Week 7 (Genetic, Malignant, and Environmental Lung Disease) Flashcards
Mortality of lung cancer
Case fatality rate >90%
Overall 5 year survival <15%
More deaths anually than colon, breast, prostate and pancreatic cancer combined!
Rates declining in men but may be reaching plateau in women
Etiology of lung cancer
Cigarette smoking causes 87% of lung cancer
Second hand smoke
Radon
Occupational exposures: asbestos, uranium, arsenic, nickel radiation, chromium, chloromethyl ether, vinyl chloride
Asbestos and smoking multiply risk of lung cancer 10+ fold
Lung cancer and tobacco risk ratio (RR)
- 5 PPD = 15%
- 5-1 PPD = 17%
1-2 PPD = 42%
>2 PPD = 64%
Cigar = 3%
Pipe = 8%
Marijuana conflicting data
Second hand smoke = 1-2%
Risk factors for lung cancer other than tobacco
Pre-existing lung disease (COPD)
Previous tobacco-related cancer (ENT)
Interstitial fibrosis?
Nutrition?
Hypothesis of field cancerization
Exposure of respiratory tract to carcinogens (smoke) induces abnormalities in multiple areas with eventual development of carcinoma
Synchronous or metachronous cancer lesions in up to 14% of patients
Second primary cancers in 3-5% of patients/year
Does having another aerodigestive tract malignancy influence chance of getting lung cancer?
As many as 35% of patients with head and neck squamous cell carcinoma develop lung cancer
Similar risk in patients with esophageal cancers
Lung cancer evolutionary model
Pluripotent epithelial stem cell –> reserve cell, mucous cell, Clara cell, type II pneumocyte
Exposure to carcinogens (tobacco smoke) –> DNA damage
Diversion to premalignant and malignant conditions
Mucosal changes indistinguishable prior to transformation to malignancy
Growth promoted by cytokines and oncogenes
Functional classification of lung cancer
Non-small cell carcinoma: surgical resection for cure
Small cell carcinoma: not curable; can’t surgically resect but do chemotherapy
Carcinoid: typically slower growing; malignant potential related to local effects
Metastatic carcinoma: rare resectable lesion
WHO classification of lung cancer
Epithelial: benign (papillomas, adenomas), pre-invasive (carcinoma in situ), malignant (squamous cell, adenocarcinoma, large cell, small cell, sarcomatoid, carcinoid, salivary gland and unclasified)
Soft tissue (fibrous tumors)
Mesothelial (benign and malignant)
Miscellaneous (hamartoma, thymoma)
Lymphoproliferative
Other (unclassified, tumor-like)
IASLC/ATS/ERS lung adenocarcinoma
Preinvasive lesions
Minimally invasive adenocarcinoma
Invasive adenocarcinoma
Variants of invasive adenocarcinoma
Lung cancer based on location and appearance on radiograph
Central: squamous cell, small cell carcinoma
Peripheral: adenocarcinoma, large cell carcinoma
Cavitating: squamous cell carcinoma, occasionally large cell carcinoma
Superior sulcus tumors: more frequently squamous cell, also adenocarcinoma
Solitary pulmonary nodule: all cell types, less likely small cell carcinoma
How often is lung cancer asymptomatic?
Only 5% of the time
Solitary pulmonary nodule: if in high risk patient then suspect malignancy
Lack of growth over 2 years suggests benign (doubling of volume = 1.26 x diameter)
Can do serial scans, biopsy or resect
Patterns of appearance of solitary pulmonary nodule
Size: most not seen until 5-7 mm on chest x-ray
Spiculation and ill-defined margins suggests malignancy
Calcifications (central, ring, popcorn) suggest benign (but eccentric (off to the side) calcifications in lung cancer)
Mass lesions (>3cm) more likely malignant
Other findings in malignancy: pleural effusion, hemidiaphragm elevation, mediastinal adenopathy, rib or bony destruction, volume loss
Benign and malignant causes of solitary pulmonary nodule
Benign: infectious granuloma (cocci, histo, TB), infection, abscess, hamartoma, Wegner’s/GPA, rheumatoid nodule, pulmonary infarction, bronchogenic cyst, pneumonia, amyloidoma
Malignant: bronchogenic cancer (adenocarcinoma, squamous cell, large cell, small cell), metastatic cancer, bronchial carcinoid, pulmonary sarcoma
Clinical presentation of lung cancer
Asymptomatic (5%)
Symptoms related to site and extent of tumor
Invasion or obstruction of local structures: pain (chest, shoulder, radiculopathy), hoarseness, Horner’s syndrome (ptosis, miosis, anhydrosis), SVC syndrome, dyspnea, cough, hemoptysis, pleural effusions, diaphragm paralysis
Metastases to distant sites (adrenal, bone, brain, liver)
Paraneoplastic effects (SIADH, hypercalcemia, ACTH, Eaton-Lambert syndrome)
Features of progressive disease in lung cancer
Intrathoracic spread: tracheal obstruction, dysphagia, recurrent laryngeal nerve (hoareness), phrenic nerve (elevated hemidiaphragm), SVC syndrome, Horner’s syndrome, superior sulcus tumor, pericardial effusion, lymphatic obstruction, pleural effusion
Extrathoracic spread: lymph nodes (supraclavicular), brain, liver, adrenal, spinal cord, bone (contiguous and distant), subcutaneous
Paraneoplastic syndromes in lung cancer
Systemic: anorexia, cachexia, dermatomyositis, polymyositis
Endocrine: hypercalcemia, hyponatremia (SIADH), ACTH production
Neurologic: Lambert-Eaton syndrome (myasthenia), peripheral neuropathy
Cutaneous: clubbing, HPO, acanthosis nigrans
Hematologic: anemia, dysproteinemia
Renal: nephrotic syndrome, glomerulonephritis
Hypercalcemia in lung cancer
Ectopic hormone, bony metastases, immobility
Most commonly associated with squamous cell carcinoma
Bony metastases more common in adenocarcinoma and small cell carcinoma but hypercalcemia is rare
PTHrP (parathyroid hormone-related peptide) is ectopically produced by squamous cell carcinoma; binds PTH receptor to increase Ca2+ mobilization; PGE2 and IL-1 may be involved; clinical manifestations are weakness, lethargy, confusion, polyuria, renal failure
SIADH in lung cancer
Related to ectopic production of ADH usually by small cell lung cancer cells
Hyponatremia hallmark of presentation
Inappropriate ADH is when serum osmolality is low (<280 mOsm/kg) and don’t need to retain water; urine Na+ is >20 mEq/L
About 11% of small cell lung cancer patients have clinical hyponatremia
ANP is also secreted and can cause hyponatremia, and in this case ADH will be normal
Obtaining tissue for diagnosis in lung cancer
Sputum for cytology
Bronchoscopy: washings, bruchings, biopsies, needle aspiration
Transthoracic needle biopsy
Thoracentesis/pleural biopsy
Mediastinoscopy
Operative specimens (open lung biopsy)
Others: soft tissue mass, bone lesions, bone marrow, lymph node
Key issues in managing lung cancer
Establish diagnosis (benign vs. malignant)
Identify tissue (small cell vs. non-small cell)
Determine stage (clinical vs. pathologic)
Determine if candidate for surgical resection
Evaluate non-surgical treatment options
Role of screening for lung cancer
Early stage disease characteristics key to survival
Primary tumor localized without invasion of vertebrae or great vessels
Tumor >2cm from carina
Nodal spread limited to hilar nodes
Mediastinal nodes limited to same side of tumor
Local extension acceptable as long as areas can be resected (ribs, chest wall, etc)
Pleural effusions acceptable if non-malignant (inflammatory)
TNM staging of lung cancer
T: tumor size; confined to lung or spread to local structures
N: nodes involved; N1 is hilar or lobar; N2 is mediastinal; N3a?is ipsilateral; N3b? is extra-thoracic
M: metastasis
Are metastatic lung cancer patients ever operable?
Patients with single solitary brain met and localized primary tumor are operable
All other metastases are inoperable
Treatment for non-small cell lung cancer
Stage I and II: surgery
Stage IIIA: surgery on select cases; chemo (adjuvant or neoadjuvant); cisplatin or carboplatin based
Stage IIIB and IV: palliative (radiation, stereotactic body radiation therapy (SBRT), chemo, thoracentesis/pleurodesis, laser therapy; bronchial stents)
EGFR-TKI
Epidermal growth factor receptor-tyrosine kinase inhibitor
Binding of TK domain produces a signal transduction cascade –> tumor growth and proliferation
Monoclonal antibodies compete with binding and therefore block signals for tumor proliferation, invasion, metastasis, angiogenesis, inhibition of apoptosis
Imatinib (Gleevac); gefitinib (Iressa), cetuximab (Erbitux), erlotinib (Tarceva)
Used alone or in conjunction with other chemotherapy
Greater response and survival with EGFR mutations treated with gefitinib and erlotinib (exon 18, 19, 21), worse (20)
Greater response in females, Asian, adenocarcinoma
Anaplastic lymphoma kinase (ALK)
Cell membrane protein involved in central and peripheral nervous systems
Present in childhood neuroblastoma, lymphoma, non-small cell lung cancer
Translocation results in fusion protein (ELM4-ALK) with activity in tyrosine kinase domain
In 3-7% of non-small cell lung cancer but in 13% of light or non-smokers
No overlap in patients with EGFR mutations
Typically adenocarcinoma, younger, male, light or non-smoker
Target therapy with crizotinib (Xalkori) effective in 60%
Limited vs. extensive small cell lung cancer (staging)
Limited (30% at presentation): primary tumor confined to hemithorax and/or mediastinum; disease confined to single radiation port; equivalent to stages I-IIIA of non-small cell carcinoma (pleural and pericardial disease not considered limited disease)
Extensive (70% at presentation): metastases to contralateral lung; distant metastases (brain, bone marrow, liver, adrenals); usually with some response to chemo and/or radiation
New staging to change to stage I-III classification
Treatment of small cell carcinoma
Surgery: usually not recommended because likely micrometastatic disease and rapid growth; rare solitary lesion amenable to resection
Chemo: always; 15-20 agents; etoposide and cisplatin most active
Radiation: improves local control from 10-60%; improved survival; prophylactic cranial radiation after chemo response
Survival in small cell carcinoma
Untreated: 6-17 weeks
Treated: 40-70 weeks; <1% at 5 years
Limited disease: 14-20 months; 20-40% at 3 years
Extensive disease: 8-13 months; <5% at 3 years
Recommendations for lung cancer screening
Middle aged (55-74 yo)
>/= 30 pack year current smokers or have quit within the past 15 years
Current smokers encouraged on smoking cessation
General good health without signs or symptoms of lung cancer
Pleural fluid formation and drainage
Lymphatic stomata insert directly into parietal pleura
Subpleural lymphatics adjacent to visceral pleura
Fluid enters pleural space through parietal pleura via Starling’s forces and drained through visceral pleura
Proteins, particles, cells drained via lymphatic stomata in parietal pleura
0.5-1L absorbed and reabsorbed from pleural space each day
Normal pleural fluid characteristics
pH > 7.6
WBC < 1500 nucleated cells/mm3 (75% macrophages, 23% lymphocytes, 1% mesothelial cells, no eosinophils)
Protein is 15% of plasma levels (1-1.5 g/dL)
Glucose = plasma levels
Transudate vs. exudate
Transudate (bland fluid): increase in hydrostatic pressure = CHF; decrease in colloid oncotic pressure = anasarca albumin or nephrotic syndrome; increased negative pressure in pleural space = atelectasis; increased transport of peritoneal fluid through diaphragm = ascites, peritoneal dialysis
Exudate (turbid fluid): results from pleural inflammation, lung inflammation (increased capillary permeability = inflammation), impaired lymphatic drainage = malignancy
Most common causes of transudate: CHF, cirrhosis, PE
Most common causes of exudate: pneumonia, cancer, PE
Formation of pneumothorax (PTX)
Breach of pleural space (trauma to parietal or visceral pleura)
Air collects within pleural cavity
Pleural pressure equilibrates with atmospheric pressure
Air slowly resorbs through vasculature
Tension pneumothorax: one way air valve is created so on inspiration, air enters one hemithorax from tear in lung or hole in chest wall and does not exit on expiration; pleural pressure exceeds atmospheric pressure during entire respiratory cycle
Presentation of pleural effusion
Blunting of costophrenic angle
Meniscus sign
Contralateral displacement of trachea and mediastinum
Free flowing vs. loculated
Presentation of pneumothorax
Loss of lung markings
Pleural reflection
Deep sulcus sign in supine patient
Tension PTX has contralateral displacement of trachea and mediastinum
Thoracentesis
Tap effusion when significant amount of fluid (>10mm on decubitus film or significant fluid on US) AND unknown diagnosis; OR when respiratory compromise
Insert thoracentesis needle above the rib because artery, nerve and vein run below the rib
Removal of more than 1-1.5L at a time may lead to re-expansion edema
Light’s criteria for exudate
Pleural/serum protein >0.5
Pleural/serum LDH >0.6
Pleural LDH > 2/3 of institution normal
Need to fulfill only 1 criteria
Where do we see the transudate in different types of pleural effusion?
CHF: bilateral R >> L
Cirrhosis and peritoneal dialysis: R side
Nephrotic syndrome, hypoalbuminemic states: bilateral with diffuse edema
Unusual transudate from over-diuresed CHF
Pleural/serum protein > 0.5
Pleural/serum LDH < 0.6
Pleural LDH < 2/3 of institution normal
Transudate if: serum-pleural albumin ratio > 1.2
Exudates masquerading as transudates (unusual transudate)
Hypothyroidism
Heart disease, ascites
PE
23% transudative due to atelectasis
Malignancy
Early lymphatic obstruction, concomitant CHF
Sarcoidosis
All causes of exudate
Infectious
Malignant
Inflammatory: connective tissue disease
PE
Pancreatitis
Postcardiotomy syndrome
Drug induced
Esophageal rupture
Subdiaphragmatic abscess
Hypothyroidism
Additional studies to evaluate an exudate in pleural effusion
Cell count and diff
pH
Glucose
Culture and sensitivity
Cytology
Hct
Amylase
Adenosine deaminase
Triglycerides
Cell count and diff for pleural effusion
Neutrophilic “acute process”: pneumonia, PE, pancreatitis
Lymphocytic: malignant, TB, fungal, chylothorax
Eosinophilic: blood, air, drug reaction (dantrolene, bromocriptine, nitrofurantoin), asbestos exposure, paragonimiasis, Churg-Strauss syndrome
Bloody: Hct 1-20% (cancer, PE, trauma), Hct > 50% of peripheral Hct (hemothorax)
Triglycerides in pleural effusion
TG >/= 110
Chylothorax: milky white fluid, chylomicrons, due to disruption of thoracic duct (iatrogenic, lymphoma), unilateral
pH and glucose in pleura effusion
Empyema: pH 5.5-7.29, glucose <40
Esophageal rupture: pH 5.5-7, glucose <60
Rheumatoid pleuritis: pH 7, glucose 0-30
Malignancy: pH 6.95-7.29, glucose 30-59
TB: pH 7-7.29, glucose 30-59
Lupus pleuritis: pH 7-7.29, glucose 30-59
Amylase in pleural effusion
Pancreatis/pancreatic pseudocyst: pancreatic amylase
Carcinoma lung: salivary amylase
Adenocarcinoma ovary: salivary amylase
Lymphoma: macroamylase/salivary amylase
Esophageal rupture: salivary amylase
Pneumonia: salivary amylase
Ruptured ectopic pregnancy: prob salivary amylase
Adenosine deaminase in pleural effusion
Elevated levels in TB pleurisy, empyema, rheumatoid pleurisy, malignancy
Normal level is highly specific for absence of TB
Parapneumonic effusions
Simple: 40-57% of patients with pneumonia will develop a simple effusion; pH > 7.2; LDH < 1000; Glucose >/= 0.5 of plasma level
Complicated: 10-15% of patients with pneumonia will develop a complicated effusion; pH < 7.2; LDH > 1000; >1/2 hemithorax; glucose <0.5 of serum level; loculations
Empyema: 5% of patients with pneumonia will develop an empyema; gram stain or culture positive; frank pus
Treatment for parapneumonic effusion
Antibiotics
Simple: no drainage, re-tap if patient is not doing well
Complicated: complete drainage (thoracentesis; chest tube +/- fibrinolytics via chest tube; VATS/decortication)
Empyema: chest tube +/- fibrinolytics via chest tube; VATS/decortication
Malignant pleural effusion
Approximately 60% of malignant effusions can be diagnosed by cytology
Increased diagnostic yield with repeat thoracentesis: 65% diagnosed with first cytology; another 27% diagnosed with second cytology (however ONLY another 5% diagnosed with third cytology, so don’t do 3)
If suspect malignant effusion, do closed pleural biopsy (dx additional 7% of malignant disease when used in addition to cytology); video assisted thoracoscopic surgery (VATS) has 90% overall diagnosis rate
Treatment: observation, therapeutic thoracentesis, chest tube insertion with intrapleural sclerosant, thoracoscopy with talc poudrage (put talc in pleural space), long term indwelling catheter drainage, pleuroperitoneal shunt, pleurectomy
Note: sclerosis causes inflammation of the pleural tissue and adherence of the visceral pleura to the parietal pleura; need to re-expand lung and have apposition of pleural surfaces prior to sclerosis
Pneumothorax
Spontaneous primary: no clinically evident lung disease, no trauma or iatrogenic cause, usually subpleural apical blebs
Spontaneous secondary: due to underlying lung disease
Iatrogenic: direct trauma to visceral or parietal pleura
Traumatic
Spontaneous pneumothorax: primary
Young thin male 10-30 years old
Smoking increases risk 20 fold
Chest imaging with subpleural blebs
R/o connective tissue disease (Marfans)
Risk of recurrence 30% after first incidence, 60% after second, 90% after third
Spontaneous pneumothorax: secondary
Airways disease: COPD, CF, status asthmaticus
Interstitial lung disease: eosinophilic granulomatosis, sarcoidosis, LAM, tuberous sclerosis, rheumatoid lung disease, IPF, radiation fibrosis
Infectious disease: PCP PNA, staphylococcal PNA, necrotizing gram negative PNA
Other: ARDS barotrauma, Marfans, EDS
Iatrogenic pneumothorax
Central line insertion: neck/subclavian
Transbronchial lung biopsy
Transthoracic lung biopsy
Mechanical ventilation
Treatment for primary spontaneous pneumothorax
First occurence:
Stable patient with small PTX (<3cm apex to cupola) –> observation in ED 3-6 hours; if no change d/c with f/u in 12-48 hours
Stable patient with large PTX (>/= 3cm apex to cupola) –> re-expand lung, hospitalization preferable but can d/c home with Heimlich valve
Unstable patient with large PTX –> re-expand lung and hospitalize patient
Consider sclerosis if activities include high risk if PTX recurred (pilot, scuba diver), persistent air leak
Second occurrence: sclerosis recommended
VATS preferred intervention for sclerosis: 95-100% success via VATS compared with 78-91% success with chest tube instillation; VATS bullectomy to remove apical bullae
Treatment for secondary spontaneous pneumothorax
Stable patient with small PTX (<3cm apex to cupola) –> hospitalize +/- re-expansion of lung
Stable patient with large PTX (>/= 3cm apex to cupola) –> re-expand lung and hospitalize patient
Unstable patient with large PTX –> re-expand lung and hospitalize patient
Proceed with VATS pleurodesis +/- bullectomy as needed
Pneumonia
Inflammation of the lung parenchyma (pneumonitis) secondary to infection
Most common cause of infectious death in US
Overall mortality rate for community-acquired bacterial pneumonia 14%
Host defenses against pneumonia
Mucocilliary covering in conducting airways
Immunoglobulin A in mucosal secretions
Macrophages in respiratory parenchyma can phagocytize microorganisms and if overwhelmed recruit neutrophils from capillaries
Consolidation
Filling of alveoli with neutrophil-rich exudate
Bronchopneumonia vs. lobar pneumonia
Bronchopneumonia: pattern of consolidation typically involves more than one lobe with bronchiolocentric distribution (patchy)
Lobar pneumonia: uncommon due to availability of antibiotics
Clues on history for pneumonia
Cough in more than 90% of patients
Dyspnea in 66% of patients
Sputum production in 66% of patients
Pleuritic chest pain in 50% of patients
Fever
Malaise
Elderly patients may have few symptoms
Physical exam in pneumonia
Inspiratory crackles is most sensitive finding with any type of pneumonia
Increased tactile fremitus over consolidated lobe
Dull percussion over consolidated lobe
Bronchovesicular, egophony, whispered pectoriloquy over consolidated lobe
Chest radiography for pneumonia
All definitions of pneumonia include visualizing an infiltrate on a radiograph
Limited value in predicting the pathogen
Great value in determining extent of pneumonia and detecting complications like parapneumonic effusions or lung abscesses
Pneumonia syndromes
1) Community acquired acute pneumonia
2) Community acquired atypical pneumonia
3) Healthcare associated pneumonia
4) Aspiration pneumonia
5) Chronic pneumonia
6) Necrotizing pneumonia and lung abscess
7) Pneumonia in the immunocompromised host
Community acquired pneumonia (CAP)
Infectious pneumonia that develops in a patient who is not hospitalized or who has been hospitalized for less than 48 hours and has not been admitted to a hospital or extended health care facility in the past 90 days
Common pathogens: Strep pneumo, H influenzae, Moraxella catarrhalis, Staph aureus, Leigonella pneumophilia, Klebsiella pneumoniae
Pneumococcus as prototypical community-acquired acute pneumonia
Strep pneumo most common cause of community-acquired pneumonia (15-25% of cases)
Most common cause of lobar pneumonia
Paired diplococci seen on sputum gram stain
Can cause “rust colored sputum”
Encapsulated organism: may disseminate quickly in asplenic patients
Staph aureus pneumonia
Typically causes bronchopneumonia with multiple abscesses
Risk factors are recent influenza infection, IVDU
Klebsiella pneumoniae pneumonia
Most common gram negative bacillus to cause bacterial pneumonia
Can cause bronchopneumonia, lobar pneumonia and/or lung abscess
Abrupt onset of symptoms
Cough productive of gelatinous currant jelly sputum
Risk factors are alcoholism, debilitation (cause aspiration), malnourishment
Legionella pneumophilia
Gram negative bacillus, lives in water
Responsible for 5% of community acquired pneumonias
Fatal in 15% of cases
Usually causes bronchopneumonia
Presents with high fever, GI symptoms (diarrhea, vomiting)
Patients commonly lethargic with headache
Lab findings: hyponatremia is common as are hematuria and proteinuria and indicators of hepatic dysfunction; sputum gram stain with many neutrophils but few if any microorganisms; positive urinary legionella antigen
Risk factors: old age, organ transplantation, chronic lung, heart, kidney disease and hematologic disease
Community acquired atypical pneumonia
Atypical symptoms: nonproductive cough, headache, myalgias, upper respiratory symptoms, walking pneumonia
Atypical physical exam, lab and radiographic findings: unremarkable physical exam, minimal leukocytosis, lack of lobar consolidation on CXR
Atypical (not pneumococcus) pathogens: bacteria that do not have a cell wall or intracellular bacteria; viruses
Atypical pathogens: mycoplasma pneumoniae, legionella, chlamydia pneumoniae, chlamydia psittaci, coxiella burnetti, (MLC) influenza A and B, parainfluenza virus (children), metapneumovirus, adenovirus, SARS virus
Mycoplasma pneumonia special features
Lacks cell wall so not visible on gram stain
Fewer than 10% of people infected develop lower respiratory tract symptoms
Most common in younger patients (school-aged children and college students)
Upper airway symptoms (rhinitis)
Notable for nonpulmonary features: erythema nodosum, erythema multiforme, neurologic abnormalities (meningitis, encephalitis, transverse myelitis, cranial nerve palsies, cerebellar ataxia), cold agglutinins occasionally with hemolysis
Influenza special features
Upper airway symptoms are cough, rhinorrhea and sore throat (viral damage to airways)
Systemic symptoms abrupt onset of fever and myalgia (caused by interferon production)
May cause lower airway infection (pneumonia) on its own: much less common than upper airway infection
Damage to lung epithelial layer also leads to risk of secondary infections (commonly pneumococcus and Staph aureus)
Most common CAP pathogens
Outpatient: strep pneumo, mycoplasma pneumoniae, H influenzae, respiratory viruses
Inpatient (non-ICU): strep pneumo, mycoplasma pneumoniae, chlamydia pneumoniae, H influenzae, Legionella, aspiration (of mixed oropharyngeal flora), respiratory viruses
Inpatient (ICU): strep pneumo, Legionella, staph aureus, gram negative bacilli, H influenzae
Initial workup for pneumonia
PA and lateral CXR
Blood cultures prior to antibiotics (3-14% will be positive in setting of CAP): quality measure tracked by medicare
Possible urine antigen testing for Legionella and Strep pneumo
Sputum culture: optional given that its useful only 14% of the time
CBC and complete metabolic panel
Thoracentesis should be done if pleural effusion present
CURB-65 score
1 point for:
Confusion
BUN > 19
RR > 30
SBP < 90 or DBP < 60
Age 65 or above
Outpatient treatment of CAP
Macrolide antibiotic preferred if patient does not have significant comorbidities (azithromycin, clarithromycin)
Respiratory fluoroquinolone if patient has comorbidities (levofloxacin, moxifloxacin)
Duration of antibiotic treatment for CAP
By convention most physicians treat for 7-10 days
One study shows levofloxacin x 5 days is equivalent
Certain organisms (Staph aureus, Legionella) may need prolonged treatment
What if patient fails to improve on this medication regimen?
If patient not improving after 48 hours of treatment, consider pathogen reisstant to chosen antibiotics or spread of infection beyond the alveoli (complicated parapneumonic effusion, empyema, suppurative pericarditis)
Vaccines
Pneumococcal polysaccharide vaccine (Pneumovax 23): given once to adults >65 decreases risk of bacteremia and death in patients who get a pneumococcal pneumonia
Influenza: recommended yearly for everybody more than 6 years old
Smoking cessation counseling
Should be addressed before patient with CAP discharged from hospital
Medicare and medicaid quality measure
Quitting smoking reduces risk of pneumococcal disease by 14% each year thereafter
What can PPIs and NSAIDs do to contribute to pneumonia?
PPIs may be emerging risk factor for community-acquired bacterial pneumonia
NSAIDs are associated with blunted inflammatory response which can lead to delay in presentation and higher risk for pleuorpulmonary complications in patients with pneumonia
Healthcare-associated pneumonia (HCAP)
Includes hospital-acquired pneumonia (HAP or nosocomial pneumonia) and ventilator-associated pneumonia (VAP), and includes patients who have resided in extended care facility or hospital in previous 90 days and those receiving outpatient hemodialysis, chemo and wound care
Hospital-acquired pneumonia (HAP or nosocomial pneumonia)
Develops more than 48 hours after hospitalization
Ventilator-associated pneumonia (VAP)
Develops more than 48 hours after intubation
Preventing hospital-acquired pneumonias
Avoid endotracheal intubation (consider BiPAP in right settings)
Keep head of bed at 30-45 degrees
Maintain patient’s oral hygiene
Hand washing by all medical staff
Risk factors for multidrug resistant pathogens causing HAP or HCAP
Antimicrobial therapy in last 90 days
Current hospitalization for longer than 5 days
High-frequency of antibiotic resistance in the hospital or the community
Immunosuppressive disease or therapy
Residence in nursing facility
Family member with multidrug-resistant pathogen
Potential pathogens for HAP and HCAP
Standard pathogens: Strep pneumo, H influenzae, E coli, Proteus, serratia marcescens, klebsiella pneumonia, legionella pneumophilia
Multidrug resistant pathogens: pseudomonas aeruginosa, MRSA, klebsiella with extended-spectrum beta lactamase (ESBL) activity, acinetobacter
Empiric antibiotic therapy for patients with risk factors for multidrug resistant HAP or HCAP
Anti-psuedomonal cephalosporin (cefepime or ceftazidime) or anti-psuedomonal carbapenem (imipenem or meropenem) or beta lactam + beta lactamase inhibitor (piperacillin/tazobactam)
PLUS
Anti-pseudomonal fluoroquinolone (ciprofloxacin) or aminoglycoside (amikacin, gentamicin, tobramycin)
PLUS
Linezolid or vancomycin
HAP/HCAP duration of treatment
Can change broad-spectrum antibiotic therapy to more tailored regimen based on identification of responsible pathogen and deliniation of drug sensitivities
Treat common pathogens for at least 7 days and multidrug-resistant pathogens for at least 14 days
Where does aspirated material go?
If patient upright: usually basal segment of lower lobe (all the way down)
If patient supine: usually posterior segment of upper lobe or apical segment of lower lobe (not all the way down)
Why do you get night sweats and not during the day?
Lowest hypothalamic set point for temperature is late at night
Body wants to be cool in the middle of the night but you’re warm because of infection so get really sweaty to try to cool down more!
Coccidiodomycosis
Caused by inhaling spores of coccidioies immitis a dimorphic fungus found in the southwestern and far western US
Granulomatous pneumonia
Lung lesions, cough, pleuritic chest pain, fever, erythema nodosum or erythema multiforme = San Joaquin Valley Fever Complex
Disseminated disease can involve skin, bone and meninges
Histoplasmosis
Dimorphic fungus endemic to the Mississippi River Valley
Lives in soils enriched by bird or bat droppings
Like M tuberculosis an intracellular parasite of macrophages
Presentation can mimic that of TB
Blastomycosis
Blastomyces dermatitidis: soil-inhabiting dimorphic fungus
Pulmonary blastomycosis can present as an abrupt illness with productive cough, fever and upper lung involvement on CXR
Macrophages have limited ability to kill B dermatitidis, thus neutrophils are recruited (suppurative granulomatous inflammation)
Can cause epithelial hyperplasia that can be mistaken for cancer
Midwest and east coast
Broad based budding yeast
Actinomyces israelii
Gram positive, thin branching filamentous bacterium
Anaerobic, not acid fast (NO and NO!)
Colonies yellow and smell bad and look like sulfur granules
Risk factor is COPD
Causes chronic pneumonia
Necrotizing pneumonia and lung abscess common pathogens
Anaerobic bacteria
Staph aureus
Klebsiella pneumoniae
Strep pyogenes
Strep pneumo type 3 (only type of strep pneumo that cavitates!)
Special consideration for lung abscesses
10-15% of abscesses are related to carcinoma obstructing an airway (so look for proximal obstructive tumor)
Right-sided bacterial endocarditis can result in lung abscess (usually see multiple abscesses)
Treat with antibiotics until radiographic resolution (do NOT stick needle into abscess to drain it)
Pneumocystis pneumonia
Now is called pneumocystis jiroveci but used to be pneumocystis carinii (PCP)
Classified as fungus (but similar to protozoa)
AIDS, occurs when CD4 count <200
Presents with non-specific symptoms: subtle onset progressive dyspnea, nonproductive cough, low-grade fever
PE has tachypnea and tachycardia but normal lung sounds
Elevated serum LDH is non-specific (released by injured lung)
Bilateral perihilar interstitial infiltrates that becomes increasingly homogeneous and diffuse as disease progresses; less often see nodules, pneumatoceles or normal CXR
Diagnose with direct fluorescent antibody (DFA) testing of sputum induced with hypertonic saline
Treatment: TMP-SMX and corticosteroids at the same time (esp in patients with PaO2 <70 on room air or A-a gradient >35)! Want to reduce inflammation that is caused by treating PCP
Aspergillus
Angioinvasive molds that often induce thrombosis and infarction with subsequent suppuration
Hematogenous spread common with involvement of heart valves and brain
Often seen in transplant patients on corticosteroids or patients with hematologic malignancies
Often diagnosed with aspergillus EIA
Treated with voriconazole and by decreasing immunosuppressant medications
Halo sign: angioinvasive causes bleeding during invasion
Aspergilloma will NOT invade, but see air crescent sign on CXR
Nontuberculous mycobacterial infection
Ubiquitous mycobacteria found in water and soil
Opportunistic pathogens in patients with cell-mediated immunodeficiency or underlying structural bronchopulmonary disease
M avium and M intracellulare grouped together as M avium complex (MAC)
HIV infected patients can get both pulmonary disease and disseminated disease
Multiple cavitary or nodular opacities on imaging
Nocardia asteroides
Gram positive, branching filaments
Aerobic and partially acid fast (YES and YES!)
Causes indolent bronchopneumonia with abscess formation
1/5 of infections involve CNS
Most infected patients have defect in T cell-mediated immunity (prolonged steroid use, HIV, diabetes)
Treated with prolonged course of TMP-SMX
Key word associations
Rust colored sputum = pneumococcus
Currant jelly sputum = klebsiella
Alcoholic = klebsiella, aspiration pneumonitis
Seizure = aspiration pneumonitis
Lung and brain infection (indolent) = nocardia
Lung and brain infection (fulminant) = aspergillus
Putrid sputum = lung abscess (anaerobes)
Sulfur granules = actinomyces
Acid fast = M. tuberculosis, atypical mycobacterium, nocardia
Pneumonia with bullous myringitis = mycoplasma
Walking pneumonia = mycoplasma
Pneumonia with unusually high LDH = PCP pneumonia
Night sweats = TB
Pneumonia after earthquake = coccidiodomycosis
Poor dentition = anaerobes
Pneumonia on ventilator = MRSA, pseudomonas
Foreign born = TB (remember, BCG called “FOB vaccine”)
Cerebrovascular accident = aspiration pneumonia
Dementia = aspiration pneumonia
Diplococci = pneumococcus
Dysphagia = aspiration pneumonia
Coughing with eating = aspiration pneumonia
Sickle cell disease = functional asplenia, risk of sepsis with encapsulated organisms (SHiNE SKiS: strep pneumo, H influenza B, Neisseria meningitidis, E coli, Salmonella, Klebsiella, group B Strep)
Pneumonia with high fever, hyponatremia, and hematuria = legionella
Bird or bat droppings = histoplasmosis
Occupational lung diseases
Occupational lung diseases: any disorder of the lungs that results from extrinsic etiology related to the workplace
Lung must eliminate particles without excessive inflammation (but appropriately respond to infectious particles)
Often found incidentally on chest imaging and radiographic findings may be out of proportion to symptoms
May exacerbate pre-existing lung disease (increased deposition and decreased clearance of fibers)
Occupational asthma and asbestos-related diseases are most common in US
Pneumoconioses
“Dust diseases” due to accumulation of inorganic dusts within the lungs and the tissue reaction to their presence
Can be fibrotic or non-fibrotic
Examples: coal worker’s pneumoconiosis, asbestos, silicosis
Primary prevention is key because no treatment other than symptomatic (eliminate hazard, use ventilator, respirator)
Clues: clusters, young age, slower progression of ILD
Easily missed: 25% of “IPF” biopsies had mineral deposits and 6% of “sarcoidosis” patients had + beryllium lymphocyte proliferation test!
Classification of occupational lung diseases
Parenchymal/interstitial lung disease: pneumoconioses, hypersensitivity pneumonitis, drug-induced lung disease
Airway: occupational asthma, COPD, bronchiolitis obliterans
Physiology: high altitude/diving
Smoking, radiation, etc –> malignancies
Fibrogenic vs. low-fibrogenic pneumoconioses
Fibrogenic: silica (silicon dioxide), silicates (asbestos is lower and talc and kaolin are upper), coal dust, aluminum
Low-fibrogenic: deposits of iron, tin, barium, titanium, glass wool; granulomatous is beryllium
Silicosis
Inhalation of crystalline silica (quartz) found in sand and rock
Seen in hard rock/coal mining, construction, quarrying, masonry, sandblasting, foundry, glass workers, ceramics, granite, stonework
Silica generates O2 radicals and injures alveolar macrophages
Note: coal workers can get CWP and silicosis!
Three presentations of silicosis
Chronic simple silicosis: latency 10-30 years, low exposure with variable course; usually see upper lung zone nodular opacities, can be calcified, have enlarged LN with eggshell calcifications
Accelerated silicosis: develops within 10 years of initial exposure, associated with high-level exposure, more severe and often progressive, progressive massive fibrosis (PMF) refers to progressive coalescence of silicotic nodules leading to respiratory impairment
Acute silicoproteinosis or acute silicosis: exposure to high concentrations of silica, symptoms occur within a few weeks to a few years after initial exposure, poor prognosis (dyspnea, cyanosis, cor pulmonale, respiratory failure and death within 4 years); see bilateral alveolar filling process in both lower lobes
Complications of silicosis
Complicated silicosis or PMF
Increased risk of TB and non-TB mycobacterial disease, connective tissue disease, lung cancer, chronic bronchitis
Caplan’s syndrome is when you have RA and silicosis
Treatment is supportive, very rarely lung transplant
Coal workers’ pneumoconiosis (CWP)
Inhalation of coal dust
More prevalent in underground workers (higher concentration)
Alveolar macrophages engulf coal dust and release toxic proteases and cytokines leading to fibrosis and emphysema
Black lung
Also ask about loading ships with coal, manufacture of carbon electrodes and graphite mining
Simple, complicated and progressive massive fibrosis
Caplan’s syndrome is also RA plus CWP
Exposure risk for CWP and silicosis
Highest exposure risk is cutting machine operator that cuts coal directly
Roof bolters drill through rock (exposed to silica too); continuous mine operator, loading machine operator, shot firer
Train operators drop sand onto tracks for traction and may develop silicosis
Motormen, brakemen, drivers, shuttle car operators have less dust exposure because coal already been cut at this point
Mechanics, electricians and maintenance men have least amount of dust exposure
CXR findings in CWP
Upper zone predominant nodules
Can develop progressive massive fibrosis and emphysema
In complicated CWP, micronodules have coalesced to form PMF (person will die soon)
Simple pneumoconiosis vs PMF
Simple pneumoconiosis: usually no functional deficits
Progressive massive fibrosis (PMF): larger (>1cm) opacities, significant functional deficits
Workers with simple pneumoconiosis have much greater risk of getting PMF
Asbestos
Asbestos is a type of silicate (“magic mineral”) that is cheap, easy to mine and multiple applications
Two forms are serpentine (chrysotile/white >90%) and amphibole (crocidolite/blue, tremolite, etc)
Astestos fiber is critical in disease pathogenesis: released during mining, milling, fabrication, installation (<3 microns in diameter)
Jobs with asbestos exposure
Shipbuilding, repair or refitting (WWII vets)
Building fireproofing, maintenance, or demolition
Brake work
Construction
Thermal insulation
Plumbers, electricians, welders, present in many rocks
Additionally: launderers of asbestos workers’ clothes, living or working in buildings constructed in early post-WWII period, houses built between 1930-50 (in inuslation), textured paint and patching in ceiling/walls before 1977, hot water and steam pipe blankets and insulation in older homes, some vinyl floor tiles/backing
Forms of asbestos-related lung disease
Asbestos plaques
Diffuse pleural thickening
Asbestosis: pulmonary parenchymal fibrosis
Bronchogenic carcinoma
Malignant mesothelioma
Benign exudative or bloody pleural effusion
Anxiety
Pleural plaques in asbestos exposure
Detectable on CXR
Very common in asbestos-exposed workers (shipyard workers)
Plaques usually develop first
Does not predispose to lung cancer?
Asbestosis
Pulmonary parenchymal fibrosis
Clear dose response relationship
Latency period ranges 15-40 years
Dyspnea, cough, crackles, clubbing
Restrictive lung disease with diffusion impairment
Biospies not required for diagnosis
20-40% progress
Higher subsequent risk of lung cancer
Progression is slower (15-20 years) compared to IPF (2-3 years)
Imaging in asbestosis
Bilateral reticular/linear opacities at lung bases
Honeycombing (cysts pulled taut)
Usually have associated pleural disease/plaques
Usually basilar and subpleural distribution
If see pleural plaques with lung fibrosis, call it asbestosis!
Malignant mesothelioma
Rare malignancy of pleura or peritoneum very closely associated with asbestos and not affected by smoking
Occurs even with low levels of exposure especially with amphibole
Presents with large pleural effusion and dyspnea
Prognosis poor with limited treatment options (only live 1-1.5 years after this)
Bronchogenic carcinoma
Strong synergy between asbestos and tobacco (up to 40-60x increase in exposed smokers)
Asbestosis markedly increases risk of lung cancer and all histologic subtypes seen
Also linked to other malignancies
Occupational airway diseases
Work-related asthma: occupational asthma (with latency/sensitization, without latency/RADS) and work-exacerbated asthma
COPD
Bronchiolitis obliterans
Diagnostic testing for occupational airway diseases
Spirometry pre and post-bronchodilator
Methacholine challenge testing
Skin testing
Specific agent inhalation challenges
Antibody tests
Occupational asthma with latency
Results from allergic sensitization to a specific workplace chemical
Once sensitized a very low dose can cause an asthma attack
Health care workers and latex
Isocyanate in auto spray paints, polyurethane foams, adhesives, surface coatings, elastomers, or in manufacture of plastics or rubber
Carpenters and wood dust
Risk factors: atopy, smoking, genetics
>50% of patients have persistent symptoms/asthma despite cessation of the exposure
Workers who remain exposed have worse prognosis so early diagnosis matters
Treated similarly to non-occupational asthma
Occupational asthma without latency
Reactive airways dysfunction syndrome (RADS)
Results from single high-level exposure to highly toxic material
Symptoms occur within 24 hours
Paper mill explosions (SO2), chlorine, mustard gas
Direct mucosal injury –> airway hyperresponsiveness
Can be fatal acutely and treated with oral/inhaled corticosteroids
May not improve with time
Occupational COPD
Not just tobacco!
Coal
Hard rock mining
Concrete products
Dust fumes, gas, diesel exhaust
Wood stoves
Chief complaint of cough in a kid
Duration of symptoms: acute vs. chronic
Characteristics: sputum production; daytime vs. nighttime symptoms (nighttime = asthma)
Associated symptoms: fever, conjunctivitis, runny nose, ear pain, sore throat, nausea, vomiting, abdominal pain, rash
Factors/tx that makes it better or worse
Additional medical history (birth history)
Upper airway diseases with cough
Viral URI
Otitis media
Sinusitis
Pharyngitis: strep, peritonsillar/retropharyngeal abscess, epiglottitis
Croup
Foreign body aspiration
Lower airways diseases with cough
Bronchiolitis
Asthma
Pneumonia
Viral URI
Pathogenesis: rhinoviruses (50%), RSV, influenza, parainfluenza, coronavirus, adenovirus, enterovirus, immune response to the virus
Symptoms: fever at onset (typically 24-48 hours), rhinorrhea, earache, sore throat, cough, malaise, headache, duration 10-14 days
Treatment: no OTC cough/cold meds for kids less than 2 yo and lack of efficacy and potential toxicity of OTC meds for kids less than 6 years old too; supportive care (anti-pyretics (Tylenol, Advil > 6mo?), cool mist humidifier, nasal bulb suction)
Otitis media
Pathogenesis: antecedent URI (AOM is a bacterial superinfection on top of viral URI?), colonization with bacterial otopathogen (strep pneumo, H influenzae, moraxella catarrhalis)
Acute otitis media (suppurative infection)
Otitis media with effusion (inflammation with effusion; can happen with any viral URI; is fluid in back of ear that makes it pop)
Diagnosis: recent, abrupt onset of signs/symptoms (fever, irritability, URI symptoms); presence of middle ear effusion (bulging TM, limited mobility of TM, air fluid level behind TM, otorrhea); signs or sx of middle ear inflammation (erythema of TM, otalgia)
Treatment: 6mo-2yr antibiotics if otorrhea w/AOM, uni/bilateral AOM with severe sx, bilateral AOM w/o otorrhea, but if unilateral AOM without otorrhea can do observation; >2yr antibiotics if otorrhea w/AOM, uni/bilateral AOM with severe sx, but if uni/bilateral AOM without otorrhea can do observation; use amoxicillin (cefdnir, azithromycin)
Sinusitis
Viral: acute, self-limited rhinosinusitis, usually less than 14 days
Bacterial: superinfection with otopathogen (Strep pneumo, nontypeable H influenzae, Moraxella catarrhalis)
Timing of sinus development: ethmoidal and maxillary at birth (maxillary sinuses are pneumatized by 4yrs); sphenoidal 5yrs; frontal 8-12yrs
Diagnosis: antecedent URI, including purulent nasal discharge, fever and cough; symptoms persisting for greater than 10-14 days without improvement
Treatment: antibiotic (amoxicillin (bactrim, azithromycin))
Pharyngitis
Viral: adenoviruses, coronaviruses, enteroviruses, rhinoviruses, RSV, HIV, EBV (infectious mononucleosis)
Bacterial: group A beta-hemolytic streptococcus, corynebacterium diphtheriae, mycoplasma pneumoniae, neisseria gonorrhoeae, H influenzae, strep pneumo
Symptoms of strep throat
Rapid onset fever and sore throat
No cough
Headache and abdominal pain, nausea or vomiting
Tonsillar enlargement, white exudates, petechiae on palate
Painful cervical lymphadenopathy
Symptoms of scarlet fever: circumoral pallor and strawberry tongue, red papular sandpaper rash
Treatment of GAS pharyngitis
Reduce clinical symptoms of fever and pain
Reduce suppurative complications (peritonsillar or retropharyngeal abscess)
Reduce non-suppurative complications (acute rheumatic fever, glomerulonephritis), however can still get glomerulonephritis even if you treat strep throat
Treatment: penicillin (amoxicillin), cephalosporins, macrolides
Epiglottitis (supraglottitis)
Pathogenesis: H influenza B (Hib), but not much anymore because we vaccinate
Symptoms: rapid onset of fever, sore throat, dyspnea, drooling, tripod-ing
Diagnosis: lateral neck radiographs (thumb sign), direct visualization
Management and treatment: establish airway (nasotracheal intubation, tracheostomy), calming measures (avoid unnecessary exams, blood draws, etc), antibiotics (third gen cephalosporin, vancomycin if MRSA is concern)
Croup (laryngotracheobronchitis)
Pathogenesis: viral infection of glottis and subglottis (parainfluenza, influenza, RSV, adenovirus, enterovirus)
Symptoms: rhinorrhea, cough, pharyngitis, fever, “barking” cough, hoarseness, inspiratory stridor (high fever at night, cough and stridor worse at night)
Treatment: supportive care (anti-pyretics, fluids, cool mist, oral dexamethasone, racemic epi)
Clinical course: improves within 5-7 days, nighttime symptoms gradually improve
Foreign body aspiration
Symptoms: initially sudden onset coughing, gagging, possible airway obstruction; in asymptomatic period object becomes lodged, reflexes fatigue out; complications are obstruction, erosion, infection (fever, hemoptysis, pneumonia, new-onset wheezing)
History is key!
Location: right bronchus >50% of cases, trachea approximately 10% of cases
High-risk objects: toys, food (nuts, globular objects (hot dogs, grapes))
Treatment: endoscopic removal
Wheezing
Inflammation (bronchiolitis): viral infections
Asthma
Anatomic abnormalities
Mucociliary clearance disorders (CF)
Aspiration
Non-pulmonary conditions: heart failure, foreign body aspiration
Bronchiolitis
Pathogenesis: acute inflammation with edema, mucus and cellular debris in the bronchioles, predominantly viral etiology (RSV >50% of cases, parainfluenza, adenovirus, mycoplasma)
90% of children infected with RSV by age 2 (40% of those will have bronchiolitis)
Risk factors for severe disease: age less than 12 wks, history of prematurity, congenital heart disease, chronic pulmonary disease, history of CF, immunodeficiency, environmental risk factors (older siblings, childcare attendance)
History: birth hx, NICU hx, prior episodes of wheezing, fam hx of wheezing, sick contacts/daycare exposure
PE: vitals (oxygenation and RR; don’t be fooled by absence of wheezing), accessory muscle use
Diagnosis: primarily clinical, chest radiograph, viral testing (RSV, influenza, parainfluenza, pertussis)
Treatment: supportive care, trial of bronchodilators, humidified air, supplemental oxygen, Palivizumab only for high risk kids and is very expensive
Palivizumab (Synagis)
Treatment for bronchiolitis
Monoclonal antibody designed to prevent serious lower respiratory tract disease caused by RSV in high-risk children only
Dose and schedule: IM injection, given monthly Nov-March, $900 per dose
Asthma
Pathogenesis: airway inflammation, bronchial hyperreactivity and reversibility of obstruction
Most diagnosed before 6yo, most who wheeze in childhood are NOT later diagnosed with asthma, AA have more ER visits, hospitalizations, deaths
Risk factors: fam hx of parental asthma, allergic history (eczema, allergic rhinitis, food allergy), bronchiolitis requiring hospitalization, penumonia, male, environmental tobacco smoke exposure, low birthweight
Symptoms: dry cough, chest tightness (persistent nighttime cough, associated with exercise), expiratory wheezing
Triggers: physical activity, airway irritants, cold or dry air, infection
Evaluation: FEV1/FVC <0.8, low FEV1, bronchodilator response (improve FEV1 >12%), exercise challenge (worsening FEV1 >15%); peak flow monitoring (daily variation >20%)
Management: assessment and monitoring of disease activity, education of patient and family, ID triggers and co-morbid conditions, appropriate meds, treat co-morbidity (allergic rhinitis, GERD)
Classification of asthma severity
Mild intermittent: daytime sx <2 days/wk
Mild persistent: daytime sx >2 days/wk but not daily
Moderate persistent: daily sx
Severe persistent: daily sx throughout the day
Classification of asthma control
Well-controleld: sx <2 days/wk and once per day
Not well-controlled: sx >2 days/wk or more than twice per day on 2 days/wk
Very poorly controlled: sx throughout the day
Asthma medications
Beta agonists: SABA. LABA
Inhaled corticosteroids: low- or medium- or high-dose inhaled corticosteroid
Oral corticosteroids
Leukotriene receptor antagonist
Cromolyn (prevents mast cell degranulation), montelukast (leukotriene receptor blocker)
Step-wise approach to management
Pneumonia
Leading cause of under-5 deaths
However, abx and vaccinations (Hib and pneumococcal conjugate) caused 97% decrease since 1939!
Treatment: empiric antibiotics based on age and risk factors, consider hospitalization (age <6mo, immunocompromised, toxic appearance, moderate-severe respiratory distress, hypoxia, vomiting/dehydration, failure of oral antibiotic therapy, social factors)
Frequent pathogens causing pneumonia
Neonates: Group B strep, E coli, Strep pneumo, H influenzae
3 wks-3mos: RSV, influenza/parainfluenza/adenovirus, strep pneumo, H influenzae, C trachomatis
4mo-4yrs: RSV, influenza/parainfluenza/adenovirus, strep pneumo, H influenzae, C trachomatis, group A strep
>5yrs: M pneumoniae, Strep pneumo, Clamydophila pneumoniae, H influenzae, influenza and other viruses, legionella
Runts may cough chunky sputum: RSV, Mycoplasma, chlamydia trachomatis, C pneumoniae, strep pneumo
Cystic fibrosis
Autosomal recessive
CF gene is CFTR protein which is expressed on epithelial cells of airways, GI tract, sweat glands, GU system
Failure to clear mucous secretions, paucity of water in mucous secretions, elevated salt content in sweat, chronic respiratory infections
Airway epithelial cell pathology in CF
Inability to secrete salt and water
Excessive reabsorption of salt and water
Insufficient water on airway surface to hydrate secretions
Altered microenvironment (more acidic) aggravates mucociliary clearance
Airway colonization with staph aureus, pseudomonas, burkholderia cepacia
Pathology of CF
Lungs develop bronchiolitis –> bronchitis –> bronchiolectasis –> bronchiectasis –> bronchiolar obliteration
Paranasal sinuses contain inflammatory products
Pancreas is usually small and fibrotic
Focal biliary cirrhosis develops with time
Uterine cervix glands are often distended with mucus
Epididymis, vas deferens, seminal vesicles are obliterated or atretic in most cases
Clinical presentation of CF
Respiratory: cough with purulent sputum, recurrent wheezing/bronchiolitis, prolonged infections, often requiring hospitalization
GI: meconium ileus (abdominal distention, emesis, failure to pass stool within 24-48 hours of life), frequent greasy stools (due to exocrine pancreatic insufficiency), failure to thrive (eat but don’t gain weight)
Diagnosis of CF
Positive quantitative sweat test
AND
Chronic obstructive pulmonary disease
Documented exocrine pancreatic insufficiency
Positive fam hx
Can do genetic testing and newborn screening
Pulmonary treatment
CFTR modulators: Ivacaftor (designed for patients with G551D mutation in at least one CFTR gnee)
Antibiotics: azithromycin, nebulized tobramycin directed at pseudomonas
Bronchodilators
Agents to promote airway secretion clearance (inhaled DNAse I cleaves long strands of denatured DNA, hypertonic saline)
Chest physiotherapy
Vaccination (influenza and pneumococcal)
Nutritional treatment: pancreatic enzyme replacement, vitamin supplementation (K, A, D, E), parenteral supplenemtation
Lung transplantation: but non-pulmonary manifestations are unchanged
Multi-disciplinary approach is critical to success (primary care, pulmonology, respiratory therapy, gastroenterology, nutrition, social work, etc)
Transition from pediatric to adult providers of care is critical to success (physical, social, economic changes and challenges need to be anticipated for success)
Normal pulmonary circulation
High compliance
Low resistance
Therefore, usually low pressures
Normal pressures:
Systolic: 15-30 mmHg
Diastolic: 3-12 mmHg
Mean: <20 mmHg
Mean PA pressure >25 mmHg = pulmonary HTN
Three factors that independently increase pulmonary blood pressure
Left atrial pressure (LAP)
Pulmonary vascular resistance (PVR)
Pulmonary blood flow (PBF)
Hemodynamic classification of pulmonary hypertension
Precapillary (increased PVR): primary PH, secondary collagen vascular disease, liver disease, HIV, thromboembolic disease, hypoxemic PH (hypoxic pulmonary vasoconstriction, lung disease)
Postcapillary (increased LA pressure): LV systolic or diastolic heart failure, aortic and mitral valve disease
Mixed: chronic LV failure, chronic aortic and mitral valvular disease
Increased pulmonary blood flow: congenital heart disease (ASD, VSD, PDA), high output failure, liver disease, anemia
WHO classification
Based on different treatment options
Pulmonary arterial HTN: problems in vasculature of lungs
Pulmonary venous HTN: cardiac conditions
Hypoxic induced: affects circulation of lungs
Thrombotic emboli: obstruct proximal portion of pulmonary circulation
Miscellaneous: tumor obstructing circulation, etc
Idiopathic/primary PH
More female than male
Etiology unclear
Genetic: familial form, AD, mutation in BMPR2
Coagulation defects, hormonal (association with pregnancy)
Secondary PH
Collagen vascular disease (scleroderma 20% (especially CREST 50%), mixed connective tissue disease 30-40%, SLE 5%)
Portal HTN (2-5% with cirrhosis, 8% at liver transplant)
Drugs (cocaine, amphetamines, anorexins)
Hemoglobinopathies (sickle cell anemia, chronic hemolytic anemia)
HIV
Congenital heart disease (L to R shunts)
Other: schistosomiasis, Gaucher’s disease, hereditary hemorrhagic telangiectasia, persistent pulmonary hypertension of the newborn and thyroid disorders
Pathogenesis of PH
Vasoconstriction: impaired synthesis of NO and prostacyclin; enhanced production of endothelin and thromboxane
Vascular wall remodeling: concentric medial hypertrophy due to smooth muscle and endothelial cell proliferation; BMPR2 genetic defect (normally inhibits vascular smooth muscle proliferation and favors apoptosis)
Thrombosis: injury to endothelium, abnormal fibrinolysis, enhanced procoagulant activity, platelet abnormalities
Vascular change in PH
Normal
Mild to moderate PH: intimal hyperplasia and medial hypertrophy
Severe PH: plexiform lesion (abnormal angiogenesis, aneurysmal formation)
Symptoms of PH
Exertional dyspnea (60%)
Decreased exercise tolerance
Dyspnea at rest
Anginal chest pain
Syncope
WHO functional status classification for PH
No limitation of usual physical activity
Mild limitation of physical activity. No discomfort at rest. Normal physical activity causes increased dyspnea and fatigue. (This is because decreased CO which is fine at rest but you feel it when you start exercising)
Marked limitation in physical activity. No discomfort at rest.
Unable to perform any physical activity. Dyspnea and/or fatigue may be present at rest.
Physical exam in PH
Accentuated pulmonary component of 2nd heart sound in >90% (louder and delayed)
Early systolic ejection click (RVH)
RV S4 gallop (RVH)
Prominent jugular “a” wave (RVH)
Diastolic murmur of pulmonary regurg, or holosystolic murmur of tricuspid regurg
Jugular “v” waves with pulsatile liver
Peripheral edema and ascites
EKG of RVH
R axis deviation
R atrial enlargement
Q wave in V1
ST-T inversion in V1-6
Of course RVH because pressing against high pressure of pulmonary circulation
CXR findings in PH
Enlarged main pulmonary artery shadows
Pruning: attenuation of peripheral vascular markings
PGI2 and TxA2
Endothelial cells have prostacyclin synthetase and make prostacyclin (PGI2), causing vasodilation and platelet aggregation inhibition
Platelets contain thromboxane synthase and make thromboxane (TxA2) causing vasoconstriction and platelet adhesion and aggregation
Medical treatment of PH
CCBs: diltiazem, nifedipine or amlodipine in large doses; avoid in pts with right heart failure; not commonly used now
Endothelin antagonists: endothelin causes pulmonary vasoconstriction and vascular smooth muscle cell proliferation; bosentan (Tracleer) is oral, nonselective endothelin receptor blocker with hepatic toxicity, contraindicated in pregnancy but first line treatment despite $$$; ambrisentan
Prostacyclin analogues: epoprostenol (Flolan; potent vasodilation, inhibits platelet aggregation, reduces SM proliferation and migration, delivered continuously through catheter via infusion pump, $$); Iloprost (Ventavis; inhaled and can be delivered via nebulizer); Treprostinil (Remodulin; subQ pump or IV administration)
NO: inhaled; potent vasodilator at the area that is being ventilated so has local action (passes from alveolus to endothelial cell causing direct relaxation and improving V/Q mismatch, inactivated by binding to Hgb and no systemic effects if gets into systemic circulation)
Phosphodiesterase inhibitors: sildenafil (Viagra), Tadalafil (Levitra), verdenafil (Cialis; inhibit PDE which converts cGMP to GMP, used in ED, contraindicated with nitrates)
Anticoagulation: pts with PH at high risk for intrapulmonary thrombosis and thromboembolism so use coumadin (warfarin)
Surgical treatment for PH
Atrial septostomy: increased CO, concomitant loss in arterial saturation, very high mortality rate
Lung transplant: indicated if pt unresponsive to medications
Virchow’s triad
1) Hypercoagulability
2) Stasis of blood turbulent flow
3) Endothelial injury
Lines of Zahn confirm thrombus occurred over time
Risk factors for DVT and PE
Immobilization (air travel)
Recent trauma and surgery in past 3 months
Previous PE or DVT
Stroke with limb paresis
Obesity
Malignancy
Significant history of cigarette smoking
Oral contraceptives, pregnancy, hormone replacement
Thrombophilia: factor V Leiden mutation (AD point mutation gives resistance to activated protein C)
Pathophysiology of PE
Most venous thrombus emboli originate in pelvis or deep veins of the leg
Large emboli can lodge at bifurcation of PAs (saddle emboli), more commonly in second, third and fourth branches
Increased PVR causes PH and acute RH failure
Impaired gas exchange (increased dead space, R to L shunting, V/Q mismatch secondary to atelectasis, lung infarct)
Alveolar hyperventilation (reflex) with low PaCO2
Bronchoconstriction
Decreased lung compliance from pulmonary edema and hemorrhage
Symptoms and signs of PE
All highly non-specific!
Dyspnea in 84%
Pleuritic chest pain in 74%
Cough
Hemoptysis
Tachypnea (>16) in 92%
Tachycardia
Accentuated pulmonic component of second heart sound
Cardiovascular collapse
Lab abnormalities in PE
ABG: hypoxemia, hypocapnia, alkalosis, if circulatory collapse then hypercapnia and acidosis
Non-specific lab findings: leukocytosis, increase ESR, elevated LDH, AST, BNP
EKG: normal but could have tachycardia, non-specific T wave changes, RH hypertrophy
CXR: atelectasis, pulmonary parenchymal abnormality and/or pleural effusion (transudate and exudate), but normal CXR in 30%
Other causes of PE
Air
CO2
Foreign particles due to IVDA (especially talc)
Amniotic fluid
Bone fragments and marrow
Fat
Cement (from ortho surgery)
FAT BAT: fat, air, thrombus, bacteria, amniotic fluid, tumor
Chronic thromboembolic pulmonary hypertension (CTEPH)
Pulmonary HTN (mean >25 mmHg) that persists 6 months after diagnosis PE
Occurs in 2-4% pts with PE
Presents with all symptoms and findings of pulmonary HTN
Treatment is pulmonary endarterectomy
Acute PE
Correct diagnosis is important because anticoagulation is life saving but also can cause morbidity
No definitive way to identify whether pt has PE (clinical eval alone inaccurate and more definitive testing may be inaccurate too) therefore treatment based on both clinical suspicion and testing
Wells criteria for PE
Suspected DVT = 3
Alternative dx less likely than PE = 3
HR > 100 = 1.5
Immobilization/surgery 4wks = 1.5
History DVT or PE = 1.5
Hemoptysis = 1
Malignancy = 1
<!--= 2 is low probability (<4%)</p-->
3-6 is moderate (20%)
>6 is high probability (66%)
Diagnostic tests for PE
Assessment for DVT: ultrasound lower extremities, D-dimer (plasmin derived fibrin degradation product that is highly sensitive for DVT)
V/Q scan
Spiral (helical) CT angiography scan: excellent with proximal arteries
Pulmonary angiogram: gold standard but rarely done today
Treatment if hemodynamically unstable
Hospital mortality 58%
Thrombolysis
Surgical embolectomy (requires cardiopulmonary bypass): restricted to pts with absolute contraindication to thrombolysis, extremely high mortality rate (only do this if absolute contraindication to thrombolysis)
Treatment if hemodynamically stable
Hydration, oxygen, monitoring
Rapid anticoagulation: unfractionated heparin, low molecular weight heparin (subQ; enoxaparin (Lovenox)), fondaparinux
Long term anticoagulation: warfarin (coumadin) for at least 3 months to indefinitely, depending on condition
In-hospital prevention of PE
Compression stockings or other pneumatic compression devices for lower extremities
Pharmacologic prophylaxis: unfractionated heparin or low molecular weight heparin, coumadin, maybe aspirin
IVC filter (umbrella)
Pertussis
Whooping cough
Bordatella pertussis infection
Clinical presentation: Catarrhal stage 1-2 weeks (common cold sx); paroxysmal stage 4-6 weeks (severe cough with distinctive “whoop”, cyanosis, post-tussive emesis); convalescent stage 4-6 weeks (gradual improvement)
Complications: apnea, seizures, death
Diagnosis: acute cough lasting 14 days with at least one: paroxysms of cough, inspiratory whoop, post-tussive emesis
Lab dx: culture of nasopharyngeal secretions, PCR
Treatment: macrolide antibiotics, most helpful if started in catarrhal stage within 1-2 weeks of coughing, post-exposure prophylaxis
Vaccination: DTaP for age 6 and younger; TdaP for ages 7 and older (just different concentrations but both diphtheria, tetanus and acellular pertussis)
When do you drain a parapneumonic effusion?
Large, free-flowing effusion
Loculated effusion
Effusion with thickened parietal pleura
You culture an organism from the effusion fluid
Pus in effusion (empyema!)
How do you rule out TB as cause of pleural effusion?
If the ADA is normal, it is NOT TB
If there are mesothelial cells in fluid, it is NOT TB (TB encases pleural space and you don’t get mesothelial cells)
How do you decide if a patient is ready for discharge?
Vitals stable for 24 hours
Able to take oral antibiotics
Able to maintain adequate hydration and nutrition
Mental status normal (or at base line level)
No other active clinical or psychosocial problems requiring hospitalization
Conditions that do NOT usually cause pleural effusion
Silicosis
Berylium exposure
Occupational asthma
Hypersensitivity pneumonitis
