Respiratory Measurements I

1
Respiratory Measurements I LUNG FUNCTION
TESTS PY3002
Dr P. KIPPELEN School of Medical
Sciences University of Aberdeen
2
LECTURE OUTLINE

• How to detect respiratory dysfunctions?
• methods available
• specificities / limits
• differential diagnosis
• Measures of lung volumes
• ? transport of O2 to the alveoli
• spirometry
• body plethysmography / helium dilution
• Gas exchanges
• ? diffusion of O2 into the bloodstream
• blood gases
• diffusing capacity
• Place of exercise tests in Respiratory Dept?

3
COMMON CHRONIC RESPIRATORY DISEASES

• Obstructive lung disorders
• ? ? airway resistance
• Asthma
• COPD (Chronic Obstructive Pulmonary Disease)
• Chronic bronchitis
• Inflammation of the bronchi
• Emphysema
• Destruction of the alveoli
• Prevalence
• 80 million people worldwide moderate to severe
  COPD
• In the UK 1, ? with age 10 in men older than
  75 (probably under-diagnosed!)

4
RESTRICTIVE RESPIRATORY DISEASES

• Loss of airway compliance
• lung stiffness
• incomplete lung expansion
• Fibrosis formation or development of excess
  fibrous connective tissue
• Cystic fibrosis (CF)
• Mutation of a gene
• ? thick and sticky mucus
• frequent lung infections
• Prevalence
• UK birth prevalence about 0.4 per
• 1,000 (300 new cases each year)

5
SPIROMETRY

• Forced expiration
• Simplest test
• One of the most informative
• Requires minimal equipment
• Trivial calculations
• Majority of patients with lung disease abnormal
  values
• Useful in differentiating between
• Obstructive
• Restrictive lung disorders

6
THE SPIROMETER

• Old version
• spirometer bell
• kymograph pen

• New version
• portable

7
RESPIRATORY MANOEUVRE
?
? Maximal breath in ? Maximal breath out
?
8
FEV1 FVC

• Forced expiratory volume in 1 second
• young trained athletes 4.0 L
• Forced vital capacity
• young trained athletes 5.0 L
• FEV1/FVC 80

FEV1
FVC
9
FLOW-VOLUME CURVE
in HEALTHY subjects
(in L/sec)
(in L)
FVC
10
FLOW-VOLUME CURVE
in respiratory patients
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REVERSIBILITY TO ?2-AGONISTS

• ?2-agonists bronchodilators
• ? Response of the bronchial smooth muscle?
• Method
• baseline spirometry (FEV1)
• inhalation of a ?2-agonists (e.g., 200mg
  salbutamol)
• 10min later spirometry (FEV1)
• if ? FEV1 ? 12 or 200ml positive test
• ? Reversibility of the obstruction (e.g., asthma
  but not COPD ? differential diagnosis)

12
BRONCHIAL PROVOCATION TESTS

• Exposure of the airways to a stimulus
• allergen
• exercise
• pharmacological bronchoconstrictive agent
• Response of the bronchial smooth muscle?
• baseline FEV1
• post-exposure FEV1
• ? Airway hyperresponsiveness

drop in FEV1
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EXERCICE TESTING
5
4
Normal subject
3
Drop in FEV1 ? 10 positive test
FEV1 in Litres
2
Asthmatic patient
Spirometry
Exercise
1
14
20
0
8
Time in Minutes
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LUNG VOLUMES
15
LUNG VOLUMES
Dead space
Tidal volume
? Residual Volume
? Total lung capacity
Expiratory reserve volume
Tidal volume
Vital capacity
Inspiratory reserve volume
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TOTAL LUNG CAPACITY

• Measured by
• body plethysmography
• helium dilution
• Body plethysmography
• mouthpiece obstructed with shutter
• rapid panting
• chest volume expand and decompress the air in
  the lungs
• changes in pressure inside the box allow
  determination of the lung volume

? By applying Boyles law (P V constant) ? TLC
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TOTAL LUNG CAPACITY
At beginning After several minutes

• Helium dilution
• - Spirometer of known volume and helium
  concentration connected to the patient
• - Closed circuit
• - Law of conservation of mass

He initial Vs He final (Vs VL)
? Unknown lung volume can be calculated
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RESIDUAL VOLUME
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INTERPRETATION of RESULTS

• In patients with obstructive diseases
• airway closure occurs at an abnormally high lung
  volume
• ? ? FRC (functional residual capacity)
• ? ? RV (residual volume)
• Patients with reduced lung compliance (e.g.,
  diffuse interstitial fibrosis)
• stiffness of the lungs recoil of the lungs to
  a smaller resting volume
• ? ? FRC
• ? ? RV

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GAS EXHANGES

• ? Blood gases
• most important measurement in the management of
  respiratory failure
• puncture of the radial artery or
• indwelling radial artery catheter
• PaO2
• normal value 95 mmHg (85-100)
• ? with age (85 mmHg at 60)
• ? VA/Q inequality
• diagnosis hypoxemia ? in PaO2
• common in patients with severe COPD
• ? oxygen therapy

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CAUSES OF HYPOXEMIA
Diffusion impairment

• Hypoventilation
• ? alveolar ventilation
• Diffusion impairment
• ? blood-gas barrier thickening
• ? contact time
• Shunt
• VA/Q inequality
• residence at high altitude

O2
Shunt
22
BLOOD GASES

• PaCO2
• normal values 37-43 mmHg
• almost unaffected by age
• Cause of ? PaCO2
• hypoventilation
• VA/Q inequality
• ? blood-gas barrier thickening
• ? contact time
• pH
• acidosis
• respiratory acidosis / metabolic acidosis
• alkalosis
• respiratory alkalosis / metabolic alkalosis

23
GAS EXHANGES

• ? Diffusing capacity
• of the lungs to CO (DLCO)
• manoeuvre
• vital capacity breath of 0.3 CO 10 helium
• breath holding for 10 sec
• full exhalation
• Why CO?
• CO taken up by the blood along the capillary
• uptake of CO determined by
• diffusion properties of the blood-gas barrier
  (thickness area)
• rate of combination of CO with blood ? number
  cells in capillaries
• DLCO ? in COPD patients
• loss of alveolar-to-capillary surface
• very severe airway obstruction

24
EXERCISE TESTS

• Why exercise?
• at rest, the normal lung has enormous reserves
  of function
• during exercise ? reserves
• ? exercise can reveal minor dysfunctions
• to assess disability
• Progressive exercise test to exhaustion
• ergocycle
• VO2max symptom-limited
• Common variables
• work load
• total ventilation
• respiratory frequency
• tidal volume

• HR
• ECG
• blood pressure
• VO2, VCO2
• arterial PO2, PCO2 and pH

25
DYSPNEA

• Sensation of difficulty with breathing
• demand of ventilation out of proportion to the
  patients ability to respond to that demand
• index of exercise tolerance
• Inability to adjust CO2 and pH
• Common in - unfit people
• elderly people
• respiratory patients
• Poor perception of dyspnea in children ?
  undiagnosed asthma (Van Gent et al., Eur Respir
  J, 2007)
• Assessment with a dyspnea scale (0-10) at the
  end of each step of a VO2max test/bronchial
  provocation test
• ? But difficult very subjective

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KEY POINTS

• To identify lung dysfunctions
• lung volumes
• gas exchanges
• adaptations to exercise
• Spirometry
• widely used test
• measurements of lung volumes (expect RV)
• differential diagnosis between
• Obstructive versus restrictive lung disorders
• COPD versus asthma

27
Respiratory Measurement II HOW TO DETECT
ASTHMA IN ATHLETES? PY3002
Dr P. KIPPELEN School of Medical
Sciences University of Aberdeen
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APPENDIX A OF THE OLYMPIC ANTI-DOPING CODE

• The List of Prohibited Substances and Prohibited
  Methods dated 1st January 2003 states that
• Formoterol,
• Salbutamol,
• Salmeterol,
• Terbutaline
• are Permitted by inhaler only to prevent and/or
  treat asthma and exercise-induced asthma.

29
2001 IOC WORKSHOP

• Recent Olympics ?? in the number of athletes
  notifying the need to inhaled a beta2-agonist
  (IBAs)

Games IBAs Athletes
Percent Los Angeles 1984 119
6802 1.7 Atlanta 1996
383 10677 3.6 Nagano
1998 128 2296 5.6
Sydney 2000 607 11087
5.5 NB At Seoul and Barcelona notification
unnecessary. Notifications from Montreal
unavailable
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2001 IOC WORKSHOP

• High prevalence of misdiagnosed asthma/EIB in
  the athletic population (Rundell et al., 2001)
• No scientific evidence to confirm that IBAs ?
  performance
• at pharmacological doses!
• but
• beta2-agonists, when administered systemically,
  do have anabolic effects
• Skewed distribution of notifications of IBAs by
  sport with a higher prevalence in endurance
  sports

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2001 IOC WORKSHOP

• MEDICATION
• - Under-use of inhaled corticosteroids
• - Daily use of IBAs may result in tolerance and
  increased airway reactivity (Inman MD et al.,
  1996 Hancox RJ et al., 1999, 2002)

(Hancox RJ et al., AJRCCM, 2002)
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MAJOR OUTCOME

• ? Since Salt Lake City (2002) athletes have to
  prove they have got asthma / EIB to be allowed to
  take IBAs
• - approval given by an independent scientific
  panel of the IOC-MC
• Which pulmonary function tests can be used ?
• baseline spirometry but (supra)normal values
  usually registered in elite athletes
• only very few with a positive reversibility
  test
• 12 FEV1 from baseline
• ? bronchial provocation tests often necessary

33
BRONCHIAL PROVOCATION TESTS

• Objective
• to detect airway hyperresponsiveness (AHR)
• Direct stimuli pharmacological
  bronchoconstrictive agents
• methacholine
• histamine
• ? only ONE mediator
• Indirect stimuli
• exercise
• hypertonic saline
• eucapnic voluntary hyperventilation
• mannitol
• ? a lot of mediators released

34
METHACHOLINE

• Inhalation of increasing doses of a
  pharmacological agent
• Response of the smooth muscle
• Dose or concentration that induce a 20 drop in
  FEV1
• Principal limits
• Non specific for the
• diagnosis of asthma
• (Langdeau JB et al., 1999)
• Do not exclude EIB

35
EXERCISE TESTING

• Methods
• High intensity exercise
• 6-8min duration
• Post-exercise spirometry (3, 5, 7, 10 15min)
• If FEV1 drop ? 10 consistent with EIB
• In the lab
• Choice limited to 2 or 3 ergometers
• Neutral air conditions
• ? False negative tests (Rundell KW et al., 2000)
• In the field
• Recommended
• But not always feasible
• ? Need surrogate challenges

36
HYPERTONIC SALINE

• Hypothesis
• changes in the osmolarity of the airways
• cells shrinks
• release of inflammatory mediators
• airway narrowing
• Methods
• exposure to a saline solution
• time progressively increased
• FEV1 recorded 1 min after each exposure
• If FEV1 fall ? 15 consistent with asthma
• ? Very messy

37
EUCAPNIC VOLUNTARY HYPERVENTILATION

• 6min of hyperpnoea
• dry air
• 4.9 CO2
• 10 fall in FEV1
• Specific for diagnosis of EIA (Rundell KW et al.,
  2004)
• Recommended by the IOC

38
MANNITOL TEST

• Principle change the osmolarity of the ASL fluid
  by inhalation of a dry powder
• ? if inflammation cells activated and mediators
  released (histamine, PG, LT)
• Inhaled agent Dry powder Mannitol (Sugar)
• Progressive Protocol 0, 5, 10, 20, 40, 80, 160,
  160 mg
• Measurements FEV1 Pre and at 1 min
  post dose
• Positive Response Fall in FEV1?15 or ?10
  for EIB
• Expression of result PD15 or PD20 for EIB
• Anderson et al., AJRCCM 1997156758-65
• Brannan et al., AJRCCM 1998 1581120-6

39
MANNITOL IN ASTHMATICS
(Anderson Brannan, Clin Rev All Immunol 2003
2427-54)
25
Severe
Moderate
Mild
?
?
gt
155 mg
35 mg
155mg
20
15
Fall FEV1
10
Normal
5
0
635
1
10
100
Cumulative dose of mannitol (mg)
40
SUMMARY
Measure spirometry (FEV1, FEV1/FVC)
FEV1 ? 75 predicted
FEV1 gt 75 predicted
Adapted from Anderson SD Kippelen P, 2004
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IBAs USE SYDNEY vs ATHENS

• SYDNEY 2000 ATHENS 2004
• (notified) (approved)
• NOC IBAs PERCENT IBAs PERCENT
• NZL 31 21.1 11 11.3
• AUS 128 20.7 65 13.7
• UK 62 19.9 62 23.3
• USA 112 18.9 50 9.1
• CAN 55 18.6 11 4.1
• FIN 10 14.3 4 6.6

Anderson SD et al., 2006
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IBAs USE WINTER GAMES
NOC TORINO SLC NAGANO 2006 2002
1998 NOR 31.9 9.9 14.5 NED
27.3 22.6 33.3 GBR 20.5 4.0 4.8 AUS
17.5 19.2 20.0 SUI 15.7 18.8
4.2 USA 12.1 12.9 16.9 IF ALL NOR
APPLICATIONS HAD BEEN APPROVED 21.0
Source IOC independent asthma panel
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ASTHMA IN TEAM GB
Dickinson JW et al., 2005
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CONSEQUENCES OF THE NEW RULE

• Dickinson JW et al., Thorax, 2005
• ? false positive diagnosis
• 21 of athletes with a previous diagnosis of
  asthma have failed to demonstrate evidence of
  asthma
• ? false negative diagnosis
• 10 of athletes with no history or previous
  diagnosis of asthma were tested positive
• ? Only athletes who need the medication get it!

45
ASTHMA MEDALS IN ATHENS

• 56 athletes met the criteria to use asthma
  medication
• They won
• - 7 Gold
• - 7 Silver
• 3 Bronze medals
• 13 athletes failed to meet the IOC criteria and
  were subsequently removed from asthma medication
  won
• 2 Gold medals
• ? Asthma and sport not incompatible !!!

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KEY POINTS

• Since Salt Lake City, compulsory for Olympic
  athletes to prove they have got asthma / EIB to
  use IBAs
• approval given by a scientific independent panel
  of the IOC-MC
• Recommended tests for the diagnosis of
  asthma/EIB in athletes
• exercise tests
• eucapnic voluntary hyperpnea
• Systematic screening for asthma in elite
  athletes
• ? number of misdiagnosis
• better management of the disease

47
FURTHER READING

• BOOKS
• Allergic and respiratory disease in sports
  medicine. Weiler JM. Clinical Allergy and
  Immunology, Marcel Dekker, 1997
• Pulmonary pathophysiology. The essentials. Fifth
  Edition. West JB. Williams Wilkins, 1995
• ORIGINAL PAPERS
• Dickinson JW, et al. Impact of changes in the
  IOC-MC asthma criteria a British perspective.
  Thorax. 2005 Aug60(8)629-32.
• Anderson SD, et al. Responses to bronchial
  challenge submitted for approval to use inhaled
  beta2-agonists before an event at the 2002 Winter
  Olympics. J Allergy Clin Immunol. 2003
  Jan111(1)45-50.
• REVIEWS
• - Anderson SD, Brannan JD. Methods for "indirect"
  challenge tests including exercise, eucapnic
  voluntary hyperpnea, and hypertonic aerosols.
  Clin Rev Allergy Immunol. 2003 Feb24(1)27-54.
• Rundell KW, Jenkinson DM. Exercise-induced
  bronchospasm in the elite athlete. Sports Med.
  200232(9)583-600.