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

INTRODUCTION: There is considerable research interest in the role of helminth infections in the development of allergic diseases. However, findings from previous studies are mixed. Existing systematic reviews of these studies are outdated. We performed a systematic review of the global literature on the association between helminth infections and development and clinical outcomes of allergic diseases. METHODS: We searched Cochrane Library, MEDLINE, EMBASE, ISI Web of Science, PubMed, Global Index Medicus, Scielo, KoreaMed, Google Scholar, and Lilacs for studies published up to January 2020. We included observational epidemiological studies (cohort, case-control and cross-sectional studies) of children and adults reporting associations between helminth infections and asthma, allergic rhinitis, eczema and atopy. We performed random-effects meta-analysis to summarize the effect estimates. RESULTS: We included 80 studies with 99,967 participants. In the meta-analyses, we did not observe an overall association between helminth infections and allergic diseases. There was, however, evidence that A. lumbricoides infections was associated with an increased risk of bronchial hyperreactivity in children (RR:1.41, 95%CI: 1.17-1.70; I2=50, p for I2=0.09), and was associated with an increased risk of atopy among helminth-infected adults (RR:1.37, 95%CI: 1.18-1.61; I2=52, p for I2=0.02). We found no study that addressed the association between helminth infection and clinical outcomes of allergic diseases. The overall strength of the underlying evidence was low to moderate. CONCLUSION: Helminth infections may increase the risk of bronchial hyperreactivity in children and atopy in adults. Well-designed longitudinal cohorts may help clarify potential causal associations between chronic helminth infections and allergic diseases.

Background: Asthma is a lung disease that has influenced more than 350 million people worldwide. Airway smooth muscle (ASM) spasm leads to airway hyperresponsiveness (AHR) and bronchial obstruction, which are clinical manifestations of an asthma attack. Botulinum toxin (BTX) is a bacteria toxin that acts as muscle relaxant and may have therapeutic effects on AHR and asthma. Objective: In this study, the effect of BTX on AHR and related gene expressions was evaluated. Material and Methods: An asthma mice model was developed which was treated with BTX in two ways: intranasally (IN) and via nebulization (N) (0.01, 0.1, and 1 U/mL and 10 U/mL, respectively) on days 25, 27 and 29. AHR was evaluated on days 24, 26, 28, and 30, and gene expressions were evaluated for TrkA, TrkB, M1–M5, α7nAChR, TNF-α, and extracellular signal-regulated kinase 2 (ERK2) proteins. For histopathology of the lungs, perivascular and peribronchial inflammation, production of mucus, and goblet cell hyperplasia were studied. Results: On day 24, treatment with BTX (for all doses) had no significant effect on AHR, but on days 26 and 28, AHR was decreased and this continued up to day 30 for all treated groups. Treatment with BTX had no significant effect on the gene expressions of TrkA, TrkB, M1–M5, α7nAChR, TNF-α, and ERK2 proteins, perivascular inflammation, peribronchial inflammation, hyperplasia of the goblet cell and production of mucus. Besides, mice administered with 10 mg/mL BTX perished. The BTX therapy controlled asthma attacks by decreasing AHR and relaxation of ASMs. Conclusion: However, BTX had no significant effect on airway inflammation and production of mucus. While using BTX, it is necessary to prescribe safe doses in order to prevent adverse reactions.

PURPOSE OF REVIEW: To communicate recent insights about the natural history of childhood asthma, with a focus on prediction of persistence and remission of childhood asthma, up to early adulthood.RECENT FINDINGS: Lung function around the age of 8-9 years is the strongest predictor: obstructive lung function predicts asthma persistence up to early adulthood, whereas normal lung function predicts remission. The ability to predict asthma remission improves when lung function is combined with blood eosinophil levels and degree of bronchial hyperresponsiveness. Interventions, such as inhaled corticosteroids and immunotherapy do not appear to alter the course of asthma. Epigenetic studies have revealed potential novel biomarkers of asthma remission, such as micro-RNA patterns in blood. Specifically, lower serum levels of mi-R221-5p, which is associated with lower IL-6 release and eosinophilic inflammation, predict remission. Higher levels of blood DNA-methylation of a CpG site in Peroxisomal Biogenesis Factor 11 Beta were associated with asthma remission.SUMMARY: Lung function, allergic comorbidity and polysensitization in childhood predict the course of asthma. Recent epigenetic studies have provided a better understanding of underlying pathological processes in asthma remission, which may be used to improve prediction or develop novel treatments aimed at altering the course of asthma.

Background: Asthma diagnosis may be challenging particularly in patients with mild symptoms without an obstructive pattern in spirometry. Detection of airway hyperresponsiveness (AHR) by a positive methacholine challenge (MCC) is still an important diagnostic tool to confirm the presence of asthma with reasonable certainty. However, it is time consuming and could be exhausting for patients. We aimed to identify the predictive factors for AHR in children with respiratory symptoms without obstructive pattern in spirometry. Methods: Data from children who had undergone MCC were analyzed retrospectively. The demographic features of patients along with laboratory results were collected. Results: A total of 123 children with a median age of 10.5 years were enrolled. AHR was detected in 81 children (65.8%). The age of the children with AHR was significantly younger. The prevalences of aeroallergen sensitization, nocturnal cough, wheezing, and a baseline forced expiratory flow at 75% of vital capacity (FEF75) 75 Conclusion: In children suspected of having asthma, but without an obstructive pattern in the spirometry, combining independent predictors, which can be easily obtained in clinical practice, might be used to identify children with AHR.

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

It is well known that supplemental oxygen used to treat preterm infants in respiratory distress is associated with permanently disrupting lung development and the host response to influenza A virus (IAV). However, many infants who go home with normally functioning lungs are also at risk for hyperreactivity after a respiratory viral infection. We recently reported a new, low-dose hyperoxia mouse model (40% for 8 days; 40×8) that causes a transient change in lung function that resolves, rendering 40×8 adult animals functionally indistinguishable from room air controls. Here we report that when infected with IAV, 40×8 mice display an early transient activation of TGFβ signaling and later airway hyperreactivity associated with peribronchial inflammation (profibrotic macrophages) and fibrosis compared with infected room air controls, suggesting neonatal oxygen induced hidden molecular changes that prime the lung for hyperreactive airways disease. Although searching for potential activators of TGFβ signaling, we discovered that thrombospondin-1 (TSP-1) is elevated in naïve 40×8 mice compared with controls and localized to lung megakaryocytes and platelets before and during IAV infection. Elevated TSP-1 was also identified in human autopsy samples of former preterm infants with bronchopulmonary dysplasia. These findings reveal how low doses of oxygen that do not durably change lung function may prime it for hyperreactive airways disease by changing expression of genes, such as TSP-1, thus helping to explain why former preterm infants who have normal lung function are susceptible to airway obstruction and increased morbidity after viral infection.

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 50% 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.

Extracellular acidification is a major component of tissue inflammation, including airway inflammation. The extracellular proton-sensing mechanisms are inherent in various cells including airway structural cells, although their physiological and pathophysiological roles in bronchial smooth muscles (BSMs) are not fully understood. In the present study, to explore the functional role of extracellular acidification on the BSM contraction, the isolated mouse BSMs were exposed to acidic pH under contractile stimulation.The RT-PCR analyses revealed that the proton-sensing G protein-coupled receptors were expressed both in mouse BSMs and cultured human BSM cells. In the mouse BSMs, change in the extracellular pH from 8.0 to 6.8 caused an augmentation of contraction induced by acetylcholine. Interestingly, the acidic pH-induced BSM hyper-contraction was further augmented in the mice that were sensitized and repeatedly challenged with ovalbumin antigen. In this animal model of asthma, upregulations of G protein-coupled receptor 68 (GPR68) and GPR65, that were believed to be coupled with Gq and Gs proteins respectively, were observed, indicating that the acidic pH could cause hyper-contraction probably via an activation of GPR68. However, psychosine, a putative antagonist for GPR68, failed to block the acidic pH-induced responses.These findings suggest that extracellular acidification contributes to the airway hyperresponsiveness, a characteristic feature of bronchial asthma. Further studies are required to identify the receptor(s) responsible for sensing extracellular protons in BSM cells.

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.

Background: Emerging evidence has indicated that small airway dysfunction (SAD) contributes to the clinical expression of asthma. Objectives: The aim of the study was to explore the relationships of SAD assessed by forced expiratory flow between 25 and 75% (FEF25–75%), with clinical and inflammatory profile and treatment responsiveness in asthma. Method: In study I, dyspnea intensity (Borg scale), chest tightness, wheezing and cough (visual analog scales, VASs), and pre- and post-methacholine challenge testing (MCT) were analyzed in asthma patients with SAD and non-SAD. In study II, asthma subjects with SAD and non-SAD underwent sputum induction, and inflammatory mediators in sputum were detected. Asthma patients with SAD and non-SAD receiving fixed treatments were prospectively followed up for 4 weeks in study III. Spirometry, Asthma Control Questionnaire (ACQ), and Asthma Control Test (ACT) were carried out to define treatment responsiveness. Results: SAD subjects had more elevated ΔVAS for dyspnea (p = 0.027) and chest tightness (p = 0.032) after MCT. Asthma patients with SAD had significantly elevated interferon (IFN)-γ in sputum (p < 0.05), and Spearman partial correlation found FEF25–75% significantly related to IFN-γ and interleukin-8 (both having p < 0.05). Furthermore, multivariable regression analysis indicated SAD was significantly associated with worse treatment responses (decrease in ACQ ≥0.5 and increase in ACT ≥3) (p = 0.022 and p = 0.032). Conclusions: This study indicates that SAD in asthma predisposes patients to greater dyspnea intensity and chest tightness during bronchoconstriction. SAD patients with asthma are characterized by non-type 2 inflammation that may account for poor responsiveness to therapy.

INTRODUCTION Asthma is a major cause of morbidity and mortality in children worldwide, but many cases may remain undiagnosed. Community health worker (CHW) programs have improved detection of other diseases such as childhood pneumonia, but none have been validated for detection of asthma in resource-poor settings. We hypothesized that a CHW administered questionnaire would be effective in case-detection of asthma in a poor Nicaraguan community. METHODS We enrolled children aged 2-17 from a small semiurban Nicaraguan community. A trained CHW administered a questionnaire based on a previously validated school-based screening questionnaire, which was compared to pediatric pulmonologist evaluation as a reference standard. We determined the questionnaire's sensitivity, specificity, and positive and negative likelihood ratios at different score cut-points. RESULTS A total of 199 out of 218 eligible children were enrolled. Total asthma prevalence based on physician diagnosis was 33%. Mean scores on the CHW questionnaire were 3.6 points out of 22 (SD = 4.3) for nonasthmatics and 11.0 points (SD = 5.3) for children with asthma (p

Background: Sensitization to allergen has long been known to be relate to childhood allergic diseases. Polysensitised children have more severe atopic diseases, whereas allergic rhinitis or asthma children with cosensitized to food and inhalant allergens were under-researched. Objective: To realize the association between sensitization to food allergens and pediatric allergic rhinitis and asthma in Taiwan. Methods: We included 138 participants with sensitized to allergen as assessed by serum-specific IgE. 87 of 138 participants had allergic rhinitis and 51 participants had asthma. All participants underwent a physical examination and measurement of serum total and specific IgE values. Besides, nasal peak expiratory flow rate (nPEFR) that was performed by the participants with allergic rhinitis and were requested to complete the Pediatric Rhinoconjunctivitis Quality of Life Questionnaires (PRQLQ). Lung function test and asthma control test (ACT)/child asthma control test (C-ACT) were performed by the participants with asthma. Results: 39 of 87 allergic rhinitis participants with sensitized to food and inhalant allergens (AR food group), 48 of 87 allergic rhinitis participants with sensitized to inhalant allergen alone (AR inhalant group). The AR food group had significantly lower nPEFR values and higher total IgE values (p

Background At present, the effect of operation intervention on pulmonary function is not clear in patients with allergic rhinitis and chronic rhinosinusitis with nasal polyps (AR&CRSwNP). This study was conducted to investigate the effect of vidian neurectomy on pulmonary function and airway hyperresponsiveness (AHR) in patients with AR&CRSwNP. Methods The incidences of AHR, bronchial asthma (BA) and pulmonary function impairment in 112 patients with AR&CRSwNP were investigated. Subsequently, we evaluated the outcome of vidian neurectomy and its effect on pulmonary function and AHR. Furthermore, we explored the correlation between postoperative level of eosinophilic cationic protein (ECP) and the changes of pulmonary function indices or dose of methacholine. Results In this study, the incidences of pulmonary function impairment, bronchial asthma, and AHR in patients with AR&CRSwNP were 61.61%, 69.64%, and 66.96%, respectively. Particularly, vidian neurectomy effectively alleviated nasal symptoms, improved pulmonary function, and reduced AHR in AR&CRSwNP patients. Furthermore, the postoperative level of ECP, IgE, Interleukin-4 and Interleukin-IL-5 was dramatically decreased, and there was an obvious inverse correlation between ECP level and pulmonary function index or dose of methacholine. Conclusions Vidian neurectomy is effective in alleviating nasal symptoms, improving pulmonary function, and reducing the risk of AHR of patients with AR&CRSwNP by decreasing the level of ECP.

BackgroundA challenge in the post-GWAS era is to assign function to disease-associated variants. However, available resources do not include all tissues or environmental exposures that are relevant to all diseases. For example, exaggerated bronchoconstriction of airway smooth muscle cells (ASMCs) defines airway hyperresponsiveness (AHR), a cardinal feature of asthma. However, the contribution of ASMC to genetic and genomic studies has largely been overlooked. Our study aimed to address the gap in data availability from a critical tissue in genomic studies of asthma.MethodsWe developed a cell model of AHR to discover variants associated with transcriptional, epigenetic, and cellular responses to two AHR promoting cytokines, IL-13 and IL-17A, and performed a GWAS of bronchial responsiveness (BRI) in humans.ResultsOur study revealed significant response differences between ASMCs from asthma cases and controls, including genes implicated in asthma susceptibility. We defined molecular quantitative trait loci (QTLs) for expression (eQTLs) and methylation (meQTLs), and cellular QTLs for contractility (coQTLs) and performed a GWAS of BRI in human subjects. Variants in asthma GWAS were significantly enriched for ASM QTLs and BRI-associated SNPs, and near genes enriched for ASM function, many with smallPvalues that did not reach stringent thresholds of significance in GWAS.ConclusionsOur study identified significant differences between ASMCs from asthma cases and controls, potentially reflecting trained tolerance in these cells, as well as a set of variants, overlooked in previous GWAS, which reflect the AHR component of asthma.

Asthma afflicts more than 300 million people. Contemporary mainstay therapies (inhaled corticosteroids and bronchodilators), prescribed empirically, control symptoms resulting from airways obstruction tolerably well in many patients but it is less clear that they alter the natural history of progressive airways inflammation and remodeling resulting in severe, therapy-resistant obstruction in a significant minority (5-10%), causing lifelong symptoms and elevated risk of recurrent hospital admission and death. Furthermore, no current anti-asthma drug targets bronchial smooth muscle hyperresponsiveness, a critical contributor to airways obstruction and the fundamental physiological abnormality characterizing asthma. Recent monoclonal antibody (biological) therapies reduce obstruction and exacerbations in some, but not all treated patients to an unpredictable extent, but are further limited by administration logistics and cost.An overview of the cellular and molecular immunopathology of asthma, highlighting the need and logic for the development of a novel, non-steroidal, small molecule drug for topical delivery targeting bronchial smooth muscle hyperresponsiveness and airways inflammation, particularly corticosteroid-refractory inflammation.This article elaborates evidence supporting the hypothesis that topically delivered, inhaled antagonists of the calcium-sensing receptor (CaSR) have the potential to meet these requirements, and the practicality of repurposing existing, small molecule CaSR antagonists (calcilytics) for this purpose.

Background: Although nurses are well described as being at risk of work-related asthma, certified nurse aides (CNAs) are understudied. Using a statewide registry in Texas, we measured prevalence and risk factors for work-related asthma and bronchial hyperresponsiveness (BHR) symptoms among CNAs. Methods: For this cross-sectional study, a questionnaire was mailed to a random sample of CNAs ( n = 2,114) identified through the Texas Department of Aging and Disability Services registry, working in health care during 2016–2017, to collect data on job history, asthma symptoms, and sociodemographics. Two outcomes were defined: (a) new-onset asthma (NOA) after entry into the health care field and (b) BHR-related symptoms. Job exposures to cleaning compounds and tasks were assigned using an externally coded CNA-specific job-exposure matrix. Logistic regression modeling was used to measure associations between cleaning exposures and the two asthma outcomes. Findings: The final sample consisted of 413 CNAs (response rate 21.6%). The prevalence of NOA and BHR symptoms were 3.6% and 26.9%, respectively. In adjusted models, elevated odds for BHR symptoms were observed for patient care cleaning (odds ratio [OR] = 1.71, 95% confidence interval [CI] = [0.45, 6.51]), instrument cleaning (OR = 1.33, 95% CI = [0.66, 2.68]), building-surface cleaning (OR = 1.39, 95% CI = [0.35, 5.60]), exposure to glutaraldehyde/orthophthalaldehyde (OR = 1.33, 95% CI = [0.66, 2.68]), and latex glove use during 1992–2000 (OR = 1.62, 95% CI = [0.84, 3.12]). There were too few NOA cases to warrant meaningful regression analysis. Conclusion/Application to Practice: Although not statistically significant, we observed elevated odds of BHR symptoms among nurse aides, associated with cleaning exposures, suggesting this is an at-risk group of health care professionals for work-related respiratory disease, meriting further study.

Functional and inflammatory measures have been recommended to corroborate asthma diagnosis in schoolchildren, but the evidence in this regard is conflicting. We aimed to determine, in real-life clinical situation, the value of spirometry, spirometric bronchial reversibility to salbutamol (BDR), bronchial responsiveness to methacholine (MCT) and fractional exhaled nitric oxide (FENO), to corroborate the diagnosis of asthma in children on regular inhaled corticosteroids (ICS) referred from primary care.One hundred and seventy-seven schoolchildren with mild-moderate persistent asthma, on treatment with regular ICS, participated in the study. Abnormal tests were defined as FENO ≥ 27 ppb, BDR (FEV1 ≥ 12%) and methacholine PC20 ≤ 4 mg/mL.The proportions of positive BDR, FENO and MCT, were 16.4%, 33.3%, and 87.0%, respectively. MCT was associated with FENO (p 0.03) and BDR (p = 0.001); FENO was associated with BDR (p = 0.045), family history of asthma (p = 0.003) and use of asthma medication in the first two years of life (p = 0.004). BDR was significantly related with passive tobacco exposure (p = 0.003).Spirometry, BDR and BDR had a poor performance for corroborating diagnosis in our asthmatic children on ICS treatment; on the contrary, MCT was positive in most of them, which agrees with previous reports. Although asthma tests are useful to corroborate asthma when positive, clinical diagnosis remains the best current approach for asthma diagnosis, at least while better objective and feasible measurements at the daily practice are available. At present, these tests may have a better role for assessing the management and progression of the condition.

Maintenance of homeostasis at body barriers that are constantly challenged by microbes, toxins and potentially bioactive (macro)molecules requires complex, highly orchestrated mechanisms of protection. Recent discoveries in respiratory research have shed light on the unprecedented role of airway epithelial cells (AEC), which, besides immune cells homing to the lung, also significantly contribute to host defence by expressing membrane‐bound and soluble pattern recognition receptors (sPRR). Recent evidence suggests that distinct, evolutionary ancient, sPRR secreted by AEC might become activated by usually innocuous proteins, commonly referred to as allergens. We here provide a systematic overview on sPRR detectable in the mucus lining of AEC. Some of them become actively produced and secreted by AECs (like the pentraxins C‐reactive protein and pentraxin 3; the collectins mannose binding protein and surfactant proteins A and D; H‐ficolin; serum amyloid A; and the complement components C3 and C5). Others are elaborated by innate and adaptive immune cells such as monocytes/macrophages and T cells (like the pentraxins C‐reactive protein and pentraxin 3; L‐ficolin; serum amyloid A; and the complement components C3 and C5). Herein we discuss how sPRRs may contribute to homeostasis but sometimes also to overt disease (e.g. airway hyperreactivity and asthma) at the alveolar–air interface., Airway epithelial cells actively contribute to protection of the respiratory tract, by locally secreting soluble pattern recognition receptors (sPRR). The sPRR play critical roles in the recognition of conserved motifs and are linked to complement activation. This article reviews the current knowledge on the involvement of sPRRs in the pathogenesis of allergic airway diseases.

Cough variant asthma (CVA) was first described by W. Corrao. CVA was described as the isolated chronic cough as the only presenting symptom responsive to bronchodilator therapy.This phenotype of asthma is present with airway hyperresponsiveness, eosinophilic inflammation airways and bronchodilator responsive coughing without typical manifestation of asthma such as wheezing or dyspnea. CVA shares common features with classic asthma such as eosinophilic inflammation and airway remodeling. Because of that, CVA is clinically considered as a variant type of asthma.Кашлевой вариант бронхиальной астмы (КВБА) впервые описан W. Corrao. КВБА определяют как изолированный хронический кашель в качестве единственного симптома бронхиальной астмы (БА), реагирующий на бронходилатационную терапию. Этот фенотип БА связан с гиперреактивностью и эозинофильным воспалением дыхательных путей, положительным ответом на прием бронходилататоров, без типичных проявлений астмы, таких как одышка или свистящее дыхание. Морфологически КВБА имеет общие черты с классическим вариантом БА, такие как эозинофильное воспаление и ремоделирование дыхательных путей. КВБА считается вариантом БА, предшественником классической астмы.

Background Firefighter applicants (FFAs) with a history of asthma may be refused entry to the fire service because of potentially putting themselves and others at risk. Aims We undertook a service evaluation to identify respiratory and employment outcomes of FFAs with a history of asthma who had undergone additional respiratory assessment at our specialist occupational lung disease clinic during 2005–19. Methods We reviewed FFA medical records and categorized them as having either no current asthma or definite/probable asthma at the time of clinic assessment. ‘No current asthma’ was defined as negative non-specific bronchial hyper-responsiveness (BHR) to histamine/methacholine, and no symptoms or treatment within the 2 years before clinic. ‘Definite/probable current asthma’ was defined as either positive BHR, or negative BHR with symptoms and/or treatment within the previous 2 years. Around 1 year later, we contacted FFAs to enquire about their application outcome and current respiratory symptoms. Results Data were available on 116 applicants; of whom, 45% (n = 52) had definite/probable current asthma and were significantly more likely to be older, atopic to common aeroallergens, report atopic disease and have a lower forced expiratory volume in one second/forced vital capacity ratio compared with applicants with no current asthma. Only two individuals’ applications were rejected due to asthma. At follow-up, just 2 (2%) of the 90 operational firefighters reported any recent trouble with asthma. Conclusions A history of asthma alone is not sufficient to determine current asthma in FFAs. Even with a diagnosis of current asthma, FFAs are mostly successful in their application to join the fire service.

Ozone is a highly reactive environmental pollutant with well-recognized adverse effects on lung health. Bronchial hyperresponsiveness (BHR) is one consequence of ozone exposure, particularly for individuals with underlying lung disease. Our data demonstrated that ozone induced substantial ATP release from human airway epithelia in vitro and into the airways of mice in vivo and that ATP served as a potent inducer of mast cell degranulation and BHR, acting through P2X7 receptors on mast cells. Both mast cell-deficient and P2X7 receptor-deficient (P2X7-/-) mice demonstrated markedly attenuated BHR to ozone. Reconstitution of mast cell-deficient mice with WT mast cells and P2X7-/- mast cells restored ozone-induced BHR. Despite equal numbers of mast cells in reconstituted mouse lungs, mice reconstituted with P2X7-/- mast cells demonstrated significantly less robust BHR than mice reconstituted with WT mast cells. These results support a model where P2X7 on mast cells and other cell types contribute to ozone-induced BHR.

BackgroundCholinergic urticaria (CholU) is classified into several subtypes: 1) conventional sweat allergy-type CholU (conventional SAT-CholU), 2) CholU with palpebral angioedema (CholU-PA), 3) CholU with acquired anhidrosis and/or hypohidrosis (CholU-Anhd), and other rare type; 1) and 2) include SAT based on pathogenesis. There have been no studies on differences in the prevalence of bronchial asthma among the CholU subtypes. This is investigated in the present study by evaluating the bronchial responsiveness of each subtype.MethodsPatients 16–80 years of age with CholU were enrolled. We analyzed bronchial responsiveness, respiratory symptoms, and exhaled nitric oxide (FeNO). Bronchial responsiveness was assessed using the methacholine dose indicator Dmin.ResultsA total of 11 patients with conventional SAT-CholU, 11 with CholU-PA, and 11 with CholU-Anhd were enrolled. Median log10 Dmin (interquartile range) of patients with conventional SAT-CholU, CholU-PA, and CholU-Anhd was 0.381 (−0.829, 1.079), 0.717 (0.249, 0.787), and 1.318 (0.121, 1.699), respectively (p=0.516). Dmin was lower in patients with SAT (conventional SAT-CholU and CholU-PA) than in those with CholU-Anhd, although the differences among the 3 types were not significant. Respiratory symptoms evaluated using the International Primary Care Airways Group questionnaire were less frequently observed in CholU-Anhd (0 [0, 1]) than in conventional SAT-CholU (1 [0–2]) or CholU-PA (1 [1–3]) (p=0.049). FeNO of patients with conventional SAT-CholU, CholU-PA, and CholU-Anhd was 23 (18.5, 65.0), 39 (32.0, 59.5), and 25 (19.0, 33.0) ppb, respectively (p=0.237). One of 11 conventional SAT-CholU patients (9.1%) and 6 of 11 CholU-PA patients (54.5%) required treatment for bronchial asthma.ConclusionsLog Dmin tended to be lower in patients with SAT-CholU than in those with CholU-Anhd. Distinguishing between CholU subtypes may reveal different degrees of bronchial responsiveness based on a distinct pathogenesis.Trial registration numberUMIN 000025669; https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000027550

Asthma treatment goals currently focus on symptom and exacerbation control rather than remission. Remission is not identical to cure, but is a step closer. This review considers the current definitions of remission in asthma, the prevalence and predictors, the pathophysiology of remission, the possibility of achieving it using the available treatment options, and the future research directions. Asthma remission is characterised by a high level of disease control, including the absence of symptoms and exacerbations, and normalisation or optimisation of lung function with or without ongoing treatment. Even in those who develop a symptomatic remission of asthma, persistent pathological abnormalities are common, leading to a risk of subsequent relapse at any time. Complete remission requires normalisation or stabilisation of any underlying pathology in addition to symptomatic remission. Remission is possible as part of the natural history of asthma, and the prevalence of remission in the adult asthma population varies between 2% and 52%. The factors associated with remission include mild asthma, better lung function, better asthma control, younger age, early-onset asthma, shorter duration of asthma, milder bronchial hyperresponsiveness, fewer comorbidities and smoking cessation or never smoking. Although previous studies have not targeted treatment-induced remission, there is some evidence to show that the current long-term add-on therapies such as biologics and azithromycin can achieve some criteria for asthma remission on treatment, at least in a subgroup of patients. However, more research is required. Long-term remission could be included as a therapeutic goal in studies of asthma treatments.

INTRODUCTION: Innate immune activation through exposure to indoor and outdoor pollutants is emerging as an important determinant of asthma severity. For example, household levels of the bacterial product lipopolysaccharide (LPS) are associated with increased asthma severity. We hypothesized that activation of the innate immune receptor TLR5 by its bacterial ligand flagellin will exacerbate airway inflammation and asthma symptoms. METHODS: We determined the effect of flagellin co-exposure with ovalbumin in a murine model of allergic asthma. We evaluated the presence of flagellin activity in house dust of asthma patients. Finally, we analyzed the association of a dominant-negative polymorphism in TLR5 (rs5744168) with asthma symptoms in patients with asthma. RESULTS: We showed that bacterial flagellin can be found in the house dust of patients with asthma and that this bacterial product exacerbates allergic airway inflammation in an allergen-specific mouse model of asthma. Furthermore, a dominant-negative genetic polymorphism in TLR5, the receptor for flagellin, is associated with decreased symptoms in patients with asthma. CONCLUSIONS: Together, our results reveal a novel genetic protective factor (TLR5 deficiency) and a novel environmental pollutant (microbial flagellin) that influence asthma severity. (Clinical trials NCT01688986 and NCT01087307).

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 Sovijarvi 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 Sovijarvi. 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): Sovijarvi 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 Sovijarvi (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.

OBJECTIVES The aim of this study was to investigate airway responsiveness and eosinophil and neutrophil inflammatory markers in clinically confirmed nonasthmatic adolescents with elevated fractional exhaled nitric oxide (FeNO), a marker of type-2 inflammation in the airways. METHODOLOGY A total of 959 subjects from a general population, aged 12 to 15 years, answered a standardised questionnaire and underwent FeNO measurements at a screening visit at school. Adolescents without asthma, who had elevated FeNO (FeNO100 > 15 ppb) (n = 19), and control subjects, with low FeNO (FeNO100

Asthma is a chronic inflammatory disorder of the airways that results, physiologically, in hyperreactivity and, clinically, in recurrent episodes of wheezing, chest tightness, or coughing. Airway inflammation, smooth-muscle contraction, epithelial sloughing, mucous hypersecretion, bronchial hyperresponsiveness, and mucosal edema contribute to the underlying pathophysiology of asthma. Diagnostic tests such as methacholine or mannitol challenges or spirometry (pre- and postbronchodilator responses) help to identify such underlying pathophysiology via assessments of bronchial hyperreactivity and lung mechanics but are imperfect and, ultimately, must be viewed in the context of a patient's clinical presentation, including response to pharmacotherapy. Asthma can be classified into either intermittent or persistent, and the latter is either mild, moderate, or severe. Some patients change, in either direction, from intermittent to persistent asthma. In addition, patients with asthma may be classified as allergic (immunoglobulin E mediated), nonallergic (often triggered by viral upper respiratory tract infections or no apparent cause), occupational, aspirin-exacerbated respiratory disease, potentially fatal, exercise-induced, and cough variant asthma. In the latter, the patients have a nonproductive cough that responds to treatment for asthma but not with antibiotics, expectorants, mucolytics, antitussives, or beta2-adrenergic agonists, and to treatment for acid reflux and rhinosinusitis. Thus, cough variant asthma is in the differential diagnosis of chronic cough.

BACKGROUND Factors attributable to the level of fraction of exhaled nitric oxide (FeNO) in different age groups of asthmatic children are still lack of report. OBJECTIVE To evaluate factors associated with FeNO and the response of FeNO to inhaled steroid in different age groups of asthmatic children with allergic rhinitis. METHODS Asthmatic children aged 5 to 12 years were recruited. FeNO, lung function and bronchial hyperresponsiveness (BHR) to methacholine, skin prick testing to a panel of aeroallergens, total immunoglobulin E (T-IgE) in serum and eosinophils in blood were tested. Correlations between FeNO and the measured parameters were assessed. FeNO was measured again after the treatment of combined inhaled corticosteroid and long-acting beta-agonist (ICS/LABA) for 4 weeks. Changes in FeNO between different age groups were compared. RESULTS A total of 121 eligible subjects were enrolled in and completed this study. Asthmatic children aged 10 to 12 years old had significantly higher FeNO than those between 8 and 9 years and 5 to 7 years of children (both P

Blood eosinophilia has been proposed as a surrogate marker for airway eosinophilia and as a predictor of treatment response in chronic obstructive pulmonary disease (COPD). The aim of the study was to assess the relationship between blood and sputum eosinophils and to investigate the association between blood and sputum eosinophil count and clinical features of mild-to-moderate COPD. We performed a retrospective analysis of blood and sputum eosinophil count, as well as demographic and lung function data in a cohort of 90 stable, steroid-naive (Global Initiative for Chronic Obstructive Lung Disease 1 or 2) COPD patients and 20 control subjects. Blood and sputum eosinophil count did not correlate both in patients with COPD (

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a disease with still not enough known pathogenesis despite the development of genetics, immunological and microbiological research. The number of patients with CRS has been constantly growing. The coexistence of CRS, bronchial asthma and aspirin intolerance (aspirin triad) is an adverse prognostic factor with higher risk of recurrences. The aim of study was to compare the severity of CRSwNP depending of coexistence of bronchial asthma and/or aspirin intolerance. The research was performed in the group of 204 patients operated 2009-2013 with 5 years follow-up. Higher nasal polyps growth in groups of patients with aspirin triad and CRSwNP and bronchial asthma in endoscopic examination (p=0,0005 and p=0,0030 respectively) and CT-scan according to Lund-Mackay point scale (p