Other Lung Diseases

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Other Lung Diseases

• Mark J. Rosen, MD, FCCP
• Chief, Divisions of Pulmonary, Critical Care and
  Sleep Medicine
• North Shore University Hospital and Long Island
  Jewish Medical Center
• Professor of Medicine
• Albert Einstein College of Medicine

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Disclosure Information
Mark J. Rosen, MD, FCCP
I have no conflicts of interest with the topics
that I am going to discuss.
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Other Lung Diseases

• Pulmonary complications of sickle cell disease
• Pulmonary complications of liver disease
• Oxygen toxicity
• Radiation-induced lung disease
• Smoke inhalation
• Carbon monoxide
• Methemoglobinemia

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Sickle Cell Hemoglobinopathies

• Sickle cell anemia (hemoglobin SS) affects 1/650
  African-Americans
• In the US, also affects Latinos from the
  Caribbean, Central America, South America

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Sickle Cell DiseasePathogenesis
Bunn HF. N Engl J Med 1997 337762-769
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Sickle Cell DiseasePathogenesis
Platt OS. N Engl J Med 20003421904-7
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Sickle Cell AnemiaPathogenesis

• Hemoglobin polymerization
• Deoxygenation degree and duration
• Hemoglobin concentration in RBC cellular
  dehydration
• Inversely proportional to hemoglobin F

8
Sickle Cell DiseasePathogenesis

• Microvascular occlusion
• Increased adhesion of RBCs and WBCs to vascular
  endothelium
• Vasoconstriction endothelin-1 expressed after
  contact with sickled RBCs
• Activation of coagulation system
  thrombocytosis, procoagulant RBC lipids
• NO dysregulation following release of arginine
  and Hgb from hemolysis

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Sickle Cell DiseaseRole of NO
Hemolysis Release free hemoglobin ? Scavenge
NO Release RBC arginase
Steudel W. Anesthesiology 1999911090-121 Griffi
ths. JD. N Engl J Med 20053532683-2695
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Sickle-Cell DiseasePulmonary syndromes

• Acute chest syndrome (ACS)
• Fat embolism syndrome
• Chronic restrictive lung disease with pulmonary
  hypertension

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CPC. N Engl J Med
12
Sickle-Cell DiseaseAcute Chest Syndrome

• Chest pain, fever, cough, often during painful
  crisis
• CXR multilobe or lower lobe opacities pleural
  effusion in 15

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Acute Chest SyndromePathogenesis

• Pulmonary infarction
• In situ thrombosis
• Thromboembolism
• Fat embolism
• Thoracic bone infarction ? pain ? atelectasis and
  pneumonia
• Pulmonary infection

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The most common pathogen identified in patients
with acute chest syndrome is

• S. pneumoniae
• H. influenzae
• C. pneumoniae
• Influenza virus

1
15
The most common pathogen identified in patients
with acute chest syndrome is

• S. pneumoniae
• H. influenzae
• C. pneumoniae
• Influenza virus

1
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Acute Chest SyndromeCauses and Outcomes

• 671 episodes in 538 patients
• Extensive diagnostic evaluation
• Blood cultures
• Nasopharyngeal cultures
• FOB cultures, fat stains
• PCR for Chlamydia
• Acute and convalescent sera mycoplasma, EB
  virus, Chlamydia, parvovirus

Vichinsky EP et al. N Engl J Med
20003421855-65.
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Acute Chest Syndrome Etiology
Established in 364/670 episodes
Vichinsky EP et al. N Engl J Med 20003421855-65
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Acute Chest SyndromePathogens Identified
Vichinsky EP et al. N Engl J Med 20003421855-65
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ACS in Patients gt 20 years

• 22 required mechanical ventilation
• Predictors gt 4 lobes involved, platelets lt
  200,000, history of cardiac disease
• 9 died

Vichinsky EP et al. N Engl J Med
20003421855-65.
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Acute Chest SyndromeNeurologic Complications

• 22 of adults developed neurologic disorders
• Altered mental status
• Seizures
• Neuromuscular
• Anoxic injury
• Hemorrhage
• Infarction

Vichinsky EP et al. N Engl J Med
20003421855-65.
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Acute Chest Syndrome Treatment

• RBC transfusion
• Analgesics
• Hydration
• Oxygen
• Antibiotics
• Incentive spirometry

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Sickle Cell DiseasePotential Therapies
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Pulmonary Hypertension in Sickle Cell Disease

• 195 adults with sickle cell disease
• Doppler-defined PH in 32
• Associated with
• Hx cardiovascular or renal complications
• Increased systolic BP
• High LDH (hemolysis?)
• High alkaline phosphatase
• Low transferrin levels
• Increase risk of death (rate ratio 10.1)

Gladwin MT, et al. N Engl J Med 2004350886-895
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Pulmonary Hypertension in Sickle Cell Disease
Gladwin MT, et al. N Engl J Med 2004350886-895
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Pulmonary Hypertension in Sickle Cell Disease
Gladwin MT, et al. N Engl J Med 2004350886-895
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Liver-Lung Syndromes

• Hepatopulmonary syndrome
• Portopulmonary hypertension
• Alpha-1 antitrypsin deficiency
• Hepatic hydrothorax

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Hepatopulmonary Syndrome

• Triad liver disease, hypoxemia, intrapulmonary
  vascular dilatations (precapillary and
  capillary)
• Diffusion-perfusion disorder
• High cardiac output
• Anatomic shunts pleural spider nevi and
  portopulmonary anastamoses (platypnea)

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Hepatopulmonary Syndrome
Mazzei JAM. PCCU Update Lesson 1, Vol 14
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Hepatopulmonary Syndrome

• Pathogenesis of vascular dilatations abnormal
  vascular mediators leaving the liver? enter the
  lungs? remodel pulmonary vessels
• Increased NO production ? vasodilation, ?CO

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Hepatopulmonary SyndromeDiagnosis

• Clinical liver disease (15-20 of patients with
  cirrhosis have HPS)
• Criteria
• Portal hypertension
• A-a DO2 gt15 mm Hg
• Vascular dilatation
• Echocardiographic air bubbles appear in left
  atrium 3-6 beats after visualization in right
  atrium, or
• Nuclear Radionucleide appears in brain 4-6
  cycles after injection

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Which of the following is most likely to improve
hypoxemia in the hepatopulmonary syndrome?

• Assuming an upright posture
• Administer supplemental O2
• Administer diltiazem
• Liver transplantation

4
32
Which of the following is most likely to improve
hypoxemia in the hepatopulmonary syndrome?

• Assuming an upright posture
• Administer supplemental O2
• Administer diltiazem
• Liver transplantation

4
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Hepatopulmonary SyndromeRole of NO
X
Methylene blue decreased cGMP ? vasoconstriction
? ? CO, ? PaO2
X
Steudel W. Anesthesiology 1999911090-121 Griffi
ths. JD. N Engl J Med 20053532683-2695
34
Portopulmonary Hypertension

• Occurs in 1-2 of patients with cirrhosis and
  portal hypertension
• Indistinguishable from IPAH
• Usually does not improve after liver
  transplantation

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Hepatic Hydrothorax

• Difficult-to-control pleural effusions in
  patients with ascites
• Probably due to congenital anatomic defects in
  the diaphragm
• Pleural fluid almost identical with ascites
• Typically transudate, rightgtleft
• Empyema may occur in patients with peritonitis

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Hepatic HydrothoraxTreatment is difficult

• Thoracentesis fluid reaccumulates
• Chest tube volume and electrolyte depletion
• Pleurodesis usually unsuccessful
• Surgical repair of diaphragm few centers have
  experience
• Peritoneovenous shunts Pleural fluid pressure lt
  venous pressure

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Hepatic HydrothoraxTreatments

• Transjugular intrahepatic portosystemic shunt
  (TIPS)

• Liver transplantation

38
Which statement about pulmonary oxygen toxicity
is true?

• The histopathologic findings are specific for
  that condition
• The airways are usually not affected
• FiO2 lt 0.6 has been shown to be nontoxic
• The lung is the most vulnerable organ to oxygen
  radical damage

5
39
Which statement about pulmonary oxygen toxicity
is true?

• The histopathologic findings are specific for
  that condition
• The airways are usually not affected
• FiO2 lt 0.6 has been shown to be nontoxic
• The lung is the most vulnerable organ to oxygen
  radical damage

5
40
Oxygen Radicals

• O2-, H2O2, ?OH-?are produced by stepwise
  reduction of O2 to water
• Beneficial roles
• used by neutrophils for phagocytosis and killing
  bacteria
• Mediate vascular tone by interactions with NO

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Oxygen RadicalsToxicity

• Cell membrane damage ??increased cell
  permeability
• Lysosomal membrane damage ? releases proteolytic
  enzymes
• Inactivates cell enzymes
• Damages DNA
• Recruits neutrophils

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Oxygen Toxicity

• Tracheobronchitis
• Damage to type I pneumocytes ??increased
  capillary permeability
• Hyaline membrane formation, type II pneumocyte
  proliferation, fibrosis

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Which of the following increases the risk of
developing pulmonary oxygen toxicity?

• Bleomycin
• Prior exposure to inhaled oxygen
• Endotoxin
• Inhaled tobramycin

6
44
Which of the following increases the risk of
developing pulmonary oxygen toxicity?

• Bleomycin
• Prior exposure to inhaled oxygen
• Endotoxin
• Inhaled tobramycin

6
45
Modulators of Lung Injury

• Protective
• Prior exposure to high FiO2
• Endotoxin (experimental)
• Additive/synergistic
• Drugs bleomycin, nitrofurantoin, mitomicin,
  amiodarone
• NO ?O2 ??ONOO-

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Radiation Pneumonitis

• Symptomatic disease in 7
• Injury to type II pneumocytes, capillary
  endothelial cells ?? cytokine response ??
  recruits immune cells ?? more inflammation ??
  fibrosis

47
All of the following influence the severity of
radiation-induced lung injury, except

• Type of malignancy treated
• Daily and total dose of radiation
• Concomitant chemotherapy
• Withdrawal of corticosteroids

7
48
All of the following influence the severity of
radiation-induced lung injury, except

• Type of malignancy treated
• Daily and total dose of radiation
• Concomitant chemotherapy
• Withdrawal of corticosteroids

7
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Radiation PneumonitisInfluences

• Irradiated volume of lung tissue
• Total dose
• lt30 Gy well tolerated
• gt40 Gy radiographic changes
• gt50 Gy symptomatic injury
• Fraction size
• Prior irradiation
• Chemotherapy
• Withdrawal of corticosteroids

50
Which statement is true about radiation-induced
lung injury?

• A. Pneumonitis rarely occurs more than six weeks
  after radiation therapy is completed
• B. Radiographic abnormalities may occur in the
  nonradiated lung
• C. The histopathology is specific for that
  disorder
• D. Corticosteroids are rarely effective

8
51
Which statement is true about radiation-induced
lung injury?

• A. Pneumonitis rarely occurs more than six weeks
  after radiation therapy is completed
• B. Radiographic abnormalities may occur in the
  nonradiated lung
• C. The histopathology is specific for that
  disorder
• D. Corticosteroids are rarely effective

8
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Radiation Pneumonitis

• Latent period up to six months
• Nonspecific symptoms
• Chest film may be typical
• Radiographic changes may occur outside the
  radiation field

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Radiation Pneumonitis in the Nonirradiated Lung

• 6 women received RT for breast cancer (mean dose
  6,560 cGy)
• Recurrent and migrating lung opacities outside
  the radiation field 6 to 17 months later
• BAL (2 patients) lymphocytosis
• Lung biopsy (5 patients) BOOP

Arbetter KR, et al. Mayo Clin Proc 19997427-36
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Radiation Fibrosis

• Usually occurs 6 months to 2 years after exposure
• Usually stable after 2 years
• Mediastinal fibrosis SVC syndrome, constrictive
  pericarditis
• Bronchiectasis, pleural thickening

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Smoke InhalationClinical Syndromes

• Inhaled toxins
• CO poisoning
• Thermal injury
• Airway disease
• Pneumonia

60
A 23-year-old man is brought to the emergency
room after rescue from a burning building. He
has second- and third-degree burns over 15 of
his body, including his face. He is conscious,
but in mild respiratory distress.
61
Which test is least likely to be helpful in his
immediate management?

• Arterial blood gas
• Carboxyhemoglobin level
• Chest radiograph
• Flexible laryngoscopy

9
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Which test is least likely to be helpful in his
immediate management?

• Arterial blood gas
• Carboxyhemoglobin level
• Chest radiograph
• Flexible laryngoscopy

9
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Smoke InhalationThermal injury

• Larynx edema, spasm
• Bronchi inflammation, edema, spasm,
  hypersecretion, impaired mucociliary function
• Does not usually affect distal airways or alveoli
• CXR usually normal initially

64
Bronchoscopy shows moderate ulceration and edema
of the larynx and bronchi. Which of the
following is most likely to benefit this patient?

• Corticosteroids
• Broad-spectrum antibiotics
• Continuous positive airway pressure
• Endotracheal intubation

10
65
Bronchoscopy shows moderate ulceration and edema
of the larynx and bronchi. Which of the
following is most likely to benefit this patient?

• Corticosteroids
• Broad-spectrum antibiotics
• Continuous positive airway pressure
• Endotracheal intubation

10
66
Burn Injury Mortality

• Review of all patients with burn injuries
  admitted to MGH and Shriners Burns Institute,
  1990-1994
• Three risk factors for death
• Age gt 60 years
• Body-surface area burn gt 40
• Inhalation injury

Ryan CM, et al. N Engl J Med 1998338362-6
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Burn Injury Mortality

• Risk factor Mortality Rate
• Inhalation injury only 5/112 (4)
• Inhalation gt 40 burn 21/79 (27)
• Inhalation gt 60 years 12/31 (39)
• All three 21/22 (95)

Ryan CM, et al. N Engl J Med 1998338362-6
68
Burn Injury Mortality

• Risk factors Mortality Rate
• 0 3/1314 (0.2)
• 1 10/218 (5)
• 2 33/111 (30)
• 3 21/22 (95)

Ryan CM, et al. N Engl J Med 1998338362-6
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Smoke InhalationThermal injury

• No role for routine corticosteroids
• Pneumonia is a common cause of death
• Pseudomonas aeruginosa
• H. simplex tracheobronchitis

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Carbon Monoxide Poisoning

• CO produced by incomplete combustion decreased
  FiO2
• Common scenarios
• Fires
• Coal, kerosene and wood-burning stoves in
  well-insulated homes
• Portable heaters

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Carbon Monoxide Poisoning

• CO affinity for Hgb 200x greater than O2
• Shifts oxyhemoglobin dissociation curve to the
  left
• PaO2 may be normal, but CaO2 is reduced ? tissue
  hypoxia
• Signs of poisoning CNS, cardiac, lactic acidosis

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Carbon Monoxide Toxicity
Acute symptoms after exposure in 196 patients

• Headache 91
• Dizziness 77
• Weakness 53
• Nausea 47
• Confusion 43

• Dyspnea 40
• Visual 25
• Chest pain 9
• LOC 6
• Abd pain 5

Ernst AE. N Engl J Med 19983391603-8
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Carbon Monoxide Poisoning Diagnosis

• Increased carboxyhemoglobin level
• Pulse oximetry cannot distinguish oxyhemoglobin
  from carboxyhemoglobin (pulse oximetry gap)

Ernst AE. N Engl J Med 19983391603-8
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Carbon Monoxide Toxicity Delayed
Neuropsychiatric Syndrome

• Cognitive and personality changes, parkinsonism,
  incontinence, dementia, psychosis
• May occur days or weeks after exposure
• Recovery within one year in 50-75
• Most commonly involves globus pallidus and deep
  white matter

Ernst AE. N Engl J Med 19983391603-8
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Carbon Monoxide Poisoning Diagnosis and Treatment

• Asymptomatic, CO lt 20 no Rx
• Symptoms, CO gt 20 100 O2
• Hyperbaric O2 in severe cases (coma, cardiac
  ischemia, arrhythmia)
• Hyperbaric O2 reduces risk of cognitive sequelae
  (N Engl J Med 20023471057)

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Methemoglobin

• Product of oxidation of Fe to Fe
• MetHb has higher affinity for oxygen, shifts
  oxyhemoglobin curve to the left
• Oxidant drugs
• Metaclopramide
• Dapsone
• Sulfonamides
• Local anesthetics
• Nitrates

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Methemoglobinemia

• Measured SpO2
• Functional SpO2

Barker SJ, et al. Anesthesiology
198970112-117 Hurford, et al. N Engl J Med
2004351380-387