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.

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.

Occupations and balance during the transition to motherhood with a lifetime chronic illness: A scoping review examining cystic fibrosis, asthma, and Type-1 diabetes.

INTRODUCTION: Throughout the transition to motherhood, changes are experienced across a woman's physical, mental, social, and occupational self. Maternal chronic illness adds the complexity of increased healthcare needs and navigating a high-risk, medicalised pregnancy, birth, and post-natal period. Literature concerning motherhood transitions in chronic illness generally focusses on the mother's medical health and pregnancy outcomes; little is known about the impacts on women's occupations, balance, and quality of life. Understanding these issues may help support women in a more tailored and holistic way. OBJECTIVE: This scoping review aims to gather, analyse, and synthesise existing empirical research on occupational engagement and occupational balance as they impact on wellbeing and quality of life in women with a lifetime chronic illness before and during pregnancy and in early motherhood. METHOD: The review follows the nine-stage framework described in the Joanna Briggs Institute Manual for Evidence Synthesis (2020). Five databases were searched: Embase, Medline, PsycINFO, CINAHL, Scopus, and OT Seeker. Data were extracted and examined via content analysis, described in narrative synthesis, summarised into a conceptual framework, and tabulated. FINDINGS: A total of 8,655 papers were discovered on initial search. Following title and abstract screening, 220 full-text studies were assessed for eligibility, and 46 papers were finally included. Analysis generated four major themes: The Disrupted Transition Journey; Adaptation, Compromise and Choice; Outcomes; and Drawing on What's Available. The themes were conceptualised into a framework to explain how women sought to balance motherhood and illness-related occupations. Adequate access to information, social support, expert care, and financial resources improved both quality of life and healthcare compliance. CONCLUSION: Findings of this scoping review deepen the understanding of occupational balance during the transition to motherhood in the context of lifetime chronic illness. Healthcare providers and supportive family and friends can use this knowledge to adapt their approach to assisting women with chronic illness on the motherhood journey. These findings may also inform further inquiry into the scope of occupational therapy practice with this population.

Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele.

BACKGROUND: Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein, and nearly 90% of patients have at least one copy of the Phe508del CFTR mutation. In a phase 2 trial involving patients who were heterozygous for the Phe508del CFTR mutation and a minimal-function mutation (Phe508del-minimal function genotype), the next-generation CFTR corrector elexacaftor, in combination with tezacaftor and ivacaftor, improved Phe508del CFTR function and clinical outcomes. METHODS: We conducted a phase 3, randomized, double-blind, placebo-controlled trial to confirm the efficacy and safety of elexacaftor-tezacaftor-ivacaftor in patients 12 years of age or older with cystic fibrosis with Phe508del-minimal function genotypes. Patients were randomly assigned to receive elexacaftor-tezacaftor-ivacaftor or placebo for 24 weeks. The primary end point was absolute change from baseline in percentage of predicted forced expiratory volume in 1 second (FEV1) at week 4. RESULTS: A total of 403 patients underwent randomization and received at least one dose of active treatment or placebo. Elexacaftor-tezacaftor-ivacaftor, relative to placebo, resulted in a percentage of predicted FEV1 that was 13.8 points higher at 4 weeks and 14.3 points higher through 24 weeks, a rate of pulmonary exacerbations that was 63% lower, a respiratory domain score on the Cystic Fibrosis Questionnaire-Revised (range, 0 to 100, with higher scores indicating a higher patient-reported quality of life with regard to respiratory symptoms; minimum clinically important difference, 4 points) that was 20.2 points higher, and a sweat chloride concentration that was 41.8 mmol per liter lower (P<0.001 for all comparisons). Elexacaftor-tezacaftor-ivacaftor was generally safe and had an acceptable side-effect profile. Most patients had adverse events that were mild or moderate. Adverse events leading to discontinuation of the trial regimen occurred in 1% of the patients in the elexacaftor-tezacaftor-ivacaftor group. CONCLUSIONS: Elexacaftor-tezacaftor-ivacaftor was efficacious in patients with cystic fibrosis with Phe508del-minimal function genotypes, in whom previous CFTR modulator regimens were ineffective. (Funded by Vertex Pharmaceuticals; VX17-445-102 ClinicalTrials.gov number, NCT03525444.).

Transition to adult care in cystic fibrosis: The challenges and the structure.

In developed countries, it is projected that there will be a 70% increase in the number of adults living with Cystic Fibrosis (CF) between 2010 and 2025. This shift in demographics highlights the importance of high-quality transition programmes with developmentally appropriate integrated health care services as the individual moves through adolescence to adulthood. Adolescents living with CF face additional and unique challenges that may have long-term impacts on their health, quality of life and life-expectancy. CF specific issues around socially challenging symptoms, body image, reproductive health and treatment burden differentiate people with CF from their peers and require clinicians to identify and address these issues during the transition process. This review provides an overview of the health, developmental and psychosocial challenges faced by individuals with CF, their guardians and health care teams considering the fundamental components and tools that are required to build a transition programme that can be tailored to suit individual CF clinics.

Redesign of the Australian Cystic Fibrosis Data Registry: A multidisciplinary collaboration.

Clinical registries that monitor and review outcomes for patients with cystic fibrosis have existed internationally for many decades. However, their purpose continues to evolve and now includes the capability to support clinical effectiveness research, clinical trials and Phase IV studies, and international data comparisons and projects. To achieve this, registries must regularly update the information that they collect and ensure design that is adaptable and flexible to changing needs. The Australian Cystic Fibrosis Data Registry commenced in 1998, and in 2018-19 undertook a transformation to enable it to meet the needs of multiple stakeholders into the future. This included a comprehensive, multidisciplinary review of the registry's data elements, and a redesign and rebuild of the registry's database. The data element review comprised the processes of alignment, comparison, selection, consolidation, revision and definition of finalised data elements. The database redesign included attention to each of the registry functions of data collection, storage and management, and reporting. The revision of a national data collection system is a time-intensive process, and requires significant clinical and other expert engagement. The resulting database, while being continually refined, is now fit for purpose to support Australian clinicians and patients with CF to receive best practice care.

ERS/TSANZ Task Force Statement on the management of reproduction and pregnancy in women with airways diseases.

This European Respiratory Society/Thoracic Society of Australia and New Zealand statement outlines a review of the literature and expert opinion concerning the management of reproduction and pregnancy in women with airways diseases: asthma, cystic fibrosis (CF) and non-CF bronchiectasis. Many women with these diseases are now living into reproductive age, with some developing moderate-to-severe impairment of lung function in early adulthood. The statement covers aspects of fertility, management during pregnancy, effects of drugs, issues during delivery and the post-partum period, and patients' views about family planning, pregnancy and parenthood. The statement summarises current knowledge and proposes topics for future research, but does not make specific clinical recommendations.

Treatable traits can be identified in a severe asthma registry and predict future exacerbations.

BACKGROUND AND OBJECTIVE: A new taxonomic and management approach, termed treatable traits, has been proposed for airway diseases including severe asthma. This study examined whether treatable traits could be identified using registry data and whether particular treatable traits were associated with future exacerbation risk. METHODS: The Australasian Severe Asthma Web-Based Database (SAWD) enrolled 434 participants with severe asthma and a comparison group of 102 participants with non-severe asthma. Published treatable traits were mapped to registry data fields and their prevalence was described. Participants were characterized at baseline and every 6 months for 24 months. RESULTS: In SAWD, 24 treatable traits were identified in three domains: pulmonary, extrapulmonary and behavioural/risk factors. Patients with severe asthma expressed more pulmonary and extrapulmonary treatable traits than non-severe asthma. Allergic sensitization, upper-airway disease, airflow limitation, eosinophilic inflammation and frequent exacerbations were common in severe asthma. Ten traits predicted exacerbation risk; among the strongest were being prone to exacerbations, depression, inhaler device polypharmacy, vocal cord dysfunction and obstructive sleep apnoea. CONCLUSION: Treatable traits can be assessed using a severe asthma registry. In severe asthma, patients express more treatable traits than non-severe asthma. Traits may be associated with future asthma exacerbation risk demonstrating the clinical utility of assessing treatable traits.

Management of Australian Adults with Bronchiectasis in Tertiary Care: Evidence-Based or Access-Driven?

PURPOSE: Australian data regarding the management of patients with bronchiectasis is scarce. We sought to compare the management of adults with bronchiectasis attending tertiary Australian centres with recent national and international guidelines. METHODS: The Australian Bronchiectasis Registry is a centralised database of patients with radiologically confirmed bronchiectasis unrelated to cystic fibrosis recruited from 14 tertiary Australian hospitals. We excluded children (<18 years) and those with incomplete data, leaving 589 adults for cross-sectional analyses. We compared the proportion of patients receiving certain therapies, as compared to the proportion eligible for those treatments according to the current guidelines and baseline clinical information available from the registry. RESULTS: Pulmonary rehabilitation was attended by 22%, although it was indicated in 67% of the cohort. Airway clearance was undertaken in 52% of patients, although 71% reported chronic productive cough. Sputum bacterial culture results were available for 59%, and mycobacterial culture results were available for 29% of the cohort. Inhaled antibiotics were used in half of potentially eligible patients. Despite guideline recommendations against routine use, inhaled corticosteroids were used in 48% of patients. Long-term macrolides were used in 28% of participants. CONCLUSIONS: Discrepancies exist between guideline recommendations and real-world treatment of bronchiectasis in Australia, even in tertiary centres. These findings suggest the need for increased patient referral to pulmonary rehabilitation, increased attention to airway clearance, increased collection of sputum samples (especially for mycobacterial culture) and rationalisation of inhaled corticosteroid use. These findings encourage a review of treatment access and will inform ongoing education to promote evidence-based care for people living with bronchiectasis.

Work environment risks for health care workers with cystic fibrosis.

In Australia and New Zealand, >50% of people with cystic fibrosis (CF) are adults and many of these people are pursuing vocational training and undertaking paid employment. More than 6% of adults with CF are working in health care. There is limited guidance in literature to support health care workers with CF (HCWcf) in training and in employment to support safe practice and to provide protection for themselves and their patients from the acquisition of health care associated infection. A multidisciplinary team of CF and Infectious Disease Clinicians, Infection Prevention and Control Practitioners, HCWcf, academic experts in medical ethics and representatives from universities, appraised the available evidence on the risk posed to and by HCWcf. Specific recommendations were made for HCWcf, CF health care teams, hospitals and universities to support the safe practice and appropriate support for HCWcf.

Pseudomonas aeruginosa Inhibits the Growth of Scedosporium and Lomentospora In Vitro.

In vitro bacterial-fungal interaction studies in cystic fibrosis (CF) have mainly focused on interactions between bacteria and Candida. Here we investigated the effect of Pseudomonas aeruginosa on the growth of Scedosporium/Lomentospora spp. Standard suspensions of P. aeruginosa (16 non-mucoid and nine mucoid isolates) were dropped onto paper disks, placed on lawns of Lomentospora prolificans (formerly Scedosporium prolificans) strain WM 14.140 or Scedosporium aurantiacum strain WM 11.78 on solid agar. The median inhibitory activity (mIz) was calculated for each fungal-bacterial combination. As a group, mIz values for non-mucoid phenotype P. aeruginosa strains were significantly lower than those for mucoid strains (P < 0.001); 14/16 (87.5%) non-mucoid strains had mIz <1.0 against both fungi versus just 3/9 mucoid strains (33.4%) (P = 0.01). One non-mucoid (PA14) and one mucoid (CIDMLS-PA-28) P. aeruginosa strain effecting inhibition were selected for further studies. Inhibition of both L. prolificans and S. aurantiacum by these strains was confirmed using the XTT (2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide) reduction assay. Following incubation with XTT, inhibition of fungal growth was determined as the ratio of absorbance in liquid culture with Pseudomonas to that in control fungal cultures. An absorbance ratio of <1.0 consistent with bacterial inhibition of fungal growth was observed for all four P. aeruginosa-fungal combinations (P < 0.05). Fluorescence microscopy, subsequent to co-culture of either fungal isolate with P. aeruginosa strain PA14 or CIDMLS-PA-28 revealed poorly formed hyphae, compared with control fungal cultures. P. aeruginosa inhibits growth of L. prolificans and S. aurantiacum in vitro, with non-mucoid strains more commonly having an inhibitory effect. As P. aeruginosa undergoes phenotype transitions from non-mucoid to the mucoid form with progression of CF lung disease, this balance may influence the appearance of Scedosporium fungi in the airways.

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.

Single nucleotide polymorphisms and outcome risk in unrelated mismatched hematopoietic stem cell transplantation: an exploration study.

Genetic risk factors contribute to adverse outcome of hematopoietic stem cell transplantation (HSCT). Mismatching of the HLA complex most strongly determines outcomes, whereas non-HLA genetic polymorphisms are also having an impact. Although the majority of HSCTs are mismatched, only few studies have investigated the effects of non-HLA polymorphisms in the unrelated HSCT and HLA-mismatched setting. To understand these effects, we genotyped 41 previously studied single nucleotide polymorphisms (SNPs) in 2 independent, large cohorts of HSCT donor-recipient pairs (n = 460 and 462 pairs) from a homogeneous genetic background. The study population was chosen to pragmatically represent a large clinically homogeneous group (acute leukemia), allowing all degrees of HLA matching. The TNF-1031 donor-recipient genotype mismatch association with acute GVHD grade 4 was the only consistent association identified. Analysis of a subgroup of higher HLA matching showed consistent associations of the recipient IL2-330 GT genotype with risk of chronic GVHD, and the donor CTLA4-CT60 GG genotype with protection from acute GVHD. These associations are strong candidates for prediction of risk in a clinical setting. This study shows that non-HLA gene polymorphisms are of relevance for predicting HSCT outcome, even for HLA mismatched transplants.

Cystic fibrosis related diabetes: potential pitfalls in the transition from paediatric to adult care.

One of the major complications of Cystic Fibrosis (CF) is CF-Related Diabetes (CFRD), which increases in incidence with age, from 1-2% below the age of 10 years to ∼20% of adolescents and 40-50% of adults. Multiple guidelines have been published over the last few years for the diagnosis and management of CFRD, from the American Diabetes Association (ADA) / US Cystic Fibrosis Foundation, International Society for Pediatric and Adolescent Diabetes (ISPAD) and the Thoracic Society of Australia and New Zealand-Australian Diabetes Society. However, little is published about the particular issues involved in transition of patients with CFRD from paediatric to adult care, nor the issues concerning the development of CFRD during the transition period. This document seeks to provide assistance to physicians, dieticians, nurses, diabetes educators, CF patients and their families by outlining the issues surrounding CFRD during transition from paediatric to adult care.

Australian standards of care for cystic fibrosis-related diabetes.

Multiple guidelines have been published over the last few years for the diagnosis and management of cystic fibrosis (CF) and cystic fibrosis related diabetes (CFRD), although some of the recommendations are based on extrapolation from other forms of diabetes and/or expert opinions. This document seeks to combine the guidelines to provide an Australian approach to the management of CFRD and establish the guidelines within the Australian CF Standards of Care. It is intended that this document will provide assistance to doctors, nurses, dietitians, physiotherapists, diabetes educators and CF patients concerning the issues surrounding CFRD, and will be reviewed and updated in 2016.

Glucagon-Like Peptide-1 Agonists and General Anesthesia: Perioperative Considerations and the Utility of Gastric Ultrasound.

Glucagon-like peptide-1 (GLP-1) agonists are very popular and useful medications for the treatment of type 2 diabetes mellitus and obesity. Potent gastric emptying delay is common with these medications, serving as a major contributor to the postprandial glycemic control and weight loss benefits of these medications. Recently, multiple case reports and studies indicating safety risks for these medications and their use in patients planning to undergo general anesthesia have been published, as retained gastric contents can lead to intraoperative aspiration. New guidelines for these medications have been released to guide clinical practice for anesthesiologists. Some degree of preoperative cessation of these medications is required. At this time, the ideal window for cessation of these medications to optimize clinical efficacy while reducing aspiration risks has not yet been well elaborated on. Aspiration of gastric contents can still occur despite appropriate preoperative fasting in patients taking GLP-1 agonists. Gastric ultrasound appears to be an effective and objective way of preoperatively assessing a patient's stomach contents to make decisions regarding anesthetic management for patients prescribed these medications. This practice is limited by a general lack of training and implementation in current anesthesiology practice.

Surgical release of the chest wall skin and fascia for sclerodermatous graft versus host disease causing restrictive lung disease: A case report.

INTRODUCTION: Graft versus host disease (GVHD) remains a significant source of morbidity and mortality in the setting of allogeneic stem cell transplantation. Skin involvement is reported to be as high as 70-95 % in this group with GVHD and the severity of the involvement varies widely. Surgical management of complications of severe cutaneous GVHD is uncommon and is rarely mentioned as a treatment option. CASE PRESENTATION: We present a case of severe sclerodermatous skin changes restricting chest expansion and exercise tolerance to the point of limiting basic activities of daily life. A 54-year-old male presents with severe restrictive lung disease from sclerodermatous graft versus host disease (GVHD) after stem cell transplant for Chronic Myeloid Leukaemia (CML). He experienced limited symptomatic relief from maximal medical therapy and photochemotherapy, and subsequently underwent a skin release and split skin grafting of his chest and abdomen in an effort to improve exercise tolerance and quality of life. CLINICAL DISCUSSION: Despite an initial improvement in functioning, the patient's spirometry and lung function continued to decline with time, possibly suggesting that he did not gain a sustained benefit from surgical release of his cutaneous GVHD. CONCLUSION: While delineating between disease progression and surgical outcome is difficult in this case, the patient would argue that by delaying or reducing further decline in function, the surgical release procedures led to improved quality of life in subsequent years. However further research is required to establish a clear role for surgery in the treatment of refractory cutaneous GVHD.

Tuning Stainless Steel Oxide Layers through Potential Cycling─AEM Water Electrolysis Free of Critical Raw Materials.

Anion exchange membrane water electrolyzers (AEMWEs) have an intrinsic advantage over acidic proton exchange membrane water electrolyzers through their ability to use inexpensive, stable materials such as stainless steel (SS) to catalyze the sluggish oxygen evolution reaction (OER). As such, the study of active oxide layers on SS has garnered great interest. Potential cycling is a means to create such active oxide layers in situ as they are readily formed in alkaline solutions when exposed to elevated potentials. Cycling conditions in the literature are rife with unexplained variations, and a complete account of how these variations affect the activity and constitution of SS oxide layers remains unreported, along with their influence on AEMWE performance. In this paper, we seek to fill this gap in the literature by strategically cycling SS felt (SSF) electrodes under different scan rates and ranges. The SSF anodes were rapidly activated within the first 50 cycles, as shown by the 10-fold decline in charge transfer resistance, and the subsequent 1000 cycles tuned the metal oxide surface composition. Cycling the Ni redox couple (RC) increases Ni content, which is further enhanced by lowering the cycling rate, while cycling the Fe RC increases Cr content. Fair OER activity was uncovered through cycling the Ni RC, while Fe cycling produced SSF electrodes active toward both the OER and the hydrogen evolution reaction (HER). This indicates that inert SSF electrodes can be activated to become efficient OER and HER electrodes. To this effect, a single-cell AEMWE without any traditional catalyst or ionomer generated 1.0 A cm-2 at 1.94 V ± 13.3 mV with an SSF anode, showing a fair performance for a cell free of critical raw materials.