key: cord-0894805-e2qkoc5g
authors: Therkorn, Jennifer; Drewry III, David; Pilholski, Thomas; Shaw‐Saliba, Kathryn; Bova, Gregory; Maragakis, Lisa L.; Garibaldi, Brian; Sauer, Lauren
title: Impact of air‐handling system exhaust failure on dissemination pattern of simulant pathogen particles in a clinical biocontainment unit
date: 2018-10-05
journal: Indoor Air
DOI: 10.1111/ina.12506
sha: 68f5f637e43c53eb37ef81749dff9a5d78368e07
doc_id: 894805
cord_uid: e2qkoc5g

Biocontainment units (BCUs) are facilities used to care for patients with highly infectious diseases. However, there is limited guidance on BCU protocols and design. This study presents the first investigation of how HVAC (heating, ventilation, air‐conditioning) operating conditions influence the dissemination of fluorescent tracer particles released in a BCU. Test conditions included normal HVAC operation and exhaust failure resulting in loss of negative pressure. A suspension of optical brightener powder and water was nebulized to produce fluorescent particles simulating droplet nuclei (0.5‐5 μm). Airborne particle number concentrations were monitored by Instantaneous Biological Analyzers and Collectors (FLIR Systems). During normal HVAC operation, fluorescent tracer particles were contained in the isolation room (average concentration = 1 × 10(4) ± 3 × 10(3)/L(air)). Under exhaust failure, the automated HVAC system maximizes airflow into areas adjacent to isolation rooms to attempt to maintain negative pressure differential. However, 6% of the fluorescent particles were transported through cracks around doors/door handles out of the isolation room via airflow alone and not by movement of personnel or doors. Overall, this study provides a systematic method for evaluating capabilities to contain aerosolized particles during various HVAC scenarios. Recommendations are provided to improve situation‐specific BCU safety.

ventilation in the spread of airborne pathogens is of utmost importance for protecting the public's health.

Air ventilation in healthcare environments presents unique challenges due to the collocation of patients, visitors, and healthcare workers because some of them may be infectious and/or immunocompromised.

Highly infectious diseases (HIDs) are defined as viral and bacterial infections that are easily transmissible, cause serious life-threatening illness, have no or few treatment options, and pose a threat to the general public. 8 Patients suspected or confirmed to be infected by HIDs require care in isolation rooms or specialized biocontainment areas in hospitals to prevent exposure of healthcare workers, visitors, and other patients to the person with the HID. 9 Standard and transmissionbased isolation precautions to prevent contact with the patient and their droplet secretions (eg, mucus from sneezing or coughing) include the use of personal protective equipment (PPE), such as gloves, masks, gowns, and eye protection. 10, 11 In addition to the use of PPE, airborne transmission-based precautions include special air-handling and ventilation systems, such as negative-pressure airborne infection isolation rooms (AIIRs), to prevent the dissemination of airborne droplet nuclei or small particles to areas where noninfected individuals are present, and to remove airborne pathogens by air filtration. 10, 11 When a patient infected with a respiratory pathogen coughs or sneezes, thousands of droplets are expelled, ranging in size from ~0.05 to 500 μm; the majority of these particles range in size from 10 to 100 μm. 12, 13 The smaller range of droplets can rapidly desiccate to form droplet nuclei (ie, particles ≤5 μm in diameter) that can contain infectious pathogens. [11] [12] [13] [14] Droplet nuclei are assumed to have such low settling velocities that this results in extended airborne suspension times, on the order of hours, resulting in particle transport over long distances (eg, >1 m). 12, 15 This long-distance aerosol dissemination is mainly determined by airflow patterns in the built environment as generated by ventilation systems and movement of personnel. 15 Previous research has illustrated the potential for widespread airborne dissemination within a hospital driven by the building's air ventilation systems, including nosocomial outbreaks of MERS and SARS. 16, 17 One type of specialized healthcare environment, a clinical biocontainment unit (BCU), is designed to care for patients infected with HIDs and incorporates specialized environmental controls and isolation protocols to prevent pathogen transmission. In response to the 2014-2015 Ebola virus disease (EVD) outbreak, Johns Hopkins Medicine created a BCU by redesigning and renovating existing clinical space. 18 The Johns Hopkins BCU (JH-BCU), along with nine others around the United States, were funded by the

(ASPR) to serve as Regional Ebola and other Special Pathogen Treatment Centers (RESPTCs). These centers have enhanced capabilities to care for patients and offer fully contained routine laboratory diagnostics and testing of bio-specimens from patients infected with or suspected to be infected with high-consequence pathogens, such as viral hemorrhagic fevers and highly drug resistant Mycobacterium tuberculosis (TB). 18, 19 Similar to other BCUs, the JH-BCU includes the capability to isolate airborne pathogen transmission via negatively pressurized patient rooms and a negative pressure laboratory space. 18 While general guidance was provided to aid RESPTCs by defining the minimum requirements needed for treating patients, such as private patient rooms with their own bathrooms, there was no specific guidance provided on engineering or HVAC (heating, ventilation and air-conditioning) design needs to maintain airborne pathogen isolation within those rooms. 20 Guidelines are available from the Centers for Disease Control and Prevention (CDC) and the American Society of Heating, Refrigerating and Air-Conditioning Engineers (ASHRAE) for preventing transmission of airborne pathogens, such as TB, in healthcare settings, 11,21 but there are currently no guidelines specific to BCUs. Furthermore, there are no formal, mandated guidelines for BCU design, construction, and capabilities; therefore, specifications vary among the facilities, and there are no data to date examining the efficiency of any BCU environment to maintain isolation of airborne infectious particles. 8, 22, 23 Practical Implications • A systematic method is provided for using fluorescent tracer particles to characterize the isolation capabilities of a clinical biocontainment unit (BCU) under two different HVAC (heating, ventilation, air-conditioning) operating conditions: normal operation and loss of negative pressure due to HVAC exhaust failure.

• During normal HVAC operation, there were no tracer particles detected outside of the patient isolation room suggesting that the patient room's negative pressure differential and exhaust vents operated sufficiently to maintain airborne isolation conditions.

• However, during HVAC exhaust failure, while the patient room still contained the majority of the contaminated air, ~6% of fluorescent tracer particles were detected in areas adjacent to the patient isolation room suggesting that the current protocols used by the HVAC automation system to increase airflow into these adjacent spaces during emergency loss of exhaust capabilities is insufficient to maintain complete airborne isolation conditions.

• Since it is hypothesized that particles were transported out of the patient room through cracks in the doors and door handles, it should be further investigated how to improve the seal on these doors to improve the airborne isolation capabilities.

• Further investigation is needed to identify safe BCU protocols that can be used during the emergency loss of negative pressure, such as required use of respiratory personal protective equipment in all areas of the BCU.

Recently, Drewry et al 24 presented a study to investigate the potential for healthcare worker (HCW) exposure to simulant airborne pathogens while working in the JH-BCU. The goal was to develop a safe and effective method that could be used by BCUs to evaluate potential failure points of PPE to reduce the risk of exposure to infectious particles. The objective of this study was to provide the first investigation of a BCU's ability to contain aerosolized simulant fluorescent pathogen particles under different F I G U R E 1 (A) An illustration of the Johns Hopkins Hospital biocontainment unit (JH-BCU) depicting room types. Red areas are the three patient rooms, labeled rooms 1-3, and the laboratory space for processing samples (room 4). There is a dedicated space for putting on personal protective equipment (PPE) (ie, donning) which is shared by patient rooms 1 and 2 (room 5), as well as a shared donning space between patient room 3 and the laboratory (room 6). Each of the red spaces have areas for removal of PPE (ie, doffing), labeled as the yellow rooms 7-10. Area 11 is a nurses' station. All green areas do not require the use of PPE according to the JH-BCU standard protocols while red areas do require PPE. For more details, see Garibaldi et al 18 (B) Overview of the JH-BCU space with the number of air changes per hour per room during normal HVAC (heating, ventilation, air-conditioning) operation, and the directional movement of personnel between spaces to minimize risk for contamination of clean zones (arrows). (C) Locations in the JH-BCU for the release of fluorescent tracer particles from the Collison nebulizer ("CN" in figure), and eight IBAC (Instantaneous Biological Analyzer and Collector, FLIR Systems) sensors for detecting and measuring fluorescent particle concentrations and dissemination pattern. The IBAC locations in order include: (1) patient room, (2) PPE doffing room, (3-6) hallway, (7) PPE donning room, and (8) nurses' station HVAC operating conditions. These experiments were conducted to investigate the airborne isolation capabilities of a JH-BCU patient room in the absence of any HCW movement or activity; that is, particle dissemination via airflow patterns alone. Considering the number of BCUs currently in operation (there are currently 11), the lack of formal guidelines for BCU safety controls, and the everpresent threat of naturally or intentionally spread HIDs, 23 there is a critical need for systematic research addressing the safety of BCU facilities and protocols. The methodologies presented below provide a testing framework that can be used across multiple BCU facilities and other indoor air environments to evaluate dispersion patterns and minimize the risk for exposure to and transmission of airborne pathogens.

The air-handling system of the JH-BCU was designed based on the airborne precautions guidance documents of the CDC and ASHRAE for preventing transmission of airborne particles containing infectious microorganisms in general healthcare settings. 11, 21 Figure 1A illustrates the different rooms and areas in the JH-BCU. Figure 1B presents the overview of the JH-BCU space, the number of air changes per hour (ACH) per room (black numbers) during normal operation, and the relative directional flow of personnel between rooms to minimize the risk for contamination of clean spaces (arrows). The main goal of the air-handling system design is to maintain the contaminated spaces of the JH-BCU (ie, the patient rooms and laboratory) at negative pressure relative to the rest of the JH-BCU and the general hospital; this is intended to prevent aerosol escape from these rooms and removes airborne pathogens by filtration. 9 The JH-BCU uses the main hospital's building supply air, but the entire JH-BCU is operated under a high efficiency particulate air (HEPA) filtered exhaust system that is separate from the general exhaust system for the rest of the hospital building. The exhaust system has two fans to maintain negative pressure in the patient rooms and laboratory, and each of these fans can operate independently in the case that one fails. Only one fan runs at a given time to operate the connected total airflow to maintain the appropriate negative In this study, three repeat trials were conducted for both HVAC test conditions. The exhaust failure trials were conducted by coordinating with the facility manager to turn off the JH-BCU HEPA exhaust system. As described above, the exhaust system has two fans; both fans were off during the exhaust failure trials. According to the exhaust failure standard operating protocol of the JH-BCU, this results in automatic shut off of the building supply air to the areas of the JH-BCU that are assumed to be contaminated (ie, the three patient rooms, laboratory, and the dirty side of the autoclave room) in order to reduce further disruption of the pressure differentials. The air-handling system's automation system maximizes airflow to the clean areas of the JH-BCU by increasing supply air to these clean areas to push particles from the rest of the unit toward the contaminated areas. In addition, an emergency backup power supply provides power to ductless cooling/heating units in the patient rooms; these units can be operated by the staff to maintain air circulation and provide comfort. During the exhaust failure trial, the effect of turning off the ductless cooling/heating units in the patient room was also investigated to observe how this influenced particle dissemination and transport. a remote switch so that the pattern of particle dissemination was not disturbed by test operator movement. The suspension was replaced in the Collison nebulizer before every new repeat trial. The temperature and relative humidity of the JH-BCU ranged from 20-22°C and 37%-40%, respectively, throughout testing.

The rationale for using the selected suspension to produce the tracer particles was fourfold. First, the use of optical brightener powder is a cost-effective option at a cost of $0.40/g of powder.

Second, the nebulized particles are fluorescent allowing for feasible real-time tracing of the airborne particle number concentrations and dissemination patterns using fluorescent aerosol sensors as described below. Third, the optical brightener powder is a safe, nontoxic material approved for release into public environments by the U.S. Department of Homeland Security. 32 Fourth, the size of particles produced by nebulizing the suspension range from 0.5 to 5 μm, with the highest number concentration of particles being ~1 μm aerodynamic diameter ( Figure 2 ). As defined by the World Health Organization, droplet nuclei are ≤5 μm in diameter. 14 Thus, the resultant particle number size distribution produced by nebulizing the suspension was representative of infectious respiratory aerosols that can be transmitted as droplet nuclei via the airborne route through breathing, talking, coughing, or sneezing. 13 

The particle number size distribution for the nebulized fluorescent suspension was investigated before conducting testing. For detailed explanation of the chamber setup used to conduct these measurements, see Ratnesar-Shumate et al 33 Briefly, the optical brightener/urea/water suspension was nebulized using a Sono-Tek ultrasonic atomizer (nozzle power setting = 3 watts, liquid injection rate = 100 μL/min) (Sono-Tek Corporation, Milton, NY, USA). The particles were allowed sufficient time to desiccate to a core particle size in aerosol capacitance chambers, well-mixed using a high chamber flowrate (2500 L/min), and sampled isokinetically to measure particle size and number concentration using a UVAPS (Ultraviolet Aerodynamic Particle Sizer, Model 3314, TSI Inc., Shoreview, MN, USA). While a Sono-Tek atomizer was used for chamber measurements, the Collison nebulizer was used during the JH-BCU experiments due to its ease of transport and setup. Also, since the experimental repeats conducted in the JH-BCU monitored particle dissemination for 20-min post-nebulization, chamber desiccation was used during the measurements of the suspension's particle number size distribution to mimic aerosol aging; thus, the nebulized particles were dried to a solid, core size to simulate droplet nuclei. 34 Further, as described below in results, nebulization of the fluorescent suspension by the Collison nebulizer during experiments at the JH-BCU was found to produce a particle number size distribution with 82.3% ± 0.8% of the particles in the 0.5 to 1.7 μm size range.

In comparison, the particle number size distribution produced by the Sono-Tek atomizer resulted in 87.4% ± 2.5% of particles in the 0.5 to 1.7 μm size range. Therefore, the chamber measurements of the fluorescent suspension's particle number size distribution are The particles are binned into two size categories: 0.5-1.7 and 1.7-10 μm. 36 The IBACs used in this study were within calibration, and particle concentration, particle sizing, and fluorescence were confirmed to be within tolerance prior to conducting testing using fluorescent polystyrene latex spheres of known size (2 μm, Thermo Scientific, Waltham, MA, USA).

As illustrated in Figure 1C HCWs, to represent areas of concern for where staff may be most likely present.

The IBACs were run continuously throughout all trials and control experiments. Following the five-min nebulization of tracer particles, the IBACs recorded fluorescent particle concentrations for 15 min after the Collison nebulizer was turned off. Therefore, each trial represents a total of 20 min. It was predetermined that this time was sufficient during normal HVAC operation for allowing the level of fluorescent particles in the JH-BCU to return to background levels before beginning the next trial. During the exhaust failure trials, the exhaust of the JH-BCU air-handling system was turned back on after the 20-min observation time and allowed to run for at least 20 min to clear the particles from the previous trial; the IBACs were used to ensure that conditions returned to background fluorescent particle levels before beginning the next test run.

Before releasing tracer particles and taking trial measurements, Across repeat trials, the peak number concentration occurred in the patient room within 2 min after the start of nebulization, and the fluorescent particle concentration began to decrease after the Collison nebulizer was stopped at minute five ( Figure 4A ). The particle sizes detected by the IBACs indicated that 82.3% ± 0.8% of the nebulized fluorescent particles were in the 0.5 to 1.7 μm IBAC size bin. The average airflow in the patient room and the donning room throughout normal HVAC operating conditions was 425 ± 3 m 3 /h and 234 ± 2 m 3 /h, respectively. It should be noted that the JH-BCU system does not measure average airflow in the doffing room.

The JH-BCU is designed to maintain the patient rooms and laboratory at a negative pressure differential compared to the other areas of the BCU of at least −5 Pa. 18 Under normal HVAC operating conditions, it was observed that the negative pressure differential threshold of -5 Pa was maintained between the patient room and donning space ( Figure 5 ). However, the patient room to doffing space corridor had a measured pressure differential that was slightly higher than the desired value (−4 Pa ± 0.4 Pa) and the pressure differential between the doffing space and the hallway corridor was about half the JH-BCU target value for sufficient containment of airborne infectious particles (−2 Pa ± 0.1 Pa). It should also be noted that the average pressure differential measured between the doffing space and hallway corridor of −2 Pa is higher than the CDC recommended pressure differential for negative pressure areas of at least −2.5 Pa. 25 F I G U R E 4 Average fluorescent particle concentration (particles/L, average ± 1SD) measured by each of the Instantaneous Biological Analyzers and Collectors (IBACs, FLIR Systems, Elkridge, MD) that detected fluorescent particle concentrations as determined after subtracting the fluorescent particle background concentration (ie, 81/L). Data are presented as concentration vs. time (min) post fluorescent tracer particle release for (A) normal HVAC (heating, ventilation, air-conditioning) operation (n = 3 repeat trials) and (B) HVAC exhaust failure condition (n = 3 repeat trials). The Collison nebulizer was run for 5 min and then turned off while the IBACs were run for 20 and 40 min, respectively, for the two test scenarios. For scenario (B), after 20 min, the HVAC exhaust system was turned back on to reduce fluorescent particle levels in the Johns Hopkins biocontainment unit (JH-BCU) back to background levels before beginning the next trial. The dotted line in both figures represents the time when the Collison nebulizer was turned off to stop fluorescent particle nebulization. The second dotted line in the Figure 4B These doors are not used when a patient is present and are taped off to alert HCWs not to enter/exit through these doors.

Supply/outlet vent placement near patients has been suggested to be a better predictor for the removal of airborne bacteria in isolation rooms than air change rate alone. 41, 42 For example, previous research has shown that ceiling level exhausts are more efficient than floor level exhausts for removing fine respiratory particles in hospital isolation rooms. 27 

During the HVAC exhaust failure trials, the average recorded patient room airflow was reduced by 96% to 17 ± 5 m 3 /h, while the average recorded donning room airflow was similar to normal HVAC operation (238 ± 3 m 3 /h). The design of the JH-BCU air-handling system is such that the loss of exhaust capabilities results in maximization of supply airflow to the clean areas of the JH-BCU; this is meant to force the air, and therefore any present aerosols, toward the patient rooms and laboratory. Thus, shutting down the exhaust system resulted in reduced airflow in the patient room, but not in the donning room adjacent to the patient room.

As illustrated in Figure 3 , the exhaust failure condition resulted in transport of particles from the patient room where the fluorescent particles were released into the doffing room and certain hallway locations (IBAC locations 2, 4, and 5 in Figure 1C ). In the patient room, the average fluorescent particle number concentration was measured as 3 × 10 4 ± 2 × 10 3 /L with a maximum peak concentration of 7 × 10 4 ± 1 × 10 4 /L (Figure 3 ). This peak occurred after about 1 min from the start of the Collison nebulizer ( Figure 4B ). One minute after detecting the appearance of fluorescent particles in the patient room, a smaller peak of fluorescent particles was observed in the doffing space (Figures 3 and 4B ; average = 4 × 10 3 ± 9 × 10 2 /L, maximum peak = 9 × 10 4 ± 2 × 10 4 /L). This is in contrast to the normal HVAC conditions during which the released fluorescent tracer particles were contained in the patient room.

These results suggest that approximately 6% of the fluorescent particles detected in the patient room were transported into the F I G U R E 5 Relative pressure (Pa, average ± 1SD) recorded between rooms of the Johns Hopkins biocontainment unit (JH-BCU) vs HVAC (heating, ventilation, air-conditioning) test condition. The data represent continuous 10-min averages recorded by the JH-BCU pressure sensors throughout each HVAC condition (normal HVAC operation: n = 29, exhaust failure: n = 10, exhaust failure (no cooling/heating unit): n = 4) doffing space, and <1% may have been transported to the hallway.

The total volume of the patient room, doffing room, and corridor space is 109.4, 54.7, and 328.1 m 3 , respectively. To estimate the percentage of the total number of particles that were transported out of the patient room, the average particle number concentrations detected by each of the IBACs throughout the exhaust failure trials were multiplied by their total room volume to estimate the number of particles in each location (ie, patient room, doffing room, and hallway). Assuming that the sum of all particle counts across the JH-BCU space was the total number of particles released, the percentages of the total that were transported out of the patient room and into the doffing space and hallway corridor were calculated. It was also assumed that the airborne particle number concentrations detected by the IBACs in each location was representative of that entire room, and that the rooms were well mixed. For the hallway, an average was calculated across the multiple IBACs located there.

Maximum peak particle counts in the hallway reached 5 ± 8/L and the presence of fluorescent particles was detected by the IBACs intermittently between 5 and 15 min from the start of the Collison nebulizer ( Figure 4B ). This represents a potential risk of airborne pathogen exposure for HCWs since respiratory PPE is removed in the doffing room and is not worn elsewhere in the JH-BCU, according to the JH-BCU protocols. For reference, Figure 1B illustrates which areas of the JH-BCU require the use of respiratory PPE (red zones), and Figure 1C illustrates the IBAC sensor locations. The yellow zones are where the PPE is removed, and the green zones are considered clean and do not require PPE. During the HVAC exhaust failure trials, tracer particles were detected outside of the patient room and in both yellow (doffing room, room #8 in Figure 1A , IBAC #2 in Figure 1C ) and green (hallway, IBAC #4 and #5 in Figure 1C) zones.

Drewry et al 24 also noted the presence of simulant pathogen particles in the JH-BCU doffing room following simulated patient care and doffing procedures. The key difference between the present study and the study of Drewry et al 24 is that there were no HCWs in the present study; that is, particle dissemination was observed as a result of airflow patterns alone while manipulating HVAC condition. Therefore, the potential for HCW exposure to airborne pathogens is of concern in the doffing room due to multiple potential scenarios for this contamination. Thus far, between the present study and Drewry et al, 24 these identified scenarios include HVAC exhaust failure, re-aerosolization of particles deposited on the outside of HCW's PPE during doffing, and/or particle transport from the patient room after opening the door between the two spaces.

The potential risk for an individual to acquire an infection depends partially on the dose of the inhaled pathogen, which is governed by the airborne pathogen concentration, the individual's breathing rate, and exposure duration in the room. 15, 44 For pathogens such as TB and variola (smallpox) virus, the infectious dose may be as low as a single microorganism. 44, 45 While it may seem unlikely for a patient to present with smallpox, the potential for F I G U R E 6 Layout plan for the patient room where the fluorescent tracer particles were released. The diagram indicates the following features: the relative locations for the doorways, direction of healthcare worker movement through these doors, patient bed and bathroom, HVAC (heating, ventilation air-conditioning) supply and exhaust vents, and the ductless cooling/heating units that staff utilize for comfort during an HVAC failure. The patient room has two exhaust vents which are located furthest from the doors and closest to the patient bed so that the net airflow of the patient room moves across the patient and exits while minimizing HCW exposure. This net airflow, illustrated by the blue arrow, has been qualitatively observed by the JH-BCU engineering team using smoke. The exhaust vents are each 0.3*0.2 m and approximately 0.3 m above the floor. The patient room has two supply air vents (0.2*0.2 m) located above two corridor doorways. These doors are not used when a patient is present and are taped off to alert HCWs not to enter/exit through these doors. Also depicted is the instrumentation used during experiments, including the IBAC sensor (FLIR Systems, Inc., Elkridge, MD) in the patient room (IBAC1) and the fluorescent particle release location from the 3-Jet Collison nebulizer (25 mL suspension, 138 kPa, 5 L/min; Mesa Laboratories, Inc., Butler, NJ). The room dimensions are as follows: length = 8.1 m, width = 5.4 m, height = 2.5 m (total room volume = 109.4 m 3 ) malicious use of infectious agents through bioterrorism, including variola virus, must be considered. 46, 47 Therefore, the identification for potential transport of the fluorescent tracer particles from the patient room to adjacent areas of the JH-BCU during HVAC failure warrants further investigation to identify methods and protocols that can be used during the emergency loss of negative pressure in the patient rooms. For example, during HVAC failure, the JH-BCU protocols can be updated to require the use of PPE and respirators in all areas of the unit. Future research will also investigate the potential for pathogen dissemination beyond the physical space of the JH-BCU into other areas of the hospital during different HVAC scenarios.

Because the IBACs that detected the presence of fluorescent tracer particles during the exhaust failure condition (IBAC locations 2, 4, and 5 in Figure 1C ) were located near patient room doorways, it is suspected that the particles were transported from the patient room into adjacent areas around the doors and door handles. This includes the two doorways that directly connect the patient room and hallway corridor. Therefore, even though these doors are not used when a patient is present, the presence of the doorways alone may be a potential source for particle leakage out of the patient room under HVAC exhaust failure.

During the exhaust failure condition, an average pressure differential was maintained between the patient room and the donning space of about −1 Pa ± 0.01 Pa ( Figure 5 ) and there were no fluorescent particles detected in the donning room. However, the donning space is also located on the opposite side of the room from where the tracer particles were released. On the other hand, the pressure differential between the patient room to the doffing space and the doffing space to the hallway corridor was close to zero (<−0.001 Pa to +0.05 Pa) ( Figure 5 ). This suggests that the exhaust failure emergency protocol of increasing airflow to the areas adjacent to the patient rooms was not sufficient enough to create a negative pressure differential between the doffing room and patient room. It should be investigated if further increasing the airflow into the doffing space can reestablish the negative pressure differential between the doffing room and patient room.

Also, since it is hypothesized that particles were transported out of the patient room through cracks in the doors, another recommendation to improve the airborne isolation capabilities of the patient rooms is to replace the hinged doors with sliding doors. 43 Previous research has demonstrated that opening doors can act as a mechanism by which infectious particles can be transported from airborne isolation rooms into adjacent spaces, particularly for hinged doors that open outward. 15, 48, 49 However, the doors in the present study were kept closed throughout all trials. Nevertheless, the influence of door cracks has been previously investigated as a means for particle transport from outdoors to indoors with particle penetration factor estimates of 0.8-1.0 for 1 μm diameter particles through window and door frame cracks in different types of buildings; the average air velocity through these cracks was estimated to be 0.3-2.2 m/s. 50 This is supported by laboratory studies which have also shown a penetration factor of 0.8-1.0 for 1 μm particles through horizontal cracks (0.5 mm high, 102 mm deep, 433 mm wide) under an applied pressure of 2 Pa across connected chambers. 51 Even though the pressure differential between the patient room and adjacent JH-BCU areas was less than that described in previous chamber studies, an air velocity of 1 m/s was observed in the present study moving in the direction out of the patient room through the cracks of the door handles which could facilitate particle transport (Velocicalc, Model 9515, TSI Inc., Shoreview, MN, USA).

Future research will further characterize the particle size-dependent penetration factors through the JH-BCU door handles under different HVAC operating conditions using monodispersed fluorescent particles of various sizes. Figure 5 ). However, the time of appearance of fluorescent particles in the doffing room was different between the two exhaust failure conditions with and without the ductless cooling/heating unit on. By shutting off the ductless cooling/heating unit, the time required for particles to transport from the patient room to the doffing space was increased by approximately 3 min ( Figure 7B ). It is hypothesized that the airflow of the ductless cooling/heating unit helped push particles into the doffing room when the patient room lost negative pressure. The ductless cooling/heating unit in the patient room as depicted in Figure 6 faces the doffing room door. Therefore, assuming the ductless cooling/heating units are necessary for maintaining the comfort of the patient and HCWs upon failure of the BCU central HVAC system, future research should investigate different placement locations for the cooling/heating unit away from locations that will promote particle transport out of the patient room.

In this study, we provide a systematic method for characterizing the isolation capabilities of a clinical BCU under two different HVAC F I G U R E 7 Time series plots for fluorescent tracer particle release as measured by the Instantaneous Biological Analyzers and Collectors (IBACs, FLIR Systems, Elkridge, MD) in the patient (IBAC1) and doffing rooms (IBAC2) during the exhaust failure condition during which the effect of turning off the ductless cooling/heating unit was investigated (n = 1 trial) vs exhaust failure with the cooling/heating units on (n = 3 repeat trials). During an exhaust failure of the HVAC (heating, ventilation, air-conditioning) system in the Johns Hopkins biocontainment unit (JH-BCU), the building supply air to the patient rooms is automatically turned off and a ductless cooling/heating unit in the patient rooms can be turned on to maintain air circulation and comfort. The dotted line in both figures represents the time when the Collison nebulizer was turned off to stop fluorescent particle nebulization

http://orcid.org/0000-0001-7742-9938

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Impact of air-handling system exhaust failure on dissemination pattern of simulant pathogen particles in a clinical biocontainment unit