Outcomes associated with antibiotic regimens for treatment of Mycobacterium abscessus in cystic fibrosis patients

Background

Mycobacterium abscessus infection is associated with declining lung function in cystic fibrosis (CF), but there is little evidence on clinical efficacy to guide treatment.

Defining palliative care in cystic fibrosis: A Delphi study

Background

The goal of palliative care is to improve quality of life for people with serious illness. We aimed to create a cystic fibrosis (CF)-specific definition of palliative care.

Predictors for surgical intervention and surgical outcomes in neonates with cystic fibrosis

Background/Purpose

To identify prenatal and perinatal predictors of surgery and describe surgical findings/outcomes of neonates with Meconium Ileus (MI) secondary to Cystic Fibrosis (CF).

Phenotypic spectrum of patients with cystic fibrosis and cystic fibrosis-related disease carrying p.Arg117His

Background

The “mild” gene variant, p.Arg117His in cystic fibrosis (CF) results in highly variable phenotypes ranging from male infertility to severe lung disease. Due to current interest to include this group in CFTR-targeted therapies, this study aims to describe the disease spectrum.

Ceftaroline pharmacokinetics and pharmacodynamics in patients with cystic fibrosis

Background

Methicillin-resistant Staphylococcus aureus (MRSA) is a prevalent pathogen in patients with cystic fibrosis (CF) associated with increased morbidity. Ceftaroline fosamil is an intravenous (IV) cephalosporin with activity against MRSA. There are minimal data regarding dosing in the CF population. The objective of this study was to determine the pharmacokinetic and pharmacodynamic profile of IV ceftaroline in patients with CF.

Management of major hemoptysis in patients with cystic fibrosis

Although bronchoscopy remains the best definitive method for localization of the site of hemorrhage in patients who have massive hemopytsis, angiography remains an important adjunct to this localization. When combined with embolization of the bleeding bronchial artery, it is an effective method of therapy for the management of massive hemoptysis in patients with cystic fibrosis.     

Anaesthesia for parturients with severe cystic fibrosis: a case series

Cystic fibrosis affects 1 in 1600–2500 live births and is inherited in an autosomal recessive manner. It primarily involves the respiratory, gastrointestinal and reproductive tracts, with impaired clearance of, and obstruction by, increasingly viscous secretions. Severe respiratory disease, diabetes and gastro-oesophageal reflux may result. Improvements in medical management and survival of cystic fibrosis patients means more are committing to pregnancies. Although guidance for anaesthesia in this patient group is available, management and outcome data associated with more severe cases are sparse. Patients with severe cystic fibrosis require multidisciplinary input and should be managed in a tertiary referral centre. Close monitoring of respiratory function and preoperative optimisation during pregnancy are mandatory. The risk of preterm labour and delivery is increased. Pregnancy and delivery can be managed successfully, even in patients with FEV1 <40% predicted. Neuraxial anaesthesia and analgesia should be the technique of choice for delivery. Postoperative care should be carried out in a critical care setting with the provision of postoperative ventilation if necessary.     

Improved glutathione status in young adult patients with cystic fibrosis supplemented with whey protein

BACKGROUND: The lung disease of cystic fibrosis is associated with a chronic inflammatory reaction and an over abundance of oxidants relative to antioxidants. Glutathione functions as a major frontline defense against the build-up of oxidants in the lung. This increased demand for glutathione (GSH) in cystic fibrosis may be limiting if nutritional status is compromised. We sought to increase glutathione levels in stable patients with cystic fibrosis by supplementation with a whey-based protein. METHODS: Twenty-one patients who were in stable condition were randomly assigned to take a whey protein isolate (Immunocal, 10 g twice a day) or casein placebo for 3 months. Peripheral lymphocyte GSH was used as a marker of lung GSH. Values were compared with nutritional status and lung parameters. RESULTS: At baseline there were no significant differences in age, height, weight, percent ideal body weight or percent body fat. Lymphocyte GSH was similar in the two groups. After supplementation, we observed a 46.6% increase from baseline (P < 0.05) in the lymphocyte GSH levels in the supplemented group. No other changes were observed. CONCLUSION: The results show that dietary supplementation with a whey-based product can increase glutathione levels in cystic fibrosis. This nutritional approach may be useful in maintaining optimal levels of GSH and counteract the deleterious effects of oxidative stress in the lung in cystic fibrosis.     

Bicarbonate in cystic fibrosis

Background

Cystic fibrosis (CF, mucoviscidosis) is caused by mutations in the gene encoding CF transmembrane conductance regulator (CFTR), which is a chloride and bicarbonate channel necessary for fluid secretion and extracellular alkalization. For a long time, research concentrated on abnormal Cl^- and Na⁺ transport, but neglected bicarbonate as a crucial factor in CF.

Gas exchange in stable patients with moderate-to-severe lung disease from cystic fibrosis

BACKGROUND: Studies using the multiple inert gas elimination technique (MIGET) to characterise the mechanisms of impaired gas exchange in CF, provide conflicting results on the importance of ventilation-perfusion (VA/Q) inequality over shunt. We hypothesise that the mechanisms of gas exchange abnormality have changed with changing CF management over the last two decades. METHODS: Detailed gas exchange was evaluated by MIGET with venous sampling in stable patients, age > 20 years, FEV1% predicted < or = 50. RESULTS: Fifteen (14 male) subjects were studied with a mean +/- SD age 28.1 +/- 8.4 years, FEV1% 32.6 +/- 10.3, TLC% 111.5 +/- 12.9, PaO2 9.3 +/- 1.3 kPa, (69.5 +/- 9.6 mm Hg), and PaCO2 6.2 +/- 0.7 kPa, (45.9 +/- 5.3 mm Hg). The predominant gas exchange abnormality was VA/Q inequality with a log SD of the distributions of perfusion 0.91 +/- 0.30 and of ventilation 0.60 +/- 0.14. Unimodal distributions were seen in nine subjects, a low VA/Q mode in five and one subject had a bimodal distribution, mean intrapulmonary shunt was negligible. CONCLUSIONS: Subjects had a lower FEV1% by comparison with previously published studies and demonstrated severe VA/Q inequality and negligible shunt. This suggests a low degree of complete obstruction of airways in adults with CF and severe stable pulmonary disease. The primary mechanism of hypoxaemia in CF subjects reaching adulthood today appears to have changed with modern management over the last two decades.     

Pulmonary exacerbations and acute declines in lung function in patients with cystic fibrosis

Background

Patients with cystic fibrosis (CF) who experience acute declines in percent predicted FEV₁ (ppFEV₁ decreased ≥10% relative to baseline) are often not treated with antibiotics for pulmonary exacerbations (PEx), whereas other patients are treated even when they have not experienced a decline in lung function.

Combined lung-liver-pancreas transplantation in a recipient with cystic fibrosis

Cystic fibrosis (CF) affects multiple organs including the lung, liver, and pancreas. Lung transplant, liver transplant, and combined lung-liver transplant have become well-established therapies for CF patients with end-stage organ failure. Thus far, however, there has been limited experience with pancreas transplantation in CF. In this report, we detail the clinical history, transplant procedure, and post-operative recovery of a patient who underwent combined lung-liver-pancreas transplant for advanced CF.     

Adults with cystic fibrosis report important and unmet needs for disease information

BACKGROUND: The informational needs of the growing population of adults with cystic fibrosis (CF) have not been previously assessed. METHODS: Adults with CF enrolled in the Project on Adult Care in CF (PAC-CF) completed a survey including 22 items in which information topics were rated on the importance of receiving more information and the satisfaction with sources of information. Unmet needs were defined as those topics rated with both high importance and low satisfaction with information sources. RESULTS: The median age of the 233 respondents was 34 years, median FEV(1) was 68% predicted, and 59% were female. The information topics with the highest mean importance ratings were on CF treatments and managing infection. The percentage of respondents rating an individual information need as unmet ranged from 2-32%. Information on "ways to deal with decreased energy, "new CF therapies," and "ways to deal with the unpredictability of the future" were reported as unmet by almost one-third of respondents. For all but four of the information topics assessed, clinical and socio-demographic factors were not significantly associated with increased likelihood of reporting unmet informational needs. CONCLUSIONS: Adults with CF rated information on treatment topics as most important. In contrast, patients were more likely to report information needs on disease self-management and future planning as unmet. Clinical and socio-demographic patient characteristics were not systematically associated with unmet informational needs. Clinicians caring for adult CF patients should not solely rely socio-demographic factors or markers of disease severity as signals for providing comprehensive information on disease self-management and future planning.     

Insights into the cystic fibrosis care in Eastern Europe: Results of survey

Background

The European cystic fibrosis (CF) Society Standards of Care were set to facilitate the delivery of high-quality care throughout Europe. However, their implementation may be difficult for less economically advantaged countries. This survey was performed to explore the gap in the knowledge of the level of CF care in Eastern Europe.

Pilot trial of tobramycin inhalation powder in cystic fibrosis patients with chronic Burkholderia cepacia complex infection

There is no effective chronic suppressive therapy Burkholderia cepacia complex infection in cystic fibrosis (CF) patients. This was a pilot, open-label clinical trial of tobramycin inhalation powder (TIP) delivered via Podhaler twice daily for 28 days in adults and children with CF and chronic B. cepacia complex infection in Toronto, Canada. A total of 10 subjects (4 pediatric, 6 adult patients) were treated. There was a mean drop of 1.4 log (CFU/ml) in sputum bacterial density (p = 0.01) and sputum IL-8 levels decreased significantly after 28 days of TIP (p = 0.04). The mean relative change in FEV₁ (L) from Day 0 to Day 28 of TIP administration was a 4.6% increase but this was not statistically significant. The majority of patients (70%) had no or mild adverse events.     

Club cell secretory protein and lung function in children with cystic fibrosis

BackgroundClub cell secretory protein (CC16) exerts anti-inflammatory functions in lung disease. We sought to determine the relation of serum CC16 deficits and genetic variants that control serum CC16 to lung function among children with cystic fibrosis (CF).MethodsWe used longitudinal data from CF children (EPIC Study) with no positive cultures for Pseudomonas aeruginosa prior to enrollment. Circulating levels of CC16 and an inflammatory score (generated from CRP, SAA, calprotectin, G-CSF) were compared between participants with the lowest and highest FEV₁ levels in adolescence (LLF and HLF groups, respectively; N = 130-per-group). Single nucleotide variants (SNVs) in the SCGB1A1, EHF-APIP loci were tested for association with circulating CC16 and with decline of FEV₁ and FEV₁/FVC% predicted levels between ages 7–16 using mixed models.ResultsCompared with the HLF group, the LLF group had lower levels of CC16 (geometric means: 8.2 vs 6.5 ng/ml, respectively; p = 0.0002) and higher levels of the normalized inflammatory score (-0.21 vs 0.21, p = 0.0007). Participants in the lowest CC16 and highest inflammation tertile had the highest odds for having LLF (p<0.0001 for comparison with participants in the highest CC16 and lowest inflammation tertile). Among seven SNVs associated with circulating CC16, the top SNV rs3741240 was associated with decline of FEV₁/FVC and, marginally, FEV₁ (p = 0.003 and 0.025, respectively; N = 611 participants, 20,801 lung function observations).ConclusionsSerum CC16 deficits are strongly associated with severity of CF lung disease and their effects are additive with systemic inflammation. The rs3741240 A allele is associated with low circulating CC16 and, possibly, accelerated lung function decline in CF.     

Year to year change in FEV1 in patients with cystic fibrosis and different mutation classes

In patients with cystic fibrosis, most treatments addressing the underlying basic defect are mutation or mutation class specific. These treatments are disease modifying if they lower the year to year change in lung function. We therefore calculated the current loss of lung function, measured by year to year change in forced expired volume in 1 s in 11,417 patients included in the European Cystic Fibrosis Society Patient Registry. Whereas patients with at least one mutation of class IV or V have on average a lower year to year change, we did not find a difference between patients with a stop codon mutation, homozygous for F508del or at least one class III mutation. These data are useful background information to discuss the impact of different disease modifying treatments.     

Attention deficit hyperactivity disorder symptoms in patients with cystic fibrosis

Background

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.