The Role of Continuous Glucose Monitoring in Detecting Early Dysglycemia and Clinical Outcomes in Patients with Cystic Fibrosis.

Cystic fibrosis-related diabetes (CFRD) is the most common comorbidity in patients with cystic fibrosis (CF). CFRD has been correlated with important clinical outcomes, including poor nutrition, reduced pulmonary function, and earlier mortality. However, clinical decline due to abnormalities of blood glucose (dysglycemia) begins early in CF, before the diagnosis of CFRD by the gold-standard oral glucose tolerance test (OGTT). Continuous glucose monitoring (CGM) has been validated in patients with CF and has been recognized as a valuable tool in detecting early glucose abnormalities in patients with CF. Several CGM parameters have been used to predict CFRD in some but not all studies, and there is no consensus regarding CGM use for diagnostic purposes. Thus, it remains a complementary test to OGTT in CFRD diagnosis. The aim of this review is to provide an update on the pathophysiological mechanisms of CFRD, recent advances in the use of CGM for CFRD screening, and the association between CGM measures and CF-related clinical outcomes.

Evaluating the contribution of the Glittre-ADL test in adults with cystic fibrosis.

BACKGROUND AND OBJECTIVES: Cardiopulmonary and skeletal muscle impairment and poor physical activity are potential contributors to reduced functional capacity in cystic fibrosis (CF). The Glittre-ADL test (TGlittre) has great potential for clinical use in adult CF adults, as it meets the need for a comprehensive assessment of physical function using tasks similar to activities of daily living. This study aimed to evaluate the performance of TGlittre in CF adults compared to the 6-min walk test (6MWT) and, secondarily, to quantify the associations of their results with pulmonary function, muscle strength, and health-related quality of life (HRQoL). METHODS: This cross-sectional study evaluated 34 CF adults and compared them with 34 subjects from a control group. The participants underwent the following assessments: functional capacity using TGlittre and 6MWT; spirometry; respiratory muscle strength; handgrip strength (HGS); and HRQoL using the Cystic Fibrosis Questionnaire-Revised (CFQ-R). RESULTS: While CF patients showed a longer time to perform TGlittre compared to controls (134 (119-150) versus 107 (95-126) % of the predicted time p = 0.0002), no difference between these groups was observed in the 6MWT. When the second TGlittre was compared to the first TGlittre, there was a significant decrease in total time for both CF patients (p < 0.0001) and controls (p = 0.0001). TGlittre time correlated with 6MWT distance (6MWD) (rs = -0.641, p < 0.0001), HGS (rs = -0.364, p = 0.034), peripheral oxygen saturation at the end of the test (rs = -0.463, p = 0.006) and the "digestive symptoms" domain of CFQ-R (rs = 0.376, p = 0.028). TGlittre time was shorter in patients who engaged in regular physical activity (3.10 (2.49-3.39) min versus 3.28 (2.95-3.53) min, p = 0.016). CONCLUSIONS: TGlittre is more effective than the 6MWT in detecting limitations during exercise. There is an important learning effect of TGlittre in adult CF patients. TGlittre time was correlated with 6MWD, HGS, oxygen saturation level, and the patient's level of physical activity.

Early glucose abnormalities revealed by continuous glucose monitoring associate with lung function decline in cystic fibrosis: A five-year prospective study.

BACKGROUND: Cystic fibrosis related diabetes (CFRD) is commonly associated with declining lung function and nutritional status. We aimed to evaluate the pulmonary impact of early glucose abnormalities by using 2-h standard oral glucose tolerance testing (OGTT) and continuous glucose monitoring (CGM) in people with cystic fibrosis (PwCF). METHODS: PwCF aged ≥10 years old without known CFRD were included in a five-year prospective multicentre study. Annual evaluation of nutritional status, lung function, OGTT and CGM was set up. Associations between annual rate changes (Δ) in lung function, ΔFEV1 (forced expiratory volume in 1 s) percentage predicted (pp) and ΔFVC (forced vital capacity) pp., and annual rate changes in OGTT or CGM variables were estimated with a mixed model with a random effect for subject. RESULTS: From 2009 to 2016, 112 PwCF (age: 21 ± 11 years, BMI (body mass index) z-score: -0.55 ± 1.09, FEV1pp: 77 ± 24 %, 2-h OGTT glucose: 122 ± 44 mg/dL, AUC (area under curve) >140 mg/dL: 1 mg/dL/day (0.2, 3.0) were included. A total of 428 OGTTs and 480 CGMs were collected. The participants presented annual decline of FVCpp and FEV1pp at -1.0 % per year (-1.6, -0.4), p < 0.001 and - 1.9 % per year (-2.5, -1.3), p < 0.001 respectively without change in BMI z-score during the study. Variation of two-hour OGTT glucose was not associated with declining lung function, as measured by ΔFEV1pp (p = 0.94) and ΔFVCpp (p = 0.90). Among CGM variables, only increase in AUC >140 mg/dL between two annual visits was associated with a decrease in ΔFVCpp (p < 0.05) and ΔFEV1pp (p < 0.05). CONCLUSIONS: This prospective study supports the fact that early glucose abnormalities revealed by CGM predict pulmonary function decline in PwCF, while 2-h standard OGTT glucose is not associated with pulmonary impairment.

Paciente varón de tres años con sibilancias y tos crónica / Three-Year-Old Male with Wheezing and Chronic Cough

Se presenta el caso de un niño de 3 años con diagnóstico de asma, rinitis alérgica, características craneofaciales dismórficas e infecciones respiratorias altas y bajas recurrentes, manejado como asma desde un inicio. Como parte del estudio de comorbilidades, se decide realizar una prueba del sudor que sale en rango intermedio y más tarde se encuentra una mutación, donde se obtiene un resultado positivo para una copia que se asocia a fibrosis quística. Se revisará el caso, así como el diagnóstico, clínica y tratamiento del síndrome metabólico relacionado con el regulador de conductancia transmembrana de fibrosis quística (CRMS).

We present the case of a 3-year-old boy with a diagnosis of asthma, allergic rhinitis, dysmorphic craniofacial characteristics and recurrent upper and lower respiratory infections, managed as asthma from the beginning. As part of the study of comorbidi-ties, it was decided to carry out a sweat test that came out in the intermediate range and later one mutation was found, where a positive result was obtained for a copy that is associated with cystic fibrosis. The case will be reviewed, as well as the diagnosis, symptoms and treatment of the metabolic syndrome related to the cystic fibrosis trans-membrane conductance regulator (CRMS).

Novel time-saving OGTT sparing HbA1c-HOMA2 based algorithm for the diagnosis of cystic fibrosis-related diabetes.

AIMS: The diagnosis of cystic fibrosis-related diabetes (CFRD) faces several challenges. We propose a novel screening algorithm to alleviate the burden of cystic fibrosis (CF). METHODS: Through a retrospective cross-sectional single-centre study, HbA1c and HOMA2 indices were assessed in multiple models as alternative diagnostic tools from OGTT data. We sought to establish specific thresholds for CFRD screening with oral glucose tolerance test (OGTT) as gold standard. We evaluated various straightforward or sequential approaches, in terms of diagnostic accuracy while also quantify the potential reduction in OGTTs through these different methods. RESULTS: HOMA indices were recovered in 72 patients. We devised a composite index that combines HbA1c and HOMA-B: Diabetes Predicting Index in cystic fibrosis (DIPIc) = (HbA1c(%) × 3.455) - (HOMA-B(%) ×  0.020) - 19.294. This index yields the highest screening accuracy according to receiver-operating characteristics curves. Using a stepwise algorithm that incorporates DIPIc decreases the requirement for annual OGTTs. A CFRD exclusion cutoff less than -1.7445 (sensitivity 98 %), in conjunction with a CFRD diagnostic threshold greater than 0.4543 (specificity 98 %) allows for 71 % OGTT sparing. CONCLUSION: The composite index DIPIc is a suitable, less invasive screening method for CFRD, which enables to avoid many OGTTs.

Unusual Cause of Hemoptysis in a Woman With Cystic Fibrosis.

CASE PRESENTATION: A 20-year-old patient with cystic fibrosis (CF) complicated by pansinusitis, pancreatic insufficiency, and diabetes presented to the local ED after an episode of large-volume hemoptysis at home. At baseline, she had advanced lung disease (FEV1, 0.97 L; 31% predicted) and upper lobe-predominant fibrocavitary changes. She was intermittently followed at a regional lung transplant center. She was previously evaluated for transplant but was not listed at the time of this presentation because of nontuberculous mycobacteria infection. She had never used tobacco, without reports of recreational inhaled drug use. Her mother had CF, and one of her brothers died in 2018 at age 24 of respiratory failure resulting from the disease.

Continuous glucose monitoring and advanced glycation endproducts for prediction of clinical outcomes and development of cystic fibrosis-related diabetes in adults with CF.

Introductions: Cystic fibrosis-related diabetes (CFRD) is associated with pulmonary decline, compromised nutritional status, and earlier mortality. Onset is often insidious, so screening for early detection of glycemic abnormalities is important. Continuous glucose monitoring (CGM) has been validated in people with CF and has been shown to detect early glycemic variability otherwise missed on 2-hour oral glucose tolerance testing (OGTT). We previously reported that CGM measures of hyperglycemia and glycemic variability are superior to hemoglobin A1c (HbA1c) in distinguishing those with and without CFRD. However, little is known about the long-term predictive value of CGM measures of glycemia for both the development of CFRD and their effect on key clinical outcomes such as weight maintenance and pulmonary function. In addition, there have been no studies investigating advanced glycation endproducts (AGE) assessed by skin autofluorescence in people with CF. Methods: In this prospective observational study, CGM and HbA1c were measured at 2 to 3 time points 3 months apart in 77 adults with CF. Participants who did not have CFRD at the time of enrollment underwent OGTT at the baseline visit, and all participants had AGE readings at baseline. Follow up data including anthropometric measures, pulmonary function and CFRD status were collected by review of medical records 1- and 2-years after the baseline visits. We applied multivariable linear regression models correlating glycemic measures to change in key clinical outcomes (weight, BMI, FEV1) accounting for age, gender and elexacaftor/tezacaftor/ivacaftor (ETI) use. We also conducted logistic regression analyses comparing baseline glycemic data to development of CFRD during the 2-year follow up period. Results: Of the 77 participants, 25 had pre-existing CFRD at the time of enrollment, and six participants were diagnosed with CFRD by the OGTT performed at the baseline visit. When adjusting for age, gender, and ETI use, multiple CGM measures correlated with weight and BMI decline after one year but not after two years. CGM and HbA1c at baseline did not predict decline in FEV1 (p>0.05 for all). In the 46 participants without a diagnosis of CFRD at baseline, two participants were diagnosed with CFRD over the following two years, but CGM measures at baseline did not predict progression to CFRD. Baseline AGE values were higher in individuals with CFRD and correlated with multiple measures of dysglycemia (HbA1c, AG, SD, CV, TIR, % time >140, >180, >250) as well as weight. AGE values also correlated with FEV1 decline at year 1 and weight decline at year 1 and year 2. Conclusions: Several key CGM measures of hyperglycemia and glycemic variability were predictive of future decline in weight and BMI over one year in this population of adults with CF with and without CFRD. None of the baseline glycemic variables predicted progression to CFRD over 2 years. To our knowledge, this is the first report correlating AGE levels with key clinical and glycemic measures in CF. Limitations of these analyses include the small number of participants who developed CFRD (n=2) during the follow up period and the initiation of ETI by many participants, affecting their trajectory in weight and pulmonary function. These results provide additional data supporting the potential role for CGM in identifying clinically significant dysglycemia in CF. Future studies are needed to investigate CGM as a diagnostic and screening tool for CFRD and to understand the implications of AGE measures in this patient population.

[Allergic bronchopullmonary aspergillosis (ABPA) - an Update]. / Allergische bronchopulmonale Aspergillose (ABPA) ­ ein Update.

Allergic bronchopulmonary aspergillosis (ABPA) is a regular occurrence in everyday pneumology. ABPA should be considered in patients with severe asthma, in mould allergic patients with very high serum IgE levels and in patients with cystic fibrosis. The aim should be to make the diagnosis as early as possible in the course of the disease to avoid late complications such as bronchiectasis and fibrotic lung remodelling. Symptoms are highly variable and rather non-specific, overlapping with those of the underlying primary disease. However, clearly defined diagnostic criteria exist, so that the diagnosis can be made relatively easily if one thinks of it. In therapy, systemic steroids and antifungals (mainly azoles) play the leading role. However, biologics have been gaining in importance in recent years, especially in cases of insufficient therapy response or occurrence of side effects to standard therapies, as well as an alternative in permanently steroid-dependent patients.

Wearable sweat chloride sensors: materials, fabrication and their applications.

Chloride is a crucial anion required for multiple functions in the human body including maintaining acid-base balance, fluid balance, electrical neutrality and supporting muscles and nerve cells. Low-chloride levels can cause nausea, diarrhoea, etc. Chloride levels are measured in different body fluids such as urine, serum, sweat and saliva. Sweat chloride measurements are used for multiple applications including disease diagnosis, sports monitoring, and geriatric care. For instance, a sweat chloride test is performed for cystic fibrosis screening. Further, sweat also offers continuous non-invasive access to body fluids for real-time monitoring of chloride that could be used for sports and geriatric care. This review focuses on wearable chloride sensors that are used for periodic and continuous chloride monitoring. The multiple sections in the paper discuss the clinical significance of chloride, detection methods, sensor fabrication methods and their application in cystic fibrosis screening, sports and geriatric care. Finally, the last section discusses the limitation of current sensors and future directions for wearable chloride sensors.

Comparison of refugee patients with cystic fibrosis and their counterpart children from Turkey during the war.

Since the outbreak of the Syrian civil war in 2011, the population of Arab refugees in Turkey has rapidly increased. While cystic fibrosis (CF) is believed to be rare among Arabs, recent studies suggest it is underdiagnosed. This study aims to present the demographic, clinical, and genetic characteristics of CF patients among Arab refugees in Turkey. Additionally, a comparison is made between the findings in the National CF Registry 2021 in Turkey (NCFRT) and the refugee CF patient group. The study included refugee patients between the ages of 0 and 18 years who were diagnosed with CF and received ongoing care at pediatric pulmonology centers from March 2011 to March 2021. The study examined demographic information, age at diagnosis, age of diagnosis of patients through CF newborn screening (NBS), presenting symptoms, CF transmembrane conductance regulator (CFTR) mutation test results, sputum culture results, weight, height, and body mass index (BMI) z score. Their results were compared with the NCFRT results. The study included 14 pediatric pulmonology centers and 87 patients, consisting of 46 (52.9%) boys and 41 (47.1%) girls. All of the patients were Arab refugees, with 80 (92%) being Syrian. All the patients were diagnosed in Turkey. The median age at diagnosis of patients was 22.33 (interquartile range, 1-258) months. The median age of diagnosis of patients through NBS was 4.2 (interquartile range, 1-12) months. The median age of older patients, who were unable to be included in the NBS program, was 32.3 (interquartile range, 3-258) months. Parental consanguinity was observed in 52 (59.7%) patients. The mutation that was most frequently found was F508del, which accounted for 22.2% of the cases. It was present in 20 patients, constituting 32 out of the total 144 alleles. There was a large number of genetic variations. CFTR genotyping could not be conducted for 12 patients. These patients had high sweat tests, and their genetic mutations could not be determined due to a lack of data. Compared to NCFRT, refugee patients were diagnosed later, and long-term follow-up of refugee CF patients had significantly worse nutritional status and pseudomonas colonization.  Conclusion: Although refugee CF patients have equal access to NBS programs and CF medications as well as Turkish patients, the median age at diagnosis of patients, the median age of diagnosis of patients through NBS, their nutritional status, and Pseudomonas colonization were significantly worse than Turkish patients, which may be related to the difficulties of living in another country and poor living conditions. The high genetic heterogeneity and rare mutations detected in the refugee patient group compared to Turkish patients. Well-programmed NBS programs, thorough genetic studies, and the enhancement of living conditions for refugee patients in the countries they relocate to can have several advantages such as early detection and improved prognosis. What is Known: • Children who have chronic diseases are the group that is most affected by wars. • The outcome gets better with early diagnosis and treatment in patients with Cystic Fibrosis (CF). What is New: • Through the implementation of a newborn screening program, which has never been done in Syria previously, refugee patients, the majority of whom are Syrians were diagnosed with cystic fibrosis within a duration of 4 months. • Despite equal access to the newborn screening program and CF medications for both Turkish patients and refugee patients, the challenges of living in a foreign country have an impact on refugees.

Rate and predictors of insufficient sweat volume in very young infants after pilocarpine gel iontophoresis: prospective, population-based study.

OBJECTIVE: To verify the rate and predictors of 'quantity not sufficient' (QNS) among Brazilian infants younger than 3 months with positive newborn screening (NBS) for cystic fibrosis (CF). DESIGN: Prospective, population-based study. SETTING: Public Statewide Newborn Screening Programme where the incidence rate of CF is ≈1:11 000. PATIENTS: Subjects with positive two-tiered immunoreactive trypsinogen. INTERVENTIONS: Sweat induction and collection were performed in the same facility; one sweat sample was obtained per individual. MAIN OUTCOME MEASURES: The QNS rate and its predictors; analysis corresponded to the day of sweat collection. RESULTS: Among the 975 participants, QNS rates for 10 and 15 µL were 3.6% (95% CI 2.5% to 4.9%) and 8.3% (95% CI 6.6% to 10.2%). Infants weighing >3056 and >3845 g and with gestational age higher than 37 weeks had a greater likelihood (5.5 and 6.7, and 2.7 and 5.8 times more, respectively) of avoiding QNS than their peers. CONCLUSION: QNS rates fulfilled the requirements, but predictors differed from those recommended by the Cystic Fibrosis Foundations guidelines.

Evaluation of the efficiency of nanomicellar formulation of fat-soluble vitamins in patients with cystic fibrosis: the study protocol for a randomized controlled trial.

BACKGROUND: Cystic fibrosis is an inherited disease, which is caused by the CFTR protein defects due to mutations in the CFTR gene. Along with CFTR dysfunction, exocrine pancreatic insufficiency plays a key role in persistent fat malabsorption in CF patients; therefore, deficiency of fat-soluble vitamins (A, D, E, and K) is still a therapeutic challenge. Even with efficient pancreatic enzyme medication and CF-specific vitamins, many patients with CF have fat-soluble vitamins deficiency. The present study aims to evaluate the efficiency of nanomicelle formulation of fat-soluble vitamins in children with CF in order to achieve the appropriate serum levels of these vitamins. METHODS: This prospective, single-blind control trial will be conducted at the Akbar Children's Hospital in Mashhad, Iran. Patients with CF will be enrolled based on the eligibility criteria. The control group will receive the standard formulation of fat-soluble vitamins similar to the routine CF treatment, and for the intervention group, the nanomicelle formulation of fat-soluble vitamins will be administered for 3 months. The primary outcome of this study is the measurement of serum levels of fat-soluble vitamins. The secondary outcomes are clinical assessment by the Shwachman-Kulczycki score, anthropometrics, and quality of life. Outcomes will be assessed before and after 3 months. DISCUSSION: Due to persistent fat-soluble vitamin deficiency in CF disease, the nanomicelle formulation could be proposed as a new delivery method of fat-soluble vitamins in the treatment of cystic fibrosis. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20220415054541N1. Registered on July 23, 2022.

Lung clearance index short-term variability in cystic fibrosis: a pre-post pulmonary exacerbation study.

BACKGROUND: Multiple Breath washout (MBW) represents an important tool to detect early a possible pulmonary exacerbation especially in Cystic Fibrosis (CF) disease. Lung clearance index (LCI) is the most commonly reported multiple breath washout (MBW) index and in the last years was used as management measure for evaluation. Our aim was to analyze clinical utility of LCI index variability in pulmonary exacerbation in CF after intravenous (IV) antibiotic therapy. METHODS: A single-center study was conducted at CF Unit of Bambino Gesù Children's Hospital among hospitalized > 3 years patients for pulmonary exacerbations and treated with antibiotic IV treatment for 14 days. MBW and spirometry were evaluated within 72 h of admission to hospital and at the end of hospitalization. Descriptive analysis was conducted and correlations between quantitative variables were investigated. RESULTS: Fifty-seven patients (M22/F35) with an average age 18.56 (± 8.54) years were enrolled. LCI2.5 was significantly reduced at the end of antibiotic treatment in both pediatric and adult populations with an average reduction of -6,99%; 37/57 patients denoted an improvement, 20/57 are stable or worsened in LCI2.5 values and 4/57 (7.02%) had a significant deterioration (> 15%) at end of treatment. On the contrary a significative elevation of FEV1 and FVC were found, respectively of + 7,30% and of + 5,46%. A positive good correlection among LCI 2.5 and Scond (rho = + 0,615, p = 0.000) and LCI 2.5 and Sacin (rho = + 0,649, p = 0.000) and a negative strong correlation between FEV1 and LCI 2.5 were found in post treatment period. A similar modification of LCI 2.5 and FEV1 was noticed in both adult and pediatric population. CONCLUSIONS: LCI may have a role in the routine clinical care of both adult and pediatric CF patients as a good tool to assess response to IV antibiotic end-therapy in the same way as FEV1.

[Cystic fibrosis carrier screening: a Health technology assessment.] / Lo screening del portatore di fibrosi cistica: una valutazione di Health technology assessment.

This project of Health technology assessment was aimed at defining the impacts of offering a cystic fibrosis (CF) carrier screening to the general population, compared to the current situation, where the test is offered to individuals at high-risk to give birth to a child with CF. Results revealed: i) a lack of robust and updated data; ii) a return on investment up to six years from the screening's introduction, despite important economic and organizational efforts; iii) a general positive attitude of healthcare professionals, people with CF, families and general population; iv) possible issues related to the social impact.

Towards a Standardized Classification of the Hepatobiliary Manifestations in Cystic Fibrosis (CFHBI): A Joint ESPGHAN/NASPGHAN Position Paper.

The broad spectrum of hepatobiliary involvement in cystic fibrosis (CF) has been commonly referred to as cystic fibrosis liver disease (CFLD). However, differences in the definitions of CFLD have led to variations in reported prevalence, incidence rates, and standardized recommendations for diagnosis and therapies. Harmonizing the description of the spectrum of hepatobiliary involvement in all people with CF (pwCF) is deemed essential for providing a reliable account of the natural history, which in turn supports the development of meaningful clinical outcomes in patient care and research. Recognizing this necessity, The European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) commissioned and tasked a committee to develop and propose a systematic classification of the CF hepatobiliary manifestations to increase uniformity, accuracy, and comparability for clinical, registry, and research purposes. This report describes the committee's combined expert position statement on hepatobiliary involvement in CF, which has been endorsed by NASPGHAN and ESPGHAN. We recommend using CFHBI (Cystic Fibrosis Hepato-Biliary Involvement) as the updated term to describe and classify all hepatobiliary manifestations in all pwCF. CFHBI encompasses the current extensive spectrum of phenotypical, clinical, or diagnostic expressions of liver involvement observed in pwCF. We present a schematic categorization of CFHBI, which may also be used to track and classify the changes and development of CFHBI in pwCF over time. The proposed classification for CFHBI is based on expert consensus and has not been validated for clinical practice and research purposes. Achieving validation should be an important aim for future research.

Genetic analysis and functional study of novel CFTR variants in Chinese children with cystic fibrosis.

OBJECTIVES: To describe the clinical characteristics of Chinese cystic fibrosis (CF) patients and to investigate the variants of CFTR and their potential pathogenicity. STUDY DESIGN: Chinese patients with potential CF diagnosis were studied. Clinical data were reviewed retrospectively from medical records. Whole exome sequencing and genetic evaluation were conducted to explore potential gene variants. The disruption of the variants to protein structure and function was explored and validated using in vitro experiments and in silico analysis. RESULTS: Four patients were recruited to the study, three of them were diagnosed as CF, and one was diagnosed as CFTR-related disorder. The age at symptom onset for the patients in this study ranged from newborn to 6 years, while the age at diagnosis varied from 3 to 11 years. All four patients exhibited bilateral diffuse bronchiectasis with Pseudomonas aeruginosa infections, and three of them had malnutrition. Finger clubbing was observed in three patients, two of whom displayed mixed ventilatory dysfunction. The CFTR variants spectrum of Chinese children with CF differs from that of Caucasian. A total of six variants were identified, two of which were first reported (c.1219G > T [p.Glu407*] and c.1367delT [p.Ala457Leufs*12]). The nonsense variants c.1219G > T, c.1657C > T and c.2551C > T and the frameshift variant c.1367delT were predicted to introduce premature stop codon and produce shorten CFTR protein, which was also first validated by in vitro truncation assay in this study. The missense variant c.1810A > C was predicted to disrupt the function of the nucleotide-binding domain 1 (NBD1) in the CFTR protein. The splicing variant c.1766 + 5G > T caused skipping of exon 13 and damaged the integrity of CFTR protein. CONCLUSIONS: Our study expands the spectrum of phenotypes and genotypes for CF of Chinese origin, which differs significantly from that of Caucasian. Genetic analysis and counseling are crucial and deserve extensive popularization for the diagnosis ofCF in patients of Chinese origin.

Eradication treatment for Pseudomonas aeruginosa infection in adults with bronchiectasis: a systematic review and meta-analysis.

INTRODUCTION: Pseudomonas aeruginosa is the most commonly isolated pathogen in bronchiectasis and is associated with worse outcomes. Eradication treatment is recommended by guidelines, but the evidence base is limited. The expected success rate of eradication in clinical practice is not known. METHODS: We conducted a systematic review and meta-analysis according to Meta-Analysis of Observational Studies in Epidemiology guidelines. PubMed, Embase, the Cochrane Database of Systematic Reviews and Clinicaltrials.gov were searched for studies investigating P. aeruginosa eradication treatment using antibiotics (systemic or inhaled) in patients with bronchiectasis. The primary outcome was the percentage of patients negative for P. aeruginosa at 12 months after eradication treatment. Cystic fibrosis was excluded. RESULTS: Six observational studies including 289 patients were included in the meta-analysis. Our meta-analysis found a 12-month P. aeruginosa eradication rate of 40% (95% CI 34-45%; p<0.00001), with no significant heterogeneity (I2=0%). Combined systemic and inhaled antibiotic treatment was associated with a higher eradication rate (48%, 95% CI 41-55%) than systemic antibiotics alone (27%, 13-45%). CONCLUSION: Eradication treatment in bronchiectasis results in eradication of P. aeruginosa from sputum in ∼40% of cases at 12 months. Combined systemic and inhaled antibiotics achieve higher eradication rates than systemic antibiotics alone.

Pseudo-Bartter syndrome as the initial presentation of cystic fibrosis in children: an important diagnosis not to be missed.

Pseudo-Bartter syndrome (PBS) is characterised by hyponatraemic, hypochloraemic metabolic alkalosis that mimics Bartter syndrome, without renal tubular disease. We present a case of an infant with a positive cystic fibrosis (CF) newborn screening, hospitalised during the summer with dehydration, oliguria and apathy. Blood analysis revealed hypochloraemic metabolic alkalosis, hypokalaemia and hyponatraemia. Urine analysis showed leucocyturia with reduced sodium and chloride excretion fraction, and urinary culture was positive for Citrobacter koseri After antibiotherapy and intravenous rehydration with additional supplementation of sodium and chloride, the patient recovered completely. PBS is one of CF complications that is especially prevalent in infants and young children with increased sweating and/or other causes of additional loss of sodium and chloride. Clinical awareness of this syndrome and its strong clinical suspicion are extremely important for an early diagnosis and treatment of CF, particularly in countries where the universal screening of CF is not routinely performed.