WEGENERS GRANULOMATOSIS

WEGENERS GRANULOMATOSIS

• Rare disease characterized by necrotizing granulomas and vasculitis of upper and lower respiratory tracts; also systemic vasculitis with focal necrotizing glomerulonephritis.
• Triad of upper respiratory tract, lung and kidney involvement is the classical mode of presentation.
• Systemic vasculitis may be manifested by skin, eye and joint findings.
• Limited form with long survival when the disease is predominantly restricted to lungs.
• Etiology is unknown.

Clinical Picture Diagnosis

• Waxing and waning lung lesions, single or multiple often with cavitation.
• CXR: Bilateral nodules ranging from 1 to 9 cm in size; may also see diffuse interstitial disease and alveolar hemorrhage.
• Antineutrophilic cytoplasmic antibodies (ANCA) Percutaneous renal biopsy; lung biopsy.
• Depending on the organ involved, necrotizing nasal lesions, glomerulonephritis, CNS or skin involvement can be seen on biopsy.

Therapy

• Cytotoxic therapy (Cyclophosphamide) with steroids produce rapid reversal of disease.

SLEEP APNEA

SLEEP APNEA

Definition

1.     Syndrome in which repetitive episodes of cessation of airflow or decreases in airflow occur during sleep in the presence of continued respiratory effort (obstructive sleep apnea). Cessation of airflow without respiratory effort is seen in central sleep apnea. A combination of these two events is seen in mixed apneas.

2.     The Apnea/Hypopnea Index (AHI) is a method of quantifying the severity of the sleep disordered breathing. It is the sum of all respiratory events occurring over a full night divided by the total sleep time recorded in hours. An AHI>5/hour is considered abnormal in most populations, and in the appropriate clinical setting, defines obstructive sleep apnea syndrome (OSAS).

3.     Recent studies have found an incidence of OSAS of approximately 4% in middle aged US males, and approximately 2% of females. Children and infants may also be afflicted. Familial clustering has been reported.

4.     Risk factors for OSAS:

o    obesity

o    advancing age

o    snoring

o    sleep deprivation

o    ethanol and sedative/hypnotic medications

o    hypothyroidism

o    general anesthetics

o    certain antihypertensive agents (methyldopa, propranolol)

o    COPD

o    ribcage and neuromuscular abnormalities

o    CNS disorders

o    nasal obstruction

o    tonsillar/adenoidal hypertrophy

o    acromegaly

o    micro and retrognathia

o    macroglossia

o    lymphoma

o    Shy-drager Syndrome

o    amyloidosis

o    congenital syndromes

Signs and Symptoms

1.     manifestations of above mentioned risk factors

2.     excessive daytime somnolence

3.     sleep maintenance problems

4.     abnormal motor activity during sleep

5.     abnormal sleep positions

6.     parasomnias

7.     signs differ in children:

o    hyperactivity

o    irritability

o    developmental delays

o    growth retardation

Pathophysiology of Obstructive Apneas

1.     Initial pharyngeal obstruction:

o    Usually occurs at level of velopharynx, may also occur in hypopharynx

o    Pharyngeal dilator muscle hypotonia, especially during REM sleep

o    Compromised anatomy of upper airway

2.     Consequences of occlusion

o    Hypoxemia

o    Hypercapnia

o    Arousal

3.     Post-apneic Ventilation

Complications of OSAS

Cardiopulmonary

• cardiac arrhythmias and conduction disturbances
• sinus arrhythmia
• second degree or complete AV Block
• prolonged sinus pauses
• paroxysmal atrial fibrillation
• ventricular tachycardia
• systemic and pulmonary hypertension
• SBP > 200mm Hg at conclusion of obstructive events
• decreased MAP during events
• increased ischemic events (associated with BP changes and gas exchange abnormalities)
• PCWP increases (may cause pulmonary edema)
• long term consequences
• pulmonary hypertension
• cor pulmonale
• systemic hypertension
• increased vascular mortality/death

Neuropsychiatric

• excessive daytime somnolence
• personality changes
• cognitive dysfunction and memory impairment
• impotence
• depression

Socioeconomic

• loss of productivity
• increased motor vehicle accidents (7-fold increase over non-apneic controls)

Diagnostic Evaluation of Patients with Suspected OSAS

1.     History

o    typical sleep-wake cycle

o    quality of sleep

o    medication ingestion

o    habits (tobacco, caffeine, alcohol)

o    stressors

o    exercise

o    sleep environment

o    associated symptoms (morning headache, dry mouth, snoring)

o    family history of sleep disorders

2.     Physical Examination

o    HEENT

o    Hypertension

o    body habitus

o    neck size

o    cardiac exam

o    mental status

o    thyroid abnormalities

o    neuropathy

3.     Sleep Questionnaire and Diary

4.     Nocturnal Polysomnography

o    ambulatory vs. laboratory

o    AHI

o    arousal index

o    desaturations

o    arrhythmias

reatment

1.     Weight Reduction

2.     Positional Treatment

3.     Correct increased nasal resistance

4.     Dental Appliances

5.     Increase Upper Airway Muscle Tone

o    avoid alcohol, sedatives and hypnotics

o    pharmacologic intervention

o    protriptyline

o    progesterone

o    theophylline

o    strychnine/nicotine

o    electrical stimulation

6.     Nasal Continuous Positive Airway Pressure

o    standard of care

o    titrated pressure

o    nasal mask vs. pillows

o    CPAP vs. BiPAP

o    "AutoPAP" or DPAP or VPAP

o    Compliance

7.     Surgical Correction of Upper Airway Anatomic Abnormalities

o    tracheostomy

o    nasal surgery

SARCOIDOSIS

A multisystem granulomatous disorder of unknown etiology.

Clinical manifestations

a.      Mostly young adults.

b.     Any organ may be involved with the lungs, lymphatics, skin, liver, eyes most commonly affected in decreasing order. Some manifestations to watch for:
- Myocardial involvement (possible conduction disturbances)
- Uveitis
- Cranial nerve VII involvement
- Erythema nodosa

c.      PFTs: Decreased volumes, compliance, DLCO, hypoxemia.

d.     BAL: Predominance of T-lymphocytes and macrophages.

e.      Immunology: Activated T-lymphocytes secrete IL-2 which, as a monocyte chemotactic factor, recruit monocytes and thus contribute to granuloma formation.

f.       CXR:
- Stage 0  Clear
- Stage I   Bilateral hilar adenopathy
- Stage II  Hilar adenopathy and parenchymal infiltrates
- Stage III Parenchymal infiltrates only
- State IV Extensive fibrosis and distortion of lung architecture

g.     Gallium-67 Imaging: increased pulmonary uptake with alveolitis.

h.     Hypercalcemia (10-15%), hypercalciuria (20-30%)

i.        Elevated ACE level (nonspecific); however, ACE may be followed for therapeutic response.

j.        Hyperglobulinemia, impaired delayed hypersensitivity.

Diagnosis: Transbronchial lung biopsy showing non-caseating granulomas with compatible clinical picture.

Therapy: Corticosteroids

a.      Indications for prednisone therapy: active alveolitis with severe symptoms, uveitis, liver disease (marked), cardiac disease, CNS disease, hypercalcemia.

b.     Secondary agent: methotrexate, antimalarial agents controversial.

Transplantation

a.      Recurrent sarcoid granulomata noted in allografts; immunosuppression for transplantation may attenuate granulomatous responses in patients having recurrent disease.

PULMONARY HYPERTENSION

Pulmonary hypertension is considered present when the mean PA pressure is greater than 25 mm Hg at rest or 30 mm Hg during exercise.

Etiology and Classification

• Secondary pulmonary hypertension is present when there is a identifiable cause with hemodynamic sequelae leading to pulmonary hypertension. Disease of the left heart, pulmonary embolism, chronic hypoxemia and left to right shunts are common etiologies.
• Primary pulmonary hypertension is obviously idiopathic. However, it is often associated with cirrhosis , AIDS and can be familial.

Pathogenesis
Elevated pressure, through endothelial cell dysfunction, produces structural changes in the pulmonary vasculature. These changes ultimately decrease pulmonary blood flow and stress the heart to the point of failure. Based on etiology, pulmonary hypertension is divided into two categories.

• Primary (idiopathic): The cause is unknown.
• Secondary: The hypertension is secondary to a variety of conditions which increase pulmonary blood flow or increase resistance to blood flow. Example: Interstitial fibrosis.

Pathology
The changes involve large and small pulmonary blood vessels and range from mild to severe. The major changes includeatherosclerosis, striking medial hypertrophy and intimal fibrosis of small arteries and arterioles, and plexogenic arteriopathy. Refer to Figure 15-7 in your textbook.

Pathophysiology 

Dyspnea and fatigue eventually give way to irreversible respiratory insufficiency,

 cyanosis and cor pulmonale

Clinical Features

• Primary pulmonary hypertension often occurs in young females. Dyspnea on exertion, fatigue, syncope, dizziness, edema and angina occur during the course of illness.
• Loud pulmonary component of the second heart sound, pulmonary ejection click, RV lift, S4 gallop, syst murmur of tricuspid regurgitation and a diastolic murmur of pulmonary regurgitation can be recognized. Findings are subtle and the diagnosis is often missed.
• Complex testing is often required to establish the presence of pulmonary hypertension and to rule out secondary causes.

Therapy

• Prognosis is poor and five year survival is between 22-33%.
• See cor pulmonale for therapeutic measures for secondary pulmonary hypertension.
• Anticoagulation, Calcium channel blocks, Nitric oxide and Prostacyclin are current therapeutic options.
• Anticoagulation has to given indefinitely.
• 20-35 % of patients respond to vasodilators acutely and benefit from their use.
• Infusion of prostacycline, continuously and chronically, improves hemodynamics, symptoms and survival. This requires implantation of a permanent central venous catheter, use of an external portable infusion pump and comprehensively trained support staff.
• Lung transplant is an option for patients refractory to medical management.

PREGNANCY AND LUNG

PREGNANCY AND LUNG

Cardiopulmonary Physiology in Pregnancy

• Profound changes occur in the cardiovascular system early in pregnancy. By the early second trimester, circulating blood volume increases 40-50%. This is due to an increase in both the circulation red cell mass and an even larger increase in the plasma volume.
• The larger increase in plasma volume leads to a dilutional anemia and a decrease in the serum colloid oncotic pressure.
• These changes increase the susceptibility of pregnant patients to the development of pulmonary edema.
• The cardiac output also increases by about 30-45% by the early second trimester. In patients with underlying cardiac disease this further worsens the tendency toward pulmonary edema.
• Gas exchange is also affected by pregnancy. Minute ventilation is increased during pregnancy (primarily an increase in tidal volume with a normal respiratory rate) for 2 reasons. First, oxygen consumption and carbon dioxide production increase 20-30% by the third trimester and up to 100% during labor, necessitating increased minute ventilation to maintain normal acid base status. In addition, progesterone directly stimulates the central respiratory center causing a further increase in minute ventilation. The net effect is a mild chronic respiratory alkalosis with a decrease in the arterial PaCO2, a slight increase in the PaO2 (alveolar gas equation), a slightly elevated pH and a slightly decreased HCO3 (renal compensation).
• FRC decreases substantially during pregnancy due to increased pressure from the gravid abdomen. This results in an increased susceptibility to atelectasis especially in the supine position. This may lead to mild arterial hypoxemia if blood gases are measured supine.

Pulmonary Problems During Pregnancy

Asthma

While there is no evidence that the inflammation underlying asthma is worse during pregnancy, the increased minute ventilatory requirements often worsen the symptoms of asthma. The fetus is especially susceptible to maternal hypoxemia so exacerbations of asthma must be treated early and aggressively. Therapy is no different than in the non-pregnant patient. Close follow up is essential.

Pulmonary Embolism

The risk of pulmonary embolism is substantially increased during the peripartum period. A high clinical suspicion must be maintained and heparin prophylaxis should be considered in patients with additional risk factors.

ARDS

Perhaps, because of the higher hydrostatic and lower oncotic pressures associated with pregnancy, pregnant patients are at increased risk of developing hypoxemia and even ARDS with systemic infections. Again concern for maternal and fetal oxygenation in the face of an already increased maternal cardiac output and oxygen consumption necessitates early aggressive supportive care.

Aspiration

Mechanical factors associated with the gravid uterus as well as hormonal effects which tend to lower esophageal sphincter tone increase the risk of aspiration of gastric contents late in pregnancy.

Tocolytic Induced Pulmonary Edema

The systemic use of (2 agonists (terbutaline, salbutamol) to interrupt preterm labor is associated with a substantial risk of pulmonary edema. The pathogenesis is unknown. Pulmonary edema generally develops within 72 hours of the initiation of therapy. It resolves within 24 hours of discontinuation of the drug. The pulmonary edema may be sever leading to respiratory failure. Given their disputed efficacy, some authors have recommended against the use of these agents.

Amniotic Fluid Embolism

This is a rare but catastrophic complication of pregnancy which presents as the acute onset of dyspnea, cyanosis and tachypnea during or immediately after labor. Mechanical obstruction or cytokine mediated constriction of the pulmonary vasculature leads to acute cardiorespiratory collapse which is often fatal. Risk factors include advanced maternal age, multiparity, amniotomy, c-section, and IUDs.

Airway Management

Endotracheal intubation is more difficult in the pregnant patients for multiple reasons. First, mild upper airway edema which narrows the caliber of the airway. Second, the risk of aspiration during endotracheal intubation is increased. Finally the rate of oxygen consumption is increased, limiting the efficacy of preoxygenation.

Cardiac Disease

The cardiopulmonary changes of pregnancy increase the susceptibility of patients with cardiac disease to pulmonary edema as outlined above. In addition, peripartum cardiomyopathy, an idiopathic diffuse cardiomyopathy may occur in the third trimester or in the 3-6 months post partum. It is therefore important to exclude pre-existing or new cardiac disease as a cause of dyspnea in the peripartum period.

Acute Respiratory Failure in the Peripartum Period

Often clinicians are faced with a patient in the peripartum period with acute hypoxemic respiratory failure and a diffuse infiltrate on chest x-ray. As in other patient populations, the approach to these patients includes supportive care, often with intubation and mechanical ventilation, followed by pulmonary artery catheterization to distinguish high versus low pressure pulmonary edema. However, the differential diagnosis in this scenario is slightly different. A specific history of tocolytic use should be sought. Respiratory failure during or immediately after labor should raise the suspicion of amniotic fluid embolism. Echocardiography should be done early to exclude a peripartum cardiomyopathy. A careful search for infection should be performed given the increased propensity to ARDS in response to sepsis. Finally, a history of witnessed aspiration events should be sought.

PNEUMOTHORAX

PNEUMOTHORAX

Classification and Etiology and Pathology

• Classified as iatrogenic (following a specific event) or spontaneous
• Iatrogenic pneumothorax follows procedures such as lung biopsy, thoracentesis, trauma, etc.
• Spontaneous pneumothorax can occur in all lung disease, e.g., lung cancer, emphysema, diffuse interstitial fibrosis, etc.  Spontaneous idiopathic pneumothorax occurs when small blebs of peripheral tissue rupture without warning or apparent cause. Young people are more commonly affected. A cough may lead to sudden pain and dyspnea.
• Mechanical ventilation with PEEP predisposes to development of barotrauma and pneumothorax.
• Spontaneous pneumothorax also is encountered in patients with apparent normal lungs. Consider in this group congenital blebs, Marfan's, Ehlers-Danlos Syndrome and endometriosis.

Clinical Features

• Patients present with sudden onset of SOB, chest pain and cough.
• Cyanosis, shift of mediastinum, larger ipsilateral hemithorax, decreased chest expansion, hyper-resonance and decreased breath sounds are characteristic physical findings.
• Tension pneumothorax is present when the air leak is progressive. Venous return decreases resulting in falling blood pressure, tachycardia, worsening SOB and hypoxemia.

Therapy

• Asymptomatic pneumothorax is due to one time entry of air into the pleural space and can resolve spontaneously in a few days. Chest tube is not required in this instance.
• Symptomatic pneumothorax however small, requires either chest tube or Heimlich valve placement immediately.

PNEUMOCONIOSIS

PNEUMOCONIOSIS

A.    Silicosis

1.     Fibrotic disease of the lungs caused by inhalation of crystalline silicone dioxide.

2.     Occupations at risk: mining, manufacturing (glass, pottery, porcelain), sandblasting.

3.     Pathogenesis: Macrophages exposed to silica release chemotactic and fibrogenic factors.

4.     Pathology: Hyaline nodule having concentric whorls of connective tissue with an acellular central zone of free silica.

5.     Clinical presentations

a.      Chronic Silicosis: apparent 20 or more years after exposure.

b.     Accelerated Silicosis: apparent 5-15 years after exposure.

c.      Acute Silicosis: develops in 6 months to 2 years after massive exposure; fulminant course.

d.     Silicoproteinosis: a variant characterized by intra-alveolar lipoproteinaceous material similar to that of pulmonary alveolar proteinosis.

6.     CXR findings

a.      Simple: reticular and nodular patterns predominantly in the upper lobes; hilar adenopathy common, occasionally with "eggshell" calcifications.

b.     Progressive massive fibrosis: coalescence of larger nodules.

c.      Silicoproteinosis: alveolar filling pattern.

7.     Higher incidence of mycobacterial disease.

8.     Dx: Compatible history and characteristic CXR.

9.     Rx:  None; INH for patients with positive PPD.

B.     Asbestos-Related Disease

1.     Asbestosis is a fibrous silicae containing silicon and oxygen.

2.     Industries at risk: construction, manufacturing, shipbuilding, insulation

3.     Chrysotile fibers (serpentine group) account for 95% of world's production of asbestos; amphibole group considered more pathogenic (fibers with greatest length-to-diameter ratio are cost carcinogenic).

4.     Clinical conditions

a.      Parenchymal Pulmonary  Fibrosis (asbestosis)
- After 10-20 years of inhalational exposure.
- Fibers and asbestos bodies (fibers coated with protein-iron complexes) in lung biopsy.
- Interstitial changes usually at lung bases with progression to upper lobes.

b.     Pleural Plaques
- Thickened fibrotic areas of pleura (visceral and parietal); may coalesce to involve large areas of the lung.
- Occasionally plaques calcify and are sometimes seen along the diaphragm.

c.      Exudative Pleural Effusion
- Recurrent, blood-tinged; associated with pleural thickening or parenchymal fibrosis.

d.     Malignancy
- Increased risk of lung cancer with asbestos exposure; dose-related.
- Smoking multiples this risk.
- Increased risk of pleural and peritoneal mesothelioma (smoking does not add to the risk of mesotheliomas).
- Increased risk of cancers of the GI tract, larynx, kidney, pancreas, ovary, and eye with asbestos exposure.

C.    Coal Worker's Pneumoconiosis

1.     Associated with coal dust exposure.

a.      Risk increases with intensity, duration and higher ranks (hardness) of coals. Anthracite is the hightest rank (mined in eastern U.S.) followed by bituminous and lignite.

b.     Although there are immunologic abnormalities (elevated IgG, IgA, C3), the pathogenesis remains unknown.

2.     Clinical manifestations (develop over 10-20 years)

a.      Simple Coal Worker's Pneumoconiosis (SCWP)
- Few symptoms.

b.     Progressive Massive Fibrosis
- Associated with anthracite coal.
- May see melanoptysis due breakdown of lesions.
- Can appear after expsoure stops.

c.      Caplan's Syndrome (Rheumatoid Pneumoconiosis)
- Associated with rheumatoid arthritis.
- Nodules (0.5-5cm) on CXR in individuals with SCWP; nodules may cavitate.
- Also occurs with other pneumoconioses.
- Rheumatoid factor positive in 70% of patients.

3.     No increased risk of TB.

4.     Dx: History of dust exposure and characteristic CXR.

D.   Berylliosis

1.     Exposures: fluorescent light industry, ceramics, nuclear control equipment, electronics

2.     Acute disease (rare): toxic, dose-related, bronchiolitis, pulmonary edema, chemical pneumonitis.

3.     Chronic disease: multisystemic granulomatous disorder which involves the lung; course variable.