spirometry interpretation inhaler particles...interpretation of spirometry 2. overview of asthma...
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Spirometry interpretationInhaler particles
Thomas G. Saba, MD
Assistant Professor
Pediatric Pulmonology
University of Michigan
Objectives
1. Understand indications and interpretation of spirometry
2. Overview of asthma pathophysiology3. Understand how delivery methods and
particle sizes of aerosolized medications affect drug delivery
SPIROMETRY
Pulmonary function testing
• Spirometry• Plethysmography• Diffusion capacity• 6-minute walk test• Infant pulmonary function testing• Nitrogen washout
Spirometry
• Can detect and quantify obstruction• Can detect restriction• Described a pattern, not a disease
Spirometry
• Technique• Record name, age, sex, race, height• Patient sitting or standing• Take a few tidal breaths• Inhale deeply • Blow air through mouthpiece as fast as possible• Continue to blow until no air is left• Repeat at least 3 times and check for acceptability and
repeatability
Demonstration
Volume-Time curve
Flow-volume loop
Flow is the slope of the volume-time curve
Volume-Time curve
Forced viral capacity (FVC)
Forced expiratory volume in 1 second (FEV1)
Forced expiratory flow between 25% and 75% of VC (FEF25-75
FVC – vital capacityFEV1 – volume exhaled in 1 secondFEV1/FVC – ratio of volumesFEF25-75% - expiratory flow during mid-portion of exhalationPEF – peak expiratory flowFET100% - forced expiratory timePIF – peak inspiratory flow
Acceptability
• Good start with extrapolated volume <5% of FVC or 0.150, whichever is greater
• No artifacts (cough, glottic closure, leak, obstructed mouthpiece)
• No early termination of FVC• Max effort
Reproducibility
• Ideally, 3 acceptable tests with FVC or FEV1 within 0.150 L of each other
At least three trials
Acceptability and reproducibility of results
Display of the best of the trials for interpretation
What are the reference values?
Spirometry reference values
• Compared to average in healthy population (height, age, sex, race/ethnicity)• NHANES III 1999• GLI 2012 (accounts for wider ethnic variability)
• What is normal?• Less than 80% of predicted represents disease?• Less than 5th percentile (LLN, z-score -1.645)
represents disease?
Volumes 5th
percentilePercent
predicted
General concepts
• Obstructive pattern• Disproportionate reduction of FEV1 in
relation to FVC• Restrictive pattern
• Proportional reduction in FEV1 in relation to FVC
Grading severity of obstruction
Degree of severity FEV1% predicted
Mild >70Moderate 60-69Moderately severe 50-59Severe 35-49Very severe <35
FEF25-75
• Earliest changes associated with airflow obstruction in small airways is a slowing in the terminal portion of the spirogram
• This parameter has not demonstrated added value for identifying obstruction
Approach to interpretation
1. Assess acceptability and reproducibility2. Any unusual shape of flow volume loop?3. Determine if normal, obstructive,
restrictive or mixed4. Determine severity5. Need for bronchodilator challenge?6. Compare to previous
Examples
FEV1 FVC Ratio Interpretation70% 90% 75% Mild obstructive
pattern65% 72% 90% Restrictive
pattern45% 65% 70% Mixed
1. Assess acceptability and reproducibility2. Any unusual shape of flow volume loop?3. Determine if normal, obstructive,
restrictive or mixed4. Determine severity5. Need for bronchodilator challenge?6. Compare to previous
ASTHMA PATHOPHYSIOLOGY
Asthma basics
ATOPY
HUMAN MICROBIOME
VIRAL INFECTIONS
GENETICS
ENVIRONMENT
ASTHMA
“Hygiene Hypothesis”
RSV, Rhinovirus
Pollution, chronic lung disease of prematurity
Airway inflammation in asthma
Fahy JV, Locksley RM, 2011. Am J Respir Crit Care Med.
Airway histopathology in asthma
Wadsworth et al, 2011. J Asthma Allergy
PARTICLE PROPERTIES
Delivery devices
Metered dose
Ellipta
Twisthaler
Respimat
RespiClick
DiskusRediHaler
Flexhaler
HandiHaler
Respules through nebulization
Which inhaler to choose???
Inhaler concepts
• Use lowest possible dose of ICS to keep asthma under control
• Metered dose inhalers should ALWAYS be used with a valved-holding chamber
• Children less than 6 should not use breath-actuated devices
The problem with inhaled medications
Using traditional MDIs, where drug is in suspension (CFC), without a valved holding chamber
80% oropharyngeal deposition
Lower airways occupy 98% of lung volume!
Asthma is a lower airway disease
Inhaled medication characteristics
• Size (MMAD)• Airway characteristics• Propellant properties (CFC vs HFA; DPI
vs MDI)• User properties
MMAD = mass median aerodynamic diameter
Particle Size
Particle behavior
• Impaction• Large particles (>6um)• As the steam of air changes at branching
points, large particles hit the walls
• Sedimentation• Mechanism of small particle (<5um)
deposition• Smaller airways• Using a breath-hold helps deposition
• Diffusion• In low flow situations, very small particles
(<0.5um) move by Brownian movement from areas of high to low concentrations
• Random collision into airway walls• Without breath-holding, particles are mostly
exhaled
• Electrostatic deposition• Mostly for larger particles in nasopharyngeal
airway• As particles become humidified, charge
dissipates
Technetium-99m-labeled monodisperse albuterol aerosols
1.5um 6um3um
Nave, 2013
Inhaler particle sizes
Inhaler particles sizes are usually 2-5 um in diameter
MMAD = mass median aerodynamic diameter
Naso/oropharynx deposition
• Oral candidiasis• Dysphonia• Pharyngitis• Decreased drug available to lower
airways• Systemic absorption
Airway characteristics
Greater risk for impaction of large particles in smaller and narrowed airwaysRottier 2013
Particle properties
Propellants
HFA (hydrofluorocarbon) vs CFC (chlorofluorocarbon)
• CFCs banned in 1987 (Montreal Protocol)• HFA is a solution that evaporates; CFC is
suspension• Offers greater proportion of small particles
for inhalation
Lung deposition
• Better lung deposition with HFA
Lung deposition
Leach, 2009
Smaller MMAD and greater lung deposition with HFA
Lung function
• Better clinical outcomes with HFA?FEV1 after formoterol administration using HFA pMDI, CFC pMDI and DPI
Langley, 2005
Fluticasone DPI (MMAD 5.4um) vs Ciclesonide HFA-MDA (MMAD 0.9um)No change in spirometry but improved lung inflammation in Ciclesonide group
Hoshino, 2010
Ciclesonide
• Small particle size, better small airway deposition
• Pro-drug (converted in airways to active metabolite)
• Once-daily dosing (improve adherence)• Improved asthma control and reduced
side effects neither demonstrated nor refuted Cochrane Database Syst Rev 2013
User properties
Slower inhalation improves proportion of particles reaching lower airways
Rottier 2013
Inhalation flow
pMDI• Slow inhalation
DPI• Rapid inhalation flow (60L/min) for some
(Flexhaler)• Low to moderate inhalation flow (30L/min)
for others (Diskus)
Valved holding chamber
Reduces velocity and size of aerosol particlesRetains non breathable particles (>10um)
Avoids need to coordinate breath with actuation
Inhalation technique
pMDI/spacer; mask not tight
nebulizer; mask not tight
pMDI/spacer; tight mask; screaming
nebulizer; tight mask; screaming
pMDI/spacer; tight mask; quietly breathing nebulizer; tight mask; quietly breathing
Erzinger S, 2007
Summary
• Spirometry helps to determine the severity of obstruction
• Asthma is a chronic inflammatory disease causing airways obstruction
• Particle sizes of 2-5um ideal for small airway deposition
• Children with asthma risk poor peripheral distribution because of small obstructed airways
Summary
• HFA particles are smaller and better distributed than CFC
• DPI particles tend to be larger than MDI particles
• Valved holding chamber is needed with MDI
• Slow inhalation with MDI; more rapid with DPI