Aerosolization
Aerosolization is the physical or chemical process by which liquids, solids, or suspensions are dispersed into fine particles or droplets (typically 0.001 to 100 micrometers in diameter) suspended in a gas, most commonly air, forming a colloidal system known as an aerosol.[1][2] This transformation occurs through mechanisms such as mechanical atomization, pneumatic nebulization, thermal vaporization, or ultrasonic dispersion, enabling efficient airborne transport and deposition of the material.[3][4] In medicine, aerosolization underpins inhalational therapies, including metered-dose inhalers, dry powder inhalers, and nebulizers, which deliver drugs directly to the lungs for treating conditions like asthma, chronic obstructive pulmonary disease, and cystic fibrosis, minimizing systemic side effects compared to oral or intravenous routes.[5][6] Industrially, it facilitates applications such as spray drying for pharmaceuticals and food processing, pesticide application in agriculture, and surface coating in manufacturing, where precise control over particle size influences efficacy and uniformity.[3] Environmentally, natural and anthropogenic aerosolization contributes to atmospheric phenomena, with particles influencing cloud formation, radiative forcing, and air quality; however, it also generates hazards like respiratory irritation, cardiovascular risks, and ecosystem disruption from inhaled pollutants or bioaerosols.[7][8] Key challenges in aerosolization include optimizing particle size distribution for desired deposition (e.g., alveolar targeting requires particles under 5 micrometers) and mitigating unintended generation of hazardous aerosols during procedures like intubation or laboratory manipulations, which can amplify pathogen transmission or chemical exposure risks.[9][4] Advances in aerosol science emphasize empirical characterization via techniques like laser diffraction and cascade impaction to enhance safety and performance across domains.[6]Fundamentals
Definition and Physical Principles
Aerosolization refers to the process of dispersing a liquid or solid substance into a gaseous medium, typically air, to form an aerosol—a colloidal suspension of fine solid particles or liquid droplets with diameters generally ranging from 0.001 to 100 micrometers.[10][11] This suspension enables particles to remain airborne for extended periods, distinguishing aerosols from larger droplets that settle rapidly under gravity.[12] The process is fundamental in fields requiring controlled dispersion, such as respiratory drug delivery, where particle size directly influences deposition sites in the lungs.[13] The physical principles underlying aerosolization are rooted in fluid dynamics, surface tension, and intermolecular forces. To generate droplets or particles, bulk material must be fragmented into smaller units, overcoming cohesive forces like surface tension through applied shear, pressure differentials, or vibrational energy; this is quantified by dimensionless numbers such as the Weber number (We = ρv²d/σ, where ρ is fluid density, v is velocity, d is characteristic length, and σ is surface tension), which indicates the ratio of inertial to surface tension forces.[1] Viscosity and density of the dispersed phase further modulate breakup efficiency, with lower viscosity fluids atomizing into finer distributions under similar conditions.[14] Resulting aerosols exhibit polydisperse size distributions, often described by log-normal models with metrics like the mass median aerodynamic diameter (MMAD), typically targeting 1-5 micrometers for deep lung penetration.[13][12] Once formed, aerosol stability depends on competing forces: Brownian diffusion prevents settling for particles below 0.1 micrometers, while gravitational sedimentation dominates for those exceeding 10 micrometers, with intermediate sizes (1-10 micrometers) persisting longest in still air.[12] Coagulation, where particles collide and merge due to van der Waals attractions or turbulent diffusion, reduces number concentration over time, as does evaporation for liquid droplets, which shrinks sizes until solidification or dissolution occurs.[15] These principles ensure aerosols' transient nature, with lifetime influenced by environmental factors like humidity and airflow, critical for applications demanding precise airborne persistence.[16]Types and Properties of Aerosols
Aerosols are suspensions of solid particles, liquid droplets, or mixtures thereof in a gaseous medium, typically air, with particle diameters ranging from nanometers to tens of micrometers. Classification by size is fundamental, as it governs transport, deposition, and interaction mechanisms: ultrafine aerosols (<0.1 μm) dominate in number concentration (e.g., global mean ~10,760 particles/cm³) and exhibit high surface-area-to-volume ratios enabling rapid diffusion and long atmospheric residence times via Brownian motion; fine aerosols (0.1–2.5 μm, often termed PM2.5) penetrate deep into respiratory tracts; coarse aerosols (2.5–10 μm, PM10) settle more quickly due to gravitational forces.[17][18] Size distributions are typically log-normal and multimodal, spanning four orders of magnitude from nucleation-mode ultrafines to accumulation and coarse modes.[19] Aerosols are further typed by physical phase and origin. Solid-phase aerosols include dry particles like mineral dust (emitted at ~2 billion metric tons annually from deserts) or soot from combustion; liquid-phase consist of droplets such as sea spray (sea salt with organics, wind-dependent formation); mixed-phase feature both, as in aged biomass smoke.[16] Primary aerosols are directly emitted (e.g., volcanic ash, smoke), while secondary form via gas-to-particle conversion (e.g., sulfates from SO2 oxidation).[16] Phase state influences reactivity, with particles transitioning from solid/semisolid (high viscosity) to liquid under humid conditions, affecting water uptake and coagulation.[20] Physical properties include concentration (0.001–104 particles/cm³), morphology (spherical to irregular), and dynamics: hygroscopicity drives growth via water condensation, quantified by growth factors or kappa values (0.1–0.6 for organics/inorganics), enhancing cloud formation and optical effects; coagulation merges particles, rate-limited by diffusion for ultrafines and inertia for coarses, altering size distributions over minutes to hours.[21][22] Chemical properties encompass composition—e.g., black carbon (absorptive, warming), organics (volatile/semisolid), inorganics (hygroscopic salts)—dictating surface reactivity, acidity, and phase partitioning, with mixing states (internal/external) modulating hygroscopicity and toxicity.[23] These traits underpin aerosol lifetime (days to weeks) and removal via dry/wet deposition.[24]Generation Methods
Mechanical and Nebulization Techniques
Mechanical aerosol generation techniques utilize physical forces such as impact, centrifugal acceleration, or vibration to disperse liquids or suspensions into fine droplets, typically without relying on high-pressure gas streams or thermal energy. These methods are employed in laboratory, industrial, and research settings to produce aerosols with controlled particle size distributions, often achieving mass median aerodynamic diameters (MMAD) in the range of 1-10 μm depending on fluid properties and device parameters. Collision nebulizers exemplify this approach, where compressed air propels liquid through multiple nozzles (commonly three to six jets) that converge and impact at a focal point, causing shear forces to fragment the liquid into droplets via turbulent collision.[25] This results in polydisperse aerosols suitable for bioaerosol studies, with output concentrations up to 10^9 particles per liter for microbial suspensions, though viability can decrease due to shear stress on fragile agents like viruses.[26] Rotary or spinning disk atomizers represent another mechanical variant, feeding liquid onto a rapidly rotating horizontal disk (speeds of 5,000-25,000 rpm) where centrifugal force spreads the fluid into a thin film that thins at the periphery, destabilizing into ligaments and subsequently droplets through Rayleigh-Plateau instability.[27] Droplet sizes are governed by disk diameter, rotation speed, and liquid viscosity, yielding MMAD as low as 5-50 μm for applications like spray drying or environmental dispersion testing.[1] These devices excel in high-throughput generation but produce broader size distributions compared to precision vibration-based systems.[28] Nebulization techniques, often overlapping with mechanical methods, focus on converting pharmaceutical solutions or suspensions into respirable aerosols for targeted delivery, emphasizing droplet sizes below 5 μm for deep lung deposition. Vibrating mesh nebulizers (VMNs) operate via a piezoelectric transducer that oscillates a microperforated mesh (aperture diameters 2-10 μm) in direct contact with the liquid reservoir, mechanically extruding uniform droplets through vibrational energy without auxiliary gas.[29] This yields high respirable fractions (50-80%) and minimal residual volume (<0.1 mL), with nebulization times of 2-5 minutes for 2-4 mL doses, making them efficient for portable medical use in conditions like asthma or COPD.[30] Unlike pneumatic systems, VMNs generate aerosols quietly and portably, though they require periodic mesh replacement to prevent clogging from viscous formulations.[31] In mechanical ventilation contexts, VMNs positioned between the ventilator Y-piece and patient wye deliver 10-30% of nominal dose, outperforming some jet types due to reduced circuit losses.[32]Pressure-Driven and Atomization Methods
Pressure-driven atomization methods rely on mechanical pressure to propel liquids through nozzles, exploiting instabilities in liquid jets or sheets to produce aerosols consisting of fine droplets suspended in air. These techniques convert the potential energy of pressurized fluids into kinetic energy, leading to shear forces and turbulence that fragment continuous liquid phases into discrete particles, typically governed by principles such as the Rayleigh-Plateau instability for cylindrical jets. Hydraulic and pneumatic variants dominate, offering scalability for applications from medical inhalation to industrial spraying, though droplet size distributions often exhibit polydispersity due to variations in fluid properties and nozzle geometry.[33] Hydraulic atomization, a purely pressure-driven approach, forces liquids through orifices or swirl chambers using pumps or pressurized reservoirs, achieving atomization via high exit velocities that destabilize the emerging liquid sheet or jet. Droplet formation occurs as surface tension-driven waves amplify into ligaments and then break into spheres, with mean diameters generally spanning 5 to 2000 μm and inversely related to applied pressure—higher pressures increase velocity, reducing size through enhanced disruptive forces. This method suits low-viscosity fluids in scenarios like fuel injection or agricultural sprayers, where pressures from 10 to 2000 bar enable efficient dispersion, but it struggles with highly viscous media without auxiliary heating.[34] Swirl atomizers, a subtype, impart tangential motion to form hollow conical sheets that atomize radially, improving uniformity over plain-orifice designs.[35] Pneumatic atomization augments liquid pressure with compressed gas streams, typically air or inert gases at 1-7 bar, to shear droplets via relative velocity differences in internal or external mixing configurations. The gas momentum imparts finer atomization than hydraulic methods alone, handling viscosities up to 1000 mPa·s and yielding sub-micrometer particles in optimized setups, as the high-speed airflow accelerates evaporation and secondary breakup.[36] Common in medical jet nebulizers, where venturi effects draw and atomize solutions into aerosols with mass median aerodynamic diameters of 2-5 μm suitable for lung deposition, this technique requires a gas supply but excels in producing respirable mists for drug delivery.[37] In industrial contexts, such as aerosol jet printing or coating, pneumatic systems enable precise control over spray angle and density by adjusting gas-to-liquid ratios. Both methods' efficacy depends on fluid dynamics parameters, including Reynolds number for turbulence onset and Weber number for inertial-to-surface tension balance, with empirical models predicting size distributions via laser diffraction validation in controlled experiments.[38] Limitations include energy inefficiency at low flow rates and potential for nozzle clogging with particulates, prompting hybrid designs for enhanced performance in aerosol generation.[35]Ultrasonic and Electrostatic Methods
Ultrasonic aerosol generation utilizes a piezoelectric transducer to vibrate a liquid reservoir at high frequencies, typically ranging from 1 to 3 MHz, creating capillary waves on the liquid surface that destabilize and eject droplets through a process known as cavitation or fountain formation.[25] The vibration amplitude and frequency determine the droplet size distribution, with higher frequencies producing smaller median droplet diameters that scale inversely with frequency and follow the capillary wavelength, often yielding particles in the 1-5 μm range suitable for respiratory deposition.[39] [40] This method generates aerosols without compressed gas, reducing shear forces on sensitive formulations, though it can elevate aerosol temperature by 10-14°C compared to pneumatic nebulizers due to energy dissipation.[41] Electrostatic aerosol generation, often via electrospray, applies a high electric potential—typically 2-5 kV—to a conductive liquid emerging from a capillary nozzle, inducing charge accumulation that overcomes surface tension and forms a conical meniscus known as the Taylor cone.[42] From the cone apex, a liquid jet emerges and undergoes Rayleigh-Plateau instability, fragmenting into highly monodisperse charged droplets whose size, often sub-micrometer to several micrometers, depends on liquid flow rate (e.g., 1-100 nL/min), conductivity, and voltage, enabling precise control for applications requiring narrow size distributions.[42] [43] The charged nature of the droplets facilitates self-dispersion and deposition via electrostatic forces, minimizing coalescence, though ambient humidity can influence charge neutralization and particle trajectory.[44]Applications
Medical and Pharmaceutical Delivery
Aerosolization enables targeted delivery of pharmaceuticals directly to the respiratory tract, achieving high local drug concentrations in the lungs while minimizing systemic exposure and first-pass metabolism effects.[45] This approach is particularly effective for treating respiratory conditions such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis, where devices like nebulizers, metered-dose inhalers (MDIs), and dry powder inhalers (DPIs) generate aerosols with particle sizes typically between 1-5 micrometers for optimal alveolar deposition.[46] Nebulizers convert liquid solutions into fine mists via mechanical or ultrasonic vibration, suitable for patients unable to coordinate inhalation, while MDIs, first commercialized in 1956 by Riker Laboratories, propel propellants carrying micronized drug particles, and DPIs rely on patient-generated airflow to disperse powder formulations.[47] Clinical studies demonstrate comparable efficacy between these devices for bronchodilators like albuterol in acute exacerbations, with MDIs and DPIs often preferred for portability and reduced treatment time over nebulizers.[48] In local therapeutic applications, aerosolized antibiotics such as tobramycin have revolutionized management of Pseudomonas aeruginosa infections in cystic fibrosis patients, delivering concentrations up to 100 times higher in sputum compared to intravenous administration, thereby improving lung function and reducing hospitalization rates in trials like the one supporting FDA approval in 1998.[49] Corticosteroids like budesonide and anticholinergics are routinely aerosolized for COPD maintenance, with DPIs showing sustained efficacy in children under 12 years when technique is mastered, as evidenced by systematic reviews of comparative studies.[50] For emergency settings, aerosol delivery of short-acting beta-agonists via MDIs with spacers achieves bronchodilation equivalent to nebulizers, with faster administration times documented in pediatric and adult respiratory distress cases.[51] Systemic delivery via aerosols has been explored for macromolecules, though challenges persist; inhaled insulin formulations, such as those tested in early 2000s clinical trials, exhibited rapid absorption but required doses 2-3 times higher than subcutaneous due to incomplete bioavailability (around 30-50%), leading to limited commercial success before regulatory withdrawals like Afrezza's post-approval restrictions in 2016.[49] Aerosolized vaccines, including intranasal formulations for influenza approved since 2007, leverage mucosal immunity but face variable immunogenicity, with recent mRNA-based pulmonary trials showing promise for higher lung-targeted antibody responses compared to intramuscular routes.[52] Advancements in nanotechnology, such as liposomal encapsulation, enhance stability and controlled release of antibiotics and gene therapies, with preclinical data indicating improved bioavailability and reduced dosing frequency in ventilator-assisted delivery.[53] Ongoing innovations focus on smart inhalers with sensors for adherence monitoring, potentially optimizing outcomes in chronic disease management.[54]Industrial and Consumer Products
Aerosolization enables the precise delivery of industrial substances such as lubricants, penetrating oils, degreasers, solvents, rust inhibitors, and corrosion protection agents, which are essential for maintenance and operation in manufacturing and automotive environments. These products reduce friction in mechanical components, facilitate access to confined spaces for repairs, and remove grease or contaminants from surfaces, thereby minimizing downtime and enhancing equipment longevity.[55][56] Adhesives, sealants, coatings, and paints delivered via aerosolization provide bonding, gap sealing, protective layers, and surface finishing in industrial processes, often through pressurized systems that ensure uniform application without direct contact.[56] In the automotive sector, aerosolized cleaners and lubricants support vehicle maintenance by delivering targeted sprays that improve performance and reduce wear, with technologies like automated filling machines enabling high-volume production of such items at low defect rates.[55] The automotive and industrial segment contributes to the broader aerosol market, which reached USD 92.97 billion globally in 2024 and is projected to grow to USD 158.42 billion by 2033 at a compound annual growth rate of 6.1%, driven by demand for efficient dispensing in these applications.[57] Consumer products leveraging aerosolization span personal care items including deodorants, antiperspirants, shaving foams, hair sprays, and skincare formulations like hydrating creams or self-tanning lotions, which benefit from contact-free, precise misting that prevents contamination and optimizes usage.[58] Household applications encompass air fresheners for odor neutralization, multi-surface cleaners for fabrics, windows, and appliances, as well as polishes, starches, and insecticides that disperse evenly for effective coverage.[58] Food-related consumer aerosols, such as whipped cream dispensers and cooking sprays, utilize the technology to achieve consistent textures and non-stick properties.[57] Aerosol dispensers in these consumer categories offer hermetic sealing for safety and sanitation, along with resource-efficient delivery that extends product shelf life and reduces waste through controlled spray mechanisms.[58] In Europe, personal care cosmetics account for over 50% of aerosol production, while household products represent more than 20%, underscoring their dominance in consumer markets.[58] The personal care segment leads global growth in the aerosol industry, reflecting sustained consumer preference for convenient, hermetically sealed formats.[57]Agricultural and Environmental Dispersion
In agriculture, aerosolization facilitates the targeted dispersion of pesticides, fungicides, and other agrochemicals via ultra-low volume (ULV) spraying systems, which atomize formulations into droplets typically 10–50 micrometers in diameter to achieve uniform coverage with minimal liquid volume, often under 2 liters per hectare.[59][60] This approach, employed since the mid-20th century for crop protection, reduces application costs by up to 50% compared to high-volume methods and improves efficacy through enhanced leaf penetration and reduced evaporation, as demonstrated in field trials for controlling pests in row crops and orchards.[61][62] For instance, ground-based ULV application of fluazinam effectively managed tomato gray mold (Botrytis cinerea) in greenhouses, achieving over 90% disease control with droplet sizes optimized for drift minimization under wind speeds below 5 m/s.[62] Aerosol techniques in enclosed agricultural spaces, such as greenhouses and warehouses, utilize cold foggers to disperse insecticides like pyrethroids, generating fogs with mass median diameters of 5–20 micrometers for rapid settling on surfaces and minimal operator exposure.[63][64] These methods are particularly suited for integrated pest management in high-density production, where traditional sprays risk phytotoxicity or uneven distribution; however, aerosol drift—defined as off-target movement of droplets smaller than 150 micrometers—can extend up to 100 meters downwind, necessitating buffer zones and wind-directed nozzles to comply with environmental regulations.[65] Empirical studies confirm that ULV aerosols maintain particle concentrations above lethal thresholds for target insects for 24–48 hours post-application, though efficacy diminishes in humid conditions due to droplet coalescence.[66] Environmentally, aerosolization supports dispersion strategies for habitat management and pollution mitigation, including the aerial release of fire retardants in wildfire suppression, where ammonium phosphate-based formulations are atomized into aerosols covering up to 10 hectares per pass from fixed-wing aircraft.[67] In dust control applications, water or polymer aerosols are generated via high-pressure nozzles to suppress particulate matter on unpaved roads and construction sites, reducing respirable dust (PM10) levels by 70–90% during application, as measured in arid agricultural regions.[68] Proposed geoengineering uses, such as stratospheric aerosol injection of sulfates to reflect sunlight, involve dispersing 1–5 million tons annually at altitudes of 20–25 km, but remain experimental with models indicating potential cooling of 0.5–1°C globally; real-world deployment has not occurred due to uncertainties in ozone depletion and regional precipitation shifts.[69] These applications highlight aerosolization's role in causal environmental modification, balanced against risks of unintended atmospheric persistence, where particles with diameters under 2 micrometers can remain aloft for weeks, influencing local albedo and radiative forcing.[70]Health and Safety Considerations
Therapeutic Benefits and Efficacy
Aerosolization facilitates targeted drug delivery to the respiratory tract, enabling high local concentrations in the lungs with substantially lower systemic doses than oral or intravenous routes, thereby minimizing off-target effects such as gastrointestinal irritation or hepatic toxicity. This method leverages the lung's extensive surface area—approximately 100 square meters in adults—for rapid absorption and onset of action, often within seconds to minutes, which is particularly beneficial for acute conditions like bronchospasm.[49][71] By avoiding first-pass metabolism, aerosolized formulations achieve greater bioavailability for macromolecules and peptides that degrade in the gut, enhancing therapeutic efficiency for pulmonary pathologies.[72] In chronic obstructive pulmonary disease (COPD), inhaled triple therapy combining inhaled corticosteroids (ICS), long-acting beta-agonists (LABA), and long-acting muscarinic antagonists (LAMA) has shown superior efficacy, reducing exacerbation rates by up to 25% and improving forced expiratory volume in one second (FEV1) compared to dual therapies, based on network meta-analyses of randomized controlled trials (RCTs) spanning at least 20 weeks.[73][74] Triple therapy also lowered all-cause mortality by 28% relative to LABA/LAMA combinations in large-scale RCTs like IMPACT (2018), with surface under the cumulative ranking curve (SUCRA) analyses ranking it highest for mortality reduction.[74] Single-inhaler triple formulations further enhance adherence and lung function gains over separate inhalers, as evidenced by meta-analyses of moderate-to-severe COPD patients.[75] For asthma and other obstructive airway diseases, aerosolized bronchodilators and anti-inflammatory agents deliver rapid symptom relief and sustained control; for instance, LAMA/LABA combinations outperform ICS/LABA in improving trough FEV1 by 50-100 mL at 12-24 weeks in head-to-head RCTs.[76] Inhaled therapies like ensifentrine, a phosphodiesterase inhibitor, improve FEV1 by 87 mL, reduce dyspnea scores, and enhance quality of life in COPD patients, per a 2024 meta-analysis of phase 3 trials.[77] In critical care settings, aerosolized surfactants and antibiotics achieve lung-specific efficacy with reduced systemic toxicity, outperforming intravenous alternatives in preterm neonates and ventilated patients by optimizing deposition via device-specific factors like particle size (1-5 μm for deep lung penetration).[78][48] Efficacy in cystic fibrosis includes nebulized antibiotics like tobramycin, which reduce Pseudomonas aeruginosa density by 1-2 log CFU/g sputum and extend exacerbation-free intervals by 20-30% in RCTs, underscoring aerosolization's role in chronic infection management.[79] Overall, these benefits hinge on precise aerosol generation—ensuring 10-20% lung deposition in optimal conditions—but real-world efficacy varies with patient technique and device, as slow inhalation maximizes deposition for particles >5 μm in asthmatics.[80] Despite advantages, aerosol therapy's success requires addressing barriers like oropharyngeal deposition, which can be mitigated by spacers or breath-actuated devices to boost delivered dose by 20-50%.[48]Inhalation Risks and Occupational Exposure
Inhalation of aerosols poses significant health risks primarily due to the deposition of particles in the respiratory tract, where particle size determines the site and extent of accumulation. Particles larger than 10 μm typically deposit in the upper airways via impaction, while respirable fractions below 5 μm, particularly 0.5–2 μm, penetrate to the alveoli through sedimentation and diffusion, enabling deep lung exposure and potential systemic absorption.[81][82] This deposition can trigger acute effects such as irritation, coughing, and bronchoconstriction, as well as chronic conditions including inflammation, oxidative stress, and fibrosis, with ultrafine particles (<0.1 μm) crossing into the bloodstream.[83][84] Occupational exposure to aerosols occurs across industries involving dust generation, spraying, welding, or machining, such as mining, construction, agriculture, and manufacturing, where workers inhale inhalable (up to 100 μm) and respirable fractions during tasks like grinding, pesticide application, or metalworking.[11][85] In food processing, for instance, bioaerosols from organic materials contribute to occupational asthma and rhinitis through sensitization and repeated irritation.[86] Cumulative exposure to mixed aerosols, including gases, fumes, and particulates, correlates with reduced lung function, airway obstruction, and impaired gas exchange, exacerbating conditions like chronic obstructive pulmonary disease (COPD).[87][88] Specific occupational lung diseases linked to aerosol inhalation include pneumoconioses such as silicosis from crystalline silica dust in mining and sandblasting, asbestosis from asbestos fibers in insulation work, and welder's lung from metal oxide fumes, all characterized by irreversible fibrosis and heightened cancer risk.[89][90] Inhalation fatalities from respiratory diseases and cancers account for about 70% of occupational disease deaths, underscoring the dose-dependent toxicity where even sub-limit exposures can accumulate over years.[91] Exposure assessments emphasize monitoring respirable dust levels, with NIOSH recommending limits like 0.05 mg/m³ for silica and OSHA permissible exposure limits (PELs) of 5 mg/m³ for respirable nuisance dust, though many substances lack tailored aerosol-specific thresholds, relying on total particulate metrics.[92][93]| Disease | Associated Aerosol | Primary Industries | Key Health Outcome |
|---|---|---|---|
| Silicosis | Crystalline silica dust | Mining, construction | Lung fibrosis, tuberculosis risk[89] |
| Occupational Asthma | Bioaerosols, metal fumes | Food processing, welding | Airway hyperreactivity, wheezing[85][86] |
| COPD Aggravation | Mixed dusts and fumes | Manufacturing, agriculture | Reduced FEV1, emphysema[87][88] |