Dataset Information

Uncovering Outcome Disparities of β₂ Adrenergic Agonists in Blacks: A Systematic Review.

ABSTRACT:

Purpose

Outcome differences driven by variation in Blacks' biologic response to treatment may contribute to persistent racial disparities in asthma morbidity and mortality. This review assessed systematic variation in β₂ agonist treatment outcomes among Blacks compared to other groups.

Methods

We conducted a systematic review of studies reporting differential response to β₂ agonists among Blacks, including studies identifying pharmacogenetic variants.

Results

Of 3158 papers, 20 compared safety or efficacy of β₂ agonists among Blacks as compared with other subgroups. Six papers evaluating efficacy of short-acting β₂ agonists (SABA) found similar or improved results among Blacks compared with other groups, while one small study found reduced response to SABA therapy among Blacks. Reports of safety and efficacy of long-acting β₂ agonists (LABA) indicated similar results among Blacks in four papers, while four reports found reduced safety among Blacks, as compared with other groups. Four papers assessed genomic variation and relative treatment response in Blacks, with two finding significant effects of the p.Arg16Gly variant in ADRB2 on β₂ agonist response and one finding significant gene-gene IL6/IL6R interaction effects on albuterol response.

Conclusions

Evidence suggests the potential for differences in β₂ agonist outcomes among Blacks compared with other groups. This literature, however, remains small and significantly underpowered for substantive conclusions. There are notable opportunities for adequately-powered investigations exploring safety and efficacy of β₂ agonists among Blacks, including pharmacogenomic modifiers of response.

SUBMITTER: Jerome RN

PROVIDER: S-EPMC7855752 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Chinese hamster ovary cell constructs expressing either the β 1-, β 2- or β 3-adrenergic receptor (AR) were used to determine whether a novel β-AR modulator, lubabegron fumarate (LUB; Experior, Elanco Animal Health) might exert greater potency for a specific β-AR subtype. EC50 values calculated based on cAMP accumulation in dose response curves indicate that LUB is highly selective for the β 3-AR subtype, with an EC50 of 6 × 10-9 M, with no detectible agonistic activity at the β 2-AR. We hypothesized that the accumulation of lipolytic markers would reflect the agonist activity at each of the β-receptor subtypes of the specific ligand; additionally, there would be differences in receptor subtype expression in subcutaneous (s.c.) and intrmuscular (i.m.) adipose tissues. Total RNA was extracted from adipose tissue samples and relative mRNA levels for β 1-, β2-, and β 3-AR were measured using real-time quantitative polymerase chain reaction. Fresh s.c. and i.m. adipose tissue explants were incubated with isoproterenol hydrochloride (ISO; β-AR pan-agonist), dobutamine hydrochloride (DOB; specific β 1-AA), salbutamol sulfate (SAL; specific β 2-AA), ractopamine hydrochloride (RAC), zilpaterol hydrochloride (ZIL), BRL-37344 (specific β 3-agonist), or LUB for 30 min following preincubation with theophylline (inhibitor of phosphodiesterase). Relative mRNA amounts for β 1-, β 2-, and β 3-AR were greater (P < 0.05) in s.c. than in i.m. adipose tissue. The most abundant β-AR mRNA in both adipose tissues was the β 2-AR (P < 0.05), with the β 1- and β 3-AR subtypes being minimally expressed in i.m. adipose tissue. ISO, RH, and ZH stimulated the release of glycerol and nonesterified fatty acid (NEFA) from s.c. adipose tissue, but these β-AR ligands did not alter concentrations of these lipolytic markers in i.m. adipose tissue. LUB did not affect glycerol or NEFA concentrations in s.c. or i.m. adipose tissue, but attenuated (P < 0.05) the accumulation of cAMP mediated by the β 1- and β 2-AR ligands DOB and SAL in s.c. adipose tissue. Collectively, these data indicate that bovine i.m. adipose tissue is less responsive than s.c. adipose tissue to β-adrenergic ligands, especially those that are agonists at the β 1- and β3-receptor subtypes. The minimal mRNA expression of the β 1- and β 3 subtypes in i.m. adipose tissue likely limits the response potential to agonists for these β-AR subtypes.

Project description:BackgroundThe widespread use of short-acting beta-2 agonists (SABA) as an as-needed treatment for asthma is well-established. However, excessive use of SABA has been linked to undesirable outcomes such as increased risk of asthma attacks, exacerbations, and even death. The availability of SABA as an over-the-counter (OTC) medication has contributed to their overuse, leading to undertreated asthma and reduced access to asthma education.ObjectiveThis systematic review aimed to summarize the prevalence, characteristic features of, and factors contributing to over-the-counter SABA purchase or overuse.MethodsThe databases searched included PubMed, Scopus, Springer Link, Google Scholar, CINAHL, and APA PsycArticles. Original research articles reporting the prevalence, characteristics features, and factors regarding over-the-counter SABA use, available as full text, published in English language between the year 2000 and April 2023 were included in this review. Commentaries, letters to editor, review articles, qualitative studies, clinical trials, and conference proceedings were excluded. Data extraction was followed by a review of the quality of studies included and data were then synthesized for meaningful findings. This systematic review had been registered in the PROSPERO with registration number CRD42023421007.ResultsA total of 18 articles were included. The prevalence range of OTC SABA users in populations were 1.4% to 39.6% and SABA over-users among OTC users were 14% to 66.4%. Factors mostly associated with this behavior were moderate-severe asthma, and less use of preventers. On top of that, not understanding the risk of SABA overuse was clear in many studies that explored this factor.ConclusionOver-the-counter purchase and overuse of SABA medication is a common problem, leading to adverse consequences such as uncontrolled asthma and increased healthcare utilization. Addressing these issues requires improved patient education about their conditions and adequate information regarding the potential long-term effects of SABA use by the healthcare providers. Management and education of asthma patients, including regular monitoring and follow-up, can help reduce overuse of SABA medication and prevent negative consequences.

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Uncovering Outcome Disparities of β₂ Adrenergic Agonists in Blacks: A Systematic Review.

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Methods

Results

Conclusions

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Uncovering Outcome Disparities of β2 Adrenergic Agonists in Blacks: A Systematic Review.

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OmicsDI is part of the ELIXIR infrastructure

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Uncovering Outcome Disparities of β₂ Adrenergic Agonists in Blacks: A Systematic Review.