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.     

Lung clearance index during hospital admission in school-age children with cystic fibrosis

BackgroundThere is currently limited information regarding lung clearance index (LCI) and its response to treatment of pulmonary exacerbations in CF. We aimed to examine the utility of LCI for assessing short term clinical response to IV antibiotic therapy in school-age children with CF.MethodsSubjects experiencing exacerbations and hospitalised for IV antibiotics performed both multiple breath nitrogen washout (MBNW) and spirometry on admission to hospital and prior to discharge.Results27 patients (aged 6–20 years) had paired data for MBNW and spirometry. Mean LCI reduced from 12.18 to 11.65 (4.4%) by time of discharge and FEV₁ z-score improved from − 3.05 to − 2.86 (6.2%). Overall, LCI improved in n = 15 (55%) patients compared with n = 18 (67%) where FEV₁ improved.ConclusionsIn summary, these findings do not support the use of LCI (or indeed, FEV₁) to gauge the short term clinical response to IV antibiotic therapy in school-age children with cystic fibrosis.     

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.     

Pooled analysis of two large randomised phase III inhaled mannitol studies in cystic fibrosis

BackgroundTo evaluate safety and efficacy of inhaled mannitol treatment in subgroups of a large global CF population.MethodsData were pooled from two multicentre, double-blind, randomised, controlled, parallel group phase III studies in which 600 patients inhaled either mannitol (400 mg) or control (mannitol 50 mg) twice a day for 26 weeks.ResultsBoth the mean absolute change in FEV₁ (mL) and relative change in FEV₁ by % predicted from baseline for mannitol (400 mg) versus control were statistically significant (73.42 mL, 3.56%, both p < 0.001). Increases in FEV₁ were observed irrespective of rhDNase use. Significant improvements in FEV₁ occurred in adults but not children (6–11) or adolescents (aged 12–17). Pulmonary exacerbation incidence was reduced by 29% (p = 0.039) in the mannitol (400 mg) group.ConclusionsSustained six-month improvements in lung function and decreased pulmonary exacerbation incidence indicate that inhaled mannitol is an important additional drug in the treatment of CF.     

Chronic Stenotrophomonas maltophilia infection and exacerbation outcomes in cystic fibrosis

BackgroundChronic Stenotrophomonas maltophilia infection is a risk factor for pulmonary exacerbation in cystic fibrosis (CF) but its impact on subsequent clinical outcomes is unknown. The aim of this study was to determine the effect of chronic S. maltophilia infection and associated antimicrobial therapy on the recovery of forced expiratory lung volume in 1 s (FEV₁) following pulmonary exacerbation.MethodsThis was a retrospective cohort study of patients with CF followed at The Hospital for Sick Children and St. Michael's Hospital from 1997 to 2008. The primary outcome was the difference in FEV₁ percent predicted from baseline to follow up after a pulmonary exacerbation. Secondary outcomes for the effect of antimicrobial therapy included time to subsequent exacerbation.ResultsThere were 1667 pulmonary exacerbations in 440 CF patients. Patients with chronic S. maltophilia infection did not recover their baseline FEV₁ following 31% of exacerbations and had an overall mean FEV₁ decline of 1.84% predicted after exacerbation. Older (p = 0.02), female (p = 0.02) patients with lower BMI z score (p = 0.002) and Burkholderia cepacia complex infection (p = 0.005), but not chronic S. maltophilia infection (p = 0.86), had a greater decrease in follow up FEV₁% pred compared to baseline. The number of days of antibiotic therapy against S. maltophilia during a pulmonary exacerbation was not associated with a significant difference in the FEV₁ recovery (p = 0.69) or with a longer time to subsequent pulmonary exacerbation (p = 0.56).ConclusionsAlthough CF patients experience a significant decline in lung function following exacerbation, chronic S. maltophilia infection and associated antimicrobial therapy do not affect subsequent lung function recovery.     

A randomized double blind,placebo controlled phase 2 trial of BIIL 284 BS (an LTB4 receptor antagonist) for the treatment of lung disease in children and adults with cystic fibrosis

BackgroundAirway inflammation, mediated in part by LTB₄, contributes to lung destruction in patients with cystic fibrosis (CF). LTB₄-receptor inhibition may reduce airway inflammation. We report the results of a randomized, double-blind, placebo-controlled study of the efficacy and safety of the leukotriene B₄ (LTB₄)-receptor antagonist BIIL 284 BS in CF patients.MethodsCF patients aged ≥ 6 years with mild to moderate lung disease were randomized to oral BIIL 284 BS or placebo once daily for 24 weeks. Co-primary endpoints were change in FEV₁ and incidence of pulmonary exacerbation.ResultsAfter 420 (155 children, 265 adults) of the planned 600 patients were randomized, the trial was terminated after a planned interim analysis revealed a significant increase in pulmonary related serious adverse events (SAEs) in adults receiving BIIL 284 BS. Final analysis revealed SAEs in 36.1% of adults receiving BIIL 284 BS vs. 21.2% receiving placebo (p = 0.007), and in 29.6% of children receiving BIIL 284 BS vs. 22.9% receiving placebo (p = 0.348). In adults, the incidence of protocol-defined pulmonary exacerbation was greater in those receiving BIIL 284 BS than in those receiving placebo (33.1% vs. 18.2% respectively; p = 0.005). In children, the incidence of protocol-defined pulmonary exacerbation was 19.8% in the BIIL 284 BS arm, and 25.7% in the placebo arm (p = 0.38).ConclusionsWhile the cause of increased SAEs and exacerbations due to BIIL 284 BS is unknown, the outcome of this trial provides a cautionary tale for the administration of potent anti-inflammatory compounds to individuals with chronic infections, as the potential to significantly suppress the inflammatory response may increase the risk of infection-related adverse events.     

The predictive potential of the sweat chloride test in cystic fibrosis patients with the G551D mutation

BackgroundIvacaftor, a cystic fibrosis transmembrane regulator (CFTR) potentiator, decreased sweat chloride concentrations and improved clinical measures in cystic fibrosis (CF) patients with the G551D mutation.ResultsSweat chloride measurements at day 15 had an overall positive predictive value (PPV) of 86.3%, a negative predictive value (NPV) of 65.5%, sensitivity of 73.9%, and specificity of 80.9% for an FEV₁ improvement of ≥ 5% from baseline at week 16. For ivacaftor patients the median FEV₁ improvement was 16.7%; for placebo patients 0.4%. For patients aged 6–11 years who received ivacaftor and who had a sweat chloride decrease of ≥ 40 mmol/L from baseline at day 15, a median weight gain of 11.2% at week 16, compared to 6% for those with a smaller decrease was observed.ConclusionsChanges in sweat chloride concentration at day 15 following treatment with ivacaftor may have sufficient predictive potential to identify individuals that show improvement in pulmonary function and weight gain after 16 weeks of treatment.     

Dietary supplementation with multiple micronutrients: No beneficial effects in pediatric cystic fibrosis patients

BackgroundCystic fibrosis (CF) patients are subjected to increased oxidative stress due to chronic pulmonary inflammation and recurrent infections. Additionally, these patients have diminished skeletal muscle performance and exercise capacity. We hypothesize that a mixture of multiple micronutrients could have beneficial effects on pulmonary function and muscle performance.MethodsA double-blind, randomized, placebo controlled, cross-over trial with a mixture of multiple micronutrients (ML1) was performed in 22 CF patients (12.9 ± 2.5 yrs) with predominantly mild lung disease. Anthropometric measures, pulmonary function, exercise performance by bicycle ergometry, muscular strength and vitamins A and E were determined.ResultsAnalysis was performed using the paired Student t-test comparing the change in each parameter during ML1 and placebo. Plasma vitamin E and A levels increased during ML1 when compared to placebo. However, no significant difference between the effect of the ML1 or placebo was observed neither for FEV₁, FVC, anthropometry, nor for the parameters for muscle performance.ConclusionsThe micronutrient mixture was not superior to placebo with respect to changes in pulmonary function or muscle performance in pediatric CF patients, despite a significant increase in plasma vitamin E concentrations.     

Cytokine gene polymorphisms and severity of CF lung disease

BackgroundThe search for modifier genes to explain inconsistencies in cystic fibrosis (CF) genotype–phenotype relationships has yielded mixed results. In a previous cross-sectional study from our centre the clinical effect (as described by FEV₁, BMI z-score, admitted days and NIH score) of single nucleotide polymorphisms (SNPs) of four cytokine genes (IL-8, TNF-α, IL-1β and IL-10) was examined in 158 children with CF. No association between cytokine genotype and any biological outcome measure was found. In this present study a cross-sectional and longitudinal examination of this relationship was undertaken to test the hypothesis that pro-inflammatory SNPs would affect longitudinal changes in CF lung disease.MethodsUsing the cohort examined in our earlier study we performed both longitudinal and cross-sectional data analyses examining the relationship between SNPs (TNF-α, IL-8, IL-10 and IL-1β) and clinical outcome measurements. In the first part of this current study, lung function data (annual decline of FEV₁ percent predicted) was compared with the cytokine genotype over a 13 year period. In the second part of this current study multiple regression was used to assess associations between clinical outcomes (best FEV₁ percent predicted and BMI at the age of 10 years) and alleles of cytokine genes, adjusting for gender, CF genotype and lung infection status.ResultsA total of 152 patients with CF were analysed in the longitudinal study and data from 130 patients at the age of 10 years were analysed in the cross-sectional study. There was evidence for an association between pro-inflammatory SNPs of the IL-8, IL-10 and IL-1β genes and more severe lung disease. Multiple regression of the longitudinal data with a total of 10,956 lung function measurements showed an additional annual decline of the percentage predicted FEV₁ of − 1.15 (IL-8, p < 0.001), − 0.24 (IL-10, p = 0.049) and − 0.41 (IL-1β, p < 0.001) for patients with any of the pro-inflammatory alleles. None of the cross-sectional data showed a significant association between the cytokine genotypes and the clinical outcomes.ConclusionPro-inflammatory alleles of three cytokine genotypes, IL-8, IL-10 and IL-1β, appear to be associated with slightly more severe lung disease in patients with CF over a 13 year period. Further studies are required to exclude influence of confounders on the severity of lung disease.     

Efficacy and safety of ivacaftor in patients with cystic fibrosis and a non-G551D gating mutation

BackgroundIvacaftor is used to treat patients with CF and a G551D gating mutation; the KONNECTION study assessed the efficacy and safety of ivacaftor in patients with CF and a non-G551D gating mutation.MethodsPatients with CF ≥6 -years- old with non-G551D gating mutations received ivacaftor 150 mg q12h or placebo for 8 weeks in this 2-part, double-blind crossover study (Part 1) with a 16-week open-label extension (Part 2). The primary efficacy outcome was absolute change in FEV₁ through 8 and 24 weeks of ivacaftor treatment; secondary outcomes were changes in BMI, sweat chloride, and CFQ-R and safety through 8 and 24 weeks of treatment.ResultsEight weeks of ivacaftor resulted in significant improvements in percent predicted FEV₁, BMI, sweat chloride, and CFQ-R scores that were maintained through 24 weeks. Ivacaftor was generally well tolerated.ConclusionsIvacaftor was efficacious in a group of patients with CF who had selected non-G551D gating mutations.     

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.     

Long-term daily high and low doses of azithromycin in children with cystic fibrosis: A randomized controlled trial

BackgroundLong-term administration of azithromycin (AZM) in children with cystic fibrosis (CF) has improved outcomes. However, the doses and schedule of administration are not very well studied in children with CF.MethodsA randomized controlled trial was conducted to compare the effect of two doses of azithromycin (5 mg/kg/day and 15 mg/kg/day) on FEV₁ and pulmonary exacerbations in children with cystic fibrosis. Enrolled children were randomly allocated to receive daily azithromycin (5 mg/kg/day or 15 mg/kg/day) for 6 months. Clinical assessment and FEV₁ measurement were performed monthly.Results56 children (28 in high dose group and 28 in low dose group) were enrolled. 47 (24 and 23 children in low and high dose groups) completed 12 months of follow up. There was no difference in clinical scores, FEV₁, pulmonary exacerbation rates between two groups at baseline, 6 months and at 12 months. Per protocol analysis revealed that pulmonary exacerbation increased after discontinuing AZM and there was significantly more increase after 12 months of enrolment in children getting high dose azithromycin. There was no improvement in FEV₁ in either group at the end of treatment period. Children tolerated daily low as well as high dose AZM well for 6 months. There was no significant side effect of azithromycin.ConclusionIn this randomized controlled trial, we did not find differences in the effect of 2 doses (5 mg/kg/day or 15 mg/kg/day) of AZM on change in percentage predicted FEV₁, clinical scores, Pseudomonas colonization rates, pulmonary exacerbations and need for antibiotics. There was increase in exacerbations after stopping azithromycin in both the groups. Our results also suggest that the decrease in the incidence of LRTI persists only till 6 months after discontinuing azithromycin.     

Evidence of diminished FEV1 and FVC in 6-year-olds followed in the European cystic fibrosis patient registry, 2007–2009

BackgroundMany infants with cystic fibrosis (CF) exhibit airway inflammation, gas trapping, bronchiectasis, and/or reduced flow, but by age 6 years have forced vital capacities (FVC) and expiratory volumes in 1 second (FEV₁) within the variability range of the normal population. We sought evidence of diminished FVC and FEV₁ in 6-year-olds with CF.MethodsGLI 2012 FVC and FEV₁ Z-scores for 6-year-olds from the European CF Patient Registry were plotted against theoretical values from the Normal distribution.ResultsMean FVC and FEV₁ Z-scores for 681 patients (322 females) were ? 0.43 (SD = 1.41) and ? 0.65 (1.40). Z-scores were consistently lower than expected for the normative population by quantile–quantile plot.ConclusionsDiminished FEV₁, and to a lesser extent FVC, is found in a large majority of this population, consistent with an established body of evidence that loss of lung function begins early in life for most, if not all, children with CF.     

Validation of a multi-sensor armband during free-living activity in adults with cystic fibrosis

BackgroundThe SenseWear Armband (SWA) provides simple and non-invasive measures of energy expenditure (EE) during physical activity, however its accuracy in adults with cystic fibrosis (CF) during free living physical activities has not been established.Methods26 CF adults (mean FEV₁ 63% predicted; 11 males) completed a series of standardised static and active tasks with simultaneous analysis of EE via the SWA and indirect calorimetry (IC).ResultsMean difference and limits of agreement between EE values from the SWA and IC across all activities were − 0.02 METs (95% CI − 1.1 to 1.1). There was moderate agreement between the two measures (ICC 0.4; 95% CI: 0 to 0.7; p = 0.03). For individual activity tasks ICC ranged from 0.1 to 0.6.ConclusionOverall, the SWA demonstrated good agreement with IC for EE estimates in CF adults during a series of free-living activities, however accuracy was variable when assessing EE for specific activities of shorter duration.     

Ancestral haplotype 8.1 and lung disease severity in European cystic fibrosis patients

BackgroundThe clinical course of cystic fibrosis (CF) lung disease varies between patients bearing identical CFTR mutations. This suggests that additional genetic modifiers may contribute to the pulmonary phenotype. The highly conserved ancestral haplotype 8.1 (8.1AH), carried by up to one quarter of Caucasians, comprises linked gene polymorphisms on chromosome 6 that play a key role in the inflammatory response: LTA + 252A/G; TNF −308G/A, HSP70-2 + 1267A/G and RAGE −429T/C. As inflammation is a key component inducing CF lung damage, we investigated whether the 8.1AH represents a lung function modifier in CF.MethodsWe analyzed the lung function of 404 European CF patients from France (n = 230), Germany (n = 95) and UK (n = 79). FEV₁ differences between 8.1AH carriers and non-carriers were calculated in each country and pooled using a random effects model.ResultsThe frequency of 8.1AH carriers was similar between French (22%), German (29%) and UK (27%) patients. We found that 8.1AH carriers had significantly lower FEV₁, adjusted for age classes and countries (P < 0.04, mean FEV₁ difference − 6.4% CI95% [− 12.4%, − 0.5%]). No difference was observed with respect to BMI Z-scores and chronic colonization with P. aeruginosa.ConclusionsThese findings support the concept that 8.1AH is an important genetic modifier of lung disease in CF. To conclude, multiple linked genes outside the CF locus might explain some of the variability in lung phenotype.     

Dynamic vascular changes following intravenous antibiotics in patients with cystic fibrosis

BackgroundAdults with cystic fibrosis (CF) have altered large artery haemodynamics which is associated with a persisting systemic inflammatory state. We hypothesized that a short-term intervention favorably influencing the inflammatory status may modify their haemodynamic state.MethodsAdult patients with CF were studied immediately preceding and following 2 weeks of intravenous antibiotics. Large artery haemodynamics, principally heart rate-adjusted augmentation index (AIx) were obtained. Blood pressure (BP), spirometry and CRP were also measured.ResultsComplete data was available for 15 patients; mean (SD) age 28 (6) years. CRP was reduced while FEV₁% predicted improved. Following treatment AIx was lower: 10.9 (10.9)% to 8.1 (10.9)% (p < 0.05) while BP was similar and a trend toward lower heart rate (p = 0.06). Change in AIx was related to baseline FEV₁% predicted (r = 0.77) and BMI (r = 0.71) (both P < 0.01).ConclusionThe abnormal central haemodynamics evident in adults with CF is modulated with a short intervention of intravenous antibiotics.     

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.     

Prognostic relevance of dynamic hyperinflation during cardiopulmonary exercise testing in adult patients with cystic fibrosis

BackgroundDynamic hyperinflation during cardiopulmonary exercise testing (CPET) in cystic fibrosis (CF) has not been well characterized, and little is known regarding its prevalence, risk factors and clinical associations.MethodsCPET data from 109 adult patients with mild-to-moderate CF was used, in this retrospective study, to characterize and determine the prevalence of dynamic hyperinflation, and evaluate its relationship with lung function and exercise tolerance, clinical symptoms, and prognosis over a two-year period.Results58% of patients responded to CPET with dynamic hyperinflation. These patients had significantly lower lung function (FEV₁ 66 ± 19 versus 79 ± 18%pred., p < 0.01) and exercise tolerance (peak oxygen uptake 28.7 ± 8.1 versus 32.9 ± 6.1 mL·kg^? 1·min^? 1, p = 0.02), and experienced greater shortness of breath at peak exercise (7 ± 3 versus 5 ± 2 Modified Borg scale, p = 0.04) compared to patients who responded without dynamic hyperinflation. Significant relationships between FEV₁, FVC, FEV₁/FVC, FEF_25–75 and dynamic hyperinflation were shown (p < 0.01; p = 0.02; p < 0.01; p < 0.01, respectively). Dynamic hyperinflation was also significantly correlated with oxygen uptake, tidal volume, work-rate and shortness of breath at peak exercise (p = 0.03; p < 0.01; p < 0.01; p = 0.04, respectively). Responding to CPET with or without dynamic hyperinflation did not significantly predict FEV₁ at 2 years beyond the FEV₁ at baseline (p = 0.06), or increase the likelihood of experiencing a pulmonary exacerbation over a two-year period (p = 0.24).ConclusionThe prevalence of dynamic hyperinflation during CPET in adult patients with mild-to-moderate CF is high, and is associated with reduced lung function and exercise tolerance, and increased exertional dyspnea. However, identifying dynamic hyperinflation during CPET had limited prognostic value for lung function and pulmonary exacerbation.     

Effect of supervised training on FEV1 in cystic fibrosis: A randomised controlled trial

BackgroundLong-term exercise interventions have been shown to improve vital capacity in cystic fibrosis (CF). Yet, no data are available indicating positive effects of long-term exercise training on FEV₁.Methods39 Swiss patients with CF were randomly divided into strength training (ST, n = 12), endurance training (AT, n = 17) and controls (CON_CH, n = 10), and also compared with age-matched Swiss (n = 35) and German (n = 701) CF registry data. A partially supervised training of 3 × 30 min/week for 6 months took place with measurements at baseline and after 3, 6, 12 and 24 months. Primary outcome was FEV₁ at 6 months.ResultsFEV₁ increased significantly in both training groups compared with CON_CH (AT:+5.8 ± 0.95, ST:+7.4 ± 2.5, CON_CH:? 11.5 ± 2.7% predicted, p < 0.001) and both registry groups at 6 months. At 24 months, changes in favour of the training groups persisted marginally compared with CON_CH, but not compared with registry data.ConclusionsA partially supervised training over 6 months improved FEV₁ but effects were basically gone 18 months off training. Regular long-term training should be promoted as essential part of treatment in CF.     

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.