Markers of nitric oxide metabolism in sputum and exhaled air are not increased in chronic obstructive pulmonary disease

416

294

Evidence suggests that eosinophilic airway inflammation is important in the pathogenesis of severe chronic obstructive pulmonary disease (COPD) exacerbations. The present authors tested the hypothesis that a management strategy that aims to reduce sputum eosinophil counts is associated with a reduction in exacerbations of COPD.A total of 82 patients with COPD were randomised into two groups. One group was treated according to traditional guidelines (British Thoracic Society (BTS) group) and the other (sputum group) was treated with the additional aim of minimising eosinophilic airway inflammation, assessed using the induced sputum eosinophil count. The primary outcome was exacerbations, which were categorised as mild, moderate or severe.The frequency of severe exacerbations per patient per year was 0.5 and 0.2 in the BTS and sputum groups, respectively (mean reduction 62%). The majority of this benefit was confined to patients with eosinophilic airway inflammation. There was no difference in the frequency of mild and moderate exacerbations. The average daily dose of inhaled or oral corticosteroids during the trial did not differ between the groups. Out of 42 patients in the sputum group, 17 required regular oral corticosteroids to minimise eosinophilic airway inflammation.A management strategy that aims to minimise eosinophilic airway inflammation, as well as symptoms, is associated with a reduction in severe exacerbations of chronic obstructive pulmonary disease.

Section: Discussionmentioning

confidence: 59%

Eosinophilic airway inflammation and exacerbations of COPD: a randomised controlled trial

Siva

Green²,

Brightling³

et al. 2007

416

294

“…No differences were found between the groups with respect to levels of the neutrophil chemoattractant leukotriene B 4 or neutrophil elastase activity, or in the activity of one of the natural inhibitors of neutrophil elastase, secretory leukoprotease inhibitor [127]. Finally, exhaled NO levels in COPD patients are higher in exsmokers than in smokers and nonsmokers [100,120,121], although one study reported no differences [98]. Since exhaled NO is thought to reflect airway inflammation, this suggests a worsening situation.…”

Section: Chronic Bronchitis or Chronic Obstructive Pulmonary Diseasementioning

confidence: 77%

“…In addition, the percentage of natural killer cells is higher in exsmokers than in smokers [93,94]. In exhaled air, exsmokers show similar nitric oxide levels to nonsmokers, in contrast to the lower levels measured in smokers [95][96][97][98][99][100]. In sputum, interleukin (IL)-8 levels are similar in exsmokers and smokers [101], but remain higher than in nonsmokers [102,103], suggesting that proinflammatory activity might not change after smoking cessation.…”

Section: Subjects Without Chronic Respiratory Symptomsmentioning

confidence: 79%

“…Only a few cross-sectional studies provide any information about the possible effects of smoking cessation in patients with chronic bronchitis or COPD [85,87,88,93,98,100,101,[119][120][121][122][123][124][125]. A major drawback in most of these studies is that they were not originally designed to compare smokers and exsmokers, and, therefore, the number of subjects was often too small to perform separate analyses.…”

Section: Chronic Bronchitis or Chronic Obstructive Pulmonary Diseasementioning

confidence: 99%

See 1 more Smart Citation

The impact of smoking cessation on respiratory symptoms, lung function, airway hyperresponsiveness and inflammation

Willemse¹,

Postma²,

Timens³

et al. 2004

381

235

Smoking is the main risk factor in the development of chronic obstructive pulmonary disease (COPD), and smoking cessation is the only effective treatment for avoiding or reducing the progression of this disease.Despite the fact that smoking cessation is a very important health issue, information about the underlying mechanisms of the effects of smoking cessation on the lungs is surprisingly scarce. It is likely that the reversibility of smoke-induced changes differs between smokers without chronic symptoms, smokers with nonobstructive chronic bronchitis and smokers with COPD. This review describes how these three groups differ regarding the effects of smoking cessation on respiratory symptoms, lung function (forced expiratory volume in one second), airway hyperresponsiveness, and pathological and inflammatory changes in the lung.Smoking cessation clearly improves respiratory symptoms and bronchial hyperresponsiveness, and prevents excessive decline in lung function in all three groups.Data from well-designed studies are lacking regarding the effects on inflammation and remodelling, and the few available studies show contradictory results. In chronic obstructive pulmonary disease, a few histopathological studies suggest that airway inflammation persists in exsmokers. Nevertheless, many studies have shown that smoking cessation improves the accelerated decline in forced expiratory volume in one second, which strongly indicates that important inflammatory and/or remodelling processes are positively affected.

“…The measurement is highly reproducible in normal and asthmatic subjects if careful attention is paid to technique [533]. However, conventionally measured eNO is less useful in COPD as the levels are usually normal or only slightly elevated, except during exacerbations [534][535][536][537][538]. This is likely to be due to the increase in oxidative stress, resulting in the formation of peroxynitrite and nitrate, so that nitric oxide (NO) is removed from the gaseous phase.…”

Section: Nitric Oxidementioning

confidence: 99%

Outcomes for COPD pharmacological trials: from lung function to biomarkers

Cazzola¹,

MacNee²,

Martínez³

et al. 2008

751

566

The American Thoracic Society/European Respiratory Society jointly created a Task Force on “Outcomes for COPD pharmacological trials: from lung function to biomarkers” to inform the chronic obstructive pulmonary disease research community about the possible use and limitations of current outcomes and markers when evaluating the impact of a pharmacological therapy. Based on their review of the published literature, the following document has been prepared with individual sections that address specific outcomes and markers, and a final section that summarises their recommendations.