“These work. The gargle is quick and feels good. Honey and lemon tea are hard to beat.” Bill Chesnut, MD
|Cleveland Clinic Newsletter, December 3, 2015|
“These work. The gargle is quick and feels good. Honey and lemon tea are hard to beat.” Bill Chesnut, MD
|Cleveland Clinic Newsletter, December 3, 2015|
“Awareness and compassion are essentials of daily living and for daily enjoying being a healthcare provider.” Bill Chesnut, MD
|Cleveland Clinic Wellness, November 21, 2015|
Memory improvement. “Recipe for Healthy Memory: Make Every Bite Count”
By Maureen Connolly
Published 9/7/2009 Cleveland Clinic Wellness newsletter.
One of the best ways to boost brain performance and recall? “Eat,” says David Grotto, RD, LDN, author of 101 Simple Foods That Could Save Your Life and 101 Optimal Life Foods. Sounds simple enough. But despite this advice from nutritionists that we must fuel our bodies and brains with a steady supply of food, many of us still skip breakfast, go too long between meals and eat too much at one sitting. All of these habits set us up for brain drain. Without proper fuel (aka glucose, the main sugar the body makes from the foods we eat and that fuels all the cells in our body), our brains have to work that much harder to complete something as simple as counting change. “The brain fuels itself on glucose, which we need to replenish from food every three to four hours,” Grotto says. “Research on breakfast eaters shows that those who eat it perform better on cognitive function and recall.” Essentially, a morning meal helps your brain function better when it comes to thinking, learning, reasoning and remembering.
Conversely, eating a large amount of calories, carbs and fat at one sitting can make you feel sluggish afterward (thanks to temporarily elevated blood sugar levels, followed by a drop-off — which people can experience as low energy, sluggishness or brain fog). If eating three large meals leaves you with brain drain, consider eating four to six mini-meals over the course of the day.
What you eat is as important as how often you eat. Here are some brain-friendly foods you won’t want to miss out on:
Eggs. The protein-packed egg is rich in vitamins E and D and is considered the optimal brain food by many nutritionists, thanks to its connection with improving memory function. Plus, the yolk is rich in the B vitamin choline, which converts to acetylcholine in the brain, a neurotransmitter that is also critical for memory function. Worried about cholesterol found in egg yolks? Some docs and nutritionists consider whole eggs such an optimal food that they suggest cutting out cholesterol in other areas of your diet (such as butter and cheese) rather than lose out on all of the benefits of whole eggs. You can also keep cholesterol to a minimum by eating one whole egg and adding egg whites to round out an omelet or scrambled eggs.
Oats. “Whole-grain oats are my go-to grain because they’re rich in B vitamins, which reduce oxidative stress to the body’s tissues,” Grotto says. When we’re stressed, our body pumps out the hormone cortisol, which causes an inflammatory response that impairs memory. Getting your whole grains is like putting a bucket of water on the hormonal fire. Slow-cooking, steel-cut oatmeal is a great choice since the grain is still intact and it tastes super yummy. Top oatmeal with walnuts for brain-boosting omega-3 fatty acids and milk or soymilk fortified with docosahexaenoic acid (or DHA) and you’ve got a home-run breakfast for your brain. Other smart choices: whole-grain breads, quinoa and whole-grain cereals such as Total.
Omega-3-rich fish. Salmon is considered one of the best sources of two types of brain-boosting omega-3 fatty acids: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These two fats are critical to brain, heart and eye function. But since we don’t manufacture DHA and EPA ourselves, we need to get them from our diet. The general recommendation is to aim for two to three three-ounce servings of omega-3-rich fish per week. Sardines, cod, haddock, tuna and halibut also contain omega-3 fatty acids. However, many fish farmers are feeding corn and soybeans to their stock, which actually lowers their overall omega-3 levels. Michael F. Roizen, MD, chief wellness officer of the Cleveland Clinic and co-author of the best-selling YOU series, recommends sticking to wild salmon and lake trout as your main source of DHA/EPA-rich fish. He also sees benefits to aiming for 13 ounces per week.
Not a fish fan? Or can’t quite meet the recommended fish servings? Incorporate flaxseed, canola oil, walnuts and soybean oil into your diet. These foods are rich in the omega-3 alpha linolenic acid (ALA). You don’t get quite the same brain benefit as you do from DHA/EPA-rich sources, but it’s better than not getting any.
While food sources allow for the best absorption of omega-3s, you can also get them in a fish oil supplement. The National Institutes of Health (NIH) says that while some initial studies look promising, it won’t have an official recommendation on omega-3 supplementation with regards to cognitive health until more research can be done. However, because omega-3s contribute to overall health and “appear to be safe for most adults at low to moderate amounts,” says the NIH, those who aren’t getting adequate amounts of omega-3s from their diets should consider supplements. Some health organizations say healthy adults can reap overall benefit from 220 mg of DHA per day or one gram total combined of DHA and EPA. Dr. Roizen would up this amount but says to consider first what you’re getting from your diet. His general guide: If you’re eating no fish, take one 600 mg supplement of DHA per day or two grams of omega-3 fish oil capsules. If you eat half the recommended amount of omega-3-rich fish on a regular basis, then you can cut that dosage in half. Vegans can get DHA from algae-based supplements that average about 200 mg per day(though DHA and EPA are more effective in combination).
It’s important to know that fish oil supplements may cause stomach upset and bloating. In super-high doses (more than three grams per day), fish oils can cause bleeding. Omega-3s can also interact with certain medications, such as blood thinners and high blood pressure drugs, so be sure to check with your doctor and/or pharmacist before taking supplements.
Chocolate. Chocolate contains cocoa that helps improve blood flow to the brain by boosting nitric oxide levels that in turn allow blood vessels to function more efficiently. Chocolate is also packed with flavonols, which reduce blood clots and fatty buildup in the arteries, and antioxidants, which lessens inflammation in the body. In one study at Northumbria University in Newcastle, England, participants who were given chocolate drinks with 500 mg of flavonols could complete math calculations more quickly and accurately than those who had nothing. Unsweetened cocoa powder (preferably organic, non-alkali) offers the most antioxidants and flavonols. Dark chocolate is the runner-up, followed by milk chocolate. Keep in mind that chocolate contains saturated fat and sugar — so don’t overdo it. Two ounces per day or two teaspoons of cocoa powder will allow you some benefits without overloading on calories, fat and sugar. And until manufacturers develop a uniform system for measuring flavonol levels, rely on percentage of cocoa content — the higher the better.
Spinach. This dark-green leaf is packed with antioxidants, flavonols and folic acid, which is a win-win food when it comes to brain health. Same goes for kale and collard greens. Aim for three servings a day (the amount you’d get in a good-size salad) and your brain will thank you.
Any fruit ending in erry. Blueberry, cranberry, raspberry, blackberry and pomegranate-erry (okay, we snuck that last erry in there). These fruits slow the aging of the brain, thanks to their high antioxidant level. Sprinkle a handful on your cereal or oatmeal each morning, add them to yogurt or mix them in a smoothie. Just find a way to eat some berries each day.
Coffee. In animal studies, caffeine (the equivalent of two cups of really strong coffee) helped improve memory in mice and even improved it in mice that were bred to have the equivalent of Alzheimer’s disease. The caffeine cut in half the levels of beta-amyloid, a protein that clumps in the brain and causes memory loss.
Green tea. To produce the effects of coffee, you’d need to drink 14 cups of tea. But even in smaller amounts, black and green tea contains brain-boosting antioxidants and theanine, an amino acid that can calm you. But be sure to let that tea bag steep. A 2007 study published in the Journal of Agricultural and Food Chemistry shows that tea brewed for seven minutes had 60 percent more flavonoids than tea brewed for only three minutes. Tea devotees are also raving about Matcha, a stone-ground powdered form of green tea that packs a serious nutritional punch, thanks to antioxidants and vitamins C and A.
Red wine. Red grapes contain resveratrol, a substance that counteracts the free radical cell damage that’s associated with aging and normal wear and tear on our bodies and brains that comes from stress, pollutants, etc. Red wine is also packed with polyphenols, which may stop brain-cell-destroying plaques from building up. Why does red wine get all the glory? Red grapes are just naturally higher in resveratrol and polyphenols than green ones are. “Part of this is also due to the red wine making process, which allows for the skin of the red grape to stay in longer contact with the fruit, and further up levels,” Grotto says. White wine has some resveratrol, but not as much as red. Docs recommend one glass of wine per day for women, one to two glasses for men. Not a wine drinker? Pour yourself a glass of Concord grape juice instead.
Just Say No . . .
To high amounts of fructose, a sugar found in concentrated juices, table sugar and processed foods made with high-fructose corn syrup. A new study out of Georgia State University says that when rats were fed a diet high in fructose they had a hard time remembering previously learned tasks. Fructose can up your triglyceride levels, and consequently impair memory.
“What patients really want–and why it’s important for their health.” Bill Chesnut, MD.
12/3/2015, 12:00 PM
Getting patients to make healthy lifestyle choices ranks high on every physician’s professional wish list. But realistically accomplishing this goal, especially in a fast-paced health care setting, requires care teams to zero in on what really matters to patients.
Thomas Lee, MD explained at TEDMED 2015 that the best place for physicians to start is building a shared sense of trust and empathy with their patients. Here’s why Dr. Lee says a clear understanding of “patient suffering” can help improve care delivery and unlock the key to successful relationships.
Meeting patient needs in a complex health system
As the chief medical officer for Press Ganey, a health company that consults more than 20,000 health care organizations on strategies to improve patient care, Dr. Lee understands the strenuous juggling act physicians must perform to manage high patient demands, deliver quality care and meet expectations for patient satisfaction in fast-paced health settings.
Increased pressures in practice can lead to missed opportunities for coordinating care, shaky handoffs or forgotten follow up with patients about questions they asked. These missteps attest to “the superficial chaos that’s arrived in health care as a result of advancements in medicine,” Dr. Lee said.
This same chaos often infiltrates daily interactions between physicians, patients and care teams, and erodes patients’ trust in the health care system, Dr. Lee said.
To counter this trend, he urges physicians to instill confidence in their patients by focusing on ways to reduce their suffering. In ideal clinical situations, Dr. Lee said his research has shown that patients often simply want four things: “Good clinicians, communication, teamwork and empathy.”
Empathy helps spur patient action
When exploring new ways to foster patient participation and improve quality care, Dr. Lee urges physicians to shift how they think about patient suffering. This will help physicians build stronger patient relationships, which also can encourage patients to more actively partner with their physicians when making decisions to improve their health.
“There’s avoidable suffering, and there’s unavoidable suffering,” Dr. Lee said. “Unavoidable suffering is driven by the patient’s disease and treatment. It includes the pain, side effects and fear of where the disease is going to go.”
But then, there’s “avoidable suffering, which has nothing to do with the patient’s treatment and everything to do with how we work together,” Dr. Lee said, stressing the importance of coordinating care and reducing patient confusion caused by poor communication.
“We have to put patients in the middle and organize around meeting their needs and reducing suffering. To do that, we need technical excellence and empathy. We have to be great at both,” Dr. Lee said. “You can’t have truly excellent care without empathy.”
Journal of the American Medical Association. January 2016.
|“_ A new hot flash aid from the Cleveland Clinic.” Bill Chesnut, MD.
Menopause Hot flashes. ” Chill out! A new remedy for hot flashes is right under your nose.”
|Feeling like a human inferno these days? For a hot-flash remedy that’s supremely safe, readily accessible, and free, take a deep breath. And another one. Practicing what’s called paced breathing — slow, deliberate, deep breathing — for 15 minutes twice a day may reduce both the intensity and frequency of hot flashes. To practice paced breathing, set a timer for 15 minutes. Lie on your back and make yourself comfortable. Slowly start to relax the muscles in your legs, hips, belly, chest, arms and neck. Start to bring attention to your breath, feeling yourself relax from the inside out. As you relax, inhale and allow your belly to rise; then slowly exhale and allow your belly to fall. Notice the pace of your breath slowing as you relax. Continue until the timer rings. Other natural strategies that may squelch the flames of hot flashes include: acupuncture, caffeine reduction, and mindfulness meditation.|
“Our personality are from our deeply held values. Our deeply held values often flourish by being good friends.” Bill Chesnut, MD.
11 Ways to Strengthen the Relationships That Will Lead You to Success. Inc. January 26, 2016.
Our leadership may come from within, but its foundation lies in relationships.
The most significant things we achieve are generally done in relationship with others. Here are 11 ways to bring the right significance to the relationships you are working to build or maintain:
At the end of the day, there is no relationship without communication; no leadership without respect; no team without trust; no venture without value; no business without respect. Make sure you keep what is important up close and personal.
Editor’s note: “The First 90 Days” is a series about how to make 2016 a year of breakout growth for your business. Let us know how you’re making the first 90 days count by joining the conversation on social media with the hashtag #Inc90Days. Published by Inc.
|January 11, 2016|
|“Feel the power of the light when skies are gray.”Bill Chesnut, MD
Cleveland Clinic Wellness, January 17, 2016
|“Enjoy yourself, it’s later than you think. Enjoy yourself while you’re still in the pink.” Tip of the hat to Guy Lombardo, 1950. Bill Chesnut, MD January 14, 2016|
| “Shifting our mood during stress and illness in this busy age is powerful. Other research shows that saying your positive words aloud will change your mood. Being kind, helpful and engaging with others is proven to improve your mood for some while.” Bill Chesnut, MD
From Cleveland Clinic Wellness, January 31, 2016
“Yes, tea can release stress. I enjoy the Celestial teas made in Denver. They have an excellent herb tea for relaxation.” Bill Chesnut, MD
L-Theanine: A Tea-riffic Way to Reduce Stress, Cleveland Clinic Wellness newsletter 1.29.16
L-theanine, a water-soluble amino acid, is found mainly in green and black tea. It has demonstrated benefit for patients diagnosed with anxiety by increasing levels of dopamine and GABA in the brain.
ADVISORY: L-theanine should be used only under a doctor’s supervision if you are taking drugs for chemotherapy. Do not take L-theanine with cholesterol lowering medications.
CONCLUSION: We conclude that L-theanine is a safe and effective way to help treat anxiety and improve concentration. We prefer drinking the tea leaves naturally to taking the supplement.
|“Going to the gymnasium every day has surprising benefits. Your metabolism rate is higher, you have more energy, your balance improves and you may retain more IQ points in the coming years.” Bill Chesnut, MD
This is from the Cleveland Clinic Wellness Newsletter January 25, 2016.
Cleveland Clinic 1.25.16
|“I am so glad to know these easy practical tips to prevent halitosis.” Bill Chesnut, MD
From the Cleveland Clinic Wellness Letter, January 2016.
Get rid of bad breath in a flash with one of these fresh foods.
|Brushing and flossing daily are the best ways to keep your mouth and teeth healthy and your breath fresh. But some foods, like that cheesy garlic toast (oh-so-tasty when the holiday bash began!), can leave you with an unpleasant aftertaste — and dragon breath. If the sour taste in your mouth has you mumbling behind your hand, and there is no convenient place to brush your teeth, here are some ways to clean your breath and party on with confidence.
I enjoy the Cleveland Clinic Newsletter. Today they address the possible benefit to type II diabetes of consuming coffee. February 2, 2016. Bill Chesnut, MD
|That coffee habit? It might just be protecting you from type 2 diabetes.|
|Can’t start your day without a cup or two of joe? Bottoms up! People who drink three to four cups of coffee a day are less likely to have developed type 2 diabetes than those who don’t drink coffee at all, and now researchers have a better understanding about why. Two compounds found in coffee — cafestol and caffeic acid — increase insulin production, which helps keep your blood sugar under control. Controlling blood sugar is crucial for diabetes prevention, since high blood sugar, or hyperglycemia, can lead to the signs and symptoms of the disease. Research also shows that coffee may help prevent diseases like stroke and certain cancers’ reduce the risk of Parkinson’s, dementia, and multiple sclerosis; and even boost concentration and memory. With so many benefits, you want to avoid adding anything unhealthy to your morning cuppa, right? That means skipping the nondairy creamers (corn syrup and trans fat alert!) and flavor shots (can you say sugar, sugar, sugar?), and limiting your use of artificial sweeteners. Instead, try unsweetened almond milk with cinnamon.|
|“Run for your mind, stay smart longer. We all underestimate the ability of our mind to grow especially if it has years to accumulate experience.” Bill Chesnut, MD|
“This brief article is about the neuroimaging research at the McGovern Institute for Brain Research at M.I.T. Functional MRI shows the patterns of activity in the brain. It is revealing differences in brain patterns that are predictive. This link is the research at McGovern; the whole area is astonishing.” Bill Chesnut, MD http://mcgovern.mit.edu/brain-disorders/psychiatric
Brain scans to catch depression before it starts
By Ben Gruber, 2.4.16.
CAMBRIDGE, MASS. (Reuters) – Researchers at MIT’s McGovern Institute are using the latest advances in brain imaging to identify children at high risk of depression before the debilitating and sometimes deadly disorder sets in.
According to the World Health Organization an estimated 350 million people of all ages suffer from depression. It’s a serious mental disorder that affects every aspect of a person’s life and in severe cases could lead to suicide.
The study involved two groups of children, one at high risk of depression due to family history and a control group with kids at low risk.
Kids from both groups were scanned to map the network pathways in their brains. The question was if the researchers could find differences in brain activity that would be an indicator for a higher risk of depression.
“They answer is there are very great differences. We saw differences that were striking in a number of circuits including those that change in depression, including those involved in feelings, other parts that are involved in thinking. The additional thing besides seeing these differences were that the differences were so strong child by child that that we were very close to perfect with being able to categorize from a brain scan itself whether a child was at risk or not,” said John Gabrieli, a professor of Brain and Cognitive Sciences at MIT.
The goal going forward is to follow these children and see who among the high risk group goes on to develop depression, tracking changes in their brain function along the way .
“Obviously the children that go on to depression the more we can identify them well the more we are hopeful that we can get preventive treatments going. Not waiting for them to be suffering but helping them beforehand,” said Gabrieli
“So we want to learn both to identify early children who are at true risk, help them before they struggle and learn from those that are resilient what is different about them because that might be a hint about how to help the children that are not resilient,” he added.
The researchers say a better understanding of how depression affects the brain will ultimately lead to better treatment options for those that are most at risk.
Here is the McGovern Institute for Brain Research at MIT: http://mcgovern.mit.edu/
This is some of the brain research they do: http://mcgovern.mit.edu/research
“People who get less than seven hours of sleep a night are three times as likely to get sick after being exposed to a cold virus as people who snooze for eight hours or more. Three times!! That is worth turning off the screens and turning in earlier.” Bill Chesnut, MD
Feeling run-down? Don’t sacrifice sleep. Getting less shut-eye is linked to a lower resistance to colds. by Cleveland Clinic Wellness Editors
The sun is shining, the weather is perfect and you’re feeling miserable. Though we usually associate colds with the winter, you can come in contact with one of the 200 viruses that cause the common cold year-round. One place where you’re likely to be exposed: long-haul flights. The more people on the plane and the more time you spend in their presence, the greater your risk of infection. According to research in the Archives of Internal Medicine, you can reduce your risk of illness by getting enough shut-eye. People who get less than seven hours of sleep a night are three times as likely to get sick after being exposed to a cold virus as people who snooze for eight hours or more. If they slept poorly, they were five times as likely to get sick. According to the researchers, a good goal to aim for is between seven and eight hours each night.
“About the safety of eating seafood: Seafood consumption has been a concern because of the increased levels of mercury in fish. This study shows that moderate intake of seafood may produce a decreased chance of developing Alzheimer’s disease.”
The best way to absorb the several findings of this critical study is this YouTube video by one of the authors at Rush Medical Center in Chicago and published in the Journal of the American Medical Association Network. First rate research. https://www.youtube.com/watch?v=m9MncHHHXpA .” Bill Chesnut, MD
Martha Clare Morris, ScD1; John Brockman, PhD2; Julie A. Schneider, MD, MPH3,4,5; Yamin Wang, PhD1; David A. Bennett, MD3,4; Christy C. Tangney, PhD6; Ondine van de Rest, PhD7
JAMA. 2016;315(5):489-497. doi:10.1001/jama.2015.19451.
Importance Seafood consumption is promoted for its many health benefits even though its contamination by mercury, a known neurotoxin, is a growing concern.
Objective To determine whether seafood consumption is correlated with increased brain mercury levels and also whether seafood consumption or brain mercury levels are correlated with brain neuropathologies.
Design, Setting, and Participants Cross-sectional analyses of deceased participants in the Memory and Aging Project clinical neuropathological cohort study, 2004-2013. Participants resided in Chicago retirement communities and subsidized housing. The study included 286 autopsied brains of 554 deceased participants (51.6%). The mean (SD) age at death was 89.9 (6.1) years, 67% (193) were women, and the mean (SD) educational attainment was 14.6 (2.7) years.
Exposures Seafood intake was first measured by a food frequency questionnaire at a mean of 4.5 years before death.
Main Outcomes and Measures Dementia-related pathologies assessed were Alzheimer disease, Lewy bodies, and the number of macroinfarcts and microinfarcts. Dietary consumption of seafood and n-3 fatty acids was annually assessed by a food frequency questionnaire in the years before death. Tissue concentrations of mercury and selenium were measured using instrumental neutron activation analyses.
Results Among the 286 autopsied brains of 544 participants, brain mercury levels were positively correlated with the number of seafood meals consumed per week (ρ = 0.16; P = .02). In models adjusted for age, sex, education, and total energy intake, seafood consumption (≥ 1 meal[s]/week) was significantly correlated with less Alzheimer disease pathology including lower density of neuritic plaques (β = −0.69 score units [95% CI, −1.34 to −0.04]), less severe and widespread neurofibrillary tangles (β = −0.77 score units [95% CI, −1.52 to −0.02]), and lower neuropathologically defined Alzheimer disease (β = −0.53 score units [95% CI, −0.96 to −0.10]) but only among apolipoprotein E (APOE ε4) carriers. Higher intake levels of α-linolenic acid (18:3 n-3) were correlated with lower odds of cerebral macroinfarctions (odds ratio for tertiles 3 vs 1, 0.51 [95% CI, 0.27 to 0.94]). Fish oil supplementation had no statistically significant correlation with any neuropathologic marker. Higher brain concentrations of mercury were not significantly correlated with increased levels of brain neuropathology.
Conclusions and Relevance In cross-sectional analyses, moderate seafood consumption was correlated with lesser Alzheimer disease neuropathology. Although seafood consumption was also correlated with higher brain levels of mercury, these levels were not correlated with brain neuropathology.
“A new drug is showing remarkable efficacy in treating allergic conditions, primarily eczema. The side effects are trivial considering the morbidity of atopic eczema. This publication shows that it’s also effective in nasal polyps for people who are affected with allergies and have sinus polyps develop. Dupilumab is in clinical trials now. The government site for clinical trials, clinical trials.gov, predicts t will be release in November 2016.
I anticipate that there will the other uses of this remarkable technique of inhibiting the blood cells involved in the inflammatory response of allergies.” Bill Chesnut, MD.
Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients With Chronic Sinusitis and Nasal PolyposisA Randomized Clinical Trial
Claus Bachert, MD, PhD1,2; Leda Mannent, MD3; Robert M. Naclerio, MD4; Joaquim Mullol, MD, PhD5; Berrylin J. Ferguson, MD6; Philippe Gevaert, MD, PhD1; Peter Hellings, MD, PhD7; Lixia Jiao, PhD8; Lin Wang, PhD8; Robert R. Evans, PharmD9; Gianluca Pirozzi, MD, PhD8; Neil M. Graham, MD, MPH9; Brian Swanson, PhD8; Jennifer D. Hamilton, PhD9; Allen Radin, MD9; Namita A. Gandhi, PhD9; Neil Stahl, PhD9; George D. Yancopoulos, MD, PhD9; E. Rand Sutherland, MD, MPH10
Importance Dupilumab has demonstrated efficacy in patients with asthma and atopic dermatitis, which are both type 2 helper T-cell–mediated diseases.
Objective To assess inhibition of interleukins 4 and 13 with dupilumab in patients with chronic sinusitis and nasal polyposis.
Design, Setting, and Participants A randomized, double-blind, placebo-controlled parallel-group study conducted at 13 sites in the United States and Europe between August 2013 and August 2014 in 60 adults with chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids with 16 weeks of follow-up.
Interventions Subcutaneous dupilumab (a 600 mg loading dose followed by 300 mg weekly; n = 30) or placebo (n = 30) plus mometasone furoate nasal spray for 16 weeks.
Main Outcomes and Measures Change in endoscopic nasal polyp score (range, 0-8; higher scores indicate worse status) at 16 weeks (primary end point). Secondary end points included Lund-Mackay computed tomography (CT) score (range, 0-24; higher scores indicate worse status), 22-item SinoNasal Outcome Test score (range, 0-110; higher scores indicating worse quality of life; minimal clinically important difference ≥8.90), sense of smell assessed using the University of Pennsylvania Smell Identification Test (UPSIT) score (range, 0-40; higher scores indicate better status), symptoms, and safety.
Results Among the 60 patients who were randomized (mean [SD] age, 48.4 years [9.4 years]; 34 men [56.7%]; 35 with comorbid asthma), 51 completed the study. The least squares (LS) mean change in nasal polyp score was −0.3 (95% CI, −1.0 to 0.4) with placebo and −1.9 (95% CI, −2.5 to −1.2) with dupilumab (LS mean difference, −1.6 [95% CI, −2.4 to −0.7]; P < .001). The LS mean difference between the 2 groups for the Lund-Mackay CT total score was −8.8 (95% CI, −11.1 to −6.6; P < .001). Significant improvements with dupilumab were also observed for the 22-item SinoNasal Outcome Test (LS mean difference between groups, −18.1 [95% CI, −25.6 to −10.6]; P < .001) and sense of smell assessed by UPSIT (LS mean difference, 14.8 [95% CI, 10.9 to 18.7]; P < .001). The most common adverse events were nasopharyngitis (33% in the placebo group vs 47% in the dupilumab group), injection site reactions (7% vs 40%, respectively), and headache (17% vs 20%).
Conclusions and Relevance Among adults with symptomatic chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids, the addition of subcutaneous dupilumab to mometasone furoate nasal spray compared with mometasone alone reduced endoscopic nasal polyp burden after 16 weeks. Further studies are needed to assess longer treatment duration, larger samples, and direct comparison with other medications.
Chronic sinusitis, an inflammatory condition of the sinuses, is common with estimates of prevalence as high as 12% in Western populations.1,2 It is characterized by specific symptoms often lasting for many years including nasal congestion, discharge and postnasal drip, decreased or lost sense of smell, facial pain and pressure, headache, and the consequences thereof.3 Based on endoscopic findings, the condition can be divided into chronic sinusitis with or without nasal polyposis. Typically observed in the context of eosinophilic inflammation of the upper airways, nasal polyps originate in the sinuses and obstruct the sinus and nasal passages.
Medical management of chronic sinusitis with nasal polyposis focuses on controlling tissue inflammation and, depending on severity, includes use of intranasal corticosteroids, nasal saline irrigation, antibiotics, or short-course oral steroids.3 In patients in whom polyps and symptoms persist despite medical treatment, surgical excision is considered. However, disease recurrence after surgery approaches 50% in patients with tissue eosinophilia,4 and resolution of symptoms, including sense of smell loss, is often incomplete.
Epidemiological data from a large European cohort indicate that chronic sinusitis is associated with a 3.5-fold increase in comorbid asthma prevalence.5 Although type 2 helper T-cell inflammation is implicated in this association, the mechanisms of this association have not been fully elucidated.6– 8
Dupilumab is a fully human monoclonal antibody to the interleukin 4 (IL-4) receptor α subunit, which inhibits signaling of IL-4 and IL-13, 2 cytokines central to type 2 helper T-cell–mediated inflammation. Dupilumab has demonstrated clinical efficacy in the type 2 helper T-cell–mediated diseases of asthma and atopic dermatitis,9– 11 and also improved sinonasal symptoms in patients with asthma.9
We hypothesized that the addition of dupilumab to intranasal corticosteroids would improve endoscopic, radiographic, and patient-reported measures of disease activity in those with chronic sinusitis and nasal polyposis, while also improving lung function and disease control in patients with comorbid asthma.