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The prevalence of asthma is high and the incidence is increasing significantly in Africa. Cases of severe exacerbations of asthma are managed as inpatients and are often used as indicators of asthma care. There is a paucity of data regarding hospitalised paediatric asthma cases in low- and middle-income countries (LMICs). This retrospective study describes the clinical presentation of children admitted to Charlotte Maxeke Johannesburg Academic Hospital in Johannesburg, South Africa, with asthma, and the association, if any, with intensive care unit (ICU) admission. Medical records between the years 2015 and 2020 were reviewed, revealing 134 admissions, with eight children being admitted to the ICU. The median age was four years (IQR 3,7) and the median duration of stay was four days (IQR 4,6). 66% of the children admitted were aged 1-5 years; 52.5% of the admissions were male. Allergic rhinitis was the most common associated comorbidity, at 42.4%. Most children presented with subcostal retractions (88.8%) and hypoxia (74.2%). Two children died from asthma complications. Children who had a known asthma diagnosis at the time of admission were more likely to have been readmitted than those who did not have a prior asthma diagnosis (p = < 0.001). Previous asthma hospitalisation was associated with ICU admission (p = 0.041). Most admissions occurred during the summer months. The trend in hospitalised asthma cases declined over the study period and paediatric asthma mortalities were rare. Further studies are needed to assess risk factors for paediatric asthma hospitalisation, especially in LMICs. [ABSTRACT FROM AUTHOR]

Objectives: To describe clinical characteristics of young children presenting to the emergency department (ED) for early recurrent wheeze, and determine factors associated with subsequent persistent wheeze and risk for early childhood asthma. Methods: Retrospective cohort study of Medicaid-enrolled children 0–3 years old with an index ED visit for wheeze (e.g. bronchiolitis, reactive airway disease) from 2009 to 2013, and at least one prior documented episode of wheeze at an ED or primary care visit. The primary outcome was persistent wheeze between 4 and 6 years of age. Demographics and clinical characteristics were collected from the index ED visit. Logistic regression was used to estimate the association between potential risk factors and subsequent persistent wheeze. Results: During the study period, 41,710 children presented to the ED for recurrent wheeze. Mean age was 1.3 years; 59% were male, 42% Black, and 6% Hispanic. At index ED visits, the most common diagnosis was acute bronchiolitis (40%); 77% of children received an oral corticosteroid prescription. Between 4 and 6 years of age, 11,708 (28%) children had persistent wheeze. A greater number of wheezing episodes was associated with an increased odds of ED treatment with asthma medications. Subsequent persistent wheeze was associated with male sex, Black race, atopy, prescription for bronchodilators or corticosteroids, and greater number of visits for wheeze. Conclusions: Young children with persistent wheeze are at risk for childhood asthma. Thus, identification of risk factors associated with persistent wheeze in young children with recurrent wheeze might aid in early detection of asthma and initiation of preventative therapies. [ABSTRACT FROM AUTHOR]

Introduction: Recent evidence indicates that Maternal Supplementation with Long-Chain n-3 Fatty Acids During Pregnancy Substantially Mitigates Offspring's Asthma. Adding information regarding its cost-utility will undoubtedly allow its adoption, or not, in clinical practice guidelines. This research aimed to determine the cost-utility of LCPUFA supplementation in the third trimester of pregnancy to reduce the risk of wheezing and asthma in infants in Colombia. Methods: A Markov model was formulated to estimate the cost and quality-adjusted life-years (QALYs) attributed to individuals with severe asthma in Colombia, with a time horizon of five years and a cycle length of two weeks. Probabilistic sensitivity analysis and a value of information (VOI) analysis were conducted to evaluate the uncertainties in the case base. Cost-utility was assessed at a willingness-to-pay (WTP) value of US$5180. All costs were adjusted to 2021 with a 5% annual discounting rate for cost and QALYs. Results: The mean incremental cost of LCPUFA supplementation versus no supplementation was US-43.65. The mean incremental benefit of LCPUFA supplementation versus no supplementation was 0.074 QALY. The incremental cost-utility ratio was estimated at US$590.68 per QALY. The outcomes derived from our primary analysis remained robust when subjected to variations in all underlying assumptions and parameter values. Conclusion: Supplementation strategy supplementation with long-chain n-3 fatty acids during pregnancy is cost-effective in reducing the risk of developing asthma during childhood in Colombia. [ABSTRACT FROM AUTHOR]

The article discusses the life course approach to early life exposures and development of chronic obstructive pulmonary disease (COPD). Topics include life-course approaches to health disparities, how COPD can be considered as a manifestation of structural violence, and research areas to address COPD across the life course.

Objective: To compare the effectiveness of inhaled Magnesium Sulfate associated with Salbutamol versus Inhaled Salbutamol alone in patients with moderate and severe asthma exacerbations. Method: Clinical, prospective and randomized study with patients between 3 and 14 years of age divided into two groups: one to receive inhaled salbutamol associated with magnesium sulfate (GSM), the other to receive inhaled salbutamol alone (GS). The sample consisted of 40 patients, 20 patients in each group. Severity was classified using the modified Wood-Downes score, with values between 4 and 7 classified as moderate and 8 or more classified as severe. Results: Post-inhalation scores decreased both in patients who received salbutamol and magnesium and in those who received salbutamol alone, with no statistically significant difference between the groups. Conclusions: Despite the benefits when administered intravenously, inhalation of the drug alone or in combination did not reduce the severity of the exacerbation. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Studies of childhood diet diversity and allergic disease have not examined additional associations with an offspring allergy‐linked maternal diet index during pregnancy. We studied both associations in a pre‐birth cohort.Offspring allergic disease diagnoses were obtained from electronic medical records. Maternal and infant diet were self‐reported. Adjusted parametric Weibull time‐to‐event models assessed associations between maternal diet index, infant diet diversity and time to development of allergic rhinitis, atopic dermatitis, asthma, wheeze, IgE‐mediated food allergy, and a combined outcome of any allergic disease except for wheeze.Infant diet diversity at 1 year was associated with the risk of the combined outcome between 1 and 4 years of age (p = .002). While both maternal diet index and infant diet diversity at 1 year were associated with the risk of the combined outcome between 1 and 4 years of age (both p < .05), infant diet diversity at 1 year did not modify the association between maternal diet index and the risk of the combined outcome between 1 and 4 years of age (p = .5). The group with the lowest risk of the combined allergy outcome had higher maternal diet index and higher infant diet diversity.The novel finding that both maternal diet index during pregnancy and infant diet diversity at 12 months are associated with the risk of a combined allergic disease outcome points to two targets for preventive interventions: maternal diet index scores during pregnancy and offspring diet diversity during infancy. [ABSTRACT FROM AUTHOR]

To conduct a systematic review and meta-analysis of the association between chorioamnionitis and respiratory outcomes of prematurely born children.Pubmed, Medline and Embase were searched for relevant studies. Studies were included if they assessed prematurely born children, who had been exposed to chorioamnionitis and had either lung function testing or assessment of wheeze or asthma following NICU discharge. Two reviewers independently screened the search results, applied inclusion criteria and assessed methodological quality. One reviewer extracted the data and these were checked by a second reviewer.1,237 studies were identified, but only eight which included 35,000 infants, fulfilled the inclusion criteria. One study looked at both lung function results and wheeze or asthma in childhood. Four of five studies found an association between wheeze/asthma in childhood and exposure to chorioamnionitis: the overall Odds Ratio (OR) for developing wheeze/asthma in childhood was OR 1.71 (95 % CI: 1.55–1.89). Four studies looked at lung function in childhood, three of which showed no statistically significant association between chorioamnionitis exposure and altered lung function. One study found lower lung function in those exposed to chorioamnionitis and lower expiratory flows with increasing levels of chorioamnionitis (forced expiratory flow at 50 % of exhaled forced vital capacity (=FEF50) p=0.012, forced expiratory flow at 25–75 % of the forced vital capacity is exhaled (=FEF25–75) p=0.014).There was a significant association between chorioamnionitis and the development of wheeze or asthma in childhood, but overall not in impairment of lung function. [ABSTRACT FROM AUTHOR]

Background: Chronic cough in children is a challenging symptom for clinicians. So, we aimed in this study to evaluate the diagnostic role of flexible bronchoscope in differentiating between the underlying causes of chronic wet cough and chronic cough associated with wheeze. Methods: This was a prospective cross-sectional study conducted on children referred to Tanta University Hospitals and Ain-Shams University Hospitals between January 2021 and January 2023, presenting with a primary complaint of chronic cough lasting more than 4 weeks. The children were further classified into two groups: the first group included children with chronic wet cough not associated with wheezing (Cohort A) and the second group included children with chronic cough associated with wheezing (Cohort B). Results: The study enrolled 64 children. During clinical evaluation, 25 (39.1%) children had a chronic cough without wheezing and 39 (60.9%) had a chronic wheezy cough. Bronchoscopic examination findings indicated a notable disparity between the two groups of patients with chronic cough (p=0.006). Among Cohort A patients, the most prevalent bronchoscopic observation was purulent inflammatory secretions in 16 cases (64.0%), followed by congenital airway anomalies in 3 cases (12.0%). Conversely, Cohort B patients exhibited congenital airway anomalies as the primary finding in 14 cases (35.9%), followed by purulent secretions in 7 cases (17.9%). Conclusion: Flexible bronchoscopy is a valuable and safe tool for diagnosing chronic cough in children. It helped differentiate between the underlying causes of chronic cough in children with and without wheezing. [ABSTRACT FROM AUTHOR]

Endotoxin, in lipopolysaccharide structure (LPS), is the main component of the outer membrane of gram negative bacteria. LPS levels were associated with inflammatory disease. Asthma is a chronic inflammatory disease involving many different cell types and cellular elements. The association between LPS serum levels and the asthma is not well known. The aim of this study was to investigate the association between the LPS serum levels and the severity of asthma, demographic data and laboratory parameters. The study included 67 patients aged >18 years with a diagnosis of asthma, and 15 healthy volunteers with no history of chronic disease as a control group. The Asthma Control Test (ACT), Respiratory Function Tests (RFTs), fractional exhaled nitric oxide (FeNO), and endotoxin levels were measured and compared between the groups. The endotoxin measurements were performed using the ELISA method. The mild-moderate asthma group included 33 patients and the severe asthma group, 34 patients. The endotoxin level was measured as 17.78 (range 3.59 to 304.55) EU/ml in the patient group and 15 (range 4.01 to 74.06) EU/ml in the control group with no statistically significant difference determined between the groups. In the subgroups, the endotoxin level was measured as 15.21 (range 3.69 to 304.55) EU/ml in the mild-moderate group and 14.46 (range 3.59 to 278.86) EU/ml in the severe asthma group with no statistically significant difference determined between the groups. The results of this study showed no relationship between serum endotoxin level and asthma or asthma severity. [ABSTRACT FROM AUTHOR]

Asthma is a common chronic respiratory diseases, and the relationship between pulmonary ventilation function and the prognosis of patients with suspected asthma is not well understood. This study aims to explore the impact of pulmonary ventilation functions on the prognosis of patients with suspected asthma. This retrospective observational study included patients with suspected asthma who were diagnosed and treated at the Guangdong Provincial Hospital of Traditional Chinese Medicine between August 2015 and January 2020. The primary outcome of interest was improvement in asthma symptoms, as measured by bronchial provocation test (BPT) results within one year after diagnosis. The impact of pulmonary ventilation functions on prognosis was explored by multivariable logistic regression analysis. Seventy-two patients were included in the study. Patients with normal (OR = 0.123, p =.004) or generally normal (OR = 0.075, p =.039) pulmonary ventilation function were more likely to achieve improvement in asthma symptoms compared with patients with mild obstruction. There were no significant differences between the improvement and non-improvement groups in baseline characteristics. These results suggest that suspected asthma patients with normal or generally normal pulmonary ventilation function are more likely to achieve improvement in asthma symptoms within one year compared to patients with mild obstruction. [ABSTRACT FROM AUTHOR]

Mepolizumab is an anti-interleukin-5 monoclonal antibody shown to reduce asthma exacerbations in adults and adolescents with severe eosinophilic asthma. To assess the impact of mepolizumab on children and adolescents over 12 months by examining steroid usage, asthma-related hospitalizations, Asthma Control Test (ACT) scores, fractional exhaled nitric oxide concentration (FeNO), forced expiratory volume in 1 s (FEV1), mid expiratory flow (FEF25–75%), and blood eosinophil count. Retrospective analysis performed between October 2015 and December 2022. Data was reviewed 12 months before and after commencing mepolizumab. Mepolizumab was offered if the patient had severe eosinophilic asthma and were unresponsive to or ineligible for omalizumab. Sixteen participants (age 7–17, 8 males, 8 females) received subcutaneous mepolizumab monthly with no serious adverse reactions. Incidence of hospital admissions fell significantly (IRR 0.33, p = 0.007). Among the 11 patients receiving daily oral corticosteroids, 3 were weaned off daily oral steroids and 3 patients' daily dose was significantly reduced (mean Δ-0.095 ± 0.071 mg/kg, p = 0.0012). Eosinophil count was decreased (mean Δ-0.85 x 109/L, p < 0.001). There was no significant change in mean overall steroid burden per patient (mean Δ-1445.63 ± 1603.18 mg, p = 0.10), ACT scores (mean Δ2.88 ± 6.71, p = 0.17), FEV1 z-scores (mean Δ-0.99 ± 1.88, p = 0.053), FEF25–75% z-scores (mean Δ-0.65 ± 1.61, p = 0.13), FeNO (mean Δ-20.09 ± 80.86, p = 0.34), or number of courses of oral steroids given for asthma attacks (IRR 0.71, p = 0.09). Among children and adolescents with severe eosinophilic asthma ineligible for or not responsive to omalizumab, mepolizumab therapy exhibited significant reduction in rate of asthma-related hospitalizations and significant decrease in daily steroid dosage. [ABSTRACT FROM AUTHOR]

Asthma remission is a potential treatment goal. Does adding azithromycin to standard therapy in patients with persistent uncontrolled asthma induce remission compared with placebo? This secondary analysis used data from the Asthma and Macrolides: the Azithromycin Efficacy and Safety (AMAZES) clinical trial—a double-anonymized placebo-controlled trial that evaluated the safety and efficacy of azithromycin on asthma exacerbations. The primary remission definition (referred to as clinical remission) was zero exacerbations and zero oral corticosteroids during the previous 6 months evaluated at 12 months and a 5-item Asthma Control Questionnaire score ≤ 1 at 12 months. Secondary remission definitions included clinical remission plus lung function criteria (postbronchodilator FEV 1 ≥ 80% or postbronchodilator FEV 1 ≤ 5% decline from baseline) and complete remission (sputum eosinophil count < 3% plus the aforementioned criteria). Sensitivity analyses explored the robustness of primary and secondary remission definitions. The predictors of clinical remission were identified. A total of 335 participants (41.5% male; median age, 61.01 years; quartile 1-3, 51.03-68.73) who completed the 12-month treatment period were included in the analysis. Twelve months of treatment with azithromycin induced asthma remission in a subgroup of patients, and a significantly higher proportion in the azithromycin arm achieved both clinical remission (50.6% vs 38.9%; P =.032) and clinical remission plus lung function criteria (50.8% vs 37.1%; P =.029) compared with placebo, respectively. In addition, a higher proportion of the azithromycin group achieved complete remission (23% vs 13.7%; P =.058). Sensitivity analyses supported these findings. Baseline factors (eg, better asthma-related quality of life, absence of oral corticosteroid burst in the previous year) predicted the odds of achieving clinical remission. Azithromycin induced remission in both eosinophilic and noneosinophilic asthma. In this study, adults with persistent symptomatic asthma achieved a higher remission rate when treated with azithromycin. Remission on treatment may be an achievable treatment target in moderate/severe asthma, and future studies should consider remission as an outcome measure. [Display omitted] [ABSTRACT FROM AUTHOR]

Background and Objective: Most evidence about difficult‐to‐treat and severe asthma (DTTA) comes from clinical trials and registries. We aimed to identify people with DTTA from a large nationally representative asthma population and describe their characteristics and healthcare utilization compared with people whose asthma was not 'difficult‐to‐treat'. Methods: We conducted a cross‐sectional survey of Australians aged ≥18 years with current asthma from large web‐based survey panels. Enrolment was stratified by gender, age‐group and state/territory based on national population data for people with asthma. Difficult‐to‐treat or severe asthma was defined by poor symptom control, exacerbations and/or oral corticosteroid/biologic use despite medium/high‐dose inhaled therapy. Outcomes included exacerbations, healthcare utilization, multimorbidity, quality of life and coronavirus disease of 2019 (COVID‐19)‐related behaviour. Weighted data were analysed using SAS version 9.4. Results: The survey was conducted in February–March 2021. The weighted sample comprised 6048 adults with current asthma (average age 47.3 ± SD 18.1 years, 59.9% female), with 1313 (21.7%) satisfying ≥1 DTTA criteria. Of these, 50.4% had very poorly controlled symptoms (Asthma Control Test ≤15), 36.2% were current smokers, and 85.4% had ≥1 additional chronic condition, most commonly anxiety/depression. More than twice as many participants with DTTA versus non‐DTTA had ≥1 urgent general practitioner (GP) visit (61.4% vs. 27.5%, OR 4.8 [4.2–5.5, p < 0.0001]), or ≥1 emergency room visit (41.9% vs. 17.9%, OR 3.8 [3.3–4.4, p < 0.0001]) in the previous 12 months. Conclusion: Our findings emphasize the burden of uncontrolled symptoms, current smoking, multimorbidity and healthcare utilization in people with DTTA in the community, who may be under‐represented in registries or clinical trials. In this cross‐sectional study of a nationally‐representative population of 6048 adults with current asthma, 21.7% had difficult‐to‐treat asthma. Burden for patients and health system was seen in poor general health status, poor asthma symptom control, frequent urgent GP and emergency department (ED)/hospital visits and high prevalence of multimorbidity, particularly anxiety and/or depression. See relatededitorial [ABSTRACT FROM AUTHOR]

Background: We investigated the individual and interaction effects of maternal plasma 훂‐ and ϒ‐tocopherol levels (vitamin E isomers) on child asthma and wheeze at age 8–9. Methods: Mother–child dyads were enrolled between 2006 and 2011 into the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) prenatal cohort. Maternal second‐trimester samples were analyzed for tocopherol and lipid concentrations. We assessed child asthma/wheeze using the International Study of Asthma and Allergies in Childhood (ISAAC) and other self‐reported Ent wheeze. In multivariable logistic regression analyses, we assessed associations between vitamin E isomers and child asthma/wheeze outcomes (n = 847 mother–child dyads) and tested for prespecified interaction terms. Results: Median cholesterol‐corrected tocopherol levels (interquartile range (IQR)) were 5.0 (4.3–5.7) and 0.8 (0.7–0.9) (umol/mmol) for 훂‐ and ϒ‐tocopherol, respectively. Associations between 훂‐tocopherol and asthma outcome variables were inverse but not statistically significant. In contrast, for ϒ‐tocopherol, associations were in the positive direction, but also nonsignificant. Interactions analysis between tocopherols did not reach statistical significance for any outcome. Among children of women with a history of asthma, the likelihood of ever asthma in the child appears to be decreasing with increasing maternal 훂‐tocopherol levels, whereas this trend was not observed among those without a history of asthma (p‐interaction =.05). Conclusion: We observed no associations for prenatal 훂‐ or ϒ‐tocopherol concentrations with child asthma/wheeze. We detected some evidence of effect modification by maternal asthma history in associations between 훂‐tocopherol and child asthma. [ABSTRACT FROM AUTHOR]

Background: Treatment of allergic bronchopulmonary aspergillosis (ABPA) is challenging. Biological therapies have been reported as adjunctive treatments for ABPA, primarily in case series or case reports. This study aimed to analyze the efficacy of biologics for managing ABPA both qualitatively and quantitatively. Methods: All articles on APBA published in October 2023 were searched in PubMed, Web of Science, ClinicalTrials.gov, and Embase databases. The effects of interest were the mean changes from baseline for outcomes, including exacerbation rates, oral corticosteroids usage (OCS), and total immunoglobulin E (IgE) levels. Reported outcomes were quantitatively synthesized by usual or individual patient data (IPD) meta-analyses. PROSPERO registration number: CRD42022373396. Results: A total of 86 studies were included in the systematic review including 346 patients. Sixteen studies on omalizumab were pooled for the usual meta-analysis. Omalizumab therapy significantly reduced exacerbation rates (− 2.29 [95%CI − 3.32, − 1.26]), OCS dosage (− 10.91 mg [95%CI − 18.98, − 2.85]), and total IgE levels (− 273.07 IU/mL [95%CI − 379.30, − 166.84]), meanwhile improving FEV1% predicted (10.09% [95%CI 6.62, 13.55]). Thirty-one studies on dupilumab, mepolizumab, or benralizumab were pooled to perform an IPD meta-analysis, retrospectively. Both dupilumab and mepolizumab significantly reduced exacerbation rates, OCS, and total IgE levels. Benralizumab showed a similar trend, but it was not statistically significant. Tezepelumab showed weak evidence of its effects on ABPA. All five biologics led to milder clinical symptoms (e.g., cough, wheezing) with serious adverse effects that happened once in omalizumab treatment. Conclusion: These results indicate the clinical benefit of omalizumab, dupilumab, and mepolizumab in patients with ABPA. Further randomized, controlled studies with a larger sample size and longer follow-up are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Purpose: Symptoms are important components in determining asthma control and in the adjustment of treatment levels. However, clinical relevance of cough in severe asthma is not well-understood. This study aimed to evaluate the severity and association of cough with patient-reported outcomes (PROs) in patients with severe asthma. Methods: This study analyzed cross-sectional data from the Korean Severe Asthma Registry. The severity of coughing and wheezing symptoms was assessed using a Visual Analog Scale (VAS) ranging from 0 to 100 for each symptom. Additionally, PROs included the Asthma Control Test (ACT), the Severe Asthma Questionnaire (SAQ), and the EuroQoL 5-Dimension (EQ-5D) index. Multivariate linear regression analysis was employed to explore the relationship between cough severity and other PRO scores. Results: A total of 498 patients with severe asthma (age: 57.9 ± 13.1 years, females: 60.2%) were analyzed. The cough VAS score was higher than the wheeze score (median 30, [interquartile range 10–50] vs. 20 [0–50]; P < 0.001). Additionally, 22.5% of patients ranked in a higher tertile for cough severity compared to wheezing, while 18.5% ranked higher for wheezing severity than cough. Significant correlations were observed between cough and wheeze VAS scores (r = 0.61, P < 0.05) and between each symptom's VAS score and the SAQ (cough: r = −0.41, P < 0.001; wheeze: r = −0.52, P < 0.001), ACT scores (cough: r = −0.50, P < 0.001; wheeze: r = −0.63, P < 0.001) and EQ-5D index (cough: r = −0.40, P < 0.001; wheeze: r = −0.45, P < 0.001). In univariate regression analysis, the cough VAS score had weaker descriptive power (R2) values than the wheeze VAS score in relation to the PRO measures. Nevertheless, cough severity remained significantly associated with ACT, SAQ scores and EQ-5D index in multivariate analyses adjusted for wheeze severity and other confounders. Conclusion: Cough frequently presents as a severe symptom in patients with severe asthma and could have distinct impact on asthma control and quality of life. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease with acute exacerbation (AECOPD) being a common sequalae which negatively impact health status, rates of hospitalization and readmission, and disease progression. N‐acetylcysteine (NAC) has been studied in COPD in both stable state and acute exacerbations, which has been shown to have small beneficial effects in stable COPD, as well as AECOPD. Yet, there has been lack of study with well‐designed protocol to assess the role of NAC in more objective outcomes in AECOPD. Methods: This is a double‐blind randomized controlled trial. Patients will be randomized in 1:1 ratio to receive oral NAC at 600 mg twice daily or placebo twice daily with standard of care. Partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (PaCO2) and the ratio of partial pressure arterial oxygen and fraction of inspired oxygen (PaO2/FiO2) will be measured on days 1 and 7. The following will be measure at baseline and on day 4 and 7: Forced expiratory volume in one second (FEV1), 24‐hour sputum volume, oxygen saturation (SaO2), end‐tidal CO2, Leicester Cough Questionnaire (LCQ) score, COPD Assessment Test (CAT) score, grading of wheeze and grade of dyspnoea; blood inflammatory markers (leucocyte count, neutrophil count, erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP) and high sensitivity CRP (hs‐CRP)). Patients will be randomized to oral NAC at 600 mg twice daily or placebo for 7 days. The main outcome measures include: The difference in PaO2 on day 7. Secondary outcome: Change in following parameters on day 4/7 from baseline: FEV1, sputum volume, CAT score, LCQ score, SaO2, grade of wheeze; mMRC Dyspnoea Scale, end‐tidal CO2, blood inflammatory marker, change in PaO2/FiO2 ratio from baseline to day 7, PaCO2 on day 7, 28 and 90 days' mortality, time to wean off supplemental oxygen, length of stay. Primary and secondary outcomes will be compared among the two treatment groups with two‐sample t‐test. Discussion: We hypothesize that NAC use in COPD exacerbation can provide benefits in clinical and laboratory parameters. Trial Registration: Name of the registry: ClinicalTrials.gov Trial registration number: NCT05706402. URL of the trial registry record for this trial: https://classic.clinicaltrials.gov/ct2/show/NCT05706402 Date of registration: Registered on 11th January 2023 Funding of the trial: The Health and Medical Research Fund (HMRF). Name and contact information for the trial sponsor: Wang Chung Kwok, Clinical Assistant Professor, Honorary Associate Consultant, Queen Mary Hospital, The University of Hong Kong, Hong Kong. Role of sponsor: The funder is not involved in the planning of the study, gathering, analysing, and interpreting the data, or in preparing the manuscript. [ABSTRACT FROM AUTHOR]

Background: The anti-IgE monoclonal antibody omalizumab is widely used for severe asthma. This study aimed to identify biomarkers that predict clinical improvement during 1 year of omalizumab treatment. Methods: One-year open-label Study of Mechanisms of action of Omalizumab in Severe Asthma (SoMOSA) involving 216 patients with severe (Global Initiative for Asthma step 4/5) uncontrolled atopic asthma (at least two severe exacerbations in the previous year) taking high-dose inhaled corticosteroids and long-acting β-agonists with or without maintenance oral corticosteroids. It had two phases: 0–16 weeks, to assess early clinical improvement by Global Evaluation of Therapeutic Effectiveness (GETE); and 16–52 weeks, to assess late responses based on ⩾50% reduction in exacerbations or mOCS dose. All participants provided samples (exhaled breath, blood, sputum, urine) before and after 16 weeks of omalizumab treatment. Measurements and Main Results: A total of 191 patients completed phase 1; 63% had early improvement. Of 173 who completed phase 2, 69% had reduced exacerbations by ⩾50% and 57% (37 of 65) taking mOCSs had reduced their dose by ⩾50%. The primary outcomes 2,3-dinor-11-β-PGF2α, GETE score, and standard clinical biomarkers (blood and sputum eosinophils, exhaled nitric oxide, serum IgE) did not predict either clinical response. Five volatile organic compounds and five plasma lipid biomarkers strongly predicted the ⩾50% reduction in exacerbations (receiver operating characteristic areas under the curve of 0.780 and 0.922, respectively) and early responses (areas under the curve of 0.835 and 0.949, respectively). In an independent cohort, gas chromatography/mass spectrometry biomarkers differentiated between severe and mild asthma. Conclusions: This is the first discovery of omics biomarkers that predict improvement in asthma with biologic agent treatment. Prospective validation and development for clinical use is justified. [ABSTRACT FROM AUTHOR]

Asthma is a heterogeneous disease, and its development is the result of a combination of factors, including genetic factors, environmental factors, immune dysfunction and other factors. Its specific mechanism has not yet been fully investigated. With the improvement of disease models, research on the pathogenesis of asthma has made great progress. Immunological disorders play an important role in asthma. Previously, we thought that asthma was mainly caused by an imbalance between Th1 and Th2 immune responses, but this theory cannot fully explain the pathogenesis of asthma. Recent studies have shown that T-cell subsets such as Th1 cells, Th2 cells, Th17 cells, Tregs and their cytokines contribute to asthma through different mechanisms. For the purpose of the present study, asthma was classified into distinct phenotypes based on airway inflammatory cells, such as eosinophilic asthma, characterized by predominant eosinophil aggregates, and neutrophilic asthma, characterized by predominant neutrophil aggregates. This paper will examine the immune mechanisms underlying different types of asthma, and will utilize data from animal models and clinical studies targeting specific immune pathways to inform more precise treatments for this condition. [ABSTRACT FROM AUTHOR]

Background: Glucocorticoids are widely used in inhalation aerosol therapy for wheezing diseases. This study aims to explore guardians' knowledge and attitude towards inhaled corticosteroids (ICS) aerosol therapy and the medication compliance of children with wheezing diseases in China. Methods: This cross-sectional study enrolled guardians of children with wheezing diseases at the First Hospital Affiliated to Shaoyang College between October 2022 and February 2023. A self-administered questionnaire was developed to collect demographic information of the participants and evaluate their knowledge and attitude towards ICS aerosol therapy. The 8-item Morisky Medication Adherence Scale was used to assess the medication compliance of children. Results: A total of 506 valid questionnaires were collected. 260 (51.38%) participants were guardians of a ≤ 3-year-old child and 327 (64.62%) were children's mothers. The knowledge, attitude, and medication compliance scores of all participants were 12.61 ± 5.78, 20.95 ± 2.37, and 4.69 ± 2.18, respectively. Multivariate logistic regression showed that knowledge scores [OR = 1.053, 95% CI (confidence interval): 1.017–1.090, P = 0.003], attitude scores (OR = 1.121, 95% CI: 1.030–1.219, P = 0.008), guardians of children aged 4–6 years (OR = 0.385, 95% CI: 0.242–0.612, P < 0.001), and grandparents of children (OR = 2.633, 95% CI: 1.104–6.275, P = 0.029) were independently associated with children's medication compliance. Conclusions: In conclusion, guardians of children with wheezing diseases in China had insufficient knowledge, unsatisfactory attitude, and poor medication compliance towards ICS aerosol therapy. Trial registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Asthma's complexity, marked by airway inflammation and remodeling, is influenced by hypoxic conditions. This study focuses on the role of Hypoxia-Inducible Factor-1 Alpha (HIF-1α) and P53 ubiquitination in asthma exacerbation. Methods: High-throughput sequencing and bioinformatics were used to identify genes associated with asthma progression, with an emphasis on GO and KEGG pathway analyses. An asthma mouse model was developed, and airway smooth muscle cells (ASMCs) were isolated to create an in vitro hypoxia model. Cell viability, proliferation, migration, and apoptosis were assessed, along with ELISA and Hematoxylin and Eosin (H&E) staining. Results: A notable increase in HIF-1α was observed in both in vivo and in vitro asthma models. HIF-1α upregulation enhanced ASMCs' viability, proliferation, and migration, while reducing apoptosis, primarily via the promotion of P53 ubiquitination through MDM2. In vivo studies showed increased inflammatory cell infiltration and airway structural changes, which were mitigated by the inhibitor IDF-11,774. Conclusion: The study highlights the critical role of the HIF-1α-MDM2-P53 axis in asthma, suggesting its potential as a target for therapeutic interventions. The findings indicate that modulating this pathway could offer new avenues for treating the complex respiratory disorder of asthma. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionTo study associations between fractional exhaled nitric oxide (FeNO) and asthma, airway symptoms, sensitization to common allergens, outdoor pollution and home environment among 380 students in eight junior high schools in two areas in Indonesia.Data on health and home were collected by a face-to face interview before measuring FeNO and performing skin prick test against common allergens. Exploratory linear mixed and logistic regression models were employed.Geometric mean of FeNO was 17.8 ppb (GSD 2.09) and 139 students (36.6%) had elevated FeNO (>20 ppb). In total, 107 students (28.2%) were sensitized to house dust mite (HDM) (Der p1 or Der f1), 4 (1.1%) to cat and 3 (0.8%) to mold (Cladosporium or Alternaria). Moreover, 20 students (5.3%) had diagnosed asthma, 38 (10.0%) had current wheeze, and 107 (28.2%) had current rhinitis. HDM sensitization, diagnosed asthma, current wheeze, and current rhinitis were associated with FeNO. In total, 281 students (73.9%) had mold or dampness, 232 (61.1%) had environmental tobacco smoke (ETS) and 43 (11.3%) had other odor at home. Indoor mold or dampness and other odor at home were associated with FeNO. ETS was negatively associated with FeNO.HDM sensitization and elevated FeNO can be common among children in this part of Indonesia. The high prevalence of elevated FeNO indicate that undiagnosed childhood asthma is common. Dampness, mold and odor at home can be associated with increased FeNO while ETS can be associated with decreased FeNO. [ABSTRACT FROM AUTHOR]

Conventional immunosuppressants are ineffective for the management of EGPA-related asthma. Tezepelumab is a human monoclonal antibody that inhibits thymic stromal lymphopoietin (TLSP) that has proven efficacy in several phase 3 studies for the treatment of asthma. We treated with off-label tezepelumab the first two patients with severe refractory EPGA-related asthma. These preliminary findings suggest that targeting upstream signaling of the T2 inflammatory pathway can improve symptoms, reduce BVAS and increase Asthma Control Test scores, even in patients with refractory asthma who have failed several previous lines of treatment. Nevertheless, by analogy with dupilumab-induced IL-4/13 blockade, the persistence of sputum eosinophilia (reported in both patients) raises questions as to whether TSLP inhibition could lead to a rebound of eosinophilia and potentially to eosinophil-related symptoms in patients with EGPA. [ABSTRACT FROM AUTHOR]

Introduction Aim Methods Results Conclusion Evidence on the early life risk factors of adult CRS, and the history of asthma and allergies across the life course, is limited.To investigate relationships between respiratory infective/allergic conditions in childhood, and asthma and allergies across the life course and CRS in middle age.Data were from the population‐based Tasmanian Longitudinal Health Study (TAHS) cohort, first studied in 1968 when aged 6–7 years (n = 8583) and serially followed into middle age (n = 3609). Using a well‐accepted epidemiological definition, participants were assigned a CRS‐severity subtype at age 53: no sinusitis/CRS (reference); past doctor diagnosis only; current symptoms without doctor diagnosis; and doctor‐diagnosed CRS with current symptoms. Relationships with infective/allergic respiratory illnesses at age 7, and previously published asthma‐allergy trajectories from 7 to 53 years, were examined using multinominal regression.In middle age, 5.8% reported current CRS symptoms with 2.5% doctor‐diagnosed. Childhood conditions associated with symptomatic doctor‐diagnosed CRS included frequent head colds (multinomial odds ratio [mOR] = 2.04 (95% confidence interval [95% CI]: 1.24, 3.37)), frequent tonsillitis (mOR = 1.61 [95% CI: 1.00, 2.59]) and current childhood asthma (mOR = 2.23 [95% CI: 1.25, 3.98]). Life course trajectories that featured late‐onset or persistent asthma and allergies were associated with all CRS subtypes in middle age; early‐onset persistent asthma and allergies (mOR = 6.74, 95% CI: 2.76, 16.4); late‐onset asthma allergies (mOR = 15.9, 95% CI: 8.06, 31.4), and late‐onset hayfever (mOR = 3.02, 95% CI: 1.51, 6.06) were associated with symptomatic doctor‐diagnosed CRS.Current asthma, frequent head colds and tonsillitis at age 7 could signal a susceptible child who is at higher risk for CRS in mid‐adult life and who might benefit from closer monitoring and/or proactive management. Concurrent asthma and allergies were strongly associated and are potential treatable traits of adult CRS. [ABSTRACT FROM AUTHOR]

Background Objectives Search Strategy Selection Criteria Data Collection and Analysis Main Results Conclusions Clinical and preclinical evidence indicate that in utero maternal asthma exposure increases progeny asthma risk. Whether maternal asthma also increases the risks of progeny allergy is unclear.To synthesise the available evidence on the relationship between in utero exposure to maternal asthma and postnatal asthma, wheezing and allergic diseases (Prospero: CRD42020201538).We systematically searched MEDLINE [PubMed], Embase [Ovid], Web of Science, Informit Health, the Cochrane Library, CINAHL [EBSCOhost], MedNar [Deep Web Technologies], ProQuest Theses and Dissertations, Scopus [Elsevier] and Trove, to the end of 2023.Studies reporting asthma, wheeze and/or allergic disease in progeny of women with and without asthma or with asthma classified by control, exacerbation or severity.Double screening, selection, data extraction and quality assessment were performed, using Joanna Briggs Institute (JBI) scoring.Of 134 non‐overlapping studies, 127 were included in ≥1 meta‐analysis. Maternal asthma ever was associated with greater risks of asthma (65 studies, risk ratio [95% confidence interval] 1.76 [1.57–1.96]), wheeze (35 studies, 1.59 [1.52–1.66]), food allergy (5 studies, 1.32 [1.23–1.40]), allergic rhinitis (7 studies, 1.18 [1.06–1.31]) and allergic dermatitis (14 studies, 1.17 [1.11–1.23]) ever in progeny. Asthma during the pregnancy, more severe, and uncontrolled maternal asthma were each associated with greater risks of progeny asthma.Children of mothers with asthma are at increased risk for the development of allergic diseases. Whether improved maternal asthma control reduces risks of child allergy as well as asthma requires further investigation. [ABSTRACT FROM AUTHOR]

Asthma, the most common chronic disease of childhood, can affect a child's physical and mental health and social and emotional development. The aim of this study was to identify factors associated with emergency department (ED) return visits for asthma exacerbations within 14 days of an initial visit. This was a retrospective review from Cerner Real-World Data for patients aged from 5 to 18 years and seen at an ED for an asthma exacerbation and discharged home at the index ED visit. Asthma visits were defined as encounters in which a patient was diagnosed with asthma and a beta agonist, anticholinergic, or systemic steroid was ordered or prescribed at that encounter. Return visits were ED visits for asthma within 14 days of an index ED visit. Data, including demographic characteristics, ED evaluation and treatment, health care utilization, and medical history, were collected. Data were analyzed via logistic regression mixed effects model. A total of 80,434 index visits and 17,443 return visits met inclusion criteria. Prior ED return visits in the past year were associated with increased odds of a return visit (odds ratio [OR] 2.12; 95% CI 2.07–2.16). History of pneumonia, a concomitant diagnosis of pneumonia, and fever were associated with increased odds of a return visit (OR 1.19; 95% CI 1.10–1.29; OR 1.15; 95% CI 1.04–1.28; OR 1.20; 95% CI 1.11–1.30, respectively). Several variables seem to be associated with statistically significant increased odds of ED return visits. These findings indicate a potentially identifiable population of at-risk patients who may benefit from additional evaluation, planning, or education prior to discharge. [ABSTRACT FROM AUTHOR]

We aimed to compare the effectiveness of three distinct counseling methods to determine the most effective approach. In this prospective cohort study with a two-month follow-up, A group of non-smoking adults, aged 19-60 years, were randomly collected at outpatients clinic with prior asthma diagnosis, based on the forced expiratory volume in one seconds to forced vital capacity ratio (FEV1/FVC) and the guidelines outlined by the Global Initiative for Asthma (GINA), At the baseline assessment, all patients, underwent FEV1/FVC measurements, asthma symptom evaluations using Asthma Control Test (ACT), Asthma Control Questionnaire (ACQ), and GINA symptoms control assessment questionnaire, and assessment of pressurized metered-dose inhaler (pMDI) usage. The patients were divided into three groups, each assigned a distinct counseling strategy: traditional verbal counseling, advanced counseling utilizing the Asthma smartphone-application, and a combination of advanced-verbal counseling. We conducted a two-month monitoring period for all three groups. Significant differences (p <.001) were observed among the three counseling groups in ACT, FEV1/FVC ratio, and GINA symptoms control assessment scores from the first month to the second month visit. Regarding ACQ, the study unveiled a noteworthy disparity in ACQ scores during the second week, with a significant difference (p =.025) observed between the verbal and advanced-verbal counseling groups. Similarly, a significant difference (p =.016) was noted between the advanced counseling group and the advanced-verbal counseling groups. The study findings indicate that the combining advanced-verbal counseling by incorporating the Asthma smartphone-application alongside traditional verbal counseling is a more effective approach for improving asthma control in adults. [ABSTRACT FROM AUTHOR]

Tailoring asthma interventions based on biomarkers could substantially impact the high cost associated with asthma morbidity. For policymakers, the main concern is the economic impact of adopting this technology, especially in developing countries. This study evaluates the budget impact of asthma management using sputum eosinophil counts in Colombia patients between 4 and 18 years of age. A budget impact analysis was performed to evaluate the potential financial impact of sputum eosinophil counts (EO). The study considered a 5-year time horizon and the Colombian National Health System perspective. The incremental budget impact was calculated by subtracting the cost of the new treatment, in which EO is reimbursed, from the cost of the conventional therapy without EO (management based on clinical symptoms (with or without spirometry/peak flow) or asthma guidelines (or both), for asthma-related). Univariate one-way sensitivity analyses were performed. In the base-case analysis, the 5-year costs associated with EO and no-EO were estimated to be US$ 532.865.915 and US$ 540.765.560, respectively, indicating savings for Colombian National Health equal to US$ 7.899.645, if EO is adopted for the routine management of patients with persistent asthma. This result was robust in univariate sensitivity one-way analysis. EO was cost-saving in guiding the treatment of patients between 4 and 18 years of age with persistent asthma. Decision-makers in our country can use this evidence to improve clinical practice guidelines, and it should be replicated to validate their results in other middle-income countries. [ABSTRACT FROM AUTHOR]

Bronchial thermoplasty (BT) decreases the incidence of asthma exacerbations, emergency room visits, and hospitalizations among patients with severe asthma. Predictors of BT effectiveness remain unclear as its mechanism of action and invasiveness remain obscure. This study aimed to identify factors that could predict BT outcomes. Two respiratory physicians treated 20 consecutive patients with severe asthma using BT. The patients were assigned to groups based on clinical remission following an expert consensus proposed in 2020. Predictors of clinical remission were analyzed using asthma control test (ACT) score, pulmonary function and blood tests, and fractional exhaled nitric oxide. At baseline, the median age was 44 years (interquartile range [IQR], 31.0–52.8), and pre-bronchodilator (pre-BD) percent predicted forced expiratory volume in one second (%FEV1) was 85.9% (IQR, 74.8–100.5). Six (30%) patients achieved clinical remission. Among the patients treated with biologics, 20% had clinical remission, and 20% discontinued biologic therapy. The pre-BT ACT score was significantly lower in the group with than without remission (11.0 [IQR, 8.0–14.5] vs. 15.0 [IQR, 11.0–17.3], p =.016). Adverse events did not significantly differ between the groups. To the best of our knowledge, this is the first study to use clinical remission as a criterion for evaluating BT efficacy. The pre-BT ACT score might a the predict response to BT in younger adult patients with severe asthma and pre-BD %FEV1 ≥ 70%. [ABSTRACT FROM AUTHOR]

Montelukast prescribing information includes a Boxed Warning issued in March 2020 regarding neuropsychiatric adverse events. A previous Sentinel System study of asthma patients from 2000 to 2015 did not demonstrate an increased risk of intentional self-harm measured using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, with montelukast compared to inhaled corticosteroids (ICS). Using a new user cohort study design, we examined intentional self-harm events in patients aged 10 years and older who were incident users of either montelukast or ICS as monotherapy, with a diagnosis of asthma, between October 1, 2015, to June 30, 2022, in the Sentinel System. We measured intentional self-harm using ICD-10-CM codes, which may have better accuracy for capturing suicide attempts than ICD-9-CM codes. We used inverse probability of treatment weighting to balance baseline covariates. We performed subgroup analyses by age group, sex, psychiatric history, and pre/post Boxed Warning era and conducted sensitivity analyses varying type of care setting of the outcome and exposure episode gaps. Among 752,230 and 724,855 patients in the montelukast and ICS exposure groups respectively, we found no association between montelukast use and self-harm compared to ICS use [Hazard Ratio (95% Confidence Interval): 0.96 (0.85, 1.08)]. This finding was consistent across all subgroups, and sensitivity analyses. Our results cannot exclude other neuropsychiatric idiosyncratic reactions to montelukast. Compared to the previous Sentinel study, this study identified about double the rate of self-harm events, suggesting a greater sensitivity of ICD-10 codes for measuring self-harm than ICD-9. [ABSTRACT FROM AUTHOR]

The ST2/IL‐33 signaling pathway has an important role in the host inflammatory response. Here we aimed to study the association of ST2 and IL‐33 polymorphisms with serum soluble (s) ST2 and IL‐33 concentrations in healthy Finnish children and, in addition, their association with childhood asthma. In total, 146 children were followed from birth to the age 7 years for the development of asthma. Single‐nucleotide polymorphisms (SNPs) in ST2 and IL‐33 were determined, and associations of the SNP variants with serum levels of sST2 and IL‐33 at age of 13 months and with recurrent wheezing and childhood asthma at 7 years of age were analyzed. Children with ST2 rs1041973 AC/AA genotypes had significantly lower level of serum sST2 (2453 pg/mL; IQR 2265) than those with CC genotype (5437 pg/mL; IQR 2575; p = < 0.0001). Similar difference was also observed with ST2 rs13408661. No differences were observed between subjects with studied IL‐33 SNPs. Children who carried genetic variants of ST2 rs1041973 or rs13408661 seemed to have a higher risk of asthma. In contrast, children who carried genetic variants of IL‐33 rs12551268 were less often diagnosed with asthma. Even though these SNPs seemed to associate with asthma, the differences were not statistically significant. [ABSTRACT FROM AUTHOR]

Introduction: A high consumption of carbonated soft drinks (i.e., soda drinks) and fast food is potentially associated with the observed global rise in adolescent allergic diseases. Thus, our study aimed to examine the potential associations between the consumption of soda drinks and fast food and allergic conditions, identifying specific relationships across subgroups and each allergic condition (asthma, allergic rhinitis, and atopic dermatitis). Methods: This study uses large-scale data from the Korea Youth Risk Behavior Web-Based Survey (total n = 865,614). Soda drinks and fast food were defined by a self-reported questionnaire and allergic conditions by physician-diagnosed within 1 year. Multivariable logistic regression was used to analyze the weighted odds ratios (ORs), along with 95% confidence intervals (CIs), for allergic diseases associated with the intake of soda drinks and fast food. Results: Among 865,614 adolescents in grades 7–12 (male, 51.40%), patients with asthma, allergic rhinitis, and atopic dermatitis were 18,568 (2.15%), 153,536 (17.74%), and 59,014 (6.82%), respectively. Current asthma was associated with soda drinks (OR, 1.07; 95% CI, 1.03–1.12) and fast food consumption (1.25; 1.17–1.33). Interestingly, stronger associations were observed for female high schoolers, compared to male high schoolers and middle schoolers, in relation to the consumption of soda drinks (1.31; 1.19–1.44) and fast food (1.46; 1.26–1.69) with asthma. Current allergic rhinitis and atopic dermatitis had no significant association with fast food consumption and soda drinks. Conclusion: This first large-scale study suggests that fast food and soda drinks consumption are potentially associated with current asthma, with stronger associations observed in females than males, underscoring the need for sex-specific allergy prevention programs. [ABSTRACT FROM AUTHOR]

Exacerbation frequency strongly influences treatment choices in patients with severe asthma. What is the extent of the variability of exacerbation rate across countries and its implications in disease management? We retrieved data from the International Severe Asthma Registry, an international observational cohort of patients with a clinical diagnosis of severe asthma. We identified patients aged ≥ 18 years who did not initiate any biologics prior to baseline visit. A severe exacerbation was defined as the use of oral corticosteroids for ≥ 3 days or asthma-related hospitalization/ED visit. A series of negative binomial models were applied to estimate country-specific severe exacerbation rates during 365 days of follow-up, starting from a naive model with country as the only variable to an adjusted model with country as a random-effect term and patient and disease characteristics as independent variables. The final sample included 7,510 patients from 17 countries (56% from the United States), contributing to 1,939 severe exacerbations (0.27/person-year). There was large between-country variation in observed severe exacerbation rate (minimum, 0.04 [Argentina]; maximum, 0.88 [Saudi Arabia]; interquartile range, 0.13-0.54), which remained substantial after adjusting for patient characteristics and sampling variability (interquartile range, 0.16-0.39). Individuals with similar patient characteristics but coming from different jurisdictions have varied severe exacerbation risks, even after controlling for patient and disease characteristics. This suggests unknown patient factors or system-level variations at play. Disease management guidelines should recognize such between-country variability. Risk prediction models that are calibrated for each jurisdiction will be needed to optimize treatment strategies. [ABSTRACT FROM AUTHOR]

The article discusses the interconnectedness of planetary health and human health, specifically focusing on the impact of indoor and outdoor pollutants on asthma-related outcomes. The European Academy of Allergy and Clinical Immunology (EAACI) conducted systematic reviews to evaluate the effects of pollution on patients with asthma and provide recommendations for prevention and patient care. The article highlights the risks associated with exposure to outdoor air pollutants, such as particulate matter and traffic-related pollutants, as well as indoor pollutants like volatile organic compounds, cleaning agents, and pesticides. The guidelines emphasize the importance of reducing exposure to pollutants and implementing personalized interventions for asthma management. Additionally, the article addresses the impact of tobacco smoke on asthma outcomes and the need for further research to establish causal relationships between pollutants and adverse asthma-related outcomes. The guidelines aim to improve asthma care and advocate for multilevel, multi-sectoral actions to reduce emissions, improve air quality, and prioritize underserved populations. [Extracted from the article]

We performed a systematic review to investigate the current evidence on the association between allergic diseases and short chain fatty acids (SCFAs), which are microbially produced and suggested as one mechanism on how gut microbiome affects the risk of allergic diseases. Medline, Embase and Web of Science were searched from data inception until September 2022. We identified 37 papers, of which 17 investigated prenatal or early childhood SCFAs and the development of allergic diseases in childhood, and 20 assessed SCFAs in patients with pre‐existing allergic diseases. Study design, study populations, outcome definition, analysis method and reporting of the results varied between papers. Overall, there was some evidence showing that the three main SCFAs (acetate, propionate and butyrate) in the first few years of life had a protective effect against allergic diseases, especially for atopic dermatitis, wheeze or asthma and IgE‐mediated food allergy in childhood. The association between each SCFA and allergic disease appeared to be different by disease and the age of assessment. Further research that can determine the potentially timing specific effect of each SCFA will be useful to investigate how SCFAs can be used in treatment or in prevention against allergic diseases. [ABSTRACT FROM AUTHOR]

Systematic review using GRADE of the impact of exposure to volatile organic compounds (VOCs), cleaning agents, mould/damp, pesticides on the risk of (i) new‐onset asthma (incidence) and (ii) adverse asthma‐related outcomes (impact). MEDLINE, EMBASE and Web of Science were searched for indoor pollutant exposure studies reporting on new‐onset asthma and critical and important asthma‐related outcomes. Ninety four studies were included: 11 for VOCs (7 for incidenceand 4 for impact), 25 for cleaning agents (7 for incidenceand 8 for impact), 48 for damp/mould (26 for incidence and 22 for impact) and 10 for pesticides (8 for incidence and 2 for impact). Exposure to damp/mould increases the risk of new‐onset wheeze (moderate certainty evidence). Exposure to cleaning agents may be associated with a higher risk of new‐onset asthma and with asthma severity (low level of certainty). Exposure to pesticides and VOCs may increase the risk of new‐onset asthma (very low certainty evidence). The impact on asthma‐related outcomes of all major indoor pollutants is uncertain. As the level of certainty is low or very low for most of the available evidence on the impact of indoor pollutants on asthma‐related outcomes more rigorous research in the field is warranted. [ABSTRACT FROM AUTHOR]

This article explores the clinical, immunological, and molecular aspects of MHC class I deficiency, a rare immunodeficiency disorder characterized by the absence or reduced expression of MHC class I molecules. These molecules play a crucial role in presenting peptides from intracellular pathogens to CD8+ T cells, which eliminate infected cells. The article presents two cases of children with MHC class I deficiency who underwent hematopoietic stem cell transplantation (HSCT) and discusses their outcomes after the transplant. MHC class I deficiency can lead to susceptibility to infections and malignancies, and its symptoms can vary from mild to severe. The role of transplantation in treating this condition is not well understood, as immune reconstitution is limited due to poor thymic function. Further research is necessary to gain a better understanding of MHC class I deficiency and its treatment options. [Extracted from the article]

Background: Viral wheezing is an important risk factor for asthma, which comprises several respiratory phenotypes. We sought to understand if the etiology of early‐life wheezing illnesses relates to childhood respiratory and asthma phenotypes. Methods: Data were collected prospectively on 429 children in the Urban Environment and Childhood Asthma (URECA) birth cohort study through age 10 years. We identified wheezing illnesses and the corresponding viral etiology (PCR testing of nasal mucus) during the first 3 years of life. Six phenotypes of respiratory health were identified at 10 years of age based on trajectories of wheezing, allergic sensitization, and lung function. We compared the etiology of early wheezing illnesses to these wheezing respiratory phenotypes and the development of asthma. Results: In the first 3 years of life, at least one virus was detected in 324 (67%) of the 483 wheezing episodes documented in the study cohort. Using hierarchical partitioning we found that non‐viral wheezing episodes accounted for the greatest variance in asthma diagnosed at both 7 and 10 years of age (8.0% and 5.8% respectively). Rhinovirus wheezing illnesses explained the most variance in respiratory phenotype outcome followed by non‐viral wheezing episodes (4.9% and 3.9% respectively) at 10 years of age. Conclusion and Relevance: Within this high‐risk urban‐residing cohort in early life, non‐viral wheezing episodes were frequently identified and associated with asthma development. Though rhinovirus wheezing illnesses had the greatest association with phenotype outcome, the specific etiology of wheezing episodes in early life provided limited information about subsequent wheezing phenotypes. [ABSTRACT FROM AUTHOR]

Acute respiratory tract infections (RTIs) are one of the most common causes of pediatric consultations/hospitalizations and a major trigger for asthma exacerbations. Some consensus statements have recommended the use of immunostimulants to boost natural defenses against severe or repeated infections. One of the most common immunostimulants is OM‐85; while several randomized clinical trials (RCTs) have evaluated its efficacy in preventing acute RTIs and wheezing/asthma exacerbations, results have been conflicting. Similarly, various systematic reviews with meta‐analyses (SRMs) on OM‐85 have used different strategies, populations, and outcomes; moreover, SRM conclusions are limited when the original studies are highly heterogeneous or have a low quality, hindering the generalizability of the findings. Here we summarize the evidence on the effect of OM‐85 to prevent acute RTIs, wheezing/asthma episodes, or loss of asthma control in children, by including and critically evaluating all SRMs published to date. We searched for SRMs on OM‐85 in three publication databases and found nine SRMs (seven for RTI, and two for wheezing/asthma). Among those, one had a high confidence evaluation of quality (AMSTAR‐2 tool) and found a reduction in the total number of acute RTIs among the OM‐85 group. Overall, no strong recommendations can be derived from the existing literature, mainly due to the high heterogeneity among included RCTs and SRMs. Further, large, high‐quality RCTs are needed to confirm the true efficacy of OM‐85 for the prevention of acute RTIs, asthma development, and asthma exacerbations. [ABSTRACT FROM AUTHOR]

Exhaled nitric oxide fraction (FeNO) is employed for the diagnosis and phenotyping of asthma as an inflammatory biomarker of the airway. Limited evidence exists regarding its behavior in the presence of asthma and obstructive sleep apnea (OSA). Our objective was to determine whether FeNO levels are associated with the severity of OSA or the coexistence of asthma and OSA in residents at high altitudes. Observational, analytical, cross-sectional study in children aged 5–16 years residing at 2600 m above sea level treated at a Sleep Study Center between 2019 and 2021. We conducted a medical history, polysomnogram, and measurement of FeNO levels. The children were categorized into four groups: OSA, asthma, asthma with OSA, and controls (without asthma or OSA). FeNO levels among the groups were compared using the Kruskal-Wallis test, and correlations were explored using the Spearman correlation coefficient. Analyses considered statistical significance at a two-tailed p-value <0.05. Among the 261 included children, 68 (26.1 %) had OSA, 42 (16.1 %) were diagnosed with asthma, 109 (41.8 %) had both asthma and OSA, and 42 (16.1 %) were controls. Their FeNO medians were 10 ppb, 18.5 ppb, 15 ppb, and 14 ppb, respectively, with no significant differences between the evaluated groups (p = 0.263). We found no correlation between FeNO and apnea-hypopnea index and obstructive apnea index even for the groups of patients with FeNO >20 ppb and FeNO >35 ppb (>75th percentile). In the adjusted model, a significant association was observed between asthma and FeNO levels. Our findings suggest that FeNO measurements in children would not allow establishing this biomarker as part of the diagnosis of OSA. However, these findings may be related to high altitude. • This study evaluates FeNO levels in children with OSA and asthma at high altitude. • FeNO levels in children would not allow establishing as part of the diagnosis of OSA. • A significant association was observed between asthma and FeNO levels. [ABSTRACT FROM AUTHOR]

Aim: This nationwide study evaluated the clinical impact that an early thymectomy, during congenital heart defect (CHD) surgery, had on the health of children and adolescents. Methods: The subjects were patients aged 1–15 years who had undergone CHD surgery at the University Children's Hospital, Helsinki, where all CHD surgery in Finland is carried out, from 2006 to 2018. The parents or the cases and population‐based controls, matched for sex, age and hospital district, completed electronic questionnaires. We excluded those with low birth weights or a known immunodeficiency. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated for prespecified outcomes. Results: We received responses relating to 260/450 (58%) cases and 1403/4500 (31%) controls and excluded 73 cases with persistent cardiac or respiratory complaints after surgery. The CHD group reported more recurrent hospitalisations due to infections (aOR 6.3, 95% CI 3.0–13) than the controls and more pneumonia episodes (aOR 3.5, 95% CI 2.1–5.6), asthma (aOR 2.5, 95% CI 1.5–4.1) and wheezing (aOR 2.1, 95% CI 1.5–2.9). Conclusion: Hospitalisation due to infections, pneumonia, wheezing and asthma was more common in children after a thymectomy due to open‐heart surgery than population‐based controls, underlining the importance of immunological follow‐ups. [ABSTRACT FROM AUTHOR]

AbstractIntroductionMethodsResultsConclusionsAsthma is a chronic inflammatory disease of the lower airways that affects more than 260 million people worldwide and has been related to more than 460,000 deaths a year. It is estimated that in 60% of asthma cases, the symptoms are not adequately controlled. The objective of this study was to determine the association between some comorbidities, habits, and health risk behaviors with uncontrolled asthma in a sample of young people with asthma.Through a cross-sectional study, data from 1,078 young people aged 17 to 19 years were analyzed. Information was collected through physical examination, direct questioning, and the application of a self-administered questionnaire.In the group of young people with asthma, the prevalence of uncontrolled asthma was 20.6%, of which 53.8% were women, 76.9% suffered from rhinitis, 46.2% were overweight and 23.1% were obese. In the group of young with uncontrolled asthma, gingivitis was detected in 53.8% and alcohol consumption in 84.6%. Logistic regression analysis showed a significant association between allergic rhinitis, gingivitis, carbohydrate intake, alcohol consumption, overweight, and obesity with uncontrolled asthma.Parents and members of the health team need to identify on time the risk factors associated with uncontrolled asthma in young people with asthma to limit its development and the negative effects it generates. The results of this study should be used to strengthen programs that promote the comprehensive health of adolescents. [ABSTRACT FROM AUTHOR]

Primary cardiac malignant tumors are extremely rare, making up about 10% of all primary cardiac tumors. Most of these tumors are primary sarcomas, with primary mesothelioma being even less common. This report details a 53-year-old male patient diagnosed with primary cardiac malignant mesothelioma. The patient had symptoms of chest pain and difficulty breathing. A CT scan showed an enlarged heart, fluid around the heart, and irregular thickening of the pericardium. Diagnosis was confirmed through a surgical biopsy, which showed the presence of malignant mesothelioma. After the procedure, the patient received appropriate cardiac support. Although stable at discharge, the patient unfortunately died three months later due to severe wheezing. There may be a potential link between exposure to radioactive iodine treatment and this outcome. This case highlights the diagnostic and treatment challenges of primary cardiac malignant tumors and reminds physicians to consider this rare disease when evaluating patients with similar symptoms. [ABSTRACT FROM AUTHOR]

Severe inherited alpha-1 antitrypsin deficiency (AATD) is an autosomal genetic condition linked to chronic obstructive pulmonary disease (COPD). The significance of heterozygous, milder deficiency variants (PiSZ, PiMZ, PiMS) is less clear. We studied AATD genotypes in 145 children (up to 72 months old) with assessed wheezing severity using the Pediatric Respiratory Assessment Measure (BCCH PRAM score). A control group of 74 children without airway obstruction was included. AAT concentration and Pi phenotype were determined from dry blood spot samples using nephelometry and real-time PCR; PiS and PiZ alleles were identified by isoelectrofocusing. Among the wheezers, the Pi*S allele incidence was 2.07% (3 cases) and the Pi*Z allele was 6.9% (10 cases). The Pi*Z allele frequency was higher in wheezers compared to controls (44.8% vs. 20.27%) and the general Lithuanian population (44.8% vs. 13.6%) and was similar to adult COPD patients in Lithuania: Pi*S 10.3% vs. 15.8% and Pi*Z 44.8% vs. 46.1%. No association was found between AAT genotypes and wheezing severity. Finding that wheezer children exhibit a frequency of Z* and S* alleles like that found in adults with COPD suggests a potential genetic predisposition that links early wheezing in children to the development of COPD in adulthood. Larger cohort studies are needed to confirm this finding.

Abstract Background Chronic cough in children is a challenging symptom for clinicians. So, we aimed in this study to evaluate the diagnostic role of flexible bronchoscope in differentiating between the underlying causes of chronic wet cough and chronic cough associated with wheeze. Methods This was a prospective cross-sectional study conducted on children referred to Tanta University Hospitals and Ain-Shams University Hospitals between January 2021 and January 2023, presenting with a primary complaint of chronic cough lasting more than 4 weeks. The children were further classified into two groups: the first group included children with chronic wet cough not associated with wheezing (Cohort A) and the second group included children with chronic cough associated with wheezing (Cohort B). Results The study enrolled 64 children. During clinical evaluation, 25 (39.1%) children had a chronic cough without wheezing and 39 (60.9%) had a chronic wheezy cough. Bronchoscopic examination findings indicated a notable disparity between the two groups of patients with chronic cough (p=0.006). Among Cohort A patients, the most prevalent bronchoscopic observation was purulent inflammatory secretions in 16 cases (64.0%), followed by congenital airway anomalies in 3 cases (12.0%). Conversely, Cohort B patients exhibited congenital airway anomalies as the primary finding in 14 cases (35.9%), followed by purulent secretions in 7 cases (17.9%). Conclusion Flexible bronchoscopy is a valuable and safe tool for diagnosing chronic cough in children. It helped differentiate between the underlying causes of chronic cough in children with and without wheezing.

Abstract Background Respiratory conditions and health symptoms associated with air pollution in children are a major public health concern, as their immune systems and lungs are not yet fully developed. This study aimed to assess self-reported respiratory conditions and health symptoms associated with air pollution sources amongst children aged six years and below in Melusi informal settlement, Tshwane Metropolitan Municipality, South Africa. Methods With a quantitative cross-sectional study design, parents/caregivers of children aged six years and below (n = 300) from eight Early Childhood Development Centres were invited to participate in the study. This study employed complete sampling, and data was collected using the modified International Study of Asthma and Allergies in Children. The chi-square and multiple logistic regression models were used to analyze data, with p

BackgroundInfants experiencing bronchiolitis are at increased risk for asthma, but few studies have identified modifiable risk factors. We assessed whether early life air pollution influenced child asthma and wheeze at age 4-6 years among children with a history of bronchiolitis in the first postnatal year.MethodsChildren with caregiver-reported physician-diagnosed bronchiolitis were drawn from ECHO-PATHWAYS, a pooled longitudinal cohort from six US cities. We estimated their air pollution exposure from age 1 to 3 years from validated spatiotemporal models of fine particulate matter (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ). Caregivers reported children's current wheeze and asthma at age 4-6 years. We used modified Poisson regression to estimate relative risks (RR) and 95% confidence intervals (CI), adjusting for child, maternal, and home environmental factors. We assessed effect modification by child sex and maternal history of asthma with interaction models.ResultsA total of 224 children had caregiver-reported bronchiolitis. Median (interquartile range) 2-year pollutant concentrations were 9.3 (7.8-9.9) µg/m 3 PM 2.5 , 8.5 (6.4-9.9) ppb NO 2 , and 26.6 (25.6-27.7) ppb O 3 . RRs (CI) for current wheeze per 2-ppb higher O 3 were 1.3 (1.0-1.7) and 1.4 (1.1-1.8) for asthma. NO 2 was inversely associated with wheeze and asthma whereas associations with PM 2.5 were null. We observed interactions between NO 2 and PM 2.5 and maternal history of asthma, with lower risks observed among children with a maternal history of asthma.ConclusionOur results are consistent with the hypothesis that exposure to modest postnatal O 3 concentrations increases the risk of asthma and wheeze among the vulnerable subpopulation of infants experiencing bronchiolitis.