• Inflammation of the nasal mucosa
• Adenovirus MCC
• Presents with sneezing, congestion, and runny nose (common cold symptoms)
• Allergic rhinitis is due to type 1 hypersensitivity due to pollen
• Characterized by an inflammatory infiltrate with eosinophils
• Associated with asthma and eczema

• Protrusion of edematous inflamed nasal mucosa
• Usually secondary to repealed bouts of rhinitis can also occur in CF and aspirin-intolerant asthma
• Aspirin intolerant asthma is characterized by the triad of asthma, aspirin-induced bronchospasms, and nasal polyps
• Seen in 10% of asthmatic adults

• Benign tumor of nasal mucosa composed of parge blood vessels and fibrous tissue
• Classically seen in adolescent makes
• Presents with profuse epistaxis (nose bleed) 

• Malignant tumor of nasopharyngeal epithelium
• Associated wtih EBV
• Classically seen in African children and Chinese adults
• Biopsy usually reveals pleomorphic keratin-positive epithelial cells in a background of lymphocytes
• Poorly differentiated squamous cell carcinoma
• Involvement of cervical lymph nodes

• Inflammation of the epiglottis
• H. influenzae type B is MCC
• Presents with high fever, sore throat, drooling with dysphagia, muffled voice, and inspiratory stridor
• Risk of airway obstruction

Laryngotracheobronchitis

Croup

• Inflammation of the upper airway
• Parainfluenza is MCC
• Presents with a hoarse, "barking" cough and inspiratory stridor  

Vocal Cord Nodule

Singers Nodule

• Nodule that arises on the true vocal cord
• Due to excessive use of vocal cords
• Usually occurs bilaterally
• Composed of degenerative (myxoid) connective tissue
• Presents with hoarsness and resolves with resting of the voice  

• Benign papillary tumor of the vocal cord
• Due to HPV 6 and 11
• Papillomas are usually single in adults in multiple in children
• Presents with hoarseness  

• SCC usually arising from the epithial linnning of the vocal cords
• Risk factors:
• Alcohol
• Tobacco
• Rarely from laryngeal papilloma
•  Presents with hoarsness, cough, stridor

• Infection of lung parenchyma
• Occurs when normal defenses are impaired
• Clinical features:
• Fever
• Chills
• Productive cough with yellow-green pus, or rusty (blood) sputum
• Tachypnea
• Pleuritic chest pain
• Decreased breath sounds
• Dullness to percussion
• Elevated WBC
•  Diagnosis is made by chest x-ray, sputum Gm stain and culture, and blood cultures
• X-ray patterns:
• Lobar pneumonia
• Bronchopneumonia
• Interstitial pneumonia

• Characterized by consolidation of an entire lobe of the lung
• Usually bacterial
• MCC's S. pneumoniae and K. pneumoniae
• Classic gross phases of lobar pneumoniae
• Congestion: due to congested vessels and edema
• Red Hepatization: Due to exudate, neutrophils, and hemorrhage filing the alveolar air spaces.  This gives the lung a solid consistency
• Gray Hepatization: Due to degradation of red cells within the exudate
• Resoluton   

• Characterized by scattered pathcy consolidation centered around the bronchioles
• Often multifocal and bilateral
• Caused by a variety of bacterial organisms 

• Characterized by diffuse interstitial infiltrates
• Presents with relatively mild upper respiratory symptoms
• Minimal sputum
• Low Fever
• Atypical presentation
• Caused by bacteria or virus 

• Seen in patients at risk for aspiration: alcoholics and comatose patients
• Most often due to anaerobic bacteria in the oropharynx
• Bacteroides
• Fusobacterium
• Peptococcus 
• Classically results in a right lower abscess
• The right main stem bronchus branches at a less acute angle than the left

• S. pneumoniae: MCC of community acquired pneumonia. 
• Middle aged adults
• K. pneumoniae: Affects malnourished and debilitated individuals
• Elderly in nursing home
• Alcoholics
• Diabetics
• Thick mucoid capsule results in gelatinous sputum (Currant jelly)
• Often complicated by abscess  

• S. aureus: MC of seconday pneumonia (bacterial pneumonia superimposed on a viral URI
• Complicated by abscess formation
• H. influenzae: common cause of secondary pneumonia and pneumonia superimposed on COPD
• P. aeruginosa: CF patients
• Moraxella calarrhalis: Community acquired pneumonia and pneumonia super imposed on COPD
• L. pneumonphila: Community acquired pneumonia superimposed on COPD or pneumonia in immunocompromised states
• Transmitted from water sources
• Intracellular organism that is best visualized by silver stain

• M. pneumoniae: MCC of atypical pneumonia
• Young adults: clasically military recruits, college students living in dorm
• Complications include autoimmune hemolytic anemia: IgM mediated
• Erythema Multiforme
• Not visible on Gm stain due to lack of cell wall
• C. pneumoniae: Young adults
•  RVS: MCC in infants
• CMV: Atypical pneumonia with post transplant immunosupressive therapy
• Influenza virus: Atypical pneumonia in the elderly, immunocompromised, and preexisting lung disease
• Increases risk for superimposed S. aureus or H. influenza bacterial pneumonia
• C. burnetti: Q fever
• Atypical pneumonia with high fever
• Seen in farmers and veterinarians
• Rickettsial organism
• Does not require arthropod vector for transmission
• Does not produce skin rash

• Due to inhalation of aerosolized M. tuberculosis
• Primary TB arises with initial exposure
• Results in focal caseating necrosis in the lower lobe of the lung and hilar lymph nodes that undergoes fibrosis and calcifications. Forms a Ghon complex
• Asymptomatic
• + PPD
• Secondary TB arises with reactivation of M. tuberculosis
• Immunocompromised individuals
• Occurs at the apex of lung (high oxygen tension)
• Forms a cavity of foci of caseous necrosis
• Can lead to miliary pulmonary TB
• Clinical Features: Weight loss, night sweats, cough with hemoptysis, and fevers
• Biopsy reveals caseating granulomas
• Acid-fast bacilli
• Systemic spread often occurs and can involve any tissue
• Meninges
• Cervical lymph nodes
• kidneys
• Lumbar Vertebrae

Chronic Obstructive Pulmonay Disease

Basic Principles

• Group of disease cahracterized by airway obstruction
• Lung does not empty, air is trapped
• Volume of air that can forcefully expired is decreased (FVC) expecially during the first second (FEV1)
• FEV:FVC ratio decreased
• Total lung capacity (TLC) is increased due to air trapping

• Chronic productive cough lasting at least 3 months over a minimum of 2 yrs
• Highly assocaited with smoking
• Characterized by hypertrophy of bronchial mucinous glands
• Leads to increased thickness of mucous glands relative to overall bronchial wall thickness
• Reid index increases >50% Normal is < 40%
• Clinical Features:
• Productive cough due to excess mucous production
• Cyanosis "blue bloaters"
• Mucus plugs trap carbon dioxide
• Increased risk of infection and cor pulmonale  

• Destruction of alveolar air sacs
• Loss of elastic recoil and collapse of airways during exhalation results in obstruction and air trapping
•  Due to an imbalance of proteases (elastase) and antiproteases (antielastase)
• Inflammation of the lung normally leads to release of proteases by neutrophils and macrophages
• α₁-antitrypsin (A1AT) neutralizes proteases
• Imbalance between oxidants and antioxidants (glutathione)
• Elastase and oxidants derive from neutrophils and macrophages
• Cigarette smoke is a chemotactic to neutrophils and macrophages
• Leads to excessive inflammation and protease-mediated damage
• Free radicals in cig smoke inactivate A1AT and antioxidants
• Produces functional A1AT deficiency
• Results in centriacinar emphysema that is most severe in upper lobes
• Excessive inflammation or lack of A1AT leads to destruction of the alveolar air sacs
• True A1AT deficiency is a rare cause of emphysema
• Lack of antiproteases leaves the air sac vunerable to protease mediated damage
• Results in panacinar emphysema that is most severe in the lower lobes
• Liver cirrhosis may also be present
• A1AT deficiency is due to misfolding of the mutated protein
• Mutatnt A1AT protein accumulates in the endoplasmic reticulum of hepatocytes resulting in liver damage
• Biopsy reveals pink, PAS (+) globules in hepatocytes
• Disease severity depends on the degree of A1AT defieicent
• PiM is the normal allele to copies are usually expressed (PiMM)
• PiZ is the most common clinically relevant mutation and results in significantly low levels of circulating A1AT
• PiMZ heterozygotes are usually asymptomatic with decreased circulating levels of A1AT but are at a sig risk of developing emphysema with smoking
• PiZZ homozygotes are at significant risk for panacinar emphysema and cirrohsis
• Clinical Features of emphysema:
• Dyspnea
• Cough with minimal sputum
• Prolonged expiration with pursed lips "pink puffer"
• Wight loss
• Increased anterior-posterior diameter of chest "barrel chest"
• Hypoxemia due to destruction of capillaries in the alveolar sac and cor pulmonale are late complications

• Reversible airway bronchoconstriction 
• Type I hypersensitivity
• Presents in childhood
• Often associated with allergic rhinitis, eczema, allergies
• Family history
• Allergens induce Th2 phenotype in CD4 T cells of genetically susceptible  
• Th2 cells secretes IL-4 which mediates class switching it IgE, IL-5 which attracts eosinophils, and IL-10 which stimulates Th2 and inhibits Th1
• Reexposure to allergens leads to IgE mediated activation of mast cells
• Release of preformed histamine granules and generation of leukotrienes C4, D4 and E4
• Leads to bronchoconstriction, inflammation, and edema (early-phase reaction)
• Inflammation, especially major basic protein released from eosinophils damages cells and perpetuates bronchoconstriction (late phase reaction)
• Clinical Features are epidodic and realted to allergen exposure:
• Dyspnea and wheezing
• Productive cough, classically with spiral shaped mucus plugs (Curschmann spirals)
• Eosinophil derived crystals (Charcot-Leyden crystals)
• Severe, unrelenting attack can result in asthmaticus and death
• Asthma may also result from non-allergic causes such as exercise, viral infection, aspirin, and occupational exposures

• Permanent dialtion of bronchioles and bronchi
• Loss of airway tone results in air trapping
• Due to necrotizing inflammation with damage to airway cells
• Causes:
• CF
• Kartagener Syndrome: Inherited defect of the dyenin arm which is necessary for ciliary movement.  Associated wtih sinusitis, infertility (poor motility of sperm) and situs inverus
• Tumor or forgein body
• Necrotizing infections
• Allergic bronchopulmonary aspergillosis
• Hypersensitivity reaction to Aspergillus
• Leads to chronic inflammatory damage
• Usually seen in individuals with asthma or CF
• Clinical Features:
• Cough
• Dyspnea
• Foul smelling sputum
• Complications include hypoxemia with cor pumlomale and secondary amyloidosis

• Characterized by restricted filling of the lung
• Decreased FEV1
• Decreased FVC- often the same value as FEV1
•  FEV1/FVC is increased bc they are teh same value so 100% and normal is 80%
• MC due to intersitial disease of the lung but can also arise with chest wall abnormalities that can be seen in massive obesity

• Fibrosis of lung interstitium
• M>F
• 40-70 yrs old
• Etiology is unknown thought to be due to:
• Repeated cycles of alveolitis caused by an unknown agent
• Releases cytokines which produces interstitial fibrosis
• Alveolar fibrosis leads to proximal dilation of the small airways
• Lung has a honeycomb appearance
• Clinical Features:
• Fever
• Dyspnea
• Cough
• Inspiratory crackles
• Fibrosis on lung CT: initially seen in subpleural patches but eventually results in diffuse fibrosis with endstage honeycomb lung
• Treatment is lung transplant

• Interstitial fibrosis due to occupational exposure
• Requires chronic exposure to small particles taht are fibrogenic
• Particles smaller than 0.5um reach the alveoli and are phagocytosed by macrophages which induces fibrosis
• Coal Workers' Pneumoconiosis
• Exposure to carbon dust seen in coal mines
• Massive exposure leads to fibrosis "black lung"
• Associated with Rheumatoid arthritis (Caplan syndrome)
• Mild exposure to carbon (pollution) results in anthracosis
• Collections of carbon-laden macrophages
• Not clinically significant
• Silicosis
• Silica is seen in sand blasters and silica miners
• Fibrotic nodules in upper lobe of the lung
• Increased risk for TB
• Silica impaires phagolysosome formation by macrophages
• Berylliosis
• Beryllium seen in beryllium miners and workres in the aerospace industry
• Noncaseating granulomas in the lung, hilar lymph nodes, and systemic organs
• Increased risk of lung cnacer
• Asbestosis
• Asbestos fibers in construction workers, plumbers, and shipyard workers
• Fibrosis of lung and pleura (plaques) with increased risk for lung carcinoma and mesothelima
• Lung carcinoma is more common than mesothelioma in exposed individuals
• Lesions may contain long golden brown fibers with associated iron called asbestos bodies
• Confirms exposure to asbestos  

• Multisystem granulomatous diseae of unknown etiology
• More common in blacks and non smokers
• W > M
• CD4 T cells interact with an unknown antigen which releases cytokines causing formation of noncaseating granulomas
• Diagnosis of exclusion-must rule out other granulomatous diseases
• Lung Disease
• Primary target organ
• Granulomas located in the interstitium and mediastinal and hilar nodes
• Multinucleated giant cells
• Schaumann bodies-laminated calcium concretions
• Asteroid bodies- Stellate inclusion
• Skin Lesions
• Nodular lesions containing granulomas
• Violaceous rash occurs on the nose and cheeks called lupus pernio
• Erythema nodosum- painful nodules on lower extremities. Inflammation of subcutaneous fat
• Eye lesions
• Liver lesions
• Enlarged salivary and lacrimal glands
• Diabetes insipidus-hypothalmic and posterior pituitary disease
• Granulomas in the bone marrow and spleen
• Increased angiotensin-converting enzyme
• Hypercalcemia (5%) via hypervitamin D b/c of increased synthesis 1-α-hydroxylase
• Dyspnea or cough (MC presenting symtom)
• Treatment is steroids
• Often resolves spontaneously without treatment

• Granulomatous reacton to inhaled organic antigens
• Presents with fever, cough, and dyspnea hours after exposure
• Resolves with removal of the exposure
• Chronic exposure leads to interstitial fibrosis
• Does not involve IgE antibodies or have eosinophilia
• Farmers Lung
• Exposure to Saccharopolypora rectivirgula in moldy hay
• First exposure: Patient develops precipitating IgG antibodies (present in serum)
• Second exposure: Antibodies combine with inhaled allergens to form immune complexes
• Type III hypersensitivity
• Produces an inflammatory reaction in lung tissue
• Chronic Exposure is type IV hypesensitivity
• Silo Fillers Disease:
• Inhalation of gases (NO) from plant material
• Immediate hypersensitivity reaction associated with dyspnea
• Byssinosis
• Occurs in textil factories
• Contact with cotton, linen, and hemp products
• Exposure to bacterial endotoxin from Gm(-) bacteria growing on the cotton
• Develop dyspnea on exposure to cotton, limen or hemp products
• Workers feel better over the weekend bc they are no longer exposed to the antigen
• Depression occurs when returning to work on Monday "Monday morning blues"

• Diffuse damage to the alveolar capillary interface- diffuse alveolar damage
• Leakage of protein rich fluid leads to edema and formation of hyaline membranes in alveoli
• Hypoxemia and cyanosis with respiratory distress due to thickened diffusion barrier and collapse of air sacs
• Increased surface tension
• White out is seen on chest x-ray
• Secondary to a variety of disease processes including sepsis, infection, shock, trauma, aspiration, pancreatitis, hypersensitivity reactions, and drugs
• Activation of neutrophils induces protease-mediated and free radical damage of Type I and Type II pneumocytes
• Treatment:
• Address underlying cause
• Ventilation with positive end expiratory pressure
• Recovery may be complicated by interstitial fibrosis, damage and loss of type II pneumocytes which can lead to scarring and fibrosis  

• Respiratory distress due to inadequate surfactant levels
• Surfactant is made by type II pneumocytes, phosphatidylcholine (lecithin) is the major component
• Surfactant decreases surface tension in the lung, preventing collapse of alveolar air sacs after expiration
• Lack of surfactant leads to collapse of air sacs and formation of hyaline membranes
• Prematurity: surfactant production begins at 28 weeks.  Adequate levels are reached until 34 weeks
• Amniotic fluid lecithin to sphingomyelin ratio is used to screen for lung maturity
• Lecithin levels increase as surfactant is produced; sphingomyelin remains constant
• A ratio of > 2 indicates adequate surfactant production
• Caesarin section delivery: Due to lack of stree induced steroids.  Steroids increase synthesis of surfactant
• Maternal Diabetes: Insulin decreases surfactant production
• Clinical Features:
• Increasing respiratory effort after birth
• Tachypnea with use of accessory muscles and grunting
• Hypoxemia with cyanosis
• Diffuse granularity of the lung (ground glass appearance) on x-ray
• Hypoxemia increases the risk for persistence of patent ductus arteriosus and nectrozing enterocolitis
• Supplemental oxygen increases the risk for free radical injury
• Retinal injury leads to blindness
• Lung damage leads to bronchopulmonary dysplasia

• MCC of cancer mortality in US
• Avg age of presentation is 60
• Risk factorse are cigarette smoke, radon, and asbestos
• Presenting symptoms can be non-specific such as: wight loss hemoptysism and postobstructiv pneumonia
• Imaging often reveals a solitary nodule (coin lesion)
• Biopsy is necessary for a diagnosis of cancer
• Benign lesions often occur in younger patients and can also produce coin lesions
• Granuloma due to TB or fungus like Histoplasma
• Bronchial hamartoma- benign tumor composed to lung tissue and cartilage olien calcified on imaging
• 2 categories:
• Small Cell Carcinoma: not amenable to surgery treated with chemotherapy
• Non-small cell carcinoma- treated upfront with surgical resection. Does not respond well to chemotherapy. 
• TNM staging
• T: Tumor size and local extension
• Pleural involvement is classically seen with adenocarcinoma
• Obstruction of SVC leads to distended head and neck veins with edema and blue discoloration of arms and face (SVC syndrome)
• Involvement of recurrent laryngeal (hoarseness) or phrenic (diaphragmatic paralysis) nerves
• Compression of sympathetic chain leads Horner syndrome characterized by ptosis, miosis, and anhidrosis uaually due to a apical (Pancoast tumor)
• N: spread to regional lymph nodes (hilar and mediastinal)
• M: Unique site of distant metastasis is the adrenal gland
• Overall 15% 5 year survival rate: often presents at a late stage due to absence of an effective screening method

• Poorly differentiated small cells
• Arise from neuroendocrine (Kulchitsky) cells
• MC in male smokers
• Central Location
• Rapid growth and early metastasis
• May produce ADH or ACTH
• Eaton-Lambert syndrome 

• Keratin pearls or intracellular bridges are seen on histology
• MC  tummor in male smokers
• Central location
• May produce PTH-related  peptide (PTHrP)

• Peripheral location
• MC in W and non-smokers
• NO RELATIONSHIP WITH SMOKING
• Glands or mucin seen on histology
• Scar Carcinomas: Develop in scars
• Bronchioloalveolar carcinoma: Derives from Clara cells (nonciliated epithelium).  Malignant cells spread along alveolar walls (look like pegs).  Radiologically mimic lobar pneumonia.

• Poorly differentiated large cells without keratin pearls, without intracellular bridges, without glands, without mucin
• Association with smoking
• Central or Peripheral location
• Poor Prognosis 

• Columnar cells that grow along preexisting bronchioles and alveoli
• Arise from Clara cells
• Not related to smoking
• Peripheral
• May present with pneumonia like consolidation on imaging
• Excellent prognosis 

• Well differentiated neuroendocrine cells
• No assocaition with smoking
• Mean age of 55
• MC primary lung tumor of children
• Central or peripheral location
• Forms a polyp-like mass in the bronchus
• Low Grade malignancy
• Rarely can cause carcinoid syndrome
• Presents with hemoptysis, cough, and carcinoid syndrome  

• Most common sources are breast and colon carcinoma
• Multiple cannon call nodules on imaging
• More common than primary tumors  

• Accumulation of air in the pleural space
• Spontaneous pneumothorax is due to rupture of an emphysematous bleb seen in young adults
• Results in collapse of a portion of the lung
• Trachea shifts to the side of collapse
• Tension pneumothorax arise with penetrating chest wall injury
• Air enters the pleural space but cannot exit
• Trachea is pushed to the opposite side of injury
• Medical emergency
• Treated with insertion of a chest tube

• Malignant neoplasm of mesothelial cells
• Highly associated with occupational exposure to asbestos
• Presents with recurrent pleurl effusions, dyspnea, and chest pain
• Tumor encases the lung