Singing for lung health in COPD: a multicentre randomised controlled trial of online delivery.

BACKGROUND: Singing for lung health (SLH) is an arts-based breathing control and movement intervention for people with long-term respiratory conditions, intended to improve symptoms and quality of life. Online, remotely delivered programmes might improve accessibility; however, no previous studies have assessed the effectiveness of this approach. METHODS: We conducted an assessor-blind randomised controlled trial comparing the impact of 12 weeks of once-weekly online SLH sessions against usual care on health-related quality of life, assessed using the RAND 36-Item Short Form Health Survey (SF-36) Mental Health Composite (MHC) and Physical Health Composite (PHC) scores. RESULTS: We enrolled 115 people with stable chronic obstructive pulmonary disease (COPD), median (IQR) age 69 (62-74), 56.5% females, 80% prior pulmonary rehabilitation, Medical Research Council dyspnoea scale 4 (3-4), forced expiratory volume in 1 s % predicted 49 (35-63). 50 participants in each arm completed the study. The intervention arm experienced improvements in physical but not mental health components of RAND SF-36; PHC (regression coefficient (95% CI): 1.77 (95% CI 0.11 to 3.44); p=0.037), but not MHC (0.86 (95% CI -1.68 to 3.40); p=0.504). A prespecified responder analysis based on achieving a 10% improvement from baseline demonstrated a response rate for PHC of 32% in the SLH arm and 12.7% for usual care (p=0.024). A between-group difference in responder rate was not found in relation to the MHC (19.3% vs 25.9%; p=0.403). DISCUSSION AND CONCLUSION: A 12-week online SLH programme can improve the physical component of quality of life for people with COPD, but the overall effect is relatively modest compared with the impact seen in research using face-to-face group sessions. Further work on the content, duration and dose of online interventions may be useful. TRIAL REGISTRATION NUMBER: NCT04034212.

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. 25 subjects (aged 29 (26 - 33) years, 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 6 (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.

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.

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.

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+.

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).

A comparison of respiratory particle emission rates at rest and while speaking or exercising.

Background: The coronavirus disease-19 (COVID-19) pandemic led to the prohibition of group-based exercise and the cancellation of sporting events. Evaluation of respiratory aerosol emissions is necessary to quantify exercise-related transmission risk and inform mitigation strategies. Methods: Aerosol mass emission rates are calculated from concurrent aerosol and ventilation data, enabling absolute comparison. An aerodynamic particle sizer (0.54-20 µm diameter) samples exhalate from within a cardiopulmonary exercise testing mask, at rest, while speaking and during cycle ergometer-based exercise. Exercise challenge testing is performed to replicate typical gym-based exercise and very vigorous exercise, as determined by a preceding maximally exhaustive exercise test. Results: We present data from 25 healthy participants (13 males, 12 females; 36.4 years). The size of aerosol particles generated at rest and during exercise is similar (unimodal ~0.57-0.71 µm), whereas vocalization also generated aerosol particles of larger size (i.e. was bimodal ~0.69 and ~1.74 µm). The aerosol mass emission rate during speaking (0.092 ng s-1; minute ventilation (VE) 15.1 L min-1) and vigorous exercise (0.207 ng s-1, p = 0.726; VE 62.6 L min-1) is similar, but lower than during very vigorous exercise (0.682 ng s-1, p < 0.001; VE 113.6 L min-1). Conclusions: Vocalisation drives greater aerosol mass emission rates, compared to breathing at rest. Aerosol mass emission rates in exercise rise with intensity. Aerosol mass emission rates during vigorous exercise are no different from speaking at a conversational level. Mitigation strategies for airborne pathogens for non-exercise-based social interactions incorporating vocalisation, may be suitable for the majority of exercise settings. However, the use of facemasks when exercising may be less effective, given the smaller size of particles produced.

Comparing aerosol number and mass exhalation rates from children and adults during breathing, speaking and singing.

Aerosol particles of respirable size are exhaled when individuals breathe, speak and sing and can transmit respiratory pathogens between infected and susceptible individuals. The COVID-19 pandemic has brought into focus the need to improve the quantification of the particle number and mass exhalation rates as one route to provide estimates of viral shedding and the potential risk of transmission of viruses. Most previous studies have reported the number and mass concentrations of aerosol particles in an exhaled plume. We provide a robust assessment of the absolute particle number and mass exhalation rates from measurements of minute ventilation using a non-invasive Vyntus Hans Rudolf mask kit with straps housing a rotating vane spirometer along with measurements of the exhaled particle number concentrations and size distributions. Specifically, we report comparisons of the number and mass exhalation rates for children (12-14 years old) and adults (19-72 years old) when breathing, speaking and singing, which indicate that child and adult cohorts generate similar amounts of aerosol when performing the same activity. Mass exhalation rates are typically 0.002-0.02 ng s-1 from breathing, 0.07-0.2 ng s-1 from speaking (at 70-80 dBA) and 0.1-0.7 ng s-1 from singing (at 70-80 dBA). The aerosol exhalation rate increases with increasing sound volume for both children and adults when both speaking and singing.

Immuno-proteomic profiling reveals aberrant immune cell regulation in the airways of individuals with ongoing post-COVID-19 respiratory disease.

Some patients hospitalized with acute COVID-19 suffer respiratory symptoms that persist for many months. We delineated the immune-proteomic landscape in the airways and peripheral blood of healthy controls and post-COVID-19 patients 3 to 6 months after hospital discharge. Post-COVID-19 patients showed abnormal airway (but not plasma) proteomes, with an elevated concentration of proteins associated with apoptosis, tissue repair, and epithelial injury versus healthy individuals. Increased numbers of cytotoxic lymphocytes were observed in individuals with greater airway dysfunction, while increased B cell numbers and altered monocyte subsets were associated with more widespread lung abnormalities. A one-year follow-up of some post-COVID-19 patients indicated that these abnormalities resolved over time. In summary, COVID-19 causes a prolonged change to the airway immune landscape in those with persistent lung disease, with evidence of cell death and tissue repair linked to the ongoing activation of cytotoxic T cells.

CT Lung Abnormalities after COVID-19 at 3 Months and 1 Year after Hospital Discharge.

Background Data on the long-term pulmonary sequelae in COVID-19 are lacking. Purpose To assess symptoms, functional impairment, and residual pulmonary abnormalities on serial chest CT scans in COVID-19 survivors discharged from hospital at up to 1-year follow-up. Materials and Methods Adult patients with COVID-19 discharged between March 2020 and June 2020 were prospectively evaluated at 3 months and 1 year through systematic assessment of symptoms, functional impairment, and thoracic CT scans as part of the PHENOTYPE study, an observational cohort study in COVID-19 survivors. Lung function testing was limited to participants with CT abnormalities and/or persistent breathlessness. Bonferroni correction was used. Results Eighty participants (mean age, 59 years ± 13 [SD]; 53 men) were assessed. At outpatient review, persistent breathlessness was reported in 37 of the 80 participants (46%) and cough was reported in 17 (21%). CT scans in 73 participants after discharge (median, 105 days; IQR, 95-141 days) revealed persistent abnormalities in 41 participants (56%), with ground-glass opacification (35 of 73 participants [48%]) and bands (27 of 73 participants [37%]) predominating. Unequivocal signs indicative of established fibrosis (ie, volume loss and/or traction bronchiectasis) were present in nine of 73 participants (12%). Higher admission serum C-reactive protein (in milligrams per liter), fibrinogen (in grams per deciliter), urea (millimoles per liter), and creatinine (micromoles per liter) levels; longer hospital stay (in days); older age (in years); and requirement for invasive ventilation were associated with CT abnormalities at 3-month follow-up. Thirty-two of 41 participants (78%) with abnormal findings at 3-month follow-up CT underwent repeat imaging at a median of 364 days (range, 360-366 days), with 26 (81%) showing further radiologic improvement (median, 18%; IQR, 10%-40%). Conclusion CT abnormalities were common at 3 months after COVID-19 but with signs of fibrosis in a minority. More severe acute disease was linked with CT abnormalities at 3 months. However, radiologic improvement was seen in the majority at 1-year follow-up. ClinicalTrials.gov identifier: NCT04459351. © RSNA, 2022 Online supplemental material is available for this article.

Physiological demands of singing for lung health compared with treadmill walking.

INTRODUCTION: Participating in singing is considered to have a range of social and psychological benefits. However, the physiological demands of singing and its intensity as a physical activity are not well understood. METHODS: We compared cardiorespiratory parameters while completing components of Singing for Lung Health sessions, with treadmill walking at differing speeds (2, 4 and 6 km/hour). RESULTS: Eight healthy adults were included, none of whom reported regular participation in formal singing activities. Singing induced acute physiological responses that were consistent with moderate intensity activity (metabolic equivalents: median 4.12, IQR 2.72-4.78), with oxygen consumption, heart rate and volume per breath above those seen walking at 4 km/hour. Minute ventilation was higher during singing (median 22.42 L/min, IQR 16.83-30.54) than at rest (11 L/min, 9-13), lower than 6 km/hour walking (30.35 L/min, 26.94-41.11), but not statistically different from 2 km/hour (18.77 L/min, 16.89-21.35) or 4 km/hour (23.27 L/min, 20.09-26.37) walking. CONCLUSIONS: Our findings suggest the acute metabolic demands of singing are comparable with walking at a moderately brisk pace, hence, physical effects may contribute to the health and well-being benefits attributed to singing participation. However, if physical training benefits result remains uncertain. Further research including different singing styles, singers and physical performance impacts when used as a training modality is encouraged. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov registry (NCT04121351).

A prospective safety and feasibility study of metered cryospray for patients with chronic bronchitis in COPD.

BACKGROUND: No currently approved intervention counteracts airway metaplasia and mucus hypersecretion of chronic bronchitis in COPD. However, metered cryospray (MCS) delivering liquid nitrogen to the tracheobronchial airways ablates abnormal epithelium and facilitates healthy mucosal regeneration. The objective of this study was to evaluate the feasibility, efficacy and safety of MCS in chronic bronchitis. METHODS: Patients with a forced expiratory volume in 1 s of 30-80% predicted who were taking optimal medication were recruited. Primary outcomes were feasibility (completion of treatments), efficacy (3-month change in St George's Respiratory Questionnaire (SGRQ)) and safety (incidence of adverse events). Secondary outcomes were lung function, exercise capacity and additional patient-reported outcomes. RESULTS: 35 patients, 19 male/16 female, aged 47-76 years, Global Initiative for Chronic Obstructive Lung Disease grade I (n=3), II (n=10) and III (n=22), underwent staggered liquid nitrogen treatments to the tracheobronchial tree. 34 patients completed three treatments, each lasting 34.3±12.1 min, separated by 4-6 weeks; one withdrew after the first treatment. ∼1800 doses of MCS were delivered. Clinically meaningful improvements in patient-reported outcomes were observed at 3 months: change in SGRQ -6.4 (95% CI -11.4 to -1.3; p=0.01), COPD Assessment Test (CAT) -3.8 (95% CI -6.4 to -1.3; p<0.01) and Leicester Cough Questionnaire (LCQ) 21.6 (95% CI 7.3 to 35.9; p<0.01). Changes in CAT were durable to 6 months (-3.4, 95% CI -5.9 to -0.9; p=0.01); changes in SGRQ and LCQ were durable to 9 months (-6.9, 95% CI -13.0 to -0.9; p=0.03 and 13.4, 95% CI 2.1 to 24.6; p=0.02, respectively. At 12 months, 14 serious adverse events were recorded in 11 (31.4%) subjects; six (43%) moderate and eight (57%) severe. Nine were respiratory-related: six exacerbations of COPD, two pneumonias and one case of increased coughing; all recovered without sequelae. None were serious device- or procedure-related adverse events. CONCLUSION: MCS is safe, feasible and associated with clinically meaningful improvements in multidimensional patient-reported outcomes.

Feasibility of portable continuous laryngoscopy during exercise testing.

Exercise-induced laryngeal obstruction (EILO) is a prevalent problem causing exertional breathlessness and wheeze. This report demonstrates the feasibility and safety of a diagnostic approach to EILO, using a portable laryngoscope during exercise. http://ow.ly/eM6L30njDst.