An aerosol comprises of soild or liquid particles suspended in a gas. Delivery of drugs in aerosolized form to the airway is a common practice in respiratory medicine. Besides delivery of the drug at the site of action, this form of therapy minimises systemic side effects and bypasses the first-pass metabolism of drugs in the gastrointestinal tract and liver.
Indications for aerosol therapy
Airway responsiveness and bronchodilator reversibility tests
Treatment of airway and lung parenchymal diseases
Systemic diseases (diabetes mellitus/diabetes inspidus)
Classification of aerosols
A) Bland aerosols include heated or cooled sterile water and saline.These aerosols are mainly used in treatment of upper airway disease, humidification of the bypassed airway and sputum induction.
B) Medicated aerosols include bronchodilators, steroids, mucokinetic agents, antiallergic agents, local anaesthetics, antimicrobials, surfactant, insulin and vasopressin.
Medicated aerosols are delivered to the upper airway for upper airway inflammation, nasal allergy or infection and before performance of procedure (bronchoscopy/intubation).
The lower airway diseases which warrant aerosol therapy include obstructive airway disease, cystic fibrosis, ARDS, sarcoidosis and infections (pneumocystis carinii and RSV infection) .
Nasal sprays of insulin and vasopressin are used in the treatment of diabetes mellitus and diabetes insipidus respectively.
The depth of aerosol delivery is a function of many variables which includes :
1. Size and physical characteristics of the aerosol
2. Amount of aerosol
3. Anatomy and geometry of the airway
4. Ventilatory pattern
Aerosols get deposited by 3 mechanisms, namely : diffusion, inertial impaction and sedimentation, The following table depicts the site of aerosol deposition depending on the size of the aerosol.
| Size (MMAD u) ||Site of deposition |
|< 0.5 u || Stable (no deposition) |
| 0.5 - 2u || Alveoli |
|2 - 5u ||Bronchi and bronchioles |
| 5 - 100u ||Mouth, nose and upper airway |
| > 100u || Filtered by the upper respiratory tract |
Size and physical characters of the aerosol
The volume/surface area ratio, mass median aerodynamic diameter (MMAD) and geometric standard deviation define the physical characteristics of an aerosol ; out of these the MMAD is the most important.
The MMAD is that diameter which divides the range of particles into half. Therapeutic/diagnostic aerosols have an MMAD ranging from 0.5 - 5 u depending on the intended site of deposition. Aerosols of a particular MMAD may be generated but their size and site of impaction are influenced by the density, temperature and humidity of the carrier gas, toxicity of the aerosol itself, the ventilatory pattern and airway geometry.
For example, an aerosol suspended in a light carrier gas like helium is in constant Brownian motion the collision of particles with one another decreases their MMAD by fragmentation and the aerosol becomes stable i.e. cannot be deposited anywhere. Likewise, a cooled aerosol gains temperature in the upper airway and decreases in size (as its kinetic activity increases) , whereas a heated aerosol cools in the airway, increases in size and is deposited in the upper airway. The diffusability of an aerosol depends on particle size with submicroionic particles being in constant Brownian motion ; the sedimentation rate is proportional to aerosol diameter and density as well as the density of the carrier gas whereas impaction occurs at sites of airway narrowing or branching.
Effect of ventilatory pattern and airway geometry on deposition
The inspiratory flow rate during quite breathing is 0.5 liters per second. This flow rate promotes aerosol deposition in the bronchi and bronchioles as the flow pattern is laminar at this rate. Higher flow rates cause turbulent flow, aerosol fragmentation and failure of deposition. Similarly, higher respiratory rates are associated with higher flow rates and poor aerosol delivery. Hence a slow, deep breath with an end inspiratory breath - hold of 5-10 seconds is optimal for aerosol impaction in the bronchi and bronchioles.
Airway narrowing due to spasm/secretions causes impaction higher up in the airway, as also inhalation through nose causes inertial impaction in the upper airway itself. Therefore, inhalation through mouth promotes better aerosol deposition. In patients with bronchospasm, an interval of 2-10 minutes between inhaler actuation helps relieve spasm and better delivery of the aerosol during subsequent actuations.
Methods of aerosol generation
i. Pneumatic : -
- Small volume
- Large volume
- Small particle aerosol generator
2. Metered Dose Inhalers (+ accessory device : spacer / chamber / spring loaded actuator)
3. Dry powder inhalers - Rotahaler / Spinhaler / Turbuhaler / Diskhaler
Pneumatic / jet nebulisers : These devices work on Bernoulli's principle wherein when a gas under pressure travels through and exits from a tube, the lateral pressure is reduced and this causes aerosol generation if a capillary tube is placed in the path of gas.
Types of Jet nebulisers
(i) Small volume nebulisers (SVN) : These are either hand - hold nebulisers or those used in IPPB/ ventilator circuits. Important features include :
a. Gas flow rates of 6-8 lpm
b. Optimal volume of nebulising solution : 4-5 ml
c. Particle size : 1-5 u
d. 10% of aerosol reaches its site of action
SVN in ventilated patients
(i)It is not the ideal mode of aerosol delivery because (a) Large amounts of drug are lost in the circuit due to baffling effect of tubings and artificial airway. Only 1-3% of the drug reaches lower airway.
(b) Attaching a nebuliser to circuit mandates alteration of setting (flow rates and pres- sure limits).
(c) An MDI with spacer is better than SVN in ventilated patients.
Guidelines for using SVN in ventilated patients n Place the SVN in the inspiratory limb at least 18�h from the artificial airway
n Reduce IFR during nebulisation
n Turn off the flowby during nebulisation
(ii) Large volume (ultrasonic) nebulisers The interface used in these nebulisers can be an aerosol mask, a face tent or a tracheostomy collar. Large volume nebulisers are eminently suitable for long duration aerosol delivery for relief of bronchospasm, upper airway edema and for humidification in tracheostomised patients.
Principle : When an electric charge is applied to a piezo electric crystal (transducer) ultrasonic vibrations are generated. These are transmitted to a couplant (water) which absorbs the heat generated as well.
The size of aerosol particles generated depends on the frequency of the transducer while the volume is related to the amplitude of the sound waves.
2. Metered Dose Inhalers
MDIs are widely used in aerosol delivery in the outpatient setting. The advantages of MDI include :
b. Multi dose
c. Less risk of infection
d. Better in mechanically ventilated patients
An MDI contains 80-300 doses of medication along with a surfactant and propellant (CFC/HFA). It has a vapor pressure of 300-500 Kpa at 20o c. Actuation of the MDI results in discharge of the drug with propellant under pressure, which on exposure to atmospheric pressure, aerosolises and reaches the respiratory tract. Only 10% of the aerosol so formed reaches the site of action.
A disadvantage of MDI is the requirement for coordination between actuation and inspiration. To overcome this problem, spacers and chambers have been developed. These devices serve the following purposes :
a. Act as a reservoir for the aerosol till the initiation of inspiration.
b. Cause a decrease in the aerosol velocity, thus generating smaller particles.
c. Offset the cold Freon effect (sudden cessation of inspiration when the cold propellant drug mixture stickes the posterior pharyngeal wall).
Optimal technique of MDI use
a. Coordination between actuation and inspiration
b. Breath hold of 4-10s at end inspiration to allow aerosol impaction.
c. 3-10 minutes between actuation (to allow for bronchodilation between doses)
d. MDIs should be stored at 37o C (preferably carried in the patients's pocket ) . At lower temperatures, the pressure inside the canister decreases resulting in
generation of larger aerosol particles.
3. Dry powder inhalers
Components - Device : (Rotahaler / Spinhaler / Turbuhaler / Diskette)
- Drug - Reservoir : Discrete - gelatin Capsules
- Multi dose strips
Advantages - Portable
- No hazard (environmental) of CFC
- Does not require synchronisation between actuation
actuation and inspiration
. Limitations : - Some devices need to be assembled before use
- Drug delivery is affected by humidity (dumping
- Oropharyngeal irritation because of the carrier (usually lactose)
- Requires generation of a high inspiratory flow rate (1lps)
which precludes DPI use in acute bronchospasm.
Hazards of Aerosol therapy
Airway obstruction (sputum induction in patients with poor cough reflex )
Over hydration (infants )
Thermal injury (heated aerosols)
Cardiotoxicity (CFC )
b. Care giver
Asthma in subjects with hyper-reactive airways
Infection / rash /bronchospasm/ conjunctivitis.
Ozone layer depletion by CFCs
Infection control practice During Aerosol Therapy
? Adequate protection to the care giver (mask, proper ventilation of the wards / ICU,HEPA filters )
? High level disinfection of nebulisation masks / chambers between patients daily disinfection even if reused in the same patient.
? Aerosol delivery within tents / chambers in case of ribavirin.
? Discard reconstituted / opened nebulising solutions daily.
Uma Maheswari, M.D. ( Medicine)
Senior Resident ( Pulm. Med.)
Dr. Uma Maheswari,