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Cited by 137Interstitial Lung Diseases and Idiopathic Pulmonary FibrosisPharmacovigilance and Adverse Drug ReactionsPulmonary Hypertension Research and Treatments

Anxiety caused by a short-life hypnotic.

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Morgan, K, Oswald, I·1982·BMJ
DOI 10.1136/bmj.284.6320.942
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Abstract

A comprehensive understanding of the changes in gene expression in cell types involved in idiopathic pulmonary fibrosis (IPF) will shed light on the mechanisms underlying the loss of alveolar epithelial cells, and development of honeycomb cysts and fibroblastic foci. We sought to understand changes in IPF lung cell transcriptomes and gain insight into innate immune aspects of pathogenesis. We investigated IPF pathogenesis using single cell RNA-sequencing of fresh lung explants, comparing human IPF fibrotic lower lobes reflecting late disease, upper lobes reflecting early disease and normal lungs. IPF lower lobes showed increased fibroblasts, and basal, ciliated, goblet and club cells, but decreased alveolar epithelial cells, and marked alterations in inflammatory cells. We found three discrete macrophage subpopulations in normal and fibrotic lungs, one expressing monocyte markers, one highly expressing FABP4 and INHBA (FABP4hi), and one highly expressing SPP1 and MERTK (SPP1hi). SPP1hi macrophages in fibrotic lower lobes showed highly upregulated SPP1 and MERTK expression. Low-level local proliferation of SPP1hi macrophages in normal lungs was strikingly increased in IPF lungs. Co-localisation and causal modelling supported the role for these highly proliferative SPP1hi macrophages in activation of IPF myofibroblasts in lung fibrosis. These data suggest SPP1hi macrophages contribute importantly to lung fibrosis in IPF, and that therapeutic strategies targeting MERTK and macrophage proliferation may show promise for treatment of this disease.

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  • Withdrawal symptoms are more severe following withdrawal from short rather than long half-life benzodiazepines.

    “These symptoms are more severe following withdrawal from short rather than long half-life BZDs [39,40,41,42,43].”

    From Cognitive behavioral therapy and acceptance and commitment therapy for the discontinuation of long-term benzodiazepine use in insomnia and anxiety disorders (2021) · cites this paper as [40]

    The Subjects, methods, and results section reports that anxiety peaked sooner after withdrawal of the shorter-lived triazolam than after withdrawal of loprazolam. The Comment likewise says faster elimination produces earlier rebound, but neither passage establishes that withdrawal symptoms are generally more severe with short- than long-half-life benzodiazepines. (LLM, conf=0.85)

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  • The prevalence of rebound insomnia is significantly lower in all benzodiazepines compared to triazolam.

    “The prevalence of rebound insomnia was found to be significantly lower in all benzodiazepines compared to triazolam [52, 60-69] and was lower than that with triazolam.”

    From Acute and Persistent Withdrawal Syndromes Following Discontinuation of Psychotropic Medications (2020) · cites this paper as [63]

    The Subjects, methods, and results section reports very poor sleep on the first night after triazolam withdrawal and poor sleep on the third night after loprazolam withdrawal. The Comment section also says rebound sleep disturbance occurs earlier with more rapidly eliminated drugs. But the paper compares only these two drugs and reports no prevalence comparison or statistically significant difference in rebound insomnia; its reported significance concerns anxiety. (LLM, conf=0.84)

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Research works printed but not linked: 2

  1. Committee on the Review of Medicines. Systematic review of the benzo- diazepines. Br MedJ' 1980;280:910-2.
  2. KEVIN MORGAN, BSC, faculty of medicine research scholar IAN OSWALD, DSC, FRCPSYCH, professor on 3 November 2023 by guest. Protected by copyright. http://www.bmj.com/ Br Med J (Clin Res Ed): first published as 10.1136/bmj.284.6320.942 on 27 March 1982. Downloaded from

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Authors
Morgan, K., & Oswald, I.
Venue
BMJ
Publisher
BMJ
Published
1982-03-27
Volume
284
Issue
6320
Pages
942-942
ISSN
  • 0007-1447 (ISSN-L)
  • 0959-8138
  • 1468-5833
DOI
10.1136/bmj.284.6320.942
OpenAlex
W2150408288
Cited by
137
References
5
Citations by year
2023: 1 · 2021: 1 · 2020: 1 · 2016: 1 · 2013: 1
FWCI
26.01
Type
journal article
Language
en
Open access
Locations
  • BMJ (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
Keywords
idiopathic pulmonary fibrosis, pulmonary fibrosis, MERTK, macrophage proliferation, myofibroblast activation, alveolar epithelial cells, macrophage subpopulations, innate immunity, gene expression, single-cell transcriptomics, honeycomb cysts
MeSH terms
Anxiety Disorders, Benzodiazepines, Benzodiazepinones, Clinical Trials as Topic, Double-Blind Method, Female, Half-Life, Humans, Male, Middle Aged, Substance Withdrawal Syndrome, Anti-Anxiety Agents, Triazolam

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