A glimpse in post-COVID pathophysiology: the role of exhaled breath condensate pH as an early marker of residual alveolar inflammation.

BACKGROUND: Residual alveolar inflammation seems to be paramount in post-COVID pathophysiology. Currently, we still lack a reliable marker to detect and track alveolar phlogosis in these patients. Exhaled Breath Condensate (EBC) pH has robust evidences highlighting its correlation with lung phlogosis in various diseases. We aim to define the reliability of alveolar and bronchial EBC pH in the assessment and in the follow up of post-COVID-related inflammation. RESEARCH DESIGN AND METHODS: We enrolled 10 patients previously hospitalized due to COVID-19 pneumonia. We performed a complete follow-up after 3 months and 6 months from discharge. Each visit included routine blood tests, arterial blood gas analysis, 6-minute walking test, spirometry, diffusing capacity and body plethysmography. Finally, bronchial and alveolar EBC were collected at the end of each visit. RESULTS: Alveolar EBC pH was significantly lower than bronchial EBC pH at T1, alveolar EBC pH tended to be more acid after 3 months from hospital discharge compared to the same sample 6 months later. Serum inflammatory biomarkers showed no significant differences from T1 to T2. Alveolar EBC pH was positively correlated with neutrophil-lymphocyte ratio. CONCLUSIONS: Collecting EBC pH could help to understand pathophysiologic mechanism as well as monitoring alveolar inflammation in the post-COVID syndrome.

Laminar flow ventilation system to prevent airborne infection during exercise in the COVID-19 crisis: A single-center observational study.

Particulate generation occurs during exercise-induced exhalation, and research on this topic is scarce. Moreover, infection-control measures are inadequately implemented to avoid particulate generation. A laminar airflow ventilation system (LFVS) was developed to remove respiratory droplets released during treadmill exercise. This study aimed to investigate the relationship between the number of aerosols during training on a treadmill and exercise intensity and to elucidate the effect of the LFVS on aerosol removal during anaerobic exercise. In this single-center observational study, the exercise tests were performed on a treadmill at Running Science Lab in Japan on 20 healthy subjects (age: 29±12 years, men: 80%). The subjects had a broad spectrum of aerobic capacities and fitness levels, including athletes, and had no comorbidities. All of them received no medication. The exercise intensity was increased by 1-km/h increments until the heart rate reached 85% of the expected maximum rate and then maintained for 10 min. The first 10 subjects were analyzed to examine whether exercise increased the concentration of airborne particulates in the exhaled air. For the remaining 10 subjects, the LFVS was activated during constant-load exercise to compare the number of respiratory droplets before and after LFVS use. During exercise, a steady amount of particulates before the lactate threshold (LT) was followed by a significant and gradual increase in respiratory droplets after the LT, particularly during anaerobic exercise. Furthermore, respiratory droplets ≥0.3 µm significantly decreased after using LFVS (2120800±759700 vs. 560 ± 170, p<0.001). The amount of respiratory droplets significantly increased after LT. The LFVS enabled a significant decrease in respiratory droplets during anaerobic exercise in healthy subjects. This study's findings will aid in exercising safely during this pandemic.

Spatiotemporal droplet dispersion measurements demonstrate face masks reduce risks from singing.

COVID-19 has restricted singing in communal worship. We sought to understand variations in droplet transmission and the impact of wearing face masks. Using rapid laser planar imaging, we measured droplets while participants exhaled, said 'hello' or 'snake', sang a note or 'Happy Birthday', with and without surgical face masks. We measured mean velocity magnitude (MVM), time averaged droplet number (TADN) and maximum droplet number (MDN). Multilevel regression models were used. In 20 participants, sound intensity was 71 dB for speaking and 85 dB for singing (p < 0.001). MVM was similar for all tasks with no clear hierarchy between vocal tasks or people and > 85% reduction wearing face masks. Droplet transmission varied widely, particularly for singing. Masks decreased TADN by 99% (p < 0.001) and MDN by 98% (p < 0.001) for singing and 86-97% for other tasks. Masks reduced variance by up to 48%. When wearing a mask, neither singing task transmitted more droplets than exhaling. In conclusion, wide variation exists for droplet production. This significantly reduced when wearing face masks. Singing during religious worship wearing a face mask appears as safe as exhaling or talking. This has implications for UK public health guidance during the COVID-19 pandemic.

Characterization of Aerosol Generation During Various Intensities of Exercise.

BACKGROUND: Characterization of aerosol generation during exercise can inform the development of safety recommendations in the face of COVID-19. RESEARCH QUESTION: Does exercise at various intensities produce aerosols in significant quantities? STUDY DESIGN AND METHODS: In this experimental study, subjects were eight healthy volunteers (six men, two women) who were 20 to 63 years old. The 20-minute test protocol of 5 minutes rest, four 3-minute stages of exercise at 25%, 50%, 75%, and 100% of age-predicted heart rate reserve, and 3 minutes active recovery was performed in a clean, controlled environment. Aerosols were measured by four particle counters that were place to surround the subject. RESULTS: Age averaged 41 ± 14 years. Peak heart rate was 173 ± 17 beat/min (97% predicted); peak maximal oxygen uptake was 33.9 ± 7.5 mL/kg/min; and peak respiratory exchange ratio was 1.22 ± 0.10. Maximal ventilation averaged 120 ± 23 L/min, while cumulative ventilation reached 990 ± 192 L. Concentrations increased exponentially from start to 20 minutes (geometric mean ± geometric SD particles/liter): Fluke >0.3 µm = 66 ± 1.8 → 1605 ± 3.8; 0.3-1.0 µm = 35 ± 2.2 → 1095 ± 4.6; Fluke 1.0-5.0 µm = 21 ± 2.0 → 358 ± 2.3; P-Trak anterior = 637 ± 2.3 → 5148 ± 3.0; P-Trak side = 708 ± 2.7 → 6844 ± 2.7; P-Track back = 519 ± 3.1 → 5853 ± 2.8. All increases were significant at a probability value of <.05. Exercise at or above 50% of predicted heart rate reserve showed statistically significant increases in aerosol concentration. INTERPRETATION: Our data suggest exercise testing is an aerosol-generating procedure and, by extension, other activities that involve exercise intensities at or above 50% of predicted heart rate reserve. Results can guide recommendations for safety of exercise testing and other indoor exercise activities.

The effect of respiratory activity, non-invasive respiratory support and facemasks on aerosol generation and its relevance to COVID-19.

Respirable aerosols (< 5 µm in diameter) present a high risk of SARS-CoV-2 transmission. Guidelines recommend using aerosol precautions during aerosol-generating procedures, and droplet (> 5 µm) precautions at other times. However, emerging evidence indicates respiratory activities may be a more important source of aerosols than clinical procedures such as tracheal intubation. We aimed to measure the size, total number and volume of all human aerosols exhaled during respiratory activities and therapies. We used a novel chamber with an optical particle counter sampling at 100 l.min-1 to count and size-fractionate close to all exhaled particles (0.5-25 µm). We compared emissions from ten healthy subjects during six respiratory activities (quiet breathing; talking; shouting; forced expiratory manoeuvres; exercise; and coughing) with three respiratory therapies (high-flow nasal oxygen and single or dual circuit non-invasive positive pressure ventilation). Activities were repeated while wearing facemasks. When compared with quiet breathing, exertional respiratory activities increased particle counts 34.6-fold during talking and 370.8-fold during coughing (p < 0.001). High-flow nasal oxygen 60 at l.min-1 increased particle counts 2.3-fold (p = 0.031) during quiet breathing. Single and dual circuit non-invasive respiratory therapy at 25/10 cm.H2 O with quiet breathing increased counts by 2.6-fold and 7.8-fold, respectively (both p < 0.001). During exertional activities, respiratory therapies and facemasks reduced emissions compared with activities alone. Respiratory activities (including exertional breathing and coughing) which mimic respiratory patterns during illness generate substantially more aerosols than non-invasive respiratory therapies, which conversely can reduce total emissions. We argue the risk of aerosol exposure is underappreciated and warrants widespread, targeted interventions.

Negative-Pressure Isolation Mask for Endoscopic Examination During the Coronavirus Disease 2019 Pandemic: A Randomized Controlled Trial.

INTRODUCTION: During the coronavirus disease 2019 (COVID-19) pandemic, endoscopists have high risks of exposure to exhaled air from patients during gastroscopy. To minimize this risk, we transformed the oxygen mask into a fully closed negative-pressure gastroscope isolation mask. This study aimed to evaluate the effectiveness, safety, and feasibility of use of this mask during gastroscopy. METHODS: From February 28, 2020, to March 10, 2020, 320 patients undergoing gastroscopy were randomly assigned into the mask group (n = 160) or conventional group (n = 160). Patients in the mask group wore the isolation mask during gastroscopy, whereas patients in the conventional group did not wear the mask. The adenosine triphosphate fluorescence and carbon dioxide (CO2) concentration in patients' exhaled air were measured to reflect the degree of environmental pollution by exhaled air. Patients' vital signs, operation time, and adverse events during endoscopy were also evaluated. RESULTS: Four patients were excluded because of noncooperation or incomplete data. A total of 316 patients were included in the final analysis. The difference between the highest CO2 concentration around patients' mouth and CO2 concentration in the environment was significantly decreased in the mask group compared with the conventional group. There was no significant difference in the adenosine triphosphate fluorescence, vital signs, and operation time between the 2 groups. No severe adverse events related to the isolation mask, endoscopy failure, or new coronavirus infection during follow-up were recorded. DISCUSSION: This new isolation mask showed excellent feasibility of use and safety compared with routine gastroscopy during the COVID-19 pandemic.

Exhaled aerosol increases with COVID-19 infection, age, and obesity.

COVID-19 transmits by droplets generated from surfaces of airway mucus during processes of respiration within hosts infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. We studied respiratory droplet generation and exhalation in human and nonhuman primate subjects with and without COVID-19 infection to explore whether SARS-CoV-2 infection, and other changes in physiological state, translate into observable evolution of numbers and sizes of exhaled respiratory droplets in healthy and diseased subjects. In our observational cohort study of the exhaled breath particles of 194 healthy human subjects, and in our experimental infection study of eight nonhuman primates infected, by aerosol, with SARS-CoV-2, we found that exhaled aerosol particles vary between subjects by three orders of magnitude, with exhaled respiratory droplet number increasing with degree of COVID-19 infection and elevated BMI-years. We observed that 18% of human subjects (35) accounted for 80% of the exhaled bioaerosol of the group (194), reflecting a superspreader distribution of bioaerosol analogous to a classical 20:80 superspreader of infection distribution. These findings suggest that quantitative assessment and control of exhaled aerosol may be critical to slowing the airborne spread of COVID-19 in the absence of an effective and widely disseminated vaccine.

Human forced expiratory noise. Origin, apparatus and possible diagnostic applications.

Forced expiratory (FE) noise is a powerful bioacoustic signal containing information on human lung biomechanics. FE noise is attributed to a broadband part and narrowband components-forced expiratory wheezes (FEWs). FE respiratory noise is composed by acoustic and hydrodynamic mechanisms. An origin of the most powerful mid-frequency FEWs (400-600 Hz) is associated with the 0th-3rd levels of bronchial tree in terms of Weibel [(2009). Swiss Med. Wkly. 139(27-28), 375-386], whereas high-frequency FEWs (above 600 Hz) are attributed to the 2nd-6th levels of bronchial tree. The laboratory prototype of the apparatus is developed, which includes the electret microphone sensor with stethoscope head, a laptop with external sound card, and specially developed software. An analysis of signals by the new method, including FE time in the range from 200 to 2000 Hz and band-pass durations and energies in the 200-Hz bands evaluation, is applied instead of FEWs direct measures. It is demonstrated experimentally that developed FE acoustic parameters correspond to basic indices of lung function evaluated by spirometry and body plethysmography and may be even more sensitive to some respiratory deviations. According to preliminary experimental results, the developed technique may be considered as a promising instrument for acoustic monitoring human lung function in extreme conditions, including diving and space flights. The developed technique eliminates the contact of the sensor with the human oral cavity, which is characteristic for spirometry and body plethysmography. It reduces the risk of respiratory cross-contamination, especially during outpatient and field examinations, and may be especially relevant in the context of the COVID-19 pandemic.

Estimation of Viral Aerosol Emissions From Simulated Individuals With Asymptomatic to Moderate Coronavirus Disease 2019.

Importance: Individuals with asymptomatic or mild coronavirus disease 2019 (COVID-19) have been reported to frequently transmit the disease even without direct contact. The severe acute respiratory syndrome coronavirus 2 has been found at very high concentrations in swab and sputum samples from such individuals. Objective: To estimate the virus levels released from individuals with asymptomatic to moderate COVID-19 into different aerosol sizes by normal breathing and coughing, and to determine what exposure could result from this in a room shared with such individuals. Design, Setting, and Participants: This mathematical modeling study combined the size-distribution of exhaled breath microdroplets for coughing and normal breathing with viral swab and sputum concentrations as approximation for lung lining liquid to obtain an estimate of emitted virus levels. Viral data were obtained from studies published as of May 20, 2020. The resulting emission data fed a single-compartment model of airborne concentrations in a room of 50 m3, the size of a small office or medical examination room. Main Outcomes and Measures: Modeling was used to estimate the viral load emitted by individuals breathing normally or coughing, and the concentrations expected in the simulated room at different ventilation rates. Results: The mean estimated viral load in microdroplets emitted by simulated individuals while breathing regularly was 0.0000049 copies/cm3, with a range of 0.0000000049 to 0.637 copies/cm3. The corresponding estimates for simulated coughing individuals were a mean of 0.277 copies/cm3 per cough, with a range of 0.000277 to 36 030 copies/cm3 per cough. The estimated concentrations in a room with an individual who was coughing frequently were very high, with a maximum of 7.44 million copies/m3 from an individual who was a high emitter. However, regular breathing from an individual who was a high emitter was modeled to result in lower room concentrations of up to 1248 copies/m3. Conclusions and Relevance: In this modeling study, breathing and coughing were estimated to release large numbers of viruses, ranging from thousands to millions of virus copies per cubic meter in a room with an individual with COVID-19 with a high viral load, depending on ventilation and microdroplet formation process. The estimated infectious risk posed by a person with typical viral load who breathes normally was low. The results suggest that only few people with very high viral load pose an infection risk in poorly ventilated closed environments. These findings suggest that strict respiratory protection may be needed when there is a chance to be in the same small room with an individual, whether symptomatic or not, especially for a prolonged period.

COVID-19: minimising contaminated aerosol spreading during CPAP treatment.

BACKGROUND: The COVID-19 pandemic has raised concern for healthcare workers getting infected via aerosol from non-invasive respiratory support of infants. Attaching filters that remove viral particles in air from the expiratory limb of continuous positive airway pressure (CPAP) devices should theoretically decrease the risk. However, adding filters to the expiratory limb could add to expiratory resistance and thereby increase the imposed work of breathing (WOB). OBJECTIVE: To evaluate the effects on imposed WOB when attaching filters to the expiratory limb of CPAP devices. METHODS: Two filters were tested on three CPAP systems at two levels of CPAP in a mechanical lung model. Main outcome was imposed WOB. RESULTS: There was a minor increase in imposed WOB when attaching the filters. The differences between the two filters were small. CONCLUSION: To minimise contaminated aerosol generation during CPAP treatment, filters can be attached to expiratory tubing with only a minimal increase in imposed WOB in a non-humidified environment. Care has to be taken to avoid filter obstruction and replace filters as recommended.

Respiratory virus shedding in exhaled breath and efficacy of face masks.

We identified seasonal human coronaviruses, influenza viruses and rhinoviruses in exhaled breath and coughs of children and adults with acute respiratory illness. Surgical face masks significantly reduced detection of influenza virus RNA in respiratory droplets and coronavirus RNA in aerosols, with a trend toward reduced detection of coronavirus RNA in respiratory droplets. Our results indicate that surgical face masks could prevent transmission of human coronaviruses and influenza viruses from symptomatic individuals.

Airborne transmission of severe acute respiratory syndrome coronavirus-2 to healthcare workers: a narrative review.

Healthcare workers are at risk of infection during the severe acute respiratory syndrome coronavirus-2 pandemic. International guidance suggests direct droplet transmission is likely and airborne transmission occurs only with aerosol-generating procedures. Recommendations determining infection control measures to ensure healthcare worker safety follow these presumptions. Three mechanisms have been described for the production of smaller sized respiratory particles ('aerosols') that, if inhaled, can deposit in the distal airways. These include: laryngeal activity such as talking and coughing; high velocity gas flow; and cyclical opening and closure of terminal airways. Sneezing and coughing are effective aerosol generators, but all forms of expiration produce particles across a range of sizes. The 5-µm diameter threshold used to differentiate droplet from airborne is an over-simplification of multiple complex, poorly understood biological and physical variables. The evidence defining aerosol-generating procedures comes largely from low-quality case and cohort studies where the exact mode of transmission is unknown as aerosol production was never quantified. We propose that transmission is associated with time in proximity to severe acute respiratory syndrome coronavirus-1 patients with respiratory symptoms, rather than the procedures per se. There is no proven relation between any aerosol-generating procedure with airborne viral content with the exception of bronchoscopy and suctioning. The mechanism for severe acute respiratory syndrome coronavirus-2 transmission is unknown but the evidence suggestive of airborne spread is growing. We speculate that infected patients who cough, have high work of breathing, increased closing capacity and altered respiratory tract lining fluid will be significant producers of pathogenic aerosols. We suggest several aerosol-generating procedures may in fact result in less pathogen aerosolisation than a dyspnoeic and coughing patient. Healthcare workers should appraise the current evidence regarding transmission and apply this to the local infection prevalence. Measures to mitigate airborne transmission should be employed at times of risk. However, the mechanisms and risk factors for transmission are largely unconfirmed. Whilst awaiting robust evidence, a precautionary approach should be considered to assure healthcare worker safety.