Dataset Information

Lack of Effect of Oral Sulforaphane Administration on Nrf2 Expression in COPD: A Randomized, Double-Blind, Placebo Controlled Trial.

ABSTRACT:

Background

COPD patients have high pulmonary and systemic oxidative stress that correlates with severity of disease. Sulforaphane has been shown to induce expression of antioxidant genes via activation of a transcription factor, nuclear factor erythroid-2 related factor 2 (Nrf2).

Methods

This parallel, placebo-controlled, phase 2, randomized trial was conducted at three US academic medical centers. Patients who met GOLD criteria for COPD and were able to tolerate bronchoscopies were randomly assigned (1:1:1) to receive placebo, 25 ?moles, or 150 ?moles sulforaphane daily by mouth for four weeks. The primary outcomes were changes in Nrf2 target gene expression (NQ01, HO1, AKR1C1 and AKR1C3) in alveolar macrophages and bronchial epithelial cells. Secondary outcomes included measures of oxidative stress and airway inflammation, and pulmonary function tests.

Results

Between July 2011 and May 2013, 89 patients were enrolled and randomized. Sulforaphane was absorbed in the patients as evident from their plasma metabolite levels. Changes in Nrf2 target gene expression relative to baseline ranged from 0.79 to 1.45 and there was no consistent pattern among the three groups; the changes were not statistically significantly different from baseline. Changes in measures of inflammation and pulmonary function tests were not different among the groups. Sulforaphane was well tolerated at both dose levels.

Conclusion

Sulforaphane administered for four weeks at doses of 25 ?moles and 150 ?moles to patients with COPD did not stimulate the expression of Nrf2 target genes or have an effect on levels of other anti-oxidants or markers of inflammation.

Trial registration

Clinicaltrials.gov: NCT01335971.

SUBMITTER: Wise RA

PROVIDER: S-EPMC5104323 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Lack of Effect of Oral Sulforaphane Administration on Nrf2 Expression in COPD: A Randomized, Double-Blind, Placebo Controlled Trial.

Wise Robert A RA Holbrook Janet T JT Criner Gerard G Sethi Sanjay S Rayapudi Sobharani S Sudini Kuladeep R KR Sugar Elizabeth A EA Burke Alyce A Thimmulappa Rajesh R Singh Anju A Talalay Paul P Fahey Jed W JW Berenson Charles S CS Jacobs Michael R MR Biswal Shyam S

PloS one 20161110 11

<h4>Background</h4>COPD patients have high pulmonary and systemic oxidative stress that correlates with severity of disease. Sulforaphane has been shown to induce expression of antioxidant genes via activation of a transcription factor, nuclear factor erythroid-2 related factor 2 (Nrf2).<h4>Methods</h4>This parallel, placebo-controlled, phase 2, randomized trial was conducted at three US academic medical centers. Patients who met GOLD criteria for COPD and were able to tolerate bronchoscopies we ...[more]

PMID: 27832073

Similar Datasets

Project description:Background and aimsObservational data indicate that diets rich in fruits and vegetables have a positive effect on inflammatory status, improve metabolic resilience and may protect against the development of non-communicable diseases. Nevertheless, experimental evidence demonstrating a causal relationship between nutrient intake (especially whole foods) and changes in metabolic health is scarce. This study investigated the pleiotropic effects of sulforaphane from broccoli sprouts, compared to pea sprouts, on biomarkers of endothelial function, inflammation and metabolic stress in healthy participants subjected to a standardized caloric challenge.MethodsIn this double-blind, crossover, randomized, placebo-controlled trial 12 healthy participants were administered 16 g broccoli sprouts, or pea sprouts (placebo) followed by the standardized high-caloric drink PhenFlex given to disturb healthy homeostasis. Levels of inflammatory biomarkers and metabolic parameters were measured in plasma before and 2 h after the caloric overload.ResultsAdministration of broccoli sprouts promoted an increase in levels of CCL-2 induced by caloric load (p = 0.017). Other biomarkers (sICAM-1, sVCAM-1, hs-CRP, and IL-10) individually showed insignificant tendencies toward increase with administration of sulforaphane. Combining all studied biomarkers into the systemic low-grade inflammation score further confirmed upregulation of the inflammatory activity (p = 0.087) after sulforaphane. No significant effects on biomarkers of metabolic stress were detected.ConclusionThis study has demonstrated that sulforaphane facilitated development of a mild pro-inflammatory state during the caloric challenge, which could be suggestive of the onset of the hormetic response induced by this phytonutrient. The use of integrative outcomes measures such as the systemic low-grade inflammation score can be viewed as a more robust approach to study the subtle and pleiotropic effects of phytonutrients.Clinical trial registration:www.clinicaltrials.gov, identifier NCT05146804.

Project description:ObjectivesDetermine the effect of twice-daily chlorhexidine oral rinses on oral and lung microbiota biomass and respiratory symptoms.SettingSingle centre.ParticipantsParticipants were aged 40-85 with chronic obstructive pulmonary disease (COPD) and chronic productive cough or COPD exacerbation within the last year. Exclusions included antibiotics in the previous 2 months and/or those with less than four teeth. Forty-four participants were recruited and 40 completed the study.InterventionParticipants were randomised 1:1 to twice-daily 0.12% chlorhexidine oral rinses versus placebo for 2 months along with daily diaries. St. George's Respiratory Questionnaire (SGRQ), blood tests, oral rinse and induced sputum were collected at randomisation and the final visit.Primary and secondary outcomesPrimary outcome was a change in oral and sputum microbiota biomass. Secondary outcomes included: sputum and oral microbiota Shannon and Simpson diversity and taxonomy; inflammatory markers; Breathlessness, Cough and Sputum Scale and SGRQ scores.ResultsNeither the oral microbiota nor the sputum microbiota biomass decreased significantly in those using chlorhexidine compared with placebo (oral microbiota mean log10 difference (SE)=-0.103 (0.23), 95% CI -0.59 to 0.38, p=0.665; sputum microbiota 0.80 (0.46), 95% CI -0.15 to 1.75, p=0.096). Chlorhexidine decreased both oral and sputum microbiota alpha (Shannon) diversity (linear regression estimate (SE) oral: -0.349 (0.091), p=0.001; sputum -0.622 (0.169), p=0.001). Chlorhexidine use did not decrease systemic inflammatory markers compared with placebo (C reactive protein (chlorhexidine 1.8±7.5 vs placebo 0.4±6.8, p=0.467), fibrinogen (22.5±77.8 vs 10.0±77.0, p=0.406) or leucocytes (0.2±1.8 vs 0.5±1.8, p=0.560)). Chlorhexidine use decreased SGRQ scores compared with placebo (chlorhexidine -4.7±8.0 vs placebo 1.7±8.9, p=0.032).ConclusionsWe did not detect a significant difference in microbiota biomass due to chlorhexidine use. Chlorhexidine decreased oral and sputum microbiota alpha diversity and improved respiratory health-related quality of life compared with placebo.Trial registrationNCT02252588.

Project description:BackgroundChronic Obstructive Pulmonary Disease (COPD) is a progressive airway disease characterised by neutrophilic airway inflammation or bronchitis. Neutrophilic bronchitis is associated with both bacterial colonisation and lung function decline and is common in exacerbations of COPD. Despite current available therapies to control inflammation, neutrophilic bronchitis remains common. This study tested the hypothesis that azithromycin treatment, as an add-on to standard medication, would significantly reduce airway neutrophil and neutrophils chemokine (CXCL8) levels, as well as bacterial load. We conducted a randomised, double-blind, placebo-controlled study in COPD participants with stable neutrophilic bronchitis.MethodsEligible participants (n?=?30) were randomised to azithromycin 250 mg daily or placebo for 12 weeks in addition to their standard respiratory medications. Sputum was induced at screening, randomisation and monthly for a 12 week treatment period and processed for differential cell counts, CXCL8 and neutrophil elastase assessment. Quantitative bacteriology was assessed in sputum samples at randomisation and the end of treatment visit. Severe exacerbations where symptoms increased requiring unscheduled treatment were recorded during the 12 week treatment period and for 14 weeks following treatment. A sub-group of participants underwent chest computed tomography scans (n?=?15).ResultsNine participants with neutrophilic bronchitis had a potentially pathogenic bacteria isolated and the median total bacterial load of all participants was 5.22×107 cfu/mL. Azithromycin treatment resulted in a non-significant reduction in sputum neutrophil proportion, CXCL8 levels and bacterial load. The mean severe exacerbation rate was 0.33 per person per 26 weeks in the azithromycin group compared to 0.93 exacerbations per person in the placebo group (incidence rate ratio (95%CI): 0.37 (0.11,1.21), p?=?0.062). For participants who underwent chest CT scans, no alterations were observed.ConclusionsIn stable COPD with neutrophilic bronchitis, add-on azithromycin therapy showed a trend to reduced severe exacerbations sputum neutrophils, CXCL8 levels and bacterial load. Future studies with a larger sample size are warranted.Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12609000259246.

Dataset Information

Lack of Effect of Oral Sulforaphane Administration on Nrf2 Expression in COPD: A Randomized, Double-Blind, Placebo Controlled Trial.

Background

Methods

Results

Conclusion

Trial registration

Publications

Lack of Effect of Oral Sulforaphane Administration on Nrf2 Expression in COPD: A Randomized, Double-Blind, Placebo Controlled Trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets