I Have Cystic Fibrosis, and CF Has Me

This Lung Life By Ella Balasa

I hear others say “I have CF. CF doesn’t have me.” This may be an accurate statement for some, the small percentage of patients who are not limited by this disease. Those who climb mountain peaks, work 60 hours a week, and raise three children. They could say this statement is true. They conquer everything, despite CF.

I am not one of these patients. I am optimistic, though. I’m optimistic that one day I will sprint faster than you (with transplanted lungs). I’m optimistic that I will leave this world having made some kind of impact on those around me, and maybe others that I am unaware of. But with this DNA in the cells of my lungs, I can’t do it all.

I’ve had significant events and minute moments in my life that have been affected by CF, although it’s not always apparent to the world around me. However, I don’t claim that CF has altered my life for the worst. Instead, I show the reality.

CF had me most recently when I was planning to go to the Cystic Fibrosis Research Inc.’s Family Education Conference. Being a director for the U.S. Adult Cystic Fibrosis Association, I wanted to connect with fellow CF directors and hear about the amazing new research the CF community is eager to benefit from. Unfortunately, due to CF infection guidelines and the bacteria I harbor in my lungs, I posed a risk to other CF patients, so I was restricted from attending.

Recently, as my form of exercise, I have been playing tennis. CF has me when it grasps my airways after just a few serves. I feel my lungs expanding but not getting enough air, exhausted from a previous sprint of just a few feet. I watch as the ball spins toward the far corner of the court. In my mind, my legs are in the air moving toward it, but in reality, they have just elevated the sole of my foot for the first step. The muscles are depleted of oxygen, waiting for the next burst for them to spring into action, but it never comes. Instead, they continue straining with what little reserve they have, for one-quarter of their potential. The quarter that comes from the lungs that function at one-quarter of what they should.

CF dictated the direction my life would take when upon graduation I was offered my dream job, but I didn’t take that career path. Spending four hours a day on breathing treatments, attending frequent doctor’s appointments, having occasional hospital stays and health insurance factors, as well as maintaining a social life and community involvement weren’t conducive to a full-time working schedule. Choosing not to advance in my career as my peers did made me feel left behind. Instead, keeping my health as the focus, I chose part-time employment.

CF has me when I have an exacerbation and lots of congestion in my lungs. On occasion during these times, I’ve taken the flight of stairs from the basement out into the sunshine after work. After a few steps outside, I feel the absence of air in my lungs. I gasp and then panic. Continue the article here. 

Cystic Fibrosis Podcast 192 Emily’s Entourage

In the latest Cystic Fibrosis Podcast, Jerry speaks with Emily Kramer-Golinkoff about the role of a patient advocate organization in driving drug development in rare disease.
Emily, a 33-year-old who has a nonsense mutation of CF, is a co-founder of Emily’s Entourage, a 501 3(c) that’s goal is to accelerate research for new treatments and a cure for CF. She is an internationally recognized patient advocate and speaker, has a Master’s degree in Bioethics and is certified in Clinical Ethics Mediation, was named “Champion of Change” by President Obama’s Precision Medicine Initiative, and has been featured by CNN.com, Time.com, AOL.com, People.com, and more for her work with her charity.

Continue reading Cystic Fibrosis Podcast 192 Emily’s Entourage

Bioengineers Are Closer Than Ever To Lab-Grown Lungs

By Robbie Gonzalez

The lungs in Joan Nichols’ lab have been keeping her up at night. Like children, they’re delicate, developing, and in constant need of attention, which is why she and her team at the University of Texas Medical Branch at Galveston’s Lung Lab have spent the last several years taking turns driving to the lab at 1:00 am to check that the bioreactors housing their experimental organs are not leaking, that the nutrient-rich soup supporting the lungs is still flowing, or that the budding sacs of tissues and veins have not succumbed to contamination. That last risk was a persistent source of anxiety: Building a lung requires suspending the thing for weeks on end in warm, wet, fungus friendly conditions—to say nothing of the subtropical climate of Galveston itself. “In this city, mold will grow on people if they sit still long enough,” Nichols says.

But their vigilance has paid off. In 2014, Nichols’ team became the first to bioengineer a human lung. A year later, the researchers implanted a single lab-built lung into a pig—another first. They’ve grown three more pig lungs since, using cells from their intended recipients, and transplanted each of them successfully without the use of immunosuppressive drugs. Taken together, the four porcine procedures, which the researchers describe in this week’s issue of Science Translational Medicine, are a major step toward growing human organs that are built to-order, using a transplant recipient’s own cells.

Bioengineering a lung is a bit like modeling with clay: Like a sculptor uses a wire armature to lend his creation form, Nichols’ team grew the tissues and blood vessels of their lab-grown lungs atop a framework of tough, flexible proteins. The researchers got that scaffolding secondhand, harvesting whole organs from dead pigs and bathing them in a concoction of sugar and detergent to strip them of the cells and blood of their previous owners like a coat of varnish from an old table.

Nichols calls the milky mass that remains the organ’s skeleton: It’s made mostly of collagen, which lends the lung strength, and elastin, which makes it flexible. Each scaffold goes into a bioreactor—one of the containers Nichols and her team built from scratch to house each of the proteinous blobs. The earliest models were little more than spruced-up fish tanks; the latest iterations still incorporate parts purchased from Home Depot.

Its humble origins notwithstanding, each bioreactor plays a vital role. “It lets you provide the organ with growth factors, media, mechanical stimulation,” says pediatric anesthesiologist Joaquin Cortiella, who co-leads the Lung Lab with Nichols. Its job is similar to that of a placenta, allowing the lung to develop in a warm, cozy, nutrient-rich environment for 30 days before it moves to the thoracic cavity of a living, breathing pig, nestled neatly beside the animal’s original lung.

Growing a lung in a bioreactor for a month is a significant accomplishment, says bioengineer Gordana Vunjak-Novakovic, director of the Laboratory for Stem Cells and Tissue Engineering at Columbia University, who was unaffiliated with the study. In an email to WIRED, she said that previous lab-grown lungs have spent a lot less time in culture before being transplanted. The extra time allowed Nichols’ and Cortiella’s bioengineered lungs to grow more blood vessels, the underdevelopment of which “is a major current limitation of lung survival,” said Vunjak-Novakovic. In past studies involving smaller animals, transplant recipients have died within a matter of hours due to fluid accumulation in the lungs. By contrast, the vasculature in Nichols’ and Cortiella’s organs allowed the pigs who received them to survive as long as two months post-transplant without any observable complications.

It’s unclear how the pigs would have fared beyond two months. The four animals in this study were euthanized 10 hours, two weeks, one month, and two months post-surgery, so the researchers could examine how each bioengineered lung had developed inside its recipient following transplantation. All signs pointed to the lungs integrating seamlessly—they continued to develop blood vessels and lung tissues and were colonized by the microbes specific to each animal’s native lung microbiome, all without respiratory symptoms or rejection by the recipient’s immune system.

A big lingering question is how well the bioengineered lungs deliver oxygen. Though each of the pigs had normal amounts of the stuff pumping through their bodies, that could have been the work of the animal’s original lung. The researchers worried the implanted organs were too underdeveloped to risk stopping each research animal from breathing on its original lung, to test the lab-grown one in isolation. That’ll have to wait for future experiments, which Cortiella and Nichols say will involve pigs living for a year or more on their transplanted organs.

Such studies will also require more animals. “It will be interesting to see how robust this technology is, as the number of animals was very low,” said Vunjak-Novakovic. Still, the results are promising. With sufficient funding, Nichols and Cortiella think they could be transplanting bioengineered lungs into humans within the decade.

But first come more experiments—and better, more reliable research facilities. High on Nichols’ wish list is a clean room for the bioreactors, accessible only to researchers clad head-to-toe in bunny suits. She’d like more automated equipment too, which would translate to less manual labor and fewer opportunities for error. And of course, she’s looking forward to the day when she and her colleagues can monitor their lungs remotely via a livestream. Babysitting bioengineered lungs may always be a 24-hour job, but at least with a video monitor the members of the Lung Lab could work remotely.

Lung Plethysmography Procedure

By HH Patel, M.Pharm

Similar to spirometry and pulse oximetry, lung plethysmography is a tool within the broad umbrella of pulmonary function tests. It is a type of diagnostic procedure used to measure the amount of air in the lungs after inhalation or exhalation.

Also referred to as body plethysmography, lung plethysmography provides an idea about how efficiently the lungs are functioning. It is also especially useful in characterizing types of pulmonary abnormality and implementing appropriate treatment approaches depending on the diagnosis.

Continue reading Lung Plethysmography Procedure

Cystic Fibrosis Podcast 191 ‘Why do you run?’ with Ben James

In his latest podcast, Jerry Cahill sat down with Ben James, a 19-year-old college student who was diagnosed with cystic fibrosis at 4 years old. Originally from Chester, VA, Ben now attends Mount Vernon Nazarene University in Ohio where he studies pre-medicine. When he isn’t focusing on school subjects like anatomy and physiology, Ben likes to play basketball and soccer, and also likes to run long distance.
Ben loves the challenge of running long distance for a number of reasons, including building character, facing challenges as an individual, and learning discipline, which helps with his overall medical compliance.
Click here to listen:
This podcast was made possible through an unrestricted educational grant from Genentech to the Boomer Esiason Foundation.

The Year Ahead – Fall 2018 Scholarship Winner Guest Blog

By Roberto De La Noval

The next year is going to be a big one. I am writing against the clock to meet deadlines for my dissertation, sending out a book manuscript to a publisher, writing my first book review for an academic journal, presenting for the first time at a national conference…and all that on top of my first semester, in the Spring, of teaching undergraduates. Suffice it to say I’ll be busy. I wouldn’t have it any other way, though. Finally—at last—I feel like less of a perpetual student (I’ve been in higher education almost 12 years) and more like someone actually enjoying the first fruits of his career. That’s why I’m grateful to be one of the recipients of this year’s Lauren Melissa Kelley Scholarship; graduate school isn’t cheap, and so these funds will be of immediate help to me.

For example, I travel to one or two academic conferences a year, and often I cannot get the university to recompense me for all of the travel. That means that some of it comes out of pocket for me. The LMK scholarship will help me recoup these costs and make it more likely that I will pursue these opportunities to engage in the academic community and share my work. Another way the LMK scholarship will make a big difference is in allowing me to continue my language education. Now that I no longer am in coursework, the simplest way for me to continue improving my languages (German and ancient Greek are the ones I’m currently working on) is to have a private tutor who can work around my dissertation-writing schedule. These lessons are not cheap, but they significantly and rapidly help me improve my language skills, which in turn allows me to access more material for my scholarship and makes it possible for me to become a truly international academic who can engage with people from various parts of the world. It would be a welcome financial relief to know I have funds to continue my education now that I have finished formal coursework and am expected to be writing a book! In short, this is a critical period in my career of transition from student to scholar, and the LMK scholarship will facilitate this ctransition with greater ease.

In many ways the academic life is well tailored for someone negotiating the scheduled and regimented life cystic fibrosis demands. And I am happy to say that I’ve encountered nothing but support and encouragement from my faculty and colleagues when it comes to managing both my illness and my career. But it’s also a support in my work and life to know that so many others with CF are living their lives to the fullest, and that behind them there is a huge community of people who care about people with CF and work incredibly hard, often behind the scenes, to make a rich life possible for them. CFRoundtable and the LMK Scholarship are outposts of this amazing community of doctors, researchers, social workers, advocates, speakers, families, and friends. I relish the opportunity to be on the receiving end of their care, and I cannot wait to pay it forward in whatever way I can.

Past USACFA Scholarship Winner’s touching poem about CF

My name is Grace Knight and I am a college student with cystic fibrosis. I am 20 years old and go to the University of Pennsylvania. This past summer, I took a few summer school classes to make up for the medical leave I had taken the year before. In one of the classes, we had to write poems for our final project. One of the poems I wrote was this poem titled “Only Morning.” It is about how it feels to wake up with CF every day. The poetic form is based upon a classical piece I used to play called Chaconne in G minor by Vitali. I have actually previously compared to this piece of music to CF because the more into the piece you play the harder it gets. I found this similar to the progressive nature of the disease.

Continue reading Past USACFA Scholarship Winner’s touching poem about CF

AIT’s Inhaled Nitric Oxide Shows Potential in Fighting Bacterial Infection Prevalent in CF Patients

By Alice Melao

Inhaled nitric oxide (NO) was shown to be an effective antibacterial agent against Mycobacterium abscessus infection in preclinical studies, as well as in a pilot clinical trial, according to AIT Therapeutics.

The company discussed the latest data on its NO product in two poster presentations during the 3rd Annual World Bronchiectasis Conference held recently at Georgetown University in Washington, D.C.

NO is a small molecule that is an important mediator of immune defense mechanisms against infections. The compound has been shown to have broad-spectrum antibacterial activity against several strains of bacteria that often infect patients with underlying lung diseases, including cystic fibrosis (CF).

Continue reading AIT’s Inhaled Nitric Oxide Shows Potential in Fighting Bacterial Infection Prevalent in CF Patients

Phage-Coated Microparticles Treats Lung Conditions like CF

By SterlingAdmin

The methods available to treat bacterial infections are many. But among those with any real and lasting effectiveness, their usage is limited. Antibiotics were once the Holy Grail of medicine to deal with devastating diseases that wiped out entire populations. With them, these suffering conditions were almost entirely wiped out and the populace began to learn how to live without the fear of most children dying at a young age. But, as is well known, the age of antibiotic cure-alls is ending and the time of antibiotic resistance is beginning to reach its peak. So, medical researchers are hard at work on all the other opportunities for dealing with bacteria that don’t require these specific groups of compounds.

The Medicine of Viruses

Phage therapy is one such alternative that has begun to see more extensive use over the past two decades.Bacteriophages are lifeforms that have crafted over evolutionary time a niche focused on using bacteria as their reproductive hosts, killing said host in the process. And since they are living beings as well, they actively engage in the selective pressures of finding ways around resistance against them, rather than being a static attack on bacteria like antibiotics are. This means that even the most feared multi-drug resistant bacterial strains have little to no protection against phages.

The primary downside to this treatment is that phages are highly specialized, having formed themselves to only target a particular host species. Therefore, to deal with certain bacteria, one also has to find and be able to cultivate a certain type of phage. Once that step is accomplished, however, it has been found that they can be altered fairly easily to give them variable methods of attack, so as to minimize any potential side effects on the human body while they are killing the bacteria. They can even be set up to synergistically interact with the human immune system to work together to wipe out the bacterial invasion.

With the right phage strain, the largest remaining issue is how to get them into the human body and to the right type of location and system that the bacteria are also attacking from. A large proportion of phage research has gone into finding new ways to do this very thing, as it is one of the inefficient areas of the therapy and, if improved, can drastically heighten the success rates of the treatment and the types of bacterial diseases that can be combated.

It is difficult and time consuming to produce modified phage, with many of them dying in this fabrication. For bacterial diseases of the lungs, such as the kinds that like to colonize those suffering from cystic fibrosis, there is currently no true delivery method of getting phage into the deep lung tissues. And, of course, getting any single treatment approved requires showing success in some sort of animal model, even though the phages may not translate well or at all to anything other than humans. This is one of the major problems this author has with the current approval setup by governments for medical trials.

Microparticles For A Micro World

Scientists at the Georgia Institute of Technology have been seeking a new method for just such a delivery system. Dry powder formulations has seen some positive benefits for effectiveness in recent years, but there lingers the issue of how to use such a powder to delivery living phages to the right spot. To do so would require a very carefully made powder indeed.

The engineering techniques they brought into play were used to make phage-loaded microparticles (phage-MPs), hollow molecular structures formed using water-oil-water emulsion to keep them stable. The bacteria being combated was the opportunistic pathogen Pseudomonas aeruginosa and several strains of phage against it were chosen for the experiment.

The microparticles were housed in a phage-containing solution, allowing them to be filled with the phage after incubation. Though they were filled in a different way than the usual method of them being inside the MPs. Instead, they cover the exterior in this method after the MPs are made, meaning no phage are lost due to solvent usage during MP fabrication from the prior ways other studies used. Three to five phages were contained on the MPs in order to reduce the likelihood of any possible bacterial resistance.

This delivery mechanism also reduces endotoxin production by the phage, thereby minimizing side impacts of their use, with the reduction bringing them down to 0.078 endotoxin units (EUs), far below the accepted FDA limit of 20 EU in treatments. The technique was first tested on petri dishes containing the bacteria to which the phage-MPs were applied. The P. aeruginosa were modified to express green fluorescent protein (GFP) to identify their living location on the plates.

A Complete Victory

After 16 hours of co-incubation, large patches of non-fluorescence showed where the phage had successfully killed off the bacteria, while the control group MPs without a phage coating had no deaths. These zones were also far larger than the applied MP area, showing that the phage were able to spread and extend to other bacteria in the dishes. The same test was done using synthetic sputum to mimic the environment of an animal lung and the bacteria and phages were applied at the same time. There was no visible growth of bacteria after application, showing that the phages were able to both control and wipe them out. A further test showed the phage are also able to get past the protective biofilms of the bacteria that they make under environmental emergencies.

The dry powder formulations were also seen to have a large burst of phages initially, with slow release for two weeks after, the perfect way to allow consistent application and treatment against the bacteria. The final experiment involved using mice infected with the bacteria. A control test using just phage-MPs showed no negative effects on the mice or their lungs after application. Fluorescent phage-MPs also showed that they were only localized to the lungs and nowhere else in the body, as desired. The control using free form phages without microparticles revealed how the dry powder still didn’t allow them to be properly applied, with no major phage levels detected in those mouse lungs, proving that the MPs as a transport vector were required.

When tested on mice infected with P. aeruginosa, the bacterial count dropped by an entire order of magnitude and 100% of the mice survived their pneumonia, while the untreated control group only had 13% survive. For mice with a cystic fibrosis genetic mutation, the same test saw their bacterial counts drop by three orders of magnitude, approaching the limit of what could be detected. The phage-MPs also saw the same effectiveness against multiple strains of the bacteria, meaning that even genetic variance in a population wasn’t enough to defend against them.

A last point of importance is that when testing against a mouse group exposed to phage-MPs long before being infected and later treated, there was no reduction in effect and no antibodies against the phages seemed to develop. So there is likely no performance loss to the treatment if used multiple times.

The New Antibiotics

As a conclusion, the researchers were able to engineer specialized biomaterials made of microparticles that, when coated with bacteriophages, were highly effective at reducing bacterial counts for lung-related diseases, including those resulting from the lowered immune system responses of cystic fibrosis. These phage-MPs are stable and can be stored for a fair amount of time with no loss in phage amounts and can be administered through simple inhalation, meaning younger patients can be treated with less complications.

For lung-related diseases, and likely for broader conditions at large in the medical community, this breakthrough might serve as a major way to allow phage therapy to become more common and used in replacement of or as a sought after alternative to antibiotics. The number of lives this should be able to save in the long run is likely incalculable.

Press Article Link

Study Link

Original article Link

Antioxidant-Enriched Multivitamin May Decrease Respiratory Illnesses

MedicalResearch.com Interview with:

Scott D Sagel MD PhD
Professor of Pediatrics
University of Colorado School of Medicine
Aurora, Colorado

MedicalResearch.com: What is the background for this study?

Response: Inflammation is an important feature of cystic fibrosis (CF) lung disease and contributes to lung damage and lung function decline in CF. We need safe and effective anti-inflammatory treatments in CF. Anti-oxidant therapy has been an area of promise, but with mixed results in CF.

This clinical trial, conducted at 15 CF centers affiliated with the cystic fibrosis Foundation Therapeutics Development Network, enrolled 73 patients who were 10 years and older (average age 22 years), with pancreatic insufficiency, which causes malabsorption of antioxidants. Subjects were randomized to either a multivitamin containing multiple antioxidants including carotenoids such as beta(β)-carotene, tocopherols (vitamin E), coenzyme Q10 (CoQ10), and selenium or to a control multivitamin without antioxidant enrichment. The antioxidants used in the study were delivered in a capsule specifically designed for individuals with difficulties absorbing fats and proteins, including those with cystic fibrosis.

MedicalResearch.com: What are the main findings?

Response: Antioxidant supplementation was safe and well-tolerated. Supplemental antioxidants increased antioxidant concentrations in the bloodstream in treated subjects and temporarily reduced inflammation in the blood at four weeks but not 16 weeks. Airway inflammation, as measured in sputum, did not change significantly with antioxidant treatment. Importantly, antioxidant treatment appeared to both prolong the time to the first respiratory illness requiring antibiotics and reduce the frequency of respiratory illnesses they experienced.

MedicalResearch.com: What should readers take away from your report?

Response: Taking a specially formulated antioxidant-enriched multivitamin, containing multiple dietary antioxidants, may decrease respiratory illnesses in people with cystic fibrosis. While more research needs to be done to find a treatment that delivers a sustained anti-inflammatory effect, we believe the prolonged time patients had before their first respiratory illness is clinically meaningful. Also, the cost of a dietary antioxidant-enriched multivitamin is relatively modest compared to other currently available therapies that have been proven to reduce pulmonary exacerbations in cystic fibrosis.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: We still don’t know the optimal dosing of these various dietary antioxidants. We also don’t know the added benefit of antioxidant supplementation in the era of CFTR modulator therapy, emerging treatments that get at the basic protein defect in cystic fibrosis.

MedicalResearch.com: Is there anything else you would like to add?

Response: This clinical trial, funded by a grant from the Cystic Fibrosis Foundation, was an investigator-initiated study led by Scott D. Sagel, MD, PhD, a Professor of Pediatrics at Children’s Hospital Colorado and Director of the University of Colorado Cystic Fibrosis Center. It was not an industry initiated or funded trial. Callion Pharma manufactured the antioxidant-enriched and control multivitamins and provided them at no charge for this study.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:
Effects of an Antioxidant-enriched Multivitamin in Cystic Fibrosis: Randomized, Controlled, Multicenter Trial
Scott D Sagel , Umer Khan , Raksha Jain , Gavin Graff , Cori L Daines , Jordan M Dunitz , Drucy Borowitz , David M Orenstein , Ibrahim Abdulhamid , Julie Noe , John P Clancy , et al
https://doi.org/10.1164/rccm.201801-0105OC PubMed: 29688760
American Journal of Respiratory and Critical Care Medicine

Published Online: April 24, 2018

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

Original interview article here.