Variability of the Pulmonary Vascular Response to Acute Hypoxia in Chronic Bronchitis

Weitzenblum, E; Schrijen, F; T, Mohan-Kumar; Francs, V. Colas Des; Lockhart, A

doi:10.1378/chest.94.4.772

Cited by 66 publications

(42 citation statements)

References 18 publications

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“…At the present time, there is no specific and effective treatment for this condition and current therapeutic success is unsatisfactory because of limited insight into disease mechanisms [43]. Several pathophysiological processes have been involved in the pathogenesis of PH in COPD, namely: a) an increase in vascular pulmonary resistance due to capillary loss (alveolar destruction), b) pulmonary arterial vasoconstriction secondary to alveolar hypoxia, and c) vascular remodelling and proliferation of SMC in pulmonary arterioles that are normally non-muscular [44,45].…”

Section: Discussionmentioning

confidence: 99%

Pulmonary hypertension in smoking mice over-expressing protease-activated receptor-2

Cunto¹,

Cardini²,

Cirino³

et al. 2010

Eur Respir J

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The mechanism(s) involved in the development of pulmonary hypertension (PH) in COPD is still the object of investigation. Cigarette smoke (CS) may lead to remodelling of intrapulmonary vessels and dynamic changes in vascular function, at least in some smokers. A role for proteases in PH has been recently put forward.We investigated, in smoking mice, the role of protease-activated receptor (PAR)-2 in the pathogenesis of PH associated with emphysema.We demonstrated that CS exposure can modulate PAR-2 expression in mouse lung. Acute CS exposure induces in wildtype (WT) and in transgenic mice over-expressing PAR-2 (FVB PAR-2-TgN ) a similar degree of neutrophil influx in bronchoalveolar lavage fluids. After chronic CS exposure WT and FVB PAR-2-TgN mice show emphysema, but only transgenic mice develop muscularisation of small intrapulmonary vessels that precedes the development of PH (,45% increase) and right ventricular hypertrophy. Smoking in FVB PAR-2-TgN mice results in an imbalance between vasoconstrictors (especially endothelin-1) and vasodilators (i.e. vascular endothelial growth factor, endothelial nitric oxide synthase and inducible nitric oxide synthase) and enhanced production of growth factors involved both in fibroblast-smooth muscle cell transaction (i.e. platelet-derived growth factor (PDGF) and transforming growth factor b) and vascular cell proliferation (PDGF). PAR-2 signalling can influence the production and release of many factors, which may play a role in the development of PH in smokers.

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Section: Discussionmentioning

confidence: 99%

Pulmonary hypertension in smoking mice over-expressing protease-activated receptor-2

Cunto¹,

Cardini²,

Cirino³

et al. 2010

Eur Respir J

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“…Right heart catheterization was separated from polysomnography by no more than 1 week, and was performed as reported previously [21]. Briefly, patients were investigated in the supine position, in the morning, after a light breakfast.…”

Section: Methodsmentioning

confidence: 99%

Sleep-related O2 desaturation and daytime pulmonary haemodynamics in COPD patients with mild hypoxaemia

Chaouat¹,

Weitzenblum²,

Kessler³

et al. 1997

Eur Respir J

157

102

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It has been hypothesized but not firmly established that sleep-related hypoxaemia could favour the development of pulmonary hypertension in chronic obstructive pulmonary disease (COPD) patients without marked daytime hypoxaemia.We have investigated the relationships between pulmonary function data, sleeprelated desaturation and daytime pulmonary haemodynamics in a group of 94 COPD patients not qualifying for conventional O 2 therapy (daytime arterial oxygen tension (Pa,O 2 ) in the range 7.4-9.2 kPa (56-69 mmHg)). Nocturnal desaturation was defined by spending ≥30% of the recording time with a transcutaneous O 2 saturation <90%. An obstructive sleep apnoea syndrome was excluded by polysomnography.Sixty six patients were desaturators (Group 1) and 28 were nondesaturators (Group 2). There was no significant difference between Groups 1 and 2 with regard to pulmonary volumes and Pa,O 2 (8.4±0.6 vs 8.4±0.4 kPa (63±4 vs 63±3 mmHg)) but arterial carbon dioxide tension (Pa,CO 2 ) was higher in Group 1 (6.0±0.7 vs 5.3±0.5 kPa (45±5 vs 40±4 mmHg); p<0.0001). Mean pulmonary artery pressure (Ppa) was very similar in the two groups (2.6±0.7 vs 2.5±0.6 kPa (19±5 vs 19±4 mmHg)). No individual variable or combination of variables could predict the presence of pulmonary hypertension.It is concluded that in these patients with chronic obstructive pulmonary disease with modest daytime hypoxaemia, functional and gasometric variables (with the noticeable exception of arterial carbon dioxide tension) cannot predict the presence of nocturnal desaturation; and that mean pulmonary artery pressure is not correlated with the degree and duration of nocturnal hypoxaemia. These results do not support the hypothesis that sleep-related hypoxaemia favours the development of pulmonary hypertension. Eur Respir J 1997; 10: 1730-1735 The worsening of hypoxaemia during sleep in patients with chronic obstructive pulmonary disease (COPD) has been documented since the early 1960s [1], and has since been confirmed by polysomnographic studies [2,3], which have included continuous monitoring of oxygen saturation from the late 1970s [4][5][6][7][8][9][10]. It must be emphasized that most of these studies have included patients with severe COPD exhibiting marked daytime hypoxaemia. Is sleep-related hypoxaemia present in patients with less severe COPD with mild or absent daytime hypoxaemia? Several studies of the literature [11][12][13] have shown that a relatively high percentage of these COPD patients exhibit significant nocturnal hypoxaemia, which naturally raises the question: Does this hypoxaemia, limited to sleep, deserve treatment with nocturnal oxygen? Such a treatment could be justified if nocturnal hypoxaemia had deleterious effects on life expectancy, which is rather controversial [14,15], and on pulmonary haemodynamics. It has been hypothesized [16,17] that isolated nocturnal hypoxaemia, occurring in patients without significant daytime hypoxaemia, could lead to permanent (daytime) pulmonary hypertension, but this hypothesis has not, so...

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“…The development of PH in COPD has been attributed to several mechanisms, including alveolar hypoxia with resultant vasoconstriction and vascular remodelling, destruction of the pulmonary vascular bed and compression of alveolar vessels in hyperinflated emphysematous lungs. Severe PH has been postulated to occur in susceptible individuals with more marked hypoxic vasoconstrictive response, such as serotonin transporter gene polymorphism [8,9], or possible co-existent lung and idiopathic pulmonary vascular disease. The 5th World Symposium on Pulmonary Hypertension suggested criteria for discriminating between World Health Organization group 1 ( pulmonary arterial hypertension (PAH)) and group 3 (PH due to lung disease) disease and a classification system for patients with severe PH and lung disease [10].…”

Section: Introductionmentioning

confidence: 99%

Severe pulmonary hypertension in lung disease: phenotypes and response to treatment

et al. 2015

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Pulmonary hypertension (PH) due to lung disease (World Health Organization (WHO) group 3) is common, but severe PH, arbitrarily defined as mean pulmonary artery pressure ⩾35 mmHg is reported in only a small proportion. Whether these should be treated as patients in WHO group 1 (i.e. pulmonary arterial hypertension) with PH-targeted therapies is unknown.We compared the phenotypic characteristics and outcomes of 118 incident patients with severe PH and lung disease with 74 idiopathic pulmonary arterial hypertension (IPAH) patients, all treated with pulmonary vasodilators.Lung disease patients were older, more hypoxaemic, and had lower gas transfer, worse New York Heart Association functional class and lower 6-min walking distance (6MWD) than IPAH patients. Poorer survival in those with lung disease was driven by the interstitial lung disease (ILD) cohort.In contrast to IPAH, where significant improvements in 6MWD and N-terminal pro-brain natruiretic peptide (NT-proBNP) occurred, PH therapy in severe PH lung disease did not lead to improvement in 6MWD or functional class, but neither was deterioration seen. NT-proBNP decreased from 2200 to 1596 pg·mL −1 ( p=0.015). Response varied by lung disease phenotype, with poorer outcomes in patients with ILD and emphysema with preserved forced expiratory volume in 1 s. Further study is required to investigate whether vasodilator therapy may delay disease progression in severe PH with lung disease. @ERSpublications Treatment of severe pulmonary hypertension associated with lung disease can improve or stabilise noninvasive outcomes

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Variability of the Pulmonary Vascular Response to Acute Hypoxia in Chronic Bronchitis

Cited by 66 publications

References 18 publications

Pulmonary hypertension in smoking mice over-expressing protease-activated receptor-2

Pulmonary hypertension in smoking mice over-expressing protease-activated receptor-2

Sleep-related O2 desaturation and daytime pulmonary haemodynamics in COPD patients with mild hypoxaemia

Severe pulmonary hypertension in lung disease: phenotypes and response to treatment

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