Chest
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The relative importance of respiratory viral infections vs inhalant allergy in asthma pathogenesis is the subject of ongoing debate. Emerging data from long-term prospective birth cohorts are bringing increasing clarity to this issue, in particular through the demonstration that while both of these factors can contribute independently to asthma initiation and progression, their effects are strongest when they act in synergy to drive cycles of episodic airways inflammation. An important question is whether susceptibility to infection and allergic sensitization in children with asthma arises from common or shared defect(s). ⋯ The effects of these defects in DCs from children wtih asthma are accentuated by parallel attenuation of innate immune functions in adjacent airway epithelial cells that reduce their resistance to the upper respiratory viral infections, which are the harbingers of subsequent inflammatory events at asthma lesion site(s) in the lower airways. An important common factor underpinning the innate immune functions of these unrelated cell types is use of an overlapping series of pattern recognition receptors (exemplified by the Toll-like receptor family), and variations in the highly polymorphic genes encoding these receptors and related molecules in downstream signaling pathways appear likely contributors to these shared defects. Findings implicating recurrent respiratory infections in adult-onset asthma, much of which is nonatopic, suggest a similar role for deficient immune surveillance in this phenotype of the disease.
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COPD is accepted to be a multicomponent disease with various comorbidities. To our knowledge, the contribution of the GI tract to the systemic manifestation of COPD has never been investigated. This metabolically active organ may experience recurring local oxygen deficits during daily life, leading to disturbed intestinal integrity in patients with COPD. ⋯ Besides an altered intestinal permeability in patients with COPD when at rest, performing ADLs led to enterocyte damage in addition to intestinal hyperpermeability in patients with COPD but not in control subjects, indicating functional alteration in the GI tract. Hence, intestinal compromise should be considered as a new component of the multisystem disorder COPD.
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Restrictive lung disease is uncommon in pregnancy. We reviewed 15 pregnancies in 12 women with restrictive disease due to kyphoscoliosis, neuromuscular disease, or parenchymal lung disease. Median FVC was 40% predicted, and six women (50%) had an FVC < 1.0 L. ⋯ There was no maternal or neonatal mortality. Women with restrictive lung disease tolerate pregnancy reasonably well, but many have premature delivery. A multidisciplinary approach is essential, with monitoring of spirometry and oxygenation and planning for labor and delivery.
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Parental smoking is known to worsen asthma symptoms in children and to make them refractory to asthma treatment, but the molecular mechanism is unclear. Oxidative stress from tobacco smoke has been reported to impair histone deacetylase-2 (HDAC2) via phosphoinositide-3-kinase (PI3K)/Akt activation and, thus, to reduce corticosteroid sensitivity. The aim of this study was to investigate passive smoking-dependent molecular abnormalities in alveolar macrophages (AMs) by comparing passive smoke-exposed children and non-passive smoke-exposed children with uncontrolled severe asthma. ⋯ Passive smoking impairs HDAC2 function via PI3K signaling activation, which could contribute to corticosteroid-insensitive inflammation in children with severe asthma. This novel mechanism will be a treatment target in children with severe asthma and stresses the need for a smoke-free environment for asthmatic children.