Omalizumab for asthma and allergic bronchopulmonary aspergillosis in adults with cystic fibrosis

BackgroundIn cystic fibrosis (CF), omalizumab has been used for difficult-to-treat asthma and allergic bronchopulmonary aspergillosis (ABPA) but safety and efficacy data are limited for this population.MethodsWe assessed patients receiving omalizumab for asthma or ABPA in the Toronto adult CF center between 2005 and 2017. We evaluated treatment safety and efficacy by analyzing changes in FEV₁% predicted (FEV₁pp) max value, slope and variability captured by the area under the curve (AUC), the cumulative dose of systemic corticosteroids (SCS), use of intravenous (IV) antibiotics and hospitalization days before omalizumab and up to 1 year after treatment initiation. Linear mixed effects model was used for FEV₁pp slope and the trapezoidal rule for FEV₁pp AUC.ResultsTwenty-seven CF patients received omalizumab, 16 (59.3%) for asthma and 11 (40.7%) for ABPA. No significant omalizumab-related adverse effects were observed. In the asthmatic group, the max value of FEV₁pp improved on omalizumab and the cumulative dose of SCS decreased. In the ABPA group, the rate of FEV₁pp decline (slope) and the variability of FEV₁pp (AUC) improved on omalizumab. In ABPA patients, the cumulative SCS dose was not significantly different but 4 (36%) patients decreased their SCS dose by >50% compared to baseline. Days on IV antibiotics and hospital days did not differ significantly before and while on omalizumab therapy.ConclusionsIn adult CF patients with difficult-to-treat asthma or ABPA, omalizumab should be considered. Larger studies are needed to identify patient characteristics that may predict response to omalizumab.     

The effect of antibiotic changes during treatment of cystic fibrosis pulmonary exacerbations

BackgroundAntibiotics are often changed during treatment of pulmonary exacerbations (PEx) in people with cystic fibrosis (CF) who have a poor clinical response. We aimed to characterize the reasons CF providers change antibiotics and examined the effects of antibiotic changes on lung function recovery.MethodsThis was a retrospective cohort study using the Toronto CF Database from 2009 to 2015 of adults and children with CF PEx treated with intravenous antibiotics. The co-primary outcome measure was absolute and relative change in forced expiratory lung volume in 1 s (FEV₁) at end of treatment and follow-up. Secondary outcome assessed the proportion of patients returning to > 90% or > 100% previous baseline FEV₁.ResultsA total of 399 PEx were included of which 105 had antibiotic changes. Reasons for antibiotic changes included change in antibiotic route prior to discharge (26%), drug reactions (20%), poor FEV₁ response (25%), targeting additional microbes (16%) and lack of symptom improvement (13%). In our multivariable analysis, among non-responders (< 90% FEV₁ recovery to baseline or lack of symptom improvement at the interim time point), a change in antibiotics was not associated with any significant difference in absolute or relative FEV₁ at end of treatment or at follow-up. Antibiotic change in non-responders was not associated with improved return to 90% or 100% baseline FEV₁ at end of treatment or follow-up.ConclusionsChanging antibiotics during CF PEx treatment in those with poor clinical response was not associated with any improved FEV₁ response or return to baseline lung function.     

An observational study of matrix metalloproteinase (MMP)-9 in cystic fibrosis

BackgroundIn cystic fibrosis (CF), cross-sectional studies have reported sputum matrix metalloproteinase (MMP)-9 to be elevated and negatively correlated with FEV₁. This longitudinal study examined the association between MMP-9 and tissue inhibitors of metalloproteinases (TIMPs) to prognostic parameters in CF.MethodA cross-sectional survey of CF and control subjects; CF patients were followed up for a median of 49 months. MMP-9 and TIMP-1 and TIMP-2 were quantified in sputum and plasma.ResultsSeventy-three patients with CF, median age 22 years, and 40 controls were recruited. Fifty-three of these CF patients were followed up. Prospectively, in CF subjects, plasma MMP-9 activity was adversely associated with FEV₁ (β − 1.15 (95% CI − 2.10, − 0.20), p = 0.019) and rate of FEV₁ decline, and plasma TIMP-1 was adversely associated with mortality: hazard ratio 3.66 (1.91–7.04), p < 0.001.ConclusionsThese associations further justify investigation of MMP-9 and TIMP-1 as biomarkers for short- to medium-term FEV₁ decline and mortality in patients with CF.     

Non-invasive ventilation and clinical outcomes in cystic fibrosis: Findings from the UK CF registry

BackgroundNon-invasive ventilation (NIV) for respiratory failure and airway clearance is an established intervention in cystic fibrosis (CF), but its therapeutic benefit on lung function and survival remains under-investigated.MethodsUsing data from the UK CF Registry between 2007 and 2015, we explored the patterns of NIV use, and assessed changes in mean percent predicted FEV₁ (ppFEV₁) prior to and after NIV use, and the survival of patients on NIV.ResultsAmong 11,079 patients, 1107 had at least one record of NIV treatment. Incidence and prevalence of NIV was lower in children and followed non-linear temporal patterns. Adjusting for other risk factors, ppFEV₁ rose by 0.70 (95%CI: -0.83, 2.24) after first NIV use in children. In adults with a low ppFEV₁ (<40%) at initiation of treatment, NIV increased mean ppFEV₁ by 2.60 (95% CI: 0.93, 4.27). Our analysis showed that NIV initiation is associated with an increased risk of death/transplant in both children (HR = 2.47; 95%CI: 1.20–5.08) and adults (HR = 1.96; 95% CI: 1.63–2.36) but effect was attenuated in children with low ppFEV₁ (<40%).ConclusionsNIV usage in CF improves spirometric values but does not benefit survival. Further studies are required to better understand survival outcomes and ultimately improve NIV outcomes in CF.     

Glycemic control and FEV1 recovery during pulmonary exacerbations in pediatric cystic fibrosis-related diabetes

RationaleWhether short-term glucose control in cystic fibrosis-related diabetes (CFRD) is associated with FEV₁ recovery during acute pulmonary exacerbations is unclear.MethodsData from all patients with CFRD ages 6–21 years hospitalized in 2010–2016 for pulmonary exacerbations at our CF Center were analyzed, including CFRD status at each encounter, all FEV₁ recorded during each exacerbation, and relevant clinical covariates. Glucose control was analyzed using meter blood glucose area under the curve (AUC) indices. The primary outcome was FEV₁ recovery.ResultsPatients with CFRD who finished IV antibiotics at home were treated for longer than those fully treated in the hospital (22.2 vs. 13.8 days). In those who finished treatment at home, poor inpatient glycemic control was associated with lower lung function improvement: when comparing the 75th to the 25th percentile of each glycemic index (i.e., “poorer” vs. “better” glycemic control), FEV₁ recovery at discharge was 20.1% lower for glucose AUC (95%CI −0.4%, −39.9%); 20.9% lower for 48-h AUC (95%CI −2.7%, −39.1%); and 28.2% lower for AUC/day (95%CI −7.1%, −49.3%). Similar results were found at the end of IV antibiotics and at clinic follow-up. Likewise, patients with poor glycemic control had a lower slope of inpatient FEV₁ recovery. Analysis in patients with normal glucose tolerance was largely non-significant. No associations were found between hemoglobin A1c and FEV₁ recovery.ConclusionsIn patients with CFRD who complete IV antibiotic treatment at home, poor inpatient glycemic control is associated with worse FEV₁ recovery despite longer duration of treatment.     

Design and powering of cystic fibrosis clinical trials using rate of FEV1 decline as an efficacy endpoint

BackgroundRate of lung function decline (RLFD) (as FEV₁ percent predicted/yr) is a robust measure of CF therapeutic efficacy rarely used as a study endpoint, in part due to uncertainty of sample size requirements.MethodsSample size requirements for 1:1 randomizations to detect RLFD treatment effects from 20% to 80% were assessed in Epidemiologic Study of CF (ESCF) patients. Effects of measuring FEV₁ 1–4 times per year in studies of 1- to 4-year durations were assessed in 399 patients age ≥ 6 years with FEV₁ ≥ 70%. Impacts of inclusion/exclusion based on risk factors in 2369 ESCF patients were assessed over 1.5 years using semi-annual FEV₁ measures.ResultsIncreasing study duration and exclusion of lower risk patients (e.g., no P. aeruginosa infection) both substantially reduced requirements.ConclusionsCF RLFD studies of 1.5 years in duration appear feasible provided that investigators account for the beneficial effects of subject inclusion/exclusion based on risk factors in power estimates.     

The effect of acute maximal exercise on the regional distribution of ventilation using ventilation MRI in CF

BackgroundThe importance of exercise in the management of people with CF is well recognised, yet the effect of exercise on lung function is not well understood. FEV₁ is insensitive to the detection of small changes in lung function. Ventilation MRI and LCI are both more sensitive to mild lung disease than FEV₁ and may be better suited to assess the effects of exercise. Here we assessed the short-term effects of maximal exercise on the distribution of ventilation using ventilation MRI and LCI.MethodsPatients with CF and a range of lung disease were assessed. Baseline LCI and ventilation MRI was followed by a maximal cardio-pulmonary exercise test (CPET). Repeated ventilation MRI was performed within 30 minutes of exercise termination, followed by LCI and finally by FEV₁.Results13 patients were recruited and completed all assessments. Mean (SD) age was 25 (10) years and mean (SD) FEV₁ z-score was -1.8 (1.7). Mean LCI at baseline was 8.2, mean ventilation defect percentage on MRI (VDP) was 7.3%. All patients performed maximal CPET. Post-exercise, there was a visible change in lung ventilation in 85% of patients, including two patients with increased ventilation heterogeneity post-CPET who had normal FEV₁. VDP and LCI were significantly reduced post-exercise (p < 0.05) and 45% of patients had a significant change in VDP.ConclusionsAcute maximal exercise directly affects the distribution of ventilation on ventilation MRI in patients with CF. This suggests that exercise is beneficial in CF and that ventilation MRI is suitable to assess airway clearance efficacy.     

Rapid lung function decline in adults with early-stage cystic fibrosis lung disease

RationaleThe prevalence of adults living with cystic fibrosis (CF) who have early-stage lung disease is increasing.ObjectivesDescribe the prevalence and evaluate spirometric risk factors associated with the subgroup of patients with early-stage lung disease and FEV₁ decline of ≥5% predicted/year.MethodsRetrospective cohort study of patients ≥18 years with FEV₁% predicted ≥80% included in the US CF Foundation Patient Registry from 2010–2013. Regression models were developed to estimate FEV₁ rate of decline. Multivariable logistic analysis was used to assess if spirometric risk factors were associated with FEV₁ decline.Measurements and main results3,029 subjects were in the study cohort. Approximately 15% of the cohort had a substantial decline in lung function ≥5% predicted/year. In multivariable models adjusted for confounders, FEV₁/FVC ratio <0.8 (Odds Ratio (OR) 1.63, 95% confidence interval (CI) 1.31 to 2.02) and history of FEV₁% predicted variability (OR 2.35,95%CI 1.74 to 3.18) were associated with rapid lung function decline.ConclusionsEven among adults with early-stage lung disease, approximately 15% are shown to progress and experience a large decline in lung function. This reinforces the concept that lung function in early-stage CF is not normal or mild. Rather, lung function decline may be delayed, but not avoided, in these individuals. Variability in FEV₁% predicted and airway obstruction as measured by FEV1/FVC ratio may identify individuals at increased risk of decline. Adults with early-stage lung disease should be followed in clinic to monitor for onset of decline.     

Temocillin in cystic fibrosis: A retrospective pilot study

BackgroundTemocillin is currently used in the treatment of acute pulmonary exacerbations caused by Burkholderia cepacia complex and multi-resistant Pseudomonas aeruginosa in cystic fibrosis (CF) patients despite little published clinical data. This study assessed if intravenous (IV) antibiotic therapy including temocillin was equivalent to standard combination therapy for an acute exacerbation.MethodsA retrospective, pilot cross-over study. Adult patients attending two CF centres between 1997 and 2006 who had received a course of IV antibiotics including temocillin (TIV) and a further IV course (within ± 1 year) which did not include temocillin (NTIV) were included. Outcome measures at the start and end of each IV course were recorded (FEV₁%, FVC%).ResultsTwenty six patients had received temocillin. Baseline values of FEV₁% predicted were comparable for both groups (TIV: 37(18%), NTIV: 39(20%)). FEV₁% increased by 7.12(11.67)% after TIV (p < 0.01) and 6.65(7.62)% after NTIV (p < 0.01). There was no significant difference between the IV courses in mean %change in lung function TIV versus NTIV (FEV₁ 0.46% [95%CI: − 4.55 to 5.48%]).ConclusionThese data suggest equivalence in the lung function outcome of IV antibiotic therapy includingtemocillin versus standard IV antibiotic therapy.     

Cystic fibrosis and pregnancy in the modern era: A case control study

BackgroundIncreasingly, women with cystic fibrosis become pregnant. Outcomes of these women need further study particularly in the setting of improved survival in CF.MethodsWe performed a case-control study of pregnant CF women including 22 matched pairs with an average follow-up of 4.5 years. Nutritional outcomes, changes in lung function, and exacerbation rates were compared.ResultsMatched pairs were similar in age, sweat chloride, FEV₁ and FVC % predicted, BMI, and diabetes status. Change in BMI, FEV₁ and FVC % predicted at the end of pregnancy and at last follow-up were similar between groups. Moreover, rates of exacerbation before, during and after pregnancy were similar. On multivariable analysis pregnancy had no effect on change in lung function over the study period. Significant predictors of decline included higher pre-pregnancy lung function and pancreatic insufficiency.ConclusionsPregnancy does not lead to immediate or medium-term adverse effects for CF patients.     

Isolation of Enterobacteriaceae in airway samples is associated with worse outcome in preschool children with cystic fibrosis

BackgroundIncreased abundance of Enterobacteriaceae(EB) in the respiratory microbiome of young CF patients was reported to precede Pseudomonas aeruginosa(PA) colonisation. We explored whether impending PA colonisation can be predicted by growth of EB in routine airway cultures and whether EB contribute to CF lung disease severity.MethodsWe retrospectively studied the records of 62 children with CF for growth of EB and PA during the first 5 years of life and subsequent best lung function at ages 5–7 and 9–11 years.ResultsAt least one EB positive month occurred in 36/62 (58%) patients. Median (IQR) age at first EB isolation was 0.4 (0.2–0.8) years. PA isolation before age 5 was more frequent in the EB positive (23/36, 54%) than in EB negative children (10/26, 38%; p = 0.048). EB isolation preceded PA isolation in 19/23 (83%) cases (p = 0.003).Median (IQRf) FEV₁ at age 5 to 7 years was 105% (94–117) in the EB positive group and 108% (102–115) in the EB negative group (p = 0.154). At age 9–11, FEV₁ was lower in EB positive children (99%(88–105) vs 105%(96–110); p = 0.035).Only PA isolation (p = 0.002) before age 5 years was a significant predictor of FEV₁ at age 5–7 years. Both EB isolation (p = 0.033) and PA isolation (p = 0.023) were predictors of the FEV₁ at age 9–11 years.ConclusionIn preschool children with CF, EB were isolated in just over half of the children. In that subgroup PA isolation was more common. Both EB and PA isolation are associated with worse lung function at later age.     

Chronic Stenotrophomonas maltophilia infection and mortality or lung transplantation in cystic fibrosis patients

BackgroundChronic Stenotrophomonas maltophilia infection is an independent risk factor for severe pulmonary exacerbations in cystic fibrosis (CF) patients. The goal of this study was to determine the effect of chronic S. maltophilia infection on mortality and the need for lung transplantation in a longitudinal study of children and adults with CF.MethodsThis was a cohort study of CF patients from the Hospital for Sick Children and St Michael's Hospital (Toronto, Canada) from 1997 to 2008. A Cox Regression model was used to estimate the hazard ratio (HR) to time of death or lung transplantation adjusting for age, gender, genotype, pancreatic status, CF related diabetes (CFRD), forced expiratory volume in 1 s (FEV₁), body mass index, number of pulmonary exacerbations, Pseudomonas aeruginosa, Burkholderia cepacia complex, Aspergillus and chronic S. maltophilia infection.ResultsA total of 687 patients were followed over the 12 year study period; 95 patients underwent a lung transplantation (of which 26 died) and an additional 49 patients died (total 144 events). In a Cox Regression model adjusting for baseline FEV₁, baseline infection with B. cepacia complex (HR 1.72, 95% CI 1.09–2.71) and baseline chronic S. maltophilia infection (HR 2.80, 95% CI 1.65–4.76) were significantly associated with death or lung transplant. However, in a time-varying model, infection with B. cepacia complex and chronic S. maltophilia infection were no longer significant.ConclusionsBaseline chronic S. maltophilia infection is associated with an almost three-fold increased risk of death or lung transplant in CF patients. It is still unclear, however, whether chronic S. maltophilia infection is simply a marker of severity of disease and ultimate mortality or whether it is causally related to disease progression.     

Pulmonary artery pressure in cystic fibrosis adults: Characteristics,clinical correlates and long-term follow-up

BackgroundWe examined pulmonary artery pressure (PAP) characteristics of CF adults, studied clinical correlates and long-term survival.MethodsComprehensive clinical data were collected and Doppler echocardiography was used to estimate PAP in 109 stable CF adults and 50 healthy controls.ResultsCF patients had lower day and night-time oxygen status, elevated CRP and BNP, and elevated PAP (27.7(13.2, 62.8) mmHg patients v 17.9(11.3, 30.9) mmHg controls, p < 0.001). Even patients with mild pulmonary disease had raised PAP. PAP measurements strongly correlated with arterial partial pressure of oxygen (PaO₂, r = − 0.673, p < 0.001), and FEV₁ percentage predicted (FEV₁%, r = − 0.642, p < 0.001) which were both independent predictors of PAP. At 10 year follow up PAP measurements were related to survival but FEV₁% and PaO₂ were both stronger predictors of death.ConclusionsPAP is raised in CF adults and correlates with pulmonary disease severity. Unlike PaO₂ and FEV₁%, it does not appear to be an independent prognostic marker.     

Diabetes mellitus and survival in cystic fibrosis patients after lung transplantation

BackgroundDiabetes mellitus (DM) is common in CF and associated with more severe disease. It is unclear whether DM influences outcome of lung transplantation (LTx).MethodsOne hundred twenty-three CF patients evaluated for LTx at our centre were included. Survival was calculated.ResultsPatients with and without DM did not differ with regard to gender, age, FEV₁ and BMI prior to LTx. Eighty patients (65%) had a diagnosis of DM before and 13 (11%) only after LTx. Recipients with DM had a significantly higher 1- and 5-year survival (89% and 71%) than those without (71% and 51%). In the multivariate Cox-regression analysis, DM had no impact on LTx-survival.ConclusionsOne- and five-year survival rates after LTx tend to be better in CF recipients with DM compared to those without DM. No impact of DM on the development of BOS was found.     

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

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

The impact of switching to the new global lung function initiative equations on spirometry results in the UK CF Registry

BackgroundThe Quanjer et al. Global Lung Function Initiative (GLI)-2012 multi-ethnic all-age reference equations for spirometry are endorsed by all major respiratory societies and are the new gold standard. Before the GLI equations are implemented for use in CF patients, the impact of changing equations from those currently used needs to be better understood.MethodsAnnual review data submitted to the UK CF Trust Registry between 2007 and 2011 were used to calculate %predicted FEV₁, FVC and FEV₁/FVC using three widely used reference equations (Wang–Hankinson and Knudson) and the new GLI-2012 equations.ResultsOverall, Knudson and Wang equations overestimated %predicted values in paediatric patients, such that a greater proportion of patients had lung function values in the normal range. Within individual patients, the impact of switching equations varied greatly depending on the patients' age, and which equations were used.ConclusionsA unified approach to interpreting spirometric lung function measurements would help facilitate more appropriate comparison both within and between centres and countries. Interpretation of longitudinal measurements using a continuous reference equation across all-ages, like the GLI, may further improve our understanding of CF lung disease.     

Baseline Cystic fibrosis disease severity has an adverse impact on pregnancy and infant outcomes,but does not impact disease progression

BackgroundWith increasing longevity and quality of life in adults with Cystic fibrosis (CF), growing maternity rates are reported. Women with severe CF are becoming pregnant, with unpredictable maternal and fetal outcomes.AimTo determine how baseline disease severity, pancreatic insufficiency (PI) and Pseudomonas aeruginosa (PA) infection affect fertility, the pregnancy course, delivery, neonatal outcome, and subsequent disease progression.MethodsA multicenter-retrospective cohort study. Data on patients that had been pregnant between 1986-2018 was collected from ten CF centers worldwide. Disease severity [mild or moderate-severe (mod-sev)] was defined according to forced expiratory volume % predicted in 1 second (FEV₁) and body mass index (BMI). Three time periods were compared, 12 months prior to conception, the pregnancy itself and the 12 months thereafter.ResultsData was available on 171 pregnancies in 128 patients aged 18-45 years; 55.1% with mod-sev disease, 43.1% with PI and 40.3% with PA. Women with mod-sev disease had more CF-related complications during and after pregnancy and delivered more preterm newborns. However, FEV₁ and BMI decline were no different between the mild and mod-sev groups. A more rapid decline in FEV₁ was observed during pregnancy in PI and PA infected patients, though stabilizing thereafter. PI was associated with increased risk for small for gestational age infants.ConclusionBaseline disease severity, PA infection and PI have an adverse impact on infant outcomes, but do not impact significantly on disease progression during and after pregnancy. Consequently, pregnancies in severe CF patients can have a good prognosis.     

Efficacy and safety of inhaled dry-powder mannitol in adults with cystic fibrosis: An international,randomized controlled study

Background: Mannitol is a mucoactive hyperosmotic agent used as add-on therapy in patients with cystic fibrosis (CF), administered twice-daily (BID) via a small, portable, breath-actuated dry-powder inhaler. This study was conducted to provide confirmatory evidence of mannitol's efficacy and safety in adults.Methods: This multicenter, double-blind, randomized, parallel-group, controlled clinical trial recruited adults (aged ≥18 years) with CF, and forced expiratory volume in 1 second (FEV₁) 40–90% predicted. Subjects received either mannitol 400 mg or mannitol 50 mg (control), BID via dry-powder inhaler for 26 weeks. Primary endpoint: FEV₁ averaged over the 26-week treatment period.Results: Of 423 subjects randomized (209 or 214 receiving mannitol 400 mg BID or control, respectively), 373 (88.2%) completed the study, with a similar proportion completing in the two groups. For FEV₁ averaged over 26 weeks, mannitol 400 mg BID was statistically superior to control (adjusted mean difference 54 mL [95% CI 8, 100 mL]; p = 0.020). This was supported by sensitivity analyses of the primary endpoint, and by observed improvements in secondary pulmonary function endpoints (eg, absolute adjusted mean difference in percent predicted FEV₁ averaged over 26 weeks 1.21% [0.07%, 2.36%]; p = 0.037). Adverse events were mainly mild or moderate in severity, with treatment-related adverse events in 15.5 and 12.2% of subjects receiving mannitol 400 mg BID and control, respectively.Conclusions: In adults with CF, mannitol 400 mg BID inhaled as a dry-powder statistically significantly improved lung function (FEV₁) compared with control, with this improvement supported by sensitivity analyses and secondary pulmonary function endpoints. Mannitol had a good overall safety and tolerability profile. ClinicalTrials.gov: NCT02134353.     

Withdrawal of dornase alfa increases ventilation inhomogeneity in children with cystic fibrosis

BackgroundThe lung clearance index (LCI) is increasingly used as an outcome in clinical trials of patients with mild cystic fibrosis (CF) lung disease. Yet, understanding the impact of standard CF respiratory therapy on LCI is needed. We assessed to what degree withdrawal of nebulised dornase alfa affected LCI in school-age children with CF not receiving CFTR modulators or hydrator therapy.MethodsA single-centre, randomised, controlled, parallel group study to determine effects of one month's withdrawal of nebulised dornase alfa (intervention) in 5-18 years old children with CF. Remaining chronic maintenance therapy stayed unchanged. Outcome measures were assessed at two visits one month apart. Primary outcome was absolute change in LCI. Secondary outcomes were FEV₁, FEF_25–75 and CF Questionnaire-revised (CFQ-R) respiratory symptom score. Possible harmful effects were assessed by comparing the occurrence of pulmonary exacerbations between groups.ResultsTwenty-eight children (median age 10.4 [interquartile range: 7.6; 13.5] years) with CF received standard care (n = 14) or intervention (n = 14). Compared with the control group, LCI increased (worsened) 1.74 (95% confidence interval: 0.62; 2.86) during withdrawal of dornase alfa, while FEV₁ (-6.8% predicted) and FEF_25–75 (-13.1% predicted) decreased significantly. Change in CFQ-R respiratory symptom score and the occurrence of pulmonary exacerbations did not differ significantly between groups.ConclusionsOne month's withdrawal of dornase alfa caused increasing ventilation inhomogeneity and deteriorating FEV₁ and FEF_25–75 in school-age children with mild CF. Hence, adherence to dornase alfa optimally needs to be addressed when using LCI and spirometric parameters as endpoints, even in short-term clinical trials.     

Do cystic fibrosis centres with the lowest FEV1 still use the least amount of intravenous antibiotics? A registry-based comparison of intravenous antibiotic use among adult CF centres in the UK

Background

The Epidemiologic Study of Cystic Fibrosis using 1995–1996 and 2003–2005 data found that CF centres with lowest FEV₁ tended to use fewer intravenous antibiotics. We repeated the analyses using 2013–2014 UK CF registry data to determine if this was still the case.