Title: Other Lung Diseases
1Other 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
2Disclosure Information
Mark J. Rosen, MD, FCCP
I have no conflicts of interest with the topics
that I am going to discuss.
3Other Lung Diseases
- Pulmonary complications of sickle cell disease
- Pulmonary complications of liver disease
- Oxygen toxicity
- Radiation-induced lung disease
- Smoke inhalation
- Carbon monoxide
- Methemoglobinemia
4Sickle 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
5Sickle Cell DiseasePathogenesis
Bunn HF. N Engl J Med 1997 337762-769
6Sickle Cell DiseasePathogenesis
Platt OS. N Engl J Med 20003421904-7
7Sickle Cell AnemiaPathogenesis
- Hemoglobin polymerization
- Deoxygenation degree and duration
- Hemoglobin concentration in RBC cellular
dehydration - Inversely proportional to hemoglobin F
8Sickle 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
9Sickle 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
10Sickle-Cell DiseasePulmonary syndromes
- Acute chest syndrome (ACS)
- Fat embolism syndrome
- Chronic restrictive lung disease with pulmonary
hypertension
11CPC. N Engl J Med
12Sickle-Cell DiseaseAcute Chest Syndrome
- Chest pain, fever, cough, often during painful
crisis - CXR multilobe or lower lobe opacities pleural
effusion in 15
13Acute Chest SyndromePathogenesis
- Pulmonary infarction
- In situ thrombosis
- Thromboembolism
- Fat embolism
- Thoracic bone infarction ? pain ? atelectasis and
pneumonia - Pulmonary infection
14The most common pathogen identified in patients
with acute chest syndrome is
- S. pneumoniae
- H. influenzae
- C. pneumoniae
- Influenza virus
1
15The most common pathogen identified in patients
with acute chest syndrome is
- S. pneumoniae
- H. influenzae
- C. pneumoniae
- Influenza virus
1
16Acute 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.
17Acute Chest Syndrome Etiology
Established in 364/670 episodes
Vichinsky EP et al. N Engl J Med 20003421855-65
18Acute Chest SyndromePathogens Identified
Vichinsky EP et al. N Engl J Med 20003421855-65
19ACS 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.
20Acute 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.
21Acute Chest Syndrome Treatment
- RBC transfusion
- Analgesics
- Hydration
- Oxygen
- Antibiotics
- Incentive spirometry
22Sickle Cell DiseasePotential Therapies
23Pulmonary 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
24Pulmonary Hypertension in Sickle Cell Disease
Gladwin MT, et al. N Engl J Med 2004350886-895
25Pulmonary Hypertension in Sickle Cell Disease
Gladwin MT, et al. N Engl J Med 2004350886-895
26Liver-Lung Syndromes
- Hepatopulmonary syndrome
- Portopulmonary hypertension
- Alpha-1 antitrypsin deficiency
- Hepatic hydrothorax
27Hepatopulmonary 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)
28Hepatopulmonary Syndrome
Mazzei JAM. PCCU Update Lesson 1, Vol 14
29Hepatopulmonary Syndrome
- Pathogenesis of vascular dilatations abnormal
vascular mediators leaving the liver? enter the
lungs? remodel pulmonary vessels - Increased NO production ? vasodilation, ?CO
30Hepatopulmonary 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
31Which 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
32Which 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
33Hepatopulmonary 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
34Portopulmonary Hypertension
- Occurs in 1-2 of patients with cirrhosis and
portal hypertension - Indistinguishable from IPAH
- Usually does not improve after liver
transplantation
35Hepatic 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
36Hepatic 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
37Hepatic HydrothoraxTreatments
- Transjugular intrahepatic portosystemic shunt
(TIPS)
38Which 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
39Which 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
40Oxygen 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
41Oxygen RadicalsToxicity
- Cell membrane damage ??increased cell
permeability - Lysosomal membrane damage ? releases proteolytic
enzymes - Inactivates cell enzymes
- Damages DNA
- Recruits neutrophils
42Oxygen Toxicity
- Tracheobronchitis
- Damage to type I pneumocytes ??increased
capillary permeability - Hyaline membrane formation, type II pneumocyte
proliferation, fibrosis
43Which of the following increases the risk of
developing pulmonary oxygen toxicity?
- Bleomycin
- Prior exposure to inhaled oxygen
- Endotoxin
- Inhaled tobramycin
6
44Which of the following increases the risk of
developing pulmonary oxygen toxicity?
- Bleomycin
- Prior exposure to inhaled oxygen
- Endotoxin
- Inhaled tobramycin
6
45Modulators of Lung Injury
- Protective
- Prior exposure to high FiO2
- Endotoxin (experimental)
- Additive/synergistic
- Drugs bleomycin, nitrofurantoin, mitomicin,
amiodarone - NO ?O2 ??ONOO-
46Radiation Pneumonitis
- Symptomatic disease in 7
- Injury to type II pneumocytes, capillary
endothelial cells ?? cytokine response ??
recruits immune cells ?? more inflammation ??
fibrosis
47All 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
48All 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
49Radiation 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
50Which 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
51Which 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
52Radiation Pneumonitis
- Latent period up to six months
- Nonspecific symptoms
- Chest film may be typical
- Radiographic changes may occur outside the
radiation field
53Radiation 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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58Radiation Fibrosis
- Usually occurs 6 months to 2 years after exposure
- Usually stable after 2 years
- Mediastinal fibrosis SVC syndrome, constrictive
pericarditis - Bronchiectasis, pleural thickening
59Smoke InhalationClinical Syndromes
- Inhaled toxins
- CO poisoning
- Thermal injury
- Airway disease
- Pneumonia
60A 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.
61Which test is least likely to be helpful in his
immediate management?
- Arterial blood gas
- Carboxyhemoglobin level
- Chest radiograph
- Flexible laryngoscopy
9
62Which test is least likely to be helpful in his
immediate management?
- Arterial blood gas
- Carboxyhemoglobin level
- Chest radiograph
- Flexible laryngoscopy
9
63Smoke 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
64Bronchoscopy 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
65Bronchoscopy 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
66Burn 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
67Burn 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
68Burn 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
69Smoke InhalationThermal injury
- No role for routine corticosteroids
- Pneumonia is a common cause of death
- Pseudomonas aeruginosa
- H. simplex tracheobronchitis
70Carbon Monoxide Poisoning
- CO produced by incomplete combustion decreased
FiO2 - Common scenarios
- Fires
- Coal, kerosene and wood-burning stoves in
well-insulated homes - Portable heaters
71Carbon 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
72Carbon 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
73Carbon Monoxide Poisoning Diagnosis
- Increased carboxyhemoglobin level
- Pulse oximetry cannot distinguish oxyhemoglobin
from carboxyhemoglobin (pulse oximetry gap)
Ernst AE. N Engl J Med 19983391603-8
74Carbon 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
75Carbon 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)
76Methemoglobin
- 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
77Methemoglobinemia
- Measured SpO2
- Functional SpO2
Barker SJ, et al. Anesthesiology
198970112-117 Hurford, et al. N Engl J Med
2004351380-387