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Alternative excitotoxic hypotheses
Abstract
It is known that asthma is a heterogeneous entity whose manifestations vary with age. Our objective was to examine changes in the manifestation of asthma and asthma-related traits in childhood by defining empirically derived childhood asthma phenotypes and examining their transitions over time. To define the phenotypes we used data on respiratory symptoms, healthcare utilisation, medications, spirometry, airway hyperresponsiveness (AHR), exhaled nitric oxide concentration and atopy from a birth cohort recruited on the basis of having a first-degree relative with asthma. Data were acquired at ages 1.5–11.5 years and analysed using latent transition analysis. In a study population of 370 participants, we classified subjects into four phenotypes: 1) nonatopic, few symptoms (prevalence range from 1.5 to 5 years: 52–60%), 2) atopic, few symptoms (3–21%), 3) nonatopic, asthma and rhinitis symptoms (13–35%), and 4) atopic, asthma and rhinitis symptoms (2–14%) in early childhood; and 1) nonatopic, no respiratory disease (prevalence range from 8 to 11.5 years: 41–46%), 2) atopic, no respiratory disease (23–33%), 3) nonatopic, asthma symptoms, no AHR or airway inflammation (8–12%) and 4) atopic asthma (19%) in mid-childhood. Transitioning between phenotypes was common in early childhood, but less common in later childhood. This analysis represents the first attempt to incorporate longitudinal patterns of several manifestations of asthma into a single model to simultaneously define phenotypes and examine their transitions over time. It provides quantitative support for the view that asthma is a heterogeneous entity, and that some children with wheeze and other respiratory symptoms in early life progress to asthma in mid-childhood, while others become asymptomatic.
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“Damage to glutamatergic neurons, in particular cell bodies and neurites in layers III and IV of the neocortex, together with damage to glutamatergically-innervated cortical and hippocampal neurons, are particularly evident in AD brain (Albin and Greenamyre 1992).”
From Alzheimer’s disease: Targeting the glutamatergic system (2020) · cites this paper as Albin and Greenamyre 1992
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Metadata
- Authors
- Albin, R. L., & Greenamyre, J. T.
- Affiliations
- University of Michigan (US)
- University of Rochester (US)
- Venue
- Neurology
- Published
- 1992-04
- Volume
- 42
- Issue
- 4
- Pages
- 733-733
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2058176457
- Cited by
- 574
- References
- 0
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 3 · 2022: 18 · 2021: 4 · 2020: 12 · 2019: 3 · 2018: 6 · 2017: 7 · 2016: 5 · 2015: 4 · 2014: 10 · 2013: 12 · 2012: 16
- FWCI
- 14.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k08ns001300-03, 5k08ns001487-03)
- National Institute of Neurological Disorders and Stroke (NS01300, NS 01487)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Occupational exposure and asthma
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory and Cough-Related Research
- Keywords
- asthma phenotypes, childhood asthma, asthma heterogeneity, phenotype transition, atopy, rhinitis, airway hyperresponsiveness, exhaled nitric oxide, wheezing, latent transition analysis, birth cohort
- MeSH terms
- Acute Disease, Amino Acids, Chronic Disease, Humans, Models, Neurological, Nerve Degeneration, Nervous System Diseases, Neurology, Neurotoxins, Receptors, Cell Surface, Receptors, Amino Acid
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