Contemporary Concise Review 2023: Asthma.

Asthma research and management needs to meet the priorities of the end user-patients, carers and clinicians. A better understanding of the natural history of asthma and the progression of disease has highlighted the importance of early identification of patients with asthma and the potential role of early intervention. Management of mild asthma requires a consistent approach with the same detail and consideration used when managing severe disease. Evidence around treatable traits approaches continues to evolve, supporting the role of a personalized medicine in asthma. Oral corticosteroid (OCS) stewardship continues to be an urgent issue in asthma management. Strategies to taper OCS doses and the implementation of biologic therapies for their steroid sparing benefits will be important steps to address this problem. The concept of remission in asthma provides an ambitious target and treatment outcome.

Diagnosis of vocal cord dysfunction/inducible laryngeal obstruction: An International Delphi Consensus Study.

BACKGROUND: Vocal cord dysfunction/inducible laryngeal obstruction (VCD/ILO) is characterized by breathing difficulties in association with excessive supraglottic or glottic laryngeal narrowing. The condition is common and can occur independently; however, it may also be comorbid with other disorders or mimic them. Presentations span multiple specialties and misdiagnosis or delayed diagnosis is commonplace. Group-consensus methods can efficiently generate internationally accepted diagnostic criteria and descriptions to increase clinical recognition, enhance clinical service availability, and catalyze research. OBJECTIVES: We sought to establish consensus-based diagnostic criteria and methods for VCD/ILO. METHODS: We performed a modified 2-round Delphi study between December 7, 2021, and March 14, 2022. The study was registered at ANZCTR (Australian New Zealand Clinical Trials Registry; ACTRN12621001520820p). In round 1, experts provided open-ended statements that were categorized, deduplicated, and amended for clarity. These were presented to experts for agreement ranking in round 2, with consensus defined as ≥70% agreement. RESULTS: Both rounds were completed by 47 international experts. In round 1, 1102 qualitative responses were received. Of the 200 statements presented to experts across 2 rounds, 130 (65%) reached consensus. Results were discussed at 2 international subject-specific conferences in June 2022. Experts agreed on a diagnostic definition for VCD/ILO and endorsed the concept of VCD/ILO phenotypes and clinical descriptions. The panel agreed that laryngoscopy with provocation is the gold standard for diagnosis and that ≥50% laryngeal closure on inspiration or Maat grade ≥2 define abnormal laryngeal closure indicative of VCD/ILO. CONCLUSIONS: This Delphi study reached consensus on multiple aspects of VCD/ILO diagnosis and can inform clinical practice and facilitate research.

Vocal cord dysfunction/inducible laryngeal obstruction-2022 Melbourne Roundtable Report.

Vocal cord dysfunction/inducible laryngeal obstruction (VCD/ILO), is a common condition characterized by breathlessness associated with inappropriate laryngeal narrowing. Important questions remain unresolved, and to improve collaboration and harmonization in the field, we convened an international Roundtable conference on VCD/ILO in Melbourne, Australia. The aims were to delineate a consistent approach to VCD/ILO diagnosis, appraise disease pathogenesis, outline current management and model(s) of care and identify key research questions. This report summarizes discussions, frames key questions and details recommendations. Participants discussed clinical, research and conceptual advances in the context of recent evidence. The condition presents in a heterogenous manner, and diagnosis is often delayed. Definitive diagnosis of VCD/ILO conventionally utilizes laryngoscopy demonstrating inspiratory vocal fold narrowing >50%. Computed tomography of the larynx is a new technology with potential for swift diagnosis that requires validation in clinical pathways. Disease pathogenesis and multimorbidity interactions are complex reflecting a multi-factorial, complex condition, with no single overarching disease mechanism. Currently there is no evidence-based standard of care since randomized trials for treatment are non-existent. Recent multidisciplinary models of care need to be clearly articulated and prospectively investigated. Patient impact and healthcare utilization can be formidable but have largely escaped inquiry and patient perspectives have not been explored. Roundtable participants expressed optimism as collective understanding of this complex condition evolves. The Melbourne VCD/ILO Roundtable 2022 identified clear priorities and future directions for this impactful condition.

Elevated blood lactate in COPD exacerbations associates with adverse clinical outcomes and signals excessive treatment with ß2 -agonists.

BACKGROUND AND OBJECTIVE: Raised blood lactate secondary to high dose ß2 -agonist treatment has been reported in asthma exacerbations but has not been investigated during acute exacerbations of COPD (AECOPD). We explored associations of blood lactate measurements with disease outcomes and ß2 -agonist treatments during AECOPD. METHODS: Retrospective (n = 199) and prospective studies (n = 142) of patients hospitalized with AECOPD were conducted. The retrospective cohort was identified via medical records and the prospective cohort was recruited during hospitalization for AECOPD. Baseline demographics, comorbidities, ß2 -agonist treatment, biochemical measurements and clinical outcomes were compared between patients with normal (≤2.0 mmol/L) versus elevated lactate (>2.0 mmol/L). Regression analyses examined associations of lactate measurements with ß2 -agonist dosages. RESULTS: Demographic data and comorbidities were similar between high versus normal lactate groups in both cohorts. The populations were elderly (mean >70 years), predominantly male (>60%) with reduced FEV1 (%) 48.2 ± 19 (prospective cohort). Lactate was elevated in approximately 50% of patients during AECOPD and not related to evidence of sepsis. In the prospective cohort, patients with high lactate had more tachypnoea, tachycardia, acidosis and hyperglycaemia (p < 0.05) and received more non-invasive ventilation (37% vs. 9.7%, p < 0.001, prospective cohort). There was a trend to longer hospitalization (6 vs. 5 days, p = 0.06, prospective cohort). Higher cumulative ß2 -agonist dosages were linked to elevated lactate levels (OR 1.04, p = 0.01). CONCLUSION: Elevated lactate during AECOPD was common, unrelated to sepsis and correlated with high cumulative doses of ß2 -agonists. Raised lactate may indicate excessive ß2 -agonist treatment and should now be investigated as a possible biomarker.

Right ventricular end-diastolic volume and outcomes in exacerbations of COPD.

BACKGROUND AND OBJECTIVE: Right ventricular (RV) volumes are crucial outcome determinants in pulmonary diseases. Little is known about the associations of RV volumes during hospitalized acute exacerbations of chronic obstructive pulmonary disease (AECOPD). We aimed to ascertain associations of RV end-diastolic volume indexed to body surface area (RVEDVI) during hospitalized AECOPD and its relationship with mortality in long-term follow-up. METHODS: This is a prospective observational cohort study (December 2013-November 2019, ACTRN12617001562369) using dynamic retrospective ECG-gated computed tomography during hospitalized AECOPD. RVEDVI was defined as normal or high using Framingham Offspring Cohort values. Cox regression determined the prognostic relevance of RVEDVI for death. RESULTS: A total of 148 participants (70 ± 10 years [mean ± SD], 88 [59%] men) were included, of whom 75 (51%) had high RVEDVI. This was associated with more frequent hospital admissions in the 12 months before admission (52/75 [69%] vs. 38/73 [52%], p = 0.04) and higher breathlessness (modified Medical Research Council score, 2.9 ± 1.3 vs. 2.4 ± 1.2, p = 0.007). During follow-up, high RVEDVI was associated with greater mortality (log-rank p = 0.001). In univariable Cox regression, increasing RVEDVI was associated with higher mortality (hazard ratio [HR]: 1.02 per ml/m2 ; 95% CI: 1.01, 1.03; p = 0.001). In multivariable Cox regression, RVEDVI was independently associated with mortality (HR: 1.01 per ml/m2 ; 95% CI: 1.00, 1.03; p = 0.050) at a borderline significance level. Adding RVEDVI to three COPD mortality prediction systems improved model fit (pooled chi-square test [BODE: p = 0.05, ADO: p = 0.04, DOSE: p = 0.02]). CONCLUSION: In patients with hospitalized AECOPD, higher RV end-diastolic volume was associated with worse acute clinical parameters and greater mortality.

Acute oxygen use in hospitalised patients with chronic obstructive pulmonary disease is guideline discordant.

Ample evidence supports an association between acute oxygen over-administration and harm. Australian and international guidelines consistently recommend lower oxygen saturation aims in populations with chronic obstructive pulmonary disease (COPD). We assessed adherence to acute oxygen use guidelines and outcomes in hospitalised patients with COPD at a large Australian metropolitan hospital network.

Virtual Reality for Pediatric Needle Procedural Pain: Two Randomized Clinical Trials.

OBJECTIVE: To assess the efficacy and safety of a virtual reality distraction for needle pain in 2 common hospital settings: the emergency department (ED) and outpatient pathology (ie, outpatient laboratory). The control was standard of care (SOC) practice. STUDY DESIGN: In 2 clinical trials, we randomized children aged 4-11 years undergoing venous needle procedures to virtual reality or SOC at 2 tertiary Australian hospitals. In the first study, we enrolled children in the ED requiring intravenous cannulation or venipuncture. In the second, we enrolled children in outpatient pathology requiring venipuncture. In the ED, 64 children were assigned to virtual reality and 59 to SOC. In pathology, 63 children were assigned to virtual reality and 68 to SOC; 2 children withdrew assent in the SOC arm, leaving 66. The primary endpoint was change from baseline pain between virtual reality and SOC on child-rated Faces Pain Scale-Revised. RESULTS: In the ED, there was no change in pain from baseline with SOC, whereas virtual reality produced a significant reduction in pain (between-group difference, -1.78; 95% CI, -3.24 to -0.317; P = .018). In pathology, both groups experienced an increase in pain from baseline, but this was significantly less in the virtual reality group (between-group difference, -1.39; 95% CI, -2.68 to -0.11; P = .034). Across both studies, 10 participants experienced minor adverse events, equally distributed between virtual reality/SOC; none required pharmacotherapy. CONCLUSIONS: In children aged 4-11 years of age undergoing intravenous cannulation or venipuncture, virtual reality was efficacious in decreasing pain and was safe. TRIAL REGISTRATION: Australia and New Zealand Clinical Trial Registry: ACTRN12617000285358p.

Coexisting chronic obstructive pulmonary disease and cardiovascular disease in clinical practice: a diagnostic and therapeutic challenge.

Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) frequently coexist but combined disease is often not recognised. Since symptoms overlap significantly, it is common for patients' presentations to be attributed to one disease alone, and for the other to be overlooked. The effect of COPD and CVD goes beyond the shared risk factors of smoking and advancing age. The presence of COPD adversely affects cardiac disease and vice versa. In comparison to individuals with one disease alone, those with both conditions have a higher mortality rate, experience more frequent exacerbations with more hospitalisations and have worse quality of life. More patients with mild and moderate COPD die from CVD than from COPD, and there is a higher rate of arrhythmias, particularly atrial fibrillation. Accurate and timely diagnosis is therefore crucial. Retrospective evidence indicates that individuals with COPD and CVD may have better outcomes with appropriate CVD pharmacotherapy, yet robust prospective evidence is lacking. Inhaled medications for patients with stable COPD improve quality of life and reduce exacerbations, but there is limited evidence that they reduce mortality. A low threshold for investigation and treatment of CVD in COPD and COPD in CVD is essential.

Airwayplasty: long-term outcome of nasal wall lateralisation.

BACKGROUND: There are a variety of surgical techniques which can be used to treat structural nasal obstruction. Airwayplasty is a procedure, combining septoplasty, turbinate surgery, and nasal wall lateralization. The article reports the long-term result of this novel approach. METHODOLOGY: Patients who have evidence of structural nasal obstruction were offered the option to have airwayplasty under the senior surgeon. Patients were asked to quantify the severity and the impact of their nasal obstruction using the Visual Analogue Scale (VAS) and the validated Sino-Nasal Outcome Test (SNOT-22) pre-operatively and post-operatively. RESULTS: The mean total SNOT-22 score and VAS score showed a reduction of more than 50% with significant p value at 6 and 12 months post-operatively. CONCLUSIONS: This novel approach to nasal obstruction can provide good long-term functional results for patients suffering from nasal obstruction.

Endoscopic ultrasound fine-needle aspiration by experienced pulmonologists: a cusum analysis.

Endobronchial ultrasound transbronchial needle aspiration (EBUS TBNA) is an established, minimally invasive way to sample intrathoracic abnormalities. The EBUS scope can be passed into the oesophagus to perform endoscopic ultrasound with bronchoscope-guided fine-needle aspiration (EUS-B-FNA). In cases of suspected lung cancer, a combination of the two techniques is now recommended by consensus guidelines. EBUS TBNA is usually performed by pulmonologists; however, the learning curve for EUS-B-FNA, which may be performed during the same procedure, has not been described.A multicentre, observational Australian study, using prospectively collected data from three experienced pulmonologists was conducted. Cumulative sum (cusum) analysis was used to generate visual learning curves.A total of 152 target lesions were sampled in 137 patients, with an overall sensitivity for malignancy of 94.8%. The sensitivity for malignant lesions outside of the 2009 International Association for the Study of Lung Cancer lymph node map (largely intraparenchymal lesions) was 92.9%. All three operators were competent by conventional cusum criteria. There was one case of pneumothorax, and no episodes of mediastinitis or oesophageal perforation were observed.Our data suggest that experienced pulmonologists can safely and accurately perform EUS-B-FNA, with a high diagnostic sensitivity for both lymph node and non-nodal lesions.

Expiratory central airway collapse in stable COPD and during exacerbations.

BACKGROUND: Tracheal obstruction resulting from expiratory tracheal deformation has been associated with respiratory symptoms and severe airway exacerbations. In chronic obstructive pulmonary disease (COPD), acute exacerbations (AECOPD) create large intrathoracic pressure swings which may increase tracheal deformation. Excessive central airway collapse (ECAC) may be diagnosed when the tracheal area on expiration is less than 50% of that on inspiration. The prevalence of ECAC in AECOPD and its temporal course have not been systematically studied. METHODS: We prospectively recruited healthy volunteers (n = 53), stable outpatients with COPD (n = 40) and patients with hospitalised acute exacerbations of COPD (AECOPD, n = 64). 17 of the AECOPD group returned for repeat evaluation when clinically well at 6-12 weeks. All subjects underwent dynamic 320-slice computed tomography of the larynx and trachea during tidal breathing, enabling quantitation of tracheal area and dimensions (mean ± SD). RESULTS: No healthy individuals had ECAC. The prevalence of ECAC in stable COPD and AECOPD was 35% and 39% respectively. Mean tracheal collapse did not differ between stable COPD (57.5 ± 19.8%), AECOPD (53.8 ± 19.3%) and in the subset who returned when convalescent (54.9 ± 17.2%). AECOPD patients with and without ECAC had similar clinical characteristics. CONCLUSIONS: Tracheal collapse in both stable and AECOPD is considerably more prevalent than in healthy individuals. ECAC warrants assessment as part of comprehensive COPD evaluation and management. Further studies should evaluate the aetiology of ECAC and whether it predisposes to exacerbations.

A double blind randomized placebo control crossover trial on the effect of dietary nitrate supplementation on exercise tolerance in stable moderate chronic obstructive pulmonary disease.

BACKGROUND: Dietary nitrate supplementation has been shown to decrease the oxygen cost of exercise and prolong exercise tolerance, as measured by sub-maximal exercise endurance distance and time at 85% V̇O2max, in both elite athletes and normal healthy subjects. Patients with chronic obstructive pulmonary disease (COPD) have reduced quality of life and ability to perform activities of daily living attributable to diminished exercise tolerance, and dietary nitrate may be able to ameliorate this. METHODS: We performed a double-blind, computer-randomized placebo control crossover trial at a tertiary Australian hospital to investigate whether dietary nitrate supplementation as beetroot juice (BR) would augment submaximal exercise endurance in individuals with spirometrically confirmed stable moderate COPD. Volunteers underwent an incremental shuttle walk test to determine V̇O2max followed by a test dose of BR to establish safety in the study population. Participants performed an endurance shuttle walk test (ESWT) at 85% V̇O2max after randomization to either a 3 day wash-in of BR (4.8 mmol twice a day) or placebo (nitrate deplete BR), with a final dose on the morning of testing. They then crossed over after 4 day washout. Repeated measures two sided paired t-tests were employed. RESULTS: 35 participants were recruited with 19 completing the trial. In the initial safety phase, we measured systolic blood pressure over four hours post first dose of BR, and found a mean 10 mmHg decrement maximal at 1 hour. One individual developed symptomatic postural hypotension and was excluded. The primary outcomes of ESWT distance and time to fatigue improved by 11% and 6% respectively; however these differences did not achieve statistical significance (p = 0.494 and 0.693 respectively). CONCLUSIONS: Our study does not support a role for routine dietary nitrate supplementation for enhancement of exercise endurance in COPD. TRIAL REGISTRATION: Australia and New Zealand Clinical Trial Register: ACTRN12611001088932.