRACT FROM AUTHOR]

Purpose: Inhaled mannitol induces bronchoconstriction and cough. This study aimed to describe the cough response to mannitol among healthy adult subjects. Methods: 125 healthy subjects (aged 18–82 years, 52% females, 50% skin prick test positive) underwent a mannitol test. The coughs were recorded both simultaneously and afterwards from video recordings by two researchers. Three indices were evaluated: The cumulative number of coughs per cumulative dose of mannitol (CDR), cumulative provocative dose of mannitol to cause at least 5 coughs, and the maximal number of coughs provoked by any single mannitol dose. The test was repeated in 26 subjects after 3–7 days. Results: CDR showed the best repeatability with an intraclass correlation coefficient of 0.829. Gender was the only characteristics that associated with the cough response: The median CDR was 2.53 (interquartile range 0.45–7.01) coughs/100 mg among females and 0.787 (0.0–3.29) coughs/100 mg among males (p = 0.002). The interquartile range upper limits were defined as the cut-off limits for a normal response. The threshold for a statistically significant change in CDR was 6.26 coughs/100 mg. There was a close correlation between simultaneous- and video-assessed CDR (intraclass correlation coefficient 0.985). Conclusion: Females cough more than males in response to mannitol. CDR is the most suitable index to describe the cough responsiveness. The repeatability of the response is good. Video recording of the coughs is not mandatory. The cut-off limits for a normal cough response to mannitol were provided. [ABSTRACT FROM AUTHOR]

Introduction: While the phenotypic diversity of childhood wheezing is well described, the subsequent life course of such phenotypes and their adult outcomes remain poorly understood. We hypothesized that different childhood wheezing phenotypes have varying longitudinal outcomes at age 26. We sought to identify factors associated with wheezing persistence, clinical remission, and new onset in adulthood. Methods: Participants were seen at birth and at 1, 2, 4, 10, 18, and 26 years in the Isle of Wight Birth Cohort (n = 1456). Information was collected prospectively on wheeze prevalence and phenotypic characteristics at each assessment. Wheeze phenotypes at 10 years were defined as participants wheezing (CW10) or not wheezing at 10 (CNW10). Multivariable regression analyses were undertaken to identify factors associated with wheezing persistence/remission in CW10 and wheeze development in CNW10 at age 26 years. Results: Childhood wheezing phenotypes showed different subsequent outcomes and associated risk factors. Adult wheeze developed in 17.8% of CNW10. Factors independently associated with adult wheeze development in CNW10 included eczema at age 4 years, family history of rhinitis, and parental smoking at birth. Conversely, 56.1% of CW10 had remission of wheeze by 26 years. Factors predicting adult wheezing remission in CW10 included absence of both atopy at age 4 years and family history of rhinitis. Conclusion: Early-life factors influence adult outcomes for childhood wheezing phenotypes, both with respect to later development of adult wheezing in asymptomatic participants and of wheeze remission in childhood wheezers. This suggests potential areas that could be targeted by early-life interventions to alleviate adult disease burden. [ABSTRACT FROM AUTHOR]

Background: The effect of inhaled corticosteroids (ICS) in stable cases of bronchiectasis without hyperresponsiveness has not been studied. The objective of the study was to assess the effect of inhaled fluticasone 500 µg twice daily on health-related quality of life (HRQoL), pulmonary function, and frequency of exacerbations in stable patients of bronchiectasis without bronchial hyperresponsiveness (BHR) diagnosed by indirect bronchoprovocation test. Materials and Methods: It was a pilot study with an open-label randomized control design conducted in a Tertiary Care Chest Hospital, with 40 patients in each arm. Bronchiectasis was diagnosed by high-resolution computed tomography chest. Patients with BHR were excluded by performing an indirect bronchoprovocation test using inhaled adenosine monophosphate. Eighty patients meeting the inclusion criteria were randomized into intervention group (IG) receiving 500 µg fluticasone propionate twice a day and control group (CG) receiving standard care without ICS. Both groups were assessed monthly till 6 months. Clinical data (mainly forced expiratory volume in 1st s [FEV1], number of exacerbations, HRQoL by St. George respiratory questionnaire (SGRQ) was collected at baseline and end of 6 months. Results: Eighty (IG - 40, CG - 40) patients of stable state noncystic fibrosis bronchiectasis completed the study. The mean age in our study was IG 49.7 ± 17.6 vs. CG 49.9 ± 16.6, males IG 62.5% vs. CG 60%, most common etiology was tuberculosis IG 40% (16/40) vs CG 37.5% (15/40). Difference in SGRQ score (baseline end of treatment) IG 5.47 vs. CG 1.65 (p = 0.00). Difference in FEV1 IG 0.054L vs. CG 0.004L (P = 0.00), mean number of exacerbations at end of treatment IG – 1 ± 0.9 vs. CG 1.2 ± 1.1. Conclusion: Patients with stable bronchiectasis without BHR, treated with inhaled fluticasone 500 µg twice daily for 6 months showed a clinically significant improvement in HRQoL. No statistically significant difference was seen in pulmonary function and frequency of exacerbations.

Printer- and copier-emitted particles have been associated with respiratory, cardiovascular, autoimmune disorders and chronic fatigue syndrome. Clinicians should consider printer-emitted particles exposure in patients with such disorders, particularly those working in copy centers, and recommend exposure control. Objectives: This study aimed to document adverse health effects among office, copy, and print shop workers using the Nano-Control, International Foundation Survey. Methods: Self-reported information on 16 health outcomes and three surrogate exposure variables were collected from 1998 individuals between 1999 and 2010. Logistic regression models, adjusted for age, gender, and smoking status, assessed the association between printer exposure and health symptoms. Results: Among the participants, 61.9% were office workers, 5.5% were technicians, and 23.3% held other professions. Technicians had a higher risk for cancer compared to office workers (odds ratio [OR], 2.5; P < 0.01). Visible toner dust exposure was associated with chronic fatigue (OR, 9.6; P < 0.01), bronchial hyperresponsiveness (OR, 5.1; P < 0.01), cardiovascular diseases (OR, 3.6; P < 0.01), asthma, allergies, and other diseases (OR range, 1.4–3.2; P < 0.01). Conclusions: The increased chronic and acute health risks among these workers warrant further investigations of causal associations. [ABSTRACT FROM AUTHOR]

Probiotics should be administered in adequate amounts to confer health benefits. Probiotic dose–response studies are still missing. Saccharomyces cerevisiae UFMG A-905 prevented asthma development; however, the ideal dose has not been investigated. We evaluated the optimal dose and administration regimen of S. cerevisiae UFMG A-905 in the prevention of asthma. Male Balb/c mice were sensitized intraperitoneally with ovalbumin (OVA) and challenged with OVA intranasally. Mice received, via gavage, daily or alternate-day S. cerevisiae UFMG A-905. In daily regimen, different concentrations (107, 108, or 109 CFU/mL) were given 10 days before OVA sensitization and during challenges. In alternate-day regimen, a concentration of 109 CFU/mL was administered three times per week for 5 weeks, starting 2 weeks prior to the first sensitization. After the last challenge, in vivo bronchial hyperresponsiveness and airway and lung inflammation were assessed. OVA-challenged mice, when compared to saline-challenged mice, presented a significant increase in bronchial hyperresponsiveness and airway and lung inflammation. Daily and alternate-day administration of 109 CFU/mL of S. cerevisiae UFMG A-905 significantly reduced bronchial hyperresponsiveness; lower concentrations of S. cerevisiae UFMG A-905 did not significantly reduce bronchial hyperresponsiveness. Daily regimen with the highest concentration significantly reduced total cell number, eosinophil count in the BAL, and the levels of IL-4, IL-5, and IL-13. Daily administration of S. cerevisiae UFMG A-905 at 107 and 108 CFU/mL and alternate-day regimen did not significantly decrease airway and lung inflammation. S. cerevisiae UFMG A-905 led to a significant attenuation of bronchial hyperresponsiveness and lung inflammation in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

Background: Significant risk factors for persistence of asthma later in life are family history of allergies, early allergic sensitization and bronchial hyperresponsiveness (BHR). The evolution of BHR in young children without allergic sensitization and with house dust mite allergy (HDM) was investigated. Methods: In this retrospective analysis, electronic charts of 4850 young children with asthma and wheezy bronchitis between 2005 and 2018 were reviewed in order to study all patients ≤6 years with BHR assessed by methacholine provocation tests (MCT) at least once (n = 1175). Patients with more than two follow‐up measurements were divided in group 1 (no allergic sensitization; n = 110) and group 2 (HDM allergy; n = 88). Additionally, skin prick test, exhaled nitrite oxide (eNO), and asthma treatment were analyzed. Results: Forty‐seven patients of group 1 aged median 4.3 years and 48 patients of group 2 aged median 4.7 years showed initially severe BHR <0.1 mg. At follow‐up, patients with HDM were more likely to show persistence of severe BHR than non‐sensitized patients (severe BHR group 1: n = 5 (10.6%) vs. group 2: n = 21 (43.8%), p <.001). In addition, 89.4% of group 1 had mild to moderate or no BHR, compared to only 56.2% of group 2. There was a significant difference in eN0 (median group 1: 9 ppb vs. group 2: 26 ppb, p <.001), at last follow‐up. Age, sex, and asthma therapy had no effect on BHR. Conclusion: In young children without sensitization BHR normalizes, whereas HDM allergy indicates a persistence of asthma beyond infancy. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) is a relevant risk factor asthma as it may frequently precede asthma onset. There is evidence that lung function may be early impaired in AR patients. In this regard, the forced expiratory flow at 25%–75% of vital capacity (FEF25-75) could be a reliable marker of bronchial impairment in AR. Therefore, the present study investigated the practical role of FEF25-75 in young people with AR. The parameters included history, body mass index (BMI), lung function, bronchial hyperresponsiveness (BHR), and fractional exhaled nitric oxide (FeNO). This cross-sectional study included 759 patients (74 females and 685 males, mean age of 29.2 years) suffering from AR. The study demonstrated a significant association between low FEF25-75 values and BMI (OR 0.80), FEV1 (OR 1.29), FEV1/FVC (OR 1.71), and BHR (OR 0.11). Stratifying the patients on the basis of the presence (or absence) of BHR, sensitization to house dust mites (OR 1.81), AR duration (OR 1.08), FEF25-75 (OR 0.94), and FeNO (OR 1.08) were associated with BHR. Stratifying patients based on high FeNO values (>50 ppb), BHR was associated with high FeNO (OR 39). In conclusion, the present study showed that FEF25-75 was associated with low FEV1 and FEV1/FVC and BHR in AR patients. Therefore, spirometry should be considered in the long-term workup of patients with allergic rhinitis as impaired FEF25-75 might suggest an initial progression toward asthma. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the presence of underlying chronic airway disease in individuals with chronic cough and dyspnea lasting longer than eight weeks and who had previously Coronavirus disease 2019 (COVID-19) and had no known lung disease. Methods: A total of 151 patients admitted to the respiratory diseases outpatient room with the complaint of cough and/or dyspnea that persisted for at least eight weeks following COVID-19 infection were accrued to the study. Demographic characteristics, smoking history, the severity of lung involvement on chest computed tomography in the acute phase of Covid-19 infection, and bronchodilator reversibility test results were recorded. Smoking history and forced expiratory volume in the first second (FEV1) were compared. Results: FEV1 increase ≥ 200 ml was observed in 40 (26.5%) patients. In 24 (15.9%) patients, an increase in FEV1 was found to be 200 ml and above, and the percentage of FEV1 was 12% or more. While 14 (9.3%) patients were diagnosed with asthma, 13 (8.6%) patients were diagnosed with nonreversible airflow obstruction (NRAO), and 1 (0.7%) patient was diagnosed with chronic obstructive pulmonary disease (COPD). Conclusions: COVID-19 infection may play a vital role in initiating asthma pathogenesis. It should be kept in mind that viral infection-related asthma may be the underlying cause of prolonged cough and dyspnea after COVID-19 infection. [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]

Diisocyanates are a group of chemicals widely used in different industrial applications. The critical health effects related to diisocyanate exposure are isocyanate sensitisation, occupational asthma and bronchial hyperresponsiveness (BHR). Industrial air measurements and human biomonitoring (HBM) samples were gathered in specific occupational sectors to examine MDI, TDI, HDI and IPDI and the respective metabolites from Finnish screening studies. HBM data can give a more accurate picture of diisocyanate exposure, especially if workers have been exposed dermally or used respiratory protection. The HBM data were used for conducting a health impact assessment (HIA) in specific Finnish occupational sectors. For this purpose, exposure reconstruction was performed on the basis of HBM measurements of TDI and MDI exposures using a PBPK model, and a correlation equation was made for HDI exposure. Subsequently, the exposure estimates were compared to a previously published dose–response curve for excess BHR risk. The results showed that the mean and median diisocyanate exposure levels and HBM concentrations were low for all diisocyanates. In HIA, the excess risk of BHR from MDI exposure over a working life period was highest in the construction and motor and vehicle industries and repair sectors, resulting in estimated excess risks of BHR of 2.0% and 2.6%, and 113 and 244 extra BHR cases in Finland, respectively. Occupational exposure to diisocyanates must be monitored because a clear threshold for DI sensitisation cannot be established. [ABSTRACT FROM AUTHOR]

Background: Bronchial hyperresponsiveness (BHR) is a key feature of asthma. Compound D, an active compound in Phlai, can bind cysteinyl leukotrienes receptors that play a role for asthma treatment. Objective: To determine the effect of Phlai capsules on BHR measured by the methacholine challenge test. Materials and Methods: A randomized, double-blind, placebo-controlled, crossover study was conducted in adult asthmatic patients with partly controlled symptoms. Each patient received four weeks of treatment with either Phlai or placebo separated by a 2-week washout period. The main outcome was provocative concentration of methacholine causing a 20% drop in FEV₁ (PC₂₀). Asthma control test (ACT) scores, and fractional exhaled nitric oxide (FeNO) levels were secondary end points. Results: Thirty patients were randomly allocated to either the Phlai or the placebo group. All patients had allergic rhinitis and received inhaled corticosteroid and long-acting beta2-agonist (ICS/LABA) or ICS alone. Four weeks after treatment, mean PC₂₀ in the Phlai group was higher than in the placebo group at 9.76±1.56 mg/mL versus 6.05±1.65 mg/mL (p=0.151). The improvement of ACT scores in the Phlai group was significantly higher than in the placebo group. FeNO levels decreased after treatment in the Phlai group. All patients tolerated the treatment well and had no side effects. Conclusion: In adult asthmatic patients with partly controlled symptoms, concomitant treatment with Phlai capsules tended to decrease BHR and significantly improve symptom scores. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the safety of an abbreviated methacholine challenge test (MCT) protocol in children., Study Design: This prospective, observational study enrolled children aged 6 through 18 years referred for the MCT. The abbreviated protocol was initiated with a methacholine dose of 0.03 mg/ml and escalated in fourfold increments, unless the forced expiratory volume at 1 second decline exceeded 10%, at which point the next dose was only doubled. The safety of this abbreviated approach was assessed by monitoring adverse events, and specifically, decreases in forced expiratory volume at 1 second over 40%, hypoxemia, or uncontrollable cough. The number of methacholine doses and test duration were recorded and compared with estimated outcomes derived from the full-length MCT protocol., Results: One hundred twelve participants, aged 13.7 years (±3.3), successfully completed the protocol. Fifty-seven (51%) presented a positive MCT response. No significant clinical adverse events were observed. Of all participants, 2.7% exhibited an exaggerated response, in line with previously reported findings for the full-length protocol. The abbreviated approach resulted in an estimated average time-savings of 18:19 minutes per participant, thus reducing test length by 22:47 minutes for a negative MCT and by 14:34 minutes for a positive outcome., Conclusions: This abbreviated MCT protocol is safe for children and effectively shortens the duration of the MCT., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aleksandra Rybka-Fraczek, Marta Dabrowska, Elzbieta M Grabczak, Katarzyna Bialek-Gosk, Karolina Klimowicz, Olga Truba, Patrycja Nejman-Gryz, Magdalena Paplinska-Goryca, Rafal Krenke Department of Internal Medicine, Pulmonary Diseases and Allergy, Medical University of Warsaw, Warsaw, PolandCorrespondence: Marta Dabrowska, Tel +48 22 599 2599, Fax +48 22 599 1069, Email mdabrowska@mp.plBackground: Eosinophilic inflammatory phenotype was thought to be the most common phenotype of cough variant asthma (CVA), nevertheless other phenotypes were also reported.Purpose: The study aimed to analyze the inflammatory phenotypes of CVA in relation to treatment response to the stepwise anti-asthmatic treatment.Patients and Methods: The study included 45 patients with chronic cough (CC) and suspicion of CVA (normal chest X-ray, presence of bronchial hyperresponsiveness and no history of wheezing or dyspnea) in whom induced sputum was successfully collected. Based on the cellular composition of the sputum, patients were divided into major inflammatory phenotypes: eosinophilic, neutrophilic, paucigranulocytic or mixed granulocytic. A stepwise treatment, including inhaled corticosteroids with long-acting β2-agonist, montelukast and short-term therapy with prednisone was initiated. Good treatment response was defined as the reduction in cough severity at least 20 mm from the baseline in visual analogue scale and improvement in cough-related quality of life assessed by the Leicester cough questionnaire at least 1.3 points after any of three steps.Results: Finally, 40/45 (88.9%) patients improved after therapy. Eosinophilic asthma was found in 13/40 (32.5%) patients, neutrophilic in 6/40 (15.0%) and paucigranulocytic pattern in 21/40 (52.5%) patients. No one demonstrated a mixed granulocytic phenotype. The response to the treatment was similar in all groups. However, the reduction in cough severity was inversely related to the percentage of sputum neutrophils (r = − 0.44, P = 0.003). We showed that the percentage of neutrophils in sputum > 46% may be considered as a predictor of poor response to anti-asthmatic therapy.Conclusion: The diversity of inflammatory phenotypes with paucigranulocytic preponderance was found in subjects with CVA. The response to anti-asthmatic treatment in patients with CVA was not related to the inflammatory phenotype. High neutrophil count in sputum may predict poor response to anti-asthmatic therapy in patients with CC and bronchial hyperresponsiveness.Keywords: bronchial hyperresponsiveness, chronic cough, cough variant asthma, paucigranulocytic, neutrophils, sputum induction

Background: Bronchial hyperresponsiveness (BHR) and asthma are frequently present in children with food allergy. We assessed BHR in children receiving oral immunotherapy (OIT) for persistent egg or peanut allergy and examined whether OIT affects asthma control. Methods: Methacholine challenge testing was performed in 89 children with persistent egg or peanut allergy diagnosed by double‐blind, placebo‐controlled food challenge and 80 control children without food allergy. Of the 89 food‐allergic children, 50 started OIT for egg allergy and 39 for peanut allergy. Sensitization to aeroallergens was evaluated by skin prick testing. Forty of the 89 children with regular controller treatment for asthma underwent methacholine challenge testing and 34 measurement of exhaled nitric oxide (FeNO) at baseline and after 6–12 months of OIT. Results: Methacholine challenge testing revealed significant BHR in 29/50 children (58%) with egg allergy, 15/39 children (38%) with peanut allergy, and 6/80 controls (7.5%). The mean cumulative dose of methacholine causing a 20% fall in FEV1 differed significantly between the egg and peanut‐allergic versus the control children (1009 μg, 1104 μg, and 2068 μg, respectively, p < 0.001). Egg or peanut OIT did not affect lung function, the degree of BHR or FeNO levels in children with asthma and had no adverse effect on asthma control. Lung function or BHR did not associate with the OIT outcome. Conclusion: BHR was significantly more frequent in children with persistent egg or peanut allergy than in children without food allergy. Oral immunotherapy did not increase BHR and was safe for children on regular asthma medication. [ABSTRACT FROM AUTHOR]

Youlim Kim,1,&ast; Hyun Lee,2,&ast; Sung Jun Chung,2,&ast; Yoomi Yeo,2 Tai Sun Park,2 Dong Won Park,2 Kyung Hoon Min,3 Sang-Heon Kim,2 Tae-Hyung Kim,2 Jang Won Sohn,2 Ji-Yong Moon,2 Ho Joo Yoon2 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University Hospital, School of Medicine, Konkuk University, Seoul, Korea; 2Department of Internal Medicine, College of Medicine, Hanyang University, Seoul, Korea; 3Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University Medical Center, Guro Hospital, Seoul, Korea&ast;These authors contributed equally to this workCorrespondence: Ji-Yong MoonDepartment of Internal Medicine, Hanyang University Guri Hospital, Gyeongchun-ro 153, Guri-si, Gyeonggi-do, 11923, KoreaTel +82-31-560-2224Fax +82-31-553-7369Email respiry@gmail.comHo Joo YoonDivision of Pulmonary Medicine and Allergy, Department of Internal Medicine, Hanyang University College of Medicine, 222-1, Wangsimni-ro, Seongdong-gu, Seoul, 04763, KoreaTel +82-2-2290-8336Fax +82-2-2298-9183Email hjyoon@hanyang.ac.krBackground and Objective: Despite the usefulness of airway hyperresponsiveness (AHR) testing in diagnosing and monitoring asthma, it is challenging to perform in a real-world setting. Forced expiratory flow between 25% and 75% of vital capacity (FEF25– 75), a pulmonary measurement that can be obtained easily during routine spirometry, represents the status of medium-sized and small airways. However, the performance of FEF25– 75 in predicting AHR has not been well elucidated. Therefore, we investigated whether FEF25– 75 can predict AHR to mannitol.Methods: We performed a retrospective cohort study of 428 patients who visited a single clinic due to cough, wheezing, or dyspnea. All patients underwent spirometry with a mannitol provocation test. We compared the area under the curve (AUC) of the percentage of the predicted values of FEF25– 75 (FEF25– 75 %pred) with that of forced expiratory volume in 1 second (FEV1%pred), FEV1/forced vital capacity (FVC), and FEF25– 75/ FVC for predicting AHR.Results: The rate of AHR to mannitol was 20.3%. In the overall study population, the AUC of FEF25– 75 %pred for predicting AHR (0.772; 95% confidence interval [CI], 0.729– 0.811) was significantly higher than that of FEV1%pred (0.666; 95% CI, 0.619– 0.710; p < 0.001), FEV1/FVC (0.741; 95% CI, 0.697– 0.782; p = 0.047), and FEF25– 75/FVC (0.741, 95% CI = 0.696– 0.782, p = 0.046). The sensitivity, specificity, positive predictive value, and negative predictive value of FEF25– 75 %pred < 81% for predicting AHR in the overall study population were 77.0% (95% CI = 66.8– 85.4%), 63.9% (95% CI = 58.6– 69.0), 35.3%, and 91.6%, respectively. When we restricted the study group to subjects with normal lung function, the results were similar.Conclusion: Our results indicate that FEF25– 75 %pred can be used as a surrogate for predicting AHR in patients with respiratory symptoms.Keywords: forced expiratory flow between 25% and 75% of vital capacity, mannitol, bronchial hyperresponsiveness

Abstract Bronchial hyperresponsiveness is a typical, but non-specific feature of cough variant asthma (CVA). This study aimed to determine whether bronchial hyperresponsiveness may be considered as a predictor of CVA in non-smoking adults with chronic cough (CC). The study included 55 patients with CC and bronchial hyperresponsiveness confirmed in the methacholine provocation test, in whom an anti-asthmatic, gradually intensified treatment was introduced. The diagnosis of CVA was established if the improvement in cough severity and cough-related quality of life in LCQ were noted.The study showed a high positive predictive value of bronchial hyperresponsiveness in this population. Cough severity and cough related quality of life were not related to the severity of bronchial hyperresponsiveness in CVA patients. A poor treatment outcome was related to a low baseline capsaicin threshold and the occurrence of gastroesophageal reflux-related symptoms. In conclusion, bronchial hyperresponsiveness could be considered as a predictor of cough variant asthma in non-smoking adults with CC.

Exposure to particulate matter (PM 10) can induce respiratory diseases that are closely related to bronchial hyperresponsiveness. However, the involved mechanism remains to be fully elucidated. This study aimed to demonstrate the effects of PM 10 on the acetylcholine muscarinic 3 receptor (CHRM3) expression and the role of the ERK1/2 pathway in rat bronchial smooth muscle. A whole-body PM 10 exposure system was used to stimulate bronchial hyperresponsiveness in rats for 2 and 4 months, accompanied by MEK1/2 inhibitor U0126 injection. The whole-body plethysmography system and myography were used to detect the pulmonary and bronchoconstrictor function, respectively. The mRNA and protein levels were determined by Western blotting, qPCR, and immunofluorescence. Enzyme-linked immunosorbent assay was used to detect the inflammatory cytokines. Compared with the filtered air group, 4 months of PM 10 exposure significantly increased CHRM3-mediated pulmonary function and bronchial constriction, elevated CHRM3 mRNA and protein expression levels on bronchial smooth muscle, then induced bronchial hyperreactivity. Additionally, 4 months of PM 10 exposure caused an increase in ERK1/2 phosphorylation and increased the secretion of inflammatory factors in bronchoalveolar lavage fluid. Treatment with the MEK1/2 inhibitor, U0126 inhibited the PM 10 exposure-induced phosphorylation of the ERK1/2 pathway, thereby reducing the PM 10 exposure-induced upregulation of CHRM3 in bronchial smooth muscle and CHRM3-mediated bronchoconstriction. U0126 could rescue PM 10 exposure-induced pathological changes in the bronchus. In conclusion, PM 10 exposure can induce bronchial hyperresponsiveness in rats by upregulating CHRM3, and the ERK1/2 pathway may be involved in this process. These findings could reveal a potential therapeutic target for air pollution induced respiratory diseases. [Display omitted] • PM 10 exposure can cause pulmonary dysfunction in rats. • PM 10 can upregulate CHRM3, thereby induce bronchial hyperresponsiveness. • U0126 can rescue bronchial hyperresponsiveness caused by PM 10 -upregualted CHRM3. • U0126 can decrease the bronchial pathological of PM 10 exposure rats. [ABSTRACT FROM AUTHOR]

Background Bronchial hyperresponsiveness (BHR), an important physiological feature of asthma, is a prognostic marker of childhood asthma. Purpose We aimed to investigate the factors associated with BHR in adolescents with childhood asthma. Methods Two hundred and fifteen adolescents (≥13 years of age; 149 males, 66 females) who were diagnosed with asthma during childhood were enrolled, underwent methacholine challenge tests, and were divided into the BHR group (

Evaluation of airway inflammation and dysfunction is important in management of allergic rhinitis (AR) since AR is a risk factor for developing asthma. Theoretical nonlinear modeling of exhaled nitric oxide (NO) has revealed extended flow-independent NO parameters that could explain where or how NO metabolism was altered. We aimed to evaluate the association between extended NO parameters and bronchial hyperresponsiveness (BHR) in children with AR. Exhaled NO was measured in 74 children with AR on the same day they underwent the provocholine challenge test (PCT). Extended NO was measured in three different exhaled flow rates (30, 100, 200 mL/s) and calculated using the Högman–Meriläinen model. We compared the extended NO parameters including bronchial NO (JawNO), airway tissue NO (CawNO), alveolar tissue NO (CaNO), and diffusing capacity of NO (DawNO) between AR with and without BHR groups, and analyzed the correlation between extended NO parameters and the response–dose ratio (RDR) of the PCT. We additionally evaluated 49 respiratory healthy controls. Among the 74 children with AR, nine showed BHR. JawNO increased more in children with AR than the control group. In children with AR, JawNO was higher in the AR with BHR than without BHR group, and was correlated positively with log RDR (r = 0.373, p =.001). Extended NO analysis including JawNO can be a useful tool for assessing BHR in AR. [ABSTRACT FROM AUTHOR]

If allergen immunotherapy (AIT) is to be considered as a treatment option for allergic asthma, it must undergo the same developmental steps as other antiasthmatic drugs. The bronchial allergen challenge model has demonstrated excellent negative predictive value for the development of new therapies for asthma. Subcutaneous immunotherapy appears to have a clinical and significant effect on the early asthmatic response to mite, cat, and birch and grass pollens in children and adults. Use of AIT in children with asthma is widely practiced but not supported by as strong a level of evidence as in adults. House dust mite sublingual immunotherapy tablets demonstrate efficacy in asthma exacerbations and other outcomes when used as add-on therapy in adult patients. Using a biologic to improve the patient's lung functions and asthma control before initiating AIT can transform unsuitable candidates for AIT into appropriate candidates. Because AIT is a form of personalized medicine, phenotyping the most suitable patient is necessary. Field studies of adults and children have suggested that polysensitized patients with rhinitis and Global Initiative for Asthma class 2 to class 4 asthma appear the most likely to be good responders. We hypothesized that AIT responders are those who demonstrate a high eosinophilic response to natural or experimental exposure. [ABSTRACT FROM AUTHOR]

BackgroundMany patients with cystic fibrosis (CF) wheeze, and are dubbed as having CF-asthma. Understanding the determinants of such wheezing may avoid unnecessary treatments and open newer treatment avenues.ObjectivesMain: To evaluate the prevalence and characteristics of wheezing and a positive bronchodilatory response (BDR) in children with CF. Secondary: To identify the predictive markers and the impact of current wheezing a positive BDR.MethodsA retrospective single-center study in children with CF. We determined the characteristics of physician-reported wheeze in patients

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.

BackgroundThe AtyPical Asthma in China (APAC) cohort is a multi-center prospective, observational cohort set-up to investigate the clinical, pathophysiological features, prognosis, and mechanisms of cough variant asthma (CVA).ObjectivesTo present the characteristics of newly physician-diagnosed adults with CVA (n = 328) compared to mild-moderate classic asthma (CA, n = 206).Methods and Main ResultsCVA subjects showed a higher proportion of female (67.1 vs. 55.3%, P = 0.0084), abnormal laryngopharyngeal sensations (71 vs. 51%, p < 0.0001) than CA, but presented with near normal spirometry and higher methacholine PD20-FEV1 values [4.2 (1, 8.6) vs. 0.8 (0.4, 4.7), P < 0.0001]. Lower fractional exhaled nitric oxide (FENO) levels [38.5 (19.8, 72.5) vs. 53. (28.5, 92.2), P = 0.0019], blood eosinophil counts [0.2 (0.1, 0.4) vs. 0.3 (0.2, 0.5), P = 0.0014], and sputum eosinophils [2.3 (0.3, 8.0) vs. 12.2 (2, 34.5), p < 0.0001] were found in CVA. Despite lower total serum IgE levels in CVA, there was similar proportion of atopy in both groups. The prevalence of cough in CA was 86.4%, while CVA reported more severe cough on Visual Analog Scale, Cough Evaluation Test, and Leicester Cough Questionnaire, similar anxiety and depression scores but better asthma control scores as reflected by Asthma Control Test compared to CA. No correlation was found between cough assessment outcomes and sputum eosinophil count, blood eosinophil count, FENO, spirometry variables, or PD20-FEV1.ConclusionCough variant asthma is distinctive from classic asthma in regard to clinical features, lung function, and airway inflammation. Quality of life is badly impaired as well in spite of better asthma control scores.

Aim: The potential for immunotherapy to prevent asthma development has become a hot topic. This prompted us to revisit data from an early study that examined allergic sensitisation on bronchial hyperresponsiveness (BHR) in children with and without respiratory symptoms. Unlike previous studies, it used both indirect and direct test methods. Methods: The study was conducted in Kuopio, Finland, in 1994 and 247 children (55.1% boys) with a mean age 10.5 ± 1.7 years were recruited using a school survey: 165 with lower respiratory symptoms and 82 healthy controls. Each child underwent a 6‐min free‐running test and a methacholine test with a cumulative dose of 4900 µg. All participants underwent skin‐prick tests: 127were sensitised and 120 were non‐sensitised. Results: There were no significant differences in lung function between the sensitised and non‐sensitised children. However, sensitisation was associated with BHR which was measured by both the methacholine test (2400 µg versus >4900 µg, p < 0.001) and the free‐running test (−3.5% versus −2.6%, p = 0.042). No such differences were observed among the healthy controls. Sensitisation was a predictor of allergic diseases, and only multisensitisation to a minimum of four allergens increased the incidence of asthma. Conclusion: Allergic sensitisation did not affect BHR in children without respiratory symptoms. [ABSTRACT FROM AUTHOR]

Diisocyanates are a group of chemicals widely used in different industrial applications. The critical health effects related to diisocyanate exposure are isocyanate sensitisation, occupational asthma and bronchial hyperresponsiveness (BHR). Industrial air measurements and human biomonitoring (HBM) samples were gathered in specific occupational sectors to examine MDI, TDI, HDI and IPDI and the respective metabolites from Finnish screening studies. HBM data can give a more accurate picture of diisocyanate exposure, especially if workers have been exposed dermally or used respiratory protection. The HBM data were used for conducting a health impact assessment (HIA) in specific Finnish occupational sectors. For this purpose, exposure reconstruction was performed on the basis of HBM measurements of TDI and MDI exposures using a PBPK model, and a correlation equation was made for HDI exposure. Subsequently, the exposure estimates were compared to a previously published dose–response curve for excess BHR risk. The results showed that the mean and median diisocyanate exposure levels and HBM concentrations were low for all diisocyanates. In HIA, the excess risk of BHR from MDI exposure over a working life period was highest in the construction and motor and vehicle industries and repair sectors, resulting in estimated excess risks of BHR of 2.0% and 2.6%, and 113 and 244 extra BHR cases in Finland, respectively. Occupational exposure to diisocyanates must be monitored because a clear threshold for DI sensitisation cannot be established.

Background: It is still debatable whether dog ownership during early childhood is a risk factor for the development of allergic diseases. Objective: We investigated the association of dog ownership in early life with sensitization and asthma in childhood. Methods: Data from the Cohort for Childhood Origin of Asthma and Allergic diseases were used to investigate the association between dog ownership at any time from pregnancy to 1 year of age and sensitization to aeroallergens at 3 and 7 years old, bronchial hyperresponsiveness (BHR), and asthma at 7 years old. We analyzed the cytokine levels in cord blood (CB) and indoor environmental measurement concentrations in the mother's residence obtained at 36 weeks of pregnancy. Results: Sensitization to dogs at age 3 and 7 did not differ between dog ownership and nonownership, but dog ownership during early life decreased the risk of sensitization to aeroallergens at age 7 (aOR = 0.44, 95% CI 0.21–0.90). Dog ownership significantly increased the risk of nonatopic BHR (aOR = 2.86; 95% CI 1.32–6.21). In addition, dog ownership was associated with asthma, especially nonatopic asthma at 7 years old (aOR = 2.73, 95% CI 1.02–7.32; aOR = 7.05, 95% CI 1.85–26.90, respectively). There were no significant differences in the concentrations of IL-13 or interferon-γ in CB or indoor environmental measurements according to dog ownership during pregnancy. Conclusion: Early-life dog exposure in this birth cohort has been shown to reduce atopy but increase the risk of nonatopic BHR and nonatopic asthma at 7 years old. [ABSTRACT FROM AUTHOR]

The diagnosis 'bronchial asthma' spans different phenotypes of this disease like an umbrella. The differentiation of these phenotypes and their overlaps is becoming increasingly important, as the phenotype-specific treatment approaches of today are not effective with every form of asthma. These approaches include the strategy of allergen avoidance, allergen immunotherapy and, most importantly, the newly available biologics for asthma. Treatable disease patterns, so-called 'treatable traits', require targeted diagnostics. The knowledge necessary to identify these traits still needs to be established in practice. [ABSTRACT FROM AUTHOR]

Background and Objective: Despite the usefulness of airway hyperresponsiveness (AHR) testing in diagnosing and monitoring asthma, it is challenging to perform in a real-world setting. Forced expiratory flow between 25% and 75% of vital capacity (FEF25– 75), a pulmonary measurement that can be obtained easily during routine spirometry, represents the status of medium-sized and small airways. However, the performance of FEF25– 75 in predicting AHR has not been well elucidated. Therefore, we investigated whether FEF25– 75 can predict AHR to mannitol. Methods: We performed a retrospective cohort study of 428 patients who visited a single clinic due to cough, wheezing, or dyspnea. All patients underwent spirometry with a mannitol provocation test. We compared the area under the curve (AUC) of the percentage of the predicted values of FEF25– 75 (FEF25– 75 %pred) with that of forced expiratory volume in 1 second (FEV1%pred), FEV1/forced vital capacity (FVC), and FEF25– 75/ FVC for predicting AHR. Results: The rate of AHR to mannitol was 20.3%. In the overall study population, the AUC of FEF25– 75 %pred for predicting AHR (0.772; 95% confidence interval [CI], 0.729– 0.811) was significantly higher than that of FEV1%pred (0.666; 95% CI, 0.619– 0.710; p < 0.001), FEV1/FVC (0.741; 95% CI, 0.697– 0.782; p = 0.047), and FEF25– 75/FVC (0.741, 95% CI = 0.696– 0.782, p = 0.046). The sensitivity, specificity, positive predictive value, and negative predictive value of FEF25– 75 %pred < 81% for predicting AHR in the overall study population were 77.0% (95% CI = 66.8– 85.4%), 63.9% (95% CI = 58.6– 69.0), 35.3%, and 91.6%, respectively. When we restricted the study group to subjects with normal lung function, the results were similar. Conclusion: Our results indicate that FEF25– 75 %pred can be used as a surrogate for predicting AHR in patients with respiratory symptoms. [ABSTRACT FROM AUTHOR]

Exposure to particulate matter 2.5 (PM2.5) potentially triggers airway inflammation by activating nuclear factor-κB (NF-κB). Sirtuin 2 (SIRT2) is a key modulator in inflammation. However, the function and specific mechanisms of SIRT2 in PM2.5-induced airway inflammation are largely understudied. Therefore, this work investigated the mechanisms of SIRT2 in regulating the phosphorylation and acetylation of p65 influenced by PM2.5-induced airway inflammation and bronchial hyperresponsiveness. Results revealed that PM2.5 exposure lowered the expression and activity of SIRT2 in bronchial tissues. Subsequently, SIRT2 impairment promoted the phosphorylation and acetylation of p65 and activated the NF-κB signaling pathway. The activation of p65 triggered airway inflammation, increment of mucus secretion by goblet cells, and acceleration of tracheal stenosis. Meanwhile, p65 phosphorylation and acetylation, airway inflammation, and bronchial hyperresponsiveness were deteriorated in SIRT2 knockout mice exposed to PM2.5. Triptolide (a specific p65 inhibitor) reversed p65 activation and ameliorated PM2.5-induced airway inflammation and bronchial hyperresponsiveness. Our findings provide novel insights into the molecular mechanisms underlying the toxicity of PM2.5 exposure. Triptolide inhibition of p65 phosphorylation and acetylation could be an effective therapeutic approach in averting PM2.5-induced airway inflammation and bronchial hyperresponsiveness. [ABSTRACT FROM AUTHOR]

Bronchial hyperresponsiveness is a typical, but non-specific feature of cough variant asthma (CVA). This study aimed to determine whether bronchial hyperresponsiveness may be considered as a predictor of CVA in non-smoking adults with chronic cough (CC). The study included 55 patients with CC and bronchial hyperresponsiveness confirmed in the methacholine provocation test, in whom an anti-asthmatic, gradually intensified treatment was introduced. The diagnosis of CVA was established if the improvement in cough severity and cough-related quality of life in LCQ were noted.The study showed a high positive predictive value of bronchial hyperresponsiveness in this population. Cough severity and cough related quality of life were not related to the severity of bronchial hyperresponsiveness in CVA patients. A poor treatment outcome was related to a low baseline capsaicin threshold and the occurrence of gastroesophageal reflux-related symptoms. In conclusion, bronchial hyperresponsiveness could be considered as a predictor of cough variant asthma in non-smoking adults with CC. [ABSTRACT FROM AUTHOR]

Background: It is unclear in which periods of life lung function deficits develop, and whether these are affected by risk factors such as asthma, bronchial hyper‐responsiveness (BHR) and allergic comorbidity. The goal of this systematic review was to identify temporal associations of asthma, BHR and allergic comorbidity with large and small lung function development from birth until peak function in early adulthood. Methods: We searched MEDLINE, EMBASE, Web of Science and CINAHL for papers published before 01.01.2020 on risk factors and lung function measurements of large and small airways. Studies were required to report lung function at any time point or interval from birth until peak lung function (age 21‐26) and include at least one candidate risk factor. Results: Of the 45 papers identified, 44 investigated cohorts and one was a clinical trial with follow‐up. Asthma, wheezing, BHR and allergic sensitization early in life and to multiple allergens were associated with a lower lung function growth of large and small airways during early childhood compared with the control populations. Lung function development after childhood in subjects with asthma or persistent wheeze, although continuing to grow at a lower level, largely tracked parallel to non‐affected individuals until peak function was attained. Clinical implications and future research: Deficits in lung function growth develop in early childhood, and children with asthma, BHR and early‐life IgE (poly)sensitization are at risk. This period is possibly a critical window of opportunity to identify at‐risk subjects and provide treatment aimed at preventing long‐term sequelae of lung function. [ABSTRACT FROM AUTHOR]

Objective: To determine long-term predictors of bronchial hyperresponsiveness (BHR) and forced expiratory volume in one second (FEV1) decline. Methods: A longitudinal study in 110 bakers in 4 industrial bakeries and 38 non-exposed workers was conducted at the workplace with a mean of 3.3 visits per subject over a period of 13 years and a mean duration of follow-up of 6 years in bakers and 8 years in non-exposed subjects. A respiratory health questionnaire was administered; occupational allergen skin prick tests, spirometry and a methacholine bronchial challenge test were performed at each visit. In each bakery, full-shift dust samples of the inhalable fraction were obtained in order to assess the exposure of each job assignment. The repeated measurements of BHR and FEV1 were analyzed using mixed effects logistic and linear regression models in subjects seen at least twice. Results: BHR, respiratory symptoms and their simultaneous occurrence depended on the duration of exposure. FEV1 significantly decreased with duration of exposure and BHR at a preceding visit. This result persisted when adjusting for the effect of BHR at the current visit. The measured exposure levels were not a significant predictor for any outcome. Occupational sensitization was only a predictor of a decline in FEV1 when duration of exposure was not included. Conclusion: In flour-exposed industrial bakers, length of exposure and smoking are long-term determinants of BHR and of the decrease in FEV1. BHR at a preceding visit predicted lower FEV1 even when accounting for the effect of BHR at the current visit. [ABSTRACT FROM AUTHOR]

BACKGROUND: A 20% reduction in the FEV1 is routinely used as an end point for methacholine challenge testing (MCT). Measurement of FEV1 is effort dependent, and some patients are not able to perform acceptable and repeatable forced expiration maneuvers. The goal of the present study was to investigate the diagnostic value of airway resistance measurement by forced oscillation technique (FOT), body plethysmography, and interrupter technique compared with the traditionally accepted standard FEV1 measurement in evaluating the responsiveness to methacholine during MCT. METHODS: We included in the study adult subjects referred for MCT because of asthma-like symptoms and with normal baseline spirometry. We modified routine MCT protocol by adding the assessment of airway resistance to the measurement of FEV1 at each step of MCT. RESULTS: We observed, in the subjects with airway hyper-responsiveness versus those with normal airway responsiveness, a significantly greater percentage change in median (interquartile range) FOT resistance at 10 Hz (25.9% [13.7%-35.4%] vs 16% [15.7%-27.2%]), plethysmographic resistance (70.2% [39.5%-116.3%] vs 37.1% [23.9%-81.9%]), and mean 6 SD conductance (241.3 6 15.4% vs 229.6 6 15.9%); and a significantly greater change in mean 6 SD FOT reactance at 10 Hz (-0.41 6 0.48 cm H2O/L/s vs -0.09 6 0.32 cm H2O/L/s) and at 15 Hz (-0.29 6 0.2 cm H2O/L/s vs -0.1 6 0.19 cm H2O/L/s). We also recorded significant differences in airway resistance parameters (FOT resistance at 10 Hz, FOT reactance at 15 Hz, plethysmographic airway resistance, and conductance indices as well as interrupter resistance) in FEV1 non-responders at the onset of respiratory symptoms during MCT compared with baseline. CONCLUSIONS: Measurements of airway resistance could possibly be used as an alternative method to spirometry in airway challenge. Significant changes in airway mechanics during MCT are detectable by airway resistance measurement in FEV1 non-responders with methacholine-induced asthma-like symptoms. (ClinicalTrials.gov registration NCT02343419.) [ABSTRACT FROM AUTHOR]

Introduction Occupational asthma (OA) is the most common occupational lung disease in industrialized countries; however, in Western Europe, a decline in the prevalence of OA and changes in etiological factors has been recorded. Data from Central Europe, where in the past healthcare and economy sectors were different, are rare. Objective The aim of this study was to discover the changes related to OA during a four decade long period in the Slovak Republic. Material and methods The study included patients whom OA was reported during 1980–2016. All cases of OA were divided into four decades. The prevalence of OA, changes in etiological factors and key diagnostic methods were evaluated. All decades were analysed separately and compared to one another. Results During 1980–2016, OA was reported in 155 patients. OA was most often found in the second decade (6.4 cases per year), the lowest number of cases was diagnosed in the third decade (2.1 cases per year). Since 1988, an increasing prevalence of OA was observed with the peak in 1992, followed by the significantly progressive decrease during subsequent years. In the fourth decade, a mild increase in OA causes was recorded again. In the first and second decades, agricultural allergens were the dominant agents, which were replaced by chemical factors in the last decade. The most frequently used key diagnostic methods in 1980–2009 were skin tests, during the fourth decade the importance of this method declined. However, specific BPT a serial BPT were more frequently used in the fourth decade Conclusion The number of OA cases induced by agricultural allergens declined, which was connected with a decrease of total OA cases. The current problem is the OA induced by the chemicals, which increased significantly in the last decade, even the possibility of underdiagnosed OA cases still exists.

Background. Bronchial asthma is one of the most common chronic multifactorial diseases of the lungs. At least 10–12 % of patients with bronchial asthma are suffering from a severe form of the disease. One aspect of inadequate severe asthma control is its phenotypic heterogeneity, interest of experts increases to the problem of exercise-induced asthma. The purpose of the study was to increase efficiency of treatment for severe exercise-induced asthma in schoolchildren based on the analysis of the attack dynamics and to achieve disease control according to main inflammatometric and spirometric indices. Materials and methods. We examined 46 children with severe persistent bronchial asthma, in particular, 15 schoolchildren suffering from severe exercise-induced asthma, the second clinical group (comparison one) consisted of 31 children suffering from severe type of the disease, with no signs of exercise-induced bronchoconstriction. Basic therapy effectiveness was determined prospectively by assessing the disease control using AST-test with an interval of 3 months. The severity of bronchial obstruction syndrome in patients on admission to hospital during exacerbation was assessed by score scale. Airway hyperresponsiveness was evaluated according to the results of bronchoprovocation with histamine. Results. Children of I clinical group had more significant manifestations of bronchial obstruction during the week of inpatient treatment than the comparison group of patients, including significantly more severe manifestations of bronchial obstruction were verified on 1st and 7th day of hospitalization. Due to the analysis of basic therapy effectiveness, only a quarter of I clinical group patients and a larger part of schoolchildren in comparison group achieved the partial control after a 3-month course of anti-inflammatory treatment. Eosinophilic inflammation was observed in most children with severe exercise-induced asthma (60.1 %) and in 47.2 % of patients from the comparison group. More significant bronchial hyperresponsiveness in schoolchildren suffering from severe exercise-induced asthma is confirmed by a significantly larger part of patients with severe airway hypersensitivity to histamine (PC20H < 0.5 mg/ml) in 1st clinical group (87.5 %) than in children with no signs of exercise-induced bronchoconstriction (54.5 %, рφ > 0.05). Exercise-induced bronchoconstriction is associated with an increased risk of severe bronchial hyperresponsiveness to histamine in schoolchildren suffering from severe asthma. For instance, the relative risk of severe bronchial hyperresponsiveness to histamine in children with severe exercise-induced asthma was 1.6 (95 % confidence interval (CI) 0.6–55.7), the odds ratio of 5.8 (95 % CI 0.6–55.7). Conclusions. Lower effectiveness of relief therapy and basic treatment of severe asthma in schoolchildren with symptoms of exercise-induced bronchoconstriction can be explained by significantly larger part of schoolchildren with hypereosinophilia in induced sputum and more severe airway hypersensitivity to histamine.

OBJECTIVE Asthma is associated with bronchial hyperresponsiveness, assessed by bronchial provocation tests such as the mannitol test. We aimed to assess the data on sensitivity and specificity of the mannitol test in diagnosing asthma. DATA SOURCES We searched electronically the Medline, Embase and Central databases from 1997 to 2019. STUDY SELECTION Inclusion criteria were the assessment of the validity of the mannitol test. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). Data were extracted according to a prespecified list and analysed qualitatively. RESULTS A total of 27 studies (4589 individuals, age 6–85 years, cross-sectional [n = 18] and case-controlled [n = 9] study design) were included. Overall sensitivity and specificity ranged from 8% (95% confidence interval [CI] 1–27) to 100% (95% CI 93–100) and 75% (95% CI 67–82) to 100% (95% CI 85–100). Excluding case-controlled design, studies conducted in a clinical setting showed a range from 19% (95% CI 14–27) to 91% (95% CI 59–100) for sensitivity and from 75% (95% CI 67–82) to 100% (95% CI 80–100) for specificity. Heterogeneity was high owing to differences in the populations examined and the methods used. CONCLUSIONS Studies on the accuracy of the mannitol test were heterogeneous. Overall specificity was higher than sensitivity and therefore the mannitol test seems to be a suitable diagnostic tool to confirm asthma. However, the high level of heterogeneity among the included studies makes a conclusive statement on the accuracy of the mannitol test difficult and further research is needed. As bronchial provocation tests can be especially useful in patients with an intermediate probability of asthma diagnosis, further studies are needed that include subjects with asthma symptoms but intermediate probability of asthma diagnosis.