Demystifying Nebulization | Jindal Chest Clinic

1

• DEMYSTIFYING NEBULIZATION
• Jindal Clinics, Chandigarh www.jindalchest.com

2

• Part A. Basic Physics and General Principles

3
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

4
Route of delivery for airway diseases
Travers et al Cochrane Database Syst Rev 2001

• Intravenous route
• no benefits
• Potential for increased adverse effects

Inhaled route preferred mode Easy, safe,
faster onset of action More effective than
parenteral routes
5
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

6
Airway Geometry Particle deposition
As aerosols move into smaller and smaller airway
at bifurcations, some particles get deposited as
they reach a point where the distance from their
center to a surface is less than their
radius. Mechanisms of deposition

• High variability of regional and total deposition
  efficiency.
• Factors for deposition
• i. Respiratory tract geometry
• ii. Breathing pattern,
• iii. Age and health,
• iv. Momentary physical activity
• iii. Aerosol properties
• Particle size, shape,
• Density,
• Hygroscopicity,
• Surface properties

7
Particle Size Lung deposition

• Most particles of 0.11 µm diffuse by Brownian
  motion deposit when they collide with the
  airway wall.
• The longer the residence time in the smaller
  airways, the greater the deposition from
  sedimentation and Brownian motion processes.
• Inhaled particles that do not deposit are
  exhaled.

• Particles gt5 µm are deposited by impaction in the
  oropharynx and swallowed.
• Particles lt5 µm (fine-particle fraction, FPF)
  have the greatest potential for lung deposition,
  usually deposited by sedimentation or gravity.

8
Inhaler Devices Classification
Dry powder inhalers
Metered dose inhalers
Nebulizer
Breath Actuated Inhalers BAIs
9
Pulmonary delivery of drugs AdvantagesTreatment
of respiratory diseases

• Inhalation

• Nebulization

• Drug delivery with an air-pump driven by power
  used to convert liquid drug into aerosols, to
  deliver medication by inhalation through a mask
• First invented in France by Sales-Girons in 1858
  to atomize the liquid medication. The pump handle
  was operated like a bicycle pump steam-driven
  nebulizer invented in Germany in 1864 - "Siegle's
  steam spray inhaler", used Venturi pump to
  atomize liquid medication.

• Deliver high concentrations directly to the
  disease site
• Rapid clinical response
• Minimizes risk of systemic side-effects
• Bypass the barriers to therapeutic efficacy, such
  as
• Poor gastrointestinal absorption and
  First-pass metabolism in the liver
• Achieve a similar or superior therapeutic effect
  at a fraction of the systemic dose

10
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.

11
Nebulization vs. Steam inhalation

• Nebulization

• Steam inhalation

• A nebulizer breaks particles up further to make
  for a finer and deeper reach.
• Particles of more than 10 µm in diameter are most
  likely to deposit in the mouth and throat, for
  those of 510 µm diameter a transition from mouth
  to airway deposition occurs, and particles
  smaller than 5 µm in diameter deposit more
  frequently in the lower airways and are
  appropriate for pharmaceutical aerosols.
• Nebulizing processes have been modeled on
  computational fluid dynamics

• Warm vapours are soothing provides moisture to
  the dry mucus membranes in the nose and throat
• Helps loosen the mucus and provides relief from
  chest congestion.
• Hot vapour can help reduce bacterial infections
  in the nasal passage and reduce common cold
  symptoms
• Excess hot vapour or steam inhalation for a long
  time can cause damage to the nose and throat
  cells. Skin issues and swelling and redness in
  the eyes.
• Greater risks in children

12
Nebulizer vs. MDI

• MDI

• Nebulizer

• Advantages Smaller in size
• Require no power source.
• Deliver the medicine more quickly than a
  nebulizer.
• With spacer, as effective as a nebulizer
• Disadvantages Require coordination
• Difficult to administer in the elderly,
  small children, patients with disabilities and
  serious cases, severe asthma attacks.
• The age of the child makes a difference in how an
  inhaler is used may require another person to
  administer

• Advantages For all age groups, normal
  ventilatory pattern and low inspiratory flow.
• Easy for patients who have difficulty using
  inhalers, such as the elderly, small children,
  patients with disabilities and serious cases,
  severe asthma attacks.
• Low operational cost.
• Disadvantages Creates more noise (often 60 dB
  during use)
• Less portable, greater weight
• Greater dose lot of wastage
• Local deposition in the mouth

13
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 10007000 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.

14
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

15
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

16
Hand-held Nebulizers/ Soft mist inhalers

• Liquid-based inhalers which produce a slow-moving
  aerosol cloud release medication
• i. in a fine mist
• ii. more slowly and
• iii. lasts longer
• For delivering treatments for short-term care
• SMI is more efficient, even with poor inhaler
  technique teaching patients to hold their breath
  as well as to inhale slowly and deeply increases
  further lung deposition

• Suitable for biologic formulations
• Gentle aerosolization for sensitive drug products
• Greater sustainability
• Can be reused
• SMIs offer a great potential for drug delivery of
  a far wider range of drug formulations with
  enhanced precision and accuracy of dosing and
  inhalation for a wider range of drugs.

17
INHALATIONAL/ NEBULIZABLE DRU

• Bronchodilators
• Beta-2 Agonists
• Anti-muscarinic Agents
• Corticosteroids
• Combinations
• Miscellaneous
• - Antibiotics
• - Mucolytics Acetyl cysteine
• - Hypertonic saline
• - Other drugs

18
Factors Associated with Non-Compliance in Asthma
and COPD

• Medication Usage
• Difficulties associated with inhalers
• Complicated regimens
• Fears about, or actual side effects
• Cost

• Patient/Physician
• Misunderstanding/lack of information
• Underestimation of severity
• Attitudes toward ill health
• Cultural factors
• Poor communication

19
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

20
Use of Jet Nebulizers Can Be as Easy as 1-2-3
(1) Open the vial and transfer all the medicine
into the nebulizer medicine cup (reservoir).
Please see accompanying full Prescribing
Information, including Boxed Warning. Medication
Guide Perforomist (formoterol fumarate)
Inhalation Solution. Napa, CA Dey Pharma, L.P.
2008.
21
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.
22
Function of Jet Nebulizers

• 1. Air from the compressor breaks the liquid
  medication into small breathable particles that
  form a mist (aerosol).

2. Upon inhalation, the inspiratory valve at the
top opens, letting air in and speeding up the
generation of mist to increase flow of medication
to the lungs.
PARI LC Reusable Nebulizer (includes Pari LC
Plus)
Adapted from PARI. Jet nebulization technology.
http//www.pari.com/pdd/jet-neb-tech.htm.
23
Function of Jet Nebulizers

• 1. Air from the compressor breaks the liquid
  medication into small breathable particles that
  form a mist (aerosol).

2. Upon inhalation, the inspiratory valve at the
top opens, letting air in and speeding up the
generation of mist to increase flow of medication
to the lungs.
3. Upon exhalation, the inspiratory valve closes,
slowing down the mist the mouthpiece flap
opens, directing the patients breath away from
the nebulizer.
PARI LC Reusable Nebulizer (includes Pari LC
Plus)
Adapted from PARI. Jet nebulization technology.
http//www.pari.com/pdd/jet-neb-tech.htm.
24
Nebulization Delivers Effective Dose

• Cumulative Dose Study
• Multiple inhalations from MDI are required to
  achieve the same amountof bronchodilation as
  from larger nebulized dose

1.0
Nebulizer
0.8
MDI
0.6
Mean change in FEV1
0.4
0.2
0
0.25
1.0
2.5
10
40
Cumulative dose (mg)
Austitz H et al. Chest. 1989961287.
25
Nebulization May Reduce Technique Errors
26
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 between the
lips (and the teeth) keep the tongue from
obstructing the mouthpiece1
Step 6 Trigger the inhaler while breathing in
deeply and slowly (this should be about 30
L/min)1

• 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. 20091876-82
2. Lavorini F et al. Respir Med.
2008102593-604.
27
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, away from the mouthpiece1
• Failure to exhale prior to inhaling (may lead to
  suboptimal drug deposition in lung)2

• Step 5 Inhale deeply and forcefully1
• Failure to achieve a forceful and rapid
  inspiratory flow at start of inhalation ? poor
  drug release and low lung deposition2
• Common in elderly patients severe airflow
  limitation cognitive impairment2,3

1. Broeders M et al on behalf of the ADMIT
Working Group. Prim Care Respir J. 20091876-82
2. Lavorini F et al. Respir Med.
2008102593-604 3. Zarowitz BJ. Geriatr Nurs.
20093045-49.
28
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 213218
29

• Part B. Applications and Indications

30
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

31
First Drug of Choice In Acute Severe Asthma

• Nebulised steroid
• 2) Nebulised salbutamol

3) Injectable theophylline 4) Injectable
dexamethasone
Can ALSO use Levosalbutamol less tachycardia
Nebulized Salbutamol/SABA
Nebulized salbutamol 2.5-5 mg every 20 min for 1hr

• Consider adding nebulised ipratropium SAMA
  bromide to SABA
• Adults
• 250 500 mcg every 4 to 6 hours
• Even safe to give every 20 30 mins for the
  first 2 hours in a severe attack.
• Also can use combination respule (SABASAMA)

Then every 1-4 hours as required
In children half the above dose
32
GC 72 years construction worker

• Dyspnea over 4 years
• Off and on bouts of cough and phlegm winter
  exacerbations
• Unable to do anything
• Smoked gt 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

33
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. Dont treat his disease is not too bad

34
Devices for treatment of airway disease
A large number of different inhaled products of
more than 20 ingredients
and many more to come
35
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

36
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
37
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 doi10.1038/npjpcrm.2014.34 published
online 4 September 2014
38
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 doi10.1038/npjpcrm.2014.34 published
online 4 September 2014
39
PIFR and DPI Use

• Muscle weakness and air trapping may decrease
  ability to generate minimal required PIFR (20-30
  L/min) when using a DPI

Air Trapping
Weiner P, Weiner M. Respiration. 200673151-156.
40
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 7883
41
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

42
Adherence to inhaled medication is
significantlyassociated with reduced risk of
death andadmission to hospital due to
exacerbations in COPD
3-year trial of inhaled medications in patients
with moderate to severe COPD
Thorax 200964939943
43
Medication delivery is use nebulize devices an
appropriate alternative ?
Eur Respir Rev 2005 14 96, 97101
44
How to translate the benefits of new medicines
into health gain for individuals?

• Adherence is defined as the extent to which
  a patients 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 2005
Med Care 2004, 42200209.
45
Efficacy and Safety of Nebulization for
Maintenance Treatment of COPD
46

• 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

47
Formoterol Delivered by Nebulizer is as
Efficacious as that Delivered by DPI
Day 1
Week 12
ITT Population
Mean FEV1 (L)
Mean FEV1 ( L)
Hours
Minutes
Hours
Minutes
Neb 20 µg (n123)
Aerolizer12 µg (n114)
Placebo (n114)
Gross NJ et al. Respir Med. 2008102189-197.
48
Arformoterol Nebulized Solution vs Salmeterol
MDI Mean Change in Morning Predose FEV1
Averaged Over 3 Visits Weeks 0, 6, and 12
30
Placebo Arformoterol 15 ?g bid Salmeterol 42 ?g
bid
25
18 (Arformoterol)
20
Mean change in FEV1from baseline ()
15
Plt.001
10
5
6 (Placebo)
0
0
24
2
4
6
8
10
12
22
Morning predose(8 AM)
Dose 1(8 AM)
Dose 2(8 PM)
Time
Baumgartner RA et al. Clin Ther. 200729261-278.
49
Formoterol Nebulization Solution Plus Tiotropium
Handihaler Mean FEV1 on Day 1 and at Week 6










FEV1 (L)

0.5
1.0
1.5
2.0
2.5
3.0
5(min)
Pre-dose
Postdose (hours)
Tolerance to the effects of inhaled ?2-agonists
can occur with regularly scheduled, chronic
use. P0.0003 vs placebo/tiotropium. Hanania
NA et al. Drugs 2009
50
Significant (4 Units) Improvements in Total
St. Georges Respiratory Questionnaire (SGRQ)
Score vs Placebo
0.8
Impactscore

-4.6
Improvement
-1.4
Activityscore
-4.8
P.03 vs placebo.
-3.0
Symptomscore

-8.7
Formoterol Solution (n123)
Placebo (n114)
A change in total score of 4 units is
clinically relevant
-0.7
Totalscore
-5.6

2
0
-2
-4
-6
-8
-10
-12
Mean change in SGRQ score from baseline
Adapted from Gross NJ et al. Respir Med.
2008102189-197 Data on file. Dey Pharma, L.P.
51
Formoterol Solution Plus Tiotropium Effect on
Dyspnea (TDI) and Health Status (SGRQ)
Responder Analysis
Health status improvement(change in total SGRQ
score 4 units)
Dyspnea improvement(TDI 1)
70
70
61.0
58.4
60
60
50
50
47.2
40
40
Responder categorization ()
Responder categorization ()
30
30
25.0
20
20
10
10
0
0
FormoterolSolution/Tiotropium (n78)
Placebo/Tiotropium (n77)
SGRQSt. Georges Respiratory Questionnaire
TDItransition dyspnea index. Hanania NA et al.
Drugs 2009
52
Rescue Albuterol Use Over 12 Weeks
2.91
Albuteroluse decreased by 42
3.0
2.86
2.82
2.80
2.71
2.5
2.0

Puffs per day


1.63
1.53
1.50
1.5
1.0
0.5
0
Screening toDay 1
Day 1 toWeek 4
Week 4 toWeek 8
Week 8 toWeek 12
Formoterol Inhalation Solution (n123)
Placebo(n114)
P.0003 vs placebo. Adapted from Gross NJ et
al. Respir Med. 2008102189-197, with permission
from Elsevier Data on file. Dey Pharma, L.P.
53
Nebulized Arformoterol Incidence and Risk of
COPD Exacerbations
Hanania NA et al. CHEST 2013
54
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)

Adverse Event (AE), n () Formoterol Inhalation Solution (n123) Formoterol Inhalation Solution (n123) Formoterol Inhalation Solution (n123) Placebo (n114) Placebo (n114)
Diarrhea Diarrhea 6 (4.9) 4 (3.5)
Nausea Nausea 6 (4.9) 3 (2.6)
Nasopharyngitis Nasopharyngitis 4 (3.3) 2 (1.8)
Dry mouth Dry mouth 4 (3.3) 2 (1.8)
Vomiting Vomiting 3 (2.4) 2 (1.8)
Dizziness Dizziness 3 (2.4) 1 (0.9)
Insomnia 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.
2008102189-197,
55
Very Severe COPD Formoterol/Budesonide Neb vs
pMDI PrB FeV1
Gogtay et al APSR 2014, NAPCON 2014
56
For the patient point of viewWhat are the most
positive aspects of chronic nebulization therapy?

1. Enables one to breathe easier/opens up airways
2. Quick relief / fast acting
3. Able to do more activities
4. Live life more normally
5. All of the Above
6. None of the Above

57
NEB Survey Data Support Patient Satisfaction With
Nebulization
Patients with COPD responded positively to
statements regarding the perceived efficacy of
nebulization
Agree
91
100
Disagree
90
79
74
80
70
60
Total patient responses ()
50
40
21
30
12
20
5
10
0
You canbreathe easier
You can be morephysically activein your daily
life
The benefits of nebulizationoutweigh any
difficultiesor inconveniences
These benefits translated across all age
groups (lt45 years, 45-64, and ?65 years) and
stages of patient-reported disease severity (not
severe and severe). N400 adults.
NEBNebulization for Easier Breathing.).
COPD 2013 10482492
58
NEB Survey The Majority of Caregivers Recognized
the Benefits of Nebulization and Its Positive
Impact on Their Patients Quality of Life
Agree
Disagree
85
86
82
Total patient responses ()
14
10
9
The benefits outweigh any difficulties or
inconveniences
Nebulization has madeit easier to help care for
friend/family member
The overall quality of life of my friend/family
member has improved since beginning nebulization
Percentages are based on rounding and reflect
only patients who responded to the given
statement. n400 caregivers. NEBNebulization
for Easier Breathing.
COPD 2013 10482492
59
Clinical Scenarios Where Maintenance Nebulization
is Preferred in Patients With COPD

• Cognitive impairment that precludes effective use
  of handheld inhalers
• Impaired manual dexterity due to arthritis,
  neurological alterations, or stroke
• Severe pain or muscle weakness due to
  neuromuscular disease
• Patient preference for nebulizers

• Failure to comply with the use of pMDIs and DPIs
• When multiple agents need to be co-administered
• Insufficient inspiratory capacity to use DPIs
• Unable to use pMDIs or DPIs in an optimal manner
  despite adequate instruction and training which
  may result in inadequate symptom relief

Dhand R et al. COPD. 2012958-72.
60
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) 177192

61
Overview Mucus-Quantity/Quality
Surfactant layer
Mucus flow
Cough or air flow
Mucus gland
Mucus gland
Int J Chron Obstruct Pulmon Dis. 2014 9 139150
62
Excessive mucus production and associated
complications
N Engl J Med. 2010 Dec 2 363(23) 22332247.
63
Mucus hypersecretion plays an important role and
is an important pathophysiological and clinical
manifestation of the following airway diseases
CYSTIC FIBROSIS
ACUTE BRONCHIOLITIS
BRONCHIEC-TASIS
64
Treatment Options for Airway mucus clearance
Pharmacological- Mucoactives
Airway clearance therapy
Mechanical devices
Mucoregulators- Carbocysteine and macrolides
Breathing techniques
Autogenic drainage
Mucokinetics-Bronchodilators, ambroxol.
Expectorants- Hypertonic Saline
Mucolytics- NAC, dornase alpha, etc.
International journal of chronic obstructive
pulmonary disease 13 (2018) 399.
65
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
  DPIs and pMDIs 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

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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

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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-11001-027
  3

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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.

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• THANK YOU