Today’s guest post is fromAlexander Peyton Nesmith, a Ph.D./M.D. student at Harvard SEAS and the University of Alabama at Birmingham. He writes…
The pharmaceutical industry is currently facing a crisis. The development of a new drug is an incredibly long and expensive process, lasting more than ten years and costing more than $1 billion US. The approval process of a new drug in the United States can roughly be split into two parts: a preclinical phase (i.e. not in human patients) and a clinical phase (i.e. in humans). Unfortunately, just ten percent of the drugs that enter clinical trials after successfully demonstrating that they are both safe and effective in preclinical trials end up getting approved by the FDA. This failure comes after investing roughly $500 million and 5+ years in the failed drug. This is just not a sustainable business model.
But the question is: why are some drugs safe and effective in animals but then go on to be dangerous or ineffective when given to you or me? The answer is probably really complex. But maybe, it is also really simple. When you see a drug get pulled from the market for being dangerous and causing side effects, those effects are usually in just a small percentage of the population. In other words, a drug that works for me may actually harm or kill you. So if there is such a drastically different response to the same drug among humans, it seems obvious to expect an even larger difference to occur between animals of different species! Well, if animals are not predictive of what will be an effective drug in a human, then what is?
At Harvard’s Wyss Institute and School of Engineering and Applied Sciences, our best bet is that the answer is a “micro-human”. That is, building on advances in fields like nanotechnology, stem cells, material science, and tissue engineering, we believe that we can build the simplest structural and functional units of organs like the heart, the lung, the liver, and the airway (and more) from human-derived cells and tissues. Individually, we call these Organs on Chips. But for Organs on Chips to be useful for pharmaceutical companies, they also need to have the ability to model disease.
With this in mind, in this study, we sought to build a device that could simulate both healthy and asthmatic airway function. We chose to focus specifically on airway muscle, as its job is to open and close the airway. As we began this work, we used the human airway as a design template. Replicating the structure of the airway muscle is extremely important for developing healthy and diseased models as there are many examples in medicine where if the normal structure of an organ is disrupted disease results. So we looked at the structure and organization of the muscle within healthy and asthmatic human airways and then used a technique called microcontact printing which enabled us to have precise control over the organization of the muscle. Once we were able to replicate the normal structure of human airway muscle, we wanted to demonstrate normal function. So we employed microfabrication techniques to build a device that would enable culture of this muscle in 2-dimensions but then perform experiments in 3-dimensions. Using a well-established mechanics theory and knowing the material properties of the polymers we used, we were able to calculate the contraction strength of the airway muscle be measuring the bending of thin polymer film.
To confirm appropriate function of our airway muscle, we designed an experiment based of one of the main lung function tests performed clinically: spirometry. In these diagnostic studies, clinicians measure the patient’s ability to blow air out of their lungs. Then, they use a drug called methacholine to cause the muscle to contract and the airway to narrow, then measure again the amount of air a patient can blow out. Here, we used a similar drug to cause our muscle to contract and we measured the contractile strength.
Then, as a proof of principle, we used a chemical released by immune cells commonly found in the airway of asthmatics, called IL-13, which causes changes within the muscle that causes hypercontraction, to induce an asthma condition. We then evaluated our ability to use known as well new drugs to either prevent or restore proper contraction strength.
Moving forward, we hope to partner with pharmaceutical companies to test new drugs.
I’m guilty. I’ve called individuals with asthma “asthmatic.”
To fund my research, I write grants. These grants usually have word limits and when I am over the page limit (which is always), I have a few trusted strategies. One of these strategies has been changing “individuals with asthma,” a phrase that I use hundreds of time into “asthmatic.”
That saves me 15 characters. Hundreds of times in a grant. It never felt right to use the word “asthmatic” but I got the point across while meeting page limits.
I once agreed to shortening the title of a paper to using the word “asthmatic” because the journal asked me to in order to decrease the word count.
I justified this behavior for a couple of reasons.
1. Is “asthmatic” a real word? I looked in the dictionary, and sure enough, asthmatic means an individual who suffers from asthma.
2. I started to ask patients if it was offensive to be called an asthmatic. Everybody I asked thought it was fine.
3. And we do use the words diabetic and arthritic. (Though I think we should stop that too.)
But we aren’t our disease. And we shouldn’t be. It’s not like the slogan, “You are what you eat.” Do we call people with high cholesterol “high cholesterolemics” or people with hypertension “hypertensionatics” or individuals suffering from cancer “cancerers?”
I’m not arguing that the word “asthmatic” should never be used. One might have an asthmatic cough or wheeze, I suppose.
But the 300 million individuals with asthma happen to have one of the most common chronic diseases in the world. They aren’t their disease.
They aren’t asthmatics.
Today’s guest post is from Ruchi Gupta, MD MPH, an associate professor of pediatrics at Northwestern and a physician at Ann & Robert H. Lurie Children’s Hospital of Chicago. She writes about a study she just published in Pediatrics that was conducted in partnership with Chicago Public Schools. The study found that children with asthma and food allergies are left without vital safety net for many hours in school.
Given the amount of time kids spend in school, it’s critical for school staff, clinicians, and parents to make sure there’s a health management plan in place for students with health conditions. Not having a health management plan leaves students without a vital safety net during the school day. With kids now returning to school, this is the time to get it done.
In order for schools to be well prepared to handle these medical conditions, including daily control of their health and emergencies, school personnel need to have a health management plan from the child’s clinician on file. Chronic medical conditions affect up to 25 percent of children in the US, with asthma and food allergies being among the most common.
A health management plan specifies special requirements for the child during school if medications are needed, and what to do in case of an emergency.
Through a partnership between Northwestern’s Center for Community Health and the Chicago Public School Office of Student Health and Wellness, the study focused on understanding the district’s chronic disease reporting and management process in order to better serve the health care needs of students with conditions such as asthma and food allergies.
We looked at the database of Chicago Public Schools, the third largest U.S. school district, to identify students with asthma and food allergies.
The study found only one in four students with asthma and half of students with food allergy had a school health management plan. Students were less likely to have a plan in place if they were a racial/ethnic minority and if they were low income, measured by whether they qualified for a free or reduced-price lunch. This critical study brings to light the underutilization of school health management plans district wide and underscores the fact that the most underserved students are left particularly vulnerable.
Many students also had more than one chronic condition. Of asthmatic students, 9.3 percent had a food allergy; of food allergic students, 40.1 percent had asthma. Students with both conditions were more likely to have a management plan on file.
This is definitely a national problem in schools around the country. We think the situation in Chicago schools is representative of schools everywhere. It’s critical for all students with any chronic condition to have a health management plan in place at school.
This study was funded by Mylan Specialty, LP and Northwestern’s Alliance for Research in Chicagoland Communities.
Today’s blog post is about a recently published study in the Journal of Clinical Immunology. The authors studied lignans and isoflavones, two plant-derived chemicals that are inversely associated with asthma and wheezing. So, the higher the levels of lignans and isoflavones, the lower likelihood of wheezing and asthma.
What are lignans and isoflavones?
- Lignans are found in flaxseeds, wine, coffee, tea, sesame, wheat, and rye.
- Isoflavones are found in soybeans, clover, and mung beans.
Why lignans and isoflavones?
- These two appear to have potent anti-inflammatory and antioxidant effects.
The authors used data from NHANES, a US based survey that included questions on dietary history and urinary levels of lignan and isoflavone metabolites. The study included 9,633 subjects ages 6 to 85 years of age.
- The odds of having current asthma was 0.69 times less if the individual had high levels of enterolactone (was in the highest tertile of enterolactone).
- The odds for nonasthmatic wheeze was half as likely if the individual had high levels of urinary enterolactone.
- And, individuals were 0.64 times likely to have nonasthmatic wheeze if they were in the highest tertile of urinary O-DMA. Nonasthmatic wheeze was defined as having wheezed or had a whistling in the chest in the past 12 months but not having a diagnosis of asthma.
Both urinary enterolactone and O-DMA (metabolite of isoflavones) were inversely associated with nonasthmatic wheezing within the past year. These results were similar among adults and children. Results were also similar among smokers and nonsmokers, having high levels of dietary fiber intake or not.
The authors concluded that interventions to increase levels of enterolactone and O-DMA may help prevent and treat asthma.
Is it time to eat foods to increase levels of enterolactone and O-DMA? I don’t know, but eating whole wheat multigrain bread with flaxseeds, sesame, wheat, and rye for breakfast with tea or coffee might not be so tough.
Yesterday’s post was about the relationship between infection and asthma. Coincidentally, a 10 year old child with asthma drew this picture for me. She said, “When I have an asthma attack, it feels like clogging in the chest. My chest gets real tight. It feels like germs are going in there.”
So, I told her about yesterday’s post — that infections can trigger asthma flares, but persons with asthma are also more likely to have infections.
Here’s her picture….
The most common trigger of an asthma exacerbation is a respiratory tract infection like the common cold. A recent review article by Young Juhn, MD MPH in the Journal of Allergy and Clinical Immunology highlights new studies that suggest people with asthma and other allergic diseases (eczema, allergies), may be at increased risk of having common and serious infections with both viruses and bacteria.
Infections and asthma and allergic diseases are interrelated in every way.
- Infections could be protective of asthma and allergic conditions.
- Infections such as the common cold (rhinovirus) could provoke asthma flares.
- Infections could be part of the context of asthma and allergic condictions.
Or, the reverse could be true. (focus of this article)
- Asthma and allergic diseases could cause the increased risk of infections.
If all of this were true, persons with asthma could end up in a vicious cycle with the asthma causing infections, which then trigger asthma flares.
This figure is Dr. Juhn’s depiction of the bidirectional causal reltionship between infections and allergic conditions.
Dr. Juhn reviews what is available in the literature currently.
- Patients with asthma, eczema, and allergic rhinitis have increased risk of pneumococcal pneumonia and invasive pneumococcal disease. This is the reason all patients with asthma ages 19 to 64 years are recommended to receive the pneumococcal vaccine (PPV23).
- Patients with asthma also have increased risk of infections with other bacteria such as Strep pyogenes, Strep pneumonia, Staph aureus, etc.
- Patients with asthma have increased risk of Bordetella pertussis infection (which causes whooping cough), Legionella, E.coli infection, and mycoplasma (walking pneumonia).
- There is even an increased risk of non-respiratory tract infections such as urinary tract infections or shingles.
What are reasons for asthma causing increased risk of infections?
- Inhaled steroids (Flovent, Pulmicort, etc) have immunosuppressive properties and are the most commonly used controller medications for asthma, but inhaled steroids do not appear to be the cause. One study suggested that inhaled steroids might actually be protective of lung infections.
- Immunologic abnormalities and dysfunctions that are associated with asthma and allergic conditions might be responsible. This is an important area of active study. Immune dysfunction at every stage from colonization to severe infections appear to be increased.
- It’s known that some asthmatic patients have impairment of innate immunity and this could lead to increased infections as the immune system does not work to its full potential.
- Patients with asthma may have increased colonization of many types of bacteria.
What are Dr. Juhn’s conclusions?
- Asthma patients aged 19 to 64 years should continue to be vaccinated with PPV23 (pneumoccocal vaccine). (Risk of pneumonia is increased and pneumonia could trigger asthma flare.)
- Potential for increased risk of infections should be assessed carefully by clinicians.
My very first blog post (18 month ago!) was entitled, “Asthma Three Ways." In this post, I explained that when you order Peking Duck, some restaurants give you the duck in 3 ways: the Peking Duck and then two more courses. This dish is the inspiration for the title of my blog.
I finally remembered to take photos during a recent family dinner.
First, we had the Peking Duck.
Next, we had stir-fried duck with vegetables.
Third, we had the duck with bones cooked in sesame oil and basil. Often this third dish is a soup so that you really get every ounce of flavor out of the bones.
A study I led was just published online in the Journal of Allergy and Clinical Immunology: In Practice.
The most commonly used medications for asthma are inhaled corticosteroids (Flovent, Pulmicort, etc), leukotriene receptor antagonists (Singulair, etc), and inhaled corticosteroid/long acting beta agonist combination therapy (Advair, Symbicort, etc). Studies have found that inhaled corticosteroids have greater efficacy than leukotriene receptor antagonists to prevent exacerbations of childhood asthma under controlled circumstances. However, few studies have compared the effectiveness of these controller medication regimens under real-life conditions.
In this study, we set out to determine the likelihood of asthma exacerbations after initiation of controller medications among children with asthma—under real-life conditions. Using electronic data from TennCare Medicaid and five large health plans (Harvard Pilgrim Health Care, HealthPartners, Kaiser Permanente Northern California, Kaiser Permanente Northwest, and Kaiser Permanente Georgia), we studied a total of 26,191 children ages 4-17 years with uncontrolled asthma. The main outcome measures were asthma-related emergency department visits or hospitalizations, or oral corticosteroid use in the year after filling a controller medication.
We found that overall adherence to controller medications was low. In patients with allergic rhinitis, subjects in TennCare Medicaid who were treated with leukotriene antagonists were less likely to experience emergency department visits compared to subjects treated with inhaled corticosteroids. For all other groups, the risk of emergency department visits, hospitalizations, and oral corticosteroids did not differ between children who initiated leukotriene antagonists and inhaled corticosteroids. These findings may be explainable by leukotriene antagonists having similar effectiveness as inhaled corticosteroids in real-life usage, by residual confounding by indication, or other unmeasured factors.
Today’s guest blog post is from Ariq Azad from Praxis Health - an online training platform that gives parents the skills and tools they need to manage asthma in their children. He’s looking for enthusiastic parents of children with asthma who want early access to the program and willing to offer feedback.
We started Praxis Health after we realized that there aren’t good online asthma management training resources. As many parents of kids with asthma can attest to, asthma management is difficult, frustrating, and requires a level of training. Parents of asthmatic children need to understand asthma, be able to manage a complex medication regimen, use inhalers correctly, clean up indoor triggers regularly, follow an asthma action plan and on top of all that follow up with their child’s doctor and school. This can be very overwhelming – and because it’s so difficult, asthma remains uncontrolled in the majority of cases.
There exists, however, some very successful Asthma home- based case management programs. These programs send nurses or other health professionals to the patients’ homes for intensive training – and research shows that they have been effective in decreasing ER rates and hospitalizations. One of the difficulties of these programs is that they require in-person home visits, which makes it difficult to reach a lot of families as resources are often limited. Praxis Health is on a mission to digitize these physical training programs as much as possible. Why? By putting the training online and using the latest in education technology, and equipping parents with the tools they need to implement these skills, Praxis Health hopes to train and reach thousands of parents in need.
So, what does the program look like? It is a 3-hour online, interactive course parents can take on their own time. By the end of the course, parents will have the skills needed to: identify and remove indoor triggers, administer medications properly, and use an asthma action plan to stop asthma attacks early. In addition to skills training, parents will be given many tools to help them manage asthma. One tool is a smartphone application to find indoor triggers and another is live video training on proper inhaler technique. We also have a staff of virtual asthma educators who will help you throughout the course and are available to answer any questions you might have.
We are looking for parents to give feedback on the program before we launch it nationwide. If you are a parent of a child with uncontrolled or newly diagnosed asthma and are interested in trying the program, please contact me at firstname.lastname@example.org. In addition to getting early access to this program, you’ll be taking part in the creation of a landmark program and making it better for many parents to come!
As I’ve talked to physicians in Taiwan, I’ve learned that asthma is even more common in Taiwan than in the U.S.. More than 20% of first graders in Taipei have asthma. I’ve also learned that vitamin D deficiency is quite common. I heard one statistic that 40% of children in Taiwan have vitamin D deficiency and an additional 50% have vitamin D insufficiency.
Naturally, I’ve wondered about a connection between vitamin D deficiency and asthma in Taiwan. Many people have asked me how people in Taiwan could be vitamin D deficient when there is no shortage of sunshine on this island that is close to the equator.
Here’s my answer in pictures to why vitamin D deficiency is common in Taiwan.
1. Men and women avoid the sun by carrying umbrellas (or at least wearing a hat).
2. There are plenty of playgrounds around Taiwan, but I’ve never seen a child playing on one.
3. The car windows have curtains.
4. Drivers wear wrist covers to avoid getting sun on their arms.
5. The milk isn’t fortified with vitamin D.