DEMYSTIFYING NEBULIZATION

Jindal Clinics, Chandigarh

www.jindalchest.com
Part A. Basic Physics and General Principles
Pulmonary Delivery of Drugs

• Inhalational therapy
involves Pulmonary
delivery of drugs
through airway route
• Pharmacokinetics of
inhalational drugs
almost parallel those
of intravenously
administered drugs
 Route of delivery for airway diseases
Intravenous route
Travers et al Cochrane Database Syst Rev 2001
- no benefits
- Potential for increased adverse effects

Favors IV Favors inhaled

Inhaled route: preferred mode
Easy, safe, faster onset of action
More effective than parenteral routes
Factors Affecting Pulmonary Drug Delivery
• Physics of inhalation: Particle size, Flow, Inspiratory
effort, Particle deposition
• Device - Related Factors
• Nature of the device (ease of use)
• Patient - Related Factors
• Technique of use of the device
• Pattern of breathing
• Geometry of the airways
• Severity of disease
 Airway Geometry & Particle deposition
As aerosols move into smaller and • High variability of regional and
smaller airway at bifurcations, some
total deposition efficiency.
particles get deposited as they reach a
point where the distance from their • Factors for deposition:
center to a surface is less than their i. Respiratory tract geometry
radius. ii. Breathing pattern,
Mechanisms of deposition iii. Age and health,
iv. Momentary physical activity
iii. Aerosol properties:
Particle size, shape,
Density,
Hygroscopicity,
Surface properties
 Particle Size & Lung deposition

• Particles >5 μm are deposited by • Most particles of 0.1–1 μm diffuse

impaction in the oropharynx and by Brownian motion & deposit when
swallowed. they collide with the airway wall.
• Particles <5 μm (fine-particle • The longer the residence time in the
fraction, FPF) have the greatest smaller airways, the greater the
potential for lung deposition, usually deposition from sedimentation and
deposited by sedimentation or Brownian motion processes.
gravity. • Inhaled particles that do not deposit
are exhaled.
 Inhaler Devices Classification

Metered dose Dry powder Nebulizer

inhalers inhalers

Breath Actuated Inhalers

BAIs
 Pulmonary delivery of drugs: Advantages
Treatment of respiratory diseases
Inhalation Nebulization
• Deliver high concentrations • Drug delivery with an air-pump
directly to the disease site driven by power used to convert
liquid drug into aerosols, to
• Rapid clinical response deliver medication by inhalation
through a mask
• Minimizes risk of systemic side-
effects
• First invented in France by Sales-
• Bypass the barriers to
Girons in 1858 to atomize the liquid
therapeutic efficacy, such as: medication. The pump handle was
Poor gastrointestinal absorption and operated like a bicycle pump; steam-
First-pass metabolism in the liver driven nebulizer invented in
• Achieve a similar or superior Germany in 1864 - "Siegle's steam
therapeutic effect at a fraction of spray inhaler", used Venturi pump to
atomize liquid medication.
the systemic dose
 Nebulization - Principle
• Bernoulli Principle: when a
pressurized flow of air is directed
through a constricted orifice, the
velocity (not the pressure) of the
airflow is increased to create a jet
stream.
• The jet stream creates a sub-
atmospheric pressure zone
(vacuum) which draws the fluid
up the capillary tube.
• Nozzles also convert liquids into
a fine mist, but do so by pressure
through small holes.
• Nebulizers generally use gas
flows to deliver the mist.
 Nebulization vs. Steam inhalation
Steam inhalation Nebulization
• A nebulizer breaks particles up
• Warm vapours are soothing;
further to make for a finer and
provides moisture to the dry mucus
deeper reach.
membranes in the nose and throat
• Particles of more than 10 μm in
• Helps loosen the mucus and
diameter are most likely to deposit
provides relief from chest congestion.
in the mouth and throat, for those
• Hot vapour can help reduce of 5–10 μm diameter a transition
bacterial infections in the nasal from mouth to airway deposition
passage and reduce common cold occurs, and particles smaller than
symptoms 5 μm in diameter deposit more
• Excess hot vapour or steam frequently in the lower airways and
inhalation for a long time can cause are appropriate for pharmaceutical
damage to the nose and throat aerosols.
cells. Skin issues and swelling and • Nebulizing processes have been
redness in the eyes. modeled on computational fluid
• Greater risks in children dynamics
 Nebulizer vs. MDI
MDI Nebulizer
Advantages: Smaller in size Advantages: For all age groups,
• Require no power source. normal ventilatory pattern and low
• Deliver the medicine more quickly inspiratory flow.
than a nebulizer. Easy for patients who have difficulty
• With spacer, as effective as a using inhalers, such as the elderly,
nebulizer small children, patients with
Disadvantages: Require coordination disabilities and serious cases,
severe asthma attacks.
Difficult to administer in the elderly,
small children, patients with Low operational cost.
disabilities and serious cases, Disadvantages: Creates more noise
severe asthma attacks. (often 60 dB during use)
The age of the child makes a difference • Less portable, greater weight
in how an inhaler is used; may • Greater dose; lot of wastage
require another person to • Local deposition in the mouth
administer
 Types of Nebulizers
I. Pneumatic
• Jet nebulizer or "atomizers” - connected by tubing to a supply of compressed
gas, to flow at high velocity through a liquid medicine
II. Mechanical
• Soft mist inhaler: Due to the very low velocity of the mist, the Soft Mist
Inhaler in fact has a higher efficiency compared to a conventional pMDI.
• Could be classified as a "hand driven nebulizer" and a "hand driven pMDI”
III. Electrical: Ultrasonic wave nebulizer
The electronic oscillator generates a high frequency ultrasonic wave which
causes the mechanical vibration of a piezo-electric element. This vibrating
element is in contact with a liquid reservoir and its high frequency vibration is
sufficient to produce a vapor mist.
• Vibrating mesh technology: With this technology a mesh/membrane with
1000–7000 laser drilled holes vibrates at the top of the liquid reservoir, and
thereby pressures out a mist of very fine droplets through the holes; more
efficient than having a vibrating piezoelectric element at the bottom of the
liquid reservoir, and thereby shorter treatment times are also achieved.
 Nebulization: Indications
I. First line treatment
1. Severe asthma attack characterized by unrelieved
airway inflammation.
2. Acute exacerbation of Chronic Obstructive Pulmonary
Disease (COPD)
3. Acute worsening of disorders that cause persistent,
often progressive, airflow obstruction
i. Airway diseases (bronchitis, bronchiolitis)
ii. Alveolar conditions (emphysema)
II. Supportive treatment for persistent respiratory
symptoms
– Wheeze, Shortness of breath,
– Chest tightness and Cough
 III. Miscellaneous disorders
• Aerosolized antibiotics for pneumonias, purulent
tracheobronchitis and alveolar infection.
• Chronic lung infection with Pseudomonas
aeruginosa in patients with cystic fibrosis or non-CF
bronchiectasis
• Liquefaction of thick, viscid bronchial secretions.
• Inhaled pentamidine (given as a 1-µm MMAD
aerosol) for Pneumocystis jirovecii pneumonia, in
patients infected with HIV
• Management of Hyperkalaemia
 Hand-held Nebulizers/ Soft mist inhalers
• Liquid-based inhalers which • Suitable for biologic
produce a slow-moving formulations
aerosol cloud; release • Gentle aerosolization for
medication sensitive drug products
i. in a fine mist
• Greater sustainability
ii. more slowly and
• Can be reused
iii. lasts longer
• For delivering treatments for
short-term care SMIs offer a great potential for
drug delivery of a far wider
• SMI is more efficient, even
range of drug formulations with
with poor inhaler technique; enhanced precision and
teaching patients to hold their accuracy of dosing and
breath as well as to inhale inhalation for a wider range of
slowly and deeply increases drugs.
further lung deposition
 INHALATIONAL/ NEBULIZABLE DRU

• Bronchodilators
• Beta-2 Agonists
• Anti-muscarinic Agents
• Corticosteroids
• Combinations
• Miscellaneous
- Antibiotics
- Mucolytics – Acetyl cysteine
- Hypertonic saline
- Other drugs
Factors Associated with Non-Compliance in
Asthma and COPD
Medication Usage Patient/Physician

 Difficulties associated  Misunderstanding/lack of

with inhalers information
 Complicated regimens  Underestimation of severity

 Fears about, or actual  Attitudes toward ill health

side effects  Cultural factors
 Cost  Poor communication
 Why consider nebulization?
A. Ease of use and technique
B. Effective and reliable drug delivery
C. Fosters patient confidence that drug is reaching
the lungs
D. Patients report positive impact
on health status
E. Use not limited by disease severity
or mental acuity
F. All of the above
 Use of Jet Nebulizers Can Be as Easy as 1-2-3

(1) Open the vial and (2) Connect the nebulizer (3) Insert mouthpiece and
transfer all the medicine reservoir to the turn on the compressor.
into the nebulizer mouthpiece and to
medicine cup (reservoir). the compressor. Breathe as calmly,
deeply, and evenly as
possible until no more
mist is formed in the
nebulizer reservoir.
Please see accompanying full Prescribing Information, including Boxed Warning.
Medication Guide: Perforomist® (formoterol fumarate) Inhalation Solution. Napa, CA: Dey Pharma, L.P.; 2008.
 Function of Jet Nebulizers
1. Air from the compressor breaks
the liquid
medication into small breathable
particles that
form a mist (aerosol).

PARI LC® Reusable Nebulizer

(includes Pari LC® Plus)

Adapted from PARI. Jet nebulization technology. http://www.pari.com/pdd/jet-neb-tech.htm.

 Function of Jet Nebulizers
1. Air from the compressor 2. Upon inhalation, the
breaks the liquid inspiratory valve at the top
medication into small opens, letting air in and
breathable particles that speeding up the generation
form a mist (aerosol). of mist to increase flow of
medication to the lungs.

Inspiration

PARI LC® Reusable Nebulizer

(includes Pari LC® Plus)

Adapted from PARI. Jet nebulization technology. http://www.pari.com/pdd/jet-neb-tech.htm.

 Function of Jet Nebulizers
1. Air from the compressor 2. Upon inhalation, the 3. Upon exhalation, the inspiratory
breaks the liquid inspiratory valve at the top valve closes, slowing down
medication into small opens, letting air in and the mist; the mouthpiece flap
breathable particles that speeding up the generation opens, directing the patient’s
form a mist (aerosol). of mist to increase flow of breath away from the nebulizer.
medication to the lungs.

Inspiration

Expiration
PARI LC® Reusable Nebulizer
(includes Pari LC® Plus)

Adapted from PARI. Jet nebulization technology. http://www.pari.com/pdd/jet-neb-tech.htm.

Nebulization Delivers Effective Dose

Cumulative Dose Study 1.0

• Multiple inhalations Nebulizer

Mean change in FEV1

0.8
MDI
from MDI are required 0.6
to achieve the same
0.4
amount
of bronchodilation as 0.2
from larger nebulized
0
dose 0.25 1.0 2.5 10 40
Cumulative dose (mg)

Austitz H et al. Chest. 1989;96:1287.

 Nebulization May
Reduce Technique Errors
 MDIs Are Frequently Associated
With Technique-Related Errors
Incorrect inhalation technique can diminish clinical efficacy of devices1
MDI technique involves 9 steps. Two commonly associated
technique-related errors are1:

Step 5: Place the inhaler mouthpiece

Step 6: Trigger the inhaler while
between the lips
breathing in deeply and slowly
(and the teeth); keep the tongue from
(this should be about 30 L/min)1
obstructing the mouthpiece1

• Unable to coordinate actuation with inspiration (this is common in elderly patients

with impaired dexterity or vision)1,2
• Aerosol is released into mouth while patient is inhaling through nose1

1. Broeders M et al; on behalf of the ADMIT Working Group. Prim Care Respir J. 2009;18:76-82;
2. Lavorini F et al. Respir Med. 2008;102:593-604.
 Most DPI Systems Require a Minimum Inspiratory Capacity to
Generate Adequate Drug Delivery

DPI technique involves 8 steps. Two commonly associated

with technique-related errors are1:

Step 3: Exhale deeply, Step 5: Inhale deeply

away from the mouthpiece1 and forcefully1
• Failure to achieve a forceful and rapid
• Failure to exhale prior to inhaling (may lead to
inspiratory flow at start of inhalation  poor
suboptimal drug deposition in lung) 2
drug release and low lung deposition 2
• Common in elderly patients; severe airflow
limitation; cognitive impairment 2,3

1. Broeders M et al; on behalf of the ADMIT Working Group. Prim Care Respir J. 2009;18:76-82;
2. Lavorini F et al. Respir Med. 2008;102:593-604; 3. Zarowitz BJ. Geriatr Nurs. 2009;30:45-49.
 Although pMDIs/DPIs are the first choice of
delivering aerosols, what do patient say…

• 46% of patients using a pMDI and 17% of those

using a DPI rated their device difficult to use.

• 50% of DPI users were ‘unsure’ as to whether

they received any clinical benefit

• 85% of older patients fail to use a spacer

device when it is prescribed.

Age and Ageing 2007; 36: 213–218

Part B. Applications and Indications
Assemble
to Adapt

Management of Acute Asthma

• Nebulizers form the main delivery system for most

emergency departments and hospitals in the developed and
developing world

• Widely used because of convenience and less patient

education or cooperation needed

• Inhaler technique problems overcome and do not become an

issue in emergency setting
30
Assemble
to Adapt
First Drug of Choice In Acute Severe Asthma

1) Nebulised steroid 3) Injectable theophylline

2) Nebulised salbutamol 4) Injectable dexamethasone

Can ALSO use Levosalbutamol

Nebulized Salbutamol/SABA – less tachycardia

Nebulized salbutamol 2.5-5 mg every • Consider adding nebulised ipratropium [SAMA]

20 min for 1hr bromide to SABA
Adults:
• 250 – 500 mcg every 4 to 6 hours
• Even safe to give every 20 – 30 mins for the first 2
Then every 1-4 hours as required hours in a severe attack.
• Also can use combination respule
(SABA+SAMA)

In children half the above dose 31

 GC: 72 years construction worker
• Dyspnea over 4 years
• Off and on bouts of cough and phlegm; winter
exacerbations
• “Unable to do anything”
• Smoked > 30 pks/ years
• Tried to use MDIs and DPIs – not able to take
medications due to tremor
• Physical exam: Decreased breath sounds, no wheezes
• BMI: 28 kg/m2 mMRC: 3 6MWD: 328m
FEV1 = 1.91 L 49% predicted BODE = 2
What are his treatment alternatives ?

A. Continue to try with different DPI device

B. Use MDI – HFA with spacers only
C. Consider nebulized therapy
D. Don’t treat his disease is not too bad
Devices for treatment of airway disease

A large number of different inhaled products

of more than 20 ingredients

……and many more

to come
The Use of Inhaled Delivery Devices

• Age is a major factor that determines correct

use of inhaler devices secondary to
decreased muscle strength, memory
problems and loss of coordination
 Mishandling of Inhaler Devices based on
patients age
Frequency of Critical Errors by Device

n = 3811 Molimard M et al. J Aerosol Med 2003; 16: 249 - 254

 The older the patients

• Significantly poorer device technique than

younger adults.
• Inadequate technique was high at baseline,
(81% demonstrating at least one observed
error)
• Correct device technique was associated with
the type of device used
• Clear statistical improvement was observed with
the active education vs. passive.

Primary Care Respiratory Medicine (2014) 24, 14034;

doi:10.1038/npjpcrm.2014.34;
published online 4 September 2014
 Technique deteriorate if it is not revisited

• Device education among older COPD patients

often neglected

• Written information, even in pictorial form,

insufficient to achieve improved inhaler use

• Acquisition and initial retention of acceptable

technique is reduced (those with a measurable
cognitive deficit)
Primary Care Respiratory Medicine (2014) 24, 14034;
doi:10.1038/npjpcrm.2014.34;
published online 4 September 2014
 PIFR and DPI Use

• Muscle weakness and

Air Trapping air trapping may
decrease ability to
generate minimal
required PIFR (20-30
L/min) when using a
DPI

Weiner P, Weiner M. Respiration. 2006;73:151-156.

In elderly patients the ability to generate sufficient
inspiratory flow across a DPI is compromised,
irrespective of the presence of COPD

Eur Respir J 2008; 31: 78–83

What are the consequences of Poor MDI/DPI
Technique ?

A. Overuse of medication
B. Wasted medication
C. Lung deposition substantially reduced
D. Overall suboptimal therapy
E. None of the above
F. All of the above
 Adherence to inhaled medication is significantly
associated with reduced risk of death and
admission to hospital due to exacerbations in COPD

3-year trial of inhaled

medications in patients with
moderate to severe COPD

Thorax 2009;64:939–943
Medication delivery: is use nebulize
devices an appropriate alternative ?

Eur Respir Rev 2005; 14: 96, 97–101

 How to translate the benefits of
new medicines into health gain
for individuals?
• Adherence is defined as the extent to which
a patient’s behavior matches the agreed
recommendations from the prescriber.

• Between 20 and 30 % of prescribed medication

is not taken as recommended?

Report for the National Co-ordinating Centre for NHS

Service Delivery and Organisation R & D (NCCSDO)
December
Med Care 2005
2004, 42:200–209.
 Efficacy and Safety of Nebulization
for Maintenance Treatment of COPD
• Patients using combined nebulizer therapy morning and night with mid-
day use of inhaler device had the most statistically significant
improvements in quality of life indices.
• Concomitant regimen provides the additional symptom relief offered by
a nebulizer with the convenience of an inhaler when patients are away
from home
 Formoterol Delivered by Nebulizer is as Efficacious as
that Delivered by DPI
ITT Population Day 1 Week 12
1.6 1.6
Mean FEV1 (L)

1.5 1.5

Mean FEV1 ( L)
1.4 1.4

1.3 1.3

1.2 1.2
1 2 3 6 9 12 1 2 3 6 9 12
Minutes Hours Minutes Hours

Neb 20 µg (n=123) Aerolizer12 µg (n=114) Placebo (n=114)

Gross NJ et al. Respir Med. 2008;102;189-197.

Arformoterol Nebulized Solution vs Salmeterol MDI: Mean %
Change in Morning Predose FEV1
Averaged Over 3 Visits: Weeks 0, 6, and 12
30
Placebo
25 Arformoterol 15 g bid
Mean change in FEV1

Salmeterol 42 g bid
from baseline (%)

20 18% (Arformoterol)

15
P<.001

10

5 6% (Placebo)

0
0 2 4 6 8 10 12 22 24
Morning
Dose 1 Time Dose 2 predose
(8 AM) (8 PM) (8 AM)

Baumgartner RA et al. Clin Ther. 2007;29:261-278.

 Formoterol Nebulization Solution Plus Tiotropium
Handihaler
Mean FEV1 on Day 1 and at Week 6

1.7
†
1.6 † † †

†
1.5 †
† †
FEV1 (L)

† †
1.4 †

1.3 Formoterol Solution/ Tiotropium Week 6

Formoterol Solution/Tiotropium Day 1
1.2
Placebo/Tiotropium Week 6
1.1 Placebo/Tiotropium Day 1

1.0
Pre- 5 0.5 1.0 1.5 2.0 2.5 3.0
dose (min)
Postdose (hours)
* Tolerance to the effects of inhaled 2-agonists can occur with regularly scheduled, chronic
use.
†
P≤0.0003 vs placebo/tiotropium.
Hanania NA et al. Drugs 2009
 Significant (≥4 Units) Improvements
in Total St. George’s Respiratory Questionnaire (SGRQ) Score vs Placebo
+0.8

Impact
score

*
-4.6

-1.4 Activity
Improvement
score
-4.8
*P≤.03 vs placebo.

-3.0
Symptom
score
*

-8.7
Formoterol Solution (n=123)

-0.7 A change in Placebo (n=114)

total score Total
of 4 units score
*

-5.6 is clinically
relevant

2 0 -2 -4 -6 -8 -10 -12
Mean change in SGRQ score from baseline

Adapted from Gross NJ et al. Respir Med. 2008;102:189-197; Data on file. Dey Pharma, L.P.
 Formoterol Solution Plus Tiotropium:
Effect on Dyspnea (TDI) and Health Status
(SGRQ) – Responder Analysis

Health status improvement

Dyspnea improvement (change in total
(TDI ≥1) SGRQ score ≥4 units)

Responder categorization (%)

Responder categorization (%)

70 70
58.4 61.0
60 60

50 47.2 50

40 40

30 30
25.0
20 20

10 10
0 0
FormoterolSolution/Tiotropium Placebo/Tiotropium
(n=78) (n=77)

SGRQ=St. George’s Respiratory Questionnaire; TDI=transition dyspnea index.

Hanania NA et al. Drugs 2009
 Rescue Albuterol Use Over 12 Weeks

3.0 2.82 2.80 2.86 2.91

2.71 Albuterol
Puffs per day

2.5 use
decreased
2.0 * by
1.63 *
1.53 *
1.50
1.5
1.0 42%
0.5
0
Screening to Day 1 to Week 4 to Week 8 to
Day 1 Week 4 Week 8 Week 12

Formoterol Inhalation Placebo

Solution (n=123) (n=114)

* P≤.0003 vs placebo.
Adapted from Gross NJ et al. Respir Med. 2008;102:189-197, with permission from Elsevier;
Data on file. Dey Pharma, L.P.
Nebulized Arformoterol : Incidence and Risk of COPD
Exacerbations

Hanania NA et al. CHEST 2013

 Overall Incidence of Adverse Events*
• Overall incidence: 51.2% (Formoterol Inhalation Solution); 57.0% (placebo).
COPD exacerbation: 4.1% (Formoterol Inhalation Solution); 7.9% (placebo).
Serious AEs: 0.8% (Formoterol Inhalation Solution); 4.4% (placebo)

Formoterol
Inhalation Solution Placebo
Adverse Event (AE), n (%) (n=123) (n=114)
Diarrhea 6 (4.9) 4 (3.5)
Nausea 6 (4.9) 3 (2.6)
Nasopharyngitis 4 (3.3) 2 (1.8)
Dry mouth 4 (3.3) 2 (1.8)
Vomiting 3 (2.4) 2 (1.8)
Dizziness 3 (2.4) 1 (0.9)
Insomnia 3 (2.4) 0

* Treatment-emergent adverse events (incidence ≥2% and greater than placebo).

†
≥1% of Perforomist® Inhalation Solution participants and with a frequency greater than placebo.
Adapted from Gross NJ et al. Respir Med. 2008;102:189-197,
Very Severe COPD: Formoterol/Budesonide Neb vs pMDI –
PrB FeV1

Gogtay et al APSR 2014, NAPCON 2014

 For the patient point of view:
What are the most positive aspects of chronic
nebulization therapy?

a. Enables one to breathe easier/opens up

airways
b. Quick relief / fast acting
c. Able to do more activities
d. Live life more normally
e. All of the Above
f. None of the Above
NEB Survey Data Support Patient Satisfaction With
Nebulization
Patients with COPD responded positively to statements
regarding the perceived efficacy of nebulization

100 91 Agree
Total patient responses (%)

90 79 Disagree
80 74
70
60
50
40
30 21
20 12
10 5
0
You can You can be more The benefits of nebulization
breathe easier* physically active outweigh any difficulties
in your daily life* or inconveniences

* These benefits translated across all age groups (<45 years, 45-64, and 65 years) and stages of patient-
reported disease severity (not severe and severe). N=400 adults. NEB=Nebulization for Easier Breathing.).

COPD 2013; 10:482–492

NEB Survey: The Majority of Caregivers Recognized the Benefits
of Nebulization and Its Positive Impact on Their Patients’ Quality
of Life
Agree
Total patient responses* (%)

100 Disagree
86 85 82
80

60

40

20
9 10 14
0
Nebulization has made The benefits The overall quality of life
it easier to help care for outweigh any of my friend/family
friend/family member difficulties or member has improved since
inconveniences beginning nebulization

* Percentages are based on rounding and reflect only patients who responded to the given statement.
n=400 caregivers.
NEB=Nebulization for Easier Breathing.
COPD 2013; 10:482–492
 Clinical Scenarios Where Maintenance Nebulization
is Preferred in Patients With COPD

• Cognitive impairment that • Failure to comply with the use

precludes effective use of of pMDIs and DPIs
handheld inhalers
• When multiple agents need to
• Impaired manual dexterity due be co-administered
to arthritis, neurological
alterations, or stroke
• Insufficient inspiratory capacity
• Severe pain or muscle to use DPIs
weakness due to
neuromuscular disease • Unable to use pMDIs or DPIs
in an optimal manner despite
• Patient preference for adequate instruction and
nebulizers training which may result in
inadequate symptom relief

Dhand R et al. COPD. 2012;9:58-72.

 Maintenance Therapy – Stable COPD

• If patients with stable COPD experience greater symptomatic

benefit with nebulizers, then withholding nebulizer therapy from
those patients may be denying them the ability to better control their
symptoms, reduce acute exacerbations, and enhance their quality of
life. We recommend well-designed comparative efficacy and safety
trials with LABA/LAMA combinations, with or without ICS,
administered by inhalers versus nebulizers to evaluate the role of
nebulizers for maintenance therapy in patients with stable COPD.

Terry PD, Dhand R. Maintenance Therapy with Nebulizers in Patients with Stable COPD: Need for
Reevaluation. Pulm Therapy 2020; 6(2): 177–192
 Overview: Mucus-Quantity/Quality

Mucus Surfactant
flow layer
Cough or
air flow

Mucus
gland Mucus
gland
Int J Chron Obstruct Pulmon Dis. 2014;
Excessive mucus production
and associated complications

N Engl J Med. 2010 Dec 2; 363(23): 2233

 Mucus
hypersecretion
plays an important
role and is an
important
pathophysiological
and clinical
manifestation of
the following
airway
diseases……

ACUTE BRONCHIEC- CYSTIC

BRONCHIOLITIS TASIS FIBROSIS
 Treatment Options for Airway
mucus clearance

Airway clearance Pharmacological-

therapy Mucoactives

Breathing Autogenic Mechanical Mucoregu Mucokine

techniques drainage devices Expecto lators- tics-
Carbocyst Bronchodil
rants-
eine and ators,
Hyperto macrolides ambroxol.
nic Mucolytics-
Saline NAC, dornase
alpha, etc.
International journal of chronic obstructive pulmonary disease 13 (2018): 399.
 Conditions where Nebulizers must be used

1. Drugs which can be delivered only by the Nebulizer route

2. Acute exacerbations of asthma or COPD requiring hospitalization.
3. Altered mental state/cognitive decline/confused state
4. Patients who are inadequately controlled on DPIs or MDIs needing high doses of
inhaled bronchodilators or corticosteroids
5. Lack of coordination while using pMDI despite best efforts to train
6. Visual factors that may limit ability to use DPI’s and pMDI’s such as Macular
degeneration, Cataracts, or Glaucoma.
7. Dexterity issues such as parkinsonism or stroke
8. Hand arthritis in elderly patients (the use of pMDI or DPI use should be encouraged if
assisted inhalation for pMDI or DPI is possible
9. Non-CF Bronchiectasis in patients requiring inhaled antibiotics
10. Bronchiolitis in patients requiring inhaled therapy
11. Cystic Fibrosis (Antibiotics and mucolytics)
12. Pulmonary arterial hypertension requiring inhaled therapy
 Drugs only by the Nebulized Route

• Antibiotics: Tobramycin, Colistin, Amikacin, Fosfomycin,

Pentamidine, Fuoroquinolones
• Mucolytics: Dornase alpha, N-Acetyl Cysteine, Hypertonic Saline
• Bronchodilators: Salbutamol, Levosalbutamol, Ipratropium,
Salbutamol-Ipratropium, Terbutaline, Formoterol, Ar-Formoterol,
Glycopyrronium, Glycopyrronium-Formoterol
• Corticosteroids: Budesonide (*should be avoided with the
ultrasonic nebulizer) (Bronchodilators and steroids can also
be given by MDI or DPI inhalers)
• Others: Interferon beta, Immunomodulators: Mycobacterium
Vaccae (to treat COVID-19), PDE-3 inhibitor: Enoximone, Surfactant
Scoring for
Nebulization
indication in Primary
Care

Jindal SK, Pawar S, Hasan

A,Ghoshal A,Dhar R, K Katiyar SK,
Satish KS,Talwar D, Salvi S.
Scoring System for the Use of
Nebulizers in the Primary Care
Settings: An Expert Consensus
Statement. Journal of the
Association of Physicians of India
(2023): 10.5005/japi-11001-0273
 SUMMARY
• Nebulization is the most efficient and convenient form
of inhalation therapy for acute asthma, exacerbation of
COPD and other conditions where use of MDIs and DPIs
is not possible.
• Nebulization is the only mode to administer certain
drugs for which inhalers are not available.
• Domiciliary nebulization is indicated as maintenance
therapy of COPD for certain categories of patients.
• A simple scoring method is now available to decide in
whom to give nebulized treatment for use in the primary
care settings with limited resources.
THANK YOU