Hypothalamic‐pituitary‐adrenal axis suppression in asthma: A glucocorticoid receptor polymorphism may protect

Akurugu, Wisdom Alemya; Heerden, Carel Jacobus Van; Mulder, Nicola; Zöllner, Ekkehard Werner

doi:10.1111/pai.13379

Cited by 9 publications

(6 citation statements)

References 24 publications

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“…This may eventually lead to depression or other neuropsychiatric disorders 18 , 19 . An example is that air pollutant triggers an immune response in an asthmatic patient may increase the release of inflammatory cytokines and initiate changes in the hypothalamic–pituitary–adrenal (HPA) axis and produce psychological effects, such as depression 20 , 21 .…”

Section: Introductionmentioning

confidence: 99%

Association of suicidal ideation and depression with the use of proton pump inhibitors in adults: a cross-sectional study

Fong

Chan²,

Lei³

et al. 2022

Sci Rep

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Proton pump inhibitors (PPIs) were found to be associated with depression. This study aimed to find the cross-sectional association between recent PPI use and suicidal ideation. Item 9 of Patient Health Questionnaire-9 (PHQ-9) of the US National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018 was used to categorize whether or not the participants had suicidal ideation. The secondary outcome of this study was depression and the scores of the PHQ-9 were used as the depression diagnostic instrument. The study population included 16,881 participants who were over 20 years old. The bivariate Rao-Scott χ2 test showed a significant association between PPI use and suicidal ideation (P < 0.001) and a stronger association was observed between PPIs and depression (P < 0.001). Multiple logistic regression analysis of the education, gender, race and age-adjusted model revealed that the PPI users had a 2.34 (95% CI 1.66–3.31) greater risk of having suicidal ideation than the non-PPI users. Middle-aged participants (40–49 years) showed the greatest number of differences in suicidal ideation between PPI and non-PPI users (P < 0.001). Future research should continue to consider the psychiatric effects of taking PPIs.

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Section: Introductionmentioning

confidence: 99%

Association of suicidal ideation and depression with the use of proton pump inhibitors in adults: a cross-sectional study

Fong

Chan²,

Lei³

et al. 2022

Sci Rep

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“…Glucocorticoid receptor polymorphisms were reported to be associated with increased sensitivity to glucocorticoids, leading to a higher prevalence of features associated with hypercortisolism and efficacy of glucocorticoids or, by contrast, a relative glucocorticoid resistance with lower rates of development of features suggestive of iatrogenic Cushing's syndrome. [133][134][135][136][137][138][139][140][141][142] Time of glucocorticoid administration during the day is another important factor that likely contributes to the risk of GI-AI. Clock related genes in circulating blood cells from patients taking exogenous glucocorticoid multiple times a day were found to be abnormal, and they partially normalized after a switch to once a day administration.…”

Section: -132mentioning

confidence: 99%

“…This variation is possibly linked—among other factors—to polymorphisms of the genes encoding the glucocorticoid and mineralocorticoid receptors 14129130131132. Glucocorticoid receptor polymorphisms were reported to be associated with increased sensitivity to glucocorticoids, leading to a higher prevalence of features associated with hypercortisolism and efficacy of glucocorticoids or, by contrast, a relative glucocorticoid resistance with lower rates of development of features suggestive of iatrogenic Cushing’s syndrome 133134135136137138139140141142. Time of glucocorticoid administration during the day is another important factor that likely contributes to the risk of GI-AI.…”

Section: Factors Affecting Likelihood Of Glucocorticoid Induced Adrenal Insufficiencymentioning

confidence: 99%

Glucocorticoid induced adrenal insufficiency

Prete

Bancos

2021

BMJ

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Synthetic glucocorticoids are widely used for their anti-inflammatory and immunosuppressive actions. A possible unwanted effect of glucocorticoid treatment is suppression of the hypothalamic-pituitary-adrenal axis, which can lead to adrenal insufficiency. Factors affecting the risk of glucocorticoid induced adrenal insufficiency (GI-AI) include the duration of glucocorticoid therapy, mode of administration, glucocorticoid dose and potency, concomitant drugs that interfere with glucocorticoid metabolism, and individual susceptibility. Patients with exogenous glucocorticoid use may develop features of Cushing’s syndrome and, subsequently, glucocorticoid withdrawal syndrome when the treatment is tapered down. Symptoms of glucocorticoid withdrawal can overlap with those of the underlying disorder, as well as of GI-AI. A careful approach to the glucocorticoid taper and appropriate patient counseling are needed to assure a successful taper. Glucocorticoid therapy should not be completely stopped until recovery of adrenal function is achieved. In this review, we discuss the factors affecting the risk of GI-AI, propose a regimen for the glucocorticoid taper, and make suggestions for assessment of adrenal function recovery. We also describe current gaps in the management of patients with GI-AI and make suggestions for an approach to the glucocorticoid withdrawal syndrome, chronic management of glucocorticoid therapy, and education on GI-AI for patients and providers.

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“…The lead NR3C1 SNV and numerous eQTLs in LD mapped to regions of strong transcriptional activity in lymphoid and myeloid cells. NR3C1 could thus act as a risk factor for severe OM through perturbation of endogenous regulation of inflammation, as seen in childhood asthma [ 20 ]. Environmental stresses also act through NR3C1-mediated endogenous corticosteroid responses.…”

Section: Discussionmentioning

confidence: 99%

Common and Rare Genetic Variants That Could Contribute to Severe Otitis Media in an Australian Aboriginal Population

Jamieson

Fakiola

Tang

et al. 2021

Clinical Infectious Diseases

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Background Our goal was to identify genetic risk factors for severe otitis media (OM) in Aboriginal Australians. Methods Illumina ® Omni2.5 BeadChip and imputed data were compared between 21 children with severe OM (multiple episodes chronic suppurative OM and/or perforations or tympanic sclerosis) and 370 individuals without this phenotype, followed by FUnctional Mapping and Annotation (FUMA). Exome data filtered for common (EXaC_all≥0.1) putative deleterious variants influencing protein coding (CADD-scaled scores ≥ 15) were used to compare 15 severe OM cases with 9 mild cases (single episode of acute OM recorded over ≥ 3 consecutive years). Rare (ExAC_all≤0.01) such variants were filtered for those present only in severe OM. Enrichr was used to determine enrichment of genes contributing to pathways/processes relevant to OM. Results FUMA analysis identified two plausible genetic risk loci for severe OM: NR3C1 (Pimputed_1000G=3.62x10 -6) encoding the glucocorticoid receptor, and NREP (Pimputed_1000G=3.67x10 -6) encoding neuronal regeneration related protein. Exome analysis showed: (i) association of severe OM with variants influencing protein coding (CADD-scaled ≥ 15) in a gene-set (GRXCR1, CDH23, LRP2, FAT4, ARSA, EYA4) enriched for Mammalian Phenotype Level 4 abnormal hair cell stereociliary bundle morphology and related phenotypes; (ii) rare variants influencing protein coding only seen in severe OM provided gene-sets enriched for “abnormal ear” (LMNA, CDH23, LRP2, MYO7A, FGFR1), integrin interactions, transforming growth factor signalling, and cell projection phenotypes including hair cell stereociliary bundles and cilium assembly. Conclusions This study highlights interacting genes and pathways related to cilium structure and function that may contribute to extreme susceptibility to OM in Aboriginal Australian children.

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Hypothalamic‐pituitary‐adrenal axis suppression in asthma: A glucocorticoid receptor polymorphism may protect

Cited by 9 publications

References 24 publications

Association of suicidal ideation and depression with the use of proton pump inhibitors in adults: a cross-sectional study

Association of suicidal ideation and depression with the use of proton pump inhibitors in adults: a cross-sectional study

Glucocorticoid induced adrenal insufficiency

Common and Rare Genetic Variants That Could Contribute to Severe Otitis Media in an Australian Aboriginal Population

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