Relationship between Exhaled Aerosol and Carbon Dioxide Emission Across Respiratory Activities.

Respiratory particles produced during vocalized and nonvocalized activities such as breathing, speaking, and singing serve as a major route for respiratory pathogen transmission. This work reports concomitant measurements of exhaled carbon dioxide volume (VCO2) and minute ventilation (VE), along with exhaled respiratory particles during breathing, exercising, speaking, and singing. Exhaled CO2 and VE measured across healthy adult participants follow a similar trend to particle number concentration during the nonvocalized exercise activities (breathing at rest, vigorous exercise, and very vigorous exercise). Exhaled CO2 is strongly correlated with mean particle number (r = 0.81) and mass (r = 0.84) emission rates for the nonvocalized exercise activities. However, exhaled CO2 is poorly correlated with mean particle number (r = 0.34) and mass (r = 0.12) emission rates during activities requiring vocalization. These results demonstrate that in most real-world environments vocalization loudness is the main factor controlling respiratory particle emission and exhaled CO2 is a poor surrogate measure for estimating particle emission during vocalization. Although measurements of indoor CO2 concentrations provide valuable information about room ventilation, such measurements are poor indicators of respiratory particle concentrations and may significantly underestimate respiratory particle concentrations and disease transmission risk.

Radiation Principles, Protection and Reporting for Interventional Pulmonology.

The use and availability of diverse advanced X-ray based imaging and guidance systems in the field of interventional pulmonology is rapidly growing. This popularity links inextricably to an increase in ionizing radiation use. Knowing ionizing radiation is hazardous, knowledge and competent use of X-ray imaging and guidance systems are important. The globally implemented As Low As Reasonably Achievable (ALARA) principle demands careful attention to minimizing radiation exposure while achieving the precise goals of the intervention and imaging therein. To allow careful and targeted weighing of risk against reward while using X-ray based equipment, proper background knowledge of physics as well as imaging system aspects are needed. This white paper summarizes the principles of ionizing radiation which are crucial to enhance awareness and interpretation of dosimetric quantities. Consecutively, a consensus on standards for reporting radiation exposure in interventional pulmonology procedures is indicated to facilitate comparisons between different systems, approaches and results. Last but not least, it provides a list of practical measures, considerations and tips to optimize procedural imaging as well as reduce radiation dose to patients and staff.

Endobronchial Valves in Treatment of Persistent Air Leak: European Case-Series Study and Best Practice Recommendations - From an Expert Panel.

INTRODUCTION: Persistent air leak (PAL) is associated with prolonged hospitalization, high morbidity and increased treatment costs. Conservative treatment consists of observation, chest tube drainage, and pleurodesis. Guidelines recommend surgical evaluation if air leak does not respond after 3-5 days. One-way endobronchial valves (EBV) have been proposed as a treatment option for patients with PAL in which surgical treatment is not feasible, high risk or has failed. We aimed to provide a comprehensive overview of reported EBV use for PAL and issue best practice recommendations based on multicenter experience. METHODS: We conducted a retrospective observational case-series study at four different European academic hospitals and provided best practice recommendations based on our experience. A systematic literature review was performed to summarize the current knowledge on EBV in PAL. RESULTS: We enrolled 66 patients, male (66.7%), median age 59.5 years. The most common underlying lung disease was chronic obstructive pulmonary disease (39.4%) and lung cancer (33.3%). The median time between pneumothorax and valve placement was 24.5 days (interquartile range: 14.0-54.3). Air leak resolved in 40/66 patients (60.6%) within 30 days after EBV treatment. Concerning safety outcome, no procedure-related mortality was reported and complication rate was low (6.1%). Five patients (7.6%) died in the first 30 days after intervention. CONCLUSION: EBV placement is a treatment option in patients with PAL. In this multicenter case-series of high-risk patients not eligible for lung surgery, we show that EBV placement resulted in air leak resolution in 6 out of 10 patients with a low complication rate. Considering the minimally invasive nature of EBV to treat PAL as opposed to surgery, further research should investigate if EBV treatment should be expanded in low to intermediate risk PAL patients.

Optimizing clinical outcomes for bronchoscopic lung volume reduction with Zephyr® valves.

Bronchoscopic lung volume reduction treatment with Zephyr one-way valves is an effective guideline-based treatment option for patients with severe emphysema and hyperinflation. However, in some cases the treatment response is less than anticipated or there might be a loss of initial treatment effect. Reasons for the lack of response can include incorrect assessment of collateral ventilation, improper valve placement, or patient related factors. Loss of initial benefit can be due to granulation tissue formation and subsequent valve dysfunction, or there may be side effects such as excessive coughing or infectious problems. Careful follow-up after treatment with valves is important and evaluation with a CT scan and/or bronchoscopy is helpful if there is no improvement after treatment or loss of initial benefit. This paper aims to describe the most important causes and provide a strategy of how to approach and manage these patients.

Feasibility of continuous bronchoscopy during exercise in the assessment of large airway movement in healthy subjects.

Excessive dynamic airway collapse (EDAC) is a recognized cause of exertional dyspnea arising due to invagination of the trachea and/or main bronchi. EDAC is typically assessed by evaluating large airway movement with forced expiratory maneuvers. This differs from the respiratory response to exercise hyperpnea. We aimed to evaluate large airway movement during physical activity, with continuous bronchoscopy during exercise (CBE), in healthy subjects and compare findings with resting bronchoscopic maneuvers and imaging techniques. Twenty-eight individuals were recruited to complete two visits including treadmill-based CBE, to voluntary exhaustion, and cine magnetic resonance imaging (MRI) with forced expiratory maneuvers at rest. Twenty-five subjects [aged 29 (26-33) yr, 52% female] completed the study (n = 2 withdrew before bronchoscopy, and one was unable to tolerate insertion of bronchoscope). The majority (76%) achieved a peak heart rate of >90% predicted during CBE. The procedure was prematurely terminated in five subjects (n = 3; elevated blood pressure and n = 2; minor oxygen desaturation). The CBE assessment enabled adequate tracheal visualization in all cases. Excessive dynamic airway collapse (tracheal collapse ≥50%) was identified in 16 subjects (64%) on MRI, and in six (24%) individuals during resting bronchoscopy, but in no cases with CBE. No serious adverse events were reported, but minor adverse events were evident. The CBE procedure permits visualization of large airway movement during physical activity. In healthy subjects, there was no evidence of EDAC during strenuous exercise, despite evidence during forced maneuvers on imaging, thus challenging conventional approaches to diagnosis.NEW & NOTEWORTHY This study demonstrates that large airway movement can be visualized with bronchoscopy undertaken during vigorous exercise. This approach does not require sedation and permits characterization of the behavior of the large airways and the tendency toward collapse during upright, ambulatory exercise. In healthy individuals, the response pattern of the large airways during exercise appears to differ markedly from the pattern of airway closure witnessed during forced expiratory maneuvers, assessed via imaging.

Low bleeding rates following transbronchial lung cryobiopsy in unclassifiable interstitial lung disease.

BACKGROUND AND OBJECTIVE: Bronchoscopic transbronchial lung cryobiopsy (TBLC) is a guideline-endorsed alternative to surgical lung biopsy for tissue diagnosis in unclassifiable interstitial lung disease (ILD). The reported incidence of post-procedural bleeding has varied widely. We aimed to characterize the incidence, severity and risk factors for clinically significant bleeding following TBLC using an expert-consensus airway bleeding scale, in addition to other complications and diagnostic yield. METHODS: A retrospective cohort study of consecutive adult outpatients with unclassifiable ILD who underwent TBLC following multidisciplinary discussion at a single centre in the UK between July 2016 and December 2021. TBLC was performed under general anaesthesia with fluoroscopic guidance and a prophylactic endobronchial balloon. RESULTS: One hundred twenty-six patients underwent TBLC (68.3% male; mean age 62.7 years; FVC 86.2%; DLCO 54.5%). Significant bleeding requiring balloon blocker reinflation for >20 min, admission to ICU, packed red blood cell transfusion, bronchial artery embolization, resuscitation or procedural abandonment, occurred in 10 cases (7.9%). Significant bleeding was associated with traction bronchiectasis on HRCT (OR 7.1, CI 1.1-59.1, p = 0.042), a TBLC histological pattern of UIP (OR 4.0, CI 1.1-14, p = 0.046) and the presence of medium-large vessels on histology (OR 37.3, CI 6.5-212, p < 0.001). BMI ≥30 (p = 0.017) and traction bronchiectasis on HRCT (p = 0.025) were significant multivariate predictors of longer total bleeding time (p = 0.017). Pneumothorax occurred in nine cases (7.1%) and the 30-day mortality was 0%. Diagnostic yield was 80.6%. CONCLUSION: TBLC has an acceptable safety profile in experienced hands. Radiological traction bronchiectasis and obesity increase the risk of significant bleeding following TBLC.

Airway wall extracellular matrix changes induced by bronchial thermoplasty in severe asthma.

BACKGROUND: Airway remodeling is a prominent feature of asthma, which involves increased airway smooth muscle mass and altered extracellular matrix composition. Bronchial thermoplasty (BT), a bronchoscopic treatment for severe asthma, targets airway remodeling. OBJECTIVE: We sought to investigate the effect of BT on extracellular matrix composition and its association with clinical outcomes. METHODS: This is a substudy of the TASMA trial. Thirty patients with severe asthma were BT-treated, of whom 13 patients were treated for 6 months with standard therapy (control group) before BT. Demographic data, clinical data including pulmonary function, and bronchial biopsies were collected. Biopsies at BT-treated and nontreated locations were analyzed by histological and immunohistochemical staining. Associations between histology and clinical outcomes were explored. RESULTS: Six months after treatment, it was found that the reticular basement membrane thickness was reduced from 7.28 µm to 5.74 µm (21% relative reduction) and the percentage area of tissue positive for collagen increased from 26.3% to 29.8% (13% relative increase). Collagen structure analysis revealed a reduction in the curvature frequency of fibers. The percentage area positive for fibulin-1 and fibronectin increased by 2.5% and 5.9%, respectively (relative increase of 124% and 15%). No changes were found for elastin. The changes in collagen and fibulin-1 negatively associated with changes in FEV1 reversibility. CONCLUSIONS: Besides reduction of airway smooth muscle mass, BT has an impact on reticular basement membrane thickness and the extracellular matrix arrangement characterized by an increase in tissue area occupied by collagen with a less dense fiber organization. Both collagen and fibulin-1 are negatively associated with the change in FEV1 reversibility.

Bronchoscopic interventions for chronic bronchitis.

PURPOSE OF REVIEW: Chronic bronchitis is a phenotype of chronic obstructive pulmonary disease (COPD), characterized by chronic cough and sputum production, associated with an increased rate of COPD exacerbations and hospital admissions, a more rapid decline in lung function and reduced life expectancy. Despite optimal medical therapy, chronic bronchitis remains difficult to treat. Interventional bronchoscopic procedures offer novel therapeutic approaches to this highly symptomatic condition. RECENT FINDINGS: A characteristic feature of chronic bronchitis is the presence of an abnormal epithelium with excessive mucus producing cells, parasympathetic overactivity, and airway inflammation. Metered cryospray and bronchial rheoplasty are designed to target this abnormal epithelium to reduce mucus production and inflammation. Targeted lung denervation aims to reduce parasympathetic overactivity, which may drive mucus hypersecretion. Here, we review the available evidence to determine the safety and efficacy across the bronchoscopic interventions. SUMMARY: Interventional bronchoscopy is a rapidly expanding field and its application in the treatment of chronic bronchitis has been recognized by the Global initiative for chronic Obstructive Lung Disease (GOLD). The outcomes from the latest clinical trials will guide future treatment approaches in patients with difficult to treat chronic bronchitis.

Clinical outcomes by supplemental oxygen use in remdesivir-treated, hospitalised adults with COVID-19.

BACKGROUND: Clinical trials show different effects of remdesivir on clinical outcomes relative to COVID-19 severity at hospital admission; in Europe, there are few real-world data. METHODS: A multicentre, multinational retrospective cohort study in adult patients hospitalised with PCR-confirmed COVID-19 was conducted to understand remdesivir clinical use in different countries and to describe outcomes for patients receiving remdesivir stratified by oxygen use. Primary endpoints were all-cause mortality at day 28 and hospitalisation duration. Patients were categorised by baseline disease severity: no supplemental oxygen (NSO); low flow oxygen ≤ 6 litres (l)/minute (LFO); high flow oxygen > 6 l/minute (HFO). RESULTS: Four hundred and forty-eight (448) patients (72 [16.1%] HFO; 295 [65.8%] LFO; 81 (18.1%] NSO) were included; median age was 65 years and 64% were male. Mortality was higher in patients on HFO (rate 23.6%) compared to LFO (10.2%; p = 0.001) or NSO (6.2%; p = 0.002). Duration of hospitalisation was longer in patients on HFO (13 days) compared to LFO (9 days; p = 0.003) and NSO (9 days; p = 0.021). Patients who initiated remdesivir ≥ 2 days compared to within a day of hospitalisation had a 4.2 times higher risk of death, irrespective of age, sex, comorbidities, and oxygen support at baseline. Requirement for mechanical ventilation/ECMO and readmission within 28 days of discharge was similar across groups. Remdesivir use and outcomes differed by country. CONCLUSIONS: A higher mortality rate and duration of hospitalisation was seen in remdesivir-treated COVID-19 patients on HFO compared to LFO and NSO. Initiation of remdesivir upon admission as opposed to delayed initiation has a mortality benefit. CLINICAL TRIALS REGISTRATION: NCT04847622.

Mitigation of Respirable Aerosol Particles from Speech and Language Therapy Exercises.

INTRODUCTION: Phonation and speech are known sources of respirable aerosol in humans. Voice assessment and treatment manipulate all the subsystems of voice production, and previous work (Saccente-Kennedy et al., 2022) has demonstrated such activities can generate >10 times more aerosol than conversational speech and 30 times more aerosol than breathing. Aspects of voice therapy may therefore be considered aerosol generating procedures and pose a greater risk of potential airborne pathogen (eg, SARS-CoV-2) transmission than typical speech. Effective mitigation measures may be required to ensure safe service delivery for therapist and patient. OBJECTIVE: To assess the effectiveness of mitigation measures in reducing detectable respirable aerosol produced by voice assessment/therapy. METHODS: We recruited 15 healthy participants (8 cis-males, 7 cis-females), 9 of whom were voice-specialist speech-language pathologists. Optical Particle Sizers (OPS) (Model 3330, TSI) were used to measure the number concentration of respirable aerosol particles (0.3 µm-10 µm) generated during a selection of voice assessment/therapy tasks, both with and without mitigation measures in place. Measurements were performed in a laminar flow operating theatre, with near-zero background aerosol concentration, allowing us to quantify the number concentration of respiratory aerosol particles produced. Mitigation measures included the wearing of Type IIR fluid resistant surgical masks, wrapping the same masks around the end of straws, and the use of heat and moisture exchange microbiological filters (HMEFs) for a water resistance therapy (WRT) task. RESULTS: All unmitigated therapy tasks produced more aerosol than unmasked breathing or speaking. Mitigation strategies reduced detectable aerosol from all tasks to a level significantly below, or no different to, that of unmasked breathing. Pooled filtration efficiencies determined that Type IIR surgical masks reduced detectable aerosol by 90%. Surgical masks wrapped around straws reduced detectable aerosol by 96%. HMEF filters were 100% effective in mitigating the aerosol from WRT, the exercise that generated more aerosol than any other task in the unmitigated condition. CONCLUSIONS: Voice therapy and assessment causes the release of significant quantities of respirable aerosol. However, simple mitigation strategies can reduce emitted aerosol concentrations to levels comparable to unmasked breathing.

Lung volume reduction surgery versus endobronchial valves: a randomised controlled trial.

BACKGROUND: Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (BLVR) with endobronchial valves can improve outcomes in appropriately selected patients with emphysema. However, no direct comparison data exist to inform clinical decision making in people who appear suitable for both procedures. Our aim was to investigate whether LVRS produces superior health outcomes when compared with BLVR at 12 months. METHODS: This multicentre, single-blind, parallel-group trial randomised patients from five UK hospitals, who were suitable for a targeted lung volume reduction procedure, to either LVRS or BLVR and compared outcomes at 1 year using the i-BODE score. This composite disease severity measure includes body mass index, airflow obstruction, dyspnoea and exercise capacity (incremental shuttle walk test). The researchers responsible for collecting outcomes were masked to treatment allocation. All outcomes were assessed in the intention-to-treat population. RESULTS: 88 participants (48% female, mean±sd age 64.6±7.7 years, forced expiratory volume in 1 s percent predicted 31.0±7.9%) were recruited at five specialist centres across the UK and randomised to either LVRS (n=41) or BLVR (n=47). At 12 months follow-up, the complete i-BODE was available in 49 participants (21 LVRS/28 BLVR). Neither improvement in the i-BODE score (LVRS -1.10±1.44 versus BLVR -0.82±1.61; p=0.54) nor in its individual components differed between groups. Both treatments produced similar improvements in gas trapping (residual volume percent predicted: LVRS -36.1% (95% CI -54.6- -10%) versus BLVR -30.1% (95% CI -53.7- -9%); p=0.81). There was one death in each treatment arm. CONCLUSION: Our findings do not support the hypothesis that LVRS is a substantially superior treatment to BLVR in individuals who are suitable for both treatments.

Favipiravir in patients hospitalised with COVID-19 (PIONEER trial): a multicentre, open-label, phase 3, randomised controlled trial of early intervention versus standard care.

BACKGROUND: COVID-19 has overwhelmed health services globally. Oral antiviral therapies are licensed worldwide, but indications and efficacy rates vary. We aimed to evaluate the safety and efficacy of oral favipiravir in patients hospitalised with COVID-19. METHODS: We conducted a multicentre, open-label, randomised controlled trial of oral favipiravir in adult patients who were newly admitted to hospital with proven or suspected COVID-19 across five sites in the UK (n=2), Brazil (n=2) and Mexico (n=1). Using a permuted block design, eligible and consenting participants were randomly assigned (1:1) to receive oral favipiravir (1800 mg twice daily for 1 day; 800 mg twice daily for 9 days) plus standard care, or standard care alone. All caregivers and patients were aware of allocation and those analysing data were aware of the treatment groups. The prespecified primary outcome was the time from randomisation to recovery, censored at 28 days, which was assessed using an intention-to-treat approach. Post-hoc analyses were used to assess the efficacy of favipiravir in patients aged younger than 60 years, and in patients aged 60 years and older. The trial was registered with clinicaltrials.gov, NCT04373733. FINDINGS: Between May 5, 2020 and May 26, 2021, we assessed 503 patients for eligibility, of whom 499 were randomly assigned to favipiravir and standard care (n=251) or standard care alone (n=248). There was no significant difference between those who received favipiravir and standard care, relative to those who received standard care alone in time to recovery in the overall study population (hazard ratio [HR] 1·06 [95% CI 0·89-1·27]; n=499; p=0·52). Post-hoc analyses showed a faster rate of recovery in patients younger than 60 years who received favipiravir and standard care versus those who had standard care alone (HR 1·35 [1·06-1·72]; n=247; p=0·01). 36 serious adverse events were observed in 27 (11%) of 251 patients administered favipiravir and standard care, and 33 events were observed in 27 (11%) of 248 patients receiving standard care alone, with infectious, respiratory, and cardiovascular events being the most numerous. There was no significant between-group difference in serious adverse events per patient (p=0·87). INTERPRETATION: Favipiravir does not improve clinical outcomes in all patients admitted to hospital with COVID-19, however, patients younger than 60 years might have a beneficial clinical response. The indiscriminate use of favipiravir globally should be cautioned, and further high-quality studies of antiviral agents, and their potential treatment combinations, are warranted in COVID-19. FUNDING: LifeArc and CW+.

Dual-energy Computed Tomographic Pulmonary Angiography Accurately Estimates Lobar Perfusion Before Lung Volume Reduction for Severe Emphysema.

PURPOSE: To assess if dual-energy computed tomographic pulmonary angiography (DECTPA) derived lobar iodine quantification can provide an accurate estimate of lobar perfusion in patients with severe emphysema, and offer an adjunct to single-photon emission CT perfusion scintigraphy (SPECT-PS) in assessing suitability for lung volume reduction (LVR). MATERIALS AND METHODS: Patients with severe emphysema (forced expiratory volume in 1 s <49% predicted) undergoing evaluation for LVR between May 2018 and April 2020 imaged with both SPECT-PS and DECTPA were included in this retrospective study. DECTPA perfused blood volume maps were automatically segmented and lobar iodine mass was estimated and compared with lobar technetium (Tc99m) distribution acquired with SPECT-PS. Pearson correlation and Bland-Altman analysis were used for intermodality comparison between DECTPA and SPECT-PS. Univariate and adjusted multivariate linear regression were modelled to ascertain the effect sizes of possible confounders of disease severity, sex, age, and body mass index on the relationship between lobar iodine and Tc99m values. Effective radiation dose and adverse reactions were recorded. RESULTS: In all, 123 patients (64.5±8.8 y, 71 men; mean predicted forced expiratory volume in 1 s 32.1 ±12.7%,) were eligible for inclusion. There was a linear relationship between lobar perfusion values acquired using DECTPA and SPECT-PS with statistical significance ( P <0.001). Lobar relative perfusion values acquired using DECTPA and SPECT-PS had a consistent relationship both by linear regression and Bland-Altman analysis (mean bias, -0.01, mean r2 0.64; P <0.0001). Individual lobar comparisons demonstrated moderate correlation ( r =0.79, 0.78, 0.84, 0.78, 0.8 for the right upper, middle, lower, left upper, and lower lobes, respectively, P <0.0001). The relationship between lobar iodine and Tc99m values was not significantly altered after controlling for confounders including symptom and disease severity, age, sex, and body mass index. CONCLUSIONS: DECTPA provides an accurate estimation of lobar perfusion, showing good agreement with SPECT-PS and could potentially streamline preoperative assessment for LVR.

Airway Inflammation Before and After Bronchial Thermoplasty in Severe Asthma.

Background: Bronchial thermoplasty (BT) is a bronchoscopic treatment for severe asthma, of which the working mechanism and responder profile are partly unknown. The aim of this study is to analyse whether BT alters airway inflammation by epithelial gene expression, inflammatory cell counts and cytokines, and whether this relates to treatment response. Methods: In this clinical trial, 28 severe asthma patients underwent bronchoscopy before and after treatment to obtain bronchial brushes and bronchoalveolar lavage fluid (BALF) from treated and untreated airways. RNA was extracted from bronchial brushes for transcriptome analysis, and BALF cells and cytokines were analysed. Asthma quality of life questionnaires were used to distinguish responders from non-responders. We compared results before and after treatment, between treated and untreated airways, and between responders and non-responders. Results: Gene expression of airway epithelium related to airway inflammation gene set was significantly downregulated in treated airways compared to untreated airways, although this did not differ for patients before and after treatment. No differences were observed in cell counts and cytokines, neither from the untreated compared to treated airways, nor before and after treatment. At baseline, compared to non-responders, the expression of genes related to glycolysis in bronchial epithelium was downregulated and both BALF and blood eosinophil counts were higher in responders. Conclusion: Local differences in gene sets pertaining to epithelial inflammatory status were identified between treated and untreated airways after treatment, not resulting in changes in differential cell counts and cytokine analyses in BALF. Secondly, baseline epithelial glycolysis genes and eosinophil counts in BALF and blood were different between responders and non-responders. The observations from this study demonstrate the potential impact of BT on epithelial gene expression related to airway inflammation while also identifying a possible responder profile.

Crossover Patient Outcomes for Targeted Lung Denervation in Moderate to Severe Chronic Obstructive Pulmonary Disease: AIRFLOW-2.

BACKGROUND: Targeted Lung Denervation (TLD) is a potential new therapy for COPD. Radiofrequency energy is bronchoscopically delivered to the airways to disrupt pulmonary parasympathetic nerves, to reduce bronchoconstriction, mucus hypersecretion, and bronchial hyperreactivity. OBJECTIVES: This work assesses the effect of TLD on COPD exacerbations (AECOPD) in crossover subjects in the AIRFLOW-2 trial. METHOD: The AIRFLOW-2 trial is a multicentre, randomized, double-blind, sham-controlled crossover trial of TLD in COPD. Patients with symptomatic COPD on optimal medical therapy with an FEV1 of 30-60% predicted received either TLD or sham bronchoscopy in a 1:1 randomization. Those in the sham arm had the opportunity to cross into the treatment arm after 12 months. The primary end point was rate of respiratory adverse events. Secondary end points included adverse events, changes in lung function and health-related quality of life and symptom scores. RESULTS: Twenty patients were treated with TLD in the crossover phase and were subsequently followed up for 12 months (50% female, mean age 64.1 ± 6.9 years). After TLD, there was a trend towards a reduction in time to first AECOPD (hazard ratio 0.65, p = 0.28, not statistically significant) in comparison to sham follow-up period. There was also a reduction in time to first severe AECOPD in the crossover period (hazard ratio 0.38, p = 0.227, not statistically significant). Symptom scores and lung function showed stability. CONCLUSIONS: AIRFLOW-2 crossover data support that of the randomization phase, showing trends towards reduction in COPD exacerbations with TLD.

Quantification of Respirable Aerosol Particles from Speech and Language Therapy Exercises.

INTRODUCTION: Voice assessment and treatment involve the manipulation of all the subsystems of voice production, and may lead to production of respirable aerosol particles that pose a greater risk of potential viral transmission via inhalation of respirable pathogens (eg, SARS-CoV-2) than quiet breathing or conversational speech. OBJECTIVE: To characterise the production of respirable aerosol particles during a selection of voice assessment therapy tasks. METHODS: We recruited 23 healthy adult participants (12 males, 11 females), 11 of whom were speech-language pathologists specialising in voice disorders. We used an aerodynamic and an optical particle sizer to measure the number concentration and particle size distributions of respirable aerosols generated during a variety of voice assessment and therapy tasks. The measurements were carried out in a laminar flow operating theatre, with a near-zero background aerosol concentration, allowing us to quantify the number concentration and size distributions of respirable aerosol particles produced from assessment/therapy tasks studied. RESULTS: Aerosol number concentrations generated while performing assessment/therapy tasks were log-normally distributed among individuals with no significant differences between professionals (speech-language pathologists) and non-professionals or between males and females. Activities produced up to 32 times the aerosol number concentration of breathing and 24 times that of speech at 70-80 dBA. In terms of aerosol mass, activities produced up to 163 times the mass concentration of breathing and up to 36 times the mass concentration of speech. Voicing was a significant factor in aerosol production; aerosol number/mass concentrations generated during the voiced activities were 1.1-5 times higher than their unvoiced counterpart activities. Additionally, voiced activities produced bigger respirable aerosol particles than their unvoiced variants except the trills. Humming generated higher aerosol concentrations than sustained /a/, fricatives, speaking (70-80 dBA), and breathing. Oscillatory semi-occluded vocal tract exercises (SOVTEs) generated higher aerosol number/mass concentrations than the activities without oscillation. Water resistance therapy (WRT) generated the most aerosol of all activities, ∼10 times higher than speaking at 70-80 dBA and >30 times higher than breathing. CONCLUSIONS: All activities generated more aerosol than breathing, although a sizeable minority were no different to speaking. Larger number concentrations and larger particle sizes appear to be generated by activities with higher suspected airflows, with the greatest involving intraoral pressure oscillation and/or an oscillating oral articulation (WRT or trilling).