Search Results (181)

Measurement of nitric oxide (NO) concentration in exhaled breath (FeNO) is a quantitative, non-invasive, simple, and safe method for assessing airway inflammation. It serves as a complementary tool to other methods for evaluating airway diseases. However, little is known about the typical NO levels in healthy individuals, including individual differences and the influence of measurement timing. Therefore, this study classified measurement times into four periods and statistically analyzed NO levels in healthy individuals. The mean values among groups were compared using repeated measures ANOVA on six participants. The analysis showed large individual variations in NO levels, resulting in no significant difference (p = 0.29). Notably, greater fluctuations were observed in the morning. These findings align with previous studies suggesting the influence of circadian rhythms and the redundancy of repeated measurements. This study highlights the need to consider timing and individual variability when using FeNO as a physiological marker in healthy populations. Full article

Asthma represents a heterogeneous disorder characterized by a dynamic balance between pro-inflammatory and anti-inflammatory forces, with allergic sensitization contributing substantially to airway hyperresponsiveness and remodeling. Central to its pathogenesis are cytokines such as IL-4, IL-5, IL-13, IL-17, and IL-33, which drive recruitment of eosinophils, neutrophils, and other effector cells, thereby precipitating episodic exacerbations in response to viral and environmental triggers. Conventional biomarkers, including blood and sputum eosinophil counts, IgE levels, and fractional exhaled nitric oxide, facilitate phenotypic classification and guide the emerging biologic era. Monoclonal antibodies targeting IgE (omalizumab) and IL-5 (mepolizumab, benralizumab, reslizumab, depemokimab) have demonstrated the ability to reduce exacerbation frequency and improve lung function, with newer agents such as depemokimab offering extended dosing intervals. Itepekimab, an anti-IL-33 antibody, effectively engages its target and mitigates tissue eosinophilia, while CM310-stapokibart, tralokinumab, and lebrikizumab inhibit IL-4/IL-13 signaling with variable efficacy depending on patient biomarkers. Comparative analyses of these biologics, encompassing affinity, dosing regimens, and trial outcomes, underscore the imperative of personalized therapy to optimize disease control in severe asthma. Full article

Asthma is a highly heterogeneous respiratory disease that, in its severe forms, is characterized by persistent symptoms, frequent exacerbations, and a significant impact on patients’ quality of life. Despite high-dose inhaled corticosteroids and long-acting bronchodilators, a subset of patients remains uncontrolled, necessitating advanced therapeutic strategies. The advent of biologic therapies has revolutionized the management of severe asthma, offering targeted interventions based on the underlying inflammatory endotypes, primarily T2-high and T2-low. However, selecting the most appropriate biologic remains challenging due to overlapping phenotypic features and the limited availability of validated biomarkers. This narrative review explores the clinical utility of key biomarkers, including blood eosinophils, fractional exhaled nitric oxide (FeNO), periostin, and total and specific IgE, in guiding biologic therapy. All the information provided is based on an extensive literature search conducted on PubMed. We also examine the clinical characteristics and comorbidities that influence therapeutic choices. Furthermore, we present a practical decision-making platform, including a clinical table matching phenotypes with biologic agents, such as omalizumab, mepolizumab, benralizumab, dupilumab, and tezepelumab. By integrating biomarker analysis with clinical assessment, based on current guidelines and our extensive real-life experience, we aim to offer a logical framework to help clinicians select the most suitable biologic treatment for patients with uncontrolled severe asthma. Future research should focus on identifying novel biomarkers, refining patient stratification, and evaluating long-term outcomes to further advance precision medicine in the management of severe asthma. Full article

Background/Objectives: Vitamin D is known to decrease the risk of contracting respiratory infections and developing exacerbations for children with asthma. This research evaluates the alterations in serum vitamin D concentrations and examines lung function in children with asthma, as indicated by clinical symptoms and paraclinical results, after experiencing SARS-CoV-2 infection or other acute respiratory infections. Material and Method: This retrospective study included 145 children with asthma. For each patient, the following variables were acquired: demographic data, serum vitamin D levels, GINA asthma control levels, the fraction of exhaled nitric oxide (FeNO), pulmonary function tests parameters, data related to allergies, and the presence of exacerbations. Children were divided into two groups, according to the presence or absence of SARS-CoV-2 infection or other acute respiratory infections. Variables were statistically processed in SPSS. Results: In total, 93 children with asthma with SARS-CoV-2 infection or other acute respiratory infections and 52 children with asthma without SARS-CoV-2 infection or other acute respiratory infections were included in the study. Median serum vitamin D values were statistically significantly lower in children with a variable airflow limitation, compared to children with normal values (p = 0.004), as well as for children with partially controlled asthma, relative to children with well controlled asthma (p < 0.0005). Similarly, children with acute respiratory infections/COVID-19 disease had lower median values of serum vitamin D, compared to children without acute respiratory infections/COVID-19 disease (p < 0.0005). A decrease in serum vitamin D value was statistically significantly associated with an increase in FeNO value for children with asthma with COVID-19 disease (p = 0.027), as well as for the entire study group (p < 0.0005). Conclusions: Children with asthma who had acute respiratory infections, including COVID-19 disease, showed considerably reduced serum vitamin D levels and were linked to more significant airflow limitation, reduced asthma control and elevated airway inflammation, suggesting its potential role in influencing asthma severity and infection response. Full article

Asthma is among the most common chronic respiratory diseases, affecting approximately 3340 individuals per 100,000 worldwide. It is a heterogeneous condition associated with airway hyperresponsiveness and chronic inflammation. Severe asthma (SA) affects 3–10% of patients, most of whom exhibit Type 2 (T2) inflammation with elevated eosinophil counts or increased fractional exhaled nitric oxide. Although the Global Initiative for Asthma provides detailed guidelines for SA, patients with marked hypereosinophilia (HE; >1500 cells/µL) who do not meet diagnostic criteria for hypereosinophilic syndrome (HES) or eosinophilic granulomatosis with polyangiitis (EGPA) remain insufficiently addressed. In such cases, oral corticosteroids, and T2-targeted monoclonal antibodies (MAbs) inhibiting interleukin-5 or its receptor are the main therapeutic options. For instance, mepolizumab is approved for EGPA, HES, and chronic rhinosinusitis with nasal polyps, but its use in hypereosinophilic SA is limited by eligibility, tolerance, or effectiveness. SA with HE not classified as HES or EGPA is exceptionally rare and may be diagnosed by the exclusion of other potential causes of HE. This review analyzes recent studies and case reports, aiming to expand the understanding of this underrecognized clinical entity, its relation to T2 inflammation and eosinophilic disorders, and to highlight the need for improved diagnostic and therapeutic strategies. Full article

The burden of chronic obstructive pulmonary disease (COPD) is increasing, especially for women in low-to-middle income countries. Biomarkers provide ever-increasing diagnostic precision for COPD and show promise for primary, secondary, and tertiary disease prevention. This review describes emerging applications for biomarkers in COPD, especially as they align with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) emphasis on prevention, early diagnosis, and response to therapy. These biomarkers include blood eosinophils; IgE; C-reactive protein; fibrinogen; procalcitonin; interleukins 6, 8, and 33; tumor necrosis factor alpha; and soluble receptor for advanced glycated products (sRAGE). They have been used in various ways to identify COPD endotypes, predict exacerbations, predict mortality, and monitor the response to therapy. The fraction of exhaled nitric oxide (FENO) is increasingly studied in eosinophilic COPD endotypes and can be a diagnostic and predictive non-invasive biomarker. Imaging biomarkers, especially the quantitative computerized tomography (QCT) assessment of airway remolding, functional small airway disease, air trapping, lung function, and volume surrogates, all serve as non-invasive biomarkers for screening, early detection, and disease progression. Biomarkers facilitate all the phases of COPD care from detecting early airflow obstruction to predicting exacerbation and mortality. Biomarkers will be increasingly used as precise diagnostic tools to improve the COPD outcomes. The aim of this narrative review is to summarize the recent investigations in COPD biomarkers and their clinical applications. Full article

Background/Objectives: Management of complex congenital heart defects with functionally single ventricle remains one of the greatest challenges of pediatric cardiology. The multistage surgical treatment completed with Fontan procedure is related to multiple complications. Due to non-pulsatile continuous pulmonary flow and chronic hypoxia, Fontan circulation may induce pulmonary endothelial dysfunction. However, the impact of Fontan physiology on respiratory system function is not well studied. The aim of the research was to assess respiratory function in Fontan pediatric patients with hypoplastic left heart syndrome (HLHS) and other morphologies of functionally single ventricle. The article presents the preliminary results drawn from the pilot study, focusing on Fontan patients, without a healthy children control group. Methods: A cross-sectional study involved Fontan patients hospitalized in the Pediatric Cardiology Clinic of the Medical University of Silesia in Katowice between August 2023 and November 2024. The exclusion criteria were lack of parental and/or patient’s consent, age < 6 years old, decompensated heart failure, asthma, atopy, respiratory infection within two weeks before the hospitalization, or significant psychomotor disability. Respiratory function assessment involved spirometry and fractional exhaled nitric oxide (FeNO) measurement. Results: A total of 32 patients who met inclusion criteria performed respiratory measurements. The mean age was 12.9 years old; there were 12 females. A total of 12 patients had HLHS and 20 patients had other morphologies of univentricular heart. FeNO values were relatively high with a mean of 30 ppb. Spirometry showed restrictive or mixed restrictive and obstructive ventilatory pattern. The mean forced vital capacity (FVC) levels were 79.2 ± 12.3% of predicted value (%pv) and forced expiratory volume in the first second (FEV1) 77.3 ± 13.8%pv. Children with HLHS presented statistically significantly lower percentages of predicted value of FEV1. There were statistically significant negative correlations between NT-proBNP concentrations and FEV1, FEV1%pv, MEF25-75 and MEF25-75%pv. Conclusions: Fontan pediatric patients present a restrictive or mixed restrictive and obstructive ventilatory pattern and relatively high FeNO levels. Patients with HLHS have worse pulmonary function than patients with other univentricular heart morphologies. This may be related to worse ventricular function in patients with HLHS. Full article

Background and objectives: Increased levels of nitric oxide (NO) are produced in various inflammatory diseases like allergic asthma. Fractional exhaled NO has been studied as a biomarker of type 2 inflammation in asthma, while the use of nasal NO (nNO) as a diagnostic tool for allergic rhinitis (AR) is less established. In the present study, we investigated nNO as a potential biomarker for differentiating AR from nonallergic rhinitis (NAR). Materials and methods: Medical students were invited to complete a questionnaire on rhinitis symptoms. Individuals who reported nasal symptoms were invited to participate in the clinical phase of the study, which included considering the patient’s medical history, clinical examination, skin-prick tests (SPTs) for the 14 most relevant allergens in the region, and nNO measurement using the NIOX VERO portable nitric oxide analyzer. Informed consent was obtained at each stage of recruitment and clinical assessment. Results: Overall, 62 out of 122 volunteers recruited reported rhinitis symptoms and were investigated further with nNO measurements and SPTs. In total, 39 had SPT-confirmed AR, while 23 were classified as NAR subjects. Both nNO measurements and SPTs were performed on the same day, during the pollen season. The comparison of mean nNO concentrations (830 ± 247 ppb and 851 ± 373 in AR and NAR groups, respectively) showed no statistically significant difference. Conclusions: we concluded that nNO is not a reliable independent biomarker in the diagnosis of AR. Full article

Background: Allergy to Alternaria alternata (Alt a), although often underdiagnosed, is a significant global health issue. In the allergen immunotherapy (AIT) field, novel therapeutic strategies are emerging, particularly with the advent of polymerized allergoids. This study aims to evaluate the efficacy of subcutaneous immunotherapy (SCIT) based on these innovative molecules in children with respiratory allergies, assessing clinical and functional parameters. Methods: We enrolled 42 patients aged between 6 and 16 years, all of whom had allergic rhinitis (AR) and concomitant asthma and all of whom were monosensitized to Alt a. Between December 2020 and December 2021, 17 patients initiated SCIT with Modigoid^® for Alt a1, while 25 patients continued with standard therapy. At the initial visit (T0), all the patients underwent nasal and bronchial evaluation, including exhaled nitric oxide (eFeNO) measurement and spirometry. The Asthma Control Test (ACT) was used to evaluate the control of asthma symptoms. Patients were followed up every 6 months, with a comprehensive re-evaluation at 24 months (T1) replicating the initial assessments. Results: After 24 months of SCIT with the new polymerized molecular allergoid Alt a1 (Modigoid^®), children showed a statistically significant reduction in eFeNO levels, improved FEV1 values, and enhanced ACT scores. Conclusions: SCIT with the new molecular allergoid Alt a1 significantly improves functional parameters (FEV1 and eFeNO) and subjective asthma symptoms (ACT scores) in children with AR and objective asthma signs. This treatment represents an effective preventive strategy that can be used to halt the progression of the classic atopic march from AR to asthma and potentially reverse the atopic march. Full article

Background: Emerging evidence suggests that nutraceuticals, alongside standard therapy, may benefit children with allergic rhinitis (AR). This study aimed to compare the efficacy of Quertal^® (Neopharmed Gentili S.p.A., Milano, Italy), a nutraceutical supplement based on Perilla frutescens, Quercetin, and vitamin D3, combined antihistamines per os versus antihistamines alone, in improving AR symptoms considering respiratory functional and laboratory biomarkers in pediatric age. Materials and Method: This study included 100 children, 50 in the case group (Quertal^® plus antihistamines) and 50 in the control group (antihistamines alone), with mild/moderate AR sensitized to grass pollens. They underwent assessments of respiratory function (rhinomanometry-AAR, spirometry), inflammation markers (Nasal Nitric Oxide [nFeNO]; exhaled Nitric Oxide [eFeNO]; nasal cytology), and laboratory assays (blood eosinophils, total IgE and specific IgE to Phl p1). Results: After three months of treatment, the case group showed statistically significant improvement in nFeNO and eFeNO values compared to controls (p < 0.001), as well as a reduction in nasal eosinophils (p < 0.001). Conclusions: Adding Quertal^® to standard antihistamine therapy may reduce nasal inflammation and improve AR symptoms in pediatric patients. This combination therapy shows promise as a practical, well-tolerated approach to managing AR and may have broader implications for enhancing long-term outcomes. Full article

Severe asthma (SA) is a chronic inflammatory condition affecting approximately 10% of asthmatic patients, and eosinophils are considered key pathogenetic actors in a significant number of patients. Biological therapies have been demonstrated to improve asthma control by decreasing exacerbation rates and reducing the use of oral corticosteroids. In this context, phenotyping and endotyping patients with SA is essential for selecting the most effective therapeutic approach. For this purpose, biomarkers such as IgE, absolute blood eosinophil count, and fractional exhaled nitric oxide (FeNO) are crucial in defining a patient’s inflammatory profile. Their integration provides a framework for classifying asthma into T2-high, T2-mild, or T2-low categories, guiding personalized treatment strategies. By incorporating multiple biomarkers into a unified model, it is possible to better stratify patients and optimize biologic therapy selection, paving the way for improved outcomes in SA management. This review aims to evaluate the role of phenotyping and endotyping SA patients, with particular attention to the impact of eosinophilic inflammation and combinatory biomarkers on decision-making processes for the selection of biological therapies. Full article

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma are mutually correlated with Type-2 inflammation. Dupilumab is effective in uncontrolled and relapsing CRSwNP. However, the precise characterization of Type-2 inflammation and the impact of previous surgery on clinical outcomes need clarification. Methods: We present a prospective observational study on a 38 CRSwNP-patient cohort, whose Type-2 endotype was confirmed after a multidisciplinary approach shared among ENTs, pneumologists and allergologists. Patients were treated with dupilumab and evaluated at 15 days and 1-3-6-12-18-24-30 months, focusing on clinical (VAS, nasal polyp score—NPS), radiological (Lund-Mackay) and quality of life (SNOT-22) parameters, as well olfactory function, asthma control, variation of Type-2 markers and number and extent (ACCESS score) of previous surgeries. Results: We confirmed the efficacy of dupilumab in total and sub-items VAS, NPS, SNOT-22 and sniffing score, as well as Lund–Mackay score improvements, observable and significant after 2 weeks of treatment (p < 0.0001) and long-lasting over 30 months. Good to excellent response criteria to biologic treatment at 6 months was observed in 30/32 patients. Comorbid asthma reached rapid control (p < 0.0001) and exhaled nitric oxide normalization was achieved. One single “not adequate” surgery showed a trend to milder improvement, as well as a higher ACCESS score to better olfactory outcome. Conclusions: The accurate selection of uncontrolled relapsing CRSwNP in terms of Type-2 endotyping by multidisciplinary approach can maximize dupilumab efficacy. The number and extent of previous surgeries may differentiate the response, although this effect is difficult to catch in real life. “Adequate” ESS surgery before dupilumab may drive mostly effective disease control. Full article

Background/Objectives: This study aimed to assess the acute effects of two isoenergetic but micronutrient-diverse meals—a Mediterranean-like meal (MdM) and a fast food-like meal (FFM)—on the autonomic nervous system (ANS), lung function, and airway inflammation response. Methods: Forty-six participants were enrolled in a randomized crossover clinical trial, consuming two isoenergetic meals: FFM (burger, fries, and sugar-sweetened drink) and MdM (vegetable soup, whole-wheat pasta, salad, olive oil, sardines, fruit, and water). Pupillometry assessed parasympathetic (MaxD, MinD, Con, ACV, MCV) and sympathetic (ADV, T75) nervous system outcomes. Lung function and airway inflammation were measured before and after each meal through spirometry and fractional exhaled nitric oxide (FeNO), respectively. Results: Mixed-effects model analysis showed that the MdM was associated with a hegemony of parasympathetic responses, with a significant increase of MaxD associated with a faster constriction velocity (ACV and MCV); on the other side, the FFM was associated with changes in the sympathetic response, showing a quicker redilation velocity (a decrease in T75). After adjusting for confounders, the mixed-effects models revealed that the FFM significantly decreased T75. Regarding lung function, a meal negatively impacted FVC (ae = −0.079, p < 0.001) and FEV1 (ae = −0.04, p = 0.017); however, FeNO increased, although after adjusting, no difference between meals was seen. Conclusions: Our study showed that the FFM counteracted the parasympathetic activity of a meal, while a meal, irrespective of the type, decreased lung function and increased airway inflammation. Full article

Exposure to traffic-related air pollution is not merely linked to respiratory health issues but also poses significant risks to cardiovascular well-being. Individuals from lower-income communities residing in high-pollution zones are particularly vulnerable to adverse cardiorespiratory health impacts. Pollutants such as fine particulate matter (PM_2.5 and PM₁₀), nitrogen dioxide (NO₂), and ozone (O₃) are recognized as a leading, yet preventable, contributor to cardiorespiratory diseases. Although research has extensively explored the short-term impact of these pollutants on respiratory health, the immediate effects on cardiovascular outcomes require further study. We explored associations of traffic-related air pollutants with airway inflammation, lung function, and cardiovascular health outcomes (metabolic syndrome [MetS]) collected from a sample of low-income participants (N = 662) from a US–Mexico border county. Airway inflammation was measured using exhaled nitric oxide tests (eNO), while lung function parameters were measured by spirometry. MetS risk factors (waist circumference, blood pressure, triglycerides, HDL, and fasting blood glucose) were also measured. While spirometry measures were negatively associated with air pollutants (p < 0.05), no associations were noted for eNO. We also found positive associations in linear and logistic models between air pollutants and obesity (BMI: p < 0.04; waist: p < 0.03), fasting blood glucose (p < 0.03), and metabolic syndrome (p < 0.04). These findings reaffirm the immediate adverse effects of air pollution on respiratory function and shed light on its broader metabolic consequences. Environmental and neighborhood conditions could potentially influence the associations with obesity. At the same time, the links between fasting glucose and metabolic syndrome might indicate underlying oxidative stress and systemic inflammation. Full article

Asthmatic children who tested positive for COVID-19 experienced changes in lung function and persistent symptoms following SARS-CoV-2 infection, even for several months after diagnosis, and with the same features as in an acute phase. This study aimed to analyze a pediatric age group (between 0 and 17 years old) diagnosed with asthma, and SARS-CoV-2 infection attending regular monitoring visits in a Pediatric Department of a Regional Tertiary Hospital (Filantropia Clinical Municipal Hospital Craiova, Romania) during the COVID-19 pandemic and post-pandemic time interval (i.e., March 2020–July 2024), and identify how the infection influenced their long-term symptoms and treatment. Materials and Methods. The following variables were recorded: demographic data (gender, age group, residence), data related to allergies (allergic rhinitis, atopic dermatitis, and food allergies), the presence of exacerbations, the fraction of exhaled nitric oxide, the ventilatory function, the asthma phenotype (allergic or non-allergic), as well as the GINA assessment of asthma control at clinical visits were analyzed. SARS-CoV-2 infections were evaluated in terms of year of infection, symptoms, cough presence and persistence, and modifications of the asthma treatment during and after COVID-19 disease. The data were statistically analyzed with SPSS, using the Mann–Whitney U, Kruskal–Wallis H, and Chi-Square tests. Results. A lower incidence of COVID-19 cases was recorded in the first pandemic of asthmatic patients (2020 and 2021), but an increase in the rate of cases was observed at the beginning of the second pandemic, in 2022. The nitric oxide values in asthmatic children who were infected with SARS-CoV-2 were statistically significantly increased (p < 0.0005), especially for children with persistent cough for more than 4 weeks. A significant increase in the number of exacerbations was also observed in patients who tested positive for SARS-CoV-2 infection (p < 0.0005). Ventilatory function values were statistically significantly different in asthmatic children with and without SARS-CoV-2 infection (p < 0.05). Conclusions. The persistence of cough after the acute phase of SARS-CoV-2 infection as well as the changes in ventilatory tests emphasize the need of periodic medical check-ups, as well as the implementation of a therapeutic regimen appropriate for each pediatric patient. Full article