inhaled and exhaled air experiment

Experiments to compare carbon dioxide content of  inhaled and exhaled air

Experimental details.

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Fun Science Projects & Experiments - Limewater Test

In these lessons, we shall learn the limewater test for carbon dioxide - how it works and how to use it.

Related Pages Alkane And Alkene Tests Science projects, videos and experiments for various grades and topics.

Science Projects or Science Experiments: Grades 5 & 6

The following diagrams show the test for Carbon Dioxide. Carbon Dioxide will turn limewater (calcium hydroxide) cloudy. Scroll down the for examples and explanations.

Limewater Test - To check for carbon dioxide in your breath

Lime Water Breath Experiment Using lime water is a fun and easy way to test for the presence of carbon dioxide. The exhaled carbon dioxide is used to produce a precipitate of calcium carbonate with the lime water.

carbon dioxide + calcium hydroxide (limewater) → calcium carbonate + water

• Add 50 ml of lime water to two 100 ml beakers.
• Bubble room air through one beaker for one minute using a pipette and pipette pump. Observe and record the results.
• With the other beaker, bubble exhaled air through the solution for 1 minute. Try to bubble the air through the same rate that you did with the first beaker. After 1 minute record your results.

Limewater & CO 2 Carbon dioxide dissolves in water to form carbonic acid (H 2 CO 3 ).

Lime water is a solution of calcium hydroxide (Ca(OH) 2 ).

They react to form calcium carbonate (CaCO 3 ) and water. Calcium carbonate is insoluble and forms a white precipitate.

If CO 2 continues to be passed, more carbonic acid forms, which then reacts with the calcium carbonate to form calcium hydrogencarbonate, which is soluble, so the precipitate is seen to dissolve.

To Investigate the Carbon Dioxide Levels of Inhaled and Exhaled Air In this experiment we will investigate the carbon dioxide levels of inhaled and exhaled air. We use limewater to test for the presence of carbon dioxide.

Carbon dioxide dissolves in water Here is some pure water, which has a pH of 7, shown by using this testing paper and matching the color to the chart on the side of the box.

If I take a straw and blow into the water, what gases are going into the water?

The one I am interested in is carbon dioxide, which can dissolve in water and react to form an acid.  CO 2 (g) + H 2 O(l) → H 2 CO 3 (aq) → H + (aq) + HCO 3 − (aq)

So after I blow into the water several times, I should have a solution which is more acid than it was before. Let’s check by retesting the pH of the solution. It is now down to 5, rather than the 7 it was as pure water. pH 5 is an acid, so the carbon dioxide has dissolved in the water and reacted.

Thus my chemical reaction really has made hydrogen ions in the water, meaning that the carbon dioxide gas dissolved and reacted.

CO 2 (g) + H 2 O(l) → H + (aq) + HCO 3 − (aq)

What does this mean about rain which passes through air with CO 2 in it?

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The reaction of carbon dioxide with water

In association with Nuffield Foundation

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In this experiment, students use their own exhaled breath to explore the reaction between carbon dioxide and water. 

This is a relatively brief and straightforward exploration of the reaction of carbon dioxide and water at a simple level, which should take no more than 15 minutes.

When carbon dioxide reacts with water a weak acid is formed. Carbon dioxide present in exhaled air is blown into a flask containing an indicator sensitive to small changes of pH in the appropriate region of the pH scale, and the consequent colour changes observed and recorded. The equation for the reaction between carbon dioxide and water may be introduced for appropriate students.

If students have not yet met the compositions of inhaled and exhaled air, this experiment can serve as part of the learning sequence for the topic of breathing and respiration in an introductory science course, using an appropriately elementary approach to the chemistry involved.

For students who have already covered the topic of breathing and respiration, and know that carbon dioxide is a significant component of exhaled air, the focus in this experiment can be transferred to the nature of the chemical reaction (other related topics could be acid rain, gas liquid reactions or indicators).

The equation for the reaction between carbon dioxide and water may be introduced for appropriate students.

• Eye protection
• Conical flask, 250 cm 3 , x2
• Indicator bottles with dropping pipettes, x3
• Ethanol (IDA – Industrial Denatured Alcohol) (HIGHLY FLAMMABLE, HARMFUL)
• Thymolphthalein indicator solution (HIGHLY FLAMMABLE), access to small bottle with dropper
• Phenol red indicator solution (HIGHLY FLAMMABLE), access to small bottle with dropper
• Sodium hydroxide solution, 0.4 M (IRRITANT), small bottle with dropper
• Distilled (or deionised) water, 125 cm 3 , x2

Health, safety and technical notes

• Read our standard health and safety guidance .
• Wear eye protection throughout.
• Phenol red indicator – see CLEAPSS Hazcard HC032 . The indicator may be purchased as a solid reagent or as a ready-made solution in ethanol. The solution may be made from the solid reagents by preparing a 5% w/v solution in ethanol (IDA). If 30 cm 3  or 60 cm 3  dropping bottles with integral dropping pipettes are available, these are ideal for dispensing the indicator solutions. While phenol red itself is not flammable, its solution in ethanol is highly flammable.
• Thymolphthalein indicator – see CLEAPSS Hazcard HC032 . The indicator may be purchased as a solid reagent or as a ready-made solution in ethanol. The solution may be made from the solid reagents by preparing a 5% w/v solution in ethanol (IDA). If 30 cm 3  or 60 cm 3  dropping bottles with integral dropping pipettes are available, these are ideal for dispensing the indicator solutions. While thymolphthalein itself is not flammable, its solution in ethanol is highly flammable.
• Ethanol (IDA – Industrial Denatured Alcohol), CH 3 CH 2 OH(l), (HIGHLY FLAMMABLE, HARMFUL) – see CLEAPSS Hazcard HC040A .
• Sodium hydroxide solution, NaOH(aq), (IRRITANT at concentration used) – see CLEAPSS Hazcard HC091a  and CLEAPSS Recipe Book RB085.

Source: Royal Society of Chemistry

• Place about 125 cm 3 of water in a 250 cm 3 conical flask.
• Add five or six drops of thymolphthalein indicator to the water.
• Add just enough sodium hydroxide solution (about two or three drops) to produce a blue colour.
• Talk or blow gently into the flask – ie add the carbon dioxide.
• Continue adding the carbon dioxide until a colour change is observed.
• Add one or two drops of phenol red to the water.
• Add two drops of sodium hydroxide solution to produce a red solution.
• Talk or blow gently into the flask – ie add carbon dioxide.

Questions for the class

• Why does the colour change not occur instantly?
• What is the reason for adding a few drops of sodium hydroxide solution (NaOH) before each experiment? 

Answers to questions

• The amount of carbon dioxide in each breath is small, so it takes a lot of breaths to react with the alkali.
• To ensure the solution is slightly alkaline at the beginning and to neutralise any CO 2  or any other acid initially present.

Teaching notes

Straws are not necessary for blowing exhaled air into the flask; simply breathing or speaking into the flask is sufficient to cause the indicator to change colour.

Phenol red indicator changes from yellow to red over the pH range 6.8–8.4. Thymolphthalein (the alternative bromothymol blue could also be used) changes from blue (alkaline) to colourless (acid) over the pH range 9.3–10.5. See CLEAPSS Recipe Book RB000, which also covers bicarbonate indicator solution.

Eventually sufficient carbon dioxide from the students’ breath dissolves and produces enough acid in the solution to change the colour of the indicator:

CO 2 (aq) + H 2 O(l) ⇌ H + (aq) + HCO 3 – (aq)

CO 2  also reacts with NaOH. This reaction produces the less alkaline Na 2 CO 3 :

2NaOH(aq) + CO 2 (g) → Na 2 CO 3 (aq) + H 2 O(l)

The equilibrium between carbon dioxide and water can be reversed by heating the weakly acidic solution to just below boiling. The solubility of carbon dioxide in water decreases as the temperature is raised, and it is driven off into the atmosphere. The concentration of dissolved carbon dioxide therefore drops, causing the equilibrium to shift to the left and the indicator colour to change back to red. On cooling the solution and blowing exhaled breath into the flask again, the sequence can be repeated.

More resources

Add context and inspire your learners with our short career videos showing how chemistry is making a difference .

Additional information

This is a resource from the  Practical Chemistry project , developed by the Nuffield Foundation and the Royal Society of Chemistry.

Practical Chemistry activities accompany  Practical Physics  and  Practical Biology .

© Nuffield Foundation and the Royal Society of Chemistry

• 11-14 years
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• 16-18 years
• Practical experiments
• Acids and bases
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Specification

• Soluble non-metal oxides dissolve in water forming acidic solutions
• (a) combustion reaction of alkanes and benefits and drawbacks relating to the use of fossil fuels, including formation of carbon dioxide, acidic gases and carbon monoxide
• (f) the roles of respiration, combustion and photosynthesis in the maintenance of the levels of oxygen and carbon dioxide in the atmosphere
• 2.9.9 investigate the chemical reactions of carbon dioxide with water producing carbonic acid and with calcium hydroxide (limewater) until carbon dioxide is in excess; and
• Carbon dioxide as an acidic oxide.
• Carbon dioxide in water - free and combined as carbonate and hydrogencarbonate.
• Demonstration of the effect of carbon dioxide on universal indicator solution.

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• Preparatory

Lesson Plan: Respiration: Gas Exchange

This lesson plan includes the objectives, prerequisites, and exclusions of the lesson teaching students how to describe the exchange of gases that occurs in the lungs, identify the composition of the inhaled and exhaled air, and explore ways to maintain a healthy respiratory system.

Students will be able to

• define gas exchange,
• identify oxygen and carbon dioxide as the main gases of respiration,
• identify bronchi and the function of the alveolar capillaries,
• perform experiments to show the presence of carbon dioxide and water vapor in exhaled air,
• describe ways to maintain a healthy respiratory system,
• highlight the harms of environmental pollution and smoking on the health of the respiratory system.

Prerequisites

Students should already be familiar with

• the basic systems of the body,
• the organs of the respiratory system,
• the process of respiration.

Students will not cover

• the circulatory system,
• cellular respiration.

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• The Human Body, Systems and Processes

Compare the Contents of Inhaled and Exhaled air

In this worksheet, students will explain the main differences between inhaled and exhaled air.

Key stage:   KS 3

Year:   Year 8 Science worksheets

Curriculum topic:   Biology: Structure and Function of Living Organisms

Curriculum subtopic:   Gas Exchange Systems (Breathing)

Popular topics:   Biology old worksheets , Human Body worksheets

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Worksheet Overview

Everyone knows that we breathe in oxygen and breathe out carbon dioxide. But that's not technically true. The truth is we breathe in air and breathe out air... so what's the difference?

Inhaled Air

So, we need oxygen to live, but do you know how much of the air is made up of oxygen? 80%? 75%? ....it actually only makes up about  21% of the air.  

So what else is in there?

The air that is all around us is made up of mostly nitrogen, about  78% nitrogen in fact. So what about the other 1%? ...The other 1% is made up of 0.04% carbon dioxide, some water vapour and other gases such as argon, helium and neon.  

Exhaled Air

The reason we breathe is to get oxygen into our bodies to allow for respiration, so you would think that the air we breathe out would have a lot less oxygen right? Well, there is less oxygen in exhaled air but probably a bit more than you would expect. Exhaled air actually contains around  16% oxygen which means we only use about 5% of the oxygen available!

The percentage of nitrogen stays at nearly  78% (as we do not have any use for nitrogen) but the main difference is the increase in carbon dioxide. The carbon dioxide in exhaled air is more-or-less 4% and the percentage of water vapour is also higher than in inhaled air.  

Experiment Time

There is a very simple experiment that we can do to prove that exhaled air contains more carbon dioxide than inhaled air.

Carbon dioxide will turn colourless limewater milky/cloudy.  

The carbon dioxide percentage in inhaled air is so small that it doesn't have an effect on the limewater, however bubble some exhaled air through it and it will turn milky/cloudy. 

Let's try some questions now.

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• Perspective
• Published: 31 August 2022

The physics of respiratory particle generation, fate in the air, and inhalation

• Lidia Morawska   ORCID: orcid.org/0000-0002-0594-9683 1 , 2 ,
• Giorgio Buonanno 1 , 3 ,
• Alex Mikszewski 1 &
• Luca Stabile   ORCID: orcid.org/0000-0003-2454-0389 3  

Nature Reviews Physics volume  4 ,  pages 723–734 ( 2022 ) Cite this article

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• Applied physics

Given that breathing is one of the most fundamental physiological functions, there is an urgent need to broaden our understanding of the fluid dynamics that governs it. There would be many benefits from doing so, including a better assessment of respiratory health, a basis for more precise delivery of pharmaceutical drugs for treatment, and the understanding and potential minimization of respiratory infection transmission. We review the physics of particle generation in the respiratory tract, the fate of these particles in the air on exhalation and the physics of particle inhalation. The main focus is on evidence from experimental studies. We conclude that although there is qualitative understanding of the generation of particles in the respiratory tract, a basic quantitative knowledge of the characteristics of the particles emitted during respiratory activities and their fate after emission, and a theoretical understanding of particle deposition during inhalation, nevertheless the general understanding of the entire process is rudimentary, and many open questions remain.

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Introduction.

Inhaling and exhaling air — breathing — is one of the basic physiological functions of the human being. Breathing is essential to nourish the body with oxygen and eliminate the waste generated in the process: carbon dioxide. Because it is a physiological function, it is normally considered in the domain of medical sciences, not physics.

However, physics, and more specifically fluid dynamics, is a critical element of the process 1 . During inhalation, air enters the respiratory tract and flows down through the upper and lower parts of the tract, finally reaching the alveolar region. During exhalation, when the passages contract, air flows in the opposite direction and is ultimately exhaled. The exhaled stream of air passes at high speed over the surface of the water-based liquid lining the respiratory tract, and aerosolizes the liquid. The particles that are generated contain, in addition to water, many other constituents, including salts, proteins, mucus, and pathogens such as bacteria or viruses. (See Box  1 for a note about terminology.) The process of particle generation during human respiratory activities — which in addition to breathing include speaking, singing or coughing — is, however, more complex than aerosolization from the surface. During exhalation, fluid blockages form in respiratory bronchioles, which burst during subsequent inhalation to produce particles; during vocalization, fluid bathing the larynx is aerosolized owing to vocal cord vibration; and during speech articulation, saliva in the mouth is aerosolized owing to interaction of the tongue, teeth, palate and lips.

After the particles are generated, some are deposited in the respiratory tract, and those that eventually leave the respiratory tract with the airflow are subjected to numerous physical processes, including hygroscopic growth and deposition; both processes change the initial particle size distribution. Once emitted through the nose or mouth, particle characteristics further change in response to the change in temperature and relative humidity between the body and the external environment. The particles are also subject to various forces that affect their fate, which may be deposition and transport within the environment or inhalation by others present there.

In the process of inhalation, particles present in the air enter the respiratory tract and can be deposited there. The particles are not only the aged particles generated from respiratory activities of other people, but also particles of natural or anthropogenic origin that constitute air pollution. Pathogens contained by the particles may cause infections; deposition of any particles on the epithelium of the respiratory tract has numerous other health implications. Therefore, to understand and quantitatively assess possible health implications, physics must provide quantitative information about the process of particle generation during respiratory activities, the fate of the particles in the air, and deposition in the human respiratory tract.

This Perspective gives an overview of the understanding of the physics of particle generation and deposition in the human respiratory tract, and identifies open questions. The aim is not to be exhaustive for experts in this very specific area (of physics or modelling). Instead, this Perspective is mostly intended for a general educated readership who need to understand the general principles of this field to be able to link to other areas such as public health or other scientific fields. Thus, not all aspects are addressed in depth. The focus is on evidence from experimental studies. We consider only human studies and do not include animal studies.

We conducted a literature search to identify experimental studies that investigated particle composition, fate and inhalation; particles emitted from human respiratory activities; and experimental data and models of particle deposition in the lung. The keywords for particle composition, fate and inhalation were: respiratory droplets, bioaerosol, particle size, exhaled breath and expiratory aerosol. The keywords for human respiratory activities were: airflow sampling, particle image velocimetry (PIV), bioaerosol, saliva droplets, biological fluid dynamics and exhaled airflow. The keywords for particle deposition in the lung were: total particle deposition, measurement, human lung, submicrometre particles and ultrafine particles. We identified studies published in English using ScienceDirect, EBSCOhost, Web of Science and Wiley Interscience search engines.

We first discuss the physics of particle generation in the respiratory tract, followed by a short discussion of the fate of these particles in the air, and conclude with physics of particle inhalation, where we consider inhalation of pathogen-laden particles generated by humans and particles that constitute air pollution.

Box 1 A note on terminology

We use the term particles, rather than aerosols or droplets, to avoid discussions of terminology that has been dividing expert communities 166 . Briefly, according to aerosol science, an aerosol is an assembly of liquid or solid particles suspended in a gaseous medium long enough to enable observation or measurement 167 . Although there is no definition of what constitutes ‘long enough’, it is considered that at a particle size of ~100 µm, gravitational deposition removes those particles from the air fast enough that they cannot be considered as suspended in the air. In aerosol science, a droplet is a liquid particle 167 . By contrast, in medical sciences, an aerosol is a smaller particle, whereas a droplet is a larger particle. A previous paper 168 provides additional explanation behind the existing communication difficulties and stresses the need to develop terminology acceptable to and understood by expert communities from all relevant fields.

Particle generation

There are two known physical mechanisms to generate the particles emitted from the human respiratory tract: turbulent aerosolization, and the breakage or burst of a fluid film, filament or bubble (FFBB) (Fig.  1 ). Turbulent aerosolization is referred to as atomization in fluid mechanics literature and is characterized by turbulent flows stripping particles from a fluid film. This process has also been defined as a shear-induced surface wave instability 2 , as first described in the work of Lord Rayleigh 3 , and more recently as turbulent droplet extraction 4 . The FFBB process generates particles during normal breathing due to clearance of fluid closures in respiratory bronchioles, and during speaking when vocal cords adduct and vibrate in the larynx and when lips open and the tongue separates from the teeth in the mouth 5 , 6 . Integral to FFBB particle generation is airway reopening following closure 7 , 8 .

a | Fluid film, filament or bubble breakage (FFBB) in the mouth during speech 165 . b | FFBB due to filament formation at the vocal cords. c | Turbulent aerosolization of viscoelastic mucus from the airway lining in the larynx and large bronchi due to turbulent airflow, based on snapshot of ligament-mediated fragmentation of viscoelastic liquid presented in ref. 40 . d | FFBB in small airway bronchioles due to clearance of fluid blockages formed during exhalation and airway reopening.

In both turbulent aerosolization and FFBB, particles originate from the airway’s surface liquid film, which is a bilayer with the top layer a mucus gel consisting of water (97%) and a mixture of mucins, non-mucin proteins, salts and cellular debris (3%), and the bottom, low-viscosity periciliary layer containing the cilia 9 . Turbulent aerosolization in the conventional sense is thought to be most active in large bronchi and the larynx owing to airflows that are partly turbulent even during breathing and with increasing velocity during speaking and coughing owing to partially adducted vocal folds 10 . In the deepest small airway bronchioles, FFBB is the dominant mechanism for particle generation 11 .

We discuss the quantity and size distribution of particles generated from these two mechanisms in the next section, but it is important to consider that these characteristics are a function of the thickness of airway lining fluid itself. In particular, it is unlikely that the diameter of generated particles will exceed the thickness of its parent fluid film 12 . The airway epithelial thickness is greatest, of the order of hundreds of micrometres, in the oral cavity where it also includes an overlying salivary layer 13 . This thickness decreases on moving deeper into the respiratory tract. In large airways of luminal diameter greater than 2 mm, the airway liquid film can be up to 50 µm thick, whereas in a small airway bronchiole the mucus gel layer is only 0.5–5.0 µm thick 9 .

Particle quantities and composition

Particles derived from the film of airway lining fluid contain components of the film itself, such as the aforementioned non-volatile material including mucins, non-mucin proteins, salts and cellular debris. Adding to the complexity of the composition, the particle mixture also contains saliva, nasal secretions, serum and blood from oral lesions, and even food debris 14 . Of public health concern, however, is that the particles may contain pathogens such as bacteria, viruses and fungi. Numerous pathogens have been measured in exhaled breath, including influenza, human rhinovirus and Mycobacterium tuberculosis 15 . In total, the typical mass or volume proportion of non-water content in a particle generated in the respiratory tract is 1–10% 14 , 16 .

The likelihood that a particle contains bacteria or viruses relates to the size of the particle, the pathogenic load in the mucus gel and saliva, and the point of origin of the particle within the respiratory tract. At a viral load of 7 × 10 6 RNA copies per millilitre oral fluid, the probability that a particle of 50 μm diameter, prior to dehydration, contains at least one virion is ∼ 37% 17 , 18 , 19 The proportionality to the particle volume results in a substantially lower probability of ~0.37% for a 10-μm particle, and ~0.01% for a 3-μm particle. Of course, particles with a diameter less than that of the pathogen itself cannot contain such a pathogen; for SARS-CoV-2 this cut-off is ~0.1 μm (ref. 20 ). This relationship is simplistic in view of the heterogeneity of viral concentrations, but it illustrates the importance of viral load in the quantification of airborne viral emissions.

These calculations can potentially lead one to dismiss particles of the order of 3 μm or less as presenting a negligible risk for secondary transmission once emitted into ambient air, as approximately 10 4 particles of 3 µm diameter would be needed in order to encounter a single virion at the referenced viral load. However, experiments using laser light scattering methods indicate that the quantities of particles generated during speech and coughing may be orders of magnitude higher than commonly assumed 17 , 21 Indeed, measurements have indicated there are of the order of 10 5 particles of 2–4 μm and 10 7 particles of 0.2–0.4 μm for a single average cough 21 . With respect to the SARS-CoV-2 virus, when considering that viral loads in respiratory fluids can exceed 10 9 RNA copies per millilitre in certain infected individuals, a single cough can potentially generate thousands of 3-μm particles containing a virion that would be emitted into ambient air. However, whereas coughing is sporadic and characteristic of symptomatic infection, we breathe continuously, which may account for a greater fraction of emitted particles over time even from those with a respiratory tract infection 22 .

Turbulent aerosolization

Turbulent aerosolization occurs when air sweeps past the liquid film at sufficient velocity to draw a portion of its mass into fine ligaments that shed particles into the airstream upon break-up (also known as fragmentation) 23 , 24 . Intuitively, one would expect greater quantities of particles generated by this mechanism from respiratory activities that involve higher air velocities, such as the cough. The physics of gas–liquid aerosolization is best understood in the context of industrial applications, most notably the combustion engine 25 , and an early pictorial description dating from the 1920s involves water and alcohol in a model of a carburettor throat 26 . At this time, a simplified atomizing characteristic quantity was defined as the ratio of the static pressure of the airstream to the surface tension of the liquid being aerosolized 26 . This quantity becomes a Weber number upon incorporating an orifice height, hydraulic diameter or shear boundary layer thickness. Dimensional analysis suggests a drop diameter law quantifying the mean particle diameter generated by turbulent aerosolization:

where σ is the liquid surface tension, ρ is the air density, U is the airstream velocity, and c is a dimensionless quantity related to the viscosity of the media 26 . Note that other predictions of the mean diameter give greater weight to the larger particles 23 , 27 . The drop diameter scaling law is consistent with more recent measurements of drop characteristics in dense sprays 28 .

Equation ( 1 ) suggests that two aspects of turbulent aerosolization are relevant to the particle generation in the human respiratory tract. First, the average size of generated particles decreases with increasing airstream velocity; and second, the average size of generated particles increases with increasing surface tension (cohesion) of the airway liquid film. The phenomena of increased particle size, and diminished quantity of generated particles, by increased surface tension has been experimentally validated 29 , 30 , although subsequent work indicates that this may be due to changes in surface viscoelasticity rather than surface tension alone 31 . Elasticity is also important: because particle size is inversely related to the flow instability mode, it should decrease with increasing surface tension 32 .

However, equation ( 1 ) and the definition of the atomizing characteristic quantity are simplified descriptions, which neglect boundary layers at the fluid interface, secondary aerosolization from ongoing liquid break-up in the airstream, and particle coalescence in the far field 33 . More importantly, such relationships apply to Newtonian fluids such as water, and airway mucus is a viscoelastic liquid 34 . A review of the rheology of airway surface liquid 35 reports viscosities much higher than water, from 0.058 to >70 Pa s, and influenced by morbidities such as chronic bronchitis and cystic fibrosis. Conversely, the surface tension of airway surface liquid is less variable and lower than water, with a range of 0.01–0.05 N m –1 (ref. 36 ), and a range of 0.001–0.01 N m –1 (ref. 37 ) for alveolar surface tension measured directly in an excised lung of a rat. Unfortunately, none of these rheological properties can be measured directly in the respiratory tract of a living human being, limiting the accuracy of numerical modelling.

In terms of such non-Newtonian surface tension effects, viscoelasticity reduces the duration of ligament stretching as compared with a viscous Newtonian fluid, thus leading to shorter and thicker ligaments that break up into particles that are larger on average 38 , 39 However, viscoelasticity also broadens the size distribution of the aerosolized particles, leading to a greater frequency of both small and large particles that is well described by a gamma distribution 40 . It then follows that the high viscoelasticity of airway surface liquid probably contributes to the heterogeneous size distribution of emitted particles, spanning several orders of magnitude for coughs, which involve high-velocity turbulent flow 21 . Furthermore, owing to interpersonal variations in viscoelastic properties that affect airway lining break-up, the overall quantity of particles emitted in exhaled breath can vary by several orders of magnitude between individuals 41 .

In closing, although the enormous quantities of particles generated from turbulent expirations 21 suggest that turbulent flows may cause considerable stripping and/or dislodging of particles from the airway lining film, we note that there is surprisingly limited direct evidence of this mechanism in the literature, and further study is needed 10 .

Fluid film, filament or bubble breakage

The bronchiole fluid film burst mechanism is a type of FFBB and was introduced to explain the asymmetry of particle generation in the breathing cycle, during which fewer particles are generated during exhalation than inhalation 11 . This asymmetry is inconsistent with the turbulence-induced aerosolization mechanism described above. The bursting mechanism begins with fluid closures that occur in respiratory bronchioles during the airway collapse following exhalation. During inhalation, a fluid blockage contracts axially as it is drawn radially outward by the expanding bronchiole, ultimately becoming a thin film or bubble. The film or bubble subsequently bursts and fragments into particles, reopening the airway. This mechanism is consistent with the observation that particle generation increases as breathing becomes deeper and faster 42 , because deeper exhalation results in more blockages that are subsequently reopened upon inhalation 11 . This explanation is further evidenced by the finding that exhalations that achieved residual volume generated far more particles than shallower exhalations at functional residual capacity 8 . The presence of biomarkers from alveolar cells in exhaled breath provides further evidence of the importance of this mechanism 7 .

In addition to the bronchiole fluid film burst, FFBB also occurs in the larynx during speaking, because of fluid films bursting and filaments breaking when the mucus-bathed vocal folds adduct and vibrate 43 . Furthermore, particle generation rates increase with increasing amplitude of vocalization 44 , although it is difficult to attribute this solely to enhanced bursting in the larynx, as speaking loudly is likely to require additional airflow, providing additional opportunity for turbulent aerosolization as well as FFBB. Likewise, singing generates more respiratory particles than talking, with the number increasing with song loudness and possibly with higher pitch 45 .

Although the physics of FFBB is less understood than that of turbulent aerosolization of Newtonian liquids, there is evidence that surface tension rather than gravity drives the collapse of viscous surface bubbles after rupture 46 . Thus, as with turbulent aerosolization, further study is merited on the surface tension of the viscoelastic film that lines airways, including how it and viscoelasticity can be manipulated to reduce emissions of pathogen-laden particles. Alternatively, rheological properties of the film could be altered to increase the size of generated particles to promote their settling to the ground, as it is unlikely that emissions can be completely eliminated 32 . However, methods of stabilizing airway lining fluid to suppress pathogenic emissions require much more in-depth research 47 , including consideration of evaporation in ambient air after emission. Additionally, such methods need not be limited to deep components of the respiratory tract. For example 6 , it was found that lip balm reduced formation of salivary filaments and subsequent particle generation during speech. It is also of great interest and importance to elucidate the mechanisms responsible for super-emitting individuals who produce substantially more particles than the average person, as has been demonstrated for breathing 29 , coughing 21 and speech 44 . For example, particle emissions from the respiratory tract seem to increase with increasing viral load of SARS-CoV-2 and body mass index multiplied by age 41 .

Respiratory particles in the air

To explain the fate in the air of particles generated from human respiratory activities, it is critical to understand what happens to the particles immediately after emission, when the condensed, warm and humid emission plume mixes with and is diluted by ambient air. In the field of aerosol science, the convergence towards developing an understanding of the initial instant of emission of respiratory particles has been long and has not yielded definitive answers 7 , 48 , mainly owing to the complexity of physical processes such as evaporation and the difficulty of measuring the particle emission in situ. In addition, different techniques are used to measure somewhat different parameters, often making comparisons of the outcomes difficult. Furthermore, when considering airborne disease transmission, the interaction of the respiratory particles with the airflow is a crucial issue, which makes the process more complex.

Measurement techniques

The exhaled airflow measurement techniques can be divided into two categories 49 : global flow-field measurements (high-speed photography, schlieren photography and PIV), and pointwise measurements 50 , 51 , 52 , 53 . The global flow-field measurement techniques provide information on the whole flow field and help us to understand the interactions between the exhaled flow, the thermal plume and the room airflow. The pointwise measurements are instead used to measure the initial temperature, initial humidity and velocity. Methods and instrumentation adopted to investigate respiratory particles using global flow-field measurements, and the main findings from the studies, are reported in Table  1 and Supplementary Table 1 reports the corresponding summary for studies of airflow.

There has been a variety of instrumentation used in studies of particle size distributions, including a laser diffraction system 21 , optical particle counter 29 , 42 , 54 , scanning mobility droplet sizer 55 , aerodynamic particle sizer 43 , 44 , 55 , 56 , electrical low pressure impactor 57 , interferometric Mie imaging 58 , PIV 58 , laser diffraction system 29 and laser light scattering system 17 .

As a final note, the problem of characterizing particles generated in the respiratory tract is further complicated by the fact that the size distribution of particles at the site of generation within the body is undoubtedly different from the distribution at the moment of emission into the environment, owing to processes such as coalescence, among others. However, the evolution of measurement techniques has also made it possible to get closer and closer to the point of emission (that is, the human face), to reduce as much as possible the effect of evaporation of the water content of the particles before they reach the point of sampling. For instance, PIV and an interferometric Mie imaging (IMI) technique have been used to measure the respiratory air-jet velocities and the size profiles of respiratory particles during speaking and coughing in close proximity (10 mm) to the mouth 58 , by reducing the effects related to evaporation and condensation.

Size distributions and quantities of particles

Increasingly accurate measurement techniques have yielded evidence of a trimodal distribution of particles emitted by speaking subjects: the B mode from particles generated in small airway bronchioles during breathing, the L mode from particles generated in the larynx, and the O mode from particles generated in the mouth 5 . Figure  2 presents graphs updated from a previous comparison, including also a dataset on varying amplitude. One study is the uncorrected BLO individual modes integrated from ref. 5 for 2-minute intervals of speaking (c-v), and the cumulative totals for all three c-v modes and for 2 minutes of intermittent, sustained vocalization (aah-v). As described in ref. 5 , ‘c-v’ represents speech (alternately 10 s of voiced counting and 10 s of naturally paced breathing), while ‘aah-v’ represents sustained vocalization (alternately 10 s of unmodulated vocalization [voiced ‘aah’] and 10 s of naturally paced breathing). A second dataset is the cumulative emission reported in ref. 17 which represents the reported rate of 2,600 ~4 µm diameter particles per second extrapolated to 2 minutes of speaking. A third dataset is Table 3 of ref. 59 , which reports particles emitted from counting loudly to 100. We adjusted the data by dividing the droplet diameter by 6 for measurements below 50 μm to eliminate Duguid’s correction for evaporation and reflect the observation that such particles would have been ~2/3 of their diameter if not for the Congo red dye. A fourth dataset is Table 2 of ref. 60 , which also reports counting to 100, reflecting the average distribution from the measurements obtained from three subjects (two experiments for each). Finally, we digitized measurements from Figure 3d of ref. 44 to depict a representative particle size distribution for one individual speaking for 2 minutes at different amplitudes.

BLO data (where B represents particles from bronchioles, L larynx and O mouth) are from ref. 5 . Other data are from refs. 44 , 59 , 60 . The BLO cumulative shaded range spans the c-v to aah-v particle totals from all three modes for uncorrected data (where c-v represents speech and aah-v represents sustained vocalization; see text for details).

Below 10 µm particle diameters, there is remarkable agreement in terms of both size distribution and cumulative quantity between different measurements of the B and L modes from ref. 44 , the adjusted data from ref. 59 and the uncorrected data from ref. 5 . Specifically, the c-v total is consistent with speaking quietly, whereas the aah-v total is consistent with speaking loudly 44 .

Although the dataset from ref. 60 has been considered an outlier for the substantially larger quantity of O mode particles measured above 10 µm, it is more in line with the recent data of ref. 17 , which quantified emission rates 2–3 orders of magnitude higher than indicated by prior studies. The substantial increase in particle counts found by laser light scattering is similar to the differences in measured cough emissions between studies 21 , 61 Thus, although there is agreement between the BLO model and more recent particle counter studies, laser light scattering results indicate that the BLO model number and mass concentrations may be inadequate. Considering that the volumetric particle emission rate is an essential component of modelling for airborne transmission risk assessment 62 , the continued advancement of laser light scattering or diffraction measurement techniques should be seen as a priority.

Particle fates

Once emitted, the fate of the particles depends on complex and interconnected effects of inertia, gravity and evaporation 24 , 63 . For isolated respiratory particles (also known as droplets), a critical size of approximately 100 μm was introduced in the 1930s 63 . Larger particles settle faster than they evaporate by depositing onto close surfaces, whereas smaller particles evaporate faster than they settle and, being small and light, can stay airborne and can be inhaled or may be transported over long distances. The critical size separating these behaviours (~50–150 μm) depends on many physical parameters such as ambient air velocity, ambient air temperature and, above all, relative humidity 64 .

This approach based on isolated particles represents the benchmark for public health agency guidelines 65 , 66 and is the basis for more recent research 67 . However, it does not consider the role of the warm and moist air of the turbulent gas puff within which the particle is exhaled and which remains coherent for a short time 68 , 69 , 70 , 71 . The fluid motion of the exhaled jet, supported by the injection of fluid momentum and buoyancy through the orifice (mouth or nose) into the surrounding environment, gradually evolves along its trajectory. It increases its volume for each subsequent respiratory activity with velocity ranging from <1 m s –1 (breathing) to tens of metres per second (sneezing) 12 . Isothermal jets of the same temperature as the surrounding environment follow a rectilinear trajectory, whereas non-isothermal jets follow a curved trajectory, with the puff evolving into a turbulent cloud 64 . The ejected particles remain suspended in the cloud even after the puff has lost its coherence because of the perturbations of drag and mass decrease due to evaporation, but their trajectories become dependent on the ambient air currents and turbulence 12 . However, the fate of larger particles within the jet is different: they move semiballistically with only minimal drag perturbations, and fall quickly down owing to gravity.

The complexity of the composition of the fluid lining airways makes it difficult to accurately estimate transport properties of particles: for example, viscosity of the fluids can be one or two orders of magnitude larger than water, thus reducing the coalescence among the particles 12 . The puff remains coherent for a longer time and thus greater distance indoors than outdoors. This is because the coherence of the puff is preserved as long as its mean velocity is higher than that of the surrounding air, and outdoor airflow velocity is usually higher than that of indoor air. After the loss of coherence, the cloud is advected by air currents, and the subsequent dynamics is governed by turbulent dispersion 67 .

As soon as the emitted particles enter the unsaturated air, they begin to evaporate, and their radius contracts over time with a decrease of the water content (except in cold and humid environments), unless the respiratory puff is supersaturated, in which case particles can first experience considerable growth, only later followed by shrinkage 72 . The rate of mass loss due to evaporation of a particle depends on various physical phenomena, such as the diffusion of the vapour layer away from the surface 73 , 74 , 75 , 76 , or evaporative cooling, in which the high latent heat of evaporation cools the particle surface by decreasing the evaporation rate and the diffusion coefficient 77 . Other relevant phenomena include Stefan’s flow, that is, induced movement of air away from the particle with increased evaporation rate 78 ; ventilation effects, in which airflow around particles larger than a few tens of micrometres enhances evaporation 78 , 79 ; and, finally, the presence of non-volatile material (mostly inorganic ions, salt, mucins, proteins, sugars, proteins, lipids, DNA and, potentially, pathogens), which lowers the vapour pressure as determined for an ideal solution through Raoult’s law and the rate of evaporation 79 , 80 .

Each particle that remains within the puff evaporates to its stable, smaller, diameter, which depends on the initial amount of non-volatile matter contained within the particle and on the temperature and relative humidity of the air. Historically, this size-stabilized particle has been called the droplet nucleus. The amount of water that remains absorbed within the particle depends on the relative humidity 81 , even if the relations among the composition, the final size and the influence of the relative humidity are impossible to quantify 82 . In any case, regardless of whether water evaporates completely leaving only the non-volatile particle content, the important consequence is that the distribution of stable sizes is narrow, on average of the order of 1 µm (ref. 12 ).

An additional complexity that must be considered is that, in reality, particles do not evaporate as if they were independent. Particles dispersed within a room can be considered independent, but this is not the case for particles in a respiratory aerosol jet where the relative humidity remains uniform and close to 100%, leading to reduced evaporation except at the spray boundaries 72 , 83 . This high relative humidity makes these particles extremely long-lived, up to 100 times the isolated particle lifetime 84 , 85 , 86 .

Finally, ventilation-induced airflows play an important role in the fate of particles emitted from respiratory activities in indoor environments: after particles evaporate to their stable size, they can remain suspended in the air for prolonged periods and be transported long distances by indoor airflows 87 . Therefore, the airflow pattern is the most important factor influencing the spatial concentration of the particles in indoor environments 88 , but it depends not only on the air distribution system and heat sources but also on the microenvironment around people 89 . However, this important and complex aspect is outside the scope of this article.

Inhalation of particles

The air that enters the respiratory tract during inhalation contains particles that come from many sources — including combustion sources such as cars and cigarettes, as well as the particles emitted by exhalation — and that vary in size, physicochemical and biological characteristics 90 . A detailed discussion of the natural and anthropogenic sources and characteristics of particles is outside the scope of this Perspective and can be found, for example, in refs. 91 , 92 , 93 , 94 , 95 . A fraction of the particles is deposited in the respiratory tract, and some of them penetrate through the epithelium to the bloodstream and, in turn, to other organs in the body 96 , 97 , 98 . Because of this, inhalation of airborne particles leads not only to respiratory effects, but many other health impacts, including allergy, effects on the immune system, cancer and effects on reproduction, irritative effects on skin and mucous membranes of eyes, nose and throat, sensory effects on nervous and neurological systems, effects on the cardiovascular system and increased mortality 99 , 100 , 101 , 102 , 103 . Airborne particulate matter is considered one of the top ten health risk factors that humans face 104 ( https://vizhub.healthdata.org/gbd-compare/ ). In addition, if the particles are pathogens such as viruses or bacteria, or contain pathogens, they can cause infectious diseases, such as common colds, influenza, tuberculosis, COVID-19 and many others 105 , 106 , 107 .

The severity of the impact due to particles deposited in the respiratory tract depends on the dose received by the exposed persons for specific physicochemical characteristics 62 , 108 , 109 , 110 . For a given exposure time, concentration of particles in air and particle size distribution, the dose of particle received is governed by the physics of particle inhalation, including transport and consequent deposition in specific parts of the respiratory tract 111 , 112 . Of the particle physical characteristics related to particle deposition in the respiratory tract, the most important are particle numbers, size distribution and particle concentration 113 , 114 . Factors that affect transport and deposition of particles in different regions of the respiratory tract during inhalation include the morphometry and thermo-hygrometric conditions of the respiratory tract, breathing patterns and particle characteristics.

Morphometry and thermo-hygrometric conditions of the respiratory system

The functions of the human respiratory system include the supply of oxygen to the alveolar region of the lungs and the exchange of gases (oxygen and carbon dioxide) between the lungs and the bloodstream. To fulfil these tasks, the system has a complex morphometry, as it is made up of a highly efficient airway network from the entry ports (nose or mouth) to the alveoli. A detailed description of the morphometry of the respiratory system is beyond the scope of this Perspective; however, for completeness of this discussion, we summarize its basic components and their roles as reported by the International Commission on Radiological Protection (ICRP) 113 . According to the ICRP, the human respiratory tract is divided into three main regions: the extrathoracic region (from the nose or the mouth to the entrance of the trachea); the tracheobronchial region (from the trachea to the terminal bronchioles), the role of which is transporting air to and from the alveolar region; and the alveolar region (from respiratory bronchioles to alveoli), the main function of which is to exchange gases.

The airway network is a repeatedly bifurcating three-dimensional asymmetrical network in which small branches of the airways are formed by the division of a larger airway. (The branches are known as generations, with the trachea being generation 0, the mainstream bronchus being generation 1 and the bronchioles being generation 4.) The diameter and length of the airway segment decrease from generation to generation. In addition, the branching angle and inclination change with each bifurcation, making the flow pattern irregular and difficult to model in detail 113 , 115 , 116 . Furthermore, the volume of tracheobronchial and alveolar airways changes substantially during the breathing cycle. In particular, the expansion and contraction that occur during inhalation and exhalation result in different velocity profiles between the two phases of the cycle, allowing for a mixing between the inhaled and reserve air and the consequent migration of particles between them. This effect is known as particle dispersion in the lungs and could partly explain the considerable interpersonal variation in particle deposition fractions 115 , 117 . An additional feature of the airways that must be considered in view of understanding the particle deposition process is the characteristic thermo-hygrometric condition: the temperature and relative humidity beyond the first few generations are estimated at approximately 37 °C and 99.5% 68 , 118 . This condition allows for substantial growth of inhaled hygroscopic particles and consequently affects their deposition 119 . Finally, the inner surfaces of the airways are covered by a lining fluid, which acts in part as a protective barrier against foreign particles, but also increases the dissolution of soluble deposited particles. It should be pointed out that the ICRP morphometric model (widely adopted to evaluate particle deposition in the lung) is characteristic of a ‘reference man‘ and uses scale factors based on body height to adjust the dimensions for other subjects, including women and children. Nonetheless, the anatomical variability documented among healthy subjects exceeds what one would assume based on ICRP 120 , 121 , 122 .

Physical properties of the particles and deposition mechanisms

An accurate prediction of the airflow in the different segments of the respiratory tract is extremely difficult. One reason is that, owing to the size of segments, the flow characteristics vary along their length and the velocity profile is not parabolic, as would be expected for channels 115 , 123 , 124 . Therefore, evaluating the deposition of particles in each airway of the respiratory tract on the basis of analytical equations of airflow is practically impossible. A rough assessment of airflows for a person breathing calmly indicates that turbulent flow typically occurs from the nose and mouth to the trachea, whereas from generation 4 (bronchioles) up to the alveoli the flow is laminar. Between these extremes, from generation 1 to 3 (larger bronchi) the flow is mostly laminar, but turbulent flow may occur because of the instability induced by the larynx and the cartilaginous rings in the trachea 115 , 125 .

The properties of the particle that are important in affecting its fate during inhalation and deposition are size (expressed as equivalent diameter), density and shape; these factors influence the aerodynamic and diffusive behaviour of the particles and therefore their transport and deposition. Regarding inhalation, experimental studies carried out considering different orientations of the nose, mouth and head with respect to the airflow showed an inhalability of 100% for particles of a few micrometres and smaller, decreasing to ~50% at 50 µm (ref. 113 ). Regarding deposition, increasing particle sizes and densities increase the inertial forces acting on the particles 114 , 125 and consequently the deposition rate of supermicrometric particles. Because of the abovementioned hygrometric conditions in the lungs, the diameter of particles can more than double after inhalation into the lung 68 , 119 .

Measuring deposition

The potential for particles to cause disease depends on the region in which they are deposited. For instance, the deposition of particles in tracheobronchial and alveolar regions is more critical than in the extrathoracic region. However, direct and experimental knowledge of deposition is mainly available only for total deposition in the whole respiratory tract.

Measuring the total deposition of submicrometre particles is not an easy task. The total deposition fraction of submicrometre particles is usually measured by comparing the particle size distributions of air inhaled and exhaled by human volunteers; typically, inhaled and exhaled air are stored in separate chambers in which particle size distribution and total concentration measurements are made continuously using mobility particle sizers. Although only a few studies have made measurements of total deposition of submicrometre particles, these studies have been carried out for different types of aerosols (ambient and combustion aerosols, and aerosol produced by generation systems designed for this purpose), different population groups (adults and children, males and females), different breathing patterns (residence time, tidal volume, breathing frequency), and different groups with respiratory disease 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 .

Measurements of total supermicrometre particle deposition fractions date back to the 1950s. For this range of particles, different methods were applied, including inhalation of particles labelled with a gamma-emitting radionuclide, and comparisons between the concentrations of inhaled and exhaled particles (similarly to those described for submicrometre particles), measured by aerodynamic particle sizers or photometers. The deposition experiments were also carried out for different types of aerosols and different breathing patterns 130 , 134 , 136 , 141 , 142 , 143 , 144 , 145 .

In adults, the total deposition is higher for ultrafine particles (<100 nm), exceeding 50% for diameters <50 nm, as well as for supermicrometre particles, whereas a minimum deposition fraction is seen in the range 100 nm to 1 µm (Fig.  3 ). The high deposition fractions of ultrafine particles are due to diffusion; the high deposition fractions of supermicrometre particles are due to sedimentation and impaction. Between these two size ranges, diffusion and inertia are less effective.

The deposition fraction is shown as a function of the particle size D obtained from reported experimental studies 113 , 126 , 129 , 130 , 132 , 134 , 136 , 141 , 142 , 143 , 144 , 145 and calculated from the ICRP 113 as average values between males and females while sitting (black solid line). ETS, environmental tobacco smoke. The studies are listed in Supplementary Table 2 .

Substantial differences between subjects were reported within the studies, and although mean deposition fractions are reported for each study, substantial differences also exist between the studies. In general, such differences are due to the different objectives of the studies, leading to differences in experimental systems and methods used, with all these factors potentially affecting the results, as summarized in a critical review of nanoparticle lung deposition measurement techniques 146 . In fact, the results are strongly affected by the aerosol source (which affects monodispersity and electrical charge, among other factors), the inhalation system (which affects factors such as particle losses, leaks and breathing patterns), and the particle detector (which affects efficiency and response time, for example). Furthermore, owing to the complexity of the experimental campaigns, the total number of volunteers involved in these studies remains limited, so interpersonal differences, due to the variability of the morphological and breathing pattern of human lungs, also play an important role. As an example, studies imposing different programmed breathing patterns 132 , 136 , 144 , 147 , 148 , 149 , 150 , 151 highlighted that longer residence times and higher tidal volumes increase the efficiency of the deposition, because they enhance the role of diffusion and sedimentation of the particles.

Unlike total deposition, regional deposition fractions cannot be measured directly, so their assessments are less accurate. They are obtained by indirect methods, such by conducting radiolabelled aerosol retention measurements, computed tomography or magnetic resonance imaging scans, and gamma scintigraphy either using hollow cast techniques or human volunteers 138 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 . However, these methods cannot adequately reproduce the complexity of the peripheral airways 113 , 160 . Therefore, to estimate regional contributions, measurements have been combined with particle deposition modelling. Detailed reviews of existing models can be found elsewhere 125 , 161 .

There is an urgent need to broaden our understanding of the physics behind breathing, one of our most fundamental physiological functions. The benefits could include better assessment of respiratory health, more precise delivery of pharmaceutical drugs, and the understanding and potential reduction of respiratory disease transmission. Our understanding of what remains to be done can be summarized as follows.

First, it is critical that new methods and technologies are developed to measure particle formation in situ in the respiratory tract. Although the theoretical understanding of the physics involved in particle generation continues to improve, including through numerical modelling, the relevant rheological properties cannot yet be measured directly in the respiratory tract of a living human being, nor can the quantity and size distribution of generated particles. Advances in nanotechnology may provide a pathway to conduct such measurements, in the form of nanobots capable of collecting and reporting relevant information from inside the respiratory tract.

Second, a much better understanding is needed of the dynamics of the initial moments of the respiratory plume, based on experimental studies and focusing on multiphase jet dynamics. This lack of knowledge has important consequences because the first seconds of the respiratory plume are critical for the airborne transmission of respiratory pathogens, particularly for people in close proximity.

Third, the dynamics of the particles in the lungs is far from being sufficiently understood. The lack of such knowledge has far-reaching consequences, one of them being that the dose–response relationships used to evaluate the risk of infection from exposure to virus-laden particles typically do not explicitly include the deposition fraction, owing to its uncertainty 162 . Focused efforts are needed experimentally, theoretically and computationally to provide a holistic approach to the physics that drives the elements of the process.

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Morawska, L., Buonanno, G., Mikszewski, A. et al. The physics of respiratory particle generation, fate in the air, and inhalation. Nat Rev Phys 4 , 723–734 (2022). https://doi.org/10.1038/s42254-022-00506-7

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Exhaled particles and small airways

1 Unit of Respiratory Medicine and Allergy, Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

2 Unit of Occupational and Environmental Medicine, Department of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

G. Ljungkvist

E. ljungström.

3 Atmospheric Science, Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden

Associated Data

All data generated or analyzed during this study are included in this published article and the appropriate references.

Originally, studies on exhaled droplets explored properties of airborne transmission of infectious diseases. More recently, the interest focuses on properties of exhaled droplets as biomarkers, enabled by the development of technical equipment and methods for chemical analysis. Because exhaled droplets contain nonvolatile substances, particles is the physical designation. This review aims to outline the development in the area of exhaled particles, particularly regarding biomarkers and the connection with small airways, i e airways with an internal diameter < 2 mm.

Generation mechanisms, sites of origin, number concentrations of exhaled particles and the content of nonvolatile substances are studied. Exhaled particles range in diameter from 0.01 and 1000 μm depending on generation mechanism and site of origin. Airway reopening is one scientifically substantiated particle generation mechanism. During deep expirations, small airways close and the reopening process produces minute particles. When exhaled, these particles have a diameter of < 4 μm. A size discriminating sampling of particles < 4 μm and determination of the size distribution, allows exhaled particle mass to be estimated. The median mass is represented by particles in the size range of 0.7 to 1.0 μm. Half an hour of repeated deep expirations result in samples in the order of nanogram to microgram. The source of these samples is the respiratory tract ling fluid of small airways and consists of lipids and proteins, similarly to surfactant. Early clinical studies of e g chronic obstructive pulmonary disease and asthma, reported altered particle formation and particle composition.

The physical properties and content of exhaled particles generated by the airway reopening mechanism offers an exciting noninvasive way to obtain samples from the respiratory tract lining fluid of small airways. The biomarker potential is only at the beginning to be explored.

Electronic supplementary material

The online version of this article (10.1186/s12931-019-0970-9) contains supplementary material, which is available to authorized users.

Exhaled air is an aerosol containing endogenously generated droplets. These droplets contain water and nonvolatile material, and “particles” is therefore the physical designation, even though they are liquid droplets. Studies of exhaled particles originally aimed to understand the transmission of airborne infections. More recently, however, interest has extended to include a search for biomarkers of pathology in the airways. The close proximity to pathological processes in the airways makes exhaled particles an attractive option for clinical investigation. Knowledge of the site of origin and mechanisms of generation of exhaled particles constitutes an important basis for exploring associated biomarkers.

Along with exhaled particles, volatile- and semi-volatile substances may carry important biomarkers such as exhaled nitric oxide [ 1 , 2 ], e g regarding the effect of the injury on small airways due to the mechanical stress following cyclic opening and closure among patients with chronic obstructive pulmonary disease (COPD) [ 3 ]. Exhaled Breath Condensate and certain physiological methods also contribute to the diagnosis of small airway disease [ 4 – 6 ]. The present review, however, focuses on endogenously produced exhaled particles originating in the respiratory tract lining fluid (RTLF) along the airways including the pharynx and mouth. It is limited to studies presenting the count number and size distribution of exhaled particles, therefore a wide range of important studies on small airways have been omitted. We have highlighted key studies reporting the increasing appreciation of the origin and characteristics of exhaled particles. We also present available information on the use of exhaled particles from small airways as biomarkers.

Particle size

It is very difficult to directly determine size of small droplets (diameter < 10 μm) floating in air. In practice, however, a measured property that depends on particle size is commonly used to indirectly estimate the size. Additional file  1 , “Technical and methodological considerations,” outlines the various sizing methods employed in the studies reported here. Presumably, particles generated in situ and then exhaled are liquid spheres. Aqueous droplets will equilibrate with the water vapor in the surrounding air. It follows that their size depends on the surrounding air temperature and humidity as well as the particles’ composition. Equilibration is a rapid process (< 1 s) for small droplets, but may be confounded by the presence of a surfactant layer covering the droplet’s surface slowing evaporation or condensation.

Collection of exhaled particles

Chemical analysis requires sampling exhaled particles. The design of the sampling equipment will inevitably affect the size range of the collected sample. For examples, long tubing, parts not at roughly 35 °C, and sharp turns will contribute to losses of particles, particularly those that are relatively large.

The impactor is a sampling device that allows the collection of a size discriminated samples from an aerosol. Details are presented in Additional file 1 .

Chemical analysis of collected exhaled particles

The great challenge analytically is the extremely low amounts of collected analytes, in the range of picogram (pg) per liter of exhaled air. Electron microscope and X-ray dispersive analysis or surface mass spectrometry, e.g. time-of-flight secondary ion mass spectrometry (TOF-SIMS) can analyze the deposited particles directly [ 7 , 8 ]. Exhaled particles collected by impaction need to be appropriately desorbed. For proteins, immunological methods have dominated so far, but mass spectrometric methods have emerged for proteins as well as for lipids [ 9 , 10 ]. Proteomics analysis has been able to quantify over 200 proteins by combining DNA-markers with PCR amplification of small amounts of particles (in the order of hundred ng) [ 11 ].

Historical perspectives

More than 70 years ago Duguid [ 12 ] aimed to assess the mechanisms of airborne transmission of infection from the mouth and throat. Five participants performed different breathing maneuvers, including normal mouth breathing, counting softly and loudly from 1 to 100, and performing various cough maneuvers. Immediately before these maneuvers, he had applied bacteria to the mucous membranes of the throat and nose. In a separate session, he applied a dye to the surfaces of the mouth, front teeth, lips, and tip of the tongue. Exhaled particles ended up either on a bacterial growth medium or on a glass slide for particle counting using a microscope.

Results from normal mouth breathing revealed no exhaled droplets > 20 μm in any of 15 one-minute tests using directly exposed culture plates. Counting softly resulted in 63 (range 0–160) stain-containing droplets between 1 and 100 μm; counting loudly resulted in 4 to 14 times higher counts. Cough results were dependent on the cough performance; “tongue-teeth cough” gave average counts of 8200, presumably depending among other things on the location and concentration of the dye . The particle counts were many times higher than the colony counts, presumably because many small particles did not contain bacteria.

Comment: Studies were on particles generated in the upper airways only. There was no information on the particles < 20  μm exhaled during normal mouth breathing. Particles > 20 μm were indeed exhaled during all other breathing activities, except for normal breathing.

About 20 years later Loudon and Roberts [ 13 ] aimed to determine the numbers and sizes of exhaled particles using a sampling technique that allowed comparisons of the frequency distribution of all particles > 1 μm. Three participants in two experiments performed a series of 15 coughs into a box and in two other experiments counted loudly from 1 to 100 into the box. Before each experiment, the participant swabbed the inside of his mouth with dye. After each experiment, the box was closed and particles settled on paper slips over 30 min. Settled particles were counted, as were the remaining airborne particles, which were deposited on a Millipore filter in the exit port of the box.

The results from the three individuals showed that the median diameter of particles generated during talking and coughing were 81 μm and 26 μm respectively. Six percent of the particles generated during talking remained airborne after 30 min versus 49% of the particles generated during coughing, indicating the importance of coughing in the transmission of bacterial infections. The number of particles produced by coughing varied broadly. The authors discussed several potentially important causes of the large variability: coughing is difficult to standardize; particle formation depends on a number of factors including the amount of secretion and its location in the mouth and the placement and movement of the lips, tongue, and teeth.

Comments: Studies were limited to particles generated in the mouth and there is no information on exhaled particles during normal breathing.

In 1997 Papineni and Rosenthal [ 14 ] presented results on droplets in exhaled breath obtained by two methods: (a) a real-time analysis by an optical particle counter (OPC) and (b) analysis of dried droplet residues by electron microscopy. The mouth was without dye, and consequently the site of origin of the exhaled particles was not necessarily the mouth region. The OPC and associated software presented particle sizes in six channels between 0.3 and 2.5 μm. Nose breathing, mouth breathing, coughing, and talking were studied in five healthy participants using the OPC and electron microscopic analysis of the mouth breathing particles was conducted with three of the participants.

Results according to the OPC method showed that mouth breathing resulted in 12.5 particles/L for diameters < 1 μm and 1.9 particles/L for diameters > 1 μm. Coughing resulted in 83.2 particles/L for diameters < 1 μm and 13.4 particles/L for diameters > 1 μm.

The results from electron microscopy showed that the size distribution was more heavily weighted towards larger particles: original droplet sizes > 1 μm constituted 64% and the largest particle was 7.6 μm. As the droplet size estimates from the electron microscope were considered to be unaffected by evaporation, the OPC method may have underestimated the original droplet size through evaporation and/or losses of large particles in the funnel.

Comments: Normal breathing does indeed exhale submicron as well as larger particles . The site of origin and mechanisms of generation are still unknown; however, X-ray dispersive analysis of the residue of one particle revealed contents of potassium, calcium, and chloride, consistent with RTLF origin.

In 2004 Edwards et al. [ 15 ] investigated the ability to transiently diminish the number of exhaled particles by administering nebulized aerosols to human participants. Particles were measured by an OPC providing counts in six bins between 0.09 – > 0.5 μm. Eleven healthy participants were investigated on three visits separated by at least a week in a crossover placebo-controlled design. An aerosol was inhaled on the two first visits, either isotonic saline with a surface tension of 72 dyne/cm or a surfactant simulant consisting of 1,2-dipalmitoyl- sn -glycero-3-phosphocholine (DPPC) or 1-palmitoyl-2-oleoyl- sn -glycero-3-phosphoglycerol with a surface tension of 42 dyne/cm. No aerosol treatment was conducted on the third visit. Participants wore nose clamps and breathed large tidal volumes of close to 1 L, inhaling particle-free air. Exhaled particles were measured for 2 min immediately before and 5 min, 30 min, 1 h, 2 h, and 6 h after inhalation.

The results showed that without aerosol treatment, particle number concentration varied among participants between 1 and 10,000/L exhaled air and also varied considerably within participants between the six measurements during each visit. The authors subdivided the results into high ( n  = 6) and low ( n  = 5) particle producers and found that saline delivery resulted in a statistically significant drop of particle emission among high producers and a tendency to increase emission among low producers. Administration of the surfactant simulant amplified particle emission by a factor of about five! No effects on particle size distribution were observed following administration of the saline or the surfactant simulant and the predominant particle size was 0.15–0.2 μm. The diminished particle emission after saline administration among high particle producers was explained by a presumed shift towards large particles outside the OPC’s range resulting in a substantial fraction of particles to deposit in the airways.

Experiments performed on a cough machine consisting of a model trachea lined on the bottom with a mucus simulant showed that saline or surfactant administration resulted in a dramatic shift in the size distribution 30–60 min after administration from 0.2 μm to about 30 μm.

Comments: Subdivision into high and low particle producers is probably misleading. Recent studies showed that exhaled particles are distributed approximately log normally with no sign of two size modes [ 16 , 17 ] . Considering all participants, there was no significant reduction of exhaled particles within the size range of the OPC. Administration of a surfactant simulant to the participants substantially increased particle emission, indicating that surface tension is important. The surfactant simulant with a surface tension of about 42 dyn/cm may in fact increase the surface tension of small airways, particularly at low lung volumes when the surface tension is normally close to zero. Increased surface tension increases particle production [ 18 , 19 ] . Conclusions from the cough machine results are relevant to coughing and forced exhalation, but not to human tidal breathing. The cough machine generates particles by the burst of air destabilizing the mucus/air interface by shear forces to form submicron droplets.

Watanabe et al. [ 20 ] studied in vitro effects, particularly of isotonic sodium chloride, on the propensity of RTLF to form small droplets of various aerosolized formulations and widely varying surface tensions and viscoelastic properties. The main experiments were performed on the cough machine used by Edwards et al. [ 15 ], which was altered by reducing the applied air pressure from about 126 kPa to about 21 kPa to simulate a less violent breathing maneuver. The model measured particle production caused by simulated breathing over the mucus mimetic trachea after the various aerosolized formulations were applied. Particle production was assessed by an OPC covering particle sizes between 0.09 and > 0.5 μm.

The results showed that application of salt solutions with and without other additives increase the surface viscoelasticity relative to the mucus mimetic alone and that gelation of the free surface of the RTLF mimetic resulted in a significant diminution of aerosol particle generation. Experiments on calf lungs confirmed that the charge-mediated gelation near the surface of the RTLF mimetic was reversible.

Comments: The simulated breathing maneuver corresponds to a rather forceful expiration. Under these circumstances, the trachea model reveals a new mechanism: the RTLF/air interface may be stabilized by gelation of the mucus by salt water, making RTLF less prone to disintegrate into very small particles.

In 2009 Morawska et al. [ 21 ] studied exhaled particle concentrations and size distributions at the mouth using a new investigation system. The system was essentially a small wind tunnel, into which participants could place their heads (see Fig.  1 ). An aerodynamic particle sizer (APS) measured particles with diameters ranging mainly from 0.5 to 20 μm. A sample of 15 healthy participants aged ≤35 years performed the following breathing exercises at a rate and depth which felt most natural: (a) in through the nose and out through the mouth, (b) in through the nose and out through the nose, (c) whispering “aah”, (d) voicing “aah”, (e) whispering counting, (f) voicing counting, and (g) coughing. Samples were counted for 2 min and repeated three times with 20 min rests between counts. The statistical analysis applied a so-called mixture model, assuming that observed results were a superposition of log normal distributions representing the various breathing maneuvers.

The Expiratory Droplet Investigation System setup used by Morawska et al. [ 21 ]. Test participants exhaled into a particle- free wind tunnel. A fan maintained at approximately 0.1 m/s controls the wind tunnel airflow. The airflow transports exhaled particles downstream to the aerodynamic particle sizer (APS) where the particles are measured. A relative humidity (RH) probe monitors the humidity. Reprinted from the original article by permission

Table ​ Table1 1 (extracted from their Fig.  5 ) presents results for concentrations of exhaled particles with diameters from 0.5 to 20 μm.

Exhaled particles during various breathing maneuvers

Breathing maneuver	Exhaled particle number concentration (n/L)
in through the nose and out through the mouth	98
whispering “aah”	672
voiced “aah”	1088
whispering counting	100
voiced counting	130
cough	678

DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) mass and exhaled sampled particle mass as determined in samples from eleven individuals that performed ten exhalations using the airway reopening maneuver. Note the linear association through the origin between the collected particle mass and collected DPPC mass. The DPPC weight percent concentration (wt%) is shown for each sample in the lower panel. By permission of the author

Voiced activities resulted in higher particle concentrations than whispered, indicating that the vibrating vocal cords during vocalization produce exhaled particles. Whispered counting produced similar concentrations as normal mouth breathing, indicating that gentle movements of the lips and tongue generate very few exhaled particles in the size range of 0.5–20 μm. Whispering “aah” generated as many exhaled particles as coughing, indicating that high air velocity passing an almost closed epiglottis is an effective particle generating mechanism. The particle size at maximum concentration was about 0.8 μm and there were few particles > 10 μm. The mixture model provided a good fit with four modes (A, B, C, D) for all breathing activities: A is associated with normal breathing; B, C, and D are associated with vocalization and epiglottis adduction. Count median diameters were ≤ 0.8 μm, 1.8 μm, 3.5 μm, and 5.5 μm respectively.

Comments: In agreement with Papineni and Rosenthal [ 14 ] the results show that normal mouth breathing generates particles but no generation mechanism is suggested. During vocalization, however, vibrating vocal cords and air passage through adducted epiglottis almost certainly produces exhaled particles.

Chao et al. [ 17 ] measured the droplet size distribution in close proximity to the mouth opening during coughing and speaking. A sample of 11 healthy volunteers under 30 years of age were asked to count loudly and slowly 10 times from 1 to 100. After a break, they coughed 50 times with lips closed before each cough.

The size measurements at 10 mm from the mouth were regarded to be unaffected by evaporation and condensation and to be representative of the “original” size profile. The particles were distributed in 16 size classes with mean values ranging from 3 to 1500 μm. The size class with the highest number count was 6 μm for both speaking and coughing, and the geometric mean diameter was 16.0 μm for speaking and 13.5 μm for coughing. The size distribution during both speaking and coughing was highly skewed with small numbers of large particles.

Comment: This study is the first to measure the size interval from about 2  μm to 2000 μm with the same measuring system and with an experimental set-up optimized to measure particles unaffected by evaporation/condensation during speaking and coughing. The counts of particles in the largest size classes were very low but represented almost all the volume and mass. It is worth bearing in mind that the mass of one particle with a diameter of 150 μm corresponds to almost 6.6 million particles with a diameter of 0.8 μm assuming similar density and spherical shapes.

Airway reopening hypothesis

At about the same time as the study discussed above, several independent groups dealt with the notion that one important mechanism for particle generation is the reopening of closed airways [ 18 , 22 – 24 ] – as previously posited by Edwards et al. [ 15 ]. The fact that small peripheral airways normally close following a deep expiration was originally shown by Milic-Emili and coworkers in 1966–1968 [ 25 – 27 ] and elegantly confirmed by Burger and Macklem [ 28 ] and Engel et al. [ 29 ]. In upright position, the apical parts of the lungs are more expanded than basal parts due to the weight of the lungs. During an expiration to low lung volumes, the basal airways collapse with the airway walls pasted together by RTLF and reopen again on inspiration. There is a simple single-breath test to determine the volume at which extensive airway closure (the closing volume) begins [ 30 ]. To the best of our knowledge, the precise location of airway closure along the airway tree is not known in humans but is generally considered to be in the small airways. In dogs, airway closure appears to take place in airways with an internal diameter of 0.4–0.6 mm [ 31 ]. Some airways may close at higher lung volumes than indicated by the closing volume [ 32 ], and massive airway closure may occur during tidal breathing [ 33 ] at low lung volumes (low functional residual capacity) as in people who are obese or whose closing volumes are increased by a disease such as COPD [ 32 ]. Then there is a risk of mechanical injury of the small airways due to the cyclic closing and reopening [ 33 ].

Johnson and Morawska [ 23 ] using the same equipment as Morawska et al. [ 21 ], including the Aerodynamic Particle sizer (APS) to determine exhaled particles in the diameter range of 0.5–20 μm. Seventeen participants between 19 and 60 years of age took part. Four different breathing activities were performed and were repeated for 2-min periods:

• Inspiring a normal breath volume via the nose and exhaling via the mouth.
• Inspiring a normal breath volume via the mouth over a 3-s period, followed immediately by a 1-s full deep exhalation.
• Rapid inspiration of a normal breath volume via the mouth, followed by holding the breath for 2, 3, 5, or 10 s and full deep exhalation over 3-s;
• Inspiring a normal breath volume via the mouth over a 3-s period, followed immediately by a 3-s full deep exhalation.

The results show that deep exhalations increased the exhaled particle concentrations. Furthermore, breath holding at mid lung volume was found to reduce the exhaled particle concentrations proportional to the duration of breath holding and to cause a shift towards smaller particles. The breath-holding results fit with the predicted effects of gravitational settling in an alveolus considering that droplet size is about two times larger in the alveolus than when measured because of shrinkage during exposure to ambient humidity. The humidity correction was later experimentally confirmed by Holmgren et al. [ 34 ]. A rather weak positive correlation with age was reported but one outlier was not included in the correlation. Nevertheless, this observation is consistent with the observation that airway closure increases with increasing age [ 30 ].

Comments: Effects of deep exhalation confirm the airway-reopening hypothesis. Breath holding causes time-dependent preferential settling of larger particles in the airways, thereby preventing their exhalation.

A Hannover research group presented two parallel studies in 2010 [ 18 , 35 ]. Schwarz et al. [ 35 ] measured exhaled particles, flow rates, and tidal volumes online during single breaths in 21 healthy participants aged 21 to 63 years. Spirometry and lung volumes were obtained. Particle concentrations and size distributions were measured online in a temperature-regulated box at 37 °C using a condensation nuclei counter and a laser spectrometer. Six diameter intervals were found ranging from 0.1 to > 5 μm. The protocol involved varying tidal volumes between 20 and 80% of the forced vital capacity. Tidal volumes < 0.7 L were disregarded because response times of the online measuring devices were too slow. One test assessed intra-participant variability through repeated breathing maneuvers after 2 h rest on the same day and during a second visit within 2 months.

The results showed that the difference between exhaled particle concentrations at the smallest and largest tidal volumes could be more than two orders of magnitude. The count median diameter was 0.3 μm and only about 2% of the particles were > 1 μm and none were > 5 μm. With decreasing expiratory flow rates at a given volume, there was a shift toward fewer and smaller particle sizes, in accordance with the increased preferential gravitational settling of larger particles. The number of particles exhaled in a breath seemed to be more influenced by how fast the exhalation started after inhalation was to RV (i.e. a shorter time for sedimentation) than how close to TLC the inhalation finished. Particle emission was positively correlated to age, as previously observed [ 23 ]. Increasing the expiratory flow from about 0.2 L/s to 0.8 L/s resulted in an increase in particle emission by a factor of 3, presumably because of a shorter transit time and less deposition of particles before exhalation. Increasing the inspiratory flow from 0.3 L/s to 1.7 L/s showed an insignificant increase in particle emission. High intra-day and inter-day reproducibility within participants was found, with an average correlation coefficient of 0.92, whereas inter-participant variability was about 2 orders of magnitude.

Comments: The airway reopening hypothesis was challenged by effects of deep exhalation and the hypothesis was strengthened. The observed inter-individual variation was large, but was assessed by correlations.

The parallel study by Haslbeck et al. [ 18 ] investigated particle formation by rupture of surfactant films using computations in a fluid dynamics model. A simplified instrument comprising a biconcave cylinder < 0.5 mm in diameter modeled the small airway structure. A liquid film was applied with uniform thickness in the middle of a cylinder and blocked the cylinder passage. The model described the thinned circular film before rupture and the associated drop formation. The critical thickness of film rupture was 0.2 μm, allowing for computations of film rupture and drop formation as a function of the parameter’s surface tension (0.1–20 dyn/cm), viscosity, and density. The model did not consider the movements of the wall and the drop in pressure across the film. Particle emission was measured in 16 healthy participants in the same way as in the study by Schwarz et al. [ 35 ].

The results showed that high surface tension increases the quantity of droplets and slightly reduces droplet sizes. There was no effect of density and almost no effect of viscosity. The count-median diameter was about 0.4 μm irrespective of parameter variation. Thus, surfactant film rupture in simulated small airways produces particles of the same size distribution as during tidal breathing. The results from the human study confirmed the results found by Schwarz et al. [ 35 ].

Comments: The results of the computational model of fluid dynamics simulating small airway opening are consistent with the airway reopening hypothesis. The effect of surface tension was later confirmed [ 19 ] .

Almstrand et al. challenged the airway reopening hypothesis by having 10 normal participants performed three strictly controlled breathing maneuvers [ 22 ]. Figure  2 illustrates the breathing maneuvers applied to challenge the airway reopening hypothesis. Each maneuver was repeated 10 times. Exhaled particles were counted by an OPC placed inside a box with a thermostat set at 36 °C, drawing a continuous sample from a cylindrical reservoir of 3.4 L capacity inside the box, as described previously in detail [ 8 ]. Figure  3 shows a schematic illustration of the equipment counting and sampling exhaled particles. The OPC and sizer determined particles in the range of 0.3 to > 2 μm in diameter subdivided into eight size intervals. Samples from the reservoir of exhaled air were taken until the count rate was close to zero after each maneuver. Then the maneuver was repeated. Count rates combined with the simultaneous flow rates allowed the calculation of the concentration of particles in the exhaled air (n/L).

At low specified flow rates the participants exhaled to ( a ) residual volume (RV), ( b ) closing point (CP), i.e., the lung volume at which extensive airway closure begins, or ( c ) normal tidal exhalation to functional residual capacity (FRC). Participants then inhaled to total lung capacity (TLC) and immediately exhaled into the equipment back to FRC. By permission of the author

Schematic presentation of the equipment Almstrand et al. [ 22 ]. Participants inhale thorough a HEPA filter and exhale into the equipment. The box containing the equipment was maintained at approximately 36 °C. An optical particle sizer and an impactor allowed for counting and sampling of exhaled particles. Exhaled air that was not directly drawn into the impactor and counter was buffered in a reservoir and subsequently drawn into the impactor and counter and replaced by humidified particle-free air. Particles < 4.6 μm were sampled and the size distribution determined. By permission of the author

Average results showed that exhaling to RV produced 8500 n/L, exhaling to closing point (CP) 2500 n/L, and exhaling to functional residual capacity (FRC) 1300 n/L. Particle concentration following the RV maneuver is the sum of the particles generated during inspiration from RV to CP, from CP to FRC, and from FRC to total lung capacity (TLC). Separating the concentrations generated during each of these inspired volume intervals and allowing for the various magnitudes of these intervals showed that the RV-CP interval generated about 85%, the CP-FRC interval about 12%, and the FRC-TLC interval about 3% of the total amount of exhaled particles. The size distributions were not substantially affected by the various maneuvers and the maximum concentration was in the size interval 0.3 to 0.4 μm and there were very few particles above 1 μm.

Comments: The airway reopening hypothesis is further strengthened. The breathing maneuvers described show that lung volumes where airway closure (and reopening) prevails generate the vast majority of the exhaled particles.

Holmgren et al. [ 36 ] measured the size distribution between 0.01 and 2 μm in 16 healthy participants using an optical particle sizer (OPS) and a scanning mobility particle sizer (SMPS) system. The experimental system was essentially located in a walk-in climate chamber set at 35 °C. The participants sat outside and the OPC measurements were corrected to better represent the actual physical dimensions of exhaled aqueous droplets after recalculation into 15 size intervals from 0.41 to > 33.1 μm. The SMPS system measured particles between 0.01 and 0.43 μm. A 30 L sampling bag collected the exhaled air. Participants performed two breathing maneuvers: (1) normal tidal breathing where the inspirations were of particle-free air and (2) a slow expiration to RV followed by a full inspiration of particle-free air followed by a measured exhalation. Participants exhaled to the sampling bag capacity as the sampling instruments consumed the air in the bag. The breathing maneuvers were repeated twice. The results revealed that during normal tidal breathing the geometric mean particle size was 0.07 μm. During the RV breathing maneuver the particle distribution was mainly between 0.2 and 0.5 μm. There was no correlation between particle emission from tidal breathing and from RV breathing.

Comments: Tidal breathing emits a mode of extremely small particles, whose mass is negligible. The widely different size distributions resulting from the two breathing maneuvers and the lack of correlation between them suggest different sites of origin.

Johnson et al. [ 37 ] extended previous work [ 21 , 23 ] and integrated results from the APS assessments of particles with diameters mainly from 0.7 to 20 μm and a droplet deposition analysis (DDA) covering diameter > 20 μm thus spanning a wide range of particle sizes. Their equipment was essentially the wind tunnel set-up described previously [ 21 ]. Fifteen healthy participants < 35 years of age participated in the APS studies. Eight were included in the DDA after an oral rinse containing a food dye. As the number of exhaled large droplets was very low, participants had to cough 50 times to produce an adequate number of droplets of each size. The APS counts were corrected for evaporative and dilution effects. Combining DDA results and results from the APS after transformation onto a common scale produced a composite size distribution. Only average results were presented from all individuals due to very large inter- and intra-individual variation. The analysis applied the mixture model assuming log normal distributions.

Results indicated three modes of particle size distributions:

• Normal and deep tidal breathing resulted in the first mode with a count median diameter of 0.8 μm interpreted to have been caused by the airway reopening mechanism.
• Speaking, unmodulated vocalization, and coughing resulted in the second mode with a count median diameter of about 1 μm interpreted to have been caused by vocal cord vibrations and aerosolization in the laryngeal region.
• Speaking and coughing also resulted the third mode with DDA stain dots with a count median diameter of about 200 μm interpreted to have been produced in the presence of saliva, i.e., between the epiglottis and the lips.

Comments: In addition to previously identified size modes, there was a mode of large particles. This mode relates to particle generation in the upper respiratory tract, including the oral cavity.

Holmgren et al. [ 38 ] extended the study by Johnson and Morawska [ 23 ] on breath holding by studying it at both low and high lung volumes. The equipment was the same as that of Almstrand et al. [ 22 ]. Ten participants held their breaths at TLC or RV. A breath-hold of 5 s at TLC reduced the exhaled concentrations by as much as 43% and more with longer breath holding, almost certainly due to the settling of particles in the airways. A breath-hold at RV, however, increased the number of exhaled particles: 5 s caused an increase of 63% over no breath-hold, and a 10-s breath-hold caused an increase of 110%. This result was interpreted as an effect of time on airway closure: the number of airways that close at RV increases with time.

Comments: One ought to consider the time-dependent generation of particles in small airways and the deposition of particles in the alveoli and airways when interpreting results or designing breathing maneuvers.

Several studies have found that the amount of exhaled particle varies between individuals by orders of magnitude [ 15 , 21 , 22 , 35 ]. Bake et al. [ 16 ] studied the inter-individual variability of exhaled particle emission in 126 healthy middle aged participants following a standardized breathing maneuver (expiration to RV, breath-holding for 3 sec, full inspiration to TLC, and immediate full expiration into the equipment for measurement of the exhaled particles). The equipment was the same used in the study by Almstrand et al. [ 22 ]. Exhaled particles were distributed log-normally with no sign of two superimposed distributions. The inter-individual variation of particle emission was within one order of magnitude, less than previously reported, presumably because of the standardized breathing pattern. Considering age, weight, and spirometry variables reduced the variability further. These predictors explained 28 to 29% of the inter-individual variation, but the remaining variation is still large.

Comments: Unexplained large inter-subject variability remains.

Figure ​ Figure4 4 Illustrates the airway reopening mechanism. As the airways widen during inspiration, closed airways reopen, producing small particles as the plug of RTLF ruptures.

Schematic illustration of the airway reopening concept. When airways close, opposing airway walls get in contact creating a plug of respiratory tract lining fluid. As the airway walls distend during inspiration, forming a meniscus that finally breaks and generate particles. By permission of the author

Chemical evidence of origin

Chemical analysis of exhaled particles can shed light on the origin and mechanisms involved in formation process. Papineni and Rosenthal [ 14 ] used electron microscopy and an X-ray dispersive technique for the elemental analysis of droplet residues. They found significant content of potassium, calcium, and chlorine, all abundant in body fluids. Almstrand et al. [ 8 ] analyzed impacted particles using the surface-active mass spectrometry, TOF-SIMS. The analysis showed strong signals from phospholipids in all samples from four healthy participants. The identified phospholipid compound groups, such as phosphatidylcholine, phophatidylglycerol, and phosphatidylinositol, are known constituents of surfactants from analyses of bronchoalveolar lavage.

Several publications have confirmed that exhaled particles contain phospholipids and proteins similarly to surfactant [ 7 – 10 , 40 ] thus supporting the origin from RTLF and the airway reopening hypothesis. Of special interest are the phospholipid dipalmitoylphosphatidylcholine (DPPC), a major component of surfactant and known to be produced by alveolar type II cells, and the surfactant protein A (SP-A). Larsson et al. have shown a linear relationship through the origin between analyzed mass of collected albumin, SP-A, DPPC and palmitoyl-oleoyl-phosphatidylcholine (POPC) and the mass of collected particles [ 10 , 41 ]. Estimations of the mass of the collected particles are based on an optical particle counter providing eight size intervals within the size range about 0.4–4.6 μm in diameter (Grimm Aerosol, Ainring, Germany). Assuming unit density (1000 kg m − 3 ) and spherical particles, the mass of the collected particles can be estimated and the particle concentration of chemical compounds may be given as weight percent (wt%). The relationship between DPPC mass and mass of exhaled particles is illustrated in Fig. ​ Fig.5 5 .

Comments: This procedure facilitate a normalization of the results and provides an estimate of the concentration in the RTLF of small airways.

Larsson et al. studied exhaled particles generated by the airway reopening mechanism and during high expiratory flows [ 10 ]. Studies were conducted on exhaled particle amounts, particle size distribution and particle content of DPPC. It was expected that the concentration of DPPC would decline with distance from the alveoli due to degradation, dilution and uptake. Exhaled particles’ sizes and concentrations were measured by the instrument previously described by Almstrand et al. [ 8 ]. A triple quadrupole mass spectrometer quantified the extracted DPPC content of exhaled particles. Eleven participants aged 28 to 75 years participated and performed four specific breathing activities in a randomized order.

• The FRC reference maneuver : tidal breathing, inspiration to TLC, and exhalation into the measuring equipment. These results served as baseline values of particle formation.
• The forced exhalation maneuver differed from the FRC reference maneuver only by the high expiratory flow rate, intended to result in exhaled particles produced during the exhalation.
• A cough maneuver was included, known to generate a high amount of particles.
• The airway reopening maneuver : expiration to RV before inspiration to TLC and exhalation into the equipment. This breathing maneuver induced high amounts of particles generated by the airway reopening mechanism.

The results showed that the forced exhalation maneuver and the cough maneuver increased the mass of exhaled particles/L exhaled air, compared to the FRC reference maneuver by 150 and 640% respectively . However, exhaled DPPC mass did not increase over the FRC reference maneuver . The airway reopening maneuver , however, resulted in a 470% increase of the mass of exhaled particles/L exhaled air over the FRC reference maneuver and there was a proportional increase in DPPC. Furthermore, the concentration of DPPC in the particles was similar for the airway reopening maneuver and the FRC reference maneuver. Thus, forced expirations induce particle formation in the range of 0.4–4.6 μm and these particles contain very little alveolar surfactant. The mass fraction of large particles ranging from 3.0 to 4.6 μm increased after a forced exhalation over the airway reopening maneuver , presumably because large particles have a higher probability of being exhaled when formed in central or upper airways during forced exhalations due to short transit times.

Comments: Central airways as well as small airways generate exhaled particles but with different compositions.

Ljungkvist et al. [ 44 ] measured concentration of methadone in exhaled particles of 13 participants receiving methadone maintenance treatment. The PExA impaction method (PExA®) measuring particle sizes from 0.4 μm to 4.6 μm was compared to an electret filtration method collecting particles of any sizes during tidal breathing [ 42 , 43 ]. All samples by the PExA method during the RV breathing pattern contained methadone. Thus, the methadone distribution includes RTLF of small airways. Interestingly, the filtration device collects substantially more methadone than the impaction instrument, almost certainly because the filtration device collects larger particles from upper airways and/or oral fluid.

Comments: It is confirmed that exhaled particles during tidal breathing include relatively large particles that dominates the exhaled mass and that is not associated to airway reopening.

Particles in exhaled breath – A potential biomarker of small airway disease?

Chemical analysis of exhaled particles provides huge possibilities to explore the biomarkers of small airway diseases, and we are probably just beginning to utilize this new biological matrix to its full extent.

Particle emission among patients with COPD appears unclear [ 39 , 45 ]. Schwarz et al. [ 39 ] reported that there were no differences in particle number concentrations between healthy nonsmokers ( n  = 16) and COPD patients ( n  = 28). However, the COPD patients presented in their Fig.  2 clearly emit less particles than the healthy non-smokers do. Lärstad et al. [ 45 ] reported substantially reduced particle emission in COPD patients ( n  = 13) compared with healthy participants ( n  = 12). Despite some ambiguity, we consider the results to indicate that COPD patients exhale fewer particles than healthy participants. One reason may be that hyperinflation in the COPD patients prevents their ability to expire to low lung volumes. When healthy participants exhale to CP rather than to RV, their particle emissions were about one third of that at RV [ 22 ]. Another reason may be that terminal bronchioles are destroyed in COPD, [ 46 ] resulting in fewer small airways to close and open. Furthermore, available airways may be injured due to the mechanical stress of cyclic closing and opening [ 3 , 33 ], possibly affecting particle composition and production.

Lärstad et al. [ 45 ] studied SP-A and albumin concentrations using PEx. SP-A is involved in many biological processes in the lung periphery associated with inflammation [ 47 ] and is an interesting potential biomarker in particles from small airways. Albumin concentrations may, among other things, be an indicator of plasma leaking into the airways [ 48 ]. SP-A was determined by enzyme-linked immunosorbent assay and the results showed that among COPD patients particle concentrations of SP-A (wt%) were lower than in healthy controls whereas albumin levels were similar.

Comments: Small airways are indeed involved in COPD, as shown by the comprehensive studies by Hogg et al [ 49 – 51 ] and several mechanisms of particle production may be operative.

Patients with asthma ( n  = 10) before and after metacholine challenge were studied by Schwarz et al. [ 39 ]. Particle emissions were found to be no different between healthy non-smoking participants ( n  = 16), and metacholine challenge did not affect particle emission despite significant bronchial obstruction. Larsson et al./ [ 41 ] studied particle emission and particle content of SP-A and albumin in birch-pollen allergic participants with asthma ( n  = 13) and healthy controls ( n  = 13). The exhaled particle emissions decreased during pollen season among asthmatic participants but was unchanged among controls. SP-A (wt%) and albumin (wt%) were no different between asthmatic participants and controls, and there were no effects of pollen season. Thus, results of particle emissions from asthmatic participants are inconsistent. At the European Respiratory Society International Congress in Milan 2017, Östling et al. presented the proteomics (SomaLogic, Inc., CO, USA) of small airway RTLF [ 11 ]. PEx was collected during the RV breathing pattern by the PExA instrument in 20 participants with asthma and 10 healthy controls. Over 200 different proteins were detected. Many proteins were different in asthmatic patients to those in controls and there was a striking age dependence in many proteins. The obtained protein profiles from the small airways suggest that the method captures pathobiologically relevant proteins and that a specific profile indicates an asthma sub-phenotype.

Comments: Proteomics from small airways offers an exciting potential to obtain a fingerprint from small airways.

Rhinovirus infected participants ( n  = 16) were studied by Fabian et al. [ 24 ]. Participants were instructed to breathe normally for 20 min into the equipment. Exhaled particles were collected on gelatin filters for rhinovirus quantification. Results were negative, indicating either that the amount of virus was below the limit of detection or that the virus was not present in the collected particles. The study included three healthy volunteers to study the effect of coughing, swallowing, tidal breathing and breathing to TLC and RV. Exhaled particle concentrations were observed to increase 10 to 70 times when participants exhaled to RV before inhalation to TLC.

Comments: Results consistent with the airway reopening hypothesis.

Patients with bronchiolitis obliterans syndrome (BOS) after lung transplants showed lower SP-A particle concentrations than the BOS free group of lung transplants [ 52 ].

Analysis by TOF-SIMS has shown that phospholipids of smokers are more protonated and sodiated than those of non-smokers [ 53 ]. As the particles were produced by the airway opening mechanism, the results indicate the effects of smoking on the RTLF of small airways. Smokers also were studied by Schwarz et al. [ 39 ] but no effects on particle emission were found.

Conclusions

Various mechanisms generate particles appearing in exhaled breath. The sites of origin differ, depending on the breathing maneuver applied. The process of reopening small airways is one scientifically substantiated particle generation mechanism. Analyzing the content of exhaled particles as generated by the airway reopening mechanism, offers an exciting noninvasive way to obtain samples of RTLF from small airways. Results from a few early and small clinical studies on COPD, asthma and BOS indicate associations with altered particle formation and particle composition. In the future, analysis of exhaled particles may provide a “fingerprint” of small airways revealing important biomarkers.

Additional file

Technical and methodological considerations. (DOCX 21.4 kb)

Acknowledgements

The ChAMP (Centre for Allergy Research Highlights Asthma Markers of Phenotype) consortium which is funded by the Swedish Foundation for Strategic Research, the Karolinska Institutet, AstraZeneca & Science for Life Laboratory Joint Research Collaboration, and the Vårdal Foundation.

The Swedish Heart Lung Foundation.

Availability of data and materials

Authors’ contributions.

BB wrote the first draft. EL wrote the Technical Considerations. PL, GL and A-CO contributed substantially to the final manuscript.

Ethics approval and consent to participate

Appropriate ethic authority approved the protocols of the referred recent publications.

Consent for publication

Not applicable.

Competing interests

The authors are shareholders of PEXA® AB ( www.PEXA.se ) and A-C Olin is a board member.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Contributor Information

B. Bake, Email: [email protected] .

P. Larsson, Email: [email protected] .

G. Ljungkvist, Email: es.ug.mma@tsivkgnujl .

E. Ljungström, Email: es.ug.bmc@treve .

A-C Olin, Email: [email protected] .

Comparing Inspired & Expired Air ( WJEC GCSE Biology )

Revision note.

Comparing Inspired & Expired Air

• Inspired and expired air has different amounts of gases in due to exchanges that take place in the alveoli and respiring cells of the body

Composition of air table

Oxygen	21%	16%	Oxygen is removed from the blood during cellular respiration so blood returning to the lungs to be expired has a lower oxygen concentration
Carbon dioxide	0.04%	4%	Carbon dioxide is diffused into the blood during cellular respiration so blood returning to the lungs to be expired has a higher carbon dioxide concentration
Nitrogen	78%	78%	Nitrogen is an inert gas and is not used by the body so the same concentration is inspired and expired
Water vapour	Varies	Saturated with water vapour	Water evaporates from the moist alveolar lining into expired air as a result of the warmth from the body

The 'huff and puff' test

• A simple test using lime water can detect the presence of carbon dioxide 
• It is used to compare the carbon dioxide content of inspired and expired air

Carbon dioxide test diagram

The limewater test for carbon dioxide

• When we breathe in, the air is drawn through boiling tube A
• When we breathe out, the air is blown into boiling tube B
• Lime water  is  colourless but becomes  cloudy  (or milky) when carbon dioxide is bubbled through it
• The lime water in   boiling tube A will remain clear , but the limewater in   boiling tube B will become cloudy
• This shows us that the   percentage of carbon dioxide in exhaled air is higher than in inhaled air

The alveoli and gas exchange

• The air entering the alveoli has a high concentration of oxygen
• The surrounding capillaries contain blood with a low concentration of oxygen : deoxygenated blood is brought to the lungs
• The oxygen diffuses from a region of  high concentration (within the alveoli) across the walls of the alveoli and capillaries and into the red blood cells where there is a low concentration of oxygen ; this oxygenated blood is then taken to the heart to be pumped all around the body
• The opposite can be said of carbon dioxide: deoxygenated blood is brought to the lungs which contains a high concentration of carbon dioxide
• The alveoli contain a low concentration of carbon dioxide 
• Carbon dioxide diffuses from a region of high concentration (the blood) into the alveoli where the is a low concentration of carbon dioxide
• Alveoli (and the capillaries around them) have thin, single layers of cells to minimise diffusion distance
• Ventilation maintains high levels of oxygen and low levels of carbon dioxide in the alveolar air space
• A good blood supply ensures a constant supply of blood high in carbon dioxide and low in oxygen
• A layer of moisture on the surface of the alveoli helps diffusion as gases dissolve
• Additionally, there are many rounded alveolar sacs within the lungs which give a very large surface area to volume ratio
• All of these adaptations maximise the rate of diffusion of oxygen and carbon dioxide

Adaptations of alveoli diagram

Alveoli are specifically adapted to maximise gas exchange

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Author: Cara Head

Cara graduated from the University of Exeter in 2005 with a degree in Biological Sciences. She has fifteen years of experience teaching the Sciences at KS3 to KS5, and Psychology at A-Level. Cara has taught in a range of secondary schools across the South West of England before joining the team at SME. Cara is passionate about Biology and creating resources that bring the subject alive and deepen students' understanding

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Breathing - Respiratory System Explained - KS3

Subject: Biology

Age range: 11-14

Resource type: Lesson (complete)

Last updated

4 September 2024

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A comprehensive and enjoyable, fully resourced lesson on respiration including an explanation of the difference between respiration and breathing.

What’s Covered

• Breathing is movement of air in and out of the lungs.
• Respiration is the release of energy from glucose.
• Breathing provides the oxygen for aerobic respiration and gets rid of waste carbon dioxide.
• Label the trachea, right bronchus, bronchiole, alveolus, intercostal muscle, rib, diaphragm.
• Label a diagram of an alveolus and show the direction of diffusion of oxygen and carbon dioxide.
• Experiment using limewater to compare the amount of carbon dioxide in inhaled and exhaled air.
• Compare the percentage of oxygen, carbon dioxide and nitrogen in inhaled and exhaled air.
• Mechanism of breathing.
• Changes in volume and pressure inside the chest during inhalation and exhalation.
• Evaluate a model of the mechanism of breathing.
• Design an investigation into how breathing rate varies with exercise. ** What’s Included**
• Animated PowerPoint for teaching with exit ticket quiz
• Flip it (pupil writes questions to given answers)
• Anticipation Guides (combined starter and plenary)
• Cut and stick activity.
• Worksheet to support the PowerPoint
• Homework plus answers
• Fact share worksheet
• Pupil progress self-assessment checklist
• Exit Ticket
• Suggested lesson plan showing choices possible between resources

This pack contains thirteen resources and it is intended that the teacher uses them to build their own unique lesson to take account of student ability and time available. Literacy, oracy, self-assessment and peer assessment are all built in to the resources. These features are clearly marked on the comprehensive one-page flow chart lesson plan which shows where the logical choices between resources can be made.

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Breathing - Respiratory System Explained - Classroom, Distance and Blended Learning

The two packs in this resource allow the same lesson to be taught to students whether they are in a classroom or distance learning at home. It facilitates blended learning and provides equality of opportunity for vulnerable students who are unable to attend school due to Covid-19. The classroom resource consists of an animated 44 slide PowerPoint and 15 varied and exciting printables including a foldable, cut-and-stick and progress check. The one-page flowchart lesson plan shows where choices can be made between the printables so that the teacher can select the activities to suit the exact needs of their class. The distance learning pack consists of a 75 slide animated PowerPoint which, not only teaches the science but also how to gain maximum benefit from distance learning. The PowerPoint has been designed to replace the teacher by providing structure, sequence, knowledge and answers. Additional worksheets, cut-outs, foldable and progress check provide a familiar medium for students to develop and test their knowledge, continue to develop their literacy skills and use their creativity to organise their learning and assess their progress. These can be printed off by the student or provided by school. There is also a short digital test/homework which can be returned to the teacher. A shortened photocopiable PDF of the PowerPoint is provided to circulate to those pupils without computers. **What’s Covered** * Breathing is movement of air in and out of the lungs. * Respiration is the release of energy from glucose. * Breathing provides the oxygen for aerobic respiration and gets rid of waste carbon dioxide. * Label the trachea, right bronchus, bronchiole, alveolus, intercostal muscle, rib, diaphragm. * Label a diagram of an alveolus and show the direction of diffusion of oxygen and carbon dioxide. * Experiment using limewater to compare the amount of carbon dioxide in inhaled and exhaled air. * Compare the percentage of oxygen, carbon dioxide and nitrogen in inhaled and exhaled air. * Mechanism of breathing. * Changes in volume and pressure inside the chest during inhalation and exhalation. * Evaluate a model of the mechanism of breathing. * Design an investigation into how breathing rate varies with exercise. **For more high quality resources visit:** [Elf Off the Shelf Resources](https://www.tes.com/teaching-resources/shop/penyrheol1)

Breathing and the Respiratory System Explained - Fully Resourced Lesson Plus Find the Pair game KS3

A comprehensive and fully resourced lesson on breathing and the respiratory system plus an enjoyable yet challenging find the pair game. **What’s Covered** * Breathing is movement of air in and out of the lungs. * Respiration is the release of energy from glucose. * Breathing provides the oxygen for aerobic respiration and gets rid of waste carbon dioxide. * Label the trachea, right bronchus, bronchiole, alveolus, intercostal muscle, rib, diaphragm. * Label a diagram of an alveolus and show the direction of diffusion of oxygen and carbon dioxide. * Experiment using limewater to compare the amount of carbon dioxide in inhaled and exhaled air. * Compare the percentage of oxygen, carbon dioxide and nitrogen in inhaled and exhaled air. * Mechanism of breathing. * Changes in volume and pressure inside the chest during inhalation and exhalation. * Evaluate a model of the mechanism of breathing. * Design an investigation into how breathing rate varies with exercise. **What’s Included** **Lesson** * Animated PowerPoint for teaching with exit ticket quiz * Answer/mark scheme PowerPoint * Flip it (pupil writes questions to given answers) * Anticipation Guides (combined starter and plenary) * Foldable * Cut and stick activity. * Worksheet to support the PowerPoint * Fact sheet * Homework plus answers * Fact share worksheet * Pupil progress self-assessment checklist * Exit Ticket * Suggested lesson plan showing choices possible between resources **Game** * 42 question and answer cards * Teacher’s answer sheet. * Instruction sheet **For more high quality resources visit:** [Elf Off the Shelf Resources](https://www.tes.com/teaching-resources/shop/penyrheol1)

Breathing and the Respiratory System Explained - Fully Resourced Lesson Plus Dominoes Game KS3

A comprehensive and fully resourced lesson on breathing and the respiratory system for middle school plus an enjoyable yet challenging dominoes game which students can either match or answer the question. **What’s Covered** * Breathing is movement of air in and out of the lungs. * Respiration is the release of energy from glucose. * Breathing provides the oxygen for aerobic respiration and gets rid of waste carbon dioxide. * Label the trachea, right bronchus, bronchiole, alveolus, intercostal muscle, rib, diaphragm. * Label a diagram of an alveolus and show the direction of diffusion of oxygen and carbon dioxide. * Experiment using limewater to compare the amount of carbon dioxide in inhaled and exhaled air. * Compare the percentage of oxygen, carbon dioxide and nitrogen in inhaled and exhaled air. * Mechanism of breathing. * Changes in volume and pressure inside the chest during inhalation and exhalation. * Evaluate a model of the mechanism of breathing. * Design an investigation into how breathing rate varies with exercise. **What’s Included** **Lesson** * Animated PowerPoint for teaching with exit ticket quiz * Answer/mark scheme PowerPoint * Flip it (pupil writes questions to given answers) * Anticipation Guides (combined starter and plenary) * Foldable * Cut and stick activity. * Worksheet to support the PowerPoint * Fact sheet * Homework plus answers * Fact share worksheet * Pupil progress self-assessment checklist * Exit Ticket * Suggested lesson plan showing choices possible between resources **Game** * 90 dominos * Animated PowerPoint explaining the rules and how to play. **For more high quality resources visit:** [Elf Off the Shelf Resources](https://www.tes.com/teaching-resources/shop/penyrheol1)

Breathing and the Respiratory System Explained - Fully Resourced Lesson Plus Wildcard & Snap Card Games KS3

A comprehensive, fully resourced lesson for middle school on breathing and the respiratory system plus a pack of cards for enjoyable and challenging games of wildcard or snap. **Prior Knowledge Required** * Breathing is movement of air in and out of the lungs. * Respiration is the release of energy from glucose. * Breathing provides the oxygen for aerobic respiration and gets rid of waste carbon dioxide. * Label the trachea, right bronchus, bronchiole, alveolus, intercostal muscle, rib, diaphragm. * Label a diagram of an alveolus and show the direction of diffusion of oxygen and carbon dioxide. * Experiment using limewater to compare the amount of carbon dioxide in inhaled and exhaled air. * Compare the percentage of oxygen, carbon dioxide and nitrogen in inhaled and exhaled air. * Mechanism of breathing. * Changes in volume and pressure inside the chest during inhalation and exhalation. * Evaluate a model of the mechanism of breathing. * Design an investigation into how breathing rate varies with exercise. **What’s Included** **Lesson** * Animated PowerPoint for teaching with exit ticket quiz * Answer/mark scheme PowerPoint * Flip it (pupil writes questions to given answers) * Anticipation Guides (combined starter and plenary) * Foldable * Cut and stick activity. * Worksheet to support the PowerPoint * Fact sheet * Homework plus answers * Fact share worksheet * Pupil progress self-assessment checklist * Exit Ticket * Suggested lesson plan showing choices possible between resources **Board Game** * 66 playing cards * Animated PowerPoint with instructions for playing wildcard and snap **For more high quality resources visit:** [Elf Off the Shelf Resources](https://www.tes.com/teaching-resources/shop/penyrheol1)

Breathing and Respiration Explained - Fully Resourced Lesson Plus 42 Question Board Game KS3

A comprehensive, fully resourced lesson for middle school on breathing and the respiratory system plus an enjoyable and challenging board game for up to six players a set. **What's Covered** * Breathing is movement of air in and out of the lungs. * Respiration is the release of energy from glucose. * Breathing provides the oxygen for aerobic respiration and gets rid of waste carbon dioxide. * Label the trachea, right bronchus, bronchiole, alveolus, intercostal muscle, rib, diaphragm. * Label a diagram of an alveolus and show the direction of diffusion of oxygen and carbon dioxide. * Experiment using limewater to compare the amount of carbon dioxide in inhaled and exhaled air. * Compare the percentage of oxygen, carbon dioxide and nitrogen in inhaled and exhaled air. * Mechanism of breathing. * Changes in volume and pressure inside the chest during inhalation and exhalation. * Evaluate a model of the mechanism of breathing. * Design an investigation into how breathing rate varies with exercise. **What’s Included** **Lesson** * Animated PowerPoint for teaching with exit ticket quiz * Answer/mark scheme PowerPoint * Flip it (pupil writes questions to given answers) * Anticipation Guides (combined starter and plenary) * Foldable * Cut and stick activity. * Worksheet to support the PowerPoint * Fact sheet * Homework plus answers * Fact share worksheet * Pupil progress self-assessment checklist * Exit Ticket * Suggested lesson plan showing choices possible between resources **Board Game** * Game board * 42 Question cards with questions of varying difficulty * Teacher answer sheet * Instruction sheet. **For more high quality resources visit:** [Elf Off the Shelf Resources](https://www.tes.com/teaching-resources/shop/penyrheol1)

Breathing and the Respiratory System Fully Resourced Lesson Plus Save the School Handyman Escape Room KS3

A comprehensive, fully resourced lesson on breathing and the respiratory system plus an innovative, enjoyable and challenging escape room lesson. Students have to work their way through the clues to find the code to a combination lock on the school tool store in which the school handyman has been accidentally locked **What’s Covered** * Breathing is movement of air in and out of the lungs. * Respiration is the release of energy from glucose. * Breathing provides the oxygen for aerobic respiration and gets rid of waste carbon dioxide. * Label the trachea, right bronchus, bronchiole, alveolus, intercostal muscle, rib, diaphragm. * Label a diagram of an alveolus and show the direction of diffusion of oxygen and carbon dioxide. * Experiment using limewater to compare the amount of carbon dioxide in inhaled and exhaled air. * Compare the percentage of oxygen, carbon dioxide and nitrogen in inhaled and exhaled air. * Mechanism of breathing. * Changes in volume and pressure inside the chest during inhalation and exhalation. * Evaluate a model of the mechanism of breathing. * Design an investigation into how breathing rate varies with exercise. **What’s Included** **Lesson** * Animated PowerPoint for teaching with exit ticket quiz * Answer/mark scheme PowerPoint * Flip it (pupil writes questions to given answers) * Anticipation Guides (combined starter and plenary) * Foldable * Cut and stick activity. * Worksheet to support the PowerPoint * Fact sheet * Homework plus answers * Fact share worksheet * Pupil progress self-assessment checklist * Exit Ticket * Suggested lesson plan showing choices possible between resources **Escape Room** * PowerPoint – scene setting and instructions (sound effects and built-in timer) * crossword * word search * dominoes activity * worksheet * code breaker sheet * answers * lesson plan. **For more high quality resources visit:** [Elf Off the Shelf Resources](https://www.tes.com/teaching-resources/shop/penyrheol1)

Breathing and the Respiratory System Explained - Fully Resourced Lesson Plus 7 Game Compendium

A comprehensive and enjoyable fully resourced lesson on breathing and the respiratory system plus a compendium of seven enjoyable and challenging games on suitable for all abilities. Each game is fully resourced, comes with full instructions and is easy to run. This versatile games pack can be used to enhance a lesson, for revision or for cover lessons, even when taken by a non-specialist as most come with answers. It is also the ideal end of term/year pack. **What’s Covered** * Breathing is movement of air in and out of the lungs. * Respiration is the release of energy from glucose. * Breathing provides the oxygen for aerobic respiration and gets rid of waste carbon dioxide. * Label the trachea, right bronchus, bronchiole, alveolus, intercostal muscle, rib, diaphragm. * Label a diagram of an alveolus and show the direction of diffusion of oxygen and carbon dioxide. * Experiment using limewater to compare the amount of carbon dioxide in inhaled and exhaled air. * Compare the percentage of oxygen, carbon dioxide and nitrogen in inhaled and exhaled air. * Mechanism of breathing. * Changes in volume and pressure inside the chest during inhalation and exhalation. * Evaluate a model of the mechanism of breathing. **What’s Included** **Lesson** * Animated PowerPoint for teaching with exit ticket quiz * Answer/mark scheme PowerPoint * Flip it (pupil writes questions to given answers) * Anticipation Guides (combined starter and plenary) * Foldable * Cut and stick activity. * Worksheet to support the PowerPoint * Fact sheet * Homework plus answers * Fact share worksheet * Pupil progress self-assessment checklist * Exit Ticket * Suggested lesson plan showing choices possible between resources **Games Included** * Find the Pair Team Game * Dominoes * 42 Question Board Game * Save the School Nurse Escape Room * Smart Board Bingo * Wildcard & Snap **For more high quality resources visit:** [Elf Off the Shelf Resources](https://www.tes.com/teaching-resources/shop/penyrheol1)

Breathing and the Respiratory System Explained - Fully Resourced lesson Plus Smart Board Bingo KS3

A comprehensive, fully resourced lesson on breathing and the respiratory system plus an innovative, enjoyable and challenging smart board bingo game. Students have to work their way through the clues to find the code to a combination lock on the school tool store in which the school handyman has been accidentally locked **Prior Knowledge Required** * Breathing is movement of air in and out of the lungs. * Respiration is the release of energy from glucose. * Breathing provides the oxygen for aerobic respiration and gets rid of waste carbon dioxide. * Label the trachea, right bronchus, bronchiole, alveolus, intercostal muscle, rib, diaphragm. * Label a diagram of an alveolus and show the direction of diffusion of oxygen and carbon dioxide. * Experiment using limewater to compare the amount of carbon dioxide in inhaled and exhaled air. * Compare the percentage of oxygen, carbon dioxide and nitrogen in inhaled and exhaled air. * Mechanism of breathing. * Changes in volume and pressure inside the chest during inhalation and exhalation. * Evaluate a model of the mechanism of breathing. **What’s Included** **Lesson** * Animated PowerPoint for teaching with exit ticket quiz * Answer/mark scheme PowerPoint * Flip it (pupil writes questions to given answers) * Anticipation Guides (combined starter and plenary) * Foldable * Cut and stick activity. * Worksheet to support the PowerPoint * Fact sheet * Homework plus answers * Fact share worksheet * Pupil progress self-assessment checklist * Exit Ticket * Suggested lesson plan showing choices possible between resources **Smart Board Bingo** * Random question generator for smart board (interactive white board) – 50 questions * Answer PowerPoint plus answer sheet * 48 bingo cards * Answers PowerPoint **For more high quality resources visit:** [Elf Off the Shelf Resources](https://www.tes.com/teaching-resources/shop/penyrheol1)

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