Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD

Grootendorst, Diana C.; Gauw, Stefanie A.; Verhoosel, Renate M.; Sterk, Peter J.; Hospers, Jeannette J.; Bredenbröker, Dirk; Bethke, Thomas D.; Hiemstra, Pieter S.; Rabe, Klaus F.
December 2007
Thorax;Dec2007, Vol. 62 Issue 12, p1081
Academic Journal
Background: Roflumilast is a targeted oral once-daily administered phosphodiesterase 4 (PDE4) inhibitor with clinical efficacy in chronic obstructive pulmonary disease (COPD). Results from in vitro studies with roflumilast indicate that it has anti-inflammatory properties that may be applicable for the treatment of COPD. Methods: In a crossover study, 38 patients with COPD (mean (SD) age 63.1(7.0) years, post-bronchodilator forced expiratory volume in 1 s (FEV1) 61 .0 (1 2.6)% predicted) received 500 μg roflumilast or placebo once daily for 4 weeks. Induced sputum samples were collected before and after 2 and 4 weeks of treatment. Differential and absolute cell counts were determined in whole sputum samples. Markers of inflammation were determined in sputum supernatants and blood. Spirometry was performed weekly. Results: Roflumilast significantly reduced the absolute number of neutrophils and eosinophils/g sputum compared with placebo by 35.5% (95% CI 15.6% to 50.7%; p = 0.002) and 50.0% (95% CI 26.8% to 65.8%; p<0.001), respectively. The relative proportion of sputum neutrophils and easinophils was not affected by treatment (p<0.05). Levels of soluble interleukin-8, neutrophil elastase, eosinophil cationic protein and α2- macroglobulin in sputum and the release of tumour necrosis factor α from blood cells were significantly reduced by roflumilast compared with placebo treatment (p<0.05 for all). Post-bronchodilator FE1 improved significantly during roflumilast compared with placebo treatment with a mean difference between treatments of 68.7 ml (95% CI 12.9 to 124.5; p = 0.018). Conclusion: PDE4 inhibition by roflumilast treatment for 4 weeks reduced the number of neutrophils and eosinophils, as well as soluble markers of neutrophilic and eosinophilic inflammatory activity in induced sputum samples of patients with COPD. This anti-inflammatory effect may in part explain the concomitant improvement in post-bronchodilator FEV1.


Related Articles

  • Nuclear localisation of p65 in sputum macrophages but not in sputum neutrophils during COPD exacerbations. Caramori, G.; Romagnoli, M.; Casolari, P.; Bellettato, C.; Casoni, G.; Boschetto, P.; K. Fan Chung; Barnes, P.J.; Adcock, I.M.; Ciaccia, A.; Fabbri, L.M.; Papi, A. // Thorax;Apr2003, Vol. 58 Issue 4, p348 

    Background: Exacerbations represent an important feature of the clinical manifestation and natural history of chronic obstructive pulmonary disease (COPD). Nuclear Iocalisation of p65 is a signal of nuclear factor-κB (NF-κB) activation. A study was undertaken to evaluate whether NF-κB...

  • A Microfluidic Platform for Evaluating Neutrophil Chemotaxis Induced by Sputum from COPD Patients. Wu, Jiandong; Hillier, Craig; Komenda, Paul; Lobato de Faria, Ricardo; Levin, David; Zhang, Michael; Lin, Francis // PLoS ONE;May2015, Vol. 10 Issue 5, p1 

    Chronic Obstructive Pulmonary Disease (COPD) is a common lung disease characterized by breathing difficulty as a consequence of narrowed airways. Previous studies have shown that COPD is correlated with neutrophil infiltration into the airways through chemotactic migration. However, whether...

  • Innate Immune Responses Are Increased in Chronic Obstructive Pulmonary Disease. Baines, Katherine Joanne; Simpson, Jodie Louise; Gibson, Peter Gerard // PLoS ONE;2011, Vol. 6 Issue 3, p1 

    Background: Chronic obstructive pulmonary disease (COPD) is characterised by irreversible airflow obstruction, neutrophilic airway inflammation and chronic bacterial colonisation, however the role of the innate immune response in the pathogenesis of COPD remains unclear. Methods: Induced sputum...

  • A Comparison of the Clinical and Induced Sputum Characteristics of Early- and Late-Onset Asthma. Rossall, Matthew; Cadden, Paul; Kolsum, Umme; Singh, Dave // Lung;Aug2012, Vol. 190 Issue 4, p459 

    Background: There are few studies describing the phenotype of late-onset asthma (LOA). We sought to investigate the clinical and induced sputum characteristics of patients with LOA. Methods: Nineteen patients with LOA diagnosed after the age of 40 years and 19 patients with early-onset asthma...

  • Effect of Yufeining (...) on Induced Sputum Interleukin-8 in Patients with Chronic Obstructive Pulmonary Disease at the Stable Phase. Hong Min-li; Yang Guo-zong; Chen Wen-xi; Gao Ling-yun; Cai Shao-hang; Dai Shun-zhen // Chinese Journal of Integrative Medicine;Sep2005, Vol. 11 Issue 3, p179 

    Objective: To evaluate the effect of Yufeining (...), a traditional Chinese medicine, on induced sputum interleukin-8 (IL-8) in patients with chronic obstructive pulmonary disease (COPD) at the stable phase. Methods: Thirty-six patients with COPD were divided into trial group (18 cases) and...

  • IL-17 mRNA in sputum of asthmatic patients: linking T cell driven inflammation and granulocytic influx? Bullens, Dominique M. A.; Truyen, Els; Coteur, Liesbeth; Dilissen, Ellen; Hellings, Peter W.; Dupont, Lieven J.; Ceuppens, Jan L. // Respiratory Research;2006, Vol. 7, p1 

    Background: The role of Th2 cells (producing interleukin (IL-)4, IL-5 and IL-13) in allergic asthma is well-defined. A distinct proinflammatory T cell lineage has recently been identified, called Th17 cells, producing IL-17A, a cytokine that induces CXCL8 (IL-8) and recruits neutrophils....

  • Human Neutrophil Peptides sputum levels in symptomatic smokers and COPD patients. PAONE, G.; CONTI, V.; LEONE, A.; SCHMID, G.; PUGLISI, G.; GIANNUNZIO, G.; TERZANO, C. // European Review for Medical & Pharmacological Sciences;2011, Vol. 15 Issue 5, p556 

    Background and Objectives: Human Neutrophil Peptides (HNP) are major neutrophils' products which may contribute to the airway inflammation and lung remodelling during chronic obstructive pulmonary disease (COPD). We aimed to assess whether HNP sputum concentrations could be used as indicators of...

  • Causes of eosinophilic bronchitis grow.  // Occupational & Environmental Medicine;Oct2007, Vol. 64 Issue 10, p680 

    The article focuses on the causes of eosinophilic bronchitis in the workplace. Respiratory tests in a foundry worker associated with workplace exposure to methylene diphenyl isocyanate had developed a non-productive chronic cough and the baker who expose to wheat flour had acquired the same...

  • Phosphodiesterase 4 inhibitors have only marginal benefits in COPD.  // British Columbia Medical Journal;Jul/Aug2011, Vol. 53 Issue 6, p293 

    The article discusses the use of oral phosphodiesterase 4 in patients with chronic obstructive pulmonary disease.


Read the Article


Sign out of this library

Other Topics