Value

Respiratory Protection

ID 50 Value

Infection Risk

1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1

00 10 20 30 40 50 60 70 µα α = 10= 10

→

µα α = 2.0= 2.0

→

µα α = 0.1= 0.1

→

4637_book.fm Page 76 Thursday, May 25, 2006 3:58 PM

Airborne Pathogens: Selection of Respiratory Protection 77

respirator. Next, a N95 FF could readily permit 5% of the inspired air volume to enter the respirator through small leaks around the face seal perimeter; none of the pathogens in this air leakage would be removed in the process. The overall pathogen penetration into the respirator is a volume-weighted average of the penetration through the face seal leaks and through the filter. Given the values offered (5% air entry through face seal leaks with 100% pathogen penetration, and 95% air entry through the filter with 0.5% pathogen penetration), the overall penetration value is 5.5%, of which the great majority (90%) is due to face seal leakage:

Overall % Penetration = + = 5.5%

The Assigned Protection Factor and Average Penetration

The degree of exposure reduction due to respirator use has traditionally been summarized by the assigned protection factor (APF), which is the inverse of the assumed overall penetration (a fraction between 0 and 1) into the respirator. For the N95 FF class, NIOSH recommends APF = 10, which signifies that the assumed overall penetration is 1÷10 = 0.1 (or 10%).¹⁴ However, a recent analysis of data collected from various workplace studies in which half-mask respirator penetration was mea- sured while subjects performed their normal job duties indicates that APF = 5 is more appropriate for the N95 FF and other halfmask respirators. ¹⁵ In addition, the μP parameter in Equation 4.5 is better estimated by 0.4 × (1÷APF). The reason involves the variability in respirator penetration from wearing to wearing, and the manner in which an APF value is statistically derived.¹⁶

In brief, respirator penetration values are thought to vary lognormally across different wearing periods, and the APF is usually equated with the inverse of the 95th percentile of the penetration values. However, the computation of unconditional infection risk properly involves the average penetration value, which is less than the 95th percentile penetration value.

If one assumes that the lognormal distribution of respirator penetration values has a geometric standard deviation value of 2, the mean penetration value is 0.4 times the 95th percentile penetration value.

Table 4.2 lists suggested APF values, along with the corresponding μP

values equal to 0.4 × (1÷APF), for several types of respirators that might be used by healthcare workers. Figure 4.2 depicts the reduction in infection risk afforded by three types of respirators across a range of pathogen ID50

values from 0.7 (μ_α = 0.99) to 70 (μ_α =.01), given that the expected dose (.05)×(100%)

Faceseal Penetration

( .0 95)×( . %)0 5 Filter Penetration

4637_book.fm Page 77 Thursday, May 25, 2006 3:58 PM

78 Emerging Infectious Diseases

without respiratory protection is μD = 10. The three respirator types are:

(1) a N100 half-mask filtering face piece, APF = 5; (2) a full face piece equipped with N100 filters, APF = 50; and (3) a hooded powered air purifying respirator equipped with high efficiency filters, APF = 1000.

Clearly, the higher the respirator’s APF value (the lower the μP value), the lower the risk of infection. Whether any of the three respirators in the Figure 4.2 scenario is deemed “adequate” depends on the acceptable risk of infection for the pathogen involved.

Estimating Exposure Intensity

Of the three input factors in Equation 4.5 (μD, μP, μ_α), the most uncertain value is the expected exposure intensity μD. For a given type of exposure scenario (for example, healthcare worker entry into a room to attend a patient), μD can vary across pathogens, across patients, across time for the same patient, across different procedures performed on the patient, and across ventilation conditions. However, it is possible to make a first pass exposure estimate if one is willing to make assumptions or has some measurement data available. Exposure estimates involving coughing by a patient and a laboratory accident are discussed below.

A Coughing Patient Cough Particles

A cough emits several hundred particles of saliva fluid that span a wide range of sizes. Table 4.3 list the average number of particles in different Table 4.2 Suggested Assigned Protection Factors and the Corresponding μμμμP

Value for Different Classes of Respirator Devices that Could Be Used in the Healthcare Environment

Class of Respirator

Assigned Protection

Factor

Mean Penetration

Value, μP Source Half-mask filtering-face piece filter types

N95, N99, and N100

5 .08 17

Half-mask elastomeric face piece filter types N95, N99, and N100

5 .08 18

Full elastomeric facepiece filter type N100 50 .008 19 Hooded powered air-purifying with high

efficiency respirator filter used in the pharmaceutical industry

1000 .0004 20

4637_book.fm Page 78 Thursday, May 25, 2006 3:58 PM

Airborne Pathogens: Selection of Respiratory Protection 79

diameter ranges emitted per cough. The original data were collected by Louden and Roberts, ²¹ and were used by this author and colleagues to examine the risk of airborne infection due to pathogens carried by respirable particles. ²² The term respirable refers to particles with aerody- namic diameters < 10 μm, which can reach and deposit in the alveolar region of the lungs. In contrast, “inspirable” particles have aerodynamic diameters in the range 10 μm to 100 μm; these larger particles do not reach the alveolar region, but can be inspired and deposit in the thoracic and head airways regions of the respiratory tract.

A brief explanation of Table 4.3 is as follows. The observed (reported) particle diameter ranges are listed in columns 3 and 4. Because emitted respiratory particles rapidly lose water by evaporation, the observed diameters are assumed to be approximately one-half the original diame- Figure 4.2 The unconditional infection risk computed by Equation 4.5 for an expected dose of 10 pathogens across a range of ID50 values from 0.7 (μμμμαααα = 0.99) to 70 (μμμμαααα =.01), given the alternative use of: (1) no respirator; (2) a half-mask N100 filtering-facepiece respirator; (3) a full face piece respirator with N100 filters; and (4) a hooded powered air-purifying respirator with high efficiency filters (equivalent to N100 filters).

ID

₅₀

Value

Infection Risk

0 10 20 30 40 50 60 70 µ_P= .08= .08

Halfmask Halfmask

→

µ_P= .008= .008 Fullface

Fullface

→

µ_P= .0004= .0004 PAPR

PAPR

→

No Respirator No Respirator

→ 10⁰

10^-1

10^-2

10^-3

10^-4

10^-5

4637_book.fm Page 79 Thursday, May 25, 2006 3:58 PM

80 Emerging Infectious Diseases

ters.²³ Therefore, columns 1 and 2 list the original particle diameter values, denoted d₀. The observed particle diameters listed in columns 3 and 4 are denoted deq, because it is assumed that the observed particle sizes were at equilibrium (water loss due evaporation equaled water gain due to condensation). The quantity in column 5 is the mean initial volume (cm³) of a particle in a given size range, based on the assumption that particle diameters were uniformly distributed across the size range. Column

Table 4.3 Characteristics of the Respiratory Particles Emitted in the Average Cough

d_0,min

μm d_0,max

μm d_eq,min

μm d_eq,max

μm cm³

Mean Number Particles

Number of Pathogens per Particle^a

2 5.81 1 2.9 3.8 × 10⁻⁵ 121 3.8 × 10^–5

5.8 11.6 2.9 5.8 3.8 × 10⁻¹⁰ 100 3.8 × 10⁻⁴ 11.6 17.4 5.8 8.7 1.7 × 10^–9 6.2 1.7 × 10^–3 17.4 22.4 8.7 11.2 4.2 × 10^–9 3.3 4.2 × 10^–3 22.4 52 11.2 26 3.1 × 10^–8 18 3.1 × 10^–2

52 112 26 56 3.2 × 10^–7 64 3.2 × 10^–1

112 170 56 85 1.5 × 10^–6 58 1.5 × 10⁰

170 228 85 114 4.2 × 10^–6 31 4.2 × 10⁰

228 288 114 144 9.1 × 10^–6 20 9.1 × 10⁰

288 346 144 173 1.7 × 10^–5 12 1.7 × 10¹

346 406 173 203 2.8 × 10^–5 5.3 2.8 × 10¹ 406 464 203 232 4.3 × 10^–5 4.3 4.3 × 10¹ 464 524 232 262 6.3 × 10^–5 3.5 6.3 × 10¹ 524 582 262 291 8.9 × 10^–5 2.7 8.8 × 10¹ 582 700 291 350 1.4 × 10^–4 5.0 1.4 × 10² 700 878 350 439 2.6 × 10^–4 0.50 2.6 × 10² 878 1172 439 586 5.8 × 10^–4 5.0 5.8 × 10² 1172 1468 586 734 1.2 × 10^–3 1.8 1.2 × 10³ 1468 1762 734 881 2.2 × 10^–3 1.3 2.2 × 10³ 1762 2058 881 1029 3.7 × 10^–3 0.33 3.7 × 10³ 2058 2352 1029 1176 5.6 × 10^–3 0.67 5.6 × 10³ 2352 2942 1176 1471 9.8 × 10^–3 1.7 9.8 × 10³ 2942 3532 1471 1766^b 1.8 × 10^–2 0.67 1.8 × 10⁴

a Expected number of pathogens per particle with volume = standard- ized to C_F = 1 × 10⁶ mL⁻¹.

b The reported range was > 1471 μm. To assign an expected number of pathogens per particle, the upper range limit was set at 1491 μm + 295 μm

= 1766 μm. The 295 μm increment equals the span of the preceding diam- eter range.

v₀

v0

v0 4637_book.fm Page 80 Thursday, May 25, 2006 3:58 PM

Airborne Pathogens: Selection of Respiratory Protection 81

6 lists the average number of particles emitted per cough in each size range; these are based on data collected for a total of 90 coughs from three subjects. Column 7 lists the expected number of pathogens carried by a single particle in each size range, based on the assumption that the viable pathogen concentration in the saliva aerosolized by coughing, denoted CSal, equals 1 × 10⁶ mL⁻¹. The value in column 7 is the product of the value in column 5 and 1 × 10⁶ mL⁻¹.

The Pathogen Emission Rate

The emission rate into air of respirable and inspirable pathogens, denoted G (# hr⁻¹), is modeled as the product of the patient’s coughing rate, denoted E (# hr⁻¹), the respirable or inspirable particle fluid volume per cough, denoted VF (mL), and the viable pathogen concentration in saliva CSal (# mL⁻¹):

G = E × VF × CSal (4.6)

Based on the Table 4.3 data, it is estimated that the respirable and inspirable particle fluid volumes emitted per cough are, respectively, 6 × 10⁻⁸ mL and 2 × 10⁻⁴ mL. However, the health status of the subjects involved in the Louden and Roberts study was not reported. ²⁴ The author suspects that the subjects did not have respiratory tract infections, and that the cited particle fluid volumes per cough underestimate the true values for patients with respiratory tract infections and more productive coughs.

A study by Louden and Brown on a series of pulmonary tuberculosis (TB) and pneumonia patients reported the coughing rates summarized in Table 4.4.²⁵ It is evident that patients can vary by an order of magnitude in their coughing rate. For most pathogens, there are no available quan- titative measurements of viable organism concentrations in saliva or other respiratory fluids. However, for Mycobacterium tuberculosis (M. tb), a study by Yeager et al., measured viable M. tb bacilli concentrations in the saliva and sputum of 22 pulmonary tuberculosis patients.²⁶ For M. tb in saliva, the range was 1 × 10² mL⁻¹ to 6 × 10⁵ mL⁻¹, with an average of 7

× 10⁴ mL⁻¹. For M. tb in sputum, the range was 6.6 × 10⁴ mL⁻¹ to 3.4 × 10⁷ mL⁻¹, with an average of 8.4 × 10⁶ mL⁻¹.

Given the differences in cough rate, the orders-of-magnitude range in pathogen concentrations in saliva and other respiratory fluids (as indicated by the M. tb bacilli data), and likely differences in the particle fluid volume per cough among respiratory disease patients, a wide range of pathogen emission rates is to be expected. It is reasonable to infer that individuals termed “superspreaders” (as used in the recent SARS literature) or “dan- gerous disseminators” (as used in the older TB literatur e) are those

v₀

4637_book.fm Page 81 Thursday, May 25, 2006 3:58 PM

82 Emerging Infectious Diseases

infrequently encountered persons with high values for the factors E, C_Sal, and/or V_F, such that their pathogen emission rates are very much higher than average.

Pathogen Removal Pathways

Particle-associated pathogens emitted into room air are removed by exhaust ventilation, by particle settling due to gravity, and by pathogen death due to environmental stress. Each loss mechanism can be quantified by a fractional removal rate with the unit of inverse time, for example, hr⁻¹. If room air were perfectly mixed, the fractional removal rate due to exhaust ventilation denoted λvent (hr⁻¹) would equal the room supply air rate denoted Q (m³ hr⁻¹) divided by the room volume denoted V_room (m³).

However, room air is seldom if ever perfectly mixed, and if the HCW were in close proximity to the patient (the pathogen emission source), λvent would be closer to 0.5 × (Q ÷ Vroom).

The fractional removal rate due to particle settling denoted λsettle (hr⁻

1) is the particle terminal settling velocity denoted V_TS (m hr⁻¹) divided by the height of the room denoted H (m).²⁷ In turn, a particle’s settling velocity depends on its aerodynamic diameter. Because particles of dif- ferent sizes are emitted in a cough, in theory one needs to separately consider all pertinent particle sizes. However, if the concern is primarily with respirable pathogens, a representa-tive particle size can be taken as an aerodynamic diameter of 4.5 μm, for which VTS = 2.2 m hr⁻¹. If the room height were 8 feet, then H = 2.44 m, and λsettle = (2.2 m hr⁻¹) ÷ (2.44 m) = 0.90 hr⁻¹.

The fractional removal rate due to pathogen die off denoted λdieoff (hr⁻

1), varies with the pathogen and environmental conditions. In general, Table 4.4 The Coughing Rate Among 96

Pulmonary Tuberculosis Patients and 48 Pneumonia Patients

Pulmonary TB

Coughs hr⁻⁻⁻⁻¹ (%)

Pneumonia (%)

< 1.5 34/96 (35%) 3/48 (6.3%) 1.5 to 3 15/96 (16%) 4/48 (8.3%) 3 to 6 12/96 (13%) 4/48 (8.3%) 6 to 12 18/98 (18%) 8/48 (17%) 12 to 24 9/98 (9.2%) 15/48 (31%) 24 to 48 6/98 (6.1%) 13/48 (27%)

> 48 2/98 (2.0%) 1/48 (2.1%)

4637_book.fm Page 82 Thursday, May 25, 2006 3:58 PM

Airborne Pathogens: Selection of Respiratory Protection 83

there is little information available on the die off rates of airborne patho- gens. Airborne M. tb bacilli exhibit a fractional die off rate of 0.12 hr⁻¹. The Airborne Concentration and Inhaled Dose

Given values for G, λvent, λsettle, λdieoff and Vroom, the estimated steady state concentration of respirable pathogens in room air, denoted CSS (# m⁻¹), is:

CSS = (4.7)

The expected number of pathogens that deposit in the respiratory tract is the product of the airborne concentration CSS, the healthcare worker’s breathing rate denoted B (m³ hr⁻¹), the healthcare worker’s duration of exposure denoted T (hr), and the fraction of inspired particles that deposit in the respiratory tract denoted fdep. Therefore, the expected dose is given by:

μD = C_SS × B × T × fdep (4.8) A Hypothetical Example — Consider a scenario in which a healthcare worker attends a patient with a viral respiratory tract infection for a total of T = 4 hours. The patient has 20 productive coughs per hour, or E = 20 hr⁻¹. Perhaps based on polymerase chain reaction analysis of saliva, it is estimated that CSal = 1.0 × 10⁷ mL⁻¹. Due to the productive coughing, the respirable particle fluid volume is VF = 3.0 × 10⁻⁷ mL. For these input factors, the respirable pathogen emission rate is G = 60 hr⁻¹. Assume that the patient room is 15 ft × 15 ft × 8 ft such that Vroom = 50 m³, and receives 6 nominal air changes per hour of dilution supply air such that Q = 300 m³ hr⁻¹. For these Vroom and Q values, λvent = 0.5 × (300 m³ hr⁻¹) ÷ (50 m³) = 3.0 hr⁻¹. If the focus is on respirable pathogens, λsettle = 0.90 hr⁻¹, as previously computed. Assume the airborne pathogen die off rate is λdieoff = 0.69 hr⁻¹, which signifies a 1-hour pathogen half life in air. Based on Equation 6, CSS = 0.26 m⁻³ for this set of input factors. Next, assume that the healthcare worker’s breathing rate is 1.2 m³ hr⁻¹, as estimated for an adult performing light work.²⁸ About 20% of 4.5-μm particles in an inhaled air volume will deposit in the alveolar region, although 90% overall will deposit in the respiratory tract. If the target site for infection is the alveolar region, then f_dep = 0.2, and based on Equation 4.7, μD = 0.25 pathogens. If the target site for infection is the entire respiratory tract, then fdep = 0.9 and μD = 1.12 pathogens.

G

vent settle dieoff Vroom

λ +λ +λ

( )

^×

4637_book.fm Page 83 Thursday, May 25, 2006 3:58 PM

84 Emerging Infectious Diseases

Based on Equation 4.3, if the virus has infectivity parameter μ_α =.069 (ID50 = 10), and if the alveolar region is the target site with μD = 0.25, the healthcare worker’s infection risk is.017 (1.7%). In the alternative, if the entire respiratory tract is the target site with μD = 1.12, the healthcare worker’s infection risk is.074 (7.4%). Wearing a half-mask filtering face piece respirator with APF = 5 (μP =.08) would reduce infection risk to 1.4

× 10⁻³ (0.14%) if the alveolar region is the target site, and to 6.2 × 10⁻³ (0.62%) if the entire respiratory tract is the target site. Wearing a hooded powered air-purifying respirator with APF = 1000 (μP = 4.0 × 10⁻⁴) would reduce these respective infection risks to 6.9 × 10⁻⁶ (.00069%) and 3.9 × 10⁻⁵ (.0039%). The choice of respirator device depends on the level of infection risk one is willing to accept. In the author’s view, the powered air-purifying respirator should be used.

A Laboratory Accident

The Airborne Concentration and Inhaled Dose — An accident such as dropping a culture tube can release a very large number of pathogen-containing particles into the air. If the pathogens rapidly disperse throughout room air, the initial airborne concentration, denoted C₀ (# m⁻

3), is the product of the volume of material aerosolized denoted V_M (mL), and the pathogen concentration in the material denoted CM (# mL⁻¹), divided by the room volume Vroom (m³):

(4.9)

Similar to the previous coughing patient scenario, pathogens will be removed from room air by exhaust ventilation, by particle settling due to gravity, and by death due to environmental stress. Assuming there is no further release of pathogens into room air, the pathogen concen- tration over time, C(t), will decrease in a manner approximated by the expression:

C(t) = C0 × (4.10)

If an individual spends T hours in the room (where T would likely be less than one hour) immediately subsequent to the release, the average exposure over the T-hr interval, denoted Caverage, is given by:

C V C

V

M M

room

0= ×

e^{−(λvent+λsettle+λdieoff)×t}

4637_book.fm Page 84 Thursday, May 25, 2006 3:58 PM

Airborne Pathogens: Selection of Respiratory Protection 85

Caverage = (4.11)

In turn, the expected dose is given by:

μD = Caverage × B × T × fdep (4.12)

A Hypothetical Example — Consider a scenario in which 5 mL of a liquid culture containing viable pathogens at C_M = 1 × 10⁸ mL⁻¹ drops onto the floor of a laboratory, and 0.01% of the fluid is aerosolized into particles with aerodynamic diameters of 10 μm. An individual will spend 15 minutes in the laboratory cleaning up the spill in a manner that will presumably not cause additional pathogens to become airborne. Assume the room has volume 100 m³ and receives 10 nominal air changes per hour such that Q = 1,000 m³ hr⁻¹. Based on Equation 4.8, the initial airborne pathogen concentration is C₀ = 5 × 10² m⁻³. Even though the laboratory air is not perfectly mixed, the lack of an ongoing point source of emission means that λvent = Q ÷ Vroom = 10 hr⁻¹. For a 10-μm aerodynamic diameter particle, VTS = 10.8 hr⁻¹. If the room height is H = 3 m, λsettle = V_TS ÷ H = 3.6 hr⁻¹. Assume the airborne pathogen death rate is λdieoff = 0.69 hr⁻¹, which signifies a 1-hour pathogen half life in air.

Based on Equation 4.10, if C0 = 5 × 10² m⁻³ and T = 0.25 hr, Caverage = 136 m⁻³. For a 10-μm aerodynamic diameter particle, fdep is approximately 0.8, where deposition is primarily in the head airways region. Assume that the breathing rate is B = 1.2 m³ hr⁻¹. Based on Equation 4.11, the expected dose is μD = 33 pathogens. If μ_α = 0.069 (ID50 = 10) and the target site for infection is the entire respiratory tract, infection risk is 0.9 (90%).

As one might suspect, this high risk level requires a highly protective respirator. Wearing a hooded powered air-purifying respirator with APF

= 1000 (μP = 4.0 × 10⁻⁴) would reduce infection risk to 1.3 × 10⁻² (1.3%), which is still substantial. Either a more protective supplied-air respirator needs to be used, or entry into the room should be delayed until the airborne pathogen concentration declines to a lower level. According to the latter strategy, one can use Equation 4.9 to find a suitable waiting time Twait; the predicted concentration C(Twait) would become the new starting concentration value in Equation 10. For example, if C₀ = 5 × 10² m⁻³ and T_wait = 0.5 hr, the airborne pathogen concentration C(0.5 hr) = 0.39 m⁻³ (which is a 99.98% reduction from the initial concentration). If an individual entered the room at this point and was present for 15 minutes (T = 0.25 hr), the new C_average = 0.11 m⁻³, the new μD = 0.026 pathogens, and the new infection risk without respirator use is 1.8 × 10^–3.

C

T ⁰ e

vent settle dieoff

vent sett

×

(

^λ +^λ +^λ

)

^{× −⎡⎣1 −(λ +λ lle+λdieoff)×T⎤⎦}

4637_book.fm Page 85 Thursday, May 25, 2006 3:58 PM

86 Emerging Infectious Diseases

For this exposure, even use of a N95 FF (μP = 0.08) might be deemed adequate because infection risk would be reduced to 1.4 × 10⁻⁴ (0.014%).

On the other hand, if there is potential for aerosolization of more pathogens during clean up activities, a more protective respirator should be considered.