A Practical Guide on the Use of Inhaler Devices for Asthma ...

8 Supplement to Journal of The Association of Physicians of India ■ Published on 1st of Every Month 1st March, 2021

A Practical Guide on the Use of Inhaler Devices for Asthma and COPDSundeep Salvi1, Madhuragauri Shevade2, Ashutosh Aggarwal3, Komalkirti Apte4, Monica Barne5, Murali BV Mohan6, Aloke Gopal Ghoshal7, Vijay Hadda8, Vikram Jaggi9, Surinder Kumar Jindal10, Indu Khosla11, Sneha Limaye12, Rajiv Paliwal13, Sujeet Rajan14, Subhasis Roy15, Bhanu Pratap Singh16, Virendra Singh17, Balamugesh Thangakunam18, Prasanna Kumar Thomas19, Pradyut Waghray20, Randeep Guleria21

AbstractInhalation therapy is the most important route of administering drugs for the treatment of asthma and chronic obstructive pulmonary disease (COPD) because of its quick onset of action, greatly enhanced safety profile and better efficacy than the oral route. Yet, most patients of asthma and COPD continue to be put on oral medications that have poor therapeutic efficacy and greater side effects. The majority of asthma and COPD patients still continue to be prescribed oral medications. This has contributed to increased suffering and deaths associated with asthma and COPD in India.

Although many physicians believe that they themselves know how to use inhaler devices correctly, the majority of them do not know the correct usage steps. In this special supplement, we describe the various types of inhaler devices available for the treatment of asthma and COPD, their advantages and disadvantages, and the steps for using them correctly. We hope that this supplement on inhaler devices will help physicians understand the importance of inhalation therapy, the various types of inhaler devices available, and guide them in prescribing the right inhaler device for their patients. Every patient of asthma and COPD must receive inhaled medications for their treatment and care must be taken to ensure good adherence and compliance.

1Director, Pulmocare Research and Education Foundation, Pune, Maharashtra; 2Respiratory Therapist Chest Research Foundation, Pune, Maharashtra; 3Professor and Head, Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh; 4Managing Partner, Excellentia Consulting Services, Pune, Maharashtra; 5Director and Head – Training Programmes, Pulmocare Research and Education Foundation, Pune, Maharashtra; 6Senior Consultant, Narayana Hrudayalaya – Mazumdar Shaw Medical Center, Bengaluru, Karnataka; 7Medical Director, National Allergy Asthma Bronchitis Institute, Kolkata, West Bengal; 8Associate Professor, All India Institute of Medical Sciences, New Delhi; 9Medical Director, Asthma Chest Allergy Centres, Delhi; 10Medical Director, Jindal Clinics, Chandigarh; 11Director, Consultant Paediatrician, Dr Indu’s New Born and Child Care Center, Mumbai, Maharashtra; 12Director, Dataction Analytics Pvt Ltd., Pune, Maharashtra; 13Professor and Head, Department of Pulmonary Medicine, Pramukh Swami Medical College, Anand, Gujarat; 14Consultant Respiratory Physician, Bombay Hospital Institute of Medical Sciences, Mumbai, Maharashtra; 15Consultant Paediatrician, Columbia Asia Hospital, Kolkata, West Bengal; 16Director and Founder, Midland Healthcare and Research Center, Lucknow, Uttar Pradesh; 17Director, Asthma Bhawan, Jaipur, Rajasthan; 18Professor, Dept. of Respiratory Medicine, Christian Medical College, Vellore, Tamil Nadu; 19Consultant Physician and Chest Specialist, Jeevanandam Clinic, Chennai, Tamil Nadu; 20Professor and Head, Department of Pulmonary Medicine, SVS Medical College, Telangana; 21Director, All India Institute of Medical Sciences, New Delhi

Introduction

Inhalation therapy is the delivery of aerosolised medications directly

into the lungs. It is the most favoured route of administration of drugs in the management of obstructive airway diseases (OADs) such as asthma and chronic obstructive pulmonary disease (COPD) as it offers faster speed of action, combined with greater safety and efficacy. Inhaled drugs are localised to the target organ, which generally allows for a lower dose than is necessary with systemic delivery and, thus, fewer and less severe adverse effects. This is a distinct advantage, especially when administering corticosteroids to reduce airway inflammation in asthma. Because the drug is directly delivered to the site of action, its effect starts within seconds to minutes. Patients of all age groups, including children and the elderly, suffering from OADs should be offered inhalation therapy. Different types of inhaler devices are

available and recommended for specific groups of patients to aid drug delivery.1 The Global Ini t ia t ive for Asthma (GINA) and the Global In i t ia t ive for Chronic Obstructive Pulmonary Disease (GOLD) guidelines strongly recommend inhalation therapy for the management of asthma and COPD, respectively.1,2

Inhalation Therapy – A Historical Perspective79,80

As early as 2000 BC, people in southern India burnt the dried leaves of the Datura plant and inhaled

the smoke for relief from symptoms of cough and breathlessness. When the British colonised India, they found this to be an effective remedy for asthma and related symptoms. They improvised on this method and made cigarettes of dried Datura leaves that were popularly marketed and used as ‘asthma cigarettes’. Dry powder inhalers (DPIs) were developed only around the 1940s and were first used to deliver inhaled penicillin powder. In 1926, a Norwegian engineer designed a pressure valve to spray insecticides. Three decades later, the valve was improvised to create the Meshburg valve used in perfumes and hairsprays to deliver specific unit amounts of the ingredient. A 13-year-old American girl with asthma was instrumental in the development of the idea of a pressurised inhaler. Her father, who was a partner with 3M Laboratories, USA, built the first pressurised metered-dose inhaler (pMDI) device with the help of an old Coke bottle, freon from an old refrigerator and the Meshburg valve on the top (1956).

T h e I n d i a n g u i d e l i n e s a l s o discourage the use of oral therapy and strongly recommend the use of inhalation therapy for the management of OADs.3,4

Pharmacokinetics of Inhaled Drugs

A r o u n d 2 0 % o f t h e i n h a l e d medication is deposited in the lungs upon inhalation, thereby exerting the desired pharmacological effect.5 Part of the dose that reaches the airways is subsequently absorbed through the pulmonary vasculature from where it eventually ends in the systemic circulation. The remaining 80% of the drug that gets deposited in the oropharyngeal airways is swallowed

9Supplement to Journal of The Association of Physicians of India ■ Published on 1st of Every Month 1st March, 2021

and absorbed from the gastrointestinal t r a c t a n d u n d e r g o e s f i r s t - p a s s metabolism in the liver before entering the systemic circulation. The amount of drug in the systemic circulation is the sum of the fraction absorbed from the lungs and the gastrointestinal tract and, for all practical purposes, is much smaller than ingested oral drugs. At recommended doses, therefore, there are very little systemic effects of inhaled medications (Figure 1).6 Factors Affecting Drug Deposition

Several factors determine what proportion of the inhaled medication reaches the target site. Factors that affect drug deposition can be classified as device-, formulation- or patient-related.7 Device-related factors include the type of device and its usability, formulation-related factors include the nature and size of the drug particle, and patient-related factors include geometry of the airways, presence of disease, and the technique for using inhaler devices.7–12

Effect of Particle Size on Drug Deposition

The size of the inhaled drug particles has a major impact on drug deposition. Particles that are greater than 20 µm in diameter are very efficiently filtered by the nose. Particles in the size range of 10–20 µm are filtered and deposited in the upper respiratory tract. As shown in Figure 2, only particles in the size range of 0.5–5 µm have the ability to deposit in the airways. The smaller the

particle, the farther it is deposited and those less than 0.5 µm diffuse into the systemic circulation (Figure 2).8

Methods of Drug Deposition in the Airways

Through inhalation, drugs reach t h e a i r wa y s a s a r e s u l t o f t h r e e physical properties: inertial impaction, sedimentation, and diffusion. These are influenced by particle size. • Inertial Impaction: Particles that

are emitted from inhaler devices generally travel at a speed of around 30 m/s or 110 km/hr.13 Due to the momentum generated, large particles of around 20 µm in size do not follow the anatomical path of the airway and get deposited in the oropharyngeal region. Particles of around 10 µm in size get deposited in the larger airways of the lungs.13

• Sedimentation: Particles between 0 .5 µm and 5 µm in s ize are deposited in the lower airways due to gravitational force and if they remain in the airways for enough t ime to a l low sedimentat ion . Particles in the 2 µm to 5 µm size range are ideal to achieve the appropriate therapeutic effect.8,13

• Diffusion: Particles of <0.5 µm in size are in erratic motion due to the Brownian diffusion effect at the alveolar surface. These particles either diffuse across the alveolar membrane into the bloodstream or are expelled out at the end of expiration.13

Effect of the Geometry of the Airways and Disease on Drug Deposition

The pattern of drug deposit ion in the lungs also varies according to the geometry of the airways. Due to the curvature of the airways and the bifurcation of the bronchi, larger particles tend to remain in the upper airways while smaller particles drift with the airflow and deposit in the lower airways. In diseases such as asthma and COPD, there is inflammation and obstruction of the airways. This alters the flow of air and the amount of drug deposited in the airways is reduced. In severe disease, narrower airways and mucus plugging increases turbulence in the a irways and reduces drug deposition.14

TerminologiesAssociatedwithParticleSizein Inhalation TherapyIt is not easy to make all the drug particles in an inhaler of the same size; therefore, drug particles are hetero-dispersed, and lie within the size range of 0.5–5 µm. Mass medianaerodynamicdiameter(MMAD)is one of the most widely adopted metrics for particle-size distribution. Particle sizes that fit the definition of MMAD are those where half the quantity of aerosol particles is greater in size, and the other half is smaller than the median aerodynamic diameter (MAD). Fine-particledose(FPD) is the dose of the aerosol particles that are <5 µm in diameter. Fine-particle fraction (FPF) is the ratio of the FPD to the emitted dose.Small-sized (fine) particles (0.5–1.5 µm) have recently attracted much attention because of their ability to reach the smaller airways. Emerging evidence suggests that asthma and COPD patients with predominant small airways obstruction may benefit from fine and ultrafine drug particles. Studies comparing fine and ultrafine particles with currently available inhaled products are yet to confirm the superiority of one over the other.

Types of Inhaler Devices

There are different types of inhaler devices, but the most common ones are the pMDIs, breath-actuated inhalers (BAIs), unit- or multidose DPIs, and nebulisers. Each device has its own working principle and a distinct set of advantages, disadvantages and technique of use (Figure 3). Role of Devices in Drug Delivery and Deposition

• pMDIs (Pressurised Metered-DoseInhalers): These devices are designed to emit a fixed amount of drug with each actuation. The drug is either in a solution or suspension form along with a propel lant hydrof luoroalkane (HFA) and other excipients and is stored in the MDI canister under high pressure (about 300–500 kPa,

Fig. 1: Pharmacokinetics of inhaled drugs (image adapted from Reference 5)

Fig. 2: Particle size and drug deposition


or 3–5 atmosphere, or 2,250–3,750 mmHg).9 With each actuation, aerosol particles are released at a high velocity of >30 m/s. Particle size of the emitted drug is usually between 2 and 4 µm.13

The quantity of drug delivered per actuation can be expressed either as the amount delivered from the valve (ex-valve,orthemetereddose), or the amount delivered from the actuator (ex-actuatororthedelivereddose). In the Indian market, the dose mentioned on the inhalers is the ex-valve dose.

• BAIs(Breath-ActuatedInhalers): BAIs are pMDIs that have been d e v e l o p e d t o o v e r c o m e t h e coordination problems faced with a pMDI, where the inspiratory pressure generated by inhalation triggers the release of a unit dose of the drug.

During inhalation, the BAIs currently available automatically actuate at a flow of 23–35 L/min (https://www.ciplamed.com/content/ synchrobreathe-technical-dossier, Accessed 18 Jan 2021). Generally, the maximum drug deposition with a pMDI or DPI or BAI is only around 15–20%. However, this is enough to produce an optimum therapeutic response. More recently, inhaler devices have been developed that have a drug deposition of up to 50%, e.g. HFA-beclomethasone pMDI8 and, therefore, the dose needs to be reduced by half.

• DPIs (Dry Powder Inhalers) : These are devices that deliver the powdered form of a drug as an aerosol. The medication used in DPIs i s formulated with a micronised drug particle attached to an excipient, e.g. lactose or mannitol. The micronised drug particles, which typically ranges from 1 to 5 µm, are blended with a larger-size excipient molecule (40 µm) such as lactose.7 During inhalation, the inspiratory flow of 60 L/minute separates or de-agglomerates the drug particle from the lactose molecule into smaller sizes. The effort required

to generate the inspiratory flow varies for different DPI devices. It is important to inhale rapidly and deeply when using a DPI.

• Nebulisers 15 ,16: These devices are broadly divided into three types , namely, je t , u l trasonic and mesh-type nebulisers, which work on different principles to produce variable-sized aerosol particles. A flow rate of about 6–8 L/minute is utilised by the device to produce an aerosol comprising drug particles of 1–5 µm in size, of which around 10% reach the lungs. If the patient alters the breathing pattern to inhale deeply and holds the breath, the deposition increases to around 14–17%. Some of the newer nebulisers are more efficient in drug deposition.16 Nebuliser drugs are avai lable as l iquid formulations. These are easier to produce and can be mixed with other liquid formulations.

• Soft Mist Inhalers (Respimat*, Boehringer Ingelheim) 7: These are devices that produce a soft mist of aerosol (without the use of propellants) for the patient to inhale. They have the properties of both pMDIs and nebulisers w h e r e i n t h e l i q u i d d r u g i s delivered as in a pMDI but at a slower rate. Studies have shown that soft mist inhalers have a higher rate of deposition (about 35–50%) compared with pMDIs.17 These are not yet available in India.

The Importance of the Inhalation Technique13

Drug deposition varies with the technique followed when using the inhaler device and is the most critical factor determining drug deposition and, consequently, disease control

and clinical outcomes. Studies have demonstrated that incorrect inhaler technique can lead to increase in symptoms, hospitalisations, deaths and economic loss. Hence, it is important to perform every step of inhalation correctly.

pMDIs

In pMDIs, the drug is stored in an aluminium canister under pressure. On actuation, the canister emits a unit dose with the help of a valve mechanism.

The unit dose is aerosolised when the pressure in the canister is released and is made available for inhalation. pMDIs were first developed in 1956 by Riker Laboratories, USA, and have revolutionised inhalation therapy across the world. The first pMDIs contained the bronchodilator epinephrine to give relief from acute episodes of bronchoconstriction. Development of inhalation devices has kept pace with advances in drug development and, now, the most commonly used drugs for the treatment of airway diseases are available via pMDIs.

T h e d r u g s a r e m a i n t a i n e d i n solution or suspension formulations under pressure, in an aluminium canister, with a capacity of 10–20 ml.18 Most of the drug formulations are in the suspension format. Apart from the drug, the canister contains a propellant, which in most cases is a hydrofluoroalkane (HFA 227 or HFA 134a) in a liquid form, stored in the canister under high pressure of about 300–500 kPa (or 3–5 atmosphere or 2,250–3,750 mmHg).9 The earlier pMDIs contained a chlorofluorocarbon (CFC) as a propellant, but because they were more ozone-depleting, they were slowly phased out. With each actuation, the Meshberg valve in the canister releases aerosol particles at a high velocity of >30 m/s. Particle size of the emitted drug is usually between 2 and 4 µm. A single pMDI canister usually contains about 100–200 doses. This makes it cost-effective both for the manufacturer as well as the user.Key Components of a pMDI18

Metering Valve: I t is the most important component of the pMDI. The metering valve is designed such that each actuation releases the specified unit dose of the formulation. Container:9 The canister is made

of inert material such as aluminium,

Fig. 3: Different types of inhalers

TYPES OF INHALERS

Pressurized Metered-Dose

Inhalers

Standard Pressurized

Metered-Dose Inhalers

Breath-Actuated Pressurized

Metered-Dose Inhalers

Dry Powder Inhaler

Unit dose Multidose

Discreet

Reservoir

Nebuliser

Small-Volume Nebuliser

Jet

Ultrasonic

Vibrating Mesh

Large-Volume Nebuliser

Propellant-Free Liquid Inhaler

Soft Mist Inhaler


which is able to withstand the high pressure generated by the propellant and also prevents adhesion of drug particles and chemical degradation of the drug. Canisters come in different sizes. Propellant:9 Propellants are gases

that are liquefied when compressed under high pressure, but regain their gaseous form under a tmospher ic pressure. Thus, when released from the canister, they rapidly evaporate, generating an aerosol of the drug that is dissolved or suspended in them. All pMDIs now use HFA 227 or HFA 134a as propellants. These have replaced the CFCs used earlier, which were banned due to their ozone-depleting effect. The HFA propellants also have the advantage of lower velocity (10–15 m/s) and are warmer as compared with CFCs. D r u g F o rm u l a t i o n s : 9 D r u g

formulations in the pMDI are available either as a suspension or a solution. In suspensions, micronised drug particles are suspended in the l iquefied or compressed gas; in the solution form, the drug is dissolved in the medium. The drug formulations also contain surfactants such as oleic acid or soya lecithin to prevent aggregation of the particles and clogging of the valve. Since surfactants are insoluble in HFA, a little ethanol is added to increase their solubility in many formulations. Actuator:The pMDI canister is fitted

into a plastic actuator. The actuator is a very important component of the pMDI. The diameter of the nozzle in the actuator from where the drug is released plays a key role in the particle size of the aerosol generated. The nozzle diameter ranges between 0.14 and 0.60 mm. pMDI Dose Definitions

• Ex-Actuator Dose: The amount of the drug leaving the actuator and delivered to the patient is the ex-actuator dose. This is the dose available to the patient for inhalation.

• Ex-ValveDose: This is the amount of drug leaving the valve, not all of which is available to the patient for inhalation.

In India, the pMDI doses are based on the ex-valve dose; in some countries like the USA, the ex-actuator dose is used as the therapeutic dose. For example, budesonide 200 mcg in India

is equivalent to budesonide ex-actuator dose of 160 mcg in the USA. Steps for the Correct Use of a pMDI19–22

Table 1 l i s t s the s teps for the correct use of a pMDI and provides the rationale for each step. Priming of the Inhaler

Priming means making a new pMDI ready for use by spraying it into the air several times to release a few doses (about two to four doses or as specified by the manufacturer). Procedure for Priming

– Open the cap of the inhaler.– Shake the inhaler up and down a

few times.– Test-fire the inhaler by pressing/

actuating it a few times (about two to four times) by spraying into the air away from the face.

pMDI Priming Instructions for the Patient

• When a new inhaler i s be ing initiated

When initiating therapy with a new pMDI, the metering chamber should be filled with the uniform dose as labelled on the device. To ensure filling of the metering chamber with this uniform dose, priming needs to be done.

• When an inhaler is being usedafteragapofafewdays23

The pMDI may have been stored in a position where the metering apparatus is above and the solution/suspension below, which can cause the metering valve to clog due to the effect of gravity. Prolonged storage even in the correct position may lead to clogging of the valve due to the liquefied propellant. Hence, to fill the metering chamber with the uniform dosage and to clear the clog, priming needs to be done.

Recommendation:All pMDI devices need to be primed whenever a new pMDI is used or if the pMDI is being re-used after a gap of 4 or more days. Priming is to be done by spraying several times into the air. The manufacturer’s manual may be referred to for the exact number of doses to be released for priming.

The Need for an Interval between Two Actuations24

It is important for the pressure in the pMDI to equilibrate between actuations and this requires some time. • Studies have shown that multiple

actuations in quick succession reduce the total quantity of drug emitted from the chamber.

• A gap of at least 15–20 seconds b e t w e e n t w o a c t u a t i o n s i s recommended in the literature.

Recommendation:We recommend a gap of 30 seconds between two actuations.

The European Respiratory Society (ERS) and the International Society for Aerosols in Medicine (ISAM) Task Force14 and the Indian guideline on management of Asthma3 recommend rinsing the mouth or gargling with water and spitting out after the use of an inhaler, especially with inhaled corticosteroids. Recommendation:We recommend rinsing of the mouth as well as gargling with water and spitting out, especially after the use of inhaled corticosteroids even when using a spacer.

Local Side Effects of pMDIs

The common local side effects caused by the use of pMDIs are attributed to inhaled corticosteroids use and includes dysphonia and oropharyngeal candidiasis. The speed of the drug emitted from the pMDIs is between 100 and 140 km/hr, because of which 80% of the inhaled drug hits the throat and gets deposited there due to the force of impaction. These side effects are attributed to the drug rather than the device. Dysphonia25

The postulated mechanisms for dysphonia are probable b i la tera l adductor myopathy, supraglot t ic h y p e r f u n c t i o n o r i n f l a m m a t o r y infiltrates in the mucosa. Oropharyngeal Candidiasis

Candidiasis is a side effect of inhaled cort icosteroids use that occurs in about 3% of patients due to their immunosuppressant properties. The occurrence of candidiasis can also lead to noncompliance to therapy. Rinsing and gargling with water to wash out the mouth and throat and the use of spacers lower the risk of Candida infections.26

Recommendation:To minimise the occurrence of side effects, the following is recommended: • T h e l o w e s t d o s a g e s o f i n h a l e d

corticosteroids should be used to control the disease.

• A spacer should be used during inhalation of the drug.

• The patient should be instructed to use the correct technique of inhalation.

• Rinsing of the mouth and gargling should be done after each inhalation.

• The patient should be instructed to keep the spacer clean.


Cold-Freon Effect

When the propellant, which is under pressure in the canister, is released out through the nozzle, the temperature of the aerosol drops to around –30°C and by the time it hits the throat, the temperature is around 0°C. When the propellant, which is moving at around 100–140 km/hr , hi ts the throat at 0°C, it causes pharyngeal spasm and stimulates cough in some subjects. This is described as the cold-freon effect and occurs only in a few people and can easily be overcome with the use of a spacer.22

Indicators that the Inhaler may be Empty

A pMDI device may actuate and release an aerosol even when the canister is devoid of the active drug. The aerosol may contain only the propellant and other excipients. When a patient continues to inhale from a canister devoid of the active drug, there may be loss of disease control, leading to an exacerbation. If the patient is having an exacerbation but the rescue inhaler is empty of medication, it can lead to significant morbidity. Hence, it is important that the patients are educated on the ways to identify an empty pMDI.

Dipping the inhaler in water to see if it floats or weighing the canister are inaccurate and harmful methods to assess the amount of drug present in the canister. However, irrespective of whether the inhaler has a dose counter or not, patients should be advised to mark the inhaler carton with the date when the first dose was taken (Figure 4). This is the simplest way to track the number of doses remaining in the canister, especially in controller therapy, when patients are regular with their inhaler use. This method also helps in evaluating the patient’s adherence to therapy by cross-checking the number of doses remaining in the

canister with the expected number of doses the patient should have taken. If the patient is on reliever therapy, the patient should keep a record of the dosages taken. Most inhalers now come with a dose counter and we recommend the use of these inhalers.Recommendation: Irrespective of whether a pMDI has a dose counter or not, the patient should mark the date of initiating the inhaler for use on the inhaler carton.

Cleaning the Actuator Mouthpiece

Removing the canister and washing the en i re inha ler device in mi ld detergent and water (as per older recommendations) is likely to damage the device, especially the newer devices with dose counters. Hence, it would be best to follow the manufacturer’s advice for cleaning the actuator mouthpiece. Recommendation:The actuator mouthpiece should be cleaned with a soft cloth or a tissue paper after each actuation. It is best to follow the manufacturer’s recommendations.

Common Errors When Using a pMDI

The commonest errors when using a pMDI include patients not exhaling out completely before inhaling, not holding their breath, and inhaling too rapidly and/or shallowly.27

Spacers

Spacers are holding chambers that allow the patient to take some extra time (2–20 seconds) to inhale the drug after it has been released from the pMDI.20,21

Advantages of Using a Spacer

Spacers act as holding chambers for the drug once it is actuated, thus eliminating the need for actuation-inhalation coordination by the patient. They are a lso useful for pat ients of any age who have di f f icul t ies with hand-breath coordination. The oropharyngeal impaction of the drug is also significantly reduced when using a spacer, which also decreases the risk of oropharyngeal candidiasis with ICS use, and eliminates the cold-freon effect. There is a possibility of reduced dysphonia when spacers are used with inhaled corticosteroids.25 The use of repeated doses of inhaled short-acting beta2-agonist bronchodilators via a pMDI + spacer has been found to be as effective as a nebuliser in controlling an acute exacerbation of asthma.

Many spacers are made up of non-static material that reduces the deposition of the drug along the inner

walls of the spacers. The drug particles have an electrical charge that works opposite to that of the spacer material; hence, they get attracted and stick to the walls of the spacer. Some spacers have a valve, also called valved-holding chambers, which are particularly useful as they allow patients to re-breathe without introducing moisture into the spacer.21,22 Re-breathing is necessary in small children and among those who are unable to hold their breath, such as during an exacerbation.

Al though spacers and holding chambers are different , the terms are used interchangeably.24 A spacer increases the distance between the actuator of the pMDI and the patient, thereby adding volume to capture the aerosol from the pMDI. A holding chamber, on the other hand, is usually a valved chamber that holds the drug for a while after actuation until the patient’s inspiration opens the valve and the drug is inhaled. It allows for some delay between actuation and inhalation.

The ideal spacer size for all age groups, including infants, is 100–700 ml.33 Most spacers available in India have a volume range between 130 and 300 ml. Techniques for Using a Spacer14

Table2 provides the correct steps for using a spacer with a pMDI.Features that Affect the Efficiency of the Spacers

Several factors affect the efficiency of the spacers. These include spacer shape, valves, the material with which the spacer is made, and spacer size and volume. Spacer Shape

Spacers are of var ious shapes , including cylindrical or tubular spacers, collapsible spacers, collapsible bag-type spacers and pear-shaped spacers. The aerosol plume released by the pMDIs has a distinct morphology that favours the theory of better drug deposition when using a pear-shaped spacer. In vitro studies have found that drug deposition improves with increasing diameter but the effect of increasing the length of the spacer tube beyond 20 cm may not have any incremental effect on drug deposition.33 Increasing the diameter also correlated with better improvement in lung function with pear-shaped spacers as compared

Fig. 4: A) Example of labelling of a pMDI by date when opened; B) Example of a pMDI dose counter

A B


with straight-tube spacers.26 A recent in vitro study, however, found that drug delivery may not be impacted by the shape of the spacer.34

Recommendation:Though the shape of the spacer is not a key determinant of its efficacy, a pear-shaped spacer should be preferred. In the absence of a pear-shaped spacer, one may use a tubular spacer.

Valves in Spacers

Spacers with valves were designed to overcome the limitations of pMDIs r e q u i r i n g a c t u a t i o n - i n h a l a t i o n coordination. Unidirectional, low-resistance valves, which open when the patient inhales and shut when the patient exhales, offer an advantage because they act as holding chambers and a few seconds of delay in inhalation is permissible. This obviates the need for actuation-inhalation coordination. Shutting of the valves during exhalation ensures that the aerosol is protected from the humidity in the exhaled air, which would otherwise make the hygroscopic aerosol particles absorb it, become heavier and settle down on the spacer floor or in the oropharynx.30

Anti-Static Spacers Improve Lung Deposition

Presence o f a s ta t i c charge in the spacers was first detected quite serendipitously.26 In the late 1980s, O’Callaghan et. al. found that spacer output increased when it was dipped in diluted household detergent solution prior to use.30 Further experiments showed that reducing the static charge on the spacers with anti-static sprays substant ia l ly increased the drug delivered by the spacer. The first anti-static spacer was patented in 1991 and involved spraying of the spacer with anti-static coating. Several methods have since been tried successfully to reduce the static charge. Use of steel spacers or spraying the drug into the spacer to coat the inner surface of the spacer reduces the static charge. The spacer can also be dipped in a mild household detergent solution in the dilution recommended by the manufacturer, thereby providing an anti-static coating. The spacer should not be washed or wiped after dipping in such detergent solution; it should be allowed to just air-dry.35

The first transparent spacer made of anti-static polymer was patented and marketed by Cipla Ltd26 – these have been shown to have a better lung deposition profile and bioavailability.33

Recommendation:Patients should, preferably, use spacers that are made of anti-stat ic material.

Spacer Size/Volume

Spacers are c lass i f ied as smal l volume (up to 100 ml), medium volume (100–350 ml) and large volume (>700 ml).30 Most spacers currently available in India are in the volume range of 130–300 ml; earlier, spacers of 600–700 ml were available.

Studies have shown that large-volume spacers are either equal36 to or better in efficacy33,37 compared with small-volume spacers, as assessed by plasma concentrations of salbutamol. This is because the plume released by the pMDI, when it comes in contact with the walls of the small-volume spacer, gets more turbulent and a large quantity of the drug gets impacted onto the wall and is thus lost to inhalation. On the other hand, the large-volume spacers offer more space for the drug to remain suspended in the form of a s tat ic , uniformly distr ibuted aerosol within the spacer and offers evenly distributed drug delivery.23,30 However, for children and patients with a low tidal volume, a small-volume spacer, which would have a higher concentration of drug, would be better than a large-volume spacer with diluted drug that will remain available for inhalation for a few seconds only.33 Also, large-volume spacers are likely to be less favoured for use due to their bulkiness.14

This review also considered the fact that in a country like India where inhaler use is still not very popular, most patients are unlikely to accept a spacer, let alone a large-volume one. Hence, the recommendations below have been made pragmatically. Recommendation:Medium-volume spacers (100–300 ml) should be used for all age groups.

Best Breathing Pattern for Spacer Use

There have been several studies conducted in the past to evaluate the effects of different inhalat ion manoeuvres and it has been found that whether taken as a single slow and deep inhalation or repeated multiple breaths through the spacer, the inhalation manoeuvres have little impact on the clinical outcomes.38-40

Recommendation:A single, slow and deep inhalation followed by breath holding for about 10 seconds14 or multiple breaths that are comfortably possible

(e.g. in an exacerbation) is recommended for adults and children over 6 years of age.Depending upon the patient’s abil i ty to take a deep breath and actuation-inhalation coordination, the physician may advise the patient to take a second breath to inhale any drug that might have remained in the spacerChildren who are unable to perform controlled breathing or adults who are unable to hold their breath may perform repeated sufficiently deep tidal breathings to open the valve.

Timing of Inhalation after Actuation

When using spacers that are not made of anti-static material, inhalation immediately after actuation is preferred as the respirable fraction falls to about 67% after a time lag of 20 seconds from actuation. It has been shown that using an anti-static spacer increases the respirable fraction by 260% even at the end of a 20-second delay compared with a spacer without an anti-static coating.29

Recommendation:A time lag of 2 seconds between actuation and inhalation is acceptable, irrespective of the static charge in the spacer.

Number of Actuations Required for Inhalation with a Spacer

Both in vitro and in vivo studies have shown that multiple actuations into a spacer actually reduces the drug availability.41-43

Recommendation:A single dose should be actuated into the spacer with one inhalation.14 If multiple doses need to be taken, the patient must repeat all the steps for using the pMDI with the spacer after a gap of about 30 seconds, as recommended in the section The Need for an Interval between Two Actuations.

Contamination of Spacers and Ways to Keep Them Clean

The American Thoracic Society and the European Respiratory Society Task Force on inhaler devices recommend weekly washing of spacers with mild dishwashing liquid and allowing them to air-dry. Spacers have been found to be contaminated with both non-pathogenic44 and pathogenic bacteria.45 Washing the spacers a f te r every use protects from contamination.45 However, the clinical implications of these infections are yet unclear.32

Recommendation:Spacers should be disassembled and washed at least once a week if being used by a single patient in a home setting.In a hospital setting, one spacer should be used for a single patient and washed weekly. It should also be washed before using it for another patient.Anti-static spacers should be washed with plain room temperature water.Static spacers should be washed with a mild detergent.


Table 1: Steps for the correct use of a pMDI and rationale for the same14

Steps Rationale

1. Hold the inhaler vertically and shake it up and down four or five times.

This ensures uniform dispersion of the drug within the canister. This is important for pMDIs with a suspension formulation and may not be required for pMDIs containing a solution. Most manufacturers do not specify whether the pMDI contains the drug in a suspension form or a solution. It is, therefore, recommended that all pMDIs be shaken well before use.

2. Remove the cap. The cap of the pMDI which protects the actuator needs to be removed, prior to inhaling the dose

3. Prime the inhaler if using a new inhaler canister. When using a new pMDI, after shaking the inhaler, actuate the device twice into the air, away from the face. Priming ensures that the required dose is available in the chamber. If the pMDI has not been used for more than a week (e.g. salbutamol), it will be necessary to prime the device even if the pMDI has been used earlier.

4. Exhale slowly and empty the lungs to functional residual capacity.

It is important that the patient exhales completely, as much as possible, before actuating the pMDI. This is because, a complete exhalation will allow the patient to inhale more and ensure greater and deeper drug deposition.

5. Hold the inhaler in an upright position. The metering chamber of the inhaler fills due to gravity; hence, it is important to hold the inhaler upright so that the chamber fills up for the next dose.

6. Place the inhaler mouthpiece in the mouth between the teeth, with the tongue flat under the mouthpiece. The neck should be kept straight, and should not be flexed.

The inhaler mouthpiece should be placed between the upper and the lower front teeth, lightly biting down on it. Neck should be kept straight, not flexed, to keep the airways open.

7. Ensure that the lips have formed a tight seal around the mouthpiece.

This is to avoid leakage of the drug.

8. Start inhaling slowly through the mouth and, at the same time, press the inhaler canister to actuate a dose.

It is important for actuation to be done at the exact point when inhalation begins because maximal drug deposition occurs during the beginning of the inhalation. Drug wastage is high if there is a lack of coordination between inhalation and actuationin.14

9. Maintain a slow and deep inhalation through the mouth until the drug is completely inhaled. This should take an adult around 4–5 seconds.

Slower inspiration over 4–5 seconds reduces the flow rate and can achieve better drug deposition compared with rapid inhalation.

10. At the end of the deep inhalation, take the inhaler out of the mouth and close the lips. Continue to hold the breath for 10 seconds or as long as comfortably possible before breathing out.

Holding the breath gives the drug enough time to deposit on the mucosa by sedimentation. Longer the breath hold, better is the drug deposition. However, during an exacerbation, children and adults may not be able to hold their breath for enough time to allow drug deposition. Use of a valved spacer is recommended here.

1. Hold the inhaler vertically and shake it up and down four or five times.

This ensures uniform dispersion of the drug within the canister. This is important for pMDIs with a suspension formulation and may not be required for pMDIs containing a solution. Most manufacturers do not specify whether the pMDI contains the drug in a suspension form or a solution. It is, therefore, recommended that all pMDIs be shaken well before use.

2. Remove the cap.

The cap of the pMDI which protects the actuator needs to be removed, prior to inhaling the dose

4. Exhale slowly and empty the lungs to functional residual capacity.

It is important that the patient exhales completely, as much as possible, before actuating the pMDI. This is because, a complete exhalation will allow the patient to inhale more and ensure greater and deeper drug deposition.

6. Place the inhaler mouthpiece in the mouth between the teeth, with the tongue flat under the mouthpiece. The neck should be kept straight, and should not be flexed.

The inhaler mouthpiece should be placed between the upper and the lower front teeth, lightly biting down on it. Neck should be kept straight, not flexed, to keep the airways open.

7. Ensure that the lips have formed a tight seal around the mouthpiece.

This is to avoid leakage of the drug.

Contd. 2

10. At the end of the deep inhalation, take the inhaler out of the mouth and close the lips.

Continue to hold the breath for 10 seconds or as long as comfortably possible before breathing out.

Holding the breath gives the drug enough time to deposit on the mucosa by sedimentation. Longer the breath hold, better is the drug deposition. However, during an exacerbation, children and adults may not be able to hold their breath for enough time to allow drug deposition. Use of a valved spacer is recommended here.


Spacers should not be wiped after washing and should simply be left for drying in the air indoors in a clean place on an adsorbent paper or cloth. After they are dry, they should be preferably stored inside the airtight container provided.Do not boil/sterilise or microwave the spacer.

eSpecial Considerations in Infants and Children

The challenges of administering inhalation therapy in children are different because their anatomy and physiology differs from adults. The oropharynx is smaller, and most infants are nose breathers. They cannot perform control led breathing manoeuvres like adults and are often distressed. According to the Asthma Training Module of the Indian Academy of Pediatrics the recommended devices for children are as follows: • Age below 4 years: pMDI + spacer

with face mask• Age above 4 years: pMDI + spacerUse of Face Masks with Spacers

Very young children (below 4 years of age) cannot perform controlled breathing using a spacer and pMDI and need to be given inhalation therapy using a face mask attached to the spacer. The mask needs to be tightly fitted onto the face; therefore, an appropriately sized mask should be selected.

Some children may be unable to generate enough peak inspiratory flow rates to open the valve of the valved holding chamber in the spacer. In such cases, it is better to use a non-valved spacer or the valved spacer may be tilted slightly to let the valve fall open due to gravity. Recommendation: In children who are unable to generate sufficient peak inspiratory flow rates, use a non-valved spacer or tilt the valved spacer slightly and let the valve fall open due to gravity. The device will then function like a non-valved spacer.

Inhalation Therapy in a Crying Child

Crying is a process of prolonged exhalation followed by shallow erratic inspiration. Inhalation therapy given to

a crying child causes the drug to deposit more in the larger airways and the upper gastrointestinal tract; so, drug deposition in the lungs is significantly reduced.46 Hence, inhalation therapy is best given to a calm infant, whenever possible.47,48 However, if there is no other option in an emergency, it is better to give inhalation therapy even to a crying child rather than giving only oral/injectable drugs.

In cases where the child is unable to generate enough peak inspiratory flow rates, it is better to use a non-valved spacer. The valved spacer may be tilted slightly to let the valve fall open due to gravity. Recommendation:Inhalation therapy should preferably be given to a child who is calm and not in distress.However, if there is no other option (which is a common scenario in an emergency), it is better to give inhalation therapy rather than not giving it just because the child is crying.

Inhalation Therapy in a Sleeping Child

To overcome the chal lenges of administering inhalation therapy to a crying or uncooperative child, one might want to resort to giving it when the child is asleep. However, it has been shown that placing a face mask onto a sleeping child’s face awakens and distresses the child. Esposito et al. found that 69% of children woke up when the face mask was placed and 75% of them were distressed.48

Recommendation:Inhalation should preferably be given when the child is awake.However, if there is no other option and the child is already asleep, it is better to give the inhalation therapy rather than skipping the dose just because the child is sleeping.

Use of Improvised Spacers such as Plastic Bottles and Paper Rolls

Idea l ly , the technica l ly tes ted and val idated ant i - s ta t ic spacers manufactured specifically to fit a pMDI should be used. However, in exceptional cases or an emergency or absolute non-availability of spacers, improvised spacers may be used. According to the

International Consensus on Asthma (ICON), if commercially produced spacers a re not ava i lab le or not affordable, a 500 ml plastic bottle may be adapted to serve as an effective spacer for patients using a pMDI. Other home objects such as a paper roll can also be improvised for use. Sheth et al. showed that there was no difference in the respirable mass using improvised spacers (bottle-holding chamber, paper towel roll, paper roll, plastic bottle, toilet paper roll) and conventional spacers, but there was signif icant reduction in oropharyngeal deposition when compared with a pMDI alone.49-51

Recommendation: Ideally, the technically tested and val idated ant i -stat ic spacers manufactured specially to obtain maximal drug deposition in the lungs should be used.However, in case of an emergency or absolute non-availabil ity of a spacer, improvised spacers may be used.

BAIs

BAIs were devised to overcome the major challenge of coordination between dose actuation and inhalation in patients using a pMDI who do not or could not use a spacer.52 BAIs can lead to a three-fold improvement in drug deposition in the lungs compared with a poor ly coordinated pMDI actuation (21% versus 7%),52 and similar deposition is seen in patients who can coordinate the pMDI well.

BAIs have a sensing mechanism that actuates the dose when the patient achieves a minimal inspiratory flow rate of around 23–35 L/min. These rates can be easily generated in children,

Steps Rationale

11. Breathe out normally.

12. After waiting for 1 minute, if another dose is required, repeat steps 4–12 It is important for the pressure in the pMDI to equilibrate between actuations and this requires some time. Studies have shown that multiple actuations in quick succession reduces the total drug emitted from the chamber. A gap of at least 15–20 seconds between two actuations is recommended in the literature.

13. If inhaled corticosteroids are used, rinse out the mouth and gargle after taking a dose.

This helps reduce the amount of steroid deposited in the mouth/throat and reduces the risk of oropharyngeal candidiasis/dysphonia.

Note: Steps 4–8 should be performed in quick succession, without a significant time gap. For children below 6 years of age, the pMDI should always be used with a spacer.

Table 1: Steps for the correct use of a pMDI and rationale for the same14 (Contd.)

Fig. 5: Internal design of a BAI (Synchrobreathe, Cipla Ltd)


the elderly population, and even those having severe-to-very severe airway obstruction.

The BAI is a pMDI with an additional breath-actuator mechanism. It consists of a mouthpiece cap, a mouthpiece, a dose-release mechanism, a body that encases the canister, and a flow-sensing mechanical feature that gets triggered on attaining the minimum inspiratory flow (Figure 5). Table3 lists the correct steps for using a BAI.

Currently, passive breath-actuated DPI devices are being developed, which actively bring about disaggregation of the dry powder and disperse the medication to be inhaled, like in the case of BAIs.7 This helps to overcome the dependence on the patient’s inspiratory flow and provides consistent drug delivery.Flow Rate Required to Actuate a Dose through a BAI

The inspiratory flow rates required to actuate the dosing mechanism in the BAI is as low as 23–35 L/min53 a flow rate that can be easily achieved by children, geriatric patients and patients with severe-to-very severe airflow obstruction. While pMDIs work independent of inspiratory flow rate, DPIs require inspiratory flow rates of 50–90 L/min.Priming of the BAI

The BAI needs to be primed once before using for the first time. It is also advisable to prime the BAI if it has not been used for over 2 weeks. All BAIs have a dose-release button, which needs to be activated to release a dose when priming. Kindly refer to the individual manufacturer’s instructions for specific and detailed instructions for priming.

DPIs

The f i rs t DPI (wi th potass ium chlorate) was patented in 1864 by an English physician, Alfred Newton, for the treatment of breathing disorders. He had observed that the medication powder that was to be used in this manner had to be very finely pulverised and kept dry at al l t imes. Today, we know that these are important prerequisites for all DPIs. The first DPI to be marketed was the Aerohaler in the year 1949, which was also the first reliever inhaler. Frederick Roe patented another dry powder device called the Carbolic Smoke Ball,55 which could be

refilled at repeated intervals. T h e f i r s t R o t a h a l e r D P I wa s

introduced in the ear ly 1977s by Allen & Hanburys.55 Subsequently, the Spinhaler was introduced by Fisons. These were all single-dose DPIs. In India, the Rotahaler was introduced by Cipla Ltd in the 1980s and this was followed in 1997 by the transparent Rotahaler. This dramatically changed the way inhaled medications were used since the new-generation Rotahaler was transparent and, for the f irst time, patients could actually see the medication and confirm visually that the medication had been taken. Thereafter, several other unit-dose DPIs were introduced, including the Revolizer (Cipla Ltd) and a number of variants of the Aerolizer (made in Italy) such as the Lupihaler (Lupin Ltd) and the Instahaler (Glenmark Pharmaceuticals Ltd) . In the meantime, global ly , multidose DPIs were developed to overcome the limitation of inserting a capsule for every inhalation. Multidose DPIs store up to a month’s supply of the medication and reduce the number of steps required to use a DPI.

Multidose DPIs can be classified as discrete multidose DPIs and reservoir multidose DPIs. While the discrete multidose DPIs have individually packed, discrete doses of medication within the device , e .g . Accuhaler (GlaxoSmithKline Ltd) and Ciphaler (Cipla Ltd), the reservoir multidose DPIs have a reservoir of the entire drug in one confined space in the device, e.g. Turbuhaler (Astra Zeneca). Principles of the Working of a DPI

The performance of a DPI is affected significantly by the particle size and flow properties of the formulation, inspiratory flow rate, drug carrier adhesion, and design of the DPI.7 During inhalation, the inspiratory flow creates turbulence in the DPI and de-agglomerates the drug particles from the carrier lactose molecules. The effort required to generate the inspiratory flow to de-agglomerate is different for different DPI devices but generally varies between 37 and 111 L/min.55

Generation of the turbulent energy is necessary to aerosolise the drug in the DPI device. The turbulent energy is the product of the resistance by the device and the inspiratory flow rate required to be generated by the patient. It is, therefore, important to inhale rapidly and deeply when using a DPI.

Apart from the patient’s inspiratory flow rates and the DPI’s resistance, de-agglomeration also depends upon the inhaled volume and the length of the inhalation.56 The inhalation volume required to completely empty the dose out of the DPI should be at least 500 ml.56 Patients who have reduced inspiratory lung volumes and inspiratory flow rates may, therefore, not be able to achieve the required lung deposition. These patients need to take a second inhalation to ensure that the dose is completely inhaled. However, this is possible only with those DPIs that have a transparent chamber, e.g. the Revolizer and the Rotahaler.Steps for the Correct Usage of a DPI and Rationale for the Same14

Table 4 presents the correct usage steps for a DPI.Taking Multiple Medications from a Unit-Dose DPI

One can take multiple medications from the same unit-dose DPI. Recommendation: If two drugs have been prescribed, i t is recommended to f inish inhalation from one capsule before using the second. It is important to note that it is better to use a unit-dose DPI and capsules from the same manufacturer.

Use of DPIs in Young Children

In order to use a DPI efficiently, the patient is required to generate an inspiratory flow rate of at least 30 L/min. Most children below the age of 5 years are unable to generate average inspiratory flow rates of ≥60 L/min and, hence, it is advisable to not prescribe DPIs to children below the age of 5 years.59 Moreover, due to a 30–35% lower lung function in the Indian population, 58 i t can be speculated that the inspiratory flow generated by Indian patients will be lower than their counterparts in the West. Hence, the Indian Academy of Pediatricis has recommended that DPIs should not be used in children below the age of 6 years. The pMDI with a spacer and with or without a face mask remains the primary choice of inhaler device in children below 6 years of age. In children aged 6 years and above, a DPI can be used. Use of DPIs during Exacerbations

D u r i n g e x a c e r b a t i o n s , t h e inspiratory flow rate and inspiratory time reduce significantly. Furthermore, patients may also not be able to perform the breath hold of 4–10 seconds . However, during exacerbations, the


1. Assemble the spacer if needed. Shake the pMDI four or five times.

2. Remove/open the cap

3. Prime the inhaler if the pMDI is being used for the first time or after a gap of 1 week.

4. Insert the mouthpiece of the pMDI into the open end of the spacer and ensure a tight fit.

5. *Empty the lungs by exhaling slowly through the mouth and hold the breath. (Do not begin inhalation)

Table 2: Correct steps for using a pMDI with a spacer14

1. Assemble the spacer if needed. Shake the pMDI four or five times.

4. Insert the mouthpiece of the pMDI into the open end of the spacer and ensure a tight fit.

5. * Empty the lungs by exhaling slowly through the mouth and hold the breath. (Do not begin inhalation)

6. * Place the mouthpiece of the spacer in the patient’s mouth – it should be placed between the front teeth and patient should be told to seal his/her lips tightly around it.

7. *Actuate one dose from the pMDI into the chamber of the spacer and ask the patient to start inhalation slowly through the mouthpiece. Some spacers will make a whistling noise if inspiration is too fast.

8. Maintain a slow and deep inhalation through the mouth, until the lungs are full of air. This should take a child 2–3 seconds and an adult about 5 seconds.

9. At the end of the inhalation, take the spacer mouthpiece out of the patient’s mouth and ask him/her to close his/her mouth.

10. Continue to hold the breath for up to 10 seconds or as long as comfortably possible before breathing out.

11. Breathe out normally.12. If another dose is required, repeat steps 1–11.13. If inhaled corticosteroids are used, ask the patient to rinse out his/her

mouth and gargle after taking a dose.*Steps 5, 6 and 7 should be done in quick succession without much time gap between steps. *Steps 6 and 7 can be interchanged. Ask the patient to actuate the inhaler into the spacer, then open the cap to hold the spacer in the mouth, and then begin inhalation. This is applicable for a valved spacer, which has a cap on the other side. Ifachild6yearsofageoraboveisunabletoholdthebreathandisfollowingatidalbreathingpattern,thenaskthechildtobreathefivetoseventidalbreaths,takingslowanddeepinhalationseachtime.

9. At the end of the inhalation, take the spacer mouthpiece out of the patient’s mouth and ask him/her to close his/her mouth.

6. * Place the mouthpiece of the spacer in the patient’s mouth – it should be placed between the front teeth and patient should be told to seal his/her lips tightly around it.

7. * Actuate one dose from the pMDI into the chamber of the spacer and ask the patient to start inhalation slowly through the mouthpiece. Some spacers will make a whistling noise if inspiration is too fast.

mean inspiratory flow generated by patients with OADs ranges between 40 and 100 L/min. As discussed earlier, drug deposition in DPIs is largely through impaction but some proportion of the drug will also deposit through sedimentation. The lack of a breath hold during an exacerbation also affects the level of drug deposition. Therefore, in case of exacerbations, with reduced inspiratory flow rates and inability to hold breath for 10 seconds, the use of DPIs remains limited. However, medium-high to high-resistance DPIs, which require inspiratory flow rates of 50 L/min or less, may have some role to play in easing exacerbations though they may not be as effective as pMDIs with a spacer or a nebuliser. It is advisable to, therefore, use a pMDI with a spacer (with or without a face mask) or a nebuliser in cases of exacerbations.59 There are limited studies on the use of DPIs in exacerbations, more specifically in milder exacerbat ions . A s tudy conducted in 153 children above 5

years of age with mild-to-moderate acute exacerbations of asthma showed that they could effectively use the Rotahaler DPI. The study concluded that the Rotahaler and a pMDI with a spacer have equal efficacy in delivering salbutamol in mild-to-moderate acute exacerbations of asthma in children. However, due to the lack of large studies, a pMDI with a spacer may, therefore, be considered as a preferred option in more severe cases.Use of DPIs in COPD Patients

DPIs can be successfully used in most pat ients with COPD. COPD patients can generate an inspiratory flow rate in the range of 26–95 L/min (lower inspiratory flow rates are associated with increasing severity of COPD).59,60 All DPIs may be used in patients with mild COPD. Almost 20–30% of patients with advanced COPD may be unable to generate a sufficient inspiratory flow/lung volume to be able to use a DPI effectively.61

Managing Cough after Using a DPI

The carr ier molecule in a DPI is lactose. In comparison with the active drug molecule, lactose has a larger particle size ranging between 10 and 40 microns. Particles with a mean diameter of over 5 microns get deposited in the oropharynx. Moreover, high inspiratory flow rates are needed when inhaling through a DPI, leading to greater oropharyngeal deposition of the particles. The deposition of the larger lactose molecules through rapid impaction stimulates the oropharyngeal epithelium, inducing cough in some patients. Rinsing/Gargling after a DPI Dose

As mentioned earlier, following the impaction of larger lactose molecules, agglomerates of the lactose molecule and the active drug remain impacted in the oropharynx. It is, therefore, imperat ive to r inse the mouth or gargle af ter inhalat ion through a DPI. Ideally, the rinsing or gargling

2. Remove/open the cap


Nebulisers

Nebulisers are devices that convert a liquid solution or suspension form of the medication into a fine mist that can be easily inhaled. They are usually used by patients during an acute exacerbation. The nebuliser device generates this aerosol, allowing the patient to inhale at his or her own pace. No actuation-inhalation coordination or breath hold or rapid/slow and deep inhalation is required. The patient can breathe at tidal volume, although deeper inhalation and breath hold for as long as possible should be encouraged.

G e n e r a l l y , c o n v e n t i o n a l j e t nebulisers are the most widely used nebulisers – these generate a continuous flow of aerosol irrespective of the breathing. This, however, leads to loss of a significant proportion of the drug into the environment during administration. The amount of drug to be administered through the nebuliser is, therefore, larger than for a pMDI and DPI (e.g. the dose of salbutamol

has been suggested after inhalation of a corticosteroid. However, it is a good practice to rinse or gargle after any drug inhalation as this will also serve the purpose of washing out the deposited lactose particles. Rarely, the deposited lactose particles may trigger symptoms in a patient with lactose intolerance.62

Common Errors when using a DPI

The commonest errors when using a DPI include patients not holding their breath, not breathing in rapidly and deeply enough, and not exhaling out completely before inhaling. Other errors include improper loading of the dose, exhaling into the device, or using the DPI when it is still wet after cleaning.

Recommendation on changing the device:Manufacturers usual ly recommend the unit-dose DPIs to be used for not more than 6 months. Multidose dry powder devices are usually manufactured for “use and throw”.

Cleaning the DPI

The uni t -dose DPIs should be cleaned once a week under running

tap water at room temperature and left to air-dry.

Storing the device under direct sunlight should be avoided as this could lead to UV degradation of the plastic. Detergents, sponge or a brush should not be used during the cleaning process . In addit ion, unnecessary handling of the device should be avoided as this may introduce an electrostatic charge on the inner surface of the device, which can reduce its functionality.

Mult idose DPIs do not require dismantl ing and cleaning as they have a fixed number of doses and are discarded after use. However, once a week, the mouthpiece of the multidose DPIs must be cleaned externally with a dry cloth.

I t i s i m p o r t a n t t o f o l l o w t h e manufacturer’s recommendations for proper cleaning.

Table 3: Correct steps for using a BAI (Synchrobreathe, Cipla Ltd) and rationale for the same

Steps Rationale1. Hold the device in an upright position and shake it up and

down four or five times.Same as for pMDI.

2. Remove/open the cap (as per the device). Pulling open the cap (as in the Synchrobreathe) loads the dose and readies the device for inhalation. It is therefore imperative to close the cap in the Synchrobreathe after inhalation is complete. This is important to load the next dose.

3. Priming When starting use of a new BAI, after shaking the inhaler, actuate the device twice into the air away from the face. Priming ensures that the required dose is available in the chamber. If the BAI has not been used for more than a week (e.g. salbutamol), it will be necessary to prime the device even if it has been used in the past.

4. Exhale completely to empty the lungs to functional residual capacity.

Place the inhaler mouthpiece between the teeth, with the tongue flat below the mouthpiece, and make a tight seal around it with the lips before inhalation.

Same as for pMDI.

5. Now inhale slowly and deeply. To be continued even after hearing a click as the click is the indication of an actuation. It should be emphasised to the patient that a continued breath after the click is mandatory.

6. Take the mouthpiece out of the mouth and close the lips. Hold the breath for 10 seconds or for as long as comfortably possible.

Same as for pMDI.

7. Breathe out normally. Same as for pMDI.

8. Put back/close the cap (as per the device). Ensures loading of the next dose.

1. Hold the device in an upright position and shake it up and down four or five times.

Same as for pMDI.

2. Remove/open the cap (as per the device).

Pulling open the cap (as in the Synchrobreathe) loads the dose and readies the device for inhalation. It is therefore imperative to close the cap in the Synchrobreathe after inhalation is complete. This is important to load the next dose.

4. Exhale completely to empty

the lungs to functional residual capacity.

Place the inhaler mouthpiece between the teeth, with the tongue flat below the mouthpiece, and make a tight seal around it with the lips before inhalation.

Same as for pMDI.

5. Now inhale slowly and deeply.

To be continued even after hearing a click as the click is the indication of an actuation. It should be emphasised to the patient that a continued breath after the click is mandatory.

8. Put back/close the cap (as per the device).

Ensures loading of the next dose.

6. Take the mouthpiece out of the mouth and close the lips. Hold the breath for 10 seconds or for as long as comfortably possible.

Same as for pMDI.


Table 4: Correct steps for using a DPI and rationale for the same

Steps Rationale1. If there is a mouthpiece cover, remove it/open it. Unless the cover or cap is removed/opened, the mouthpiece of the device will not

be accessible for use.2. Load/prepare a dose for delivery. Every DPI has its unique step for preparing a dose prior to inhaling. Patients

should follow the steps mentioned in the patient information leaflet supplied with the device. The two images given here are an example of dose preparation when using the Rotahaler (Cipla Ltd).

3. Exhale completely, prior to inhalation. Before taking a deep inhalation through the DPI, it is necessary for the patient to exhale up to his/her functional residual capacity. This will ensure good inhalation volume. As the drug in the DPI is vulnerable to humidity, which may affect the performance of the DPI, it is advised to not exhale into the device. It is also important to remember that the DPI should be held only in the upright position, as the drug powder prepared in the holding chamber would otherwise be wasted.

4. Place the mouthpiece between the teeth, with the tongue flat below the mouthpiece, and make a tight seal around it with the lips before inhalation.

Positioning the mouthpiece firmly between the teeth, with the tongue flat under the mouthpiece, and making a tight seal around it with the lips helps in generating the high inspiratory flow rate required when inhaling from a DPI and thereby ensures good drug delivery.

5. Inhale rapidly and deeply until the lungs are full. The patient must be instructed to inhale as fast and as deep as possible. The inhalation effort of the patient generates an inspiratory flow. In order to aerosolise the powder in a DPI, turbulent energy is essential.

6. At the end of the deep inhalation, take the mouthpiece out of the mouth and close the lips. Continue to hold the breath for 10 seconds or as long as comfortably possible before breathing out.

Larger drug particles deposit in the airways by inertial impaction but the particles between 4 and 5 microns deposit in the bronchial and conducting airways mainly by sedimentation due to gravity.

7. Breathe out normally.8. After each use, rinse out the mouth and gargle thoroughly. As mentioned earlier, following the impaction of larger lactose molecules,

agglomerates of the lactose molecule and the active drug remain impacted in the oropharynx. Rinsing out of the mouth and gargling is recommended after inhalation of a corticosteroid.

6. At the end of the deep inhalation, take the mouthpiece out of the mouth and close the lips. Continue to hold the breath for 10 seconds or as long as comfortably possible before breathing out.

Larger drug particles deposit in the airways by inertial impaction but the particles between 4 and 5 microns deposit in the bronchial and conducting airways mainly by sedimentation due to gravity.

5. Inhale rapidly and deeply until the lungs are full.

The patient must be instructed to inhale as

fast and as deep as possible. The inhalation

effort of the patient generates an inspiratory

flow. In order to aerosolise the powder in a

DPI, turbulent energy is essential.

4. Place the mouthpiece between the teeth, with the tongue flat below the mouthpiece, and make a tight seal around it with the lips before inhalation.

Positioning the mouthpiece firmly between the teeth, with the tongue flat under the mouthpiece, and making a tight seal around it with the lips helps in generating the high inspiratory flow rate required when inhaling from a DPI and thereby ensures good drug delivery.

2. Load/prepare a dose for delivery.

Every DPI has its unique step for preparing a dose prior to inhaling. Patients should follow the steps mentioned in the patient information leaflet supplied with the device. The two images given here are an example of dose preparation when using the Rotahaler (Cipla Ltd).

2. Load/prepare a dose for delivery.

Every DPI has its unique step for preparing a dose prior to inhaling. Patients should follow the steps mentioned in the patient information leaflet supplied with the device. The two images given here are an example of dose preparation when using the Rotahaler (Cipla Ltd).

3. Exhale completely, prior to inhalation.

Before taking a deep inhalation through the DPI, it is necessary for the patient to exhale up to his/her functional residual capacity. This will ensure good inhalation volume. As the drug in the DPI is vulnerable to humidity, which may affect the performance of the DPI, it is advised to not exhale into the device. It is also important to remember that the DPI should be held only in the upright position, as the drug powder prepared in the holding chamber would otherwise be wasted.

when given via a nebuliser is 2,500 mcg versus 200 mcg when given through a pMDI or DPI). Generally, at least a 2 ml volume of the liquid containing the drug is required for nebulisation. An increase in fill volume increases the aerosol output. However, it also increases nebulisation time. Hence, the optimal range of fill volume should be 2–4 ml. Generally, it takes 10–15 minutes to nebulise one unit of the inhalation solution or suspension of the medication. Types of Nebulisers

Nebul isers are avai lable as je t nebulisers, ultrasonic nebulisers and mesh nebulisers.Jet Nebulisers

Jet nebulisers are pneumatically powered aerosol delivery systems

that have been in use now for several decades and, therefore, remain the most widely used nebulisers. They generate the desired aerosol particles with the help of pressurised gas flow created by the nebuliser compressor or the supply of gas flow through high-flow systems (Figure 6). Generally, a gas flow of 6–8 L/min is required to create the necessary aerosol particles. The biggest advantage is that they eff ic iently nebulise drugs in solution as well as in suspension formulations.

In a jet nebuliser, compressed gas passes through the liquid medication at high pressure. This causes a region of negative pressure, in which the solution or suspension is entrained into the gas stream and is sheared into an unstable liquid film, which breaks into aerosol particles due to surface tension

forces.64 These are further broken down into smaller particles with the help of the baffle within the medication cup. Larger particles are returned to the liquid drug reservoir while the patient inhales the smaller particles.

Jet nebulisers can be driven by both air as well as oxygen. However, care must be taken to avoid the overuse of oxygen in patients with COPD. Jet nebulisers can be used along with mechanical ventilators in the acute-care setting

The equipment required for jet nebulisation includes the following:• Jet nebuliser or gas source with

flowmeter• Nebuliser interface, which includes

face mask or mouthpiece, and nebuliser cup with baffle


Ultrasonic Nebulisers

Ultrasonic nebul isers ut i l i se a piezoelectric crystal (a crystal that v i b r a t e s w h e n s u p p l i e d w i t h a n electr ical charge) to generate the aerosol . This crystal vibrates at a frequency of 1–3 MHz when supplied with electrical energy and creates ripples in the medication cup, which contains the liquid drug reservoir (Figure 7) . These vibratory ripples create a fountain and break down the medication into smaller particles, which is then delivered to the patient during inhalation. This type of nebuliser can be used along with a mechanical ventilator.Mesh Nebulisers

This is a new type of nebuliser, which contains a mesh with many tiny holes through which the drug is passed to create the desired aerosol. Typically, these devices are categorised as either static mesh nebulisers or vibrating mesh nebulisers (Figure 8) . Static mesh or passive nebulisers push the liquid drug through the mesh holes to create the aerosol; in the vibrating mesh or active nebuliser, a piezoelectric element creates vibrations, which pushes the drug through the mesh. Table 5 presents a comparison of various nebulisers.24

Medications used in Nebulisers

Nebulisers are predominantly used to administer bronchodilators and inhaled corticosteroids. However, r ecent advances have l ed to the development of inhaled forms of mucolytics and antibiotics that can be delivered via the nebuliser (Table6).56,72,73

Understanding the Difference between a Ready-to-Use Solution for Inhalation and Concentrated Respirator Solution66

A respule (as it is commonly known in India) is a ready-to-use form of solution for inhalation via nebulisation. It is a plastic container that contains a liquid drug, which is pre-diluted with 0.9% normal saline. Respules are easy to use and can be used directly for nebulisation. There is also less chance of contamination. Generally, these respules contain 2–4 ml of the solution, which is appropriate for all nebuliser devices (Figure 9).

A concentrated respirator solution is also used for nebulisation, where

Fig. 7: Schematic diagram of an ultrasonic nebuliser

Table 5: Comparison of various nebulisers

Jet(conventional)nebuliser Ultrasonicnebuliser Vibratingmeshnebuliser

FeaturesPower source Compressed gas or electrical

mainsElectrical mains Batteries or electrical

mainsPortability Restricted Restricted PortableTreatment time Long Intermediate ShortOutput rate Low Higher HighestResidual volume 0.8–2.0 ml Variable but low ≤0.2 mlEnvironmentalcontaminationContinuous use High High HighBreath-activated Low Low LowPerformance variability High Intermediate LowOther CharacteristicsCleaning Required, after single use Required, after multiple use Required, after single useCost of the device Very low (approx.

Rs. 1,000–4,000)High (approx. Rs. 6,000–25,000)

High (approx. Rs. 10.000–25.000)

Fig. 6: Schematic diagram of a jet nebuliser

• Oxygen tubing• Medicine respule or respirator

solution

Recommendation: Ideally, a mouthpiece is preferred to be used during nebulisation. It avoids the loss of drug due to filtration in the nose as seen with the use of a face mask. Further, it is also more comfortable for a patient in acute exacerbation who, typically, breathes through the mouth.


the solution needs to be diluted with normal saline in the proportion of one part drug and three parts 0.9% normal saline. They are not easy to use and have high chances of contamination. Using distilled water or tap water as a diluent is not recommended as it has been shown to irritate the bronchi and cause bronchoconstriction (Figure 9).

Volume of Drug to be Added to the Nebulisation Chamber

At least 2 ml volume of drug is required for nebulisation. As the fill volume increases, the aerosol output increases – but the nebulisation time also increases. Hence, an optimal range would be 2–4 ml. Generally, it takes 15–20 minutes to nebulise one respule of medication (i.e. 2–3 ml) and once a splutter is heard, nebulisation can be stopped.Continuous and Intermittent Nebulisation Therapy

In a stable situation, no significant difference has been found between i n t e r m i t t e n t a n d c o n t i n u o u s nebulisations and both are considered equally effective as they reduce the hospital stay and improve pulmonary

function.67 Continuous therapy has been shown to significantly improve peak f low values and reduce the frequency of hospitalisations in severe asthma exacerbations.63 Generally, continuous bronchodilator therapy is given to patients who do not respond to the standard dose of bronchodilator therapy. These patients are nebulised with higher doses of bronchodilators, typically 5–15 mg/hr until the patient is relieved of the bronchospasm.70 Patients on continuous nebulisation should be monitored for beta-agonist side effects such as tachyarrhythmias, tremors, hyperglycaemia and hypokalaemia.

Intermittent therapy is when a patient is administered nebulisation every 20 minutes for the first hour.68 Table7lists the steps for using jet,

ultrasonic and mesh nebulisers.69

Common Errors when Using a Nebuliser63

C o m m o n e r r o r s i n c l u d e t h e following: • I n c o r r e c t l y a s s e m b l i n g a n d

operating the nebuliser.• Under-filling or over-dilution of

the medicine in the medication cup.

• Errors with compatibility between the device and drug formulation.

• Improper use of the nebuliser and its interface, usage technique and the pattern of breathing. Lack of regular cleaning and disinfection of the device can also lead to the spread of infection.

Importance of Cleaning and Disinfection of the Nebuliser and its Parts

It is recommended to follow the manufacturer’s guidelines for cleaning and disinfecting the nebuliser and its parts. The nebuliser unit should be wiped with a clean cloth and a surface disinfectant daily (e.g. sodium hypochlor i te so lut ion) . The drug chamber /medicat ion cup should ideally be washed and discarded as per the manufacturer’s recommendations. However, they may be reused with proper disinfection and storage for up to 3 months or as per manufacturer’s recommendations.63 Multiple methods can be used to clean and disinfect the parts of the nebuliser (face mask, mouthpiece, medicine cup). Any one of the fol lowing methods can be adopted:69

Fig. 8: Schematic diagram of a vibrating mesh nebuliser

Table 6: Drugs available for nebulisation in India

Drugtype Class Nameofmolecule DoseBronchodilators Short-Acting Beta2

Agonists (SABAs)Salbutamol 2.5 mg/2 mlLevosalbutamol 0.31 mg/2 ml

0.63 mg/2 ml1.25 mg/2 ml

Long-Acting Beta2 Agonists (LABAs)

Formoterol 12 mcg/2 ml20 mcg/2 ml

Aformoterol 15 mcg/2 mlShort-Acting Muscarinic Antagonists (SAMAs)

Ipratropium Bromide 500 mcg/2 ml

Long-Acting Muscarinic Antagonists (LAMAs)

Glycopyrronium 25 mcg/1 ml

Inhaled Corticosteroids (ICS)

Budesonide 0.5 mg/2 ml1 mg/2 ml

Fluticasone Propionate 0.5 mg/2 ml 2 mg/2 ml

Combination SABA + SAMA Salbutamol + Ipratropium 2.5 mg + 500 mcg/2.5 mlLevosalbutamol + Ipratropium 1.25 mg + 500 mcg/2.5 ml

ICS + SABA Budesonide + Levosalbutamol 0.5 mg + 1.25 mg/2 ml1 mg + 1.25 mg/2 ml

Budesonide + Formoterol 0.5 mg + 20 mcg1 mg + 20 mcg

Mucolytics Ambroxol 15 mg/2 mlN-Acetylcysteine Each ml contains 200 mcg

Antibiotics Tobramycin 300 mg/5 mlColistimethate Sodium 1 MIU in a 10 ml vial

MIU=million international units

Fig. 9: Nebulisation – ready-to-use solution for inhalation (respule) and concentrated respirator solution

Pre-Diluted Solution for Inhalation (Respule)

Concentrated Respirator Solution


• They can be boiled in water for 5 minutes.

• They can be soaked in a solution of one part household bleach and 50 parts water for 3 minutes.

• T h e y c a n b e s o a k e d i n 7 0 % isopropyl alcohol for 5 minutes.

• They can be immersed in 3% hydrogen peroxide solution for 30 minutes to disinfect.

It is important to remember that when using a mesh nebuliser, one should not touch the mesh during cleaning as it can get damaged. Mesh and ultrasonic nebulisers can only nebulise solutions and not suspensions due to the risk of clogging and breaking up of the drug particles with the use of a suspension. Corticosteroid products are usually in a suspension form and it is, therefore, preferable to administer them through a jet nebuliser.

Selection of the Right Device, Ensuring Compliance, and Patient Counselling

Once a correct diagnosis of asthma or COPD is made, choosing an appropriate inhaler device for a patient is critical for successful treatment outcomes. For disease management, an ideal inhaler would be one that is compact in size, provides the maximum doses, is preferably breath-activated, has inspiratory flow-independent lung deposit ion, is suitable for al l age groups, uses inhaler techniques that are easy to learn, teach and remember, has a dose counter, a reminder system and is cost-effective.70 So far, a perfect inhaler device like this does not exist and, therefore, there is a constant drive to develop newer and newer inhaler devices. Selection of the Right Device

T h e g u i d e l i n e s r e c o m m e n d individualising inhaled therapy for each patient, taking into consideration

patient preferences in conjunction with training and regular monitoring of inhaler technique.19 Choosing the correct inhaler device for the patient is crucial to ensure compliance and adherence to treatment and thereby achieve control of symptoms. Very little research has been carried out on how physicians should select the right inhaler device for the patient. The choice depends on several factors, including availability of the drugs in a particular device, the ability of the patient to use it (age, disease severity, education, and understanding), cost, and the likes and preferences of the treating physician.

Each type of inhaler requires a different inhalation technique and breathing pattern to achieve optimal del ivery of the medicat ion to the lungs. A pMDI requires slow and deep inhalation and actuation-inhalation coordination, whereas a DPI requires rapid and deep inhalation. It is seen that errors are made not only in inhalation technique but also in the handling of

Table 7: Correct steps for using a nebuliser

1. Assemble the apparatus.2. Load the prescribed medication in the medication

cup/medication reservoir. Dilute if required. Hold the cup stationary and screw on the cap of the medication cup.

Dilution of the nebulisation drug is to be done only with sterile saline and not with water. Dilution with water can cause bronchospasm.

3. Attach the mouthpiece/face mask to the nebuliser cup/reservoir. Attach the oxygen tubing (if required) to the nebuliser and the nebuliser cup/reservoir.

4. Sit in an upright position. Ensures better deposition of medication in the lungs.5. Switch on the nebuliser and begin treatment.

Although it is okay to breathe normally (tidal breathing), it is advisable to inhale deeply and slowly through the mouth as the aerosol begins to flow, and then exhale slowly.

Allows the drug particles to reach the small airways.

6. When the treatment is complete (you will hear a sputter), switch off the unit and then properly clean and disinfect the device for reuse.

There is a small residual volume of drug, which remains in the medication cup at the end of nebulisation that cannot and should not be nebulised. Helps avoid spread of infection and damage to the device (for more details, please see the paragraph Importance of Cleaning and Disinfection of the Nebuliser and its Parts).


• Acute symptoms or very severe airflow limitation (FEV1 < 30% of predicted);

• Patient is unable to take rapid and deep inspiration*

Patient’s ability to inhale voluntarily

• Chronic maintenance, mild to severe airflow limitation (FEV1 > 30% of predicted);

• Patient is able to breathe in deeply and rapidly*

pMDI + spacer ± face mask

Nebuliser

BAI#

pMDI ± spacerDPI

Yes

DPI pMDI ± spacer

BAI

DPI (Multidose)

pMDI + Spacer + Mask

Nebuliser

No

Can Coordinate Cannot Coordinate

Unable to prepare DPI for inhalation

pMDI – Pressurized metered dose inhaler; DPI – Dry powder inhaler; BAI – Breath-actuated inhaler* This is a general guidance but can vary between patients. The final decision should be based on clinical judgement# After checking that patient can actuate the BAI

Fig. 10: Selection of device: A practical guide by the authors to choose a device for the patient based on the inspiratory technique or ability of a patient

Table 8: Common myths about inhalers

Myths FactsInhalers are addictive Inhalers are not addictive. Medications delivered through inhalers help to

control the symptoms of the disease and the quality of life without causing significant side effects. They must be taken regularly to help lead a near-normal life.

Inhalers cause a lot of side effects

When used at the recommended doses, inhalers rarely cause side effects. Inhalers are the safest, fastest and most effective way of delivering medications directly to the lungs. The amount of drug used in inhalers is in micrograms, a fraction of that used in oral drugs

Why should a patient use inhalers when tablets and syrups are available?

Inhalers are the safest, fastest and more effective way of taking medication than oral medications. This is because inhalers provide better disease control at doses up to 20 times lower as compared with oral formulations.

Inhalers are the last resort for the treatment of asthma or COPD

No. In fact, inhalers are the first and foremost form of medications to be given in all patients with asthma and COPD, as recommended in the GOLD and GINA guidelines.

Inhalers are very costly In developing countries like India, inhalers are available at a very low cost and per dose cost of inhaled therapy is as affordable as tablets and syrups.

inhaler devices, such as preparing the device for use and subsequent usage. In addit ion, healthcare providers may also not know how to use the inhalers correctly. Importantly, poor inhalation technique can be associated with a marked (up to 50%) decrease in the amount of drug deposited in the lungs.71

A systematic review of randomised, controlled clinical trials on inhaler selections by the Joint Committee of the American College of Chest Physicians (ACCP) and the American College of Asthma, Allergy and Immunology (ACAAI) to provide recommendations to clinicians to aid them in selecting a particular aerosol delivery device for their patients has given an overview of

the type of devices suitable for different pat ients based on their abi l i ty to perform the inhalation techniques.72 The pMDIs are convenient for delivering a wide variety of drugs to a broad spectrum of patients. The crucial steps in the inhalation technique appear to be deep inhalation following complete e x h a l a t i o n ( f u n c t i o n a l r e s i d u a l capacity), which has to coincide with device actuation and at a slow and steady inspiratory f low rate . For patients who have trouble coordinating the inhalation with device actuation, the use of a spacer with a valve may prevent this difficulty. The use of spacers, however, is mandatory for infants and young children. The choice of inhaler device should be based on

the child’s age and capability. The preferred device is a pMDI and spacer with a face mask for children below 4 years of age and a pMDI with a spacer for children over 4 years of age. DPIs, on the other hand, are usually easier for patients to handle, but the key issue in dry powder inhalation is generating an adequate inspiratory flow rate. Severely ill patients who are confused and uncooperative, or those with advanced respiratory disease and very young patients may not be good candidates for a DPI due to their inability to generate an adequate inspiratory flow or volume.The Device Checklist

A g o o d s t r a t e g y f o r t r e a t i n g physicians will be to get familiar with all the available inhaler devices that their patients may need and adapt a methodical systematic approach towards se lec t ion o f the inha ler device. A device checkl ist can be useful to facilitate device selection, individualised for each patient for the short-term or long-term management of the disease. Questions on the patient’s device preference, availability of the drug in the preferred device format in the geographical location of the patient, the patient’s abil ity to coordinate actuation and inhalation and also generate sufficient inspiratory flow,


Table 9: Advantages and disadvantages of inhaler devices16,23,75–78

Advantages DisadvantagespMDIs• Portable and convenient to carry. • pMDIs require proper coordination between

actuation and inhalation, which may be a challenge, especially in children and the elderly.

• Reproducible dosing with each actuation throughout the life of the inhaler canister.

• Requires use of propellants such as HFA (hydrofluoroalkanes)

• Aerosol dose released is independent of the patient’s inspiratory effort.

• Excipients in the inhaler may occasionally cause paradoxical cough and bronchoconstriction.

• Usable in almost all clinical situations, both acute and chronic, and across age groups with suitable add-on devices such as spacers and face masks.

• The drug, when released under pressure, is at a low temperature and can cause pharyngeal irritation.

• Since it contains many doses and can last for a long period, it is economical when considering per dose cost.

• Nearly 75% of the drug from the pMDIs is deposited in the oropharyngeal region and this may lead to local/systemic side effects in a small proportion of patients when high doses are used.

• Irrespective of the manufacturing company, the technique for using a pMDI remains the same.

• High oropharyngeal deposition leads to side effects such as oral candidiasis, change in voice quality, and increased hoarseness of voice.

• The contents of the inhaler canister are protected from contamination or oxidation.

BAIs• No coordination required between actuation and

inhalation. • Patients may stop inhaling as soon as they hear

a click (as seen with some BAIs) or feel the medication in their mouth.

• No need to use a spacer. • Though these devices are auto-actuated, BAIs involve a step of manually loading the dose.

• Low inspiratory effort required. • Are more expensive than pMDIs or unit-dose DPIs.

• Delivered dose is independent of inspiratory flow.

• Increased lung deposition (21%) as compared with an incorrectly used pMDI (7%).

• Simple to learn and use. • Can be used across all age groups, including

children and the elderly.DPIs• No need for patient coordination. • High oropharyngeal deposition, leading to side

effects such as oral candidiasis, change in voice quality, and increased hoarseness of voice, etc.

• Easy to teach: The general perception is that the DPI is simpler to use compared with a pMDI.

• Vulnerable to ambient humidity as well as exhaled air. This may reduce the efficiency of the DPI.

• Fewer device-handling steps, thereby reducing the chances of errors. Fewer errors may improve patient adherence and treatment efficacy.

• If the DPI is held incorrectly after dose preparation, the dose may fall from the inhaler, leading to drug wastage.

• Use of discrete multidose inhalers reduces the chances of error by patients.

• Dependent on the patient’s inspiratory flow rate. Insufficient flow rates lead to reduced lung deposition of medication.

Nebulisers• Nebulisers can be used during acute

exacerbations of asthma and COPD, when the patient is critical or unconscious, and when the required medication is not available in an inhaler format.

• Possible toxicity caused due to high dosages compared with inhalers.

• Nebulisers can also be used when high doses of bronchodilators are required to be given along with supplementary oxygen in patients with asthma.

• High oral deposition.

• Risk of transmission of airborne infections. • Nebulisers typically require longer time for drug

delivery (15–20 minutes).• Requires regular maintenance of the device.

and affordability of the device should be considered (Figure 10).73

Is the desired device affordable to the patient?

I n d e v e l o p i n g c o u n t r i e s l i k e India, the cost of medical care and

affordability of the prescribed treatment is a huge concern amongst the majority of the patients, especially in chronic disease conditions requiring long-term treatment. Affordability has a direct impact on patient compliance with

treatment, which, in turn, impacts t h e d i s e a s e c o n t r o l o r s y m p t o m improvement and, hence, plays a major role in disease management. Would the patient be able to generate good inspiratory flow?

The inspiratory technique or the ability to actuate is one of the key factors in choosing an inhaler device for the patient. Figure 10 details a practical guide by the authors to choose a device for the patient based on his/her inspiratory technique or ability.73

In what device is the desired drug available in the patient’s city/geographical location?

If the prescribed device or drug combination is not available easily to the patient, the risk of non-adherence and non-compliance to therapy or the patient taking a wrong replacement device or drug given by a dispensing pharmacy as an alternative treatment is very high.Will the patient be able to coordinate the actuation and inhalation?

This is a crucial requirement when only a pMDI is used. When in doubt, adding a spacer to the pMDI or using a BAI would be a more beneficial approach for the patient.Does the patient have a preference for any particular device?

Offering a choice of inhalers to patients can be a problem for those who do not have a clear understanding on the different types of inhalers and their advantages or disadvantages. A patient might go by the look and feel of the product rather than considering practical points such as ease of use and affordability. A choice of inhalers could be offered only to those patients who are well informed about the disease and the available treatment options. Can the patient generate sufficient inspiratory flow?

Due to the ease of use and availability of a better range of combinations, DPIs are very widely prescribed inhalers in India. In order to be able to prescribe a DPI to a patient, it is important for the physician to understand whether the patient is able to generate a sufficient inspiratory flow required for successful drug delivery by a DPI. A fast and prolonged inspiration from the start is essential for DPI use. A visual inspection during the first follow-up visit wherein the patient is requested to take his/her regular dose via a DPI


in front of the physician can provide a fair idea as to whether the patient is a good candidate for a DPI prescription.Does the patient understand the importance of the inhaler technique?

Incorrect inhaler technique is an independent risk factor for exacerbation in asthma and COPD patients.1,2 A physician’s responsibility does not end with a one-time teaching of the inhaler technique to the patient. Emphasis has to be laid on the practice and use of the correct inhalation technique by the patient by checking the same repeatedly, at intervals. Therefore, scheduling the first follow-up visit within 7–10 days of prescribing and teaching an inhaler technique to the patient gives the treating physician an opportunity to recheck and correct any incorrect inhaler technique of the pat ient and a lso provides an opportunity for patient counselling to address all the concerns of the patient and family members/caregivers and thus improve the treatment outcomes. Now, there are inhaler education videos and virtual educators available through the manufacturers and many associations and, hence, patients should be encouraged to visit the appropriate websites to access information on correct inhalation technique.Adherence to Inhalation Treatment

P o o r p a t i e n t c o m p l i a n c e w i t h inhaled medication therapy is a known cause of morbidity and mortality in OADs.

Various factors contributing to poor compliance or poor adherence in inhalational treatment for OADs include the following:• Chronic nature of the disease

requiring long-term treatment and follow–up.

• Myths associated with the use of inhalers that deter patients from long-term use.

• Lack of knowledge about the diseases.

• A false sense of wel lbeing or a c h i e v e m e n t o f c u r e a f t e r b r o n c h o d i l a t o r s c o n t r o l t h e symptoms.

• Poor inhaler technique affecting drug deposition and efficacy.

Patient education and awareness on the disease, benefits of inhalation therapy and need for good treatment compliance are the keys to ensure good

patient adherence to treatment and thereby help improve health outcomes in patients with asthma and COPD.74

Recommendation:Healthcare providers, espec ia l ly t reat ing physic ians , need to understand and appreciate the role of patient counselling and patient education in the management of OADs. Educating the patient on the correct inhaler technique and dispelling the common myths or concerns that patients have about inhaler therapy are key to the successful management of OADs in patients (Tables8and9).

Conclusion and Summary

Inhalation therapy is the safest, fastest and most effect ive way to deliver drugs directly to the airways in patients with asthma and COPD. All patients with asthma and COPD must, therefore, receive inhalation therapy, be it bronchodilator drugs such as beta-adrenergic agonists or muscarinic antagonists, or anti-inflammatory drugs such as corticosteroids. Inhalation therapy can be delivered by different devices and are largely divided into three groups, viz. pMDIs (including BAIs), DPIs (unit dose or multidose) and nebulisers. Each of these devices has its own advantages and drawbacks. Spacers and face masks are accessories that can be used with the pMDIs. When using the pMDI, the inhaled breath needs to be slow and deep; with the DPI, it should be rapid and deep. In infants and children, pMDIs are preferred with a face mask or spacer. Spacers should preferably be conical in shape and should be made of non-static material. They overcome the need for actuation-inhalation co-ordination, reduce oropharyngeal deposition and eliminate the cold-freon effect. When using high doses of inhaled corticosteroids in asthma, pMDIs and spacers are the devices of choice as they reduce the s ide effects of oropharyngeal deposition significantly. There are several myths and misconceptions about inhalation therapy and these need to be cleared up by the treating physician through proper education and counselling. Physic ians must choose the r ight device for their patient, taking into consideration the patient’s skill and ease in using the device correctly. It is important for the physician to check the inhaler technique during every visit to ensure that the patient is using i t correct ly . Maintaining adherence to inhalation therapy is a challenge and must be overcome through good communication and

counselling. Inhalation therapy for asthma and COPD can save lives and reduce the suffering and economic loss associated with these very common OADs and must, therefore, be widely used in our country.Sources of financial support

T h i s d o c u m e n t wa s p r e p a r e d through an unrestricted educational grant from Cipla Ltd.

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