Demystifying Nebulization | Jindal Chest Clinic

Demystifying Nebulization: Its Principle, Classification, Applications, etc. For more information, please contact us: 9779030507.

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 Intravenous route no benefits Potential for increased adverse effects Inhaled route: preferred mode Easy, safe, faster onset of action More effective than parenteral routes Favors IV Favors inhaled Travers et al Cochrane Database Syst Rev 2001

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 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 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

7. Particle Size & Lung deposition Most particles of 0.1–1 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 >5 μm are deposited by impaction in the oropharynx and swallowed. Particles <5 μm ( fine-particle fraction, FPF) have the greatest potential for lung deposition, usually deposited by sedimentation or gravity.

8. Metered dose inhalers Dry powder inhalers Nebulizer Inhaler Devices Classification Breath Actuated Inhalers BAIs

9. Pulmonary delivery of drugs: Advantages Treatment of respiratory diseases Inhalation 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 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.

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 Steam inhalation 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 Nebulization 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 5–10  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

12. Nebulizer vs. MDI MDI 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 Nebulizer 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 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.

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). (3) Insert mouthpiece and turn on the compressor. Breathe as calmly, deeply, and evenly as possible until no more mist is formed in the nebulizer reservoir. (2) Connect the nebulizer reservoir to the mouthpiece and to the compressor. 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). Adapted from PARI. Jet nebulization technology. http://www.pari.com/pdd/jet-neb-tech.htm. PARI LC ® Reusable Nebulizer (includes Pari LC ® Plus)

22. Function of Jet Nebulizers 1. Air from the compressor breaks the liquid medication into small breathable particles that form a mist (aerosol). Adapted from PARI. Jet nebulization technology. http://www.pari.com/pdd/jet-neb-tech.htm. 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. Inspiration PARI LC ® Reusable Nebulizer (includes Pari LC ® Plus)

23. Function of Jet Nebulizers 1. Air from the compressor breaks the liquid medication into small breathable particles that form a mist (aerosol). Adapted from PARI. Jet nebulization technology. http://www.pari.com/pdd/jet-neb-tech.htm. 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 patient’s breath away from the nebulizer. Inspiration Expiration PARI LC ® Reusable Nebulizer (includes Pari LC ® Plus)

24. Nebulization Delivers Effective Dose Austitz H et al. Chest. 1989;96:1287. 0.2 0.4 0.6 0.8 1.0 Mean change in FEV 1 Cumulative dose (mg) Nebulizer 0.25 1.0 2.5 10 40 MDI Cumulative Dose Study Multiple inhalations from MDI are required to achieve the same amount of bronchodilation as from larger nebulized dose

25. Nebulization May Reduce Technique Errors

26. MDIs Are Frequently Associated With Technique-Related Errors Incorrect inhalation technique can diminish clinical efficacy of devices 1 MDI technique involves 9 steps . Two commonly associated technique-related errors are 1 : Step 5 : Place the inhaler mouthpiece between the lips (and the teeth); keep the tongue from obstructing the mouthpiece 1 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 nose 1 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.

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 are 1 : Step 3 : Exhale deeply, away from the mouthpiece 1 Failure to exhale prior to inhaling (may lead to suboptimal drug deposition in lung) 2 Step 5 : Inhale deeply and forcefully 1 Failure to achieve a forceful and rapid inspiratory flow at start of inhalation  poor 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.

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: 213–218

29. Part B. Applications and Indications

30. 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. 31 First Drug of Choice In Acute Severe Asthma Nebulised steroid 2) Nebulised salbutamol 3) Injectable theophylline 4) Injectable dexamethasone Nebulized Salbutamol/SABA Nebulized salbutamol 2.5-5 mg every 20 min for 1hr Then every 1-4 hours as required In children half the above dose Can ALSO use Levosalbutamol – less tachycardia 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 (SABA+SAMA)

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 > 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. Don’t 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 Molimard M et al. J Aerosol Med 2003; 16: 249 - 254 Frequency of Critical Errors by Device n = 3811

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; doi:10.1038/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; doi:10.1038/npjpcrm.2014.34; published online 4 September 2014

39. PIFR and DPI Use Air Trapping Muscle weakness and 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.

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: 78–83

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 significantly associated with reduced risk of death and admission to hospital due to exacerbations in COPD Thorax 2009;64:939–943 3-year trial of inhaled medications in patients with moderate to severe COPD

43. Medication delivery: is use nebulize devices an appropriate alternative ? Eur Respir Rev 2005; 14: 96, 97–101

44. 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 2005 Med Care 2004, 42:200–209.

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. 1 2 3 6 9 12 1.6 1.5 1.4 1.3 1.2 Formoterol Delivered by Nebulizer is as Efficacious as that Delivered by DPI Hours Minutes Hours Minutes Day 1 Week 12 Mean FEV 1 (L) Mean FEV 1 ( L) ITT Population Gross NJ et al. Respir Med . 2008;102;189-197. Neb 20 µg (n=123) Aerolizer12 µg (n=114) Placebo (n=114) 1 2 3 6 9 12 1.6 1.5 1.4 1.3 1.2

48. Arformoterol Nebulized Solution vs Salmeterol MDI: Mean % Change in Morning Predose FEV 1 5 10 15 20 25 30 Mean change in FEV 1 from baseline (%) Time 6% (Placebo) 18% (Arformoterol) P <.001 24 2 4 6 8 10 12 22 Averaged Over 3 Visits: Weeks 0, 6, and 12 Dose 1 (8 AM ) Dose 2 (8 PM ) Morning predose (8 AM ) Placebo Arformoterol 15  g bid Salmeterol 42  g bid Baumgartner RA et al. Clin Ther . 2007;29:261-278.

49. Formoterol Nebulization Solution Plus Tiotropium Handihaler Mean FEV 1 on Day 1 and at Week 6 * 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 Formoterol Solution/Tiotropium Day 1 Placebo/Tiotropium Day 1 Placebo/Tiotropium Week 6 Formoterol Solution/ Tiotropium Week 6 FEV 1 (L) 1.7 1.3 1.2 1.1 1.0 1.4 1.5 1.6 † † † † † † † † † † † 0.5 1.0 1.5 2.0 2.5 3.0 5 (min) Pre- dose Postdose (hours)

50. Significant (≥4 Units) Improvements in Total St. George’s Respiratory Questionnaire (SGRQ) Score vs Placebo Adapted from Gross NJ et al. Respir Med . 2008;102:189-197; Data on file. Dey Pharma, L.P. Improvement Formoterol Solution (n=123) Placebo (n=114) * P ≤.03 vs placebo. Mean change in SGRQ score from baseline Activity score 2 -2 -4 -6 -8 -10 -12 Symptom score * Impact score * -5.6 Total score -0.7 -8.7 -3.0 -4.8 -1.4 -4.6 +0.8 A change in total score of 4 units is clinically relevant *

51. Formoterol Solution Plus Tiotropium : Effect on Dyspnea (TDI) and Health Status (SGRQ) – Responder Analysis SGRQ=St. George’s Respiratory Questionnaire; TDI=transition dyspnea index. Hanania NA et al. Drugs 2009 Responder categorization (%) 10 20 30 40 50 70 FormoterolSolution/Tiotropium (n=78) Placebo/Tiotropium (n=77) Responder categorization (%) 10 30 40 50 60 70 58.4 47.2 60 20 61.0 25.0 Dyspnea improvement (TDI ≥1) Health status improvement (change in total SGRQ score ≥4 units)

52. Rescue Albuterol Use Over 12 Weeks * 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. Screening to Day 1 Day 1 to Week 4 3.0 2.5 Puffs per day Formoterol Inhalation Solution (n=123) Placebo (n=114) 2.0 1.5 1.0 0.5 Week 4 to Week 8 Week 8 to Week 12 * * * 2.82 2.80 1.63 2.86 1.53 2.91 1.50 2.71 Albuterol use decreased by 42%

53. Nebulized Arformoterol : Incidence and Risk of COPD Exacerbations Hanania NA et al. CHEST 2013

54. Overall Incidence of Adverse Events* Adverse Event (AE), n (%) Formoterol Inhalation Solution (n=123) Placebo (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) * 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, 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)

55. Very Severe COPD: Formoterol / Budesonide Neb vs pMDI – PrB FeV1 Gogtay et al APSR 2014, NAPCON 2014

56. For the patient point of view: What are the most positive aspects of chronic nebulization therapy? Enables one to breathe easier/opens up airways Quick relief / fast acting Able to do more activities Live life more normally All of the Above None of the Above

57. NEB Survey Data Support Patient Satisfaction With Nebulization You can breathe easier* You can be more physically active in your daily life* The benefits of nebulization outweigh any difficulties or inconveniences Total patient responses (%) 91 74 79 5 21 12 10 20 30 40 50 60 70 80 90 100 Agree Disagree * 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.). Patients with COPD responded positively to statements regarding the perceived efficacy of nebulization COPD 2013; 10:482–492

58. NEB Survey: The Majority of Caregivers Recognized the Benefits of Nebulization and Its Positive Impact on Their Patients’ Quality of Life * Percentages are based on rounding and reflect only patients who responded to the given statement. n=400 caregivers. NEB=Nebulization for Easier Breathing. Nebulization has made it easier to help care for friend/family member The benefits outweigh any difficulties or inconveniences The overall quality of life of my friend/family member has improved since beginning nebulization Total patient responses * (%) 86 85 82 9 10 14 Agree Disagree COPD 2013; 10:482–492

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 . 2012;9:58-72.

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): 177–192

61. Overview: Mucus-Quantity/Quality Cough or air flow Mucus gland Mucus flow Surfactant layer Mucus gland Int J Chron Obstruct Pulmon Dis.  2014; 9: 139–150

62. Excessive mucus production and associated complications N Engl J Med. 2010 Dec 2; 363(23): 2233–2247.

63. Mucus hypersecretion plays an important role and is an important pathophysiological and clinical manifestation of the following airway diseases…… ACUTE BRONCHIOLITIS BRONCHIEC-TASIS CYSTIC FIBROSIS

64. Treatment Options for A irway mucus clearance Airway clearance therapy Breathing techniques Autogenic drainage Mechanical devices Pharmacological- Mucoactives Expectorants- Hypertonic Saline Mucoregulators- Carbocysteine and macrolides Mucolytics- NAC, dornase alpha, etc. Mucokinetics - Bronchodilators, ambroxol. 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 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

66. 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

67. 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

68. 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.

69. THANK YOU