Frequency of Euroglyphus maynei sensitization in respiratory allergies: a real-life study with bioinformatic analysis and geographical exploration of allergen prevalence.

BACKGROUND: Dermatophagoides pteronyssinus and Dermatophagoides farinae belong to the family Pyroglyphidae (subfamily: "Dermatophagoidinae") and have the respective allergenic proteins of Der p1, Der p2, and Der p23 and Der f1 and Der f2. Euroglyphus maynei, belongs to the family Pyroglyphidae (subfamily: "Pyroglyphinae") and its main allergenic protein is Eur m1, a source of sensitization. Sensitization to D. pteronyssinus and D. farinae is assessed through skin tests, while sensitization to E. maynei is assessed less frequently. OBJECTIVE: This experimental work aims to analyze the prevalence of sensitization to E. maynei in patients with respiratory allergies treated at M. Albanesi Allergy and Immunology Unit in Bari, Italy, and the sequence homology of major allergenic proteins of E. maynei with D. farinae and D. pteronyssinus was analyzed. METHODS: In this real-life study, 65 patients were enrolled. In particular, patients with respiratory allergy were subjected to skin prick tests for common respiratory allergens, including Euroglyphus maynei. The sequence homology analysis was performed between the major allergenic proteins of E. maynei and those of D. pteronyssinus and D. farinae. RESULTS: Sensitization to E. maynei accounts for 41.5% of patients. All patients with E. maynei sensitization had concomitant sensitization to D. farinae and D. pteronyssinus. The analysis of sequence homology of Der p1 and Der f1 proteins with the sequence of Eur m1 protein demonstrated an identity of 84.4% and 86%, respectively. CONCLUSIONS: Nearly 50% of house dust mites-sensitized patients have a concomitant sensitization to E. maynei. The cross-sensitization could be due to Der f1, Der p1, and Eur m1 similarity.

Effect of overweight/obesity on relationship between fractional exhaled nitric oxide and airway hyperresponsiveness in Chinese elderly patients with asthma.

Purpose: This retrospective study investigates the influence of overweight and obesity status on pulmonary function, airway inflammatory markers, and airway responsiveness in elderly asthma patients. Methods: Patients with asthma older than 65 years old who completed a bronchial provocation test (BPT) or bronchial dilation test (BDT) and a fractional exhaled nitric oxide (FeNO) test between December 2015 and June 2020 were identified retrospectively for this study. All of the patients were categorized into overweight/obesity and non-obesity groups based on their BMI. Pulmonary function test (PFT) and FeNO measurements were accomplished according to the 2014 recommendations of the Chinese National Guidelines of Pulmonary Function Test and American Thoracic Society/European Respiratory Society recommendations, respectively. Results: A total of 136 patients with an average age of 71.2 ± 5.40 years were identified. The average BMI was 23.8 ± 3.63, while the value of FeNO was 42.3 ± 38.4 parts per billion (ppb). In contrast to the non-obesity group, which had a value of 48.8 ± 43.1 ppb for FeNO, the overweight/obesity group had a significant lower value of 35.4 ± 31.4 ppb. There was no significant difference in the proportion of individuals with high airway hyperresponsiveness between the overweight/obesity and non-obesity groups (96 patients in total). Multiple linear regression analysis established an inverse correlation between FeNO and Provocation concentration causing a 20% fall in FEV1(PC20) but excluded significant relationships with age and BMI. The model's R is 0.289, and its p value is 0.045. Conclusion: The elderly Chinese Han asthmatics with overweight/obesity had lower FeNO levels than those with non-obese according to our findings. In addition, the FeNO level was inversely correlated between FeNO levels and PC20 in elderly asthmatics.

Is allergen immunotherapy a model of personalized treatment in pediatric respiratory allergy?

PURPOSE OF REVIEW: To review recent evidence on allergen immunotherapy (AIT) as a model of personalized medicine in the treatment of children and adolescents with respiratory allergies. RECENT FINDINGS: Meta-analysis and systematic review studies continue to point out that AIT is an effective treatment for children with respiratory allergies. Molecular allergy allows the understanding of patient sensitization profiles that frequently change the prescription of AIT. There is still a lack of evidence showing that this personalized prescription of AIT is associated with better clinical outcomes. The nasal allergen challenge has extended the indications of AIT for a new group of subjects with local allergic rhinitis. Patient selection of allergens involved in the increasingly personalized composition of extracts to be used in AIT increasingly characterizes it as personalized medicine. SUMMARY: Despite the numerous studies carried out to identify the best biomarker to evaluate the response to AIT, there is still much disagreement, and clinical assessment (symptoms, quality of life, among others) continues to be the best way to evaluate the therapeutic success of AIT.

The link between early childhood lower airway symptoms, airway hyperresponsiveness, and school-age lung function.

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

Risk factors for asthma in patients with allergic rhinitis in eastern China.

BACKGROUND: Asthma is one of the most common chronic diseases among children and adults and can lead to a high health and socioeconomic burden. Allergic rhinitis (AR) often precedes the development of asthma. This study aims to clarify the risk factors for cocurrent asthma in patients with AR in eastern China. METHODS: A cross-sectional study of 3739 patients with AR was performed in eastern China. Patients meeting the criteria for AR were evaluated using a skin-prick test (SPT) of 16 common aeroallergens. A logistic regression analysis was used to assess the risk factors of asthma in patients with AR. RESULTS: The prevalence of asthma in patients with AR was 14.23%. The patients sensitive to dust mites (D. farinae and D. pteronyssinus) had the highest prevalence (76.84% and 73.68%). A significant difference was found in sensitization to four types of allergens (D. farinae, D. pteronyssinus, dog dander, Alternaria alternata) in patients with AR with and without asthma. The strongest risk factor for asthma in patients with AR was an allergy to Aspergillus fumigatus (adjusted OR, 2.42; 95% CI, 1.50-3.90), followed by allergy to D. pteronyssinus (adjusted OR, 2.06; 1.30-3.27), and allergy to dog dander (adjusted OR, 1.92; 1.24-2.97). Various risk factors that are independently associated with asthma in patients with AR were found in different age groups. CONCLUSIONS: We observed a difference in risk factors in patients with AR with and without asthma. Clarifying the risk factors for asthma in patients with AR is important and may be beneficial to the optimal interventions of asthma.

Prevention of IL-6 signaling ameliorates toluene diisocyanate-induced steroid-resistant asthma.

BACKGROUND: Accumulating evidence indicated the crucial role for interleukin 6 (IL-6) signaling in the development of allergic asthma. Yet, the role of IL-6 signaling in toluene diisocyanate (TDI)-induced mixed granulocytic airway inflammation still remains unclear. Thus, the aims of this study were to dissect the role of IL-6 signaling and to evaluate the effect of tocilizumab on TDI-induced steroid-resistant asthma. METHODS: TDI-induced asthma model was prepared and asthmatic mice were respectively given IL-6 monoclonal antibody, IL-6R monoclonal antibody (tocilizumab, 5 mg/kg, i.p. after each challenge) for therapeutic purposes or isotype IgG as control. RESULTS: TDI exposure just elevated IL-6R expression in the infiltrated inflammatory cells around the airway, but increased glycoprotein 130 expression in the whole lung, especially in bronchial epithelium. Moreover, TDI inhalation increased airway hyperresponsiveness (AHR) to methacholine, coupled with mixed granulocytic inflammation, exaggerated epithelial denudation, airway smooth muscle thickening, goblet cell metaplasia, extensive submucosal collagen deposition, dysregulated Th2/Th17 responses, as well as innate immune responses and raised serum IgE. And almost all these responses except for raised serum IgE were markedly ameliorated by the administration of IL-6 neutralizing antibody or tocilizumab, but exhibited poor response to systemic steroid treatment. Also, TDI challenge induced nucleocytoplasm translocation of HMGB1 and promoted its release in the BALF, as well as elevated lung level of STAT3 phosphorylation, which were inhibited by anti-IL-6 and anti-IL-6R treatment. CONCLUSIONS: Our data suggested that IL-6 monoclonal antibody and tocilizumab might effectively abrogate TDI-induced airway inflammation and remodeling, which could be used as a clinical potential therapy for patients with severe asthma.

Blood eosinophils, FeNO and small airways dysfunction in predicting airway hyperresponsiveness in patients with asthma-like symptoms.

PURPOSE: In patients with suspected asthma and no airflow limitation in spirometry, methacholine challenge testing (MCT) for airway hyperresponsiveness (AHR) is an option of documenting variable airflow limitation. The goal of the study was to assess the ability of blood eosinophils, fractional concentration of exhaled nitric oxide (FeNO) and distal airways function to discriminate patients with AHR from those with normal airway responsiveness (AR). METHODS: We analyzed baseline data from 42 participants who underwent MCT because of asthma-like symptoms and no airflow limitation in spirometry. RESULTS: Eosinophil count was higher among participants with borderline AHR comparing to those with normal AR (340 cells/µL, IQR 285-995 vs. 125 cells/µL, IQR 75-180, post-hoc p = 0.041). FeNO and percent predicted of functional residual volume (FRC%pred) were higher in participants with moderate-marked AHR compared to those with normal AR (40 ppb, IQR 30.5-100.5 vs. 18 ppb, IQR 13-50, post-hoc p = 0.008; 140.1%±17.0% vs. 107.3%±20.7%, post-hoc p < 0.001, respectively). Percentage predicted of the maximal expiratory flow at 25% of the forced vital capacity (MEF25%pred) was lower in participants with mild AHR and borderline AHR compared to those with normal AR (72.9%±16.9% vs. 113.0%±36.8%, post-hoc p = 0.017; 73.3%±15.9% vs. 113.0%±36.8%, post-hoc p = 0.045; respectively). Level of AHR correlated with eosinophil count, FeNO, MEF25%pred, forced expiratory flow between 25% and 75% of vital capacity (FEF25-75%pred), FRC%pred and specific airway resistance (sRaw). CONCLUSIONS: Blood eosinophils, FeNO and small airways dysfunction markers are related to the level of AR to methacholine in patients with asthma-like symptoms and no airflow limitation in spirometry.

A Helminth-Derived Chitinase Structurally Similar to Mammalian Chitinase Displays Immunomodulatory Properties in Inflammatory Lung Disease.

Immunomodulation of airway hyperreactivity by excretory-secretory (ES) products of the first larval stage (L1) of the gastrointestinal nematode Trichuris suis is reported by us and others. Here, we aimed to identify the proteins accounting for the modulatory effects of the T. suis L1 ES proteins and studied six selected T. suis L1 proteins for their immunomodulatory efficacy in a murine OVA-induced allergic airway disease model. In particular, an enzymatically active T. suis chitinase mediated amelioration of clinical signs of airway hyperreactivity, primarily associated with suppression of eosinophil recruitment into the lung, the associated chemokines, and increased numbers of RELMα + interstitial lung macrophages. While there is no indication of T. suis chitinase directly interfering with dendritic cell activation or antigen presentation to CD4 T cells, treatment of allergic mice with the worm chitinase influenced the hosts' own chitinase activity in the inflamed lung. The three-dimensional structure of the T. suis chitinase as determined by high-resolution X-ray crystallography revealed high similarities to mouse acidic mammalian chitinase (AMCase) but a unique ability of T. suis chitinase to form dimers. Our data indicate that the structural similarities between the parasite and host chitinase contribute to the disease-ameliorating effect of the helminth-derived chitinase on allergic lung inflammation.

Systemic and local cytokine profile and risk factors for persistent allergic airway inflammation in patients sensitised to house dust mite allergens.

OBJECTIVE: To evaluate cytokine profile, vitamin D status, symptom score and quality of life in patients with persistent allergic airway diseases sensitised to house dust mites (HDM) in comparison with healthy individuals. MATERIAL AND METHODS: Patients sensitized to HDM with persistent AR and having symptoms for at least 2 years with or without AA were involved into the study. Measurements of vitamin D level in serum and IL-10, IL-13, IL-17, IL-22, IL-33 and IFN-gamma in serum and nasal lavage were performed by ELISA. RESULTS: Eighty-one subjects were involved into the study. Serum IL-10 concentration was higher in patients with AR than in patients with AR and AA (6.71 ± 1.73 vs. 1.98 ± 0.24, p < 0.05). IFN-gamma level in nasal lavage was higher in patients with AR and AA than in patients with AR (p < 0.01) and healthy individuals (p < 0.05) (7.50 ± 0.37 vs. 6.80 ± 0.99 vs. 6.50 ± 0.22). Serum IL-22 negatively correlated with IL-22 in nasal lavage, whereas serum IFN-gamma positively correlated with IFN-gamma in nasal lavage. Positive correlation between serum IL-17 and total IgE and negative correlation between IL-17 in nasal lavage and eosinophils in nasal smear were found in patients with AR and AA. Serum IFN-gamma decreased the risk of AR for healthy individuals. Serum IL-10 and vitamin D decreased risk for development of AA for patients with AR. IL-22 in serum and IL-10 and IL-33 in nasal lavage increased this risk. CONCLUSION: Novel cytokines such as IL-22, IL-17 and IL-33 and vitamin D may be involved in pathogenesis of persistent airway inflammation in patients sensitized to HDM.

Variation in pulmonary function tests among children with sickle cell anemia: a systematic review and meta-analysis.

INTRODUCTION: the spectrum of pulmonary complications in sickle cell anemia (SCA) comprises mainly of acute chest syndrome (ACS), pulmonary hypertension (PH) and airway hyper-responsiveness (AHR). This study was conducted to examine the abnormalities in pulmonary function tests (PFTs) seen in children with SCA. METHODS: electronic databases (Cochrane library, PubMed, EMBASE, Scopus, Web of Science) were used as data sources. Two authors independently reviewed studies. All case-control studies with PFT performed in patients with SCA and normal controls were reviewed. Pulmonary functions were assessed with the help of spirometry, lung volume and gas diffusion findings. RESULTS: nine studies with 788 SCA children and 1101 controls were analyzed. For all studies, the pooled mean difference for forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, peak expiratory flow rate (PEFR), total lung capacity (TLC) and carbon mono-oxide diffusing capacity (DLCO) were -12.67, (95% CI: -15.41,-9.94), -11.69, (95% CI: -14.24, -9.14), -1.90, (95% CI: -4.32, 0.52), -3.36 (95% CI: -6.69, -0.02), -7.35, (95% CI: -14.97, -0.27) and -4.68, (95% CI -20.64, -11.29) respectively. FEV1 and FVC and were the only parameters found to be significantly decreased. CONCLUSION: sickle cell anemia was associated with lower FEV1 and FVC, thus, supporting the role of routine monitoring for the progression of lung function decline in children with SCA with ACS. We recommend routine screening and lung function monitoring for early recognition of pulmonary function decline.

Contribution of Regulatory T Cell Methylation Modifications to the Pathogenesis of Allergic Airway Diseases.

Regulatory T (Treg) cells are a subtype of CD4+ T cells that play a significant role in the protection from autoimmunity and the maintenance of immune tolerance via immune regulation. Epigenetic modifications of Treg cells (i.e., cytosine methylation at the promoter region of the transcription factor, Forkhead Box P3) have been found to be closely associated with allergic diseases, including allergic rhinitis, asthma, and food allergies. In this study, we highlighted the recent evidence on the contribution of epigenetic modifications in Treg cells to the pathogenesis of allergic diseases. Moreover, we also discussed directions for future clinical treatment approaches, with a particular emphasis on Treg cell-targeted therapies for allergic disorders.

Local Respiratory Allergy: From Rhinitis Phenotype to Disease Spectrum.

Local respiratory allergy (LRA) is defined by the negativity of atopy tests, a clinical history suggestive of airway allergy and a positive response to the nasal and/or bronchial allergen challenge. The clinical spectrum of LRA is comprised of three conditions: local allergic rhinitis (LAR) and local allergic asthma in non-atopic patients, and dual allergic rhinitis (coexistence of allergic rhinitis and LAR) in atopic individuals. LRA is an independent disease phenotype not progressing to atopy over time, but naturally evolving to the clinical worsening and the onset of comorbidities. Published data suggests that LRA is mediated through the mucosal synthesis of allergen-specific (s)IgE, which binds to FcϵRI on resident mast cells, and in >50% of cases traffics to the blood stream to sensitize circulating basophils. To date, 4 clinical trials have demonstrated the capacity of allergen immunotherapy (AIT) to decrease nasal, conjunctival and bronchial symptoms, to improve quality of life, to increase the threshold dose of allergen eliciting respiratory symptoms, and to induce serum sIgG4 in LRA individuals. Collectively, these data indicate that local allergy is a relevant disease mechanisms in both atopic and non-atopic patients with airway diseases.

Atypical food protein-induced enterocolitis syndrome in children: Is IgE sensitisation an issue longitudinally?

BACKGROUND: Food Protein-Induced Enterocolitis Syndrome (FPIES) is a clinically well-characterised, non-Immunoglobulin E (IgE)-mediated food allergy syndrome, yet its rare atypical presentation remains poorly understood. OBJECTIVE: Aim of this study was to present the 10-year experience of a referral centre highlighting the atypical FPIES cases and their long-term outcome. METHODS: FPIES cases were prospectively evaluated longitudinally in respect of food outgrowth and developing other allergic diseases with or without concomitant IgE sensitisation. RESULTS: One hundred subjects out of a total of 14,188 referrals (0.7%) were identified. At presentation, 15 patients were found sensitised to the offending food. Fish was the most frequent eliciting food, followed by cow's milk and egg. Tolerance acquisition was earlier for cow's milk, followed by egg and fish, while found not to be protracted in atypical cases. Resolution was not achieved in half of the fish subjects during the 10-year follow-up time. Sensitisation to food was not related to infantile eczema or culprit food, but was related to sensitisation to aeroallergens. In the long-term evaluation, persistence of the FPIES or aeroallergen sensitisation was significantly associated with an increased hazard risk of developing early asthma symptoms. CONCLUSION: Sensitisation to food was related neither to eczema or culprit food nor to tolerance acquisition but rather to the development of allergic asthma through aeroallergen sensitisation. In addition to an IgE profile at an early age, FPIES persistence may also trigger mechanisms switching FPIES cases to a T-helper 2 cells immune response later in life, predisposing to atopic respiratory symptoms; albeit further research is required.

Long-chain non-coding RNA n337374 relieves symptoms of respiratory syncytial virus-induced asthma by inhibiting dendritic cell maturation via the CD86 and the ERK pathway.

BACKGROUND: In this study, we investigated the relationship between long-chain non-coding RNAs (lncRNAs) and respiratory syncytial virus (RSV)-exacerbated asthma. METHODS: Transcriptome microarray was used to detect differentially expressed lncRNAs in dendritic cells (DCs) co-cultured with RSV-infected human airway epithelial cells and DCs infected with RSV. The identified downregulation of lncRNA n337374 was validated using fluorescence RT-qPCR. LncRNA n337374-overexpressing DCs and RSV-exacerbated asthmatic mouse models were established. Airway hyper-reactivity and bronchoalveolar lavage fluid (BALF) were examined, and pathological changes in lung tissues were observed in mice. Surface molecules in DCs were detected by flow cytometry and RT-qPCR and the expression of CD86 and mitogen-activated protein kinases was determined by western blot. RESULTS: In an RSV-exacerbated asthmatic mouse model, the airway wall was thickened, luminal stenosis was observed, a large number of inflammatory cells were infiltrated in the lung tissue, lung function was impaired, and counts of inflammatory cells in the BALF were increased. The overexpression of lncRNA n337374 ameliorated these pathological changes and improved impaired lung function and inflammation in an asthmatic mouse model. In DCs co-cultured with RSV-infected human airway epithelial cells, CD86 expression was promoted and ERK was markedly phosphorylated. When lncRNA n337374-overexpressing DCs were used in the co-cultures, the expression of CD86 and phosphorylated ERK was decreased. CONCLUSION: The results suggest that lncRNA n337374 overexpression may suppress DC maturation by downregulating the CD86 and ERK pathway, subsequently relieving the symptoms of RSV-induced asthma. LncRNA n337374 may be a promising target in the treatment of RSV infection-induced asthma.

Comparison of spirometry and impulse oscillometry in methacholine challenge test for the detection of airway hyperresponsiveness in adults.

INTRODUCTION: Airway hyper-responsiveness (AHR) is a characteristic feature of asthma. The aim of this study was to compare the impulse oscillometry (IOS) and spirometry to methacholine for AHR detection among individuals with clinically hyper-reactive airway disease suggestive of bronchial asthma and baseline spirometry were normal. MATERIALS AND METHODS: Adults with symptoms suggestive of AHR and normal baseline spirometry test were selected. The short protocol of methacholine challenge test (MCT) was performed for all subjects using IOS and spirometry simultaneously. The primary endpoint was to compare the methacholine dosage causing a 20% drop in forced expiratory volume in one second (FEV1), with methacholine dosage that causing 40% increasing the baseline respiratory resistance at 5 hertz (R5), as measured by IOS. RESULT: A total of 235 participants were analyzed, 184 (78.2%) had positive test results with R5, while 81 (34.4%) had positive MCT results with FEV1.The sensitivity and specificity of MCT with R5were 87.3%, 64.6%, and MCT with FEV1 were 39.1%, 85.4%, respectively. The area under the receiver operating characteristic (ROC) curve was greater at lower doses of MCT at R5, (AUROC: 0.653; p= 0.01). CONCLUSIONS: The results showed higher sensitivity, negative predictive value, and earlier response of the short protocol of MCT with IOS, compared to MCT with spirometry. Our study suggested the utility of IOS in addition to conventional spirometry as a method of choice in MCT for detection of AHR.

Chitinase-Induced Airway Hyperreactivity and Inflammation in a Mouse Model of Nonallergic Asthma.

INTRODUCTION: Environmental exposure to mites and fungi has been proposed to critically contribute to the development of IgE-mediated asthma. A common denominator of such organisms is chitin. Human chitinases have been reported to be upregulated by interleukin-13 secreted in the context of Th2-type immune responses and to induce asthma. We assessed whether chitin-containing components induced chitinases in an innate immune-dependent way and whether this results in bronchial hyperresponsiveness. MATERIALS AND METHODS: Monocyte/macrophage cell lines were stimulated with chitin-containing or bacterial components in vitro. Chitinase activity in the supernatant and the expression of the chitotriosidase gene were measured by enzyme assay and quantitative PCR, respectively. Non-sensitized mice were stimulated with chitin-containing components intranasally, and a chitinase inhibitor was administered intraperitoneally. As markers for inflammation leukocytes were counted in the bronchoalveolar lavage (BAL) fluid, and airway hyperresponsiveness was assessed via methacholine challenge. RESULTS: We found both whole chitin-containing dust mites as well as the fungal cell wall component zymosan A but not endotoxin-induced chitinase activity and chitotriosidase gene expression in vitro. The intranasal application of zymosan A into mice led to the induction of chitinase activity in the BAL fluid and to bronchial hyperresponsiveness, which could be reduced by applying the chitinase inhibitor allosamidin. DISCUSSION: We propose that environmental exposure to mites and fungi leads to the induction of chitinase, which in turn favors the development of bronchial hyperreactivity in an IgE-independent manner.

Updated review of reported cases of reactive airways dysfunction syndrome.

BACKGROUND: A previous systematic review of the diagnosis of reactive airways dysfunction syndrome (RADS), undertaken from 1985 to 2004, found a lack of standardization of case reporting, thus misattribution of symptoms can occur. AIMS: We aimed to update the systematic review, update the list of reported causes and see whether a more structured approach to reporting has been adopted. METHODS: We undertook a systematic literature review, using the databases EMBASE and Ovid MEDLINE, with search terms 'reactive airways dysfunction syndrome' or 'asthma AND acute irritant', and reported according to PRISMA guidelines. We included papers and abstracts published from January 2005 to September 2019, and articles were grouped by the presence or absence of diagnostic features: 'definite' RADS (met Brooks' criteria) or 'possible' RADS (Brooks' criteria not met or insufficient data). We collected demographic and diagnostic data for cases, where given. RESULTS: Eleven papers and six conference abstracts met the inclusion criteria, 13 of which were case series or reports, and comprised 752 cases in total; seven articles met Brooks' criteria for RADS diagnosis. A variety of agents were implicated, with chlorine or chlorine-releasing molecules most frequently reported. CONCLUSIONS: A lack of standardized reporting of RADS remains. The majority of published articles and conference abstracts either do not meet, or contain insufficient data to judge against, Brooks' criteria, particularly in relation to onset of symptoms and bronchial hyper-reactivity or variability of airflow obstruction. Some novel agents are described, in keeping with recognized structural taxonomies.

Effect of maternal sleep, physical activity and screen time during pregnancy on the risk of childhood respiratory allergies: a sex-specific study.

BACKGROUND: Early life exposure in the uterus had a long-term effect on children's health. As the prevalence of allergies is increasing with a remarkable sex difference, very few studies have traced back to their early origins. We sought to investigate if maternal behavioral exposure, herein sleep, physical activity, and screen time during pregnancy is associated with childhood respiratory allergies. The sex difference would be examined. METHODS: Six thousand two hundred thirty-six mother-child pairs from Shanghai Children Allergy Study (SCAS) were enrolled, The International Study of Asthma and Allergies in Childhood questionnaire was adopted to evaluate respiratory allergic diseases. RESULTS: 14.6, 16.2, and 21.0% of children had asthma, wheeze, and allergic rhinitis, respectively. Maternal short sleep duration, lack of physical activity, and too much screen exposure during pregnancy could increase the risk of childhood respiratory allergies, however, the significance was found only in males. Moreover, a dose-response trend was clearly shown, any two of the three combined could increase the risk (OR,1.921; 95% CI,1.217-3.033), and the coexistence of all three further amplified the risk (OR,2.412; 95% CI,1.489-3.906). The findings can be verified in allergen test subgroup and each single type of respiratory allergies in most cases. CONCLUSIONS: Maternal unhealthy behaviors during pregnancy could increase the risk of childhood respiratory allergies with a dose-response pattern. Males were more susceptible to the association. The identification of modifiable maternal risk behaviors lies in the emphasis of intervention in early life to face up increasing childhood allergies.

Outcomes of Paradoxical Vocal Cord Motion Diagnosed in Childhood.

OBJECTIVES: To explore long-term patient reported outcome (PRO) measures of pediatric paradoxical vocal cord motion (PVCM) including ease of diagnosis, management, symptom duration and effect on quality of life. METHODS: All children >8 years of age diagnosed with PVCM at a tertiary pediatric hospital between 2006 and 2017 were invited to complete a survey addressing study objectives. RESULTS: 21/47 eligible participants could be contacted and 18/21 (86%) participated. 78% were female with a mean age at diagnosis of 11.6 and 15.0 years at survey completion. Common PVCM symptoms reported were dyspnea (89%), globus sensation (56%), and stridor (50%). The median time to diagnosis was 3 months (IQR 2-5 months). Nearly all reported being misdiagnosed with another condition, usually asthma, until being correctly diagnosed usually by an otolaryngologist. Participants reported undergoing 3.7 diagnostic studies (range 0-8); pulmonary function testing was most common. Of numerous treatments acknowledged, breathing exercises were common (89%) but only reported helpful by 56%. Use of biofeedback was recalled in 1/3 of subjects but reported helpful in only 14% of them. Anti-reflux, allergy, anticholinergics, inhalers and steroids were each used in >50%, but rarely reported effective. PVCM was reportedly a significant stressor when initially diagnosed but despite 2/3 of participants still reporting ongoing PVCM symptoms, the perceived stress significantly decreased over time (Z = 3.26, P = 0.001). CONCLUSIONS: This first PVCM PRO study endorses that diagnosis is often delayed and prescribed treatments often viewed as ineffective. While biofeedback and breathing exercises may be critical for short-term control of PVCM episodes, lifestyle changes and stress reduction are likely necessary for long-term management. Increased awareness and improvements in management are needed for this condition.