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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.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.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).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.LifeArc and CW+.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has brought renewed attention to respiratory aerosol and droplet generation. While many studies have robustly quantified aerosol (20 µm diameter) generated by a cohort of 76 adults and children using a water-sensitive paper droplet deposition approach. Unvoiced and voiced activities spanning different levels of loudness, different lengths of sustained phonation, and a specific manner of articulation in isolation were investigated. We find that oral articulation drives >20 µm droplet generation, with breathing generating virtually no droplets and speaking and singing generating on the order of 250 droplets min−1. Lip trilling, which requires extensive oral articulation, generated the most droplets, whereas shouting “Hey,” which requires minimal oral articulation, generated relatively few droplets. Droplet size distributions were all broadly consistent, and no significant differences between the children and adult cohorts were identified. By comparing the aerosol and droplet emissions for the same participants, the full size distribution of respiratory aerosol (0.5–1000 µm) is reported. Although 20 µm droplets dominate the mass concentration. Accurate quantification of aerosol concentrations in the 10–70 μm size range remains very challenging; more robust aerosol analysis approaches are needed to characterize this size range.

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 (e.g. 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.MethodsWe 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 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. ResultsAerosol 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 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 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.ConclusionsAll 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).

Some patients hospitalized with acute COVID-19 suffer respiratory symptoms that persist for many months. We delineated the immune-proteomic landscape in the airway 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 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. 1 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 ongoing activation of cytotoxic T cells., Graphical Abstract, Many individuals recovering from acute SARS-CoV-2 infection suffer prolonged respiratory dysfunction for months to years after viral clearance. Vijayakumar, Boustani, Ogger, Papadaki et al. show that individuals with persistent symptoms 3-6 months after infection have an altered airway immune cell landscape and evidence of ongoing lung damage. Importantly, different immune cell types correlate with the severity of distinct aspects of ongoing respiratory disease.

Respiratory particles produced by breathing, coughing, and speaking or generated during medical procedures serve as important routes for disease transmission. Characterising the number of particles generated as well as their size distribution is fundamental for guiding policy on infection control. However, sampling such particles carries inherent challenges. Respiratory particles are polydisperse in size, temporally and spatially variable, and emitted in very low concentrations, usually lower than the pre-existing aerosol concentration in indoor environments. In addition, they are typically emitted in a highly dynamic, warm and humid jet, leading to further rapid processes, such as dispersion and evaporation. Here, we discuss important considerations for sampling respiratory aerosol, focusing on sampling particles < 20 µm in diameter. Instruments capable of counting single-particles within this size range are commercially available. We provide recommendations for experimental protocols and demonstrate the limitations behind such approaches. We highlight the importance of a measurement space with as low a background aerosol concentration as possible, and of sampling for as long as possible to enable accurate quantitation of the size distribution of an aerosol plume. This is particularly important for the larger particles (> 5µm diameter) that are so low in concentration that they may require hours of sampling time to be accurately quantified. We explore the relationship between the flow rates of the exhalation and the sampling instrument and the consequent quantification of particle flux. We also discuss the transport and evaporation dynamics of liquid particles within respiratory jets, and their impacts on conducting aerosol sampling studies.

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−1from breathing, 0.07–0.2 ng s−1from speaking (at 70–80 dBA) and 0.1–0.7 ng s−1from singing (at 70–80 dBA). The aerosol exhalation rate increases with increasing sound volume for both children and adults when both speaking and singing.

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

SummarySome patients hospitalized with acute COVID19 suffer respiratory symptoms that persist for many months. To characterize the local and systemic immune responses associated with this form of ‘Long COVID’, we delineated the immune and proteomic landscape in the airway and peripheral blood of normal volunteers and patients from 3 to 6 months after hospital discharge. The bronchoalveolar lavage (but not peripheral blood) proteome was abnormal in patients with post-COVID19 lung disease with significantly elevated concentration of proteins associated with apoptosis, tissue repair and epithelial injury. This correlated with an increase in cytotoxic lymphocytes (especially tissue resident CD8+T cells), lactate dehydrogenase and albumin (biomarkers of cell death and barrier integrity). Follow-up of a subset of these patients greater than 1-year post-COVID19 indicated these abnormalities resolved over time. Collectively, these data indicate that COVID-19 results in a prolonged change to the airway immune landscape in those with persistent lung disease, with evidence of cell death and tissue repair linked to ongoing activation of cytotoxic T cells.HighlightsThe post-COVID19 airway is characterized by increased cytotoxic lymphocytes.Distinct airway proteomes are associated with the airway immune cell landscape.The peripheral blood does not predict immune-proteome alterations in the airway post-COVID19.Persistent abnormalities in the airway immune-proteome post-COVID19 airways correlate with ongoing epithelial damage.

IntroductionParticipating 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.MethodsWe compared cardiorespiratory parameters while completing components of Singing for Lung Health sessions, with treadmill walking at differing speeds (2, 4 and 6 km/hour).ResultsEight 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.ConclusionsOur 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 numberClinicalTrials.gov registry (NCT04121351).

Exercise-induced laryngeal obstruction (EILO) is a prevalent and yet still under-recognised cause of exertional breathlessness [1]. The transient closure of the larynx, which develops during EILO, results in dyspnoea, cough, inspiratory wheeze (i.e. stridor) and tightness in the throat on physical exertion. It is estimated that EILO is present in 6% of adolescents and as many as one in four athletes with unexplained respiratory symptoms [1, 2]. Despite improved recognition over the past 5 years [3, 4], it remains frequently misdiagnosed and mistreated as asthma [2, 5]., 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

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted in an unprecedented shutdown in social and economic activity, with the cultural sector particularly severely affected. Restrictions on musical performances have arisen from a perception that there is a significantly higher risk of aerosol production from singing than speaking, based upon high-profile examples of clusters of COVID-19 following choral rehearsals. However, comparing aerosol generation from different types of vocalization, including singing, across a range of volumes is a rapidly evolving area of research. Here, we measured aerosols from singing, speaking and breathing from a large cohort of 25 professional singers in a range of musical genres in a zero-background environment, allowing unequivocal attribution of aerosol production to specific vocalizations. We do not assess the relative volumes at which people speak and sing. However, both showed steep increases in mass concentration with increase in loudness (spanning a factor of 20–30 across the dynamic range measured, p < 0.001). At the quietest volume (50 to 60 dBA), neither singing (p = 0.19) nor speaking (p = 0.20) were significantly different to breathing. At the loudest volume (90 to 100 dBA), a statistically significant difference (p < 0.001) was observed between singing and speaking, but with singing only generating a factor of between 1.5 and 3.4 more aerosol mass. Guidelines for musical performances should be based on the loudness and duration of the vocalization, the number of participants and the environment in which the activity occurs, rather than the type of vocalization. Mitigations such as the use of amplification and increased attention to ventilation should be employed where practicable. Copyright © 2021 American Association for Aerosol Research

The performing arts have been significantly restricted due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. We report measurements of aerosol and droplet concentrations generated when playing woodwind and brass instruments and comparisons with breathing, speaking, and singing. These measurements were conducted in a room with zero number concentration aerosol background in the 0.5-20 µm diameter size range, allowing clear attribution of detected particles to specific activities. A total of 13 instruments were examined across 9 participants. Respirable particle number concentrations and size distributions for playing instruments are consistent with those from the participant when breathing, based on measurements with multiple participants playing the flute and piccolo as well as measurements across the entire cohort. Due to substantial interparticipant variability, we do not provide a comparative assessment of the aerosol generated by playing different instruments, instead considering only the variation in aerosol yield across all instruments studied. Both particle number and mass concentrations from playing instruments are lower than those from speaking and singing at high volume, and no large droplets >20 µm diameter are detected. Combined, these observations suggest that playing instruments generates less aerosol than speaking or singing at high volumes. Moreover, there is no difference between the aerosol concentrations generated by professional and amateur performers while breathing, speaking, or singing, suggesting conclusions for professional singers may also apply to amateurs.

Preprint also available at Research Square: In Review. Scientific Reports, in press. doi: 10.21203/rs.3.rs-124158/v1. This work is licensed under a CC BY 4.0 License. Participating in singing is considered to have a range of social and psychological benefits. However, the physiological demands of singing, whether it can be considered exercise, and its intensity as a physical activity are not well understood. We therefore compared cardiorespiratory parameters while completing components of Singing for Lung Health (SLH) sessions, with treadmill walking at differing speeds (2, 4, and 6km/hr). Eight healthy adults were included, none of whom reported regular participation in formal singing activities. Singing induced physiological responses that were consistent with moderate intensity activity (METS: median 4.12, IQR 2.72 - 4.78), with oxygen consumption, heart rate, and volume per breath above those seen walking at 4km/hr. Minute ventilation was higher during singing (median 22.42L/min, IQR 16.83 - 30.54) than at rest (11L/min, 9 - 13), lower than 6km/hr walking (30.35L/min, 26.94 - 41.11), but not statistically different from 2km/hr (18.77L/min, 16.89 - 21.35) or 4km/hr (23.27L/min, 20.09 - 26.37) walking. Our findings suggest the metabolic demands of singing may contribute to the health and wellbeing benefits attributed to 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. KP was supported by the Imperial College Clinician Investigator Scholarship. DF was supported by the Wellcome Trust [205407/Z/16/Z]. The funders had no say in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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, RejuvenAir system treatment for individuals with chronic bronchitis in COPD is safe, feasible, well tolerated, and resulted in clinically meaningful improvements in multidimensional measures of cough, sputum production, breathlessness and quality of life https://bit.ly/30KBfPs

Introduction: Chronic bronchitis (CB) is a phenotype of chronic obstructive pulmonary disease characterised by bronchial epithelial hyperplasia. Metered cryospray (MSC) (RejuvenAir® system) is a novel, bronchoscopic treatment that utilises titrated sprays of liquid nitrogen to enact controlled epithelial ablation, triggering the regeneration of bronchial tissue from pulmonary progenitors. Objective: To investigate the effect of MCS on human bronchial epithelium gene expression in patients with CB. Methods: Endobronchial brushings were collected from subjects at baseline and at 3-months post-MCS (n=7). The relative expression of 4 genes associated with remodelling: MUC5AC, TP63, S100A4 and TGFB1, was assessed by RT-qPCR. SGRQ and 6MWT were performed at baseline and at 3, 6, 9 and 12 months post-MCS. Results: The relative expression of MUC5AC (p=0.02), TP63 (p=0.02), S100A4 (p=0.03) and TGFB1 (p=0.02) were increased at 3-months post-MCS, relative to baseline. Significant improvement in 6MWT was demonstrated over the regime period (p=0.0043). Significant reduction in SGRQ total score was demonstrated over the regime period (p=0.0143). Significant reduction in SGRQ symptom score was recorded at 12 months relative to baseline (-19.9 points; p=0.031). Conclusions: The expression of genes associated with epithelial remodelling were increased at 3-months post-MCS, indicating epithelial repopulation continues far longer than traditionally considered. In conjunction with the significant improvement found in clinical parameters, the changes in gene expression potentially allude to the post-MCS repopulated epithelium expressing a reduced phenotypic aberrancy.

Rationale: Chronic bronchitis (CB) is characterized by productive cough with excessive mucus production, resulting in quality-of-life impairment and increased exacerbation risk. Bronchial rheoplasty uses an endobronchial catheter to apply nonthermal pulsed electrical fields to the airways. Preclinical studies have demonstrated epithelial ablation followed by regeneration of normalized epithelium. Objectives: To evaluate the feasibility, safety, and initial outcomes of bronchial rheoplasty in patients with CB. Methods: Pooled analysis of two separate studies enrolling 30 patients undergoing bilateral bronchial rheoplasty was conducted. Follow-up through 6 months (primary outcome) and 12 months included assessment of adverse events, airway histology, and changes in symptoms using the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test and St. George’s Respiratory Questionnaire (SGRQ). Measurements and Main Results: Bronchial rheoplasty was performed in all 30 patients (63% male; mean [SD] age, 67 [7.4]; mean [SD] postbronchodilator FEV1, 65% [21%]; mean [SD] COPD Assessment Test score 25.6 [7.1]; mean [SD] SGRQ score, 59.6 [15.3]). There were no device-related and four procedure-related serious adverse events through 6 months, and there were none thereafter through 12 months. The most frequent nonserious, device- and/or procedure-related event through 6 months was mild hemoptysis in 47% (14 of 30) patients. Histologically, the mean goblet cell hyperplasia score was reduced by a statistically significant amount (P

Introduction: Increasing CPAP makes breathing out difficult leading to air trapping. This can be uncomfortable and limit CPAP device use. We have studied lung mechanics pressures with CPAP and non-invasive ventilation (NIV) and abdominal muscle activity (EMG) to identify if there are changes with CPAP. Methods: We studied 10 normal male subjects sitting at rest and measured mouth pressure Pmo, oesophageal pressure Poes, gastric pressure Pga, trans-diaphragmatic pressure Pdi and ΔPdi, and abdominal EMG with surface electrodes during and after CPAP at 5,10, and 15 cmH2O and NIV,15/5cm H2O with a NIPPY3 ventilator. Results: Mean Pmo increases with CPAP, less than indicated on NIPPY3 settings, 5=4.2cmH2O, 10=8.8cmH2O, 15=13.1cmH2O, NIV 4.3cmH2O. Poes and Pga increase with CPAP and NIV and fall after CPAP/NIV ceases: 10-8.9cmH2O P Conclusion: We have shown CPAP increases trans-pulmonary pressure. Abdominal expiratory muscle activity increased with CPAP of 15 may assist expiration. This is similar to changes in expiratory muscle activity with external expiratory load (EJM Campbell ) J. Physiol. 1957,136,563. It is unlikely that fall in Pga when CPAP is removed versus before CPAP is due to abdominal wall relaxation as EMG activity is similar. Increased abdominal EMG may show the point at which CPAP leads to active expiration to counter air trapping non-invasively.

Background: No current medication counteracts the excessive mucus secretion or reverses the airway metaplasia of Chronic Bronchitis (CB) in COPD. Metered Cryospray (RejuvenAir® System) is a novel procedure delivering liquid N2 to the bronchial airways to target mucus overproduction, ablate abnormal epithelium, reduce chronic airway inflammation and promote regeneration of a healthy mucosal lining. Methods: This is a prospective, multicenter single-arm study of CB patients with an FEV1 of 30-80% predicted. Primary outcomes were safety and feasibility; secondary outcomes, SGRQ and 6MWT, were measured. Results: We included 35 subjects with Gold Grade II (31.4%) and III (68.6%) COPD (mean age 67.2+7.0 years, FEV1% 50.2±14.5, 54% male). Full treatment was accomplished of intended lobes with median times of 34 (right lower), 30 (left lower) and 41 minutes (upper lobes + trachea) during 3 separate outpatient visits. Approximately 1800 doses of MCS were delivered without inducing pneumothorax or unanticipated device-related serious adverse events (SAEs). Efficacy data showed clinically meaningful improvements of SGRQ-symptom score of -9.5±22.0 (95% CI; -17.7 to -1.3; p=0.025), SGRQ-impact score of -10.2±19.4 (95% CI: -17.5 to -3.0; p=0.007) and SGRQ-total score of -7.9±16.8 (95% CI: -14.2 to -1.6; p=0.008); most pronounced when baseline SGRQ-total ≥50 points (n=19). 6MWT significantly improved by 28 meters (95% CI: 3.0 to 62.0; Wilcoxon signed rank, p=0.034; n=25). Conclusions: These data indicate MCS treatment is safe, feasible and associated with clinically significant improvements in health-related quality of life in COPD patients with CB over 9 months.