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Demonstration of the heterogeneous distribution of asthma in the lungs using CT and hyperpolarized helium-3 MRI.

Asthma is a chronic inflammatory disease that affects both the large and small airways and results in bronchoconstriction, mucous hypersecretion, smooth muscle hypertrophy, and subepithelial fibrosis.

To gain insight into the pathophysiology of asthma, chest computed tomography (CT) has been investigated as a noninvasive method to evaluate airway wall thickness of medium and large airways. Hyperpolarized gas MRI can assess the functional alterations of airflow within the lung resulting from the structural changes in the airways. In this article, we review the application of CT-based techniques and hyperpolarized gas MRI to study structural and functional changes in asthma. From the result of studies with CT and hyperpolarized gas MRI, it is becoming apparent that asthma has a regional distribution within the lung, that is, some areas of the lung are more affected than others. Furthermore, there appears to be some persistence to this distribution which may explain the observed patterns of airway remodeling and provide targets for localized therapies such as local application of anti-inflammatory agents or bronchial thermoplasty.

Thus, cross sectional imaging in asthma is providing new insights into the pathophysiology of the disease and has the potential to become essential in the guidance of localized treatments.

Asthma related to Alternaria sensitization: an analysis of skin-test and serum-specific IgE efficiency based on the bronchial provocation test.

It is difficult to find a causal relationship between exposure to Alternaria spores and the development of asthma symptoms in sensitized individuals due to the complexity of clinical situations in which positive diagnostic tests are often found.

Objective : To analyse the diagnostic efficiency of skin testing (ST) and serum-specific IgE to Alternaria, based on the results of a bronchial specific challenge with Alternaria extracts.

Methods : Seventy-four asthmatic patients sensitized to Alternaria underwent a specific bronchial challenge with this mould. Skin-testing weal sizes, serum-specific IgE values (CAP-system) and bronchial challenge results were analysed by receiver operating characteristics curves (ROC curves) and logistic regression. The sensitivity, specificity, positive and negative predictive values were calculated for different cut-off points.

Results : Bronchial challenges to Alternaria elicited a positive result in 45 patients (61%). Skin prick testing almost perfectly predicted the outcome of bronchoprovocation tests (area under the ROC curve of 0.957), whereas intradermal skin testing had moderate efficacy. A negative result for skin prick test (SPT) showed a 4% probability of a positive bronchial challenge in the logistic regression analysis. However, weals around 5.5 mm in diameter had 90% probability of a positive challenge. Quantification of serum-specific IgE correctly classified 86% of the cases. In the logistic regression analysis, a CAP value 16 kU(A) /L predicted a positive bronchial challenge result with 99% accuracy, whereas for a CAP value <0.35 kU(A) /L, this probability was 33%.

Conclusions and Clinical Relevance : Most asthmatic patients with positive SPT results to Alternaria would have a positive bronchial challenge. As atmospheric mould levels may vary significantly with the weather conditions, sensitized patients should be instructed on the risk situations, environmental control measures and the importance of correct medication compliance. Immunotherapy with Alternaria could also be taken into account as a valid therapeutic option.

Targeting small airways in asthma: Improvement in clinical benefit?

Background and Aim:  Disease control is not achieved in a substantial proportion of patients with asthma. Recent advances in aerosol formulations and delivery devices may offer more effective therapy.

This review will focus on the importance and potential clinical benefit of targeting the lung periphery in adult asthma by means of ultrafine aerosols.

Results:  Ultrafine formulations of inhaled corticosteroids have improved lung deposition up to at least 50 %, primarily in the peripheral airways. Ultrafine formulations of ICS provide equivalent asthma control to non-ultrafine ICS at approximately half the daily dose with no increased risk of systemic effects. Clinical studies of adults with asthma have shown a greater effect of ultrafine ICS, compared with non-ultrafine ICS, on quality of life, small airway patency, and markers of pulmonary and systemic inflammation, but no difference with regard to conventional clinical indices of lung function and asthma control.

Conclusions:  Asthma patients treated with ultrafine ICS, compared with non-ultrafine ICS, have at least similar chance of achieving asthma control at a lower daily dose. Further clinical studies are needed to explore whether treatment with ultrafine formulations of ICS will change the natural history of asthma and prevent airway remodelling in both the large and small airways.

Diagnosis and definition of severe refractory asthma: an international consensus statement from the Innovative Medicine Initiative (IMI).

Patients with severe refractory asthma pose a major healthcare problem. Over the last decade it has become increasingly clear that, for the development of new targeted therapies, there is an urgent need for further characterisation and classification of these patients.

The Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) consortium is a pan-European public-private collaboration funded by the European Commission Innovative Medicines Initiative of the European Union. U-BIOPRED aims to subphenotype patients with severe refractory asthma by using an innovative systems biology approach. This paper presents the U-BIOPRED international consensus on the definition and diagnosis of severe asthma, aligning the latest concepts in adults as well as in children. The consensus is based on existing recommendations up to 2010 and will be used for the selection of patients for the upcoming U-BIOPRED study.

It includes the differentiation between 'problematic', 'difficult' and 'severe refractory' asthma, and provides a systematic algorithmic approach to the evaluation of patients presenting with chronic severe asthma symptoms for use in clinical research and specialised care.

Respiratory Viruses, Eosinophilia and Their Roles in Childhood Asthma.

With the advent of highly sensitive and specific screening of respiratory specimens for viruses, new viruses are discovered, adding to the growing list of those associated with wheezing illness and asthma exacerbations. It is not known whether early childhood infections with these viruses cause asthma, and, if so, what exactly are the pathophysiologic mechanisms behind its development.

The current consensus is that respiratory viral infection works together with allergy to produce the immune and physiologic conditions necessary for asthma diasthesis. One link between viruses and asthma may be the eosinophil, a cell that plays a prominent role in asthma and allergy, but can also be found in the body in response to viral infection. In turn, the eosinophil and its associated products may be novel therapeutic targets, or at the very least, used to elucidate the complex pathophysiologic pathways of asthma and other respiratory illnesses. Together or separately, they can be used for diagnosis, treatment and monitoring.

Not only symptoms, but also the underlying disease mechanisms must be taken into consideration for the optimal care of a patient.

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