Search Results (27)

Inborn errors of immunity (IEIs), also known as primary immunodeficiencies, are a group of genetic disorders affecting the development and function of the immune system. While IEIs traditionally present with recurrent infections, an increasing number of cases manifest with early-onset severe atopy, including atopic dermatitis, food allergies, asthma, and allergic rhinitis—features that are often overlooked. This can lead to delayed diagnosis and treatment, which is crucial for IEI patients due to the risk of severe infections. We conducted a literature search and reviewed all IEIs that can present with early-onset severe atopy. The hallmark features of these disorders often include early-onset, persistent, and severe atopic dermatitis, food allergies, and recurrent episodes of asthma, which may be refractory to treatments. Additionally, we discuss the importance of recognizing such severe atopy as a potential indicator of an underlying immune deficiency, particularly when accompanied by unusual infections, growth failure, or autoimmunity. This review aims to raise awareness of this association and emphasize the need for early diagnosis and genetic testing in patients with atypical or treatment-resistant allergic diseases, allowing for more timely diagnosis of underlying immunodeficiencies and appropriate treatments. Full article

Objectives: This study aims to demonstrate the role of case-level American College of Medical Genetics (ACMG) criteria, such as familial segregation and pathology data, in providing conclusive evidence for the pathogenicity of ultrarare GLA variants causing Anderson–Fabry disease when gene-level and variant-level criteria provide ambiguous or discrepant results. Case/family description: A 52-year-old woman presented with new-onset shortness of breath, chest pain, and palpitations. Echocardiography revealed mild left ventricular wall thickening (14 mm) and mild diastolic dysfunction. She was the second of three siblings born to unrelated parents, both of whom died from malignancies. Family screening identified brothers, one affected 55-year-old with hypertension and asthma and one unaffected 47-year-old. The 15-year-old son of the proband complained of exercise-induced burning feet acral pain his electrocardiogram showed a short PR interval and signs of early hypertrophy. Results: Endomyocardial biopsies of the proband and the affected sibling demonstrated substrate accumulation (globotriaosylceramide). The anti-α-galactosidase-A immunostain showed a total loss of the enzyme in the hemizygous male and a mosaic pattern in the heterozygous female. The next-generation sequencing short-read multigene panel identified the c.547+3A>G variant in the GLA gene and excluded variants in other genes; Oxford-Nanopore long-read sequencing excluded known pathogenic deep intronic variants. A Multiplex-Ligation-dependent-Probe-Amplification assay excluded copy number variations. Based on the variant-level and gene-level ACMG criteria, the variant was classified as a Variant of Uncertain Significance or Likely Benign using different bioinformatic tools. By adding case-level functional data (endomyocardial biopsy, PS3_VeryStrong) and familial data (segregation of genotype with phenotype, PP2_Moderate), the variant was classified as Likely Pathogenic/Pathogenic. Conclusion: ACMG case-level data can unambiguously resolve uncertain interpretations of GLA variants. Full article

Asthma and adolescence are two sensitive points and are difficult to manage when they coexist. The first is a chronic respiratory condition, with frequent onset in early childhood (between 3 and 5 years), which can improve or worsen with age. Adolescence is the period between childhood and adulthood (12–19 years), marked by various internal and external conflicts and a limited capacity to understand and accept any aspect that is delimited by the pattern of the social circle (of the entourage) frequented by the individual. Therefore, the clinician is faced with multiple attempts regarding the management of asthma encountered during the adolescent period, starting from the individualization of the therapy to the control of compliance (which depends equally on the adverse reactions, quality of life offered and support of the close circle) and the social integration of the subject, communication probably having a more important role in the monitoring and evolution of the condition than the preference for a certain therapeutic scheme. Current statistics draw attention to the increase in morbidity and mortality among children with bronchial asthma, an aspect demonstrated by the numerous hospitalizations recorded, due either to an escalation in the severity of this pathology or to faulty management. The purpose of this article is to review the delicate aspects in terms of controlling symptoms and maintaining a high quality of life among teenagers. Full article

Background: Nasal cytology at birth and in the pediatric age is barely investigated regarding its association with the onset of common pediatric diseases. Methods: We enrolled 241 newborns within their first 24 h of life, studying their nasal cellular composition and repeating this at 1 and 3 years of life. We collected anamneses of perinatal factors and external factors (parental smoking, passive smoking, breastfeeding), and the prevalence of otitis, rhinosinusitis, bronchitis, asthma, and allergy at all timepoints. Results: 204 children completed the study. At birth, there was a prevalence of ciliated cells and rare neutrophils. At 1 and 3 years, ciliated cells started reducing in favor of muciparous cells and neutrophils. We found that caesarian delivery and nasogastric tube usage for choanal patency are significantly related to a certain cellular nasal composition. Additionally, development of upper respiratory tract infections, AOM (acute otitis media) and allergy correlates with specific cytological compositions which may predict those pathologies. Conclusions: Our study is the first to show the normal nasal mucosa cellular composition and development in the first 3 years of life in a large cohort. Nasal cytology may be a tool for early risk assessment in the occurrence of upper airway disease. Full article

Background: Recent advances in biologics have provided new insights into the clinical course of asthma, including disease modification, clinical remission (CR), and deep remission (DR). However, the extent to which biologics achieve CR and DR in severe asthma patients is poorly understood. Methods: To assess the achievement rate and predictors of CR and DR using long-term biologics, we retrospectively evaluated 54 severe asthma patients recently started on biologics. “CR” denotes the achievement of all three criteria: (1) absence of asthma symptoms, (2) no asthma exacerbations, and (3) no use of oral corticosteroids. DR denoted CR plus (4) normalized pulmonary function and (5) suppressed type 2 inflammation. Results: CR and DR achievement rates were 68.5% and 31.5%, respectively. Compared with the non-deep remission group, the DR group had higher adult-onset asthma rates (94.1% vs. 70.3%, p = 0.078), shorter asthma duration (5 vs. 19 years, p = 0.006), and higher FEV₁ (91.5% vs. 71.5%, p < 0.001). There were no significant differences in the Asthma Control Questionnaire scores, exacerbation frequency, or type 2 inflammation at baseline between groups. Asthma duration combined with FEV₁ can stratify the achievement rates of CR and DR. Conclusions: the early introduction of biologics in severe asthma patients may help achieve CR and DR. Full article

Few studies have focused on the consequence of exposure to general anesthesia (GA) in children’s early life with the risk of asthma and disease outcomes. The present study examines the correlation between exposure to GA under three years old and the subsequent course of asthma in a nationwide population-based cohort study. Our cases were acquired from Taiwan’s National Health Insurance Research Database (NHIRD). Children under three years old with either GA exposure or not during in-patient treatment from 1997 to 2008 were included. The study group was age- and sex-matched with a ratio of 1:2 to create the control group for comparison. The cohort included 2261 cases with GA and 4522 cases without GA as a control group. The incidence of asthma onset was significantly reduced in patients with GA exposure under 3 three years old (hazard ratio 0.64 (95% confidence interval 0.57~0.72), p < 0.001). In addition, regardless of whether the asthmatic clinical visits were before or after GA exposure, asthma onset patients before GA exposure have significantly fewer clinical visits than those without GA exposure (both p < 0.001, respectively). Using the Kaplan–Meier method, we also demonstrated that GA exposure was associated with favorable clinical visits in patients with asthma, whether their asthma was onset before GA (p = 0.0102) or after GA exposure (p = 0.0418) compared to non-GA-exposed controls. In the present study, we demonstrated that children with early GA exposure under three years old were at a reduced risk of developing asthma compared to the general population. Furthermore, we first reported that GA exposure significantly reduced clinical visits in patients with asthma regardless of whether their asthma onset was before or after GA exposure. It is indicated that GA exposure at a younger age could have potential clinical benefits for asthma than non-GA-exposed controls. Full article

Τhe importance of the gut microbiome and its functions has only recently been recognized and researched in greater depth. The establishment of the human gut microbiome begins in utero, forming its adult-like phenotype in the first 2–3 years of life. Several factors affect and alter the gut microbiome composition and its metabolic functions, such as early onset of breastfeeding, mode of delivery, antibiotic administration, or exposure to chemical substances, among others. Existing data support the important connection between health status and gut microbiome homeostasis. In cases when this balance is disturbed, several disorders may arise, such as inflammatory reactions that lead to atopy, eczema, or allergic asthma. The so-called gut-brain axis refers to the complex biochemical pathways between the central nervous system and the gastrointestinal system. One of the most fascinating areas of ongoing research is the broad spectrum of neurodevelopmental disorders (NDDs) and how gut health may be associated with such disorders. The prevalence of NDDs, such as autism spectrum disorder or attention deficit hyperactivity disorder, has increased over recent years. Whether gut microbiota homeostasis plays a role in these disorders is not yet fully understood. The aim of this narrative review is to provide an account of current knowledge on how gut health is linked with these disorders. We performed a literature review in order to identify and synthesize available data that highlights the potential association between NDDs and a balanced gut microbiome in terms of composition and proper function. The connection between the gut microbiome and NDDs offers promising new opportunities for future research. Full article

Introduction: Early-life antibiotic exposure is common and impacts the development of the child’s microbiome and immune system. Information on the impacts of early-life antibiotics exposure on childhood asthma is lacking. Methods: This study examined associations between early-life (0–24 months) antibiotics exposure with childhood (6–15 years) asthma trajectories through the Australian Longitudinal Study of Australian Children (LSAC) and their linked data from the Pharmaceutical Benefits Scheme. Asthma phenotypes were derived by group-based trajectory modeling. Results: Of 5107 LSAC participants, 4318 were included in the final analyses (84.6% retention). Four asthma phenotypes were identified: Always-low-risk (79.0%), early-resolving asthma (7.1%), early-persistent asthma (7.9%), and late-onset asthma (6.0%). Any early-life antibiotic exposure increased risk 2.3-fold (95% CI: 1.47–3.67; p < 0.001) for early-persistent asthma among all children. In subgroup analyses, early-persistent asthma risk increased by 2.7-fold with any second-generation cephalosporin exposure, and by 2-fold with any β-lactam other than cephalosporin or macrolide exposure. Conclusion: We concluded that early-life antibiotic exposure is associated with an increased risk of early-persistent childhood asthma. This reinforces scrutiny of early-life antibiotic use, particularly for common viral infections where no antibiotics are required. Full article

Reactive oxygen species, including singlet oxygen, play an important role in the onset and progression of disease, as well as in aging. Singlet oxygen can be formed non-enzymatically by chemical, photochemical, and electron transfer reactions, or as a byproduct of endogenous enzymatic reactions in phagocytosis during inflammation. The imbalance of antioxidant enzymes and antioxidant networks with the generation of singlet oxygen increases oxidative stress, resulting in the undesirable oxidation and modification of biomolecules, such as proteins, DNA, and lipids. This review describes the molecular mechanisms of singlet oxygen production in vivo and methods for the evaluation of damage induced by singlet oxygen. The involvement of singlet oxygen in the pathogenesis of skin and eye diseases is also discussed from the biomolecular perspective. We also present our findings on lipid oxidation products derived from singlet oxygen-mediated oxidation in glaucoma, early diabetes patients, and a mouse model of bronchial asthma. Even in these diseases, oxidation products due to singlet oxygen have not been measured clinically. This review discusses their potential as biomarkers for diagnosis. Recent developments in singlet oxygen scavengers such as carotenoids, which can be utilized to prevent the onset and progression of disease, are also described. Full article

The main risk factor for chronic obstructive pulmonary disease (COPD) is active smoking. However, a considerable amount of people with COPD never smoked, and increasing evidence suggests that adult lung disease can have its origins in prenatal and early life. This article reviews some of the factors that can potentially affect lung development and lung function trajectories throughout the lifespan from genetics and prematurity to respiratory tract infections and childhood asthma. Maternal smoking and air pollution exposure were also analyzed among the environmental factors. The adoption of preventive strategies to avoid these risk factors since the prenatal period may be crucial to prevent, delay the onset or modify the progression of COPD lung disease throughout life. Full article

Most patients with childhood asthma present their first symptoms at preschool age. Identifying modifiable risks and protective factors at an early age may help develop asthma prevention and control strategies. This study aimed to identify factors at preschool age that are associated with persistent asthma at school age. This retrospective observational study included preschool children with asthma from 2015 to 2020 at a university hospital in Southern Thailand. In total, 189 eligible participants (70.9% boys; median age, 7.6 [6.7, 8.5] years) were included. Wheeze characteristics included early transient wheeze, persistent wheeze, and late-onset wheeze that accounted for 55%, 27.5%, and 19.5% of the patients, respectively. Approximately 20% of the participants had persistent asthma. Breastfeeding was a protective factor (odds ratio [OR] 0.4 [0.2, 0.9], p = 0.04). The modifiable risk factors were siblings living in the same household (OR 2.6 [1.1, 6.2], p = 0.02) and residence in an industrial area (OR 3.8 [1.4, 10.5], p = 0.009). Additionally, presence of allergic rhinitis was associated with an increased risk of persistent asthma at school age (OR 3.6 [1.6, 8.2], p = 0.002). Early therapeutic interventions targeting modifiable factors provide a window of opportunity to prevent persistent asthma at school age. Full article

Late-onset asthma (LOA) differs from early-onset asthma (EOA) in terms of prognosis and the treatment response because it has a much worse prognosis and a poorer response to standard asthma treatment. This study sought to investigate the characteristics and clinical outcomes of asthma patients with phenotypes distinguished by age at onset and atopy status. We prospectively recruited patients with asthma who were registered in a pay-for-performance program operated by Taiwan’s National Health Insurance Administration (NHIA). These patients received regular outpatient treatment for at least 1 year at every outpatient clinic visit since 2019. Baseline characteristics and clinical outcomes were compared between patients with LOA (≥40 years) and those with EOA (<40 years). Of the consecutive 101 patients with asthma, 21 patients (20.7%) had EOA and 80 (79.3%) had LOA. In the 12-month period, patients with EOA had higher declines in forced expiratory volume in one second (FEV₁; −2.1 ± 8.4 vs. 6.8 ± 13.1, % of predicted value, p = 0.037) and forced vital capacity (FVC; −4.6 ± 12.0 vs. 6.1 ± 13.6, % of predicted value, p = 0.023) than patients with LOA. Patients with nonatopic EOA had a significantly higher exacerbation rate at 12 months than patients with nonatopic LOA (50% vs. 11.8%, p = 0.012). Identification of different phenotypes of asthma is important in clinical practice because treatment responses may differ. Full article

To determine phenotype-related dupilumab response in adult patients with atopic dermatitis (AD), this multicenter, retrospective study included 111 adults with moderate-to-severe AD in Taiwan, with median age of 31.5 years (18–87) and 71 (64.0%) males. Patients received dupilumab 300 mg per two to three weeks up to 12 months. We found a significant improvement after 4 and 16 weeks of treatment in all patients for all the assessed scores, including eczema area and severity index (EASI) improvement ≥50% (EASI-50) and 75% (EASI-75), EASI reaching minimal clinically important difference (MCID), and Investigator’s Global Assessment (IGA) improvement ≥2. Importantly, prior to asthma, early AD onset and 3-week drug intervals were significantly associated with a high proportion of EASI-75 at month 12, while prurigo and lichenoid phenotypes were associated with a lower proportion of EASI-75 at month 12. However, the majority of adverse events were mild in severity. In conclusion, our study results identify phenotype-related dupilumab response at month 12 in adults with moderate-to-severe AD, and we suggest that treatment should not be discontinued until reaching a satisfactory clinical response. Full article

Childhood asthma is a major chronic non-communicable disease in infants and children, often triggered by respiratory tract infections. The nasal cavity is a reservoir for a broad variety of commensal microbes and potential pathogens associated with respiratory illnesses including asthma. A healthy nasal microenvironment has protective effects against respiratory tract infections. The first microbial colonisation in the nasal region is initiated immediately after birth. Subsequently, colonisation by nasal microbiota during infancy plays important roles in rapidly establishing immune homeostasis and the development and maturation of the immune system. Dysbiosis of microbiota residing in the mucosal surfaces, such as the nasopharynx and guts, triggers immune modulation, severe infection, and exacerbation events. Nasal microbiome dysbiosis is related to the onset of symptomatic infections. Dynamic interactions between viral infections and the nasal microbiota in early life affect the later development of respiratory infections. In this review, we summarise the existing findings related to nasal microbiota colonisation, dynamic variations, and host–microbiome interactions in childhood health and respiratory illness with a particular examination of asthma. We also discuss our current understanding of biases produced by environmental factors and technical concerns, the importance of standardised research methods, and microbiome modification for the prevention or treatment of childhood asthma. This review lays the groundwork for paying attention to an essential but less emphasized topic and improves the understanding of the overall composition, dynamic changes, and influence of the nasal microbiome associated with childhood asthma. Full article

Atopic eczema (AE) is an inflammatory skin disorder affecting approximately 20% of children worldwide and early onset can lead to asthma and allergies. Currently, the mechanisms of the disease are not fully understood. Metabolomics, the analysis of small molecules in the skin produced by the host and microbes, opens a window to observe the mechanisms of the disease which then may lead to new drug targets for AE treatment. Here, we review the latest advances in AE metabolomics, highlighting both the lipid and non-lipid molecules, along with reviewing the metabolites currently known to reside in the skin. Full article