Publications by authors named "Peter le Souef"

Article Synopsis
  • Early respiratory assessments during the neonatal period can indicate future lung function and asthma risk, reflecting both prenatal lung development and limited environmental influences.
  • Factors like maternal smoking during pregnancy are linked to decreased lung function and higher asthma rates, especially in girls with specific genetic traits.
  • Despite the association between preschool lung function and later asthma development enhancing our understanding of asthma physiology, practical challenges have hindered routine lung function testing in young children for asthma prediction.
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The twenty-first century has seen a fundamental shift in disease epidemiology with anthropogenic environmental change emerging as the likely dominant factor affecting the distribution and severity of current and future human disease. This is especially true of allergic diseases and asthma with their intimate relationship with the natural environment. Climate change-related variables including increased ambient temperature, heat waves, extreme weather events, air pollution, and rainfall distribution, all can affect asthma in children, but each of these variables also affects asthma via alterations in pollen production and release, outdoor allergen exposure or the microbiome.

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  • A systematic review and meta-analysis was conducted to assess vitamin D levels and deficiency rates among children with asthma in Asia and Africa, responding to inconsistent findings from previous studies.
  • The review included data from 33 studies involving 3,432 children, revealing an average serum vitamin D level of 21.9 ng/ml, with over half of the children (53.7%) categorized as vitamin D deficient.
  • Results indicated geographic disparities: children in Asia had lower average vitamin D levels (18.5 ng/ml) compared to their African counterparts (28.7 ng/ml), highlighting potential regional health disparities.
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Real-world data on the range and impact of comorbid health conditions that affect pediatric asthma are scant, especially from developing countries. Lack of data hinders effective diagnosis, treatment, and overall management of these complex cases. We, hereby, describe the common pediatric asthma comorbid conditions in terms of evidence for association, potential mechanisms of impact on asthma control, and treatment benefit.

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Introduction: Recurrent wheezing disorders including asthma are complex and heterogeneous diseases that affect up to 30% of all children, contributing to a major burden on children, their families, and global healthcare systems. It is now recognized that a dysfunctional airway epithelium plays a central role in the pathogenesis of recurrent wheeze, although the underlying mechanisms are still not fully understood. This prospective birth cohort aims to bridge this knowledge gap by investigating the influence of intrinsic epithelial dysfunction on the risk for developing respiratory disorders and the modulation of this risk by maternal morbidities, exposures, and respiratory exposures in the first year of life.

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Monitoring is a major component of asthma management in children. Regular monitoring allows for diagnosis confirmation, treatment optimization, and natural history review. Numerous factors that may affect disease activity and patient well-being need to be monitored: response and adherence to treatment, disease control, disease progression, comorbidities, quality of life, medication side-effects, allergen and irritant exposures, diet and more.

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Introduction: The global human population is still growing such that our collective enterprise is driving environmental catastrophe. Despite a decline in average population growth rate, we are still experiencing the highest annual increase of global human population size in the history of our species-averaging an additional 84 million people per year since 1990. No review to date has accumulated the available evidence describing the associations between increasing population and environmental decline, nor solutions for mitigating the problems arising.

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Background: Children are more vulnerable than adults to climate-related health threats, but reviews examining how climate change affects human health have been mainly descriptive and lack an assessment of the magnitude of health effects children face. This is the first systematic review and meta-analysis that identifies which climate-health relationships pose the greatest threats to children.

Objectives: We reviewed epidemiologic studies to analyse various child health outcomes due to climate change and identify the relationships with the largest effect size.

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Article Synopsis
  • - Modern urbanization is altering the human microbiome, which may be linked to rising rates of chronic inflammatory diseases, like asthma and allergies, in both developed and developing countries.
  • - Studying immigrant populations can provide insights into microbiome changes as individuals move from low to high asthma prevalence areas, offering a unique perspective on this health issue.
  • - Researching the role of prebiotics and probiotics in relation to the microbiome and epigenetic factors is crucial for understanding and possibly preventing allergic conditions in modern environments.
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Background: Impaired interferon response and allergic sensitization may contribute to virus-induced wheeze and asthma development in young children. Plasmacytoid dendritic cells (pDCs) play a key role in antiviral immunity as critical producers of type I interferons. pDCs also express the high-affinity IgE receptor through which type I interferon production may be negatively regulated.

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Rhinoviruses (RVs) can cause severe wheezing illnesses in young children and patients with asthma. Vaccine development has been hampered by the multitude of RV types with little information about cross-neutralization. We previously showed that neutralizing antibody (nAb) responses to RV-C are detected twofold to threefold more often than those to RV-A throughout childhood.

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Asthma exacerbations in children are associated with respiratory viral infection and atopy, resulting in systemic immune activation and infiltration of immune cells into the airways. The gene networks driving the immune activation and subsequent migration of immune cells into the airways remains incompletely understood. Cellular and molecular profiling of PBMC was employed on paired samples obtained from atopic asthmatic children (n = 19) during acute virus-associated exacerbations and later during convalescence.

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Article Synopsis
  • Malaria, caused by Plasmodium spp., shows genetic links to resistance, particularly through certain blood phenotypes.
  • A study examined 187 SNPs in 37 candidate genes among 349 infants in Mozambique to find genetic associations with malaria.
  • Results pinpointed TLR4 and associated genes as significant factors in clinical malaria incidence, suggesting TLR4's crucial role and the need for further research on it and related genes for potential treatments.
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Introduction: Recurrent wheezing disorders including asthma are complex and heterogeneous diseases that affect up to 30% of all children, contributing to a major burden on children, their families, and global healthcare systems. It is now recognized that a dysfunctional airway epithelium plays a central role in the pathogenesis of recurrent wheeze, although the underlying mechanisms are still not fully understood. This prospective birth cohort aims to bridge this knowledge gap by investigating the influence of intrinsic epithelial dysfunction on the risk for developing respiratory disorders and the modulation of this risk by maternal morbidities, exposures, and respiratory exposures in the first year of life.

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Introduction: Transcriptomic analyses from early human immunodeficiency virus (HIV) infection have the potential to reveal how HIV causes widespread and lasting damage to biological functions, especially in the immune system. Previous studies have been limited by difficulties in obtaining early specimens.

Methods: A hospital symptom-based screening approach was applied in a rural Mozambican setting to enrol patients with suspected acute HIV infection (Fiebig stage I-IV).

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Article Synopsis
  • * Researchers analyzed data from 64 low- and middle-income countries to explore how factors like availability and quality of family planning, female education, and socio-economic conditions correlate with fertility rates.
  • * The study found that increased infant mortality and larger household sizes tend to raise fertility rates, while better access to contraception generally lowers them; female education also plays a significant role in these dynamics.
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Longitudinal studies have demonstrated that altered indices of airway function, assessed shortly after birth, are a risk factor for the subsequent development of wheezing illnesses and asthma, and that these indices predict airway size and airway wall thickness in adult life. Pre- and postnatal factors that directly alter early airway function, such as extreme prematurity and cigarette smoke, may continue to affect airway function and, hence, the risks for wheeze and asthma. Early airway function and an associated asthma risk may also be indirectly influenced by immune system responses, respiratory viruses, the airway microbiome, genetics, and epigenetics, especially if they affect airway epithelial dysfunction.

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Asthma imposes a heavy morbidity burden during childhood; it affects over 10% of children in Europe and North America and it is estimated to exceed 400 million people worldwide by the year 2025. In clinical practice, diagnosis of asthma in children is mostly based on clinical criteria; nevertheless, assessment of both physiological and pathological processes through biomarkers, support asthma diagnosis, aid monitoring, and further lead to better treatment outcomes and reduced morbidity. Recently, identification and validation of biomarkers in pediatric asthma has emerged as a top priority across leading experts, researchers, and clinicians.

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Allergen exposure may exacerbate asthma symptoms in sensitized patients. Allergen reduction or avoidance measures have been widely utilized; however, there is ongoing controversy on the effectiveness of specific allergen control measures in the management of children with asthma. Often, allergen avoidance strategies are not recommended by guidelines because they can be complex or burdensome, although individual patients may benefit.

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Human rhinovirus (RV)-induced exacerbations of asthma and wheeze are a major cause of emergency room presentations and hospital admissions among children. Previous studies have shown that immune response patterns during these exacerbations are heterogeneous and are characterized by the presence or absence of robust interferon responses. Molecular phenotypes of asthma are usually identified by cluster analysis of gene expression levels.

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Background: Dire forecasts predict that an increasingly hostile environment globally will increase the threats to human health. Infants and young children are especially at risk because children are particularly vulnerable to climate-related stressors. The childhood diseases most affected, the breadth and magnitude of future health problems and the time frame over which these problems will manifest remain largely unknown.

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Background: Acute wheezing is one of the most common hospital presentations for young children. Respiratory syncytial virus (RSV) and rhinovirus (RV) species A, B and the more recently described species C are implicated in the majority of these presentations. However, the relative importance and age-specificities of these viruses have not been defined.

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Introduction: Clinical recommendations for childhood asthma are often based on data extrapolated from studies conducted in adults, despite significant differences in mechanisms and response to treatments. The Paediatric Asthma in Real Life (PeARL) Think Tank aspires to develop recommendations based on the best available evidence from studies in children. An overview of systematic reviews (SRs) on paediatric asthma maintenance management and an SR of treatments for acute asthma attacks in children, requiring an emergency presentation with/without hospital admission will be conducted.

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Background: The burden of HIV is especially concerning for Eastern and Southern Africa (ESA), as despite expansion of test-and-treat programmes, this region continues to experience significant challenges resulting from high rates of morbidity, mortality and new infections. Hard-won lessons from programmes on the ground in ESA should be shared.

Objectives: This report summarises relevant evidence and regional experts' recommendations regarding challenges specific to ESA.

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