l-Arginine supplementation in severe asthma

Liao, Shu‐Yi; Showalter, Megan R.; Linderholm, A.; Franzi, Lisa M.; Kivler, Celeste; Yao, Li; Michael, R.; Kons, Zachary A.; Fiehn, Oliver; Qi, Lihong; Zeki, Amir A.; Kenyon, Nicholas J.

doi:10.1172/jci.insight.137777

Cited by 22 publications

(20 citation statements)

References 47 publications

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“…In a more recent study, oral L-arginine supplementation in severe asthmatics and low FeNO also did not reduce asthma exacerbation rates. However, the higher plasma L-citrulline levels in this study were associated with increased FeNO (Liao et al, 2020).…”

Section: Asthmacontrasting

confidence: 74%

Arginine Therapy for Lung Diseases

et al. 2021

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Nitric oxide (NO) is produced by a family of isoenzymes, nitric oxide synthases (NOSs), which all utilize L-arginine as substrate. The production of NO in the lung and airways can play a number of roles during lung development, regulates airway and vascular smooth muscle tone, and is involved in inflammatory processes and host defense. Altered L-arginine/NO homeostasis, due to the accumulation of endogenous NOS inhibitors and competition for substrate with the arginase enzymes, has been found to play a role in various conditions affecting the lung and in pulmonary diseases, such as asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), pulmonary hypertension, and bronchopulmonary dysplasia. Different therapeutic strategies to increase L-arginine levels or bioavailability are currently being explored in pre-clinical and clinical studies. These include supplementation of L-arginine or L-citrulline and inhibition of arginase.

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Section: Asthmacontrasting

confidence: 74%

Arginine Therapy for Lung Diseases

et al. 2021

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“…In a subgroup of 28 subjects, 8 individuals responded to the treatment with at least 33% reduction in exacerbation [74]. Although no significant decrease in asthma exacerbation was observed, potential biomarkers including prostaglandin H2 and Nα-acetyl-L-arginine were found to distinguish responders versus non-responders [74]. Further work is required to validate these markers, and a larger sample size would allow for determination of the significance of L-arginine treatment in patients with severe asthma.…”

Section: Targeting Arginine Metabolismmentioning

confidence: 94%

“…As CS exposure alters arginine metabolism in asthma, targeting arginine metabolism in treating severe asthma was a potential approach. Liao and his colleagues have examined clinical effects of L-arginine supplement in patients with severe asthma [74]. Because high fractional exhaled NO (FeNO) attributed to iNOS activity indicates an increase of arginine turnover and worse clinical outcomes, L-arginine supplement was given to asthmatic patients with low or high FeNO, and their accidents of exacerbation were evaluated after 3-month treatment [74].…”

Section: Targeting Arginine Metabolismmentioning

confidence: 99%

“…Liao and his colleagues have examined clinical effects of L-arginine supplement in patients with severe asthma [74]. Because high fractional exhaled NO (FeNO) attributed to iNOS activity indicates an increase of arginine turnover and worse clinical outcomes, L-arginine supplement was given to asthmatic patients with low or high FeNO, and their accidents of exacerbation were evaluated after 3-month treatment [74]. In a subgroup of 28 subjects, 8 individuals responded to the treatment with at least 33% reduction in exacerbation [74].…”

Section: Targeting Arginine Metabolismmentioning

confidence: 99%

“…Because high fractional exhaled NO (FeNO) attributed to iNOS activity indicates an increase of arginine turnover and worse clinical outcomes, L-arginine supplement was given to asthmatic patients with low or high FeNO, and their accidents of exacerbation were evaluated after 3-month treatment [74]. In a subgroup of 28 subjects, 8 individuals responded to the treatment with at least 33% reduction in exacerbation [74]. Although no significant decrease in asthma exacerbation was observed, potential biomarkers including prostaglandin H2 and Nα-acetyl-L-arginine were found to distinguish responders versus non-responders [74].…”

Section: Targeting Arginine Metabolismmentioning

confidence: 99%

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Metabolic reprogramming: A driver of cigarette smoke-induced inflammatory lung diseases

Yang

Chen

2021

Free Radical Biology and Medicine

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Cigarette smoking is a well-known risk factor for pulmonary diseases, including chronic obstructive pulmonary disease (COPD), asthma and pulmonary fibrosis. Despite major progress in dissecting the mechanisms associated with disease development and progression, findings only represent one aspect of multifaceted disease. A crucial consequence of this approach is that many therapeutic treatments often fail to improve or reverse the disease state as other conditions and variables are insufficiently considered. To expand our understanding of pulmonary diseases, omics approaches, particularly metabolomics, has been emerging in the field. This strategy has been applied to identify putative biomarkers and novel mechanistic insights. In this review, we discuss metabolic profiles of patients with COPD, asthma, and idiopathic pulmonary fibrosis (IPF) with a focus on the direct effects of cigarette smoking in altering metabolic regulation. We next present cell-and animal-based experiments and point out the therapeutic potential of targeting metabolic reprogramming in inflammatory lung diseases. In addition, the obstacles in translating these findings into clinical practice, including potential adverse effects and limited pharmacological efficacy, are also addressed.

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L‐arginine as a potential GLP‐1‐mediated immunomodulator of Th17‐related cytokines in people with obesity and asthma

Liao

Linderholm

Showalter

et al. 2021

Obesity Science & Practice

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Obesity is considered as a risk factor for COVID-19 with insulin resistance and increased production of inflammatory cytokines as likely mechanisms. Glucagon-like peptide-1 (GLP-1) agonists and inhaled nitric oxide are proposed therapeutic approaches to treat COVID-19 because of their broad anti-inflammatory effects. One approach that might augment GLP-1 levels would be dietary supplementation with L-arginine. Beyond cytokines, multiple studies have started to investigate the relationship between new-onset diabetes and COVID-19. In a posthoc analysis of a randomized, placebo-controlled human clinical trial of L-arginine supplementation in people with asthma and predominantly with obesity, the results showed that 12 weeks of continuous L-arginine supplementation significantly decreased the level of IL-21 (p = 0.02) and increased the level of insulin (p = 0.02). A high arginine level and arginine/ADMA ratio were significantly associated with lower CCL-20 and TNFα levels. The study also showed that L-arginine supplementation reduces cytokine levels and improves insulin deficiency or resistance, both are two big risk factors for COVID-19 severity and mortality. Given its safety profile and ease of accessibility, L-arginine is an attractive potential therapeutic option that allows for a costeffective way to improve outcomes in patients. An expedition of further investigation or clinical trials to test these hypotheses is needed.

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l-Arginine supplementation in severe asthma

Cited by 22 publications

References 47 publications

Arginine Therapy for Lung Diseases

Arginine Therapy for Lung Diseases

Metabolic reprogramming: A driver of cigarette smoke-induced inflammatory lung diseases

L‐arginine as a potential GLP‐1‐mediated immunomodulator of Th17‐related cytokines in people with obesity and asthma

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