Aerosol Particle Deposition in the Human Respiratory Tract AIRPOLIFE PhD Course Air Pollution and Health Copenhagen, 21

1. Aerosol Particle Deposition in the Human Respiratory TractAIRPOLIFE 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. Toxicological studies Epidemiological studies Linking Emissions to Health Effects Lung Deposition Emission Exposure Health effect Dose Concentration Dose to a target tissue depends on deposition and subseqent retention of the particles.

4. Aerosol - Definition “A collection of liquid or solid particles suspended in a mixture of gases - normally air.” An aerosol is a multi-phase system gas - liquid - solid

5. Size range of aerosol particles The criterion of suspension determines the size range of aerosol particles: Smallest particle: 1 nm (0.001 µm or 10-9 m) Largest particle: 100 µm (10-4 m) Spanning: 5 orders of magnitude in size 15 orders of magnitude in mass/volume !!

6. One litre of urban air ... … contains ca. 10 million particles (104 cm-3) We inhale 10-25 m3 of air per day ca. 100 billion (1011) particles per day Mass loading in polluted atmospheres ca. 100 µg/ m3 = ca. 1 mg/ day

7. The Human Respiratory Tract Head Airways Nasopharyngeal Humidification Heating Removal Lung Airways Flow may be turbulent Branching Clearance Laminar flow (not fully developed) Pulmonary Gas Exchange

8. The Human Respiratory Tract Characteristics of the various regions in the respiratory system. The diameter and the length decrease while the number of branchings increases. This increase results in a decreasing velocity and increasing residence time that have great impact on the "effective mechanisms" responsible for deposition.

9. The purpose of the upper airways is to • 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).

10. The Human Respiratory Tract Normal Adult Processes 10-25 m3 of air per day Surface area for gas exchange: 75 m2 (1/2 singles tennis court) 2000 km of capillaries Tidal volume at rest : 0.5 litre (3x at heavy work) Breathing rate at rest : 12 per minute (3x at heavy work) 2.4 litre reserve air is not exhaled (1/2 at forced exhalation)

11. Clearance of Deposited Particles • Head airways and tracheobronchial regions • Covered with mucus (salts, lactate, glycoproteins). • Mucociliary escalator: Ciliary action moves mucus towards the pharynx, where it is swallowed into the gastrointestinal tract. • Clearance within hours. • Alveolar region • No mucus layer, no cilia. • Insoluble particles cleared very slowly (up to months or years). • Clearance of soluble particles: dissolve and enter the blood stream. • Clearance of insoluble particles by macrophages. (phagocytosis) or surface tension effects (up to the mucociliary escalator).

12. Solubleparticles The response from the body depends on the particlemass, composition and number The particles lose their original shape and physical propertiesafter deposition Number of deposited particles can affect the physiological response Epithelial cell in alveoli

13. Epithelial Cell Insolubleparticles The response from the body depends on the particlesurface properties and number The particles keep their original shape and physical properties even after deposition Number of deposited particles can affect the physiological response Epithelial cell in alveoli

14. Photographer: Lennart Nilsson Soot particles (yellow) deposited in the alveoli.

15. A macrophage attacks the soot particle and tries to engulf it. Photographer: Lennart Nilsson

16. Insoluble particles may enter the blood Epithelial lining fluid Alveolar epithelium Blood vessel

17. Examples of non-spherical particles TEM (Transmission Electron Microscopy) pictures Kerosene lamp (soot agglomerate) Particle from tire wear

18. Equivalent Particle DiameterRelates to the sedimentation velocity vTS Aerodynamic equivalent sphere dae = 8.6 µm p = 1 g/cm3 Volume Equivalent Diameter Shape Factor = 1.36 de = 5.0 µm p = 4 g/cm3 Stokes equivalent sphere ds = 4.3 µm p = 4 g/cm3 vTS=0.22 cm/s vTS=0.22 cm/s vTS=0.22 cm/s

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. Inertial Impaction • 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. Sedimentation (Settling) • 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. Brownian Diffusion • 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. Interception • 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. Electrostatic Deposition • 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. Impaction Diffusion Settling Total Particle Deposition in the Respiratory Tract Particle diameters are aerodynamic (MMAD) for those > 0.5 μm and geometric (or diffusion equivalent) for those < 0.5 μm. Source: Modified from Schlesinger (1989). Interception

27. Extrathoracic Particle Deposition 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. Deposition in the alveolar region • 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

31. PEF: Peak Inspiratory Flow PEF: Peak Expiratory Flow VT: Tidal Volume

32. Effect of Breathing Pattern on Deposition 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).

33. Empirical Deposition Models • ICRP: • International Commission on Radiological Protection • http://www.icrp.org/ • ”Human Respiratory Tract Model for Radiological Protection”, • Annals of the ICRP (1994), Publication 66, Elsevier Science • NCRP: • National Council on Radiation Protection and Measurements • http://www.ncrponline.org/ • ”Deposition, Retention and Dosimetry of Inhaled Radioactive Substances”, • Report S.C. 57-2, NCRP, Bethesda, MD (1997). • Total and Regional Deposition (Size-resolved) • Different Breathing Conditions • ”Typical” Adults and Children • Differences between ICRP and NCRP models usually smaller than differences between individuals.

34. Settling Impaction Diffusion Total Deposited Particle Fraction Alveoli Particle Diameter (µm) ICRP Deposition Model International Commission on Radiological Protection

35. Aerosol Particle Separation - Conventions IPM: Inhalable particle fraction (fraction inhaled through nose and mouth) TPM: Thoracic particle fraction (fraction passing the larynx) RPM: Respirable particle fraction (fraction reaching the alveoli)

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

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

38. Lung Deposition av particles - ICRP • The lung deposition efficiency is highly • size-dependent • The relevant size is that to which the particles grow in the humid environment. • Important parameters: • Dry particle size distribution • The hygroscopic properties as a function of particle dry size Total

39. Humidified particle RH=90% Dry particle Cloud drop RH>100% Salt Water solution The more water-soluble material the particle contains, the more it will grow.

40. RH Hysteresis Effect

41. Köhler theory for cloud droplet formation Raoult´s term Kelvin term Kelvin term Raoult´s term

42. Particle hygroscopic properties Importance for deposition in the lungs Hygroscopic particles shift the minimum in the deposition curve to smaller sizes. Lung Deposition and Hygroscopic Growth (at RH=99.5%) • Hygroscopic particles affect deposition: • More particle mass (>200 nm) is deposited in the upper airways. • Fewer very small (<100 nm) particles are deposited in the lower airways (number). Hygroscopic Growth Factor (at RH=99.5%) Deposited Fraction Deposition – Humidified Deposition – Dry Growth Factor Deposition decreases Deposition increases Dry Particle Diameter (nm)

43. Transient EffectsParticle Hygroscopic Growth Broday and Georgopoulos AST(2001)

44. Division of Nuclear Physics, Lund University

45. Sulfuric Acid Sulfate 104 Particle Number Concentration 1/cm3 Organic Sea Salt Nitrate 103 Mineral Carbonaceous 102 101 1 10 100 1000 10000 Particle Diameter (nm) Elevated RH Particle Number Concentration Wet Dp Dry Dp Chemical composition and hygroscopicity

46. The Lund H-TDMA – Measures hygroscopic properties

47. Furuvik Lycksele, northern Sweden, Jan-March 2002, Measurement sites Sites Central Södermalm Norrmalm Vindeln SE Forsdala

48. Forsdala – Particle sampling Hygroscopic properties (TDMA) Size distribution (DMPS) Soot Elemental composition (SAM) (filter, fine and coarse, PIXE) Main ions (filter, IC) Particle mass (TEOM) (PM10 / PM2.5) Chemical composition (Hi-Vol PM10)

49. Hygroscopic properties (H-TDMA) Dry size=265 nmResidential area with wood combustionForsdala, Lycksele, Sweden 2002 Pure salts Background Growth factor at 90% RH Poor combustion Hydrophobic “Soot mode”  Wood combustion particles nearly hydrophobic Easily distiguished from accumulation mode “background” particles Aerosol fraction Date 2002 Hygroscopic Intermediate Hydrophobic

50. Particle hygroscopic propertiesLung deposition (Forsdala) Particle lung deposition (number, surface area,volume) can be calculated with a time resolution of 10 minutes. Number Deposited Number Surface Deposited Surface Volume Deposited Volume Dry Particle Diameter (nm)