Bacterial colonization increases daily symptoms in patients with chronic obstructive pulmonary disease.

RATIONALE: Respiratory pathogens are frequently isolated from the airways of patients with chronic obstructive pulmonary disease (COPD) in the absence of an exacerbation. This bacterial "colonization" by potential pathogens is associated with host inflammatory and immune responses, which could increase respiratory symptoms. OBJECTIVES: To study whether bacterial colonization impacts daily respiratory symptoms in COPD. METHODS: In a longitudinal prospective observational study of COPD, patients recorded daily symptoms electronically on the Breathlessness, Cough, and Sputum Scale (BCSS). Sputum cultures and quantitative polymerase chain reaction (PCR) were performed every 2 weeks. The relationship of BCSS and bacterial colonization was analyzed with generalized linear mixed effects models, after controlling for exacerbations, weather conditions, lung function, and demographic variables. MEASUREMENTS AND MAIN RESULTS: A total of 41 patients recorded daily symptoms for 12,527 days. The average BCSS score was higher during the periods of colonization, determined by sputum culture with one or more of the following pathogens: nontypeable Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and Pseudomonas aeruginosa, compared to periods without colonization (5.28 vs. 4.46; P = 0.008) after controlling for confounding variables. The finding did not change when colonization was defined by quantitative PCR (average BCSS, 4.77 vs. 4.25; P = 0.006). Sputum IL-8 levels were elevated with bacterial colonization. CONCLUSIONS: Even in the absence of clinical exacerbation, colonization by bacterial pathogens in COPD was associated with a clinically significant moderate increase in daily symptoms, likely mediated by increased airway inflammation. Novel therapies that decrease bacterial colonization in COPD could improve daily symptoms and quality of life.

Pneumococcal interactions with epithelial cells are crucial for optimal biofilm formation and colonization in vitro and in vivo.

The human nasopharynx is the main reservoir for Streptococcus pneumoniae (the pneumococcus) and the source for both horizontal spread and transition to infection. Some clinical evidence indicates that nasopharyngeal carriage is harder to eradicate with antibiotics than is pneumococcal invasive disease, which may suggest that colonizing pneumococci exist in biofilm communities that are more resistant to antibiotics. While pneumococcal biofilms have been observed during symptomatic infection, their role in colonization and the role of host factors in this process have been less studied. Here, we show for the first time that pneumococci form highly structured biofilm communities during colonization of the murine nasopharynx that display increased antibiotic resistance. Furthermore, pneumococcal biofilms grown on respiratory epithelial cells exhibited phenotypes similar to those observed during colonization in vivo, whereas abiotic surfaces produced less ordered and more antibiotic-sensitive biofilms. The importance of bacterial-epithelial cell interactions during biofilm formation was shown using both clinical strains with variable colonization efficacies and pneumococcal mutants with impaired colonization characteristics in vivo. In both cases, the ability of strains to form biofilms on epithelial cells directly correlated with their ability to colonize the nasopharynx in vivo, with colonization-deficient strains forming less structured and more antibiotic-sensitive biofilms on epithelial cells, an association that was lost when grown on abiotic surfaces. Thus, these studies emphasize the importance of host-bacterial interactions in pneumococcal biofilm formation and provide the first experimental data to explain the high resistance of pneumococcal colonization to eradication by antibiotics.

Moraxella catarrhalis, a human respiratory tract pathogen.

Moraxella catarrhalis is an exclusively human pathogen and is a common cause of otitis media in infants and children, causing 15%-20% of acute otitis media episodes. M. catarrhalis causes an estimated 2-4 million exacerbations of chronic obstructive pulmonary disease in adults annually in the United States. M. catarrhalis resembles commensal Neisseria species in culture and, thus, may be overlooked in samples from the human respiratory tract. The prevalence of colonization of the upper respiratory tract is high in infants and children but decreases substantially in adulthood. Most strains produce beta-lactamase and are thus resistant to ampicillin but susceptible to several classes of oral antimicrobial agents. Recent work has elucidated mechanisms of pathogenesis and focused on vaccine development to prevent otitis media in children and respiratory tract infections caused by M. catarrhalis in adults with chronic obstructive pulmonary disease.

Antifungal agents in hematopoietic stem cell transplantation.

Invasive fungal infections are major complications of stem cell transplantation associated with significant morbidity and mortality. Allogeneic stem cell transplant recipients are at a significantly greater risk for fungal infection than recipients of autologous transplantation. Although with the wide use of fluconazole prophylaxis the incidence and associated mortality of invasive candidiasis has been minimized, mold diseases remain a significant complication during periods of prolonged immunosuppression for graft versus host disease. Posaconazole prophylaxis during periods of high risk was recently demonstrated to be effective in preventing fungal infections and associated mortality. Preemptive strategy employing laboratory markers and serial CT scans to identify mold infection at an early stage is promising. However its efficacy has to be validated in clinical trials. Several new antifungal agents have been introduced lately, characterized by improved safety profile and broader antifungal spectrum. Voriconazole has become the standard of care for the treatment of invasive aspergillosis. Finally there has been increasing interest on combination therapy for invasive aspergillosis due to the high rate of failure of the currently available antifungals, especially in the profoundly immunocompromised host.

Infections in chronic lung diseases.

Chronic lung diseases are prevalent worldwide and cause significant mortality and suffering. This article discusses infections that occur in three chronic lung diseases: chronic obstructive pulmonary disease, bronchiectasis, and cystic fibrosis. Rather than discussing the role of infections as etiology of these diseases, this article focuses on infections that occur in the background of established chronic lung disease.

Pulse oximetry as a potential screening tool for lower extremity arterial disease in asymptomatic patients with diabetes mellitus.

BACKGROUND: Lower extremity arterial disease (LEAD) is common and underdiagnosed in patients with diabetes mellitus and is associated with higher total mortality. METHODS: We compared the accuracy of pulse oximetry, the ankle-brachial index (ABI), and the combination of the two to diagnose LEAD in consecutive outpatients with type 2 diabetes who had no symptoms of LEAD, in a primary care setting. Exclusions were age younger than 40 years, known LEAD, or typical symptoms of LEAD. Fifty-seven patients were enrolled. All patients had (1) ABI measurement; (2) pulse oximetry to measure Sao2 of their index fingers and big toes in the supine position and at 12-in elevation; and (3) Doppler waveform analysis of the lower extremity arteries. The ABI was considered abnormal if it was less than 0.9. Pulse oximetry of the toes was considered abnormal if the Sao2 was more than 2% lower from the finger or on 12-in elevation of the foot. The combination was considered positive if either the ABI or pulse oximetry was positive for LEAD and negative if both were negative. We defined LEAD as monophasic waveforms on waveform analysis. RESULTS: Of our patients, 31% had LEAD. Pulse oximetry had a sensitivity of 77% (95% confidence interval [CI], 61%-88%) and a specificity of 97% (95% CI, 91%-99%); ABI had a sensitivity of 63% (95% CI, 46%-77%) and a specificity of 97% (95% CI, 91%-99%). Positive likelihood ratios were 30 (95% CI, 7.6-121) for pulse oximetry and 24.8 (95% CI, 6.2-99.8) for ABI; negative likelihood ratios were 0.23 (95% CI, 0.12-0.43) for pulse oximetry and 0.38 (95% CI, 0.25-0.59) for ABI. For the combination, sensitivity was 86% (95% CI, 71%-94%) and specificity was 92% (95% CI, 84%-96%). CONCLUSIONS: Pulse oximetry of the toes seems as accurate as ABI to screen for LEAD in patients with type 2 diabetes. Combination of the two tests increases sensitivity.