Search Results (97)

Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infections (ALRIs) in young children, especially bronchiolitis, with significant global health and economic impact. Increasing evidence links early-life RSV infection to long-term respiratory complications, notably recurrent wheezing and asthma. This narrative review examines these associations, emphasizing predictive factors and emerging biomarkers for risk stratification. Early RSV infection can trigger persistent airway inflammation and immune dysregulation, increasing the likelihood of chronic respiratory outcomes. Risk factors include severity of the initial infection, age at exposure, genetic susceptibility, prematurity, air pollution, and tobacco smoke. Biomarkers such as cytokines and chemokines are showing promise in identifying children at higher risk, potentially guiding early interventions. RSV-related bronchiolitis may also induce airway remodeling and promote Th2/Th17-skewed immune responses, mechanisms closely linked to asthma development. Advances in molecular profiling are shedding light on these pathways, suggesting novel targets for early therapeutic strategies. Furthermore, passive immunization and maternal vaccination offer promising approaches to reducing both acute and long-term RSV-related morbidity. A deeper understanding of RSV’s prolonged impact is essential to develop targeted prevention, enhance risk prediction, and improve long-term respiratory health in children. Future studies should aim to validate biomarkers and refine immunoprophylactic strategies. Full article

Human metapneumovirus (hMPV), a member of the Pneumoviridae subfamily, has emerged as a significant etiological agent of acute respiratory tract infections across diverse age groups, particularly affecting infants, the elderly, and immunocompromised individuals. Since its initial identification in 2001, hMPV has been recognized globally for its seasonal circulation pattern, predominantly in late winter and spring. hMPV is a leading etiological agent, accounting for approximately 5% to 10% of hospitalizations among pediatric patients with acute respiratory tract infections. hMPV infection can result in severe bronchiolitis and pneumonia, particularly in young children, with clinical manifestations often indistinguishable from those caused by human RSV. Primary hMPV infection typically occurs during early childhood; however, re-infections are frequent and may occur throughout an individual’s lifetime. hMPV is an enveloped, negative-sense RNA virus transmitted through respiratory droplets and aerosols, with a 3–5-day incubation period. The host immune response is marked by elevated pro-inflammatory cytokines, which contribute to disease severity. Advances in molecular diagnostics, particularly reverse transcription–quantitative polymerase chain reaction (RT-qPCR) and metagenomic next-generation sequencing (mNGS), have improved detection accuracy and efficiency. Despite these advancements, treatment remains largely supportive, as no specific antiviral therapy has yet been approved. Promising developments in vaccine research, including mRNA-based candidates, are currently undergoing clinical evaluation. This review synthesizes current knowledge on hMPV, highlighting its virological, epidemiological, and clinical characteristics, along with diagnostic advancements and emerging therapeutic strategies, while underscoring the critical role of continued research and sustained preventive measures—including vaccines, monoclonal antibodies, and non-pharmaceutical interventions—in mitigating the global burden of hMPV-related disease. Full article

Respiratory syncytial virus (RSV) continues as the major cause of acute lower respiratory tract infections in children around the world, and its substantial morbidity, particularly among infants and high-risk children, poses a significant burden on healthcare systems worldwide. RSV infections occur as a spectrum, ranging from mild upper respiratory symptoms to severe bronchiolitis and pneumonia, and the number of infections shows seasonal variations in different latitudes, as well as lasting impacts, reflecting the COVID-19 pandemic. The pathogenesis of the virus involves epithelial cell invasion and/or fusion to form syncytia, along with exaggerated immune-mediated responses. Disease severity is known to depend on viral load, strain variation, and host immune immaturity. Severe RSV infection during infancy is notably linked with long-term respiratory sequelae such as recurrent wheezing and asthma. Diagnosis is based on clinical suspicion and laboratory confirmation using rapid antigen testing or nucleic acid amplification tests, namely PCR. Non-pharmaceutical interventions, maternal vaccination, and prophylaxis with monoclonal antibodies, e.g., palivizumab and nirsevimab, a newly introduced long-acting agent, are efficient protective and preventive measures. Treatment is still, for the most part, supportive in nature and focuses on oxygen supplementation, hydration, and respiratory support for patients with more severe disease courses; however, the development of immunoprophylaxis and vaccine candidates shows promise for reducing the global burden of RSV. Full article

Parainfluenza virus (PIV) infections contribute to the overall childhood morbidity from acute respiratory illness, yet virus-specific epidemiologic data are lacking across many regions globally. Here, we describe the clinical manifestations, seasonality, and meteorologic associations with PIV infections in Ecuadorian children. Between July 2018 and July 2023, we documented demographic and clinical information from children younger than 5 years seen in a single public health clinic with signs and symptoms consistent with an acute respiratory infection. Nasopharyngeal swabs collected at study enrollment underwent multiplex polymerase chain reaction-based diagnostic testing (Biofire FilmArray v. 1.7™). Regional meteorological data from the same period were provided by Ecuador’s Instituto Nacional de Meteorologia e Hidrologia. Parainfluenza viruses were detected in 9% of the 1251 enrolled subjects. PIVs were most frequently detected between March and July, with no change in seasonality following SARS-CoV-2 pandemic onset. Clinical manifestations of PIV infections included non-specific upper respiratory illness (82%), laryngotracheitis (3%), and bronchiolitis (11%). Events of PIV detection were negatively associated with ambient temperature and rainfall. Our findings highlight the contribution that PIVs play in the morbidity associated with pediatric medically attended outpatient respiratory tract infection and provide new insights into the seasonal epidemiology of PIV infections in coastal Ecuador. Full article

Respiratory syncytial virus (RSV) and rhinovirus (RV)—the two primary causative viruses of bronchiolitis in children—have been studied extensively in terms of their associations with disease severity and serious late disease outcomes. In this study, we explored the differences in the clinical values of IFN-γ and IL-10 serum levels in RSV and RV bronchiolitis in the Bulgarian childhood population. Eighty-eight children with acute bronchiolitis, aged two months to two years, who were admitted to the General Pediatrics Clinic of University Hospital “Prof. St. Kirkovich”, Stara Zagora, Bulgaria served as this study’s subjects. The degree of wheezing and respiratory failure were classified. Naso-pharyngeal swabs were collected from all participants, and molecular identification of viruses was performed using real-time PCR. Serum samples were used to determine IFN-γ and IL-10 quantities using ELISA kits, and data are presented as the median IQR (25–75%). The total serum IL-10 levels were significantly enhanced in RSV-infected children compared to those infected with RV (14.4 (12.2–24.0) vs. 8.9 (7.2–12.5); p < 0.001) and the other viral bronchiolitis groups (14.4 (12.2–24.0) vs. 6.65 (3.9–15.3); p = 0.003). The highest IL-10 levels (14.4 (12.8–27.9)) were found in RSV-positive patients with first-degree respiratory failure. Almost identical serum IFN-γ levels were determined for RSV- and RV-positive bronchiolitis patients (3.2 (1.6–6.8) and 2.8 (1.1–7.3); p = 0.781). Variance analysis of IL-10 serum levels revealed statistically significant differences among the patient groups depending on the type of viral infection, concerning respiratory failure (p = 0.005) and wheezing severity (p = 0.017). Our findings show that the IL-10 levels and the type of virus have a combined effect on disease severity. These data might contribute to patients’ personalized/individualized therapy and the prevention of recurrent wheezing later in life. Full article

Background/Objectives: Human parainfluenza virus type 1 (hPIV-1) is a major cause of serious respiratory diseases in young children. Annually, hPIV-1 results in approximately 10,000 hospitalizations in the United States due to croup, bronchiolitis, and/or pneumonia, and 10,000 deaths worldwide due to acute lower respiratory tract infections among children less than 5 years of age. Despite the burden of disease, no vaccine for hPIV-1 is currently approved. Sendai virus (SeV) is a murine PIV-1. It has structural similarities with hPIV-1 and is currently under clinical development as an hPIV-1 Jennerian vaccine. Attributes of SeV include the following: (a) needleless delivery, (b) rapid and durable serum antibody responses after a single intranasal administration, (c) durable IgG and IgA responses in the nasal mucosa, and (d) use as a platform for recombinant vaccines against multiple pediatric pathogens. Evaluation of the tolerability, safety, and immunogenicity of intranasal SeV in healthy adults and seropositive children 3 to 6 years of age was previously conducted and supported vaccine advancement to evaluation in younger children. Methods: Three seropositive children 1 to 2 years of age received a single intranasal dose of 5 × 10⁵ EID₅₀ SeV (SENDAI, Clinicaltrials.gov NCT00186927). Adverse events were collected for 28 days post-vaccine administration using diary cards and participants were followed for six months in total. Sera were collected longitudinally for clinical laboratory and virus-specific antibody tests. Nasal swabs were collected longitudinally for virus and mucosal antibody tests. Results: Intranasal SeV was well tolerated, with only mild grade 1–2 events that resolved spontaneously. No serious adverse events, medically attended adverse events, or adverse events causing protocol termination were reported. One participant had positive nasal swabs for inoculated SeV during the first week after vaccination. Although children had measurable PIV-1-specific serum antibodies at baseline, intranasal SeV vaccination resulted in significant serum antibody increases in all participants. Similarly, there were significant increases in PIV-1-specific nasal IgG and IgA levels in all participants. Elevated antibody levels persisted through the six months of follow-up. Conclusions: Intranasal SeV was well tolerated and uniformly immunogenic in seropositive children 1 to 2 years of age. Results encourage the further evaluation of SeV and SeV-based recombinants as potential intranasal vaccines for the prevention of infection by hPIV-1 and other serious respiratory pathogens. Full article

Interstitial lung diseases (ILD) represent a diverse group of disorders that primarily affect the pulmonary interstitium and, less commonly, involve the alveolar and vascular epithelium. Overlapping clinical, radiological and histopathological features make proper classification difficult, requiring multiple complementary methodologies, including flow cytometry of bronchoalveolar lavages (BAL). This retrospective study analyzed BAL flow cytometry data from 1074 real-life patients, quantifying alveolar macrophages, CD4/CD8 lymphocytes, neutrophils, eosinophils, and CD1a+ Langerhans cells, with the aim of evaluating its diagnostic utility in ILD and pulmonary infection. Clustering and logistic regression analyses identified seven distinct leukocyte profiles: lymphocytic (associated with hypersensitivity pneumonitis, cryptogenic organizing pneumonia, and lymphocytic interstitial pneumonia), sarcoidosis, macrophagic (including nonspecific interstitial pneumonia, desquamative interstitial pneumonitis, pneumoconiosis, and unclassifiable ILD), neutrophilic (including usual interstitial pneumonia, respiratory bronchiolitis ILD, and acute interstitial pneumonia), infectious diseases, eosinophilic ILD, and Langerhans cell histiocytosis. The estimated leukocyte profiles were associated with different overall survival (OS) outcomes. Neutrophilic profiles, both infectious and non-infectious, correlated with poorer OS, particularly in patients without pulmonary fibrosis. Furthermore, corticosteroids and other immunosuppressive therapies did not show significant OS differences across leukocyte profiles. Although the gold standard in BAL cytology continues to be cytopathology, these results support BAL flow cytometry as a rapid and reliable complementary tool to aid in the classification of interstitial lung diseases based on immune cell profiles, providing valuable predictive information and contributing to personalized therapeutic approaches. Full article

Background: Lower airway diseases in children are one of the major causes of hospitalisation. This study aimed to evaluate the characteristics of children admitted to a tertiary pediatric hospital diagnosed with lower airway disease and to identify differences between age groups and the two years of the study. Methods: In this single-centre retrospective observational study, demographic and clinical information about children hospitalised in the emergency pediatric ward and diagnosed with lower respiratory disease from 1 June 2021 to 30 June 2023 were retrospectively reviewed. Results: A total of 410 episodes of hospitalisation for lower airway diseases were registered. In 83.9% of cases, the patient needed hospitalisation for respiratory failure, and children <1 year of age were at higher risk. Rhinovirus and respiratory syncytial virus (RSV) were the leading causes of lower respiratory tract infections. No death has been recorded. In 8.8% of cases, the patient was admitted to the Pediatric Intensive Care Unit. In 2021–2022, we recorded more hospitalisations for bronchiolitis with RSV as the primary pathogen detected and more patients were admitted to the hospital for respiratory failure. In 2022–2023, we registered more admissions for bacterial pneumonia and the need for intravenous therapy. Conclusions: Lower respiratory tract diseases are frequent in the pediatric population, and the risk of respiratory failure is higher. Analysing the differences between the two years of study, we underline how the COVID-19 pandemic has changed the epidemiology of acute respiratory infections in children. Full article

Background: SARS-CoV-2 infection is generally associated with less severe forms of disease in children, where most cases only require symptomatic treatment. However, there is a paucity of information regarding the impact and clinical course of COVID-19 in neonate patients. This study aimed to analyze the epidemiological and clinical aspects of COVID-19 in this particular age group who were patients treated in our department. Materials and methods: This is a retrospective observational study that includes neonates (aged less than 1 month) who were diagnosed with COVID-19. The patients were admitted between 1 January 2022 and 31 December 2023, to the Infectious Diseases Pediatric Department of the Hospital Clinic of Pneumophthisiology and Infectious Diseases in Brașov, Romania. All the patients were tested for SARS-CoV-2 infection at admission, using either a real-time PCR (RT-PCR) or rapid antigen testing, according to the national COVID-19 protocol in use at the time. We collected the following data: demographic data, clinical picture and laboratory values at presentation, clinical course, complications, and other significant data. All the data were extracted from existing hospital administrative databases or electronic medical records. Results: Nine neonates were hospitalized with COVID-19, of which five were boys, and four were girls; the mean age was 18.89 days (ranging between 6 and 28 days). The clinical picture at admission mainly consisted of fever (eight cases) and nasal obstruction and cough (five cases each). Only one patient required oxygen support. Co-infections with Streptococcus pneumoniae and Haemophilus influenzae (one case), respiratory syncytial virus (RSV, one case), and rotavirus (one case) were identified. Complications were represented by acute bronchiolitis in three patients. Biologically, lymphopenia was found in three cases, monocytosis in five cases, and increased ferritin values in five cases. The clinical outcome was favorable in all the cases. The patients were discharged in improved condition after an average stay of 5.11 days (ranging between 3 and 10 days). Conclusions: Our data support the observation that infection with SARS-CoV-2 in neonates is a relatively benign condition with a good prognosis. Our study has several limitations and establishes a foundation for future studies on a larger sample of term and premature neonates with different comorbidities. Full article

The aim of our research was to evaluate and analyze serum 25(OH) vitamin D and parathyroid hormone (PTH) levels to investigate whether vitamin D deficiency serves as a risk factor for an increased incidence of acute respiratory infections (ARI) in children. Serum PTH levels were used as an indicator of vitamin D sufficiency, as normal PTH levels require an optimal concentration of 25(OH) vitamin D. The study included 129 children, divided into five subgroups: children with acute bronchopneumonia (n = 42), acute laryngotracheitis (n = 7), acute bronchiolitis (n = 32), acute bronchitis (n = 18), and a control group (n = 30). No statistically significant differences in 25(OH)D levels were observed between the overall population of children with ARI and the control group (p = 0.073). However, significant differences in 25(OH)D levels were identified between the control group and children with bronchopneumonia, acute bronchitis, and laryngotracheitis (p < 0.01, p < 0.05). Regarding PTH levels, statistical significance was found between the control group and the acute bronchiolitis group, due to the high percentage of children with hypervitaminosis in this subgroup. These results highlight the crucial role of vitamin D in the onset and progression of acute respiratory tract infections in children, emphasizing its impact on their overall respiratory health. Full article

Background: The respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants and is associated with an increased risk of asthma development. Palivizumab, an RSV prophylactic, reduces RSV-related hospitalizations in high-risk infants, but its impact on long-term asthma outcomes remains unclear. This study compares asthma-related healthcare utilization in preschool children born prematurely between those who received Palivizumab (the Prophylaxis (+) group) and those who did not (the Prophylaxis (–) group). Methods: This nationwide, population-based retrospective cohort study utilized data from Clalit Healthcare Services in Israel. The study included children born between 32 + 6 and 34 + 6 weeks of gestational age from 2011 to 2018. Descriptive analysis, univariate analysis, and multivariate logistic regression were performed to compare the Prophylaxis (+) and the Prophylaxis (–) groups. Results: In total, 4503 children were included, with 3287 in the Prophylaxis (+) group and 1216 in the Prophylaxis (–) group. Palivizumab administration was associated with reduced hospitalizations for RSV bronchiolitis (1.8% vs. 3.3%, p = 0.003). However, no significant differences were observed in multivariate analysis for long-term asthma outcomes, including asthma diagnosis (OR = 1.04, CI = 0.84–1.30, p = 0.7) or emergency department visits for asthma (OR = 0.79, CI = 0.54–1.17, p = 0.2). Similarly, Palivizumab administration was not associated with the purchase of short-acting beta-agonists (OR = 1.14, 95% CI 0.98–1.32, p = 0.084), inhaled corticosteroids (OR = 1.1, CI = 0.93–1.32, p = 0.3), or oral corticosteroids (OR = 1.09, CI = 0.94–1.26, p = 0.3). Conclusions: While Palivizumab effectively reduces RSV acute bronchiolitis in preterm infants, it does not significantly impact long-term preschool asthma-related healthcare utilization. Full article

Background: Acute viral respiratory tract infections constitute a significant challenge in pediatric healthcare globally, with rhinovirus representing one of the primary etiological agents. In this context, we conducted a study with the objective of identifying the clinical characteristics and outcomes of rhinovirus infection in comparison with other respiratory viruses in children hospitalized in one of the largest pediatric hospitals in the capital of Romania. Methods: We conducted a retrospective study among children hospitalized for influenza-like illness symptoms and who were tested by multiplex RT-PCR with a nasopharyngeal swab between May 2020 and December 2021. Results: A total of 496 children were eligible for inclusion in the study, and the positivity rate for at least one virus was 58.5%. The rhinovirus was identified in 138 patients (median age 12.5 months), representing 27.8% of all children tested and 49.3% of all positive samples. Although the clinical features of children with rhinovirus were dominated by cough (63.7%) and dyspnea (51.6%), no symptoms were identified that were strongly associated with rhinovirus infection in comparison to other respiratory viruses. The probability of receiving an antibiotic prescription was 1.92 times lower (p = 0.011) in children who tested positive for rhinovirus compared to children with negative RT-PCR results. The incidence of acute bronchiolitis or acute bronchitis, acute respiratory failure, and acute otitis media was higher among rhinovirus-positive children than among those who tested negative via RT-PCR. However, the incidence of these conditions was similar among children who tested positive for other respiratory viruses. Conclusions: Rhinovirus was the most prevalent virus identified in children hospitalized with influenza-like illness symptoms. The utilization of multiplex RT-PCR molecular tests is instrumental in elucidating etiology with precision and implementation of these advanced diagnostic methods, which can bring significant benefits in practice. A positive result for rhinovirus helps to reduce the unnecessary administration of antibiotics and optimizes patient management, thus decreasing the risk of severe complications such as acute respiratory failure and acute otitis media. Full article

(1) Background: Helmet Continuous Positive Airway Pressure (H-CPAP) has primarily been used in intensive care settings to treat moderate-to-severe bronchiolitis in infants. We aim to report on the feasibility of H-CPAP for selected infants with bronchiolitis in a pediatric ward. (2) Methods: A retrospective, observational, consecutive case series was studied of 26 patients who received H-CPAP on the pediatric ward from October 2022 to February 2023, including a description of patient outcomes and costs. (3) Results: Of 130 infants with bronchiolitis admitted to Bambino Gesù Hospital in Rome, 34 were hospitalized for moderate to severe bronchiolitis, and 26 began H-CPAP on the ward. Among the 26 pediatric patients who received H-CPAP on the ward, 4 out of 26 (15%) required transfer to the PICU within the first hours of care due to clinical deterioration. No problems with the H-CPAP interface or side effects attributable to H-CPAP were reported. Pharmacological sedation with a single dose of dexmedetomidine was required for 15/26 patients (57%) following failure of non-pharmacological anxiety reduction strategies. After introducing H-CPAP in our pediatric ward, we achieved total cost savings of approximately EUR 147,120. (4) Conclusions: Treatment with H-CPAP for infants with bronchiolitis may be feasible in non-intensive care settings with trained staff, appropriate monitoring, and rapid access to pediatric intensive care. Full article

Background: Identifying mediators between obesity-related traits and lower respiratory tract infections (LRTIs) would inform preventive and therapeutic strategies to reduce the burden of LRITs. We aimed to recognize whether lung function and inflammatory factors mediate their associations. Methods: We conducted a two-step, two-sample Mendelian randomization (MR) analysis. Two-sample MR was performed on (1) obesity-related traits (i.e., body mass index [BMI], waist circumference [WC], and waist-to-hip ratio [WHR]) and LRTIs (i.e., acute bronchitis, acute bronchiolitis, bronchiectasis, influenza, and pneumonia), (2) obesity-related traits and potential mediators, and (3) potential mediators and LRTIs. Next, two-step MR was applied to infer whether the mediation effects exist. Results: We found that C-reactive protein (CRP), interleukin-6 (IL-6), and forced expiratory volume in the first second (FEV1) mediated 32.59% (95% CI: 17.90%, 47.27%), 7.96% (95% CI: 1.79%, 14.14%), and 4.04% (95% CI: 0.34%, 7.74%) of the effect of BMI on pneumonia, and they mediated 26.90% (95% CI: 13.98%, 39.83%), 10.23% (95% CI: 2.72%, 17.73%), and 4.67% (95% CI: 0.25%, 9.09%) of the effect of WC on pneumonia, respectively. Additionally, CRP, forced vital capacity (FVC), and FEV1 mediated 18.66% (95% CI: 8.70%, 28.62%), 8.72% (95% CI: 1.86%, 15.58%), and 8.41% (95% CI: 2.77%, 14.06%) of the effect of BMI on acute bronchitis, and they mediated 19.96% (95% CI: 7.44%, 32.48%), 12.19% (95% CI: 2.00%, 22.39%), and 12.61% (95% CI: 2.94%, 22.29%) of the effect of WC on acute bronchitis, respectively. Conclusions: Health interventions linked to reducing inflammation and maintaining normal lung function could help mitigate the risk of obesity-related LRTIs. Full article

Respiratory viral infections pose a significant public health threat, particularly in children and older adults, with high mortality rates. Some of these pathogens are the human respiratory syncytial virus (hRSV), severe acute respiratory coronavirus-2 (SARS-CoV-2), influenza viruses (IV), human parvovirus B19 (B19V), and human bocavirus 1 (HBoV1). These viruses cause various respiratory symptoms, including cough, fever, bronchiolitis, and pneumonia. Notably, these viruses can also impact the central nervous system (CNS), leading to acute manifestations such as seizures, encephalopathies, encephalitis, neurological sequelae, and long-term complications. The precise mechanisms by which these viruses affect the CNS are not fully understood. Glial cells, specifically microglia and astrocytes within the CNS, play pivotal roles in maintaining brain homeostasis and regulating immune responses. Exploring how these cells interact with viral pathogens, such as hRSV, SARS-CoV-2, IVs, B19V, and HBoV1, offers crucial insights into the significant impact of respiratory viruses on the CNS. This review article examines hRSV, SARS-CoV-2, IV, B19V, and HBoV1 interactions with microglia and astrocytes, shedding light on potential neurological consequences. Full article