Publications by authors named "James Fingleton"

58 Publications

Mitral Valve Blood Cyst Diagnosed with the Use of Multimodality Imaging.

CASE (Phila) 2021 Jun 20;5(3):173-176. Epub 2021 Feb 20.

Department of Cardiology and Cardiothoracic Surgery, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island.

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http://dx.doi.org/10.1016/j.case.2021.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236382PMC
June 2021

New Zealand COPD Guidelines: Quick Reference Guide.

N Z Med J 2021 02 19;134(1530):76-110. Epub 2021 Feb 19.

Auckland District Health Board.

The purpose of the Asthma and Respiratory Foundation of New Zealand's COPD Guidelines: Quick Reference Guide is to provide simple, practical, evidence-based recommendations for the diagnosis, assessment, and management of chronic obstructive pulmonary disease (COPD) in clinical practice. The intended users are health professionals responsible for delivering acute and chronic COPD care in community and hospital settings, and those responsible for the training of such health professionals.
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February 2021

ICS-formoterol reliever ICS and short-acting β-agonist reliever in asthma: a systematic review and meta-analysis.

ERJ Open Res 2021 Jan 25;7(1). Epub 2021 Jan 25.

Medical Research Institute of New Zealand, Wellington, New Zealand.

Background: The Global Initiative for Asthma recommends as-needed inhaled corticosteroid (ICS)-formoterol as an alternative to maintenance ICS plus short-acting β-agonist (SABA) reliever at step 2 of its stepwise treatment algorithm. Our aim was to assess the efficacy and safety of these two treatment regimens, with a focus on prevention of severe exacerbation.

Methods: We performed a systematic review and meta-analysis of all randomised controlled trials (RCTs) comparing as-needed ICS-formoterol with maintenance ICS plus SABA. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrials.gov were searched from database inception to 12 December 2019. The primary outcome was time to first severe exacerbation. RCTs were excluded if they used as-needed budesonide-formoterol as part of a maintenance and reliever regimen, or did not report on severe exacerbations. The review is registered with PROSPERO (identifier number CRD42020154680).

Results: Four RCTs (n=8065 participants) were included in the analysis. As-needed ICS-formoterol was associated with a prolonged time to first severe exacerbation (hazard ratio 0.85, 95% CI 0.73-1.00; p=0.048) and reduced daily ICS dose (mean difference -177.3 μg, 95% CI -182.2--172.4 μg). Asthma symptom control was worse in the as-needed group (Asthma Control Questionnaire-5 mean difference 0.12, 95% CI 0.09-0.14), although this did not meet the minimal clinically important difference of 0.50 units. There was no significant difference in serious adverse events (OR 1.07, 95% CI 0.84-1.36).

Conclusion: As-needed ICS-formoterol offers a therapeutic alternative to maintenance low-dose ICS plus SABA in asthma and may be the preferred option when prevention of severe exacerbation is the primary aim of treatment.
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http://dx.doi.org/10.1183/23120541.00701-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836558PMC
January 2021

Engaging Māori with qualitative healthcare research using an animated comic.

Health Promot Int 2020 Dec 10. Epub 2020 Dec 10.

Medical Research Institute of New Zealand, Wellington 6021, New Zealand.

This article reports an effective strategy for recruiting patients with asthma to a qualitative study using an animated comic advertised on social media. An ad spend of NZ$432 on Facebook resulted in 101 study enquiries, and 27 participants taking part in the focus groups, of which 16 (56%) were Māori, the Indigenous Peoples of New Zealand. Representation of Māori amongst participants was over five times higher than their proportion in the local population (9.7%), resulting in data fulfilling the principle of equal explanatory power, an approach to research which can help advance Māori health development and address inequity. The success of this campaign is of particular interest for health researchers in New Zealand where Māori continue to be disproportionately affected by poorer health outcomes compared with non-Māori, particularly those with asthma. Approaches that better engage and support participation of under-represented communities in clinical research are of wider global interest. We reflect on the recruitment strategy and outcomes within a Kaupapa Māori framework, explore how this can be applied more widely in healthcare, and suggest direction for future study and implementation. Lay summary We designed an animated comic to advertise a study for patients with asthma. This was shared locally with a Facebook ad. The approach was highly engaging with the public, and resulted in rapid recruitment. Interestingly, participation of Māori (the Indigenous People of New Zealand) was over five times higher than their proportion in the local population. Māori have poorer health outcomes and increased barriers to healthcare access compared with non-Māori, particularly those with asthma. Approaches which can engage and support under-represented communities to participate in clinical research are of wider global interest. In this article, we reflect on the recruitment strategy and outcomes, and suggest direction for future study and implementation.
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http://dx.doi.org/10.1093/heapro/daaa111DOI Listing
December 2020

Combination budesonide/formoterol inhaler as sole reliever therapy in Māori and Pacific people with mild and moderate asthma.

N Z Med J 2020 08 21;133(1520):61-72. Epub 2020 Aug 21.

Associate Professor, University of Auckland, Auckland.

Aim: In the PRACTICAL study, as-needed budesonide/formoterol reduced the rate of severe exacerbations compared with maintenance budesonide plus as-needed terbutaline. In a pre-specified analysis we analysed the efficacy in Māori and Pacific peoples, populations with worse asthma outcomes.

Method: The PRACTICAL study was a 52-week, open-label, parallel group, randomised controlled trial of 890 adults with mild to moderate asthma, who were randomised to budesonide/formoterol Turbuhaler 200/6mcg one actuation as required or budesonide Turbuhaler 200mcg one actuation twice daily and terbutaline Turbuhaler 250mcg two actuations as required. The primary outcome was rate of severe exacerbations. The analysis strategy was to test an ethnicity-treatment interaction term for each outcome variable.

Results: Seventy-two participants (8%) identified as Māori, 36 participants (4%) as Pacific ethnicity. There was no evidence that ethnicity was an effect modifier for severe exacerbations (P interaction 0.70).

Conclusion: The reduction in severe exacerbation risk with budesonide-formoterol reliever compared with maintenance budesonide was similar in Māori and Pacific adults compared with New Zealand European/Other.
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August 2020

Patient preferences for asthma management: a qualitative study.

BMJ Open 2020 08 16;10(8):e037491. Epub 2020 Aug 16.

Department of Medicine, University of Otago, Wellington, New Zealand.

Objective: Preference for asthma management and the use of medications is motivated by the interplay between lived experiences of asthma and patients' attitudes towards medications. Many previous studies have focused on individual aspects of asthma management, such as the use of preventer and reliever inhalers. The aim of this qualitative study was to explore the preferences of patients with mild-moderate asthma for asthma management as a whole and factors that influenced these preferences.

Design: A qualitative study employing qualitative descriptive analysis situated within a constructionist epistemology to analyse transcribed audio recordings from focus groups.

Setting: Three locations within the greater Wellington area in New Zealand.

Participants: Twenty-seven adults with self-reported doctor's diagnosis of asthma, taking short-acting beta-agonists alone or inhaled corticosteroids with or without long-acting beta-agonist, who had used any inhaled asthma medication within the last month.

Results: Four key areas described preferences for asthma management. Preferences for self-management: participants wanted to be in control of their asthma and developed personal strategies to achieve this. Preferences for the specific medications or treatment regimen: participants preferred regimens that were convenient and reliably relieved symptoms. Preferences for inhaler devices: devices that had dose counters and were easy to use and portable were important. Preferences for asthma services: participants wanted easier access to their inhalers and to be empowered by their healthcare providers. Participant preferences within each of these four areas were influenced by the impact asthma had on their life, their health beliefs, emotional consequences of asthma and perceived barriers to asthma management.

Conclusions: This study illustrates the interaction of the lived experience of asthma, factors specific to the individual, and factors relating to asthma treatments in shaping patient preferences for asthma management. This aids our understanding of preferences for asthma management from the patient perspective.

Trial Registration Number: Australian New Zealand Clinical Trials Registry (ACTRN12619000601134).
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http://dx.doi.org/10.1136/bmjopen-2020-037491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430405PMC
August 2020

What matters most to patients when choosing treatment for mild-moderate asthma? Results from a discrete choice experiment.

Thorax 2020 10 27;75(10):842-848. Epub 2020 Jul 27.

Asthma Programme, Medical Research Institute of New Zealand, Wellington, New Zealand.

Background: An as-needed combination preventer and reliever regimen was recently introduced as an alternative to conventional daily preventer treatment for mild asthma. In a subgroup analysis of the PRACTICAL study, a pragmatic randomised controlled trial of budesonide-formoterol reliever therapy versus maintenance budesonide plus terbutaline reliever therapy in adults with mild asthma, we recently reported that about two-thirds preferred as-needed combination preventer and reliever therapy. The aim of this study was to determine the relative importance of attributes associated with these two asthma therapies in this subgroup of participants who indicated their preferred treatment in the PRACTICAL study.

Methods: At their final study visit, a subgroup of participants indicated their preferred treatment and completed a discrete choice experiment using the Potentially All Pairwise RanKings of all possible Alternatives method and 1000minds software. Treatment attributes and their levels were selected from measurable study outcomes, and included: treatment regimen, shortness of breath, steroid dose and likelihood of asthma flare-up.

Results: The final analysis dataset included 288 participants, 64% of whom preferred as-needed combination preventer and reliever. Of the attributes, no shortness of breath and lowest risk of asthma flare-up were ranked highest and second highest, respectively. However, the relative importance of the other two attributes varied by preferred therapy: treatment regimen was ranked higher by participants who preferred as-needed treatment than by participants who preferred maintenance treatment.

Conclusions: Knowledge of patient preferences for treatment attributes together with regimen characteristics can be used in shared decision-making regarding choice of treatment for patients with mild-moderate asthma.

Trial Registration Number: ACTRN12616000377437.
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http://dx.doi.org/10.1136/thoraxjnl-2019-214343DOI Listing
October 2020

Asthma and Respiratory Foundation NZ Adolescent and Adult Asthma Guidelines 2020: a quick reference guide.

N Z Med J 2020 06 26;133(1517):73-99. Epub 2020 Jun 26.

University of Otago, Dunedin.

The purpose of the 2020 Asthma and Respiratory Foundation NZ Adolescent and Adult Asthma Guidelines is to provide simple, practical and evidence-based recommendations for the diagnosis, assessment and management of asthma in adolescents and adults (aged 12 and over) in a quick reference format. The intended users are health professionals responsible for delivering asthma care in the community and hospital settings, and those responsible for the training of such health professionals. The main changes in the 2020 update are: 1) combining the recommendations for both adolescents and adults in a single document, 2) the recommendation to avoid SABA-only treatment in the long-term management of asthma, 3) the use of budesonide/formoterol reliever, with or without maintenance budesonide/formoterol, is preferred to SABA reliever, with or without maintenance ICS or ICS/LABA, across the spectrum of asthma severity, 4) introduction of the terminology 'anti-inflammatory reliever (AIR)' therapy to describe the use of budesonide/formoterol as a reliever medication, with or without maintenance budesonide/ formoterol therapy. This approach encompasses and extends the 'Single combination ICS/LABA inhaler Maintenance And Reliever Therapy' (SMART) approach recommended in the previous guideline, 5) the inclusion of two stepwise management algorithms, 6) a clinical allergy section, 7) the role of LAMA therapy in severe asthma, 8) the role of omalizumab in severe allergic asthma and mepolizumab in severe eosinophilic asthma, 9) an appendix detailing educational materials.
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June 2020

Self-titration of inhaled corticosteroid and β-agonist in response to symptoms in mild asthma: a pre-specified analysis from the PRACTICAL randomised controlled trial.

Eur Respir J 2020 10 8;56(4). Epub 2020 Oct 8.

Medical Research Institute of New Zealand, Wellington, New Zealand.

Introduction: In mild asthma, as-needed budesonide-formoterol is superior or noninferior to maintenance budesonide plus as-needed short-acting β-agonist in reducing severe exacerbations. In this pre-specified analysis, we investigated patterns of inhaled corticosteroid (ICS) and β-agonist use in PRACTICAL, a randomised controlled trial.

Methods: Participants were randomised 1:1 to as-needed budesonide-formoterol (200/6 μg Turbuhaler, one actuation) or maintenance budesonide (200 μg Turbuhaler, one actuation twice a day) with as-needed terbutaline (250 μg, two actuations) for 52 weeks. 110 participants had electronic monitors attached to their study inhalers which captured the time and date of every actuation. Key outcome measures were patterns of ICS and β-agonist use. One actuation of budesonide-formoterol was considered to be an equivalent bronchodilator dose as two actuations of terbutaline.

Results: Participants randomised to as-needed budesonide-formoterol had more days with no ICS use compared with maintenance budesonide (median total days of no use 156 22 days, respectively), lower median daily budesonide dose (164 328 μg, respectively) and a greater median number of days of ≥4 budesonide actuations (4 1 days, respectively). Participants randomised to as-needed budesonide-formoterol took higher equivalent doses of β-agonist both overall (median number of actuations 0.8 0.3 per day, respectively) and in response to worsening asthma (total number of "overuse days" of >8 or >16 actuations of budesonide-formoterol or terbutaline 33 10 days, respectively).

Conclusions: The timing of ICS dose when self-titrated to β-agonist use is more important than total ICS dose in reducing severe exacerbation risk in mild asthma, when associated with greater overall use of as-needed β-agonist.
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http://dx.doi.org/10.1183/13993003.00170-2020DOI Listing
October 2020

Severe asthma assessment, management and the organisation of care in Australia and New Zealand: expert forum roundtable meetings.

Intern Med J 2021 Feb;51(2):169-180

National Health and Medical Research Council Centre of Excellence in Severe Asthma, Newcastle, Australia.

Severe asthma imposes a significant burden on individuals, families and the healthcare system. Treatment is complex, due to disease heterogeneity, comorbidities and complexity in care pathways. New approaches and treatments improve health outcomes for people with severe asthma. However, emerging multidimensional and targeted treatment strategies require a reorganisation of asthma care. Consensus is required on how reorganisation should occur and what areas require further research. The Centre of Excellence in Severe Asthma convened three forums between 2015 and 2018, hosting experts from Australia, New Zealand and the UK. The forums were complemented by a survey of clinicians involved in the management of people with severe asthma. We sought to: (i) identify areas of consensus among experts; (ii) define activities and resources required for the implementation of findings into practice; and (iii) identify specific priority areas for future research. Discussions identified areas of unmet need including assessment and diagnosis of severe asthma, models of care and treatment pathways, add-on treatment approaches and patient perspectives. We recommend development of education and training activities, clinical resources and standards of care documents, increased stakeholder engagement and public awareness campaigns and improved access to infrastructure and funding. Further, we propose specific future research to inform clinical decision-making and develop novel therapies. A concerted effort is required from all stakeholders (including patients, healthcare professionals and organisations and government) to integrate new evidence-based practices into clinical care and to advance research to resolve questions relevant to improving outcomes for people with severe asthma.
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http://dx.doi.org/10.1111/imj.14806DOI Listing
February 2021

Patient preferences for symptom-driven or regular preventer treatment in mild to moderate asthma: findings from the PRACTICAL study, a randomised clinical trial.

Eur Respir J 2020 04 16;55(4). Epub 2020 Apr 16.

Medical Research Institute of New Zealand, Wellington, New Zealand.

Symptom-driven low-dose inhaled corticosteroid-formoterol is safe and effective in mild asthma and has been recommended as one of the preferred treatment regimens at steps 1 and 2 in the 2019 update of the Global Initiative for Asthma. However, there are no data on patient preferences for this regimen.A subgroup of participants in the PRACTICAL study (ACTRN12616000377437), a randomised controlled trial comparing symptom-driven budesonide-formoterol with maintenance budesonide plus as-needed terbutaline completed a survey on treatment preferences, satisfaction, beliefs and experience at their final study visit.306 (75%) out of 407 eligible participants completed the survey. Regimen preference was strongly associated with randomised treatment, as were preferences for and beliefs about preventer inhaler use. Combination preventer and reliever as-needed therapy was preferred by 135 (90%, 95% CI 85.2-94.8%) out of 150 who were randomised to as-needed budesonide-formoterol, and by 63 (40%, 95% CI 32.7-48.1%) out of 156 who were randomised to maintenance budesonide. By contrast, twice-daily preventer inhaler with a reliever inhaler as required was preferred by 15 (10%) out of 150 of those randomised to as-needed budesonide-formoterol and 93 (60%) out of 156 of those randomised to maintenance budesonide. Satisfaction with all study inhalers was high. Of patients randomised to as-needed budesonide-formoterol 92% (n=138) were confident using it as a reliever at the end of the study.Although most participants preferred the regimen to which they had been randomised, this association was much stronger for those randomised to budesonide-formoterol as needed, indicating that most patients preferred as-needed corticosteroid-formoterol therapy if they had experienced it.
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http://dx.doi.org/10.1183/13993003.02073-2019DOI Listing
April 2020

Pre-apneic capnography waveform abnormalities during procedural sedation and analgesia.

J Clin Monit Comput 2020 10 30;34(5):1061-1068. Epub 2019 Sep 30.

Toronto General Hospital, University Health Network, Toronto, Canada.

Capnography monitoring is recommended for use during procedural sedation. This study examined associations between capnography waveform abnormalities and the onset of apnea. Capnography waveforms from a sample of 102 participants undergoing moderate procedural sedation with bolus doses of midazolam and fentanyl were analyzed using a mixed effects Cox model. Patients were at increased risk of apnea (classified as end-tidal carbon dioxide concentration of zero) while demonstrating a capnography waveform abnormality classified as hypopnea (more than 10% increase or decrease from baseline end-tidal carbon dioxide concentration) (Hazard Ratio 2.14; 95% CI 1.75 to 2.62). Risk of apnea was not increased during capnography waveform abnormalities classified as bradypnea (capnography-derived respiratory rate less than 8 breaths/min) (Hazard Ratio 0.64; 95% CI 0.33 to 1.25). These estimates were similar when apneic episodes were defined as only those that lasted more than 20 s duration. Deciphering which capnography waveform abnormalities should promote intervention (and therefore alarms to signal the event to clinicians) from those that do not is an essential step towards successful implementation of this technology into practice. Our results indicate that using information about the history of previous capnography waveform abnormalities may be a promising solution to assist prediction of apneic episodes.
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http://dx.doi.org/10.1007/s10877-019-00391-zDOI Listing
October 2020

Skeletal muscle microvasculature response to β-adrenergic stimuli is diminished with cardiac surgery.

Surgery 2020 02 4;167(2):493-498. Epub 2019 Sep 4.

Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI. Electronic address:

Background: Cardiac surgery and cardiopulmonary bypass are associated with alterations in blood pressure in the perioperative period, which, if uncontrolled, can result in end organ damage or dysfunction. Microvessels, significant contributors to blood pressure, both in the myocardium and peripheral skeletal muscle, have diminished responsiveness to major mediators of vascular tone, including thromboxane and serotonin after cardiopulmonary bypass. Responsiveness of these vessels to β-adrenergic stimulation, a major mediator of vascular tone, has not yet been studied. In this report, we investigated the role of β-adrenergic receptors in vascular tone regulation in human skeletal muscle microvessels before and after β-adrenergic stimulation.

Methods: Skeletal muscle microvessels were isolated from patients undergoing cardiac surgery before and after cardiopulmonary bypass. Vessels were exposed in an ex vivo model to the β-adrenergic agonist isoproterenol, or the direct adenylyl cyclase activator, forskolin, and the selective β-receptor antagonist ICI18.551 hydrochloride plus isoproterenol. Immunofluorescence of β receptors and Western blotting were also performed.

Results: Microvessels showed diminished responsiveness to isoproterenol (10 to 10M) after cardiopulmonary bypass (n = 8/group, P = .01). Pretreatment with the selective β-2 blocker ICI18.551 (10M) prevented isoproterenol-induced microvascular relaxation (P = .001). Forskolin-induced relaxation response was also significantly diminished after cardiopulmonary bypass (n = 4/group, P < .05 versus before cardiopulmonary bypass). No significant changes in the total protein expression of β-1, β-2, and β-3 receptors were detected by western blotting or immunofluorescence.

Conclusion: Microvessels isolated from human skeletal muscle show diminished responsiveness to isoproterenol and its downstream activator forskolin after cardiopulmonary bypass, suggesting there is an alteration in β-adrenergic receptor responsive in adenylate cyclase. The relaxation response to isoproterenol was via activation β-2 receptors without changes in β-adrenergic receptor abundance.
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http://dx.doi.org/10.1016/j.surg.2019.07.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002023PMC
February 2020

Budesonide-formoterol reliever therapy versus maintenance budesonide plus terbutaline reliever therapy in adults with mild to moderate asthma (PRACTICAL): a 52-week, open-label, multicentre, superiority, randomised controlled trial.

Lancet 2019 09 23;394(10202):919-928. Epub 2019 Aug 23.

Medical Research Institute of New Zealand, Newtown, Wellington, New Zealand; Capital and Coast District Health Board, Wellington, New Zealand. Electronic address:

Background: In adults with mild asthma, a combination of an inhaled corticosteroid with a fast-onset long-acting β-agonist (LABA) used as reliever monotherapy reduces severe exacerbations compared with short-acting β-agonist (SABA) reliever therapy. We investigated the efficacy of combination budesonide-formoterol reliever therapy compared with maintenance budesonide plus as-needed terbutaline.

Methods: We did a 52-week, open-label, parallel-group, multicentre, superiority, randomised controlled trial at 15 primary care or hospital-based clinical trials units and primary care practices in New Zealand. Participants were adults aged 18-75 years with a self-reported doctor's diagnosis of asthma who were using SABA for symptom relief with or without maintenance low to moderate doses of inhaled corticosteroids in the previous 12 weeks. We randomly assigned participants (1:1) to either reliever therapy with budesonide 200 μg-formoterol 6 μg Turbuhaler (one inhalation as needed for relief of symptoms) or maintenance budesonide 200 μg Turbuhaler (one inhalation twice daily) plus terbutaline 250 μg Turbuhaler (two inhalations as needed). Participants and investigators were not masked to group assignment; the statistician was masked for analysis of the primary outcome. Six study visits were scheduled: randomisation, and weeks 4, 16, 28, 40, and 52. The primary outcome was the number of severe exacerbations per patient per year analysed by intention to treat (severe exacerbations defined as use of systemic corticosteroids for at least 3 days because of asthma, or admission to hospital or an emergency department visit because of asthma requiring systemic corticosteroids). Safety analyses included all participants who had received at least one dose of study treatment. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12616000377437.

Findings: Between May 4, 2016, and Dec 22, 2017, we assigned 890 participants to treatment and included 885 eligible participants in the analysis: 437 assigned to budesonide-formoterol as needed and 448 to budesonide maintenance plus terbutaline as needed. Severe exacerbations per patient per year were lower with as-needed budesonide-formoterol than with maintenance budesonide plus terbutaline as needed (absolute rate per patient per year 0·119 vs 0·172; relative rate 0·69, 95% CI 0·48-1·00; p=0·049). Nasopharyngitis was the most common adverse event in both groups, occurring in 154 (35%) of 440 patients receiving as-needed budesonide-formoterol and 144 (32%) of 448 receiving maintenance budesonide plus terbutaline as needed.

Interpretation: In adults with mild to moderate asthma, budesonide-formoterol used as needed for symptom relief was more effective at preventing severe exacerbations than maintenance low-dose budesonide plus as-needed terbutaline. The findings support the 2019 Global Initiative for Asthma recommendation that inhaled corticosteroid-formoterol reliever therapy is an alternative regimen to daily low-dose inhaled corticosteroid for patients with mild asthma.

Funding: Health Research Council of New Zealand.
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http://dx.doi.org/10.1016/S0140-6736(19)31948-8DOI Listing
September 2019

Sequence analysis of capnography waveform abnormalities during nurse-administered procedural sedation and analgesia in the cardiac catheterization laboratory.

Sci Rep 2019 07 15;9(1):10214. Epub 2019 Jul 15.

Medical Research Institute of New Zealand, Wellington, New Zealand.

Identifying common patterns in capnography waveform abnormalities and the factors that influence these patterns could yield insights to optimize responses to sedation-induced respiratory depression. Respiratory state sequences for 102 patients who had a procedure in a cardiac catheterisation laboratory with procedural sedation and analgesia were developed by classifying each second of procedures into a state of normal breathing or other capnography waveform abnormalities based on pre-specified cut-offs for respiratory rate and end-tidal CO concentration. Hierarchical clustering identified four common patterns in respiratory state sequences, which were characterized by a predominance of the state assigned normal breathing (n = 42; 41%), hypopneic hypoventilation (n = 38; 38%), apnea (n = 15; 15%) and bradypneic hypoventilation (n = 7; 7%). A multivariable distance matrix regression model including demographic and clinical variables explained 28% of the variation in inter-individual differences in respiratory state sequences. Obstructive sleep apnea (R = 2.4%; p = 0.02), smoking status (R = 2.8%; p = 0.01), Charlson comorbidity index score (R = 2.5%; p = 0.021), peak transcutaneous carbon dioxide concentration (R = 4.1%; p = 0.002) and receiving an intervention to support respiration (R = 5.6%; p = 0.001) were significant covariates but each explained only small amounts of the variation in respiratory state sequences. Oxygen desaturation (SpO < 90%) was rare (n = 3; 3%) and not associated with respiratory state sequence trajectories.
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http://dx.doi.org/10.1038/s41598-019-46751-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629622PMC
July 2019

Protocol for a randomised, single-blind, two-arm, parallel-group controlled trial of the efficacy of rhinothermy delivered by nasal high flow therapy in the treatment of the common cold.

BMJ Open 2019 06 19;9(6):e028098. Epub 2019 Jun 19.

Medical Research Institute of New Zealand, Wellington, New Zealand.

Introduction: The common cold is the most common infectious disease affecting humans. It is usually a self-limiting disease; however, the common cold can cause significant morbidity and has a substantial economic impact on society. Human rhinoviruses (HRVs), which cause up to two-thirds of colds, have temperature-dependent replication and most HRV strains replicate optimally at 33°C. Delivery of heated, humidified air to the upper airways has the potential to reduce viral replication, but evidence of the effectiveness of this treatment of the common cold is inconclusive. We plan to test the hypothesis that delivery of humidified air heated to 41°C at high flow, nasal high flow rhinothermy (rNHF), for 2 hours daily for five days is more effective in reducing common cold symptom severity and duration than five days of 'sham' rhinothermy.

Methods And Analysis: This is a randomised, single-blind, parallel-group trial comparing rNHF to 'sham' rhinothermy in the treatment of common cold. We plan to recruit 170 participants within 48 hours of the onset of symptoms of common cold and randomise them 1:1 to receive one of the two treatments for five days. The study duration is 14 days, which includes clinic visits on the first day of randomisation and four days post-randomisation, and a phone call on the 14th day. Participants will complete daily symptom diaries which include a symptom score, the Modified Jackson Score (MJS). The primary outcome is the MJS after four days.

Ethics And Dissemination: New Zealand Ethics Registration: 17/STH/174. Results will be published in a peer-reviewed medical journal, presented at academic meetings, and reported to participants.

Trial Registration Number: U1111-1194-4345 and ACTRN12617001340325; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2018-028098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589000PMC
June 2019

Nasal high-flow therapy compared with non-invasive ventilation in COPD patients with chronic respiratory failure: A randomized controlled cross-over trial.

Respirology 2019 11 13;24(11):1081-1087. Epub 2019 May 13.

Medical Research Institute of New Zealand, Wellington, New Zealand.

Background And Objective: Non-invasive ventilation (NIV) is part of the standard of care for hypercapnic respiratory failure secondary to COPD, but may be poorly tolerated. Preliminary evidence suggests nasal high-flow (NHF) therapy may improve hypercapnia in COPD and be well tolerated. We compared NHF and NIV in people with COPD and chronic hypercapnic respiratory failure.

Methods: Single-blind randomized controlled two-way cross-over single-centre trial was conducted in New Zealand. Twenty-four participants with stable hypercapnic COPD received: NHF at 45 L/min and NIV at 15/4 cm H O, each for 60 min with a 15-min washout in between. The primary outcome was transcutaneous partial pressure of carbon dioxide (PtCO ) at 60 min, adjusted for baseline.

Results: NIV reduced the PtCO more than NHF (mean (SD) at 60 min by -5.3 (5.0) vs -2.5 (3.5) mm Hg; difference: -2.8 (-5.0 to -0.5) P = 0.021). Difference across all time points was -2.5 mm Hg (95% CI -4.5 to -0.5, P = 0.016). There was no significant difference in the proportion of participants with a reduction of PtCO  ≥ 4 or ≥ 8 mm Hg. Participants rated NHF significantly better for ease of application, comfort and fit.

Conclusion: In stable COPD patients with chronic hypercapnia, NIV resulted in a greater reduction in PtCO compared with NHF, which was of uncertain clinical significance. NHF was better tolerated than NIV and may be a therapeutic option for some people with hypercapnic respiratory failure.

Clinical Trial Registration: ACTRN12616001701415 at www.anzctr.org.au.
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http://dx.doi.org/10.1111/resp.13575DOI Listing
November 2019

Severe Asthma Global Evaluation (SAGE): An Electronic Platform for Severe Asthma.

J Allergy Clin Immunol Pract 2019 May - Jun;7(5):1440-1449. Epub 2019 Apr 4.

Allergy, Asthma & Clinical Immunology, The Alfred Hospital, Melbourne, Australia; Public Health & Preventive Medicine, Monash University, Melbourne, Australia.

Severe asthma is complex and heterogeneous; ad hoc outpatient assessment can be suboptimal. Systematic evaluation improves outcomes and is recommended by international guidelines. Electronic templates improve physician performance and clinical processes, and may be useful in severe asthma systematic evaluation. We developed the Severe Asthma Global Evaluation (SAGE) electronic platform to streamline this process, via Research Electronic Data Capture (REDCap). It incorporates: a questionnaire battery for patient completion before clinical consultation; asthma and comorbidity modules; a clinical summary page in an asthma management module; a nurse educator module; a structured panel discussion record; and an automatically generated report incorporating all key data. SAGE incorporates 282 clinician input fields, with a typical consultation requiring completion of 169. To streamline the process SAGE contains 34 autocalculations and 20 decision support tools. It incorporates all 95 core variables of the International Severe Asthma Registry, with which it is directly compatible. SAGE improves symptom control and exacerbations in patients with difficult asthma. In conclusion, we developed and validated an electronic platform that facilitates a comprehensive but streamlined systematic evaluation of severe asthma that is available for free download via REDCap. Its use enhances management of patients with severe asthma and facilitates audit and international research collaboration.
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http://dx.doi.org/10.1016/j.jaip.2019.02.042DOI Listing
August 2020

Treatable traits: a new paradigm for 21st century management of chronic airway diseases: Treatable Traits Down Under International Workshop report.

Eur Respir J 2019 05 9;53(5). Epub 2019 May 9.

Priority Research Centre for Healthy Lungs and Centre of Excellence in Severe Asthma, Faculty of Health and Medicine, University of Newcastle, Newcastle, Australia.

"Treatable traits" have been proposed as a new paradigm for the management of airway diseases, particularly complex disease, which aims to apply personalised medicine to each individual to improve outcomes. Moving new treatment approaches from concepts to practice is challenging, but necessary. In an effort to accelerate progress in research and practice relating to the treatable traits approach, the Treatable Traits Down Under International Workshop was convened in Melbourne, Australia in May 2018. Here, we report the key concepts and research questions that emerged in discussions during the meeting. We propose a programme of research that involves gaining international consensus on candidate traits, recognising the prevalence of traits, and identifying a potential hierarchy of traits based on their clinical impact and responsiveness to treatment. We also reflect on research methods and designs that can generate new knowledge related to efficacy of the treatable traits approach and consider multidisciplinary models of care that may aid its implementation into practice.
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http://dx.doi.org/10.1183/13993003.02058-2018DOI Listing
May 2019

Serum periostin levels in adults of Chinese descent: an observational study.

Allergy Asthma Clin Immunol 2018 18;14:87. Epub 2018 Dec 18.

1Medical Research Institute of New Zealand, Private Bag 7902, Newtown, Wellington, 6242 New Zealand.

Background: Periostin has been shown to be a marker of Type 2 airway inflammation, associated with airway eosinophilia. It has a potential role in identifying asthmatics who may be responsive to treatment with monoclonal antibody therapy directed against Type 2 cytokines, such as interleukin (IL)-13, IL-4 receptor subunit-α and immunoglobulin E. The clinical utility of periostin measurements depends on better understanding of factors that may affect serum periostin levels, such as race. We aimed to identify the ranges of serum periostin in Chinese adults both with and without asthma, and compare them with those previously identified in Caucasian adults.

Methods: A two-centred cross-sectional study, recruiting 188 Chinese adults, aged 18 to 75 years. 120 participants had no history of asthma or chronic obstructive pulmonary disease. 68 participants had a doctor's diagnosis of asthma and were on current treatment. Univariate comparisons of periostin by dichotomous variables were made using t-tests with logarithmic transformation as the distribution of periostin was skewed.

Results: In the Chinese non-asthma group, periostin levels were sex-, but not age-dependent, with females having higher periostin levels. The individual predicted (90% CI) reference range for periostin in females was 61.1 ng/ml (41.6 to 89.8) ng/ml and in males was 53.2 ng/ml (36.1 to 78.3) ng/ml. There was no difference in median serum periostin levels between Chinese non-asthmatics and Chinese asthmatics, 57.0 versus 56.8 ng/ml, difference (95% CI) 0.1 (- 4.2 to 4.2) ng/ml, P = 0.94. The median serum periostin levels were higher in Chinese non-asthmatics than Caucasian non-asthmatics, 57.0 versus 49.7 ng/ml, difference (95% CI) 8.2 (5.8-10.6) ng/ml, P < 0.001.

Conclusions: Serum periostin does not discriminate between asthmatics and non-asthmatics and is therefore not a good biomarker to diagnose asthma. Serum periostin levels were higher in the Chinese compared to the Caucasian non-asthma group, and also sex dependent in the Chinese participants. There was no difference in serum periostin levels between Chinese non-asthma and asthma groups. This suggests that ethnicity should be considered in the interpretation of periostin levels in asthma patients and sex is an additional consideration in Chinese patients. This trial was prospectively registered with Australian New Zealand Clinical Trials Registry (ACTRN12614000122651).
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http://dx.doi.org/10.1186/s13223-018-0312-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299536PMC
December 2018

Oxygen versus air-driven nebulisers for exacerbations of chronic obstructive pulmonary disease: a randomised controlled trial.

BMC Pulm Med 2018 Oct 3;18(1):157. Epub 2018 Oct 3.

Capital and Coast District Health Board, Wellington, New Zealand.

Background: In exacerbations of chronic obstructive pulmonary disease, administration of high concentrations of oxygen may cause hypercapnia and increase mortality compared with oxygen titrated, if required, to achieve an oxygen saturation of 88-92%. Optimally titrated oxygen regimens require two components: titrated supplemental oxygen to achieve the target oxygen saturation and, if required, bronchodilators delivered by air-driven nebulisation. The effect of repeated air vs oxygen-driven bronchodilator nebulisation in acute exacerbations of chronic obstructive pulmonary disease is unknown. We aimed to compare the effects of air versus oxygen-driven bronchodilator nebulisation on arterial carbon dioxide tension in exacerbations of chronic obstructive pulmonary disease.

Methods: A parallel group double-blind randomised controlled trial in 90 hospital in-patients with an acute exacerbation of COPD. Participants were randomised to receive two 2.5 mg salbutamol nebulisers, both driven by air or oxygen at 8 L/min, each delivered over 15 min with a 5 min interval in-between. The primary outcome measure was the transcutaneous partial pressure of carbon dioxide at the end of the second nebulisation (35 min). The primary analysis used a mixed linear model with fixed effects of the baseline PtCO, time, the randomised intervention, and a time by intervention interaction term; to estimate the difference between randomised treatments at 35 min. Analysis was by intention-to-treat.

Results: Oxygen-driven nebulisation was terminated in one participant after 27 min when the PtCO rose by > 10 mmHg, a predefined safety criterion. The mean (standard deviation) change in PtCO at 35 min was 3.4 (1.9) mmHg and 0.1 (1.4) mmHg in the oxygen and air groups respectively, difference (95% confidence interval) 3.3 mmHg (2.7 to 3.9), p < 0.001. The proportion of patients with a PtCO change ≥4 mmHg during the intervention was 18/45 (40%) and 0/44 (0%) for oxygen and air groups respectively.

Conclusions: Oxygen-driven nebulisation leads to an increase in PtCO in exacerbations of COPD. We propose that air-driven bronchodilator nebulisation is preferable to oxygen-driven nebulisation in exacerbations of COPD.

Trial Registration: Australian New Zealand Clinical Trials Registry number ACTRN12615000389505 . Registration confirmed on 28/4/15.
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http://dx.doi.org/10.1186/s12890-018-0720-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171193PMC
October 2018

Accuracy and precision of transcutaneous carbon dioxide monitoring: a systematic review and meta-analysis.

Thorax 2019 02 12;74(2):157-163. Epub 2018 Sep 12.

Medical Research Institute of New Zealand, Wellington, New Zealand.

Background: Transcutaneous carbon dioxide (TcCO) monitoring is a non-invasive alternative to arterial blood sampling. The aim of this review was to determine the accuracy and precision of TcCO measurements.

Methods: Medline and EMBASE (2000-2016) were searched for studies that reported on a measurement of PaCO that coincided with a measurement of TcCO. Study selection and quality assessment (using the revised Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2)) were performed independently. The Grading Quality of Evidence and Strength of Recommendation approach was used to summarise the strength of the body of evidence. Pooled estimates of the mean bias between TcCO and PaCO and limits of agreement with outer 95% CIs (termed population limits of agreement) were calculated.

Results: The mean bias was -0.1 mm Hg and the population limits of agreement were -15 to 15 mm Hg for 7021 paired measurements taken from 2817 participants in 73 studies, which was outside of the clinically acceptable range (7.5 mm Hg). The lowest PaCO reported in the studies was 18 mm Hg and the highest was 103 mm Hg. The major sources of inconsistency were sensor location and temperature. The population limits of agreement were within the clinically acceptable range across 3974 paired measurements from 1786 participants in 44 studies that applied the sensor to the earlobe using the TOSCA and Sentec devices (-6 to 6 mm Hg).

Conclusion: There are substantial differences between TcCO and PaCO depending on the context in which this technology is used. TcCO sensors should preferentially be applied to the earlobe and users should consider setting the temperature of the sensor higher than 42°C when monitoring at other sites.

Systematic Review Registration Number: PROSPERO; CRD42017057450.
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http://dx.doi.org/10.1136/thoraxjnl-2017-211466DOI Listing
February 2019

Impaired coronary contraction to phenylephrine after cardioplegic arrest in diabetic patients.

J Surg Res 2018 10 22;230:80-86. Epub 2018 May 22.

Division of Cardiothoracic Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island. Electronic address:

Background: We have previously found that hyperkalemic cardioplegic arrest in the setting of cardiopulmonary bypass (CP/CPB) is associated with impairment of the coronary arteriolar response to phenylephrine in nondiabetic (ND) patients. We hypothesized that diabetes may alter coronary arteriolar response to alpha-1 adrenergic agonist in the setting of CP/CPB. In this study, we further investigated the effects of diabetes on the altered coronary arteriolar response to phenylephrine in patients undergoing cardiac surgery.

Methods: Coronary arterioles (90-150 μm in diameter) were harvested pre- and post-CP/CPB from the ND and diabetic mellitus (DM) patients (n = 8/group) undergoing cardiac surgery. In-vitro microvascular reactivity was examined in response to phenylephrine. The protein expression/localization of the alpha-1 adrenergic receptors in the atrial myocardium was measured by Western blotting and immunohistochemistry.

Results: Phenylephrine (10 to 10 M) induced a dose-dependent contractile response in both ND and DM vessels pre- and post-CP/CPB. There was no significant difference in the pre-CP/CPB contractile responses to phenylephrine between ND and DM groups. The post-CP/CPB contractile response was significantly diminished in both ND and DM groups compared with the respective pre-CP/CPB response (P < 0.05 versus pre-CP/CPB). This diminished contractile response was more pronounced in vessels from DM patients compared with vessels from ND patients (P < 0.05 versus ND). There were no significant differences in the protein expression of alpha-1A and alpha-1B receptors in the atrial myocardium between the ND and DM groups or tissue harvested pre- or post-CP/CPB.

Conclusions: Diabetes is associated with a decreased contractile response of coronary arterioles to phenylephrine in the setting of CP/CPB versus that observed in ND patients. This alteration may contribute to the vasomotor dysfunction of coronary microcirculation seen early after CP/CPB in patients with diabetes.
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http://dx.doi.org/10.1016/j.jss.2018.04.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310168PMC
October 2018

Serum periostin levels following small bone fractures, long bone fractures and joint replacements: an observational study.

Allergy Asthma Clin Immunol 2018 26;14:30. Epub 2018 Jul 26.

1Medical Research Institute of New Zealand, Private Bag 7902, Newtown, Wellington 6242 New Zealand.

Background: In asthma, serum periostin may potentially be used as a biomarker in the management of patients with Type-2 eosinophilic airway inflammation. However, serum periostin may be influenced by factors other than Type 2 inflammation, potentially confounding its interpretation. We aimed to measure change in periostin following bone injury.

Methods: 102 adults without asthma were recruited into three groups: joint replacement surgery, long bone fracture, short bone fracture. Participants underwent seven measurements of serum periostin over 26 weeks after bone injury, and prior to surgery in the joint replacement group. Differences in periostin were measured using a ratio of geometric mean (RGM), with comparison made with pre-surgery (joint replacement) or 26 week (long and short fracture) reference measurements.

Results: In the joint replacement group, periostin fell within 48 h (RGM 0.80, 95% CI 0.75-0.86), then increased to a maximum at 8 weeks (RGM 1.89, 1.77-2.02) and by 26 weeks remained above the reference measurement (RGM 1.27, 1.19-1.36). In the long bone fracture group, periostin was reduced at 48 h (RGM 0.76, 0.71-0.83) and then progressively increased to a maximum at 8 weeks (RGM 1.15, 1.06-1.23) compared with the reference measurement. In the short bone fracture group, periostin was reduced at 48 h (RGM 0.9, 0.85-0.95) but was not different from after week 1 compared with the reference measurement.

Conclusions: Serum periostin levels are influenced by bone injury. The timing and extent of bone injury needs consideration if periostin is used as a biomarker in the management of eosinophilic asthma. This trial was prospectively registered with the Australia New Zealand Trials Registry on Feb 7 2014, (ACTRN12614000151639: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363881).
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http://dx.doi.org/10.1186/s13223-018-0254-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6060508PMC
July 2018

Change in biomarkers of type-2 inflammation following severe exacerbations of asthma.

Thorax 2019 01 18;74(1):95-98. Epub 2018 Jul 18.

Medical Research Institute of New Zealand, Wellington, New Zealand.

We investigated the time course of change of type-2 asthma biomarkers after a severe asthma exacerbation. Blood eosinophils were lowest immediately after treatment was initiated (0.07 vs 0.33×10/L, p<0.001) while serum IgE levels were at their highest (339 vs 249 U/L, p<0.001). Fractional exhaled Nitric Oxide levels were lowest 2 weeks after treatment (23 vs 33 ppb, p=0.06) and serum periostin levels were lowest 1 week after treatment (45·9 vs 50·9 ng/mL, p<0.001). A delay of 4-8 weeks following a severe exacerbation is required if these biomarkers are used to guide the ongoing management of patients with asthma. TRIAL REGISTRATION NUMBER: Post-results; The Australia New Zealand Trial Registry, >ACTRN12614000443695.
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http://dx.doi.org/10.1136/thoraxjnl-2018-211657DOI Listing
January 2019

Anti-inflammatory duration of action of fluticasone furoate/vilanterol trifenatate in asthma: a cross-over randomised controlled trial.

Respir Res 2018 07 13;19(1):133. Epub 2018 Jul 13.

Medical Research Institute of New Zealand, Private Bag 7902, Newtown, Wellington, 6242, New Zealand.

Background: Fluticasone furoate/Vilanterol trifenatate (FF/VI) is an inhaled corticosteroid/long-acting beta-agonist combination with a prolonged bronchodilator duration of action. We characterised the time-course of onset and offset of airway anti-inflammatory action of FF/VI, as assessed by fraction of exhaled nitric oxide (FeNO), and compared this to the bronchodilator duration of action.

Methods: A single-centre, randomised, double-blind, placebo-controlled, two-period, crossover study was undertaken in 28 steroid-naïve adults with asthma. Participants with an FEV ≥ 60% predicted, reversible airway disease, and FeNO > 40 ppb received FF/VI 100/25 mcg or placebo once daily for 14 days. FeNO and peak expiratory flow were measured twice-daily during treatment and during a 21-day washout period. FEV was measured for five days from treatment cessation. The primary outcome measure was FeNO change from baseline ratio for 21 days following treatment cessation.

Results: In the 27 subjects who completed the study, median (range) baseline FeNO was 87 ppb (42-212). FF/VI 100/25 mcg reduced FeNO by day 3, ratio FF/VI versus placebo 0.72 (95% confidence interval 0.61-0.86) with the maximum reduction occurring at day 14, 0.32 (0.27-0.37). Following cessation of treatment FeNO remained suppressed for 18 days, ratio on day 18 0.77 (0.59-1.00), whereas improvements in FEV and peak flow were maintained for 3 to 4 days post-treatment.

Conclusions: The anti-inflammatory duration of action of FF/VI is consistent with the high glucocorticoid receptor affinity and long lung retention of fluticasone furoate. The anti-inflammatory effect of FF/VI was of greater duration than its bronchodilator effect in adults with mild asthma. Funding GlaxoSmithKline (201499).

Trial Registration: Prospectively registered on ClinicalTrials.gov registry number NCT02712047 .
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http://dx.doi.org/10.1186/s12931-018-0836-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044077PMC
July 2018

Type 2 Biomarkers and Prediction of Future Exacerbations and Lung Function Decline in Adult Asthma.

J Allergy Clin Immunol Pract 2018 Nov - Dec;6(6):1982-1988.e1. Epub 2018 Mar 30.

Medical Research Institute of New Zealand, Wellington, New Zealand; Capital & Coast District Health Board, Wellington, New Zealand. Electronic address:

Background: Type 2 biomarkers that predict both likelihood of future severe exacerbations and response to mAb therapy in asthma would be useful clinically in identifying patients both at greater risk of hospitalization and most likely to benefit from mAb therapy.

Objective: To describe the association between type 2 biomarkers, blood eosinophils, fractional exhaled nitric oxide (Feno), serum periostin, and serum IgE, and time to severe exacerbation in a broad asthma population.

Methods: Participants from 2 adult asthma cohorts with baseline measurements of blood eosinophils, Feno, serum periostin, and serum IgE were reviewed after at least 12 months to obtain an exacerbation history, corroborated with general practitioner and hospital medical records. The association between baseline type 2 biomarkers and time to exacerbation was described by Cox proportional hazard ratios (HRs) using multivariate models.

Results: A total of 212 participants were followed for a median (range) 3.8 (1.1-5.3) years; 67 of 212 (32%) had at least 1 severe exacerbation. The HRs (95% CI) of baseline type 2 biomarkers and time to exacerbation were as follows: blood eosinophils per 0.1 × 10/L increase, 0.89 (0.76-1.05), P = .17; log Feno per 0.693 increase, 0.65 (0.52-0.81), P < .001; log serum periostin per 0.693 increase, 0.62 (0.35-1.09), P = .10; log serum IgE per 0.693 increase, 0.89 (0.80-1.00), P = .05.

Conclusions: The positive association between type 2 biomarkers and risk of severe exacerbations in populations with severe refractory asthma does not extend to mild and moderate asthma. Non-type 2 asthma may represent a phenotype associated with an increased risk of severe exacerbations in a broad asthma population.
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http://dx.doi.org/10.1016/j.jaip.2018.03.004DOI Listing
November 2019

Randomised controlled trial of rhinothermy for treatment of the common cold: a feasibility study.

BMJ Open 2018 03 27;8(3):e019350. Epub 2018 Mar 27.

Medical Research Institute of New Zealand, Wellington, New Zealand.

Objective: To determine the feasibility of a randomised controlled trial (RCT) of rhinothermy for the common cold.

Design: Open label, randomised, controlled feasibility study.

Setting: Single-centre research institute in New Zealand recruiting participants from the community.

Participants: 30 adult participants with symptoms of a common cold, presenting within 48 hours of the onset of symptoms.

Interventions: Participants were randomly assigned 2:1 to receive either 35 L/min of 100% humidified air at 41°C via high flow nasal cannulae, 2 hours per day for up to 5 days (rhinothermy), or vitamin C 250 mg daily for 5 days (control).

Primary And Secondary Outcome Measures: The primary outcome was the proportion of screened candidates who were randomised. Secondary outcomes included: proportion of randomised participants who completed the study; modified Jackson scores from randomisation to 10 days after initiation of randomised regimen; time until feeling 'a lot better' compared with study entry; time until resolution of symptoms or symptom score at 10 days postrandomisation; proportion of organisms identified by PCR analysis of nasal swabs taken at baseline; the patterns of use of the rhinothermy device; estimated adherence of the control group; and rhinothermy device tolerability.

Results: In all 30/79 (38%, 95% CI 27% to 50%) of potential participants screened for eligibility were randomised. Rhinothermy was well tolerated, and all randomised participants completed the study (100%, 95% CI 88% to 100%). The reduction from baseline in the modified Jackson score was greater with rhinothermy compared with control at days 2, 3, 4, 5 and 6, with the maximum difference at day 4 (-6.4, 95% CI -9.4 to -3.3). The substantial clinical benefit threshold for modified Jackson score was a 5-unit change.

Conclusions: This study shows that an RCT of rhinothermy compared with low-dose vitamin C in the treatment of the common cold is feasible.

Trial Registration Number: ACTRN12616000470493; Results.
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http://dx.doi.org/10.1136/bmjopen-2017-019350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5875674PMC
March 2018
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