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Sweat chloride concentration, a diagnostic feature in cystic fibrosis (CF), reflects CF transmembrane conductance regulator (CFTR) activity. CFTR modulator therapies, especially elexacaftor/tezacaftor/ivacaftor (ETI), has improved CF outcomes. We report nationwide, real-world data on sweat chloride concentration in people with CF (pwCF) with and without modulator therapies. All Danish pwCF with a minimum of one F508del allele were included. Sweat chloride measurements were stratified by genotype and modulator treatment. Differences were assessed using mixed-effects models. We included 977 sweat chloride measurements from 430 pwCF, 71% of which were F508del homozygous. Heterozygous and homozygous ETI-treated pwCF had an estimated mean sweat chloride concentration of 43 mmol/L (95% confidence interval: 39; 48) and 43 mmol/L (39; 47), respectively-48% and 59% lower than those without treatment. High variation in concentrations remained regardless of treatment status. Despite ETI treatment, 27% heterozygous and 23% homozygous pwCF had elevated concentrations (≥60 mmol/L). These real-world data confirm a substantial decrease in sweat chloride concentration during modulator treatment, especially ETI, where mean concentrations halved. However, large variation remained, including persistently high concentrations. These findings emphasize the potential of sweat chloride concentration as a treatment response biomarker and the need to explore its heterogeneity and relationship with clinical outcomes.
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BACKGROUND: The Danish National Patient Registry (DNPR) serves as a valuable resource for scientific research. However, to ensure accurate results in cystic fibrosis (CF) studies that rely on DNPR data, a robust case-identification algorithm is essential. This study aimed to develop and validate algorithms for the reliable identification of CF patients in the DNPR. METHODS: Using the Danish Cystic Fibrosis Registry (DCFR) as a reference, accuracy measures including sensitivity and positive predictive value (PPV) for case-finding algorithms deployed in the DNPR were calculated. Algorithms were based on minimum number of hospital contacts with CF as the main diagnosis and minimum number of days between first and last contact. RESULTS: An algorithm requiring a minimum of one hospital contact with CF as the main diagnosis yielded a sensitivity of 96.1 % (95 % CI: 94.2 %; 97.4 %) and a PPV of 84.9 % (82.0 %; 87.4 %). The highest-performing algorithm required minimum 2 hospital visits and a minimum of 182 days between the first and the last contact and yielded a sensitivity of 95.9 % (95 % CI: 94.1 %; 97.2 %), PPV of 91.0 % (95 % CI: 88.6 %; 93.0 %) and a cohort entry delay of 3.2 months at the 75th percentile (95th percentile: 38.7 months). CONCLUSIONS: The DNPR captures individuals with CF with high sensitivity and is a valuable resource for CF-research. PPV was improved at a minimal cost of sensitivity by increasing requirements of minimum number of hospital contacts and days between first and last contact. Cohort entry delay increased with number of required hospital contacts.
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BACKGROUND: Improved growth in children with CF may have resulted from advances in treatment for cystic fibrosis (CF) over the past two decades, including the implementation of newborn screening in Denmark in 2016. This observational cohort study focuses on changes in early growth in Danish children with CF born between 2000 and January 2022. METHODS: Age, length/height, and weight data of children 0-5 years old were obtained from the Danish CF Cohort. Data were stratified to four birth cohorts born between 2000 and 2022. Weight-for-age (WAZ), length-for-age (LAZ), height-for-age (HAZ) and body-mass-index (BMZ) z-scores were computed using WHO growth curves. Cubic spline mixed effects models were used to evaluate growth over 5 years between birth cohorts. RESULTS: We included 255 children in the analyses. Cubic spline mixed effects models show that catch-up growth improved in birth cohorts over time, with the 2016-2022 birth cohort achieving growth reference curve values in WAZ, LAZ/HAZ and BMZ the earliest. The proportion of underweight and stunting observations among children born 2000-2004 decreased by the 2016-2022 birth cohort, while the proportion of overweight, low BMZ and high BMZ observations increased. CONCLUSION: Advances in care for young children with CF have led to improvements in growth - with the 2016-2022 birth cohort approaching potential for overweight. Nonetheless, low BMZ remains. Immediate, individualized nutrition care throughout early childhood remain crucial in mitigating malnutrition.
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Estatura , Fibrosis Quística , Humanos , Fibrosis Quística/epidemiología , Fibrosis Quística/fisiopatología , Fibrosis Quística/terapia , Dinamarca/epidemiología , Masculino , Femenino , Preescolar , Lactante , Recién Nacido , Peso Corporal , Desarrollo Infantil/fisiología , Trastornos del Crecimiento/etiología , Trastornos del Crecimiento/epidemiología , Trastornos del Crecimiento/diagnóstico , Estudios de Cohortes , Tamizaje Neonatal/métodos , Índice de Masa CorporalRESUMEN
BACKGROUND: Cystic Fibrosis (CF) is an inherited multiorgan disease that causes lung damage and early death. People with CF (pwCF) experience diminished exercise capacity compared to the general population. This is due to an accelerated decline in lung function resulting from recurrent lung infections, declining lung function and nutritional challenges. Since 2020 the CFTR-modulator Elexacaftor/Tezacaftor/Ivacaftor (ETI) has been approved for pwCF aged 12 and above in Denmark. Initial experiences with the medication have shown promising results, including improved lung function and disease stability. To date a limited number of studies have evaluated the impact of CFTR-modulators on exercise capacity in pwCF. OBJECTIVE: The study aims to assess the impact of one year of ETI treatment, without any further intervention, on exercise capacity measured through cardiopulmonary exercise test (CPET) in pwCF aged 12 years and above. METHODS: A Danish prospective registry cohort study including pwCF from CF-Center Copenhagen, Copenhagen University Hospital and CF-Center Aarhus, Aarhus University Hospital. Participants underwent CPET before initiating ETI and at follow up one year later. Primary outcomes were VO2 peak (ml/kg/min), secondary outcomes were VO2 peak (ml/min), VO2 peak (% pred), watt-max, HR-max and saturation at max. The difference between baseline and follow-up was assessed using a paired-sample t-test and regression analyses were applied to relevant outcomes. RESULTS: We included 229 pwCF in the analyses. An increase in oxygen uptake, VO2 peak (ml/kg/min) from baseline to follow-up was observed; 0.6, 95% CI [0.06; 1.09] p = 0.03. Moreover, significant increase was noted for all other CPET outcomes. Regression analysis showed that changes in FEV1% pred and BMI could explain some of the differences, 0.05 ml/kg/min, 95% CI [0.01, 0.1] p = 0.02 and -0.5 ml/kg/min, 95% CI [-0.8, -0.2] p = 0.002 respectively. CONCLUSION: Among Danish pwCF we found a significant, but not clinically relevant, increase in oxygen uptake, after one year of ETI treatment.
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BACKGROUND: Past and ongoing advancements in cystic fibrosis (CF) care warrant long-term analysis of the societal impact of the condition. This study aims to evaluate changes in key socioeconomic factors across three decades among people living with CF (pwCF), compared with both the general population and an early-onset chronic disease population. METHODS: This nationwide, registry-based, matched cohort study included all pwCF ≥ 18 years in Denmark in the years 1990, 2000, 2010, and 2018. Each person living with CF was matched to five individuals in the general population and five individuals living with type 1 diabetes or juvenile arthritis based on age, sex, and municipality. RESULTS: The Danish adult CF population increased nearly fourfold from 88 in 1990 to 331 in 2018, and mean age increased by ten years. The educational level of pwCF was similar to the two comparator cohorts, while pwCF were less often in employment and more often permanently outside the labor force. Personal and household income levels of the CF cohort were higher than those of the comparator cohorts. CONCLUSIONS: The disadvantage in employment for pwCF remained, but, over time, the societal profiles of the one-year CF cohorts increasingly converged with those of the comparator cohorts, indicative of improved clinical management, extended life expectancy, and the supportive role of the Danish welfare system in reducing health inequalities. Further research should be done to evaluate the effects of the newly introduced modulator therapies on employment, considering the broader societal impact and impact on quality of life.
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Cystic fibrosis (CF) care in Denmark has been characterized by close monitoring and pre-emptive treatment of lung disease and other CF-related complications. Continuous evaluation through data collection and commitment to clinical research has incrementally improved outcomes. This approach has been in line with best practices set forth by European Standards of Care but has also gone beyond Society standards particularly pertaining to early treatment with high-dose combination antimicrobial therapy. Despite a high prevalence of severe CF variants, lung function has been among the best in Europe. In this review, the Danish approach to management of CF prior to the introduction of new CF modulator treatment is explained and benchmarked. Downsides to the Danish approach are discussed and include increased burden of treatment, risk of antimicrobial resistance, side-effects and costs.
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Antiinfecciosos , Fibrosis Quística , Humanos , Fibrosis Quística/complicaciones , Europa (Continente) , Antiinfecciosos/uso terapéutico , DinamarcaRESUMEN
BACKGROUND: Elexacaftor/tezacaftor/ivacaftor (ETI) has improved the clinical status of individuals with cystic fibrosis (CF), however, whether ETI impacts glucose tolerance remains unknown. We aimed to study the change in glycated hemoglobin (HbA1c) and CF related diabetes (CFRD) status after initiation of ETI. METHODS: We included individuals ≥12 years treated with ETI in Denmark in a longitudinal observational study. HbA1c was measured at baseline, 3, 6, 9 and 12 months after treatment initiation. Change in HbA1c was assessed in mixed models adjusted for age, sex, glucose tolerance and prior CFTR modulator treatment. In a sub-population with CFRD, we assessed the change in insulin usage, hypoglycemic events and the 30-day continuous glucose monitoring (CGM) parameters (i.e., average blood glucose, time below (≤3.9 mM) and above (>10.0 mM) normal range, and the variation in glucose) after 12 months of treatment. RESULTS: Among 321 individuals with CF, HbA1c declined by 2.1 mmol/mol [95 % confidence interval (CI): -2.6; -1.5 mmol/mol] after 3 months and by 2.3 mmol/mol [95 %CI: -2.8; -1.9 mmol/mol] after 12 months of ETI treatment. The decline was independent of glucose tolerance status at baseline. In 26 individuals with CFRD at baseline, the mean decline in HbA1c was 3.6 mmol/mol [95 %CI: -6.9; -0.4 mmol/mol] after 12 months, but we did not observe any change in insulin usage, weekly number of hypoglycemic events or CGM parameters. CONCLUSION: In the Danish CF cohort, HbA1c declined over 12 months of ETI treatment, however, among a subset with CFRD, we observed no change in insulin usage and CGM glucose levels.
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Glucemia , Fibrosis Quística , Indoles , Pirazoles , Piridinas , Pirrolidinas , Quinolonas , Humanos , Automonitorización de la Glucosa Sanguínea , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/epidemiología , Hemoglobina Glucada , Insulina , Hipoglucemiantes/uso terapéutico , Glucosa , Dinamarca/epidemiología , Regulador de Conductancia de Transmembrana de Fibrosis Quística , Benzodioxoles , Mutación , Aminofenoles/uso terapéuticoRESUMEN
Background: Cystic fibrosis (CF) lung disease starts in infancy and can be assessed for structural lung abnormalities using computed tomography or magnetic resonance scans, or for lung function impairment using multiple breath washout (MBW). However, in infancy these two methods are not well correlated. Trajectories of CF lung disease assessed by MBW in infants and toddlers remain poorly described, which is why we aimed to 1) describe the trajectory of lung function, 2) explore risk factors for progression and 3) explore the real-life effect of lumacaftor/ivacaftor. Methods: This was a nationwide observational cohort study (2018-2021) using data collected as part of the routine clinical surveillance programme (including MBW and monthly endo-laryngeal suction sampling for bacterial pathogens) in children born after implementation of newborn screening for CF (May 2016). Lumacaftor/ivacaftor commenced from age 2â years in children homozygous for F508del. Ventilation distribution efficiency (VDE), recently described to have advantages over lung clearance index (LCI), was reported as the primary MBW outcome after z-score calculations based on published reference data. Mixed effect linear regression models were the main statistical analyses performed in this study. Results: 59 children, aged 2-45â months, contributed with 211 MBW occasions (median (interquartile range (IQR)) 3 (2-5) MBW occasions per child) with a median (IQR) follow-up time of 10.8 (5.2-22.3)â months. An overall mean annual deterioration rate of -0.50 (95% CI -0.78- -0.22) z-VDE was observed, starting from an estimated mean z-VDE of -1.68 (95% CI -2.15- -1.22) at age 0.0â years (intercept). Pseudomonas aeruginosa "ever" (n=14, MBWs 50) had a significantly worse z-VDE trajectory versus P. aeruginosa "never" (mean difference 0.53 (95% CI 0.16-0.89)â per year; p=0.0047) and lumacaftor/ivacaftor treatment (n=22, MBWs 46) significantly improved the trajectory of z-VDE (mean difference 1.72 (95% CI 0.79-2.66)â per year; p=0.0004), leading to a stable mean z-VDE trajectory after start of treatment. Conclusions: Infants and toddlers with CF demonstrated progressive deterioration in z-VDE over the first years of life. P. aeruginosa isolation "ever" was associated with an accelerated deterioration in lung function, while lumacaftor/ivacaftor therapy significantly improved and stabilised the trajectory.
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RATIONAL: People with cystic fibrosis carrying residual function (RF) mutations are considered to have a mild disease course. This may influence caregivers and patients on how intensive the treatments should be. OBJECTIVES: Characterize disease severity of patients carrying RF mutations, using the European CF Society Patient Registry (ECFSPR) data. METHODS: Demographic, clinical characteristics, lung function and death probability of patients carrying at least one RF mutation were analyzed and compared to patients homozygous to minimal function mutations (MF). MAIN RESULTS: Of the 44,594 eligible patients (median age 19.5 years, IQR 10-29.8), 6,636 (14.6%) carried RF mutations, and 37,958 (85.1%) MF mutations. Patients carrying RF mutations were older, diagnosed at a later age, had lower sweat chloride at diagnosis and better FEV1pp at each age group. However, their FEV1pp declined with age and rates of chronic Pseudomonas aeruginosa increased with age. A significant number of patients with RF had FEV1pp similar to patients with MF at each age group. 4.5% of RF patients were treated with oxygen and 2.61% had a lung transplant. With increasing age, 26.6% of RF patients were treated with pancreatic enzymes associated with a more severe lung disease. RF patients had shortened life spans, with mortality starting around the age of 20 years. CONCLUSIONS: Patients carrying an RF mutations experience a decline of pulmonary function with age, leading to life-shortening. Standard of care therapies and augmenting CFTR function may improve their survival and quality of life.
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Fibrosis Quística , Humanos , Adulto Joven , Adulto , Fibrosis Quística/diagnóstico , Fibrosis Quística/epidemiología , Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/uso terapéutico , Calidad de Vida , Mutación , Gravedad del Paciente , Sistema de RegistrosRESUMEN
BACKGROUND: In cystic fibrosis (CF), renal base excretion is impaired. Accordingly, challenged urine bicarbonate excretion may be an in vivo biomarker of cystic fibrosis transmembrane conductance regulator (CFTR) function. OBJECTIVE: To evaluate the association between challenged bicarbonate excretion and clinical characteristics at baseline, quantify the CFTR modulator drug elexacaftor/tezacaftor/ivacaftor-induced changes of challenged bicarbonate excretion after 6 months of treatment, and characterize the intraindividual variation in healthy adults. DESIGN: Prospective observational study. SETTING: Cystic fibrosis clinic, Aarhus University Hospital, Denmark. PATIENTS: Fifty adult patients with CF starting CFTR modulator therapy with elexacaftor/tezacaftor/ivacaftor between May 2020 and June 2021. MEASUREMENTS: Quantification of urine bicarbonate excretion after an acute oral sodium bicarbonate challenge before and 6 months after elexacaftor/tezacaftor/ivacaftor treatment. RESULTS: At baseline, challenged urine bicarbonate excretion was associated with several CF disease characteristics. Bicarbonate excretion was higher in patients with residual function mutations. A higher bicarbonate excretion was associated with better lung function, pancreatic sufficiency, and lower relative risk for chronic pseudomonas infections. Elexacaftor/tezacaftor/ivacaftor treatment increased bicarbonate excretion by 3.9 mmol/3 h (95% CI, 1.6 to 6.1 mmol/3 h), reaching about 70% of that seen in healthy control participants. In healthy control participants, individual bicarbonate excretion at each visit correlated with the individual mean bicarbonate excretion. The median coefficient of variation was 31%. LIMITATION: Single-center study without a placebo-controlled group. CONCLUSION: Although further studies are needed to address the performance and sensitivity of this approach, this early-stage evaluation shows that challenged urine bicarbonate excretion may offer a new, simple, and safe quantification of CFTR function and the extent of its pharmacologic improvement. Elexacaftor/tezacaftor/ivacaftor partially restores renal CFTR function in patients with CF, likely resulting in decreased risk for electrolyte disorders and metabolic alkalosis. PRIMARY FUNDING SOURCE: Innovation Fund Denmark.
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Regulador de Conductancia de Transmembrana de Fibrosis Quística , Fibrosis Quística , Humanos , Adulto , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/farmacología , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/genética , Bicarbonatos/metabolismo , Bicarbonatos/uso terapéutico , Agonistas de los Canales de Cloruro/farmacología , Agonistas de los Canales de Cloruro/uso terapéutico , Combinación de Medicamentos , MutaciónRESUMEN
BACKGROUND: Paediatric track and trigger tools (PTTTs) based on vital parameters have been implemented in hospitals worldwide to help healthcare professionals identify signs of critical illness and incipient deterioration in hospitalised children. It has been documented that nurses do not use PTTT as intended, but deviate from PTTT protocols because, in some situations, PTTT observations make little sense to them. The present study aimed to reach consensus on whether automatically generated PTTT scores that are higher than deemed reasonable by healthcare professionals according to their professional experience and clinical expertise may be downgraded. METHODS: A two-round modified Delphi technique was used to explore consensus on 14 patient cases for hospitalised children with a high PTTT score that did not raise concerns by systematically collating questionnaire responses. Participants rated their level of agreement on a 9-point Likert scale. IQR and median were calculated for each case. FINDINGS: A total of 221 participants completed round 1 and 101 participants completed round 2. Across the two rounds, majority of the participants were from paediatric departments, nurses and women. In round 1, consensus on inclusion was reached on 2 of the 14 cases. In round 2, consensus was reached on one additional patient case. Three of the 11 non-consensus cases remaining after rounds 1 and 2 were included by the research group based on predefined criteria. CONCLUSION: In conclusion, a consensus opinion was achieved on six patient cases where the child had a high PTTT score but where the healthcare professionals were not as concerned as indicated by the PTTT score.
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Niño Hospitalizado , Personal de Salud , Niño , Consenso , Técnica Delphi , Femenino , Humanos , Factores DesencadenantesRESUMEN
BACKGROUND: Since 2015, when the first cystic fibrosis transmembrane conductance regulator (CFTR) modulators were approved for people with cystic fibrosis (CF) homozygous for F508del-CFTR, studies have shown improved lung function after initiation of the treatment and patients experience improved physical capacity. The aim of this study was to investigate change in exercise capacity after initiation of Lumacaftor/Ivacaftor and Tezacaftor/Ivacaftor treatment (LUM/IVA, TEZ/IVA). METHODS: We performed a single group prospective observational cohort study with follow-up at six and 12 months. The study examined change in exercise capacity in people with CF initiating treatment with LUM/IVA and TEZ/IVA, measured by cardio-pulmonary exercise testing (CPET). Inclusion criteria were people with CF homozygous for F508del-CFTR aged 12 years or older eligible for LUM/IVA and TEZ/IVA treatment from June 2017 until June 2019. Primary outcomes were change in VO2peak and maximal workload. Secondary outcomes were change in muscle strength, muscle power and body composition in a subgroup of the study population. RESULTS: A total of 91 patients were included in the analysis. The mean change in VO2peak and VO2peak divided by body weight from baseline to 12-months follow-up was 145.7 (91.2;200.2) ml/min and 1.07 (95% CI 0.19;1.95) ml/min/kg, respectively. The mean change in maximal workload between baseline and 12 months was 14.2 Watt (95% CI 9.1;19.2). All improvements in exercise capacity were statistically significant. CONCLUSIONS: Patients in this study improved their exercise capacity by a statistically significant increase in VO2peak and maximal workload 12 months after initiation of treatment with LUM/IVA and TEZ/IVA.
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Regulador de Conductancia de Transmembrana de Fibrosis Quística , Fibrosis Quística , Aminofenoles/uso terapéutico , Aminopiridinas/uso terapéutico , Toxinas Bacterianas , Benzodioxoles/uso terapéutico , Fibrosis Quística/diagnóstico , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Dinamarca , Combinación de Medicamentos , Prueba de Esfuerzo , Tolerancia al Ejercicio , Humanos , Indoles , Mutación , Estudios Prospectivos , QuinolonasRESUMEN
AIM: Newborn screening represents a paradigm shift in the treatment of children with cystic fibrosis. This study aimed to explore parents' everyday life experiences from the time of diagnosis and in the following months. METHODS: Narrative interviews were conducted at Aarhus University Hospital, Denmark, with parents (mothers = 15 and fathers =14) of 15 term-born children with a mean age of 2 weeks (range 1-3.5 weeks). Participant observation and field notes were used to complement interview data. The analysis was inspired by Kvale and Brinkmann. RESULTS: Three themes were identified. First, on diagnosis, a profound difference in parents' experience was observed depending on whether the diagnosis was communicated by a medical doctor from the cystic fibrosis team or by a paediatrician from another hospital. Second, during the initial meetings and subsequent relationships with the cystic fibrosis team, the knowledge and calmness exhibited by the doctors and nurses were very valuable. Third, regarding everyday life after the diagnosis, most parents described experiencing anxiety and concern for their child's future. CONCLUSION: The parents' experiences highlighted essential elements that should be implemented to optimise the patient care pathway as they are fundamental to parents' ability to cope with the new living conditions.
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Fibrosis Quística , Adaptación Psicológica , Niño , Fibrosis Quística/diagnóstico , Femenino , Humanos , Recién Nacido , Madres , Tamizaje Neonatal , PadresRESUMEN
BACKGROUND: Nasal tracheal aspiration (NTA) is a frequently used diagnostic method to assess of infections in the lower airways. However, the validity of the method has not previously been compared to bronchoalveolar lavage (BAL) in non-intubated children with a lung disease. We hypothesised that NTA performed by health professionals using the nares vocal cord distance to be placed at the entrance of the trachea, will result in same finding of bacteria in the lower airways as the gold standard of BAL. METHODS: In a prospective study, 173 paired samples of NTA and BAL were obtained between June 2016 to August 2018. Samples were collected from all patients undergoing bronchoscopy with spontaneous breathing during general anaesthesia. This study compares the microbiological results from the cultures obtained by investigating complete concordance i.e. identical pathogenic bacteria and coherence i.e. absence or presence of pathogenic bacteria growth between NTA and BAL. RESULTS: Samples were collected in 164 patients, 158 children between 21 days and 18 years of age and six young adults still treated at the paediatric department. The overall similarity (complete agreement) was found in 49% [41-56], sensitivity was 35% [27-45], specificity was 66% [55-76], positive predictive value was 36% [27-46] and negative predictive value was 64% [54-64] concerning complete pathogenic bacteria concordance. If we only considered coherence growth of pathogenic bacteria, similarity was 71% [63-79], sensitivity was 74% [64-81], specificity was 66% [55-76], positive predictive value was 75% [65-82] and negative predictive value was 65% [54-75]. Patients with cystic fibrosis showed a similarity of 88% [73-95], a sensitivity of 92% [76-99], a specificity of 71% [36-95], a positive predictive value of 92% [76-99] and a negative predictive value of 71% [36-95] concerning coherence growth of pathogenic bacteria. CONCLUSION: The study indicates that NTA compared to BAL as the gold standard is not clinically useful to assess positive findings of specific bacteria in the lower airway tract. Statistically significantly increased sensitivity and positive predictive value were found in cystic fibrosis patients concerning coherence growth. The clinical usage of NTA remains important as negative findings are of clinical value. However, BAL continues to be preferred as a significantly superior diagnostic tool.
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Fibrosis Quística , Bacterias , Lavado Broncoalveolar , Líquido del Lavado Bronquioalveolar/microbiología , Broncoscopía , Niño , Fibrosis Quística/microbiología , Humanos , Estudios Prospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
INTRODUCTION: Multiple breath washout (MBW) is used for early detection of cystic fibrosis (CF) lung disease, with SF6 MBW commonly viewed as the reference method. The use of N2 MBW in infants and toddlers has been questioned for technical and physiological reasons, but a new correction of the N2 signal has minimized the technical part. The present study aimed to assess the remaining differences and the contributing mechanisms for the differences between SF6 and N2 MBW,corrected-such as tidal volume reduction during N2 washout with pure O2 . METHOD: This was a longitudinal multicenter cohort study. SF6 MBW and N2 MBW were performed prospectively at three CF centers in the same visits on 154 test occasions across 62 children with CF (mean age: 22.7 months). Offline analysis using identical algorithms to the commercially available program provided outcomes of N2,original and N2,corrected for comparison with SF6 MBW. RESULTS: Mean functional residual capacity, FRCN2,corrected was 14.3% lower than FRCN2, original , and 1.0% different from FRCSF6 . Lung clearance index, LCIN2,corrected was 25.2% lower than LCIN2,original , and 7.3% higher than LCISF6 . Mean (SD) tidal volume decreased significantly during N2 MBWcorrected , compared to SF6 MBW (-13.1 ml [-30.7; 4.6], p < 0.0001, equal to -12.0% [-25.7; 1.73]), but this tidal volume reduction did not correlate to the differences between LCIN2,corrected and LCISF6 . The absolute differences in LCI increased significantly with higher LCISF6 (0.63/LCISF6 ) and (0.23/LCISF6 ), respectively, for N2,original and N2,corrected , but the relative differences were stable across disease severity for N2,corrected , but not for N2,original . CONCLUSION: Only minor residual differences between FRCN2,corrected and FRCSF6 remained to show that the two methods measure gas volumes very similar in this age range. Small differences in LCI were found. Tidal volume reduction during N2 MBW did not affect differences. The corrected N2 MBW can now be used with confidence in young children with CF, although not interchangeably with SF6 .
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Fibrosis Quística , Pruebas Respiratorias/métodos , Preescolar , Estudios de Cohortes , Fibrosis Quística/diagnóstico , Humanos , Lactante , Pulmón , Nitrógeno/análisisRESUMEN
BACKGROUND: Viral infections can cause significant morbidity in cystic fibrosis (CF). The current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic could therefore have a serious impact on the health of people with CF (pwCF). METHODS: We used the 38-country European Cystic Fibrosis Society Patient Registry (ECFSPR) to collect case data about pwCF and SARS-CoV-2 infection. RESULTS: Up to 30 June 2020, 16 countries reported 130 SARS-CoV-2 cases in people with CF, yielding an incidence of 2.70/1000 pwCF. Incidence was higher in lung-transplanted patients (n=23) versus non-transplanted patients (n=107) (8.43 versus 2.36 cases/1000). Incidence was higher in pwCF versus the age-matched general population in the age groups <15, 15-24, and 25-49 years (p<0.001), with similar trends for pwCF with and without lung transplant. Compared to the general population, pwCF (regardless of transplantation status) had significantly higher rates of admission to hospital for all age groups with available data, and higher rates of intensive care, although not statistically significant. Most pwCF recovered (96.2%), however 5 died, of whom 3 were lung transplant recipients. The case fatality rate for pwCF (3.85%, 95% CI: 1.26-8.75) was non-significantly lower than that of the general population (7.46%; p=0.133). CONCLUSIONS: SARS-CoV-2 infection can result in severe illness and death for pwCF, even for younger patients and especially for lung transplant recipients. PwCF should continue to shield from infection and should be prioritized for vaccination.
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COVID-19/epidemiología , Fibrosis Quística/complicaciones , Adolescente , Adulto , COVID-19/diagnóstico , COVID-19/terapia , Niño , Preescolar , Cuidados Críticos , Fibrosis Quística/mortalidad , Fibrosis Quística/terapia , Europa (Continente)/epidemiología , Femenino , Hospitalización , Humanos , Incidencia , Lactante , Recién Nacido , Trasplante de Pulmón , Masculino , Persona de Mediana Edad , Sistema de Registros , Estudios Retrospectivos , Adulto JovenAsunto(s)
Fibrosis Quística , Infecciones por Pseudomonas , Infecciones del Sistema Respiratorio , Antibacterianos/uso terapéutico , Niño , Fibrosis Quística/complicaciones , Fibrosis Quística/terapia , Humanos , Pulmón/diagnóstico por imagen , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/etiología , Pseudomonas aeruginosaRESUMEN
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with cystic fibrosis (pwCF) can lead to severe outcomes. METHODS: In this observational study, the European Cystic Fibrosis Society Patient Registry collected data on pwCF and SARS-CoV-2 infection to estimate incidence, describe clinical presentation and investigate factors associated with severe outcomes using multivariable analysis. RESULTS: Up to December 31, 2020, 26 countries reported information on 828 pwCF and SARS-CoV-2 infection. Incidence was 17.2 per 1000 pwCF (95% CI: 16.0-18.4). Median age was 24â years, 48.4% were male and 9.4% had lung transplants. SARS-CoV-2 incidence was higher in lung-transplanted (28.6; 95% CI: 22.7-35.5) versus non-lung-transplanted pwCF (16.6; 95% CI: 15.4-17.8) (p≤0.001).SARS-CoV-2 infection caused symptomatic illness in 75.7%. Factors associated with symptomatic SARS-CoV-2 infection were age >40â years, at least one F508del mutation and pancreatic insufficiency.Overall, 23.7% of pwCF were admitted to hospital, 2.5% of those to intensive care, and regretfully 11 (1.4%) died. Hospitalisation, oxygen therapy, intensive care, respiratory support and death were 2- to 6-fold more frequent in lung-transplanted versus non-lung-transplanted pwCF.Factors associated with hospitalisation and oxygen therapy were lung transplantation, cystic fibrosis-related diabetes (CFRD), moderate or severe lung disease and azithromycin use (often considered a surrogate marker for Pseudomonas aeruginosa infection and poorer lung function). CONCLUSION: SARS-CoV-2 infection yielded high morbidity and hospitalisation in pwCF. PwCF with forced expiratory volume in 1â s <70% predicted, CFRD and those with lung transplants are at particular risk of more severe outcomes.
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BACKGROUND: Several studies have assessed safety and efficacy outcomes for lumacaftor/ivacaftor therapy. We report on lumacaftor/ivacaftor's impact on lung function, physical performance, and health-related quality of life (HRQOL) in a subpopulation of Danish people with Cystic Fibrosis (CF; PWCF) with advanced pulmonary disease who would not fulfill inclusion criteria for these studies. METHODS: This follow-up study examined lumacaftor/ivacaftor's effect in a highly selected CF population. Inclusion criteria included low percent predicted forced expiratory volume in one second (ppFEV1 ), fast deteriorating ppFEV1 , low body mass index (BMI), and difficult-to-treat infections. Primary endpoints included change in ppFEV1 slope, cardiopulmonary exercise testing (CPET), and all domains of the Cystic Fibrosis Questionnaire-Revised (CFQ-R). Secondary outcomes included change in ppFEV1 , BMI Z-score, and sweat chloride concentration. RESULTS: A total of 21 patients homozygous for the F508del mutation and a median ppFEV1 of 38.7 were included. We found significant improvements in ppFEV1 (+4.2 p < .01, +5.8 p < .01, +4.8 p < .01 and +3.8 p = .03 ppFEV1 after 3, 6, 9, and 12 months of treatment compared to baseline), ppFEV1 slope (+6.84 ppFEV1 /year between the year before and the year after treatment initiation; p = .02), and saturation at CPET initiation (+1.4%, p < .02) and termination (+2.6%, p < .01) after 6 months of treatment. Finally, HRQOL improved significantly in all CFQ-R domains except Emotion and Treat. CONCLUSIONS: Our findings suggest that lumacaftor/ivacaftor reduces lung function decline, improves lung function, physical performance, and HRQOL to a greater extent in PWCF with severe lung disease than previously recognized.
Asunto(s)
Aminofenoles/uso terapéutico , Aminopiridinas/uso terapéutico , Benzodioxoles/uso terapéutico , Agonistas de los Canales de Cloruro/uso terapéutico , Fibrosis Quística/tratamiento farmacológico , Quinolonas/uso terapéutico , Adolescente , Adulto , Fibrosis Quística/genética , Fibrosis Quística/fisiopatología , Regulador de Conductancia de Transmembrana de Fibrosis Quística/agonistas , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Combinación de Medicamentos , Femenino , Volumen Espiratorio Forzado , Humanos , Pulmón/efectos de los fármacos , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Calidad de Vida , Adulto JovenRESUMEN
BACKGROUND: Cystic fibrosis related diabetes (CFRD) has implications for morbidity and mortality with several risk factors identified. We studied the epidemiology of CFRD in the large dataset of the European Cystic Fibrosis Society Patient registry. METHODS: Data on CF patients were investigated for the prevalence of CFRD as well as for any association with suggested risk factors and effects. RESULTS: CFRD increased by approximately ten percentage points every decade from ten years of age. Prevalence was higher in females in the younger age groups. CFRD was associated with severe CF genotypes (ORâ¯=â¯3.11, 95%CI: 2.77-3.48), pancreatic insufficiency (ORâ¯=â¯1.46, 95%CI: 1.39-1.53) and female gender (ORâ¯=â¯1.28, 95%CI: 1.21-1.34). Patients with CFRD had higher odds of being chronically infected with Pseudomonas aeruginosa, Burkholderia cepacia complex and Stenotrophomonas maltophilia than patients without CFRD, higher odds of having FEV1% of predicted <40% (ORâ¯=â¯1.82, 95%CI: 1.70-1.94) and higher odds of having BMI SDS ≤-2 than patients without CFRD (ORâ¯=â¯1.24, 95%CI: 1.15-1.34). CONCLUSIONS: Severe genotype, pancreatic insufficiency and female gender remain considerable intrinsic risk factors for early acquisition of CFRD. CFRD is associated with infections, lower lung function and poor nutritional status. Early diagnosis and aggressive treatment of CFRD are more important than ever with increasing life span.