As Both Patient and Scientist, I’m Putting Nature’s Medicine to the Test

By Ella Balasa

I peered into one of the incubators that stored my petri dishes for 24 hours, anxious to see whether I would discover discoloration and unevenness on the surface, which would have indicated that my experiment produced favorable results. I wanted to see a visual representation of whether manuka honey kills the stubborn Pseudomonas bacterium, which dwells in nearly half of the lungs affected by CF.

I’m a microbiology lab scientist, plus an inquisitive writer. I also consider myself an informed, self-advocating realist. Life experiences have taught me that I am solely responsible for my health. I strive to keep my health stable through prescribed medications, healthy diet, and some natural supplements.

During my college years, I focused on the environment, especially the living parts that we can’t see but that are essential to the cycle of life — bacteria. It just so happens that certain ones are, understatedly, little pests for people with CF. The lung bacteria of people with CF birth many symptoms and infections.

I continually fight Pseudomonas aeruginosa, my nemesis bacterium that spikes fevers within days of overwhelming my immune system and that has caused countless infections, leaving my lungs with pockets of dead tissue. I take antibiotics frequently, but I also believe that naturally derived compounds can have positive effects. So, despite my disdain and nausea, I sometimes supplement garlic, which contains the antibacterial compound ajoene. I’ve also consumed manuka honey; this I’ve done more religiously, as it tastes more like candy than any “medication.” Manuka honey contains the natural antibiotic methylglyoxal, a compound that fights relentless Pseudomonas by causing its cells to burst and die. I took a spoonful a day for a few years until recently. Maybe I stuck to this exorbitantly priced, palatable remedy merely because of its taste and the flawed logic that expensiveness is indicative of effectivity.

I had the idea to test the effectiveness of the honey on my sputum. My mucus grows many species of bacteria, but Pseudomonas is a primary component, so it’s easy to propagate in the lab setting.

Yes, I took a sputum cup of mucus into work. When inoculating the vials with the bacteria, I was slightly anxious that my lab mates might freak out at the sight of the hazardous and vile-looking green blobs. Then again, they work with wastewater from treatment plants, so it really shouldn’t phase them.

I tested a concentration of 15 percent weight per volume of manuka honey, a choice informed by published studies. I tested half of the petri dishes with honey mixed into the nutrients for the bacteria and the other half without the honey. The dishes with the honey should have less bacterial growth if the treatment works. (If you want more detail on the process, drop a comment below this column.)

The yellow dish has the honey added and the white dish doesn’t. (Photo by Ella Balasa)

After the 24-hour incubation period, I was excited to see the results of science that we as patients typically do not participate in. We provide our sputum samples during doctor’s appointments, then labs perform antibiotic resistance tests, and results are returned as values on a piece of paper indicating resistance or susceptibility. We don’t see the process. I was doing this same research on my own, and in a sense, taking the utmost control of my health.

To continue reading, click here.

Antibiotic plus probiotic combination may kill off superbugs

By 

Every year, over 2 million people in the United States develop infections that are resistant to treatment, and approximately 23,000 people die as a result.

These statistics have prompted the Centers for Disease Control and Prevention (CDC) to deem drug resistance “one of the biggest public health challenges of our time.”

Therefore, researchers are hard at work trying to develop ingenious ways of tackling so-called superbugs — bacteria that have become immune to antibiotic treatment.

Lately, researchers have added probiotics to their arsenal against superbugs. Probiotics are beneficial bacteria found in foods, such as yogurt, kefir, pickles, or miso soup.

Only a month ago, for example, a study suggested that simply consuming probiotics on a regular basis could reduce the need for antibiotics, thus helping to curb the drug resistance crisis. Continue reading Antibiotic plus probiotic combination may kill off superbugs

Livestreaming of the North American Cystic Fibrosis Conference (NACFC)

North American Cystic Fibrosis Conference
Opportunity: Register Now for the Livestream Content
Dates: NACFC will be held October 18-20
The North American Cystic Fibrosis Conference (NACFC) brings together researchers and health care professionals from around the world to discuss the latest in cystic fibrosis research, care, infection, treatment, and drug development.
You can explore conference sessions along with the experts! Join us online for three livestreamed plenaries, follow-up Facebook Live Q&As with the speakers, and additional livestreamed workshops and symposia that were hand-selected by members of the CF community, including members of Community Voice. You will find the schedule for these sessions below. The plenary sessions are the major keynote sessions that are presented to all attendees. Each plenary will be followed by a Facebook live Q&A session with the plenary presenters.
During the third plenary session, keep an eye out for Community Voice Melanie Abdelnour, who will be sharing about the importance of partnering with her care team.
Additionally, you will have access to view the content from all other sessions where speakers have consented to share their presentations through the sync-to-slide feature 6 weeks after the conference. Stay tuned for more details!
Register now to livestream the plenaries, workshops, and symposia.
Thursday, October 18, 2018
  • Advancing Basic Science Toward a ‘One-Time’ CF Cure – 09:45 am – 11:05 am MT
  • Pro/Con: Current Debate in Pulmonary Treatments – 09:45 am – 11:05 am MT
  • Controversial Practices – Helpful or Harmful – 02:00 pm – 03:25 pm MT
  • Healthy Habits: Promoting Physical & Mental Health Through Sleep, Exercise, & Nutrition – 02:00 pm – 03:25 pm MT
  • Plenary 1: Improving Outcomes of Infections in the Age of CFTR Modulators – 04:30 pm – 06:00 pm MT (6:30-8 ET)
  • Facebook Live: Infection Research: Mission Possible,  6:30 pm MT (8:30 pm ET) 
Friday, October 19, 2018 
  • Plenary 2: Anti-inflammatories & Mucociliary Clearance Therapies in the Age of CFTR Modulators – 9:00 – 10:00 am MT (11:00 – 12:00 pm ET)
  • Facebook Live: Glad You Brought It Up: Mucus and Inflammation, 12:15 pm MT (2:15 pm ET)
  • The Changing Face of Pulmonary Exacerbation Treatment – 10:30 am – 11:55 am MT
  • Progress & Promise of the CFTR Modulator Pipeline – 10:30 am – 11:55 am MT
  • Novel Approaches to Modulate CFTR – 02:00 pm – 03:20 pm MT
  • Nutrition Research – 02:00 pm – 03:20 pm MT
Saturday, October 20, 2018 
  • Plenary 3: Partnering: The Oldest New Idea to Improve CF Care – 9:00 – 10:00 am MT (11:00 – 12:00 pm ET) 
  • Facebook Live: Howdy, Partner! A Live Q&A, 12:15 pm MT (2:15 pm ET)
  • CF Airway Inflammation – 10:30 am – 11:50 am MT
  • Progress in CF Pulmonary Disease – 10:30 am – 11:50 am MT
  • Pain Management in CF – 02:30 pm – 03:55 pm MT
  • ‘Adulting’ With CF – 02:30 pm – 03:55 pm MT
If you have any questions, please email communityvoice@cff.org.
Best,
The Community Voice Team

I’m Drowning – A researcher-patient’s plea for broader inclusion in cystic fibrosis trials

By: Ella Balasa

I’ve always known cystic fibrosis (CF) is a progressive disease; it destroys lung cells, tightens the small airways in the bottom of my chest, and each day takes me closer to the time when it will have ravaged my lungs. I had never really questioned if there was some way this process could be altered. I accepted that it couldn’t.

Recently, however, this has changed. The epicenter of new CF research is the development of medications that will slow, stop, and hopefully even reverse the effects and damage that CF inflicts on the body. The possibility of the cells in my lungs functioning to their full potential — with CF transmembrane conductance regulator protein function restored and working correctly, expelling chloride out of my cells, hydrating the surface of my lungs, and halting the thick sticky mucus that has caused my airways to be enveloped in a suffocating cloak for all these years — is like a feeling of being rescued when you are drowning.

Unfortunately, I am still drowning.

“I’m very sorry, Ms. Balasa, but you will not be able to be a participant in this clinical trial.” This was the response I received during one of my searches for these drug trials. Excited by the possibility of participating, finding one recruiting at my local adult clinic, I reached out to study coordinators and was informed that I met all but one criterion to participate in the studies. This specific criterion has prevented me from prior trial participation involving other investigational medications treating the symptoms of CF, including anti-infectives and anti-inflammatories.

Most CF studies, including phase I, II, and III trials, require a lung function minimum of at least 40% FEV1 (forced expiratory volume in one second). My FEV1 is 25%, so I am excluded from these trials. Many patients face a similar situation. The 40% threshold biases samples toward a young patient population, as this degenerative condition causes steadily decreasing lung function with time. Furthermore, as CF treatment has rapidly progressed and increased patients’ life expectancies, there are now more adults with CF in the U.S. than children, according to the CF Foundation Patient Registry.

As a patient who works in the science field, I started to ask myself: Where does that number come from? Should this one variable be such a deciding factor? Are we getting comprehensive results from these studies if a subset of patients is omitted? Are investigators using eligibility criteria from a prior study without determining whether the exclusions are scientifically justifiable?

To continue reading, please visit MedPage Today.

Triclosan, often maligned, may have a good side — treating cystic fibrosis infections

By Chris Waters

Maybe you’ve had the experience of wading in a stream and struggling to keep your balance on the slick rocks, or forgetting to brush your teeth in the morning and feeling a slimy coating in your mouth. These are examples of bacterial biofilms that are found anywhere a surface is exposed to bacteria in a moist environment.

Besides leading to falls in streams or creating unhealthy teeth, biofilms can cause large problems when they infect people. Biofilms, multicellular communities of bacteria that can grow on a surface encased in their own self-produced matrix of slime, can block immune cells from engulfing and killing the bacteria or prevent antibodies from binding to their surface.

On top of this, bacteria in a biofilm resist being killed by antibiotics due to the sticky nature of the matrix and activation of inherent resistant mechanisms, such as slow-growing cells or the ability to pump antibiotics out of the cell.

Biofilms are one of the primary growth modes of bacteria, but all antibiotics currently used clinically were developed against free-swimming planktonic bacteria. This is why they do not work well against biofilms.

My laboratory studies how and why bacteria make biofilms, and we develop new therapeutics to target them. Because antibiotic resistance is the most problematic aspect of biofilms during infections, we set out to identify novel molecules that could enhance antibiotic activity against these communities.

We discovered that an antimicrobial that has recently obtained a bad reputation for overuse in many household products could be the secret sauce to kill biofilms.

The hunt for antibiotic superchargers

To find such compounds, we developed an assay to grow plates of 384 tiny biofilms of the bacterium Pseudomonas aeruginosa. We did this to screen for molecules that enhance killing by the antibiotic tobramycin. We chose this bacterium and this antibiotic as our test subjects because they are commonly associated with cystic fibrosis lung infections and treatment.

People with cystic fibrosis (CF) are at particular risk from biofilm-based infections. These infections often become chronic in the lungs of cystic fibrosis patients and are often never cleared, even with aggressive antibiotic therapy.

After we screened 6,080 small molecules in the presence of tobramycin, we found multiple compounds that showed the antibiotic enhancement activity we were searching for. Of particular interest was the antimicrobial triclosan because it has been widely used in household products like toothpaste, soaps and hand sanitizers for decades, indicating that it had potential to be safely used in CF patients. Triclosan has also garnered a bad reputation due to its overuse, and states like Minnesota have banned it from these products. The Food and Drug Administration banned its use from hand soaps in September 2016. This ruling was not based on safety concerns, but rather because the companies that made these products did not demonstrate higher microbial killing when triclosan was added, compared to the base products alone.

Another fact that piqued our interest is that P. aeruginosa is resistant to triclosan. Indeed, treatment with either tobramycin or triclosan alone had very little activity against P. aeruginosa biofilms, but we found that the combination was 100 times more active, killing over 99 percent of the bacteria.

We further studied this combination and found that it worked against P. aeruginosa and other bacterial species that had been isolated from the lungs of CF patients. The combination also significantly enhanced the speed of killing so that at two hours of treatment, virtually all of the biofilm is eradicated.

Our efforts are now focused on pre-clinical development of the tobramycin-triclosan combination. For CF, we envision patients will inhale these antimicrobials as a combination therapy, but it could also be used for other applications such as diabetic non-healing wounds.

Although questions about the safety of triclosan have emerged in the mainstream media, there are actually dozens of studies, including in humans, concluding that it is well tolerated, summarized in this extensive EU report from 2009. My laboratory completely agrees that triclosan has been significantly overused, and it should be reserved to combat life-threatening infections.

The next steps for development are to initiate safety, efficacy and pharmacological studies. And thus far, our own studies indicate that triclosan is well tolerated when directly administered to the lungs. We hope that in the near future we will have enough data to initiate clinical trials with the FDA to test the activity of this combination in people afflicted with biofilm-based infections.

We think our approach of enhancing biofilm activity with the addition of novel compounds will increase the usefulness of currently used antibiotics. Learning about how these compounds work will also shed light on how bacterial biofilms resist antibiotic therapy.

Original article here.

Cystic Fibrosis Disease Severity Linked to Immune Overreaction to Fungus, Study Reports

By Ana Pena

Disease severity in cystic fibrosis (CF) may be associated with an overreaction of the immune system to the fungus Aspergillus fumigatus, particularly due to a type of white blood cell called a phagocyte — which ingests and kills invading organisms — a study suggests.

U.K. researchers found that phagocytes from CF patients release higher amounts of harmful reactive oxygen species in response to Aspergillus fumigatus, a common cause of lung infection in these patients.

The study, “Aspergillus-induced superoxide production by cystic fibrosis phagocytes is associated with disease severity,” was published in the journal ERC Open Research.

Recent studies have supported the idea that the widespread environmental fungus Aspergillus fumigatus may play a critical role in CF lung disease.

Up to 58% of CF patients are colonized with this fungus, and an estimated 47.7% of adult patients are affected by either allergic reactions or infection caused by the fungus.

Persistent infections with A. fumigatus are also known to be adversely correlated with lung function and hospitalization in CF patients.

Researchers hypothesized that the anti-fungal defense mechanism in CF patients might be altered and have an impact on the progression of lung disease.

To investigate this hypothesis, the team compared the immune response of phagocytes from CF patients with those of healthy individuals used as controls, and tried to correlate them to clinical metrics of disease severity.

For original article please visit CF News Today.

Toothpaste ingredient may bust up cystic fibrosis biofilms

By Chris Waters and Sarina Gleason

A common antibacterial substance in toothpaste may combat life-threatening diseases such as cystic fibrosis when combined with an with an FDA-approved drug, researchers report.

Researchers have found that when triclosan, a substance that reduces or prevents bacteria from growing, combines with an antibiotic called tobramycin, it kills the cells that protect the CF bacteria, known as Pseudomonas aeruginosa, by up to 99.9 percent.

CF is a common genetic disease with one in every 2,500 to 3,500 people diagnosed with it at an early age. It results in a thick mucus in the lungs, which becomes a magnet for bacteria.

These bacteria are notoriously difficult to kill because a slimy barrier known as a biofilm, which allows the disease to thrive even when treated with antibiotics, protects them.

“The problem that we’re really tackling is finding ways to kill these biofilms,” says Chris Waters, lead author of the study and a microbiology professor at Michigan State University.

According to Waters, there are many common biofilm-related infections that people get, including ear infections and swollen, painful gums caused by gingivitis. But more serious, potentially fatal diseases join the ranks of CF including endocarditis, or inflammation of the heart, as well as infections from artificial hip and pacemaker implants.

Waters and his coauthors grew 6,000 biofilms in petri dishes, added in tobramycin along with many different compounds, to see what worked better at killing the bacteria. Twenty-five potential compounds were effective, but one stood out.

“It’s well known that triclosan, when used by itself, isn’t effective at killing Pseudomonas aeruginosa,” says coauthor Alessandra Hunt, a postdoctoral associate of microbiology and molecular genetics. “But when I saw it listed as a possible compound to use with tobramycin, I was intrigued. We found triclosan was the one that worked every time.”

Triclosan has been used for more than 40 years in soaps, makeup, and other commercial products because of its antibacterial properties. Recently, the FDA ruled to limit its use in soaps and hand sanitizers due to insufficient data on its increased effectiveness and concern about overuse. Clear evidence has shown, though, that its use in toothpaste is safe and highly effective in fighting gingivitis, and it is still approved for use.

“Limiting its use is the right thing to do,” says coauthor Michael Maiden, a graduate student in medicine. “The key is to avoid creating resistance to a substance so when it’s found in numerous products, the chances of that happening increase.”

Tobramycin is currently the most widely used treatment for CF, but it typically doesn’t clear the lungs of infection, Waters says. Patients typically inhale the drug, yet still find themselves chronically infected their whole lives, eventually needing a lung transplant.

“Most transplants aren’t a viable option though for these patients and those who do have a transplant see a 50 percent failure rate within five years,” he says. “The other issue is that tobramycin can be toxic itself.” Known side effects from the drug include kidney toxicity and hearing loss.

“Our triclosan finding gives doctors another potential option and allows them to use significantly less of the tobramycin in treatment, potentially reducing its use by 100 times,” Hunt says.

Within the next year, Waters and his colleagues will begin testing the effectiveness of the combination therapy on mice with hopes of it heading to a human trial soon after since both drugs are already FDA approved.

Just brushing your teeth with toothpaste that has triclosan won’t help to treat lung infections though, Maiden says.

“We’re working to get this potential therapy approved so we can provide a new treatment option for CF patients, as well as treat other biofilm infections that are now untreatable. We think this can save lives,” he says.

The research appears in the journal Antimicrobial Agents and Chemotherapy.

The National Institutes of Health, Cystic Fibrosis Foundation, and Hunt for a Cure in Grand Rapids, Michigan funded the research.

Source: Michigan State University

Defining chronic Pseudomonas aeruginosa infection in cystic fibrosis

By Valerie Waters and Keith Grimwood

Cystic fibrosis (CF) is a genetic, multi-system disease due to mutations in the cystic fibrosis conductance regulator (CFTR) gene, leading to ineffective anion channel activity [1]. The resulting impaired mucociliary clearance permits initial acquisition of Pseudomonas aeruginosa and, if untreated, the establishment of persistent infection in the CF airways. It has long been recognized that chronic infection, often characterized by a mucoid P. aeruginosa phenotype, is associated with more rapid lung function decline and earlier death in individuals with CF [[2], [3], [4]]. Defining chronic P. aeruginosa infection is, therefore, an important step in identifying CF patients most at risk of lung disease progression. Traditionally, the Leed’s criteria has been used to define chronicity (as having >50% of sputum cultures being P. aeruginosa positive in the preceding 12 months), as it is the only clinically validated definition [5]. However, the Leed’s criteria are difficult to implement in young children unable to provide sputum and further limited by the required number of sputum samples and follow-up time [6].

In this issue of the Journal, studies by Heltshe et al. and Boutin et al. aim to re-define what chronic P. aeruginosa infection means in CF. In a retrospective cohort study using data from the US CF Foundation Patient Registry, Heltshe et al. followed close to 6000 early-diagnosed CF children for approximately 6 years [7]. Two-thirds acquired P. aeruginosa infection and of those, 6% had an initial mucoid phenotype. Furthermore, the majority (87%) of children who developed mucoid infection did so before meeting the definition of chronic infection (at least 3 yearly quarters P. aeruginosa positive in the preceding year). Initial P. aeruginosa infection with a mucoid phenotype has been previously described and is a recognized risk factor for failure of antimicrobial eradication therapy [[8], [9], [10]]. Whether this initial acquisition of a mucoid phenotype represents prior adaptation of P. aeruginosa in the CF host (either undetected or transmitted from a patient with chronic infection) or simply infection with an environmental strain particularly well-suited to the CF airways, is as of yet unknown [11]. It is clear, though, that mucoid P. aeruginosa does have an adaptive advantage in early CF infection as mucoidy was associated with an almost three-fold increased risk of transition to chronic infection in this current study. Despite the presence of this risk factor, however, only 13% of P. aeruginosa infected patients went on to develop chronic infection. Although Heltshe et al. did not provide details as to eradication strategies used in this cohort, this low incidence of persistent infection does speak to the overall effectiveness of current antimicrobial treatment for early P. aeruginosa infection.

Boutin et al. took their investigation a step further by using molecular methods, specifically quantitative polymerase chain reaction (qPCR), to define chronic P. aeruginosa infection [12]. In their study, patients with chronic infection had significantly higher levels of P. aeruginosa as measured by qPCR compared to those with intermittent infection. A single P. aeruginosa qPCR measurement in sputum had a sensitivity of 84% (with a specificity of 85%) in detecting chronic infection using a threshold of 103.4 colony forming units (CFU)/ml. A single sputum PCR measure had the advantage of not requiring 12 months of culture results as per the Leed’s criteria [5]. Furthermore, in their small study sample size, PCR was more discriminatory than mucoidy status in predicting chronicity, not surprisingly, given that alginate production (conferring mucoidy) is only one of several virulence factors contributing to the establishment of persistent P. aeruginosa infection in CF [13]. When used in throat swab samples, qPCR had a considerably lower sensitivity (82%) and specificity (56%) in detecting chronic infection, likely due in part to the lower bacterial burden observed in this specimen, compared to sputum. The low specificity of PCR in this setting (positive PCR, negative culture) may reflect the fact that a molecular signal may precede culture positivity. Early detection of P. aeruginosa infection, before culture conversion, in CF patients was originally suggested decades ago using serologic and, more recently, molecular methods [[14], [15], [16]]. Serology, however, has proven disappointing at identifying early P. aeruginosa infection [17]. Nevertheless, early detection may still be possible using highly-sensitive PCR techniques for identifying lower airway P. aeruginosa infection in a young, non-expectorating child. In the study by Boutin et al., P. aeruginosa detection in throat swabs by PCR alone was linked to a positive culture in sputum in three-quarters of cases. Previous studies comparing oropharyngeal cultures to bronchoalveolar lavage (BAL) cultures in children with CF demonstrated that oropharyngeal cultures had a positive predictive value of only 44%, but a negative predictive value of 95% in diagnosing lower airway P. aeruginosa infection [18]. Performing P. aeruginosa qPCR on culture negative throat swabs may further improve the diagnosis of lower airway infection in young children with CF who are unable to produce sputum, but this approach will still need to be validated by comparative studies employing BAL fluid samples. Unfortunately, using confirmatory induced sputum samples as suggested by Boutin et al., may produce unreliable results as these specimens are poor predictors of lower airway pathogens cultured from BAL specimens in young children with CF [19]. Finally, it is yet to be determined whether an earlier diagnosis of P. aeruginosa infection leads to improved eradication success rates and superior clinical outcomes.

In summary, the recent studies by Heltshe et al. and Boutin et al. further our understanding of how chronic P. aeruginosa infection develops in CF and how to better recognize it [7,12]. Ultimately, prevention of chronic P. aeruginosa infection and its deleterious effects on lung function and survival is the goal.

Original article in Journal of Cystic Fibrosis here.

I’m on the transplant list, now what?

In Jerry Cahill’s latest edition of The Path Forward with Cystic Fibrosis, Dr. Selim Arcasoy from Columbia University Medical Center discusses what happens once a patient is on the transplant list.
The first three major steps are:
  1. Create a strict exercise program with the hospital rehab center and integrate it into the patient’s schedule.
  2. Meet with a nutritionist in order to maintain proper weight.
  3. Educate! Meet with the care team in order to understand the entire process – both pre and post transplant.
The transplant process is a long one – and thoroughly detailed – in order to increase the chances of success. Tune in to learn more from Dr. Arcasoy.

This video podcast was made possible through an unrestricted educational grant from Columbia University Medial Center and the Lung Transplant Project.

Ground-Breaking Procedure. A major step for science, medicine, the human condition

by Mary Bulman; Independent UK

“Woman spends record six days without lungs thanks to ground-breaking procedure”

Yes you’ve read that correctly.
Yes, it reads six days.

A true miracle! Definitely an understatement.

Though it’s been over a year since this procedure was carried out, it’s one that I believe cannot be shared enough. A huge step for medicine and science- but perhaps a larger one for the human condition and the willingness to live and fight.

“I still don’t believe it happened. It seems very surreal.” says patient Melissa Benoit.
And that’s because it is, Ms. Benoit.

After coming down with the flu the last year 2016, Ms. Benoit was taken from her home in Burlington, Canada to the ICU in a nearby hospital located right outside of Toronto, Canada.  Doctor’s made the spilt decision to go through with a first time procedure in order to save her life. After becoming resistant to most antibiotics, bacteria began to move throughout her body, eventually causing her to lapse into septic shock. One by one her organs started shutting down, due to the decline of her blood pressure.

“Although it had never been carried out before, doctors decided to remove her lungs entirely.”

“What helped us is the fact that we knew it was a matter of hours before she would die,” said Dr Shaf Keshavjee, one of three surgeons who operated on her. “That gave us the courage to say — if we’re ever going to save this woman, we’re going to do it now.”

To learn more about Ms. Benoit and the new breed of surgery that was carried out please continue onto the article below:
https://www.independent.co.uk/news/world/americas/woman-six-days-without-lungs-waiting-list-donor-organ-burlington-ontario-melissa-benoit-world-first-a7547936.html