Reducing the toll of inflammatory lung disease

Toll-like receptors (TLRs) are pivotal in human response to microbial stimuli. Their activation and signaling underpin much of the observed epidemiologic data generated by the hygiene hypothesis, and their contribution to infectious exacerbations of airways disease is likely to be highly important. Our growing knowledge in this field will have a significant impact on the understanding of the pathogenesis of inflammatory diseases, and TLR-based therapies are already in early clinical trials to modify atopic disease severity.     

Obstructive sleep apnea and type 2 diabetes: interacting epidemics

Type 2 diabetes is a major public health concern with high morbidity, mortality, and health-care costs. Recent reports have indicated that the majority of patients with type 2 diabetes also have obstructive sleep apnea (OSA). There is compelling evidence that OSA is a significant risk factor for cardiovascular disease and mortality. Rapidly accumulating data from both epidemiologic and clinical studies suggest that OSA is also independently associated with alterations in glucose metabolism and places patients at an increased risk of the development of type 2 diabetes. Experimental studies in humans and animals have demonstrated that intermittent hypoxia and reduced sleep duration due to sleep fragmentation, as occur in OSA, exert adverse effects on glucose metabolism. Based on the current evidence, clinicians need to address the risk of OSA in patients with type 2 diabetes and, conversely, evaluate the presence of type 2 diabetes in patients with OSA. Clearly, there is a need for further research, using well-designed studies and long-term follow-up, to fully demonstrate a causal role for OSA in the development and severity of type 2 diabetes. In particular, future studies must carefully consider the confounding effects of central obesity in examining the link between OSA and alterations in glucose metabolism. The interactions among the rising epidemics of obesity, OSA, and type 2 diabetes are likely to be complex and involve multiple pathways. A better understanding of the relationship between OSA and type 2 diabetes may have important public health implications.     

Conventional transbronchial needle aspiration decreases the rate of surgical sampling of intrathoracic lymphadenopathy

BACKGROUND: Previous studies have suggested a decreased need for the surgical biopsy of intrathoracic lymph nodes (LNs) due to improved diagnostic rates utilizing transbronchial needle aspiration (TBNA) with endobronchial ultrasound and endoscopic ultrasound. The goal of this study was to determine whether conventional TBNA using combined cytologic and histologic analysis of tissue specimens impacted the rates of surgical diagnostic biopsies of patients with intrathoracic lymphadenopathy. METHODS: Retrospective review at a single academic center. All mediastinal and hilar tissue samples submitted for pathologic analysis over an 8.4-year period were analyzed. Patients were categorized into a "before" group and an "after" group based on two different time periods. The before group underwent only cytologic analysis of Wang needle (19-gauge or 21-gauge) aspirates. The after group had cytologic analysis of aspirates as well as histologic analysis of needle "core" (19 gauge) biopsy specimens. The groups were compared for the rate of intrathoracic LNs sampled by surgical means vs TBNA and the number of times that TBNA averted the need for a surgical diagnostic procedure. RESULTS: The success of TBNA increased significantly in the after group compared to that in the before group. The yield for the successful sampling of mediastinal and hilar LNs increased from 53 to 91% (p < 0.001) in the before group vs the after group. TBNA averted a surgical biopsy in 35% of the before cases compared to 66% of the after cases (p < 0.001). CONCLUSIONS: Conventional TBNA using large-bore needles with both cytology and surgical pathology evaluation decreases the need for surgical sampling of the mediastinum to diagnose thoracic lymphadenopathy.     

The effects of 1-year treatment with a herbst mandibular advancement splint on obstructive sleep apnea, oxidative stress, and endothelial function

BACKGROUND: Obstructive sleep apnea (OSA) is associated with endothelial dysfunction. In the current study, we assessed the effect of long-term modified Herbst mandibular advancement splint (MAS) treatment on OSA, oxidative stress markers, and on endothelial function (EF). METHODS: A total of 16 subjects participated (11 men and 5 women; mean [+/- SD] age, 54.0 +/- 8.3 years; mean body mass index, 28.0 +/- 3.1 kg/m(2)), 12 of whom completed the 1-year evaluation. Apnea severity, levels of oxidative stress markers, and EF were assessed after 3 months and 1 year of receiving treatment. For comparison, 6 untreated patients underwent two evaluations 9 months apart, and 10 non-OSA individuals were assessed once as a reference group. The results are presented as the mean +/- SD. RESULTS: The mean apnea-hypopnea index (AHI) decreased significantly from 29.7 +/- 18.5 events/h before treatment to 17.7 +/- 11.1 events/h after 3 months of treatment and 19.6 +/- 11.5 events/h after 1 year of treatment (p < 0.005 for both). The mean Epworth sleepiness scale score decreased significantly from 12.4 +/- 6.0 before treatment to 10.2 +/- 6.6 after 3 months of treatment and 7.8 +/- 3.8 after 1 year of treatment (p < 0.001 for both). The mean EF improved significantly from 1.77 +/- 0.4 before treatment to 2.1 +/- 0.4 after 3 months of treatment (p < 0.05) and 2.0 +/- 0.3 after 1 year of treatment (p = 0.055), which were similar to the values of the reference group. Thiobarbituric acid-reactive substance (TBARS) levels decreased from 18.8 +/- 6.2 nmol malondialdehyde (MDA)/mL before treatment to 15.8 +/- 3.9 MDA/mL after 3 months of treatment (p = 0.09) and 15.5 +/- 3.2 nmol MDA/mL after 1 year of treatment (p < 0.05). There was a correlation between the improvement in AHI and in EF or TBARS levels (r = 0.55; p = 0.05). The untreated control group remained unchanged. CONCLUSIONS: The Herbst MAS may be a moderately effective long-term treatment for patients with OSA. EF improved to levels that were not significantly different than reference levels, even though apneic events were not completely eliminated. We think that these data are encouraging and that they justify the performance of larger randomized controlled studies.     

Discrepant results between pyrazinamide susceptibility testing by the reference BACTEC 460TB method and pncA DNA sequencing in patients infected with multidrug-resistant W-Beijing Mycobacterium tuberculosis strains

BACKGROUND: Mycobacterium tuberculosis strains belonging to the W-Beijing family have received broad clinical and public health attention because of their rapid worldwide spread and their frequent association with outbreaks, multidrug resistance, and treatment failures and relapses. METHODS: The present study examined a large number of multidrug-resistant strain-W isolates (isolates of 29 patients) by susceptibility testing for pyrazinamide (PZA) using the reference BACTEC 460TB method (Becton Dickinson Diagnostic Instrument Systems; Sparks, MD) and also by DNA sequencing of the pncA gene. RESULTS: We found that despite of the presence of a strain W-specific Thr47Ala in the pncA gene, all strains showed susceptibility to PZA in the reference BACTEC 460TB system due to their higher minimum inhibitory concentrations (relative to BACTEC 460TB PZA-susceptible strains). CONCLUSIONS: Our results suggest that the current radiometric reference method cannot reproducibly detect PZA resistance in patients infected with W-Beijing strains. Therefore, PZA susceptibility testing should instead be based on analysis of the pncA gene for resistance-associated mutations.