Number Of Respiratory Exacerbations Research Articles

Conventional chest physiotherapy compared to other airway clearance techniques for cystic fibrosis.

Conventional chest physiotherapy compared to other airway clearance techniques for cystic fibrosis.

Long-Term Azithromycin Treatment in Pediatric Primary Ciliary Dyskinesia: A Retrospective Study.

ObjectivesPrimary ciliary dyskinesia (PCD) is a rare genetic disease mainly involved in lung dysfunction. PCD patient outcomes after azithromycin (AZM) treatment have rarely been reported. This study was aimed to assess AZM treatment effects on disease progression of pediatric PCD patients.Study DesignThis retrospective follow-up study involved PCD patients diagnosed from 2009 to 2021. Changes of clinical outcomes, pulmonary function, and chest computed tomography findings were compared between untreated and AZM-treated patients.ResultsOf 71 enrolled patients (median follow-up duration of 3.1 years), 34 received AZM (AZM-treated group) and 37 received no AZM (AZM-untreated group). At diagnosis, no significant intergroup differences in age, sex, height, weight, number of respiratory exacerbations, and FEV1% and FVC% predicted values were found, although FEF25–75% predicted was lower in AZM-treated group. Between treatment initiation and follow-up, patients in AZM-treated group had less respiratory exacerbations than that of AZM-untreated group (mean ± SD, 1.4 ± 0.8 vs. 3.0 ± 2.1, times/year P = 0.001) and fewer AZM-treated group patients exhibited exercise intolerance. Increases above baseline of AZM-treated FEV1% and FVC% predicted values exceeded that of AZM-untreated group, but intergroup differences were insignificant (FEV1% predicted: (median, IQR) 5.3 [−13.4, 9.4] vs. 1.8 [−12.1, 9.5], P = 0.477; FVC% predicted: (median, IQR) 6.7 [−7.6, 18.8] vs. 1.6 [−5.6, 7.6], P = 0.328).ConclusionLong-term AZM treatment can reduce respiratory infection frequency and may maintain pulmonary diseases stable in pediatric PCD patients with worse lung function.

Positive expiratory pressure physiotherapy for airway clearance in people with cystic fibrosis.

Positive expiratory pressure physiotherapy for airway clearance in people with cystic fibrosis.

Real-world effectiveness of ivacaftor in children with cystic fibrosis and the G551D mutation

Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator that has been shown to improve the nutritional status and lung function of cystic fibrosis patients with the G551D mutation in clinical trials. The objective of this study was to describe the real-world progress of children receiving ivacaftor. We describe the real-world progress of four children with cystic fibrosis and the F508del/G551D genotype comparing data during ivacaftor treatment with baseline and with the year before commencing treatment. Our sample comprised 4 children aged between 6 and 14 years and including one with a recent diagnosis of CF and other with persistent Mycobacterium abscessus (M. abscessus) and recurrent allergic bronchopulmonary aspergillosis. The baseline FEV1 was 58.5% to 81.8% of the predicted value, and ivacaftor was taken for a mean 24 months (range, 12-30 months). All patients experienced a significant and sustained improvement in lung function. Compared to baseline, the weight z-score improved by 1.53 points, and the BMI z-score by 1.6 points. Compared to the year before starting ivacaftor, the frequency of Pseudomonas aeruginosa (P. aeruginosa) isolates decreased (-0.4/patient/year), as did the number of respiratory exacerbations (-1.8/patient/year). The weight-adjusted dose of lipase per kilogram decreased progressively in all patients. In 1 patient, a previously persistent M. abscessus infection and recurrent allergic bronchopulmonary aspergillosis resolved during treatment. Children with cystic fibrosis and the F508del/G551D genotype receiving treatment with ivacaftor experienced a real-world improvement in lung function, nutritional status, respiratory exacerbations, isolation of P. aeruginosa, and dose of pancreatic enzymes.

Real-world effectiveness of ivacaftor in children with cystic fibrosis and the G551D mutation

IntroductionIvacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator that has been shown to improve the nutritional status and lung function of cystic fibrosis patients with the G551D mutation in clinical trials. The objective of this study was to describe the real-world progress of children receiving ivacaftor. MethodsWe describe the real-world progress of four children with cystic fibrosis and the F508del/G551D genotype comparing data during ivacaftor treatment with baseline and with the year before commencing treatment. ResultsOur sample comprised 4 children aged between 6 and 14 years and including one with a recent diagnosis of CF and other with persistent Mycobacterium abscessus (M. abscessus) and recurrent allergic bronchopulmonary aspergillosis. The baseline FEV1 was 58.5–81.8% of the predicted value, and ivacaftor was taken for a mean 24 months (range, 12–30 months). All patients experienced a significant and sustained improvement in lung function. Compared to baseline, the weight z-score improved by 1.53 points, and the BMI z-score by 1.6 points. Compared to the year before starting ivacaftor, the frequency of Pseudomonas aeruginosa (P. aeruginosa) isolates decreased (−0.4/patient/year), as did the number of respiratory exacerbations (−1.8/patient/year). The weight-adjusted dose of lipase per kilogram decreased progressively in all patients. In 1 patient, a previously persistent M. abscessus infection and recurrent allergic bronchopulmonary aspergillosis resolved during treatment. ConclusionsChildren with cystic fibrosis and the F508del/G551D genotype receiving treatment with ivacaftor experienced a real-world improvement in lung function, nutritional status, respiratory exacerbations, isolation of P. aeruginosa, and dose of pancreatic enzymes.

Topical cystic fibrosis transmembrane conductance regulator gene replacement for cystic fibrosis-related lung disease.

Cystic fibrosis is caused by a defective gene encoding a protein called the cystic fibrosis transmembrane conductance regulator (CFTR), and is characterised by chronic lung infection resulting in inflammation and progressive lung damage that results in a reduced life expectancy. To determine whether topical CFTR gene replacement therapy to the lungs in people with cystic fibrosis is associated with improvements in clinical outcomes, and to assess any adverse effects. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings.Date of most recent search: 05 May 2016.An additional search of the National Institutes for Health (NIH) Genetic Modification Clinical Research Information System (GeMCRIS) was also performed for the years 1992 to 2015.Date of most recent search: 20 April 2016. Randomised controlled studies comparing topical CFTR gene delivery to the lung, using either viral or non-viral delivery systems, with placebo or an alternative delivery system in people with confirmed cystic fibrosis. The authors independently extracted data and assessed study quality. Authors of included studies were contacted and asked for any available additional data. Meta-analysis was limited due to differing study designs. Four randomised controlled studies met the inclusion criteria for this review, involving a total of 302 participants lasting from 29 days to 13 months; 14 studies were excluded. The included studies differed in terms of CFTR gene replacement agent and study design, which limited the meta-analysis. One study only enrolled adult males, the remaining studies included both males and females aged 12 years and over.Risk of bias in the studies was moderate. Random sequence generation and allocation concealment was only described in the more recent study; the remaining three studies were judged to have an unclear risk of bias. All four studies documented double-blinding to the intervention, but there is some uncertainty with regards to participant blinding in one study. Some outcome data were missing from all four studies.There were no differences in either the number of respiratory exacerbations or the number of participants with an exacerbation between replacement therapy or placebo groups at any time point. Meta-analysis of most respiratory function tests showed no difference between treatment and placebo groups, but the smallest study (n = 16) reported forced vital capacity (litres) increased more in the placebo group at up to 24 hours. A further study reported a significant improvement in forced expiratory volume at one second (litres) at 30 days after participants had received their first dose of favouring the gene therapy agent, but this finding was not confirmed when combined with at second study in the meta-analysis. The more recent study (n = 140) demonstrated a small improvement in forced vital capacity (per cent predicted) at two and three months and again at 11 and 12 months for participants receiving CFTR gene replacement therapy compared to those receiving placebo. The same study reported a significant difference in the relative change in forced expiratory volume at one second (per cent predicted) at two months, three months and 12 months.One small study reported significant concerns with "influenza-like" symptoms in participants treated with CFTR gene replacement therapy; this was not reported on repeated use of the same agent in a larger recent study.There was no other evidence of positive impact on outcomes, in particular improved quality of life or reduced treatment burden.Two studies measured ion transport in the lower airways; one (n = 16) demonstrated significant changes toward normal values in the participants who received gene transfer agents (P < 0.0001), mean difference 6.86 (95% confidence interval 3.77 to 9.95). The second study (n = 140) also reported significant changes toward normal values (P = 0.032); however, aggregate data were not available for analysis. In the most recent study, there was also evidence of increased salt transport in cells obtained by brushing the lower airway. These outcomes, whilst important, are not of direct clinical relevance. One study of liposome-based CFTR gene transfer therapy demonstrated some improvements in respiratory function in people with CF, but this limited evidence of efficacy does not support this treatment as a routine therapy at present. There was no evidence of efficacy for viral-mediated gene delivery.Future studies need to investigate clinically important outcome measures.

Positive expiratory pressure physiotherapy for airway clearance in people with cystic fibrosis.

Chest physiotherapy is widely prescribed to assist the clearance of airway secretions in people with cystic fibrosis. Positive expiratory pressure (PEP) devices provide back pressure to the airways during expiration. This may improve clearance by building up gas behind mucus via collateral ventilation and by temporarily increasing functional residual capacity. Given the widespread use of PEP devices, there is a need to determine the evidence for their effect. This is an update of a previously published review. To determine the effectiveness and acceptability of PEP devices compared to other forms of physiotherapy as a means of improving mucus clearance and other outcomes in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. The electronic database CINAHL was also searched from 1982 to 2013.Most recent search of the Group's Cystic Fibrosis Trial Register: 02 December 2014. Randomised controlled studies in which PEP was compared with any other form of physiotherapy in people with cystic fibrosis. This included, postural drainage and percussion, active cycle of breathing techniques, oscillating PEP devices, thoracic oscillating devices, bilevel positive airway pressure (BiPaP) and exercise. Studies also had to include one or more of the following outcomes: change in forced expiratory volume in one second; number of respiratory exacerbations; a direct measure of mucus clearance; weight of expectorated secretions; other pulmonary function parameters; a measure of exercise tolerance; ventilation scans; cost of intervention; and adherence to treatment. Three authors independently applied the inclusion and exclusion criteria to publications and assessed the risk of bias of the included studies. A total of 26 studies (involving 733 participants) were included in the review. Eighteen studies involving 296 participants were cross-over in design. Data were not published in sufficient detail in most of these studies to perform any meta-analysis. These studies compared PEP to active cycle of breathing techniques (ACBT), autogenic drainage (AD), oral oscillating PEP devices, high frequency chest wall oscillation (HFCWO) and Bi level PEP devices (BiPaP) and exercise.Forced expiratory volume in one second was the review's primary outcome and the most frequently reported outcome in the studies. Single interventions or series of treatments that continued for up to three months demonstrated no significant difference in effect between PEP and other methods of airway clearance on this outcome. However, long-term studies had equivocal or conflicting results regarding the effect on this outcome. A second primary outcome was the number of respiratory exacerbations. There was a lower exacerbation rate in participants using PEP compared to other techniques when used with a mask for at least one year. Participant preference was reported in 10 studies; and in all studies with an intervention period of at least one month, this was in favour of PEP. The results for the remaining outcome measures were not examined or reported in sufficient detail to provide any high-level evidence. The only reported adverse event was in a study where infants performing either PEP or postural drainage with percussion experienced some gastro-oesophageal reflux. This was more severe in the postural drainage with percussion group. Many studies had a risk of bias as they did not report how the randomisation sequence was either generated or concealed. Most studies reported the number of dropouts and also reported on all planned outcome measures. Following meta-analyses of the effects of PEP versus other airway clearance techniques on lung function and patient preference, this Cochrane review demonstrated that there was a significant reduction in pulmonary exacerbations in people using PEP compared to those using HFCWO in the study where exacerbation rate was a primary outcome measure. It is important to note, however, that there may be individual preferences with respect to airway clearance techniques and that each patient needs to be considered individually for the selection of their optimal treatment regimen in the short and long term, throughout life, as circumstances including developmental stages, pulmonary symptoms and lung function change over time. This also applies as conditions vary between baseline function and pulmonary exacerbations.However, meta-analysis in this Cochrane review has shown a significant reduction in pulmonary exacerbations in people using PEP in the few studies where exacerbation rate was a primary outcome measure.

Bronchiectases at early chest computed tomography in children with cystic fibrosis are associated with increased risk of subsequent pulmonary exacerbations and chronic pseudomonas infection

BackgroundChildren with cystic fibrosis (CF) are often Pseudomonas aeruginosa (PsA) free and exhibit normal spirometry between the ages of 5 and 7. It is reported that computed tomography (CT) is more sensitive than FEV1 as an instrument in the identification of pulmonary disease. It is not known whether CF-CT scores in childhood may be used to highlight children at risk of developing severe disease. Aims1 — To assess the number of respiratory exacerbations (RTEs) during a follow-up period of 6years and their correlation with the CF-CT scores in young CF children. 2 — To assess whether PsA-negative CF children with high chest CF-CT scores are more likely to develop chronic PsA lung infection. Methods68 chest CT performed in patients without chronic PsA infection were scored. All patients (median age 7.8years) had at least 4 clinical, functional and microbiologic assessments/year in the subsequent 6years. RTE was defined as hospitalization and IV antibiotic treatment for respiratory symptoms. Results86.8% patients had <3 RTEs in the 6year follow-up period. The number of RTEs in the 6years subsequent to the CT scan was correlated to the bronchiectasis CT score (BCTS) (r=0.612; p<0.001) and to FEV1 at baseline (r=−0.495, p<0.001). A BCTS ≥17.5 identified patients with >3 RTEs during follow-up (sensitivity: 100%, specificity: 85%), while FEV1 did not. Only BCTS was significant in a logistic multivariate model (RR 1.15). BCTS was significantly lower and FEV1 higher in patients who did not develop chronic PsA infection by the end of the study. ConclusionIn CF children free from chronic PsA, both CT scores and FEV1 values demonstrate significant correlation with disease severity in the subsequent 6years but CT score has higher predictive value in the identification of patients at risk.

Development, clinical utility, and place of ivacaftor in the treatment of cystic fibrosis

Cystic fibrosis (CF) is a life-limiting, multisystem disease characterized by thick viscous secretions leading to recurrent lung infections, bronchiectasis, and progressive deterioration in lung function. CF is caused by loss or dysfunction of the CF transmembrane conductance regulator (CFTR) protein which is responsible for transepithelial chloride and water transport. Improved understanding of CFTR protein dysfunction has allowed the development of mutation-specific small-molecule compounds which directly target the underlying CFTR defect. Ivacaftor is the first licensed small-molecule compound for CF patients which targets the CFTR gating mutation Gly551Asp (previously termed G551D) and has the potential to be truly disease-modifying. Ivacaftor is an oral medication given twice daily and has shown benefit in terms of an increase in lung function, decreased sweat chloride, weight gain, improvement in patient-reported quality of life, and reduction in number of respiratory exacerbations in clinical trials. Although ivacaftor is currently only licensed for use in approximately 5% of the CF population (those who have at least one Gly551Asp mutation), the developmental pathway established by ivacaftor paves the way for other CFTR modulators that may benefit many more patients. In particular, a CFTR modulator for those with the Phe508del deletion (previously ∆F508) would allow 90% of the CF population to benefit from disease-modifying treatment.

Validation of the Spanish Version of the Revised Cystic Fibrosis Quality of Life Questionnaire in Adolescents and Adults (CFQR 14+ Spain)

Background The aim of this study was to assess the validity and reliability of the Spanish version of the revised disease-specific health related quality of life questionnaire for adolescents and adults with cystic fibrosis (CFQR 14+ Spain). Patients and methods A total of 43 cystic fibrosis (CF) patients completed the CFQR 14+ Spain. Forced expiratory volume in 1 second, in percentage of predicted - FEV 1 (%) -, number of respiratory exacerbations, 6-minute walk test, Bhalla score (based on computerized tomography of the chest), fat-free mass index, body mass index (BMI), faecal fat and St George's Respiratory Questionnaire were included as measurements of health status. Results Ten out of the twelve scales had alpha coefficients above 0.70. Test-retest correlations (Spearman) ranged from 0.49 to 0.95 and they were significant in all scales. Intraclass correlations ranged from 0.47 to 0.95 (ten out of the twelve scales were >0.70) forty out of the fifty items have correlations between items and scale above 0.70. All the CFQR 14+ scales, except the digestive symptoms scale, discriminated significantly between patients with mild, moderate and severe disease (according to FEV 1 [%]). Other respiratory parameters also discriminated significantly between patients with mild-moderate and severe disease. Only some scales discriminated significantly between nourished and malnourished patients. All of the scales met standards for floor effects (<15% of the responders with the lowest score) but not for ceiling effects (only five out of the twelve). Conclusion The Spanish CFQR 14+ (Spain) is a reliable and valid instrument for measuring the health-related quality of life in Spanish adolescents and adults with CF, though with the exception of a few of its subscales.

Validación de la versión española del cuestionario revisado de calidad de vida para fibrosis quística en adolescentes y adultos (CFQR 14+ Spain)

Background The aim of this study was to assess the validity and reliability of the Spanish version of the revised disease-specific health related quality of life questionnaire for adolescents and adults with cystic fibrosis (CFQR 14+ Spain). Methods A total of 43 cystic fibrosis (CF) patients completed the CFQR 14+ Spain. Forced expiratory volume in 1 second, in percentage of predicted - FEV 1 (%)-, number of respiratory exacerbations, 6-minute walk test, Bhalla score (based on computerized tomography of the chest), fat-free mass index, body mass index (BMI), faecal fat and St George's Respiratory Questionnaire were included as measurements of health status. Results Ten out of the twelve scales had alpha coefficients above 0.70. Test–retest correlations (Spearman) ranged from 0.49 to 0.95 and they were significant in all scales. Intraclass correlations ranged from 0.47 to 0.95 (ten out of the twelve scales were >0.70) forty out of the fifty ítems have correlations between items and scale above 0.70. All the CFQR+14 scales, except the digestive symptoms scale, discriminated significantly between patients with mild, moderate and severe disease (according to FEV 1 (%)). Other respiratory parameters also discriminated significantly between patients with mild-moderate and severe disease. Only some scales discriminated significantly between nourished and malnourished patients. All of the scales met standards for floor effects (<15% of the responders with the lowest score) but not for ceiling effects (only five out of the twelve). Conclusion The Spanish CFQR14+ (Spain) is a reliable and valid instrument for measuring the health-related quality of life in Spanish adolescents and adults with CF, though with the exception of a few of its subscales.

Do inhaled corticosteroids impair long-term growth in prepubertal cystic fibrosis patients?

Despite absence of clear proof of efficacy, the use of inhaled corticosteroids (ICS) is widespread in cystic fibrosis (CF) patients. Therefore, the effect of ICS on lung function and other clinical variables was studied in 27 prepubertal CF children with mild to moderate lung disease. In a prospective double-blind case-controlled study, fluticasone propionate 500 microg or placebo were administered twice daily during 12 months. The mean (standard error of the mean, SEM) patient age was 8.2 (0.6) years in the placebo group and 9.0 (0.5) years in the fluticasone group. The mean (SEM) forced expiratory volume in 1 s (FEV(1)) was 91% (4%) in the placebo group and 86% (4%) in the fluticasone group. There was no statistically significant difference in the evolution of lung function and the number of respiratory exacerbations between groups. However, longitudinal growth in fluticasone patients was significantly slower than in placebo patients: 3.96 (0.29) cm versus 5.49 (0.38) cm [p<0.005, analysis of variance (ANOVA)] over the 12-month study duration. This resulted in a significant change in height standard deviation score (SDS) of -0.38 (0.09) in the fluticasone group versus -0.01 (0.07) in the placebo group (p<0.003, ANOVA). No catch-up growth was noted 1-2 years after discontinuation of inhaled steroids. The use of high-dose ICS in CF patients with mild lung disease may lead to persistent growth impairment.

Fluticasone Improves Pulmonary Function in Children under 2 Years Old with Risk Factors for Asthma

This study assessed the effects of treatment with fluticasone in children younger than 2 years old with recurrent wheezing and risk factors of developing asthma. This double-blind placebo-controlled study randomized children to receive fluticasone (125 mug; n = 14) or placebo (n = 12) twice daily for 6 months. Pulmonary function was assessed at the beginning and end, and parents filled out a daily diary recording respiratory symptoms, need for rescue medication, and emergency care. The SD score of maximum flow at functional residual capacity was -0.74 +/- 0.6 at the beginning and 0.44 +/- 1 at the end for the fluticasone group (p = 0.001), and -0.79 +/- 0.3 at the beginning and -0.78 +/- 1.4 at the end for the placebo group (p = 0.97). A statistically significant difference (p = 0.02) was observed between treatments. The percentage of symptom-free days was 91.3 +/- 7% for fluticasone and 83.9 +/- 10% for placebo (p = 0.05). The number of respiratory exacerbations was 2.1 +/- 1.7 and 4.1 +/- 3 (p = 0.04), and the percentage of days on albuterol was 8.6 +/- 6% and 16.3 +/- 9% (p = 0.028). Treatment with fluticasone twice daily for 6 months improves pulmonary function and clinical outcomes in children with asthma younger than 2 years.

Recombinant human deoxyribonuclease for cystic fibrosis.

Recombinant human deoxyribonuclease (rhDNase) is currently used to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis. To determine whether the use of rhDNase in cystic fibrosis is associated with improved mortality and morbidity compared to placebo or other mucolytics and to identify any adverse events associated with its use. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and abstracts from conferences. Date of the most recent search of the Group's register: January 2003. All randomized and quasi-randomized controlled trials where rhDNase was compared to either placebo, standard therapy or another mucolytic. Trials were independently assessed for inclusion criteria and the lead reviewer and a colleague carried out analysis of methodological quality and data extraction. The searches identified 38 trials, of which 12 trials met our inclusion criteria, including a total of 2294 participants. Three additional studies examined the health care cost from one of the clinical trials. Ten studies compared rhDNase to placebo; one compared daily rhDNase with hypertonic saline and alternate day rhDNase; and one compared daily rhDNase to hypertonic saline. Study duration varied from six days to two years. The number of deaths was not significant between treatment groups. Lung function improved in the treated groups, with significant differences at one month, three months, six months and two years. The mean percentage change in FEV1in the two largest trials were 5.80 (95% CI 3.99 to 7.61) and 3.24 (95% CI 1.03 to 5.45). There was no excess of adverse effects except voice alteration (and rash, which were reported more frequently in one trial in the treated groups. Insufficient data were available to analyse differences in antibiotic treatment, inpatient stay and quality of life. There is evidence to show that therapy with rhDNase over a one month period is associated with an improvement in lung function in CF, results from a trial lasting six months also showed the same effect. Therapy over a two year period (based on one trial) significantly improved FEV1 in children and there was a non-significant reduction in the risk of infective exacerbations. Voice alteration and rash appear to be the only adverse events reported with increased frequency in randomised controlled trials.

Impact of inhaled corticosteroids on the risk of early Pseudomonas aeruginosa acquisition in cystic fibrosis

Aim: To investigate the role of inhaled corticosteroids (IC) on the risk of Pseudomonas aeruginosa acquisition before the age of 10 y in cystic fibrosis (CF) patients. Methods: For each subject the cumulative dose kg‐1 of IC received for each year of age was calculated until the end of follow‐up. The age at CF diagnosis, the nutritional status (NS) and the number of respiratory exacerbations (RE) were used as surrogate measures for the severity of CF. Results: A total of 83 patients (40 M, 43 F) entered the study. Their median length of follow‐up was 4.4 y, for a total of 386 person‐years at risk. Twenty‐three patients acquired P. aeruginosa at a median age of 4.6 y (range 0.4‐9.9 y). The estimated survival without P. aeruginosa acquisition was 65% at 10 y of age. The effect of different risk factors (IC, NS, RE and age at CF diagnosis) on the probability of P. aeruginosa acquisition was evaluated: none of them was significantly associated with the risk of P. aeruginosa acquisition. In particular, patients receiving very high cumulative doses of IC (4th quartile) had a non‐significantly increased risk of P. aeruginosa acquisition compared with those receiving low doses of IC (1st quartile) (hazard ratio = 1.73, 95% confidence limits 0.40‐7.38). Conclusion: This retrospective study was not able to demonstrate any role of IC in increasing the risk of P. aeruginosa acquisition. This complication seems to occur at a constant pace that is independent of CF severity and age. Prospective multi‐institutional randomized studies are needed to investigate the effects of high‐dose IC in CF patients.

Impact of inhaled corticosteroids on the risk of early Pseudomonas aeruginosa acquisition in cystic fibrosis.

To investigate the role of inhaled corticosteroids (IC) on the risk of Pseudomonas aeruginosa acquisition before the age of 10 y in cystic fibrosis (CF) patients. For each subject the cumulative dose kg(-1) of IC received for each year of age was calculated until the end of follow-up. The age at CF diagnosis, the nutritional status (NS) and the number of respiratory exacerbations (RE) were used as surrogate measures for the severity of CF. A total of 83 patients (40 M, 43 F) entered the study. Their median length of follow-up was 4.4 y, for a total of 386 person-years at risk. Twenty-three patients acquired P. aeruginosa at a median age of 4.6 y (range 0.4-9.9 y). The estimated survival without P. aeruginosa acquisition was 65% at 10 y of age. The effect of different risk factors (IC, NS, RE and age at CF diagnosis) on the probability of P. aeruginosa acquisition was evaluated: none of them was significantly associated with the risk of P. aeruginosa acquisition. In particular, patients receiving very high cumulative doses of IC (4th quartile) had a non-significantly increased risk of P. aeruginosa acquisition compared with those receiving low doses of IC (1st quartile) (hazard ratio = 1.73, 95% confidence limits 0.40-7.38). This retrospective study was not able to demonstrate any role of IC in increasing the risk of P. aeruginosa acquisition. This complication seems to occur at a constant pace that is independent of CF severity and age. Prospective multi-institutional randomized studies are needed to investigate the effects of high-dose IC in CF patients.

Effect of long term treatment with azithromycin on disease parameters in cystic fibrosis: a randomised trial

Background: Relentless chronic pulmonary inflammation is the major contributor to morbidity and mortality in patients with cystic fibrosis (CF). While immunomodulating therapies such as prednisolone and ibuprofen may be beneficial,...