Info from the Internet

Compiled By Laura Tillman

This issue brings a potpourri of articles from the Internet


Cystic Fibrosis Treatment Options Detailed in Updated 2018 GeneFo Guide

GeneFo has put together an updated 2018 guide on treatment options for people with cystic fibrosis (CF) after recent developments again focused attention on the high price tag of some of these medications and the difficulties patients face in accessing them. The guide includes information on financial and clinical resources to help patients afford CF medications, such as assistance funds, clinical programs and free insurance counseling/tax reduction programs, as well as access programs that provide free treatments in return for patient feedback. GeneFo created the guide to keep patients and caregivers updated on the various opportunities available for help with funding CF medication, treatments and gear.

Cystic Fibrosis-Related Pathogen Risk With Chronic Azithromycin Use

Compared with azithromycin nonusers, azithromycin users had a significantly lower risk for detection of new nontuberculous mycobacteria. In addition, there was a trend noted toward higher risks for new multidrug-resistant Pseudomonas aeruginosa (MDR-Pa) in azithromycin users compared with nonusers. The investigators found no differences between azithromycin users and nonusers for risk for acquisition of the other study pathogens: Pseudomonas aeruginosa (Pa), Stenotrophomonas maltophilia, Aspergillus species and Achromobacter xylosoxidans. Azith-romycin users also had significantly higher rates of exacerbations compared with nonusers in the Aspergillus matched cohorts. The authors found that azithromycin users had lower risks for new acquisition of three key CF pathogens (nontuberculous mycobacteria, methicillin-resistant Staphylococcus aureus and Burkholderia cepacia complex), a trend toward higher rates of acquisition for one pathogen (MDR-Pa), and no difference for four other pathogens. The authors also noted that patients who regularly received azithromycin were sicker on average compared with nonusers.

Gene Panel Predicts Course Of Cystic Fibrosis

Researchers at National Jewish Health have identified 10 immune-related genes whose activity during a respiratory infection predict the long-term prognosis for cystic fibrosis patients better than conventional measures. Five years after being evaluated, patients in the lowest-risk group were all alive and doing well, whereas 90 percent of patients in the highest risk cluster had been admitted to an intensive care unit, put on mechanical ventilation, referred for lung transplant, had a transplant or died. By looking at the underlying biology of the immune response, this panel allows subsets of CF patients to be identified who are likely to do better or worse in the long term. This information can help guide treatment plans in order to deliver the best outcomes for patients. FEV1 and exacerbation history tell about a patient’s disease history and existing lung damage. The gene panel tells more about a patient’s biological response to infection, which provides valuable information about the future course of the disease.

CF Severity Linked To Variations In Patients’ Airway Bacteria Mix

Researchers have linked variations in the mix of microorganisms in cystic fibrosis patients’ airways to their disease outcomes. CF patients typically have particular strains of bacterial and fungus in their airways. The usual bacteria suspects include Pseudomonas, Achromobacter, Burkholderia, Haemo-philus, Staphylococcus and Steno-trophomonas. Other bacteria and fungi also inhabit CF patients’ airways, including anaerobic species that do not need oxygen to grow and spread. Not only do the microbial communities in CF patients’ airways vary by type of microorganism, but also in the relative abundance of each species. Researchers decided to see if the prevalence and relative abundance of typical CF pathogens and anaerobic microorganisms play a role in the severity of patients’ disease and their lung function. The team classified the stage of patients’ disease on the basis of their lung function scores. Researchers classified disease aggressiveness — mild, moderate or severe — on the basis of change in FEV1 relative to age. They discovered a link between variations in the prevalence of the six typical CF pathogens, plus nine anaerobic species and changes in a patient’s disease stage and lung function. One finding was an increase in the relative abundance of anaerobic microorganisms when patients were experiencing pulmonary exacerbations before antibiotic treatment and a decrease during treatment and patients’ post-treatment recovery phase.

Lung Function In Cystic Fibrosis Improved Via Autogenic Drainage, Study Says

Autogenic drainage physiotherapy can effectively improve the underlying lung mechanical impairment of cystic fibrosis (CF), a study shows. Autogenic drainage is a commonly used, self-administered airway clearance technique based on repetitive exercises of controlled inhalation and exhalation to move mucus buildup from the small to the large airways. In the study, researchers evaluated the respiratory changes induced by a single session of autogenic drainage. Participants’ lung function was evaluated before and after the treatment session based on the respiratory system resistance and reactance measured using the forced oscillations technique (FOT). This technique consists of applying repetitive oscillatory forced signals to the subject’s airways during normal respiration opening and measuring the pressure, flow and volume of the lungs. Results showed that all participants had moderate-to-severe obstructive respiratory disorder, characterized by reduced forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) ratio — all specific measures of lung function. They also all experienced increased bronchial resistance and decreased reactance. After the physiotherapy session, patients who performed autogenic drainage showed small but significant improvements in FEV1 and FVC measures compared with CF patients who did not. Similar positive effects were also reported in inspiratory resistance and reactance.

Drug For Cystic Fibrosis Patients Associated With Higher Hospitalization

Long-term use of a class of drugs that suppress stomach acid is associated with an increased risk of hospitalization for cystic fibrosis patients. The study looked at a class of acid-suppressive drugs called proton pump inhibitors, which are used to treat reflux, heartburn, ulcers and other conditions. The study found patients using PPIs long term were more often hospitalized for complications of the disease than patients not on the drugs. This research underlines the need for physicians to more closely evaluate whether a cystic fibrosis patient can benefit from the acid-suppressant drugs or if other alternatives might be available.

Oral Antibiotics Associated With Increased Risk For Kidney Stones

Use of five classes of antibiotics is associated with increased risk for kidney stone disease (nephrolithiasis). After multivariable adjustment, use of sulfas, fluoroquinolones, cephalosporins, nitrofurantoin/methenamine and broad-spectrum penicillins was associated with higher risk for nephrolithiasis, compared with nonuse. The authors speculate that antibiotic-induced alteration of the gut microbiome could change macronutrient metabolism, thus leading to kidney stones.

CF Patients, Especially Post-transplant, At High Risk Of Gastrointestinal Cancers, Study Finds

Patients with cystic fibrosis (CF) are at higher-than-average risk of developing gastrointestinal cancers, especially those who underwent a lung transplant. Transplant patients with CF were found in this retrospective study to have a five-times greater risk of gastrointestinal cancer than those who have not had a transplant, emphasizing a need for careful screening for small intestine and colon cancers particularly, but also for biliary tract and pancreatic cancers. Compared to the public-at-large, all CF patients had a 20 times higher risk of cancer of the small intestine, and 10 times higher for colon cancer.

Toothpaste Ingredient May Bust Up Cystic Fibrosis Biofilms

A common antibacterial substance in toothpaste may combat life-threatening diseases such as cystic fibrosis when combined with an FDA-approved drug. 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 Pseudomonas aeruginosa by up to 99.9 percent.


Common Toothpaste Ingredient May Promote Colon Cancer

Researchers claim that there is an “urgent need” to test triclosan. After preliminary studies, scientists conclude that it might cause colonic inflammation and promote colon cancer. Although generally considered safe, the chemical has become worryingly universal. Because of its potential role in antimicrobial resistance and endocrine disruption, and its theoretical effects on the immune system, it has been deemed a ‘‘minant of emerging concern’’ by the United States Geological Survey. A study tested whether triclosan might have any negative effects on gut health. In order to investigate, they tested the impact of small doses of triclosan on a range of mouse models. The scientists gave each mouse model a brief, low-level exposure to triclosan. In all mouse models used, triclosan prompted inflammation of the colon, worsened symptoms of colitis (inflammation of the lining of the colon) and promoted colitis-associated tumor growth. Next, the scientists wanted to understand exactly why triclosan seemed to have this pro-tumor, pro-inflammation effect. They found that triclosan altered the composition of the gut microbiome significantly.

Antioxidant-enriched Vitamin Reduces Respiratory Illnesses In Patients With Cystic Fibrosis

The study looked at the effects of a “cocktail” of multiple antioxidants on inflammation and health outcomes in patients with CF. CF patients ordinarily do not adequately absorb important dietary antioxidants including carotenoids such as beta-carotene, tocopherols (vitamin E), coenzyme Q10 (CoQ10) and selenium that help to neutralize inflammation in the body. To address this issue, the antioxidants used in the study were delivered in a capsule specifically designed for individuals with difficulties absorbing fats and proteins. 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. Antioxidant treatment appeared to both prolong the time to the first respiratory illness requiring antibiotics and reduce the frequency of respiratory illnesses. Half as many of the patients taking the supplemental antioxidants experienced a pulmonary exacerbation (or respiratory illness) requiring antibiotics compared to the group taking the control multivitamin without added antioxidants at 16 weeks. In addition, the antioxidant treated group experienced a lower frequency of respiratory illnesses compared to the control group.


Cystic Fibrosis Severity Linked To Immune Overreaction To Fungus, Study Reports

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. Researchers found that phagocytes from CF patients release higher amounts of harmful reactive oxygen species in response to Aspergillus fumigatus. 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. The data suggest that a hyperresponsive state in CF phagocytes plays a crucial role in the hyperinflammatory response upon exposure to A. fumigatus.

Natural Sniper Kills Hospital Bacterium

Bacteria produce proteins to take out specific competitors. One of these proteins can kill the hospital bacterium Pseudomonas aeruginosa. Microbial geneticists have unraveled how this protein launches its attack and ensures that the bacteria die very quickly. In the long term, these proteins hold potential for new antibiotic cocktails. One type of these proteins — LIpA bacteriocins — is highly effective in eliminating the hospital bacterium Pseudomonas aeruginosa. The LIpA protein has a specific target in the outer wall of the bacterial cells. That target is a protein as well: the BamA protein, which is involved in maintaining the bacterial cell wall. Without the BamA protein, bacteria cannot survive. LlpA binds to that BamA protein and, by doing so, shuts it down. Unlike standard antibiotics, LIpA proteins don’t even need to get inside the bacteria; they recognize their target and then sabotage it from the outside.

Guidelines Needed For Listing CF Patients With Nontuberculous Mycobacteria Infections For Lung Transplants, Survey Finds

Clinical centers around the world differ in the standards they use when considering cystic fibrosis (CF) patients with nontuberculous mycobacteria (NTM) infections for lung transplants, and few have a clear written policy. Researchers found that most centers surveyed do not consider NTM infections in cystic fibrosis as an absolute contraindication for transplants. However, NTM infection in cystic fibrosis patients has been regarded by some clinicians as an absolute contraindication for lung transplant due to poor post-transplant outcomes. In particular, the presence of M. abscessus complex before a transplant has been linked with severe complications and poor outcomes after the procedure. But some single-center case series have indicated that patients with an NTM infection who undergo a lung transplant have similar outcomes to those without an NTM infection. Because different approaches can be taken, researchers in this study investigated current worldwide practices concerning the listing of cystic fibrosis patients with NTM for lung transplants. Results showed that only 29% of centers have a clear written policy regarding NTM. In addition, 16 centers, or 76%, require molecular identification of specific NTM species. Only four centers considered infection with M. abscessus complex a contraindication for listing, but 76% regard it as a relative contraindication, which means additional caution should be used if other conditions or contraindications are present. Results also revealed that 86% of centers require treatment before the transplant. Only 61% of the clinical centers surveyed reported having policies in place regarding the segregation of patients depending on NTM status before a transplant, and just 48% reported having such a policy for patients after the procedure. In order to better inform decision-making, the team emphasized that there is an urgent need for further high-quality clinical research to comprehensively investigate the outcomes and international experience of patients with NTM after lung transplantation.

CF Therapy Maker JHL Plans Phase 1 Trial Of Its Biosimilar To Pulmozyme

JHL Biotech plans to start a Phase 1 clinical trial of its cystic fibrosis (CF) therapy JHL1922, a biosimilar to Pulmozyme (dornase alfa) that is designed to improve lung function. Pulmozyme (marketed by Genentech) was one of the first approved treatments for CF shown to prevent mucus accumulation. It is an engineered enzyme, called recombinant human deoxyribonuclease I or rhDNase I, which selectively breaks down DNA molecules in mucus. This helps thin the thick secretions. The result is better airway flow, improved ability to expel mucus and better ability to prevent bacterial infections. JHL Biotech expects JHL1922 to be a less expensive but equally effective alternative to Pulmozyme. JHL1922 was designed to achieve biochemical and safety profiles, as well as therapeutic activity, similar to those reported for Pulmozyme. Experts estimate that the average cystic fibrosis patient has to spend between $12,000 and $40,000 a year just on Pulmozyme. This underscores patients’ need for more affordable therapies.

CF Therapy RPL554 Improves Lung Function, Phase 2a Trial Shows

Verona Pharma’s nebulized RPL554 can significantly improve lung function in patients with cystic fibrosis, according to data from a Phase 2a clinical trial. The latest results revealed that single administration of both high and low doses of the investigative drug significantly increased patients’ average forced expiratory volume in one second (FEV1). This significant positive effect was sustained for at least eight hours. In addition, RPL554 displayed favorable stability and distribution profiles, and was well tolerated by the patients. RPL554 is an inhaled dual inhibitor of two enzymes, phosphodiesterase 3 and 4, which Verona designed to act as an anti-inflammatory as well as bronchodilator.

Proteostasis Stock Soars On Cystic Fibrosis Breakthrough Status

Regulators handed out breakthrough status to the company’s cystic fibrosis therapy. The drug, called PTI-428, is meant to boost levels of the CFTR protein, which is lacking in cystic fibrosis patients. The therapy is an add-on treatment for patients with the F508del mutation in the CFTR gene who are already taking an approved CFTR modulator or as part of Proteostasis’s triple combo regimen that includes PTI-808, a potentiator, and PTI-801, a corrector. PTI-428 can potentially be added to current and future standards of care.


Potential CFTR Corrector PTI-801, Plus Orkambi, Seen To Treat CF Patients In Phase 1 Trial

Treatment for 14 days with Proteostasis Therapeutics’ PTI-801 in cystic fibrosis (CF) patients also being treated with Orkambi (lumacaftor/ivacaftor) led to statistically significant improvements in sweat chloride, body mass index and rescued blood glucose levels in a subgroup of patients with diabetes, Phase 1 trial data show. PTI-801 is a third-generation CFTR corrector. The trial’s primary objectives are to assess the therapy’s safety, tolerability and pharmacokinetics. Parameters like sweat chloride and body mass index (BMI) and changes in percent predicted FEV1 (ppFEV1, a measure of lung function) will also be analyzed. Patients with CF-related diabetes (CFRD) were also analyzed for changes in blood glucose levels. Results in the patients showed that PTI-801 was generally well-tolerated, with only mild or moderate adverse effects. The most common was pulmonary exacerbations. Patients randomized to the therapy’s highest dose, 400 mg, showed significant improvements in both sweat chloride and BMI. At a dose of 200 mg, improvements were found to be significant only for the sweat chloride. Participants treated with PTI-801 also showed improvements in ppFEV1 across all treatment doses, although the difference didn’t reach statistical significance. In hyperglycemic CFRD patients, all three doses of PTI-801 were effective in normalizing the glucose levels.


Laurent Pharmaceuticals Reaches Agreement With U.S. Cystic Fibrosis Foundation To Increase Development Award To $5M

Laurent Pharmaceuticals, Inc., announced that it has reached an agreement to receive an additional $2 million commitment from US-based Cystic Fibrosis Foundation to further support the upcoming Phase 2 clinical study aimed at demonstrating the safety and efficacy of the company’s lead compound LAU-7b in adult patients with cystic fibrosis (CF). LAU-7b is a once-a-day oral pro-resolving therapy with potential to treat chronic pulmonary inflammation that leads to irreversible lung damage in patients with CF, regardless of their CFTR genotype. As opposed to typical anti-inflammatory drugs that inhibit the activation of the inflammatory response, LAU-7b uses the body’s own ability to timely terminate inflammation without interfering with the natural defense mechanisms. LAU-7b was tested in adults with CF in a dose-ascending Phase 1b study, showing good safety and pharmacokinetic profiles, coupled with promising positive effects on specific markers of inflammation. The goal of the upcoming Phase 2 trial is to evaluate LAU-7b’s effect on the preservation of lung function in patients with CF by reducing persistent, unresolved inflammation in the lung and stimulating its return to homeostasis.

UC Researcher Granted Patent For Potential Pulmonary Infection Treatment

A researcher in the University of Cincinnati (UC) College of Medicine has been granted a U.S. patent for a potential treatment for a pulmonary infection in patients with cystic fibrosis (CF). The treatment, known as AB569, is a potential treatment for many antibiotic-resistant organisms, including Pseudomonas aeruginosa (P. aeruginosa). Earlier work on CF found that P. aeruginosa was susceptible to destruction by slightly acidified sodium nitrite. The researcher also discovered a synergistic effect by adding disodium ethylenediaminetetraacetic acid to acidified sodium nitrite, which led to the development of AB569. AB569 is to be administered to patients as a nebulized (inhaled) solution or powder.




USFDA Approves Proteostasis’s Triple Combination Program For CF

Proteostasis Therapeutics’ proprietary triple combination includes a novel cystic fibrosis transmembrane conductance regulator (CFTR) amplifier, third generation corrector and potentiator, known as PTI-428, PTI-801 and PTI-808, respectively. The FDA’s Fast Track program is designed to facilitate the development and expedite the review of new drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs.

Improved Treatment Targeting Root Cause Of Cystic Fibrosis May Be On Horizon

A clinical trial led by a pharmaceutical company has shown that a combination of two medications provides significant clinical benefit in a subgroup of patients with cystic fibrosis (CF). Using knowledge of the different CFTR mutations, scientists have developed candidate medicines that may help restore sufficient CFTR function to partially alleviate CF symptoms. The current study tested a combination of ivacaftor and a promising new (not yet FDA-approved) CFTR-stabilizing drug, tezacaftor, in people who have one copy of Phe508del and one copy of a residual-function CFTR mutation. The researchers found that the amount of air that participants were able to exhale per second — a standard measure of lung function in people with CF — rose by an average 4.7 percentage points with ivacaftor treatment alone, and 6.8 percentage points with the combined ivacaftor-tezacaftor treatment, compared to a placebo.

CF Study Identifies Possible Shortcoming Of Orkambi’s Dual-component Approach

The two components of Orkambi act separately to trigger a liver enzyme that decreases the therapy’s ability to fight cystic fibrosis, a study reported. One concern the researchers found is that the therapy’s combination strategy may be limited due to antagonistic drug-drug interactions. The team has been looking at how ivacaftor and lumacaftor work in the body, as well as the workings of a CFTR regulator called tezacaftor (VX-661). They found that ivacaftor is broken down into two main components in the liver — an active metabolite called hydroxymethyl-ivacaftor (M1) and an inactive one called ivacaftor-carboxylate (M6). The enzymes CYP1A2 and CYP3A4 play the main role in breaking down ivacaftor. The key finding was that ivacaftor-M6 and lumacaftor trigger the CYP3A4 liver enzyme. This leads to patients who receive Orkambi having significantly less ivacaftor in their system, reducing the treatment’s effectiveness against CF.

ProQR Announces Presentations At ECFS On Eluforsen For F508del Cystic Fibrosis And At CFF Research Conference

Eluforsen, formerly known as QR-010, is a first-in-class RNA-based oligonucleotide designed to address the underlying cause of the disease by targeting the mRNA in CF patients that have the F508del mutation. Eluforsen is a single agent designed to bind to the defective CFTR mRNA and to restore CFTR function. Eluforsen is designed to be self-administered via an optimized eFlow® Nebulizer.

AmpliPhi Biosciences Announces Presentation Of AB-PA01 Bacteriophage Therapy Case Study At 41st European Cystic Fibrosis Conference

The presentation describes the case of a 26-year-old patient with cystic fibrosis (CF) listed for a double lung transplant, who developed multiple episodes of multi-drug resistant (MDR) P. aeruginosa pneumonia and had multiple CF exacerbations. Prior to treatment with AB-PA01, the patient received multiple courses of antibiotics, including colistin, but due to renal failure, colistin administration was discontinued. The U.S. FDA granted an emergency IND to administer AmpliPhi’s AB-PA01 as an adjunctive treatment to systemic antibiotics. AB-PA01 was administered via intravenous route every six hours for eight weeks. Treatment with AB-PA01 was well tolerated and the patient’s infection resolved. No recurrence of pneumonia or CF exacerbation was reported during the two-month follow-up period after the completion of treatment with AB-PA01. The patient’s renal failure resolved. In this case study, bacteriophage therapy has demonstrated to hold much promise for patients with cystic fibrosis suffering from multidrug- resistant pulmonary bacterial infections.

HOPE-1 Trial Shows Potential Of SPX-101 To Improve Lung Function In CF Patients

Results of a Phase 2 trial showed that treatment with Spyryx’s investigative drug SPX-101 can improve lung function in patients with cystic fibrosis, regardless of their background genetic mutation causing the disease. SPX-101 is a small protein fragment that was developed to target epithelial sodium channels (ENaC) in the lungs and prevent them from taking up sodium. The drug reduces sodium absorption, allowing fluids to be retained on the airway surface, making mucus clearance an easier task. The effectiveness and safety of SPX-101 is currently being evaluated in the HOPE-1 trial (NCT03229252). During the trial, SPX-101 was found to be safe and well-tolerated. The most common adverse events reported were increased sputum production and cough.


Prevalence Of Severe Fatigue Among Adults With Cystic Fibrosis: A Single Center Study. Merel M. Nap-van der Vlist, Marcella Burghard, H.J. Hulzebos, Wytze R. Doeleman, Harry G.M. Heijerman, Cornelis K. van der Ent, Sanne L. Nijhof. Journal of Cystic Fibrosis. May 2018Volume 17, Issue 3, Pages 368–374

With life expectancy increasing among patients with cystic fibrosis (CF), the prevalence of complications such as fatigue is also expected to increase. The aim of this study was to investigate the prevalence of severe fatigue among adults with CF and to identify factors associated with fatigue. Fatigue is a clinically important and highly prevalent issue among adults with CF and is associated with a significant reduction in health-related quality of life and participation in society. In addition, fatigue is associated more strongly with the patient’s perception of symptoms and well-being than with clinically measured parameters.

A Prospective Analysis Of Unplanned Patient-initiated Contacts In An Adult Cystic Fibrosis Centre. Espérie Burnet, Dominique Hubert, Isabelle Honoré, Reem Kanaan, Rosewilta Panzo, Pierre-Régis Burgel. Journal of Cystic Fibrosis. Article in press.

Timely response should be provided when patients contact the cystic fibrosis (CF) center in between scheduled visits. Little data exist on unplanned patient-initiated contacts in CF adults. Answering unplanned patient-initiated contacts represented a significant workload for CF caregivers. Increased disease severity was associated with high contact frequency.

16S rRNA Gene Sequencing Reveals Site-specific Signatures Of The Upper And Lower Airways Of Cystic Fibrosis Patients. Sarah K. Lucas, Robert Yang, Jordan M. Dunitz, Holly C. Boyer, Ryan C. Hunter. Journal of Cystic Fibrosis. March 2018 .Volume 17, Issue 2, Pages 204–212

The authors compare bacterial communities of matched sinus and lung mucus samples from cystic fibrosis (CF) subjects undergoing endoscopic surgery for treatment of chronic sinusitis. The findings indicate that while the lung may be seeded by individual sinus pathogens, airway microenvironments harbor distinct bacterial communities that should be considered in selecting antimicrobial therapies.

The Effect Of Enteral Tube Feeding In Cystic Fibrosis: A Registry-Based Study. Denis Libeert, Dimitri Declercq, Simeon Wanyama, Muriel Thomas, Sabine Van daele, Frans De Baets, Stephanie Van Biervliet. Journal of Cystic Fibrosis. March 2018. Volume 17, Issue 2, Pages 264–270

Long-term effect of enteral tube feeding (ETF) in cystic fibrosis (CF) remains equivocal.

ETF introduction improved BMI z-score and stabilized FEV1, was associated with fewer hospitalizations and IVAB treatments. Higher mortality and transplantation in the ETF cases, leading to drop-outs, made determination of the effect size difficult.

Attention Deficit Hyperactivity Disorder Symptoms In Patients With Cystic Fibrosis. Malena Cohen-Cymberknoh, Tzlil Tanny, Oded Breuer, Hannah Blau, Huda Mussaffi, Diana Kadosh, Silvia Gartner, Alma Salinas, Lea Bentur, Vered Nir, Michal Gur, Joel Reiter, David Shoseyov, Eitan Kerem, Itai Berger. Journal of Cystic Fibrosis. March 2018Volume 17, Issue 2, Pages 281–285

Cystic fibrosis (CF) is a chronic life-threatening disease. In patients who suffer from chronic disease, Attention Deficit Hyperactivity Disorder (ADHD) is associated with functional impairment that can affect adherence to treatment and consequently influence prognosis. The occurrence of ADHD symptoms in patients with CF is substantially higher than in the general population and should be recognized as a co-morbidity of CF. As ADHD can impair adherence to therapy, further research is needed to investigate the effect of ADHD therapy on adherence.

Risk Of Gastrointestinal Cancers In Patients With Cystic Fibrosis: A Systematic Review And Meta-analysis. Akihiro Yamada, MD, Yuga Komaki, MD, Fukiko Komaki, MD, Dejan Micic, MD, Samantha Zullow, MD, Atsushi Sakuraba, MD. The Lancet Oncology. Published: 26 April 2018

The management and life expectancy of patients with cystic fibrosis have improved substantially in the past three decades, which has resulted in an increased number of these patients being diagnosed with malignancies. The aim of this study was to assess the risk of gastrointestinal cancers in patients with cystic fibrosis. Results suggests that patients with cystic fibrosis had a significantly increased risk of gastrointestinal cancer compared with the general population, including small bowel, colon, biliary tract and pancreatic cancers. These findings highlight the need to develop individualized screening strategies for site-specific gastrointestinal cancers in patients with cystic fibrosis.


Lumacaftor/Ivacaftor In Patients With Cystic Fibrosis And Advanced Lung Disease Homozygous For F508del-CFTR. Jennifer L. Taylor-Cousar, Manu Jain, Tara Lynn Barto, Tarik Haddad, Jeffrey Atkinson, Simon Tian, Rui Tang, Gautham Marigowda, David Waltz, Joseph Pilewski on behalf of the VX14-809-106 Investigator Group. Journal of Cystic Fibrosis. March 2018. Volume 17, Issue 2, Pages 228–235

The objective of this investigation was to evaluate the safety, tolerability and efficacy of lumacaftor/ivacaftor in patients with cystic fibrosis (CF) with severe lung disease. Compared with patients with higher lung function, respiratory events were more common in patients with ppFEV1 < 40; aside from these events, the lumacaftor/ivacaftor safety profile was consistent with previous studies. Results suggest that patients with ppFEV1 < 40 may benefit from treatment initiation at a lower dose with augmented monitoring before increasing to the full dose.

Data From The US And UK Cystic Fibrosis Registries Support Disease Modification By CFTR Modulation With Ivacaftor. Leona Bessonova, Nataliya Volkova, Mark Higgins, Leif Bengtsson, Simon Tian, Christopher Simard, Michael W Konstan, Gregory S Sawicki, Ase Sewall, Stephen Nyangoma, Alexander Elbert, Bruce C Marshall, Diana Bilton. Thorax. May 23, 2018

Ivacaftor is the first cystic fibrosis transmembrane conductance regulator (CFTR) modulator demonstrating clinical benefit in patients with cystic fibrosis (CF). As ivacaftor is intended for chronic, lifelong use, understanding long-term effects is important for patients and healthcare providers. This ongoing, observational, post-approval safety study evaluates clinical outcomes and disease progression in ivacaftor treated patients using data from the US and the UK CF registries following commercial availability. Analyses revealed favorable results for clinically important outcomes among ivacaftor treated patients, adding to the growing body of literature supporting disease modification by CFTR modulation with ivacaftor.

Exploring Probiotic Use In A Regional Cystic Fibrosis Consortium. K.D. Gonzalez, J.B. Zuckerman, E.H. Sears, B.S. Prato, M. Guill, W. Craig, C. Milliard, E. Parker, T. Lever, M.M. Griffin, L.W. Leclair. Journal of Cystic Fibrosis. March 2018. Volume 17, Issue 2, Pages e20–e21

Studies in cystic fibrosis (CF) patients have reported reduced rates of pulmonary exacerbation and hospitalization with probiotic use. Furthermore, regular intake of probiotics has been associated with improvements in gastrointestinal (GI) symptoms, levels of inflammatory markers and quality of life. However, little has been published about clinical use of probiotics in CF, and a recent review highlighted the need to better understand the appropriate role of these agents in long-term disease management.

Colistin Resistance In Pseudomonas aeruginosa And Achromobacter spp. Cultured From Danish Cystic Fibrosis Patients Is Not Related To Plasmid-mediated Expression Of mcr-1. Maya G. Pedersen, Hanne V. Olesen, Søren Jensen-Fangel, Niels Nørskov-Lauritsen, Mikala Wang. Journal of Cystic Fibrosis. March 2018. Volume 17, Issue 2, Pages e22–e23

The emergence and global spread of a new plasmid-mediated resistance mechanism to colistin, the mcr-1 gene, can have significant implications for the treatment of pulmonary infections in cystic fibrosis (CF) patients. The polymyxins, colistin (polymyxin E) and polymyxin B, are antimicrobial peptides with broad-spectrum activity against Gram negative bacteria, including common CF pathogens as Pseudomonas aeruginosa and Achromobacter species and are frequently administered as inhaled antimicrobial therapy to CF patients. A transfer of colistin resistance to multidrug-resistant CF pathogens would limit treatment options.

Treatment Of Chronic Rhinosinusitis With Dornase Alfa In Patients With Cystic Fibrosis: A Systematic Review. Gopi B. Shah MD, MPH Linde De Keyzer MD Joy A. Russell PhD, MLS Ashleigh Halderman MD. International Forum of Allergy & Rhinology Volume 0, Issue 0. 11 January 2018

A major component of sputum in cystic fibrosis (CF) patients is polymerized DNA, a byproduct of degraded neutrophils. Dornase alfa (dornase) selectively cleaves extracellular DNA and reduces the viscosity of sputum. It improves mucociliary clearance and pulmonary function. The benefit of dornase on CF-associated sinusitis is less clear. Therefore, the objective of this study was to systematically review the use of dornase on chronic rhinosinusitis (CRS) in CF patients. Findings indicate that topical intranasal dornase appears to improve sinonasal symptoms in CF patients to a greater degree than saline alone.

Treatment Compliance In Cystic Fibrosis Patients With Chronic Pseudomonas aeruginosa Infection Treated With Tobramycin Inhalation Powder: The FREE Study. Francesco Blasi, Vincenzo Carnovale, Giuseppe Cimino, Vincenzina Lucidi, Donatello Salvatore, Barbara Messore, Marta Bartezaghi, Elisa Muscianisi, Pasquale Alberto Porpiglia. Respiratory Medicine. May 2018. Volume 138, Pages 88–94

A high treatment burden with nebulized therapies in cystic fibrosis (CF) patients is the major limitation for treatment compliance; moreover, studies on treatment compliance with inhaled antibiotics are limited. This study assessed compliance to TOBI® Podhaler™ (TIP) treatment in CF patients with chronic Pseudomonas aeruginosa (Pa) infections in a real-world setting. The authors concluded that TIP was convenient to use and led to improved treatment adherence in CF patients with chronic Pa-infection.


Prevalence Of Hypoglycemia During Oral Glucose Tolerance Testing In Adults With Cystic Fibrosis And Risk Of Developing Cystic Fibrosis-related Diabetes. Lisa A. Mannik, Kristy A. Chang, Pascalyn Q.K. Annoh, Jenna Sykes, Julie Gilmour, Ronalee Robert, Anne L. Stephenson. Journal of Cystic Fibrosis. Article in press

Hypoglycemia in cystic fibrosis (CF) patients during the oral glucose tolerance test (OGTT) has been reported. Few studies have examined whether hypoglycemia during the OGTT increases the risk of developing CF-related diabetes (CFRD). Objectives of this study were to describe the characteristics of CF patients with hypoglycemia during the OGTT and to determine the incidence and time to development of CFRD in those with hypoglycemia. Results show that hypoglycemia following OGTT is common in CF; however, the 10-year risk of developing CFRD in these patients was low. Males and those who were heterozygous deltaF508 were at higher risk for hypoglycemia. s

Laura Tillman has CF. She is a former Director of USACFA. Her email is: