Publications by authors named "Sara Fontanella"

Background: Component-resolved diagnostics allow detailed assessment of IgE sensitization to multiple allergenic molecules (component-specific IgEs, or c-sIgEs) and may be useful for asthma diagnosis. However, to effectively use component-resolved diagnostics across diverse settings, it is crucial to account for geographic differences.

Objective: We investigated spatial determinants of c-sIgE networks to facilitate development of diagnostic algorithms applicable globally.

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Background: Many studies used information on wheeze presence/absence to determine asthma-related phenotypes. We investigated whether clinically intuitive asthma subtypes can be identified by applying data-driven semi-supervised techniques to information on frequency and triggers of different respiratory symptoms.

Methods: Partitioning Around Medoids clustering was applied to data on multiple symptoms and their triggers in school-age children from three birth cohorts: MAAS (n = 947, age 8 years), SEATON (n = 763, age 10) and ASHFORD (n = 584, age 8).

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Background: Out-of-hospital cardiac arrest (OHCA) is associated with high mortality, highlighting the importance of identifying prognostic factors to guide treatment escalation plans. This study investigates the short-term prognostic potential of transthoracic echocardiogram (TTE), a commonly performed investigation in OHCA patients. This study is among the first to report left ventricle (LV) global longitudinal strain (LVGLS) in OHCA patients.

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Background: The association between allergic sensitization and asthma is well-documented, but its precise role in asthma remains uncertain. Component-resolved diagnostics allows detailed assessment of IgE-sensitization to multiple allergenic molecules (c-sIgE). We applied advanced network embedding techniques to investigate the dynamics of temporal development of multiple c-sIgE and identify networks associated with asthma.

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Background: Lung function during childhood is an important predictor of subsequent health and disease. Understanding patterns of lung function and development of airflow limitation through childhood is necessary to inform lung function trajectories in relation to health and chronic airway disease. We aimed to derive trajectories of airflow limitation from childhood (age 5-8 years) into early adulthood (age 20-26 years) using repeated spirometry data from birth cohorts.

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Background: Post hoc analysis of clinical trials shows blood eosinophil counts (BEC) predict future preschool wheeze attacks; however, prospective usefulness in a clinical setting is unreported. We assessed the feasibility of point-of-care (POC) eosinophil measurements in preschool wheezers and related BEC to symptoms, lung function, and utility in predicting attacks.

Methods: Children aged 1-5 years with recurrent wheeze underwent finger-prick sampling during the outpatient clinic for POC eosinophils, forced oscillation technique (FOT) and/or spirometry, and symptom score (TRACK questionnaire).

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Background: Wheezing is common in early life, but most children stop wheezing by school age. However, the prediction of course of wheezing through childhood is difficult.

Objective: To investigate whether urinary EPX (a marker of eosinophil activation) in children at age 3 years may be useful for the prediction of wheeze persistence and future asthma diagnosis.

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Rationale: Lung function in early adulthood is associated with subsequent adverse health outcomes.

Objectives: To ascertain whether stable and reproducible lung function trajectories can be derived in different populations and investigate their association with objective measures of cardiovascular structure and function.

Methods: Using latent profile modelling, we studied three population-based birth cohorts with repeat spirometry data from childhood into early adulthood to identify trajectories of forced expiratory volume in 1 s (FEV)/forced vital capacity (FVC).

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Article Synopsis
  • One in ten COVID-19 infections lead to long COVID, characterized by prolonged symptoms, but the underlying mechanisms remain unclear.
  • In a study of 657 individuals, certain inflammatory markers were linked to long COVID symptoms, revealing connections to cardiorespiratory issues, fatigue, anxiety, gastrointestinal problems, cognitive impairments, and potential nerve tissue repair disturbances.
  • Findings suggest that targeting specific inflammatory pathways could offer new therapeutic options for treating different subtypes of long COVID in future clinical trials.*
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Background: Single nucleotide polymorphisms (SNPs) in genes on chromosome 17q12-q21 are associated with childhood-onset asthma and rhinovirus-induced wheeze. There are few mechanistic data linking chromosome 17q12-q21 to wheezing illness.

Objective: We investigated whether 17q12-q21 risk alleles were associated with impaired interferon responses to rhinovirus.

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Background: Previous studies which applied machine learning on multiplex component-resolved diagnostics arrays identified clusters of allergen components which are biologically plausible and reflect the sources of allergenic proteins and their structural homogeneity. Sensitization to different clusters is associated with different clinical outcomes.

Objective: To investigate whether within different allergen component sensitization clusters, the internal within-cluster sensitization structure, including the number of c-sIgE responses and their distinct patterns, alters the risk of clinical expression of symptoms.

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Purpose Of Review: To review the current state of knowledge on the relationship between allergic sensitization and asthma; to lay out a roadmap for the development of IgE biomarkers that differentiate, in individual sensitized patients, whether their sensitization is important for current or future asthma symptoms, or has little or no relevance to the disease.

Recent Findings: The evidence on the relationship between sensitization and asthma suggests that some subtypes of allergic sensitization are not associated with asthma symptoms, whilst others are pathologic. Interaction patterns between IgE antibodies to individual allergenic molecules on component-resolved diagnostics (CRD) multiplex arrays might be hallmarks by which different sensitization subtypes relevant to asthma can be distinguished.

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Background: Spirometric obstruction and restriction are two patterns of impaired lung function which are predictive of poor health. We investigated the development of these phenotypes and their transitions through childhood to early adulthood.

Methods: In this study, we analysed pooled data from three UK population-based birth cohorts established between 1989 and 1995.

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Preschool wheezing and childhood asthma create a heavy disease burden which is only exacerbated by the complexity of the conditions. Preschool wheezing exhibits both "curricular" and "aetiological" heterogeneity: that is, heterogeneity across patients both in the time-course of its development and in its underpinning pathological mechanisms. Since these are not fully understood, but clinical presentations across patients may nonetheless be similar, current diagnostic labels are imprecise-not mapping cleanly onto underlying disease mechanisms-and prognoses uncertain.

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Article Synopsis
  • Longitudinal studies on childhood eczema reveal various phenotypes, but characteristics often vary between different research.
  • The study aims to provide a detailed analysis of eczema development patterns rather than just indicating its presence or absence over time.
  • By analyzing data from 7464 participants, researchers identified five distinct eczema clusters and confirmed the stability and unique characteristics of each, highlighting the influence of risk factors like parental eczema.
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The field of medicine is witnessing an exponential growth of interest in artificial intelligence (AI), which enables new research questions and the analysis of larger and new types of data. Nevertheless, applications that go beyond proof of concepts and deliver clinical value remain rare, especially in the field of allergy. This narrative review provides a fundamental understanding of the core concepts of AI and critically discusses its limitations and open challenges, such as data availability and bias, along with potential directions to surmount them.

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Background: Many genes associated with asthma explain only a fraction of its heritability. Most genome-wide association studies (GWASs) used a broad definition of 'doctor-diagnosed asthma', thereby diluting genetic signals by not considering asthma heterogeneity. The objective of our study was to identify genetic associates of childhood wheezing phenotypes.

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Article Synopsis
  • * A man in his 60s experienced a painless swelling in the right parotid area, leading to a fine-needle aspiration that indicated potential malignancy, prompting partial superficial parotidectomy.
  • * The diagnosis of intraductal carcinoma was confirmed through immunohistochemistry, and the authors note that recent findings in cytology and histopathology may influence the classification and treatment of this condition in the future.
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Background: Guidelines recommend intramuscular injection of 500 μg adrenaline (epinephrine) for anaphylaxis in teenagers and adults; however, most autoinjectors deliver a maximum 300 μg dose. We evaluated plasma adrenaline levels and cardiovascular parameters (including cardiac output) following self-injection with 300 μg or 500 μg adrenaline in teenagers at risk of anaphylaxis.

Methods: Subjects were recruited to a randomized, single-blind two period crossover trial.

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Allergic diseases and asthma are intrinsically linked to the environment we live in and to patterns of exposure. The integrated approach to understanding the effects of exposures on the immune system includes the ongoing collection of large-scale and complex data. This requires sophisticated methods to take full advantage of what this data can offer.

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Background: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced.

Methods: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia.

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Article Synopsis
  • Scientists wanted to understand how owning pets, especially dogs, affects asthma risk in kids who have a certain gene (called rs2305480).
  • They studied over 9,000 children and found that having the G version of this gene usually means a higher chance of wheezing, especially in kids without pets.
  • However, among kids who owned dogs, that higher risk disappeared, suggesting that having a dog might protect those kids from asthma problems linked to that gene.
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The relationship between eczema, wheeze or asthma, and rhinitis is complex, and epidemiology and mechanisms of their comorbidities is unclear. To investigate within-individual patterns of morbidity of eczema, wheeze, and rhinitis from birth to adolescence/early adulthood. We investigated onset, progression, and resolution of eczema, wheeze, and rhinitis using descriptive statistics, sequence mining, and latent Markov modeling in four population-based birth cohorts.

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