Search

A pilot study to identify bacterial biofilm in the lacrimal sacs of patients with chronic dacryocystitis, and in patients with epiphora but without discharge, using scanning electron microscopy. Five patients: two with nasolacrimal duct obstruction without dacryocystitis, and three with dacryocystitis refractory to antibiotics, underwent external dacryocystorhinostomy. One control patient without infection was included. Bacterial cultures were obtained from the lumen of the lacrimal sac to analyze possible bacterial growth, including antibiotic resistance. Biopsies were taken from all lacrimal sacs and prepared for light and scanning electron microscopy. Scanning electron microscopy of all the lacrimal sac samples revealed structures consistent with bacterial communities and adjacent extracellular material, indicating biofilm formation. This was most prominent in one of the patients with chronic dacryocystitis. Bacteria were found not only on the luminal surface of the sac, but also within the tissue of the sac. Bacterial growth was identified in samples from two patients with chronic dacryocystitis, whereas samples from the other three patients showed no bacterial growth. Lack of patency of the lacrimal duct predisposes to bacterial growth, even in patients with no clinically confirmed infection of the lacrimal sac. The finding of a biofilm in patients with chronic dacryocystitis explains the lack of efficiency of antibiotic treatment at the concentrations used in clinical practice. [ABSTRACT FROM AUTHOR]

Background: In atopic asthma, chronic Th2‐biased inflammation is associated with an increased risk of pneumococcal infection. The anionic phosphoglycoprotein osteopontin (OPN) is highly expressed in asthma and has been ascribed several roles during inflammation. This study aimed to investigate whether OPN affects inflammation and vulnerability to pneumococcal infection in atopic asthma. Methods: House dust mite (HDM) extract was used to induce allergic airway inflammation in both wild‐type (Spp1+/+) and OPN knockout (Spp1−/−) C57BL/6J mice, and the airway was then infected with Streptococcus pneumoniae. Parameters reflecting inflammation, tissue injury, and bacterial burden were measured. In addition, samples from humans with allergic asthma were analyzed. Results: Both allergen challenge in individuals with allergic asthma and the intranasal instillation of HDM in mice resulted in increased OPN levels in bronchoalveolar lavage fluid (BALF). More immune cells (including alveolar macrophages, neutrophils, eosinophils, and lymphocytes) and higher levels of proinflammatory cytokines were found in Spp1−/− mice than in Spp1+/+ mice. Moreover, OPN‐deficient mice exhibited increased levels of markers reflecting tissue injury. Upon infection with S. pneumoniae, Spp1+/+ mice with allergic airway inflammation had a significantly lower bacterial burden in both BALF and lung tissue than did Spp1−/− mice. Furthermore, Spp1−/− mice had higher levels of cytokines and immune cells in BALF than did Spp1+/+ mice. Conclusion: OPN reduces inflammation, decreases tissue injury, and reduces bacterial loads during concurrent pneumococcal infection and allergic airway inflammation in a murine model. These findings suggest that OPN significantly affects vulnerability to pneumococcal infection in atopic asthma. HDM‐instillation to the airways causes increased inflammation and tissue damage in osteopontin‐deficient mice. Osteopontin‐deficient mice (Spp1‐/‐) with an ongoing allergic airway inflammation are more prone to pneumococcal infection. The findings suggest that osteopontin plays important roles, modulating inflammation, tissue damage, and host defense against pneumococcal infection during allergic asthma. [ABSTRACT FROM AUTHOR]

Exacerbations present a major clinical problem in many patients suffering from chronic obstructive pulmonary disease (COPD). Roflumilast, an inhibitor of phosphodiesterase 4, has shown beneficial effects in several clinical trials and is currently widely used to prevent exacerbations in severe COPD. Roflumilast has anti-inflammatory properties that may interfere with potentially important host defense functions, including cytotoxic properties of neutrophils at sites of inflammation. Since chronic bacterial infection is prevalent in severe COPD, Pseudomonas aeruginosa being a major pathogen, we hypothesized that this drug could impair host defense against P. aeruginosa. In this study, mice were pretreated with vehicle alone or roflumilast at doses of 5 mg/kg or 10 mg/kg, followed by instillation of P. aeruginosa in the airways. Bacterial load and dissemination, as well as inflammatory markers and immune cells, present in the airways were monitored. Roflumilast increased mortality, bacterial load, and dissemination in mice infected with P. aeruginosa. In addition, roflumilast-treated mice had significantly lower numbers of neutrophils in the bronchi, but not in the lung tissue airways, compared with untreated mice. Several proinflammatory cytokines decreased in roflumilast-treated mice but in neither the neutrophil-recruiting chemokine KC nor IL-6. These findings show that roflumilast treatment impairs host defense against P. aeruginosa in the airways, which may indicate that patients suffering from chronic bacterial infection of the airways could benefit from withholding of treatment with roflumilast., (Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.)