Dataset Information

Inflammatory response mechanisms exacerbating hypoxemia in coexistent pulmonary fibrosis and sleep apnea.

ABSTRACT: Mediators of inflammation, oxidative stress, and chemoattractants drive the hypoxemic mechanisms that accompany pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis commonly have obstructive sleep apnea, which potentiates the hypoxic stimuli for oxidative stress, culminating in systemic inflammation and generalized vascular endothelial damage. Comorbidities like pulmonary hypertension, obesity, gastroesophageal reflux disease, and hypoxic pulmonary vasoconstriction contribute to chronic hypoxemia leading to the release of proinflammatory cytokines that may propagate clinical deterioration and alter the pulmonary fibrotic pathway. Tissue inhibitor of metalloproteinase (TIMP-1), interleukin- (IL-) 1?, cytokine-induced neutrophil chemoattractant (CINC-1, CINC-2?/?), lipopolysaccharide induced CXC chemokine (LIX), monokine induced by gamma interferon (MIG-1), macrophage inflammatory protein- (MIP-) 1?, MIP-3?, and nuclear factor- (NF-) ?B appear to mediate disease progression. Adipocytes may induce hypoxia inducible factor (HIF) 1? production; GERD is associated with increased levels of lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and tumor necrosis factor alpha (TNF-?); pulmonary artery myocytes often exhibit increased cytosolic free Ca2+. Protein kinase C (PKC) mediated upregulation of TNF-? and IL-1? also occurs in the pulmonary arteries. Increased understanding of the inflammatory mechanisms driving hypoxemia in pulmonary fibrosis and obstructive sleep apnea may potentiate the identification of appropriate therapeutic targets for developing effective therapies.

SUBMITTER: Adegunsoye A

PROVIDER: S-EPMC4402194 | biostudies-other | 2015

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Inflammatory response mechanisms exacerbating hypoxemia in coexistent pulmonary fibrosis and sleep apnea.

Adegunsoye Ayodeji A Balachandran Jay J

Mediators of inflammation 20150405

Mediators of inflammation, oxidative stress, and chemoattractants drive the hypoxemic mechanisms that accompany pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis commonly have obstructive sleep apnea, which potentiates the hypoxic stimuli for oxidative stress, culminating in systemic inflammation and generalized vascular endothelial damage. Comorbidities like pulmonary hypertension, obesity, gastroesophageal reflux disease, and hypoxic pulmonary vasoconstriction contribute to chron ...[more]

PMID: 25944985

Similar Datasets

Project description:PurposeObstructive sleep apnea (OSA) is independently associated with increased risk for stroke and other cardiovascular diseases. Since activated platelets play an important role in cardiovascular disease, the objective of this study was to determine whether platelet reactivity was altered in OSA subjects with intermittent nocturnal hypoxemia.MethodsThirty-one subjects, without hypertension or cardiovascular disease and not taking medication, participated in the study. Subjects were stratified based on OSA-related oxygen desaturation index (ODI) recorded during overnight polysomnography. Platelet reactivity to a broad panel of agonists (collagen, thrombin, protease-activated receptor1 hexapeptide, epinephrine, ADP) was measured by monitoring platelet aggregation and ATP secretion. Expression of platelet activation markers CD154 (CD40L) and CD62P (P-selectin) and platelet-monocyte aggregates (PMA) was quantified by flow cytometry.ResultsEpinephrine-induced platelet aggregation was substantially decreased in OSA subjects with significant intermittent hypoxemia (ODI ≥ 15) compared with subjects with milder hypoxemia levels (ODI < 15) (area under curve, p = 0.01). In addition, OSA subjects with ODI ≥ 15 exhibited decreased thrombin-induced platelet aggregation (p = 0.02) and CD40L platelet surface expression (p = 0.05). Platelet responses to the other agonists, CD62P platelet surface expression, and PMA levels were not significantly different between groups. Reduction in platelet responses to epinephrine and thrombin, and decreased CD40L surface marker expression in significant hypoxemic OSA individuals, is consistent with their platelets being in an activated state.ConclusionsIncreased platelet activation was present in otherwise healthy subjects with intermittent nocturnal hypoxemia due to underlying OSA. This prothrombotic milieu in the vasculature is likely a key contributing factor toward development of thrombosis and cardiovascular disease.Trial registrationNCT00859950.

Project description:ImportanceThere are no established measures to prevent nocturnal breathing disturbances and other altitude-related adverse health effects (ARAHEs) among lowlanders with chronic obstructive pulmonary disease (COPD) traveling to high altitude.ObjectiveTo evaluate whether nocturnal oxygen therapy (NOT) prevents nocturnal hypoxemia and breathing disturbances during the first night of a stay at 2048 m and reduces the incidence of ARAHEs.Design, setting, and participantsThis randomized, placebo-controlled crossover trial was performed from January to October 2014 with 32 patients with COPD living below 800 m with forced expiratory volume in the first second of expiration (FEV1) between 30% and 80% predicted, pulse oximetry of at least 92%, not requiring oxygen therapy, and without history of sleep apnea. Evaluations were performed at the University Hospital Zurich (490 m, baseline) and during 2 stays of 2 days and nights each in a Swiss Alpine hotel at 2048 m while NOT or placebo treatment was administered in a randomized order. Between altitude sojourns, patients spent at least 2 weeks below 800 m. Data analysis was performed from January 1, 2015, to December 31, 2018.InterventionDuring nights at 2048 m, NOT or placebo (room air) was administered at 3 L/min by nasal cannula.Main outcomes and measuresCoprimary outcomes were differences between NOT and placebo intervention in altitude-induced change in mean nocturnal oxygen saturation (SpO2) as measured by pulse oximetry and apnea-hypopnea index (AHI) measured by polysomnography during night 1 at 2048 m and analyzed according to the intention-to-treat principle. Further outcomes were the incidence of predefined ARAHE, other variables from polysomnography results and respiratory sleep studies in the 2 nights at 2048 m, clinical findings, and symptoms.ResultsOf the 32 patients included, 17 (53%) were women, with a mean (SD) age of 65.6 (5.6) years and a mean (SD) FEV1 of 53.1% (13.2%) predicted. At 490 m, mean (SD) SpO2 was 92% (2%) and mean (SD) AHI was 21.6/h (22.2/h). At 2048 m with placebo, mean (SD) SpO2 was 86% (3%) and mean (SD) AHI was 34.9/h (20.7/h) (P < .001 for both comparisons). Compared with placebo, NOT increased SpO2 by a mean of 9 percentage points (95% CI, 8-11 percentage points; P < .001), decreased AHI by 19.7/h (95% CI, 11.4/h-27.9/h; P < .001), and improved subjective sleep quality measured on a visual analog scale by 9 percentage points (95% CI, 0-17 percentage points; P = .04). During visits to 2048 m or within 24 hours after descent, 8 patients (26%) using placebo and 1 (4%) using NOT experienced ARAHEs (P < .001).Conclusions and relevanceLowlanders with COPD experienced hypoxemia, sleep apnea, and impaired well-being when staying at 2048 m. Because NOT significantly mitigated these undesirable effects, patients with moderate to severe COPD may benefit from preventive NOT during high altitude travel.Trial registrationClinicalTrials.gov Identifier: NCT02150590.

Dataset Information

Inflammatory response mechanisms exacerbating hypoxemia in coexistent pulmonary fibrosis and sleep apnea.

Publications

Inflammatory response mechanisms exacerbating hypoxemia in coexistent pulmonary fibrosis and sleep apnea.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets