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