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Characteristics of eosinophilic and non-eosinophilic asthma during treatment with inhaled corticosteroids.

eosinophilObjective: Eosinophilic inflammation in the respiratory tract is a hallmark of bronchial asthma. In naïve cases, the inflammatory profile is associated with disease severity and reactivity to inhaled corticosteroids (ICS). Sustained airway eosinophilia has been reported during ICS treatment. However, how this contributes to asthma control is unclear, nor are the immunologic characteristics of these cases known. This study was performed to determine the answer these questions.

Methods: To compare phenotypes of eosinophilic and non-eosinophilic asthma (EA and NEA, respectively) under ICS treatment, clinical data were obtained from asthmatic subjects (n = 22) and healthy controls (n = 10), and the leukocyte compositions of induced sputum and peripheral blood were determined. T lymphocyte profiles in systemic blood were assessed by flow cytometry.

Results: A higher frequency of emergency room visits was observed in the NEA group, which had a higher neutrophil count relative to the total inflammatory cell population in induced sputum than the EA group (59.5% vs. 36.6%; P < 0.01). The fraction of helper T (Th)17 lymphocytes as well as the ratio of Th17 to regulatory T cells (Treg) in the peripheral blood was higher in the NEA than in the EA group (0.24 vs. 0.13; P < 0.05).

Conclusions: Th17 were more prevalent than Treg cells in the peripheral blood of NEA patients under ICS treatment, corresponding to neutrophil-dominant airway inflammation and a severe asthmatic phenotype. Thus, an imbalance in Th17/Treg may be associated with the pathogenesis of NEA in patients undergoing ICS treatment.

PMID: 25329682 [PubMed - as supplied by publisher]

NEXThaler, an innovative dry powder inhaler delivering an extrafine fixed combination of beclometasone and formoterol to treat large and small airways in asthma.

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NEXThaler, an innovative dry powder inhaler delivering an extrafine fixed combination of beclometasone and formoterol to treat large and small airways in asthma.

Expert Opin Drug Deliv. 2014 Sep;11(9):1497-506

Authors: Corradi M, Chrystyn H, Cosio BG, Pirozynski M, Loukides S, Louis R, Spinola M, Usmani OS

Abstract
INTRODUCTION: Airway inflammation and remodelling in asthma occur in the large airways and also in the small airways. The small airways are those < 2 mm in diameter and are significant sites of chronic asthmatic inflammation. It is important, therefore, to target the small as well as the large airways in any strategy for effective treatment of this disease.
AREAS COVERED: The present review deals with the recently developed fixed dose drug combination of beclometasone dipropionate/formoterol fumarate that emits extrafine particles when delivered from an innovative dry powder inhaler (DPI), NEXThaler®. The aim is to present the technical and clinical aspects of aerosolized drug delivery to the lungs.
EXPERT OPINION: The data show that the NEXThaler DPI is an efficient device for the management of persistent asthma. The evaluation of the inhalation profiles through the NEXThaler DPI demonstrates that device activation and consistent dose delivery occurs at patient achievable inhalation flow rates, and supports the broad utility of the NEXThaler DPI in patients with asthma. Overall, all the effectiveness, efficiency and satisfaction outcomes demonstrate the NEXThaler DPI is easy to use.

PMID: 24921434 [PubMed - indexed for MEDLINE]

Vanishing lung syndrome in one family: Five cases with a 20-year follow-up.

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Vanishing lung syndrome in one family: Five cases with a 20-year follow-up.

Mol Med Rep. 2014 Oct 16;

Authors: Gao X, Wang H, Gou K, Huang B, Xia D, Wu X, Wei M, Zheng S, Ma S, He J

Abstract
Vanishing lung syndrome, also known as idiopathic giant bullous emphysema, is a rare disease characterized by giant emphysematous bullae. The disease is diagnosed by radiological findings of giant bullae in one, or both, of the upper lobes of the lung, occupying at least one‑third of the hemithorax. There have been several reports of vanishing lung syndrome, however it remains to be determined whether genetic inheritance is associated with the disease. In the present study, five patients within one family, with vanishing lung syndrome, were reported during a follow‑up period of ~20 years. All of the patients were diagnosed by radiological findings, which showed diffuse bullae in the lungs, which were of varying size and asymmetrical distribution, and the occurrence of pneumothorax or emphysema. The Medical Ethics Committee of the People's Hospital of Zhangye Municipality (Zhangye, China) approved this study, and all subjects gave their informed consent During the follow‑up period of 20 years, bullae in these patients were shown to progressively increase, and no other pulmonary diseases, including lung cancer, tuberculosis, pneumoconiosis and chronic bronchitis were observed. Autosomal dominant inheritance was observed in five cases, and autosomal recessive inheritance was observed in one case. The present study suggests that vanishing lung syndrome may be associated with autosomal dominant and recessive genetic inheritance.

PMID: 25322795 [PubMed - as supplied by publisher]

Early-life origins of chronic respiratory diseases: understanding and promoting healthy ageing.

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Early-life origins of chronic respiratory diseases: understanding and promoting healthy ageing.

Eur Respir J. 2014 Oct 16;

Authors: Carraro S, Scheltema N, Bont L, Baraldi E

Abstract
Chronic obstructive respiratory disorders such as asthma and chronic obstructive pulmonary disease often originate early in life. In addition to a genetic predisposition, prenatal and early-life environmental exposures have a persistent impact on respiratory health. Acting during a critical phase of lung development, these factors may change lung structure and metabolism, and may induce maladaptive responses to harmful agents, which will affect the whole lifespan. Some environmental factors, such as exposure to cigarette smoke, type of childbirth and diet, may be modifiable, but it is more difficult to influence other factors, such as preterm birth and early exposure to viruses or allergens. Here, we bring together recent literature to analyse the critical aspects involved in the early stages of lung development, going back to prenatal and perinatal events, and we discuss the mechanisms by which noxious factors encountered early on may have a lifelong impact on respiratory health. We briefly comment on the need for early disease biomarkers and on the possible role of "-omic" technologies in identifying risk profiles predictive of chronic respiratory conditions. Such profiles could guide the ideation of effective preventive strategies and/or targeted early lifestyle or therapeutic interventions.

PMID: 25323240 [PubMed - as supplied by publisher]

Inhaled antibiotics: dry or wet?

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Dry powder inhalers (DPIs) delivering antibiotics for the suppressive treatment of Pseudomonas aeruginosa in cystic fibrosis patients were developed recently and are now increasingly replacing time-consuming nebuliser therapy. Noninferiority studies have shown that the efficacy of inhaled tobramycin delivered by DPI was similar to that of wet nebulisation. However, there are many differences between inhaled antibiotic therapy delivered by DPI and by nebuliser.

The question is whether and to what extent inhalation technique and other patient-related factors affect the efficacy of antibiotics delivered by DPI compared with nebulisers. Health professionals should be aware of the differences between dry and wet aerosols, and of patient-related factors that can influence efficacy, in order to personalise treatment, to give appropriate instructions to patients and to better understand the response to the treatment after switching. In this review, key issues of aerosol therapy are discussed in relation to inhaled antibiotic therapy with the aim of optimising the use of both nebulised and DPI antibiotics by patients. An example of these issues is the relationship between airway generation, structural lung changes and local concentrations of the inhaled antibiotics.

The pros and cons of dry and wet modes of delivery for inhaled antibiotics are discussed.

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