Efficacy of inhaled medications in asthma and COPD related to disease severity.

Expert Opin Drug Deliv. 2016 Jun 13;

Authors: Hajian B, Backer J, Vos W, Aerts J, Cluckers J, De Backer W

Abstract
INTRODUCTION: The administration of medication by inhalation has become the most important route in treating airway diseases. The efficacy of this route depends on several factors like correct inhalation techniques, compliance and the size of the particles. The flow properties and internal flow distribution contribute to the deposition pattern.
AREAS COVERED: What has been less well studied is the effect of the internal flow distribution. We know from recent studies that using systemic anti-inflammatory compounds that open up the distal airways redistributes flow internally and enhances the deposition of inhaled particles to the active site of bronchoconstriction or airway inflammation. We discuss this in more detail in this paper, and also make reference to the use of functional respiratory imaging (FRI) that allows for the description of this flow pattern starting from chest CT followed by post processing with segmentation software and the application of fluid dynamics.
EXPERT OPINION: The method that was previously validated does show the importance of redistribution of flow in the final clinical results that could be obtained with inhaled medication, especially in more severe obstructive airway diseases. Based on these insights and novel diagnostic tools, patients in end stage respiratory failure would benefit from a personalized approach with inhaled medication.

PMID: 27292454 [PubMed - as supplied by publisher]

Mycoplasma pneumoniae and Streptococcus pneumoniae caused different microbial structure and correlation network in lung microbiota.

J Thorac Dis. 2016 Jun;8(6):1316-22

Authors: Wang H, Dai W, Qiu C, Li S, Wang W, Xu J, Li Z, Wang H, Li Y, Yang Z, Feng X, Zhou Q, Han L, Li Y, Zheng Y

Abstract
Pneumonia is one of the most serious diseases for children, with which lung microbiota are proved to be associated. We performed 16S rDNA analysis on broncho-alveolar lavage fluid (BALF) for 32 children with tracheomalacia (C group), pneumonia infected with Streptococcus pneumoniae (S. pneumoniae) (D1 group) or Mycoplasma pneumoniae (M. pneumoniae) (D2 group). Children with tracheomalacia held lower microbial diversity and accumulated Lactococcus (mean ± SD, 45.21%±5.07%, P value <0.05), Porphyromonas (0.12%±0.31%, P value <0.05). D1 and D2 group were enriched by Streptococcus (7.57%±11.61%, P value <0.01 when compared with D2 group) and Mycoplasma (0.67%±1.25%, P value <0.01) respectively. Bacterial correlation in C group was mainly intermediated by Pseudomonas and Arthrobacter. Whilst, D1 group harbored simplest microbial correlation in three groups, and D2 group held the most complicated network, involving enriched Staphylococcus (0.26%±0.71%), Massilia (0.81%±2.42%). This will be of significance for understanding pneumonia incidence and progression more comprehensively, and discerning between bacterial infection and carriage.

PMID: 27293852 [PubMed]

Related Articles

Update in lung cancer: epilogue to a modern review series.

Respirology. 2016 May 30;

Authors: Fong KM, van Zandwijk N

PMID: 27242135 [PubMed - as supplied by publisher]

Related Articles

Hypoxia and tissue destruction in pulmonary TB.

Thorax. 2016 May 31;

Authors: Belton M, Brilha S, Manavaki R, Mauri F, Nijran K, Hong YT, Patel NH, Dembek M, Tezera L, Green J, Moores R, Aigbirhio F, Al-Nahhas A, Fryer TD, Elkington PT, Friedland JS

Abstract
BACKGROUND: It is unknown whether lesions in human TB are hypoxic or whether this influences disease pathology. Human TB is characterised by extensive lung destruction driven by host matrix metalloproteinases (MMPs), particularly collagenases such as matrix metalloproteinase-1 (MMP-1).
METHODS: We investigated tissue hypoxia in five patients with PET imaging using the tracer [(18)F]-fluoromisonidazole ([(18)F]FMISO) and by immunohistochemistry. We studied the regulation of MMP secretion in primary human cell culture model systems in normoxia, hypoxia, chemical hypoxia and by small interfering RNA (siRNA) inhibition.
RESULTS: [(18)F]FMISO accumulated in regions of TB consolidation and around pulmonary cavities, demonstrating for the first time severe tissue hypoxia in man. Patlak analysis of dynamic PET data showed heterogeneous levels of hypoxia within and between patients. In Mycobacterium tuberculosis (M.tb)-infected human macrophages, hypoxia (1% pO2) upregulated MMP-1 gene expression 170-fold, driving secretion and caseinolytic activity. Dimethyloxalyl glycine (DMOG), a small molecule inhibitor which stabilises the transcription factor hypoxia-inducible factor (HIF)-1α, similarly upregulated MMP-1. Hypoxia did not affect mycobacterial replication. Hypoxia increased MMP-1 expression in primary respiratory epithelial cells via intercellular networks regulated by TB. HIF-1α and NF-κB regulated increased MMP-1 activity in hypoxia. Furthermore, M.tb infection drove HIF-1α accumulation even in normoxia. In human TB lung biopsies, epithelioid macrophages and multinucleate giant cells express HIF-1α. HIF-1α blockade, including by targeted siRNA, inhibited TB-driven MMP-1 gene expression and secretion.
CONCLUSIONS: Human TB lesions are severely hypoxic and M.tb drives HIF-1α accumulation, synergistically increasing collagenase activity which will lead to lung destruction and cavitation.

PMID: 27245780 [PubMed - as supplied by publisher]