Codevelopment of a model of care for adults living with cystic fibrosis-related diabetes.

BACKGROUND: Cystic fibrosis (CF) related diabetes affects up to half of all adults with CF and is associated with higher morbidity and mortality. Our aim is to codevelop an ideal model of care that integrates diabetes technology and better meets the needs of adults living with the condition to improve attendance, engagement, service satisfaction, and clinical outcomes. METHODS: Using qualitative research methods, we evaluated disease perceptions, barriers, and enablers to optimal CF-related diabetes management and service delivery. Integration of continuous glucose monitoring (CGM) was also explored. An initial broad purposive consumer survey was followed by focus groups with end-users. Grounded theory approach was utilized with major problem areas identified then explored, coded, and grouped into requisites for an "ideal model of care" for adults living with CF-related diabetes. RESULTS: Two key themes emerged (i) an ideal model of care consisted of a dual-specialty service co-led by endocrinology and CF physicians and supported by diabetes educator and CF dietitian with a goal to provide consistent and personalized diabetes management and (ii) CGM was acceptable for use in adults with CF-related diabetes with many perceived benefits and should be integrated into the model of care. Barriers to optimizing glycemic control included diet, finger-prick testing, reduced access to CGM, and pulmonary exacerbations. End-user feedback on CGM was overwhelmingly positive with regard to operability. CGM was also identified as a tool that could be used to engage, educate, and empower adults living with CF-related diabetes and facilitate constructive and personalized clinical decision-making by healthcare providers. CONCLUSION: For adults living with CF, a diagnosis of diabetes is associated with increased treatment burden. Our findings suggest an "ideal model of care" for CF-related diabetes would be co-led by endocrinology services integrated within a pre-existing CF service, incorporating CGM.

Effects of modulator therapies on endocrine complications in adults with cystic fibrosis: a narrative review.

Cystic fibrosis is a monogenic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which transports chloride ions in secretory organs. Modulator therapies are small molecules that correct CFTR dysfunction and can lead to a wide range of benefits for both pulmonary and extrapulmonary complications of cystic fibrosis. With advancements in airway, antimicrobial and nutritional therapies and now introduction of modulator therapies, most people living with cystic fibrosis in Australia are now adults. For adults with cystic fibrosis, endocrine manifestations such as cystic fibrosis-related diabetes, metabolic bone disease, and reproductive health are becoming increasingly important, and emerging evidence on the endocrine effects of CFTR modulator therapies is promising and is shifting paradigms in our understanding and management of these conditions. The management of cystic fibrosis-related diabetes will likely need to pivot for high responders to modulator therapy with dietary adaptions and potential use of medications traditionally reserved for adults with type 2 diabetes, but evidence to support changing clinical care needs is currently lacking. Increased attention to diabetes-related complications screening will also be required. Increased exercise capacity due to improved lung function, nutrition and potentially direct modulator effect may have a positive impact on cystic fibrosis-related bone disease, but supporting evidence to date is limited. Fertility can improve in women with cystic fibrosis taking modulator therapy. This has important implications for pregnancy and lactation, but evidence is lacking to guide pre-conception and antenatal management. Provision of multidisciplinary clinical care remains ever-important to ensure the emergence of endocrine and metabolic complications are optimised in adults with cystic fibrosis.

Outpatient parenteral antibiotic therapy (OPAT) for the management of bronchiectasis.

Background: Patients with bronchiectasis often require hospitalisation for the administration of intravenous antibiotics for the management of acute exacerbations. Increasingly, Outpatient Parenteral Antibiotic Therapy (OPAT) services have become available as a potential alternative for domiciliary management. Aims: This study assessed outcomes in both cystic fibrosis (CF) and non-CF bronchiectasis patients who received OPAT for the management of an acute exacerbation of bronchiectasis. Methods: A retrospective study of consecutive subjects was done in both CF and non-CF groups in a large metropolitan Health Service in Australia from 2016 to 2022. Results: There were 51 episodes of care in the non-CF group (22 subjects) and 73 episodes in the CF group (13 subjects). The non-CF group were nearly all treated with once daily domiciliary intravenous (IV) ceftriaxone (49/51 episodes) for a duration of 9.1 ± 3.0 days (mean and standard deviation (SD)) via a peripherally inserted venous canula (84% of episodes). In contrast, the CF group generally received dual IV antibiotics (64% of episodes), with an average duration of 16.8 ± 6.3 days via central venous access (100%). In the non-CF group, the admission rate to hospital after 1 month was 9.6% and in the CF group was 0%. At 3 and 6 months the readmission rate for the non-CF group was 15.7% and 19.6% and CF group was 21.9% and 31.5%. There was a low rate of complications for the OPAT admissions (2% for the non-CF group and 7% for CF group). Conclusions: OPAT is a viable alternative for the management of bronchiectasis exacerbations.

Continuous glucose monitoring versus self-monitoring of blood glucose in the management of cystic fibrosis related diabetes: A systematic review and meta-analysis.

BACKGROUND: Treatment of cystic fibrosis related diabetes (CFRD) can improve outcomes and use of continuous glucose monitoring (CGM) can positively impact glycemic control. We conducted a systematic review to assess current evidence on CGM compared to self-monitoring of blood glucose (SMBG) in the management of CFRD to determine its effect on glycemic, pulmonary, non-pulmonary and quality of life outcomes. METHODS: Using pre-defined selection criteria, we searched MEDLINE, Embase, CENTRAL, Evidence-Based Medicine Reviews, grey literature and six relevant journals for studies using CGM and/or SMBG in CFRD with greater than 6 weeks of follow-up and reported change in HbA1c. The primary outcome was weighted mean difference (WMD) in plasma HbA1c between CGM and SMBG groups. Secondary outcomes included exploring interrelationships between CGM metrics and effects on disease-specific pulmonary, non-pulmonary and quality of life outcomes. RESULTS: A total of 1671 references were retrieved, 862 studies screened and 124 full-texts assessed for eligibility. No studies directly compared CGM to SMBG. A meta-analysis of seventeen studies of 416 individuals (CGM = 138, SMBG = 278) found CGM group had 4.1 mmol/mol (95% CI -7.9 to -0.30, p = 0.034) lower HbA1c compared to SMBG group. Most studies demonstrated moderate-to-high risk of bias. Publication bias was also present. Heterogeneity was high and meta-regression identified duration of follow-up in SMBG group as main contributor. CONCLUSION: Our findings suggest use of CGM may be associated with improved glycemic control compared to SMBG in CFRD, however evidence of benefit on pulmonary, non-pulmonary and psychosocial outcomes are lacking.

Comparison of continuous glucose monitoring to reference standard oral glucose tolerance test for the detection of dysglycemia in cystic Fibrosis: A systematic review.

Aims: Increasing evidence for benefit of early detection of cystic fibrosis related diabetes (CFRD) coupled with limitations of current diagnostic investigations has led to interest and utilisation of continuous glucose monitoring (CGM). We conducted a systematic review to assess current evidence on CGM compared to reference standard oral glucose tolerance test for the detection of dysglycemia in people with cystic fibrosis without confirmed diabetes. Methods: MEDLINE, Embase, CENTRAL, Evidence-Based Medicine Reviews, grey literature and six relevant journals were searched for studies published after year 2000. Studies reporting contemporaneous CGM metrics and oral glucose tolerance test results were included. Outcomes on oral glucose tolerance tests were categorised into a) normal, b) abnormal (indeterminate and impaired) or c) diabetic as defined by American Diabetes Association criteria. CGM outcomes were defined as hyperglycemia (≥1 peak sensor glucose ≥ 200 mg/dL), dysglycemia (≥1 peak sensor glucose ≥ 140-199 mg/dL) or normoglycemia (all sensor glucose peaks < 140 mg/dL). CGM hyperglycemia in people with normal or abnormal glucose tolerances was used to define an arbitrary CGM-diagnosis of diabetes. The Quality Assessment of Diagnostic Accuracy Studies tool was used to assess risk of bias. Primary outcome was relative risk of an arbitrary CGM-diagnosis of diabetes compared to the oral glucose tolerance test. Results: We identified 1277 publications, of which 19 studies were eligible comprising total of 416 individuals with contemporaneous CGM and oral glucose tolerance test results. Relative risk of an arbitrary CGM-diagnosis of diabetes compared to oral glucose tolerance test was 2.92. Studies analysed were highly heterogenous, prone to bias and inadequately assessed longitudinal associations between CGM and relevant disease-specific sequela. Conclusions: A single reading > 200 mg/dL on CGM is not appropriate for the diagnosis of CFRD. Prospective studies correlating CGM metrics to disease-specific outcomes are needed to determine appropriate cut-points.

Continuous glucose monitoring indices predict poor FEV1 recovery following cystic fibrosis pulmonary exacerbations.

BACKGROUND: Little is known about the effect of dysglycemia during cystic fibrosis pulmonary exacerbation (PEx) on recovery of FEV1 percentage predicted (ppFEV1) METHODS: Continuous glucose monitoring (CGM) was commenced at the time of admission to hospital for PEx and continued for 6 weeks. The CGM indices, percentage of time glucose greater than 7.8 mmol/L (%T>7.8) and mean glucose were evaluated as predictors of absolute ppFEV1 change following treatment of PEx. RESULTS: Of the 20 participants who completed the study 13 (65%) had cystic fibrosis related diabetes (CFRD). The mean of both CGM indices were highest during the first week of pulmonary exacerbation and continued to decline over the first 4 weeks at which point they plateaued. Using multivariate regression models, factors which were predictive of maximum attained ppFEV1 change over 6 weeks were %T>7.8, mean glucose, HbA1c and preadmission ppFEV1 change from baseline. These relationships were independent of a diagnosis of CFRD, which was not associated with ppFEV1 recovery. In a longitudinal model of ppFEV1 change at weeks 1, 2 and 6, the CGM index %T>7.8 approached significance as a predictive variable. CONCLUSIONS: Hyperglycemia during PEx in adult CF patients is associated with poorer ppFEV1 recovery. Conversely, there was no association observed between CFRD diagnosis and ppFEV1 improvement, suggesting that optimization of glycemic control in CFRD patients may positively influence recovery of lung function. Further clinical trials are required to evaluate the merits of intensive glycemic control in CFRD during PEx.

C-reactive protein levels in acute respiratory exacerbations of cystic fibrosis.

C-reactive protein (CRP) levels increase in response to bacterial infection and have been used to guide the use of antibiotics. We assessed CRP levels in a cohort of patients with cystic fibrosis (CF) admitted to hospital with an exacerbation of their lung disease, requiring treatment with broad-spectrum antibiotics. In this group, most subjects had CRP levels of less than 20 mg/L, including patients who had pneumonia. The clinical utility of the CRP in guiding antibiotic use in exacerbations of CF is limited.

Subclinical Left Ventricular Dysfunction is Influenced by Genotype Severity in Patients with Cystic Fibrosis.

BACKGROUND AND OBJECTIVE: Over 2000 genotypes in the cystic fibrosis (CF) gene have been described. These genotypic differences result in variable clinical manifestations of CF, with severity of disease dependent on CF transmembrane conductance (CFTR) protein function. CFTR is widely distributed in nucleated cells, including cardiac myocytes, but the effect of genotype on cardiac function is not known. METHODS: This retrospective review of echocardiographic data is from a single adult CF centre between 2000 and 2015. Patients were cohorted based on the functional classification of genotype. 'Severe' patients had both CF genes from functional classification groups 1-3; 'mild' patients had one or no gene from these groups, or in the event of the second gene being unknown were pancreatic sufficient. RESULTS: Genotype and echocardiography were recorded during the inclusion period in 100 patients, 79 of whom were classified as having severe genotypes. Although the severe group were younger they had a lower fractional shortening (33.66 ± 6.6 vs 36.9 ± 6.3, P < .05), left atrial area (14.9 ± 3.6 versus 18.0 ± 4.2 cm2; P < .01) and volume (39.9 ± 18.7 versus 51.0 ± 18.7 mL; P < .05) and showed a trend to lower left ventricular ejection fraction. CONCLUSIONS: This study is the first to show that in CF, severity of genotype (functional classification) is associated with cardiac impairment. Patients with severe CF genotype and cardiac dysfunction should be identified to evaluate cardiac response to gene-modifying treatments prior to consideration for lung transplantation.

Is non-invasive ventilation safe in acute severe asthma?

BACKGROUND AND OBJECTIVE: The effect of non-invasive ventilation (NIV) in acute severe asthma is unclear and there are concerns regarding its safety. METHODS: We undertook a 5-year case-control review of mortality and morbidity associated with NIV use in acute severe asthma and compared this with asthma requiring invasive mechanical ventilation (IMV) and a control group with less severe asthma without ventilatory support. RESULTS: Eight hundred seventy-three patients had acute severe asthma of whom 30 were treated with NIV, 17 with IMV and 90 served as controls. The mean duration of NIV was 9.5 ± 7.3 h with inspiratory positive airway pressure and expiratory positive airway pressure of 11.9 ± 1.4 and 5.8 ± 1.2 cmH2 O respectively. Mortality was zero in the NIV and control groups, compared with 41% in the IMV group. None of the NIV or control groups required escalation to invasive ventilation. There were no instances of haemodynamic compromise in the NIV or control groups. Length of hospital stay was 121 ± 96 h in the NIV group and similar to the severe IMV group (136 ± 99 h, P > 0.05) and significantly longer than the control group (42 ± 40 h, P < 0.05). CONCLUSIONS: NIV can be safely used in acute severe asthma although further work is needed to delineate the precise patient selection process.

Noninvasive ventilation in acute asthma.

Noninvasive ventilation (NIV) has well-recognized benefits in acute exacerbation of chronic obstructive pulmonary disease and pulmonary edema. Its utilization in acute asthma, however, remains controversial. In this review, we describe the physiological basis to justify NIV use in acute asthma and contribute a critical appraisal of the available literature relating to this practice. A discussion of some of the more pertinent, clinically relevant practicalities is also provided. Original research articles were identified using the electronic PubMed database. Randomized controlled trials of NIV in the setting of acute asthma were selected. Retrospective observational studies were also included if they were considered to contribute to the literature review. The use of NIV in the acute asthma setting has been shown to be associated with improvements in important physiological variables including measures of airflow and respiratory rate, and lends support to further study in this field. Improvements in airflow may be a direct effect of applied positive airway pressure or an indirect effect secondary to better dispersal of aerosolized medication. Reductions observed in respiratory rate and dyspnea are likely influenced by the amount of pressure support provided. Evidence suggestive of any improvement in mortality, intubation rate, or hospital/intensive care unit length of stay, however, is lacking. Studies to date have been hampered by small numbers and a lack of demonstrable meaningful clinical outcomes. Data relating to mortality, endotracheal intubation rates, and hospital length of stay/admission should be sought in future large clinical trials.

Comparison of a novel non-contact biomotion sensor with wrist actigraphy in estimating sleep quality in patients with obstructive sleep apnoea.

Ambulatory monitoring is of major clinical interest in the diagnosis of obstructive sleep apnoea syndrome. We compared a novel non-contact biomotion sensor, which provides an estimate of both sleep time and sleep-disordered breathing, with wrist actigraphy in the assessment of total sleep time in adult humans suspected of obstructive sleep apnoea syndrome. Both systems were simultaneously evaluated against polysomnography in 103 patients undergoing assessment for obstructive sleep apnoea syndrome in a hospital-based sleep laboratory (84 male, aged 55 ± 14 years and apnoea-hypopnoea index 21 ± 23). The biomotion sensor demonstrated similar accuracy to wrist actigraphy for sleep/wake determination (77.3%: biomotion; 76.5%: actigraphy), and the biomotion sensor demonstrated higher specificity (52%: biomotion; 34%: actigraphy) and lower sensitivity (86%: biomotion; 94%: actigraphy). Notably, total sleep time estimation by the biomotion sensor was superior to actigraphy (average overestimate of 10 versus 57 min), especially at a higher apnoea-hypopnoea index. In post hoc analyses, we assessed the improved apnoea-hypopnoea index accuracy gained by combining respiratory measurements from polysomnography for total recording time (equivalent to respiratory polygraphy) with total sleep time derived from actigraphy or the biomotion sensor. Here, the number of misclassifications of obstructive sleep apnoea severity compared with full polysomnography was reduced from 10/103 (for total respiratory recording time alone) to 7/103 and 4/103 (for actigraphy and biomotion sensor total sleep time estimate, respectively). We conclude that the biomotion sensor provides a viable alternative to actigraphy for sleep estimation in the assessment of obstructive sleep apnoea syndrome. As a non-contact device, it is suited to longitudinal assessment of sleep, which could also be combined with polygraphy in ambulatory studies.

Assessment of sleep-disordered breathing using a non-contact bio-motion sensor.

Obstructive sleep apnoea is a highly prevalent but under-diagnosed disorder. The gold standard for diagnosis of obstructive sleep apnoea is inpatient polysomnography. This is resource intensive and inconvenient for the patient, and the development of ambulatory diagnostic modalities has been identified as a key research priority. SleepMinder (BiancaMed, NovaUCD, Ireland) is a novel, non-contact, bedside sensor, which uses radio-waves to measure respiration and movement. Previous studies have shown it to be effective in measuring sleep and respiration. We sought to assess its utility in the diagnosis of obstructive sleep apnoea. SleepMinder and polysomnographic assessment of sleep-disordered breathing were performed simultaneously on consecutive subjects recruited prospectively from our sleep clinic. We assessed the diagnostic accuracy of SleepMinder in identifying obstructive sleep apnoea, and how SleepMinder assessment of the apnoea-hypopnoea index correlated with polysomnography. Seventy-four subjects were recruited. The apnoea-hypopnoea index as measured by SleepMinder correlated strongly with polysomnographic measurement (r = 0.90; P ≤ 0.0001). When a diagnostic threshold of moderate-severe (apnoea-hypopnoea index ≥15 events h(-1) ) obstructive sleep apnoea was used, SleepMinder displayed a sensitivity of 90%, a specificity of 92% and an accuracy of 91% in the diagnosis of sleep-disordered breathing. The area under the curve for the receiver operator characteristic was 0.97. SleepMinder correctly classified obstructive sleep apnoea severity in the majority of cases, with only one case different from equivalent polysomnography by more than one diagnostic class. We conclude that in an unselected clinical population undergoing investigation for suspected obstructive sleep apnoea, SleepMinder measurement of sleep-disordered breathing correlates significantly with polysomnography.