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The Use of Electrocautery as the Primary Ablation Modality for Malignant and Benign Airway Obstruction.

Laser has been the main ablative modality in the airways, but a growing experience with endobronchial electrocautery suggests a comparable efficacy and safety profile.

OBJECTIVES:: To evaluate the efficacy and safety of electrocautery as the primary heat therapy for malignant and benign airway obstruction.

METHODS:: A retrospective review of all patients undergoing endobronchial electrocautery, alone or in combination with other airway tools, at Duke University Medical Center between April 2004 and November 2009. Data on efficacy (luminal patency, symptomatic, radiographic, or physiologic improvement) and safety (complication rate) were collected.

RESULTS:: Ninety-four patients underwent 117 procedures with endobronchial electrocautery for endobronchial malignant and nonmalignant disease. Endoscopic improvement was seen in 94% of cases. Seventy-one percent of patients reported symptomatic improvement. Radiographic studies demonstrated luminal improvement in 78% of patients on chest computed tomography, improved aeration on chest computed tomography and chest x-ray in 63% and 43% of patients, respectively. The rate of major complications was 0.8%, whereas minor complications occurred in 6.8% of cases. There was no perioperative mortality.

CONCLUSIONS:: Endobronchial electrocautery is effective and safe when used as an ablative modality in malignant and benign airway obstruction and has a comparable profile to laser with the advantage of lower cost.

Advancing respiratory research.

Respiratory diseases remain a major public health problem in the United States and worldwide, with increasing morbidity and mortality. Substantial progress has been made to advance understanding of the basic mechanisms of lung disease and to optimize clinical management of patients with a range of respiratory diseases.

Despite this progress, our knowledge of how to predict disease prior to symptoms, improve disease definition and subclassification, and target novel and new treatments in a more personalized manner still remains inadequate. This article highlights several future opportunities and challenges related to genomics and molecular characterization of lung disease, lung injury and repair, translational lung research, the microbiome, and sleep and circadian biology as potential frontiers to advance progress in respiratory biology in health and disease.

Recent Insights into the Pathobiology of Innate Immune Deficiencies.

Primary immunodeficiencies are a heterogeneous group of genetically inherited diseases affecting the innate and adaptive immune systems that confer susceptibility to infection, autoimmunity, and cancer. Innate immunity includes neutrophils, macrophages, dendritic cells, natural killer cells, and natural killer T cells in conjunction with natural barriers (mostly skin and gastrointestinal and respiratory mucosa), as well as antimicrobial agents, opsonins (e.g., complement), and cytokines.

Although somewhat primitive, innate immune cells can orchestrate discrete immune responses through the recognition of diverse pathogens by different pattern-recognition receptors. In this review, we discuss the most recent discoveries as well as the already established pathophysiologic mechanisms underlying innate immunity defects associated with primary immunodeficiencies.

Reduced mortality in cystic fibrosis patients treated with tobramycin inhalation solution.

Though tobramycin inhalation solution has been used for over a decade to improve lung function and reduce exacerbations in patients with cystic fibrosis (CF), its effects on mortality have not been well-described. This study aimed to assess the association between use of tobramycin inhaled solution and mortality in patients with CF and chronic Pseudomonas aeruginosa (PA) infection.

METHODS: Longitudinal logistic regression was used to assess the association between current-year reported use of tobramycin inhalation solution and subsequent-year mortality of patients meeting recommended criteria for tobramycin inhalation solution use in the United States Cystic Fibrosis Foundation's Patient Registry (1996-2008).

RESULTS: Among 12,740 patients meeting inclusion criteria, 2,538 deaths were observed during a median follow-up of 6 years. After regression adjustment, use of tobramycin inhaled solution was associated with a 21% reduction in the odds of subsequent year mortality (odds ratio (95% CI): 0.79 (0.72-0.88), P < 0.001). In our model, use of dornase alfa was also associated with a 15% reduction in the odds of subsequent year mortality (odds ratio (95% CI): 0.85 (0.76-0.95), P = 0.005). Underweight for age, CF-related diabetes, female gender, worse lung function and cultures positive for Pseudomonas aeruginosa or Burkholderia cepacia complex, among multiple other patient characteristics, were associated with significantly increased mortality. Adjusted mortality rates for patients reporting tobramycin inhalation solution use in all versus none of the follow-up years were 1.3% versus 2.1% at 2 years, 5.2% versus 8.0% at 5 years, and 9.9% versus 15.0% at 10 years.

CONCLUSION: After adjustment for multiple patient characteristics and known risk factors, use of tobramycin inhalation solution was associated with significantly reduced mortality among patients with CF. Pediatr Pulmonol. © 2011 Wiley-Liss, Inc.

European Academy of Allergy and Clinical Immunology task force report on ‘dose–response relationship in allergen-specific immunotherapy’

To cite this article: Calderón MA, Larenas D, Kleine-Tebbe J, Jacobsen L, Passalacqua G, Eng PA, Varga EM, Valovirta E, Moreno C, Malling HJ, Alvarez-Cuesta E, Durham S, Demoly P. European Academy of Allergy and Clinical Immunology task force report on ‘dose–response relationship in allergen-specific immunotherapy’. Allergy 2011; DOI: 10.1111/j.1398-9995.2011.02669.xAbstractBackground:  For a century, allergen-specific immunotherapy (SIT) has proven to be an effective treatment for allergic rhinitis, asthma, and insect sting allergy. However, as allergen doses are frequently adapted to the individual patient, there are few data on dose-response relationship in SIT. Allergen products for SIT are being increasingly required to conform to regulatory requirements for human medicines, which include the need to demonstrate dose-dependent effects.Methods:  This report, produced by a Task Force of the EAACI Immunotherapy Interest Group, evaluates the currently available data on dose-response relationships in SIT and aims to provide recommendations for the design of future studies.Results:  Fifteen dose-ranging studies fulfilled the inclusion criteria and twelve reported a dose-response relationship for clinical efficacy. Several studies also reported a dose-response relationship for immunological and safety endpoints. Due to the use of different reference materials and methodologies for the determination of allergen content, variations in study design, and choice of endpoints, no comparisons could be made between studies and, as a consequence, no general dosing recommendations can be made.Conclusion:  Despite recently introduced guidelines on the standardization of allergen preparations and study design, the Task Force identified a need for universally accepted standards for the measurement of allergen content in SIT preparations, dosing protocols, and selection of clinical endpoints to enable dose-response effects to be compared across studies.

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