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Chronic Obstructive Pulmonary Disease

Realizing the Potential of Vendor Engagement with ELRIG's Vendor Strategy Work Group Lead

Nick Clare

In this interview conducted in anticipation of ELRIG's Drug Discovery 2023 Conference, we spoke to Nick Clare, Vendor Strategy Work Group Lead for ELRIG, about what vendors can gain from attending ELRIG events, such as Drug Discovery 2023.

Dear Doctor: What Symptoms Indicate Chronic Obstructive Pulmonary Disease?

DEAR DR. ROACH: What signs and/or symptoms do you need for a doctor to determine you have chronic obstructive pulmonary disease (COPD)? -- R.K.

ANSWER: The diagnosis of COPD is suspected in people who are at risk for the disease and note one of two cardinal symptoms: cough or dyspnea. (A "symptom" is what a patient identifies by history, while a "sign" is noted on a physical exam. Cough can be both a symptom and a sign.) Dyspnea is usually described as shortness of breath, a sensation that a person can't get enough air, like they have just run very fast. Some people with COPD may have very subtle symptoms.

Smoking is the biggest risk factor for COPD, but there are other causes, including other chemical exposures (industrial exposures and home cooking fires are less common now, but are historically important causes of COPD); scarring lung disease; and a genetic cause, a condition called alpha-1 antitrypsin deficiency.

The diagnosis is confirmed most often by tests of lung function, which are breathing tests to look at the physiology of the lung and its ability to exchange oxygen and carbon dioxide. Sometimes, the diagnosis can be supported by an X-ray or CT scan, but pulmonary function testing is the best way to determine the severity of COPD and follow the course.

We do have ways of slowing down lung decline in COPD, one way being smoking cessation for current smokers, but some of the medications we use also help reduce ongoing damage.

DEAR DR. ROACH: Please help! Is it true that Trulicity may cause serious side effects, including thyroid tumors and cancer, as well as pancreatitis? -- J.R.

ANSWER: Dulaglutide (Trulicity), like semaglutide (Ozembic) and liraglutide (Victoza), are in a class of drugs called GLP-1 receptor agonists, which have several actions, such as increasing insulin release by the pancreas in response to meals. Initial studies on laboratory rats did show an increase in an unusual type of thyroid cancer, but studies have not yet shown an increased rate in humans. Still, people at an increased risk for this type of thyroid cancer (a family history of medullary thyroid cancer or of multiple endocrine neoplasia, type 2A or 2B) are not recommended to take this medication.

Similarly, there are reports of pancreatitis in people taking this medication, but it isn't clear whether the medicine is responsible for the pancreatitis. It's unwise to use this class of medication in people with a history of pancreatitis.

DEAR DR. ROACH: I am 93 and in excellent health. I am taking atorvastatin daily. My cholesterol results are excellent. I am wondering if I should continue the statin. -- B.F.

ANSWER: If you were started on a statin because of blockages in the arteries, especially if you had a heart attack or stroke, I recommend continuing it. If you have been on the medication to prevent a heart attack or stroke, I say it is up to you. If the medication is causing side effects, or if it really bothers you to take it, you can certainly stop.

However, I believe the atorvastatin continues to reduce your risk of a heart attack and still gives you some benefit. There is no need to stop it simply because of your age.

Remember, your cholesterol results are excellent on the medicine and aren't going to be as good if you stop it.

Dr. Roach regrets that he is unable to answer individual letters, but will incorporate them in the column whenever possible. Readers may email questions to ToYourGoodHealth@med.Cornell.Edu or send mail to 628 Virginia Dr., Orlando, FL 32803.

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New Organ Models Open Up Avenues Of Research For Lung Disease

3D Illustration Concept of Human Respiratory System Lungs Anatomy

getty

Lung diseases like emphysema or chronic obstructive pulmonary disease are a leading cause of death worldwide. With the advent of COVID-19, these diseases have only become more prevalent. Despite the severity of lung diseases, there are few available treatments that can alleviate or cure them. Now, a pre-printed paper under review by the Journal of Biomaterials Research suggests that researchers are one step closer to creating an accurate model of the lungs. Phan et al. Developed an improved lung organoid model that may help us learn more about lung diseases and how we can treat them.

What are organoids?

Organoids are more realistic models of human organs created in a laboratory. These models are often formed from stem cells. Stem cells are a unique type of cell that has the capability to develop into nearly any other cell type in the body. For instance, a single stem cell has the potential to develop into a brain cell or muscle cell simply depending on the environment it is exposed to. Given the correct chemical and environmental cues, these stem cells can be coaxed into any cell line, tissue, or organoid of scientific interest.

Figure 1: Scientists can use stem cells to study cells, tissues, and organs of interest.

Ramírez-Flores & Knoll, PLOS Pathogens (2021), DOI: 10.1371/journal.Ppat.1010080

While this seems simple enough, current organoids are far from perfect. Existing lung organoids are either too simple and neglect essential features in human lungs or they are too complex, making them difficult to reproduce and work with.

Creating a lung organoid

To create an ideal lung organoid model, Phan et al. Cultured several different critical lung cell types and measured how accurately the cell-to-cell interactions resembled how cells interact and organize themselves within human lungs.

The researchers found that there were two cell types that accurately modeled cellular interactions in human lungs—bronchial epithelial cells and human lung fibroblasts. Bronchial epithelial cells are a major cell that forms lung tissue while human lung fibroblasts are responsible for producing proteins that support the structure of tissues and organs. Phan et al. Speculated that by culturing the two cell lines together, they could form a lung organoid that was representative of human lungs.

The next challenge was to determine what the organoids would grow in. An innovative feature of Phan et al.'s model is that it incorporated a microfluidic system.

Microfluidic devices are small materials that are imprinted with microscopic channels and chambers. These tiny, imprinted channels allow researchers to easily control properties of liquids like pressure and flow. By incorporating a microfluidic device in their cell culture, Phan et al. Could grow their cells in a liquid that continuously flowed. This gave the researchers the ability to mimic the dynamic environment of cell growth in the human body.

Figure 2: Example of a microfluidic device and its microscopic channels.

By Richard Wheeler (Zephyris) - Own work (Original text: self-made), CC BY-SA 3.0, https://commons.Wikimedia.Org/w/index.Php?Curid=7514808

With microfluidics incorporated into their model, Phan et al. Were ready to form full organoids. The researchers were interested in growing both a model of healthy lungs and a model that captured the physiological effects of lung disease.

After sampling and culturing cells from a healthy patient and a patient with chronic obstructive pulmonary disease, the resulting bronchial epithelial cells and human lung fibroblasts self-organized into 3D structures and formed organoids. These organoids were unique because the diseased organoid actually emulated biological characteristics of chronic obstructive pulmonary disease.

In the diseased organoid, the epithelial cells were not as structurally sound, causing a weakened cell barrier in the lung tissue. Similarly, the diseased organoid exhibited overproduction of goblet cells and reduced cilia. Goblet cells are responsible for creating mucus. Cilia are tiny hair-like structures that line some cells and help remove mucus from the lungs to prevent buildup and respiratory infection.

Conclusion

Overall, while this study is still under review, Phan et al.'s results represent real progress in the development of accurate models for human diseases. This innovative method of organoid growth may soon allow us to understand lung diseases more deeply and hopefully develop new treatments and medications that can alleviate or prevent disease.

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