Search Results (16)

Background/Objectives: In children, gastroesophageal reflux disease (GERD) may lead to epithelial barrier dysfunction and the release of thymic stromal lymphopoietin (TSLP), interleukin-25 (IL-25), interleukin-33 (IL-33) and periostin, known as alarmins. These cytokines are associated with type 2 inflammation and may contribute to respiratory and allergic conditions. The main purpose of this study is to evaluate serum concentrations of TSLP, IL-25, IL-33, and periostin in children with and without GERD and to assess their relationships with bronchial hyperresponsiveness (BHR) and sensitization to inhaled allergens. Methods: The study included 93 children aged 7–17 years. GERD was diagnosed based on 24-h esophageal pH impedance monitoring. Serum levels of TSLP, IL-25, IL-33, and periostin were measured using enzyme-linked immunosorbent assay (ELISA). It should be noted that the assay used does not distinguish between TSLP isoforms, which represents a limitation of the study. BHR was assessed via a methacholine challenge test, and allergen sensitization was determined using skin prick tests and allergen-specific immunoglobulin E (asIgE). Results: Serum TSLP levels were significantly higher in children with GERD compared to those without, whereas IL-25, IL-33 and periostin did not differ notably between groups. Periostin was associated with the degree of sensitization to inhalant allergens, but no significant links were found between cytokine levels and bronchial hyperresponsiveness. Conclusions: Significantly higher TSLP levels were noted in children with GERD than in those without. Hence, TSLP may have a potential role as a biomarker of epithelial immune activation in pediatric GERD. In addition, periostin was associated with sensitization to inhalant allergens, although it did not differentiate between children with and without GERD. Full article

Background: Small airway dysfunction (SAD) is associated with impaired asthma control, but small airway physiology is not routinely assessed in clinical practice. Previously, we demonstrated impulse oscillometry (IOS)-defined small airway dysfunction (SAD) in dual responders (DRs) upon bronchoprovocation with various allergens. Aim: To compare lung physiology using spirometry and IOS following bronchoprovocation with methacholine (M) and inhaled house dust mite (HDM) extract in corticosteroid-naïve asthmatic subjects. Methods: Non-smoking, clinically stable HDM-allergic asthmatic subjects (18–55 years, FEV₁ > 70% of pred.) underwent an M and inhaled HDM challenge on two separate days. Airway response was measured by IOS and spirometry, until a drop in FEV₁ ≥ 20% (PC₂₀) from post-diluent baseline (M), and up to 8 h post-allergen (HDM). Early (EAR) and late asthmatic response (LAR) to HDM were defined as ≥20% and ≥15% fall in FEV₁ from post-diluent baseline during 0–3 h and 3–8 h post-challenge, respectively. IOS parameters (Rrs5, Rrs20, Rrs5-20, Xrs5, AX, Fres) were compared between mono-responders (MRs: EAR only) and dual responders (EAR + LAR). Correlations between maximal % change from baseline after the two airway challenges were calculated for both FEV₁ and IOS parameters. Results: A total of 47 subjects were included (11 MRs; 36 DRs). FEV₁ % predicted did not differ between MR and DR at baseline, but DR had lower median PC₂₀M (0.84 (range 0.07–7.51) vs. MR (2.15 (0.53–11.29)); p = 0.036). During the LAR, DRs had higher IOS values than MRs. For IOS parameters (but not for FEV₁), the maximal % change from baseline following M and HDM challenge were correlated. PC₂₀M was inversely correlated with the % change in FEV₁ and the % change in Xrs5 during the LAR (r= −0.443; p = 0.0018 and r= −0.389; p = 0.0075, respectively). Conclusions: During HDM-induced LAR, changes in small airway physiology can be non-invasively detected with IOS and are associated with increased airway hyperresponsiveness and changes in small airway physiology during methacholine challenge. DRs have a small airways phenotype, which reflects a more advanced airway disease. Full article

Background/Objectives: Cough variant asthma (CVA) is characterized by nonspecific symptoms and normal spirometric values, which makes diagnosis challenging. To diagnose CVA it is necessary to document airway hyperreactivity (AHR). The aim of our study was to evaluate the diagnostic value of body plethysmography in the assessment of AHR using the methacholine challenge test (MCT). Methods: In CVA-suspected patients, a bronchodilation test (BDT), an MCT with spirometry, and body plethysmography were performed. The MCT was considered positive if there was a 20% decrease in forced expiratory volume in 1 s from the baseline value (PC₂₀FEV₁) or a 40% reduction in specific conductance (PC₄₀sGaw) after inhaling methacholine of concentration < 8 mg/mL. Sensitivity and specificity were generated for different cut off points of sGaw (PC₄₀sGaw, PC₄₅sGaw, PC₅₀sGaw). Anti-asthma treatment was started for those with proven AHR. The diagnosis of asthma was made after one year of follow-up based on the response to treatment. Results: AHR was diagnosed in 83.5% (91/109) of patients by either a BDT, PC₂₀FEV₁, or PC₄₀sGaw. After one year of follow-up, asthma was confirmed in 76 patients. The sensitivities of the BDT, PC₂₀FEV₁, and PC₄₀sGaw were 25%, 64%, and 97%, respectively. The specificities of the BDT, PC₂₀FEV₁ and PC₄₀sGaw were 94%, 88%, and 67%, respectively. The sensitivities for a PC₄₅sGaw and PC₅₀sGaw were 88% and 63%, and the specificities were 82% and 91%, respectively. Conclusions: Body plethysmography is a valuable tool in the assessment of AHR in CVA, with the best sensitivity-to-specificity ratio found at a PC₄₅sGaw. Full article

Treatment-resistant asthma remains an unresolved clinical problem and a challenge for current medical science. Consequently, there is a growing and urgent need to develop novel or alternative therapeutic options for the treatment of asthma. The research problem raised in this study was to assess and compare mycophenolate mofetil (MMF), an inhibitor of inosine monophosphate dehydrogenase, and tofacitinib (TFB), a Janus kinase inhibitor, for anti-asthmatic properties, and consequently to determine whether these agents may have potential as alternative options for treatment of allergic asthma. For this purpose, we assessed the effect of administration of MMF and TFB on the development of a mouse model of allergic airway inflammation (AAI) and accompanying CD4⁺ (cluster of differentiation 4) T-cell immune response in the lung-draining mediastinal lymph nodes (MLNs) and lungs, i.e., in the inductive and effector sites, respectively, of the immune response underlying the development of allergic asthma. The results from a histopathological scoring system demonstrated that the administration of MMF and TFB did not prevent or abolish ovalbumin-induced AAI, but strongly attenuated its severity. The pulmonary function tests revealed that the treatment with MMF and TFB significantly reduced methacholine-induced bronchoconstriction. These results indicate that the treatment with TFB and MMF attenuated the development of ovalbumin-induced AAI. The magnitude of the anti-asthmatic effect was comparable between both agents. The study revealed that the impairment of the clonal expansion of effector CD4⁺ T cells in the MLNs is a critical event in the mechanism underlying the anti-asthmatic effect of MMF and TFB. Apart from this, the findings of the study strongly suggest that the suppression of the interleukin-33/suppression of tumorigenicity-2 signaling pathway may constitute an additional mechanism responsible for producing this effect. In turn, the results indicate that the anti-asthmatic action induced by the studied agents is not mediated by the generation of forkhead box protein 3-expressing CD4⁺ regulatory T cells. Clinical implication of the results: the results suggest that MMF and TFB may exert anti-asthmatic action, and thus they may be considered therapeutic options for the treatment of allergic asthma cases resistant to conventional/existing treatment. Full article

Airway hyperresponsiveness (AHR) and inflammation are both observed in human and equine asthma. The aim of this study was to assess the timeline and relationship of both features at the subclinical onset of severe equine asthma (SEA). First, the repeatability of the pulmonary function test (PFT) using impulse oscillometry system, and the methacholine bronchoprovocation test (BPT) were assessed at a 1-day interval on six SEA horses in clinical remission and six control horses. Then, clinical and ancillary tests were performed before and after a 1-week low-dust environmental challenge, including weighted clinical score, respiratory endoscopy, bronchoalveolar fluid cytology, PFT, and BPT. Both PFT and BPT showed acceptable repeatability. No test allowed SEA horses in clinical remission to be distinguished from control, unlike in human patients. Because of the low-dust environment, no significant difference was observed in the results of clinical and conventional ancillary examinations after the challenge. However, SEA horses showed increased AHR after the environmental challenge. At that stage, no signs of inflammation or changes in pro-inflammatory cytokines profiles (quantification and gene expression) were observed, suggesting AHR is present at an earlier stage of equine asthma than airway inflammation. This feature indicates SEA could present in a different disease pathway than neutrophilic human asthma. Full article

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

Introduction: Asthma is characterized by persistent inflammation, airway hypersensitivity and remodelling. Bone Morphogenetic Proteins belong to the Transforming Growth Factor Superfamily and have a similar signalling transduction pathway and common co-mediating protein. However, the BMPs role in the remodelling remains unclear; they appear to be involved in the airway inflammation and fibrogenesis process. Material and Methods: 60 patients with asthma and 48 healthy volunteers were recruited for the study. Blood samples were collected before, 1 h, 24 and 48 h after the allergen or the methacholine challenge test. Evaluation of BMP-4 and BMP-7 serum concentration and expression was performed using ELISA and real time PCR methods, respectively. Results: Statistically significant differences in BMP-7 concentration between healthy controls and asthmatics before the chal-lenge were noted. We found two statistically significant correlations: between the basal BMP-4 concentration and the FEV1(L) raw value and FEV1/FVC(%) index. We did not observe significant changes in the gene expression of BMP-4 and BMP-7 in different time points. Conclusions: Observed differences in BMP-7 concentration between asthmatic and healthy groups and correlations between BMP-4 concentration and some lung function test values may indicate the role of the BMPs in the etiopathogenesis of asthma. The unique characteristic of our study is the evaluation of BMPs serum levels, not in the bronchial epithelium. Full article

Occupational asthma (OA) represents one of the major public health problems due to its high prevalence, important social and economic burden. The aim of this review is to summarize current data about clinical phenotypes, biomarkers, diagnosis and management of OA, a subtype of work-related asthma. Most studies have identified two phenotypes of OA. One is sensitizer-induced asthma, occuring after a latency period and caused by hypersensitivity to high- or low-molecular weight agents. The other is irritant-induced asthma, which can occur after one or more exposures to high concentrations of irritants without latency period. More than 400 agents causing OA have been identified and its list is growing fast. The best diagnostic approach for OA is a combination of clinical history and objective tests. An important tool is a specific inhalation challenge. Additional tests include assessments of bronchial hyperresponsiveness to methacholine/histamine in patients without airflow limitations, monitoring peak expiratory flow at- and off-work, sputum eosinophil count, exhaled nitric oxide measurement, skin prick tests with occupational allergens and serum specific IgE. Treatment of OA implies avoidance of exposure, pharmacotherapy and education. OA is a heterogeneous disease. Mechanisms of its different phenotypes, their diagnosis, role of new biomarkers and treatment require further investigation. Full article

Neurotensin (NT) demonstrates ambiguous activity on inflammatory processes. The present study was undertaken to test the potential anti-inflammatory activity of NT in a murine model of non-atopic asthma and to establish the contribution of NTR1 receptors. Asthma was induced in BALB/c mice by skin sensitization with dinitrofluorobenzene followed by intratracheal hapten provocation. The mice were treated intraperitoneally with NT, SR 142948 (NTR1 receptor antagonist) + NT or NaCl. Twenty-four hours after the challenge, airway responsiveness to nebulized methacholine was measured. Bronchoalveolar lavage fluid (BALF) and lungs were collected for biochemical and immunohistological analysis. NT alleviated airway hyperreactivity and reduced the number of inflammatory cells in BALF. These beneficial effects were inhibited by pretreatment with the NTR1 antagonist. Additionally, NT reduced levels of IL-13 and TNF-α in BALF and IL-17A, IL12p40, RANTES, mouse mast cell protease and malondialdehyde in lung homogenates. SR 142948 reverted only a post-NT TNF-α decrease. NT exhibited anti-inflammatory activity in the hapten-induced asthma. Reduced leukocyte accumulation and airway hyperresponsiveness indicate that this beneficial NT action is mediated through NTR1 receptors. A lack of effect by the NTR1 blockade on mast cell activation, oxidative stress marker and pro-inflammatory cytokine production suggests that other pathways can be involved, which requires further research. Full article

Airway hyperreactivity (AHR) related to environmental exposure is a significant public health risk worldwide. Similarly, metabolic syndrome (MetSyn), a risk factor for obstructive airway disease (OAD) and systemic inflammation, is a significant contributor to global adverse health. This prospective cohort study followed N = 7486 World Trade Center (WTC)-exposed male firefighters from 11 September 2001 (9/11) until 1 August 2017 and investigated N = 539 with newly developed AHR for clinical biomarkers of MetSyn and compared them to the non-AHR group. Male firefighters with normal lung function and no AHR pre-9/11 who had blood drawn from 9 September 2001–24 July 2002 were assessed. World Trade Center-Airway Hyperreactivity (WTC-AHR) was defined as either a positive bronchodilator response (BDR) or methacholine challenge test (MCT). The electronic medical record (EMR) was queried for their MetSyn characteristics (lipid profile, body mass index (BMI), glucose), and routine clinical biomarkers (such as complete blood counts). We modeled the association of MetSyn characteristics at the first post-9/11 exam with AHR. Those with AHR were significantly more likely to be older, have higher BMIs, have high intensity exposure, and have MetSyn. Smoking history was not associated with WTC-AHR. Those present on the morning of 9/11 had 224% increased risk of developing AHR, and those who arrived in the afternoon of 9/11 had a 75.9% increased risk. Having ≥3 MetSyn parameters increased the risk of WTC-AHR by 65.4%. Co-existing MetSyn and high WTC exposure are predictive of future AHR and suggest that systemic inflammation may be a contributor. Full article

Recent studies have highlighted the potential protective role of omega-3 polyunsaturated fatty acids (n-3 PUFA) in asthma. This study aimed at determining the association between seafood intake, serum PUFA composition and clinical endpoints of asthma in adults. A cross-sectional study of 642 subjects used the European Committee Respiratory Health Survey (ECRHS) questionnaire, skin prick tests, spirometry and methacholine challenge tests following ATS guidelines. Sera was analysed for n-3 and n-6 PUFA composition. Subjects had a mean age of 34 years, were largely female (65%) and 51% were current smokers. While 99% reported fish consumption, rock lobster, mussels, squid and abalone were also consumed less frequently. The prevalence of asthma symptoms was 11%, current asthma (ECRHS definition) was 8% and non-specific bronchial hyperresponsiveness (NSBH) was much higher (26%) In adjusted models the n-3 PUFAs 20:5 (EPA) and 22:5 (DPA) were significantly associated with a decreased risk of having NSBH. Total n-3 PUFA composition was associated with decreased NSBH risk (OR = 0.92), while high n-6 PUFA composition was associated with an increased risk (OR = 1.14). Full article

Introduction: Global Initiative for Asthma (GINA) reports emphasize the use of validated and simple tools in order to assess the level of asthma control, as the Asthma Control Test (ACT). However, an ACT does not include assessment of airway inflammation, which is better reflected when measuring nonspecific bronchial hyperresponsiveness (BHR). The authors aimed to find out if the level of asthma control quantified by an ACT correlates with BHR and pulmonary function tests. Materials and Methods: 118 asthmatics participated in the study. All patients completed an ACT. The scores of the ACTs were compared with pulmonary function tests and BHR assessed with the methacholine challenge test and expressed as a provocative concentration of methacholine, inducing a 20% decline in the FEV1 (PC₂₀M in mg/ml). Results: Patients with controlled asthma amounted to 52 (44%) while those with uncontrolled asthma amounted to 66 (56%). In patients with controlled asthma (ACT score ≥ 20) the mean geometric value of PC₂₀M was 2.72 mg/ml (range from 0.25 to > 8.0), whereas 0.94 mg/ml (range from 0.28 to 8.0) (p = 0.02) was observed in patients with uncontrolled asthma (ACT score < 20). Almost 64% (21/33) of uncontrolled asthmatics achieved normal lung function (FEV₁ > 80% pred. value) while 19% (5/26) patients with controlled asthma presented an FEV₁ < 80% predicted value. Asthma duration in years in controlled asthmatics was significantly shorter than in uncontrolled patients (6.2 ± 8.9 vs. 12.0 ± 11.4, p = 0.005). Conclusion: In determining the most accurate level of asthma control it is reasonable to use an ACT in conjunction with BHR, which provides more accurate assessment of bronchial inflammation than ventilatory parameters alone. Full article

Introduction: Indirect airway challenge tests are commonly used in the diagnostics of exercise-induced bronchoconstriction (EIB), defined as a post-exercise decrease in FEV₁ ≥ 10%. The aim of this study was to evaluate the diagnostic value of bronchial hyperreactivity tests in the diagnosis of EIB. Material and methods: Forty-two subjects were allocated into 3 groups: A—19 steroid-naive asthma patients; D—11 non-asthma patients reporting symptoms suggestive of EIB (dyspnoea, wheezing, and cough provoked by exercise); and K—12 healthy controls. Subjects filled a questionnaire regarding symptoms related to exercise and underwent: inhaled bronchial challenge to methacholine (Mch), adenosine 5’-monophosphate (AMP), and exercise challenge on a treadmill. With a cut-off of ≥ 10% and ≥ 15% decrease in FEV₁, EIB was diagnosed in 47% and 37% of asthma patients, respectively. Exercise-induced bronchoconstriction was found in 27% of subjects in group D and in none of the controls, irrespectively of the FEV₁ criterion. Results: The analysis of the questionnaire revealed that a single symptom cannot be used to predict EIB. Symptoms occurring after termination of exercise, but not during exercise, characterize EIB more precisely. The analysis showed that the most useful measure to diagnose EIB can be a combination of bronchial challenge to AMP and typical symptoms of exercise-induced bronchoconstriction (i.e., dyspnoea, wheezing, and coughing provoked by exercise) with a sensitivity of 70%, specificity of 94%, PPV of 78%, NPV of 91%, and LR of 11.2. Conclusions: Symptoms suggestive of EIB do not have acceptable sensitivity and specificity for the diagnosis of exercise-induced bronchoconstriction. The most useful measure to diagnose EIB is the combination of typical symptoms of EIB with a positive challenge to AMP.
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Introduction: Based on the normal values for inflammatory cell counts in induced sputum produced by healthy individuals living in the region of Silesia, Poland, we assessed the usefulness of cytological examination of induced sputum in the diagnostic evaluation of asthma, chronic obstructive pulmonary disease (COPD) and chronic bronchitis. Material and methods: We analyzed the results of examinations performed in 96 healthy individuals (controls), 42 patients with asthma, 49 with COPD and 30 with chronic bronchitis. We performed spirometry with salbutamol reversibility testing and examination of induced sputum in all the subjects. Those without contraindications underwent methacholine challenge testing. Results: We found a significantly elevated percentage of eosinophils in all the patient groups compared to the controls (p < 0.00001). Median values were 10.3% for asthma, 1.5% for COPD, 1.6% for chronic bronchitis and 0.3% for the controls. We found statistically significant differences in the mean neutrophil percentages in induced sputum between healthy individuals and asthma patients, COPD patients and chronic bronchitis patients (p < 0.05). The median values were 45.75%, 38.1%, 77.5% and 58.1%, respectively. The percentage of subjects with positive eosinophil counts (>2.8%) in the sputum of patients with asthma, COPD, chronic bronchitis and in the controls was 85%, 38%, 20% and 6%, respectively. Conclusions: 1. Cytological examination of induced sputum is a good test supporting the diagnostic evaluation of chronic inflammatory diseases of the respiratory tract. 2. The percentage of eosinophils in induced sputum exceeding 2.8% is a very good indicator of asthma. Full article

Introduction: Airway remodeling is a characteristic feature of asthma. It is believed that airway remodeling affects lung function and bronchial hyper-responsiveness. Therefore, the relationship between remodeling and lung function is still a matter of extensive research. However, the results of many studies are inconsistent. The aim of the study was to assess the relationship between lung function parameters and basement membrane (BM) thickness in patients with asthma. Material and Methods: Twenty asthma patients were chosen for the study (ten male, ten female, mean age 37 ± 15 yrs). Ten were newly diagnosed, steroid-naive patients and the other ten were patients known to have asthma who had not been treated with steroids for at least three months. The study group was selected based on the results of: clinical assessment, allergic skin-prick tests, lung function testing and bronchial challenge with methacholine. Nine (45%) patients had chronic mild, nine (45%) had moderate and two (10%) had intermittent asthma. Mean FEV₁% pred. was 83 ± 18, mean FEV₁%VC 69 ± 9, mean FVC% pred. 101 ± 14. All patients underwent research fiberoptic bronchoscopy with BAL and bronchial mucosal biopsies. Light-microscopic measurements of BM thickness were performed in hematoxylin-eosin stained slides of bronchial wall specimens with semi-automatic software analysis MultiScan Base 08.98. Results: Mean BM thickness was 12.8 ± 2.8 μm (range: 8.5–20.7 μm). No significant correlations between BM thickness and FEV₁% pred., FEV₁%VC, FVC% pred., RV% pred., TLC% pred., Raw (pre- and post-bronchodilator) and PC₂₀ were observed. Conclusions: In our group of asthma patients, mean BM was significantly thickened. No relationship between BM thickness and lung function tests, including hyper-responsiveness, was found. Full article