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Table I Main Characteristics of Pressurized Metered-Dose Inhalers
表 I 加压计量吸入器的主要特点
Formulation 配方

悬浮或溶解在推进剂中的药物(含表面活性剂和助溶剂)
Drug Suspended or Dissolved in
Propellant (With Surfactant and
Cosolvent)
Drug Suspended or Dissolved in Propellant (With Surfactant and Cosolvent)| Drug Suspended or Dissolved in | | :--- | | Propellant (With Surfactant and | | Cosolvent) |
Metering system 计量系统 Metering valve and reservoir
计量阀和储液器
Propellant 推进剂 HFA or CFC 氢氟烷烃或氟氯化碳
Dose counter 剂量计数器 Sometimes 有时
Priming 打底 Variable priming requirements
不同的启动要求
 温度依赖性
Temperature
dependence
Temperature dependence| Temperature | | :--- | | dependence |
Low 
 湿度依赖性
Humidity
dependence
Humidity dependence| Humidity | | :--- | | dependence |
Low 
Actuator orifice 致动器孔

致动器的设计和尺寸对 pMDI 的性能影响很大
The design and size of the actuator significantly
influences the performance of pMDIs
The design and size of the actuator significantly influences the performance of pMDIs| The design and size of the actuator significantly | | :--- | | influences the performance of pMDIs |
Lung deposition 肺部沉积 8 % 53 % 8 % 53 % 8%-53%8 \%-53 \%
MMDA I.22 μ m 8 μ m μ m 8 μ m mum-8mum\mu \mathrm{m}-8 \mu \mathrm{~m}
 气溶胶出口速度
Aerosol exit
velocity
Aerosol exit velocity| Aerosol exit | | :--- | | velocity |
High (more than 3 m/s)
高(超过 3 米/秒)
Lung distribution 肺部分布 Central and peripheral regions
中部和周边地区
 内在阻力
Intrinsic
resistance
Intrinsic resistance| Intrinsic | | :--- | | resistance |
Low 
 吸气流速
Inspiratory flow
rate
Inspiratory flow rate| Inspiratory flow | | :--- | | rate |
20 20 ∼20\sim 20 L/min  20 20 ∼20\sim 20 升/分钟
Advantages 优势

结构紧凑,便于携带,配料稳定,输送迅速
Compact and portable, consistent dosing, and
rapid delivery
Compact and portable, consistent dosing, and rapid delivery| Compact and portable, consistent dosing, and | | :--- | | rapid delivery |
Disadvantages 缺点 Not breath-actuated, require coordination
非呼吸驱动,需要协调
Formulation "Drug Suspended or Dissolved in Propellant (With Surfactant and Cosolvent)" Metering system Metering valve and reservoir Propellant HFA or CFC Dose counter Sometimes Priming Variable priming requirements "Temperature dependence" Low "Humidity dependence" Low Actuator orifice "The design and size of the actuator significantly influences the performance of pMDIs" Lung deposition 8%-53% MMDA I.22 mum-8mum "Aerosol exit velocity" High (more than 3 m/s) Lung distribution Central and peripheral regions "Intrinsic resistance" Low "Inspiratory flow rate" ∼20 L/min Advantages "Compact and portable, consistent dosing, and rapid delivery" Disadvantages Not breath-actuated, require coordination| Formulation | Drug Suspended or Dissolved in <br> Propellant (With Surfactant and <br> Cosolvent) | | :--- | :--- | | Metering system | Metering valve and reservoir | | Propellant | HFA or CFC | | Dose counter | Sometimes | | Priming | Variable priming requirements | | Temperature <br> dependence | Low | | Humidity <br> dependence | Low | | Actuator orifice | The design and size of the actuator significantly <br> influences the performance of pMDIs | | Lung deposition | $8 \%-53 \%$ | | MMDA | I.22 $\mu \mathrm{m}-8 \mu \mathrm{~m}$ | | Aerosol exit <br> velocity | High (more than 3 m/s) | | Lung distribution | Central and peripheral regions | | Intrinsic <br> resistance | Low | | Inspiratory flow <br> rate | $\sim 20$ L/min | | Advantages | Compact and portable, consistent dosing, and <br> rapid delivery | | Disadvantages | Not breath-actuated, require coordination |
Abbreviations: pMDI, pressurized metered-dose inhaler; HFA, hydrofluoroalkane; CFC, chlorofluorocarbon; MMAD, mass median aerodynamic diameter; m/s, meter per second; μ m μ m mum\mu \mathrm{m}, micrometer; L / min L / min L//min\mathrm{L} / \mathrm{min}, liter per minute.
缩写:pMDI,加压计量吸入器;HFA,氢氟烃;CFC,氯氟化碳;MMAD,质量中值空气动力学直径;m/s,米/秒; μ m μ m mum\mu \mathrm{m} ,微米; L / min L / min L//min\mathrm{L} / \mathrm{min} ,升/分钟。

performed inhalation correctly. 68 68 ^(68){ }^{68} For the main DPI devices, the published lung deposition rates from individual studies (without direct comparisons) are as follows: Accuhaler B 7.6 % , 70 B 7.6 % , 70 ^(B)7.6%,^(70){ }^{\mathbb{B}} 7.6 \%,{ }^{70} Aerolizer ® 13 % 20 % , 34 , 71 ® 13 % 20 % , 34 , 71 ^(®)quad13%-20%,^(34,71)quad{ }^{\circledR} \quad 13 \%-20 \%,{ }^{34,71} \quad Breezhaler B 26.8 % 39 % B 26.8 % 39 % ^(B)quad26.8%-39%^{\mathbb{B}} \quad 26.8 \%-39 \%, 24 , 29 24 , 29 ^(24,29){ }^{24,29} Easyhaler R 18.5 % 31 % , 71 , 72 R 18.5 % 31 % , 71 , 72 ^(R)18.5%-31%,^(71,72){ }^{\mathbb{R}} 18.5 \%-31 \%,{ }^{71,72} Genuair ® 30.1 % 51.1 % , 27 , 73 , 74 ®  30.1 % 51.1 % , 27 , 73 , 74 ^("® ")30.1%-51.1%,^(27,73,74)^{\text {® }} 30.1 \%-51.1 \%,{ }^{27,73,74} Handihaler R 9.8 % 46.7 % , 19 , 24 , 71 R 9.8 % 46.7 % , 19 , 24 , 71 ^(R)9.8%-46.7%,^(19,24,71){ }^{\mathbb{R}} 9.8 \%-46.7 \%,{ }^{19,24,71} Ingelheim inhaler ( 8 ) 16 % ( 8 ) 16 % ^((8))16%-{ }^{(8)} 16 \%- 59 % 75 59 % 75 59%^(75)59 \%{ }^{75} NEXThaler R 39.4 % 56 % , 11 , 76 R 39.4 % 56 % , 11 , 76 ^(R)39.4%-56%,^(11,76){ }^{\mathbb{R}} 39.4 \%-56 \%,{ }^{11,76} Spinhaler B 11.5 % , 75 B 11.5 % , 75 ^(B)11.5%,^(75)^{\mathbb{B}} 11.5 \%,{ }^{75} Turbuhaler ® 14.2 % 69.3 % , 21 , 42 , 77 79 ® 14.2 % 69.3 % , 21 , 42 , 77 79 ^(®)14.2%-69.3%,^(21,42,77-79){ }^{\circledR} 14.2 \%-69.3 \%,{ }^{21,42,77-79} and Twisthaler ® 36 % ® 36 % ^(®)36%-{ }^{\circledR} 36 \%- 37 % . 80 37 % . 80 37%.^(80)37 \% .{ }^{80} Similarly to all inhaler devices, other factors are probably influencing the lung deposition rate. 81 81 ^(81){ }^{81} Although some studies have compared lung deposition in pMDIs and DPIs, their results are contradictory. 19 , 33 19 , 33 ^(19,33){ }^{19,33}
正确进行吸入。 68 68 ^(68){ }^{68} 对于主要的干粉吸入器,个别研究(无直接比较)公布的肺沉积率如下:喷雾器 B 7.6 % , 70 B 7.6 % , 70 ^(B)7.6%,^(70){ }^{\mathbb{B}} 7.6 \%,{ }^{70} 喷雾器 ® 13 % 20 % , 34 , 71 ® 13 % 20 % , 34 , 71 ^(®)quad13%-20%,^(34,71)quad{ }^{\circledR} \quad 13 \%-20 \%,{ }^{34,71} \quad 微喷器 B 26.8 % 39 % B 26.8 % 39 % ^(B)quad26.8%-39%^{\mathbb{B}} \quad 26.8 \%-39 \% 24 , 29 24 , 29 ^(24,29){ }^{24,29} Easyhaler R 18.5 % 31 % , 71 , 72 R 18.5 % 31 % , 71 , 72 ^(R)18.5%-31%,^(71,72){ }^{\mathbb{R}} 18.5 \%-31 \%,{ }^{71,72} Genuair ® 30.1 % 51.1 % , 27 , 73 , 74 ®  30.1 % 51.1 % , 27 , 73 , 74 ^("® ")30.1%-51.1%,^(27,73,74)^{\text {® }} 30.1 \%-51.1 \%,{ }^{27,73,74} Handihaler R 9.8 % 46.7 % , 19 , 24 , 71 R 9.8 % 46.7 % , 19 , 24 , 71 ^(R)9.8%-46.7%,^(19,24,71){ }^{\mathbb{R}} 9.8 \%-46.7 \%,{ }^{19,24,71} Ingelheim 吸入器 ( 8 ) 16 % ( 8 ) 16 % ^((8))16%-{ }^{(8)} 16 \%- 59 % 75 59 % 75 59%^(75)59 \%{ }^{75} NEXThaler R 39.4 % 56 % , 11 , 76 R 39.4 % 56 % , 11 , 76 ^(R)39.4%-56%,^(11,76){ }^{\mathbb{R}} 39.4 \%-56 \%,{ }^{11,76} Spinhaler B 11.5 % , 75 B 11.5 % , 75 ^(B)11.5%,^(75)^{\mathbb{B}} 11.5 \%,{ }^{75} Turbuhaler ® 14.2 % 69.3 % , 21 , 42 , 77 79 ® 14.2 % 69.3 % , 21 , 42 , 77 79 ^(®)14.2%-69.3%,^(21,42,77-79){ }^{\circledR} 14.2 \%-69.3 \%,{ }^{21,42,77-79} 和 Twisthaler ® 36 % ® 36 % ^(®)36%-{ }^{\circledR} 36 \%- 37 % . 80 37 % . 80 37%.^(80)37 \% .{ }^{80} 与所有吸入器类似、其他因素也可能影响肺沉积率。 81 81 ^(81){ }^{81} 尽管一些研究对 pMDIs 和 DPIs 的肺沉积进行了比较,但其结果却相互矛盾。 19 , 33 19 , 33 ^(19,33){ }^{19,33}
Table 2 Main Characteristics of Dry Powder Inhalers
表 2 干粉吸入器的主要特点
Formulation 配方 Drug/Lactose Blend, Drug Alone, Drug/ Excipient Particles
药物/乳糖混合物,药物本身,药物/辅料颗粒
Metering system 计量系统 Capsules, blisters, multi-dose blister packs, reservoirs
胶囊、泡罩、多剂量泡罩包装、贮液器
Propellant 推进剂 No 没有
Dose counter 剂量计数器 Yes 
Priming 打底 Variable priming requirements
不同的启动要求
Temperature dependence 温度依赖性 Yes 
Humidity dependence 湿度依赖性 Yes 
Actuator orifice 致动器孔 Does not apply 不适用
Lung deposition 肺部沉积 20 % 20 % ∼20%\sim 20 \%
MMDA 1.8 μ m 4.8 μ m 1.8 μ m 4.8 μ m 1.8 mum-4.8 mum1.8 \mu \mathrm{~m}-4.8 \mu \mathrm{~m}
Aerosol exit velocity 气溶胶出口速度 Depends on inspiratory flow rate
取决于吸气流速
Lung distribution 肺部分布 Central and peripheral regions
中部和周边地区
Intrinsic resistance 内在阻力 Low/medium/high 低/中/高
Inspiratory flow rate 吸气流速 Minimum of 30 L / min 30 L / min 30L//min30 \mathrm{~L} / \mathrm{min} to > 100 L / min > 100 L / min > 100L//min>100 \mathrm{~L} / \mathrm{min}
最小值为 30 L / min 30 L / min 30L//min30 \mathrm{~L} / \mathrm{min} > 100 L / min > 100 L / min > 100L//min>100 \mathrm{~L} / \mathrm{min}
Advantages 优势 Compact and portable Some are multi-dose devices. Do not require coordination of inhalation with activation or hand strength
小巧便携 有些是多剂量装置。不需要协调吸入与启动或手部力量
Disadvantages 缺点

要求最低吸气流量 患有认知障碍或身体衰弱的患者可能无法产生足够高的吸气流量 大多数人对湿度敏感
Require a minimum inspiratory flow
Patients with cognitive or debilitating conditions might not generate sufficiently high inspiratory flows
Most are moisture-sensitive
Require a minimum inspiratory flow Patients with cognitive or debilitating conditions might not generate sufficiently high inspiratory flows Most are moisture-sensitive| Require a minimum inspiratory flow | | :--- | | Patients with cognitive or debilitating conditions might not generate sufficiently high inspiratory flows | | Most are moisture-sensitive |
Formulation Drug/Lactose Blend, Drug Alone, Drug/ Excipient Particles Metering system Capsules, blisters, multi-dose blister packs, reservoirs Propellant No Dose counter Yes Priming Variable priming requirements Temperature dependence Yes Humidity dependence Yes Actuator orifice Does not apply Lung deposition ∼20% MMDA 1.8 mum-4.8 mum Aerosol exit velocity Depends on inspiratory flow rate Lung distribution Central and peripheral regions Intrinsic resistance Low/medium/high Inspiratory flow rate Minimum of 30L//min to > 100L//min Advantages Compact and portable Some are multi-dose devices. Do not require coordination of inhalation with activation or hand strength Disadvantages "Require a minimum inspiratory flow Patients with cognitive or debilitating conditions might not generate sufficiently high inspiratory flows Most are moisture-sensitive"| Formulation | Drug/Lactose Blend, Drug Alone, Drug/ Excipient Particles | | :---: | :---: | | Metering system | Capsules, blisters, multi-dose blister packs, reservoirs | | Propellant | No | | Dose counter | Yes | | Priming | Variable priming requirements | | Temperature dependence | Yes | | Humidity dependence | Yes | | Actuator orifice | Does not apply | | Lung deposition | $\sim 20 \%$ | | MMDA | $1.8 \mu \mathrm{~m}-4.8 \mu \mathrm{~m}$ | | Aerosol exit velocity | Depends on inspiratory flow rate | | Lung distribution | Central and peripheral regions | | Intrinsic resistance | Low/medium/high | | Inspiratory flow rate | Minimum of $30 \mathrm{~L} / \mathrm{min}$ to $>100 \mathrm{~L} / \mathrm{min}$ | | Advantages | Compact and portable Some are multi-dose devices. Do not require coordination of inhalation with activation or hand strength | | Disadvantages | Require a minimum inspiratory flow <br> Patients with cognitive or debilitating conditions might not generate sufficiently high inspiratory flows <br> Most are moisture-sensitive |
Abbreviations: DPI, dry powder inhaler; MMAD, mass median aerodynamic diameter; m/s, meter per second; μ m μ m mum\mu \mathrm{m}, micrometer; L/min, liter per minute.
缩写:DPI,干粉吸入器;MMAD,质量中值空气动力学直径;m/s,米/秒; μ m μ m mum\mu \mathrm{m} ,微米;L/min,升/分钟。
Respimat ( ® ) ( ® ) ^((®))^{(®)} (SMI) has largely exhibited high lung deposition rates that range from 39.2 % 39.2 % 39.2%39.2 \% to 67 % , 27 , 38 , 48 , 49 , 74 , 82 84 67 % , 27 , 38 , 48 , 49 , 74 , 82 84 67%,^(27,38,48,49,74,82-84)67 \%,{ }^{27,38,48,49,74,82-84} with different inspiratory flow rates (high and low) and irrespective of humidity. 85 85 ^(85){ }^{85} Compared with other devices, SMI showed higher lung deposition than pMDIs (including those with a chamber or spacer) or DPIs. 27 , 48 , 74 , 83 , 86 27 , 48 , 74 , 83 , 86 ^(27,48,74,83,86){ }^{27,48,74,83,86}
Respimat ( ® ) ( ® ) ^((®))^{(®)} (SMI)在很大程度上表现出较高的肺沉积率,在不同吸气流速(高和低)和湿度条件下,肺沉积率从 39.2 % 39.2 % 39.2%39.2 \% 67 % , 27 , 38 , 48 , 49 , 74 , 82 84 67 % , 27 , 38 , 48 , 49 , 74 , 82 84 67%,^(27,38,48,49,74,82-84)67 \%,{ }^{27,38,48,49,74,82-84} 不等。 85 85 ^(85){ }^{85} 与其他设备相比,SMI 的肺沉积率高于 pMDIs(包括带有腔体或隔板的设备)或 DPIs。 27 , 48 , 74 , 83 , 86 27 , 48 , 74 , 83 , 86 ^(27,48,74,83,86){ }^{27,48,74,83,86}
We also evaluated the AEV. Inhalation devices with a high AEV might have a short spray duration and vice versa. With pMDIs, the aerosol exits through a nozzle at
我们还对 AEV 进行了评估。AEV 高的吸入装置可能喷雾持续时间短,反之亦然。使用 pMDIs 时,气溶胶从喷嘴喷出的速度为
Table 3 Main Characteristics of the Soft Mist Inhaler
表 3 软雾吸入器的主要特点
Formulation 配方 Aqueous Solution or Suspension
水溶液或悬浮液
Metering system 计量系统 Reservoirs 水库
Propellant 推进剂 No 没有
Dose counter 剂量计数器 Yes 
Priming 打底 Actuate the inhaler toward the ground until an aerosol cloud is visible and then to repeat the process three more times
将吸入器推向地面,直至看到气溶胶云,然后再重复该过程三次
Temperature dependence 温度依赖性 No 没有
Humidity dependence 湿度依赖性 No 没有
Actuator orifice 致动器孔 -
Lung deposition 肺部沉积 39.2 % 67 % 39.2 % 67 % 39.2%-67%39.2 \%-67 \%
MMDA 3.7 μ m 3.7 μ m ∼3.7 mum\sim 3.7 \mu \mathrm{~m}
Aerosol exit velocity 气溶胶出口速度 0.72 0.84 m / s 0.72 0.84 m / s 0.72-0.84m//s0.72-0.84 \mathrm{~m} / \mathrm{s}
Lung distribution 肺部分布 Central and peripheral regions
中部和周边地区
Intrinsic resistance 内在阻力 Low/none 低/无
Inspiratory flow rate 吸气流速 Independent 独立
Advantages 优势

便携、小巧。多剂量装置。 可重复使用。与干粉吸入器相比,只需较小剂量的复合支气管扩张剂,就能获得相同的疗效和安全性
Portable and compact. Multi-dose device.
Reusable. Compared with dry powder inhalers, a considerably smaller dose of a combination bronchodilator results in the same level of efficacy and safety
Portable and compact. Multi-dose device. Reusable. Compared with dry powder inhalers, a considerably smaller dose of a combination bronchodilator results in the same level of efficacy and safety| Portable and compact. Multi-dose device. | | :--- | | Reusable. Compared with dry powder inhalers, a considerably smaller dose of a combination bronchodilator results in the same level of efficacy and safety |
Disadvantages 缺点 Needs to be primed if not in use for over 21 days
如果超过 21 天未使用,则需要填料
Formulation Aqueous Solution or Suspension Metering system Reservoirs Propellant No Dose counter Yes Priming Actuate the inhaler toward the ground until an aerosol cloud is visible and then to repeat the process three more times Temperature dependence No Humidity dependence No Actuator orifice - Lung deposition 39.2%-67% MMDA ∼3.7 mum Aerosol exit velocity 0.72-0.84m//s Lung distribution Central and peripheral regions Intrinsic resistance Low/none Inspiratory flow rate Independent Advantages "Portable and compact. Multi-dose device. Reusable. Compared with dry powder inhalers, a considerably smaller dose of a combination bronchodilator results in the same level of efficacy and safety" Disadvantages Needs to be primed if not in use for over 21 days| Formulation | Aqueous Solution or Suspension | | :---: | :---: | | Metering system | Reservoirs | | Propellant | No | | Dose counter | Yes | | Priming | Actuate the inhaler toward the ground until an aerosol cloud is visible and then to repeat the process three more times | | Temperature dependence | No | | Humidity dependence | No | | Actuator orifice | - | | Lung deposition | $39.2 \%-67 \%$ | | MMDA | $\sim 3.7 \mu \mathrm{~m}$ | | Aerosol exit velocity | $0.72-0.84 \mathrm{~m} / \mathrm{s}$ | | Lung distribution | Central and peripheral regions | | Intrinsic resistance | Low/none | | Inspiratory flow rate | Independent | | Advantages | Portable and compact. Multi-dose device. <br> Reusable. Compared with dry powder inhalers, a considerably smaller dose of a combination bronchodilator results in the same level of efficacy and safety | | Disadvantages | Needs to be primed if not in use for over 21 days |
Abbreviations: SMI, soft mist inhaler; MMAD, mass median aerodynamic diameter; m/s, meter per second; μ m μ m mum\mu \mathrm{m}, micrometer; L/min, liter per minute.
缩写:SMI,软雾吸入器;MMAD,质量中值空气动力学直径;m/s,米/秒; μ m μ m mum\mu \mathrm{m} ,微米;L/min,升/分钟。

a very high rate of more than 3 m / s . 87 3 m / s . 87 3m//s.^(87)3 \mathrm{~m} / \mathrm{s} .{ }^{87} However, the AEV of the SMI is much slower, at 0.84 0.72 m / s 0.84 0.72 m / s 0.84-0.72m//s0.84-0.72 \mathrm{~m} / \mathrm{s}, and the aerosol cloud lasts longer. 88 90 88 90 ^(88-90){ }^{88-90}
然而,SMI 的 AEV 要慢得多,为 0.84 0.72 m / s 0.84 0.72 m / s 0.84-0.72m//s0.84-0.72 \mathrm{~m} / \mathrm{s} ,气溶胶云持续的时间也更长。 88 90 88 90 ^(88-90){ }^{88-90}
It has also been observed that the distribution of the deposition sites of inhaled particles is strongly dependent on their aerodynamic diameters. 69 69 ^(69){ }^{69} This SLR found that pMDIs generally produce at least medium-sized particles, with a significant rate of extrafine particles. The observed MMAD of conventional pMDIs varies from 1.22 to 8 μ m , 35 , 91 , 92 μ m , 35 , 91 , 92 mum,^(35,91,92)\mu \mathrm{m},{ }^{35,91,92} from 1.19 to 3.57 μ m 3.57 μ m 3.57 mum3.57 \mu \mathrm{~m} when a valved holding chamber or spacer is used, 31 , 35 , 93 31 , 35 , 93 ^(31,35,93){ }^{31,35,93} and from 0.72 to 2.0 μ m 2.0 μ m 2.0 mum2.0 \mu \mathrm{~m} with Modulite ® . 65 , 66 ® . 65 , 66 ^(®).^(65,66){ }^{\circledR} .{ }^{65,66} Regarding particle size data for DPIs, depending on the device and drug, MMDAs vary from 1.40 to 4.8 μ m . 11 , 19 , 21 , 24 , 27 29 , 36 , 37 , 74 , 76 4.8 μ m . 11 , 19 , 21 , 24 , 27 29 , 36 , 37 , 74 , 76 4.8 mum.^(11,19,21,24,27-29,36,37,74,76)4.8 \mu \mathrm{~m} .^{11,19,21,24,27-29,36,37,74,76} Conversely, SMI
另据观察,吸入颗粒的沉积点分布在很大程度上取决于其空气动力学直径。 69 69 ^(69){ }^{69} 该 SLR 发现,pMDIs 通常至少会产生中等大小的微粒,并产生大量超细微粒。传统 pMDIs 观察到的 MMAD 从 1.22 到 8 μ m , 35 , 91 , 92 μ m , 35 , 91 , 92 mum,^(35,91,92)\mu \mathrm{m},{ }^{35,91,92} 3.57 μ m 3.57 μ m 3.57 mum3.57 \mu \mathrm{~m} 31 , 35 , 93 31 , 35 , 93 ^(31,35,93){ }^{31,35,93} 不等,使用 Modulite 时从 0.72 到 2.0 μ m 2.0 μ m 2.0 mum2.0 \mu \mathrm{~m} ® . 65 , 66 ® . 65 , 66 ^(®).^(65,66){ }^{\circledR} .{ }^{65,66} 关于 DPIs 的粒度数据,根据设备和药物的不同,MMDA 从 1.40 到 4.8 μ m . 11 , 19 , 21 , 24 , 27 29 , 36 , 37 , 74 , 76 4.8 μ m . 11 , 19 , 21 , 24 , 27 29 , 36 , 37 , 74 , 76 4.8 mum.^(11,19,21,24,27-29,36,37,74,76)4.8 \mu \mathrm{~m} .^{11,19,21,24,27-29,36,37,74,76} 不等。
Table 4 Main Factors Associated to Inspiratory Flow Rate
表 4 与吸气流速有关的主要因素

与患者有关 吸气能力 吸气力度 并发症 吸入技术
Patient-related
Inspiratory capacity
Inspiratory effort
Comorbidities
Inhalation technique
Patient-related Inspiratory capacity Inspiratory effort Comorbidities Inhalation technique| Patient-related | | :--- | | Inspiratory capacity | | Inspiratory effort | | Comorbidities | | Inhalation technique |
COPD-related 慢性阻塞性肺病相关
Severity 严重性
Hyperinflation 恶性通货膨胀
Exacerbations 病情恶化
Respiratory muscle alterations
呼吸肌改变
Inhalation device-related
与吸入装置有关
Internal resistance 内部电阻
Disaggregation of the powdered drug dose (DPIs)
粉末状药物剂量的分解(干粉吸入器)
"Patient-related Inspiratory capacity Inspiratory effort Comorbidities Inhalation technique" COPD-related Severity Hyperinflation Exacerbations Respiratory muscle alterations Inhalation device-related Internal resistance Disaggregation of the powdered drug dose (DPIs)| Patient-related <br> Inspiratory capacity <br> Inspiratory effort <br> Comorbidities <br> Inhalation technique | | :--- | | COPD-related | | Severity | | Hyperinflation | | Exacerbations | | Respiratory muscle alterations | | Inhalation device-related | | Internal resistance | | Disaggregation of the powdered drug dose (DPIs) |
Abbreviations: COPD, chronic obstructive pulmonary disease; DPIs, dry powder inhalers.
缩写:缩写:COPD,慢性阻塞性肺病;DPIs,干粉吸入器。

generates a cloud that contains an aerosol with a fine particle fraction of around 3.7 μ m . 74 3.7 μ m . 74 3.7 mum.^(74)3.7 \mu \mathrm{~m} .{ }^{74} It is estimated that 60 % 60 % 60%60 \% of the particles reach a MMAD < 5 μ m < 5 μ m < 5mum<5 \mu \mathrm{~m} with SMI. 85 85 ^(85){ }^{85} The reported rate with pMDIs and DPIs (indirect comparison) is not that high. 27 , 28 , 74 , 94 27 , 28 , 74 , 94 ^(27,28,74,94){ }^{27,28,74,94}
据估计, 60 % 60 % 60%60 \% 的颗粒会到达使用 SMI 的 MMAD < 5 μ m < 5 μ m < 5mum<5 \mu \mathrm{~m} 85 85 ^(85){ }^{85} 报告的 pMDIs 和 DPIs 的比率(间接比较)并不高。 27 , 28 , 74 , 94 27 , 28 , 74 , 94 ^(27,28,74,94){ }^{27,28,74,94}
Another relevant outcome when using inhalation devices is the lung distribution pattern (through the central and peripheral regions). All inhalation devices have been shown to reach both central and peripheral areas. SMI data suggest that lung distribution pattern might be better than pMDIs, with a higher distribution in bronchial trees and peripheral regions. 11 , 28 , 49 , 60 , 65 , 66 , 73 , 74 , 82 , 95 , 96 11 , 28 , 49 , 60 , 65 , 66 , 73 , 74 , 82 , 95 , 96 ^(11,28,49,60,65,66,73,74,82,95,96){ }^{11,28,49,60,65,66,73,74,82,95,96} More specifically, a comparative study found mean peripheral, intermediate and central lung deposition, and peripheral zone/ central zone ratio of 5.0 % 9.4 % , 4.8 % 11.3 % , 4.5 % 5.0 % 9.4 % , 4.8 % 11.3 % , 4.5 % 5.0%-9.4%,4.8%-11.3%,4.5%-5.0 \%-9.4 \%, 4.8 \%-11.3 \%, 4.5 \%- 10.4 % , 1.01 1.16 10.4 % , 1.01 1.16 10.4%,1.01-1.1610.4 \%, 1.01-1.16 with Respimat ( R ) ( R ) ^((R)){ }^{(R)} vs 3.8 % , 4.9 % , 5.6 % 3.8 % , 4.9 % , 5.6 % 3.8%,4.9%,5.6%3.8 \%, 4.9 \%, 5.6 \%, 1.36 with pMDIs, respectively. 49 49 ^(49){ }^{49} Comparative data between pMDIs and DPIs are conflicting. 33 , 46 33 , 46 ^(33,46){ }^{33,46}
使用吸入装置的另一个相关结果是肺部分布模式(通过中心和外围区域)。所有吸入装置都已证明可到达中心和外周区域。SMI 数据表明,肺部分布模式可能优于 pMDIs,在支气管树和外周区域的分布较多。 11 , 28 , 49 , 60 , 65 , 66 , 73 , 74 , 82 , 95 , 96 11 , 28 , 49 , 60 , 65 , 66 , 73 , 74 , 82 , 95 , 96 ^(11,28,49,60,65,66,73,74,82,95,96){ }^{11,28,49,60,65,66,73,74,82,95,96} 更具体地说,一项比较研究发现,Respimat ( R ) ( R ) ^((R)){ }^{(R)} 与 pMDIs 的 3.8 % , 4.9 % , 5.6 % 3.8 % , 4.9 % , 5.6 % 3.8%,4.9%,5.6%3.8 \%, 4.9 \%, 5.6 \% 5.0 % 9.4 % , 4.8 % 11.3 % , 4.5 % 5.0 % 9.4 % , 4.8 % 11.3 % , 4.5 % 5.0%-9.4%,4.8%-11.3%,4.5%-5.0 \%-9.4 \%, 4.8 \%-11.3 \%, 4.5 \%- 10.4 % , 1.01 1.16 10.4 % , 1.01 1.16 10.4%,1.01-1.1610.4 \%, 1.01-1.16 的平均外周、中间和中心肺沉积以及外周区/中心区比率分别为 5.0 % 9.4 % , 4.8 % 11.3 % , 4.5 % 5.0 % 9.4 % , 4.8 % 11.3 % , 4.5 % 5.0%-9.4%,4.8%-11.3%,4.5%-5.0 \%-9.4 \%, 4.8 \%-11.3 \%, 4.5 \%- 10.4 % , 1.01 1.16 10.4 % , 1.01 1.16 10.4%,1.01-1.1610.4 \%, 1.01-1.16 3.8 % , 4.9 % , 5.6 % 3.8 % , 4.9 % , 5.6 % 3.8%,4.9%,5.6%3.8 \%, 4.9 \%, 5.6 \% 和 1.36。 49 49 ^(49){ }^{49} pMDIs 和 DPIs 之间的比较数据相互矛盾。 33 , 46 33 , 46 ^(33,46){ }^{33,46}

Inspiratory Flow Rate 吸气流速

The other main focus of this project was the inspiratory flow rate. First, it is important to consider the factors associated with inspiratory flow rate (Table 4). Similar to lung deposition, some of these factors relate to the patient’s and COPD’s characteristics, while other factors relate to the inhaler device, such as the intrinsic resistance. 6 , 10 , 13 17 , 43 , 45 , 97 , 98 6 , 10 , 13 17 , 43 , 45 , 97 , 98 ^(6,10,13-17,43,45,97,98){ }^{6,10,13-17,43,45,97,98}
本项目的另一个重点是吸气流速。首先,必须考虑与吸气流速相关的因素(表 4)。与肺沉积类似,其中一些因素与患者和慢性阻塞性肺病的特征有关,而其他因素则与吸入器装置有关,例如内在阻力。 6 , 10 , 13 17 , 43 , 45 , 97 , 98 6 , 10 , 13 17 , 43 , 45 , 97 , 98 ^(6,10,13-17,43,45,97,98){ }^{6,10,13-17,43,45,97,98}
Overall, two main driving forces can affect the performance of DPIs: the inspiratory flow generated by the patient and the turbulence produced inside the device, the latter of which solely depends on the original technical
总之,有两种主要驱动力会影响干粉吸入器的性能:患者产生的吸气流量和设备内部产生的湍流,后者完全取决于原始技术。
Table 5 General Conclusions Regarding Lung Deposition and Inspiratory Flow Rate in Chronic Obstructive Pulmonary Disease
表 5 有关慢性阻塞性肺病肺沉积和吸气流速的一般结论
# Conclusion 结论
I The lung deposition profile and required inspiratory flow rate are key factors to be considered when selecting an inhalation device
在选择吸入装置时,肺沉积情况和所需的吸气流速是需要考虑的关键因素
2 COPD is a progressive disease with specific pathophysiological features that impact patients' lung deposition and inspiratory flow rate
慢性阻塞性肺病是一种进展性疾病,具有特定的病理生理特征,会影响患者的肺部沉积和吸气流速
3 In COPD patients, obstruction severity and especially hyperinflation are decisive pathophysiological factors
在慢性阻塞性肺病患者中,阻塞严重程度,尤其是过度充气是决定性的病理生理因素
4 During the course of COPD, some situations, notably exacerbations, impact the inspiratory flow rate
在慢性阻塞性肺病的治疗过程中,某些情况(尤其是病情加重)会影响吸气流速
5 An homogeneous drug distribution through the airways is essential, not only because of the COPD pathophysiology but also because of the different distribution of cholinergic and β 2 β 2 beta2\beta 2 receptors
由于慢性阻塞性肺病的病理生理学原因,以及胆碱能受体和 β 2 β 2 beta2\beta 2 受体的不同分布,在气道中均匀分布药物至关重要。
6 COPD treatment requires inhalation devices capable of delivering particles with a MMAD comprised between 0.5 and 5 μ m μ m mum\mu \mathrm{m} to achieve high lung deposition
慢性阻塞性肺病的治疗要求吸入设备能够输送 MMAD 在 0.5 到 5 μ m μ m mum\mu \mathrm{m} 之间的微粒,以实现高肺部沉积。
7 The patients' ability to perform a correct inhalation maneuver (inspiratory effort, coordination, etc.) is decisive to achieve an adequate inspiratory flow rate and lung deposition
患者做出正确吸气动作的能力(吸气力度、协调性等)对获得足够的吸气流速和肺部沉积起着决定性作用。
8 Inhalation maneuvers that are similar to physiological/standard inspiratory flow are more likely associated with reduced oropharyngeal deposition and therefore increased lung deposition
与生理/标准吸气流量相似的吸气动作更有可能导致口咽沉积减少,从而增加肺部沉积
9 Inhalation devices present different characteristics that define the required inspiratory flow rate and influence lung deposition
吸入装置具有不同的特性,这些特性决定了所需的吸气流速,并影响肺部沉积物
10 The inspiratory flow rate required for drug dispersion with a given DPI is inversely proportional to the intrinsic resistance of the DPI
使用特定干粉吸入器分散药物所需的吸气流速与干粉吸入器的固有阻力成反比
II The faster the exit speed of the drug delivered from the device (initial acceleration of the inhalation maneuver by the patient or directly by the device), the greater the risk of oropharyngeal deposition and the lesser the lung deposition
从设备输送的药物出口速度越快(患者或设备直接对吸入动作进行初始加速),口咽部沉积的风险就越大,肺部沉积的风险就越小
12 The SMI requires a low inspiratory flow rate. Therefore, compared with other inhaler devices, when performing a correct maneuver, oropharyngeal deposition is lower and lung deposition is higher
SMI 要求的吸气流速较低。因此,与其他吸入器装置相比,在进行正确操作时,口咽部沉积物较少,而肺部沉积物较多
# Conclusion I The lung deposition profile and required inspiratory flow rate are key factors to be considered when selecting an inhalation device 2 COPD is a progressive disease with specific pathophysiological features that impact patients' lung deposition and inspiratory flow rate 3 In COPD patients, obstruction severity and especially hyperinflation are decisive pathophysiological factors 4 During the course of COPD, some situations, notably exacerbations, impact the inspiratory flow rate 5 An homogeneous drug distribution through the airways is essential, not only because of the COPD pathophysiology but also because of the different distribution of cholinergic and beta2 receptors 6 COPD treatment requires inhalation devices capable of delivering particles with a MMAD comprised between 0.5 and 5 mum to achieve high lung deposition 7 The patients' ability to perform a correct inhalation maneuver (inspiratory effort, coordination, etc.) is decisive to achieve an adequate inspiratory flow rate and lung deposition 8 Inhalation maneuvers that are similar to physiological/standard inspiratory flow are more likely associated with reduced oropharyngeal deposition and therefore increased lung deposition 9 Inhalation devices present different characteristics that define the required inspiratory flow rate and influence lung deposition 10 The inspiratory flow rate required for drug dispersion with a given DPI is inversely proportional to the intrinsic resistance of the DPI II The faster the exit speed of the drug delivered from the device (initial acceleration of the inhalation maneuver by the patient or directly by the device), the greater the risk of oropharyngeal deposition and the lesser the lung deposition 12 The SMI requires a low inspiratory flow rate. Therefore, compared with other inhaler devices, when performing a correct maneuver, oropharyngeal deposition is lower and lung deposition is higher| # | Conclusion | | :---: | :---: | | I | The lung deposition profile and required inspiratory flow rate are key factors to be considered when selecting an inhalation device | | 2 | COPD is a progressive disease with specific pathophysiological features that impact patients' lung deposition and inspiratory flow rate | | 3 | In COPD patients, obstruction severity and especially hyperinflation are decisive pathophysiological factors | | 4 | During the course of COPD, some situations, notably exacerbations, impact the inspiratory flow rate | | 5 | An homogeneous drug distribution through the airways is essential, not only because of the COPD pathophysiology but also because of the different distribution of cholinergic and $\beta 2$ receptors | | 6 | COPD treatment requires inhalation devices capable of delivering particles with a MMAD comprised between 0.5 and 5 $\mu \mathrm{m}$ to achieve high lung deposition | | 7 | The patients' ability to perform a correct inhalation maneuver (inspiratory effort, coordination, etc.) is decisive to achieve an adequate inspiratory flow rate and lung deposition | | 8 | Inhalation maneuvers that are similar to physiological/standard inspiratory flow are more likely associated with reduced oropharyngeal deposition and therefore increased lung deposition | | 9 | Inhalation devices present different characteristics that define the required inspiratory flow rate and influence lung deposition | | 10 | The inspiratory flow rate required for drug dispersion with a given DPI is inversely proportional to the intrinsic resistance of the DPI | | II | The faster the exit speed of the drug delivered from the device (initial acceleration of the inhalation maneuver by the patient or directly by the device), the greater the risk of oropharyngeal deposition and the lesser the lung deposition | | 12 | The SMI requires a low inspiratory flow rate. Therefore, compared with other inhaler devices, when performing a correct maneuver, oropharyngeal deposition is lower and lung deposition is higher |
Abbreviations: COPD, chronic obstructive pulmonary disease; MMAD, mass median aerodynamic diameter; μ m μ m mum\mu \mathrm{m}, micrometer; DPI, dry powder inhaler; SMI, soft mist inhaler.
缩写:缩写: COPD,慢性阻塞性肺病;MMAD,质量中值空气动力学直径; μ m μ m mum\mu \mathrm{m} ,微米;DPI,干粉吸入器;SMI,软雾吸入器。

also taking into account all the factors and bases that determine the effectiveness of the inhaled route of administration.
还要考虑到决定吸入给药途径有效性的所有因素和依据。
Table 6 Experts’ Recommendations for the Selection of the Appropriate Inhalation Device in Chronic Obstructive Pulmonary Disease
表 6 专家对慢性阻塞性肺病患者选择适当吸入装置的建议
# # #\# It is Strongly Recommended to ...
强烈建议...
I

在选择吸入装置时,考虑慢性阻塞性肺疾病的病理生理学方面以及患者的临床状况和疾病严重程度/发展情况
Consider COPD pathophysiological aspects as well as patients'
clinical status and disease severity/evolution when selecting an
inhalation device
Consider COPD pathophysiological aspects as well as patients' clinical status and disease severity/evolution when selecting an inhalation device| Consider COPD pathophysiological aspects as well as patients' | | :--- | | clinical status and disease severity/evolution when selecting an | | inhalation device |
2

考虑到每种吸入装置的具体特点
Take into account the specific characteristics of each inhalation
device
Take into account the specific characteristics of each inhalation device| Take into account the specific characteristics of each inhalation | | :--- | | device |
3

评估患者进行正确吸入操作的能力以及每种吸入装置的具体要求
Assess patients' ability to perform a correct inhalation
maneuver and the specific requirements for each inhalation
device
Assess patients' ability to perform a correct inhalation maneuver and the specific requirements for each inhalation device| Assess patients' ability to perform a correct inhalation | | :--- | | maneuver and the specific requirements for each inhalation | | device |
4

在选择吸入装置前评估患者的吸气流速或吸气容量
Evaluate patients' inspiratory flow rate or inspiratory capacity
before selecting an inhalation device
Evaluate patients' inspiratory flow rate or inspiratory capacity before selecting an inhalation device| Evaluate patients' inspiratory flow rate or inspiratory capacity | | :--- | | before selecting an inhalation device |
5

考虑患者的病情加重史或其他可能影响其充分吸入能力的事件
Take into account patients' history of exacerbations or other
events that may affect their ability to perform adequate
inhalation
Take into account patients' history of exacerbations or other events that may affect their ability to perform adequate inhalation| Take into account patients' history of exacerbations or other | | :--- | | events that may affect their ability to perform adequate | | inhalation |
6

定期检查患者的吸入操作,并检查吸入装置是否满足他们的需求
Regularly review patients' inhalation maneuver and check
whether the inhalation device meets their needs
Regularly review patients' inhalation maneuver and check whether the inhalation device meets their needs| Regularly review patients' inhalation maneuver and check | | :--- | | whether the inhalation device meets their needs |
7

对吸气能力下降的患者使用主动吸入装置,如 pMDI 或 SMI
Use an active inhalation device, such as pMDI or SMI, in patients
with reduced inspiratory capacity
Use an active inhalation device, such as pMDI or SMI, in patients with reduced inspiratory capacity| Use an active inhalation device, such as pMDI or SMI, in patients | | :--- | | with reduced inspiratory capacity |
8

对于有吸气和/或协调困难的脆弱患者,考虑使用带阀保持腔和 SMI 或 pMDI 设备
Consider using a valved holding chamber with SMI or pMDI
devices in fragile patients with inspiratory and/or coordination
difficulties
Consider using a valved holding chamber with SMI or pMDI devices in fragile patients with inspiratory and/or coordination difficulties| Consider using a valved holding chamber with SMI or pMDI | | :--- | | devices in fragile patients with inspiratory and/or coordination | | difficulties |
9

使用能产生低口咽沉积和高肺沉积的吸入装置
Use inhalation devices that generate a low oropharyngeal and
high lung deposition
Use inhalation devices that generate a low oropharyngeal and high lung deposition| Use inhalation devices that generate a low oropharyngeal and | | :--- | | high lung deposition |
10

在每次就诊时检查患者的吸入操作,必要时纠正错误甚至更换吸入器
Check patients' inhalation maneuver during every visit and,
where necessary, resolve errors or even change the inhaler
Check patients' inhalation maneuver during every visit and, where necessary, resolve errors or even change the inhaler| Check patients' inhalation maneuver during every visit and, | | :--- | | where necessary, resolve errors or even change the inhaler |
# It is Strongly Recommended to ... I "Consider COPD pathophysiological aspects as well as patients' clinical status and disease severity/evolution when selecting an inhalation device" 2 "Take into account the specific characteristics of each inhalation device" 3 "Assess patients' ability to perform a correct inhalation maneuver and the specific requirements for each inhalation device" 4 "Evaluate patients' inspiratory flow rate or inspiratory capacity before selecting an inhalation device" 5 "Take into account patients' history of exacerbations or other events that may affect their ability to perform adequate inhalation" 6 "Regularly review patients' inhalation maneuver and check whether the inhalation device meets their needs" 7 "Use an active inhalation device, such as pMDI or SMI, in patients with reduced inspiratory capacity" 8 "Consider using a valved holding chamber with SMI or pMDI devices in fragile patients with inspiratory and/or coordination difficulties" 9 "Use inhalation devices that generate a low oropharyngeal and high lung deposition" 10 "Check patients' inhalation maneuver during every visit and, where necessary, resolve errors or even change the inhaler"| $\#$ | It is Strongly Recommended to ... | | :--- | :--- | | I | Consider COPD pathophysiological aspects as well as patients' <br> clinical status and disease severity/evolution when selecting an <br> inhalation device | | 2 | Take into account the specific characteristics of each inhalation <br> device | | 3 | Assess patients' ability to perform a correct inhalation <br> maneuver and the specific requirements for each inhalation <br> device | | 4 | Evaluate patients' inspiratory flow rate or inspiratory capacity <br> before selecting an inhalation device | | 5 | Take into account patients' history of exacerbations or other <br> events that may affect their ability to perform adequate <br> inhalation | | 6 | Regularly review patients' inhalation maneuver and check <br> whether the inhalation device meets their needs | | 7 | Use an active inhalation device, such as pMDI or SMI, in patients <br> with reduced inspiratory capacity | | 8 | Consider using a valved holding chamber with SMI or pMDI <br> devices in fragile patients with inspiratory and/or coordination <br> difficulties | | 9 | Use inhalation devices that generate a low oropharyngeal and <br> high lung deposition | | 10 | Check patients' inhalation maneuver during every visit and, <br> where necessary, resolve errors or even change the inhaler |
Abbreviations: COPD, chronic obstructive pulmonary disease; pMDI, pressurized metered-dose inhaler; SMI, soft mist inhaler.
缩写:缩写: COPD,慢性阻塞性肺病;pMDI,加压计量吸入器;SMI,软雾吸入器。
The delivery of drugs by inhalation is an integral component in the treatment of COPD. A growing number of inhalation devices, whose designs and characteristics vary, have been engineered in recent years to treat COPD and other respiratory diseases. 111 111 ^(111){ }^{111} Therefore, selecting the most appropriate device that meets each individual patient’s needs is vital in clinical practice. Several factors have been proposed that should be considered when choosing an inhalation device. These include the patient’s lung function, device handling, inhalation technique, and preferences. 8 8 ^(8){ }^{8} However, according to a published expert opinion, the two most important characteristics for an inhaler used by patients with COPD are that the device permits a high pulmonary deposition of the drug and allows its delivery at low inspiratory flows. 9 9 ^(9){ }^{9}
吸入给药是治疗慢性阻塞性肺病不可或缺的组成部分。近年来,用于治疗慢性阻塞性肺病和其他呼吸系统疾病的吸入装置越来越多,其设计和特性也各不相同。 111 111 ^(111){ }^{111} 因此,在临床实践中,选择最合适的设备以满足每个患者的需求至关重要。已经提出了在选择吸入装置时应考虑的几个因素。这些因素包括患者的肺功能、装置操作、吸入技术和偏好。 8 8 ^(8){ }^{8} 然而,根据已发表的专家意见,慢性阻塞性肺病患者使用的吸入器有两个最重要的特征,即吸入器允许药物在肺部高度沉积,并允许在低吸气流量下给药。 9 9 ^(9){ }^{9}