Publications

Group 2 innate lymphoid cells (ILC2s) have an important role in acute allergic lung inflammation. Given their distribution and function, lung ILC2s are hypothesized to coordinate epithelial responses to the external environment; however, how barrier surveillance is linked to ILC2 activation remains unclear. Here, we demonstrate that alveolar type II cells are the main source of interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP) generated in response to chitin or migratory helminths. IL-33 and TSLP synergistically induce an interferon regulatory factor 4 (IRF4)-IL-9 program in ILC2s, and autocrine IL-9 promotes rapid IL-5 and IL-13 production required for optimal epithelial responses in the conducting airways. Thus, ILC2s link alveolar function to regulation of airway flow, revealing a key interaction between resident lymphoid and structural cells that might underlie similar organizational hierarchies in other organs.

We present the case of a 67-year-old man with concomitant stroke and pulmonary embolism 1 day after radiofrequency catheter ablation for refractory atrial tachycardia. A chest computed tomographic angiogram revealed "thrombus-in-transit" across a patent foramen ovale, confirming the diagnosis of paradoxical embolism. Paradoxical embolism is a rare definitive diagnosis. Our case is a key demonstration of the even rarer instance where such a diagnosis is confirmed at multidetector computed tomography.

PURPOSE OF REVIEW

Studies have illustrated that the healthy human microbiome (i.e. the communities of microbes, their genomic content and interaction with the host) plays a role in the maintenance of immune homeostasis. Perturbation of these communities is an emerging characteristic of an increasing number of inflammatory diseases. The goal of this article is to review the current literature on both respiratory and gut microbiomes and their established relationship with allergy and asthma.

RECENT FINDINGS

Multiple studies have demonstrated airway microbiota dysbiosis, characterized by Proteobacteria expansion in the lower airways, to be a consistent trait of established adult asthma. Members of this phylum are associated with disease features such as bronchial hyperreactivity or corticosteroid resistance. Emerging evidence implicates the neonatal gut microbiome as playing a significant role in the development of childhood atopy, a common precursor to asthma. Murine studies have demonstrated that specific bacterial species (e.g. Lactobacillus johnsonii, Bacteroides fragilis) and microbial metabolites (e.g. the short-chain fatty acid propionate), when supplemented to animals, confer protection against allergen-induced airway disorders.

SUMMARY

The emerging view of atopy and asthma is one consistently related to inappropriate microbial community composition and function in both the airway and gastrointestinal tract. This opens up the possibility that strategies to rationally manipulate microbiota at these sites may represent a novel approach to disease prevention or management.

The fifth Jack Pepys Workshop on Asthma in the Workplace focused on the similarities and differences of work-related asthma (WRA) and non-work-related asthma (non-WRA). WRA includes occupational asthma (OA) and work-exacerbated asthma (WEA). There are few biological differences in the mechanisms of sensitization to environmental and occupational allergens. Non-WRA and OA, when due to high-molecular-weight agents, are both IgE mediated; it is uncertain whether OA due to low-molecular-weight agents is also IgE mediated. Risk factors for OA include female sex, a history of upper airway symptoms, and a history of bronchial hyperresponsiveness. Atopy is a risk factor for OA due to high-molecular-weight agents, and exposure to cleaning agents is a risk factor for both OA and non-WRA. WEA is important among workers with preexisting asthma and may overlap with irritant-induced asthma, a type of OA. Induced sputum cytology can confirm airway inflammation, but specific inhalation challenge is the reference standard diagnostic test. Inhalation challenges are relatively safe, with the most severe reactions occurring with low-molecular-weight agents. Indirect health care costs account for about 50% of total asthma costs. Workers with poor asthma control (WRA or non-WRA) are less likely to be employed. Income loss is a major contributor to the indirect costs of WRA. Overall, asthma outcomes probably are worse for adult-onset than for childhood-onset asthma but better for OA than adult-onset non-WRA. Important aspects of management of OA are rapid and proper confirmation of the diagnosis and reduction of exposure to sensitizers or irritants at work and home.