For Cystic Fibrosis Lung Infections, How Well Antibiotics Work May be Affected by pH, Oxygen

By Heather Buschman, PhD

People living with cystic fibrosis (CF) spend their entire lives battling chronic lung infections that are notoriously resistant to antibiotic therapy. Yet a one-size-fits all approach to wiping out the offending bacterium may not be the best approach for all patients with the disease, according to a new study by researchers at University of California San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences. Continue reading For Cystic Fibrosis Lung Infections, How Well Antibiotics Work May be Affected by pH, Oxygen

Be Involved in a Meeting with FDA on CF!

On October 29th, individuals with cystic fibrosis and their families will have a unique and pivotal opportunity to share their experiences with representatives of the FDA during a live-streamed interactive meeting.

CFRI is very honored to host an Externally-Led Patient-Focused Drug Development Meeting on Cystic Fibrosis with the FDA on Monday, October 29th. This is an amazing and singular opportunity to share the patient experience with FDA representatives. They want and need to know the impacts and burden of the disease, your hopes for new therapies, and what you are willing to go through to find these new drugs.

PLEASE register to participate in this free live-streamed meeting! We need your input and participation You will have the opportunity to participate in live polling, and to email and call in to share your experiences. Those who do not have CF/a family member with CF should also feel free to join us.

You can register and log in for any or all of the day’s presentations and discussions. The day begins at 9:45 am. Please note: all times listed are East Coast time, as the meeting will be held at the College Park Marriott Hotel and Conference Center in Hyattsville, Maryland.

Here is the link:  http://cfri.org/advocacy/advocacy-events/

Speakers/Panelists
Jen Caruso
Lise-Courtney D’Amico
Boomer Esiason
Gunnar Esiason
Joseph Klausing, JD
Emily Kramer-Golinkoff
Robert Lim, MD
Jane Mitchell
Anna Payne
Kat Quinn Porco, MS
Tejashri Purohit-Sheth, MD
Arek Puzia, CPA, MBA
Emily Schaller
Isa Stenzel Byrnes, LCSW, MPH
Ahmet Uluer, DO, MPH
James Valentine, JD, MHS

Thank you for having an impact upon those who are assessing the safety and efficacy of new CF therapies, and making recommendations for their movement to market. 

Your voices matter!

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.

Sound Pharmaceuticals to present initial data on the STOP Ototoxicity Study at Cystic Fibrosis Conference

SEATTLESept. 25, 2018 /PRNewswire/ — Sound Pharmaceuticals (SPI) is pleased to announce that its recent submission to the upcoming North American Cystic Fibrosis Conference (NACFC) Oct. 18-20 has been selected as a late-breaking abstract. This presentation will focus on the incidence and severity of ototoxicity in CF patients undergoing intravenous (IV) tobramycin treatment for acute pulmonary exacerbation. Ototoxicity (hearing loss, tinnitus, vertigo or dizziness) is a common side effect of tobramycin and other aminoglycoside antibiotics (amikacin, gentamycin and streptomycin). Currently, there are no FDA approved therapies for the prevention or treatment of ototoxicity or any other type of sensorineural hearing loss, tinnitus, or dizziness. Continue reading Sound Pharmaceuticals to present initial data on the STOP Ototoxicity Study at Cystic Fibrosis Conference

Telavancin Promising Potential Treatment Option for MRSA in Cystic Fibrosis Patients

By Kristi Rosa

Responsible for several issues ranging from skin infections and sepsis to pneumonia and bloodstream infections, methicillin-resistant Staphylococcus aureus continues to plague patients in the health care and community setting, as well as the providers who treat them.

When acquired in patients with cystic fibrosis, clinical outcomes are known to be even worse, affecting several organs—primarily the lungs—and resulting in an increased rate of declined respiratory function as well as infections that can have severe, and sometimes deadly, consequences.

Now, however, for the first time, investigators have found that telavancin—a drug that is currently used to treat skin infections and hospital-acquired pneumonia—has potent in vitro activity and low resistance development potential when used against S aureus isolates in patients with cystic fibrosis, making it a promising potential treatment option for this population.

“Telavancin (TLV) is a lipoglycopeptide antibiotic approved by the US Food and Drug Administration in 2009 for the treatment of complicated skin and skin structure infections and in 2013 for the treatment of cases of nosocomial pneumonia, however its application for the treatment of CF-MRSA pneumonia infections was not known, so our studies are contributing to extending the application of TLV for CF treatment,” Adriana E. Rosato, PhD, associate professor in the department of Pathology and Genomic Medicine at Houston Methodist Research Institute told Contagion®. “We were also inspired by the fact that CF patients have a short life time—until 40 to 50 [years]—so our priority is to contribute to better treatment in this patient population.”

Dr. Rosato and her team hypothesized that TLV might be a promising treatment option for CF-patient-derived MRSA and MSSA infections, as in vitro studies have shown that TLV has activity against MRSA.

To prove this, the investigators screened a total of 333 strains of CF patient-derived S aureus of the wild-type or small-colony-variant phenotype, collected from both adults and children at 3 different cystic fibrosis centers: Houston Methodist Research Institute, UW Health and the Center for Global Infectious Disease Research. TLV was found to display activity against all 333 strains collected.

When testing the activity of the drug against 23 MRSA strains, the investigators observed intermediate resistance to ceftaroline (CPT)—a new beta-lactam antibiotic that targets PBP 2a in MRSA—in 20 of the strains, and high-level resistance to CPT in 3 of the strains. The authors note that although high levels of resistance to CPT is rare, intermediate resistance is more common in patients who have chronic infections.

“Among all strains, the TLV MIC90 was 0.06 mg/liter, i.e. 8-fold lower than the daptomycin (DAP) and CPT MIC90 and 25-fold lower than the linezolid (LZD) and vancomycin (VAN) MIC90,” the authors write.

Using time-kill experiments, the investigators assessed the in vitro effectiveness of TLV compared with DAP, VAN, and CPT. They found that TLV showed activity against all tested strains and displayed rapid bactericidal activity as well. The activity profile for the drug at a free serum concentration of 8 mg/liter showed that TLV performed better than VAN (16 mg/liter), LZD (10.4 mg/liter), and CPT (16 mg/liter).

The investigators also set out to determine the fate of mutation selection that could be projected by the potential prolonged use of TLV in patients with cystic fibrosis. To do this they looked at 3 specific strains: AMT 0114-48, WIS 664, and TMH 5007. They found that due to the ease of mutation selection which had been noted in control strains, TLV mutant resistance is independent of the CF patient background of the strains.

“We demonstrated that TLV has bactericidal activity against the S aureus strains tested, including those against which CPT and LZD displayed reduced activity, which might provide TLV a significant advantage over the drugs currently used to eradicate those strains and prevent future exacerbations,” the study authors write.

A clinical trial is currently underway to assess the pharmacokinetic profile of TLV in patients with cystic fibrosis, who usually need dose adjustment because of an increase in the volume of distribution and clearance.

“[The next step for our research is] to perform in-vivo analyses studies that could lead to translational application/clinical trial,” Dr. Rosato added. “However, we are limited in research funds to continue our investigations.”

Original article here.

Monitoring Pulmonary Exacerbation in Cystic Fibrosis: The Hunt for Urine-based Biomarkers Begins

By Michele Wilson PhD

The buildup of mucus in the lungs is an ongoing challenge faced by people with cystic fibrosis, and knowing whether they should seek medical attention is not always clear.

Recently, Mologic – a developer of personalized diagnostics – have developed a tool which they hope will help guide people with cystic fibrosis so they can avoid unnecessary stays in hospital.

The app-embedded algorithm converts data collected from a urinary test to a traffic light result, which indicates whether a patient is stable or in need of medical intervention.

Recently, Mologic, announced that they are launching a clinical trial to assess the company’s urine-based diagnostic tool, ‘HeadsUp’.

To learn more about how this point-of-care diagnostic tool could help improve healthcare for people with cystic fibrosis, we spoke with Gita Parekh, Head of R&D at Mologic.

How do you define pulmonary exacerbation, and why is it important that it is monitored in people with cystic fibrosis? Continue reading Monitoring Pulmonary Exacerbation in Cystic Fibrosis: The Hunt for Urine-based Biomarkers Begins

The open door policy – An important and under-recognized activity of the adult CF center

By Anna Sze Tai and Sue Morey

Improvement in survival in cystic fibrosis (CF) has led to a substantial increase in numbers of the adults with CF past few decades [12]. In many parts of the world, the number of adults now exceeds the numbers of children with CF [12]. Adults with CF face the daily challenge in balancing education, work and family commitments with their disease management. Patients often need to contact the Adult CF specialist team for advice on disease management and coordination of care around their work and family time-table. Current ECFS guideline recommends patients have ready access to the CF center for telephone advice for emergency management or consultation [34]. The ‘open-door’ policy of adult CF centers is an important component of ambulatory care in adults with CF, ensuring a timely and expert-level response to patient queries. Management of unscheduled patient-initiated contacts is an important and often under-recognized function of the adult CF team. There is a paucity of data on the nature and frequency of these unscheduled contacts and their potential impact (and demands) on the organization of the CF team.

In this issue of the Journal of Cystic Fibrosis, Burnet et al. reported the results of a two-staged prospective study of unplanned patient-initiated contacts in a single adult CF center (n = 410 patients) [5]. During the first stage, all patient-initiated contacts were prospectively recorded over a four-month period. Four physicians and three nurses prospectively documented how and why patients contacted the team and the time spent responding to these requests. During the second stage, contacts generated from a subset of 212 patients were prospectively recorded to explore the association between contact frequency and disease severity.

During the first stage, 259/410 (65%) patients initiated 1067 contacts over 4 months, averaging 13.3 contacts per day. Average time spent addressing patient contacts by all participants combined was 8 h and 7 min per work week. This was likely an underestimate given not all team members (e.g. allied health specialists) who might be contacted by patients participated, and data collection was limited to working hours during weekdays. Nevertheless, the result confirmed that managing unscheduled contacts added a significant workload to the CF team. Factors associated with greater contacts (≥5 contacts/year) included female sex and greater disease severity, reflected in severe airflow obstruction (FEV1 ≤ 30% predicted), ≥ 5 physician visits/year and ≥ 1 hospital admission/year.

The frequency of unscheduled contact in adults with CF was markedly higher than that observed amongst high-risk COPD patients, reflecting the greater healthcare demand of adults with CF [6]. Interestingly, only <20% of requests were related to medical issues (e.g. exacerbations), whereas the bulk of requests were related to daily management issues (e.g. script renewal), intravenous antibiotic requests, administrative queries and non-urgent miscellaneous matters. This perhaps reflects that the adult CF center has generally provided comprehensive, primary up to expert-level tertiary care to their adults with CF. The adult CF center can be viewed by the patient as ‘the one-stop shop’ for both their CF and non-CF related healthcare needs. Patients may not be aware of the need for a family physician for their non-CF related healthcare needs, including travel vaccinations, women health issues, age-specific screening (e.g. mammograms, monitoring for hypertension).

This is the first study which demonstrates the significant burden of unplanned contacts on the organization of the adult CF centre. The strength of the study is the prospective design which enables differentiation between planned and unplanned contacts. There was a comprehensive recording of response time in the clear majority of patient contacts (>95%) by the team members as they carry out their day-to-day services within a large CF centre which is an impressive undertaking. The key limitation is the single centre nature of the study which limits its comparability to other centres in other health settings internationally. Nevertheless, Burnet et al. has clearly revealed the burden of unscheduled contacts and highlighted the need for more efficient management strategies. Firstly, development of an effective centralised triaging system (e.g. collective ‘CF Team’ email inbox and phone line) managed by experienced CF staff who prioritise and streamline all incoming requests to appropriate team members can maximize efficiency of the CF team. Secondly, involvement of administrative staff to assist with relevant non-medical requests (e.g. clinic rescheduling, etc) will lighten the burden on the clinical team. Thirdly, ultilisation of new telecommunication and health informatics technologies can potentially improve communication and data transparency. Telehealth technologies (e.g. Smartphone apps, Skype or WhatsApp) have already shown significant promise in improving patient access to care and early treatment in CF, particularly in setting where distance from centre to the patients is considerable and pop-in clinics are likely to be impractical [[7][8][9]]. Some of these telehealth technologies can potentially serve as communication platforms to provide education resources on commonly-asked questions.

To continue reading please visit: https://www.sciencedirect.com/science/article/pii/S1569199318306982

Airway Clearance Vests Fail to Show Measurable Short-term Lung Benefits in Study

A note from CF Roundtable: Please do not stop using your Vest or other HFCWO device because of this impractical study. There are important differences in this study that make it not applicable to CF and therefore, not meaningful for us. First, healthy volunteers without CF were enrolled. Too many adults with CF have experienced significant benefits with these HFCWO devices, not to mention the preventive benefits. To imply these devices worsen lung function when used by a healthy nonCF person vs one with CF – with the usual accompanying inflammation, mucus +/- bronchiectasis, etc – is not practical. Second, these healthy subjects tested all 4 HFCWO devices in one day. Even when I repeat spirometry in one day, my lung function numbers most often decline over time, even with rest periods in between. The researchers tested lung function with a rest period of 15 minutes on these healthy individuals after use of the HFCWO device then moved on to the next device. Very impractical and again – not applicable to use by individuals with CF.

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By Iqra Mumal

A clinical study into high-frequency chest wall oscillation vests — assessing their short-term impact on standard measures of lung function before and during use — challenges the view that these devices work through airflow bias in the lungs, the process responsible for mucus movement when breathing.

Findings, using established tests that include forced vital capacity (FVC), forced expiratory volume (FEV1), and forced expiratory flow (FEF25%-75%), suggest “that the concept of HFCWO vest-induced cephalad airflow bias is not supported by standard spirometry measurements,” researchers concluded. “None of the vest groups showed statistically significant increased airflow in the lungs.” Continue reading Airway Clearance Vests Fail to Show Measurable Short-term Lung Benefits in Study

Mutations in Genes Regulating Digestion Prevalent in CF Patients with Pancreatitis

By Vijaya Iyer

In addition to mutations in the CFTR gene, cystic fibrosis (CF) patients with pancreatitis also have a high prevalence of mutations in genes regulating pancreatic function, according to researchers.

Conducted by a research team in Italy, the study, “Trans-heterozygosity for mutations enhances the risk of recurrent/chronic pancreatitis in patients with Cystic Fibrosis,” was published in the journal Molecular Medicine Continue reading Mutations in Genes Regulating Digestion Prevalent in CF Patients with Pancreatitis