Airway Obstruction In Chronic Obstructive Pulmonary Disease Research Articles

New Concepts in the Radiological Assessment of COPD

Chronic obstructive pulmonary disease (COPD) is a complex genetic disorder in which environmental factors, such as tobacco smoke, interact with genetic susceptibility to cause disease. Airway obstruction in COPD is due to an exaggerated inflammatory response that ultimately destroys the lung parenchyma (emphysema) and increases airway resistance by remodeling the airway wall. Until recently, assessment of these disease processes required the examination of resected tissue. However, computed tomography (CT) now allows researchers to measure the structure of the lung parenchyma and airway wall without having to remove the tissue. This review describes some of the new CT techniques for quantitative assessment of lung structure. These techniques are extremely important to study the pathogenesis of COPD as well as differentiate patients with predominantly emphysema disease from those with airway wall remodeling, and to assess the effects of therapeutic interventions.

Airway remodelling assessed by sputum and high-resolution computed tomography in asthma and COPD

It is not known whether sputum elastase, metalloproteinase (MMP)-9 and tissue-inhibitor metalloproteinase (TIMP)-1 are related to structural changes of the airways, as assessed by high-resolution computed tomography (HRCT) scan. The relationships between these markers and the magnitude of structural changes of the airways in asthma and chronic obstructive pulmonary disease (COPD) were assessed. Induced sputum and HRCT scan were performed in 30 asthmatics (14 mild and 16 severe) and in 12 patients with COPD. A greater extent of HRCT scan abnormalities was found in COPD than in severe and mild asthmatics. HRCT scan abnormalities correlated with the degree of airway obstruction in COPD and in severe asthma. HRCT scan abnormalities also correlated with the levels of sputum elastase both in COPD and in severe asthma. HRCT scan abnormalities were associated with sputum MMP-9/TIMP-1 ratio in mild asthma, severe asthma and COPD. In conclusion, this study demonstrates that sputum elastase and the metalloproteinase-9/tissue-inhibitor metalloproteinase-1 ratio are associated with the magnitude of high-resolution computed tomography scan abnormalities of the airways in asthma and chronic obstructive pulmonary disease, and suggests that the levels of these markers reflect the extent of structural changes of the airways.

Novel Cytoplasmic Proteins of Nontypeable Haemophilus influenzae Up-regulate Human MUC5AC Mucin Transcription via a Positive p38 Mitogen-activated Protein Kinase Pathway and a Negative Phosphoinositide 3-Kinase-Akt Pathway

Nontypeable Haemophilus influenzae (NTHi) is an important human pathogen that causes chronic otitis media with effusion (COME) in children and exacerbation of chronic obstructive pulmonary disease (COPD) in adults. Mucin overproduction, a hallmark of both diseases, has been shown to directly cause conductive hearing loss in COME and airway obstruction in COPD. The molecular mechanisms underlying mucin overproduction in NTHi infections still remain unclear. Here, we show that NTHi strongly up-regulates MUC5AC mucin transcription only after bacterial cell disruption. Maximal up-regulation is induced by heat-stable bacterial cytoplasmic proteins, whereas NTHi surface membrane proteins induce only moderate MUC5AC transcription. These results demonstrate an important role for cytoplasmic molecules from lysed bacteria in the pathogenesis of NTHi infections, and may well explain why many patients still have persistent symptoms such as middle ear effusion in COME after intensive antibiotic treatment. Furthermore, our results indicate that activation of p38 mitogen-activated protein kinase is required for NTHi-induced MUC5AC transcription, whereas activation of phosphoinositide 3-kinase-Akt pathway leads to down-regulation of NTHi-induced MUC5AC transcription via a negative cross-talk with p38 mitogen-activated protein kinase pathway. These studies may bring new insights into molecular pathogenesis of NTHi infections and lead to novel therapeutic intervention for COME and COPD.

Anticholinergic drugs in therapy of chronic obstructive lung disease (COPD)

Chronic obstructive pulmonary disease (COPD) is a severe respiratory disorder responsible for a significant morbidity and mortality in western societies. In the vast majority of patients, COPD is caused by tobacco smoke. Contributing factors leading to airway obstruction and lung hyperinflation in COPD differ from those observed in asthma, with a major role of hypersecretion and peripheral airway obstruction due to increased cholinergic airway smooth muscle tone. Therefore, anticholinergics are considered the firstline therapy to improve airway obstruction in COPD. In addition to effects on lung function, anticholinergics may also improve exercise tolerance, quality of life and sleep quality in these patients. When compared with other classes of bronchodilators, anticholinergics show an equal potency of bronchodilation, with a favorable safety profile. Due to their unique mechanism of action, anticholinergics can also be combined with different types of bronchodilators. Novel, long-acting anticholinergics may hold a future potential for further improvement of therapy in COPD, particularly in terms of user friendliness and compliance.