Search

Background: In people with cystic fibrosis (CF), regular nebulisation of 6% or 7% saline improves lung function; however, these concentrations are not always tolerable. Clinically, some CF patients report using lower concentrations of saline to improve tolerability, yet the effects of lower concentrations are unknown. This study therefore aimed to evaluate the relative effectiveness and tolerability of 0.9% versus 3% versus 6% saline nebulised twice daily with an eFlow rapid nebuliser., Methods: This was a randomised, blinded, placebo-controlled, parallel-group, multicentre study where subjects inhaled 4 mL of 0.9%, 3% or 6% saline twice daily for 16 weeks. The primary outcome was forced expiratory volume in 1 s. The secondary outcomes were: forced vital capacity (FVC) and forced expiratory flow at 25-75% of FVC; quality of life; exercise capacity; acquisition or loss of bacterial organisms in expectorated sputum; tolerability of nebulised saline; pulmonary exacerbations; and adverse events., Results: 140 participants were randomised to 0.9% (n=47), 3% (n=48) or 6% (n=45) saline. 134 participants (96%) contributed to the intention-to-treat analysis. 3% saline significantly improved lung function and increased the time to first pulmonary exacerbation compared with 0.9% saline but did not improve quality of life. 6% saline had similar benefits to 3% saline but also significantly improved quality of life compared with 3% saline. Only 6% saline delayed the time to intravenous antibiotics for pulmonary exacerbation. Tolerability and adherence were similar., Conclusions: Dilution of 6% saline to 3% maintains the benefits for lung function and exacerbation prevention; however, the positive impacts of 6% saline on quality of life and time to i.v. antibiotics for pulmonary exacerbations are lost., Competing Interests: Conflict of interest: None of the authors has a conflict of interest to disclose apart from the funding and sources of support listed., (Copyright ©The authors 2023. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: In people with and without Cystic Fibrosis (CF), does side lying during nebulisation change: the proportion of the dose loaded in the nebuliser that is deposited in the lungs; the uniformity of deposition throughout the lungs; or the apical drug density as a percentage of the drug density in the remaining lung? Do these effects differ depending on the degree of lung disease present?, Methods: A randomised crossover trial with concealed allocation, intention-to-treat analysis and blinded assessors, involving 39 adults: 13 healthy, 13 with mild CF lung disease (FEV 1  > 80%pred), and 13 with more advanced CF lung disease (FEV 1  < 80%pred). In random order, 4 mL of nebulised radioaerosol was inhaled in upright sitting and in alternate right and left side lying at 2-min intervals, for 20 min., Results: Compared to sitting upright, lung deposition and the uniformity of deposition were not significantly altered by side lying in any of the three groups. In sitting, the density of the deposition was significantly less in the apical regions than in the rest of the lung in all participants. Side lying significantly improved apical deposition in healthy adults (MD, 13%; 95% CI, 7 to 19), and in minimal CF lung disease (MD, 4%; 95% CI, 1 to 7) but not in advanced disease (MD, 4%; 95% CI, - 2 to 9)., Conclusion: Alternating between right and left side lying during nebulisation significantly improves apical deposition in healthy adults and in adults with mild CF lung disease, without substantial detriment to overall deposition., Trial Registration: ACTRN12611000674932 (Healthy), ACTRN12611000672954 (CF) Retrospectively registered 4/7/2011.

Background: Inhalation of nebulised medications is performed in upright sitting to maximise lung volumes. The pattern of deposition is poor for inhaled medications in people with Cystic Fibrosis. The pattern tends to be non-uniform and typically the upper lobes receive a reduced dose compared to the rest of the lung. One strategy that has been proposed as having the potential to improve homogeneity of deposition is to adopt an alternate side lying position for the inhalation procedure. This study sought to determine whether, among adults with Cystic Fibrosis, there is any disadvantage to delivery time of nebulised medications with a strategy of alternate side lying, compared to upright sitting., Methods: A randomised crossover trial with concealed allocation, intention-to-treat analysis and blinded assessors was undertaken. The participants were 24 adults with stable Cystic Fibrosis. They inhaled 4 mL of normal saline via an LC Star™ nebuliser twice within 24 h. In random order, participants sat upright throughout nebulisation, or alternated between left and right side lying at each minute during the nebulisation period. The nebuliser was stopped and weighed each minute until the residual volume was reached. The primary outcome was the time required for 3.5 mL to be delivered. The secondary outcomes were: respiratory rate; ratio of the volume delivered on right and left sides; and calculation of how long the periods in side lying can be extended without causing greater than 20% discrepancy in dose delivered in the two positions., Results: The delivery time did not significantly differ between sitting and side lying (mean difference 0.58 min, 95% confidence interval (CI) -1.40 to 0.24). There was no significant correlation between delivery time, lung function or subject height (all R 2  < 0.4). Increasing side lying duration from 1 to 2 min did not significantly impact the dose delivered on each side. Turning each 3 min however, significantly worsened the disparity (mean ratio 1.32, 95% CI 1.24 to 1.40)., Conclusion: Side lying during inhalation therapy does not prolong nebulisation time. 2-min periods should provide an equal dose in the two side lying positions., Trial Registration: Prospectively registered on 4 July 2011; ACTRN12611000672954 .

Background: The mucoactive effects of hypertonic saline should promote exacerbation resolution in people with cystic fibrosis (CF)., Objectives: To determine the effects of hypertonic saline inhalation during hospitalisation for exacerbation of CF on length of stay, lung function, symptoms, oxygenation, exercise tolerance, quality of life, bacterial load and time to next hospitalisation., Methods: 132 adults with an exacerbation of CF were randomised to inhale three nebulised doses a day of either 4 mL 7% saline or a taste-masked control of 0.12% saline, throughout the hospital admission. The primary outcome measure was length of hospital stay., Results: All participants tolerated their allocated saline solution. There was no significant difference in length of stay, which was 12 days in the hypertonic saline group and 13 days in controls, with a mean between-group difference (MD) of 1 day (95% CI 0 to 2). The likelihood of regaining pre-exacerbation FEV1 by discharge was significantly higher in the hypertonic saline group (75% vs 57%), and the number needed to treat was 6 (95% CI 3 to 65). On a 0-100 scale, the hypertonic saline group had significantly greater reduction in symptom severity than the control group at discharge in sleep (MD=13, 95% CI 4 to 23), congestion (MD=10, 95% CI 3 to 18) and dyspnoea (MD=8, 95% CI 1 to 16). No significant difference in time to next hospitalisation for a pulmonary exacerbation was detected between groups (HR=0.86 (CI 0.57 to 1.30), p=0.13). Other outcomes did not significantly differ., Conclusions: Addition of hypertonic saline to the management of a CF exacerbation did not reduce the length of hospital stay. Hypertonic saline speeds the resolution of exacerbation symptoms and allows patients to leave hospital with greater symptom resolution., Trial Registration Number: ACTRN12605000780651., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Recent molecular-typing studies suggest cross-infection as one of the potential acquisition pathways for Pseudomonas aeruginosa in patients with cystic fibrosis (CF). In Australia, there is only limited evidence of unrelated patients sharing indistinguishable P. aeruginosa strains. We therefore examined the point-prevalence, distribution, diversity and clinical impact of P. aeruginosa strains in Australian CF patients nationally. 983 patients attending 18 Australian CF centres provided 2887 sputum P. aeruginosa isolates for genotyping by enterobacterial repetitive intergenic consensus-PCR assays with confirmation by multilocus sequence typing. Demographic and clinical details were recorded for each participant. Overall, 610 (62%) patients harboured at least one of 38 shared genotypes. Most shared strains were in small patient clusters from a limited number of centres. However, the two predominant genotypes, AUST-01 and AUST-02, were widely dispersed, being detected in 220 (22%) and 173 (18%) patients attending 17 and 16 centres, respectively. AUST-01 was associated with significantly greater treatment requirements than unique P. aeruginosa strains. Multiple clusters of shared P. aeruginosa strains are common in Australian CF centres. At least one of the predominant and widespread genotypes is associated with increased healthcare utilisation. Longitudinal studies are now needed to determine the infection control implications of these findings.

Pseudomonas aeruginosa is a common cause of chronic respiratory infection in cystic fibrosis (CF) patients. Infection is established within the lung epithelial mucus layer through adhesion to mucins. Terminal residues on mucin oligosaccharide chains are highly sulfated and sialylated, which increases their resistance to degradation by bacterial enzymes. However, a number of microbes, including P. aeruginosa, display mucin sulfatase activity. Using ion chromatography, the levels of sulfation on different respiratory mucins and the availability of inorganic sulfate to pathogens in sputum from CF patients were quantified. The ability of clinical isolates of P. aeruginosa to desulfate mucin was tested by providing mucin as a sole sulfur source for growth. All tested P. aeruginosa strains isolated from the lungs of CF patients were able to use human respiratory mucin as a source of sulfur for growth, whereas other non-clinical species of the genus Pseudomonas were not. However, measured levels of inorganic sulfate in sputum from CF patients suggested that bacteria resident in the lung have sufficient inorganic sulfate for growth and are unlikely to require access to mucin sulfur as a sulfur source during chronic infection. This was confirmed when expression of sulfate-repressed P. aeruginosa genes atsK and msuE was found to be repressed in the sputum of CF patients, which was detected by using quantitative RT-PCR. These results indicate that sulfate starvation is unlikely to occur in pathogens residing in the sputum of CF patients and, therefore, mucin desulfation may have an alternative purpose in the association between P. aeruginosa and the airways of CF patients.

Question: Among adults with cystic fibrosis, does the timing of hypertonic saline relative to airway clearance techniques affect lung function, perceived efficacy, tolerability, or satisfaction with the entire airway clearance regimen, and is the preferred timing regimen stable over time?, Design: A randomised crossover trial with concealed allocation, intention-to-treat analysis, and blinded assessors., Participants: 50 adults with cystic fibrosis and stable lung function at the end of a hospital admission., Intervention: Participants performed 3 sessions of airway clearance techniques per day for 3 days. On each day, participants were randomised to inhale hypertonic saline either before, during, or after the airway clearance techniques. Participants readmitted within one year repeated the 3-day study., Outcome Measures: The primary outcome was the change in forced expiratory volume in one second (FEV(1)) from before to 2 hours after an entire airway clearance session. Secondary outcomes were change in forced vital capacity, perceived efficacy, tolerability, satisfaction, adverse events, and adherence., Results: All 50 participants completed the study. The effects on lung function were non-significant or were of borderline statistical significance favouring inhalation of hypertonic saline before airway clearance techniques. Satisfaction was rated significantly worse on a 100mm scale when hypertonic saline was inhaled after the airway clearance techniques: mean differences 20mm (95% CI 12 to 29) compared to before the airway clearance techniques and 15 mm (95% CI 6 to 24) compared to during the techniques. Perceived effectiveness showed similar effects but other outcomes were unaffected. All 14 participants who were readmitted repeated the study and most preferred the same timing regimen. Conclusion People with cystic fibrosis could be encouraged to time hypertonic saline before or during airway clearance techniques to maximise perceived efficacy and satisfaction, even though lung function may not be better with these timing regimens., Trial Registration: ACTRN12611000673943., (Copyright © 2012 Australian Physiotherapy Association. Published by .. All rights reserved.)

Purpose of Review: Consensus statements about the care of people with cystic fibrosis (CF) recommend exercise as part of a wider management strategy. Many of these recommendations are based on high-quality evidence that regular exercise improves some important clinical outcomes, such as lung function and quality of life. However, the evidence about the effect of exercise on other clinical outcomes is less extensive or lower in quality. This article will review the physiological effects of exercise on a range of outcomes in people with CF, the mechanisms by which exercise may improve these outcomes and the quality and findings of clinical research into the effects of exercise in the management of CF., Recent Findings: Substantial evidence confirms that exercise significantly reduces the rate of decline in lung function in people with CF, at least in part by increasing mucus clearance. Regular exercise training over 6 months improves aerobic exercise capacity. Bone health is often poor in people with CF, but only indirect evidence supports that increasing the amount of exercise will have a beneficial effect on bone density. CF-related diabetes is also a common sequela of the disease, but again only evidence from type-2 diabetes exists to support exercise as a way of managing it., Summary: Although its effects on some outcomes are unclear, the overall effect of exercise on quality of life is substantially beneficial and the evidence available for other specific outcomes is directly or indirectly supportive, so it appears appropriate to recommend it in clinical practice., (© 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins)

Objective: Determine the SenseWear Pro3 Armband (SWA) accuracy for estimating energy expenditure (EE) and step count during treadmill walking in cystic fibrosis (CF) compared to healthy adults., Hypothesis: SWA estimation of EE would be less accurate for CF, than for healthy subjects, due to interference with the SWA skin sensors caused by the high salt concentration in the sweat of CF subjects., Methods: 17 CF (mean age 26 yr; FEV1 54% predicted) and 17 age-matched control subjects walked slightly faster than their comfortable pace on a treadmill for 20 min, whilst simultaneously wearing the SWA and breathing through an open-circuit indirect calorimetry (IC) system. Subjects' steps were manually counted., Results: Combined EE data from all subjects showed no significant difference in EE measured by IC (6.0+/-3.4 kcal min(-1)) compared to the SWA estimate (6.3+/-2.5 kcal min(-1)), however the SWA significantly overestimated EE at low exercise intensities and underestimated EE at high exercise intensities. Correlations between EE values, estimated by the SWA and measured by IC, were greater than 0.85 (p<0.001) for both the CF and control group. Standard multiple regression showed that diagnosis of CF independently predicted less than 0.1% of the difference between the IC measure of EE and the SWA estimate. The SWA recorded slightly but significantly fewer steps (113+/-12 steps min(-1)) than the manual count (119+/-9 steps min(-1))., Conclusion: Diagnosis of CF had no significant negative impact on the accuracy of the SWA estimate of EE. The SWA provided a reasonably accurate estimate of EE and step count during treadmill walking.

Pseudomonas aeruginosa is an important cause of pulmonary infection in cystic fibrosis (CF). Its correct identification ensures effective patient management and infection control strategies. However, little is known about how often CF sputum isolates are falsely identified as P. aeruginosa. We used P. aeruginosa-specific duplex real-time PCR assays to determine if 2,267 P. aeruginosa sputum isolates from 561 CF patients were correctly identified by 17 Australian clinical microbiology laboratories. Misidentified isolates underwent further phenotypic tests, amplified rRNA gene restriction analysis, and partial 16S rRNA gene sequence analysis. Participating laboratories were surveyed on how they identified P. aeruginosa from CF sputum. Overall, 2,214 (97.7%) isolates from 531 (94.7%) CF patients were correctly identified as P. aeruginosa. Further testing with the API 20NE kit correctly identified only 34 (59%) of the misidentified isolates. Twelve (40%) patients had previously grown the misidentified species in their sputum. Achromobacter xylosoxidans (n = 21), Stenotrophomonas maltophilia (n = 15), and Inquilinus limosus (n = 4) were the species most commonly misidentified as P. aeruginosa. Overall, there were very low rates of P. aeruginosa misidentification among isolates from a broad cross section of Australian CF patients. Additional improvements are possible by undertaking a culture history review, noting colonial morphology, and performing stringent oxidase, DNase, and colistin susceptibility testing for all presumptive P. aeruginosa isolates. Isolates exhibiting atypical phenotypic features should be evaluated further by additional phenotypic or genotypic identification techniques.

This review examines specific mucoactive agents from three classes: expectorants, which add water to the airway; ion-transport modifiers, which promote ion and water transport across the epithelium of the airway; and mucokinetics, which improve cough-mediated clearance by increasing airflow or reducing sputum adhesivity. The agents are isotonic and hypertonic saline, mannitol, denufosol and beta-agonists. Our understanding of these agents has recently improved through pre-clinical research, clinical trials and, in particular, extensive research into the nature of the liquid lining the surface of the airway, both in health and in cystic fibrosis (CF). For each agent, recent research is reviewed, highlighting the evidence for possible mechanisms of action and for clinical efficacy in CF, as well as the implications for the optimal clinical application of the agent.

Purpose of Review: The beneficial effect of a short course of nebulized hypertonic saline on lung function for people with cystic fibrosis was first identified in 1996. At that time, competing hypotheses about the pathogenesis of cystic fibrosis lung disease predicted very different responses to long-term inhalation of hypertonic saline., Recent Findings: Recent benchtop research supports the hypothesis that the liquid layer lining the airways is depleted in cystic fibrosis. In addition to osmotically restoring this liquid layer, hypertonic saline improves the rheological properties of the mucus and stimulates cough. The net result is accelerated mucus clearance that is short-lived for single doses but sustained with regular inhalation. Long-term use improves lung function mildly but has marked benefits with respect to exacerbations, quality of life and absenteeism, without promoting infection or inflammation., Summary: Hypertonic saline appears broadly applicable as an inexpensive therapy for most patients with cystic fibrosis.

Background: Chest physiotherapy is widely prescribed to assist the clearance of airway secretions in people with cystic fibrosis (CF). Positive expiratory pressure (PEP) devices provide constant back pressure to the airways during expiration. This may improve clearance by building up gas behind mucus via collateral ventilation. Given the widespread use of PEP devices, there is a need to determine the evidence for their effect., Objectives: 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 CF., Search Strategy: 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 2001. Most recent search of the Group's register: February 2006., Selection Criteria: Randomised controlled studies in which PEP was compared with any other form of physiotherapy in people with CF., Data Collection and Analysis: Two authors independently applied the inclusion and exclusion criteria to publications and assessed the quality of the included studies., Main Results: Forty studies were identified and twenty-five studies involving 507 participants met the review inclusion criteria. Most included studies had low scores on a scale of study quality. Twenty of these studies involving 300 participants were cross-over in design. Data were not published in sufficient detail in most of these studies to perform meta-analysis.Forced expiratory volume in one second (FEV1) was the most frequently measured outcome. Single interventions or series of treatments continued for up to three months demonstrated no significant difference in effect between PEP and other methods of airway clearance on FEV1. Long-term studies had equivocal or conflicting results regarding the effect on FEV1. Participant preference was reported in nine studies. In all studies with an intervention period of at least one month, measures of participant preference were 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., Authors' Conclusions: There was no clear evidence that PEP was a more or less effective intervention overall than other forms of physiotherapy. There was limited evidence that PEP was preferred by participants compared to other techniques, but this finding is from studies of low quality.

Background: Inhaled hypertonic saline acutely increases mucociliary clearance and, in short-term trials, improves lung function in people with cystic fibrosis. We tested the safety and efficacy of inhaled hypertonic saline in a long-term trial., Methods: In this double-blind, parallel-group trial, 164 patients with stable cystic fibrosis who were at least six years old were randomly assigned to inhale 4 ml of either 7 percent hypertonic saline or 0.9 percent (control) saline twice daily for 48 weeks, with quinine sulfate (0.25 mg per milliliter) added to each solution to mask the taste. A bronchodilator was given before each dose, and other standard therapies were continued during the trial., Results: The primary outcome measure, the rate of change (slope) in lung function (reflected by the forced vital capacity [FVC], forced expiratory volume in one second [FEV1], and forced expiratory flow at 25 to 75 percent of FVC [FEF25-75]) during the 48 weeks of treatment, did not differ significantly between groups (P=0.79). However, the absolute difference in lung function between groups was significant (P=0.03) when averaged across all post-randomization visits in the 48-week treatment period. As compared with the control group, the hypertonic-saline group had significantly higher FVC (by 82 ml; 95 percent confidence interval, 12 to 153) and FEV1 (by 68 ml; 95 percent confidence interval, 3 to 132) values, but similar FEF25-75 values. The hypertonic-saline group also had significantly fewer pulmonary exacerbations (relative reduction, 56 percent; P=0.02) and a significantly higher percentage of patients without exacerbations (76 percent, as compared with 62 percent in the control group; P=0.03). Hypertonic saline was not associated with worsening bacterial infection or inflammation., Conclusions: Hypertonic saline preceded by a bronchodilator is an inexpensive, safe, and effective additional therapy for patients with cystic fibrosis. (ClinicalTrials.gov number, NCT00271310.), (Copyright 2006 Massachusetts Medical Society.)

Maximum expiratory pressure (MEP) and peak expiratory flow rate (PEFR) are used as surrogate measures of cough and huff strength. Some body positions (particularly head-down tilt) significantly affect these measures in people with normal respiratory function and with chronic obstructive pulmonary disease. This may have implications for people with cystic fibrosis (CF), who use coughing and huffing and may use gravity-assisted drainage positions for airway clearance. Previous research concluded that body position does not affect MEP in people with CF, although head-down tilt was not examined and PEFR was not measured. This study investigated the effect of body position on MEP and PEFR in 20 adults with stable CF. Repeated measures of MEP and PEFR were performed across seven positions (standing, chair-sitting, sitting in bed with backrest vertical, sitting in bed with backrest at 45 degrees , supine, side-lying, and side-lying with head-down tilt 20 degrees ) in random order. During testing, reflux sensation and oxygenation were monitored. MEP was significantly reduced in side-lying and in the head-down tilt position. PEFRs were significantly reduced in the three-quarters sitting, supine, side-lying, and head-down positions. Oxygenation and reflux scores were worst in the head-down position. Despite statistical significance, the differences observed between positions in this stable population were of small magnitude. The effect of body position on MEP and PEFR may be more relevant during airway clearance treatments of the acutely unwell person with CF., ((c) 2005 Wiley-Liss, Inc.)

Since the role of respiratory viruses in lung exacerbations of patients with cystic fibrosis has been hampered by the difficulty of detecting viruses in viscous sputum specimens, a multiplex reverse transcriptase PCR (RT-PCR) assay combined with colorimetric amplicon detection was tested for the identification of seven common respiratory viruses in the sputa of cystic fibrosis patients. Of 52 sputa from 38 patients, 12 (23%) samples from 12 patients were positive for a respiratory virus (4 for influenza B, 3 for parainfluenza 1, 3 for influenza A and 2 for respiratory syncytial virus). These results suggest that the RT-PCR method carried out on sputum may provide a convenient means of investigating the role of virus infection in lung exacerbations of cystic fibrosis patients.

Background: Chest physiotherapy is widely prescribed to assist the clearance of airway secretions in people with cystic fibrosis (CF). Positive expiratory pressure (PEP) devices provide constant back pressure to the airways during expiration. This may improve clearance by building up gas behind mucus via collateral ventilation. Given the widespread use of PEP devices, there is a need to determine the evidence for their effect., Objectives: 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 CF., Search Strategy: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register comprising of references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. The electronic database CINAHL was also searched from 1982 to 2001. Most recent search of the Group's register: November 2003., Selection Criteria: Randomised controlled trials in which PEP was compared with any other form of physiotherapy in people with CF., Data Collection and Analysis: Two reviewers independently applied the inclusion and exclusion criteria to publications and assessed the quality of the included studies., Main Results: Thirty-three studies were identified and twenty studies involving 429 participants met review inclusion criteria. Most included studies had low scores on a scale of study quality. Sixteen of these studies involving 257 participants were cross-over in design. Data were not published in sufficient detail in these studies to perform meta-analysis.Forced expiratory volume in one second (FEV1) was the most frequently measured outcome. Single interventions or series of treatments continued for up to one month demonstrated no significant difference in effect between PEP and other methods of airway clearance on FEV1. Long-term studies had equivocal or conflicting results regarding the effect on FEV1. Patient preference was reported in nine studies. In all studies with an intervention period of at least one month, measures of patient preference were 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., Reviewer's Conclusions: There was no clear evidence that PEP was a more or less effective intervention overall than other forms of physiotherapy. There was limited evidence that PEP was preferred by participants compared to other techniques but this finding is from studies of low quality.