methodology-for-sputum-induction-and-laboratory-processing

Methodology for Sputum Induction and Laboratory Processing

The technique of sputum induction and processing is a recognized non-invasive method allowing the collection and analysis of cells from the airways, which ...

University of Liege

Tiotropium is a long-acting anticholinergic bronchodilator, inhaled only once a day, which produces relaxation of airway smooth muscle through antagonism of acetylcholine at M3-muscarinic receptors. Its duration of action is at least 24 h with once daily administration of tiotropium. Several studies have shown its efficacy and its good tolerance in the treatment of patients who are suffering from moderate to very severe chronic obstructive pulmonary disease (COPD). Tiotropium improves spirometric measurements and quality of life, and reduces dyspnea and exacerbation rate in COPD patients.

[Tiotropium: a new therapeutic option in chronic obstructive pulmonary disease].

This study evaluates the accuracy of [F]fluorodeoxyglucose positron emission tomography (F-FDG PET) imaging with semi-quantitative analysis for differentiating benign from malignant pleural exudates and for guiding the search for the primary tumour of pleural metastases.

18F-FDG PET imaging in assessing exudative pleural effusions.

Exacerbations of chronic obstructive pulmonary disease (COPD) play a very important role. Unfortunately they were neglected a long time in the therapeutic tests. However exacerbations influence the decline of the respiratory function over time, cause important deterioration of the quality of life of the patients, increase morbidity and mortality of COPD, and finally represent a burden for health care. Reducing the number of exacerbations could potentially slow down the progression of the disease. Thus the prevention of exacerbations should be the "corner stone" of the maintenance treatment of the COPD. In this review we propose to recall the importance of exacerbations in COPD and to present the treatment which have been shown to reduce exacerbation rate in COPD.

[Exacerbations in COPD: a burden to curtail].

Several chemoattractants have been measured in exhaled breath condensate (EBC) from patients with COPD. The aim of this study was to compare the eosinophil and neutrophil chemotactic activity contained in EBC from healthy subjects and patients with COPD.

Granulocyte chemotactic activity in exhaled breath condensate of healthy subjects and patients with COPD.

The TORCH study (Towards a Revolution in COPD Health) was a double-blind, randomised, placebo-controlled clinical trial, investigating the combination of salmeterol/fluticasone propionate for 3 years in COPD. The primary end point was on all-cause mortality. Secondary end points included COPD exacerbation rate, lung function and health status. More than 6000 patients were randomised. In this article, we briefly report the most significant results of the study. The efficacy on mortality (reduction of the risk of death of 17.5%) was near the predetermined level of statistical significance (p = 0.052); the combination had a significant effect on the three pillars of COPD management, that is: improvement of quality of life and respiratory function, and reduction of the rate of exacerbations. In addition to being effective, the combination salmeterol/fluticasone (50/500 microg 2x/day) is well tolerated in COPD and had a favourable benefit/risk ratio.

[Clinical study of the month: the TORCH study (TOwards a Revolution in COPD Health)].

We evaluate the accuracy of pleural interleukine-6 (IL-6), transforming growth factor-beta 1 (TGF-beta1), and vascular endothelial growth factor (VEGF) levels for differentiating benign from malignant pleural exudates.

Diagnostic value of interleukine-6, transforming growth factor-beta 1 and vascular endothelial growth factor in malignant pleural effusions.

The intensity of the [F]fluorodeoxyglucose (F-FDG) uptake is an independent prognostic indicator in non-small cell lung cancer (NSCLC). We evaluate the relationship between the metabolic activity of the primary and the pleurisy in T4 NSCLC.

Prognostic value of metabolic imaging in non-small cell lung cancers with neoplasic pleural effusion.

The current treatment of chronic obstructive pulmonary disease (COPD) patients must comprise, in addition to an optimal pharmacological treatment, a pulmonary rehabilitation, if possible multidisciplinary, and a program of post-rehabilitation in order to maintain the outcomes. Today pulmonary rehabilitation has proved to be effective in improving dyspnoea, exercise capacity and quality of life in COPD patients, and reducing the use of health services and thus the cost. In this article we want to present pulmonary rehabilitation, its indications and results, and the way by which it is held in the CHU of Liege.

[Pulmonary rehabilitation in chronic obstructive pulmonary disease].

The UPLIFT study (Understanding Potential Long-term Impacts on Function with Tiotropium) was a double-blind, randomised, international, multicentric, placebo-controlled clinical trial, investigating with tiotropium (Spiriva) the change in the annual rate of decline in FEV1 in chronic obstructive pulmonary disease (COPD). Secondary end points included COPD exacerbation rate with or without hospitalisation, lung function, quality of life and mortality. 5.993 patients were randomized. In this article, we briefly describe the most important results of the study. While tiotropium did not alter the annual rate of decline in FEV1 (pre and postbronchodilatation), it improved lung function and quality of life, and reduced exacerbations and hospitalisations by comparison with control for up to 4 years. Tiotropium also reduced respiratory and cardiac morbidity.

[The UPLIFT study (Understanding Potential Long-term Impacts on Function with Tiotropium)].

Neutrophils have been implicated in the pathogenesis of COPD. Several chemoattractants for neutrophils have been measured in samples of exhaled breath condensate (EBC) and induced sputum (IS) from patients with COPD. The aims of this study were to compare EBC and IS supernatant neutrophil chemotactic activity (NCA) from ex-smoking subjects with COPD and healthy ex-smokers, and to assess the contribution of leukotriene B(4) (LTB(4)) to this activity.

Leukotriene B4 contributes to exhaled breath condensate and sputum neutrophil chemotaxis in COPD.

Indacaterol is a novel ultra long-acting beta 2-agonist (ultra-LABA), given once-daily, developed for the treatment of Chronic Obstructive Pulmonary Disease (COPD). The clinical studies suggest that indacaterol produces a rapid (within 5 minutes) and sustained bronchodilation (at least 24 hours) in patients with COPD. It improves also several important parameters as lung function, the quality of life, symptoms, exercise capacity, resting and dynamic hyperinflation, and exacerbations, while being well tolerated. These outcomes justify its use in moderate to very severe COPD patients. This review will give a brief summary of recent clinical data on the indacaterol, its comparison with other pharmacological agents used in the treatment of COPD, and also some information about its use in routine.

[Medication of the month. Indacaterol (Onbrez Breezhaler) and chronic obstructive pulmonary disease].

To assess the outcomes of a 6-month comprehensive multidisciplinary outpatient pulmonary rehabilitation programme in patients with chronic obstructive pulmonary disease according to age.

Should we exclude elderly patients with chronic obstructive pulmonary disease from a long-time ambulatory pulmonary rehabilitation programme?

Smoking is the main environmental risk factor of COPD and accounts for 85% to 90% of COPD. However, 10-15% of COPD patients have never smoked and only a fraction of smokers ever develop COPD. Indeed, genetic and environmental (pollution, occupational and infectious) factors, also influence the risk of developing COPD. Finaly COPD must be considered as the clinical consequence of multiple complex interactions between environmental factors and genetic susceptibility. The latter is not clearly understood, with the exception of alpha-1 antitrypsin deficiency. In this article, we present the different aspects of this complex disease which is primarily environmental.

[COPD: genetics and environmental interactions].

Neurotrophins (NTs) modulate the growth of human malignancies, including lung cancers. Our prospective study evaluated the accuracy of pleural NTs [nerve growth factor, brain-derived neurotrophic factor (BDNF), neurotrophin 3 (nT3) and 4 (nT4)] levels for differentiating benign from malignant pleural exudates. Levels of NTs were measured by ELISA in 170 patients with non-neutrophilic (<50%) exudative benign or malignant pleurisies diagnosed by pleuroscopy. Fifty-nine benign (9 infections and 50 inflammatory diseases) and 111 malignant (50 extrathoracic tumors, 51 lung cancers and 10 mesotheliomas) pleural exudates were diagnosed by thoracoscopy. Levels of BDNF were significantly higher in malignant than in benign effusions [17 pg/ml (0-367) vs. 8 pg/ml (0-51), p<0.05]. ROC analysis showed an area under the curve of 0.609 (p=0.012; best threshold 44 pg/ml). Pleural BDNF levels were significantly higher in pleural metastasis of pulmonary tumors and in mesothelioma than in pleural benign effusions. Finally, a higher proportion of pleural nT3 was detected in squamous cell lung carcinoma in comparison to that in non-squamous cell lung carcinoma (72.7 vs. 10%, p<0.0001). NTs and particularly BDNF may play a role in the pathogenesis of malignant pleural effusions.

Diagnostic value of neurotrophin expression in malignant pleural effusions.

Neutrophils have been involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Underlying mechanisms of neutrophil accumulation in the airways of stable and exacerbated COPD patients are poorly understood. The aim of this study was to assess exhaled breath condensate (EBC) neutrophil chemotactic activity, the level of two chemoattractants for neutrophils (GRO-α and LTB4) during the course of an acute exacerbation of COPD (AECOPD).

Increased of exhaled breath condensate neutrophil chemotaxis in acute exacerbation of COPD.

Patients with chronic airway disease may present features of both asthma and COPD, commonly referred to as asthma-COPD overlap syndrome (ACOS). Recommendations on their diagnosis are diffuse and inconsistent. This survey aimed to identify consensus on criteria for diagnosing ACOS.

A Belgian survey on the diagnosis of asthma-COPD overlap syndrome.

Chronic obstructive pulmonary disease (COPD) is a chronic airway disease characterized by a profound airway remodelling that leads to airway obstruction. A role for transforming growth factor-β1 (TGF-β1) has been proposed in airway remodelling of COPD. Regarding the TGF-β1 production at local level, the results seemed to be controversial. In this study, an original model of sputum cell culture thought to maintain important cells interactions, was used. We investigated the production of TGF-β1 from sputum cell culture in 33 COPD encompassing the whole severity spectrum and compared the results with those found in 39 healthy controls. Sputum was induced by inhalation of saline, the cellular fraction cultured for 24 h and the spontaneous production of total TGF-β1 was assessed by ELISA. Using, a TGF-β1 reporter cell assay, we also compared the levels of active and total TGF-β1 in the sputum cell culture supernatants of COPD and controls. Moreover, as a combination of tumor necrosis factor-α (TNF-α) and TGF-β1 have been shown to have a cumulative impact on the severity of airflow limitation in COPD, the TNF-α release was also measured in a representative subgroup of patients. Our results indicated that the use of sputum cell culture was a reliable and reproducible method to assess TGF-β1 production at airway level. Sputum cells from COPD produced greater amount of total TGF-β1 than those of healthy controls (p<0.001). This result was confirmed using the cell reporter assay which also showed a higher level of active TGF-β1 in the COPD group compared to controls. In addition, total TGF-β1 production was increased according to GOLD stage and was inversely related to FEV1/FVC ratio (p<0.05). By contrast, the production of this growth factor was not correlated with the functional markers of emphysema nor with demographic characteristics such as age, BMI or smoking status. Interestingly, the production of total TGF-β1 was inversely related to that of TNF-α (r=-0.53, p<0.05) which was decreased in COPD. In summary, COPD patients displayed a raised production of total and active TGF-β1 from their airway cells. Total TGF-β1 correlates with the severity of airway obstruction without evidence of a link with emphysema. .

Article	Year
[Tiotropium: a new therapeutic option in chronic obstructive pulmonary disease]. Revue medicale suisse\| PubMed ID: 16200941	2005
18F-FDG PET imaging in assessing exudative pleural effusions. Nuclear medicine communications\| PubMed ID: 17088683	2006
[Exacerbations in COPD: a burden to curtail]. Revue medicale de Liege\| PubMed ID: 17209501	2006
Granulocyte chemotactic activity in exhaled breath condensate of healthy subjects and patients with COPD. Chest\| PubMed ID: 17565017	2007
[Clinical study of the month: the TORCH study (TOwards a Revolution in COPD Health)]. Revue medicale de Liege\| PubMed ID: 17566394	2007
Diagnostic value of interleukine-6, transforming growth factor-beta 1 and vascular endothelial growth factor in malignant pleural effusions. Respiratory medicine\| PubMed ID: 18760578	2008
Prognostic value of metabolic imaging in non-small cell lung cancers with neoplasic pleural effusion. Nuclear medicine communications\| PubMed ID: 18836376	2008
[Pulmonary rehabilitation in chronic obstructive pulmonary disease]. Revue medicale de Liege\| PubMed ID: 19112994	2008
[The UPLIFT study (Understanding Potential Long-term Impacts on Function with Tiotropium)]. Revue medicale de Liege\| PubMed ID: 19317104	2009
Leukotriene B4 contributes to exhaled breath condensate and sputum neutrophil chemotaxis in COPD. Chest\| PubMed ID: 19429719	2009
[Medication of the month. Indacaterol (Onbrez Breezhaler) and chronic obstructive pulmonary disease]. Revue medicale de Liege\| PubMed ID: 21995240	2011
Should we exclude elderly patients with chronic obstructive pulmonary disease from a long-time ambulatory pulmonary rehabilitation programme? Journal of rehabilitation medicine\| PubMed ID: 22549658	2012
[COPD: genetics and environmental interactions]. Revue medicale de Liege\| PubMed ID: 22891481	2012
Diagnostic value of neurotrophin expression in malignant pleural effusions. Experimental and therapeutic medicine\| PubMed ID: 22977602	2011
Increased of exhaled breath condensate neutrophil chemotaxis in acute exacerbation of COPD. Respiratory research\| PubMed ID: 25260953	2014
A Belgian survey on the diagnosis of asthma-COPD overlap syndrome. International journal of chronic obstructive pulmonary disease\| PubMed ID: 28243078	2017
Increased production of TGF-β1 from sputum cells of COPD: Relationship with airway obstruction. Cytokine\| PubMed ID: 28668545	2017

Jean-Louis Corhay

Biography

JoVE Journal Publications

Other Publications