Prevalence and diversity of filamentous fungi in the airways of cystic fibrosis patients – A Dutch,multicentre study

Background

Progressive lung injury in Cystic Fibrosis (CF) patients can lead to chronic colonization with bacteria and fungi. Fungal colonization is obtained from the environment which necessitates locally performed epidemiology studies. We prospectively analyzed respiratory samples of CF patients during a 3-year period, using a uniform fungal culture protocol, focusing on filamentous fungi and azole resistance in Aspergillus fumigatus.

Incidence and risk factors of cancer in individuals with cystic fibrosis in the UK; a case-control study

To assess cancer incidence in the UK cystic fibrosis (CF) population and determine the associated risk factors, we undertook a nested case-control study of patients with CF, registered with the UK CF Registry. Each case with a first reported cancer between 1999 and 2017 was matched with up to 4 controls: by age (±2-years) and year of cancer diagnosis. Conditional logistic regressions were adjusted for sex, lung function (FEV₁%), CF related diabetes (CFRD), F508del status, transplant status, DIOS, gastro-oesophageal reflux disease, meconium ileus, Pseudomonas aeruginosa infection, pancreatic insufficiency, proton pump inhibitor (PPI) use, IV antibiotic days and BMI.Results: From 12,886 registered patients, 146 (1.1%) cases of malignancy were identified with 14.3% of cases occurring post solid organ transplant. Site of primary cancer was available for 98 patients: 22% were gastro-intestinal in origin (77% lower, 23% upper GI), 13% skin, 13% breast and 11% lymphomas/leukaemia. In univariable analysis, transplantation increased the odds of reporting any cancer by 2.46 times (95%CI: 1.3-4.6). CFRD also increased the odds of reporting any cancer (OR 2.35; CI: 1.37-4.0) and PPI use (OR 2.0; CI 1.28-3.19). In the multivariable models significant associations with CFRD and transplant remained, while PA infection, PPI use and being overweight showed increased, but statistically insignificant risks. The incidence of GI cancer was strongly associated with CFRD (OR=4.04; 1.47-11.1).Conclusions: We observed a high incidence of lower GI cancers in our cohort which was significantly affected by the presence of CFRD. Screening for gastrointestinal cancers could benefit patients at higher risk.     

CFTR-function and ventilation inhomogeneity in individuals with cystic fibrosis

BackgroundIncreased (abnormal) ventilation inhomogeneity in individuals with mild Cystic Fibrosis (CF) lung disease may become a treatable trait for small-molecule therapeutics improving Cystic Fibrosis Transmembrane Regulator (CFTR) function. The relationship between CFTR function and ventilation inhomogeneity is unknown. We aimed to identify and quantify increased ventilation inhomogeneity in relation to CFTR function.MethodsThis was an international, multi-center, cross-sectional study. We collated data from individuals aged 3–25 years with minimal (CFTR-MF) or residual (CFTR-RF) function of a variety of CFTR genotypes and FEV₁ ≥ 70% predicted. We measured lung function using nitrogen multiple-breath washout and spirometry. We compared lung clearance index (LCI) and FEV₁ between individuals with CFTR-MF vs CFTR-RF using a mixed effects multi-variable linear regression model to account for study differences and a logistic model based on propensity-score matching to adjust for possible confounding.ResultsWe included 141 with CFTR-MF and 35 with CFTR-RF. LCI (> 1.96 z-score) was elevated in 71.6% individuals with CFTR-MF and in 40.0% with CFTR-RF. FEV₁ (< -1.96 z-score) was reduced in 11.3% individuals with CFTR-MF and in 5.7% with CFTR-RF. The mean difference (95% CI) of LCI and FEV₁ between CFTR-MF and CFTR-RF was 3.71 (1.63 to 5.79) and -0.40 (-0.83 to 0.02) z-score. The LCI differences were similar after adjustment for confounders and in individuals with normal FEV₁.ConclusionIncreased ventilation inhomogeneity is associated with less CFTR function. In individuals with mild CF lung disease, LCI can identify and quantify increased ventilation inhomogeneity, a candidate treatable trait.     

Prevalence of dyslipidemia in adults with cystic fibrosis

BackgroundA high fat calorie diet is advocated for patients with cystic fibrosis (CF) however the lipid profiles of individuals with CF, including those with CF-related diabetes (CFRD), are not well studied.MethodsWe conducted a retrospective review of adult CF patients attending St Michael's Hospital between January 2005 and December 2007.Results334 patients (77% pancreatic insufficient (PI)) were included in the study. Mean HDL cholesterol was significantly lower in males (p < 0.0001) with 44% of males having HDL cholesterol < 38.7 mg/dL(1 mmol/L). Pancreatic sufficient patients were more likely than PI subjects to have total cholesterol > 201 mg/dL(5.2 mmol/L) (p < 0.01). 5% of subjects had triglyceride concentrations > 195 mg/dL(2.2 mmol/L). Diabetes was diagnosed in 23% of subjects. Lipid profiles were similar between diabetics and non-diabetics. Total cholesterol and triglycerides both increased with increasing age and increasing BMI (p < 0.01).ConclusionDyslipidemia occurs in CF patients however no differences in lipid profiles were seen between those with diabetes and those without. Fasting lipids should be monitored in CF patients, particularly those with PS, older age, and high BMI. As survival in CF increases, the prevalence of dyslipidemia may increase resulting in clinically important complications.     

Prevalence of pain in adults with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) may strongly condition the life of affected people. CF may be associated with relevant painful conditions caused by complications of the illness and also by therapy itself, which may represent an additional load of suffering. This study was aimed at evaluating the prevalence of pain symptoms in adult CF patients, if they are noticed and treated, and the influence of pain symptoms on patients' life. METHOD: Using a questionnaire, we examined 239 adults with CF (17% of the whole Italian adult CF population). RESULTS: We found a high prevalence of painful episodes among CF adult patients, as for both intensity and frequency. In a 2 months period 32.6% of patients experienced episodes of pain described as intense to severe, and 29.7% had more than 10 occurrences of pain in the same location. Headache, gastric pain and backache were the most frequently reported kind of pain. 59.8% of subjects perceived pain episodes as the cause of unfavorable effects on their life. Only 42.6% of those with pain asked a CF center physician for help and another 3.5% a general practitioner. CONCLUSION: Painful symptoms can be the cause of a worsening of the quality of life for adults with CF; the relevance of pain in CF adult patients may often be underestimated; the assessment of pain should be routinely performed as a part of care in CF centers.     

Prevalence of hypoglycemia during oral glucose tolerance testing in adults with cystic fibrosis and risk of developing cystic fibrosis-related diabetes

Background

Hypoglycemia in cystic fibrosis (CF) patients during the oral glucose tolerance test (OGTT) has been reported; however, these patients have not been well-characterized. 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.

Prevalence of cystic fibrosis pathogens in the oropharynx of healthy children and implications for cystic fibrosis care

ObjectiveTo describe the prevalence of the CF pathogens Pseudomonas aeruginosa, Staphylococcus aureus and Haemophilus influenzae in OP cultures from healthy children.MethodsOropharyngeal (OP) swabs were collected from 100 healthy children ≤ 18 years of age undergoing a clinically indicated procedure.ResultsP. aeruginosa was isolated from the OP swab of one participant, S. aureus from 48 participants (including 4 methicillin-resistant) and H. influenzae from 47 participants. Cultures from 75 participants grew one or more of these organisms (55 grew one, 19 grew 2 and one grew 3 organisms).ConclusionP. aeruginosa is rarely recovered from the oropharynx of healthy children ≤ 18 years of age, while recovery of S. aureus and H. influenzae is common. It is important to understand what the “normal” prevalence of CF pathogens is in the oropharynx in order to aid interpretation of OP cultures in CF patients.     

Prevalence and factors associated with overweight and obesity in adults with cystic fibrosis: A single-center analysis

BackgroundThe relation between malnutrition and pulmonary death in patients with cystic fibrosis (CF) has resulted in intensive nutritional intervention over the last few decades, leading to a significant decline in underweight and the emergence of overweight/obesity as a potential new problem.MethodsWe performed a cross-sectional database analysis of 484 adults with CF seen at the University of Minnesota CF Center between January 2015-January 2017, to determine the prevalence and pulmonary/cardiovascular risk factors associated with overweight and obesity in this population.ResultsMean age was 35.2 ± 11.6 years. 5.2% were underweight (BMI<18.5 kg/m²), 62.6% normal weight (BMI ≥ 18.5–24.9 kg/m²), 25.6% overweight (BMI ≥ 25–29.9 kg/m²) and 6.6% obese (BMI ≥ 30 kg/m²). In the subgroup with severe genotypes, 25% had BMI ≥ 25 kg/m². In the entire cohort, overweight/obese were likely to be older (OR = 1.04, p < 0.0001) and to have a mild CFTR genotype (OR = 3.33, p = 0.0003) and modestly elevated triglyceride levels (OR = 1.008, p < 0.0001). The prevalence of hypertension was higher in overweight (25%) and obese (31%) than normal (17%) or underweight (16%), p = 0.01. Total cholesterol levels were higher in overweight/obese versus normal/underweight (144–147 vs 123–131 mg/dL, p = 0.04) as were LDL levels (70–71 vs 53–60 mg/dL, p = 0.02), but all were within the normal range. Percent predicted FEV1 was higher in overweight/obese (78–81%) versus underweight (59%) and normal (70%), p < 0.0001, and overweight/obese experienced significantly fewer acute pulmonary exacerbations.ConclusionsOverweight/obesity is common in adults with CF including those with severe genotypes. Lung function is better in the overweight/obese and lipid levels are within the normal range, albeit higher than in normal/underweight.     

Year-to-year changes in lung function in individuals with cystic fibrosis

BackgroundWe examined the year-to-year change in FEV₁ for individuals and the overall cystic fibrosis population to better understand how individual trends may differ from population trends.MethodsWe calculated individual yearly changes using the largest annual FEV₁ percent predicted (FEV₁%) measurement in 20,644 patients (6–45 years old) included in the Epidemiologic Study of Cystic Fibrosis. We calculated yearly population changes using age-specific medians.ResultsFEV₁% predicted decreased 1–3 points per year for individuals, with maximal decreases in 14–15 year olds. Population changes agreed with individual changes up to age 15; however after age 30, yearly population change approximated zero while individual FEV₁% predicted decreases were 1–2 points per year.ConclusionsAdolescents have the greatest FEV₁% predicted decreases; however, loss of FEV₁ is a persistent risk in 6–45 year old CF patients. Recognizing individual year-to-year changes may improve patient-specific care and may suggest new methods for measuring program quality.     

Development of selective media for the isolation of yeasts and filamentous fungi from the sputum of adult patients with cystic fibrosis (CF)

Yeasts and filamentous fungi are beginning to emerge as significant microbial pathogens in patients with cystic fibrosis (CF), particularly in relation to allergic-type responses, as seen in patients with allergic bronchopulmonary aspergillosis (ABPA), Aspergillus bronchitis and in invasive fungal disease in lung transplant patients. Four fungal media were compared in this study, including Sabouraud Dextrose Agar (SDA) and Medium B, with and without the addition of selective antibiotics, where antibiotic-supplemented media were designated with ⁺. These media were compared for their ability to suppress contaminating, mainly Gram−ve pathogens, in CF sputa (Pseudomonas aeruginosa, Burkholderia cepacia complex [BCC] organisms) and to enhance the growth of fungi present in CF sputum. Medium B consisted of glucose (16.7 g/l), agar (20 g/l), yeast extract (30 g/l) and peptone (6.8 g/l) at pH 6.3 and both SDA⁺ and Medium B⁺ were supplemented with cotrimethoxazole, 128 mg/l; chloramphenicol, 50 mg/l; ceftazidime, 32 mg/l; colistin, 24 mg/l). Employment of SDA⁺ or Medium B⁺ allowed an increase in specificity in the detection of yeasts and moulds, by 42.8% and 39.3%, respectively, over SDA when used solely. SDA⁺ had a greater ability than Medium B⁺ to suppress bacterial growth from predominantly Gram−ve co-colonisers. This is a significant benefit when attempting to detect and isolate fungi from the sputum of CF patients, as it largely suppressed any bacterial growth, with the exception of the BCC organisms, thus allowing for an increased opportunity to detect target fungal organisms in sputum and represented a significant improvement over the commercial medium (SDA), which is currently used. Overall, both novel selective media were superior in their ability to suppress bacteria in comparison with the commercially available SDA medium, which is routinely employed in most clinical microbiology diagnostic laboratories presently. Alternatively, Medium B⁺ had a great ability to grow fungi than SDA⁺ and when employed together, the specificity of combined use was 82%, with a sensitivity for yeasts, filamentous fungi, and combined overall fungi of 96.0%, 92.3% and 96.0%, respectively. Overall, when employing one fungal selective medium for the routine detection of yeasts and filamentous fungi in the sputum of CF patients, we would recommend employment of Medium B⁺. However, we would recommend the combined employment of SDA⁺ and Medium B⁺, in order to synergistically isolate and detect the greatest number of fungi present in CF sputa.     

Prevalence of urinary incontinence in women with cystic fibrosis.

OBJECTIVE: To determine the prevalence of urinary incontinence (UI) in female patients (aged > or = 15 years) attending a cystic fibrosis (CF) centre, in whom stress UI could be common, as chronic coughing and sputum production are frequent symptoms associated with progressive lung disease in these patients. PATIENTS AND METHODS: An anonymous questionnaire was completed by 176 women with CF (mean age 24.6 years, SD 5.8) during routine assessments as outpatients. RESULTS: In all, 72 patients (41%) were classified as never incontinent; occasional UI was reported in 61 women (35%). Regular UI, occurring twice or more a month for at least two consecutive months in the last year, was reported in 43 patients (24%). Regular UI was associated with increasing age and a lower mean (SD) forced expiratory volume/s (of that predicted) than in women with no urinary symptoms, at 26.9 (6.5) years and 53.5 (23.5)%, and 23.1 (5.4) years and 65.5 (23.2)%, respectively (P < 0.01 and P < 0.05, respectively). All incontinent women recorded stress UI; coughing, laughing and physical activity were associated with UI in 92%, 33% and 21% of the patients, respectively. CONCLUSION: Stress UI is a common symptom in women with CF. As urine loss can be under-reported to the healthcare providers, women should be asked about incontinence as part of their routine follow-up. Pelvic floor muscle exercises are effective in treating stress UI and should be considered for those with CF and regular UI.     

Prevalence of Helicobacter pylori infection in patients with cystic fibrosis

IntroductionHelicobacter pylori (H. pylori) is one of the most common bacterial infections worldwide. The prevalence of Hp infection in cystic fibrosis (CF) is unclear. Thus, the aim of our study was to determine the prevalence of H. pylori infection in CF patients and to correlate H. pylori presence with CF expression.Material and methodsThe presence of H. pylori infection was assessed using a breath test with isotope-labeled urea in CF 79 patients compared to 302 healthy control subjects (HS).ResultsFifteen (19.0%) CF patients were H. pylori positive. No statistical differences in the basic clinical parameters or in their distribution were documented. No clinical factor was an independent risk factor of H. pylori infection. The corrected prevalence of H. pylori infection in pediatric CF patients and HS was 14.4% and 9.8%, respectively.ConclusionThe prevalence of H. pylori infection in CF patients is not different from that in healthy subjects.     

Prevalence and correlates of vertebral fractures in adults with cystic fibrosis

INTRODUCTION: Osteoporosis associated with cystic fibrosis (CF) is becoming increasingly important as the life expectancy of patients continues to increase. MATERIALS AND METHODS: We studied 191 adults with CF (18-50 years old; 100 men, 91 women). Total body, lumbar spine, and total proximal femur bone mineral density (BMD) were measured by dual-energy X-ray absorptiometry, and lateral spinal radiographs were taken for assessment of vertebral fractures. A range of anthropometric, clinical and biochemical variables were evaluated as potential correlates. RESULTS: BMD T score values at the lumbar spine lower than -2.5 SD were observed in 27.3% and 11.2% of male and female patients, respectively. These proportions fell to 14% and 9.9% for total hip and 10.4% and 12.1% for total body, in men and women, respectively. Vertebral deformities were identified in 26.7% of the patients with a slightly higher prevalence in males (32%) than in females (21%, P = 0.058). Multiple vertebral deformities were observed in 12% and 7.7% of men and women, respectively. BMD values were significantly related to body weight, FEV1, age of puberty and occasionally to cumulative steroid dose in both genders. BMD values were also significantly related with serum albumin, IgG and cholinesterase. Serum estradiol levels were found below the normal range in 23% of the women and 27% of the men, and was significantly related to femur BMD values in both women and men. Significantly lower serum estradiol and free testosterone levels were observed in men with vertebral fractures. Serum osteocalcin was below the normal range in 36% and urinary deoxypyridinoline above the normal range in 51% of the patients. CONCLUSIONS: This study indicates that osteoporosis is a common complication of CF, being related to disease progression and apparently due to both excess bone resorption and inadequate bone formation. Estradiol deficiency may have a significant role in the pathogenesis in both genders. Vertebral fracture prevalence is high and greater than expected from prevalent BMD values.     

Prevalence of unmet palliative care needs in adults with cystic fibrosis

BackgroundPhysical and emotional burdens impair quality of life (QoL) in many adults with cystic fibrosis (CF). Palliative care (PC) improves QoL in other serious illnesses, yet the full array of palliative needs amenable to PC are unknown in CF.MethodsWe surveyed 164 adults with CF using the Supportive Care Needs Survey 34 (SCNS-34) to assess unmet PC needs across five domains, the Edmonton Symptom Assessment System (ESAS) to assess symptom burden, and the Cystic Fibrosis Questionnaire—Revised (CFQ-R) to assess CF-specific QoL. We assessed associations between SCNS-34 domain scores and respondent characteristics, including symptom burden and FEV₁.ResultsMedian age was 29 years; 56% of respondents were male. Median FEV₁ was 57% predicted. 78% of respondents reported ≥1 unmet PC need; physical and daily living (72%) and psychological (66%) needs were most prevalent. Symptom burden was correlated with all SCNS-34 domains scores, and strongly correlated with the physical (r = 0.79) and psychological (r = 0.72) domain scores. FEV₁ was moderately inversely correlated with the physical domain score (r = −0.41). Forty-four of the 45 inverse correlations between SCNS-34 domain scores and CFQ-R domain scores were significant. Patient-reported depressive and anxiety symptoms were significantly associated with higher scores in five and four SCNS-34 domains, respectively.ConclusionsAdults with CF have substantial unmet PC needs. Patient-reported symptom burden is more strongly associated with reporting unmet PC needs than FEV₁. Routine screening of unmet PC needs, using tools such as the SCNS-34, may enable CF care teams to optimize the provision of primary and specialist PC.     

Risk factors for post-transplant lymphoproliferative disease in patients with cystic fibrosis

The objective of this study was to retrospectively analyze risk factors associated with post-transplant lymphoproliferative disease (PTLD) in a cohort of 112 lung transplant recipients with cystic fibrosis (CF). Prior to transplantation, patients were tested for Epstein-Barr virus (EBV), human herpesvirus (HHV types 1, 2, 3, 6, and 8), herpes zoster virus, and cytomegalovirus (CMV) serologies. PTLD diagnosis was established based on increased EBV viral charge plus clinical/radiographic findings and confirmed by biopsy. Negative EBV and HHV serologies at the time of lung transplantation (LTx) were significant risk factors associated with development of PTLD in patients with CF in the univariate logistic regression analysis (p < 0.05) and also in the multivariate analysis (odds ratio of 77.5 and 12.5, respectively). CMV serology, CMV mismatch, acute rejection in the first three months following LTx, HLA-A3 antigen expression, and female gender did not affect PTLD. Our study confirmed the presence of a strong association between negative EBV serology at the time of LTx and PTLD and suggested an independent effect of negative HHV serology on PTLD.     

Pneumothorax in cystic fibrosis: Prevalence and outcomes in Scotland

BackgroundPneumothorax is a feared complication of cystic fibrosis. With improved survival into adult life the incidence of pneumothorax is expected to increase. The optimal management of these patients is unclear.MethodsCase review of patients from the three Scottish adult CF centres.ResultsA total of 22 episodes of pneumothorax occurred in 20 patients over a 12 year period. 2 patients died as a result of the pneumothorax. 16 pneumothoraces were treated by insertion of an intercostal drain and 8 by observation. 8 patients suffered a prolonged air leak. 5 patients were treated with pleurodesis. Pneumothorax was associated with a small decline in lung function which persisted for at least 1 year.ConclusionPneumothorax can present a challenge to treat in adult CF. However successful outcomes can be achieved even in cases of prolonged air leaks. Current national guidelines help in selecting optimal pleural interventions.