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Agreement and mortality prediction in high-resolution CT of diffuse fibrotic lung disease.

The prognosis of diffuse fibrotic lung disease (DFLD) is known to be variable, but there is a paucity of literature on prognostic markers independent of precise clinical diagnosis. This study aimed to assess the mortality prediction of three high-resolution computed tomography (HRCT) scores in a heterogeneous population of patients with DFLD. A large radiologist and physician reader group was used to determine agreement among readers of varying background in applying these scores.

METHODS: Institutional review board approval was obtained. Informed consent was waived for this retrospective study. Eighty HRCTs in 68 patients with DFLD (35 men, mean age 72.9 years) were evaluated retrospectively by 18 readers. Readers included thoracic and general radiologists, respiratory physicians and radiology trainees. Features scored were honeycombing, extent of disease and traction bronchiectasis. Demographics, diagnosis and pulmonary function data were collected. Patients were categorised as having either idiopathic pulmonary fibrosis, fibrosis relating to connective tissue disease, 'miscellaneous' DFLD or 'undefined', where no single entity was felt entirely or confidently to explain the pulmonary disease. Agreement was assessed using the kappa statistic. Associations with mortality were analysed using the Cox marginal model.

RESULTS: Agreement was better for honeycombing (kappa = 0.44) and disease extent (kappa = 0.47) than traction bronchiectasis (kappa = 0.24). Honeycombing presence (P < 0.0005) and disease extent >30% (P = 0.002) predicted increased mortality independent of clinical diagnosis. Traction bronchiectasis was non-predictive. Clinical diagnosis was not an independent predictor, but age was independently associated with mortality (P = 0.004). Pulmonary function data were only available for 43 patients, but in a limited subanalysis, the diffusion capacity of carbon monoxide was independently predictive of increased mortality (P = 0.005).

CONCLUSIONS: The presence of honeycombing and a greater extent of fibrotic lung disease predict increased mortality independent of clinical diagnosis. Our large, mixed-expertise reader group shows moderate interobserver agreement, comparable with agreement values for these scores in the literature.

Devices for Dry Powder Drug Delivery to the Lung.

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Dry powder inhalers (DPIs) are an important and increasingly investigated method of modern therapy for a growing number of respiratory diseases. DPIs are a promising option for certain patient populations, and may help to overcome several limitations that are associated with other types of inhalation delivery systems (e.g., accuracy and reproducibility of the dose delivered, compliance and adherence issues, or environmental aspects).

Today, more than 20 different dry powder inhalers are on the market to deliver active pharmaceutical ingredients (APIs) for local and/or systemic therapy. Depending on the mechanism of deagglomeration, aerosolization, dose metering accuracy, and the interpatient variability, dry powder inhalers demonstrate varying performance levels. During development, manufacturers focus on improving aspects characteristic of their specific DPI devices, depending on the intended type of application and any particular requirements associated with it. With the wide variety of applications related to specific APIs, there exists a range of different devices with distinct features. In addition to the routinely used multi-use DPIs, several single-use disposable devices are under development or already approved. The recent introduction of disposable devices will expand the range of possible applications for use by including agents such as vaccines, analgesics, or even rescue medications.

This review article discusses the performance and advantages of recently approved dry powder inhalers as well as disposable single-use inhalers that are currently under development.

Streptococcus pneumoniae triggers progression of pulmonary fibrosis through pneumolysin.

RATIONALE: Respiratory tract infections are common in patients suffering from pulmonary fibrosis. The interplay between bacterial infection and fibrosis is characterised poorly.

OBJECTIVES: To assess the effect of Gram-positive bacterial infection on fibrosis exacerbation in mice.

METHODS: Fibrosis progression in response to Streptococcus pneumoniae was examined in two different mouse models of pulmonary fibrosis.

MEASUREMENTS AND MAIN RESULTS: We demonstrate that wild-type mice exposed to adenoviral vector delivery of active transforming growth factor-β1 (TGFß1) or diphteria toxin (DT) treatment of transgenic mice expressing the DT receptor (DTR) under control of the surfactant protein C (SPC) promoter (SPC-DTR) to induce pulmonary fibrosis developed progressive fibrosis following infection with Spn, without exhibiting impaired lung protective immunity against Spn. Antibiotic treatment abolished infection-induced fibrosis progression. The cytotoxin pneumolysin (Ply) of Spn caused this phenomenon in a TLR4-independent manner, as Spn lacking Ply (SpnΔply) failed to trigger progressive fibrogenesis, whereas purified recombinant Ply did. Progressive fibrogenesis was also observed in AdTGFβ1-exposed Ply-challenged TLR4 KO mice. Increased apoptotic cell death of alveolar epithelial cells along with an attenuated intrapulmonary release of antifibrogenic prostaglandin E2 was found to underlie progressive fibrogenesis in Ply-challenged AdTGFβ1-exposed mice. Importantly, vaccination of mice with the non-cytotoxic Ply derivative B (PdB) substantially attenuated Ply-induced progression of lung fibrosis in AdTGFβ1-exposed mice.

CONCLUSIONS: Our data unravel a novel mechanism by which infection with Spn through Ply release induces progression of established lung fibrosis, which can be attenuated by protein-based vaccination of mice.

CHILDHOOD ASTHMA BIOMARKERS: Present knowledge and future steps

(Source: Paediatric Respiratory Reviews)

Characteristics and Clinical Management of a Cluster of 3 Patients With Ebola Virus Disease, Including the First Domestically Acquired Cases in the United States.

Conclusion: Early diagnosis, prompt initiation of supportive medical care, and moderate clinical illness likely contributed to successful outcomes in both survivors. The inability to determine the potential benefit of investigational therapies and the effect of patient-specific factors that may have contributed to less severe illness highlight the need for controlled clinical studies of these interventions, especially in the setting of a high level of supportive medical care. Primary Funding Source: None. PMID: 25961438 [PubMed - as supplied by publisher] (Source: Annals of Internal Medicine)

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