Asthma-like Symptoms Research Articles

Dyspnea and nocturnal cough due to esophageal diffuse leiomyomatosis in a girl with hematuria.

A 7-year-old girl with hematuria and clinical suspicion of Alport syndrome (AS) presented with dyspnea and nocturnal cough, initially diagnosed and treated as asthma. Despite inhaled corticosteroid therapy, her symptoms persisted, and spirometry indicated obstructive lung function without bronchodilator response. Chest CT revealed diffuse thickening of the esophageal wall, tracheal compression, with involvement of the gastric cardia, suggestive of diffuse leiomyomatosis. Subsequent genetic reanalysis confirmed the presence of a contiguous deletion of COL4A5 and COL4A6 genes, solidifying the diagnosis of AS. Diffuse leiomyomatosis, a rare benign neoplasm associated with AS, typically manifests as dysphagia, but in this case, it presented initially with asthma-like symptoms. This case emphasizes the importance of imaging when asthma treatment fails, particularly in patients with coexisting conditions of another system.

(FEV3-FEV1)/FVC: A Terminal-Airflow Variable for Airway Hyperresponsiveness and Inflammation Prediction in Patients With Symptoms Despite Preserved Spirometry

BackgroundSmall-airway function assessment is crucial for asthma diagnosis and management. Abnormalities in terminal airflow deserve attention. ObjectiveThis study investigated whether the ratio of forced expiratory volume in the second and third seconds to forced vital capacity ([FEV3-FEV1]/FVC) correlates with airway hyperresponsiveness (AHR) and inflammation in patients with preserved spirometry. MethodsThis cross-sectional study enrolled patients with FEV1 ≥ 80% predicted, FEV1/FVC ≥ 0.7, and recurring asthma-like symptoms. Data included demographics, fractional exhaled nitric oxide (FeNO), impulse oscillometry, and spirometry. Univariate and combined models predicting AHR was analyzed in 553 patients and validated in 561. Correlations between sputum inflammation and spirometrics were also assessed. ResultsAHR+ patients exhibited higher (FEV3-FEV1)/FVC ratios compared to AHR-. This ratio showed the strongest association with the methacholine dose causing a 20% FEV1 decrease (PD20) and the response dose ratio (RDR)(r = -0.26 and 0.39, respectively; P < .001, both). The area under the receiver operating characteristic curve for AHR diagnosis using (FEV3-FEV1)/FVC was 0.751, increasing to 0.821 when combined with FeNO, confirmed in the validation cohort. (FEV3-FEV1)/FVC was superior to maximal expiratory flow at 50% of forced vital capacity for identifying eosinophilic airway inflammation characterized by elevated FeNO levels. It correlated better with sputum eosinophil count than with the other spirometrics. ConclusionElevated (FEV3-FEV1)/FVC were evident in AHR+ patients with preserved FEV1/FVC ratios. It serves as a sensitive marker of AHR and airway inflammation correlating with RDR, PD20, and sputum eosinophils, suggesting its utility in monitoring patients at risk for uncontrolled asthma.

The association between ibuprofen administration in children and the risk of developing or exacerbating asthma: a systematic review and meta-analysis

BackgroundIbuprofen is one of the most commonly used analgesic and antipyretic drugs in children. However, its potential causal role in childhood asthma pathogenesis remains uncertain. In this systematic review, we assessed the association between ibuprofen administration in children and the risk of developing or exacerbating asthma.MethodsWe searched MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science, and Scopus from inception to May 2022, with no language limits; searched relevant reviews; and performed citation searching. We included studies of any design that were primary empirical peer-reviewed publications, where ibuprofen use in children 0–18 years was reported. Screening was performed in duplicate by blinded review. In total, 24 studies met our criteria. Data were extracted according to PRISMA guidelines, and the risk of bias was assessed using RoB2 and NOS tools. Quantitative data were pooled using fixed effect models, and qualitative data were pooled using narrative synthesis. Primary outcomes were asthma or asthma-like symptoms. The results were grouped according to population (general, asthmatic, and ibuprofen-hypersensitive), comparator type (active and non-active) and follow-up duration (short- and long-term).ResultsComparing ibuprofen with active comparators, there was no evidence of a higher risk associated with ibuprofen over both the short and long term in either the general or asthmatic population. Comparing ibuprofen use with no active alternative over a short-term follow-up, ibuprofen may provide protection against asthma-like symptoms in the general population when used to ease symptoms of fever or bronchiolitis. In contrast, it may cause asthma exacerbation for those with pre-existing asthma. However, in both populations, there were no clear long-term follow-up effects.ConclusionsIbuprofen use in children had no elevated risk relative to active comparators. However, use in children with asthma may lead to asthma exacerbation. The results are driven by a very small number of influential studies, and research in several key clinical contexts is limited to single studies. Both clinical trials and observational studies are needed to understand the potential role of ibuprofen in childhood asthma pathogenesis.

The Early Appearance of Asthma and Its Relationship with Gut Microbiota: A Narrative Review.

Asthma is, worldwide, the most frequent non-communicable disease affecting both children and adults, with high morbidity and relatively low mortality, compared to other chronic diseases. In recent decades, the prevalence of asthma has increased in the pediatric population, and, in general, the risk of developing asthma and asthma-like symptoms is higher in children during the first years of life. The "gut-lung axis" concept explains how the gut microbiota influences lung immune function, acting both directly, by stimulating the innate immune system, and indirectly, through the metabolites it generates. Thus, the process of intestinal microbial colonization of the newborn is crucial for his/her future health, and the alterations that might generate dysbiosis during the first 100 days of life are most influential in promoting hypersensitivity diseases. That is why this period is termed the "critical window". This paper reviews the published evidence on the numerous factors that can act by modifying the profile of the intestinal microbiota of the infant, thereby promoting or inhibiting the risk of asthma later in life. The following factors are specifically addressed in depth here: diet during pregnancy, maternal adherence to a Mediterranean diet, mode of delivery, exposure to antibiotics, and type of infant feeding during the first three months of life.

Ism1 deficiency in mice exacerbates bleomycin-induced pulmonary fibrosis with enhanced cellular senescence and delayed fibrosis resolution

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease with high morbidity and mortality but unclear etiology and incomplete pathophysiological understandings, making the discovery of effective therapeutics arduous. Currently, two drugs, nintedanib and pirfenidone, are available for IPF treatment which can slow down the fibrotic scarring in the lung but are unable to provide disease resolution. Hence, further revelation of the molecular mechanisms of IPF is critical for the development of novel therapeutics. Isthmin-1 (ISM1) is a secreted anti-inflammatory protein highly expressed in the mouse and human lung. Ism1−/− mice presented spontaneous and progressive lung emphysema, as well as heightened acute lung injury (ALI) upon lipopolysaccharide (LPS) treatment with an accompanied increase of post-LPS-ALI pulmonary fibrosis. ISM1 is important for lung homeostasis with airway-delivered recombinant ISM1 (rISM1) suppressing cigarette smoke-induced emphysema, LPS-ALI, and house-dust mites (HDM)-induced asthma-like symptoms in mice. However, the role of ISM1 in pulmonary fibrosis is yet to be clearly understood. In this work, we show that Ism1−/− mice presented heightened bleomycin-induced pulmonary fibrosis (BIPF), with enhanced immune cell infiltration, myofibroblast accumulation, and collagen deposition. ISM1 deficiency also led to increased cellular senescence in mouse lungs, isolated primary alveolar type II epithelial cells, and primary lung fibroblasts upon bleomycin treatment. Ism1−/− mice also showed delayed resolution of pulmonary fibrosis with reduced lipofibroblasts and downregulation of lipid synthesis-related genes. These results are in congruence with the RNA-seq data which demonstrated gene expression alterations in Ism1−/− lung that are linked to predisposition to pulmonary fibrosis and dysregulation of lipid metabolism pathways. Gene expression analyses showed that Ism1 is similarly dysregulated in the lungs of BIPF and human IPF patients. These findings reveal an anti-fibrotic role of ISM1 in mouse lungs and provide the foundation to further investigate possible therapeutic applications of ISM1 for pulmonary fibrosis in the future.

The unusual connection between Right-Sided Aortic Arch and bronchial asthma

This work describes a rare clinical case of anomalous positioning of the aortic arch in a female patient with asthma. It highlights literature suggesting that this anomaly may sometimes mimic bronchial asthma, underscoring the importance of conducting bronchodilator reversibility tests more frequently to identify underlying asthma. The patient, a woman presenting with asthma symptoms, was found to have a Right-Sided Aortic Arch (RSAA), which is an unusual finding in the absence of congenital heart disease. Given the rarity of this presentation, it underscores the need for thorough evaluation and consideration of alternative diagnoses in patients with atypical asthma symptoms. This case emphasizes the importance of comprehensive diagnostic approaches, including spirometry and bronchodilator testing, to accurately diagnose and manage patients with asthma-like symptoms associated with rare anatomical variations such as RSAA.

Pilot study to determine asthma-like symptoms in the Sverdlovsk region

Introduction. Bronchial asthma (BA) occupies one of the leading places in the structure of chronic nonspecific lung diseases in children. At an early age it develops in a relationship between genetic and environmental factors and often does not have a characteristic clinical picture. Allergic rhinitis (AR) increases the risk of developing and severity of asthma. Assessing the risk of developing BA and AR in children is necessary for timely diagnosis. Purpose of the study. To identify the prevalence of symptoms of bronchial asthma in children in the Sverdlovsk region using the example of Yekaterinburg and Nizhny Tagil using Russian versions of the Asthma Prediction Tool and ISAAC questionnaires and analyze the data obtained. Materials and methods. 64 children aged 6-8 years who did not have chronic lung diseases were studied: 30 people - in the Children's Hospital No. 8 of Yekaterinburg and 34 - in kindergarten No. 201 of Nizhny Tagil using Russified versions of the “Asthma Prediction Tool” and ISAAC questionnaires, filled out official representatives of children after informed consent to conduct the study. 64 correctly completed questionnaires were analyzed. Results. The proportion of children with an average and high risk of developing asthma: in Yekaterinburg 26.67%, in Nizhny Tagil - 35.29%. Symptoms of AR were detected in 60% of children from Yekaterinburg and in 82.35% from Nizhny Tagil, which is 2.5 and 1.6 times more common than the established diagnosis of AR, respectively. In Yekaterinburg, a high risk of asthma is associated with an allergic phenotype based on the frequency of concomitant atopic dermatitis (16.67% compared with 10% in the low-risk group, p = 0.0159) or its absence (63.33% and 10%, respectively, p= 0.0159), in Nizhny Tagil this relationship was not confirmed when tested by a two-sided Fisher test. The frequency of cases of hereditary predisposition to allergic pathology does not have significant differences between high (medium) and low risk groups in both cities. Conclusion. In Russia, 4.8 additional cases of asthma and status asthmaticus per 100 thousand children are associated with air quality. In 2021, the Sverdlovsk region is noted as one of the priority subjects of the Russian Federation in terms of the number of asthma diseases associated with the aerogenic factor in the environment of children. Although the observed trend in the predominance of cumulative symptoms of asthma and AR in children in Nizhny Tagil, in comparison with Yekaterinburg, is not statistically significant, it correlates with a higher level of aerogenic air pollution, this indirectly confirms the absence of a statistically significant relationship with a family history of allergic pathology. However, the connection with man-made pollutants is not taken into account in the ISAAC questionnaires. To confirm that the prevalence of asthma and AR symptoms is higher than those obtained in multicenter studies among children of a similar age, a survey of at least 350 people will be required. In any case, it is necessary to study the role of priority pollutants in the formation of airway hyperresponsiveness, asthma and AR, in order to find effective preventive measures.

Environmental impact and human health effects of polycyclic aromatic hydrocarbons and remedial strategies: A detailed review

Polycyclic Aromatic Hydrocarbons (PAHs) profoundly impact public and environmental health. Gaining a comprehensive understanding of their intricate functions, exposure pathways, and potential health implications is imperative to implement remedial strategies and legislation effectively. This review seeks to explore PAH mobility, direct exposure pathways, and cutting-edge bioremediation technologies essential for combating the pervasive contamination of environments by PAHs, thereby expanding our foundational knowledge. PAHs, characterised by their toxicity and possession of two or more aromatic rings, exhibit diverse configurations. Their lipophilicity and remarkable persistence contribute to their widespread prevalence as hazardous environmental contaminants and byproducts. Primary sources of PAHs include contaminated food, water, and soil, which enter the human body through inhalation, ingestion, and dermal exposure. While short-term consequences encompass eye irritation, nausea, and vomiting, long-term exposure poses risks of kidney and liver damage, difficulty breathing, and asthma-like symptoms. Notably, cities with elevated PAH levels may witness exacerbation of bronchial asthma and chronic obstructive pulmonary disease (COPD). Bioremediation techniques utilising microorganisms emerge as a promising avenue to mitigate PAH-related health risks by facilitating the breakdown of these compounds in polluted environments. Furthermore, this review delves into the global concern of antimicrobial resistance associated with PAHs, highlighting its implications. The environmental effects and applications of genetically altered microbes in addressing this challenge warrant further exploration, emphasising the dynamic nature of ongoing research in this field.

Infant lung function and early skin barrier impairment in the development of asthma at age 3 years.

Largely unexplored, we investigated if lower lung function, impaired skin barrier function by transepidermal water loss (TEWL), eczema, and filaggrin (FLG) mutations in infancy were associated with asthma in early childhood. From the factorially designed randomized controlled intervention study PreventADALL, we evaluated 1337/2394 children from all randomization groups with information on asthma at age 3 years, and at age 3 months either lung function, TEWL, eczema, and/or FLG mutations. Lower lung function was defined as the time to peak tidal expiratory flow to expiratory time (tPTEF /tE ) <0.25, and skin barrier impairment as a high TEWL >9.50 g/m2 /h. Eczema was clinically observed, and DNA genotyped for FLG mutations. Asthma was defined as asthma-like symptoms (≥3 episodes of bronchial obstruction) between age 2-3 years as well as a history of doctor-diagnosed asthma and/or asthma medication use. Associations were analyzed in logistic regression models, presented with adjusted ORs (aOR) and 95% confidence intervals (CI). Lower lung function and skin barrier impairment were associated with asthma in general; aOR (95% CI) 5.4 (2.1, 13.7) and 1.6 (1.1, 2.5), while eczema and FLG mutations were associated with asthma in children with atopic dermatitis or allergic sensitization only. Stratifying for sex, the risk of asthma was only increased in boys with lower lung function; aOR (95% CI) 7.7 (2.5, 23.6), and in girls with FLG mutations; aOR (95% CI) 3.5 (1.5, 8.2). Lower lung function and impaired skin barrier function in infancy may increase the risk of asthma at age 3 years.

Predictive Value of Fractional Exhaled Nitric Oxide (FeNO) in the Diagnosis of Asthma for Epidemiological Purposes-An 8-Year Follow-Up Study.

The follow-up included 128 (out of 447) children, 70 girls and 58 boys. The FeNO was measured at baseline only. The prevalence of asthma-like symptoms was measured with the adopted version of the ISAAC questionnaire. After 8 years of FeNO measurement, 5 new cases of asthma, 2 cases of attacks of dyspnoea, 1 case of wheezy in the chest, and 18 cases of allergic rhinitis occurred. The FeNO values, measured at the baseline of the study, for new cases of the above diseases were 53.4 ± 75.9 ppb, 11 ± 1.5 ppb, 12.0 ppb, and 16.3 ± 12.4 ppb, respectively. The best diagnostic accuracy parameters were found in the new cases of asthma, where the sensitivity was 40.0%, the specificity was 98.6%, and the AUC was 66.6%. The diagnostic odds ratio was 46.9 when considering the FeNO cut-off >35 ppb. The FeNO measurement is a fair method for asthma prognosis in early school-aged children with asthma-like symptoms measured on the population level but requires further confirmation at the clinical level with more accurate diagnostic tools.

Establishment of a juvenile mouse asthma model induced by postnatal hyperoxia exposure combined with early OVA sensitization

ObjectiveTo establish a juvenile mouse asthma model by postnatal hyperoxia exposure combined with early ovalbumin (OVA) sensitization. MethodsFemale C57BL/6J newborn mice were exposed to hyperoxia (95 % O2) from postnatal day-1 (PND1) to PND7; intraperitoneally injected with OVA suspension on PND21, PND28; and stimulated by nebulized inhalation of 1 % OVA from PND36 to PND42. Within 48 h of the last challenge, we observed their activity performance and evaluated airway responsiveness (AHR). All mice were executed at PND44. Female (n = 32) were divided into four groups as follows: room air（RA）+phosphate-buffered saline (PBS) group; O2 (hyperoxia, 95 % O2) + PBS group; RA + OVA group; O2+OVA group. We obtained the serum, bronchoalveolar lavage fluid (BALF), and lung tissues. The Wright-Giemsa staining was performed for leukocyte classification in BALF and HE staining for pathological examination. The levels of IL-2, IL-5, IL-13, IL-17A and IL-10 in BALF and tIgE and sIgE in serum were detected by ELISA. ResultsCompared with OVA sensitization or hyperoxia exposure alone, the mice in the model group (O2+OVA) showed asthma-like symptoms and increased airway hyperreactivity,The levels of IL-5,IL-13 IL-17A were increased in BLAF,and total leukocyte and eosinophil counts were also significant increasesed. The levels of tIgE and sIgE in serum were increased. ConclusionPostnatal hyperoxia exposure combined with early OVA sensitization might establish a juvenile mouse asthma model.

Key risk factors of asthma-like symptoms are mediated through infection burden in early childhood

Risk factors of asthma-like symptoms in childhood may act through an increased infection burden because infections often trigger these symptoms. We sought to investigate whether the effect of established risk factors of asthma-like episodes in early childhood is mediated through burden and subtypes of common infections. The study included 662 children from the Copenhagen Prospective Studies on Asthma in Childhood 2010 mother-child cohort, in which infections were registered prospectively in daily diaries from age 0 to 3 years. The association between established risk factors of asthma-like episodes and infection burden was analyzed by quasi-Poisson regressions, and mediation analyses were performed for significant risk factors. In the first 3 years of life, the children experienced a median of 16 (interquartile range, 12-23) infectious episodes. We found that the infection burden significantly (PACME< .05) mediated the association of maternal asthma (36.6% mediated), antibiotics during pregnancy (47.3%), siblings at birth (57.7%), an asthma exacerbation polygenic risk score (30.6%), and a bacterial airway immune score (80.2%) with number of asthma-like episodes, whereas the higher number of episodes from male sex, low birth weight, low gestational age, and maternal antibiotic use after birth was not mediated through an increased infection burden. Subtypes of infections driving the mediation were primarily colds, pneumonia, gastroenteritis, and fever, but not acute otitis media or acute tonsillitis. Several risk factors of asthma-like symptoms in early childhood act through an increased infection burden in the first 3 years of life. Prevention of infectious episodes may therefore be beneficial to reduce the burden of asthma-like symptoms in early childhood.

Role of bronchial hyperresponsiveness in patients with obstructive sleep apnea with asthma-like symptoms

BackgroundObstructive sleep apnea (OSA) is one of the major co-morbidities and aggravating factors of asthma. In OSA-complicated asthma, obesity, visceral fat, and systemic inflammation are associated with its severity, but the role of bronchial hyperresponsiveness (BHR) is unclear. We investigated the involvement of BHR and mediastinal fat width, as a measure of visceral fat, with OSA severity in patients with OSA and asthma-like symptoms. MethodsPatients with OSA who underwent BHR test and chest computed tomography scan for asthma-like symptoms were retrospectively enrolled. We evaluated the relationship between apnea–hypopnea index (AHI) and PC20 or anterior mediastinal fat width, stratified by the presence or absence of BHR. ResultsOSA patients with BHR (n = 29) showed more obstructive airways and frequent low arousal threshold and lower mediastinal fat width, and tended to show fewer AHI than those without BHR (n = 25). In the overall analysis, mediastinal fat width was significantly positively correlated with AHI, which was significant even after adjustment with age and gender. This was especially significant in patients without BHR, while in OSA patients with BHR, there were significant negative associations between apnea index and airflow limitation, and hypopnea index and PC20. ConclusionsRisk factors for greater AHI differed depending on the presence or absence of BHR in OSA patients with asthma-like symptoms. In the presence of BHR, severity of asthma may determine the severity of concomitant OSA.

Development of Asthma-Like Symptoms After COVID-19: A Cross-Sectional Study in Dubai, United Arab Emirates

Development of Asthma-Like Symptoms After COVID-19: A Cross-Sectional Study in Dubai, United Arab Emirates

Narrowing Down the Symptomatology of Isolated Vascular Rings in Children.

Vascular rings may cause respiratory or gastrointestinal symptoms due to compression of the trachea and/or esophagus. Advances in imaging have enabled early detection in asymptomatic patients posing new management dilemmas. Surgery is expected to relieve symptoms, although this has not been well studied. We sought to evaluate the presence and pattern of symptoms associated with vascular rings before surgical intervention and todetail symptom resolution after surgery. A10-year retrospective review of patients diagnosed with an isolated vascular ring was performedbetween January 2010 and December 2019. 100 patients were identified; 35 double aortic arch (DAA) and 65 right aortic arch and left ligamentum arteriosum (RALL). 73 patients were symptomatic on presentation; 47 had respiratory, 5 had gastrointestinal, and 21 had both types of symptoms. Surgical repair was performed in 75 patients; 74 were symptomatic. Respiratory symptoms were more likely in patients with preoperative tracheal narrowing (p < 0.001). Moderate-severe respiratory symptoms led to surgery in RALL patients (OR 10.6, p = 0.0001). DAA patients were more likely to undergo surgery (p < 0.001) irrespective of symptom severity. At a median post-surgical follow-up of 4months, there was a significant reduction in symptom burden (p < 0.001), except for asthma symptoms (p = 0.131). Symptom resolution was not dependent on the vascular ring anatomy (p = 0.331) or the age at operation (p = 0.158). Vascular rings are typically accompanied by respiratory symptoms and less commonly GI symptoms, both of which resolve in most patients after surgery. Those who present predominantly with asthma-like symptoms may not achieve resolution after surgery.

Frequency of non-asthma-like symptoms of allergic diseases based on ISAAC results in adolescents of the Khabarovsk region, Russia

Background. In the course of the ISAAC standardized survey, not only asthma-like symptoms are revealed, but also other atopy symptoms, the prevalence of which in their relationship with asthma-like symptoms is of great interest for determining the likelihood of developing BA. This work presents the first study of the frequency of symptoms occurrence in school students of the Khabarovsk Territory (Russia).Materials and methods. The survey involved 696 teenagers living in the city of Khabarovsk and Khabarovsk rural district who meet the requirements of the ISAAC program method by age (13–14 years).Results. The prevalence of symptoms of allergic rhinitis in all interviewed adolescents of the Khabarovsk Territory was 69.3 %. In the group with asthma-like symptoms it is significantly higher (77.2 % versus 56.6 %). Complications in the form of conjunctivitis with non-infectious rhinitis occurred in 12.6 % of cases, and also much more often in children with asthma-like symptoms (30.1 % versus 8.9 %). Symptoms of atopic dermatitis occur in 11.8 % of adolescents, 4.6 times more often when combined with asthma-like symptoms (22 % versus 4.8 %), and localize in typical places of atopic dermatitis in 5.3 % of cases, which happens more often in case of asthma-like symptoms (11.4 % versus 3.9 %).Conclusion. Studies using the ISAAC standard continuous survey showed that prevalence of non-asthma-like symptoms of atopy among adolescents in Khabarovsk and Khabarovsk Krai is higher than in most countries where this study was conducted. The frequency and structure of non-asthma-like symptoms revealed in the course of the survey is characteristic of industrially developed countries. It should be noted that the prevalence and severity of non-asthma-like symptoms in Khabarovsk is significantly higher than in the Khabarovsk rural area, however, the symptoms of non-infectious rhinitis in the countryside are more severe.

Effects of early postnatal hyperoxia exposure combined with early ovalbumin sensitization on lung inflammation and bacterial flora in a juvenile mouse model of asthma.

The aim of this study is to explore the effects of early postnatal hyperoxia exposure combined with early ovalbumin (OVA) sensitization on lung inflammation and bacterial flora in neonatal mice on a juvenile mouse model of asthma. Thirty-two newborn female C57BL/6 J mice were randomly divided into four groups, which including room air+phosphate-buffered saline (PBS) group, hyperoxia+PBS group, room air+OVA group, and hyperoxia+OVA group, according to the hyperoxia exposure and/or OVA induction. Mice were exposed to either 95% O2 or room air for 7 days after birth; after 7 days, they were exposed to air and received an intraperitoneal injection of OVA suspension or PBS solution on postnatal days 21 (P21) and 28 (P28). From P36 to P42, the mice were allowed to inhale of 1% OVA or 0.9% NaCl solution. The mice were observed after the last excitation. HE staining was performed to observe the pathological changes in lung tissues. Wright-Giemsa staining was used to perform bronchoalveolar lavage fluid (BALF) leukocyte sorting. Enzyme-linked immunosorbent assay was used to determined the cytokines levels of interleukin (IL)-2, IL-5, IL-13, IL-17A, and IL-10 and serum IgE levels in BALF. Additionally, 16S rRNA sequencing was used to analyze the characteristics of lung microbiota. Mice in the hyperoxia+OVA group showed asthma-like symptoms. HE staining results revealed a significant thickening of the airway wall and airway inflammation. BALF analysis of cellular components showed significant increases in total leukocyte and eosinophil counts and the levels of cytokines related to Th2 (IL-5 and IL-13) and Th17 (IL-17A); 16S rRNA sequencing revealed that the main members of the pulmonary microflora were Actinobacteriota, Proteobacteria, Firmicutes, and Bacteroidota at the phylum level. In addition, the bacteria with a major role were Acinetobacter and Moraxellaceae in the O2 + OVA group. The mouse suffering from postnatal hyperoxia exposure and early OVA sensitization, changes in symptoms, pathology, leukocyte and eosinophil counts, and levels of different T-cell cytokines in BALF and lung microbiota, which may provide a basis for the establishment of a juvenile mouse model of asthma.

Desert particulate matter from Afghanistan increases airway obstruction in human distal lungs exposed to type 2 cytokine IL-13.

Deployment related asthma-like symptoms including distal airway obstruction have been described in U.S. military personnel who served in Iraq and Afghanistan. The mechanisms responsible for the development of distal airway obstruction in deployers exposed to desert particulate matter (PM) is not well understood. We sought to determine if respiratory exposure to PM from Afghanistan (PMa) increases human distal airway hyperresponsiveness (AHR) with or without exposures to IL-13, a type 2 cytokine. We further tested whether mitochondrial dysfunction, such as ATP signaling and oxidative stress, may contribute to PMa- mediated AHR. Precision-cut lung slices from donors without a history of lung disease, tobacco smoking, or vaping were pre-treated with IL-13 for 24 h. This was followed by exposure to PMa or PM from California (PMc, control for PMa) for up to 72 h. The role of hydrogen peroxide and ATP in AHR was assessed using the antioxidant enzyme catalase or an ATP receptor P2Y13 antagonist MRS2211. AHR in response to methacholine challenges as well as cytokine IL-8 production were measured. PMa alone, but not PMc alone, trended to increase AHR. Importantly, the combination of PMa and IL-13 significantly amplified AHR compared to control or PMc+IL-13. PMa alone and in combination with IL-13 increased IL-8 as compared to the control. PMa increased H2O2 and ATP. MRS211 and catalase reduced AHR in PCLS exposed to both PMa and IL-13. Our data suggests that PMa in a type 2 inflammation-high lung increased AHR in part through oxidative stress and ATP signaling.

Inhaled corticosteroids to improve lung function in children (aged 6–12 years) who were born very preterm (PICSI): a randomised, double-blind, placebo-controlled trial

Despite the substantial burden of lung disease throughout childhood in children who were born very preterm, there are no evidence-based interventions to improve lung health beyond the neonatal period. We tested the hypothesis that inhaled corticosteroid improves lung function in this population. PICSI was a randomised, double-blind, placebo-controlled trial at Perth Children's Hospital (Perth, WA, Australia) to assess whether fluticasone propionate, an inhaled corticosteroid, improves lung function in children who had been born very preterm (<32 weeks of gestation). Eligible children were aged 6-12 years and did not have severe congenital abnormalities, cardiopulmonary defects, neurodevelopmental impairment, diabetes, or any glucocorticoid use within the preceding 3 months. Participants were randomly assigned (1:1) to receive 125 μg fluticasone propionate or placebo twice daily for 12 weeks. Participants were stratified for sex, age, bronchopulmonary dysplasia diagnosis, and recent respiratory symptoms using the biased-coin minimisation technique. The primary outcome was change in pre-bronchodilator forced expiratory volume in 1 s (FEV1) after 12 weeks of treatment. Data were analysed by intention-to-treat (ie, all participants who were randomly assigned and took at least the tolerance dose of the drug). All participants were included in the safety analyses. This trial is registered at the Australian and New Zealand Clinical Trials Registry, number 12618000781246. Between Oct 23, 2018, and Feb 4, 2022, 170 participants were randomly assigned and received at least the tolerance dose (83 received placebo and 87 received inhaled corticosteroid). 92 (54%) participants were male and 78 (46%) were female. 31 participants discontinued treatment before 12 weeks (14 in the placebo group and 17 in the inhaled corticosteroid group), mostly due to the impact of the COVID-19 pandemic. When analysed by intention-to-treat, the change in pre-bronchodilator FEV1 Z score over 12 weeks was -0·11 (95% CI -0·21 to 0·00) in the placebo group and 0·20 (0·11 to 0·30) in the inhaled corticosteroid group (imputed mean difference 0·30, 0·15-0·45). Three of 83 participants in the inhaled corticosteroid group had adverse events requiring treatment discontinuation (exacerbation of asthma-like symptoms). One of 87 participants in the placebo group had an adverse event requiring treatment discontinuation (inability to tolerate the treatment with dizziness, headaches, stomach pains, and worsening of a skin condition). As a group, children born very preterm have only modestly improved lung function when treated with inhaled corticosteroid for 12 weeks. Future studies should consider individual phenotypes of lung disease after preterm birth and other agents to improve management of prematurity-associated lung disease. Australian National Health and Medical Research Council, Telethon Kids Institute, and Curtin University.

Maternal and paternal tuberculosis is associated with increased asthma and respiratory symptoms in their offspring: a study from Northern Europe.

Given the profound impact of tuberculosis (TB) on immunity and given murine studies suggesting that infections may influence immunity across generations, we hypothesize that parental TB might impact health and disease in future offspring. This study investigated the impact of maternal and paternal TB on offspring asthma and respiratory symptoms. We included data from the third follow-up of the Respiratory Health in Northern Europe study (RHINE). Information on own asthma status, asthma-like symptoms and other respiratory symptoms, as well as information about parental TB and asthma, were collected using standardized questionnaires. The associations between parental TB and RHINE participants' asthma and respiratory symptoms were analyzed using multiple logistic regression, with adjustment for parental education, smoking habits and asthma. Of 8,323 study participants, 227 (2.7%) reported only paternal TB, 282 (3.4%) only maternal TB, and 33 (0.4%) reported that both parents had TB. We found a higher risk of asthma (aOR: 1.29, 95% CI: 1.05-1.57) in offspring with a history of parental TB as compared to offspring without parental TB., Parental TB was significantly associated with allergic asthma in offspring (aOR: 1.58, 95% CI: 1.29-2.05), while no significant association between parental TB and asthma without allergy (aOR: 1.00, 95% CI: 0.76-1.32) in offspring was observed. Results from this study indicate that parental TB might be a risk factor for offspring's asthma and respiratory symptoms. We raise the hypothesis that the immunological impact of infections might be transmitted to influence offspring phenotype in humans.