Tag Archives: Lungs

2018 Summer of Science – Out of Breath

Research Project

My research project this summer has focused on evaluating lung function in patients with cystic fibrosis (CF), a disease that causes excessive mucus build-up in the lungs and digestive organs. Symptoms include substantial breathing difficulty and exercise intolerance, and patients with CF undergo hours of treatment per day that involve medication, chest physiotherapy, and exercise. One important medication is albuterol, a bronchodilator that ensures the delivery of antibiotics, steroids, and other inhaled treatments to airway tissues.

To assess lung function, these patients regularly do breathing tests where, after taking in a full breath, they breathe out as hard and fast as possible. I have been using a mathematical measure, called “slope ratio”, to evaluate these breathing tests and investigate the impact of albuterol and/or exercise on lung function. Lower slope ratios indicate improved airway function, and we hypothesized that albuterol and exercise would decrease slope ratios. My research may aid understanding of how albuterol and exercise affect the lung, which might eventually lead to better treatment strategies for lung disease.

Patients with CF performed the above-mentioned breathing tests during three separate visits: 1) after inhaling albuterol, 2) after exercise, and 3) after both albuterol and exercise. Following this data collection, research has been heavily data-based: the data from just nine patients took weeks to fully analyze. However, developing a conceptual understanding of “slope ratio” kept me engaged; I also developed my skills with writing code (i.e. macros in Excel) to streamline my data analysis, which was a fun learning experience. The results we obtained from our slope ratio analyses closely matched our research hypotheses, were quite interesting to interpret and made logical sense regarding the effects of albuterol and moderate-intensity exercise. Briefly, we found that albuterol decreased slope ratios significantly, suggesting albuterol improves airflow and drug delivery in previously congested airways.

Realities of Research

Mentally, scientists have to remain vigilant; when they encounter contradictions to their prior knowledge, they critically re-evaluate their hypotheses and conceptual understanding. I enjoyed interpreting results and discussing hemoglobin/slope ratio concepts with post-docs in the lab, both one-on-one and in daunting lab meetings. And while it was difficult to work with seemingly-endless data, learning how to write macros helped me to be productive, learn a new coding language, and keep myself engaged.

 

Winston Guo is a junior and Neuroscience major at the University of Minnesota- Twin Cities in Minneapolis, MN. He is a 2018 Undergraduate Research Excellence Fellowship (UGREF) recipient, and is working in Dr. Michael Joyner’s Human Integrative Physiology Lab at the Mayo Clinic in Rochester, MN. Winston’s fellowship is funded by the APS. After graduation, Winston hopes to attend medical school and eventually become a practicing physician.
Ozone: Protector or Pollutant?

We usually hear that we want more ozone in our atmosphere to protect us from the sun’s ultraviolet rays, but ozone isn’t always a good thing. That protective ozone is found in the stratosphere, while ozone on ground level is a harmful air pollutant caused by emissions from cars and factories. Ozone can do a lot of damage to human lungs, causing shortness of breath, coughing, inflammation and damage to airways, aggravation of lung diseases like asthma, and permanent lung damage. In response to ozone-induced injury, macrophages (immune cells which eat and break down viruses, bacteria, and dead cells) accumulate in the lung and contribute to inflammation and toxicity. Inflammation is important to get rid of any dangerous invaders or cell debris, but macrophages can also have damaging effects in the lungs.

We want to find out what can be done to reduce that inflammation and toxicity, so we are investigating valproic acid. Valproic acid is a fatty acid which has been shown to be anti-inflammatory and an antioxidant. My research project involves testing our hypothesis that valproic acid will reduce lung inflammation and toxicity caused by ozone-induced injury. To evaluate the effects of valproic acid on inflammation and toxicity, I stain thin slices of lung tissue by immunohistochemistry. In immunohistochemistry, the goal is to determine if alveolar macrophages are expressing markers of inflammation or toxicity – the more expression of a certain marker, the darker the macrophage should be stained. We expect that the lungs of mice treated with valproic acid will be less stained than the untreated if inflammation and toxicity are mitigated.

https://www.edf.org/health/why-smog-standards-are-important-our-health

Caption: Smog over LA. Ozone is the main component in smog.(1)

 

Realities of Research

Like the bad and good faces of ozone, doing a research in the lab is slow-going, but also rewarding. The pace is slow because I dedicate a lot of time to troubleshooting the immunohistochemistry process. For each marker of interest, the protocol needs to be optimized. This is time-consuming because it means going through the immunostaining process repeatedly, changing small details each time. It was especially frustrating when the results were not what we expected. When our controls were repeatedly turning out different from how they had looked in previous experiments, we had to figure out if it was the fault of the sample, a detail in the protocol, or the antibody. I’m currently still working on figuring out the discrepancy by testing samples from other labs and different antibodies. If it’s the samples that are faulty, we will put a hold on the immunohistochemistry until we can use the samples from an animal exposure we have planned in a couple of weeks. If the antibodies are the problem, we will order new ones. If I’m doing something in the protocol incorrectly, my research mentor will watch me go through the steps and find out. This complication has been slowing down our progress, but it’ll be rewarding to finally figure it out and get data.

Life of a Scientist

Even excluding the satisfaction of getting data, I feel like I’ve grown a huge amount working as a scientist this summer since it was completely new for me. It’s my first experience working full-time, in addition to taking place in the unique environment of a research lab. I was happily surprised by the amount of flexibility in schedule – each person comes in and leaves when they need to, depending on the work they need to get done that day. Some days are a typical 9 to 5, some might be much shorter, and some might go late into the night. It can become overwhelming meeting new people, catching up on literature, and learning new lab techniques. However, it’s also satisfying to soak up so much new information so quickly and see myself developing as a scientist and a student every week. In my experience so far, the best part of working full-time is the people I have been able to get to know. Seeing the lab tech, the faculty, the grad students, the undergrads, and the high school students every day gives me the chance to really learn about what they do inside and outside the lab. Because of them, coming into the lab every day is welcoming and exciting, which makes all the difference when I’m frustrated with my experiments. Working with them is easy and most of all, fun, and I’m grateful I was able to do research with such encouraging and friendly people.

 

References:

  1. Why smog standards are important for our health. (2018). Retrieved July 27,2018, from https://www.edf.org/health/why-smog-standards-are-important-our-health
Jordan Lee is a junior studying molecular biology and biochemistry at Rutgers University in New Brunswick, NJ. She is a 2018 Undergraduate Summer Research Fellow, funded by the APS. Jordan is working in Dr. Debra L. Laskin’s lab at the Ernest Mario School of Pharmacy at Rutgers. After graduation, she plans to continue doing research and exploring her interests in healthcare and science.
It’s Getting Harder and Harder to Breathe! ~Maroon 5

This summer I have been hard at work in the Student Development Complex, here at Michigan Tech. It is a closed room with no windows, kind of odd for an exercise nut, but some of the best things are happening there! We have research going on testing the human body to its limits. Specifically, my research is testing the limits of our respiratory system during exercise. I believe that respiratory muscles are important in performance and if we can understand the limiting factors of the respiratory then we can help people with asthma, chronic obstructive pulmonary disease (COPD), and team and endurance athletes. I am taking members from our cross-country ski team and putting them through two arm cycling trials to failure, i.e. biking for your arms. One trial their whole body is 100% fresh, the second their respiratory muscles have been fatigued ~20%. During the trials, I track the time and all their respiratory and metabolic functions and compare them between the trials. I have had six people go through the tests and have seen a surprising decrease in time to failure when respiratory muscles were fatigued. Additionally, their breathing rate was low and volume high during the normal condition and it flipped during the fatigued condition, showing that when the muscles are already fatigued they work even harder trying to sustain performance. The next step in my study is finding out how and why this happens.

Tom Bye performing equipment tests while designing his protocol, Michigan Technological University

Here in the Upper Peninsula of Michigan it can get hot, for us at least. Our lab is air conditioned, unlike most buildings up here, so we can have a consistent climate for testing and it is the place to be somedays. Research in the lab is a blast! When I have subjects in for testing we keep the mood light and keep them determined with some tunes, conversation, and cheering. There are also pros and cons to the lab, because I have ski team commitments to come accomplish, my mornings arriving in the lab for set-up are as early as 6:15 AM and nights can be the same, ending late, crunching numbers or safety checking our laboratory. I have been learning a lot over the summer about different programs and technology we use in the lab. I’ve been fortunate enough to use ultrasound, metabolic carts, NIRS devices, and EMG. Currently my task at hand is to learn SigmaPlot, a graphing program that is Excel on steroids; I’m getting good at it! The main tests that I am running on subjects are maximum aerobic capacity and maximum upper-body exercise tolerance tests. Using flow meters I have also been able to test their basic respiratory function, one subject’s lungs could take in over 8 liters of air! A normal person his size would normally take in 5-6 liters of air. Our results are looking like we expect when we plot them out, but statistically only some are significant. The next step is to keep trucking on and see if the results stay consistent!

Tom Bye pushing a subject to their max during pilot data collection, Michigan Technological University

Our lab isn’t just me and my research host, we are a team of many undergraduate, graduate, and doctoral students! It is amazing to see how we transfer knowledge and share ideas with each other. It is great that I can go to a doctoral student (a goal of mine) and get info on schooling and my research. I have been in the lab a while now and teach some of the undergraduate and graduate students how the equipment works with their research project protocols. In a few weeks, we will have a testing blitz for my project and get five participants through five days of testing each! My worst experience so far is troubleshooting our metabolic carts and lab computer… It was supposed to take an hour and ended being the whole day. My favorite part of lab also surprises me too, it is the intensity that all the team members bring to the lab, but when we have a BBQ we are all relaxing and playing yard games.

Thomas Bye is a senior studying Exercise Science at Michigan Technological University in Houghton, MI. He is a research fellow in Dr. Steven Elmer’s laboratory at Michigan Technological University in Houghton, MI. He is supported by the American Physiology Society Undergraduate Summer Research Fellowship. After graduating, he plans on becoming a physical therapist and being involved with research in sports. Later in life, he would like to be a professor to pass on what he has learned.