Aerosol therapy

1. Aerosol therapy Ri 曾杏榕

2. Outlines • 比較metered-dose inhaler through a valved holding chamber (MDI+VHC)與small-volume nebulizer (SVN) • 噴霧治療簡介及器材介紹 • 臨床使用half-saline inhalation的理由

3. Automatic replacement of albuterol nebulizer therapy by metered-dose inhaler and valved holding chamber • Purpose • Experiments and comparison • Results Data was from Shands Hospital at the University of Florida (SHUF) American Society of Health-System Pharmacists-Vol 62 May 15, 2005

4. Purpose • MDI+VHC is more efficient, faster, and more convenient than SVN. • Nevertheless, physicians have been slow to adopt MDI+VHC. • The purpose of this report is to discuss the scientific evidence supporting the use of MDI+VHC in place of SVN to deliver bronchodilators Am J Health-Syst Pharm—Vol 62 May 15, 2005

5. Experiments

6. Am J Health-Syst Pharm—Vol 62 May 15, 2005

7. Practical advantages of MDI+VHC • Cost: compressor rented for $50 per month purchased for $150 VHC costs only $20 through medical equipment (about $60 if purchased from a pharmacy). • Portability • Setting Am J Health-Syst Pharm—Vol 62 May 15, 2005

9. Conversion policy on intensivecare units (ICUs) • a pilot program allowing automatic conversion by respiratory therapists in all ICUs, including the medical ICU, for all adult patients receiving SVN, not just those on ventilators • Patient excluded: 1.continuous nebulization or more than four doses per hour 2. bronchodilators were mixed with other drugs (e.g., N-acetylcysteine) 3. Physician specified that MDI+VHC should not be used Am J Health-Syst Pharm—Vol 62 May 15, 2005

10. Hospitalwide conversion policy • Respiratory therapist use MDI+VHC for the first 24 hours, followed by assessment of the patient’s or caregiver’s ability to use it effectively. • The patient’s nurse subsequently observes the administration of each dose and records it in the medication administration record.

11. Outcomes • The conversion policy was initiated on all ICUs during November and December of 2003. • In the following six-month period: the use of SVN decreased (from 27,591 to 19,159 treatments, a 30% decline) the use of MDI increased (from 5,908 to 9,023 treatments, a 53% jump) compared with the same period a year before the policy change.

12. Similar data are not available for the hospital wards (non-ICU patients), but a single-day assessment indicated that none of the patients were switched from SVN to MDI+VHC, while only 9% met exclusion criteria. • The lack of adherence to the policy was a result of personnel changes and failure of the respiratory therapy supervisor to train new staff.

13. Conclusion • Delivery of albuterol by MDI+VHC is at least as effective as delivery by SVN and is faster, more convenient, and less expensive. • A policy to switch patients from SVN to MDI+VHC for bronchodilator administration at one hospital met with limited success.

14. 噴霧治療Aerosol therapy • 噴霧（Aerosol） 利用噴霧器將粉末狀或液狀藥物氣霧化並傳送到呼吸道，以維持呼吸道的通暢。 • 治療目的 補充額外的水分（濕化氣體及稀釋痰液） 給藥- 解除支氣管痙攣 預防或治療氣喘疾病 使支氣管分泌物易被排除 給予抗生素 口腔喉部及氣管支氣管之局部麻醉

15. 危險性 • 原本乾黏的痰,因噴霧吸水膨脹, 造成呼吸道阻塞(Aiwway obstruction) • 因吸入微小的氣霧粒子造成支氣管痙攣(Bronchospasm) • 持續給予噴霧治療時造成呼吸道水分過多(Over hydration) ,尤其嬰兒 • 感染(Infection) • 使用熱的噴霧治療不慎,導致燙傷(Thermal injury)

16. Size (MMAD um) Site of deposition 0.5 - 2um Alveoli 2 - 5um Bronchi and bronchioles 5 - 100um Mouth, nose and upper airway > 100um Filtered by the upper respiratory tract • 治療目標： 希望可以到達預定作用的組織，以達效果

17. Safety of sputum induction with isotonic saline in adults withacute severe asthma • Introduction • Method • Results • Discussion Clinical and Experimental Allergy, 2001, Volume 31, pages 1745-1753

18. Introduction • Sputum induction is a safe and effective technique to study airway inflammation in stable asthma. • However, it has the potential to induce bronchospasm and the safety and efficacy of the technique in acute asthma has not been determined. • The objective of this study was to evaluate the safety and efficacy of a protocol to induce sputum using isotonic saline in adults with acute exacerbations of asthma.

19. Method • Adults (n=47), aged 16-81 years, presenting to the emergency room with acute asthma and an FEV1>1.0 L underwent supervised sputum induction with 0.9% saline delivered by an ultrasonic nebuliser. • Excluding criteria: • If they were on daily maintenance oral corticosteroids for asthma • If they had a coexisting physician diagnosis of chronic obstructive pulmonary disease. • If they had an infiltrate on chest radiograph suggesting pneumonia • If their FEV1 was less than 1 L after salbutamol 200 μg • If they had another contraindication to sputum induction in acute asthma .

20. The nebuliser output was 1.8 mL/min and particle size (MMAD) , 5um. • Saline was nebulised for 30 s, 1 min and then for 2X2-min periods. • Salbutamol 200 μg was given following the induction if there had been a fall in FEV1 of at least 15% from baseline or if the subject requested it for symptoms • Sputum induction was ceased when an adequate sample was obtained after nebulisation, if FEV1 fell below 20% of pre-induction baseline, or at the subject's request.

22. Results

27. Predictors for a fall in FEV1 with sputum induction • No relationship with a fall in FEV1 • Baseline FEV1 prior to induction (r＝-0.14, P= 0.3) • The time of nebulization (r=0.1, P=0.8) • The dose of saline delivered (r=0.02, P=0.9)

29. Discussion • Despite β2-agonist pre-treatment, and despite the use of isotonic saline, 28% of subjects had a significant fall in FEV1, all subjects could be rescued with salbutamol and had returned to within 10% of their baseline FEV1 by 15 min after induction. • Popov et al. reported that using isotonic saline was better tolerated than hypertonic saline. • An adequate sputum was obtained less often, in only 36% of inductions compared with 79% with 5% hypertonic saline

30. In view of the unstable nature of subjects with acute asthma, we considered that the risks from hypertonic saline might be excessive. • It must be stressed that we used a number of additional procedures to ensure the safety of subjects during sputum induction in acute asthma.

31. The cellular and mediator profile of induced sputum can change with increasing doses of hypertonic saline. • Using hypertonic saline 3%, the proportion of sputum neutrophils is significantly lower and the proportion of macrophages significantly higher.

32. The mechanism of this interesting and unexpected effect is not clear. • It is known that long-acting β2-agonists reduce exacerbations and may reduce levels of IL-8. • IL-8 is a key mediator in acute severe asthma that promotes neutrophil recruitment and vascular leakage

33. 臨床使用half-saline inhalation的理由 • 文獻資料少得可憐 • 從以上paper得知，使用saline inhalation對sputum induction是有效的 • 使用越高濃度的saline inhalation，引起bronchospasm的機率越高,即使使用越高濃度saline inhalation，sputum induction rate越高 • 即使使用normal saline inhalation被證明是安全的，考慮現有醫療人力、器具配置，因此降低inhalation濃度？？？

34. Thanks for your attention

35. Popov TA, Pizzichinini MMM, Pizzichini E et al. Some technical factors influencing the induction of sputum for cell analysis. Eur Respir J 1995; 8:559-65.