Pediatric Asthma by liaoqinmei


									Pediatric Asthma

   • This presentation focuses on medication and prevention specifically as they relate
      to children with asthma

Guidelines Update: An Overview of the Pathogenesis of Asthma
   • ―Asthma is a chronic inflammatory disease of the airways that has created a
      significant public health burden.‖
   • Many cells and cellular elements, in particular, mast cells, eosinophils, T
      lymphocytes, neutrophils, and epithelial cells, play a role in the inflammation
      associated with asthma.
   • In susceptible individuals, inflammation causes:
          – Increased bronchial hyperresponsiveness to various stimuli
          – Recurrent episodes of wheezing, breathlessness, chest tightness,
              and cough
          – Widespread, variable airflow obstruction that often is reversible
              with treatment

Asthma Predictive Index (API)
   • The API was originally developed by Castro-Rodriguez et al based on data from
     the Tucson Children’s Respiratory Study.
         – A stringent index requires frequent wheezing in the first 3 years of life
             plus 1 of 2 major criteria (parental diagnosis of asthma, diagnosis of
             eczema in the child) or 2 of 3 minor criteria (diagnosis of allergic rhinitis
             in the child, eosinophilia [ie, eosinophils 4% of the total white blood
             cells], wheezing apart from colds).
         – A loose index for the prediction of asthma requires any wheezing during
             the first 3 years of life plus 1 of 2 major criteria or 2 of 3 minor criteria.
         – Children with a positive loose index were up to 5.5 times more likely to
             have active asthma between 6 and 13 years of age compared with children
             with a negative loose index. Children with a positive stringent index were
             up to 9.8 times more likely.
   • The Prevention of Early Asthma in Kids (PEAK) criteria for a modified API
     (mAPI) were adapted from the Tucson Children’s Respiratory Study’s original
     tool and are more specific than the original API criteria.
         – The mAPI criteria specifiy the frequency of wheezing as >3 exacerbations
             of wheezing in the past 12 months or at least 1 physician-confirmed
         – Additionally, the mAPI specifies allergic sensitization to 1 aeroallergen
             among the major criteria and replaces allergic rhinitis as a minor criterion
             with allergic sensitization to milk, egg, or peanuts.
   • The PEAK study was designed to investigate the role of ICSs in preventing
     persistent asthma in children with a positive mAPI.
When to Consider Long-term Treatment for Infants and Children
  • Diagnosing asthma in infants and children can be clinically challenging.
  • The NAEPP provides special considerations for when initiation of long-term
      controller treatment should be considered for children 5 years and younger.
  • Along with asthma symptoms and objective measures (if feasible), treatment
      should be considered in the following situations:
          – Positive API and more than 3 wheezing episodes lasting more than 1 day
              and affecting sleep
          – Consistent requirement for symptomatic treatment more than 2 times per
          – Severe exacerbations less than 6 weeks apart requiring inhaled 2-
              adrenergic agonist treatment more than every 4 hours for 24 hours
  • When it has been determined that ICS therapy is necessary for the treatment of
      asthma in children, several treatment options are available.

Stepwise Approach to Asthma Therapy for Children Aged 5 Years
   • For all patients at all severity levels, step-up and step-down therapy should be
          – Step down—review treatment every 1 to 6 months to determine if gradual
             stepwise reduction in treatment is possible.
          – Step up—consider if control is not maintained, after review of patient
             medication technique, adherence, and environmental control.
          – Gain control as quickly as possible; then, step down to the least
             medication necessary to maintain control.
Advantages of Inhaled Therapy in Patients With Asthma
  • The inhaled route for asthma medication delivery is generally preferred because
         – Higher concentrations can be delivered more effectively to the airways
         – Systemic side effects are avoided or minimized
         – The onset of action of short-acting β2-adrenergic agonists (SABAs) is
             substantially shorter when inhaled
  • The National Asthma Education and Prevention Program (NAEPP) and the
     American Academy of Allergy, Asthma and Immunology recommend the use of
     inhaled therapies for patients with any severity of asthma.
  • The NAEPP recommends the use of inhaled therapies for all severities of asthma
     in patients of every age.
         – Inhaled therapy is recommended for the long-term control and
             prophylactic treatment of asthma (eg, ICSs, long-acting β2-adrenergic
             agonists [LABAs]) and for the quick relief of asthma symptoms (SABAs).

Factors Affecting Inhaled Corticosteroid Delivery to the Lungs
   • Patient acceptance of and adherence to the use of a particular inhalation device
      and ability to properly use the device can affect medication delivery.
   • The aerodynamic size of aerosolized drug particles emitted from an inhalation
      device is one of the most important factors influencing lung deposition.
   • Particle velocity also may affect lung deposition, with lower velocity emissions
      reducing deposition in the oropharynx and optimizing drug delivery to the lungs.
   • pMDIs, DPIs, and nebulizers are available for the delivery of inhaled asthma
   • The inability to coordinate pMDI actuation and inhalation can result in high
      aerosol deposition in the oropharynx and variability in lung delivery. The use of
      spacers and holding chambers can help overcome this problem.

Patient Variables
   • A patient’s physical and cognitive abilities and willingness to use a particular
       inhalation device should be considered when prescribing asthma therapy.
   • Physical characteristics of a particular patient population may lead to less
       effective drug delivery with specific inhalation devices. For example, dry-powder
       inhalers may be less effective in very young children, and unmodified pMDIs
       may be less effective in patients with arthritis.
   • Inspiratory flow rate, upper airway anatomy, and degree of airway obstruction are
       additional patient variables that influence drug deposition in the upper and lower
Challenges of Inhaled Therapies for Young Children
  • Delivery of inhaled therapy to infants and young children is associated with
      unique challenges due to anatomy, physiology, and cognitive development in this
      patient population.
  • Because infants have small airways, it is likely that drug deposition will be
      greatest in the upper and central airways; however, lower inspiratory volumes and
      flows in infants may lessen drug impaction in the upper and central airways.
          – High inspiratory flow rates (>30 L/min) can increase drug impaction in the
              upper airways and reduce the lung deposition.
  • A breathing pattern comprising slow inhalation coupled with breath holding can
      improve lung deposition of medication administered via a pMDI.
  • Infants and young children prefer nasal to mouth breathing; filtering of
      aerosolized drug in the nose may reduce deposition in the lungs.
  • Distress caused by the use of a face mask by infants and young children can lead
      to breaking of the face mask seal or alteration in breathing pattern, both of which
      may reduce the efficiency of lung deposition.
  • Drug deposition studies demonstrate greatly reduced drug deposition in the lungs
      of crying infants.

Aerosol Characteristics: Particle Size
   • The MMAD of aerosolized particles should be <5 m; particles 1 to 5 m in
      diameter are considered to be within the respirable range.
   • Particles between 1 and 0.1 m are too large to diffuse significantly and too small
      to be deposited by gravity in the airways. These particles remain suspended in the
      airstream and are generally exhaled.

Correlation Between Particle Size and Thoracic Deposition
   • This figure shows the percentage of aerosol deposited in the lungs, as a
      percentage of total body deposition, versus volume median diameter of inhaled
      aerosols for the studies listed.
   • A correlation exists such that greater particle diameter correlates with reduced
      lung deposition.
Particle Velocity and Patient Breathing Requirements by Device
   • This slide summarizes particle velocity and breathing techniques for the
       nebulizer, DPI, and MDI.3
   • Nebulizers generate particles at a slow velocity.
           – The optimal breathing technique for use of a nebulizer involves slow tidal
               breathing with occasional deep breaths, as well as use of a mouthpiece or
               tightly fitting face mask.
           – Use of nebulizers is less dependent on patient coordination or cooperation
               than use of MDIs or DPIs.
   • Particle delivery from DPIs is dependent on the patient’s inspiratory flow rate.
           – Generally, a high inspiratory flow rate needs to be produced by the patient
               to generate sufficient force to aerosolize the powder in the device.
           – Children younger than 4 years may not be able to generate the inspiratory
               force necessary to effectively use a DPI. Although some 4-year-old
               children can use a DPI effectively, children
               5 years and older are more likely to consistently produce a sufficient
               inspiratory effort.
   • Compared with a DPI, particle delivery from a pMDI is less dependant on the
       patient’s inspiratory flow.
           –   The optimal breathing technique for use of a pMDI is actuation during a
               slow (30 L/min) deep inhalation, followed by a 10-second breath hold.
               However, slow inhalation may be difficult.
           – The high velocity of aerosol being emitted from a pMDI after actuation
               makes it difficult to coordinate inhalation with device actuation; use of a
               spacer can help to slow drug delivery.
   •   The optimal breathing technique for using each device should be taught to the
       patient when the device is selected and reviewed regularly.

Inhalation Velocity Affects Lung Deposition With Nebulizer
   • This slide demonstrates the effect of inspiratory flow rate on the distribution of
       radiolabeled aerosol in the lungs of patients with asthma.
   • In a study by Laube et al, 9 patients aged 23 to 36 years with a history of allergic
       or exercise-induced asthma inhaled radiolabeled (99mTc sulfur) 0.9% buffered
       saline aerosol administered by a No. 42 De Vilbiss at a rapid (60 L/min) or slow
       (12 L/min) inspiratory flow rate on 2 study days.
   • Aerosol distribution in the airways was quantified by gamma-camera scan.
   • Methacholine challenge was performed after gamma scan; albuterol was
       administered to reverse airway obstruction after each challenge.
   • The amount of radiolabeled aerosol deposited in the trachea and lungs was
       reduced in 6 of 9 patients during rapid versus slow inhalation, but mean values
       were similar (5.1  3.0 L versus 5.2  2.3 L).
   • As shown in the scans, rapid inspiration resulted in greater heterogeneity in lung
       deposition and regions of higher-density labeling compared with slow inspiration.
   • Rapid inhalation resulted in greater aerosol deposition in the inner lung and less
       penetration to the lung periphery. The ratio of inner zone (large, central airways)
       to outer zone (peripheral airways and alveoli) deposition was 2.91  0.51 during
       rapid inhalation, compared with 1.84  0.30 during slow inspiration (P.001).
Examples of Delivery Devices for Inhaled Medications
   • Types of delivery devices for inhaled medications include pMDIs, (with and
     without holding chambers and spacers), DPIs (single capsules, multidose disks,
     and multidose reservoirs), and nebulizers (jet and ultrasonic).

Types of Nebulizers
   • There are 2 types of nebulizers currently available for use at home: jet nebulizers
      and ultrasonic nebulizers. Jet nebulizer/compressor systems provide a simple way
      to deliver inhaled medication to children and are the most common type of
      nebulizer used.
   • Some ICS preparations are suitable for oral inhalation use via a jet nebulizer
      connected to an air compressor with an adequate airflow, equipped with a
      mouthpiece or suitable face mask.
          – Suspensions and highly viscous solutions decrease the propagation of
              ultrasonic sound waves, thus decreasing effective output from ultrasonic
              nebulizers.20 In addition, these devices only nebulize the water and not
              the drug in a suspension; such devices may not be able to make a spray
              from viscous drug solution and may damage certain drugs.
Jet Nebulizer: Description
    • A jet nebulizer delivery system consists of a nebulizer and a source for
       compressed air. Air flow to the nebulizer changes the medication solution to a
       mist, which can be inhaled over 5 to 10 minutes.
    • Nebulizers are recommended for use in infants and very young children, as well
       as any patient unable to properly use an inhaler.
    • Nebulized medications can be delivered via face mask to facilitate medication
       delivery in very young children.

Some Advantages of Nebulizers
   • Because their use depends less on coordination and cooperation than inhalers,
      they are easy to use and can be used at any age.
   • Administration of high drug doses is possible, including continuous nebulization.
   • No chlorofluorocarbons are involved in the drug delivery mechanism.
   • Nebulizers can be used with supplemental oxygen.

Some Disadvantages of Jet Nebulizers
   • Jet nebulizers are less portable than inhalers; a power source and pressurized gas
      source are required.
   • Contamination is possible if the nebulizer components are not carefully cleaned.
   • The treatment time for small-volume jet nebulizers is longer than that for inhalers.
      However, ultrasonic nebulizers provide faster delivery than jet nebulizers.
   • Output is device dependent, with substantial internebulizer and intranebulizer
      output variances.3 Delivery may take 5 to 10 minutes or longer.

Technique for Optimal Nebulizer Use
   • Maximizing the efficiency of aerosol delivery from a nebulizer involves slow
      tidal breathing with occasional deep breaths, as well as use of a mouthpiece or
      tightly fitting face mask.
Blow-By Technique Reduces Inhaled Drug Exposure
   • The Sophia Anatomical Infant Nose–Throat (SAINT) model of the upper airway
      of a 9-month-old, nose-breathing infant was coupled with a PARI COMPAS™
      breath simulator to study the lung and throat deposition of Pulmicort Respules®
      (budesonide inhalation suspension [BIS]) from several nebulizer–face mask

Advances in Nebulizer Technology
  • Nebulizer technology continues to evolve, as evidenced by newer models that are
     more portable.
  • The devices shown in this slide are compact, lightweight, portable, and battery-
Some Advantages of pMDIs
   • Compared with most nebulizers, pMDIs are small and portable.
   • pMDIs provide efficient dose-dose reproducibility, can be used quickly, and are at
      least as effective as other delivery devices when used correctly.
   • pMDIs (and DPIs) are less time consuming than nebulizer systems.

Some Disadvantages of pMDIs
   • Because of the coordination of actuation and inhalation required to effectively use
      pMDIs, they can be difficult for elderly and very young patients to use correctly.
         – Elderly patients with physical (eg, decreased hand strength) and cognitive
            decline may have problems with pMDI use.
         – In children 5 years of age, pMDIs should be used with a spacer.
   • Many patients use their pMDIs incorrectly.45 Improper technique, such as open
      mouth versus closed mouth, affects dosing.
         – The procedure for using a pMDI is difficult to teach, and even health care
            providers are unclear about how to correctly use these devices.
         – High aerosol velocity leads to deposition of 80% of the actuated dose in
            the oropharynx. To reduce systemic absorption, mouthwashing is

Some Advantages of Valved Holding Chambers and Spacers
   • Valved holding chambers and spacers
          – Minimize the need for coordination between actuation of the pMDI and
          – Slow the velocity of the aerosol, which decreases oropharyngeal
              deposition to 5%-10%
          – Although the terms are often used interchangeably, a spacer is an
              extending device that allows the aerosol cloud to decelerate; whereas, a
              holding chamber is a ―valved spacer allowing breathing from a standing
              cloud of aerosol.‖
   • Valved holding chambers and spacers, therefore, allow pMDIs to be used by
      children (with closely fitted face masks), elderly patients, and handicapped
      patients, as well as any patient who experiences difficulty using a pMDI.

Steps Performed Improperly: MDI + Holding Chamber
   • The ability of children and adolescents to demonstrate proper technique when
       using an MDI with or without a holding chamber (HC) and a peak flow meter
       (PFM) was prospectively evaluated among children who presented to the
       emergency department for an acute asthma exacerbation.
   • A greater emphasis must be placed on teaching methods to optimize drug delivery
       and to instruct patients about the importance of monitoring disease severity.
Appropriate Inhalation: Timing Affects Drug Availability
  • Inappropriate use of a pMDI can affect drug delivery.

Some Advantages of DPIs
   • Advantages of DPIs include
        – Small size and portability enhance convenience
        – Can be quickly administered (1-2 seconds)
        – Less patient coordination required, compared with metered-dose inhalers,
           because they are breath actuated
        – Easy to use and teach
        – Do not require propellants, which may harm the earth’s ozone layer

Some Disadvantages of DPIs
   • The primary DPIs is the high rate of inhalation (60 L/min) required to use these
   • The particle size and velocity of the drug aerosolized are related to the patient’s
      rate of inhalation.
   • Because of the high inspiratory flow rate required, use of DPIs may not be
      suitable for children younger than 5 years; however, some 4-year-old children
      may be able to use a DPI.

Percentage of Children With Peak Inspiratory Flow 50 L/min
   • In a randomized, crossover study, Agertoft et al investigated the peak inspiratory
      flow (PIF) rate generated by 198 children aged 3 to 15 years.
   • In conclusion, drug delivery to a child with asthma varies with age, as well as the
      delivery device.
Measures of Inhalation Device Efficiency
  • Agents and devices that produce finer particles provide greater lung deposition
     than those that produce larger particles.18
  • Consistency in delivery of the dose from the device contributes to optimal
  • A treatment cannot be optimally effective if administration issues or side effects
     limit patient adherence.18
  • Regardless of the device selected, the ultimate outcome of asthma treatment is the
     achievement of therapeutic goals (eg, symptom relief).

Relevant Errors in Drug Delivery Device Use
   • Kofman et al interviewed 150 children and parents about aerosolized drug
      treatment after outpatient encounters at a hospital in Buenos Aires (4-5/2001).56
   • The interview questionnaire covered parents’ knowledge about disease, utility of
      treatment, and cleaning techniques for relevant delivery device. Children were
      interviewed when appropriate.56
   • A hands-on evaluation of inhalation technique also was performed. Patients using
      DPIs had peak inspiratory flow checked.56
   • Mistakes that could dramatically affect intrapulmonary drug deposition were
      deemed relevant.56
   • Proper use for each device is outlined below56:
          – Nebulizers – 81% demonstrated proper use.
          – MDIs with spacer/holding chamber – 64% demonstrated proper use.
          – DPIs – 42% demonstrated proper use.
Aerosol Characteristics Summary: Particle Size and Particle Velocity
   • Both particle size and particle velocity affect aerosol deposition in the
   • Particle size and velocity can be influenced by the inhalation device25,35 and
      patient variables.18,19,21
   • Increasing the proportion of small to large particles will improve the therapeutic
      index of an inhaled medication because there will be less impaction due to large
      (>5 m) particles in the oropharynx and greater deposition of small particles in
      the lower airways.19
   • Although lung deposition is generally greater with particles <5 m, very small
      particles (ie, with a mass median aerodynamic diameter of <1 m) may remain
      suspended in the airstream, with the majority (80%) being exhaled.7
   • At high speeds, large particles are more likely to deposit in the oropharynx.7
   • Individual patient variables and capability should be considered when selecting
      inhalation devices to ensure optimal lung deposition of aerosolized medications.
      Thus, the device selected should be appropriate for the needs of the patient.
          – While each device has its advantages and disadvantages for younger
              children, nebulizers are easy to use and are faster than once believed (with
              many models taking between 5-10 minutes).33,35
          – pMDIs are difficult to teach, learn, and use consistently because of the
              need to coordinate actuation with inhalation; use of a spacer facilitates
              proper use.3
          – DPIs are appropriate, however, for older children (5 years of age).6

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