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Immunoevasive Aspergillus Virulence Factors.

Aspergillus-associated_diseaseIndividuals with structural lung disease or defective immunity are predisposed to Aspergillus-associated disease. Manifestations range from allergic to cavitary or angio-invasive syndromes.

Despite daily spore inhalation, immunocompetence facilitates clearance through initiation of innate and adaptive host responses. These include mechanical barriers, phagocyte activation, antimicrobial peptide release and pattern recognition receptor activation. Adaptive responses include Th1 and Th2 approaches. Understanding Aspergillus virulence mechanisms remains critical to the development of effective research and treatment strategies to counteract the fungi. Major virulence factors relate to fungal structure, protease release and allergens; however, mechanisms utilized to evade immune recognition continue to be important in establishing infection. These include the fungal rodlet layer, dihydroxynaphthalene-melanin, detoxifying systems for reactive oxygen species and toxin release.

One major immunoevasive toxin, gliotoxin, plays a key role in mediating Aspergillus-associated colonization in the context of cystic fibrosis. Here, it down-regulates vitamin D receptor expression which following itraconazole therapy is rescued concurrent with decreased Th2 cytokine (IL-5 and IL-13) concentrations in the CF airway.

This review focuses on the interaction between Aspergillus pathogenic mechanisms, host immune responses and the immunoevasive strategies employed by the organism during disease states such as that observed in cystic fibrosis.

Update in lung transplantation 2013.

Research in pulmonary transplantation is actively evolving in quality and scope to meet the challenges of a growing population of lung allograft recipients. In 2013, research groups leveraged large publicly available datasets in addition to multicenter research networks and single-center studies to make significant contributions to our knowledge and clinical care in the areas of donor use, clinical transplant outcomes, mechanisms of rejection, infectious complications, and chronic allograft dysfunction.

Update in sepsis and pulmonary infections 2013.

The Journal has been in the vanguard of publications of the respiratory microbiome, including a National Institutes of Health Workshop report, establishing the normal microbiome in patients with various risks, and in the correlation of microbiome changes with disease exacerbations and lung transplant.

A new classification scheme for healthcare-associated pneumonia, risks for nosocomial Pseudomonas pneumonia, and associations between community-acquired pneumonia and risks or outcomes have been reported. The increasingly recognized role of viral respiratory tract infections was reflected in publications regarding incidence rates, risk factors, and associations with other respiratory diseases. Significant contributions to understanding and treating sepsis emerged in 2013.

The role of tissue damage was highlighted in a series of publications. A much greater understanding of the importance of pathways that directly impact the pathogen at the site of infection and subsequent pathogen clearance has emerged. The Journal published important contributions across the spectrum of ineffective therapy (activated protein C), novel therapeutic ideas (statins and extracorporeal membrane oxygenation), and solidly beneficial approaches (early protocolized care).

Biomarker development is maturing to include a wide array of molecular measurements increasingly aimed at aiding improved therapy.

Noninfectious Pulmonary Complications of Human Immunodeficiency Virus Infection.

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Human immunodeficiency virus type 1 (HIV-1) is the retrovirus responsible for the development of AIDS. Its profound impact on the immune system leaves the host vulnerable to a wide range of opportunistic infections not seen in individuals with a competent immune system.

Pulmonary infections dominated the presentations in the early years of the epidemic, and infectious and noninfectious lung diseases remain the leading causes of morbidity and mortality in persons living with HIV despite the development of effective antiretroviral therapy. In addition to the long known immunosuppression and infection risks, it is becoming increasingly recognized that HIV promotes the risk of noninfectious pulmonary diseases through a number of different mechanisms, including direct tissue toxicity by HIV-related viral proteins and the secondary effects of coinfections. Diseases of the airways, lung parenchyma and the pulmonary vasculature, as well as pulmonary malignancies, are either more frequent in persons living with HIV or have atypical presentations.

As the pulmonary infectious complications of HIV are generally well known and have been reviewed extensively, this review will focus on the breadth of noninfectious pulmonary diseases that occur in HIV-infected individuals as these may be more difficult to recognize by general medical physicians and subspecialists caring for this large and uniquely vulnerable population.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

Pulmonary function impairment in patients with chronic heart failure: Lower limit of normal versus conventional cutoff values

Objective : To determine the prevalence of pulmonary function abnormalities in patients with chronic heart failure (HF) according to recent American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines using the lower limit of normal (LLN) compared to conventional cutoff values.

Background : Recent ATS/ERS guidelines recommend the use of the LLN instead of the conventional cutoff values to define pulmonary function impairment to avoid misclassification of patients. However, studies addressing the prevalence of pulmonary function abnormalities according to both definitions in patients with chronic HF are lacking.

Methods : In this prospective cross-sectional study, 164 chronic HF outpatients (age 68 ± 10 years, 78% men, 88% New York Heart Association class I–II) with left ventricular ejection fraction < 40% underwent spirometry and measurement of diffusing capacity. Body plethysmography was performed in patients with abnormal spirometry results.

Results : Diffusion impairment and airway obstruction were found in 44–58% and 26–37% of the patients, respectively, depending on the definition used (LLN versus conventional cutoff values, p < 0.05). However, restriction was infrequent, irrespective of the definition used (7% versus 5%, respectively, p > 0.05). The LLN identified fewer patients with abnormal lung function, whereas the conventional cutoff values classified more patients with diffusion impairment, airway obstruction, or a mixed category. Twenty-seven percent of patients were misclassified by the conventional cutoff values.

Conclusion : Pulmonary function abnormalities, especially diffusion impairment and airway obstruction, were highly prevalent in patients with chronic HF. Conventional cutoff values classified more patients with diffusion impairment, airway obstruction, or a mixed category compared to the LLN.

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