News Beyond Our Pages – July 2010

Article Outline

• Wound repair in lungs of asthmatic subjects
• Is allergy protective against cancer? Part I
• Is allergy protective against cancer? Part 2
• Air quality and virus infections
• Flu transmission in guinea pigs
• Seasonality of influenza infection
• Influenza epidemiology

Back to Article Outline

Wound repair in lungs of asthmatic subjects 

• 
  • View Large Image
  • Download to PowerPoint

Remodeling is defined by ad integrum or abnormal repair. Remodeling in asthma is a relatively old concept, but the role of the epithelium in this process requires better understanding. Airway epithelium from children with asthma does not heal adequately. Now Kicic et al (Am J Respir Crit Care Med 2010;181:889-98) identify fibronectin as an abnormal extracellular matrix component causing impaired wound healing in airway epithelial cells (AECs) from asthmatic subjects. The authors identified differentially expressed gene sets associated with wound healing in AECs from healthy nonatopic, healthy atopic, and atopic asthmatic subjects. A number of the wound-healing gene sets showed significantly decreased expression in asthmatic epithelium, including genes associated with Toll-like receptor signaling and cytokine expression. Fibronectin (FN-1) was the only extracellular matrix component that had significantly downregulated expression. The authors demonstrated that fibronectin was necessary and sufficient for wound repair in normal AECs and that AECs from asthmatic subjects had impaired fibronectin expression and production. They also showed that in vitro wound repair improved when extraneous fibronectin was added to AECs from asthmatic subjects.

• 
  • View Large Image
  • Download to PowerPoint

• Anthony Kicic, Telethon Institute for Child Health Research

Anthony Kicic, PhD, lead author, gave us this comment: “Utilizing a global gene expression analysis we demonstrated that … dysregulated wound healing response is related to reduced capacity of the asthmatic epithelium to produce the extracellular matrix protein, fibronectin. Our findings provide further mechanistic support for the concept that compromised repair processes and other abnormalities occur very early in disease pathogenesis.”

Back to Article Outline

Is allergy protective against cancer? Part I 

ElMasri et al (Arch Environ Occup Health 2010;65:101-5) reported the results of a case-control study that looked at the association between asthma and ovarian cancer using a statewide Florida hospital discharge database. The authors found that patients with ovarian cancer were 30% less likely to be given a diagnosis of asthma compared with one control group and 38% less likely to be given a diagnosis compared with a second control group, suggesting that patients with asthma were less likely to have cancer of the ovary. ElMasri and coauthors suggest an IL-4 link to the apparent protective effect of asthma, which has been shown to have tumor inhibition activity. (This article is summarized in more detail on the NBOP blog: www.jaci-nbop.blogspot.com.)

Back to Article Outline

Is allergy protective against cancer? Part 2 

Linabery et al (Am J Epidemiol 2010;171:749-64) presented findings from a broad-scope meta-analysis that examined associations between clinical manifestations of atopy, including allergies, asthma, eczema, “hay fever,” and hives and childhood/adolescent leukemia, acute lymphoblastic leukemia (ALL), and acute myeloid leukemia. Ten case-control studies were identified from multiple databases. For any atopy/allergies, 31% were less likely to have ALL. Each atopic disease also had a significant inverse association with ALL. The authors also found that an inverse relationship existed between any atopy/allergy and acute myeloid leukemia but that it did not reach significance. There was no overall association between any atopy/allergy and any leukemia. Linabery et al pointed out that the commonality shared by both atopy and leukemia is the working hypothesis that both are linked to the maturation rate of the immune system. (This article is summarized in more detail on the NBOP blog: www.jaci-nbop.blogspot.com.)

Back to Article Outline

Air quality and virus infections 

Seasonal patterns of influenza infections have been largely characterized by changes in social behavior patterns during the winter. In the following series of articles, 3 research groups looked at the effect of ambient air qualities on transmission and survival of influenza virus.

Back to Article Outline

Flu transmission in guinea pigs 

• 
  • View Large Image
  • Download to PowerPoint

Lowen et al (PLoS Pathog 3:e151.doi:10.1371/journal.ppat.0030151) published the first examination of the effect of relative humidity (RH) and temperature on the efficiency of flu virus transmission. They determined that efficiency of transmission was RH dependent, with maximum efficiency at low RH. Additionally, transmission efficiency was inversely correlated to temperature, and viral shedding from the animals was increased at lower temperatures. This article presented the idea that modification of indoor humidity might be a way to minimize transmission.

Back to Article Outline

Seasonality of influenza infection 

“Flu season” peaks during winter months in temperate regions, when both indoor and outdoor humidity is low. Shaman and Kohn (Proc Natl Acad Sci U S A 2009;106:3243-8) discovered that absolute humidity (AH) or vapor pressure constrained influenza transmission and survival with greater significance than RH. They commented that low AH permitted the increased formation of viral droplet nuclei, which are produced by evaporation of viral droplets, causing increased amounts of airborne viruses that stay afloat longer. This increase in viral survival, in turn, allows for increased transmission. The authors suggested that humidification of indoor air in places where there is increased risk of flu, such as nursing homes, could help decrease the spread of flu during the winter flu season.

• 
  • View Large Image
  • Download to PowerPoint

Back to Article Outline

Influenza epidemiology 

Shaman et al (PLoS Biol 8:e100316.doi:10.1371/journal.pbio.100316) used meteorologic data correlated to influenza epidemic data from 1972-2002 to show that flu outbreaks are associated strongly with anomalous AH and increased solar insolation. Using 5 states to represent the different climates in the Unites States, the authors then showed that a transmission model with AH as the driver reliably produced simulations that captured the observed influenza cycle in the 5 representative states. Shaman et al cross-validated their findings by running further simulations for the 48 contiguous states. Their results produced good best-fit simulations that mirrored the flu data for the majority of the states. The authors suggested that short-term probabilistic forecasts could be developed by using the AH model.

• 
  • View Large Image
  • Download to PowerPoint

• Jeffrey Shaman, Oregon State University

Lead author Jeffrey Shaman, PhD, provided this comment: “The findings implicate absolute humidity as a key determinant of seasonal influenza transmission. … Seasonal flu variation is also linked with seasonal variations of other diseases and conditions, such as pneumococcal and meningococcal infection, chronic obstructive pulmonary disorder and cardiovascular disease. This covariability indicates that these other infections and conditions, which develop as sequela to influenza infection, may ultimately be responding to absolute humidity variations.”