We seek to better quantify each step of the aerosol generation, deposition and clearance processes to underpin the measurement of exposure and biologically active doses.
The research further seeks to place human dose in context with in vitro models of disease, placing the relative dose concentrations, durations and positions in context.
Being able to align doses in humans with validated in vitro disease models should also produce useful data to help develop more useful risk assessment models.
Tobacco smoke is a complex, dynamic medium with droplets of a mixture of organic chemicals, suspended in a mixture of gases and organic vapours. These droplets are produced in a very concentrated cloud with up to 1012 particles generated per cigarette - typically between 100 and 250nm in diameter which is less than the wavelength of visible light.
These properties mean the aerosol is continually changing, with droplets colliding and growing, and with complex vapour-particle equilibria, allowing evaporation and condensation.
The formation of a smoke aerosol is a complex process:
Size measurement of tobacco smoke has been a significant challenge and has often been limited by measurement technology. This has tended to lead to a compromise where the aerosol to allowed to age to a point where it is temporally stable - or has been diluted - so that coagulation is no longer significant.
Particle size is typically defined as a log-normal distribution with a median diameter or d50 - that is 50% of the particles measured are less than the median value and 50% are greater than the median value. The other defining characteristic of the log-normal distribution is its width, defined as the geometric standard deviation.
The figure below shows normalised cumulative frequency plot for tobacco smoke aerosol from four replicates of two different cigarette types with median diameter represented at the d50 (50th percentile) point and the geometric standard deviation of the distribution defined by relative width at the d16 and d84 percentile points. The geometric standard deviation (σg) equals the square root of the (d84 /d16) ratio and is typically 1.6-1.8 for mainstream smoke.
In practice, the d50 may be defined by different physical properties of the aerosol such as number, surface area, volume or mass. This will give different diameter values for the same aerosol, but can often be a useful tool in determining which property of the aerosol behaviour is dominant.
The small diameter of particles in tobacco smoke means the behaviour is driven by Brownian motion, suggesting the number - or count median diameter (CMD) - is of principal interest.
Fresh smoke droplets are generally accepted to be smaller than the wavelength of visible light, limiting the effectiveness of light scattering technologies. But reproducible measurements have been carried out by a series of authors and reported in the scientific literature with results typically between 180nm and 240nm.
Similarly, the small size means transport properties are driven by Brownian motion, compromising measurements using standard aerosol impaction technologies. A new generation of low pressure impactors with improved size resolution has recently become available, although values are yet to appear in the scientific literature.
The images below show aluminium foil-covered impaction stages from the Electrical Low Pressure Impactor (ELPI : Dekati, Finland) showing collection of tar aerosol at different size cut-points in the range from 36 – 10000nm and the internal cascade impactor, with each stage electrically isolated allowing size distributions to be measured by mass or electrical mobility.
Particle diameter can also be measured using electrical mobility technologies at very high dilution factors. Measurement technology has significantly advanced, and this is the method that we currently use for smoke aerosol measurement.
The figure below shows the operating principle of the Electrical Mobility Spectrometer with charged particles of known charge : mass ratio deflected to a series of insulated isolated electrometers each representing a sub-size fraction of the smoke.
We used the Cambustion DMS-500 Fast Mobility Spectrometer (Cambustion, Cambridge, UK), which offers a size resolution from 10 to 1000nm across 32 channels, with a time resolution of 100ms. It has allowed us to measure smoke within 200ms of it leaving the end of the cigarette, using a combined smoke engine-diluter at 50:1 dilution ratios.
Initial studies were conducted with square-wave flow profiles and clean air dilution (Matter Engineering MD-19E, Wohlen, Switzerland). But more recent measurements have used the smoke vapour phase as diluent and regulatory bell-shaped flow profiles or true measured human profiles (Cambustion Smoking Cycle Simulator, Cambridge, UK) [ 1 ].
The screenshot below from Smoking Cycle Simulator shows compliance of a replicated puff with an original SA7 measurement. Simultaneous measurement of electrical mobility diameter is seen in the background.
These new electrical mobility techniques offer the ability to reproducibly discriminate particle size diameter puff by puff. Early puffs contain larger particles due to longer coagulation time in the tobacco and filter rod. This size discrimination can also be measured where different flows are generated through the cigarette.
Aerosol sizes from the ISO smoking regime can be larger than those from the higher flow Canadian and Massachusetts regimes. Similarly, increased filter ventilation reduces the flow through the rod, and can increase both residence time and particle size [ 2 ].
Measured particle diameters are therefore dependent on cigarette design and smoking behaviour, with flow through the rod being a controlling factor. A series of cigarettes of different ventilations - smoked under flow conditions of the ISO regime of 1.05 l per min - give count median diameters of between 190 and 270nm [ 2 ].
A different batch of cigarettes which used a series of measured human smoking profiles at higher flows gave count median diameters from 138 to 180nm [ 3 ].
The evolving particle size is of particular importance because it is a key factor in where and how efficiently smoke and its components are deposited in the respiratory tract. It may also alter the subsequent rate of clearance of the smoke particle and its constituents.
The principal physical behaviours governing particle deposition in the lung include:
Interception and electrostatics are the other significant methods for particle deposition in the lung but are not considered important for tobacco smoke aerosol.
The size of the tobacco aerosol allows it to penetrate the alveolar region of the lung, although the highest doses per unit surface area will typically occur in the upper airways.
The accurate measurement of exhaled particle size is an important new area of research. It allows an understanding of the cumulative behaviour of the aerosol in the lung and applies a boundary condition for modelling of aerosol behaviour.
Current measurements using electrical mobility spectrometry show exhaled particle diameters ranging from 215 to 275nm CMD and, in the sample set, where inhaled particle diameters ranged from 138 to 180nm CMD .
This boundary with more than 95% of particles less than 500nm CMD supports the hypothesis that particle deposition in the lung is driven by sedimentation and Brownian motion processes. It is an important early step in building a coherent model of aerosol dosimetry for tobacco smoke.