Lecture 1: Microbiology of Respiratory

Respiratory tract is the most common site of infections  exposure to many airborne pathogens [breathing/ hand to nose/mouth contact]

Professional Invaders: Secondary Invaders:

 Can infect HEALTHY respiratory tract
– Adhesion to normal mucosa
– Ability to interfere with cilia
– Resist destruction by alveolar M
[macrophages]
– Ability to damage local tissues
• Mucosal or sub mucosal
 Secondary cause infections when the host defenses are impaired
– 2° infection after damage by respiratory virus
• Influenzae virus
– Local defenses impaired
• Cystic fibrosis
– Depressed immune function
• HIV especially if you moving into AIDS
– Pneumocystis jiroveci [PCP]
– Depressed resistance
• Age
• Alcoholism
• Renal or hepatic disease

Otitis Media • May be primary infection

• More likely 2° bacterial infection
• Most common reason for pediatric antibiotics
– <5 years may have several per year
*More likely to occur in children  adults have changes in eustachian tube that make it less likely but still possible
Otitis externa [psuedomonas in adults]
– >5 years incidence drops
• Patient present with
– Fever
– Ear pain
• Toddler “ear tugging”; tipping their head
– Headache
– Otoscopic examination will reveal bulging tympanic membrane and poor mobility
– Young children/ infants only sign may be irritability
– Usually spontaneously resolves
• Treatment lessens duration
• Most common causes
– Streptococcus pneumoniae [most common <3 months] – Haemophilus influenza-non-typable [> 3months]
• Manifest suddenly with high fever and Otalgia (ear pain)
• Not likely to spontaneously resolve
– Moraxella catarrhalis – milder disease with spontaneous resolution [older children]
• Moraxaella is gram negative and both diplococci. Grows on McConkeys
• 3 Types
– Acute – almost always bacterial complication of viral URI [upper respiratory infection]
– Chronic – unresolved acute
• Prolonged by inadequate treatment
• Host factors – Eustachian tube dysfunction, allergy, immunodeficiency
• Progressive middle ear destruction may occur
• Significant permanent hearing loss
– Serous (secretory) – may be chronic or allergy related inflammation
• Associated with hearing loss
• Thick non-purulent secretions in the middle ear can transform purulent as secondary infections
• Management
– Empirical antibiotic treatment
– Extreme pressure/ severe pain
• Drainage of exudates may be required
• Incision of tympanic membrane
Sinusitis • >24 million cases per year, Children <15 years and Adults 25-64 most likely
• Can have Subacute, Acute and Chronic forms Management:
• Acute duration of 4 weeks or less
• Usually viral or bacterial Empirical treatment for
• Most often URI of viral origin potentially leading to bacterial *** uncomplicated cases
• >7 days likely hood of 2° bacterial infection increases as cause Amoxicillin or Augmentin
• Chronic last 12 or more weeks [amoxicillin + clavulanic acid]
• Wide range Allergic or non-allergic causes
• Subacute is the transition between Acute and Chronic Severe cases require culture
• 4-12 weeks for sensitivity testing
• Other Causes include allergies, air pollution, or structural problems Surgery may be required
Common causes Impacted sinus
• Respiratory viruses
• Direct cause
• Rhinovirus (nonenveloped RNA), Influenza A virus, Parainfluenza, RSV (infants), Adenoviruses (nonenveloped DNA)
• More often predisposing factor
• <7 days bacterial superinfection unlikely Patient presents with:
• Bacteria  Fever
• Streptococcus pneumoniae - Haemophilus influenza  Purulent discharge
Bacterial Sinusitis:
• Responsible for more than 70% of cases  Sinus tenderness and pain
1. Persistence: >10 days
• Hib?? Non-encapsulated Haemophilus 2. Severity [mover severe than viral] - Maxillary toothache
• Moraxella catarrhalis 3. Worsening of respiratory symptoms [upper molars start to
• About 80% cases in older children - Biphasic presentation really ache]
Others: Streptococcus pyogenes, Staphylococcus aureus - Crap-feel better-crap  Fetid breath
Chronic forms:  Headache
– Usually compromised patient  Tenderness to percussion
• Severe diabetes or immunocompromised - Frontal or maxillary
– Fungal infections are being increasingly seen sinuses
• Aspergillus, Mucormycoses [really bad], Rhizopus 
Rhinitis • Manifestation of the common cold
• Characterized by
– Variable fever
– Inflammatory edema of the nasal mucosa
– Increased mucous secretion
• Initially clear and watery
• Thick purulent (because of the transformation to bacterial secondary infection) over next 5-10 days
• Most common causes
– Rhinoviruses, Adenoviruses, Coronaviruses, Parainfluenza viruses, Influenza viruses (C) – the influenza that we don’t vaccinate against,
RSV and Coxsackie A virus
• Management
– Treat symptoms
– Reduce fever
– Maintain patient comfort
Pharyngitis • 70 – 90% Viral origin***
– Rhinovirus and Adenovirus leading causes
– Seasonal Fall/Winter but can happen anytime of year
• Bacterial only 10-30%
– GAS leading cause [Strep. Pyogenes]
– Non-group A Streptococcus C and G
– Neisseria gonorrhoeae
• Orogenital sex with infected individual
– 70% women asymptomatic [their partner comes down with pharyngitis]
– DOES NOT MEAN the PHARYNGITIS is SYMPOTMATIC
• Prepubescent child think sexual abuse
• In young children < 3 years old most often due to viral infection
– Rhinovirus, Adenovirus and RSV
• Older children (5-15 years) Streptococcus pyogenes is most common etiologic agent
– GAS
– GABHS – beta hemolytic strep
– EBV
– Other Viruses and Mycoplasma pneumonia less common
• Patients present with erythema and swelling of the throat
• May have exudates of inflammatory cells
• Petechial hemorrhages on the mucosal membranes
• Regional spread to anterior cervical lymph nodes may occur
– Tender swelling of the nodes
• Management
– Only S. pyogenes must be diagnosed****
• Prevent sequelae – rheumatic fever
• Rapid test or culture
– Treat symptoms and maintain patient comfort
Laryngitis/Croup • Mainly associated with respiratory viruses
– Parainfluenza, Influenza, Adenovirus
– Sometimes RSV (more common in the very young), Rhinovirus and Coronavirus
– Rarely bacterial
• Children <2 years – croup
• Adults - laryngitis
• Presents with either abrupt onset or slow development over hours to days
• Patients present with
– Variable fever
– Inspiratory stridor
– Hoarseness
– Harsh barking cough
– Inflammation is limited to subglottic laryngeal structures
• Vocal cords
• Management – Self-limiting
– Maintain airway
– The really young will require hospitalization
– Relief may be provided by cold humidified air and oxygen
Tracheobronchitis/ • Two types based on whether patient has COPD or not
Bronchitis
• Normal patients • COPD patients
– May be a primary or secondary infection [more likely secondary] – Most cases bacterial origin
– Presents with • Long standing damage to
• cough bronchial epithelium
• Variable fever – Mucociliary clearance not
• Sputum production functioning
– Clear initially and becomes purulent later on – Chronic bronchitis
• Auscultation reveals coarse bubbling rhonchi/ gurgles • sign of serious lung disease
– Inflammation and increased fluid production in • may be slowed but cannot be
larger airways cured
– Mainly viral agents – Major etiologies
• Same as for croup • Haemophilus influenza
– Parainfluenza, Influenza, Adenovirus • Staphylococcus aureus
– Sometimes RSV, Rhinovirus and Coronavirus • Bordetella pertussis
• Infants more likely RSV • Morxella cartarrhalis
– Adults as vaccine immunity wanes a bacteria may present
• What bacteria?
– Bordetella pertussis
• GET THE BOOSTER so that you don’t give it to
child too young to be vaccinated
Pneumonia • Inflammation of the lungs that involves the lung parenchyma (alveolae)
• Most common infectious cause of death in the USA
• Age is most important factor in determining likely etiologic agent involved
• Commonly divided into Community Acquired (CAP) and Nosocomial
• Also divided into 2 types of presentation

Typical pneumonia Atypical pneumonia “walking pneumonia”

– Sudden onset – Presents with gradual onset

• Shaking Chills** • Non-productive cough
• Fever • Dyspnea
• Dyspnea – Patients may present on physical exam
• Productive cough • Fever
– Purulent sputum with or without blood • Tachypenea
tinged • Tachycardia
» Review the different colored sputum • X-rays reveal patchy or interstitial
[klebsiella red etc…] infiltrates without consolidation
• Pleuritic chest pain – have EXTRA-pulmonary signs***
– Patient will present with • Headache
• Tachypnea • Sore-throat
• Tachycardia • Diarrhea
• Rales on lung examination
• X-rays will reveal chest consolidation Etiologic agents
Caused by: • Mycoplasma pneumonia
• Chlamydia
– CAP (community acquired pneumonia) • Legionella
• Streptococcus pneumoniae • Mycoplasma and Chlamydia are more common in young adults
– Most common cause in adults
– Sputum brown rust colored • Viral causes are more common in infants and children
– Nosocomial – RSV
• Staphylococcus aureus (MRSA) – Influenza
– Sputum  pink salmon – Viral causes rare in adults
• Klebsiella pneumoniae TB – Mycobacterium tuberculosis
– Sputum  bright red and can be necrotic • Occurs in both immunocompetent and immunocompromised
– Anaerobes individuals
• Sputum  foul smelling • Relates to exposure history
• Associated with lower socioeconomic status
• Should be considered in atypical cases that are NOT improving with
antibiotic treatment with bloody sputum and weight loss
Special Risks
– These factors provide insight into
– Gross aspiration
• Frequently present as anaerobic infections or lung abscesses
– Alcoholism
• Aspiration due to epiglottic and cough reflexes
• Streptococcus pneumoniae
• Klebsiella pneumoniae
• Anaerobes
– IV drug use
• Staphylococcus aureus
– Post viral infection
• Staphylococcus aureus
– Neutropenia
• Aspergillus spp.
– Chronic steroids
 Nocardia : gram + catalase + rod
Lecture 2: Parasitic Lung Infections
Trematodes
(flukes) Paragonimus Kellicotti – lunmg fluke found in Kentucky ; Paragonimus westermani – india
 Human infection occurs by eating inadequately cooked or pickled crab or crayfish that harbor metacercariae of the parasite.
Adults live and mate
in the lungs

Tx: praziquantel
 Lesions are
either absorbed
or replaced by
fibrotic tissue

Nematodes Necator Americanus: New world hookworm Necatoriasis Ancylostoma duodenale: old world hookworm [Middle east, Africa, india]
(roundworms) • Lives in the Small intestines causing Necatoriasis

Larvae migrate
through lungs to
reach digestive tract

Persistent
Cough
 foot→ blood→ heart→ lungs→
swallowed epiglottis→ SI

• Egg-laden feces must land on shady, well-drained soil being favored by warm and humid (tropical) conditions
• i.e. southern US
• esp. Texas
• Adults in intestines cause abdominal pain, diarrhea, cramps, and weight loss that can lead to anorexia.
• Heavy infections can lead to the development of iron-deficiency and hypochromic microcytic anemia.
• This form of anemia in children can give rise to physical and mental retardation.
• Infection caused by cutaneous larvae migrans, [“creeping eruption”]a skin disease in humans, is characterized by skin ruptures and severe itching
Infected by canine or cat type

Strongyloides Stercoralis*******
Foot  blood  lungs  gut
• This nematode worm has a life cycle similar to hookworms (Necator and Anclystoma) in that infection is through the foot from contaminated soil.
• The larvae follow the bloodstream to the lungs where they penetrate the alveolar spaces.
• They continue their migration through the bronchioles to the trachea, over the epiglottis and down the esophagus to develop into adults in the
small intestines.
• Pulmonary symptoms (including Loeffler’s syndrome) can occur during pulmonary migration of the filariform larvae.
• Löffler syndrome***** = eosinophilic pneumonia results from eosinophil accumulation in the lungs in response to a parasitic infection.
• FEVER, COUGH, DYSPNEA, NIGHT SWEATS

Ascaris Lumbricoides
Egg ingestion  larvae penetrate gut  circulation  lungs  GI ; also has Loffler’s Syndrome
• In this parasite’s life cycle, the eggs are ingested (rather than foot penetration by soil larvae), hatch in the SI and migrate through the intestinal
wall to enter the circulatory system via mesenteric vessels.
• Later in the cycle, they migrate through lung alveoli to return to the SI to become mating adults, passing eggs in the feces
• COUGH, FEVER, DYSPNEA, NIGHT SWEATS
 Loa Loa Filariasis [L1 microfilaria demonstrate diurnal migration between the lungs and peripheral circulation]
• Filarial nematode (roundworm) responsible for Loa loa filariasis, commonly known as the “eye worm” subconjunctiva

The microfilariae have been recovered from

- Spinal fluids
- Urine Tx: Diethylcarbamazine
- Sputum
or surgical removal

• ♂ & ♀ mate in human host

• ♀ gives live birth to blood-borne L1 microfilaria
• L1 moves to peripheral circulation during day
• L1 moves to lungs during night
• Ingested during blood meal by tabanid fly [bite a chunk of tissue, vomit digestive enzymes and then eat it]
• (genus Chrysops = day feeder)
• Develops to infective L3 stage over 10-12 days
• Move from fly’s gutthoracic musclesmouthparts
• Falls onto human skin during fly’s next feeding
• Enters human through bite wound
• Develops to adult in subcutaneous tissue
• Adults migrate (painful) through subcutaneous tissue (occasionally through eye conjuntivia or nose bridge), causes Calabar swellings
• ♂ & ♀ mate
Caliber Swellings
• Patches of localized subcutaneous edema known as
Calabar swellings (originally noted in natives of Calabar city
in SE Nigeria) measuring ≤20 cm in diameter may occur.
• Calabar swellings typically last for 1-3 days and are
characterized by redness, heat, pain and
itching.
• On occassion, Loa loa can be seen moving under the skin in
the Calabar swelling.
• Calabar swellings result from an allergic reaction to either
dead worms or the metabolic products of live worms.
• Calabar swellings appear most frequently on the back of
the hand or on the arm.
• Complications: abscess, endocarditis, glomerulonephritis

Bayliascariasis
• Human baylisascariasis is caused by larvae of Baylisascaris procyonis, an intestinal nematode of raccoons.
• Humans become accidentally infected when they ingest infective eggs from the environment; typically this occurs in young children playing in the
dirt.
• Migration of the larvae through a wide variety of tissues (liver, heart, lungs, brain, eyes) results in VLM and OLM syndromes.
• Visceral larvae migrans
• Ocular larvae migran
• Baylisascaris larvae continue to grow during their time in the human host.
• Tissue damage and the signs and symptoms of baylisascariasis are often severe because of the size of Baylisascaris larvae, their tendency to
wander widely, and the fact that they do not readily die.
• Diagnosis is usually made by serology, or by identifying larvae in biopsy or autopsy specimens.
Cestodes Echinococcus  Hyatid disease [multiple lung cysts]; US primarily found in Southwest and Alaska [foxes, coyotes, wolves, [sylvantic: sled dogs]
(tapeworms) • Transmission: ingestion of food contaminated with dog stool (infected with Echinococcus)
• Biology: cyst-like larvae live in human tissue (usually lung or liver); adult is small tapeworm in dogs
• Clinical: large space occupy lesion (1-15 cm) in liver or lung with pain and at times rupture
Chesrt pain,
abdominal pain, 4 types • Members of the dog family are the
cough that won’t go – Echinococcus granulosus causes cystic definitive host = where adult tapeworms
away, unintended echinococcosis (CE), the form most frequently (2-7 mm) reproduce (small intestines)
weight loss, jaundice, encountered in rural, grazing animals in areas • Intermediate hosts include herbivores
where dogs ingest organs from infected such as sheep, deer, moose, kangaroos,
bloody stools,
seizures animals; and wallabies, and any other organism
– E. multilocularis causes alveolar echinococcosis (including humans) that may ingest dog
(AE) which occurs in the northern hemisphere, feces.  cysts
including central Europe, and the northern • In a sylvatic cycle, Echinococcus moves
parts of Europe, Asia, and North America; between reindeer/caribou and wolves.
– E. vogeli causes polycystic echinococcosis • When an Eskimo/Inuit butchers a caribou,
occurs in Central and South America; and the infected entrails are fed to sled dogs.
– E. oligarthrus, an extremely rare cause of • Sled dogs develop adult tapeworms that
human echinococcosis, found in Central and pass eggs in the feces.
South America. • Human food is contaminated when wild
game is butchered on ground covered
with canine feces/egg.
• Ingested eggs hatch and form cysts (slow
Tx: growing = 10-20 years) in lungs, liver, and
Removal: Hydatid sand can produce another cyst [don’t cut even the brain!
it open anymore they inject formalin/ scolicidal solution and
then remove it]
Drugs: mebendazole, albendazole., praziquantel
Multilocularis responds poorly to drug therapy
Anti-helminthics
Mebendazole
• Wide spectrum antihelminthic with few side effects
• 10% absorption: protein-bound and quickly inactivated by
liver
• Plasma T½ = 2-6 h
• Excreted in urine and bile
• Action enhance when ingested with a fatty meal
• Inhibits microtubule synthesis
• 100 mg once, repeated in 2 wks for pinworms
• 200mg twice daily for 3 wks for parasites of intestinal
capillaries
Albendazole
• Broad spectrum oral antihelminthic
• USDA approved for hydatidiasis and cysticercosis
• Useful for pinworm, hookworm, acariasis, trichuriasis,
strongyloidiasis
• Peak response in 3 h with an 8-12 plasma half life.
• Acts by blocking microtubule synthesis
• Ingest on an empty stomach for luminal parasites and with
a fatty meal for tissue parasites
Lecture 3 & 4: Pathology of Lower Respiratory Tract Infections
Morphological Patterns of tissue response to infections
 Purulent or suppurative inflammation
 Neutrophil response to most bacteria, liquefactive
necrosis of tissues
 Mononuclear and Granulomatous inflammation
 Lymphocyte response to viruses and atypical bacteria
 Activate macrophages (epithelioid cells), giant cells,
caseous necrosis with M. tuberculosis, fungal infections
 Cytopathic-cytoproliferative reaction: Inclusion bodies in viral
infections, cell fusion with giant cells, cell proliferation in warts
 Tissue necrosis: some bacterial toxins cause massive necrosis with
little inflammation; ex, C. perfringens [gas gangrene]
 Chronic inflammation and scarring: ex, hepatitis B or C with liver
cirrhosis
Factors increasing susceptibility to infection
 Chronic disease (CHF, COPD, diabetes)
 Immune deficiencies, congenital or acquired.
 Decreased or absent splenic function (sickle cell disease or post-
splenectomy) puts at risk for encapsulated organisms, i.e.
pneumococcus..
 Treatment with immunosuppressive drugs
 Leukopenia.
 Extremes of age.
Complications of Pneumonia
 Abscess formation
 Empyema – spread of infection to the pleural cavity with formation
of fibrinopurulent exudate
 Bacteremic dissemination causing endocarditis, meningitis,
suppurative arthritis or metastatic abscesses to other sites.
Bronchopneumonia  Gross – patchy consolidated areas (slightly elevated, dry, granular, gray-red to yellow areas with poorly delineated margins) throughout one lobe
or multiple lobes, usually lower lobes.
 Histology – Bronchi, bronchioles and adjacent alveoli filled with neutrophils
Praziquantel
• Effective (safe) for most trematode (flukes) and cestode
infections using a single dose
• Rapidly absorbed and 80% effective (increased by
carbohydrate ingestion)
• 2-3h plasma peak
• Plasma T½ = 0.8-1.5h
• Renal and bile excretion
• Increases cell membrane calcium permeability leading to
paralysis, dislodgement, and death
Diethylcarbamazine
• Used in treatment of filariasis, loiasis, and tropical eosinophilia
• Rapidly absorbed by GI tract at 0.5mg/kg
• Peak plasma levels in 2-3 h (acidic urine) to 10h (alkaline
urine) urinary excretion unmetabolized
• DEC immobilizes microfilariae, enhances tissue ejection and
alters surface structure to increase susceptibility to host’s
immune system
Factors Affecting Local lung defense mechanisms
 Decreased cough reflex
 Due to coma, anesthesia, neuromuscular disorders,
drugs or chest pain
 Injury to mucociliary apparatus
 Impairment of ciliary function or destruction of ciliated
epithelium due to cigarette smoke, inhalation of hot or
corrosive gases, viral diseases or genetic defects of
ciliary function.
 Interference with phagocytic or bactericidal action of alveolar
macrophages due to alcohol, tobacco smoke, anoxia, oxygen
intoxication.
 Accumulation of secretions (e.g., cystic fibrosis [thick tonacious
secretions], obstructive processes)
 Pulmonary edema and congestion
Terminology of lung infections
 Pneumonia – any infection of the lung
 Pleuritis – Pleural fibrinous reaction to underlying inflammation ,
may resolve or become permanent adhesions
 Bronchopneumonia – patchy consolidation of the lung
 Lobar pneumonia – consolidation of the entire lobe (or a large
portion of it).
 Interstitial pneumonias (localized within the walls of the alveoli) are
frequently caused by viruses or atypical bacteria.
Bronchopneumonia
 Red and congested
=inflammation
 Patchy spots are the
infection
 Make sure you palpate
Lobar Pneumonia Four stages:
1. Congestion –
 Gross - Lung is heavy, boggy and red.
 Histology – Vascular engorgement with intra-alveolar fluid with a few neutrophils and bacteria
2. Red hepatization –
 Gross – red, firm and airless (resembles liver; hence “hepatization”)
 Histology – intra-alveolar exudate with neutrophils, red cells and fibrin.
3. Gray hepatization –
 Gross – grayish brown firm lung
 Histology – Persistent fibrinopurulent exudate with disappearance of red cells
4. Resolution – Exudate is resolving with debris ingested by macrophages, expectorated or organized by infiltrating fibroblasts. [scarring and
regeneration]
Effective antibiotic therapy may slow or halt progression through these 4 stages.

Grey hepatization

Red hepatization:
The congested septal
capillaries and extensive
neutrophil exudation into
alveoli corresponds to early
red hepatization. [some
RBCs] Fibrin nets have not
yet formed.

Alveolar walls are

congested with RBCs

Early organization:
Fibroblastic tissue is laid
down
-Pores of Kohn = gaps
between alveoli

Advanced organization
Transformation of exudates
to fibromyxoid masses richly
infiltrated by macrophages
and fibroblasts
 A, Gram stain of sputum from a patient with pneumonia. There are gram-positive cocci in clusters (Staphylococcus aureus) with degenerating neutrophils.
B, Gram stain of sputum from a patient with pneumonia. Gram-positive, elongated cocci in pairs and short chains (Streptococcus pneumoniae) and a neutrophil
are seen
D, Gram stain of a bronchoalveolar lavage specimen showing gram-negative intracellular rods typical of Enterobacteriaceae such as Klebsiella pneumoniae or
Escherichia coli

Bacterial Pneumonia  Streptococcus pneumoniae (aka pneumococcus)

 Most common cause of community-acquired pneumonia
 Gram-positive diplococci (lancet shaped)
 Part of endogenous flora in 20% of adults
 Pneumococcal vaccine available for common serotypes
 Haemophilus influenza
 Pleomorphic gram-negative organism which are encapsulated and nonencapsulated
 6 serotypes, type b most virulent, significant decline in type b since vaccine introduced
 Infections due to nontypable forms (nonencapsulated) have increased.
 Pneumonia is severe and may follow URI in pediatrics
 Most common bacterial cause of COPD exacerbation
 Moraxella catarrhalis: gram-negative diplococcus, second most common cause of acute COPD exacerbation; being increasingly recognized as a
cause of pneumonia in the elderly
 Third most common cause of otitis media in children
 Staphylococcus aureus:
 clusters of gram-positive cocci, cause of secondary bacterial infection after a viral respiratory illness, pneumonia may be complicated
by abscess and empyema, Staph infection may occur with endocarditis in IV drug abusers, important cause of hospital acquired
pneumonia
 Klebsiella pneumoniae:
 Most common gram-negative pneumonia; seen in debilitated, especially chronic alcoholics
 Pseudomonas aeruginosa:
 gram-negative bacilli, common cause of hospital- acquired infections; common in cystic fibrosis, neutropenia, or severe burns; invades
vessels
 Legionella pneumophila:
 gram-negative bacillus, thrives in artificial water environments such as water-cooling towers and tubing for domestic water supply;
inhale aerosolized bacteria or aspirate while drinking contaminated water; those with underlying medical conditions and
immunosuppressed are susceptible to infection, especially organ transplant patients; high mortality in immunosuppressed
Lung Abscesses 1. A local suppurative process characterized by necrosis of lung tissue.
2. Organisms commonly isolated include:
Complications: 1. S. aureus, gram negative organisms, aerobic and anaerobic streptococci and other anaerobic oral flora
(exclusive isolates in 60% of cases)
-Extends into pleural How are these organisms introduced?
cavity 3. ASPIRATION (most frequent cause) common in alcoholism, coma, anesthesia, sinusitis, gingivodental sepsis and debilitation with decreased cough
reflex.
-Hemorrhage 4. ANTECEDENT LUNG INFECTION – especially with S. aureus, Klebsiella pneumoniae and type 3 pneumococcus.
5. SEPTIC EMBOLISM – right sided bacterial endocarditis or infected venous thrombi.
-Septic emboli with 6. NEOPLASIA – a cancer obstructing a bronchus (postobstructive pneumonia).
brain abscesses or 7. Miscellaneous: Direct trauma to lungs, contiguous spread of infection from a neighboring organ, hematogenous seeding of lung with organism.
meningitis 8. No known cause : Primary cryptogenic lung abscess.
Gross :
-Rarely, secondary  Size – a few mm to large cavities of 5 or 6 cm or more
amyloidosis (type AA  Single or multiple in any part of lung.
seen in many chronic  Abscess due to aspiration more common on right due to more vertical right mainstem bronchus.
inflammatory  Abscess cavity filled with purulent material and debris, may have an air-fluid level if communicates with air passage and continued infection produces
conditions) large, fetid, green-black, multi-locular cavities called gangrene of the lungs.
Histology: Destruction of lung parenchyma with central area of cavitation filled with neutrophils. Chronically, may develop fibrous wall around abscess..

Viral Respiratory  Upper respiratory infections - Swollen red mucosa with secretions. Histologically, lymphomonocytic and plasmacytic infiltration of submucosa,
Infections excessive mucus production
 Laryngotracheobronchitis – Vocal cord swelling with increased mucus production, impaired bronchociliary function, increased mucus,
inflammatory cells.
 Bronchiolitis – plugging of airways with fibrin, cell debris and inflammatory exudate.
 Pneumonia – interstitial type pneumonia but bacterial overgrowth may occur with bacterial pneumonia.
Atypical Commonly caused by virus or mycoplasma
Pneumonias/  Most common organism causing primary atypical pneumonia is Mycoplasma pneumoniae.
Interstitial  Examples of other organisms causing interstitial pneumonias include viruses (influenza type A and B, the respiratory syncitial viruses, human
Pneumonias metapneumovirus, adenovirus, rhinovirus and rubeola, and varicella), and other bacteria including chlamydia pneumoniae and Coxiella burnetii (Q
fever).
 Secondary bacterial infection may occur due to damage and denudation of respiratory epithelium inhibiting mucociliary clearance.

Gross – patchy lung involvement or lobar, bilateral or unilateral, with affected areas blue-red and congested.
Histology- alveolar septa are widened with edema and inflammatory cells consisting of lymphocytes, macrophages, plasma cells and sometime neutrophils in
acute cases.
 May have an intra-alveolar proteinaceous material and a cellular exudate.
 ARDS with hyaline membranes may be a complication.
 Some viruses (herpes simplex, varicella, and adenovirus) may have necrosis of bronchial and alveolar epithelium and acute inflammation with viral
cytopathic changes with nuclear and/or cytoplasmic inclusions.
Mycoplasma pneumonia:

Expanded alveolar
walls
Hard to culture
and gram stain is
usually negative
Cold agglutinins
will be elevated

Viral Pneumonia

RSV

Immunostain for RSV Herpes Simplex

Measles pneumonia: cowdry

Warthin-Finkeldy cells
Found in lymph nodes, lungs
and sputum in measles.
-Cell of origin not completely
known but some have stained
for B lymphocyte markers
and some have stained for T
lymphocyte markers
Influenza  Necrotizing tracheobronchitis and bronchiolitis
 Influenza viral pneumonia characterized by interstitial edema and inflammatory infiltrates, diffuse alveolar damage with hyaline membranes, intra-
alveolar edema and/or hemorrhage, capillary and small vessel thromboses.
 Later stages show organizing diffuse alveolar damage, fibrosis, epithelial regeneration and squamous metaplasia.
 Secondary bacterial pneumonias.
Opportunistic
Pneumonias

HIV Associated
 Infectious organism associated with CD4+ counts.
 CD4+ >200
 Bacterial and tuberculosis
 CD4+<200
 Pneumocystis pneumonia (most common opportunistic infection in HIV)
 CD4+<50 Pneumocystis jiroveci
 Cytomegalovirus (CMV)
 Mycobacterium avium complex

CMV in the lung

Histoplasmosis  The most common endemic fungal infection in humans –caused by histoplasma capsulatum
 Infection occurs after inhaling spores in bat or bird droppings
 Locations – Ohio and Mississippi river valleys and in the Caribbean
Fungal  Clinical picture and morphologic lesions resemble tuberculosis.
Pathogenesis
 Intracellular pathogen of macrophages. Spores transform into yeast in the macrophage.
 Despite fusion with lysosomes, multiplication continues within phagosome.
 Helper T cells recognize fungal antigens and secrete interferon activating macrophages to kill the intracellular yeast.
 Macrophages secrete TNF which recruits and stimulates more macrophages to kill the yeast
 As cell-mediated response matures (T cell mediated Type IV hypersensitivity) delayed-type hypersensitivity to histoplasma antigens occurs 3 to 6
weeks after exposure.
 Over weeks to month, the inflammatory response produces calcified fibrinous granulomas with caseous necrosis.
Morphology
 Granuloma formations occur with persistent or nondegradable antigen
 Activated macrophages morphologically change into epithelioid cells
 Aggregates of epithelioid cells (some coalesce into giant cells) are surrounded by a cuff of lymphocytes forming a granuloma
 May have caseating central necrosis.
 The granulomas under go fibrosis and concentric calcification.
 In immunocompromised, NO granulomas, but accumulations of yeast forms in mononuclear phagocytes throughout various organs and tissues.
Disease course
 Self-limited (may have calcified granulomas in lungs or other locations)
 Chronic, progressive secondary lung disease with fever, cough, night sweats
 Widely disseminated disease in immunocompromised patients.

Macrophages filled with yeast spores

Calcification indicates inactive

Fibrinosis and concentric calcification disease

Blastomycosis • Blastomyces dermatitidis – hard to isolate, soil-inhabiting, dimorphic fungus

• Geographic locations – central and southeastern US and may also occur in Canada, Mexico, Middle East, Africa and India.
• Common infection in dogs in endemic areas (also seen in horses, cows, cats, bats and lions)
• Infection occurs after inhalation of conidial forms from soil
• Transform to yeast form in the body
• Thick cell wall gives survival advantage, resistance to phagocytosis.**
• Yeast express an adhesion and virulence factor (BAD-1 or blastomyces adhesin 1) on the cell surface which suppresses phagocyte inflammatory
response
• Yeast multiply and disseminate.
Morphology Clinical Forms:
 Normal host – lungs show suppurative granulomas. Pulmonary blastomycosis – Asymptomatic in many
 limited ability of macrophages to ingest and kill this yeast (BAD1 virulence factor) with some developing varying degrees of pulmonary
 Continued recruitment of neutrophils continues due to persistence of B. dermatitidis. and systemic symptoms.
 B. dermatitidis morphology in tissue
 5 to 15 um yeast cell Disseminated blastomycosis – occurs in chronic
 Thick, double-contoured cell wall with multiple nuclei pulmonary disease and immunocompromised.
 BROAD BASED BUDDING****
**Cutaneous form – direct innoculation into skin or
occurs from dissemination.
- Epithelial hyperplasia may occur in skin
and larynx involvement leading to a
mistaken diagnosis of squamous cell
carcinoma
Coccidioidomycosis • Endemic to regions of N. and S. America (Western and Southwestern USA)
• Infection occurs from inhalation of spores of Coccidioides immitis or C. posadasii (morphologically identical but genetically different)
• Isolated from rodent burrows in desert like areas.
San Joaquin Valley • Most primary infections are asymptomatic.
fever complex • More than 80% or people in endemic areas have a positive skin test.
• High infectivity rate due to the infective arthroconidia ingested by macrophages blocking fusion of the phagosome and lysosome thereby resisting
intracellular killing.
Clinical
• San Joaquin Valley fever complex – develops in 10% of infected people with lung lesions, fever, cough, pleuritic pain with erythema nodosum or
erythema multiforme
• Rarely have disseminated disease involving multiple organs which frequently involves the skin and meninges.
• immunosuppressed AT RISK as well as certain ethnic groups, e.g., Filipinos and African Americans
• Erythema Nodosum
• panniculitis, inflammation of subcutaneous tissues, associated with certain diseases, infections, drugs, etc.

Morphology
• Granulomatous lesions similar to histoplasmosis occur
• Inside macrophages or giant cells, Coccidioides appear as thick-walled, nonbudding spherules 20 to 60 um in diameter containing endospores
• Rupture of the spherule releasing the endospores causes a pyogenic reaction.  neutrophils respond
• Therefore, histologically may have a purely granulomatous reaction, pyogenic (purulent with neutrophils), or mixed

Pulmonary  Caused by mycobacterium tuberculosis

Tuberculosis  Mycobacterium are slender, aerobic bacilli with a unique waxy wall composed of mycolic acid which makes them acid fast (resist decolorization
with acidified alcohol once they have been stained with carbolfuchsin)
 Weakly gram positive.
Primary Tuberculosis
 Ghon focus – focal lung consolidation resulting after implantation of inhaled bacilli in the lower part of upper lobes or upper part of lower lobes,
usually sub-pleural [initial infection is usually subpleural].
 Ghon complex - lymph node involvement combined with lung lesion.
 Ghon complex fibroses and calcifies (Ranke complex)
Secondary Tuberculosis
 Occurs in a previously sensitized host usually from re-activation of a latent infection or from exogenous reinfection
 Classically involves the apex of the upper lobes of one or both lungs.
 Cavitary lesions are common.
 Initial lesion is a focal well circumscribed firm gray-white or yellow consolidation (~2cm or less) within 1-2 cm of apical pleura
 May have caseating necrosis and peripheral fibrosis
 Microscopically, caseating granulomas with positive acid fast staining
 May resolve with fibrosis or become progressive infection.

Histology of tuberculosis
• Granulomas composed of epithelioid histiocytes with giant cells surrounding central caseation.
• Fibrous encapsulation with a rim of lymphocytes
• Eventually, fibrocalcific scar.
• Tuberculous granulomas may exist without central caseation.
• Stain granulomas for acid fast organisms.

Progressive Pulmonary Tuberculosis

• Elderly and immunosuppressed
• Expanding apical lesion with large caseous center, cavitation, erosion into blood vessels.
• With adequate Rx, will heal with fibrosis/scarring.
• If inadequate treatment or poor host defenses, TB may spread via the airways, lymphatic channels or hematogenously
• Endobronchial, endotracheal and laryngeal TB may develop
• Pleural involvement likely
• Pleural effusions, tuberculous empyema or obliterative fibrous pleuritis
Miliary Tuberculosis [looks like millet seeds]
 Pulmonary
 Organisms enter lymphatics, then venous blood and returns to lung via circulation
 Lungs show multiple scattered tiny foci (few millimeters) of yellow-white consolidation which may expand and coalesce
 Systemic
 Organisms disseminate throughout body via the systemic arterial circulation.
 Most prominently involved sites are liver, bone marrow, spleen, adrenals, meninges, kidneys, fallopian tubes and epididymis.
 Other manifestations of TB
 Isolated disease
 TB presenting in another organ
 Most common are meninges, kidneys, adrenal (used to be important cause of Addison’s), bones, fallopian tubes
 POTT disease, vertebral involvement
 Spine tuberculosis
 Lymphadenitis –
 Most frequent extrapulmonary presentation, particularly in cervical region (Scrofula)
 Intestinal tuberculosis –
 Drinking contaminated milk or swallowing infected sputum.

Mycobacterium • Two different species but lumped together since so similar

Avium- • MAC common in soil, water, dust and domestic animals.
Intracellulare • Uncommon infection except in people with AIDS and a CD4+ count of <60.
Complex (MAC) • In severe immune deficiency, MAC infection widely disseminated throughout the mononuclear phagocyte system with enlargement of lymph
nodes, liver and spleen.
• Lung and GI tract involvement is common
• Histologic hallmark is abundant acid-fast bacilli within macrophages
• Minimal to no granuloma formation

.
Lecture 8: Upper Respiratory Tract Infections
Presentation of URI
• Sneezing
• Rhinorrhea
• Nasal congestion
• Hyposmia/Anosmia
• Facial Pressure
• Post nasal drip
• Sore throat
• Cough
• Ear fullness
• Fever
• Myalgia
Sinusitis
Pathophysiology
Tx: Often is Amoxicillin first line. Alternatives to amoxicillin are Bactrim or TMP/SMX,
chronic sinusitis the better antibiotic choice may be Amoxicillin plus clavulanate (Augmentin), or one of the 3rd generation cephalosporins or one of the
respiratory flouroquinolones.
Rhinitis
Allergic rhinitis the nasal mucosa is pale and boggy instead of red and swollen with an infection.
Clinical Presentation
Pathophysiology of URI Role of Somatic Dysfunction Host Treatment of the URI
• The common cold is an infection of the • The role of somatic dysfunction Treatment should be focused at symptomatic
mucosa on the upper respiratory tract. alters the body’s normal defense relief and the normalization of the host that will
There are numerous changes that mechanisms by numerous ways. allow the patient’s natural defenses and help the
occur when the mucosa is infected by The two most common ways patient get better. Osteopathic treatments should
a virus or bacteria. consist of deep tissue restriction be focused at normalizing the structures of the
• The most common agents decreasing lymphatic drainage head with cranial. The next area of focused should
that cause of infection of and viscero-somatic reflexes be lymphatics and the tissues of the neck including
the upper respiratory altering autonomic flow. the thoracic inlet with the thoracic/lymphatic
system are viruses. pump should be normalized. The next area of
• URIs are transmitted by hand contact • Increased sympathetic focus would be autonomic flow. Some procedures
with infected persons, breathing small innervation of the upper or treatment types are
particles that linger in the air, and by thoracic spine will result in • Suboccipital myofascial release
breathing large particles directly from vasospasm of the mucosal blood • Trigeminal nerve procedures
an infected person. vessels and thick secretions. • Anterior neck soft tissue procedures
• Those at risk those with [increased thick sticky • Thoracic lymphatic pump
underlying chronic secretions]
disease, congenital
immunodeficiency • Increased parasympathetic
disorders, malnutrition, innervation results in thin and
and those that smoke watery secretions. Inhibition or
cigarettes. excitation of this process
Acute canitis has a relatively rapid
rhinosinus
• 1 The natural defenses of the body
TABLE alter the ons
body’s normally of four weeks’ duration or
et, isnatural
Signs and include
Symptomsa secretion wash and
Associated a layer
with the Diagnosis defenses.less and symptomstotally resolve. Most cases
of beating cilia that moves secretions.
of Rhinosinusitis are viral in origin. Resolution of symptoms
usually occurs within five to seven days, and
Major Minor most patients recover without medical inter-
• pain/pressure/fullness*
Facial Hyposmia Headaches vention.6 The subcategory of acute bacterial
• obstruction/blockage
Nasal Nasal congestion/drainage Fever (other than acute rhinosinusitis) rhinosinusitis is more likely to evolve into
• al or pos
Nas tnasal discharge/purulence
Postnasal drip Halitosis chronic disease or to spread outside the
(by history or physical examination) Fatigue
• Fever sinusesto theorbital areaor to themeninges.
Hyposmia/anosmia Dental pain
• Cough Acute bacterial rhinosinusitis is suggested by
Fever (in acute rhinosinusitis only)! Cough
• Fatigue symptoms including purulent drainage that
Ear pain/pressure/fullness
• Dental pain [infecting nerves of the face] worsens after five days or persists beyond
• Ear fullness/pressure 10days,and/or symptomsthat areout of pro-
* —Facial pain/pressure alone does not constitute a suggestive history in the
absence of another finding listed in the Major category. portion to those typically associated with a
• ever Obstruction
! —F of sinusalone
in acute rhinosinusitis drainage pathways
does not that
constitute preventshistory
a suggestive normal in drainage
viral and
uppe causes hypoxia
r respira within
tory proce ss.sinus
6 causes
Recurre nt ciliary dysfunction and alterations
the absencein mucous
of anotherproduction.
finding listed in the Major category. acuterhinosinusitisisdefined asfour or more
•
Adapted Ciliary
with impairment
permission which JisA,unable
from Hadley SchaefertoSD.
move waste
Clinical and infectious
evaluation of rhi- bi-products
episodes of out of dis
acute sinuses.
ease within a 12-month
• Mucous
nosinusitis: quantity/quality
history and physical examination. Otolaryngol Head Neck Surg 1997; period,with resolution of symptomsbetween
117(3 pt 2):S8-S11. each episode (each episode of at least seven
days’ dura and erythromycin.
tion). Subacute Ifrhinos
thereinus
is poor
itis response
is or of the patient has
TABLE 2
Classification of Adult Rhinosinusitis
Classification Duration History, examination Special notes
Acute Up to four weeks The presence of two or more Major Fever or facial pain/pressure does not constitute a
signs and symptoms; one Major and suggestive history in the absence of other nasal
two or more Minor signs or symptoms; signs and symptoms. Consider acute bacterial
or nasal purulence on examination* rhinosinusitis if symptoms worsen after five days,
if symptoms persist for 10 days or with symptoms
out of proportion to those typically associated
with viral infection.
Subacute Four to <12 weeks Same Complete resolution after effective medical therapy.
Recurrent Four or more episodes Same —
acute per year with each
episode of at least
seven days’ duration;
absence of intervening
signs and symptoms
Chronic 12 weeks or more Same Facial pain/pressure does not constitute a
suggestive history in the absence of other nasal
signs and symptoms.
* —S
• ee Table 1 for listingof
Inflammation of the
Major and mucosa.
nasal Minor signs
It and symptoms.
is often just a presenting symptom of the common cold.
•
Adapted with permission
Rhinitis can befrom
seenLanza D, Kennedy
in a patient withDW. Adult
what rhinosinusitiscalled
is commonly defined. Otolaryngol
seasonal Head Neck
allergies and itSurg 1997;117(3
is called pt 2):S
Allergic 1-7.
rhinitis.
• Symptoms include primarily:
70 AMERICAN FAMILY PHY•SICIAN Rhinorrhea www.aafp.org/afp VOLUME 63, NUMBER 1 / JANUARY 1, 2001
• Sneezing
• Pruritis
• Congestion.
• The patient may also have facial pressure or pain with altered sense of smell and post nasal drainage.
• The patient can also have a sore throat, tearing and burning of eyes, malaise, and cough.
Pharyngitis Causes for viral pharyngitis
• Rhinoviruses Causes of Bacterial Pharyngitis
• Coronaviruses • Group A Strep (Streptococcus pyogenes)
• Adenoviruses • Group C Strep
• Herpes Simplex (HSV) • Neisseria gonnorrhea
• Parainfluenza • Corynebacterium diphtheriae
• Influenza • Mycoplasma pneumoniae
• EBV • Chlamydophila pneumoniae
• HIV • Archanobacterium haemolyticum
Presentation • Fusobacterium necrophorum
• Low grade fever Presentation
• Erythema of the pharynx • Tonsillar edema and erythema
• Occasional tonsillar enlargement • Tonsillar exudates
• Occasional cervical adenopathy but usually minimal • Anterior cervical lymphadenopathy
• Rarely Exudate (almost exclusively in Mono) • Fever or history of fever
- The only virus that looks like strep • Absence of cough** [if they cough, not likely to be strep]

1. Rapid Mono Spot

=cheap
2. Complete Blood Count
(CBC)
3. Epstein-Barr titers
(Seen on the next
mono slide)
- IgM = new
infection
- IgG = late
infection and
immunity
-
Reactive lymphocytes *Results indicate infection with EBV at some time (VCA IgG positive).
However, the time of the infection cannot be predicted (ie, recent or past)
since antibodies to EBNA usually develop after primary infection (recent) or,
Penicillin treatment may alternatively, approximately 5% to 10% of patients with EBV never develop
cause a rash in MONO antibodies to EBNA (past).

Management
• Antibiotic management should be narrow spectrum and broad spectrum antibiotics should be avoided if possible.
• Penicillin G and VK
• Amoxicillin
• For Penicillin allergies
• Clindamycin, Azithromycin (Broad)
Complications of GAS
• Acute Rheumatic Fever
- An autoimmune disease brought on by inappropriate treatment of Streptococcal A throat infection.
- It causes future heart disease in patients.
 Mitral valve stenosis
 Congestive heart failure
 Atrial Fibrillation
- Fever, muscle aches, swollen joints are some of the symptoms. Jones Criteria is used to diagnose ARF.
• Scarlet Fever (Scarletina)
- A rash and systemic response to the exotoxins caused from a prevailing streptococcal infection.
- A palpable “sand paper rash”
- Other HEENT findings commonly seen in scarlet fever.
 Circumoral palor
 Beefy red tongue

• Acute Glomerulonephritis
• Otitis Media
• Peritonsilar abscess
- Often see trouble swallowing, and hot potato voice. Fevers and general malaise.
 Hoarseness/Laryngitis Acute laryngitis,
- Which is self-limited and related to acute respiratory illness or acute voice misuse
Chronic laryngitis
- which is related to irritants, reflux, chronic infection (such as fungal), or habitual vocal misuse
• Benign vocal fold lesions
• Malignancy
• Neurologic dysfunction
• Non-organic ("functional") issues
• Systemic conditions and rare causes
Red flags of Chronic Hoarseness
- Hoarseness longer than three weeks needs a complete otolaryngolic evaluation.
- There are also certain warning signs like shortness of breath, stridor, cough, hemoptysis, throat pain, dysphagia, odynophagia, and
weight loss that may warrant further workup

• Almost always Benign in the acute setting with upper respiratory tract infection.
• Almost always viral. (No antibiotic)
• If hoarseness lasts longer than a few weeks, work up for something serious like malignancy.

Epiglottitis Symptoms:
• Difficulty breathing (80 percent)
• Stridor (80 percent)
• Muffled or hoarse voice (79 percent)
• Hot potato voice
• Pharyngitis (73 percent)
• Fever (57 percent)
• Sore throat (50 percent)
• Tenderness of anterior neck (38 percent)
• Cough (30 percent)
• Difficulty swallowing (26 percent)
• Change in voice (20 percent)
Signs:
(Toxic Appearance)
• Stridor= upper airway obstruction
• On inspiration
• Drooling/Inability to handle secretions
• Ages 2, 3, 4 or older be worried
• Fever
• Hypoxia
• Severe pain over upper neck
• Cough
• Tachycardia
Etiology:
• Children
• Haemophilus influenzae type b (Hib) is the most common infectious cause of epiglottitis in children. Hib epiglottitis can still occur in
immunized children!
• H. influenzae (types A, F, and nontypeable),
• Streptococci
• Staphylococcus aureus
• Adults –
• broad range of bacteria (Hib is most common)
• viruses
• combined viral-bacterial infections
• fungi
• noninfectious causes
• Immunocompromised hosts –
• Pseudomonas aeruginosa
• Candida species

Procalcitonin test
• Procalcitonin (ProCT) is a precursor to Calcitonin
• During bacterial infections ProCT is secreted in large quantities by many different tissues.
• ProCT levels are generally not elevated even in viral infections.
• ProCT is used determine early sepsis in patients and preventing death from sepsis.
• Unfortunately not widely available and expensive when available.
Lectures 5, 6, 7: Pharmacology of Respiratory Infections

• 1st Generation Ceph • Carbapenems Agents that interfere with 30 S Agents that interfere with 50S
• Vancomycin •
• • Doripenem • Aminoglycosides Macrolides
• Beta-lactamase inhibitors Cefazolin
•
• • Ertapenem • Amikacin Azithromycin
• Clavulanic Cephalexin
•
• 2nd Generation Ceph • Imipenem/ • Gentamicin Clarithromycin
Acid •
• cilastatin • Neomycin Erythromycin
• Sulbactam Cefoxitin
•
• • Meropenem • Streptomycin Chloramphenicol
• Tazobactam Cefuroxime
•
• • Aztreonam • Tobramycin Clindamycin
• Penicillin Cefaclor
•
• 3rd Generation Ceph • Sulfonamides and • Tetracyclines Oxazolidinone
• Penicillin G •
• Sulfones • Demeclocycline Linezolid
• Penicillin V Ceftazidime
• • Sulfamethoxazole • Doxycycline
• Aminopenicillins Ceftriaxone
• • Dihydrofolate reductase • Minocycline
• Ampicillin Cefotaxime
• 4th Generation Ceph inhibitors • Tetracycline
• Amoxicillin
• • Trimethoprim • Glycylcycline
• Antistaphlococcal PCN Cefepime
• 5th Generation Ceph • Fluoroquinolones • Tigecycline
• Oxacillin
• Ceftaroline • Ciprofloxacin –
• Nafcillin
best for anti-
• Antipseudomonal PCN
pseudo [not resp]
• Ticarcillin
• Gemifloxacin
• Piperacillin
• Levofloxacin
• Moxifloxacin
[resp, bacteroides,
not anti-pseudo]
• Nalidixic Acid
•

Mechanisms • Cell wall synthesis Inhibitors

- Vancomycin: binds D-Ala-D-Ala to prevent peptidoglycan synthesis
- Beta Lactams, Aztreonam: binds peptidoglycan binding proteins and prevent crosslinking
• Protein Synthesis Inhibitors
- 30S
- 50S
• DNA Topoisomerase Inhibitors
- Inhibit II and IV
- Fluoroquinolones
• Folic Acid Synthesis Inhibitors
- Sulfonamides: PABA antimetabolites inhibit dihydropteroate
- Trimethoprim: inhibits dihydrofolate reductase
• Inhibition of DNA dependent RNA polymerase
- Rifampin
Mechanisms • Beta-lactams:
of Resistance • beta lactamases, ESBL, Carbapenemase, MRSA has altered PBP
• Vancomycin:
• bacterial modification of D-ala-D-ala to D-ala D-lactate (oritavancin binds both!)
• Sulfonamides:
• altered bacterial dihydropteroate synthase, decreased uptake or increased PABA synthesis
• Fluoroquinolones: mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps
• Protein Synthesis Inhibitors
• Aminoglycosides: enzymatic inactivation
• Tetracyclines: decreased uptake or increased efflux
• Macrolides: methylation of 23S rRNA binding site to prevent binding
• Chloramphenicol: plasma encoded enzymatic inactivation

Adverse • Beta lactams: hypersensitivity reactions, Type I IgE mediated reactions, rash, hemolysis
Effects • Carbapenems: seizures (especially imipenem)
• Vancomycin: nephrotoxic, ototoxic, red man syndrome
• Too quickly and not enough fluid [red man; direct stimulation of the mast cells]
• Aminoglycosides: nephrotoxicity, neuromuscular blockade, ototoxicity, teratogenic

• Tetracyclines: GI distress, discoloration of teeth and inhibition of bone growth, photosensitivity, contraindicated in pregnancy

• Chloramphenicol: anemia, aplastic anemia, gray baby syndrome

• Clindamycin: psdueomembranous colitis (C. difficile overgrowth), diarrhea, fever

• Macrolides: GI (direct motilin receptor agonists), prolonged QT interval, hepatotoxic, erythro and clarithro inhibit CYP450

• Fluoroquinolones: Photosensitivity, chelation, QT prolongation, tendinitis [risk of aortic dissections]

• Sulfonamides: Stevens-Johnson Syndrome, rash, crystaluria, photosensitivity, hemolytic anemia in G6PD deficiency, nephrotoxicity, kernicterus in infants

• Trimethoprim: leukopenia, megaloblastic anemia

Phototoxicity = Sulfonamides, Tetracyclines, Fluoroquinolones

Spectrum • Penicillin G, V:
• mostly gram-positive (S. pneumoniae, S. pyogenes, and Actinomyces) also N. meningitidis and T. pallidum
• Aminopenicillins:
• Haemophilus influenzae, E. coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, enterococci (adding beta-lactamase inhibitor
increases coverage of H. influenzae and Enterobacteriaceae
• Antistaphlococcal Penicillins (Penicillinase-Resistant):
• S. aureus (NOT MRSA due to altered PBP)
• Oxacillin, dicloxacillin, methicillin, naficillin
• Antipseudomonal penicillins:
• Pseudomonas and gram – rods. Use with beta lactamase inhibitor
• Beta Lactamase inhibitors:
• non except sulbactam vs Acinetobacter
• Aztreonam:
• gram – rods only
• Carbapenems:
• gram positve cocci, ESBL gram negatives, Pseudomonas, Acinetobacter, anarobes
• Ertapenem doesn’t cover Pseudomonas, Enterococcus, and Acinetobacter
• Not effective vs atypical pneumonia, Legionella, MRSA
• Vancomycin:
• gram positive ONLY (Orally for C. difficile pseudomembranous colitis)
• Give IV will not cover C.diff and covers everything else
• Aminoglycosides:
• aerobic gram negatives (remember how this relates to mechanism of action? Porin channels)
• Tetracyclines:
• broad, many gram + (including CA-MRSA), gram – (resistance building), toxin secreters (cholera), rickettsiae, spirochetes, mycoplasma, and
chlamydia, Borrelia burgdorferi, acne)
• Macrolides:
• atypical pneumonia (Mycoplasma, Chlamydia, Legionella), streptococcal infections
• Chloramphenicol:
• Rocky Mountain spotted fever, rickettsial infections, H. influenzae, Neisseria meningitidis, S. pneumoniae
• Try to avoid this unless absolutely necessary because it is so toxic
• Clindamycin:
• gram +, some gram -, anarobes, CA-MRSA
• TMP/SMX:
• Pneumocystis jiroveci, Nocardia, CA-MRSA, E. coli, Klebsiella, Enterobacter, Proteus, Moraxella, Haemophilus, protozoal, shigella, salmonella
• Fluoroquinolones: gram negative aerobes
• Respiratory fluoroquinolones cover S. pneumoniae, M. pneumoniae, C. pneumoniae, L pneumonophillia
• Moxifloxacin: covers Bacteroides but no pseudomonas
 Colistin
• Not review but basic pharm…
• Inactive prodrug which is hydrolyzed to colistin
• Binds to lipopolysaccharide and phospholipids in the outer cell membrane of gram-negatives.
• Completely displaces divalent cations (Ca and Mg) from phosphate groups of membrane lipids which leads to disruption of outer cell
membrane, leakage of intracellular contents and bacterial cell death
• Hydrophilic (rifampin, carbapenems, glycopeptides, and tetracyclines) work synergistically
• TOXIC!!!!!!
• Neurotoxicity, nephrotoxicity (up to 26%), acute renal failure (up to 60%), apnea, respiratory arrest (mechanism unknown)
• Drug interactions due to nephrotoxic and neurotoxic additive effects
• Mostly active vs gram -
Acute • Reserve abx for those with confirmed Group A strep
Pharyngitis • No resistance to penicillin has been reported for GAS
• Penicillin or amoxicillin
• 1st generation cephalosporin (minor allergy)
• Clindamycin or macrolide (if anaphylaxis)

Acute • Risk for ABX resistance

Bacterial • Age < 2 or > 65, daycare
Rhinosinusitis • Prior abx within the past month
• Prior hospitalization within the past 5 days
• Comorbidities
• Immunocompromised
• ABX when
• Persistent and not improving ≥10 days
• Severe (≥3-4 days) or worsening or “double sickening”
• Prevalence of pathogens
• Streptococcus pneumoniae (38% adults, 21-33% kids)
• Haemophilus influenzae (36% adults, 31-32% kids)
• No growth (36% adults, 29% kids)
• Mycoplasma
• Moraxella catarrhalis (16% adults, 8-11% kids)
• Amoxicillin/Clavulanate
 Better than using fluoroquinolone because they are more toxic; last resort
 Avoid using macrolides first high rates of resistance against S. pneumo
 TMP/SMX high rates of resistance against S. pneumo
 Doxycyclin can be used in ADULTS as an alternative
 2nd and 2rd generation cephalosporins  resistance to s.pneumo
• Why amoxicillin/clavulanic acid vs amoxicillin?
• Increased prevalence of H. influenzae (vs. S. pneumoniae)
• More resistant organism
• High prevalence of beta-lactamase-producing respiratory pathogens in acute bacterial rhinosinusitis (H. influenzae and Moraxella catarrhalis)
• Lesson on Resistance
• Beta-lactamases cleave the beta lactam ring (“wimpy” ones i.e. penicillinase generally only do penicillins)
• Extended Spectrum Beta Lactamases (ESBL) are “stronger” beta lactamases that cleave the ring on penicillins and cephalosporins
 • Carbapenemases inactivate carbapenems
• Remember… clavulanate or clavulanic acid is a beta lactamase inhibitor
• Also.. Sulbactam, tazobactam
• No antibiotic activity on their own except sulbactam vs acinetobacter
Children allergic to penicillin:
• Combination of a 3rd generation (e.g. cefixime or cefpodoxime) plus clindamycin for children with non-type I penicillin allergy may be used
• 3rd gen ceph covers H. influenzae and M. catarrhalis (inactive against penicillin resistant S. pneumoniae)
• Clindamycin is active against S. pneumoniae (if resistant, switch to levofloxacin)
• Levofloxacin is recommended for children with a history of type I hypersensitivity to penicillin
• No evidence with moxifloxacin and doxycycline will stain teeth
• Use of a fluoroquinolone in a child or adolescent may be justified when there is no safe alternative
• Macrolides and TMP/SMX were previously preferred but increasing resistance…
• True Type I hypersensitivity is relatively uncommon… skin testing should be performed if possible
Pneumonia in Outpatient
Inpatient Non-ICU Inpatient ICU
adults • Streptococcus pneumoniae
• Streptococcus pneumoniae • Streptococcus pneumoniae
• Mycoplasma pneumoniae
• Mycoplasma pneumoniae • Staphylococcus aureus
• Haemophilus influenzae
• Clamydophila pneumoniae • Usually Mrsa
• Chlamydophila pneumoniae
• Haemophilus influenzae • Legionella species
• Respiratory viruses
• Legionella species • Gram-negative bacilli
• Influenza A and B
• Aspiration • Klebsiella, E. coli,
• Adenovirus
• Respiratory viruses Enterobacter,
• Respiratory syncytial virus
• Influenza A and B Serratia, P.
• parainfluenza
• Adenovirus aeruginosa, and
• Respiratory syncytial virus Acinetobacter
• Parainfluenza • Haemophilus influenzae

Therapy:
• Therapy is almost always empiric initially
• S. pneumoniae is associated with higher rates of morbidity and mortality so important to make sure its covered
• Check local prevalance of macrolide resistance
• “Atypical” pathogens more common in older children and adults

DO NOT COVER MRSA: Ceftriaxone, Levo/moxifloxacin, ampicillin/sulfbactam, ertapenem

Cover MRSA:
Pneumonia in • Up to 1 month
Babies • Consider vaginal flora
• Group B strep
• H. influenzae
• E. coli
• S. aureus
• L. monocytogenes
• Ampicillin/Sulbactam
• Cephalosporin (if not listeria… remember they’re LAME)
• Carbapenem
• 1-3 months
• Atypicals
• S. aureus
• S. pneumoniae
• Azithromycin
• SMX/TMP
Community • Antimicrobial therapy is not routinely required for preschool-aged kids with CAP because its highly likely its viral
Acquired • Amoxicillin should be first line for previously healthy, immunized infants and preschool-aged children with mild to moderate CAP. Most common
Pneumonia in pathogen is S. pneumoniae and amoxicillin provides coverage
kids – Also used for school-aged children and adolescents
• Atypical pathogens suspected
- Macrolides
• Fully immunized, local data says S. pneumoniae susceptible, then ampicillin or penicillin G
• Not immunized or local strains of S. pneumoniae are resistant
– 3rd generation parenteral cephalosporin (ceftriaxone or cefotaxime)
– Add macrolide for suspected M. pneumoniae and C. pneumoniae are considerations
– Add vancomycin or clindamycin if clinical, lab, or imaging is consistent with S. aureus

Influenza • Zanamivir & Oseltamivir

• Inhibit influenza neuraminidase which results in clumping of newly release virions to each other and membrane of infected cell. Ultimately leads to
decrease released of progeny virus
• Early administration is crucial, replication peaks 24-72 hrs after onset of illness
• Used for treatment and prevention of influenza A and B (though resistance is increasing)

Cystic Fibrosis Most common Pathogens:

• Pseudomonas aeruginosa (initial cultures realted to increased morbidity and mortality)
• Staphlococcus Aureus
• Haemophilus influenza
• Stentrophomonas maltophilia
• Burkholderia cepacian
Therapy
• Inhaled antibiotics
• Tobramycin
• Aminoglycoside
• Improves lung function and reduces exacerbations
• Recommended for patients ≥6 years old with P. aeruginosa persistently present in cultures
• Low risk of adverse events
• Aztrenonam
• Monobactam
• Active against P. aeruginosa
• Azithromycin
• Improves lung function and reduces exacerbations
• Recommended for patients ≥6 years old with P. aeruginosa persistently present in cultures
Goals:
• Goals
• Eliminate bacterial proliferation
• Reduce bacterial load (complete eradication unlikely)
• Decrease sputum production
• Restore lung function to baseline
• Treatment options
• S. aureus or H. influenzae early in the disease, P. aeruginosa later in the disease
• IV: give 2 anti-pseudomonal agents
• Aminoglycosides + extended spectrum penicillin/ beta lactamase inhibitor
• Oral: TMP/SMX, Amoxicillin/Clav, Oral Cephalosporins

Allergic H1 and H2 Receptors

Rhinitis • Widely distributed in the periphery and in the CNS
“Hay fever” • Histamine can exert local or widespread effects on smooth muscle glands
• Causes itching and stimulates secretion from nasal mucosa
• Contracts smooth muscles (those in the bronchi and gut)
• Relaxes other smooth muscles (small blood vessels)
• Potent stimulus of gastric acid secretion
• Bronchoconstriction and contraction of the gut = H1
• Gastric secretion = H2
• Vascular dilation are both
Anti-histamines
• Effective at controlling all symptoms associated with allergic rhinitis except nasal congestion
• Less effective than intranasal corticosteroids
• Can be used daily or as needed
• Called antagonists…. Inverse agonists
• Shift the equilibrium from active form of H1 receptor to inactive form (down regulate activity)
 1st generation 2nd generation
• Diphenhydramine, dimenhydrinate, Doxylamine, • Loratidine, cetirizine, azelastine (nasal or
hydroxyzine ophthalmic), olopatadine,(nasal or ophthalmic)
• Lipophilic, easily cross the blood brain barrier • Onset is 1 hour and peak in 2-3 hours
• CNS symptoms in >20% of patients • Longer acting and less sedating
• Avoid in small children and the elderly • Metabolites (3rd gen?): fexofenadine, desloratidine,
• Can have a paradoxical excitation in children levocetirizine – designed to have fewer CNS effects
[rather than depressing them] but not confirmed
• Infants: CNS depression can lead to SIDS • Lipophobic developed to avoid CNS effects
• In the elderly increase the risk of falls • Popular especially with mild or intermittent
• Which increases risk of infection and need symptoms
for surgery • Chronic and or more significant symptoms use
• Role in therapy limited to due adverse effects intranasal glucocorticoids
• Antinausea and antiemetic actions • Adverse Effects: less sedating though cetirizine ~10%
• Motion sickness prevention doxylamine (Unisom®) • Varying degree of anticholinergics (dry
was used widely in pregnancy eyes most noticeable)
• Serotonin blocking actions
• Adverse Effects
• SEDATION!!!! impairments that impact work and
driving
• Effects on intellectual and motor function even in
the absence of subjective awareness of sedation
• Problematic in children due to impact on school
work
• Paradoxical agitation in very young
children
• Problematic in elderly who are more susceptible to
the anticholinergic effects: dry mouth, dry eyes,
urinary hesitancy, confusion

Antihistamine Nasal Spray

• Azelastine and olopatadine
• Onset of action less than 15 minutes
• Have some anti-inflammatory effect and can improve nasal congestion
• Guidelines still generally prefer INGCs (Intranasal glucocorticoids)
• Noninferiority trials both compare favorably with fluticasone

Decongestants

Alpha 1 selective agonist: Alpha 1 > alpha 2

• Phenylephrine and oxymetazoline
• Used topically as nasal or ophthalmic decongestant
• Phenylephrine also as a systemic decongestant
• Ophthalmic mydriatic, topically for hemorrhoids, iv to maintain blood pressure. (Was once used for the treatment of SVT)
• Systemic side effects: increased BP, decreased heart rate, anxiety, piloerection, insomnia
When topical nasal decongestants are used for a protracted period "rebound" congestion may occur despite continued use.
Limit to max of 3 days
• Down regulation of alpha-adrenergic receptor
• They become horribly decongested when they stop if they have been using it chronically and addicted physiologically to it now
Nonselective agonist: Alpha and Beta
Pseudoephedrine
• In pharmacies only (some states Rx only)
• Precursor in methamphetamine synthesis
• Used orally as a nasal decongestant (once used off label to increase urinary sphincter tone in urinary stress incontinence)
• Side effects: mydriasis, dry mouth, hypertension, tachycardia, insomnia, myocardial ischemia, anxiety
• Based on mechanism of action, could you have predicted any of these???
Corticosteroid • Intranasal: budesonide, triamcinolone (first generation), beclomethasone, flunisolide, fluticasone furoate, fluticasone propionate (second generation),
mometasone, ciclesonide
- Used for both asthma and COPD (limited use in COPD) and allergic rhinits
- Block late-phase reaction to allergen, reduce airway hyperresponsiveness, and inhibit inflammatory cell migration and activation
- Most potent and effective anti-inflammatory medication currently available
- Most effective single maintenance therapy for allergic rhinitis and cause few side effects at recommended doses (UpToDate)
- For severe/persistent rhinitis, short burst of oral steroids might be needed if symptoms are preventing the patient from sleeping or working (more
widely used before nasal glucocorticoids and nonsedating antihistamines became available)
- 1st Gen systemic bioavailability 10-50%, 2nd Gen < 1%
 [systemic effects most likely with 1st generation, that is why fluticasone is the one that is most often used]
- Onset: most a few hours, maximal effect may require several days or weeks in patients with long-standing untreated symptoms
- No improvement by one month indicates efficacy is unlikely
- Significant adrenal suppression reported with intranasal fluticasone and strong inhibitors of CYP3A4 enzymes in small number of case reports (use
something other than fluticasone with strong inhibitors i.e. ritonavir, itraconazole and watch for signs of Cushing’s syndrome)
- Patients with severe symptoms will require daily use on chronic basis (step down to lowest effective dose)
ADE:
 Headache
 Pharyngitis
 Nose bleed
• Inhaled: beclomethasone, budesonide, fluticasone, triamcinolone
• Systemic: dexamethasone, prednisone, prednisolone, methylprednisolone
Leukotrienes • Cysteinyl leukotrienes are released from the nasal mucosa following allergen exposure leading to symptoms associated with allergic rhinitis
• Generally 3rd line after intranasal steroid and oral antihistamines due to side effect risks and lower efficacy
• Leukotrienes cause airway smooth muscle contraction which leads to increased airway resistance
Leukotriene Antagonists: Montelukast
• Selective leukotriene receptor antagonists that inhibits the cysteinyl leukotriene receptor
• Montelukast: does not strongly inhibit CYP450 (zafirlukast does)
• Side Effects: psychiatric disturbances, headache, eosinophilia, and vasculitis
• Postmarketing reports of behavoral changes (abnomral dreams agitation, aggression, depression, halluciniations, etc)
• Systemic eosinophilia (consistent with Chrug-Strauss syndrome), vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or
neuropathy
Mast Cell • Cromolyn, nedocromil
Stabilizer • MOA: poorly understood, may involve decrease in release of mediators (leukotrienes and histamine)
Not absorbed (only local effects)****
• May cause cough and irritation of airway
• Alternative agent for mild asthma and preventive treatment prior to exercise or unavoidable exposure to known allergens
• Onset of action = weeks
• Not doing anything with the inflammatory mediators or blocking receptors, you are trying to prevent the initial release of the mast cells; this is
given in advance if someone has a seasonal allergy etc…
Less efficacious than intranasal steroids
Cough • Antitussives
• Hydrocodone • Block cough signal transmission through medullary cough
• Codeine center
• Act centrally to decrease the sensitivity of the
cough center
• Two examples of opiates used to suppress cough
• RESPIRATORY DEPRESSION!!
• Sedating, euphoric
• Addiction/dependence* potential

• Dextromethorphan
 Stops opioid-related sigma receptor mediated transmission of cough impulse
 Also NMDA glutamate receptor antagonist
No euphoria/addiction potential
 It is abused
 Metabolized by CYP2D6 (inhibitors decrease metabolism)
 RISK OF SEROTONIN SYNDROME
 Other serotoninergics
 Agents that block metabolic break-down
• Benzonatate
 Related to local anesthetics – thought to reduce activity at peripheral cough receptors (respiratory stretch receptors)
 Safe at therapeutic doses, but VERY TOXIC in overdose!! (convulsions within 20 min, death within 60) Not approved for kids < 10
yo
• Expectorant
• Guaifenesin
 Expectorant
 Increases respiratory fluid secretion
 Thought to decrease viscosity of mucous, facilitating expectoration
 One small trial demonstrated reduction in urge to cough
 Adequate hydration may improve response
 Side effects: nausea, headache
• N-actylcystine – another mucolytic
 N-Acetylcysteine (Mucomyst®)
 Reduces viscosity of mucus and sputum by cleaving disulfide bonds
 Delivered via nebulizer and modestly reduces COPD exacerbation rates by roughly 30%
 IV or PO N-acetylcysteine is used as an antidote for acetaminophen toxicity
Lecture 9 Lower Respiratory Tract Infections

• Pneumonia is an infection of the pulmonary parenchyma.

• Pneumonia results from a combination of proliferation of pathogens at the alveolar level and the host response to the pathogens.
• The microbes gain access to the respiratory tract by 1 of 3 ways.
• Small volume aspiration from the oropharynx
• Inhaled in droplets*** most common
• From Hematogenous spread (rarely)
• Spread from a infected pleural or mediastinal space (rarely)
• Pathophysiology
• Initial phase; composed of proteinaceous exudate and bacteria.
• Red Hepatization; exudate with the addition of erythrocytes and neutrophils with the occasional bacteria
• Gray Hepatization; predominantly neutrophils and fibrin. The erythrocytes have been lysed and the bacteria are usually absent.
• Resolution; macrophages are the predominant cell type with an absence of bacteria and other inflammatory products.
• Clinical Presentation of a Pneumonia
• Fever
• Tachycardia
• Chills or sweats
• Cough productive (Sometimes nonproductive)
• Dyspnea
• GI symptoms of Nausea, Vomiting, or Diarrhea
• The pneumonia patient may also have other symptoms like:
• Fatigue
• Headache
• Myalgias
• Arthralgias
• Assessing Severity of Pneumonia
• The CPIS (Clinical Pulmonary Infection Score) is used to estimate infection in patients that may have a ventilator associated pneumonia
• This is just an example of a severity index score to assist in management.
CURB-65
• Confusion = 1 point
• Urea, BUN > 19 = 1 point
• Respiratory rate >30 = 1 point
• Blood Pressure < 90/60 = 1 point
• > 65 years of age = 1 point
• With a score of 2 the 30 day mortality is
9.2% and they should be admitted.
Patients with a score of 3 or greater have
a mortality rate of 22%.

• Deciding whether to admit or not

• Hypoxic?
• Signs of systemic infection? (indicated by CURB-65)
• Comorbidities
• History
• Treatment of Pneumonias
• Treatment is usually empiric by covering the most common organisms.
• Isolating a cause of a pneumonia is difficult. It is hard to obtain accurate microbial cultures. Sputum cultures have a positive yield of less than 50%.
• Blood cultures are routine with the suspicion of a pneumonia. They are part of most hospital guidelines.
• Urine antigen tests for Strep. pneumoniae and Legionella are available and have a high sensitivity and specificity.
 Types of Pneumonia
o Community Acquired Pneumonia (CAP)
 An infection that a patient acquires in the community or any setting other than a health care setting.
 Present in a patient who has limited or no exposure to any healthcare systems.
 Most common form of pneumonia
 There are two types of CAP, typical (lobar, consolidating) and atypical (patchy interstitial infiltrates).
 Risk factors:
 Alcoholism
 Asthma
 Immunosuppression
 insitiutionalization
 > 70 years of age
 Atypical CAP
 More often caused by bacterial categorized as atypical;
o Mycoplasma pneumoniae, Chlamydophila (formerly Chlamydia) pneumoniae, Chlamydophila psittaci, Legionella
pneumophila, Francisella tularensis, and Coxiella burnetii.
 Atypicals are intrinsically resistant to B-lactam agents!!!!!!!!!.
 May present atypically, and sometimes referred to as walking pneumonia.
 Can also be caused by viruses, fungi, and protozoans.
 Treatment
 Uncomplicated outpatients can be treated with macrolides in one drug management like Azithromycin.
o Recent antibiotic usage might require the usage of a respiratory flouroquinolone like Levaquin or Avelox.
 Uncomplicated inpatient treatments can include Ceftriaxone and Azithromycin or a respiratory flouroquinolone.

o Health Care Associated Pneumonia (HCAP)

 An infection that occurs when patients are exposed to organisms different from those in the community because of the patient’s interaction with
healthcare facilities.
 A newer class of pneumonias that represents patients with co-morbid diseases being exposed to resistant bacteria.
 Resistant microbes are becoming more common.
 Methicillin resistant Staph. aureus (MRSA) is becoming more and more common.
 Exposure to health care facilities increase the chances the someone will be exposed to unique virulent microbes like pseudomonas.
 Patients that have had intravenous therapy, wound care, or intravenous chemotherapy within the last 30 days.
 Living in long-term care facility or nursing home.
 Hospitalized for 2 or more days in the past 90 days.
 Has attended hospital or hemodialysis clinic within the previous 30 days.
 Pseudomonas
 An opportunistic microbe that loves warm and moist environments. It thrives in situations where catheters and endotracheal tubes are
used.
 Pulmonary Infections from pseudomonas require double gram negative antibiotic coverage
o (two different classes of antibiotics that cover gram negatives used at the same time like fluoroquinolones and
aminoglycosides)
 MRSA
 A strain of Staphylococcus aureus that is resistant to the beta-lactam class of antibiotics. They are becoming difficult to treat.
 New strains have emerged in the community and are genetically distinct from the hospital strains. It is called community acquired
methicillin resistant staph aureus. (CA-MRSA.)
 MRSA pneumonias are covered/treated with Linezolid or Vancomycin.
 Antibiotic coverage
 Double gram negative coverage, pick 1 member from 2 of the 4 classes.
o 1st drug choice being a antipseudomonal cephalosporin (Cefepime, or Ceftazidime) or an antipseudomonal carbapenems
(Imipenem, or Meropenem) or beta-lactam/beta-lactamase inhibitor (Piperacillin/Tazobactum) zosyn
o 2nd drug choice being a Flouroquinolone (Ciprofloxacin or Levofloxicin) or aminoglycoside (Amikacin, Gentamicin, or
Tobramycin)
 Add coverage for suspected MRSA by adding either Linezolid or Vancomycin.
o Hospital Acquired Pneumonia (HAP)
 A parenchymal infection that a patient contracts after being hospitalized.
 Hospital acquired pneumonia is a pneumonia that occurs 48 hours after admission to the hospital.
 They had no such symptoms upon admission
 It is mostly likely to be caused by resistant advantageous organisms.
 The antibiotic regimens will imitate HCAP regimens depending on the suspected infectious agent.
o Ventilator Associated Pneumonia (VAP)
 A parenchymal infection that a patient contracts after being placed on a ventilator
 Coverage is extremely variable. There is a diverse amount of pathogens that can cause VAP.
 Presentation is most commonly fever and infiltrates on CXR. Cultures may be easier to obtain secondary to possibility of bronchoscopy.
 Empiric coverage includes Carbapenem or Zosyn + Flouroquinolone or aminoglycoside.

o Aspiration Pneumonia:
 An infection that occurs after the patient aspirates stomach contents in the respiratory system.
 Now you have to cover anaerobes and GI bugs
 Zocin or clindamycin may be used now
  Aspiration is an accidental movement of gastric contents in the respiratory tract.
 Occurs commonly when patients are obtunded or have loss control of the swallowing mechanism.
 Aspiration places anaerobic bacterial in the respiratory tract. This can cause a pneumonia by unusual culprits.
 Aspiration pneumonia is one of the most deadly complications from stroke.
 Common bacteria; Anaerobes 34%, Gram Positive Cocci 26%, S. milleri 16%, Klebsella pneumonia 25%, and Nocardia 3%
 Antibiotic coverage is primarily with Zosyn (Piperacillin + Tazobactum), alternatives are Clindamycin, and Ceftriaxone + Metronidazole.
o Pneumonia in the Cystic Fibrosis patient:
 A different infection secondary to the environment of the CF lung. The amount of infections and the organisms differ from CAP.
 Common agents early in disease is Staphylococcus aureus, and haemophilus influenza.
 Pseudomonas aeruginosa is more common later in the disease.
 Sputum for culture is usually abundant.
 Treatment involves coverage with two drugs that cover pseudomonas if pseudomonas is the culprit.
 Staph can be covered oxacillin or nafcillin for MSSA or vancomycin for MRSA.

o Pneumonia in HIV patients
 Differ in the fact that the immune systems inhibits fighting the infections and the list of organisms can be different from the immunocompetent
patient.
 Most common pathogen is Pneumocystis carinii/jiroveci. Patients generally present with progressive shortness of breath and diffuse infiltrate.
 Drug of choice for PCP is TMP-SMX (Bactrim)
 Other agents include Mycobacterium tuberculosis, diverse fungi.
 Patients may also have Kaposi’s Sarcoma or lymphoma.
 Induced sputum or bronchial wash may guide therapy.
 Physical Exam
o General evaluation of the patient, (very ill, respiratory distress)
o Vitals; tachycardia, tachypnia, hypotension, fever, hypoxia
o Respiratory; rales or crackles in area of infiltrate, decreased breath sounds,
o Osteopathic; facilitation in T1-T6, AGRs, evaluate rib mechanics and vertebral dysfunctions.
 Normalize mechanics of the pump and they will oxygenate better
 Treatment of Host
o Primary goal is to normalize the patient’s mechanics.
o Treat the sequence of areas of greatest restriction. Do your best to normalize the patient’s thoracic region. A somatic dysfunction in the rib cage could cause
restrictive pulmonary mechanics. Normalizing the mechanics could significantly reduce the patients distress and potential save the patient’s life.
o The treatments may need to be modified to treat the patient as they are lying flat
 Incentive Spirometry
o Incentive spirometry is a great tool to help the patient get better. The amount of exudate and secretions in the parenchyma alter diffusion and increase surface
tension in the alveolus. Surfactant is a natural liquid covering in the alveolus to keep the alveolus open and distended.
o The excess exudate and bi-products overwhelm the surfactant and collapses the alveolus. The collapsed alveolus becomes a pocket of infection almost like an
abscess. It also reduces O2 and CO2 diffusion. The small popping open of the alveolus during respiration makes the audible rales during auscultation.
o Incentive spirometry encourages patient to take an excessive amount of air into the lungs and pop open the alveoli. A correct technique almost always produces
a cough and some sputum production. The more compliant the patient the sooner they become free from need of supplemental oxygen.
 Influenza
o Clinical Features
 Abrupt onset of fever
 Headache
 Myalgia
 Malaise after an incubation period of one to four days
 Respiratory Symptoms
 Nonproductive cough
 Sore throat
 Nasal discharge
o Complications
 Bacterial Pneumonia
 Reye’s Syndrome
 Myositis
 Rhabdomyolysis
 Myoglobinuria
o High Risk groups
 Children from birth to 4 years
 Pregnant women
 Persons > 65
 Children/Adolescents 6 months to 18 years of age on Aspirin therapy
 Adults and Children with chronic disorders
 Asthma
 Immunodeficiency
 Diabetes mellitus
 Residents of nursing homes
 Bronchiectasis
o Irreversible airway dilation
o Two types;
 Focal
 Caused by obstruction to a local airway.
o Aspirated foreign body
o Tumor/mass
o Compression by adjacent lymphadenopathy
o Scarred or stenotic airway
o Bronchial atresia
 Diffuse
 Infection
o Bacterial
o Nontuberculous mycobacteria
 Immunodeficiency
o Hypogammaglobulinemia
o HIV infection
  Genetic causes
o Cystic fibrosis
o Kartagener’s syndrome
o Alpha 1 antitrypsin deficiency
 Autoimmune or Rheumatic disorders
o Rheumatic arthritis
o Sjogrens syndrome
o Inflammatory bowel disease
o Immune mediated (like Allergic bronchopulmonary aspergillosis)
 Recurrent Aspiration
 Miscellaneous
o Postradiation fibrosis
o Idiopathic pulmonary fibrosis
o Yellow nail syndrome
o Idiopathic
o Clinical Manifestations
 Persistent productive cough
 Thick secretions
 Foul smelling
 Adventitious signs
 Crackles
 Wheezes
 Clubbing of the digits
 Mild to moderate airflow obstruction on pulmonary function tests
 Acute exacerbations may not manifest fever and infiltrates
o Diagnosis
 Clinical symptoms with radiographic evidence
 Chest radiograph can be helpful
 CT can confirm the presence of the disease
o Treatment
 Normalization of secretions
 Antibiotic treatment of acute exacerbations
 Organisms commonly isolated
o Haemohilus influenza
o P. aeruginosa
 Anti-inflammatory therapy
 Systemic glucocorticoids
 Inhaled glucocorticoids?

 Lung Abscess
o Cavitary infections in lung parenchyma
o Two types
 Primary: Occur in the absence of underlying pulmonary lesions
 Secondary: caused by systemic conditions or pulmonary lesions
o Diagnosed by standard imaging
 Chest radiograph
 CT scan of the Chest
o Clinical features
 Fatigue
 Cough
 Sputum production
 Fever
 Putrid smelling sputum (Anaerobic causes)
 Pleurisy (Pleuritic chest pain)
Lecture 10 &11 Lung Tumors
Upper respiratory tract
Nasopharyngeal • Rare, benign, usually adolescent males
Angiofibroma • Commonly express androgen receptor, but variable estrogen or progesterone receptors
• Commonly posterolateral wall of roof of nose
Stellate and staghorn • Locally aggressive, may grow into nasopharynx, orbit or cranial cavity
blood vessels • May regress after puberty, especially after incomplete surgical excision or radiation therapy
• Commonly presents with nasal obstruction, epistaxis
• Treatment: Surgery
BENIGN • Benign but recurs in 40%, usually within 1 year, particularly if not completely removed
Sinonasal (Schneiderian) • Benign neoplasm of respiratory mucosa
Papilloma • Usually adults, 2/3 men, with nasal obstruction, stuffiness or epistaxis; also children
• Three subtypes: Inverted (Most common), fungiform and oncocytic
• Usually unilateral
• Often HPV 6/11 positive (particularly fungiform subtypes); EBV negative
Benign
• Nasal septum tumors: Usually exophytic with thin central core of connective tissue

• Lateral wall of nose: Usually inverted, with inward epithelial growth

Olfactory Neuroblastoma • Rare, **malignant neuroectodermal tumor

(Esthesioneuroblastoma) • Probably arise from olfactory membrane or olfactory placode
• Not related to neuroblastomas elsewhere in body
Malignant • Median age 50 years, range 3-79 years; no gender preference
• Usually upper nasal vault; rarely in nasopharynx, maxillary or ethmoid sinus
• Presentations
 Nasal (obstruction, epistaxis, etc)
 Neurologic (headache, nausea)
 Cervical mass, etc
• Locally invasive into paranasal sinuses, nasopharynx, palate, orbit, base of skull, brain
• May develop distant metastases, usually to cervical lymph nodes and lung
• Late recurrence (after 10 years) common
•
NUT midline carcinoma • Aggressive subset of squamous cell carcinoma defined by rearrangement of NUT (NUclear protein in Testis) gene on #15 to other genes,
usually BRD4 on #19
- AKA NUclear Protein In Testis
- Function unclear
- Translocation resulting into fusion with other proteins, such as BRD4 [t(15;19)] BRD3, and BRD9, etc
- Normally expression highly restricted to testes
• Originally thought to be limited to mediastinum, but 35% occur in head and neck
• Median survival of 7 months due to ineffective chemotherapy
• Must rule out for any poorly differentiated epithelioid mediastinal tumor, regardless of age
• No effective treatment

Nasopharyngeal • Arising from the epithelium of the nasopharynx

Carcinoma • Rare in the states but common in certain areas of Africa and Asia
• Rare in the States and Western Europe, but incidence increasing among black teenagers
• Common in South Asia, North Africa, Middle East and the Arctic
• More common in men
• Bimodal age distribution, a small peak in late childhood, and second peak around 50-59
• Associated with Epstein-Barr virus infection
• Other risk factors:
- Consumption of salt-preserved fish containing carcinogenic nitrosamines, family history, specific HLA class I genotypes, tobacco
smoking, chronic respiratory tract conditions and low consumption of fresh fruits and vegetables
• Most common symptoms: Headache, diplopia, or facial numbness
• Mass in the neck if neck lymph nodes metastasis • LOH at 9p and 3p prior to EBV infection
• Other presentations: - LOH= loss of heterozygosity
 Nasal symptoms: Bleeding, obstruction, and discharge • EBV genome products
 Ear symptoms: Infection, deafness, and tinnitus
 Painless neck mass
 Often bilateral neck involvement
 Cranial nerve palsy
 Nasopharynx mass by nasopharyngoscopy
• Three histologic subtypes:
 Keratinizing squamous cell carcinoma (WHO type 1)

 Nonkeratinizing-undifferentiated (WHO type 3)

 Nonkeratinizing-differentiated (WHO type 2)

Need to know the markers to know what it is

- Express Keratin, EMA, EBV antigens, EBER (EBV encoded RNA)****

- Negative for lymphocytic markers (CD45)
 Diagnosis and Differential
• EBV studies: IgG against early EBV antigen; IgA against viral capsid
antigen
• Radiologic studies
• Blind biopsies, particularly in fossa of Rosenmuller
• Differential diagnosis:
 Nasal Polyps
 Pediatric Non-Hodgkin Lymphoma
 Pediatric Rhabdomyosarcoma
Treatment
• Radiation therapy: Mainstay of treatment
• Chemotherapy for advanced cases
• Usually unresectable by surgery
• Poor prognostic factors: High staging, keratinized type, metastasis,
older age, high plasma/serum EBV DNA titers

Vocal Cord Polyps • Also called laryngeal nodule or singer’s nodule

******* • Noninflammatory response to injury causing hoarseness
• More common in heavy smokers or singers due to inflammation, allergic or immunologic causes, possibly secondary to hemorrhage
• Generalized and persistent hoarseness: Most common presentation***
• Almost never transforms to malignancy
• Treatment: Surgery, or vocal rest

Squamous Papilloma • Warty outgrowths of laryngeal surface epithelium

• Commonly multiple in children by solitary in adults
• More common in men
• Associated with human papillomavirus (HPV) infection, usually HPV 6 and 11
• Dysplasia might be seen in adults
• Likely recur
Sqaumous Carcinoma of • Majority of laryngeal cancers
the Larynx • 13,000 new cases annually in US; 40% mortality
• Predominantly male; usually ages 40+
• Major risk factors: Smoking, enhanced by heavy alcohol consumption
• HPV is not an early factor, but positive in 20%, usually HPV 16
• EBV a factor in 40% of hypopharyngeal carcinomas**
• Metastases to regional lymph nodes and lungs; direct extension to thyroid gland and jugular vein
• Treatment and Prognosis
- If possible, the goal of treatment is to remove the tumor and prevent recurrence while maintaining laryngeal function
- Surgery, radiation or chemotherapy
- Advanced cases: Total laryngectomy, reconstruction, and adjuvant postoperative chemoradiation therapy
- Poor prognostic factors: High initial staging, tumor grade, vascular invasion, negative HPV testing [positive has a better prognosis]
-

Branchial Pouch/ Cleft • Congenital lesions due to incomplete obliteration of the branchial apparatus
Anomalies • May be cyst, sinus, fistula or cartilage in anterolateral neck****
• Usually 20-40 years old
• Cysts much more common
• May be bilateral
• Cysts derived from branchial cleft have squamous epithelium;
- Congenital epithelial cysts
- Arise on the lateral part of the neck
- Due to failure of obliteration of the second branchial cleft
- Usually presents as a solitary, painless mass in the neck of a child or a young adult
- May have intermittent swelling and tenderness during upper respiratory tract infection
- May form fistula after inflammation
- Treatment: Surgery, antibiotics if infected

• Cysts derived from branchial pouch have respiratory epithelium, with or without squamous metaplasia

Thyroglossal duct cyst • Most common congenital neck mass

• Mean age 30-40
• Midline*** neck developmental anomaly due to persistence and cystic dilation of thyroglossal duct
• Usually asymptomatic
• May have heterotopic thyroid tissue
• May appear as blind tubular structure in mid neck or as sinus tract connected to foramen cecum or suprasternal notch skin
• Treatment: Surgery
Malignant tumors of the lung are the leading cause of CANCER death in the US
 Risk Factors
o Cigarette smoking: Most common risk factor
 Associated with 80-85% lung cancers in the States,
 10-30 times greater risk than non smokers
 Quantity of cigarette smoking summarized by the number of packs of cigarettes smoked per day multiplied by the number of years smoked
 Secondhand smoke
o Radiation at home: Radon
 Occupational and environmental factors: wood/coal fuels, asbestos, arsenic, radiation, dusts and fumes from nickel, chromium, etc
 Family and genetic factors
 Epithelial tumors****
o Adenocarcinoma
o Squamous cell carcinoma
o Neuroendocrine carcinoma
o Adenosquamous cell carcinoma, sarcomatoid carcinoma, salivary gland type tumor, etc
 Mesenchymal tumors
o Inflammatory myofibroblastic tumor
o Synovial sarcoma
o Myoepithelial tumor, etc
 Lymphohistiocytic tumors: Lymphomas, etc
 Tumors of ectopic origin: Teratoma, etc
 Metastatic tumors
 Molecular basis of Malignant tumors
o AKA EGFR, ERBB1, HER1, etc
 Transmembrane glycoprotein
 Protein tyrosine kinase
 Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF
 Most mutations affect the ATP-binding cleft
 Resulted in ligands independent homodimerization and activation of EGFR
 Tyrosine kinase inhibitor may compete for binding of ATP and block activation of down-stream signaling pathways
 Tx:- tinib (gef, erlo, afat, osimer)
o EMLF4-ALK fusion
 Commonly results of Inv(2)(p21p23) involves EML4 and ALK
 EML4: Strongly expressed during mitosis, microtubule binding protein
 ALK: Anaplastic lymphoma receptor tyrosine kinase, function unclear, probably involved in central and peripheral nervous system development and
maintenance
 Tyrosine kinase domain of ALK and various part of EML4
 Results in consistent activation of ALK tyrosine kinase domain
 Inhibition of apoptosis
 Promotion of cellular proliferation
 Tx: -tinib (criz, cer, alec)
o KRAS
 Kirsten rat sarcoma viral oncogene homolog
 GTPases, RAS family member, involved in RAS/MAPK pathway
 Control cellular signaling pathways responsible for cell division, cell differentiation, and the self-destruction of cells (apoptosis)
 Mutations identified in cardiofaciocutaneous syndrome, Noonan syndrome and malignancies of lung, pancreas, colon and rectum due to uncontrolled
proliferation
 Tx: MEK inhibitors
o BRAF
 A member of raf/mil family of serine/threonine protein kinase
 Regulate MAP kinase/ERKs pathway
 Affects cell division, differentiation, and secretion
 Germline mutations associated with cardiofaciocutaneous syndrome, a disease characterized by heart defects, mental retardation and a distinctive
facial appearance
 Mutations also associated with various cancers, including non-Hodgkin lymphoma, colorectal cancer, malignant melanoma, thyroid carcinoma, non-
small cell lung carcinoma, and adenocarcinoma of lung
 Tx: -fenib (vemura, dabra)

SVC Syndrome • Due to obstruction of blood flow through the superior vena cava
• A medical emergency and most often manifests in patients with a malignant disease process within the thorax
• Requires immediate diagnostic evaluation and therapy
• Lung cancer, particularly adenocarcinoma, is now the underlying process in approximately 70% of patients with SVCS
• Presentations: Dyspnea (most common), facial swelling, head fullness, cough, arm swelling, etc
 • Management: Relieve symptoms and to attempt cure of the primary malignant process, corticosteroids, diuretics, radiation therapy,
surgical bypass, etc
Horner Syndrome • Results from an interruption of the sympathetic nerve supply to the eye
• Classic triad of miosis (ie, constricted pupil), partial ptosis, and loss of hemifacial sweating (ie, anhidrosis)
• Causes: Neuronal defects, trauma, tumors or infection of the lung apex, dissecting aneurysm, etc
• Treatment: Treat underlying diseases
Biopsy is more preferred because the findings
are more specific than sputum

Non-small Cell Carcinoma • Approximately 85% of all lung cancers

• Including adenocarcinoma, squamous cell carcinoma (SCC) and large cell carcinoma
• Most common clinical presentations: Cough, chest pain, coughing up blood, hoarseness, etc
• Diagnosis made by image studies followed by endoscopic and pathological examinations
• Sputum cytological examination usually with low sensitivity
• Usually require a complete staging workup to evaluate the extent of disease to determine the choice of treatment
• Managements: Surgery, chemotherapy and radiation therapy
Prognosis
• Highly lethal
• Distant metastasis commonly seen in adrenal glands, brain, contralateral lung, bone and liver
• Cessation smoking improve prognosis
• Prognostic factors
• Stage at presentation
• Poor performance scores
• Weight loss
Squamous Cell Carcinoma
• Arising from squamous epithelial cells
• Used to be most common type of lung cancer in Western countries
• Rates are declining due to reduction in tobacco use
• Usually men, closely correlated with smoking history
• Symptoms: Bronchial obstruction (pneumonitis, atelectasis)
• Hypercalcemia without bone metastases usually due to squamous cell carcinoma production of parathyroid hormone-related
protein****

Adenocarcinoma
• Arising from the bronchi, bronchioles and alveolar cells with or without mucin production
• Most common type of lung cancer in females, nonsmokers and younger males
• EGFR mutation and EML4/ALK fusion common
• KRAS mutation and MET amplification associated with poor prognosis and acquired EGFR inhibitor resistance
 Large Cell Carcinoma of Lung
• Undifferentiated malignant epithelial tumor composed of large, atypical cells [high grade]
• Approximately 10% of bronchogenic carcinoma
• More common in men
• May be negative for both squamous and adenocarcinoma markers
• Diagnosis of exclusion***

Small Cell Carcinoma of Lung • Also called oat cell carcinoma

• Poorly differentiated neuroendocrine tumor
• Derived from primitive cells of basal bronchial epithelium
• 10-20% all of lung carcinoma
• More common in men, median age 60
• Strong association with tobacco smoking
• Most common lung cancer associated with uranium mining, probably associated with radon
• Associated with paraneoplastic syndromes due to production of ACTH, ADH, calcitonin, etc
• Treatment: Chemotherapy, radiation
• Poor prognostic factors: Elevated serum LDH/alkaline phosphatase, relapsed disease, weight loss of greater than 10% of baseline body
weight, poor performance status, hyponatremia
• Smoking cessation associated with improved survival
Paraneoplastic Syndromes:
1. Lambert Eaton Myasthenic Syndrome
- Presynaptic disorder of neuromuscular transmission
- Autoimmune process against voltage-gated calcium channels*** (VGCCs) causing loss of functional VGCCs at the motor nerve
terminals
- Occasionally antibodies against acetylcholine receptor, but usually low titers (High titer seen in myasthenia gravis)
- Resulting in impaired release of acetylcholine
- Presentations: Proximal muscle weakness, depressed tendon reflexes, posttetanic potentiation, and autonomic changes
2. Acanthosis nigricans: Brown, velvety and verrucous plaques in axillae, back of neck and other skin folds, associated with visceral
malignancies, endocrine diseases and congenital disorders
3. Leukemoid reactions: Reactive leukocytosis due to tumor produced bioactive factors
4. Trousseau syndrome: Acquired blood clotting disorder that results in migratory thrombophlebitis, commonly associated with internal
malignancy, probably due to cancer caused imbalance of coagulative system
5. Hypertrophic pulmonary osteoarthropathy: Syndrome of clubbing of the digits, periostitis of the long (tubular) bones, and arthritis,
probably associated with tumor released cytokine, growth factor, etc
Carcinoid • Well-differentiated neuroendocrine carcinoma
• Benign
• <5% of primary lung tumors
• Locally invasive, rarely metastasizes
• Usually age <40 years old
• No gender predilection, NOT related to smoking
• Treatment: Resection
• Prognosis: Usually good prognosis
Metastatic Tumors to Lung • Most common lung malignancy***
• Usually multiple, bilateral, sharply outlined, rapidly growing, more pleomorphic and necrotic than lung primaries
• Same immunohistochemistry profiles as original tumor, but different from lung primary
• Negative for TTF1

Mesothelioma • Arises from mesothelial lining of pleura, peritoneum, pericardium and tunica vaginalis
• Pleura most common location
• Approximately 3000 cases of malignant mesothelioma are diagnosed annually
• Risk much higher with occupational asbestos exposure
• History of working in a shipyard
• Other risk factors: Radiation, Erionite, SV40 virus
• More common in men, 50-80 years old
• Peak age 35-45 years after asbestos exposure
• Pediatric cases rare, probably not associated with asbestos
• Gene: CDKN2A (P16/P14)
• Clinical Features
- Most common presentations: Dyspnea and nonpleuritic chest wall pain
- Other presentations: Chest discomfort, pleuritic pain, sweat, etc
- Diagnosis: Radiologic studies, thoracentesis, thoracoscopical biopsy, serum markers (mesothelin, megakaryocyte potentiating
factor)
- Managements: Surgery, chemotherapy, radiation
- Usually fatal, recurrence common
- Poor prognostic indicators: Performance status > 2; male; older than 75; nonepithelial histology; anemia; high serum LDH, etc
-
Solitary Fibrous Tumor • Pleural based, but usually NO pleural effusion
• May occur in other organs
• Associated with pulmonary osteoarthropathy, digital clubbing and hypoglycemia, which regress after tumor resection
• Most likely fibroblastic and not mesothelial in origin, arising from submesothelial mesenchyme
• Not associated with asbestos
• Treatment: Surgery
• May recur locally
• May cause death due to extensive intrathoracic growth or malignant type

CD99 also associated with Ewing sarcoma

Lecture 12 Tuberculosis
 Cannot get TB from fomites, clothing, or eating utensils
 At risk populations
o Foreign born - from endemic countries - < 5 years here
 Typicaltyy get boosters which are effective 85% of the time for the first 15 years of life
o Frequent travel/visits - endemic areas
o Shelters/jails/drug rehab/hospitals/LTC facilities
o Drug users - especially injection
o Health care workers - exposure in high risk procedures
o Children under 4 - exposed to high risk adults
o Clinical/medical conditions*
 Carcinoma of head and neck, bypass, chronic renal failure, leukemia, lymphoma, diabetes, HIV, immunosuppressive therapy, malabsorption syndromes,
silicosis, organ transplant
 Countries and Areas of High incidence
o Africa
o Eastern Mediterranean
o Europe
o Central and south America
o Southeast Asia
o Western pacific
 TB Skin Test:
o Mantoux tuberculin test/PPD; intradermal, safe during pregnancy ; can still do an X-RAY on a pregnant woman, just cover the womb ; no band aid and no blood
should be there
o  must document name time, date and the info on the bottle
o Reading a TB Skin Test
 Delayed hypersensitivity [TYPE IV; like poison ivy] reaction, NOT an antibody test
 Read at 48 – 72 hours
 Look/feel for induration
 Use ink pen technique
 Measure and mark down diameter in mm
 Do not put + or -
 Specify the actual size in mm
o PPD is a SCREENING test, does not tell you if you have TB, just that there was an exposure
o If positive  Report to the Health department and get chest X-ray
 Positive is based on the table below
Low Risk ≥15
NO RISK FACTORS
No need to test these people unless required as baseline for job or school.

Moderate Risk ≥10

 Recent immigration (<5 years)
 Potential for boosters
 Patients with diabetes, renal failure, certain cancers* (Leukemia, lymphoma or cancer of the head or neck or lung)
 IV drug users
 Employees/residents of hospitals, nursing homes , shelters or jails
 Excessive weight loss
 Gastrectomy or Jejuno-ileal bypass
 Child < age 4 (especially is they are living in conditions with someone who has high risk)

High Risk ≥ 5 mm
 HIV infection
 Fibrosis on Chest X-ray
 Recent contact with a person who has active TB
 Immunosuppression
- Immunosuppression treatment equivalent to prednisone 15 mg/day or greater [this is steroid immunosuppression]
 Considerations in Results of the TB skin test
o False Positives
 BCG
 Non-TB mycobacterium
o False Negatives
 Too soon after exposure
o Retesting
 Negative test but you are not convinced (if they were sick at the time)
 Too soon after exposure
 Some schools/jobs want a two step
o Two –Step: sometimes the first wakes up the immune system, to make the second one positive
 Can be done within a year
 Normal chest film. Abnormalities on chest radiographs may be suggestive of,
but are never diagnostic of, TB.
However, chest radiographs may be used to rule out the possibility of
pulmonary TB in a person who has a positive reaction to the tuberculin skin test
and no symptoms of disease
Need a culture!!!!! To DX

Calcified Granulomas
Nodules and fibrotic scars may contain slowly
multiplying tubercle bacilli with the potential for future
progression to active tuberculosis.
Persons with these findings, if they have a positive
tuberculin skin test reaction, should be considered high-
priority candidates for treatment of latent infection
regardless of age.
Conversely, calcified nodular lesions (calcified
granuloma) pose a very low risk for future progression
to active tuberculosis.

XRAY is NOT DEFINITIVE

Clinical Manifestations
 No Symptoms
 Low-grade Fever
Some people with TB so not have symptoms
 Weight loss
-These 3 symptoms if present together should
 Night Sweats indicate a need for a PPD
 Cough
 Hemoptysis

Interferon Gamma Release Assays

 Blood test – no 2-3 day return for PPD reading
 Not affected by BCG or non-TB mycoplasma
 No distinguishing between latent/active
 Sensitivity higher T-Spot in HIV patients
 QuantiFERON TB Gold-in-tube assay*******
 If this test is positive, then its TB but you do not know if its active or not
Nucleic Acid Amplification
 Test for rapid diagnosis of M. tuberculosis
 Can distinguish between TB and non-TB
 Finds TB in 50-80% of AFB neg smears
 Culture still required for susceptibility
 Need to get phlegm, not spit as a sample
 Extremely expensive
Other methods for Identification of TB
 Sputum smear
 Sputum cultures
 Bronchoscopy
o With lavage, if you can’t get sputum
 Gastric aspirate
o Preferred in children because they swallow the phlegm

Tuberculosis Infection
1. Primary Infection
2. Latent tuberculosis infection (LTBI)
a. NOT contagious when latent
b. Even if it is not contagious, if we find a positive PPD, we treat to prevent the 5% chance of reactivation in 2 years or 10% in 10 years
 Ghon focus is subpleural location of caseous necrosis whereas Ghon complex is combination of Ghon focus
+ hilar lymphadenopathy
Usually prefers the upper part of the lower lobe or the lower part of the upper lobe.****
This radiograph shows a classic Ghon complex in a child infected with Mycobacterium tuberculosis about 6
months previously, based on results of a contact investigation.
There is a calcified parenchymal lesion and calcification of the regional hilar lymph node.
Although a Ghon complex contains live organisms, the number is small (as seen in infection rather than
disease), so management with isoniazid alone as for latent infection is sufficient.
Ghon complex – calcified hilar lymph node and peripheral granuloma

Tuberculosis Disease
 Progressive Primary Disease
  Reactivated latent (Secondary)
o Most common presentation
o Likes the posterior upper lobe better
 Prefers the apical-posterior segments of the upper lobes (80-90 %)
 Followed by superior segment of the lower lobes
 And the anterior segment of the upper lobes
o Harder to clear upper lobes because of the pressures and decreased lymphatic flow

 Reinfection
 Endobronchial
 Miliary
o nodules of millet size (1 to 2 millimeters)
distributed throughout the parenchyma.
 Lymph node involvement

 Cavitary TB
o In active pulmonary TB, infiltrates or consolidations and/or cavities are often seen in the upper lungs with or without mediastinal or hilar lymphadenopathy

Extrapulmonaery
 Lymphatic
 Pleural
 Meninges
 Miliary
 Skeletal - Pott’s
 Spine collapses
 Genitourinary
 Gastrointestinal
 Cutaneous

Treatment of TB
 Latent Four drugs form core of first-line regimens
o INH (isoniazid)
o RIF (Rifampin) Pleural effusion Rifampin (RIF)
o Rifapentine
 Active Pulmonary (HIV negative) Isoniazid (INH)
o Initial Phase: two month regimen Pyrazinamide (PZA)
 RIF, INH, PZA, EMB Ethambutol (EMB)
o Continuation phase – 4-7 months
 INH, RIF
o When you are done treated, you need two consecutive negative cultures to prove its gone *****
 Special Circumstances
o Children
o Pregnancy
o Drug Resistance
o Diabetes mellitus
o Culture Negative TB
o Chronic Renal Insufficiency
o HIV Positive
o Hepatic Disease
o Malnutrition
Preventing transmission
 Adequate Ventilation
 Cough etiquette / Respiratory hygiene
 TB Risk Assessment
 TB Skin Testing / Screening Programs
 Reporting all + skin tests and active cases
 Health Care Worker education programs
 BCG vaccine program in endemic countries
 Nutritional counseling / enhancement
 Proper sterilization and disinfection techniques
 Airborne Infection Rooms - negative-pressure rooms
 Directly Observed Therapy
 Follow up - contacts with exposure to active cases
Protection
 Masks – N95
o High efficiency particulate filters
 Decrease visitors
 Outpatient Setting - isolation
 Hospital setting – isolation room –
 Postpone non-urgent procedures
 Coughs covered/respiratory hygiene
 Ventilator usage – still isolation procedures
 Filter on endotrach tube or ventilator
 Closed system suction catheter
Lecture 13: Respiratory infections
• Opportunistic
• Ubiquitous in environment
• Tend to cause disease only in immuno-compromised hosts
• Dimorphic
• May depend on temperature-a mold/spore at 70°and germinate at 98.6°to become a yeast
• Spores inhaled via respiratory tract and germinate to yeast form in lungs
• Can cause disease in immuno-competent host
• Fungal agents are generally found in soil and inhaled via respiratory tract
• Host defenses (mostly cell mediated immunity) arrest but often do not eradicate organism.
• Immunocompetent patients are often asymptomatic of have mild, self-limited symptoms
• Disease can lie in latent phase and if patient becomes immunosuppressed, infection can reactivate
• Disease disseminates in immunocompromised host
• Diagnosis is difficult
• Diagnosis is often overlooked because fungal infections are rare
• Routine labs do not identify
• Culturing organisms is time consuming and difficult

Histoplasmosis Pathogenic Dimorphic Fungi

Epidemiology
– Endemic in Mississippi and Ohio River Valley
• Very high prevalence in Indianapolis
– Associated with large flocks of birds
• Landscaping, cleaning attics and barns
• Tearing down structures where birds nest
– Cave explorers (spelunking)
• Bats
Pathogenesis
– Microconidia is infectious form
• Inhaled into alveoli and engulfed by neutrophils and macrophages
– Yeast phase
• Exists intracellular in macrophages
• Spreads to hilar and mediastinal nodes and hematogenously to reticulo-
endothelial system (RES)
– Cell mediated immunity
• Internally controls the disease
• Exists in latent infection and reactivates in immunocompromised
• Severe disease in CMI deficient
Clinical course
• Asymptomatic– 95% of cases
• Pulmonary Infection
– Acute
• Fever, chills, fatigue, myalgia, dyspnea, non-productive cough
– Chronic
• COPD, older men – progressive disease with cavitation,
necrosis
– Mediastinal Granuloma (rare)
• Very bad prognosis
– Fibrosing Mediastinitis (rare)
• Disseminated Infection
– Seen mostly in immunocompromised patients
• AIDS, transplants, TNF inhibitor, steroids
– Symptoms
• Chills, fever, malaise, anorexia, weight loss, dyspnea
• Hypotension, ARDS, sepsis syndrome, DIC
– Involvement liver, spleen, lymph nodes, bone marrow, adrenal glands, GI tract, CNS
(most frequent)
• Other Manifestations
– Pericarditis
– Arthritis/Arthralgia
– Erythema Nodosum / Erythema Multiforme
Diagnosis
• The clinical and radiographic findings in pulmonary histoplasmosis and sarcoidosis may be similar.
• A mistake in diagnosis can be disastrous if the patient is treated with corticosteroids or other
immunosuppressive medications
• The evaluation should include the following:
– Antigen testing of urine, serum, and bronchoalveolar lavage fluid
– Culture of bronchoalveolar lavage fluid, or other respiratory secretions, for fungi and
mycobacteria
– Biopsy of involved tissues for histopathologic examination by an experienced pathologist
– Serologic testing for histoplasmosis
– Growth on tissue or fluid samples
• Definitive diagnosis
• 6 weeks to grow
– Stains
• Bone marrow, hepatic, lung, lymph tissue
• Methenamine silver or Periodic Acid-Schiff (PAS)
– Urine antigen
• Useful for disseminated infection
– Antibody tests
• Immunodiffusion (H or M antibodies)
• Complement fixation
• Useful for chronic disseminated or pulmonary disease
Treatment
• Severe
• Amphotericin B
• Mild to Moderate
• Azoles (Itraconazole, Fluconazole, Voriconazole)
• Echinocandins
• Inactive
Coccidiomycoses Pathogenic Dimorphic Fungi
Epidemiology
• Dimorphic Fungus
• Arthroconidia (spores)
• Region
• Southwestern USA: San Joaquin Valley, Arizona, New Mexico, Texas
• Ecology
• Soil organism (arthroconidia)
• Dispersed in air
• Persons at risk
• Occupation with soil exposure
• Immunocompromised patients
• AIDS
• Transplants
• TNF antagonists
Pathogenesis
• Arthroconidia are inhaled (a single one can cause infection)
• Ingested by pulmonary macrophages
• Convert to spherule with hundreds of asexual endospores
• Spherule ruptures
• Endospores disseminate hematogenously to other organs
• Host control is through cell-mediated immunity
Clinical course
• Outcomes of Primary Infection
• Chronic pulmonary coccidiomycosis
• 5% of cases
• May smolder over years
• Nodules may cavitate and fibrose and destroy lung
• Occasionally requires pulmonary resection resection
• Disseminated disease
• All regions of body except GI
• Mortality high
• CNS
• Life long therapy
• Outcomes of Primary Infection
• Uneventful healing-May take weeks
• Progressive or persistent pneumonia
• Usually in immunocompromised
• Infiltrates are present for months and progress to cavitation
• Coccidioidoma
• Benign mass-like lesion (positive PET scan)
• Clinical Manifestations
• Primary pulmonary infection
• Asymptomatic
• Resembles community acquired pneumonia or influenza
• Fever, cough, pulmonary infiltrates
• In AZ, accounts for one third of community
acquired pneumonia
• Often called Valley Fever
• Extrapulmonary Symptoms
• Arthralgias (“desert rheumatism”)
• Erythema nodosum
• Most symptomatic cases resolve spontaneously
Diagnosis
• Culture
• Most definitive for diagnosis (one week to grow and ID)
• Histopathologic findings
• Methenamine silver, PAS
• Spherules with endospores
• Immunologic
• Complement fixation
• 1:16 or > worsening disease
• Immunodiffusion
• ELISA, IgG, IgM (sensitive and specific)
Treatment
• Therapy-For progressive disease
• Amphotericin B
• Primary disease
• CNS involvement
• Azoles
• Itraconazole
• Fluconazole
• Primary disease
• Voriconazole
• Posaconazole
Blastomycosis Pathogenic Dimorphic Fungi
Epidemiology
• Endemic in South Central and North Central USA
• Wisconsin, Minnesota, Southern Ontario, Manitoba, Alberta
• Natural habitat
• Soil, decaying wood
• Large outbreak in beaver pond
• Exposure to water, whether by recreation (outdoorsmen) or occupation
(excavators)
Pathogenesis
• Acquired through inhalation of mold form into alveoli
• Changes to yeast form in lungs and multiplies
• Disseminates hematogenously before immunity develops
• Immunity
• Neutrophils
• Cell mediated immunity with T cells, macrophages
Clinical course
• Pulmonary Infection
• Asymptomatic
• Sub-acute, chronic pneumonia
• Fever, night sweats, fatigue, productive cough, dyspnea
• Acute pneumonia
• Atypical presentation without response to antibiotics
• Overwhelming severe infection
• ARDS
• Cutaneous Disease
• Well circumscribed, nonpainful papules, nodules, plaques
[cutaneous]
• May be verrucous with microabscess
• Often ulcerate
• May be confused with:
• squamous cell cancer
• atypical pyoderma
• gangrenosum or nontuberculous mycobacterial
lesions
• Disseminated disease
• Prostatitis
• Septic arthritis
• Osteomyelitis
Diagnosis
• Growth of organism from tissue biopsy, sputum, or body fluid is definitive
• Histopathology from tissue biopsy
• Early diagnosis
• Yeasts are large, thick-walled, and buds single and broad based
• Stain with methenamine silver or PAS
• Serology
• Antibody tests not sensitive or specific
• Urine antigen is available
Treatment
• Mild to moderate disease
• Azoles
• Itraconazole preferred
• Fluconazole higher dose 800 mg q.d.
• Severe disseminated disease
• Amphotericin B
Aspergillosis Opportunistic fungi; immunocompromise + neutropenia
Epidemiology
• Aspergillus species is ubiquitous in the environment, both soil and air
• Exposure is inhalation of spores which, upon reaching tissue, germinate to form invasive
hyphal filaments
• Illness develops in immunocompromised patients
• Highest Risk
o Allogeneic Hematopoetic Stem Cell Transplant (HSCT)
o Hematologic malignancies and neutropenia***
• Lower risk
o Autologous HSCT
o Solid organ transplant
o HIV
o Prolonged steroids
Clinical course
• Invasive
• Bronchopneumonia
• Necrotizing tracheobronchitis
• Invasive sinusitis
• Chronic necrotizing aspergillosis
• Aspergilloma
• Disseminated aspergillosis (most common CNS)
• Clinical Manifestation
Halo sign o Invasive pulmonary disease
 Fever, cough, pleuritic pain, hemoptysis
o Invasive sinus disease
 Headache, stuffiness, fever, epistaxis
 Cranial nerve palsies resulting from cavernous
sinus thrombosis

• Allergic
• Allergic bronchopulmonary aspergillosis
• Allergic aspergillus sinusitis
• Extrinsic allergic alveolitis
Diagnosis
• Cultures
• Positive culture interpreted with risk factors
• Significant in hematologic malignancies, neutropenia, HSCT
• Histology
• Dichotomous acute-angle branching hyphae
• Serology
• Galactomannan assay (a heteropolysaccharide biomarker)
• Radiology
• CT scan (ground-glass attenuation surrounding a pulmonary nodule “Halo sign”)
Treatment
• Amphotericin B
• Azoles
• Itraconazole
• Voriconazole – drug of choice in adults
• Posaconazole
• Echinocandins
• Caspofungin
• Micafungin
• Combination Therapy
Cryptococcus Opportunistic Fungi
Epidemiology
• General
• World wide – usually in excreta of birds (pigeons)
• Species
• Cryptococcus neoformans var. grubii (immunosuppressed)
• Cryptococcus var. gatti (immunocompetent)
• Tropical regions, outbreak Pacific Northwest
• Immunity
• Cell mediated
• Th1 response
• Production of TNF, IFN, IL2
• Predisposing Factors
• HIV infection
• Corticosteroids
• Solid organ transplant
• Hematologic malignancies
• Connective tissue diseases
• Sarcoid, SLE, RA
• Tumor Necrosis Factor Inhibitors
Clinical course
• Common
• Respiratory
• CNS
 Usually immunocompromised patient
 Headache
 Nuchal rigidity
 Lethargy
 Confusion
 Fever only in 50%

• Rare
• Prostate
• Skin
• Bone
• Urinary tract
• Blood
• Asymptomatic
• Symptomatic Respiratory Infection
• Fever
• Nonproductive cough
• Chest pain
• Weight loss
• Acute respiratory failure

Diagnosis
• Direct exam of specimens
• Round encapsulated yeast cells (5 – 20 mm)
• Histopathology
• Pulmonary nodules, lung tissue
• Silver stain
• Culture: Takes several days
• Serology
• Serum Cryptococcal antigen (CRAG)
• Very sensitive in AIDS patients
• Less sensitive in competent patients with localized
respiratory infection
• Cryptococcal antibody
• False positive with blastomycosis, histoplasmosis

Pulmonary treatment
• Asymptomatic with positive respiratory secretions
• Observe vs. therapy
• Immunocompromised or symptomatic
• Fluconazole
• Itraconazole
• Amphotericin B
• Severe immunocompromised with symptoms
• Amphotericin B plus flucytosine for 2 weeks, then fluconazole
for 10 weeks
Neurological treatment
• Induction: Amphotericin B and Flucytosine
• Consolidation/Maintenance: Fluconazole
• Dosage and Duration-Depends on HIV status
Nontuberculous Mycobacteria Atypical Mycobacterium (mycobavcterium avium complex, M. Kanasaii, M. Abcessus
• Ubiquitous in soil and water
Risk factors
• HIV with low CD4 (<50)
• Incidence now less with HAART
• Genetic mutations affecting synthesis of interferon and interleukin
• Tumor Necrosis Factor Inhibitors
• Used in RA, Crohn’s disease, Ulcerative Colitis
Clinical course
• Pulmonary
• Symptoms are similar to TB – hemoptysis, cough, cavitary lung disease
• Cervical Lymphadenopathy
• Skin/Soft Tissue
• Disseminated disease
Diagnosis
• Suggestive but not diagnostic
• Positive PPD
• Positive AFB smears
• Chest x-ray is similar to TB, nodules, cavitation
• Do bronchoscopy and do a DNA probe ****** to see if it is atypical mycobacterium or TV
• Method 1
• Pulmonary symptoms, nodular or cavitary opacities on chest radiograph, or
a high-resolution computed tomography scan that shows multifocal
bronchiectasis with multiple small nodules
• Exclusion of other diagnoses
• Method 2
• At least 2 positive cultures from sputum
• OR positive culture result from at least one bronchial wash or lavage
• OR lung biopsy with mycobacterial histopathologic features
“Elderly frail female patient with a chronic cough and terminal bronchioles are filled with mucus“
Treatment
• Guidelines from the CDC, NIH, HIV Medicine Association and IDSA suggest that at least
two drugs should be used for the initial treatment
• Clarithromycin is the preferred first agent, since it has been studied more
extensively than azithromycin.
• Ethambutol is the recommended second drug.
• Some clinicians may consider adding rifabutin as a third drug due
Prophylaxis
• In HIV infected patients, begin prophylaxis when CD4 is less than 50:
• Azithromycin 1200 mg weekly (preferred)
• Can block potassium channels  increased QT interval
• Clarithromycin 1000 mg daily
• Rifabutin 300 mg daily
Lecture 14: Lung Cancer

The clinical presentation of lung cancer Small Cell Lung Cancer (Central)
 Chronic cough  Smokers and uranium miners are at high risk
 Chest pain  Associated with many paraneoplastic syndromes
 SOB o SIADH
 Hemoptysis o ACTH productions
 Weight loss o Myasthenic Syndrome [Eaton Lambert Syndrome]
 Fatigue  Occurs in 15-20% of lung cancer cases
 Surgical tx is NOT an option
 Tx:
Cough o Radiotherapy
 Cough that is generally dry or non-productive o Chemotherapy
 Progressively worsens over time
o Just occasional at first then occurs more
often as time passes
 An irritating cough that just keeps coming
 The cough with cancer is often called “persistent”
 There is a multitude of causes of cough in a cancer patient
Chest pain
 The chest pain with cancer patients tends to be constant
and progressive
 Cancer pain is usually in chest or lumbar spine
 Not an early sign of lung cancer,
o More likely found in late disease
Shortness of Breath
 Usually an early symptom in lung cancer Non-Small Cell Lung Cancer
 Between 50-70% of the patients with lung cancer
experience dyspnea 1. Squamous Cell Carcinoma (central)
 Around 90% of patients with advanced disease have SOB a. Symptoms appear early in the disease course
Hemoptysis b. Hilar mass arising from bronchus
 Usually mild in cancer c. Smoking is a risk factor
 It is caused by erosion of small mucosal vessels d. Hemoptysis
o Bronchial erosion e. Cavitation is present in about 35% of the time
Weight loss/cancer cachexia f. Proximal mass 66%, peripheral 33%
 The weight loss is progressive g. Parathyroid-like activity (PTHrP)
 In starvation, the weight loss is from using fat stores as i. Associated with hypercalcemia
fuel h. Treatment and evaluation
 In cancer cachexia, the weight loss is primarily from i. Bronchoscopy is an important test for dx and possibly tx
reduction of skeletal muscle mass ii. Treatment involves resection with radiation and chemotherapy
Fatigue 2. Large Cell Carcinoma
a. Large, rapidly growing malignancy
 Fatigue in cancer patients is multifaceted.
b. LEAST COMMON
 Caused by things like anemia, pain, depression, sleep
c. Clubbing is present 25% of the time
problems, medicines, nutrition, and nutritional deficits.
d. HOA is common
 Cancer can cause fatigue by producing toxic substances
e. The tumor is regarded as UNDIFFERENTIATED
that change the way the cells of the body work
f. Prognosis is usually poor
g. Not as responsive to chemotherapy
i. Often removed surgically
Cancer staging: 3. Adenocarcinoma (peripheral)
 Lung cancer uses the TNM classification scale, which a. Usually a solitary peripheral nodule
denotes several characteristics. Larger numbers mean the b. Sputum cytology not often helpful
tumor is more advanced c. Hypertrophic osteoarthropathy (HOA) is more common that it is in a squamous
 The more common staging scale uses Roman numerals cell carcinoma
i. Periosteal bone formation
ii. Clubbing
iii. Symmetrical arthralgias
d. Symptoms present late in the disease and when they occurs, they represent
advanced disease [bad prognosis]
e. The most common type of lung cancer in NON-SMOKERS**

Carcinoid Tumor*****
 Usually a young adult with cough and hemoptysis
 Can cause production of
o ACTH  Cushing and HTN
o PTH  hypercalcemi
 Secretes serotonin
 This can cause “carcinoid” or serotonin syndrome
o Diarrhea
o Flushing
o Salivation
o Wheezing
 Can damage right side heart

Mesothelioma
 Malignancy of pleura caused by chronic asbestos exposure
 Pleural thickening*
 Bloody pleural effusions*
Paraneoplastic Syndromes Pancoast Tumor
 A set of symptoms caused by an immune response to a malignancy or the body’s response to  A cause of shoulder pain **
chemicals produced by a malignancy  A tumor that is found in the apex of the lung
 Primary lung cancer is the most common cause of paraneoplastic syndromes  Can block the cervical sympathetic plexus causing Horner’s Syndrome
o Ptosis
o Miosis
o Anhidrosis
 Can cause superior subclavian syndrome

Solitary Pulmonary Nodule*****

 Single well defined, round or oval lesion found on chest radiograph that is <3cm and
surrounded by lung parenchyma
o 60% benign
 Granulomatous secondary to old fungal or TB infection
o 40% malignant
 Bronchogenic carcinoma
o >3cm, 90% malignant
 The patient is almost always asymptomatic
 It is usually an unexpected finding on a chest radiograph
Key History Features
 Age
 Smoking
 Occupational exposure
 Hx of cancer
 Travel hx
 Living in the endemic area
o Mississippi and Ohio river valley
 Histoplasmosis
 Blastomycosis
o Southwestern US
 Coccidioidomycosis