Search Results (309)

Asthma is the most prevalent chronic respiratory disease in childhood, and the objective assessment of airway inflammation remains a major challenge, particularly in younger children in whom conventional lung function testing is often not feasible. The aim of this narrative review is to evaluate the clinical role of fractional exhaled nitric oxide (FeNO) in pediatric asthma, focusing on its diagnostic utility, role in treatment guidance, and value in disease monitoring. A structured literature search was conducted in PubMed for studies published between January 2015 and October 2025, using predefined keywords related to FeNO, asthma, and pediatric populations. After applying the eligibility criteria, 47 studies were included in the final synthesis. Evidence from systematic reviews and clinical studies indicates that FeNO has moderate-to-good diagnostic accuracy for childhood asthma, with a pooled sensitivity of 0.79 and specificity of 0.81, and is most useful as an adjunct to clinical assessment and lung function testing. FeNO-guided therapy may reduce exacerbation rates in selected pediatric populations, although its effects on symptom control and corticosteroid use remain inconsistent. In the monitoring setting, serial FeNO measurements may provide additional information on inflammatory control, treatment adherence, and risk of future exacerbations. However, interpretation is influenced by multiple confounding factors, including atopy, allergic rhinitis, corticosteroid therapy, and asthma phenotype. In conclusion, FeNO is a valuable complementary biomarker in pediatric asthma, with particular utility in improving diagnostic and therapeutic precision. Its optimal use requires careful integration within a multimodal clinical framework rather than reliance as a standalone tool. Full article

Efferocytosis—the tightly regulated clearance of apoptotic cells by phagocytes—maintains tissue homeostasis and is impaired in chronic obstructive pulmonary disease (COPD), where it contributes to persistent inflammation and increases the risk of comorbidities, including lung cancer. Inhaled corticosteroids (ICS) and long-acting β2 agonists (LABAs) are cornerstones of COPD therapy, but their effects on efferocytosis and on the COPD–lung cancer interface are incompletely understood. The primary objective of this study was to determine whether the ICS fluticasone propionate and the LABA salmeterol xinafoate, alone or in combination at clinically informed concentrations (10⁻⁸–10⁻⁶ M; 10⁻⁴ M reserved for cytotoxicity screening), modulate efferocytic capacity and inflammatory cell survival across diverse phagocyte models. We performed standardized in vitro efferocytosis assays using murine peritoneal and alveolar macrophages, the murine macrophage line J774A.1, PMA-differentiated human THP-1 macrophages, human blood-derived neutrophils, and the human alveolar adenocarcinoma cell line A549. Apoptosis was induced in Jurkat T cells by UV irradiation (100 mJ/cm²) and in murine thymocytes by dexamethasone (1 µM, 4 h); apoptotic and necrotic populations were characterized by annexin-V/propidium iodide and Sytox Green/Hoechst H-33342 staining. Peritoneal macrophages showed the highest efferocytic activity (~75%), followed by J774A.1 (~75% at 24 h), THP-1 (~30% at 2 h; ~60% at 24 h), alveolar macrophages (~40%), and A549 cells (<20%). Neither fluticasone nor salmeterol, individually or in combination, significantly altered efferocytic capacity in any phagocyte tested (all ANOVA p > 0.26). Fluticasone (10⁻⁸ and 10⁻⁶ M) significantly improved 24 h neutrophil survival and reduced early apoptosis (p < 0.05) but did not translate this survival benefit into enhanced efferocytosis. Salmeterol was cytotoxic at 10⁻⁴ M and inactive at 10⁻⁸–10⁻⁶ M. These findings indicate that the established anti-inflammatory benefits of ICS/LABA in COPD do not extend to augmentation of efferocytosis in this acute, serum-free in vitro setting and that pharmacological restoration of efferocytosis in COPD—a defect implicated in the pathogenesis and progression of comorbid lung cancer—will likely require strategies targeting the efferocytic machinery itself (e.g., MerTK, Rac-1, MFG-E8) rather than relying on current inhaled therapy. Full article

Asthma represents a chronic inflammatory condition of the respiratory tract, where long-term bronchial inflammation serves as a primary driver of progressive airway remodeling. This complex pathology emerges from the intricate synergy between host genetic susceptibility and diverse environmental triggers, ultimately impairing pulmonary function. At the cellular level, asthmatic responses are orchestrated by a dynamic crosstalk among various immune and structural populations, including airway epithelial cells, T-lymphocytes, eosinophils, and mast cells, which collectively perpetuate the inflammatory milieu. Although inhaled corticosteroids are the conventional cornerstone of therapy, their clinical application is frequently hindered by potential systemic toxicity and the emergence of steroid-resistant phenotypes. Consequently, botanical extracts derived from both aerial and underground plant organs have gained attention as versatile multi-target candidates capable of modulating the multifaceted pathophysiological networks of asthma. This scoping review critically synthesizes the pharmacological efficacy of these plant-based interventions in regulating pivotal signaling cascades, such as MAPK, NF-κB, STAT3/6, and GATA3. Based on a systematic literature search covering the period from 2005 to 2025, this study provides a focused quantitative analysis of preclinical literature from the last decade (2016–2025) to evaluate the in vitro and in vivo models employed to validate these therapeutic effects. The assessment reveals that the vast majority of current research continues to rely on crude botanical preparations, with only a limited subset of studies utilizing enriched fractions or fully characterized isolated compounds. This predominance of unrefined extracts underscores a significant gap in chemical standardization and highlights the necessity for more rigorous mechanistic validation. Ultimately, this paper outlines strategic pathways for translating preclinical findings into clinical practice, offering a robust framework for the development of standardized plant-derived interventions in asthma management. Full article

Background: Eosinophilic granulomatosis with polyangiitis (EGPA), formerly Churg–Strauss syndrome, is a rare necrotizing vasculitis characterized by asthma, eosinophilia, and systemic granulomatosis vasculitis. Perioperative risk is primarily driven by airway hyperreactivity, potential cardiac disease, chronic immunosuppressive therapy, and reported alterations in plasma cholinesterase activity. Evidence specifically addressing anesthetic management remains scarce and largely limited to case-based reports. Methods: A focused narrative review was conducted by searching MEDLINE (via PubMed), Scopus, and Embase from inception to January 2026 for publications reporting perioperative anesthetic management in patients with EGPA/Churg–Strauss syndrome. Case reports and case-based descriptions providing explicit anesthetic details were qualitatively synthesized. Results: Available evidence consists predominantly of isolated case reports across heterogeneous surgical settings, including ENT, abdominal, orthopedic, ambulatory, pediatric, and rare cardiac procedures. Recurring perioperative principles include optimization of bronchial disease and continuation of inhaled therapy; minimization of airway stimulation and avoidance of histamine-releasing drugs; selection of induction agents preserving hemodynamic stability in the presence of myocardial involvement; preference for non-depolarizing neuromuscular blockade with quantitative monitoring (and consideration for sugammadex when appropriate); individualized corticosteroid management and multimodal, opioid-sparing analgesia, often supported by regional techniques. Conclusions: In the absence of dedicated perioperative guidelines, anesthetic care for EGPA should be individualized based on clinical phenotype and organ involvement. A structured approach targeting airway protection, cardiovascular stability, safe neuromuscular management, and opioid-sparing analgesia may represent a pragmatic risk-mitigation framework. These considerations are illustrated by an institutional experience in mitral valve surgery. Full article

Background/Objectives: Inhaled corticosteroids (ICS) increase the risk of pneumonia caused by various pathogens in patients with chronic obstructive pulmonary disease (COPD). Treatment may also increase the risk of infection with non-tuberculous mycobacteria (NTM), although evidence remains limited. The aim of this study was to assess the association between ICS treatment and the risk of NTM isolation among patients with COPD. Methods: This retrospective register-based cohort study included patients with a specialist-verified COPD diagnosis between 2008 and 2021. ICS exposure was based on redeemed prescriptions during the year preceding the index date. Exposure was calculated as the mean daily budesonide-equivalent dose and categorized as none, low, medium, or high. A cause-specific Cox proportional hazards regression model with death as a competing risk was applied, adjusted for potential confounders. Sensitivity analyses included, among others, an inverse probability of treatment weighted model, and a time-dependent Cox regression model. Results: A total of 120,006 patients were included, with a median follow-up time of 4.9 years. During follow-up, 378 (0.32%) patients reached the primary endpoint. Medium- and high-dose ICS were associated with an increased hazard of NTM isolation, with hazard ratios of 1.39 (95% CI 1.06–1.88, p = 0.020) and 1.52 (95% CI 1.14–2.04, p = 0.005), respectively. This association remained significant for high-dose ICS across all sensitivity analyses. Conclusions: In patients with COPD, ICS treatment was associated with an increased and dose-dependent hazard of NTM isolation, particularly at high doses. High-dose ICS should, therefore, be prescribed with caution. Full article

Background/Objectives: Therapeutic adherence to asthma and COPD medications remains worryingly low and varies widely across patient groups, underscoring persistent challenges in chronic respiratory care. The aim of this nationwide study is to quantify real-world adherence and to identify its demographic and clinical determinants using the Belgian health care claims database of the National Institute for Health and Disability Insurance (NIHDI). Methods: Adherence was assessed using the Continuous Multiple Interval Measure of Medication Availability (CMA) among patients treated between 2020 and 2023. Mixed-effects logistic regression was applied to identify determinants of adherence. Results: Only 30.5% of patients achieved good adherence (CMA ≥ 0.8). Adherence varied substantially across pharmacological classes, ranging from 8.1% for inhaled corticosteroids to 66.4% for triple therapy. Age emerged as a major determinant, with adherence increasing steadily across age groups: only 4.0% of children and 15.7% of adolescents reached good adherence, compared with progressively higher rates in adults. Mixed-effects logistic regression confirmed age, sex, and pharmacological class as robust predictors of adherence. Conclusions: These findings highlight the magnitude of the therapeutic adherence gap in chronic respiratory diseases and clearly identify children, adolescents, and ICS or LABA + ICS users as the highest-risk groups. Recognizing these profiles has direct implications for clinical practice, as it provides concrete targets for future patient-centered interventions and guideline-concordant adherence-enhancing strategies. Full article

Background: CD8A-related CD8α deficiency (Immunodeficiency 116) is a rare autosomal recessive primary immunodeficiency disease characterized by absent CD8⁺ T cells and variable sinopulmonary disease. Case Presentation: A seven-year-old boy from a consanguineous family was referred for chronic wet cough and “uncontrolled asthma” despite being prescribed high-dose inhaled corticosteroids and montelukast. He was hospitalized seven times over a two-year period for presumed asthma exacerbations complicated by pneumonia. An examination revealed bilateral crackles without wheezing. Throat culture tested positive for Haemophilus influenzae. CT imaging showed signs of chronic rhinosinusitis (maxillary mucosal thickening) and chronic airway disease with bronchiectatic changes. The patient’s immunoglobulin levels were within normal ranges for his age group. Flow cytometry revealed profound CD8⁺ T-cell lymphopenia (CD8⁺ 0.21%; 11 cells/µL; near-absent after excluding dual-positive cells) with expansion of CD3⁺CD4⁻CD8⁻ T cells (29.5%). CD8A gene sequencing identified a novel homozygous nonsense variant NM_001768.7:c.319C>T (p.Arg107Ter; GRCh38: chr2:86790412G>A), consistent with loss of CD8α and secondary loss of CD8β surface expression. A literature review identified three previously reported symptomatic patients (and two asymptomatic sisters in the first family), all with recurrent respiratory infections and variable structural lung disease. Conclusions: This case highlights CD8A deficiency as a rare mimic of pediatric asthma and expands the genotype spectrum with a truncating CD8A variant. Early lymphocyte immunophenotyping in children with recurrent sinopulmonary infections may prevent delayed diagnosis and progressive airway damage. Full article

Background: The low-dose Synacthen stimulation test (LD-SST) is the reference dynamic test for diagnosing glucocorticoid-induced adrenal insufficiency (AI) in children, but it is resource-intensive and costly. This study aimed to establish morning cortisol thresholds predictive of hypothalamic–pituitary–adrenal (HPA) axis response to LD-SST in pediatric patients receiving chronic corticosteroid therapy. Methods: We conducted a prospective study including 71 children (mean age 6.23 ± 3.49 years; 57.7% male) receiving prolonged oral or inhaled corticosteroids. All patients underwent LD-SST with cortisol measurements at 0, 30, and 60 min. Patients were classified as having AI (peak cortisol < 18 μg/dL at T30 or T60, n = 39) or normal adrenal function (peak cortisol ≥ 18 μg/dL, n = 32). ROC curve analysis determined optimal cortisol thresholds for predicting AI. Results: Among the 71 patients, 44 received inhaled corticosteroids (62%) and 27 oral corticosteroids (38%). Asthma (61.9%) and autoimmune diseases (18.3%) were the main indications. The prevalence of AI was 54.9% (n = 39). Mean morning cortisol was significantly lower in the AI group compared to the normal group (6.69 ± 1.99 vs. 9.21 ± 2.49 μg/dL, p < 0.001). ROC analysis identified a morning cortisol <6 μg/dL as predictive of AI with 96.9% sensitivity and 46.2% specificity (AUC = 0.823), while a threshold >13 μg/dL predicted normal HPA function with 100% specificity. Using these thresholds would have avoided LD-SST in 29.6% of patients. The cortisol increment following stimulation also demonstrated diagnostic value (AUC = 0.822), with an increment <9 μg/dL suggesting AI and ≥9 μg/dL likely excluding the diagnosis. Conclusions: In this North African pilot study, morning cortisol measurement at 7 days after oral corticosteroid withdrawal predicted LD-SST response. A threshold of ≤6 μg/dL identified patients with persistent HPA suppression with high sensitivity (97.4%), while ≥13 μg/dL identified patients with preserved function with high specificity (100%). However, the 7-day washout period might be insufficient for complete HPA recovery; therefore, these thresholds reflect residual suppression rather than permanent adrenal insufficiency. Full article

Background: Severe asthma remains associated with substantial morbidity despite optimized inhaled therapy. Biologic agents targeting type 2 inflammation improve clinical outcomes; however, real-world evidence regarding the durability of these effects beyond the first treatment year remains limited. The present study extends the follow-up of a previously reported real-world cohort in which 12-month outcomes of biologic therapy were evaluated. Methods: We conducted a retrospective observational longitudinal study of adults with severe asthma treated with omalizumab, benralizumab, or dupilumab at a tertiary center in Târgu-Mureș, Romania, between 2020 and 2025, extending follow-up of a previously published real-world cohort. The same patient cohort was followed for an additional period, with longitudinal data collected up to 24 months after biologic therapy initiation. Clinical, functional, and biomarker outcomes were assessed at baseline, 12 months, and 24 months, including Asthma Control Test (ACT) score, forced expiratory volume in one second (FEV₁% predicted), annual exacerbation rate, blood eosinophil count, and fractional exhaled nitric oxide (FeNO). Remission was defined as clinical (ACT ≥ 20, no severe exacerbations, and no maintenance oral corticosteroids), biological (FeNO < 20 ppb and blood eosinophils < 150/µL), and complete (both clinical and biological). Longitudinal changes were analyzed using the Friedman test with post hoc Wilcoxon signed-rank tests. Results: Forty-eight patients were included at baseline, and 41 had available data at 24 months. ACT scores improved from 12 (IQR 11–14) at baseline to 23 (21–25) at 12 months and remained stable at 22 (20–25) at 24 months (p < 0.001). Predicted FEV₁% increased from 50 (39–59) to 78 (68–88) at 12 months and 79 (66–96) at 24 months (p < 0.001). Blood eosinophil counts were markedly suppressed, and FeNO levels continued to decrease over time. Exacerbations declined from 2 (2–3) per year at baseline to 0 and 0.5 (0–1) at 12 and 24 months, respectively (p < 0.001). At 24 months, clinical, biological, and complete remission were observed in 61.0%, 78.0%, and 41.5% of patients with available paired data, respectively. Conclusions: Biologic therapy was associated with sustained clinical and functional improvement over 24 months, accompanied by sustained improvement in type 2 airway inflammation and increasing proportions of patients meeting remission criteria in real-world practice. Full article

Extremely preterm infants often require prolonged respiratory support due to lung immaturity and inflammation, placing them at high risk of lung injury and development of bronchopulmonary dysplasia (BPD). In many of these infants, systemic postnatal corticosteroids are used to reduce lung inflammation, facilitate mechanical ventilation (MV) weaning and extubation, and improve short-term pulmonary outcomes. However, despite decades of clinical use, substantial variation persists in timing, choice of agent and dosing. These inconsistencies reflect a lack of strong evidence and a limited understanding of the systemic and organ-specific effects of therapy for a highly heterogenous population usually exposed to this medication. This narrative review addresses these gaps by integrating current knowledge of the inflammatory and respiratory effects of postnatal corticosteroids in extremely preterm infants. We explore how corticosteroids modulate pulmonary inflammation, their effects on lung development, and how they affect key clinical outcomes such as extubation success and BPD severity. We also examine evolving approaches to corticosteroid administration and dosing, highlighting the importance of individualized strategies informed by developmental and disease-specific considerations. Comparative data from randomized controlled trials are reviewed, including the efficacy and side-effect profiles of commonly used regimens. Current evidence supports judicious use of late low-dose dexamethasone, while early prophylaxis with inhaled or intratracheal steroids remains experimental and is not routinely advised. In line with a physiology-driven approach, we also discuss emerging domain-specific monitoring tools that may enhance patient selection and optimize timing of intervention. By synthesizing mechanistic insights with clinical evidence, this review supports a more nuanced, individualized approach to postnatal corticosteroid therapy in extremely preterm infants, balancing therapeutic benefits with potential systemic trade-offs. Full article

Background: Coronary artery disease (CAD) commonly coexists with chronic obstructive pulmonary disease (COPD), but may be under-recognised, since symptoms such as dyspnoea and chest discomfort are often attributed to lung disease. We hypothesised that coronary artery disease is highly prevalent in patients with COPD, even in the absence of typical angina symptoms. Methods: This study aimed to detect CAD in patients with COPD. We conducted a single-centre observational study, including 76 patients with no known previous cardiovascular events. To detect ischaemic heart disease, three methods were used, according to standard clinical indications: coronary angiography, coronary CT, and calcium score analysis on chest CT. The findings were categorised according to lesion severity and vessel involvement. Results: A substantial proportion of patients with COPD harboured previously undiagnosed atherosclerotic coronary disease (78%). However, most detected disease was non-obstructive atherosclerosis (56%), whereas severe stenosis was present in approximately one-third of patients (32%). Single-vessel disease accounted for 37% of cases, while the remaining patients exhibited multi-vessel involvement. Nevertheless, only a small proportion of patients had typical angina symptoms (11.8%), and the most frequent complaint was effort dyspnoea (50%). Patients not receiving inhaled corticosteroid therapy were more likely to have extensive coronary artery disease (χ² (6)= 14.228, p = 0.027). Conclusions: These findings support our hypothesis that atherosclerotic coronary disease is often under-recognised in patients with COPD. ICS-containing therapy appeared to be associated with less extensive coronary artery involvement; however, this observation should be interpreted cautiously. Full article

Background/Objectives: To summarize the available evidence on the use of corticosteroids in the treatment of pediatric Mycoplasma pneumoniae pneumonia, including severe and refractory forms. Methods: We conducted a narrative literature review of studies published between 2000 and 2024 that investigated corticosteroid therapy in children with Mycoplasma pneumoniae pneumonia, including various clinical presentations such as severe Mycoplasma pneumoniae pneumonia and refractory Mycoplasma pneumoniae pneumonia. Both randomized controlled trials and observational studies were included. Results: Early administration of corticosteroids, particularly within 24–36 h of hospital admission, was associated with improved clinical outcomes, including faster fever resolution, shorter hospital stay, and enhanced radiological recovery. High-dose regimens (≥5 mg/kg/day) or pulse therapy appeared effective in severe or refractory cases, while inhaled corticosteroids showed benefit in milder forms. Predictive factors for corticosteroid response included elevated C-reactive protein, lactate dehydrogenase, and ferritin levels. The overall safety profile was acceptable, with minimal adverse effects reported in most studies. Conclusions: Corticosteroids may play a beneficial role as adjunctive therapy in pediatric Mycoplasma pneumoniae pneumonia, especially in selected cases. However, further high-quality studies are required to define optimal timing, dosage, and patient selection. Full article

Background: Bilateral optic neuritis is a rare condition generally associated with inflammatory, demyelinating, or toxic causes. Its association with glyphosate exposure has rarely been documented. Case Presentation: A 66-year-old man with hypertension, hypercholesterolemia, and hypothyroidism developed rapid bilateral vision loss within hours after acute inhalational exposure to glyphosate during agricultural work. MRI showed bilateral optic nerve hyperintensity consistent with optic neuritis. Cerebrospinal fluid and serum anti-NMO antibody tests were negative, while visual evoked potentials demonstrated increased latencies. High-dose corticosteroid therapy led to progressive clinical improvement. At follow-up, MRI revealed no new lesions and the patient experienced near-complete visual recovery. Conclusion: This case suggests a possible link between acute glyphosate exposure and reversible bilateral optic neuritis. Early recognition and corticosteroid therapy may support full functional recovery even in severe presentations. Full article

Background/Objectives: Clinical remission (CR) is an ambitious and attainable treatment goal for asthma; however, CR definitions vary. Evidence of CR in Japanese patients with moderate-to-severe asthma on inhaled therapies is lacking and was evaluated based on three guideline definitions: the United States Workgroup consensus statement, Japanese Guidelines for adult asthma (JGL), and Practical Guidelines for Asthma Management (PGAM). Methods: Post hoc analysis of Phase III studies including Japanese participants: Japanese subpopulation of CAPTAIN (NCT02924688) and a 52-week Japanese long-term safety study (NCT03184987). CAPTAIN randomized participants to once-daily fluticasone furoate/vilanterol (FF/VI) regimens ± umeclidinium (UMEC). The long-term safety study allocated participants to once-daily FF/UMEC/VI based on asthma control status. All three CR definitions assessed systemic corticosteroid use, severe exacerbations, and asthma control (Asthma Control Questionnaire-5 <1.5 [Workgroup] or ≤0.75 [JGL/PGAM]); Workgroup and JGL also assessed lung function (change from baseline in trough forced expiratory volume in 1 s of ≥0 [stabilized] or ≥100 mL [optimized]). Results: CR attainability varied on definition and thresholds used. At Week 24 in the CAPTAIN Japanese subpopulation, 34–59% and 18–45% of participants (Workgroup; stabilized and optimized), and 21–34% and 8–24% (JGL; stabilized and optimized) met CR criteria across treatment arms. At Week 52 in the long-term safety study, equivalent figures for CR achievement were 33–60%, 22–45%, 11–28%, and 11–23%. Conclusions: This analysis demonstrates that CR, using different definitions and criteria, is an attainable treatment goal with inhaled therapy in Japanese patients with moderate-to-severe asthma not yet eligible for biologics. Full article

Background: Impedance pneumography (IP) is a non-invasive technique for assessing tidal breathing in young children and enables home-based recordings without active patient cooperation. By deriving tidal breathing flow–volume (TBFV) curves and indices such as the expiratory variability index (EVI), IP has been proposed as a tool for identifying obstructive breathing patterns and monitoring airway function in early childhood. However, its clinical role in asthma and wheezing disorders has not been systematically evaluated. This review aimed to assess the evidence of IP in differentiating healthy children from those with asthma or recurrent wheeze, in reflecting treatment-related changes or acute bronchial obstruction, and in relation to other lung function tests. Methods: A systematic literature search of PubMed, Medline, Embase, and the Cochrane Library databases was conducted on 5 January 2026. Original studies using IP in children aged 0–7 years with asthma or wheeze were eligible. Study selection followed PRISMA guidelines, and risk of bias (RoB) was assessed using the Newcastle–Ottawa Scale (NOS). Due to substantial heterogeneity in study design, populations, and outcome measures, results were synthesized narratively. Results: Five studies were included, with a total of 376 participants aged 0.5–7.0 years. Three studies reported significantly lower EVI values and TBFV profile variation in children with asthma or recurrent wheeze compared with healthy controls. Two studies found an association between EVI and markers of airway obstruction. Changes in IP measures following inhaled corticosteroid treatment or medication withdrawal were reported, suggesting sensitivity to treatment-related changes. However, study quality was moderate to low, with small sample sizes, heterogeneous outcome definitions, and limited diagnostic validation. Conclusions: Current evidence suggests that IP-derived indices, particularly EVI, capture clinically relevant features of obstructive breathing patterns in young children and may be useful for longitudinal monitoring of airway function. However, evidence supporting a diagnostic role for IP in childhood asthma remains limited. Larger, independent, and methodologically robust studies are needed before IP can be integrated into routine clinical practice. Full article