Jl Black

Viral infections and asthma: an inflammatory interface?

Asthma is a chronic inflammatory disease of the airways in which the majority of patients respond to treatment with corticosteroids and &bgr;2-adrenoceptor agonists. Acute exacerbations of asthma substantially contribute to disease morbidity, mortality and healthcare costs, and are not restricted to patients who are not compliant with their treatment regimens. Given that respiratory viral infections are the principal cause of asthma exacerbations, this review article will explore the relationship between viral infections and asthma, and will put forward hypotheses as to why virus-induced exacerbations occur. Potential mechanisms that may explain why current therapeutics do not fully inhibit virus-induced exacerbations, for example, &bgr;2-adrenergic desensitisation and corticosteroid insensitivity, are explored, as well as which aspects of virus-induced inflammation are likely to be attenuated by current therapy. Why do virus-induced asthma exacerbations occur? Mechanisms and interventions http://ow.ly/zh126

Asthma: Airways That Are Hyperactive by Design

populations described as originating either from the lungs (pulmonary DCs and alveolar macrophages) or from blood monocytes (monocyte-derived cells and tissue monocytes). Desch and colleagues describe alveolar macrophages as a single population. Although the M1/M2 paradigm is too simplistic (1, 7), it highlights that macrophages have plasticity and can be influenced by external stimuli such as cytokines. Alveolar macrophages were identified in the bronchoalveolar lavage and tissue digest; these cells may serve different functions in these two locations under the influence of the local environments. These influences will be amplified or altered in disease, such as chronic obstructive pulmonary disease, where alveolar macrophages display defective bacterial efferocytosis (9) and phagocytosis (13). The authors also identified two distinct MPS cells populations in the lung draining lymphnodes: One population resembled pulmonary DCs, with HLA-DR CD1cCD1aCD14CD206 expression, whereas the other resembled pulmonary monocyte/macrophages with CD14CD141CD206CD64CD1c expression. High CCR7 expression, which regulates homing to lymph nodes (14), was detected in the former population, suggesting that pulmonary DCs migrate into lymph nodes, but this was not studied. Nevertheless, the location of both populations indicated close interactions with T cells, linking innate and adaptive immune responses. A potential criticism of this work is that patients with lung disease were not studied. However, a detailed description of theMPS in healthy human lungs was required before one can contemplate understanding disease pathophysiology. This comprehensive MPS analysis in the lung, blood, and lymph nodes will now provide a basis for studies examining the function of these cells in lung for maintaining homeostasis and how they may be skewed or altered during disease.n

BIBF1120 inhibits proliferation and fibulin-1 production from fibroblasts

Aim: PBB and bronchiectasis are distinct clinical entities but share commonclinical and laboratory features. It is postulated, but remains unproven, that protracted bacterial bronchitis is antecedent to a diagnosis of bronchiectasis. In a cohort of children with PBB, our aims were to: a) determine the medium-term risk of bronchiectasis and b) identify risk factors for bronchiectasis and recurrent episodes of PBB. Methods: 106 children with PBB and 25 controls were prospectively recruited (2008–2012) and followed for 2 years. Flexible bronchoscopy, bronchoalveolar lavage (BAL) and basic immune function tests were performed at baseline. Cough diaries were completed during periods of illness and monthly contact with parents was made to capture respiratory exacerbations. HRCT chest was undertaken in those with clinical features suggestive ofbronchiectasis. Results: Of the 106 children with PBB (70% male), followed for median 25 months (IQR 24, 28), 12% (n=13) were diagnosed with BE on CT chest. Over half (62%) of children with PBB had recurrent episodes (>3 per year). The major risk factors for BE, on multi-variate analysis, were H. influenzae lower airway infection (p=0.012) and having 2+siblings (p=0.040). H. influenzae lower airway infection conferred greater than 6 times higher risk of BE, com-pared to H. influenzae negative state [hazard ratio 6.80 (95% CI 1.50 –30.80), p=0.013]. No risk factors for recurrent PBB were identified. Conclusion: PBB is antecedent to a diagnosis of bronchiectasis in a sub-group of children. H. influenzae lower airway infection and having multiple siblings appear to be risk factors. Clinicians should be cognisant of the need to monitor children with PBB for future occurrence of bronchiectasis. Grant Support: NHMRC grant and Financial Markets Foundation for chil-dren (project), TSANZ/Allen & Hanburys, QCMRI and NHMRC (for DW),NHMRC (AC). Conflict: None.