Thoracic Society of Australia and New Zealand position statement: The safe clinical use of sputum induction for bio-sampling of the lower airways in children and adults.

Sputum induction is widely used in clinical settings for collection of biological samples from the lower airways. However, in recent years sputum induction has been associated with serious adverse events and even death. This position statement was commissioned by the Thoracic Society of Australia and New Zealand to address major adverse events of two deaths associated with sputum induction that have occurred in Australia in 2021, and outlines best practice for the safe use of sputum induction. The statement resulted from systematic literature searches by a multi-disciplinary group including respiratory physicians, nurses and physiotherapists (paediatric and adults focused). Consumers had input to an advanced draft of the position statement. The position statement covers indications for sputum induction, informed consent, scope of practice of personnel administering the procedure, infection control considerations, details about the sputum induction procedure, safety considerations and risk assessment in clinical settings.

Impact of cystic fibrosis multidisciplinary virtual clinics on patient experience, time commitments and costs.

BACKGROUND AND AIMS: The experience of outpatient care may differ for select patient groups. This prospective study evaluates the adult patient experience of multidisciplinary outpatient cystic fibrosis (CF) care with videoconferencing through telehealth compared with face-to-face care the year prior. METHODS: People with CF without a lung transplant were recruited. Patient-reported outcomes were obtained at commencement and 12 months into the study, reflecting both their face-to-face and telehealth through videoconferencing experience, respectively. Three patient cohorts were analysed: (i) participants with a regional residence, (ii) participants with a nonregional including metropolitan residence and (iii) participants with colonised multiresistant microbiota. RESULTS: Seventy-four patients were enrolled in the study (mean age, 37 ± 11 years; 50% male; mean forced expiratory volume in the first second of expiration, 60% [standard deviation, 23]) between February 2020 and May 2021. No differences between models were observed in the participants' rating of the health care team, general and mental health rating, and their confidence in handling treatment plans at home. No between-group differences in the Cystic Fibrosis Questionnaire - Revised (CFQ-R) were observed. Travel duration and the cost of attending a clinic was significantly reduced, particularly for the regional group (4 h, AU$108 per clinic; P < 0.05). A total of 93% respondents preferred to continue with a hybrid approach. CONCLUSION: In this pilot study, participants' experience of care and quality of life were no different with face-to-face and virtual care between the groups. Time and cost-savings, particularly for patients living in regional areas, were observed. Most participants preferred to continue with a hybrid model for outpatient care.

Screening for Cystic Fibrosis Related Complications in the Context of a Pandemic and Altered Models of Care.

Background: Standard of care recommend that patients with cystic fibrosis (CF) require screening investigations to assess for complications. Changing models of care due to the COVID19 pandemic may have impacted completion of recommended screening. Objective: To compare the frequency of screening investigations completed in people with CF before and after the onset of the COVID19 pandemic. Methods: Medical records were reviewed at 4 CF-specialist centers to identify screening investigations completed in the 12-months before and after pandemic onset. Results: Records of 625 patients were reviewed. Prior to pandemic onset, there was between center variability in completion of screening investigations. There was greatest baseline variation between centers in performing oral glucose tolerance test (OGTT); range 38%-69%, exercise tests; 3%-51% and sputum screening for non-tuberculous mycobacteria; 53%-81%. Following pandemic onset, blood tests, and sputum cultures were maintained at the highest rates. Exercise testing, CXR and OGTT exhibited the greatest declines, with reductions at individual centers ranging between 10%-24%, 22%-43%, and 20%-26%, respectively. Return to in-person visits following pandemic onset was variable, ranging from 16% to 74% between centers. Conclusion: Completion of screening investigations varies between CF centers and changes in models of care, such as increased virtual care in response to COVID19 pandemic was associated with reduction in completion of investigations. Centers would benefit from auditing their adherence to standards of care, particularly considering recent changes in care delivery.

Saline at lower tonicity in cystic fibrosis (SALTI-CF) trial comparing 0.9% versus 3% versus 6% nebulised saline.

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.

Web-based physical activity promotion in young people with CF: a randomised controlled trial.

BACKGROUND: Physical activity levels are known to decline following hospitalisation for people with cystic fibrosis (pwCF). However, optimal physical activity promotion strategies are unclear. This study investigated the effect of a web-based application (ActivOnline) in promoting physical activity in young pwCF. METHODS: Multicentre randomised controlled trial with assessor blinding and qualitative evaluation. People with CF (12-35 years) admitted to hospital for a respiratory cause were eligible and randomised to the 12-week ActivOnline intervention (AO) or usual care (UC). The primary outcome was change in device-based time spent in moderate-to-vigorous physical activity (MVPA) from baseline to post-intervention. Follow-up was at 6 months from hospital discharge when qualitative evaluation was undertaken. RESULTS: 107 participants were randomised to AO (n=52) or UC (n=55). Sixty-three participants (59%) contributed to the intention-to-treat analysis. Mean (SD) age was 21 (6) years (n=46, <18 years). At baseline, physical activity levels were high in both groups (AO 102 (52) vs UC 127 (73) min/day). There was no statistically significant difference in MVPA between groups at either timepoint (post-intervention mean difference (95% CI) -14 mins (-45 to 16)). Uptake of the intervention was low with only 40% (n=21) of participants accessing the web application. CONCLUSION: A web-based application, including individualised goal setting, real-time feedback and motivation for behavioural change, was no better than usual care at promoting physical activity in young pwCF following hospital discharge. High levels of baseline physical activity levels in both groups, and limited engagement with the intervention, suggest alternative strategies may be necessary to identify and support young pwCF who would benefit from enhanced physical activity. TRIAL REGISTRATION NUMBER: ACTRN12617001009303, 13 July 13 2017.

Quality of home spirometry performance amongst adults with cystic fibrosis.

Spirometry is usually performed under the supervision of a trained respiratory scientist to ensure acceptability and repeatability of results. To evaluate the quality of spirometry performance by adult cystic fibrosis (CF) patients with and without observation by a trained respiratory scientist, an observational, single centre study was conducted between February to December 2020. 74 adults were recruited and instructed to perform spirometry without supervision within 24 h of their remote CF clinic consultation. Spirometry was repeated at their consultation, supervised by a respiratory scientist using video conferencing. The majority of patients achieved grade A (excellent) or B (very good) spirometry quality with (95%) and without supervision (93%) independent of lung function severity. Similarly, forced expiratory volume in 1 second demonstrated no significant differences with paired spirometry performed within a 24 hour period. For a large proportion of adult CF patients, unsupervised portable spirometry produces acceptable and repeatable results.

Timing of dornase alfa inhalation for cystic fibrosis.

BACKGROUND: Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis. This is an update of a previously published Cochrane Review. OBJECTIVES: To determine whether the timing of dornase alfa inhalation (in relation to airway clearance techniques or morning versus evening inhalation) has an impact on objective and subjective measures of clinical efficacy in people with cystic fibrosis. SEARCH METHODS: Relevant randomised and quasi-randomised controlled trials were identified from the Cochrane Cystic Fibrosis Trials Register, the Physiotherapy Evidence Database (PEDro), clinical trial registries and international cystic fibrosis conference proceedings. Date of the most recent search: 12 October 2020. SELECTION CRITERIA: Any trial of dornase alfa in people with cystic fibrosis where timing of inhalation was the randomised element in the trial with either: inhalation before compared to after airway clearance techniques; or morning compared to evening inhalation.  DATA COLLECTION AND ANALYSIS: Both authors independently selected trials, assessed risk of bias and extracted data with disagreements resolved by discussion. Relevant data were extracted and, where possible, meta-analysed. We assessed the quality of the evidence using GRADE. MAIN RESULTS: We identified 115 trial reports representing 55 trials, of which five trials (providing data on 122 participants) met our inclusion criteria. All five trials used a cross-over design. Intervention periods ranged from two to eight weeks. Four trials (98 participants) compared dornase alfa inhalation before versus after airway clearance techniques. Inhalation after instead of before airway clearance did not significantly change forced expiratory volume at one second (very-low quality evidence). Similarly, forced vital capacity (low-quality evidence) and quality of life (very-low quality evidence) were not significantly affected; forced expiratory flow at 25% was significantly worse with dornase alfa inhalation after airway clearance, mean difference -0.17 litres (95% confidence interval -0.28 to -0.05), based on the pooled data from two small trials in children (7 to 19 years) with well-preserved lung function. All other secondary outcomes were statistically non-significant. In one trial (25 participants), morning versus evening inhalation had no impact on lung function or symptoms (low-quality evidence). AUTHORS' CONCLUSIONS: The current evidence derived from a small number of participants does not indicate that inhalation of dornase alfa after airway clearance techniques is more or less effective than the traditional recommendation to inhale nebulised dornase alfa 30 minutes prior to airway clearance techniques, for most outcomes. For children with well-preserved lung function, inhalation before airway clearance may be more beneficial for small airway function than inhalation after. However, this result relied on a measure with high variability and trials with variable follow-up. In the absence of strong evidence to indicate that one timing regimen is better than another, the timing of dornase alfa inhalation can be largely based on pragmatic reasons or individual preference with respect to the time of airway clearance and time of day. Further research is warranted.

Timing of hypertonic saline inhalation for cystic fibrosis.

BACKGROUND: Inhalation of hypertonic saline improves sputum rheology, accelerates mucociliary clearance and improves clinical outcomes of people with cystic fibrosis. This is an update of a previously published Cochrane Review. OBJECTIVES: To determine whether the timing of hypertonic saline inhalation (in relation to airway clearance techniques or in relation to time of day) has an impact on its clinical efficacy in people with cystic fibrosis. SEARCH METHODS: We identified relevant randomised and quasi-randomised controlled trials from the Cochrane Cystic Fibrosis Trials Register, the Physiotherapy Evidence Database (PEDro), and international cystic fibrosis conference proceedings. Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register: 28 February 2019. SELECTION CRITERIA: Any trial of hypertonic saline in people with cystic fibrosis where timing of inhalation was the randomised element in the study protocol with either: inhalation up to six hours before airway clearance techniques compared to inhalation during airway clearance techniques compared to inhalation up to six hours after airway clearance techniques; or morning compared to evening inhalation with any definition provided by the author. DATA COLLECTION AND ANALYSIS: Both authors independently assessed the trials identified by the search for potential inclusion in the review. The certainty of the evidence was assessed using GRADE. MAIN RESULTS: The searches identified 104 trial reports which represented 51 trials, of which three cross-over trials (providing data on 77 participants) met our inclusion criteria. We present three comparisons: inhalation before versus during airway clearance techniques; inhalation before versus after airway clearance techniques; and inhalation during versus after airway clearance techniques. One trial (50 participants), given its three-arm design, was eligible for all three comparisons. No trials compared morning versus evening inhalation of hypertonic saline. The evidence from the three trials was judged to be of low quality downgraded for limitations (high risk of bias due to blinding) and indirectness (all participants are adults, and therefore not applicable to children). Intervention periods ranged from one treatment to three treatments in one day. There were no clinically important differences between the timing regimens of inhaling hypertonic saline before, during or after airway clearance techniques in the mean amount of improvement in lung function or symptom scores (77 participants), with the between-group comparisons being non-significant (low-certainty evidence). While there may be little or no difference in the rating of satisfaction when hypertonic saline was inhaled before versus during the airway clearance techniques (64 participants) (with the 95% confidence interval including the possibility of both a higher and lower rating of satisfaction), satisfaction may be lower on a 100-mm scale when inhaled after the airway clearance techniques compared to before: mean difference (MD) 20.38 mm (95% confidence interval (CI) 12.10 to 28.66) and when compared to during the techniques, MD 14.80 mm (95% CI 5.70 to 23.90). Perceived effectiveness showed similar results: little or no difference for inhalation before versus during airway clearance techniques (64 participants); may be lower when inhaled after the airway clearance techniques compared to before, MD 10.62 (95% CI 2.54 to 18.70); and also when compared to during the techniques, MD 15.60 (95% CI 7.55 to 23.65). There were no quality of life or adverse events reported in any of the trials. AUTHORS' CONCLUSIONS: Timing of hypertonic saline inhalation makes little or no difference to lung function (low-certainty evidence). However, inhaling hypertonic saline before or during airway clearance techniques may maximise perceived efficacy and satisfaction. The long-term efficacy of hypertonic saline has only been established for twice-daily inhalations; however, if only one dose per day is tolerated, the time of day at which it is inhaled could be based on convenience or tolerability until evidence comparing these regimens is available. The identified trials were all of very short intervention periods, so longer-term research could be conducted to establish the effects arising from regular use, which would incorporate the influence of changes in adherence with long-term use, as well as generating data on any adverse effects that occur with long-term use.

Side lying during nebulisation can significantly improve apical deposition in healthy adults and adults with mild cystic fibrosis lung disease: a randomised crossover trial.

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 (FEV1 > 80%pred), and 13 with more advanced CF lung disease (FEV1 < 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.

Timing of dornase alfa inhalation for cystic fibrosis.

BACKGROUND: Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis. This is an update of a previously published Cochrane Review. OBJECTIVES: To determine whether the timing of dornase alfa inhalation (in relation to airway clearance techniques or morning versus evening inhalation) has an impact on objective and subjective measures of clinical efficacy in people with cystic fibrosis. SEARCH METHODS: Relevant randomised and quasi-randomised controlled trials were identified from the Cochrane Cystic Fibrosis Trials Register, Physiotherapy Evidence Database (PEDro), clinical trial registries and international cystic fibrosis conference proceedings.Date of the most recent search: 06 June 2018. SELECTION CRITERIA: Any trial of dornase alfa in people with cystic fibrosis where timing of inhalation was the randomised element in the trial with either: inhalation before compared to after airway clearance techniques; or morning compared to evening inhalation. DATA COLLECTION AND ANALYSIS: Both authors independently selected trials, assessed risk of bias and extracted data with disagreements resolved by discussion. Relevant data were extracted and, where possible, meta-analysed. MAIN RESULTS: We identified 115 trial reports representing 55 trials, of which five trials (providing data on 122 participants) met our inclusion criteria. All five trials used a cross-over design. Intervention periods ranged from two to eight weeks. Four trials (98 participants) compared dornase alfa inhalation before versus after airway clearance techniques. Inhalation after instead of before airway clearance did not significantly change forced expiratory volume at one second (very-low quality evidence). Similarly, forced vital capacity (low-quality evidence) and quality of life (very-low quality evidence) were not significantly affected; forced expiratory flow at 25% was significantly worse with dornase alfa inhalation after airway clearance, mean difference -0.17 litres (95% confidence interval -0.28 to -0.05), based on the pooled data from two small trials in children (7 to 19 years) with well-preserved lung function. All other secondary outcomes were statistically non-significant.In one trial (25 participants), morning versus evening inhalation had no impact on lung function or symptoms (low-quality evidence). AUTHORS' CONCLUSIONS: The current evidence derived from a small number of participants does not indicate that inhalation of dornase alfa after airway clearance techniques is more or less effective than the traditional recommendation to inhale nebulised dornase alfa 30 minutes prior to airway clearance techniques, for most outcomes. For children with well-preserved lung function, inhalation before airway clearance may be more beneficial for small airway function than inhalation after. However, this result relied on a measure with high variability and trials with variable follow-up. In the absence of strong evidence to indicate that one timing regimen is better than another, the timing of dornase alfa inhalation can be largely based on pragmatic reasons or individual preference with respect to the time of airway clearance and time of day. Further research is warranted.

Use of extracorporeal membrane oxygenation in cystic fibrosis in an Australian cystic fibrosis centre.

Extracorporeal membrane oxygenation (ECMO) support is used in selected patients with cystic fibrosis (CF) as a bridge to transplantation. Our aim was to describe briefly treatment and outcomes of six CF patients who received ECMO. One patient received a lung transplant and another recovered from acute respiratory failure. Four died despite ECMO support. Lack of timely availability of suitable donor lungs and patient selection are contributing factors.

The use of an alternate side lying positioning strategy during inhalation therapy does not prolong nebulisation time in adults with Cystic Fibrosis: a randomised crossover trial.

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 R2 < 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 .

Timing of dornase alfa inhalation for cystic fibrosis.

BACKGROUND: Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis. This is an update of a previously published Cochrane review. OBJECTIVES: To determine the effect of timing of dornase alfa inhalation on measures of clinical efficacy in people with cystic fibrosis (in relation to airway clearance techniques or time of day). SEARCH METHODS: Relevant randomised and quasi-randomised controlled trials were identified from the Cochrane Cystic Fibrosis Trials Register, Physiotherapy Evidence Database (PEDro), and international cystic fibrosis conference proceedings.Date of the most recent search: 25 April 2016. SELECTION CRITERIA: Any trial of dornase alfa in people with cystic fibrosis where timing of inhalation was the randomised element in the study with either: inhalation before compared to after airway clearance techniques; or morning compared to evening inhalation. DATA COLLECTION AND ANALYSIS: Both authors independently selected trials, assessed risk of bias and extracted data with disagreements resolved by discussion. Relevant data were extracted and, where possible, meta-analysed. MAIN RESULTS: We identified 115 trial reports representing 55 studies, of which five studies (providing data on 122 participants) met our inclusion criteria. All five studies used a cross-over design. Intervention periods ranged from two to eight weeks. Four trials compared dornase alfa inhalation before versus after airway clearance techniques. Inhalation after instead of before airway clearance did not significantly change forced expiratory volume at one second. Similarly, forced vital capacity and quality of life were not significantly affected; forced expiratory flow at 25% was significantly worse with dornase alfa inhalation after airway clearance, mean difference -0.17 litres (95% confidence interval -0.28 to -0.05), based on the pooled data from two small studies in children (seven to 19 years) with well-preserved lung function. All other secondary outcomes were statistically non-significant.In one trial, morning versus evening inhalation had no impact on lung function or symptoms. AUTHORS' CONCLUSIONS: The current evidence derived from a small number of participants does not indicate that inhalation of dornase alfa after airway clearance techniques is more or less effective than the traditional recommendation to inhale nebulised dornase alfa 30 minutes prior to airway clearance techniques, for most outcomes. For children with well-preserved lung function, inhalation before airway clearance may be more beneficial for small airway function than inhalation after. However, this result relied on a measure with high variability and studies with variable follow up. In the absence of strong evidence to indicate that one timing regimen is better than another, the timing of dornase alpha inhalation can be largely based on pragmatic reasons or individual preference with respect to the time of airway clearance and time of day. Further research is warranted.

Physiotherapy for cystic fibrosis in Australia and New Zealand: A clinical practice guideline.

Physiotherapy management is a key element of care for people with cystic fibrosis (CF) throughout the lifespan. Although considerable evidence exists to support physiotherapy management of CF, there is documented variation in practice. The aim of this guideline is to optimize the physiotherapy management of people with CF in Australia and New Zealand. A systematic review of the literature in key areas of physiotherapy practice for CF was undertaken. Recommendations were formulated based on National Health and Medical Research Council (Australia) guidelines and considered the quality, quantity and level of the evidence; the consistency of the body of evidence; the likely clinical impact; and applicability to physiotherapy practice in Australia and New Zealand. A total of 30 recommendations were made for airway clearance therapy, inhalation therapy, exercise assessment and training, musculoskeletal management, management of urinary incontinence, managing the newly diagnosed patient with CF, delivery of non-invasive ventilation, and physiotherapy management before and after lung transplantation. These recommendations can be used to underpin the provision of evidence-based physiotherapy care to people with CF in Australia and New Zealand.

A randomised trial of hypertonic saline during hospitalisation for exacerbation of cystic fibrosis.

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.

Timing of hypertonic saline inhalation for cystic fibrosis.

BACKGROUND: Inhalation of hypertonic saline improves sputum rheology, accelerates mucociliary clearance and improves clinical outcomes of people with cystic fibrosis. OBJECTIVES: To determine whether the timing of hypertonic saline inhalation (in relation to airway clearance techniques or in relation to time of day) has an impact on its clinical efficacy in people with cystic fibrosis. SEARCH METHODS: We identified relevant randomised and quasi-randomised controlled trials from the Cochrane Cystic Fibrosis Trials Register, the Physiotherapy Evidence Database (PEDro), and international cystic fibrosis conference proceedings.Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register: 19 December 2016. SELECTION CRITERIA: Any trial of hypertonic saline in people with cystic fibrosis where timing of inhalation was the randomised element in the study protocol with either: inhalation up to six hours before airway clearance techniques compared to inhalation during airway clearance techniques compared to inhalation up to six hours after airway clearance techniques; or morning compared to evening inhalation with any definition provided by the author. DATA COLLECTION AND ANALYSIS: Both authors independently assessed the trials identified by the search for potential inclusion in the review. MAIN RESULTS: The searches identified 97 trial reports which represented 46 studies, of which two studies (providing data on 63 participants) met our inclusion criteria. Both studies used a cross-over design. Both studies had low risk of all types of bias except the participants and the therapists who applied the treatments were not blinded. Intervention periods ranged from one treatment to three treatments in one day. The effects of the various regimens on lung function were non-significant. Satisfaction was rated significantly lower on a 100-mm scale when hypertonic saline was inhaled after the airway clearance techniques: mean differences 20.38 mm (95% confidence interval 12.10 to 28.66) compared to before airway clearance techniques and 14.80 mm (95% confidence interval 5.70 to 23.90) compared to during the techniques. Perceived effectiveness showed similar significant results. Other outcomes were unaffected by the timing regimen used. No trials compared morning versus evening inhalation of hypertonic saline. AUTHORS' CONCLUSIONS: People with cystic fibrosis could be encouraged to inhale hypertonic saline before or during airway clearance techniques to maximise perceived efficacy and satisfaction, even though these timing regimens may not have any better effect on lung function than inhalation after airway clearance techniques. Given the long-term efficacy of hypertonic saline has only been established for twice-daily inhalations, clinicians should advise patients to inhale hypertonic saline twice daily. However, if only one dose per day is tolerated, the time of day at which it is inhaled could be based on convenience or tolerability until evidence comparing these regimens is available.

Inspiratory muscle training facilitates weaning from mechanical ventilation among patients in the intensive care unit: a systematic review.

QUESTION: Does inspiratory muscle training improve inspiratory muscle strength in adults receiving mechanical ventilation? Does it improve the duration or success of weaning? Does it affect length of stay, reintubation, tracheostomy, survival, or the need for post-extubation non-invasive ventilation? Is it tolerable and does it cause adverse events? DESIGN: Systematic review of randomised trials. PARTICIPANTS: Adults receiving mechanical ventilation. INTERVENTION: Inspiratory muscle training versus sham or no inspiratory muscle training. OUTCOME MEASURES: Data were extracted regarding: inspiratory muscle strength and endurance; the rapid shallow breathing index; weaning success and duration; duration of mechanical ventilation; reintubation; tracheostomy; length of stay; use of non-invasive ventilation after extubation; survival; readmission; tolerability and adverse events. RESULTS: Ten studies involving 394 participants were included. Heterogeneity within some meta-analyses was high. Random-effects meta-analyses showed that the training significantly improved maximal inspiratory pressure (MD 7 cmH2O, 95% CI 5 to 9), the rapid shallow breathing index (MD 15 breaths/min/l, 95% CI 8 to 23) and weaning success (RR 1.34, 95% CI 1.02 to 1.76). Although only assessed in individual studies, significant benefits were also reported for the time spent on non-invasive ventilation after weaning (MD 16 hours, 95% CI 13 to 18), length of stay in the intensive care unit (MD 4.5 days, 95% CI 3.6 to 5.4) and length of stay in hospital (MD 4.4 days, 95% CI 3.4 to 5.5). Weaning duration decreased in the subgroup of patients with known weaning difficulty. The other outcomes weren't significantly affected or weren't measured. CONCLUSION: Inspiratory muscle training for selected patients in the intensive care unit facilitates weaning, with potential reductions in length of stay and the duration of non-invasive ventilatory support after extubation. The heterogeneity among the results suggests that the effects of inspiratory muscle training may vary; this perhaps depends on factors such as the components of usual care or the patient's characteristics.

Timing of dornase alfa inhalation for cystic fibrosis.

BACKGROUND: Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis. OBJECTIVES: To determine the effect of timing of dornase alfa inhalation on measures of clinical efficacy in people with cystic fibrosis (in relation to airway clearance techniques or time of day). SEARCH METHODS: Relevant randomised and quasi-randomised controlled trials were identified from the Cochrane Cystic Fibrosis Trials Register, Physiotherapy Evidence Database (PEDro), and international CF conference proceedings.Date of the most recent search: 22 February 2013. SELECTION CRITERIA: Any trial of dornase alfa in people with cystic fibrosis where timing of inhalation was the randomised element in the study with either: inhalation before compared to after airway clearance techniques; or morning compared to evening inhalation. DATA COLLECTION AND ANALYSIS: Both authors independently selected trials, assessed risk of bias and extracted data with disagreements resolved by discussion. Relevant data were extracted and, where possible, meta-analysed. MAIN RESULTS: We identified 99 trial reports representing 48 studies, of which five studies (providing data on 122 participants) met our inclusion criteria. All five studies used a cross-over design. Intervention periods ranged from two to eight weeks. Four trials compared dornase alfa inhalation before versus after airway clearance techniques. Inhalation after instead of before airway clearance did not significantly change FEV1. Similarly, FVC and quality of life were not significantly affected; FEF25 was significantly worse with dornase alfa inhalation after airway clearance, MD -0.17 litres (95% CI -0.28 to -0.05), based on the pooled data from two small studies in children (7 to 19 years) with well-preserved lung function. All other secondary outcomes were statistically non-significant.In one trial, morning versus evening inhalation had no impact on lung function or symptoms. AUTHORS' CONCLUSIONS: The current evidence derived from a small number of participants does not indicate that inhalation of dornase alfa after airway clearance techniques is more or less effective than the traditional recommendation to inhale nebulised dornase alfa 30 minutes prior to airway clearance techniques, for most outcomes. For children with well-preserved lung function, inhalation before airway clearance may be more beneficial for small airway function than inhalation after. However, this result relied on a measure with high variability and studies with variable follow up. In the absence of strong evidence to indicate that one timing regimen is better than another, the timing of dornase alpha inhalation can be largely based on pragmatic reasons or individual preference with respect to the time of airway clearance and time of day. Further research is warranted.

Timing of hypertonic saline inhalation for cystic fibrosis.

BACKGROUND: Inhalation of hypertonic saline improves sputum rheology, accelerates mucociliary clearance and improves clinical outcomes of people with cystic fibrosis. OBJECTIVES: To determine whether the timing of hypertonic saline inhalation (in relation to airway clearance techniques or in relation to time of day) has an impact on its clinical efficacy in people with cystic fibrosis. SEARCH METHODS: We identified relevant randomised and quasi-randomised controlled trials from the Cochrane Cystic Fibrosis Trials Register, the Physiotherapy Evidence Database (PEDro), and international cystic fibrosis conference proceedings.Date of the last search of the Group's Cystic Fibrosis Trials Register: 6 December 2011. SELECTION CRITERIA: Any trial of hypertonic saline in people with cystic fibrosis where timing of inhalation was the randomised element in the study protocol with either: inhalation up to six hours before airway clearance techniques compared to inhalation during airway clearance techniques compared to inhalation up to six hours after airway clearance techniques; or morning compared to evening inhalation with any definition provided by the author. DATA COLLECTION AND ANALYSIS: Both authors independently assessed the trials identified by the search for potential inclusion in the review. MAIN RESULTS: The search strategy identified 50 trial reports which represented 24 unique studies. One study, published only as an abstract, is awaiting further assessment. None of the other studies compared timing regimens for the inhalation of hypertonic saline and we excluded these from the review. AUTHORS' CONCLUSIONS: This review did not identify any evidence comparing the timing of hypertonic saline inhalation in relation to airway clearance physiotherapy. Until such evidence becomes available, clinicians could advise patients to inhale hypertonic saline before airway clearance, because this is the only regimen evaluated in the studies that established the efficacy of the use of hypertonic saline. This review also did not identify any evidence comparing the timing of hypertonic saline inhalation in relation to time of day. Until such evidence becomes available, clinicians could advise patients to inhale hypertonic saline morning and evening; but if only one dose per day is tolerated, the time of day at which it is inhaled could be based on convenience or tolerability.Given the competing theoretical rationales about why hypertonic saline could be more effective if inhaled at certain times, a trial comparing these various timing regimens should be conducted.

Adults with cystic fibrosis prefer hypertonic saline before or during airway clearance techniques: a randomised crossover trial.

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.