Pulmonary vascular dysfunction in end-stage cystic fibrosis: role of NF-κB and endothelin-1

Henno, Priscilla; Maurey, Christelle; Danel, Claire; Bonnette, Peter C.; Souilamas, Rédha; Stern, M.; Delclaux, Christophe; Lévy, Marilyne; Israël‐Biet, Dominique

doi:10.1183/09031936.00186908

Cited by 30 publications

(25 citation statements)

References 43 publications

(56 reference statements)

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“…It is likely that use of a threshold value of S pO 2 Ͻ 90% identifies a group with lower absolute oxyhemoglobin saturation during exercise and may reflect a greater impairment of the pulmonary vasculature, thought to occur frequently in end-stage CF. 20 This highlights the importance of using standardized definitions for desaturation, in order to compare data across trials.…”

Section: Discussionmentioning

confidence: 99%

Desaturation During the 3-Minute Step Test Predicts Impaired 12-Month Outcomes in Adult Patients With Cystic Fibrosis

et al. 2011

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BACKGROUND:The 3-minute step test is a simple test of exercise capacity for children with cystic fibrosis (CF), but no data have been reported regarding its usefulness in adults or its prognostic value. OBJECTIVE: To determine the feasibility and acceptability of the 3-minute step test as a test of exercise capacity in adults with CF and whether test performance is associated with 12-month clinical outcomes. METHODS: From our out-patient clinic we prospectively recruited consecutive adult patients with CF in stable health. The 3-minute step test was conducted with a standardized protocol that included a 15-cm high step and external pacing at 30 steps/min. We measured heart rate, dyspnea, and S pO 2 . With multiple linear regression analyses we assessed the relationships between step-test performance and change in FEV 1 and hospital days at 12 months. RESULTS: The participants were 101 adults: 56 male, mean ؎ SD age 29 ؎ 9 years, percent-of-predicted FEV 1 61 ؎ 23%, body mass index 22 ؎ 4 kg/m 2 . Only 42% of the participants with mild CF achieved 70% of the predicted maximum heart rate during the 3-minute step test, compared to 77% of those with FEV 1 < 60% of predicted. The 22 patients who desaturated to < 90% during the 3-minute step test had a larger number of hospital days over the following 12 months than did those who did not (median 28 d vs 11 d, P < .001). Those who desaturated also had a greater FEV 1 decline (mean difference ؊117 mL, 95% CI ؊215 to ؊19 mL). Desaturation during the 3-minute step test was an independent predictor of both FEV 1 decline and days spent in hospital. CONCLUSIONS: Desaturation during the 3-minute step test is associated with long-term pulmonary deterioration and more hospital days in adults with CF. The 3-minute step test may be a useful screening test for patients with moderate to severe CF lung disease, who require increased intervention and monitoring.

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Section: Discussionmentioning

confidence: 99%

Desaturation During the 3-Minute Step Test Predicts Impaired 12-Month Outcomes in Adult Patients With Cystic Fibrosis

et al. 2011

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“…accordingly to previous experiments done in an historical group of non smokers. We previously demonstrated that the decrease in vascular reactivity was not due to endothelial damage during manipulations [7].…”

Section: Arterial Experimentsmentioning

confidence: 92%

“…Arterial rings were evaluated immediately after dissection, whereas bronchial rings were placed in oxygenated Krebs's solution and stored overnight at 4°C, as previously described [5,7,8].…”

Section: Pharmacological Studiesmentioning

confidence: 99%

Association of ex vivo vascular and bronchial dysfunctions in smokers

Oualha¹,

Boitiaux²,

Tadié³

et al. 2011

Pulmonary Pharmacology & Therapeutics

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Word count: 204Background. It has recently been shown that systemic endothelial dysfunction is associated with airflow limitation in COPD. We conducted this ex vivo study to assess whether endothelial dysfunction of pulmonary arteries of former smokers was associated with modifications of airway functions. Conclusion. Endothelial dysfunction of pulmonary arteries is associated with increasedresting tone and impaired cGMP-mediated dilation of airways in former smokers, suggesting common underlying mechanisms of pulmonary arterial and bronchial dysfunctions.

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“…It has also been shown to be induced by oxidants with such induction also lowered by antioxidants [202][203][204]. e activity of ET-1 has been shown to be increased by both NF-B action and also the action of another in�ammatory cytokine activated pathway [205][206][207]. us, the in�ammatory part of the NO/ONOO − cycle has a powerful role in increasing ET-1 activity.…”

Section: Principlementioning

confidence: 99%

“…It increases oxidative stress [211][212][213][214][215][216][217], superoxide [211,[213][214][215][216], the ONOO − marker 3-nitrotyrosine [211,212], NF-B activity [211,217], and NO [211,213,218], lowers levels of BH4 [213-215, 217, 219], stimulates iNOS induction [211,217], increases TRP receptor function [220,221], increases levels of intracellular calcium [222][223][224], increases NMDA activity [225,226], produces mitochondrial dysfunction [227,228], and increases in�ammatory cytokine levels [206,207,217]. All of these provide evidence for elevation of each of the NO/ONOO − cycle elements.…”

Section: Principlementioning

confidence: 99%

Pulmonary Hypertension Is a Probable NO/ONOO⁻Cycle Disease: A Review

Pall

2013

ISRN Hypertension

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e NO/ONOO − cycle is a primarily local biochemical/physiological vicious cycle that appears to cause a series of chronic in�ammatory diseases. is paper focuses on whether the cycle causes pulmonary arterial hypertension (PAH) when located in the pulmonary arteries. e cycle involves 12 elements, including superoxide, peroxynitrite (ONOO − ), nitric oxide (NO), oxidative stress, NF-B, in�ammatory cytokines, iNOS, mitochondrial dysfunction, intracellular calcium, tetrahydrobiopterin depletion, NMDA activity, and TRP receptor activity. 10 of the 12 are elevated in PAH (NMDA?, NO?) and 11 have documented causal roles in PAH. Each stressor that initiates cases of PAH acts to raise cycle elements, and may, therefore, initiate the cycle in this way. PAH involves a primarily local mechanism as required by the cycle and the symptoms and signs of PAH are generated by elements of the cycle. Endothelin-1, which acts as a causal factor in PAH, acts as part of the cycle; its synthesis is stimulated by cycle elements, and it, in turn, increases each element of the cycle. is extraordinary �t to the principles of the NO/ONOO − cycle allows one to conclude that PAH is a NO/ONOO − cycle disease, and this �t supports the cycle as a ma�or paradigm of chronic in�ammatory disease.

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Pulmonary vascular dysfunction in end-stage cystic fibrosis: role of NF-κB and endothelin-1

Cited by 30 publications

References 43 publications

Desaturation During the 3-Minute Step Test Predicts Impaired 12-Month Outcomes in Adult Patients With Cystic Fibrosis

Desaturation During the 3-Minute Step Test Predicts Impaired 12-Month Outcomes in Adult Patients With Cystic Fibrosis

Association of ex vivo vascular and bronchial dysfunctions in smokers

Pulmonary Hypertension Is a Probable NO/ONOO⁻Cycle Disease: A Review

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Pulmonary vascular dysfunction in end-stage cystic fibrosis: role of NF-κB and endothelin-1

Cited by 30 publications

References 43 publications

Desaturation During the 3-Minute Step Test Predicts Impaired 12-Month Outcomes in Adult Patients With Cystic Fibrosis

Desaturation During the 3-Minute Step Test Predicts Impaired 12-Month Outcomes in Adult Patients With Cystic Fibrosis

Association of ex vivo vascular and bronchial dysfunctions in smokers

Pulmonary Hypertension Is a Probable NO/ONOO−Cycle Disease: A Review

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Pulmonary Hypertension Is a Probable NO/ONOO⁻Cycle Disease: A Review