Update on non-cystic fibrosis bronchiectasis.
ABSTRACT There is growing awareness in both adult and paediatric respiratory clinics regarding the importance of non-cystic fibrosis bronchiectasis. There has been debate regarding the requirement for investigations to establish an underlying cause of bronchiectasis. Furthermore, there has been growing interest in establishing the role of bacteria in disease progression.
Post-infection is no longer the most common cause of bronchiectasis in developed countries in children or adults and the importance of identifying immunodeficiency has been underlined. Nontuberculous mycobacteria are recognized as both causing and complicating non-cystic fibrosis bronchiectasis. It has been suggested that infection with Pseudomonas aeruginosa may confer a worse prognosis compared with other pathogens but recent publications produce conflicting views. There is increasing recognition that patients with non-cystic fibrosis bronchiectasis do not necessarily respond to cystic fibrosis treatment regimens in the same way as patients with cystic fibrosis regimens.
Non-cystic fibrosis bronchiectasis can be approached in a systematic fashion to establish the underlying cause and develop treatment strategies.
- SourceAvailable from: Jann Mortensen[Show abstract] [Hide abstract]
ABSTRACT: Mucociliary clearance has long been known to be a significant innate defence mechanism against inhaled microbes and irritants. Important knowledge has been gathered regarding the anatomy and physiology of this system, and in recent years, extensive studies of the pathophysiology related to lung diseases characterized by defective mucus clearance have resulted in a variety of therapies, which might be able to enhance clearance from the lungs. In addition, ways to study in vivo mucociliary clearance in humans have been developed. This can be used as a means to assess the effect of different pharmacological interventions on clearance rate, to study the importance of defective mucus clearance in different lung diseases or as a diagnostic tool in the work-up of patients with recurrent airway diseases. The aim of this review is to provide an overview of the anatomy, physiology, pathophysiology, and clinical aspects of mucociliary clearance and to present a clinically applicable test that can be used for in vivo assessment of mucociliary clearance in patients. In addition, the reader will be presented with a protocol for this test, which has been validated and used as a diagnostic routine tool in the work-up of patients suspected for primary ciliary dyskinesia at Rigshospitalet, Denmark for over a decade.Clinical Physiology and Functional Imaging 09/2013; DOI:10.1111/cpf.12085 · 1.33 Impact Factor
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ABSTRACT: P. aeruginosa infections are commonly associated with cystic fibrosis, pneumonias, neutropenia and burns. The P. aeruginosa quorum sensing molecule N-(3-oxo-dodecanoyl) homoserine lactone (C12) cause multiple deleterious host responses, including repression of NF-κB transcriptional activity and apoptosis. Inhibition of C12-mediated host responses is predicted to reduce P. aeruginosa virulence. We report here a novel, host-targeted approach for potential adjunctive anti-Pseudomonal therapy based on inhibition of C12-mediated host responses. A high-throughput screen was developed to identify C12 inhibitors that restore NF-κB activity in C12-treated, lipopolysaccharide (LPS)-stimulated cells. Triazolo[4,3-a]quinolines with nanomolar potency were identified as C12-inhibitors that restored NF-κB-dependent luciferase expression in LPS- and TNF-stimulated cell lines. In primary macrophages and fibroblasts, triazolo[4,3-a]quinolines inhibited C12 action to restore cytokine secretion in LPS-stimulated cells. Serendipitously, in the absence of an inflammatory stimulus, triazolo[4,3-a]quinolines prevented C12-mediated responses, including cytotoxicity, elevation of cytoplasmic calcium, and p38 MAPK phosphorylation. In vivo efficacy was demonstrated in a murine model of dermal inflammation involving intradermal C12 administration. The discovery of triazolo[4,3-a]quinolines provides a pharmacological tool to investigate C12-mediated host responses, and a potential host-targeted anti-Pseudomonal therapy.Cellular Microbiology 08/2013; 48. DOI:10.1111/cmi.12176 · 4.82 Impact Factor
Article: Bronchiectasis in COPD patients[Show abstract] [Hide abstract]
ABSTRACT: BackgroundCOPD and brochiectasis are characterized by fixed airway obstruction and chronic cough. The finding of bronchiectasis on HRCT scan in the patient with COPD may indicate the presence of more advanced airway dysfunction, frequent exacerbation and bacterial colonization.Objective The aim of this study to evaluate the incidence of bronchiectasis on high resolution computed tomography (HRCT) scanning in patients with moderate and severe COPD, and to relate this with the presence of lower airway bacterial colonization, exacerbation frequency, severity.Patients and methodsThis study was carried out on 69 patients diagnosed with COPD. All cases were subjected to through history taking, lung function test, sputum culture, HRCT scan of the chest to diagnose bronchiectasis, All the test were performed in a stable phase.Results69 COPD patients, 32 patients had moderate COPD, 37 patients had severe COPD, 33 patients (47,8%) presented with brochiectasis, (31.3%) of the patients with moderate COPD and 62.2% of the patients with severe COPD with statistically significant difference, the more severe functional impairment (FEV1 ⩽ 50%) the greater prevalence of brochiectasis, also the greater bacterial colonization and more exacerbation were associated with the presence of brochiectasis.10/2012; 61(4):307–312. DOI:10.1016/j.ejcdt.2012.07.001