Exhaled leukotrienes and prostaglandins in COPD

Montuschi, Paolo

doi:10.1136/thorax.58.7.585

Cited by 261 publications

(205 citation statements)

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“…Chronic obstructive pulmonary disease is associated with increased PGE 2 production (Montuschi et al, 2003). The precise sources of PGE 2 production in the lungs of COPD patients are unclear, although it is very probable that other cellular sources contribute to the elevated levels reported to occur in COPD (Martey et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Prostaglandin-E2, an arachidonic acid metabolite that profoundly influences DC function and promotes inflammatory lung responses, is found in elevated concentrations in the exhaled breath of patients with COPD (Montuschi et al, 2003). To determine whether cigarette smoke alters PGE 2 production by maturing DCs, immature and LPS or CD40L-matured human DCs were incubated for 18 hours in the presence or absence of CSE.…”

Section: Cigarette Smoke Extract Induces Pge 2 Production and Intra-cmentioning

confidence: 99%

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Nicotine and oxidative cigarette smoke constituents induce immune-modulatory and pro-inflammatory dendritic cell responses

Vassallo

Kroening

Parambil

et al. 2008

Molecular Immunology

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Chronic airway inflammation is a cardinal feature of chronic obstructive pulmonary disease (COPD), a destructive cigarette smoke-induced lung disease. Although it is apparent that dendritic cells (DCs) are an important constituent of the chronic inflammatory cell influx found in airways of COPD patients, the functional roles of DCs in the pathogenesis of smoking-induced emphysema are unknown. We postulated that DCs activated by cigarette smoke constituents directly participate in the chronic inflammation that characterizes COPD airways. Concordant with this hypothesis, we observed that incubation of DCs with cigarette smoke extract (CSE), and chronic exposure of mice to cigarette smoke, both augmented the generation of neutrophilic chemokines by immature and lipopolysaccharide (LPS) or CD40L-matured DCs. The generation of interleukin-8 (CXCL8/IL-8) by human DCs conditioned with CSE was suppressed by the antioxidant n-acetyl cysteine (NAC), implying the involvement of oxidant sensitive pathways as a primary mechanism involved in the enhanced CXCL8/IL-8 generation. Cigarette smoke extract and nicotine also augment the production of secreted prostaglandin E 2 and intracellular cyclooxygenase-2 (COX-2) in maturing DCs. Whereas NAC suppressed production of CXCL8 by CSEconditioned DCs, it augmented production of PGE 2 and cellular COX-2 levels in maturing DCs. These studies indicate that the stimulation of DCs by cigarette smoke-induced oxidative stress and nicotine promote the generation of pro-inflammatory responses that promote chronic inflammation in smokers. Certain pharmacologic strategies such as anti-oxidant therapy may be only partially effective in mitigating cigarette smoke-induced pro-inflammatory DC-mediated responses in smokers.

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Section: Discussionmentioning

confidence: 99%

Section: Cigarette Smoke Extract Induces Pge 2 Production and Intra-cmentioning

confidence: 99%

Nicotine and oxidative cigarette smoke constituents induce immune-modulatory and pro-inflammatory dendritic cell responses

Vassallo

Kroening

Parambil

et al. 2008

Molecular Immunology

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“…Recent studies have shown the usefulness of induced sputum [8] and exhaled breath condensate [21] for monitoring airway inflammation in COPD patients. Although these methods are noninvasive and useful for examining local inflammation of the airways, they require time and are not suitable for studying large numbers of patients.…”

Section: Discussionmentioning

confidence: 99%

Increased serum concentrations of tissue inhibitor of metalloproteinase-1 in COPD patients

Higashimoto

Yamagata²,

Iwata³

et al. 2005

European Respiratory Journal

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Matrix metalloproteinase (MMP)-9 and tissue inhibitors of metalloproteinase (TIMP)-1 concentrations are increased in the sputum of asthma and chronic bronchitis patients, and are thought to be related to airflow obstruction. However, serum concentrations of these enzymes have not been clearly evaluated in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to examine the serum concentrations of these enzymes in COPD and asthmatic patients in order to determine their relationship with airway obstruction.Serum samples were obtained from 72 patients with COPD: 66 control subjects and 26 patients with asthma. Smoking histories of control subjects were matched with those of COPD patients. Serum concentrations of TIMP-1 and MMP-9 were determined by ELISA.The circulating TIMP-1 concentration was significantly higher in stable COPD patients than in control and asthmatic subjects, and was significantly negatively correlated with forced expiratory volume in one second/forced vital capacity in COPD patients. The molar ratio between MMP-9 and TIMP-1 was significantly lower in COPD patients than in control subjects. In patients with COPD, the serum TIMP-1 concentration was significantly increased during disease exacerbation.In conclusion, the current findings suggest that serum tissue inhibitors of metalloproteinase-1 concentration can be used as a serum marker of airway obstruction and exacerbation in chronic obstructive pulmonary disease patients.KEYWORDS: Bronchial asthma, chronic obstructive pulmonary disease, exacerbation, metalloproteinases, serum markers, tissue inhibitors of matrix metalloproteinases P ulmonary emphysema, the major contributor to morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD), is characterised by progressive destruction of the extracellular matrix (ECM) of the lung [1-4]. The most widely accepted theory of the pathogenesis of pulmonary emphysema is a proteinase-antiproteinase imbalance. Although a number of studies have demonstrated the important role of increased elastolytic activity derived from neutrophils in emphysema [4,5], recent studies have shown that matrix metalloproteinases (MMPs) play key roles in tissue remodelling of the airways in COPD and asthma patients [2,[6][7][8]. MMPs are a family of structurally related enzymes that are capable of degrading all components of the ECM [9]. Members of the MMP family are selectively inhibited by tissue inhibitors of metalloproteinases (TIMPs). TIMP-1 has been shown to bind to both the active and precursor form of MMP-9, in a 1:1 proportion, and to inhibit its enzymatic activity. Sputum concentrations of MMP-9 and TIMP-1 are increased in patients with COPD and asthma [2,10]. RUSSELL et al. [11] showed that alveolar macrophages from patients with COPD release larger amounts of MMP-9 with greater enzymatic activity than those from healthy smokers. Two recent studies found that the MMP-9/TIMP-1 ratio was correlated with the degree of airway obstruction. BOSSE et al. [12]...

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“…In asthma patients, there are no changes in the levels of prostaglandins F 2α and E 2 , (19) whereas these levels are elevated in COPD patients. (20) It is possible that the opposite is true for leukotriene E4, elevated levels of which have been reported in asthma patients but not in COPD patients.…”

Section: Discussionmentioning

confidence: 90%

Temperatura do ar exalado, um novo biomarcador no controle da asma: um estudo piloto

2010

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Objective: To evaluate whether the exhaled breath temperature (EBT), measured by a noninvasive method, is an effective means of monitoring patients with uncontrolled asthma. Methods: A pilot study comprising nine patients (seven women and two men; mean age: 39 years) diagnosed with asthma at least one year prior to the beginning of the study and not having been under maintenance therapy for the last three months. In the first visit, the patients underwent spirometry and measurement of EBT. The patients were then instructed to use inhaled budesonide/formoterol (200/6 µg) every 12 h for six weeks. In addition, the patients with severe asthma (FEV 1 < 60% of predicted) were instructed to use oral prednisolone (40 mg/day) for five days. After six weeks, the patients underwent the same tests. Results: All of the patients reported an improvement in the symptoms of asthma, as confirmed by a statistically significant increase in FEV 1 from the first to the second visit (mean, 56.1% vs. 88.7% of predicted; p < 0.05). Five patients used oral prednisolone for the first five days of the treatment period. Six patients used additional doses of inhaled budesonide/formoterol (mean duration, 2.5 weeks). The EBT decreased significantly from the first to the second visit (mean EBT: 35.1°C vs. 34.1°C; p < 0.05). Conclusions: Uncontrolled asthma, especially during exacerbations, is followed by an increase in EBT, which decreases after appropriate asthma control, as demonstrated by an increase in FEV 1 and an improvement of the reported symptoms. These preliminary results suggest that EBT can be used as a parameter for the assessment of asthma control.Keywords: Asthma; Biomarkers, pharmacological; Hydroxycorticosteroids. ResumoObjetivo: Avaliar se a temperatura do ar exalado (TAE), medida por um método não invasivo, é efetiva no monitoramento de pacientes com asma não controlada. Métodos: Estudo piloto com nove pacientes (sete mulheres e dois homens; média de idade: 39 anos) com diagnóstico de asma por pelo menos um ano e sem uso de tratamento de manutenção por pelo menos três meses antes do início do estudo. Na primeira visita, os pacientes foram submetidos à espirometria e à medida da TAE. Todos os pacientes foram orientados a iniciar tratamento com budesonida/formoterol (200/6 µg) inalatório a cada 12 h por seis semanas. Além disso, os pacientes com asma grave (VEF 1 < 60% do previsto) foram orientados a utilizar prednisolona oral (40 mg/dia) por cinco dias. Após seis semanas, os pacientes foram submetidos aos mesmos testes. Resultados: Todos os pacientes relataram melhora dos sintomas de asma; confirmada por um aumento significativo de VEF 1 da primeira para a segunda visita (média de VEF 1 : 56,1% vs. 88,7% do previsto; p < 0,05). Cinco pacientes utilizaram prednisolona oral, mas somente nos cinco dias iniciais do tratamento. Seis pacientes utilizaram doses extras da medicação inalatória (média de tempo de uso de medicação adicional = 2,5 semanas). Houve uma diminuição significativa da TAE entre os momentos de avaliação ...

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Exhaled leukotrienes and prostaglandins in COPD

Cited by 261 publications

References 23 publications

Nicotine and oxidative cigarette smoke constituents induce immune-modulatory and pro-inflammatory dendritic cell responses

Nicotine and oxidative cigarette smoke constituents induce immune-modulatory and pro-inflammatory dendritic cell responses

Increased serum concentrations of tissue inhibitor of metalloproteinase-1 in COPD patients

Temperatura do ar exalado, um novo biomarcador no controle da asma: um estudo piloto

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