A. Obstructive Diseases

1. Emphysema
   1. Pathologic diagnosis with airspace enlargement and loss of lung elasticity
   2. Lung destruction distal to terminal bronchiles
   3. Pathologies include panacinar, distal acinar, and centriacinar
   4. Characterized by decreased DLCO and moderate to severe obstruction, air trapping
2. Chronic Bronchitis
   1. Chronic cough and sputum production for at least 3 months per year over 2 years
   2. Edema, goblet cell a nd mucus gland hyperplasia, infection and inflammation
   3. Characterized by airway obstruction (increased resistance) with decreased FEV1
   4. Unaffected (until very late) DLCO; possible change in FVC
3. Asthma
   1. Airway hyper-responsiveness (increased resistance)
   2. Unaffected DLCO; decreased FEV1 and/or FEV25-75 or MMF, unchanged or decreased FVC
   3. Characterized by airway inflammation, eosinophilia, neutrophilia

B. Restrictive Lung Diseases

1. All have reduced Diffusing Capacity and FVC
2. Idiopathic pulmonary fibrosis (IPF)
   1. Lesions are primarily peripheral, lateral (not hilar/medial)
   2. Usually divided into chronic and acute / subacute diseases
   3. Rapid progression of disease with respiratory failure = Hamman-Rich Syndrome
3. Sarcoidosis
   1. Non-caseating idiopathic granulomas, mainly affect lung
   2. Primary lesions are primarily hilar, paratracheal, mediastinal
   3. Secondary lesion: lung parenchymal involvement with resolution of primary
4. Adult Respiratory Distress Syndrome (ARDS)
   1. Defined as non-cardiogenic exudative capillary leak syndrome
   2. Lungs have much decreased compliance with normal left ventricular filling pressure
5. Transudative Processes
   1. Left heart failure (CHF)
   2. Low albumin conditions - liver failure, nephrotic syndrome, chronic disease
   3. Non-cardiogenic capillary leak syndromes (drug induced, ARDS)
   4. These are not true restrictive "diseases", but rather processes with restrictive PFTs
6. Langerhan's Cell Histiocytosis
   1. Also called Eosinophilic Granuloma, Histiocytosis X, Langerhan's Cell Granuloma
   2. Usually upper lobe focal involvement with epidermoid histiocytes
   3. Macrophages with Langerhans Cell Histiocytosis
   4. Usually also have skull involvement with lytic lesions
7. Lymphadenopathy
   1. Infection, HIV Lymphadenopathy, fungal, TB etc.
   2. Lymphoma - usually Hodgkin's Disease
   3. Renal Cell CA, Thyroid CA
   4. Sarcoidosis
8. Pulmonary Eosinophilia Pneumonia Syndromes
   1. Loffler's Syndrome: simple pulmonary eosinophilia, fever, prompt recovery
   2. Chronic Eosinophilic Pneumonia: bronchial asthma, peripheral eosinophilia
   3. Allergic Bronchopulmonary Aspergillosis (APBA): bronchial asthma
   4. Churg-Strauss Vasculitis: allergic granulomatosus with eosinophilia
   5. Idiopathic hypereosinophilic syndrome
   6. Severe Asthma
   7. May be due to overproduction of eotaxin, IL-5, and other eosinophil stimulants

C. Pulmonary Infection

1. Broad Categories
   1. Traceobronchitis - including croup
   2. Pneumonia
   3. Normal versus Immunocompromised Host
2. Bronchitis
   1. Non-smokers - usually viral
   2. Smokers - often bacterial (or viral with bacterial superinfection)
   3. Of bacteria, S. pneumoniae, M. catarrhalis, H. influenza are most common
3. Pneumonia
   1. Typical Organisms - defined by mainly neutrophil inflammation
   2. Atypical Organisms - macrophages, lymphocyte inflammation
   3. Immune competent versus incompetent hosts
   4. Aspiration Syndromes [5]
   5. Non-infectious pneumonias also occur (inflammatory lesions) [1]
4. Viral Agents
   1. Influenza
   2. Measles
   3. Respiratory syncytial virus (RSV)
   4. Adenovirus
5. Typical Bacterial Agents
   1. Streptococcus pneumoniae is very common, regardless of host age or immune status
   2. H. influenza - most common in smokers
   3. Staphylococcus aureus - wall destruction; often hospital acquired
   4. Moraxella catarrhalis - usually in smokers, often with bronchitis
   5. Gram Negative Rods - Pseudomonas, E. coli, Klebsiella
6. Atypical Bacterial Agents
   1. Mycoplasma pneumoniae - may be most common cause of pneumonia in young persons
   2. Legionella pneumonphilia
   3. Chlamydia pneumonia (TWAR Agent)
   4. Tuberculosis
7. Immunocompromised Hosts
   1. Pneumocystis carinii
   2. Atypical Mycobacteria
   3. Cytomegalovirus
   4. Nocardia asteroides
   5. Gram Negative Rods
   6. Fungal Infection
8. Cavitation may occur, particularly in chronic and/or severe infections [9]

D. Lung Mass

1. Malignant Parenchymal Neoplasm
   1. Small Cell / Oat cell Carcinoma: fastest growing, some response to chemotherapy
   2. Large Cell / undifferentiated or differentiated: usually slower growing than SCLC
   3. Adenocarcinoma
   4. Squamous Cell Carcinoma (from epidermoid metaplasia)
   5. Alveolar Cell (Bronchoalveolar) Ca
2. Lymphoma
3. Mesothelioma: most common in smokers exposed to asbestos
4. Carcinoid (usually causes obstruction)
5. Inflammatory Pseudotumor (usually <12 yrs old)
6. Sarcoidosis (uncommon true mass)
7. Echinococcal Cyst [11]
8. Foreign-Body reactions - may appear as pseudotumor [1]

E. Alveolar (Pulmonary) Hemorrhage [2,7,10]

1. Due to injury and destruction of alveolar epithelial cells and basement membrane
2. Hemosiderin laden macrophages are hallmark
3. Causes of Diffuse Pulmonary Hemorrhage
   1. Pulmonary - Renal Syndromes
   2. Cardiovascular Disorders
   3. Coagulation Disorders - hemophilia, von WIllebrand's disease
   4. Idiopathic Pulmonary Hemosiderosis [7,10]
   5. Heiner's Syndrome - allergy to cow's milk protein
   6. Many additional causes have been reported (Table 3, Ref [7])
4. Pulmonary - Renal Syndromes
   1. Goodpasture's Syndrome
   2. Wegener's Granulomatosis
   3. Microscopic Polyangiitis
   4. Henoch-Schonlein Purpura
   5. Systemic Lupus Erythematosus
5. Cardiovascular Disorders
   1. Congenital heart disease
   2. Pulmonary hypertension
   3. Pulmonary embolism
   4. Pulmonary-capiallary hemangiomatosis
   5. Mitral valve stenosis (severe)
6. Causes of Focal Pulmonary Hemorrhage
   1. Pneumonia, especially supperative infection: Staphylococcus, Mycobacterium
   2. Bronchitis
   3. Bronchiectasis (mainly in cystic fibrosis)
   4. Bronchogenic or parenchymal lung carcinoma or pulmonary carcinoid tumor
   5. Trauma: Secondary to other pulmonary injury
   6. High altitude pulmonary edema (usually mild hemorrhage)
   7. Pulmonary infarction
   8. Arteriovenous malformation (AVM)
   9. Bronchogenic cyst
   10. Foreign body
   11. Broncholithiasis can cause hemoptysis [8]

F. Aspiration Syndromes [5]

1. Aspiration pneumonitis (Mendelson's Syndrome) - chemical injury
2. Aspiration pneumonia - infection with oropharyngeal bacteria
3. Airway obstruction - mucus plugging
4. Lung abscess
5. Exogenous lipoid pneumonia
6. Chronic interstitial fibrosis
7. Mycobacterium fortuitum pneumonia

G. Pulmonary Vascular Diseases

1. Cor Pulmonale: Pulmonary Hypertension, Right heart failure, due to intrinsic lung disease
2. Essential Pulmonary Hypertension
3. Emboli - usually from deep leg vein thrombosis
4. Vasculitis
   1. Churg-Strauss Syndrome (variant of polyarteritis)
   2. Wegener's Granulomatosis
5. Pulmonary Venous Congestion
   1. Uncommon, idiopathic disease in most cases
   2. Mitral stenosis, Left Atrial Myxoma, severe mitral regurgitation may underlie
   3. Presentation with hemoptysis not uncommon
   4. Pulmonary hypertension and hemosiderosis are usually found
6. High altitude pulmonary edema [6]

H. Disturbances of Respiratory Pattern

1. Hyperventilation / tachypnea is common response to many insults
   1. Hypoxia
   2. Inhalation exposure
   3. Hypercarbia (respiratory acidosis) and/or metabolic acidosis
   4. Panic Attack / Anxiety
2. Hypoventilation is uncommon in conscious patients
   1. Mild hypoventilation in metabolic acidosis
   2. Mild hypoventilation during sleep
3. Abnormal respiratory patterns are common in unconscious patients
   1. Kussmaul Breathing
   2. Cheyne-Stokes Respiration
   3. Central neurogenic hyperventilation associated with midbrain damage
   4. Ataxic breathing (agonal gasps) commonly associated with pontine-medullary junction
   5. Hypoventilation or apnea commonly associated with medullary dysfunction
4. Kussmaul Breathing
   1. Rapid, deep breathing in unconscious patients
   2. Associated with metabolic encephalopathy (acidosis)
   3. Diabetic ketoacidosis frequently produces this pattern
   4. Also found with pontomesencephalic lesions
5. Cheyne-Stokes Respiration
   1. Periodic (cyclical) breathing pattern usually found in severe disease
   2. Apenas or hypopneas alternate with hyperventilation in cresecendo-decrescendo pattern
   3. Bilateral cortical dysfunction including coma
   4. Sedative drug intoxication
   5. Heart Failure
   6. Sleep Apena
   7. Direct vascular lesions
   8. Theophylline has been shown to effectively alleviate this condition [3,4]
   9. Oxygen or carbon dioxide may also be effective
6. Brain dead patients may have shallow respiratory-like movements with back arching

I. Congenital Pulmonary Diseases

1. Dysplastic Lung
2. Lobar Emphysema
3. Tracheo-esophageal Fistula
4. Bronchogenic Cyst
5. Congenital Surfactant hypoproduction
   1. Atelectasis - closing of small alveoli
   2. Compliance reduced; fluid in lungs / transudate

References

1. Wain JC and Mark EJ. 1997. NEJM. 337(17):1220 (Case Record)
2. Sherter CB and Mark EJ. 2001. NEJM. 344(3):212 (Case Record)
3. Pesek CA, Cooley R, Narkiewicz K, et al. 1999. Ann Intern Med. 130(5):427
4. Javaheri S, Parker TJ, Wexler L, et al. 1996. NEJM. 335:562
5. Marik PE. 2001. NEJM. 344(9):665
6. Hackett PH and Roach RC. 2001. NEJM. 345(2):107
7. Silverman ES and Mark EJ. 2002. NEJM. 347(21):1693 (Case Record)
8. Meyer M and O'Regan A. 2003. NEJM. 348(4):318 (Case Report)
9. Cao AY, Munandar R, Ferrara SL, et al. 2005. NEJM. 352(25):2628 (Case Record)
10. Boyer D, Westra SJ, Kinane B, Stone JR. 2007. NEJM. 356(4):398 (Case Record)
11. Yeh WW, Saint S, Weinberger SE. 2007. NEJM. 357(5):489 (Case Record)