Researchers at Johns Hopkins have evidence that curbed activity from several key chemicals on the inner lining of the nose are linked to chronic sinusitis that fails to respond to the usual current treatments.
An estimated 32 million Americans know the misery of persistent inflammation of the moist tissue that lines the nose and sinus cavities. The result is clogged passages and recurring infections, according to the U.S. Centers for Disease Control and Prevention.
Because nearly one in 10 of those treated see symptoms return within weeks or months after drugs or surgery fail to keep the sinus passages open, scientists have long suspected that these resistant cases had some underlying problem with the immune system contributing to the ailment.
In a study to be described on Sept. 19 at the annual scientific sessions of the American Academy of Otolaryngology, Head and Neck Surgery, the Hopkins team found that in chronic sufferers who failed to respond to treatment, the activity of at least four genes in the body's nasal immune defense system were severely decreased, and their production of two proteins critical to this defense was 20 to 200 times less than normal.
Comparing nasal epithelial cell samples from nine patients who benefited from surgery with nine who did not, the Hopkins team discovered suppressed levels of human beta defensin 2 (HBD2) and mannose binding lectin (MBL) in those whose symptoms returned. The proteins are naturally produced in the nose whenever the immune system detects foreign bacteria or fungi, binding to invading pathogens, inactivating them and making them easily disposed of.
An earlier study published by the same team in the March-April issue of the American Journal of Rhinology also showed that sinus tissue from people with chronic sinusitis that resisted treatment had 30 times lower than normal activity of a so-called toll-like receptor gene, TLR9.
Inside the nose, researchers say, toll-like receptor proteins (TLRs) detect invading bacteria and other pathogens in the air by attaching to their trace byproducts. Once a threat is identified, the receptors stimulate the epithelial cells to produce antibiotic proteins, such as HBD2 and MBL, to fight the invading organisms. This innate response helps prevent airborne bacteria or fungi from settling in the nose and sinus cavities, causing infection.
"Colonization with microorganisms is a common problem in patients with chronic sinusitis and polyps, but the reasons for this are incompletely understood," says Andrew Lane, M.D., an associate professor at The Johns Hopkins University School of Medicine and director of its rhinology and sinus surgery center. "Now we are uncovering new clues as to what might be wrong and perhaps, ultimately, how it might be treated.
"The nose's first line of defense is the epithelium, and when the local innate immune function is curtailed, infections can get a head start, which might serve to worsen the sinus inflammation.
"The potential is there to manipulate these chemical receptors and proteins to see if this makes patients more responsive to conventional therapy," says Lane.
The study, led by Lane, was believed to be the first to determine levels of each TLR - there are 10 - by directly measuring messenger RNA expression in sinusitis patients and those more fortunate to not have it. Scientists have known for more than a year that TLRs were present in both the healthy and sinusitis-wracked nose, but not which receptors or proteins were more important than others in the condition's chronic form. That study involved 30 men and women, mostly from the Baltimore region, who had surgery for chronic sinusitis at Hopkins. (Another 10 had no sinus problem and served as study controls.)
Those who underwent surgery did so after standard therapy using antibiotics, decongestants and steroids had failed to stop their symptoms and keep their infections from coming back. Indeed, 20 participants in the study had developed nasal polyps, which have no known cause and are especially hard to treat, researchers say. They note that polyps must often be surgically removed to allow the sinuses to drain normally.
All patients were monitored for a minimum of six months to see if any symptoms or polyps returned. Thirteen in the surgery group had recurrent inflammation within three months to one year after surgery, while the rest remained symptom free.
The Hopkins team took samples during surgery of the mucous membrane lining the nose, and using real-time polymerase chain reaction, analyzed the samples for any genetic differences between the groups.
"Surgically treating sinusitis is much like plumbing, in the sense that we try to restore normal sinus cavity drainage pathways," adds study presenter Murugappan Ramanathan Jr., M.D., a resident in otolaryngology - head and neck surgery at Hopkins. "But for the intractable cases, surgery may fail because the problem is not so much about plumbing as it is inflammation, and for this we need research at the molecular level to find a solution."
David March | EurekAlert!
Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University
Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017
25.04.2017 | Laser Zentrum Hannover e.V.
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
25.04.2017 | Physics and Astronomy
25.04.2017 | Materials Sciences
25.04.2017 | Life Sciences