Oxygen in Restrictive Lung Disease

1
Oxygen in Restrictive Lung Disease

• Katherine Hendra, MD
• Division of Pulmonary Medicine, Critical Care and
  Sleep Medicine
• Tufts Medical Center

2
Objectives

• Review oxygenation pathophysiology in restrictive
  lung diseases
• Use of supplemental oxygen and ventilator support
• Oxygenation and sleep in restrictive lung disease
• Therapy outcomes

3
Defining a restrictive ventilatory defect

• Characteristic
• Decreased vital capacity
• Relatively normal expiratory flow rates
• Decreased total lung capacity

• Supportive
• Decreased total lung capacity
• Decreased lung compliance
• Alveolar hypoventilation
• Increased alveolar-arterial difference in oxygen
  tension
• Abnormal distribution of inspired gas
• Decreased carbon monoxide diffusing capacity

4
Common causes

• Intrinsic lung disease
• Interstitial pneumonitis
• Fibrosis
• Pneumoconiosis
• Granulomatosis
• Edema
• Pleural disease
• Pneumothrax
• Hemothorax
• Pleural effusion
• Fibrothorax

• Chest wall disease
• Injury
• Kyphoscoliosis
• Neuromuscular disease
• Extrathoracic causes
• Obesity
• Peritonitis

5
Oxygenation and hypoxemia

• Adequate oxygen from inspired air to sustain
  aerobic metabolic activity
• Oxygenation-oxygen diffusion from alveolus to
  capillary binds to red blood cells or dissolves
  in plasma
• Oxygen delivery-rate of transport from lung to
  periphery
• Oxygen Consumption-rate removed from blood cells
  for use by tissue

6
Impaired oxygenation mechanisms

• Hypoventilation
• Ventilation/perfusion mismatch
• Right-Left shunt
• Diffusion impairment
• Reduced inspired oxygen tension

7
Hypoventilation

• Decreased alveolar oxygen, normal
  alveolar-arterial difference
• CNS depression
• Obesity-hypoventilation
• Impaired neural conduction
• Muscular weakness
• Decreased chest wall elasticity

8
Ventilation-perfusion mismatch
Degree of ventilationperfusion mismatch
increased Increased alveolar-arterial difference
9
Right-left shunt

• Fraction of venous blood entering arterial
  circulation without contact with ventilated lung
• May be intra-pulmonary, intra-cardiac anatomic
  and functional

10
Diffusion impairment
Movement of oxygen from alveolus to capillary is
compromised Insufficient time for
oxygenation to occur Unable to recruit
additional capillary surface area
11
Consequences of hypoxia

• PaO2 lt55 mmHg increases minute ventilation,
  decreasing PaCO2
• Cardiac output, erythropoeitin increase
• Regional pulmonary vasoconstirction restores V/Q
  matching
• Above results in polycythemia, pulmonary
  hypertension and right ventricular failure

12
Clinical findings in intrinsic lung disease
Radiograph of idiopathic pulmonary fibrosis
Chest CT scan IPF
Digital clubbing
13
Pathophysiology and clinical features of
decreased oxygenation

• Pathophysiology
• ventilation perfusion mismatch
• right-left shunts
• diffusion impairment

• Clinical features
• Breathlessness
• Headaches
• Palpitations
• Restlessness
• Tremor
• Sleep disturbances
• Neuro-cognitive defects

14
Arterial blood gases

• Resting values
• Hypoxemia
• Carbon dioxide retention unusual
• Respiratory alkalosis
• Normal value not reliable to exclude sleep or
  exercise induced hypoxia

• Exercise assessment
• Arterial oxygen desaturation
• Failure to decrease dead space
• Relatively increased respiratory rate
• Lower recruitment of tidal volume

15

• Pulmonary function tests
• Decreased total lung capacity, functional
  residual capacity and residual volume
• Usually decreased diffusion capacity for carbon
  monoxide(effacement of alveolar units,
  ventilation/perfusion mismatching)

• MEFV curve of patient with interstitial lung
  disease FEV1 and FVC values are low relative to
  predicted values, but FEV1 to FVC ratio is
  increased. However, at any given lung volume, the
  flow rates are higher than expected because of
  elevated driving pressure due to an increased
  elastic recoil.
• MEFV curve for a patient with chronic
  obstructive lung disease. The FEV1 and FVC values
  are low relative to the predicted values, and the
  lung volumes are increased.

16
Breathing patterns and gas exchange
Table 3 Mean (SD) gas exchange and ventilation
values in three groups of patients with
interstitial lung diseases grouped according to
percentage of predicted forced vital
capacity Group I Group 2 Group 3 Pao2 (mm
Hg) 76 (12) 71 (14) 74 (17) Paco2 (mm Hg)
37 (4) 36 (3) 39 (5) H (nEq/l) 39-0
(2-4) 37-6 (1-8) 38-0 (2-0) LHC03- (mEq/l)
23 (2) 24 (2) 25 (3) Vo /BSA (ml/minIm')
135 (17) 147 (28) 142 (21) Vo2/BSA
(ml/min/m') 109 (14) 120 (24) 115
(21) RER 0-81 (0-03) 0-82 (0-04) 0-81
(0-04) TC (ml/min/mmHg) 17 (7) 14 (7) 12
(6) LCO( predicted) 64 (20) 54 (26) 49
(34) RR (min) 17 (4) 20 (4) 23
(5) VT (ml) 484 (131) 460 (139) 377
(109) VD (ml/kg) 2-4 (1-1) 2-7 (1-2)
2-7 (0-8) VD/VT () 34 (12) 37 (10) 42
(7) VE/BSA (1/min/m2) 4-4 (0-8) 5-2 (1-5)
5-1 (0 9) VA/BSA (1/min/m2) 2-8 (0-3) 3-2
(0 4) 3-0 (0-4) BSA body surface area Vo2
oxygen consumption VCo2 carbon
dioxide production TLCO transfer factor for
carbon monoxide RER respiratory
exchange ratio VE minute ventilation VA
alveolar ventilation. Vo2, Vco2, and TLCO are
at STPD. Ventilatory values are at
BTPS. Thorax 19924793-97
17
Clinical findings in bony chest wall
disease-Kyphscoliosis

• Kyphosis-spinal deformity with
• AP angulation
• Scoliosis-lateral displacement of
• the spine
• Severity defined by measurement
• of the Cobbs angle

18
Oxygenation and hypoxia

• Arterial blood gases
• Hypoxemia, hypercapnia and V/Q mismatch (Cobbs
  angle gt65)
• Respiratory pattern and PFTs
• Decreased TV, increased RR, alveolar
  hypoventilation
• Reduced TLC, VC, preserved RV results in
  increased RV/TLC ratios
• Chest wall and lung compliance
• Decreased due to deformity and progressive
  atelectasis, worsens with age

19
Limitations to oxygen delivery
20
Neuromuscular restrictive lung disease

• Multiple causes
• -may be related to dysfunction in spinal cord,
  motor neurons, neuromuscular junction or muscle
  tissue
• Varying clinical course
• Muscles in upper airway and those involved in
  inspiration and expiration are impaired

21
Physiology of hypoxia-inadequate ventilation

• Weakness of inspiratory muscles
• Tidal volume decreases
• Respiratory rate increases to maintain alveolar
  ventilation
• Hypoventilation leads to hypoxia
• Atelectasis from low TV, decreased sigh causes
  right-left shunt

22
Bulbar dysfunction and inadequate cough

• Bulbar difficulty swallowing, facial weakness,
  abnormal secretion clearance
• Inadequate cough expiratory, inspiratory, upper
  airway weakness
• Predisposed to aspiration
• Results in ventilation-perfusion mismatch,
  right-left shunts

23
Oxygen therapy in restrictive disease
24
Indications for long-term oxygen therapy
25
Prescribing long-term oxygen therapy

• Oxygen flow at rest, during exercise, and during
  sleep, where appropriate
• Oxygen delivery systems, including
• Stationary unit
• Portable or ambulatory equipment.
• Oxygen-conserving device, if desired.
• Nasal cannula or transtracheal catheter
• Justification for portable or ambulatory oxygen,
  if requested
• Reevaluation for possible changes in the
  prescription

26
Benefits of LTOT?

• MRC and NOTT survival benefit in oxygen
  treated patients using O2 gt15 hours/day
• Both enrolled patient with COPD only
• No benefit on PFT, ABG, CO or PA pressures
• PVR (17) and hemotocrit (7) decreased in NOTT
• Not controlled for continued smoking

Medical Research Council Lancet 1981
Nocturnal oxygen therapy trial group Ann Int
Med 1980
27
Overall mortality in COPD patients enrolled in
NOTT
continuous oxygen therapy
nocturnal oxygen therapy
12- and 24 month mortality were higher in the
nocturnal oxygen group (21 versus 12 and 41
versus 22, respectively)
28
LTOT in interstitial lung disease?

• Single, non-published RCT identified
• Long-term or domiciliary oxygen therapy compared
  with control group
• Patients included IPF, ILD or pulmonary fibrosis
• Mortality after 3 years 91 in both groups
• QOL, physiologic parameters not reported

Cochrane Database Syst Rev. 2001(3)CD002883.
29
QOL and rehabilitation

• 35 patients with interstitial lung diseas using
  LTOT had improved treadmill testing during
  pulmonary rehabilitation at 8 weeks as compared
  to non-users
• QOL COPD patients-reduction of dyspnea, sleep
  consolidation, improved mood and cognitive
  function

J Cardiopulm Rehabil. 2006 Jul-Aug26(4)237-43
30
Survival in patients with KS receiving LTOT or HMV

• 244 patients, starting therapy with HMV or LTOT
• Age 69 /-11 years, majority women
• 33 of HMV patients with other respiratory
  condition, 65 on LTOT
• PaO2 and PaCO2 higher in HMV (56 vs.48 mmHg, 57
  vs.52 mmHg)
• HMV lt10 hrs, LTOT gt16 hrs
• 
  Chest 2006 13018281833

31
Chest 2006 13018281833
32
Table 3. Multivariate Analyses of Relative Risk
of Death Among Patients With Kyphoscoliosis
Chest 2006 13018281833
33
Oxygen therapy in neuromuscular disease

• 8 patients (poliomyelitis, ALS, inflammatory
  motor neuropathy) and diaphragmatic dysfunction
• Arterial blood gas analysis before and after
  low-flow oxygen (.5-2.0 L/min)
• Mean PaCO2 increased by 28 /- 23 torr
• Nocturnal ventilation allowed daytime oxygen use
• Low flow oxygen should be used with caution

Mayo Clin Proc 1995 Apr70(4)327-30
34
ANTADIR observatory

• Included patients with fibrotic and chest wall
  disease
• Followed outcomes on LTOT and/or HMV for 10 years
• 912 kyphscoliosis, 941 neuromuscular and 1663
  intersitial fibrosis patients

Chest 1996109741-749
35
ANTADIR observatory patient characteristics
Chest 1996109741-749
36
Actuarial survival by etiology of restrictive
lung disease-ANTADIR observatory
survival
Years of LTOT/HMV
Chest 1996109741-749
37
ANTADIR observatory predictors of survival

• Kyphoscoliosis - better prognosis female,
  younger, high BMI, higher FEV1/VC, higher
  PaO2/PaCO2
• Neuromuscular disease - worse prognosis higher
  BMI, increased PaCO2, decreased VC, older
• Fibrosis - worse prognosis decreased VC, higher
  FEV1/VC, lower PaO2/PaCO2

Chest 1996109741-749
38
Improving oxygenation -Conclusions

• Differing pathophysiology between disease states
  should be considered
• Recommendations for LTOT use and initiation
  drawn largely from obstructive lung disease
• Add life to years, not years to life

39
Ventilation in sleep

• PaCO2 3-10 mmHg
• PaO2 2-8 mmHg
• Apneic threshold for PaCO2
• Periodic breathing in stages 1 and 2
• Irregular breathing pattern in REM

40
Ventilation in sleep

• NREM
• Decreased ventilation due to
• BMR
• Decreased ventilatory drive
• Increased upper airway resistance

41
Ventilation in sleep

• REM
• Decreased brainstem respiratory output
• Hypotonia of intercostals and accessory muscles
  of respiration
• Marked decrease in hypoxic and hypercarbic
  ventilatory responses

42
Ventilatory changes in sleep

• Decreases in
• PEFR
• Minute ventilation
• TV
• FRC
• Respiratory muscle tone
• Most significant during REM sleep

43
Sleep in restrictive lung diseases

• Chest wall deformities
• Decrease in VC, TV and ERV
• Increase in pulmonary vascular resistance
• Hypercarbia and hypoxemia
• V/Q mismatch
• Rapid shallow breathing

44
Sleep in restrictive lung diseases

• Chest wall deformities
• Sleep hypoxemia correlates with awake oxygen
  saturation
• Prolonged apneas, esp in REM
• PFTs do not correlate with sleep disordered
  breathing

45
Sleep in restrictive lung diseases

• Chest wall deformities treatment
• Tracheotomy
• CPAP/NIV
• Nocturnal mechanical ventilation

46
Sleep in restrictive lung diseases

• Intrinsic lung disease
• Decreased sleep efficiency
• Increased spontaneous arousals
• Increased stage 1 sleep
• Increased oxygen desaturation during REM sleep

47
Sleep in restrictive lung diseases

• Intrinsic lung disease treatment
• Sleep study not indicated unless symptoms
  suggestive of OSA
• Nocturnal oximetry is adequate
• Supplemental oxygen if saturation lt88 for gt 5
  minutes
• Consider if wake PaO2 decreased

48
Sleep in restrictive lung diseases

• Neuromuscular disorders
• Decrease in FRC, TV, ERV, lung compliance
• Increase in RR
• Pharyngeal and laryngeal muscles involved
  increase in OSA
• Hypoventilation, esp in REM
• Hypoxia and hypercarbia

49
Sleep in restrictive lung diseases

• Neuromuscular disorders, management
• Respiratory stimulants
• TCA
• NIV (CPAP/BiPAP)
• Nocturnal mechanical ventilation

50
Why sleep is important in restrictive respiratory
disease

• Vulnerable time for respiratory system
• Increased morbidity and mortality
• Small changes in ventilation during sleep for
  normal subjects can have dire consequences for
  patients with chronic respiratory illness