Indoor hospital air and the impact of ventilation on bioaerosols: a systematic review.

J Hosp Infect. 2019 Jul 04;:

Authors: Stockwell RE, Ballard EL, O'Rourke P, Knibbs LD, Morawska L, Bell SC

Abstract
Hospital-acquired infections (HAI) continue to persist in hospitals, despite the use of increasingly strict infection control precautions. Opportunistic airborne transmission of potentially pathogenic bioaerosols may be one possible reason for this persistence. Therefore, we aimed to systematically review the concentrations and compositions of indoor bioaerosols in different areas within hospitals and the effects of different ventilation systems. Electronic databases (Medline and Web of Science) were searched to identify articles of interest. The search was restricted to articles published from 2000 to 2017 in English. Aggregate data was used to examine the differences in mean colony forming units per cubic metre (CFU/m3) between different hospital areas and ventilation types. A total of 36 journal articles met the eligibility criteria. The mean total bioaerosol concentrations in the different areas of the hospitals were highest in the inpatient facilities (77 CFU/m3, 95% confidence interval (CI), 55-108) compared with the restricted (4 CFU/m3, 95% CI, 10-15) and public areas (14 CFU/m3, 95% CI, 10-19). Hospital areas with natural ventilation had the highest total bioaerosol concentrations (201 CFU/m3, 95% CI, 135-300) compared with areas using conventional mechanical ventilation systems (20 CFU/m3, 95% CI, 16-24). Hospital areas using sophisticated mechanical ventilation systems (such as increased air changes per hour, directional flow and filtration systems) had the lowest total bioaerosol concentrations (9 CFU/m3, 95% CI, 7-13). Operating sophisticated mechanical ventilation systems in hospitals contributes to improved indoor air quality within hospitals, which assists in reducing the risk of airborne transmission of HAI.

PMID: 31279762 [PubMed - as supplied by publisher]

Seasonal respiratory virus testing in management of adult cystic fibrosis patients.

J Hosp Infect. 2019 Jul 04;:

Authors: Gohil S, Donaghy B, Tature D, Kowal J, Lea S, Lai FY, Range S, Tang JW

PMID: 31279759 [PubMed - as supplied by publisher]

Taskforce recommends coordinated effort to improve clinical research conduct and find highly effective CFTR-directed treatment for rare mutations.

J Cyst Fibros. 2019 Jul 03;:

Authors: Solomon GM, Nichols DP

PMID: 31279576 [PubMed - as supplied by publisher]

High Dose Cholecalciferol Supplementation In Adults With Cystic Fibrosis.

Pharmacotherapy. 2019 Jul 06;:

Authors: Janzen KM, Sakon C, Lehman A, Sommer B, Brown C

Abstract
INTRODUCTION: Despite the availability of consensus guidelines for treatment of vitamin D deficiency, there is a lack of prospective trials examining alternative dosing strategies for adult patients with cystic fibrosis (CF) who do not meet therapeutic goals with standard regimens.
OBJECTIVES: The primary objective of this study was to determine the efficacy of high-dose cholecalciferol supplementation in increasing serum vitamin D (25-OHD) levels in adult patients with CF.
METHODS: Patients were eligible for inclusion if they were ≥18 years old, had baseline 25-OHD levels less than 30 ng/mL, and were diagnosed with CF and pancreatic insufficiency. Patients were given a single dose of cholecalciferol 300,000 or 500,000 IU based on baseline 25-OHD levels. Response was defined by 25-OHD and ionized calcium levels at 3 months. At 6 months, responders received a second dose of the same strength, and non-responders were given a weekly supplement of cholecalciferol 50,000 IU in addition to cholecalciferol 500,000 IU. A second 25-OHD level was obtained at 9 months.
RESULTS: Of 46 patients enrolled, 32 patients (70%) completed the study. Baseline levels of 25-OHD significantly increased over time in the per-protocol population at 3 months and 9 months. A total of 16 patients (50%) were considered non-responders and required weekly supplementation.
CONCLUSION: A protocol using high-dose cholecalciferol or high-dose plus weekly cholecalciferol is safe and effective in treating adult patients with CF and pancreatic insufficiency. This article is protected by copyright. All rights reserved.

PMID: 31278763 [PubMed - as supplied by publisher]

Diagnosing Allergic Bronchopulmonary Aspergillosis: A Review.

Cureus. 2019 Apr 27;11(4):e4550

Authors: Patel AR, Patel AR, Singh S, Singh S, Khawaja I

Abstract
Dr. Hinson and his colleagues first described allergic bronchopulmonary aspergillosis (ABPA) in 1952. Later in 1977, Rosenberg proposed a diagnostic criteria for ABPA that even today remains widely acknowledged. Despite these steps taken, there still isn't a standardized diagnostic criteria set for ABPA although many have been proposed by various physicians over the years. ABPA is a condition caused by hypersensitivity to Aspergillus fumigatus antigens. It is seen most commonly in patients with either asthma or cystic fibrosis. In susceptible hosts, repeated inhalation of Aspergillus spores can cause an allergic response. Although a standardized diagnostic criteria is re-quired, there is no single test that establishes the diagnosis oth-er than a demonstration of central bronchiectasis (CB) with nor-mal tapering bronchi, a feature that is still considered pathognomonic of ABPA. Because of lack of standardized diagnostic criteria and screening, even today ABPA is under diagnosed and often times treatment for it is delayed. This can lead to complications in patients like pulmonary fibrosis, bronchiectasis with chronic sputum production, and increasingly severe persistent asthma with loss of lung function. For this alone, it becomes imperative that the diagnostic criteria guidelines need to be reviewed and standardized preferably with the help of larger research studies. In the following review article, we address the epidemiology, pathophysiology, and the current cumulative view regarding the diagnosis of ABPA.

PMID: 31275774 [PubMed]

Ventilation efficiency to exercise in patients with cystic fibrosis.

Pediatr Pulmonol. 2019 Jul 05;:

Authors: Kampouras A, Hatziagorou E, Avramidou V, Georgopoulou V, Kirvassilis F, Hebestreit H, Tsanakas J

Abstract
INTRODUCTION: Exercise ventilation efficiency index in cardiopulmonary exercise testing (CPET) is elevated in patients with heart failure providing useful information on disease progression and prognosis. Few data, however, exist for ventilation efficiency index among cystic fibrosis (CF) patients.
AIMS: To assess ventilation efficiency index (ΔVE/ΔVCO2 or V'E/V'CO2 slope) and intercept of ventilation (VE-intercept) in CF patients with mild, moderate, and severe cystic fibrosis (CF) lung disease. To assess possible correlations with ventilation inhomogeneity and structural damages as seen on high resolution computed tomography (HRCT).
METHODS: CF patients with mild (FEV1  > 80%, n = 47), moderate (60% < FEV1  < 80%, n = 21), and severe (FEV1  < 60%, n = 9) lung disease, mean age 14.9 years participated. Peak oxygen uptake (VO2 peak), pulmonary ventilation at peak exercise (VE), respiratory equivalent ratios for oxygen and carbon dioxide at peak exercise (VE/VO2 , VE/VCO2 ), end-tidal CO2 (PetCO2 ), and ΔVE/ΔVCO2 , ΔVE/ΔVO2 in a maximal CPET along with spirometry and multiple breath washout indices were examined. HRCT scans were performed and scored using Bhalla score.
RESULTS: Mean ΔVE/ΔVCO2 showed no significant differences among the three groups (P = .503). Mean VEint discriminated significantly among the different groups (p 2 < 0.001). Ventilation efficiency index did not correlate either with LCI or Bhalla score. However, VE together with ΔVE/ΔVCO2 slope could predict Bhalla score (r 2  = 0.869, P = .006).
CONCLUSION: No significant differences were found regarding ΔVE/ΔVCO2 slope levels between the three groups. Ventilation intercept (VEint ) was elevated significantly as disease progresses reflecting increased dead space ventilation. CF patients retain their ventilation efficiency to exercise even as lung function deteriorates by adopting a higher respiratory rate along with increased dead space ventilation.

PMID: 31276310 [PubMed - as supplied by publisher]

FDG PET/CT of Gardnerella vaginalis Infection.

Clin Nucl Med. 2019 Aug;44(8):660-662

Authors: Foret T, Dhomps A, Dauwalder O, Skanjeti A, Tordo J

Abstract
We report the case of a 23-year-old woman with a history of cystic fibrosis and bilung transplantation, who presented clinically cervical swollen lymph nodes with alteration of her general state. F-FDG PET/CT was performed because of lymphoma suspicion and showed cervical and pelvic hypermetabolic lymphadenopathies, with linear vaginal hypermetabolism. There was an increase of lactate dehydrogenase, and Epstein-Barr virus detection was negative. A right cervical lymph node biopsy was performed, with no lymphoma involvement. Complementary microbiological investigations showed positive results for Gardnerella vaginalis. F-FDG PET/CT lymphatic node hypermetabolism is not specific to lymphoma, particularly in immunocompromised patients.

PMID: 31274617 [PubMed - in process]

Interventions for treating neuropathic pain in people with sickle cell disease.

Cochrane Database Syst Rev. 2019 Jul 05;7:CD012943

Authors: Asnani MR, Francis DK, Brandow AM, Hammond Gabbadon CE, Ali A

Abstract
BACKGROUND: Pain is the hallmark of sickle cell disease (SCD) and it can be severe, frequent and unpredictable. Although nociceptive pain is more common, at times, people with SCD may have neuropathic pain. The latter can occur due to peripheral or central nerve injury. This review is focused on identifying treatment of only painful sensory neuropathy in people with SCD.
OBJECTIVES: To determine the effectiveness and safety of any pharmacological or non-pharmacological therapies for treating neuropathic pain in people with SCD.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched trial registries, the reference lists of relevant articles and reviews and contacted experts in the field.Date of last search: 31 January 2019.
SELECTION CRITERIA: Randomised controlled trials (RCTs) (parallel or cross-over in design), quasi-RCTs of pharmacological or non-pharmacological therapies for treating neuropathic pain in people with SCD compared to placebo or another intervention in any category (i.e. pharmacological or non-pharmacological).
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed all trials identified by the searches and extracted relevant data. Two authors independently assessed the risk of bias in the selected trials using the Cochrane risk of bias tool. Two review authors independently rated the quality of the evidence for each outcome using the GRADE guidelines.
MAIN RESULTS: One RCT of 22 participants with SCD, conducted in the USA was included in this review. Participants were randomly assigned to either pregabalin (n = 11) or placebo (n = 11). Oral pregabalin was administered at an initial dose of 75 mg twice daily. The drug was titrated at increments of 75 mg to a maximum of 600 mg daily or decreased by 75 mg per day if necessary, based on clinical presentation and pain level. Neuropathic pain was assessed using self-reports on the Leeds Assessment of Neuropathic Symptoms and Signs (S-LANNS) scale and the Neuropathic Pain Symptom Inventory (NPSI), where higher scores were indicative of more pain. Outcomes included self-reported pain, quality of life and withdrawal due to adverse effects measured at baseline and monthly for three months post-intervention. The overall risk of bias was low with a high risk of bias due to attrition.In relation to this reviews primary outcomes, for self-reported neuropathic pain relief, given the paucity of data, we are very uncertain whether there is a difference between the pregabalin and placebo groups at the end of three months as measured by the S-LANSS scale, mean difference (MD) -2.00 (95% confidence interval (CI) -9.18 to 5.18), or the NPSI scale, MD -11.10 (95% CI -33.97 to 11.77) (very low-quality evidence). There was no report of 'Patient Global Impression of Change' in the included trial.Although the mean quality of life scores (Short Form-36) at three months showed small increases in seven of the eight domains post-intervention in the pregabalin group as compared to the placebo group, this was very low-quality evidence and we are very uncertain whether pregabalin increases quality of life. Neither of our pre-defined outcomes of 'time to improvement of symptoms' or 'changes in sleep quality', were measured in the included trial.While treatment-related adverse effects appeared higher in pregabalin group than the placebo group at three months, this was very low-quality evidence and we are very uncertain whether there is a difference, RR 1.33 (95% CI 0.39 to 4.62) (very low-quality evidence). There was one withdrawal for adverse effects in the pregabalin group while three people withdrew or dropped out from the placebo group due to adverse effects and complications and hospitalisation related to SCD.
AUTHORS' CONCLUSIONS: The included trial provided very low-quality evidence. Self-reported pain relief was greater in the pregabalin group compared to the placebo control group but only using the S-LANSS scale and we are very unsure whether there is a difference. While the pregabalin group tended to have improved quality of life over the duration of the trial, this was very low-quality evidence and we are uncertain whether there is a difference. Adverse effects and withdrawals were similar across the treatment and placebo control group in trial. There are both insufficient trials addressing this review question and insufficient outcomes addressed in the single included RCT. Therefore, there is still a significant gap in evidence on interventions for neuropathic pain in people with SCD.

PMID: 31273755 [PubMed - as supplied by publisher]

Time trends in diagnostic testing for PCD in Europe.

Eur Respir J. 2019 Jul 04;:

Authors: Halbeisen FS, Shoemark A, Barbato A, Boon M, Carr S, Crowley S, Hirst R, Karadag B, Koerner-Rettberg C, Loebinger MR, Lucas JS, Maitre B, Mazurek H, Özçelik U, Martinů V, Schwerk N, Thouvenin G, Tschanz SA, Yiallouros P, Goutaki M, Kuehni CE

PMID: 31273043 [PubMed - as supplied by publisher]

Pregnancy outcome in women with cystic fibrosis and poor pulmonary function.

J Cyst Fibros. 2019 Jul 01;:

Authors: Reynaud Q, Rousset Jablonski C, Poupon-Bourdy S, Denis A, Rabilloud M, Lemonnier L, Nove-Josserand R, Durupt S, Touzet S, Durieu I, Participating Centers of the French Cystic Fibrosis Registry

Abstract
BACKGROUND: To investigate how poor pre-gestational pulmonary function influenced pregnancy outcome and clinical status evolution in women with cystic fibrosis.
METHODS: Pregnancies in women without lung transplantation with a first delivery reported to the French cystic fibrosis registry between 2000 and 2012 were identified. Pregnancy outcomes and clinical trends (body mass index - BMI, and pulmonary function) over a 4-year follow-up in women with poor pre-gestational pulmonary function, defined as forced expiratory volume (FEV1) ≤ 50%, were compared to those in women with FEV1 ˃ 50%.
RESULTS: A total of 149 women had a first delivery and 36 (24.2%) of these had pre-gestational FEV1 ≤ 50%. There was no significant difference in age or frequency of assisted conception between the 2 groups. The rate of cesarean section was significantly higher in women with FEV1 ≤ 50% (43.7% vs. 21.1%, p = .01). The frequency of preterm birth did not differ significantly between the two groups, but median infant birthweight was significantly lower in women with FEV1 ≤ 50% (2705 g; range: 650-3700 vs. 3044 g; range: 1590-3860, p = .003). Despite significantly lower FEV1 and BMI the year before pregnancy for women with poor pulmonary function, the decline in these parameters during the study period did not differ significantly between the two groups.
CONCLUSION: Poor pre-gestational pulmonary function in women with cystic fibrosis was associated with a higher rate of cesarean section and a clinically significant impact on fetal growth, but was not associated with more important pulmonary and nutritional decline over the study period.

PMID: 31272894 [PubMed - as supplied by publisher]

Inhaled corticosteroids for cystic fibrosis.

Cochrane Database Syst Rev. 2019 Jul 04;7:CD001915

Authors: Balfour-Lynn IM, Welch K, Smith S

Abstract
BACKGROUND: The reduction of lung inflammation is one of the goals of cystic fibrosis therapy. Inhaled corticosteroids are often used in this respect to treat children and adults with cystic fibrosis. The rationale for this is their potential to reduce lung damage arising from inflammation, as well as their effect on symptomatic wheezing. It is important to establish the current level of evidence for the risks and benefits of inhaled corticosteroids, especially in the light of their known adverse effects on growth. This is an update of a previously published review; however, due to the lack of research in this area, we do not envisage undertaking any further updates.
OBJECTIVES: To assess the effectiveness of taking regular inhaled corticosteroids compared to not taking them in children and adults with cystic fibrosis.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We requested information from pharmaceutical companies manufacturing inhaled corticosteroids and authors of identified trials.Date of most recent search of the Group's Trials Register: 19 November 2018.
SELECTION CRITERIA: Randomised or quasi-randomised trials, published and unpublished, comparing inhaled corticosteroids to placebo or standard treatment in individuals with cystic fibrosis.
DATA COLLECTION AND ANALYSIS: Two independent authors assessed methodological quality and risk of bias in trials using established criteria and extracted data using standard pro formas. The quality of the evidence was assessed using the GRADE criteria.
MAIN RESULTS: The searches identified 35 citations, of which 27 (representing 13 trials) were eligible for inclusion. These 13 trials reported the use of inhaled corticosteroids in 525 people with cystic fibrosis aged between 6 and 55 years. One was a withdrawal trial in 171 individuals who were already taking inhaled corticosteroids. Methodological quality and risk of bias were difficult to assess from published information.Objective measures of airway function were reported in most trials but were often incomplete and reported at different time points. We found no difference in forced expiratory volume in one second (FEV1) or forced vital capacity (FVC) % predicted in any of the trials, although the quality of the evidence was low due to risks of bias within the included trials and low participant numbers. We are uncertain whether inhaled corticosteroids result in an improvement in exercise tolerance, bronchial hyperreactivity or exacerbations as the quality of the evidence was very low. Data from one trial suggested that inhaled corticosteroids may make little or no difference to quality of life (low-quality evidence).Three trials reported adverse effects, but the quality of the evidence is low and so we are uncertain whether inhaled corticosteroids increase the risk of adverse effects. However, one study did show that growth was adversely affected by high doses of inhaled corticosteroids.
AUTHORS' CONCLUSIONS: Evidence from these trials is of low to very low quality and insufficient to establish whether inhaled corticosteroids are beneficial in cystic fibrosis, but withdrawal in those already taking them has been shown to be safe. There is some evidence they may cause harm in terms of growth. It has not been established whether long-term use is beneficial in reducing lung inflammation, which should improve survival, but it is unlikely this will be proven conclusively in a randomised controlled trial.

PMID: 31271656 [PubMed - as supplied by publisher]

Personalized exercise training in chronic lung diseases.

Respirology. 2019 Jul 03;:

Authors: Armstrong M, Vogiatzis I

Abstract
Chronic respiratory diseases (CRD) are characterized by exertional dyspnoea, exercise limitation and reduced health-related quality of life (QoL). Exercise training is essential for improving symptoms, physical function and QoL. Current research available supports the effectiveness of exercise training in patients with chronic obstructive pulmonary disease (COPD), cystic fibrosis and interstitial lung disease (ILD). However, recent studies have also shown safety and effectiveness of exercise training in patients with pulmonary arterial hypertension (PAH) and asthma. Despite the lack of clinical guidelines for exercise training in PAH, a recent Cochrane review has reported improvements in functional capacity and effective reductions in mean pulmonary arterial pressure. In the other CRD, a number of Cochrane reviews, supported by numerous randomized controlled trials, have been published outlining the benefits of different types of exercise training. The aim of this review is to establish the principles and modalities of personalized exercise training and the effects of exercise training across a number of CRD. In addition, this review provides information on personalized exercise prescription for CRD patients with co-morbidities.

PMID: 31270909 [PubMed - as supplied by publisher]

Functional and metabolic impairment in cigarette smoke-exposed macrophages is tied to oxidative stress.

Sci Rep. 2019 Jul 03;9(1):9624

Authors: Aridgides DS, Mellinger DL, Armstrong DA, Hazlett HF, Dessaint JA, Hampton TH, Atkins GT, Carroll JL, Ashare A

Abstract
Cigarette smoke inhalation exposes the respiratory system to thousands of potentially toxic substances and causes chronic obstructive pulmonary disease (COPD). COPD is characterized by cycles of inflammation and infection with a dysregulated immune response contributing to disease progression. While smoking cessation can slow the damage in COPD, lung immunity remains impaired. Alveolar macrophages (AMΦ) are innate immune cells strategically poised at the interface between lungs, respiratory pathogens, and environmental toxins including cigarette smoke. We studied the effects of cigarette smoke on model THP-1 and peripheral blood monocyte derived macrophages, and discovered a marked inhibition of bacterial phagocytosis which was replicated in primary human AMΦ. Cigarette smoke decreased AMΦ cystic fibrosis transmembrane conductance regulator (CFTR) expression, previously shown to be integral to phagocytosis. In contrast to cystic fibrosis macrophages, smoke-exposed THP-1 and AMΦ failed to augment phagocytosis in the presence of CFTR modulators. Cigarette smoke also inhibited THP-1 and AMΦ mitochondrial respiration while inducing glycolysis and reactive oxygen species. These effects were mitigated by the free radical scavenger N-acetylcysteine, which also reverted phagocytosis to baseline levels. Collectively these results implicate metabolic dysfunction as a key factor in the toxicity of cigarette smoke to AMΦ, and illuminate avenues of potential intervention.

PMID: 31270372 [PubMed - in process]

CFTR-PTEN-dependent mitochondrial metabolic dysfunction promotes Pseudomonas aeruginosa airway infection.

Sci Transl Med. 2019 Jul 03;11(499):

Authors: Riquelme SA, Lozano C, Moustafa AM, Liimatta K, Tomlinson KL, Britto C, Khanal S, Gill SK, Narechania A, Azcona-Gutiérrez JM, DiMango E, Saénz Y, Planet P, Prince A

Abstract
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor best known for regulating cell proliferation and metabolism. PTEN forms a complex with the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) at the plasma membrane, and this complex is known to be functionally impaired in CF. Here, we demonstrated that the combined effect of PTEN and CFTR dysfunction stimulates mitochondrial activity, resulting in excessive release of succinate and reactive oxygen species. This environment promoted the colonization of the airway by Pseudomonas aeruginosa, bacteria that preferentially metabolize succinate, and stimulated an anti-inflammatory host response dominated by immune-responsive gene 1 (IRG1) and itaconate. The recruitment of myeloid cells induced by these strains was inefficient in clearing the infection and increased numbers of phagocytes accumulated under CFTR-PTEN axis dysfunction. This central metabolic defect in mitochondrial function due to impaired PTEN activity contributes to P. aeruginosa infection in CF.

PMID: 31270271 [PubMed - in process]

[Value of sweat conductivity testing in the diagnosis of cystic fibrosis in children].

Zhonghua Er Ke Za Zhi. 2019 Jul 02;57(7):548-552

Authors: Wang XL, Yin ZF, Shen YL, Liu H, Mogayzel PJ, Zhao SY

Abstract
Objective: To assess the diagnostic value of sweat conductivity testing in Chinese children with cystic fibrosis (CF). Methods: This is a retrospective study. Sweat conductivity tests were conducted in 45 CF children (CF group) and 200 non-CF children (non-CF group) diagnosed with other chronic pulmonary diseases at the No. 2 Department of Respiratory Medicine, Beijing Children's Hospital from May 2014 to June 2018. Pearson's chi-square test was used to assess the differences between CF and non-CF groups. A receiver operating characteristic curve was constructed to calculate the best cut-off value to diagnose or rule out CF. The pulmonary function parameters (forced expiratory volume in the first second, forced vital capacity,forced expiratory flows at 75% of exhaled vital capacity) of CF children over 6 years old were analyzed. The relationship between sweat conductivity and pulmonary function was compared between the two groups (80-120mmol/L vs.>120mmol/L). Results: The age of CF group was 9 (7,12) years old, 19 males (42%) and 26 females(58%); the age of non-CF group was 8 (5,11) years old, 106 males (53%) and 94 females(47%). The results of sweat conductivity test showed that sweat conductivity in CF group 108(99, 122) mmol/L was significantly higher than that in non-CF group 43(36, 52) mmol/L (χ(2)=207, P<0.01). A cut-off value of 80 mmol/L for CF diagnosis showed a sensitivity of 93.3% and a specificity of 98.5%. The receiver operating characteristic curve analysis suggested the best conductivity cut-off value for the diagnosis of CF was at 83.5 mmol/L,with a sensitivity of 93.3% and a specificity of 100%,and an area under the curve of 0.993 (95% confidence interval 0.985-1.000). The best conductivity cut-off value to rule out CF diagnosis was at 63.5 mmol/L,with a sensitivity of 97.8% and a specificity of 90.5%. There was no correlation between the level of sweat conductivity and the extent of pulmonary function decline. Conclusions: Sweat conductivity testing can be used for the screening of CF in Chinese children. A diagnosis of CF should be considered if the value is greater than 80 mmol/L.

PMID: 31269556 [PubMed - in process]

Missense mutation within cystic fibrosis transmembrane conductance regulator (CFTR) gene is associated with selected parameters of the frozen-thawed sperm in Holstein-Friesian bulls.

Pol J Vet Sci. 2019 Jun;22(2):221-225

Authors: Kaminski S, Hering DM, Kordan W, Lecewicz M

Abstract
In our previous Genome-wise Association Study we found that Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) is a candidate gene for sperm motility in fresh semen of Holstein-Friesian bulls. Since in cows thawed semen is commonly used for the artificial insemination (AI) we have decided to find out whether functional polymorphism within CFTR gene coding sequence is associated with selected parameters of thawed sperm, including their motility evaluated by computer-assisted sperm analysis (CASA), the activity of three antioxidant enzymes: glutathione peroxidase (GPx) catalase (CAT), superoxide dismutase (SOD), ATP content and integrity of sperm membranes. One hundred twenty Holstein Friesian bulls kept in uniform environmental conditions (one AI company) were included in the study. Significant associations between genotypes of missense mutation within exon 11 of the CFTR gene (Met468Leu) and the activity of antioxidant enzymes and sperm mitochondrial function were revealed. No effect of CFTR genotypes on sperm motility was observed. Significant differences in CAT and SOD activity were found between AA and TT homozygous individuals. Bulls with TT genotype had the lowest activity of both antioxidant enzymes. The same bulls also showed the lowest number of sperm with active mitochondria. Our results demonstrate that missense mutation Met468Leu within CFTR gene is associated with antioxidant enzyme activity and mitochondrial function of bovine thawed sperm without affecting their motility.

PMID: 31269333 [PubMed - in process]

Effect of changes in tidal volume on multiple breath washout outcomes.

PLoS One. 2019;14(7):e0219309

Authors: Ratjen F, Jensen R, Klingel M, McDonald R, Moore C, Benseler N, Wilson D, Stanojevic S

Abstract
The lung clearance index (LCI), measured by multiple breath washout (MBW), reflects global ventilation inhomogeneity and is a sensitive marker of early obstructive airway disease. For the MBW test to accurately reflect a subject's gas mixing within the lungs, the breathing pattern should represent physiologically appropriate tidal volumes (VT) and respiratory rate (RR). We aimed to assess whether changes in VT impact MBW outcome measures with a series of prospective and retrospective studies. MBW testing was performed using the Exhalyzer ® D (EcoMedics AG, Switzerland). Healthy adult subjects performed MBW with uninstructed tidal breathing and a series of instructed tidal breathing tests, designed to isolate specific features of the breathing pattern. In addition, we retrospectively analyzed MBW data from two pediatric multi-centre interventional studies of cystic fibrosis (CF) subjects to determine the range of VT observed during uninstructed breathing, and whether breathing outside this range impacted results. The LCI was lower, but not significantly different between deep breathing at 20 ml/kg body weight and uninstructed tidal breathing; whereas LCI was significantly higher during shallow breathing compared with normal tidal breathing. For the majority of subjects with CF (80%), VT ranged from 9-15mL/kg. Within the observed VT range, LCI was similar in trials with mean VT /kg below this range compared to trials with VT /kg within the range. If subjects breathe naturally and are not instructed to use specific targets, the range of VT is within physiologically appropriate limits and normal variations observed do not impact MBW outcomes.

PMID: 31269068 [PubMed - in process]

Acute Recurrent and Chronic Pancreatitis as Initial Manifestations of Cystic Fibrosis and Cystic Fibrosis Transmembrane Conductance Regulator-Related Disorders.

Pancreas. 2019 Jul 01;:

Authors: Baldwin C, Zerofsky M, Sathe M, Troendle DM, Perito ER

Abstract
OBJECTIVES: Recurrent pancreatitis is considered a rare manifestation of cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction; this case series highlights that pancreatitis can be a presenting symptoms of cystic fibrosis (CF) or a CFTR-related disorder (CFTR-RD).
METHODS: Retrospective review of patients younger than 30 years diagnosed as having acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP) and subsequently diagnosed as having CF or CFTR-RD.
RESULTS: Among 18 patients, median time from diagnosis of ARP/CP to diagnosis of CF was 0.4 years (range, 0-33 years). Eight were classified as having CF by elevated sweat chloride testing (SCT). Five had intermediate SCT (30-59 mmol/L) with 2 pathogenic mutations. Five had CFTR-RD with intermediate SCT and 0 to 1 pathogenic mutations. Eight patients (44%) had exocrine pancreatic insufficiency, and pancreatic fluid collections were more common in this group. Based on the CFTR mutation, 6 patients were eligible for CFTR potentiator therapy, although none received it during the study period. Nine of the 18 had ≥1 other likely CF manifestations, including sinusitis (33%), nasal polyps (11%), pneumonia (22%), and gallbladder disease (22%).
CONCLUSIONS: Cystic fibrosis or CFTR-RD can present as ARP/CP. Complete diagnostic testing for CFTR-RD in patients with ARP/CP will broaden treatment options and help to identify comorbid illness.

PMID: 31268981 [PubMed - as supplied by publisher]

Inhibition of CFTR-mediated intestinal chloride secretion as potential therapy for bile acid diarrhea.

FASEB J. 2019 Jul 03;:fj201901166R

Authors: Duan T, Cil O, Tse CM, Sarker R, Lin R, Donowitz M, Verkman AS

Abstract
Bile acid diarrhea (BAD) is common with ileal resection, Crohn's disease, and diarrhea-predominant irritable bowel syndrome. Here, we demonstrate the efficacy of cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor (R)-benzopyrimido-pyrrolo-oxazine-dione-27 (BPO-27) in reducing bile acid-induced fluid and electrolyte secretion in colon. Short-circuit current measurements in human T84 colonic epithelial cells and planar colonic enteroid cultures showed a robust secretory response following mucosal but not serosal addition of chenodeoxycholic acid (CDCA) or its taurine conjugate, which was fully blocked by CFTR inhibitors, including (R)-BPO-27. (R)-BPO-27 also fully blocked CDCA-induced secretory current in murine colon. CFTR activation by CDCA primarily involved Ca2+ signaling. In closed colonic loops in vivo, luminal CDCA produced a robust secretory response, which was reduced by ∼70% by (R)-BPO-27 or in CFTR-deficient mice. In a rat model of BAD produced by intracolonic infusion of CDCA, (R)-BPO-27 reduced the elevation in stool water content by >55%. These results implicate CFTR activation in the colon as a major prosecretory mechanism of CDCA, a bile acid implicated in BAD, and support the potential therapeutic efficacy of CFTR inhibition in bile acid-associated diarrheas.-Duan, T., Cil, O., Tse, C. M., Sarker, R., Lin, R., Donowitz, M., Verkman, A. S. Inhibition of CFTR-mediated intestinal chloride secretion as potential therapy for bile acid diarrhea.

PMID: 31268738 [PubMed - as supplied by publisher]

Symptom Burden and Unmet Existential Needs in Adults With Cystic Fibrosis.

West J Nurs Res. 2019 Jul 03;:193945919852585

Authors: Trandel ET, Pilewski JM, Dellon EP, Moreines LT, Yabes JG, Jeong K, Arnold RM, Kavalieratos D

Abstract
Although patients with cystic fibrosis (CF) experience many symptoms and impaired quality of life, little is known about existential distress. This multivariable logistic regression evaluated the relationship between symptom burden and five existential needs representing existential distress in 164 adults with CF. Eleven percent of participants reported no symptom burden, 61% mild burden, and 28% moderate/severe burden. The most prevalent existential needs were fears about CF worsening (50%) and uncertainty about the future (39%). Participants with moderate/severe symptom burden were likelier to report needing support with all five needs than participants with no or mild burden. For each six-point increase in burden, there was an increased odds of reporting need for support with learning to feel in control, feelings about death and dying, fears about CF worsening, uncertainty about the future, and concerns about worries of others. CF-specific palliative care support based on these prevalent unmet existential needs should be developed and provided.

PMID: 31267835 [PubMed - as supplied by publisher]