Aerosol Particle Deposition in the Human Respiratory Tract AIRPOLIFE PhD Course Air Pollution and Health Copenhagen, 2

1. Aerosol Particle Deposition in the Human Respiratory Tract AIRPOLIFE PhD CourseAir Pollution and HealthCopenhagen, 21 March 2006 Erik Swietlicki Professor Division of Nuclear Physics, Lund University P.O. Box 118, SE-21100 Lund, Sweden Erik.Swietlicki@nuclear.lu.se

2. Co-workers Jakob Löndahl, Andreas Massling, Joakim Pagels, Jenny Rissler Steffen Loft, Elvira Vaclavik, Peter Vinzents

3. Advantages, disadvantages with epidemiology/toxicology, such as epi: quantifies effects, tox: understand mechanisms) Measurements of Dose is rarely performed in toxicology (Schliesinger 2005) – as we will see it sometimes makes huge differenceAdvantages, disadvantages with epidemiology/toxicology, such as epi: quantifies effects, tox: understand mechanisms) Measurements of Dose is rarely performed in toxicology (Schliesinger 2005) – as we will see it sometimes makes huge difference

4. Aerosol - Definition “A collection of liquid or solid particles suspended in a mixture of gases - normally air.”

5. Size range of aerosol particles The criterion of suspension determines the size range of aerosol particles:

6. One litre of urban air ... We inhale 10-25 m3 of air per day ca. 100 billion (1011) particles per day

9. Heat and humidify the inhaled air (Conditioning). Remove particles from the inhaled air by deposition (act as a filter). Clear away the deposited particles efficiently into the gastrointestinal tract (clearance via mucociliary escalator). Particles should ideally NOT reach the alveoli where the gas exchange takes place! Particles > 10 µm generally do not reach the alveoli (? PM10 standard).

17. Examples of non-spherical particles

18. Equivalent Particle DiameterRelates to the sedimentation velocity vTS

19. Particle Deposition in theHuman Respiratory Tract Relies on the same basic mechanisms as particle collection in a filter, but with different relative importance Filter: Fixed geometry, constant flow rate Respiratory system: Changing geometry, variable flow rate (also direction), dead volumes, high relative humidity

20. Particle Deposition Mechanisms Particles may deposit within the respiratory tract by five mechanisms: Inertial impaction Sedimentation (settling) Diffusion Interception Electrostatic precipitation Particles that contact the airway walls are not reentrained.

21. Air flows through bends. Particles leave their original flow line due to their inertia, and impact on the airway walls. Stopping distance increases with particle size (proportional to d2) Most important in large airways (large velocities, bifurcations) Most deposition on mass basis.

22. Particles settle by gravitation onto the airway walls. Most important in smaller airways and the alveoli (low flow velocities, small airway dimensions), and horizontally oriented airways. Settling velocity proportional to d2

23. Particles leave their original flow lines by diffusion and deposit onto the airway walls. Most important deposition mechanism for particles < 0.5 µm. Governed by geometric, not aerodynamic particle diameter Most important in smaller airways (short distances, long residence time). Displacement from flow line proportional to ?(1/d).

24. Without deviating from their original flow lines, particles contact the airway surface because of their physical size. Long fibres: Small aerodynamic particle diameter, large in one dimension.

25. Charged particles are attracted towards the airway walls by the electrostatic image charges they induce in the airway surface. Unipolar charged aerosols with high number concentrations repel each other and drive particles towards the walls. Ambient aerosols normally in charge equilibrium (Bolzmann). Normally not important. Only for freshly generated (and charged) aerosols, for instance from nebulizers.

26. Total Particle Deposition in the Respiratory Tract

27. All values are means with standard deviations, when available. Particle diameters are aerodynamic (MMAD) for those > 0.5 µm and geometric (or diffusion equivalent) for those < 0.5 µm. Modified from Schlesinger (1989).

28. The inhaled air never flows into the alveoli. Gas exchange takes place by molecular diffusion over the last millimeter. Inhaled submicrometer-sized particles should therefore not deposit efficiently in the alveolar region, since settling is low and their diffusion is orders of magnitude slower than for gas molecules. Alveolar deposition is controlled by their transfer from inhaled (tidal) air to the reserve air ? enough time.

29. Factors governing the dose of inhaled particles to the respiratory tract: Exposure concentration Exposure duration Respiratory tract anatomy Breathing pattern Particle properties (e.g., particle size, shape, density, hygroscopicity, and solubility in airway fluids and cellular components). Besides particle size, breathing pattern (tidal volume, breathing frequency, route of breathing, length of pause between inhalation and exhalation) is the most important factor affecting lung deposition.

30. Breathing Pattern

32. Total deposition fraction as a function of particle size in 22 healthy men and women under six different breathing patterns. For each breathing pattern, the total deposition fraction is different (p < 0.05) for two successive particle sizes. Vt is tidal volume (mL); Q is respiratory flow rate (mL/s); T is respiratory time (s); and f is breathing frequency in breaths/min (bpm).Jacques and Kim (2000).

36. Total deposition DF (ICRP) Inhalable Fraction IF ICRP Deposition Model

37. Regional Deposition - Deposited Fraction Deposited Fraction for the head airways DFHA For the tracheobronchial region DFTB For the alveolar region DFAL

41. Köhler theory for cloud droplet formation

43. Transient EffectsParticle Hygroscopic Growth

47. Measurements performed in Lycksele, northern Sweden, where large PM2.5 levels have been measured due to domestic wood combustion, especially during cold periods in the winter. The different sites are selected as source specific (background=Vindeln, traffic=Central site, The other places=domestic burning). The meteorology is not favourable for good ventilation, the city is trapped in a valley, often stable conditions in wintertime in northern Sweden.Measurements performed in Lycksele, northern Sweden, where large PM2.5 levels have been measured due to domestic wood combustion, especially during cold periods in the winter. The different sites are selected as source specific (background=Vindeln, traffic=Central site, The other places=domestic burning). The meteorology is not favourable for good ventilation, the city is trapped in a valley, often stable conditions in wintertime in northern Sweden.

48. Forsdala – Particle sampling

49. Hygroscopic properties (H-TDMA) Dry size=265 nm Residential area with wood combustionForsdala, Lycksele, Sweden 2002 Rena salter?Rena salter?

52. Lung Deposition MeasurementsRESPI instrument

53. RESPI

54. DMPS – huvud saken H-TDMA – elle ranna kemiska bestämning Fördel med H-TDMA: * tidsupplösning, * olika moder – external mixtures DMPS – huvud saken H-TDMA – elle ranna kemiska bestämning Fördel med H-TDMA: * tidsupplösning, * olika moder – external mixtures

56. RESPI Accuracy

57. Previous measurements of deposition of ultrafine particles

58. Our Measurements 30 subjects (21 men, 9 women) both rest and exercise both hydrophobic and hygroscopic particles

59. Largest number of subjects (prev. 18) First measurement of respiratory deposition of hygroscopic particles during spontanous breathing (and exercise) Large size interval (15-300 nm) Lung function tested Most complete study of respiratory deposition of ultrafine particles in healthy human subject.

60. Inter-subject variabilityDEHS Oil Particles

61. Mean values

62. Rest/Exercise

63. ICRP Deposition Model

65. NaCl DEHS

67. Poor Wood CombustionExposure Chamber – Umeå University

69. Particle sizing Evaporation: Fractions of particles can evaporate at body temperature depending on their chemical composition. Coagulation: Particles can coagulate during the measurement period depending on their concentration. Restructuring: Particles can restructure while being exposed to high relative humidity in the human airways depending on their state of agglomeration. Hygroscopic growth: Particles will grow in size while being exposed to high relative humidity in the human airways depending on their chemical deposition.

70. Positive size-shift (5 %)

71. Error because of size-shift(between the dry diameters)

72. Sketch of the H-TDMA-system first DMA to select a quasi-monodisperse fraction of aerosol particles from a polydisperse aerosol population in combination with a first CPC (I) a conditioning system increasing the relative humidity in the sheath air flow and aerosol flow to a well defined level (II) an analyzer consisting of a second DMA in conjunction with a second CPC (III)

73. H-TDMA-system Specification DMA1 size range: Dp = 20 - 300nm Aerosol RH range: between 20 and 95% Sheath air RH range: between 20 and 95% DMA2 size range: Dp = 20 - 700nm Derived parameters Hygroscopic growth factor: wet diameter / dry diameter Number fraction: peak area of one mode / peak area of entire distribution Mixing state: internal / external

75. Total deposition DF (ICRP) Inhalable Fraction IF Inhalability of particles

76. Regional Deposition

77. Total DepositionA particle entering our respiratory system is subject to all the deposition mechanisms described previously. The actual deposition efficiency of a given particle size has been determined experimentally. Several models have been developed to predict the deposition based on experimental data. Two advanced and widely used ones are those developed by the International Commission on Radiological Protection (ICRP) and the National Council on Radiation Protection and Measurement (NCRP). The total deposition fraction (DF) in the respiratory system according to ICRP model is

78. Total deposition DF (ICRP) Inhalable Fraction IF Inhalability of particles