Pulmonology - Study Guide.pdf

1 – Pulmonology

Physical Exam ↓ temperature Hb has greater affinity for O2 Decreased temperature slows transfer of O2 blood  – ↓ CO2 ↑ O2blood = ↓ O2tissue = hypoxia tissue ↑ pH Hyperventilation ↑ temperature ↓ O2blood = hypoxemia Right Shift Fever – tissues req. more O2 ↑ CO2 Hypoventilation ↓ pH Vesicular Soft, low-pitched Heard over most lung fields Inspiration > expiration Bronchovesicular Medium pitched Heard over main bronchus and (R) upper posterior lung Inspiration = expiration Bronchotracheal Loud, high-pitched Only heard over trachea Expiration slightly > inspiration Discontinuous Heard more often in inspiration Crackles (Rales) Not usually cleared by coughing Small airways forced open in destructive fashion Dry or wet Fine, medium or coarse Continuous Rhonchi Fog horn or snoring quality Air passing through obstructed airway Usually clear with cough Continuous Musical, high-pitched sound Wheezes Forceful airflow through a constricted airway Most commonly heard with asthma – diffuse, usually bilateral Unilateral wheezing in pediatrics  – FB aspiration Pleural sound Like leather rubbing together Rub Inflamed pleural spaces rubbing together Evanescent Dependent on amount of fluid in pleural space “E” heard as A Egophany AKA transmitted voice sounds Bronchophany “99” sounds l ouder and clearer Assess anywhere that adventitious sounds are heard Increased transmission of voice  airless lung Whispered pectoriloquey Whispered sounds are clearer Left shift

Oxygen Dissociation Curve Breath Sounds Normal

Breath Sounds Adventitious

Vocal Resonance

Compiled by Abbie Pettigrew, class of 2016

2 – Pulmonology

Function

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Causes

Pathophysiology

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Timing

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Complications Evaluation Treatment Definition

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Timing

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Pathophysiology

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Treatment

Common Symptoms Clears the tracheobronchial tree of mucous, foreign particles, and n oxious aerosols May impair sleep, social functioning Acute respiratory infection Pulmonary embolism Acute Pneumonia Pulmonary edema Aspiration Low-grade chronic bronchitis Smokers Increased intensity, intractability of pre-existing cough  lung cancer Chronic Upper airway cough syndrome (PND) GERD Non-Smokers Asthma ACE-I induced Initiated through a complex reflex arc Involuntary Stimulated cough centers in respiratory tract send impulses to cough center in medulla Gender-related differences differences in cough reflex sensitivity  – F>M to develop chronic cough Acute 8 weeks Fatigue Headache Rib fractures (ribs 5-7) Insomnia Urinary incontinence Timing of cough Nasal discharge H&P Wheezing Sputum production Frequent throat clearing CXR Especially in smokers, patients with fever or weight loss Unexplained cough >3-6 weeks Eliminate irritant exposures – smoke, Persistent cough after URI – Treat underlying cause occupational agents think asthma An uncomfortable awareness of breathing, not appropriate to the level of exertion Acute Onset minutes-hours Chronic Develops over weeks-months Bronchospasm Pulmonary edema Respiratory Pulmonary infection (bronchitis, pneumonia) Pneumothorax Pulmonary embolism Upper airway obstruction Acute Acute MI Cardiovascular Cardiac tamponade CHF Anemia Deconditioning Other DKA Anxiety disorder Asthma Interstitial lung disease Chronic COPD Cardiomyopathy Fever Chest pain H&P Cardiac/chest exam Cough Vital signs Oximetry CBC Spirometry Diagnostics ABG CXR ECG

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Treat the cause

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Oxygen

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Pulmonary rehabilitation

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Treat anxiety

Compiled by Abbie Pettigrew, class of 2016

3 – Pulmonology

Definition Types

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Pathophysiology Causes

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o Origins

H Evaluation Treatment Tumor Risk Factors

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Expectoration of blood originating below the vocal cords Ranges from blood streaking of sputum to gross blood without sputum Trivial Mild Massive/life-threatening Massive/life-threatening (200-600 mL in 24 h) Most likely from bronchial arteries Mimics = URI bleeding, upper GI bleeding Bronchitis Pneumonia Bronchogenic carcinoma Infection Parenchymal Goodpasture’s syndrome Disease Other auto-immune d/o Pulmonary AV malformation Vascular Disorders Pulmonary embolism Foreign body Other Airway or parenchymal trauma H&P Hematocrit CXR UA, renal function Treat underlying cause >40 years Warrants aggressive work-up >40 pack-year smoking history >1 week of hemoptysis

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Iatrogenic (drugs, radiation) Cocaine

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Elevation pulmonary capillary pressure (MS, LVH) Iatrogenic (e.g. PA catheter) Fistula formation (vessel-tracheobronchial tree) Idiopathic Coag studies Bronchoscopy, HRCT

Compiled by Abbie Pettigrew, class of 2016

4 – Pulmonology

General Spirometry

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Obstructive Airway Disease Inflammation  narrowed airway  reduced airflow More distal involvement can create alveolar destruction Low FEV1/VC ratio – below 70% predicted (based on age, age, sex, height) Episodic wheezing and SOB Definition Wheezing due to air forced through narrow airways, worse on expiration Allergies (IgE) – dust mite, cockroach droppings Hyper-reactive airways from… Induced – occupation exposure, viruses, environment, exercise, inhaled toxins Etiology Mast cells Cellular Elements Eosinophils CD4 lymphs Environment Infection Stress Triggers Allergies Sinuses Exercise GERD Childhood allergic asthma Dissipates as immune system “grows up” Natural Waxes/wanes depending on inducing causes History Acquired Asthma Persistent reactivity predisposes to COPD Reduced FEV1/FCV Spirometry Increased RV Allergens Control of Sulfite sensitivity – no shrimp, dried fruit, processed potatoes, beer, Tobacco smoke Factors wine Rhinitis – IN steroids + antihistamine/decongestants Contributing Medication interactions – no BB; risk reaction to ASA/NSAIDs Sinusitis – promote drainage; abx when appropriate to Asthma Occupational exposures – avoidance, ventilation, respiratory protection GERD – no eating within 3h bed, elevate head 6-8in, Severity Viral respiratory infections – annual influenza vaccine meds

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Intermittent

Treatment

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SABA PRN

Step Preferred Alternative 2 Low-dose ICS Cromolyn, LTRA, Nedocromil, Theophylline Persistent – 3 Low-dose ICS + LABA or medium-dose ICS Low-dose ICS + either LTRA, Theophylline, or Zileutron Daily 4 Medium-dose ICS + LABA Medium-dose ICS + either LTRA, Theophylline, or Zileutron Medications 5 High-dose ICS + LABA AND co nsider Omalizumab for patients with allergies 6 High-dose ICS + LABA + oral corticosteroid AND consider Omalizumab for patients with allergies Consult with asthma specialist if step 4+ care req. (consider at step 3) Before stepping up, check adherence, environmental control, comorbid conditions) Step down if possible (and asthma well-controlled at least 3 months) At each step, patient education + environmental control + management of comorbidities Steps 2-4: consider subQ allergen immunotherapy for patients with allergic asthma

Compiled by Abbie Pettigrew, class of 2016

5 – Pulmonology

Triggers

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Infections Acute exposures to allergens

Exacerbations

Treatment

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Exercise/cold air Stress

Progressive worsening (1-3 days) History of near fatal asthma/intubations Risk Factors Frequent hospitals/ED (>2/years) Co-morbidities (CV, COPD, psych, drug abuse)) Beta-agonists Backbones Steroids Severity (% Baseline Peak Flow)  Mild (>80%) Moderate (50-80%) Increase beta agonist Severe (2 puffs/month) Poor socio-economic status

Treatment If on inhaled steroid, double dose Add/increase oral steroid Add/increase oral steroid Proceed to ED

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a m ht s A

Staging (> 12 years)

Intermittent, mild, moderate, severe Based on symptoms, night-time wakening, need for rescue i nhalers, interference with normal activity, lung function Classification of Severity Components of Severity Persistent Intermittent Mild Moderate Severe >2 days/week but Symptoms < 2 days/week Daily Throughout the day not daily Nighttime >1x/week but not < 2x/month 3-4x/month Often 7x/week awakenings nightly >2 days/week, but Impairment SABA use for not daily and not Several times per symptom control Normal FEV1/FVC: < 2 days/week Daily more than 1x on any day (not EIB prevention) 8-19 years = 85% day 20-39 years = 80% Interferes with 40-59 years = 75% None Minor limitation Some limitation Extremely limited normal activity 60-80 years = 70% Normal FEV1 FEV1 > 60% but < between FEV1 < 60% predicted FEV1 > 80% predicted 80% predicted Lung function exacerbations FEV1/FVC reduced FEV1/FVC normal FEV1/FVC reduced FEV1 > 80% predicted >5% 5% FEV1/FCV normal 0-1/year >2/year Exacerbations Consider severity and interval since last exacerbation Risk requiring oral Frequency and severity may fluctuate over time for patients in any severity category corticosteroids Relative annual risk of exacerbations may be related to FEV 1

Compiled by Abbie Pettigrew, class of 2016

6 – Pulmonology

 A systemic disease

Chronic airway inflammation “spills” inflammatory cytokines into circulation, which can injury other organs

Chronic Bronchitis

Etiology

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Natural History

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D C

Fixed airway obstruction involving alveoli

Distal predominant (alveoli/small airways)

Active respiratory drive (= dyspnea)

“Pink puffer”

Distant breath sounds

Middle age/elderly

Reduced DLCO

Hyperinflation

Cor pulmonale late

Near normal PO2/PCO2 until late

Reduced respiratory drive

“Blue bloater”  

Wheeze/rhonchi

Hyperinflation

Cor pulmonale

Lo PO2/hi PCO2 chronically

Proximal predominant (large airways) Cough, phlegm (mucous Middle age/elderly gland hypertrophy) Inhaled toxins – tobacco, indoor cooking Anti-protease deficiencies (only 40% of smokers get COPD) Airway “remodeling” in persistent asthma Depends on tobacco exposure and sensitivity I: Mild Fixed airway obstruction

Based on spirometry

GOLD Staging

FEV1/FVC < 70% FEV1 > 80% With or without symptoms

Staging Airway Beyond Spirometry Function

Spirometry is insensitive to: CT scan Chest Exercise intolerance Risk of exacerbations

Combined Assessment of COPD Radiology

ASCVD Renal insufficiency Neuro-myopathy Osteoporosis Cachexia, debility

Disease  dyspnea  deconditioning

Downward spiral in function

Emphysema

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Classes A, B, C, D

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II: Moderate

III: Severe

FEV1/FVC < 70% 50% < FEV1 < 80% With or without symptoms

FEV1/FVC < 70% 30% < FEV1 < 50% With or without symptoms

IV: Very Severe FEV1/FVC < 70% FEV1 < 30% or presence of chronic respiratory failure or R heart failure

Alveolar destruction/emphysema Trapped gas

Dyspnea vs cough vs hypoxemia Impairments that may/may not be rel. to COPD Spirometry only loosely tied Spirometry (GOLD) Dyspnea (mMRC, CAT) Exacerbation risk (per exacerbation history)

Not that useful Air trapping

Compiled by Abbie Pettigrew, class of 2016

7 – Pulmonology

NonPharmacologic

Pharmacologic Treatment

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Oxygen

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Surgery

Overview

Management Acute Exacerbation

Consequences

Prevention

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Tobacco cessation (+ pharmacologic treatment) Physical activity Pulmonary rehabilitation (classes B, C, D)  – education, exercise, psycho-social support Flu and pneumococcal vaccination Patient Recommended 1 st Choice Alternative Other Possible Treatments LAMA or SAMA PRN or A LABA or Theophylline SABA PRN SABA and SAMA LAMA or SABA and/or SAMA B LAMA and LABA LABA Theophylline LAMA and LABA or ICS + LABA or SABA and/or SAMA C LAMA and PDE4-inh. or LAMA Theophylline LABA and PDE4-inh. ICS + LABA and LAMA or Carbocysteine ICS + LABA and PDE4-inh. or D ICS + LABA and/or LAMA SABA and/or SAMA LAMA + LABA or Theophylline LAMA and PDE4-inh. For hypoxemia (< 89%) Clear reduction in mortality in patients with fixed hypoexmia Data not present for episodic hypoexmia, but prescribed and paid for by Medicare) Transplantation Reserved for very select patients Lung Volume Removes overdistended, non-functional lungs to allow more room for normal lung to expand and puts Reduction diaphragm at a better rest point Surgery Works to improve mortality and exercise tolerance if hyper -inflated areas are present at the apices (?) Defined clinically Usually have an infectious trigger Must rule out PE, CHF, PNA, etc. The same medications as Bronchodilators Antibiotics maintenance, but increased Steroids (PO or IV) NPPV (cautiously) doses Oxygen (PRN) Negative impact on quality of life Increased mortality Impact on symptoms and lung function Accelerated lung function decline Increased economic costs Clinical Proper diagnosis/staging/prescribing per guidelines Understanding complex medication regimens Patient Barriers to Effective Adherence to treatment plans COPD Management Access to clinicians System Proper discharge planning Access to pulmonary rehabilitation

Compiled by Abbie Pettigrew, class of 2016

8 – Pulmonology

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Definition

Etiology

Presentation

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Treatment

Abnormal dilation of the bronchi resulting from inflammation and permanent destructive changes in elastic and muscular layers of the bronchial walls May be localized or diffusion Usually caused by recurrent or chronic severe infections – necrotizing pneumonia (i.e. S. aureus), TB, atypical mycobacteria infection (MAI), viral (measles), fungal (histoplasmosis, coccidiodomycosis) Allergic bronchopulmonary aspergillosis Localized – anatomic obstruction (FB, tumor, broncholith), extrinsic compression (LAD) Chronic cough, foul-smelling sputum, SOB, abnormal chest sounds, fatigue Blood-streaked sputum common; massive hemoptysis may occur Clubbing may be present Periodic exacerbations d/t bacterial infections (P. aeruginosa, S. pneumo, H. flu) common PFTs Varying degrees of obstruction Normal or increased interstitial markings CXR Tram tracks classic (parallel lines in peripheral lung fields) Test of choice for diagnosis, more sensitive for detection of dilated airways HRCT Lack of airway tapering at lung periphery, airways larger in diameter than accompanying blood vessel Bronchoscopy Maybe for localized, to assess for endobronchial abnormalities Assess for fungal, mycobacterial organisms Sputum Culture ID bacterial pathogens during exacerbation Underlying Cause Remove obstruction, treat infection, etc. Aerosolized Antibiotics Suppression of bacterial growth if associated with CF Airway Clearance, Questionable benefit Postural Drainage Bronchodilators Symptomatic relief Removal of badly damaged, isolated segment of bronchietic lung Surgery Resection of obstruction Occasionally salvage therapy in resection of site with u ncontrolled hemorrhage Airway protection Hemoptysis ID bleeding site Bronchial artery angiography + embolization of causative bleeding vessels

Compiled by Abbie Pettigrew, class of 2016

9 – Pulmonology

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Genetics

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Diagnostic Tests

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Cystic fibrosis transmembrane regulator  gene is located on chromosome 7 Encodes a glycoprotein that is a chloride and bicarbonate transporter >2,000 known mutations – only 250 are known to cause CF Mutations are autosomal recessive Most common lethal genetic disorder in white population (1:29 carriers, 1:3,000 li ve births affected; 1,000 new diagnoses/year) Defect Result Example Classification Normal Protein at cell surface, with an open channel that allows flow of Cl - and HCO3I No synthesis G542X Most common II F508del Block in processing Golgi degrades protein d/t abnormalities III Block in regulation Dysfunctional channel at cell surface G551D Doesn’t move chloride well, can move HCO 3-  IV Altered conductance R117H Functional protein that is 1) under-produced, or V Reduced synthesis A445E 2) not remaining at cell surface proper length of time Immunoreactive Blood test trypsinogen (IRT) Pancreatic enzyme that is elevated in pancreatic-insufficient CF patients Newborn Second tier Screening Genetic Testing For 23 most common alleles Identifies 90% CF cases (lower for African or Hispanic Americans) Confirmation of Newborn Screening Sweat 60 – positive for CF Cannot be done until 3 weeks of age Buccal smear/serum DNA Testing For remaining mutations Assess CFTR function in airways  looking at Cl- and Nasal Over age 9, requires cooperative patient Na+ movement at the epithelial layer of the n ose and Potential Causes with borderline sweat test, only one mutation lungs Difference Primarily a research test CFTR gene defect  defective ion transport  airway surface liquid depletion  defective mucociliary clearance  mucus obstruction Mucus obstruction  infection  inflammation  mucus obstruction, etc. Innate immune system of lungs Normal Function Hydrates epithelial surfaces, binds and clears bacteria through ciliary movement, detoxifies and clears Airway particulates, protects against oxidants and proteases Mucus Decreased sol layer (periciliary liquid) means cilia stick together and aren’t able to fully extend, propel CF Patient mucus  defective mucus clearance Other Organs Cilia problems hold true for other organs with cilia = sinuses, GI tract, pancreas Newborn screening Failure to thrive Recurrent pulmonary infections Meconium ileus Poorly controlled asthma Compiled by Abbie Pettigrew, class of 2016

10 – Pulmonology

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Each mutation is associated with a certain percent of CFTR function, leading to various clinical manifestations As CFTR function decreases < 5%, disease manifestations emerge Don’t have great severity scale for lung function, talk about severity in terms of pancreatic function Classification % Normal CFTR Function CF Manifestations 50-100% No known abnormality – asymptomatic heterozygotes, normal persons Normal 10-49% No known abnormality Mild 70 Nephrotic syndrome Varicose veins Obesity Severe medical illness (i.e. CHF, ARDS) Oral contraceptives Reduced mobility Prolonged bed rest Antithrombin III deficiency Prothrombin G20210A mutation Protein C deficiency Hyperhomocysteinemia Inherited Protein S deficiency Elevated factor XI levels Heparin cofactor 2 deficiency Elevated factor VIII levels Activated protein C resistance Myeloproliferative disease Lupus anticoagulant Acquired Hyperhomocysteinemia Anticardiolipin antibodies Antiphospholipid antibodies No other risk factors Who should be Young patients Helps determine treatment course tested? Unusual clot location Acquired thrombophilia Lupus anticoagulant Hormonal Oral contraceptive HRT Tamoxifen Surgery/trauma CHF, MI Conditions Cancer Nephrotic syndrome and inflammatory bowel Immobility Leg or arm Pain, tenderness, swelling, warmth/erythema Sensation of muscle cramping May be acute, or develop over days Symptoms neither sensitive nor specific for DVT Risk factors, often, but not always obvious & may not be present at all DVT Trauma/hematoma Postphlebetic syndrome Muscle cramp Baker’s cyst Cellulitis Ultrasound

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Most common Most practical

Contrast venography

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Gold standard Rarely done

MRI

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Very accurate

CT Scan

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Also accurate Compiled by Abbie Pettigrew, class of 2016

15 – Pulmonology

Physiologic Effects

Symptoms

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Hypoxemia Pulmonary vascular resistance, pulmonary arterial pressure increase: Areas of lung are ventilated but underperfused, resulting in 1. Anatomic reduction in cross-sectional area of pulmonary V/Q mismatch vascular bed Pulmonary blood flow is redistributed to regions with lower 2. Functional hypoxia-induced pulmonary vasoconstriction V/Q  arterial hypoexmia RV Failure R heart failure is cause of death Pressure overload on RV  dilation, hypokinesis, tricuspid regurgitation When severe, elevated RVEDP can compress R coronary artery  subendocardial ischemia Less Common Cough Classic: sudden onset dyspnea + pleuritic chest pain Leg swelling Angina (RV ischemia) Leg pain Hemoptysis (pulmonary infarction) Palpitations Syncope/presyncope (cor pulmonale) Wheezing “Anginal” CP -

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Most common: tachypnea, tachycardia 10-20% have signs of proximal DVT

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RV lift Inspiratory crackles Loud pulmonary component of P2 Expiratory wheezing Pleural rub

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Diaphoresis Hypotension Fever Homans’ sign Cyanosis

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Pleural effusion

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Pulmonary infiltrates

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Depends on the settings Acute PE may occur in the setting of other disorders that may cause similar symptoms  – symptoms may be falsely blamed on underlying condition

Physical Exam

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CXR

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Atelectasis

Differential

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Pneumonia/infection Obstructive lung disease CHF MSK disease

Wells’ Criteria

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Diagnostics

Imaging

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Acute MI Anxiety Any cardiopulmonary disease causing dyspnea, CP, hemoptysis, etc.

Prior DVT or PE = +1.5 Alternative diagnosis less likely = +3 Score 0-1 = low risk HR >100 = +1.5 Hemoptysis = +1 Score 2-6 = intermediate risk Recent surgery/immobility = +1.5 Cancer = +1 Score >6 = high risk Signs of DVT = +3 Breakdown product of a thrombus Negative – VTE unlikely; positive – could be a number of things D-Dimer Sensitive, not specific Order with low-moderate suspicion Sinus tachycardia Atrial arrhythmia, A fib, sinus tach, PAC, SVT ECG R heart strain, RAD, RBBB, S1Q3T3 Inferior q waves, TWI, large p wave, P wave pulmonale ABG Hypoxemia Respiratory alkalosis High alveolar-to-arterial oxygen tension gradient Pulmonary arteriogram Gold standard Rarely done Ventilation-perfusion Ventilation-perfusion scan See smaller vessels better than on CT CT Angiography Most common test Spiral CT misses smaller PEs If can’t do lung study Compression ultrasound MRI Less data Compiled by Abbie Pettigrew, class of 2016

16 – Pulmonology

Options Severity st

LMWH

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Warfarin DTI

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IVC Filter

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ms Treatment

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Reversal of Agents

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Massive Submassive Nonmassive Heparin

NOACS Heparin Warfarin Dabigatran (DTI) Factor Xa inhibitors

Acute Treatment

ml u P

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ACCP Prevention Admission Orders

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If history of HIT Via IV Bivalirudin, argatroban If anticoagulation is absolutely contraindicated or with recurrence on therapy DTI = dabigatran Factor Xa inhibitors = rivaroxaban, apixiban, edoxaban Wears off quickly, can reverse with protamine sulfate Vitamin K, FFP, prothrombin complex concentrate FFP won’t help

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No reversal Advantages over UFH: Increased bioavailability (LMWH > UFH) QD or BID subQ delivery Monitoring not gen. required Outpatient therapy facilitated Lower rate of HIT Longer duration decreases recurrence, but increases risk of bleeding 3 months if condition reversible After 3 months, risk is 25% over next 5 years Low-moderate risk of bleeding continues indefinitely Consider continuing indefinitely (40% recurrence at 5 years)

LMWH ACCP: “For patients with high clinical suspicion of DVT or PE, we recommend treatment with anticoagulants while awaiting the outcome of diagnostic tests”

Provoked

Duration

UFH/warfarin IVC filter LMWH/warfarin Systemic thrombolytic therapy Direct thrombin inhibitors Local thrombolytic therapy Consider thrombolytics, embolectomy, pressors, anticoagulants, filter Consider thrombolytics (systemic vs. catheter-directed) Anticoagulation If high bleeding risk or very unstable and considering lytics Caution with renal insufficiency Enoxaparin, tinzaparin, dalteparin, fondaparinux (subQ)

Unprovoked

Recurrent For acutely ill CHF patients Severe respiratory distress admitted with… Or confined to bed with 1+ add’l RF, incl. active CA, previous VTE, sepsis, acute neurologic disease, IBD …we recommend thromboprophylaxis with LMWH, LDUH, or fondaparinux

Every patient admitted should be considered for prophylaxis – prophylaxis – most  most will require it

Enoxaparin, rivaroxaban, or heparin Pneumatic compression, elastic stockings

Compiled by Abbie Pettigrew, class of 2016

17 – Pulmonology

Pulmonary Vascular Disease High blood pressure in the lungs -

Not specific with regards to arteries vs veins, or to causation May be more commonly pulmonary venous, associated with left heart/valve disease, or other parenchymal lung disorders

1. Pulmonary Artery Hypertension

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H P( n oi

2. PH Owing to L Heart Disease

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Idiopathic vs heritable vs drug/toxin Associated with PAH: connective tissue disease, congenital heart disease, portal HTN, HIV infection, schistosomiasis (5%) Associated with significant venous/capillary involvement (PVOD, PCH) and persistent PH of the newborn L heart or valvular disease Most common cause of PH Pulmonary venous etiology Treating with specific pulm. artery vasodilator may worsen pulm. venous congestion and cause pulmonary edema

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Parenchymal lung disease No long-term data for pulmonary vasodilator use Correlates better with low O2 levels than PFTs Protective mechanism VQ matching Destruction of lung and vascular tissue Muscularization of pulmonary arteries Hypercapnia increases Mortality increased significantly

4. Chronic Thromboembolic PH (CTEPH)

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Best therapy is surgical, not medical

5. PH with Unclear or Multifactorial Causes

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Sarcoid Myeloproliferative

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3. PH Owing to Lung Disease and/or Hypoxemia

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Obstructive Lung Diseases: COPD, asthma, CF, bronchiectasis, bronchiolitis obliterans

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“Central Origin” of Resp. Insuffiency : Central alveolar hypoventilation, obesityhypoventilation syndrome, sleep apnea syndrome

Restrictive Lung Diseases: Neuromuscular diseases, kyphoscoliosis, thoracoplasty, sequelae of pulmonary TB, sarcoidosis, pneumoconiosis, drug-rel. lung diseases, extrinsic allergic alveolitis, CT diseases, idiopathic interstitial pulmonary fibrosis

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ESRD Sarcoma hemoglobinopathy

Compiled by Abbie Pettigrew, class of 2016

18 – Pulmonology

Very specific disease Pathology attributable to abnormal vascular process >25 mmHg at rest 3 woods units (240 dynes)

Progressive, incurable disease of the small pulmonary arteries characterized by vascular cell proliferation, aberrant remodeling, and thrombus in situ

WHO Definition

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A

H Natural History

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Via cardiac catheterization

Mean pulmonary artery pressure Pulmonary capillary wedge pressure Pulmonary vascular resistance

Progressive elevation of PAP Gradual onset of symptoms DOE Limitation of exercise capacity Progressive deterioration Increased RV afterload RV failure and progressive decline in C.I. Symptoms at rest Death Collagen vascular disease 1. Risk factors and Congenital heart disease associated conditions Portal HTN Susceptibility Abnormal BMPR2 gene

Pathology

H yr A

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et Progression

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Vascular injury

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Disease progression

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Common Initial Symptoms

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Mild: can be asymptomatic More advanced: SOB, CP, (pre)syncope

P Physical Exam

Vascular smooth muscle dysfunction Loss of response to short-acting vasodilator trial

HIV Drugs and toxins Pregnancy Other genetic factors ↓ nitric oxide synthesis ↓ prostacyclin production ↑ thromboxane production ↑ endothelin production Impaired voltage-gated K+ channel

Presymptomatic/compensated  Symptomatic/decompensating  Declining/decompensating

a n

Endothelial dysfunction

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Presence of PH

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Most common: exertional SOB Dyspnea Alter activity to accommodate symptoms Fatigue Progression leads to heart failure symptoms Syncope or near-syncope RHF – swelling, early satiety, fatigue, syncope Dizziness Chest pain Palpitations May be insidious, not recognized, or attributed to other Leg edema conditions Cough Loud pulmonary component of P2 (listen at apex) RV lift (L parasternal) Systolic murmur (TR, inspiratory augmentation) Diastolic murmur (PR) RV S3, RV S4 Early systolic click Midsystolic ejection murmur Compiled by Abbie Pettigrew, class of 2016

19 – Pulmonology

Presence of RV Failure

Physical Exam General EKG

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CXR

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Echo

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Diagnostic Studies Cardiac Cath

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Other

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Predictors of Mortality

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R axis deviation R atrial enlargement

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RV enlargement into retrosternal clear space

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Peripheral hypovascularity (pruning)

Info about severity (estimated pulmonary artery pressure, RV dimensions and function)

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Higher pulmonary artery pressure Depressed cardiac index (CI < 2.0 L/min/m2) Elevated RA pressure (> 20 mmHg)

o ml P

Prominent proximal pulmonary arteries

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Peripheral edema Ascites Pulsatile liver Low BP, low PP, cool extremities Crackles Hyperinflation R ventricular hypertrophy RV strain

Info about potential causes (LV failure, valvular lesions, congenital heart tises with L-to-R shunts) Confirm echo findings Required when PAH Survey for L heart disease (measure wedge pressure or LVEDP) suspected  Measure CO, calculate PVR 1. Look for WHO Exclude systemic to pulmonary shunts classification parameters Establish severity and prognosis 2. Acute vasodilator -  Acute vasodilator challenge challenge Refine diagnosis PFTs, V/Q scans, polysomnography or overnight oximetry, autoantibody tests, HIV To determine other causes serology, LFTs

n u

JVD with V wave, increased A wave Hepatojugular reflux RV S3 Hepatomegaly Cyanosis Clubbing

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Goals of Therapy

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Treatment Management

Absence of response to vasodilators Poor NYHA or WHO (class IV) functional status at diagnosis

Poor 6-minute walk results Improve of symptoms Prevent clinical worsening Not curable, but is Improve functional Improve survival treatable class/exercise capacity Support/reverse acute decompensated R heart Improve hemodynamics failure, hypoxemia Treat any underlying contributing disorders and O2 (all pt w/ hypoxemia) manage respiratory or heart failure symptoms Salt and volume intake, diuretics Only acute vasodilator responders should be t ried on CCB therapy (use in low output could worsen RHF) Risk stratify and consider specific pulmonary Fall in mPAP > 10 mmHg Vasodilator vasodilator therapy +PAPm (absolute) > 40 mmHg Response + normal CO Oxygen – rest, exertion, sleep Salt and fluid restriction/diuretics Sleep study (CPAP, BiPAP) Oral anticoagulation Ancillary Therapy Cardiopulm. rehab when out of acute Some data for digoxin failure (aerobic activity) Exercise/activity prescription based on Weight management/dietary stability -

Compiled by Abbie Pettigrew, class of 2016

20 – Pulmonology

Class

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FDA-Approved Therapies

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Epoprostenol (IV) Treprostinil (IV, SQ) Iloprost (inhaled) Treprostinil (inhaled or oral)

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Bosentan (PO) Ambrisentan (PO) Macitanten (PO)

PDE5 Inhibitors

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Sildenafil (PO) Tadalafit (PO)

Guanylase Cyclase stimulator

-

Riociquat

Endothelin Receptor Antagonists

n et r

Nitric Oxide Pathways

e p y H yr

Oral CCBs

et r A yr

Follow-Up

a n o ml u

Lung Transplant

P

Acute Decompensated RHF

Side Effects

-

Prostacyclin Derivatives

A

Options -

Flushing Headache N/V/D Jaw pain Leg pain Hypotension Nasal congestion Abnormal hepatic function

-

Epistaxis HA Dyspepsia Flushing

-

-

Dizziness Syncope Delivery site complications (pain, infection, cough, thrombosis, infusion interruption) Anemia Edema Teratogenic Diarrhea Visual change Contraindicated with use of nitrates, cannot use both PDE5 and GC

-

Indicated in small subset of p atients with mild-moderate symptoms who demo significant reduction i n pulmonary pressure with acute CCB challenge Careful evaluation and follow-up are necessary to continually titrate therapy At 4 weeks Repeat 6 minute walk at each visit Severely ill with IV therapy Then monthly or up to 3 Labs to assess chemistry, BNP months Echo Q6-12 months Other studies (PFTs, CXR, CT) PRN symptoms Oral therapy Every 3-4 months -

Vasodilator therapy delays or obviates need Only for patients with severe disease despite intensive medical therapy

-

At some point, may be an option, but presents a new “disease” state

-

Correct secondary causes Most often (even with low BP), giving volume is not useful and may worsen the outcome Support systemic blood pressure (pressor) Initiate or increase specific vasodilator therapy as soon as safely possible with nitric oxide, prostacyclins

el n

a

Hypertrophy/enlargement of the R ventricle related to hypoxic lung disease -

ml

o

Most often seen with COPD, but now extended to others, including kyphoscoliosis, interstitial lung disease, PSA

r

P

u Physiology

C

o

-

-

May result in edema Pretends poor prognosis in all cases

Lung vasculature constricts in response to low O2, high CO2, acidosis May be protective in COPD, ILD, sarcoid, acute lung injury, or infection Body attempts to best match ventilation and perfusion Selective pulmonary vasodilators may create VQ mismatch (inhaled less likely to do so because get greatest delivery to ventilated areas) Compiled by Abbie Pettigrew, class of 2016

21 – Pulmonology

Acid Base Disorders Carbonic acid (H 2CO3)

Types of Acids & Bases

Buffers HendersonHasselbach Equation Kidney Function

Noncarbonic acid Organic Acids Organic Bases Mineral Acids Mineral Bases HA ↔ H+ + AHA = acid, H+ = cation, A- = anion +

H  +

HCO3-

↔ H2CO3 ↔ H2O + CO2

HCO3-, lactate, β-hydroxybutyrate H+, HCl, H2SO4, H2PO4 OH-, NH3, SO4-, HPO4-

Ammoniagenesis

2. What is the pH? 3. What is the primary process?

4. Is the compensation adequate?

5. What is the anion gap?

Compound that binds H+ when [H+] rises and releases it when [H+] falls Body buffers are primarily weak acids

pH = 6.1 + log [HCO3-]/[CO2] Base/Acid Metabolic/Respiratory

to maintain pH, if HCO3- rises, then CO 2 has to decrease (and vice versa)

Cell: H2O + CO2 → H2CO3  HCO3- + H+

Acidifying Urine

1. What is the clinical scenario?

Analysis of Acid-Base Status

CO2 produced by metabolism of carbohydrates and fats Majority of acid produced each day Exhaled as CO2 at the lungs Acid produced by metabolism of proteins (i.e. sulfur-containing AA  H2SO4) Must be excreted by the kidneys (nonvolatile) CO2, lactic acid, β -hydroxybutyric acid

Protein metabolis m  NH3 -

HCO3- → blood

H2CO3  HCO3- + H+

H+  urine NH3 + H+

NH4+ (urine)

Vomiting, diarrhea, renal failure, toxin ingestion, respiratory failure, hyperventilation

7.4 = alkalemia Primary Process Metabolic Acidosis Metabolic Alkalosis Respiratory Acidosis Respiratory Alkalosis

Winter’s Formula

Na+ - (HCO3- + Cl-) Calculate ΔAG =

pH ↓ ↑ ↓ ↑ Metabolic acidosis Metabolic alkalosis Acute respiratory acidosis Chronic respiratory acidosis Acute respiratory alkalosis Chronic respiratory alkalosis

HCO3 ↓ ↑ ↑ ↓

CO2 ↓ ↑ ↑ ↓

pCO2 = 1.5 x HCO 3 + 8 + 2 For every ↑ pCO2 of 10 mm, pH ↓ by 0.08 For every ↑ pCO 2 of 10 mm, pH ↓ by 0.03 For every ↓ pCO 2 of 10 mm, pH ↑ by 0.08 For every ↓ pCO 2 of 10 mm, pH ↑ by 0.08 Normal = 12

Corrected HCO3- =

If corrected HCO3- = 24

Pure AGMA Compiled by Abbie Pettigrew, class of 2016

22 – Pulmonology

Uses

Arterial Blood Gas

Measures Bicarb

Condition

Patients AG – normal AG (12)

ΔAG + patients HCO 3-

If corrected HCO3- < 24

AGMA + NAGMA AGMA + add’l metabolic If corrected HCO3- > 24 acidosis Help in diagnosis Monitor acid-base balance Measure respiratory function Assess oxygenation Make changes in treatment (i.e. ventilator settings) Assess pressure of O2 for therapy pH HCO3H+ concentration 7.35-7.45 Bicarbonate 22-26 pCO2 SaO2 Pressure of CO2  35-45 Oxygen saturation 95-100 pO2 BE Pressure of O 2  80-100 Base excess +/-2 Calc. from pH and pCO 2 (Ø directly measured) So compare to level on Chem7 – if is btw 1-2, means chemically possible to eval. ABG

6. What is the corrected bicarbonate?

pH

HCO3-

CO2

Primary Alteration

Secondary Response

Mechanism of Secondary Response

↓

↓

↓

↓ [HCO3-]plasma

↓ paCO2

Hyperventilation

↑

↑

↑

↑ [HCO3-]plasma

↑ paCO2

Hypoventilation

Respiratory Acidosis

↓

↑

↑

↑ paCO2

↑ [HCO3-]plasma

Respiratory Alkalosis

↑

↓

↓

↓ paCO2

↓ [HCO3-]plasma

Metabolic Acidosis Metabolic Alkalosis

Condition

Signs and Symptoms

-

Metabolic Acidosis

-

Metabolic Alkalosis

-

↓ LOC  coma Weakness, ↓ DTRs Tachycardia  ↑ CO  ↓ CO  hypotension, dysrhythmia Kussmaul’s respirations Warm, flushed skin and mucous membranes Anorexia, nausea, vomiting ↑ K+ ↑ HCO3- with rising pCO2 Shallow, slow breathing Anxiety and irritability + Chvostek’s sign + Trousseau’s sign ↓ [K+], ↓ [Ca2+] Paresthesias, muscle cramping, weakness Tetany and seizures Tachycardia, + hypotension, palpitations

Acid titration of tissue buffers Transient ↑ in acid excretion and sustained enhancement of HCO 3- reabsorption by kidney Alkaline titration of tissue buffers Transient suppression of acid excretion Sustained ↓ of HCO 3- reabsorption by kidney

Treatment

Causes

MUDPILERS Methanol Uremia Diabetic/starvation ketoacidosis Paraldehyde/phenoformin Isopropryl alcohol, isoniazid

A M

-

G A

Hydration Correction of underlying cause (Sodium bicarbonate not routinely given)

USEDCRAP A M G A N

-

Antiemetic medications Monitor electrolytes and replace as indicated – potassium-sparing diuretic Seizure precautions Chloride responsive – NaCl Chloride resistant – adrenalectomy vs. potassium-sparing diuretic

Lactic acidosis Ethylene glycose/ethyl alcohol Rhabdomyolysis Salicylates Hyperalbuminemia, iatrogenic

Chloride Responsive

Ureterosigmoidostomy Small bowel fistula Excess chloride Diarrhea GI: vomiting, NG suction, Cl wasting diarrhea, villous adenoma Exogenous alkali Cystic fibrosis Chloride Resistant

Carbonic anhydrate inhibitor/CRF Renal tubular acidosis Addison’s disease Pancreatic fistula Renal: diuretic use, carbenicillin, PCN, sulfate, phosphate, post-hypercapnia Achlorhydria

Hypertensive

Adrenal disease

Exogenous steroids

Normotensive

Bartter or Gitelman syndrome Hypokalemia Milk-alkali syndrome

Refeeding alkalosis Excessive alkali administration

Compiled by Abbie Pettigrew, class of 2016

23 – Pulmonology

Respiratory Acidosis

Respiratory Alkalosis

-

↓ LOC Weakness, ↓ DTRs Ineffective respiratory efforts ↑ [K+] in acute respiratory acidosis Tachycardia  ↑ CO  ↓ CO  hypotension, dysrhythmia

-

-

Maintain patient’s airway with enhanced gas exchange: meds, O2, pulmonary toilet, ventilatory support Monitor ABGs to make appropriate adjustments Modify diet to low carb, high fat

Acute

Chronic

CNS depression Neuromuscular disease Impaired lung mechanics COPD Pickwickian syndrome

Acute airway obstruction Acute respiratory disease Thoracic cage limitations Chronic neuromuscular disease

-

Rapid, deep respirations CHEAPCHIPS Anxiety and irritability Monitor ABGs periodically CNS Hypermetabolic Hypermetabolic state + Chvostek’s sign + Trousseau’s sign Decrease respiratory rate: focused Hypotension Insufficient oxygenation + 2+ ↓ [K ], ↓ [Ca ] breathing, decrease breaths/minute Excess mechanical ventilation Psychogenic Atelectasis Paresthesias, muscle cramping, weakness on ventilator, O2 therapy Salicylates Pain Tetany and seizures Antianxiety medications Sepsis Cirrhosis Tachycardia, + hypotension, palpitations COPD: chronically ↑ pCO2, acidosis; elevated pCO 2 is the only stimulus Lungs fail to eliminate CO2 (hypoventilation) Respiratory Most commonly caused by a d isturbance of for their respiratory drive, so if you normalize CO2 the brain no longer Acidosis alveolar ventilation (lung, CNS, neuromuscular) sense the need to breath and patient may become somnolent

Respiratory Alkalosis

-

Physiology Metabolic Acidosis

Lungs eliminate too much CO2 (hyperventilation) Loss of bicarbonate without change in net charge (H+ binds a base  we do not pee sparks! ) Acid without Cl- added Anion Gap HCO3- used to buffer acidic byproducts (i.e. ketoacids, lactic acid, methanol), Na+ - (HCO3- + Cl-) > 12 resulting in formation of unmeasured anions  (Cl- + HCO 3-) term ↓ = anion (AGMA) gap Pure loss of HCO 3- in exchange for Cl -, so (Cl- + HCO 3-) term Δ Results in hyperchloremia Renal tubular acidosis  kidney not acidifying the urine Renal Cause Kidney achieves acid/base balance by secreting NH 4+ Diarrhea  HCO3- loss Extra-Renal Kidney responds by ↑ HCO 3- production  ↑ NH4+ urinary Cause secretion UAG = U[Na] + U[K]  – U[Cl] Non-Anion Gap Normal = -10 to +10 Na+ - (HCO3- + Cl-) < 12 (NAGMA) Used to detect NH4+ excreted with Cl - (NH4+ not measured) To Na + K < Cl distinguish, Means there’s electrical room for NH 4+ calculate < -10 = extra-renal and kidney making it  – acidifying urine in urine anion face of acidemia gap (UAG) Na + K > Cl > + 10 = renal Means less room for NH 4+ and kidney not making it, not doing job Compiled by Abbie Pettigrew, class of 2016

24 – Pulmonology

By either: Due to ↑ reabsoprtive threshold  ↑ Addition of bicarbonate, Na+ reabsorption at distal tubule  H+ Loss of acid, or and K+ leaking into urine Loss of fluid containing proportionally more Cl- than HCO3The kidney has a functional, reabsorptive threshold for HCO3-  if [HCO 3-]plasma is high, HCO3- spills into urine Hypochloremia – ↑ HCO3- displaces ClHypokalemia – H+ leaves cell (to acidify alkalotic blood), K+ enters cell (to maintain electrical neutrality) o Also ↑ aldosterone = ↑ Na+ = ↓ K+ H+ loss from ECF space Generation Contraction alkalosis HCO3- retention Pathogenesis – Chronic Decreased ECF/Cl- depletion Hypercapnia Maintenance Persistent mineralocorticoid Potassium depletion (profound) excess Urine chloride < 15 mEq/L Loss of HCl from emesis Metabolic In hypovolemia, kidneys try to consider Na+, H2O, and Cl-  low ( alkalosis + hypovolemia ) U[Cl] Alkalosis Chloride Responsive Loss of Cl- in emesis = r elatively more HCO3Saline responsive (corrects ↑ relative HCO 3- because HCO 3- in pancreatic juices not released volume contraction) due to low acidity of chyme entering duodenum) Extracellular fluid contraction Urine chloride > 15 mEq/L HCO3- absorbed  Cl- dumped (maintain electric neutrality) Associated with minteralcorticoid ↑ aldosterone production  ↑ Na+ resorption at DCT  Saline unresponsive (no hypernatremia  excess HCO3- absorption  alkalosis Chloride Resistant o volume loss) Heart corrects by sensing excess Na+, H2O  ANP release  Na+, H2O diuresis Associated with hypokalemia To maintain neutrality: ↑ HCO 3- absorption  ↑ K+ excretion H+ moves cell  blood, so K+ moves blood  cell Normal = 12 Difference between unmeasured anions and Na+ + UC. = Cl- + HCO 3- + UA  More unmeasured cations than anions unmeasured cations Na+ - (HCO3- + Cl-) = UA – UC = anion gap Unmeasured cations (UC): Ca2+, Mg2+ Unmeasured anions (AC): albumin3-, PO3-, SO42A primary ↑ in HCO3-

Physiology

Anion Gap

Compiled by Abbie Pettigrew, class of 2016

25 – Pulmonology

Lower Respiratory Tract Infections s es . lm n ef u P e D

Mechanical

-

Epiglottis Cough reflex Mucociliary clearance

Innate Immune System

-

Humoral (lysozyme, lactoferrin, IgA, collectins, e.g. surfactant proteins) Cellular (alveolar macrophages, PPRs)

Symptoms

Infection at the level of the alveoli

Exam CXR

Community Acquired Pneumonia (CAP)

Outpatients Inpatients

ai n

Health Care Associated Pneumonia (HCAP)

m u e

Pneumococcal Pneumonia

n P

Altered temperature, rigors, sweats, cough + sputum, dyspnea, chest pain Fatigue, myalgias, abdominal pain (esp. peds), anorexia, headache Rales

Opacity Patient in ambulatory setting Patient in extended care, on home infusion therapy, long -term hemodialysis within past 30 days, home wound care, exposure to family members with resistant pathogens, hospitalization >2 days within past 90 days Onset >48 hours after hospital admission Onset >48 hours after initiation of intubation and mechanical ventilation

Hospital Acquired Pneumonia (HAP) Ventilator Associated Pneumonia (VAP) #1 – Streptococcus pneumoniae CAP

HAP/HCAP

o

-

Etiology Haemophilus influenzae

Mycoplasma  pneumoniae  pneumoniae Legionella  pneumophila  pneumophila

-

Gram negative enterics (E. coli, K. pneumoniae, Enterobacter  spp.)  spp.) Other gram negative aerobics ( Acinetobacter, Citrobacter, Proteus, Serr atia, Pseudomonas spp.) S. aureus (including MRSA) S. pneumo colonizes 5-10% of healthy adults Most common etiology of CAP & a likely etiology in ‘culture negative’ Complications: bacteremia, meningitis, CAP otitis media, sinusitis High mortality post-splenectomy Sputum: Gram-positive diplococci Vaccination available (PCV13, PPSV23) – recommended for all adults CXR: local infiltrates > 65 & younger with co-morbid risks (including all smokers) Serotype B and nontypable cause most pneumonias Sputum: small, Gram-negative rods Not distinguishable from other causes (clinical/radiographic) Treatment: covered adequately by most More common in smokers empiric regimens Hib vaccinations have decreased carriage rates “Atypical” May have associated non-respiratory Typical presentation syndromes (CNS, transverse myelitis, Occurs in up to 1/3 CAP outpatients when serologic testing immune hemolytic anemia) performed Atypical, intracellular organism Urinary antigen – diagnostic, only detects Found in aquatic environments serogroup 1 (~80%) Incidence vary, likely due to di fferences in local epidemiology CXR: often has multi-lobar appearance

Compiled by Abbie Pettigrew, class of 2016

26 – Pulmonology

Gram negative pneumonia

-

Staphylococcal Pneumoniae

-

Chlamydia  pneumoniae  pneumoniae

Etiology

-

ai

“Atypical” TWAR agent Diagnosis difficult (true incidence unknown) 50% of 20 year olds have evidence of past infection Re-infection throughout life appears common Uncommon in outpatients 10% CAP patients admitted (highest in ICU) Increased risk (enterics, P. aeruginosa): medical co-morbidities (diabetes, EtOH, heart disease, lung disease), recent abx therapy Uncommon in CAP Relatively common complication post-influenza Increasing cases of CA-MRSA (think about if have 1) Staph risk factors and 2) very fulminant pneumonia) Enteric Gram-negative organisms Anaerobes

o

-

P

May cavitate or produce empyema

-

May cause necrotizing infiltrates May cause pneumatoceles in children

Risk Factors -

Neurologic dysphagia Anatomic or functional abnormalities abnormalities of upper GI tract (GERD, s/p esophagectomy) esophagectomy) Nursing home residence

-

Changes in consciousness (drug overdose, general anesthesia, LOC; cannot protect airway as well)

-

XR: changes in dependent lung segments May leads to necrotizing pneumonia, empyema, or lung abscess

-

Clinical Symptoms

-

Not a good tool for discriminating etiology

-

About 30% with ‘viral prodrome’

Physical Signs

-

Not different enough to be discriminatory

-

Mental status changes Degree of fever, hypertension, shock

u n

-

5-15% of CAP After inhalation of oropharyngeal or gastric contents (event not usually witnessed) Correlates with volume of aspirated material

m e

Organism associated with chronic inflammatory disease (atherosclerosis)

-

Aspiration Pneumonia

n

-

CXR Tests for Etiologic Agent

Evaluation

Labs

Sputum Sample

Urinary Antigens

Outpatient

None considered standard

Hospitalized

2 pre-treatment blood cultures

Serologic tests not considered helpful If hospitalized: CBC, BUN, electrolytes, LFTs, O2 saturation, HIV (15-54 years) Get before initiating antibiotic treatment Negative – not helpful Positive – may be helpful More invasive sampling (transthoracic aspiration, bronchoscopy) – reserve for selected patients Induced sputum for M. tuberculosis, Pneumocystic carinii -

Expectorated sputum Gram stain and culture

Deep cough specimen Transported and processed within a few hours of collection Culture contingent on cytologic exam, except for Mycobacteria, Legionella

Pneumococcal: polysaccharide cell wall antigen 50-80% sensitive, 90% specific (poor in peds); u sed to augment blood cultures and sputum Legionella: tests for serogroup 1 only Compiled by Abbie Pettigrew, class of 2016

27 – Pulmonology

Are Diagnostic When…

Evaluation

ai

Cultures

1st - In vs Outpatient

n o m P

influenza virus, RSV, parainfluenza, adenovirus, SARS coronavirus, coronavirus, Histoplasma capsulatum, Coccidioides immitis, Blastomyces Blastomyces dermatitidis)

Compatible clinical syndrome with… …stain or culture of likely pulmonary pathogen in respiratory secretions (expectorated Are Probably Diagnostic sputum or bronchoscopic secretions) When… Should be significant growth with quantit ative culture or moderate/heavy growth with semiquantitative culture Will influence antibiotic choices Assess pre-existing conditions that co mpromise safety of home care Make a clinical judgment  (takes precedence over scoring/prediction formulas) Formulas: CURB-65 vs PSI (home-care risk classes) Risk-Class Mortality Rates for Pt w/ PNA Developed largely for ED Class I-II Low mortality, recommend out-patient care populations Class III Recommend brief in-patient care Port Prediction - Use an online tool Class IV-V Recommend in-patient care Model for CAP - Considers: co-morbid Stratifies patients into high and low risk for pneumonia mortality mortality illnesses, certain exam Prediction Prediction rule focuses on recognizing low risk  patients  patients and not overestimating severity of illness findings, certain labs Has been extrapolated from ED use for use in defining need for hospitalization -

u n

Probable etiologic agent from uncontaminated specimen (blood, pleural fluid) A likely pathogen that doesn’t colonize upper airways (M. tuberculosis, Legionella spp., P carinni ,

-

-

e

-

ICU Admission

-

Treatment

Septic shock requiring vasopressors Respiratory failure requiring mechanical ventilation

Also Consider…

-

RR > 30 PaO2/FiO2 < 250 Multilobar infiltrates Confusion Uremia (BUN > 20) Leukopenia (< 4,000)

-

-

Thrombocytopenia (< 100 K) Hypothermia (core temp < 36⁰ C) Hypotension with aggressive fluid resuscitation

-

Antibiotic Regimen

Initial Therapy  – Empiric  – Empiric

Based on treatment out-patient vs in-patient floor vs in-patient ICU Underlying co-morbidities and risk for specific pathogen Age > 65 Immune-suppressive illness Factors that ↑ Risk of β-lactam therapy within past 6 (including therapy with Drug-Resistant months corticosteroids) Pneumococci Infection Alcoholism Exposure to a child in a day care Multiple medical co-morbidities center Residence in nursing home Underlying cardiopulmonary disease Enterics Multiple medical co-morbidities Factors that ↑ Risk of  Recent antibiotic therapy Infection with Gram Structural lung disease (bronchiectasis) Negatives Corticosteroid therapy (> 10d prednisone) P. aeruginosa Broad-spectrum abx (> 7d in past month) Malnutrition Compiled by Abbie Pettigrew, class of 2016

28 – Pulmonology

Location

Modifiers No cardiopulmonary disease or other modifying factors

Outpatient

Cardiopulmonary disease or other modifying factors

ai

Organisms -

S. pneumoniae M. pneumoniae C. pneumoniae (alone or mixed) H. influenzae Respiratory viruses Misc. (Legionella, M. tuberculosis, endemic fungi) 50-90% - no etiology identified Same plus… Drug resistant S. pneumoniae Enteric Gram-negatives Misc. (M. catarrhalis, aspirations (anaerobes) 50-90% - no etiology identified

o

n m

-

e

u

Treatment

Antibiotic Regimen

Resistance

-

n P Inpatient

Therapy Advanced generation macrolide (azithromycin (azithromycin or clarithromycin) clarithromycin)

OR Doxycycline (if allergic to or intolerant of macrolides)

Anti-pneumococcal fluoroquinolone OR Macrolide + β-lactam (oral cepodoxime, cefuroxime, high-dose amoxicillin (1 g Q8h), amox/clav, or parenteral ceftriaxone followed by PO cefpodoxime) (High dose amox, macrolide (azith., clarith.) added to cover H. flu)

Alternative: doxycycline Difference between between the groups is driver by possibility of drug resistant S.  pneumoniae  – any opportunity to treat more narrowly may ↓ emergence of resistant strains Increased mortality and suppurative complications with more resistant S. pneumo Antipneumococcal fluoroquinolone (covering for DR organisms)

Same as basic outpatient 33-50% - no etiology identified

OR Macrolide + β-lactam (cefotaxime, ceftriaxone, ampicillin/sulbactam, highdose ampicillin)

Alternative: doxycycline

ICU

No risks for P. aeruginosa

-

S. pneumoniae (DRSP) Legionella spp. H. influenzae Enteric Gram-negatives S. aureus M. pneumoniae Respiratory viruses Misc.: C. pneumoniae, M. tuberculosis, Pneumocystis, endemic fungi 33-50% - no etiology identified

β-lactam AND Macrolide (azithromycin)

OR Fluoroquinolone PCN allergic: cefotaxime, ceftriaxone, aztreonam Compiled by Abbie Pettigrew, class of 2016

29 – Pulmonology

β-lactam ICU

Risks for P. aeruginosa

-

Antibiotic Regimen

Duration of Therapy

ai n m

o

-

Should be anti-pseudomonal & anti-pneumococcal (Cefipime, imipenem, meropenem, piperacillin/tazobactam, piperacillin/tazobactam, aztreonam)

AND Antipseudomonal quinolone (ciprofloxacin)

CAP: Most will respond within 3 days Initial antibiotics don’t require change in first 72 hours (unless deteriorate, specific organism identified) Up to 10% CAP patients won’t respond to initial

Usually 5 days and afebrile 4872 hours

Treatment

P

n

e

u

Duration of Hospitalization

During 24 hours prior to discharge home, patient should have no more than 1 of the following… (unless baseline) -

OR

-

Anti-pseudomonal β-lactam AND Aminoglycoside AND Macrolide (azithromycin) or nonpseudomonal fluoroquinolone

S. pneumoniae

Until afebrile 72 hours

M. pneumoniae

No well established

C. pneumoniae

7-14 days

Legionella spp.

10-21 days

Pathogens that cause pulmonary necrosis – S. aureus, P. aeruginosa, Klebsiella, anaerobes Complications (lung abscess, empyema) Temperature > 37.8 ⁰ C Pulse > 100 Respiratory rate > 24 Systolic BP < 90 O2 < 90%

> 2 weeks  Antibiotics  Antibiotics don’t penetrate penetrate necrotic tissue well 

Extended therapy

Inability to maintain oral intake

Causes of Delayed Response

NonResponders Causes of Deterioration/ Early Progression

Early Deterioration (< 72 hours) Delayed Deterioration

-

Resistant organism Parapneumonic effusion/empyema (repeat CXR) Nosocomial superinfection Misdiagnosis Drug fever More severe illness at presentation (may develop organ failure) Resistant organism Metastatic infection (empyema, meningitis, arthritis; due to bacteremia) Misdiagnosis (PE, vasculitis, CHF) ARDS Nosocomial superinfection Exacerbation of underlying disease Intercurrent acute illness (PE, MI, renal failure)

Compiled by Abbie Pettigrew, class of 2016

30 – Pulmonology

ai

Parapneumonic Effusions and Empyema

n

Complications

o m

Lung Abscess

u P

n

e Performance Guidelines Follow-Up Etiologies

-

oi tc ef l

ul

Uncomplicated  – Signs and Symptoms

az n

nI e f

V

i

ar

-

Parapneumonic effusions big enough to tap should be tapped at presentation Light’s Criteria (pH, protein, LDH, glucose) to assess whether effusion is likely to become complicated (indicates drainage) Adequate drainage, even in absence of empyema, is done with goal of preventing formation of a pleural rind and a ‘trapped lung’ – don’t wait to drain Empyema: requires prolonged therapy (at least 4-6 weeks)

-

Necrotized, has formed a wall around it Complication of aspiration usually Require prolonged therapy (at least 4-6 weeks) Include empiric therapy for anaerobics

-

Blood cultures prior to antibiotic therapy Antibiotic therapy initiated within 4 hours after registration for Smoking cessation counseling hospitalized patient Pneumococcal screening and/or vaccination Initial antibiotics consistent with current recommendations Influenza screening/vaccination Assessment of oxygenation within 8 hours of admission Follow to radiologic resolution (may take 2-3 months) Be sure not to miss lung cancer  mimicking  mimicking pneumonia, post-obstructive  pneumonia, and pneumonia that was actually vasculitis Influenza RSV Coronavirus (SARS, MERS) Primary varicella infection

Epidemiology

n

-

nI

-

-

Cause of ~226,000 hospitalizations/year in US Hospitalizations highest in patients > 65 years and < 0-4 years Associated with ~36,000 deaths/year in US

Incubation period = 1-4 days Resolution = 3-7 days

Common

-

-

-

Death rates highest in persons < 2 years, > 65 years, with chronic medical conditions Death rates have almost doubled in recent years Peak activity in Nov-May

Abrupt onset of constitutional and respiratory symptoms Fever, myalgia, headache, malaise, nonproductive cough, sore throat, rhinitis Children: OM, nausea, vomiting Cough and malaise can persist >2 weeks Susceptible patients (hyper-reactive airway, + asthma diagnosis) may cough for 4-6 weeks

Febrile seizures

Encephalopathy Myocarditis, pericarditis Transverse myelitis Reye’s syndrome Myositis Exacerbation of underlying medical conditions (pulmonary, cardiac) Primary viral pneumonia Secondary bacterial infection (pneumococcus, S. aureus) – during flu or 7-14 days after clinical resolution MRSA superinfection (rel. to increased ped deaths in 2006-07)

Uncommon

Complications -

Compiled by Abbie Pettigrew, class of 2016

31 – Pulmonology

1918 Pandemic

Diagnosis

n oi

Treatment

tc az

nI ul

ef n e f

l nI

i

ar V

Vaccination

Influenza A (H1N1) by recent molecular analysis, strain origin unclear Mutation in hemagglutinin gene conferred Similar to 2009’s H1N1 binding preference for predominant sialic acid in the human RT and likely contributed to extreme virulence Viral cultures are optimal from nasopharyngeal specimens and require specific viral media Rt-PCR widely available with sensitivity in mid-90s Collect specimen within first 4 days of illness Rapid Diagnostic Tests ( 50 years Chronic medical conditions (various) increased risk for Pregnancy Nursing home residents Who needs one? complications: Long-term ASA therapy Those living with or caring for high risk individuals Healthcare workers Inactivated vaccine (>6 months) Healthy individuals only Not in children 5 mm > 10 mm > 15 mm

Compiled by Abbie Pettigrew, class of 2016

33 – Pulmonology

Small number of persons soon after infection 5-10% persons with untreated LTBI sometime during infection ~10% patients with HIV and untreated LTBI per year Cough Hemoptysis Weight loss Fatigue Other lung infections (anaerobic) Fever Decreased appetite and carcinoma can mimic Night sweats Chest pain Upper lobe infiltrates (particularly apical and posterior segments) Cavitation common Miliary pattern seen in hematogenous spread (very immune compromised; only on CT) Pay attention to infection control during collection Obtain 3 specimens for smear and culture, at least 8 hours Nucleic Acid Amplification can speed diagnosis, apart doesn’t r/o TB in smear ( -) disease Positive AFB smear gives presumptive diagnosis in proper Interferon based assays can’t distinguish latent vs setting (not definitive) active Culture = gold standard Routine drug susceptibility testing

LTBI progresses to active TB disease in… -

Clinical Presentation

CXR -

Lab Evaluation Sputum

-

si ol

s uc

When to consider initiating

b

e

r

Reactivation TB Disease Basic Principles

u T Treatment

-

Positive AFB smear Don’t delay because of negative AFB smear if high clinical suspicion – 1) history cough + weight loss, 2) characteristic findings on CXR, 3) emigration from high-incidence country

-

Provide safety, most effective therapy in shortest time Multiple drugs to which organisms are susceptible Never add a single drug to failing regimen Ensure adherence to therapy (i.e. DOT)

First-Line

Antituberculosis Drugs Second-Line (for MDR, lower cure rates)

-

Isoniazid (INH) Rifampin (RIF) Pyrazinamide (PZA) Ethambutol (EMB) Rifapentine

-

Streptomycin (SM)) Cycloserine p-aminosalicyclic acid Ethionamide Capreomycin Not FDA-approved for TB use: amikacin or kanamycin, levofloxacin, moxifloxacin, gatifloxacin

Compiled by Abbie Pettigrew, class of 2016

34 – Pulmonology

Standard 4 drug regimens for 2 months One excludes PZA Additional 4 months (or 7 months) Cavitary pulmonary disease and + sputum cultures at completion o f initial phase When Once-weekly INH and rifapentine started in continuation phase and sputum to specimen collected at end of initial phase is culture positive Continuation extend? HIV infection with positive 2-month sputum culture Phase Initial phase excluded PZA Cavitary disease and positive sputum culture at 2 months associated with Why increased relapse in clinical trials extend? Extended continuation phase decreased relapses in silicotuberculosis (20%  3%) 4 regimens recommended to treat culture-positive TB differ primarily in d osing intervals in continuation phase High clinical suspicion for active T despite negative CXR No other diagnosis smears based on: Clinical symptoms Positive TST Initial Phase

Preferred Regimen

si ol

s uc

Treatment

T

u

b

e

r

Reactivation TB Disease

Algorithm to Guide Treatment of CultureNegative TB

-

Patient placed on initial phase regimen (INH, RIF, EMB, PZA) for 2 months YES

Continue treatment for culture-positive TB Give continuation-phase treatment of Was there Is initial YES INH/RIF daily or twice weekly for 2 months symptomatic or culture CXR improvement NO Discontinue treatment positive? after 2 months of NO Patient presumed to have LTBI treatment? Treatment completed Monthly sputum for AFB smear and culture (until 2 consecutive cultures negative) Serial sputum smears Q2 weeks to assess early response Additional drug-susceptibility tests if culture-positive after 3 months of treatment Periodic (minimum monthly) evaluation to assess adherence and ID adverse reactions At completion of initial treatment phase for patient with initial negative cultures Monitoring Repeat CXR At end of treatment for patient with culture-negative TB Generally not necessary for patients with culture-positive TB Renal function, AST/ALT, bilirubin, PLT count if abnormalities at baseline Visual acuity & color vision monthly if EMB used (>2 months or doses >15-20 mg/kg) Completion primarily defined by number of ingested doses within specific time frame Determining Consider therapy interrupted if target doses not met within specified time period Drug 3 months – initial phase Compliance Specified doses must be administered within… 6 months – 4-month continuation phase Drug resistance Renal insuffiency HIV Special Situations Liver disease Children and adolescents Extrapulmonary TB Pregnancy and breastfeeding Compiled by Abbie Pettigrew, class of 2016

35 – Pulmonology

Occupational Lung Disease Interstitial lung disease following exposure to “inorganic” dusts

si s oi n oc

-

Some combination of inflammation and fibrotic injury, with later almost always predominating Defined pathologically

Documentation of fibrosis

o m u

Clinical Definition requires…

e n

History of significant exposure Absence of confounders

P Acute

Chronic

si s oc il i S Pathology Diagnosis

Imaging

Mycobacterial Silicosis Lung Cancer

-

-

-

Classic: silicosis, coal worker’s pneumoconiosis, asbestos is Symmetric on imaging (particle distribution is symmetrical)

CXR (radiologist or B reader) CT scan of chest Know industries, job titles, descriptions Cigarette smoking Granulomatous disease Interstitial lung disease

Not seen often anymore

10 years Mining, foundry work Diagnosis Evidence of fibrosis demands… History of exposure Lack of confounders Fibrotic disease of the lungs following silica exposure Simple No attributable mortality XR, CT, pathology Small opacities, up to 10 mm in diameter Symptoms Most frequently asymptomatic No changes in PFTs usually No changes in ABGs Characterized by lesions larger than 10 mm in diameter Chronic There can be mortality Symptoms Shortness of breath  cough, productive of phlegm  wheezes Restriction most common Exam Can be normal Crackles, wheezes Silica nodule (whirled  collection  collection of collagen) Polarizable Evidence of fibrosis (pathology, CXR, CT) Can have a negative CXR  – mild, usually have positive CT Can have negative CT  – very mild Simple CXR or CT Profusion of small opacities (< 10 mm) Rounded Upper lobe predominance Complicated or Progressive Massive Fibrosis Large opacity (> 10 mm diameter) Mycobacterial infection can complicate the clinical course -

IARC has classified silica as a carcinogen (1.2-1.4 relative risk) A mass in patients with silica exposure should be biopsied (don’t assume it is complicated silicosis) Compiled by Abbie Pettigrew, class of 2016

36 – Pulmonology

Overview

A group of 6 commercially valuable fibers Amphiboles and serpentines – differential in biological effect, human disease (amphiboles > serpentines) Current uses: rare in US; roofing, cement, and brakes uses chrysotile (serpentine) Related Diseases Pleural plaques/thickening Asbestosis Laryngeal cancer Mesothelioma Lung cancer Pleural effusion, rounded atelectasis Pleural plaques and thickening Mesothelioma Parenchymal Bronchitis, “small airway” disease, pneumonitis Asbestosis Lung cancer Dose of Asbestos US Incidence Disease 1,000 Daltons Symptoms consistent with asthma High MW (usually 25-50 kD) Immediate or dual reactions (rarely late alone) Cross-shift decrements in pulmonary function Diagnosis: ↓ peak flow >20% after working Mediated by IgE or IgG antibodies Positive skin test reaction = exposure + sensitization Specific antigens = exposures only Skin tests, ELISA, RAST available for only a few proteins Animal, bird, fungal proteins Lab workers, pigeon breeders, bakery workers, farmers, grain handlers, poultry workers, woodworkers, detergent workers, pharmaceutical workers MW < 1,000 Daltons Symptoms consistent with asthma Low MW ↓ pulmonary function  during/after exposure Methalcholine positive and diminishes after removal from worksite (2 weeks) Testing is difficult because hapten activity and variable latency Some act as haptens, combining with carrier proteins to become allergenic Highly variable latency Many more antigens Metals, isocyanates, acid anhydrides, pharmaceuticals (TDI, MDI, HIDI, fluxes, Cr, Ni, Co, Pt) Exposure to NO2, “brown gas” An occupational hazard in farm silos, especially within first 2 weeks of silo being filled with fresh silage

Latent Illness Phase

-

Typically occurring within 1st hour post-exposure Symptom severity is dose related Resolves over 2-8 weeks Mild cough and wheezing

li

Delayed Illness Phase

-

Sudden onset of fever, chills, cough, dyspnea and generalized lung crackles

Acute Illness Phase

F-

-

S

i

ol

-

Low-concentration

Cough, dyspnea, fatigue, upper airway irritation, ocular irritation Medium concentration and duration Cyanosis (MetHb), vomiting, vertigo, LOC High concentration ARDS, laryngeal spasm, bronchiolar spasm, reflex respiratory arrest, asphyxia May be totally asymptomatic -

Lung biopsy: BOOP

Compiled by Abbie Pettigrew, class of 2016

38 – Pulmonology

Medical Disease

“Black Lung”

iss io

Diagnosis

n oc o m

Imaging

u e n P ’s r e

Simple

kr o W l a o C

Chronic

Pathology Absent Features

Mixed Dust Pneumoconiosis Berylliosis

Flock Worker’s Lung

Popcorn Worker’s Lung

Interstitial lung disease Diffuse fibrotic lung reaction to coal dust Accumulation of dust in the lungs and tissue reaction to its presences Need tenure of 10 years in underground mining Lay term for collected of diseases defined legally as associated ILD, COPD, PNA, any lung disease impacted by coal with coal dust exposure dust Need 10 years in underground mining All disease associated with lung cancer Dependent on available tissue and pathological interpretation, or Evidence of fibrosis (CT, CXR) meeting the same 3 criteria for clinical diagnosis of History of exposure (10+ years) pneumoconiosis Lack of confounders Small, rounded opacities 10 mm diameter

-

Symptoms: SOB, cough Exam: may be abnormalities on lung exam Mortality: can be increased PFTs: can show changes, most frequently restrictive Pathology: “a fluid like ink emitting following cutting of mass” Coal macule localized to the region of the terminal bronchus Inflammation, fibrosis, dust Equivalent of acute silicosis Complication of Mycobacterial infection Issue of lung cancer

-

Most frequently refers to lung disease following exposure to silicate and some other dust

-

Can be accompanied by cutaneous problems (ulcer, granuloma) Can be acute, subacute, chronic Miners, aerospace industry Presentation can be comparable to sarcoidosis Workers in nylon flocking industry Increased risk for interstitial disease, designated FWL  – ILD after exposure to synthetic textile fibers -

Bronchiolitis obliterans – obliterans – inflammatory  inflammatory and fibrotic obstruction of small airways

-

Symptoms: SOB Exam: crackles PFTs: Restriction CXR/CT: evidence of diffuse fibrotic injury Treatment: systemic corticosteroids, removal from exposure Initiated by damage to epithelium of small airways Unrecognized exposures participate NOx, Cl2, COCl2, O3, H2S, SO2, organic and inorganic dusts

Compiled by Abbie Pettigrew, class of 2016

39 – Pulmonology

Reactive Airway Dysfunction Syndrome

Irritant induced asthma with a non -immunologic mechanism History of exposure to irritant preceding onset of respiratory symptoms in subject without prior respiratory symptoms

-

Symptoms: asthma-like, hyper-reactivity, within 24 hours of exposure (no latency period) Treatment: inhaled and oral steroids Follow-up: necessary, because significant number won’t improve and require continued therapy

-

Smoke Inhalation

Carbon Monoxide Poisoning

Immediate ABC assessment, with CPR PRN Intubation if: stridor, use of accessory respiratory muscles, significant respiratory distress, h ypoexmia, hypoventilation, deep burns to face/neck, blistering or edema of oropharynx  look for edema or blistering on laryngoscopy  if present, intubate 100% FiO2 supplemental O2 if don’t require ventilation; send ABG and standard labs (incl. lactate, toxicology screen), do H&P, CXR Monitor for development of upper airway compromise (d/t thermal injury; often within 24 hours, manage by intubation until upper edema subsides) and lower airway sequelae (d/t direct toxin damage, damage, tends to occur within 12 -36 hours, manage with aerosolized bronchodilators) Potential complications (3-4 days later): increased secretions, o bstruction of distal airways, atelectasis, bronchopneumonia, ARDS, hypermetabolism CO binds hemoglobin with affinity 210 times greater than that of O2 and causes L shift of Hb dissociation curve Should be presumed in any patient who presents after smoke inhalation until excluded by normal carboxyhemoglobin level Clinical CNS (acute and delayed), cardiovascular, renal (myoglobinuria), pulmonary Depend on % HbCO level Diagnosis Good occupation and environmental history High suspicion, especially in unconscious patients in right setting Measure HbCO by CO-oximetry (not detected on pulse ox or ABG; active smoker – up to 8-10%) Treatment Oxygen Half-life of HbCO Room air: 4-6 hours 100% O2: 40-80 min HBO: 15-30 min Hyperbaric O2 Transient or prolonged LOC Neurologic signs (incl. delayed neuropsychiatric symptoms) Cardiovascular dysfunction (arrhythmias, ischemia) Severe lactic acidosis HbCO level >20-25%

Compiled by Abbie Pettigrew, class of 2016

40 – Pulmonology

Interstitial Lung Disease Interstitium

y g ol oi s y h p o ht a P

Differential Diagnosis

Course of Illness

-

A virtual space between the alveoli, containing the capillary bed Bounded by basement membranes of 1) alveolar and 2) capillary endothelial cells Involving interstitium, alveolar space, small airways, vessels, pleura More accurate name is Diffuse Parenchymal Lung Disease (DPLD) Broad spectrum of ~200 separate clinical entities Diffuse Common Features Affect parenchyma primarily (not airway) Variable amounts of inflammation (treatable) and fibrosis (scar) Normal lung parenchyma = neat, lacy, thin alveolar walls Pathology Fibrosis = interstitial thickening o f alveolar walls (increased diffusion distance for O2/CO2) Injury  inflammation  repair…  resolution Biology of Lung  fibrosis  architectural distortion – progressive fibrosis Injury/Repair Unresolved issues… Does it require recurrent injury? Uncontrolled inflammation? Unresolved fibroproliferation? Reduced compliance  stiff lungs, smaller volumes Physiologic Consequences Restrictive lung pathology Impaired gas exchange Exercise-induced hypoexmia of Tissue Remodeling Secondary pulmonary HTN 1. Something the patient has been exposed to (environmental, med, Stop exposure What is the cause? chemo, occupational)? Mild immunosuppression 2. The patient’s body attacking itself (autoimmune, sarcoid, vasculitis) Heavy immunosuppression 3. A disease of poorly understood etiology (idiopathic pulmonary fibrosis) No treatment available (classically) Now – anti-fibrotic meds

Mimics of DPLD

-

Diffuse neoplasia (lymphoma, lymphagitis carcinomatosis, bronchoalveolar cell carcinoma) Infections (PCP) Bronchiolitis CHF Chronic aspirations

Acute, Subacute

-

Acute = days-weeks, subacute = weeks-months Dyspnea + cough, rapid progression to respiratory failure Infiltrates, fever

-

Months-years Inspiratory crackles Subtle interstitial infiltrates Fibrotic, occupational lung disease

Chronic

Mimics of infection pneumonia and ARDS AIP, acute eosinophilic pneumonia, acute hypersensitivity pneumonitis, COP, subacute hypersensitivity, drug-induced ILD, Lofgren’s syndrome

IPF, NSIP, chronic hypersensitivity, occupational lung disease, connective tissue disease-related ILD

Compiled by Abbie Pettigrew, class of 2016

41 – Pulmonology

Demographics

Gender Age Family history Smoking history

Medications

History

Environmental Occupational

Respiratory

Females Male Young Age > 60 Age 50-60 Familial PF, Hermansky-Pudlak, metabolic storage disease

LAM exclusive IPF, PLCH (slight predominance) Sarcoidosis, PLCH IPF NSIP

Smokers Non-smokers

IPF, DIP, RB-ILD, PLCH Hypersensitivity Hypersensitivity pneumonia

-

Some with well-known associations (www.pneumotox.com www.pneumotox.com)) Chemotherapy, some antibiotics, anti-arrhythmics Hypersensitivity pneumonitis Pigeons, parakeets Damp basement Hot tubs, saunas, humidifiers Woodworking Pneumoconioses, hypersensitivity Mining pneumonitis Sandblasting Welding, shipyard, pipe fitters, electricians, automatic mechanics Poultry workers Aerospace, nuclear industry, computer, other electronics Farming Animal handling Productive, hemoptysis Broncheoalveolar carcinoma, bronchiectasis, granulomatosis with Cough polyangiitis Almost all

Wheeze

Extrapulmonary

Associated Symptoms

Physical Exam

Labs PFTs

-

HEENT Respiratory Cardiovascular Extremities Skin Musculoskeletal Neurologic ESR, CRP ANA

Restrictive spirometry

Acid reflux Muscle weakness Raynaud’s phenomenon Sicca syndrome Rash Joint pain, swelling, deformity GI symptoms Hematuria Dry eyes, dry mouth, hair loss Crackles, wheeze, inspiratory squeak Split, accentuated 2nd heart sound; elevated JVD, LEE Clubbing, cyanosis Rashes (especially on hands and face) Muscle weakness; joint swelling Focal changes RF, CCP RNP Scl-70 Ro/La

-

Chronic eosinophilic pneumonia, Churg-Strauss, Allergic Bronchopulmonary Aspergillosis IPD, scleroderma, MCTD Polymyositis Scleroderma, MCTD Sjogren’s, other CTD Sarcoidosis, dermatomyositis RA, scleroderma, lupus, sarcoidosis Inflammatory bowel disease Pulmonary-renal syndrome

Scarring of lungs and distortion of parenchyma  shrunken lungs

-

CPL, aldolase Anti-tRNA-synthetase antibodies

Reduced DLCO Compiled by Abbie Pettigrew, class of 2016

42 – Pulmonology

CXR Conventional CT High-Resolution CT

Imaging Biopsy

-

-

Abnormal in most cases

-

Findings can be subtle

-

Greater sensitivity

-

Lower resolution than HRCT

-

Details at the level of the pulmonary lobule Inspiratory/expiratory (delineates air trapping vs GGO) Prone (atelectasis vs fibrosis in dependent regions)

Sensitive and specific Fine-tune with added protocols

Multisystem granulomatous disorder of unknown etiology

Most commonly affects young and middle-aged adults of A frican American and northern European descent Well-formed, non-caseating, epitheloid cell granulomas Exclude local sarcoid-like reactions and known causes of granuloma (tumor, fungus, mycobacterial infection) Usually seen on bronchoscopic biopsy Bilateral hilar lymphadenopathy Common Pulmonary infiltrates Ocular lesions Clinical Skin lesions: erythema nodosum (acute; raised, red, tender bumps on anterior legs), lupus pernio (chronic; discolored, indurated plaques on nose, cheeks, lips, ears) Manifestations Liver Salivary glands Muscles Less Common Spleen Heart Bones Lymph nodes Nervous system CXR With BHL s HRCT Various patterns: GGO, nodules, fibrosis, mass, consolidation, cysts, bronchial wall thickening e g Upper/mid lung predominance, bronchocentric distribution at S Septal beading ic Stage Finding Spontaneous Resolution Stage I – usually incidental finding on CXR h p Stage IV – scarring doesn’t improve; see 0 Normal ? ar architectural distortion g I BHL 75% io II BHL + pulmonary infiltrate 50% d a III Pulmonary infiltrate alone 90% of cases Renal insufficiency, hematuria, proteinuria Asymptomatic hematuria + normal/near normal renal function: mild focal and segmental glomerulonephritis AKI: diffuse necrotizing and crescentic glomerulonephritis Rapid renal insufficiency, cough, pulmonary infiltrates, occasional hemoptysis Systemic signs and symptoms typically absent Nonspecific patchy GGO (diffuse hemorrhage; typically sparing subpleural space) Anti-GBM (anti-glomerular basement membrane) Ab – present in >90% of cases Renal insufficiency, hematuria, proteinuria Crescending glomerulonephritis Immunofluorescence microsopy: linear deposition of IgG along glomerular capillaries and occasionally the distal tubules

Compiled by Abbie Pettigrew, class of 2016

44 – Pulmonology

Pulmonary Neoplasms

el u d o yr

N Evaluation

a n o ml u P yr at il o S

50% probability of cancer Costly Big surgery with significant pain and long recovery Morbidity

Complications Resection

Malignant

Causes Benign

-

Primary lung cancer (esp. adenocarcinoma), bronchial carcinoid tumors and metastatic foci from extrapulmonary malignancies (metastatic melanoma, melanoma, sarcoma, colon, kidney, breast, testicle

-

Benign tumors of the lung (hamartomas), infectious granulomas, lung abscess, vascular abnormalities, rounded atelectasis, pseudotumor Compiled by Abbie Pettigrew, class of 2016

45 – Pulmonology

Age Smoking history

-

Probability of an SPN being malignant increases with patient age

-

Probability of lung cnacer is greater when SPN in individual with heavy smoking history -

Larger lesions area more likely to be malignant Absence of change in size for >2 years dramatically ↓ likelihood of malignancy Benign Smooth, discrete Malignant Spiculated, irregular Benign Diffuse, central, laminated (onionskin), popcorn Malignant Peripheral eccentric

Size

N

Benign vs Malignant

P S

Radiographic Findings

Borders

Calcification

Demographics

sr

EGFR mutation

e kr a

TKI Treatment

M r o m

KRSA Mutation

u T

ALK Translocation

Epidemiology

Etiology

-

Associated with adenocarcinoma Women Non-smokers Asian Excludes possibility of KRAS mutation Erlotinib, Gefitinib A PO chemotherapy with minimal side effects Superior progression-free survival Median 2 year survival is 50% with TKI therapy in stage IV

-

Smoker Worse prognosis Higher mortality if treated with EGFR inhibitors Occurs downstream of EGFR, meaning usually don’t have EGFR mutation Fusion gene between ALK (anaplastic lymphoma kinase) and EML4 (echinoderm microtubule-associated protein-like 4) genes produces a protein that functions like an oncokinase in NSCLC EML4-ALK fusion gene is detected in 5% NSCLC Crizotinib, an ALK inhibitor, has been associated with a favorable response 1.3 million cases/year worldwide (2009) Estimated 221,200 new cases/year (2015) Estimated 158,040 deaths/year (2015) Most common cancer death in US 90% Benzo-a Pyrene = 1⁰ carcinogen Tobacco, active exposure 10-30x risk a non-smoker Dose-dependent risk 5% Tobacco, passive exposure

Genetic predisposition Occupational exposure Environmental exposure

10-15% PAH, asbestos, chromium, arsenic, nickel Radon, asbestos, indoor air pollution, cooking with wood Compiled by Abbie Pettigrew, class of 2016

46 – Pulmonology

Small cell carcinoma

Histologic Types  – Bronchogenic Carcinoma

20% Squamous  Adenocarcinoma Large cell Mixed

Non-small cell carcinoma Metastatic Other

Carcinoid, bronchial gland, sarcoma

Epidemiology

Presentation

Association -

-

Small Cell

Squamous Cell

Adenocarcinoma

-

Most common in males >95% of patients are smokers

-

30-40% of primary tumors Most common cell type in females Weakest association with tobacco (but still primarily tobacco related)

-

20-30% 30-40% 10%

Generally hilar/mediastinal origin; also neuroendocrine

-

Usually hilar/endobronchial in origin

-

Generally peripheral in origin

Associated with paraneoplastic syndromes – SIADH, Cushing syndrome, myopathy/neuropathy (i.e. Eaton-Lambert), CNS dysfunction

Treatment -

-

Most chemotherapy sensitive cell type (also returns quickly) No evidence that surgery improves outcomes

Prognosis -

-

-

Cavitation common May be associated with hypercalcemia (paraneoplastic)

-

Bronchoalveolar subtype may resemble pneumonia  – adenocarcinoma in situ, which is pneumonia-like but doesn’t clear; it can take years to grow or cause trouble, ground glass on CT

-

Radiosensitive, chemotherapy resistant Resectable if caught early

-

Large Cell

-

-

~12% primary tumors

Usually peripheral in origin

-

Resectable if caught early (rare) -

-

Lung Cancer Symptoms

Primary Tumor

Very early metastasis, very aggressive Likes to metastasize to the brain

Poorer prognosis than other nonsmall cell tumors Rapidly growing

None until advanced disease

Central/Endobronchial Peripheral

-

Cough SOB Hemoptysis Chest wall pain Cough

-

Wheezing/stridor Post-obstructive pneumonia

Compiled by Abbie Pettigrew, class of 2016

47 – Pulmonology

-

Nodal Spread

Regional Spread Local Spread

Lung Cancer Symptoms

Brain Mets

Extrathoracic Bony Mets Adrenal Mets Weight loss Anorexia Fatigue Fever Hypercalcemia Hyponatremia Cushing Syndrome Eaton-Lambert Neuropathy

Systemic

Paraneoplastic Syndromes

Endocrine Neurologic

Tracheal/esophageal Tracheal/esophageal obstruction Hoarseness Paralyzed hemidiaphragm SVC syndrome Chest wall pain Pleural effusion Horner’s syndrome (ptosis, miosis, anhidrosis) Brachial plexopathy Seizure Headache Aphasia, paresis Confusion Pathologic fracture Spinal cord compression Bone marrow invasion Addison’s (unuual)

PTH hormone SIADH ACTH-like Small cell All types

Squamous cell Small cell Small cell

Skeletal/connective tissue ~4 new cases/year/100 patients with history of h eavy smoking, > 45 years 80% detected by CXR, 20% by serology Tend to be “resectable” No difference in survival in large, randomized study Age 55-80 30 pack year smoking history Screening Eligibility Quit smoking 3 cm Tumor >3 , > 5 Tumor > 3 cm or involved mainstem bronchus T2a cm or causes collapse of lung to hilum T2b Tumor > 5, < 7 cm Tumor > 7 cm or invading chest wall, diaphragm, mediastinal pleura, pericardium or < 2 cm from carina, or atelectasis of entire lung, or separate nodule in same lung Tumor invading mediastinum, heart, trachea, carina, vertebral body, or satellite lesion in different lobe of ipsilateral lung No positive lymph nodes Tumor < 3 cm

T1a T1b

-

Ipsilateral peribronchial or hilar nodes Ipsilateral mediastinal or subcarinal nodes Contralateral mediastinal or hilar nodes, any scalene or supraclavicular nodes No distant metastases Distant M1a Pleural effusion (ipsi or contralateral), metastases pulmonary nodule in contralateral lung present M1b Distant metastases Carcinoma in situ T1N0M0 T2aN0M0 IB IIB T1N1M0, T2aN1M0, T2bN0M0 T2bN1M0, T3N0M0 IIIB T3N1M0, T1-3N2M0, T4N0-1M0 T1-4N3M0, T4N2M0

Any T, any N, M1a-b CT, PET, other diagnostic procedures No surgery Primarily via assessment of lymph nodes (improved 5 -year survival for stage IA disease compared to clinical)

Nodes

CT Scanning ~60% sensitive ~80% specific PET Scanning ~80% sensitive ~80% specific Low specificity means appropriate staging requires some kind of mediastinal invasion, unless done via endosonography, performing LN needle biopsy

Metastases Pathologic Staging Physiologic Staging

-

Abdominal CT, head CT, bone scan, PET scan Required for every patient To determine ability to undergo surgery

-

Bronchoscopy with needle aspirate, mediastinocopy, resection

-

Spirometry, blood gases, quantitative VQ scans, exercise testing Compiled by Abbie Pettigrew, class of 2016

49 – Pulmonology

SCLC

Limited Stage Extensive Stage

NSCLC

Stages I and II Stage IIIA

Treatment

-

Stage IIIB -

Stage IV

-

New Agents -

Combination chemotherapy/XRT Prophylactic brain irradiation Combination chemotherapy Radiation for brain mets if present Resection Chemotherapy (stage IB, II) Resection if possible Neoadjuvant chemo often used ~30% patients technically resectable High dose radiotherapy for those with disease confined to chest Chemo often given in conjunction Radiotherapy to symptomatic site + chemotherapy Targets for specific, antibody-based therapy (EGFR-TKI, EML4-ALK inhibitor) Low associated side effects

-

5 year survival  – 15-25% 50% patients with complete remission 5 year survival < 5% 30% complete remission

-

5 year survival - ~50%

-

5 year survival - ~30% (if resected)

-

Median survival - ~12 months 5 year survival - ~5% (disease confined to chest) Median survival - < 6 months Median survival with chemo – 8-12 months

-

Roughly double progression-free survival No change in long-term mortality

Pleural Disease Pleural Anatomy

Visceral pleura Parietal pleura Microscopic

Malignant Pleural Mesothelioma

Normally produces small amount of fluid

Serous membrane covering chest wall

Normally secretes and reabsorbs pleural fluid

5 layers

1. Mesothelial cells, 2. Submesothelial connective tissue layer, 3. Superficial elastic layer, 4. Loose connective tissue layer, 5. Deep fibroelastic layer

-

Allows movement of lung relative to chest wall Provides a route for removal of lung edema

-

Normal fluid formation = 0.02 mL/kg/hour Normally formed and absorbed by parietal pleura Formation described by Starling’s law –  fluid flux is related to hydrostatic pressure (vasculature  pleural space) and osmotic pressure (pleural space  vasculature)

Incidence

-

Rare, with declining incidence in US but increasing worldwide

Etiology

-

Strong association with occupational asbestos exposure (amphibole > chyrsotile) 25-50% off cases are sporadic disease

Physiology

-

Arises from parietal pleural; may also involve peritoneum, tunica vacinalis Epithelioid, sarcomatoid, biphasic

Prognosis

-

Poor response to surgery and chemotherapy

Functions

Pleural Physiology

Serous membrane covering lung

Pleural Fluid Formation

Compiled by Abbie Pettigrew, class of 2016

50 – Pulmonology

Pain caused by acute pleural inflammation resulting from irritation of the parietal pleura -

Pain

Pleuritis

Causes

-

Treatment

Localized, sharp, and fleeting Worsened by coughing, sneezing, deep breathing, and movement May be referred to ipsilateral shoulder when central portion of diaphragmatic pleura is irritated Young and otherwise healthy – viral respiratory infections, pneumonia Rib fracture Presence of pleural effusion, pleural thickening, or air in the pleural space – requires further diagnostic and therapeutic measures Treating underlying disease Pain relief: analgesics, anti-inflammatory drugs Cough control in pleuritic chest pain: codeine, codeine, other opioids (if retention of airway secretions secretions not likely) Intercostal nerve blocks: sometimes helpful, benefit usually transient

Pleural fluid formation exceeds reabsorption -

Pleural Effusion

Causes

Excess production of fluid Plugged lymphatic reabsorption (normally have ability to absorb 20x normal production) One of the most common causes Usually bilateral, occasionally R > L Treatment: diuretics Increased Phydrostatic (little Δ Poncotic)  ↑ fluid movement capillary beds to pleural space CHF Exceeds ability of lymphatics to reabsorb fluid May also be direct flow from fluid leaking into alveolar space, through lung parenchyma, and into pleural space (not clear) Other most common cause Lung ~40%, breast ~25%, lymphoma ~10% Diagnosis: pleural fluid cytology (occasionally needle or surgivvcal biopsy) Can be quite symptomatic (SOB) Treatment: therapeutic thoracentesis, drainage with sclerosis, tunneled pleural Malignancy catheter Hydrostatic: Pparietal = Pvisceral Tumor cytokines  leaky vasculature (including proteins)  oncotic Ppleural ↑  decrease fluid reabsorption to vasculature Tumor may also line pleural space and obstruct the route of fluiud reabsorption Associated with pneumonia Treatment: tap if > 1 cm free flowing fluid on CXR Parapneumonic Complicated: pus in pleural space, positive Gram stain, pleural glucose < 50, pleural fluid pH < 7.2; treatment – immediate chest tube placement Usually R-sided Cirrhosis Often due to “sump” mechanism Causes volume overload Renal Insufficiency - Usually associated with CHF too Often seen in dialysis patients with poor diet compliance, insufficient dialysis Compiled by Abbie Pettigrew, class of 2016

51 – Pulmonology

Transudative – Transudative – CHF, cirrhosis, renal insufficiency Exudative – Exudative – parapneumonic, malignancy, mesothelioma, TB, PE, rheumatic (lupus, RA), viral, post-surgical Inflammatory Exudative Meets > 1 Light’s criteria Hydrostatic problem Transudative Meets 0 Light’s criteria Pleural protein/serum protein > 0.5 Light’s Pleural LDH/serum LDH > 0.6 Criteria Pleural LDH >2/3 upper limit of normal for serum

-

Types

Pleural Effusions

Symptoms

-

SOB, + chest pain (most common complaints)

Thoracentesis

Diagnosis

CXR US Transudative

Treatment

Exudative

Hemothorax

Pleural fluid with hematocrit > 50% of serum hematocrit

Spontaneous

Causes

-

Determine exudative vs transudative Fluid cent for cell count, glucose, gram stain, cytology, amylase, pH, cholesterol and triglycerides

-

Decubitus films show fluid well

-

More sensitive; lets you mark position for thoracentesis Diuretics Treat underlying cause More complicated, because of various causes

-

Causes: trauma, TB, tumor, PE Usually requires chest tube to prevent scarring Associated with subpleural blebs, smoking, tall stature 54% risk of recurrence in 4 years Primary Men: 18-28/100,000 Women: 1-6/100,00 Associated with pulmonary fibrosis, emphysema Secondary

Traumatic Iatrogenic

Other

Tension

Pneumothorax British Thoracic Society Guidelines

Treatment -

-

-

Related to procedures Can cause cardiovascular compromise Requires emergent surgical treatment to prevent death

Small: < 2 cm from chest wall Large: > 2 cm from chest wall

Asymptomatic, small Observation Symptomatic or large Aspiration Recurrent or failed repeat aspiration Chest tube Asymptomatic, small, < 50 yo Aspiration Secondary Symptomatic, large, > 50 yo Chest tube Avoid suction for 48 hours if pneumothorax has been present > 24 hours, to prevent re -expansion pulmonary edema, which can throw the patient into respiratory failure

Primary

Compiled by Abbie Pettigrew, class of 2016

52 – Pulmonology

Obstructive Sleep Apnea Sleep Disordered Breathing Apnea Hypopnea

Sleep Apnea

A group of conditions associated with abnormal respiratory function due to heightened physiologic variation during sleep Affects > 5% US population Complete cessation of airflow for 10 seconds -

Obstructive

Central

Mixed

Influences on Ventilation

-

-

-

Hypoxic drive to breath reduced Ventilatory response to PaCO2 diminished Behavioral control system input diminished

Everyone experiences occasional episodes of apnea and hypopnea while sleeping

Significant decrease in airflow

Increased frequency and duration of apneic and hypopnic episodes

Normal physiologic variations during sleep:

Ventilatory effort persists but not airflow because of transient obstruction of upper airway

-

Most common Men > women Overweight, obese Complete airway occlusion  airflow stops  hypoexmia, hypercapnia Ventilatory effort is absent for Rare duration of apneic episode Seen mostly in men Usually have normal body habitus Due to decreased central respiratory drive Absent ventilatory effort precedes upper airway obstruction during apneic episode

Arterial pCO2, pH, pO2, and brainstem tissue pH Monitored by peripheral and central chemoreceptors

Obesity-Hypoventilation Syndrome (Pickwickian Syndrome) Hyperventilation Syndromes

-

-

Alveolar hypoventilation appears to result from a combination of 1) blunted ventilator drive and 2) increased mechanical load imposed upon the chest by obesity Voluntary hyperventilation returns the PCO 2 and PO 2 toward normal values Most also suffer from OSA

Treatment: Weight loss NPPV helpful for some Respiratory stimulates may be helpful Goals of Therapy Improvement in hypoexmia, hypercapnia, erythrocytosis, and cor pulmonale Caused by variety of conditions

An increase in alveolar ventilation that leads to hypocapnia Monotonous, sustained pattern of rapid and deep breathing seen in comatose patients with Central Neurogenic brainstem injury of multiple causes Hyperventilation Hyperpnea, paresthesias, Exclude organic causes Acute carpopedal spasm, tetany, anxiety

Chronic

-

-

Breathing through pursed lips or through nose with one nostril pinched, rebreathing expired gas from paper bag (↓ respiratory alkaemia and assoc. sx) Anxiolytic drugs may be useful Various nonspecific symptoms, including fatigue, dyspnea, anxiety, palpitations, and dizziness Diagnosis established if symptoms reproduced during voluntary hyperventilation Compiled by Abbie Pettigrew, class of 2016

53 – Pulmonology

Pathophysiology

Causes of Occlusion

Risk Factors

a e n p e

p

A Presentation

el S e vi ur

tc Clinical Exam

O

STOP-Bang Scoring

b

ts

-

Cyclic episodes of airway occlusion  hypoxia and hypercapnia  arousal from sleep  occlusion resolved  airway opened Sympathetic tone ↑ during airway occlusion  hypertension, vasoconstriction Intrathoracic pressure increasingly more negative with inspiration

Loss of pharyngeal tone Narrow upper airway

Pharynx passively collapses during inspiration

-

Micrognathia Macroglossia Obesity Tonsillary hypertrophy

-

Male gender Age (middle aged, older adults) Obesity Abnormal upper airway anatomy (increased neck diameter) Alcohol and sedatives and increase/contribute to loss of pharyngeal tone Also Associated: URIs may cause narrowing of upper airway Tobacco abuse Hypothyroidism Daytime somnolence Recent weight gain Patient Complaints Complaints Recurrent awakenings Cognitive impairment Morning headaches Impotence Fatigue Loud snoring Personality changes Sleep Partner Episodic breathing cessation Depressive symptoms Complaints Restlessness (movement) during sleep Often normal Elevated BP May observe: Pulmonary HTN, peripheral edema (signs of R heart failure) 1. 2.

3.

Consequences

-

-

Stratify patients for unrecognized OSA Guide perioperative precautions Triage patients for diagnosis and treatment

Snoring

-

Tired

-

Observed

-

blood Pressure BMI Age Neck circumference Gender

-

Hypertension Nocturnal arrhythmias Pulmonary HTN Increased risk for CV event (CAD)

Do you snore loudly (louder than talking or loud enough to be heard through closed doors)? Do you often feel tired, fatigued, or sleepy during daytime? Has anyone observed you stopping breathing during sleep? Do you have or are you being treated for high BP?

-

> 35

-

> 50 years

-

> 40

-

Male

-

Results High risk: yes to 3+ items Low risk: yes to < 3 items

These conditions should prompt provider to consider presence of other clinical evidence of OSA Compiled by Abbie Pettigrew, class of 2016

54 – Pulmonology

Overnight Polysomnography

Diagnosis

-

ECG, EEG, limb movements, and O2 saturations measured during sleep

-

-

CXR, PFTs

Lab Findings

e

a

Treatment

p

May be normal Erythrocytosis CO elevated (Pickwickian) ABG showing hypercapniea, hypoxia Behavioral - Weight loss Avoid sedative use

A p e

Continuous Positive Airway Pressure (CPAP)

el S e vi tc

Bilevel Ventilation (BiPAP)

ur ts O

b

Not helpful in most cases

-

Medical

n

-

Required for formal diagnosis OSA = airflow cessation occurs despite repeated muscular efforts to breath (confirmed on EEG) Will distinguish central vs obstructive and can r/o other sleep disturbances

Surgical

Tobacco cessation Avoid alcohol use Positive pressure splints the upper airway First line therapy Proper fit is the key to compliance (high non-compliance rates) Increased FRC allowing alveoli to be recruited tduring ventilation, Mechanism increasing oxygenation, decreaseing work of breathing, and increase in intrathoracic pressure = decrease cardiac workload Nasal congestion Complications Mouth breathing Claustrophobia Non-invasive positive airway pressure ventilation One pressure for inspiration and another, lower pressure for expiration (the difference between the 2 pressures = pressure support, which can result in ↑/↓ ventilation) Patients with comorbid pulmonary disease or Pickwickian

To address narrow upper airway Uvulopalatopharyngoplasty Uvulopalatopharyngopl asty (UPPP) -

Nasal Septoplasty

-

-

Limited evidence for effective relief Can be very successful in pt w/ specific anatomical abnormality that can be corrected

Definitive treatment Reserved for patients with life-threatening arrhythmias or severe disease that has failed all other treatment options Consequences: scarring, stoma and airway infections, speech difficulty Difficult to care for and maintain, especially in obese patients Supplemental O2 is not adequate (may prolong apneic episodes) Mouthguards (hold mandible forward) have modest evidence to suggest efficacy in relieving apnea, but compliance generally poor

Tracheostomy

Etc.

Resect soft tissue of pharynx and soft palate, including uvula May be helpful when nasal septum abnormality present

-

Compiled by Abbie Pettigrew, class of 2016

55 – Pulmonology

Pulmonary Imaging Inspiratory CXR Expiratory CXR Silhouette Sign

-

Standard protocol Best images of lungs due to high contrast with air With lungs expanded, more tissue in the path of the XR beam Expiratory films used to identify air trapping, by a foreign body for example (lung appears hyper-inflated) Bronchovascular crowding, mediastinum appears enlarged Can obscure disease Often seen with pts on ventilators Cannot distinguish between two adjacent structures of the same radiographic density that are adjacent to one another

Abnormal diaphragm position may indicate serious pathology

Abnormal Diaphragm Findings

Obscured hemi-diaphragm hemi-diaphragm

-

Maybe due to adjacent lung disease

Pneumoperitoneum

-

Free intra-abdominal air under the diaphragm, a sign of bowel obstruction Seen as crescents of relatively low density (black) R shoulder be slightly above L Causes: damage to phrenic nerve, lung disease causing volume loss, congenital causes (i.e. diaphragmatic hernia), trauma to diaphragm

Raised hemi-diaphragm

Disorder

XR

COPD Pneumothorax Pulmonary edema Pleural effusion Pneumonia Atelectasis Bronchitis

Viral Infectious

CT Increased lung space

Air outside the lung space Best demo’d on expiratory film Increased opacity of the lung Increased opacity outside the lung fields, particularly in costophrenic margins Lateral decubitus film shows layering out of free pleural fluid Increased lucency outside the lung fields, particularly in the Spine – fluid layers and apical cap costophrenic margins Minimum fluid for detection: lateral = 75 mL, frontal = 200 mL Increased opacity (lightness) in the lung field (could be atelectasis)

Increased lucency in the lung field

Collapse of pulmonary alveoli is evident as white patches or lines in the lung fields Increased density with reduced volume of lung ti ssue Subtle prominence of central bronchial markings; peribronchial cuffing Thickening of bronchial walls and peribronchial cuffing  visible ring shadows, tram tracks (parallel lines)

Pulmonary TB

Usually in the upper lobes Chronic – associated with calcification

Lung Tumors Lymphoma

Soft-tissue masses in the lung fields

Sarcoid

Often large soft tissue masses in the anterosuperior mediastinum Bilateral hilar lymphadenopathy, pulmonary infiltrate, pulmonary fibrosis

Various patterns (GGO, nodules, fibrosis, masses, consolidation, cysts, bronchial wall thickening); upper/mid lung predominance, bronchocentric distribution; septal beading Compiled by Abbie Pettigrew, class of 2016

56 – Pulmonology

Pulmonary CT

Common Indications

-

Pulmonary Embolism

CXR

-

CT with contrast (Angiography) -

Thoracentesis

CXR abnormality Lung tumor Mediastinal mass Aortic injury, dissection, or aneurysm Complicated infection (septic embolic, immunocompromised, recent thoracic surgery) PE (Spiral CT – CT pulmonary arteriography) Often normal Most common and most preferred Patient needs good kidney function (Cr < 1.5) Be sure no contrast allergy

V/Q Scan

-

Preferred if patient has contrast allergy or is pregnant PE is characterized by ventilation but no perfusion = VQ mismatch Studies based on probability depending on percent Ventilation = inhaled radiotracer; perfusion = venous injection of another radiotracer

Pulmonary Arteriogram

-

Gold standard Rarely used

MRI

-

Not a lot of data on use Generally not first line choice

Invasive procedure that entails insertion of needle into pleural space for removal of fluid

Diagnostic Therapeutic

In patient with pleural effusion of unknown cause Drain large effusion leading to respiratory compromise

Compiled by Abbie Pettigrew, class of 2016

57 – Pulmonology

Pulmonary Function Testing Pulse Oximetry

Used to monitor arterial O2 saturation levels (SaO2) in patients at risk for hypoxemia

Measures amount of gas a subject can voluntarily move

FVC FEV1

Spirometry Post-Medication

Flow-Volume Curve (“Loop”)

Diffusing Capacity (DLCO)

Goals of PFTs

Measuring functional residual capacity (lung gas volume at rest point) -

-

FEV1/FVC

Lung Volume Testing Peak Expiratory Flow Rate (PEFR)

Increased fraction of inspired oxygen (FiO 2), hyperventilation Hypoventilation, inadequate O2 in inspired air (suffocation), atelectasis, mucus plug, bronchospasm, PTX, pulmonary edema, Decreased ARDS, restrictive lung disease, atrial or ventricular cardiac septal defects, severe hypoventilation states, PE 6 seconds as normal to get vital capacity out Initially measuring “large airway” function, towards the end measuring “small airway” function Amount of air that can be forcefully expelled from a maximally inflated lung position Increased

Volume forced exhaled in the first second of FVC Should always be > 0.7 If < 0.7 because 1) too weak for test, 2) narrow major airways Broncho-Dilators (4 puffs β agonist) Increase by 15% considered significant Diagnostic of asthma when FEV 1 > 20% Methacholine (up to 8 mg/mL) Dose response defines severity Allows better assessment of airway characteristics at low lung volumes FEV25-75 = mean flow during midIn setting of normal FEV1/FVC, abnormal exhalation flow volume curve suggests early airway disease Techniques

-

Plethysmography Inert gas dilution Nitrogen washout

Maximum airflow rate during forced expiration

-

Diffusing capacity of the lung  – amount of gas exchanged across the alveolar-capillary membrane per minute CO used because CO has high Hb affinity and small concentration necessary Vc: capillary blood volume Inhaling small concentrations CO CO Uptake Measured CO Uptake Dependent On Dm: alv-cap membrane Holding breath 10 seconds By: properties, surface areas Measuring exhaled CO Airflow obstruction (COPD, asthma) Characterize Disease - Lung restriction (pleural and parenchymal disorders) Does not diagnose disease Neuro-muscular dysfunction (e.g. weakness) Pathophysiology Vascular disorders (PE, pulmonary HTN)

Quantitate Dysfunction

-

Disability assessment Risk evaluation (surgery, medications) Compiled by Abbie Pettigrew, class of 2016

58 – Pulmonology

PFT Value Predicted by…

-

95% Confidence Intervals for Normal

Normal Values Grading Severity

Disease Asthma Obstructed

Bronchitis Emphysema Restricted Neuromuscular Vascular

Age, height, sex

Spirometry: 80-120% of predicted Others: 70-130% of predicted Mild Moderate Severe Very severe

> 80% of predicted value 50-80% of predicted value 30-50% of predicted value < 30% of predicted value

FEV1/FVC

FVC

RV

DLCO

Normal Decreased*

Normal

Increased*

Normal

Decreased

Normal

Increased

Normal

Decreased

Normal

Increased

Decreased

Reversible to large degree with bronchodilator use COPD: ↓ rates (F EV1, FEF25-75, FEF2001200), abnormal airflow curves, ↑ RV and ERV, ↓ VC

Normal

Decreased

Decreased

Normal/Decreased

Restricted = reduction of lung volume

Decreased

Decreased

Increased

Normal

Normal

Normal

Normal

Decreased Decreased

*during exacerbations, methacholine

Sputum Cultures Sputum Sampling

Sputum Cultures

Expectorated matter from the trachea, bronchi, and lungs through the mouth

-

Best collected when patient awakes in the morning Collect at least 1 teaspoon in a sterile container + alcohol Usually obtain by having patient cough after taking several deep breaths

Endotracheal

-

Suctioned sputum from ET or tracheostomy tube

-

Small amounts of physiologic solution are injected through a fiberoptic bronchoscope into a specific area of the lung , while the rest of t he lung is sequestered by an inflated balloon Bronchoalveoelar Bronchoalveoelar lavage (BAL) The fluid is then aspirated and inspected for pathogens, malignant cells, and mineral bodies Preliminary reports in 24 hours, cultures Obtained to determine the presence of 1st – Gram stain take at least 48 hours nd 2  – bacterial culture pathogenic bacteria in patients with Sputum cultures for fungus, M. respiratory infections, such as pneumonia - Also, drug sensitivity testing tuberculosis – 4-6 weeks Culture never indicated Bronchitis Consider CAP vs HAP, aspiration, age or Indications immunocompromised patient, “atypical” Pneumonia infections (culture “negative”) Communicate suspicion of “unusual” - Skilled initiative against anticipated pathogens Empiric Treatment - Important factors: cost, yield, expected agent infections to lab Compiled by Abbie Pettigrew, class of 2016

59 – Pulmonology

Clinical Pearls – Respiratory Cultures

Reasons to Obtain Culture

Acid-Fast Bacilli (AFB) Stain KOH/Wet Prep

Epidemiologic significance Antimicrobial susceptibilities to detect resistance Provides targets treatment  – helpful in multiple drug allergies, drug interactions, renal or hepatic insufficiencies, immunocompromised

-

Consider alternative test to culture (e.g. serologic study) Aspiration pneumonia treatment takes into consideration lack of anaerobic culture CXR findings not always pathognomonic CAP vs HAP critical

Squamous epithelial cells

-

Oral mucosal contamination

Neutrophils

-

Absences not predictive in neutropenic or immunocompromised patient Numerous WBC = infection

Macrophages Eosinophils

-

Activated phagocytic cells common in fungal, acid-fast, and some atypical bacterial infections

-

Allergic reaction or parasitic infection

Mucus strands

-

Mechanically cleanse respiratory tract Direct attack of inhaled bacteria via antibodies (primarily IgA) and lysosomes

Bacteria, fungi, or AFB

-

Distinguish normal flora from pathogens

Sputum – Cellular Elements

Gram Stain

-

Done to evaluate lower respiratory tract specimen quality to culture -

-

Acceptable: < 10 squamous epithelial cells/low power field Induced specimens, BAL, and bronchial brushings or biopsy don’t require “screening” gram stain

Mycobacterium tuberculosis

Fungal Cultures

S. pneumoniae

Lancet-shaped Gram positive cocci in pairs

M. catarrhalis

Gram-negative diplococci, often visible within cytoplasm of neutrophils

Meningococci H. influenzae

-

Collect serial early AM sputum cultures x3 Cultures incubated 5 weeks for final report + TB always reported to state health department for contact evaluation

-

Important in immunocompromised, immunosuppressed, or post-antibiotic patients Cultures incubated for several weeks before culture results finalized

-

Often visible within cytoplasm of neutrophils

-

If positive, presumptively treat for TB in appropriate clinical picture

-

Stain as low as 20% sensitive

Candida albicans Aspergillus

Histoplasmosis Blastomycosis

Coccidiosis Zygomycosis

Compiled by Abbie Pettigrew, class of 2016

60 – Pulmonology

Tuberculosis Testing -

Goal of Testing

Who should be tested?

Mantoux Method

Tuberculin Skin Testing (TST)

Positive Reactions

Anergy

Detect latent TB and treat patients who would benefit from Only test individuals that would benefit from treatment treatment – presume a positive TST would require Detecting Mycobacterium tuberculosis complex treatment Suspected of having TB (suspicious CXR, productive cough with negative routine cultures, hemoptysis, undetermined weight loss) At risk for progression to active TB At increased risk for LTBI ( HC workers, recent transplant organ recipients, HIV patients, recent immigrants, I VDA, those in close contact to someone known to have TB) At low risk for LTBI, but tested for other reasons (e.g., entrance to college) Geographically high risk, housing high risk (shelters, migrant farm camps, prison/jail, nursing homes) Administer 5 units (0.1 mL) of PPD intradermal to the volar forearm Measure induration, not erythema at 48-72 hours If positive, check again 4-5 days later to be certain a severe skin reaction hasn’t occured Requires 2-12 weeks to develop an immune response to TB = delayed type hypersensitivity mediated by T cells Once positive, reaction usually persists for life HIV+ patients, recent +TB contact, fibrotic CXR findings, s/p organ transplant, immunocompromised Induration > 5 patient, medications (TNF alpha antagonists, prednisone >15 mg/day) mm

Induration > 10 mm

-

Immigrants 80% < 20% > 80% 20-30% > 60% - 30% < 60% > 30%

< 2 days/week < 2 nights/month > 2/week but < 1/day > 2 nights/month Daily > 1 night/week Continual/frequency

SABA PRN Step Preferred Alternative 2 Low-dose ICS Cromolyn, LTRA, Nedocromil, Theophylline 3 Low-dose ICS + LABA or Low-dose ICS + either LTRA, Theophylline, or Zileutron medium-dose ICS 4 Medium-dose ICS + LABA Medium-dose ICS + either LTRA, Theophylline, Theophylline, or Zileutron 5 High-dose ICS + LABA AND consider Omalizumab for patients with allergies 6 High-dose ICS + LABA + oral corticosteroid AND consider O malizumab for patients with allergies Consult with asthma specialist if step 4+ care req. (consider at step 3) Before stepping up, check adherence, environmental control, comorbid conditions) Step down if possible (and asthma well-controlled at least 3 months) At each step, patient education + environmental control + management of comorbidities Steps 2-4: consider subQ allergen immunotherapy for patients with allergic asthma Shift from PRN inhaler to scheduled inhaler… Quick-relief inhaler > 2x/week Awaken at night > 2x/month Refill quick-relief inhaler > 2x/year

Medications

Information

Short-Acting Inhaled β2 Agonists

Albuterol (Ventolin, Proventil) Levoalbuterol (Xopenex) Pirbuterol (Maxair)

-

Anticholinergics

Ipratropium (Atrovent; short-acting) Tiotropium (Spiriva; long-acting)

Systemic Corticosteroids

Prednisone Methylprednisolone Prednisolone

-

e R

Symptoms: Day/Night

-

Indicated for intermittent episodes of bronchospasm Used PRN for chronic asthma Treatment of choice for management of EIB is albuterol 15 min. before exercise Increasing up or > 1 canister/month – need to intensify anti-inflammatory therapy May have added benefit with β agonist in severe exacerbations No long-term effectiveness shown Tiotropium – no role for asthma Same mechanism as inhaled corticosteroids Continue until patient achieves 80% of personal best or symptoms resolve (usually 3-10 days) Adults: 40-80 mg/day oral prednisone Compiled by Abbie Pettigrew, class of 2016

63 – Pulmonology

Action Plans

-

Integrate into every step of care

Patient Education

t

Goal Class Inhaled corticosteroids

n e mt a er T

oL

n

g

T

e

mr Leukotriene Modifiers Mast Cell Stabilizers Long-Acting Inhaled β2 Agonists

Guide to be used at home/school Based on personal best

-

Decrease inflammation

> 80% Green zone 50-80% Yellow zone 80% predicted FEV1/FVC < 0.70 50% < FEV1 < 80% predicted FEV1/FVC < 0.70 30% < FEV1 < 50% predicted FEV1/FVC < 0.70 FEV1 2 years, adults > 65 years Chronic conditions Immunosuppression (d/t medications, HIV infection) Pregnant or postpartum (within 2 weeks after delivery) -

Zanamivir (Relenza, INH)

High rates of resistance among both S. pneumo and H. flu (~30-40%) Allergy No activity against atypical respiratory tract pathogens

-

GI intolerance Allergy CI in children Use restricted to patients with: moderate-mild infection & low risk resistance 40) Residents of nursing homes and oth er chronic-care facilities

-

All hospitalized patients with suspected influenza Severe, complicated, progressive illness Populations at risk for complications Outpatients – consider for any previously healthy, symptomatic outpatient not at high risk with confirmed/suspected illness on basis of clinical judgment within 72 hours in children with uncomplic ated flu illness Oseltamivir up to 4-5 days after illness associated with lower risk for severe outcomes DON’T WAIT FOR LAB CONFORMATION

-

5 days Longer courses for patients remaining severely ill after 5 d ays of treatment can be considered

Neuraminidase Inhibitors Osteltamivir (Tamiflu, PO)

-

Use

Population

Treatment

Any age

Chemoprophylaxis

> 3 months

Treatment

> 7 years

Chemoprophylaxis

> 5 years

Not Recommended Recommended N/A

Underlying respiratory disease (e.g., COPD, asthma)

Adverse Events Nausea, vomiting Periodic skin reactions Sporadic, transient neuropsychiatric neuropsychiatric events Oropharyngea Bronchitis, l or facial cough edema HA, dizziness Diarrhea, ENT infections nausea Sinusitis, nasal S&S

Compiled by Abbie Pettigrew, class of 2016

70 – Pulmonology

Peramivir (Rapivab,

Treatment

> 18 years

N/A

Diarrhea Serious skin reactions Sporadic, transient neuropsychiatric neuropsychiatric events

ul

IV)

F

Post-Exposure Prophylaxis/ Outbreaks

Annual vaccination is best way to prevent influenza

Condition COPD/Smoking

ai

Advanced age

n

Critical Care

P

n

HIV Infection

e

Alcoholism

u

m

o

Aspiration Structural lung dz (bronchiectasis, CF)

Principles

-

Post-exp. Prophylaxis for high-risk patients = 7 days after most recent known exposure if started within 48 hours of exposure Control of outbreaks in LTC facilities, hospitals = minimum 2 weeks chemoprophylaxis, up to 1 week after most recent known case ID’d

Common Agents H. flu, P. aeruginosa, Legionella spp., S. pneumo, M. cat, C. pneumo S. pneumo, H. flu, gram-negative bacilli, S. aureus S. pneumo, oral anaerobes, K. p neumo, Acinetobacter spp., M. tuberculosis Gram-negative bacilli, S. aureus S. pneumo, H. flu, tuberculosis, PCP, endemic fungi Gram-negative enteric pathogens, oral anaerobes P. aeruginosa, B. cepacia, S. aureus

Expand Coverage To Pseudomonas and other Gram-negatives Gram-negatives Gram-negatives MRSA, Pseudomonas and other Gramnegatives Gram-negative, PCP (only if indicated), fungi, TB Anaerobes MRSA, Pseudomonas and other Gramnegatives

Population

Preferred Treatments

er

d

Previously healthy, no antimicrobial < 3 months

qc

u

i

Empiric Antibiotic Treatment  – Outpatient

A yt

Comorbidities or antimicrobial < 3 months Or region with high-rate of infection with high-level macrolide-resistance S. pneumo

Population/Special Concerns

i m

u

n C

o

m

Empiric Antibiotic Treatment  – Inpatient

Inpatient, non-ICU treatment

Inpatients, ICU treatment

Macrolide (azithromycin, clarithromycin) Doxycycline Respiratory fluoroquinolone (gemifloxacin, levofloxacin, moxifloxacin) β-lactam (high-dose amoxicillin, high-dose amox/clav; cefpodoxime, cefuroxime) + macrolide

Preferred Treatments Respiratory fluoroquinolone (gemifloxacin, levofloxacin, moxifloxacin) β-lactam (cefotaxime, ceftriaxone, ertapenem IV) + macrolide (azithromycin, clarithromycin) β-lactam (cefotaxime, ceftriaxone, ertapenem IV) + azithromycin (PO, IV)

Respiratory fluoroquinolone Ciprofloxacin or levofloxacin Compiled by Abbie Pettigrew, class of 2016

71 – Pulmonology

If suspected Pseudomonas

If suspected CA-MRSA Overall improvement Leukocytosis resolves

Appropriate Response to Therapy

Switch to Oral Therapy

-

Antipneumococcal, antipseudomonal β-lactam (cefepime, ceftazidime, piperacillintazobactam, meropenem, imipenem, doripenem IV) PLUS EITHER To above, add…

3 days 4-5 days

Hemodynamically stable

-

Fever disappears CXR improvement

Improving clinically

Pneumonitis

Aspiration

m

CA-MSRA CAP

o

n

ai u

Pneumonia

e

NOT ROUTINE for empiric therapy (unless severe, ICU)

Age

n P d i

er

5 years

Patient Factors/Site of Care

C

o

Inpatient

H. influenzae type B, S.  pneumoniae  pneumoniae immunized

Local PCN resistance in invasive strains of pneumococcus minimal

Aminoglycoside (gentamicin, tobramycin) + azithromycin Aminoglycoside + respiratory fluoroquinolone

Vancomycin Linezolid 2-4 days 30 days (6 mo in elderly)

-

Able to ingest medications

-

Supportive therapy (O2) Prevention Role of antibiotics unclear β-lactam + β-lactamase inhibitor (Amox/Clav PO, Piperacillin-tazobactam) Empiric therapy: vancomycin, linezolid

-

Presumed Bacterial

Normally functioning GI tract

Presumed Atypical

Amoxicillin PO (90 mg/kg/day mg/kg/day in 2 doses)

Azithromycin PO

Alternatives: amoxicillin (90/mg/kg/day in 2 doses)/clavulanate PO

Alternatives: clarithromycin PO

Amoxicillin PO (90 mg/kg/day in 2 doses to max of 4 g/day) + macrolide

Azithromycin POO

Alternatives: amoxicillin (90/mg/kg/day in 2 doses, max 4 g/day)/clavulanate PO

Alternatives: clarithromycin PO, erythromycin, doxycycline (children >7 years)

Presumed Bacterial

Presumed Atypical

Ampicillin or PCN G

Azithromycin + β-lactam

Alternatives: ceftriaxone or cefotaxime; addition of vancomycin or clindamycin for suspected CA-MRSA

Alternatives: clarithromycin or erythromycin; doxycycline (>7 years), levofloxacin (reach growth maturity or can’t tolerate macrolides) Compiled by Abbie Pettigrew, class of 2016

72 – Pulmonology

Not fully immunized for H. flu type b and S. pneumo Local PCN resistance in invasive strains of pneumococcus is significant

p ar e h T

No Known RF for MDR Pathogens, Early Onset, Any Disease Severity

icr i p m

ai E

n o y

m p

u ar

e e

Late Onset, or Risk Factors for MDR Pathogens, All Disease Severity

n h T

P ci

l ri p m

m E

oc os o N

t int mt

Clinical Improvement at 4872 Hours?

d n e e u a C

o

n

Azithromycin (in addition to βlactam, if diagnosis in doubt)

Alternatives: levofloxacin; addition of vanc or clinda for susp. CA-MRSA

Alternatives: clarithromycin or erythromycin; doxycycline (>7 years), levofloxacin (reach growth maturity or can’t tolerate macrolides)

Late onset (> 5 days) or risk factors for MDR pathogens

y

ai

Ceftriaxone or cefotaxime Addition of vancomycin or clindamycin for suspected CA-MRSA

T

er Duration of Therapy

NO Limited spectrum YES Broad spectrum S. pneumo Ceftriaxone H. flu Or MRI Levo, moxi, or ciprofloxacin Abx-sensitive, enteric, Gram-neg Or bacilli (E. coli, K. pneumoniae, Ampicillin/sulbactam Enterobacter  spp.,  spp., Proteus spp., S. Or marcescans) Ertapenem See above Antipseudomonal cephalosphorin (cefepime, ceftazidime) MDR pathogens (P. aeruginosa, K. Or  pneumoniae (ESBL+), Acinteopacter  Antipseudomonal carbepenem (imipenem or meropenem) spp, MRSA) Or L. pneumophila Beta-lactam/beta-lactamase Beta-lactam/beta-lactamase inhibitor (piperacillin-tazobactam) Plus Antipseudomonal FQ (Cipro, levo) Or Aminoglycoside (amikacin, gent, tobra) Plus Linezolid or vancomycin NO Cultures negative Search for other pathogens, complications, diagnoses or sites of infection Cultures positive Adjust antibiotic treatment Search for other pathogens, complications, diagnoses or sites of infection YES Cultures negative Consider stopping antibiotics Cultures positive De-escalate antibiotics, if possible Treat selected patients 7-8 days and reassess Improvement with appropriate therapy anticipated in 48-72 hours “Traditional” duration = 10 -14 days Trend toward greater rates of relapse with P. aeruginosa, Acinetobacter   – may shorten to as short as 7 days Good response, no P. aeruginosa or Acinetobacter  – Aminoglycoside-containing regiment? Stop therapy after 5-7 days if improving

Compiled by Abbie Pettigrew, class of 2016

73 – Pulmonology

Acute Bronchitis  – Adults

Inhaled bronchodilators/corticosteroids

-

Insufficient data for routine use

Antitussives

-

Questionable benefit in productive cough

Antibiotics

-

NO

Controversial

-

No role for long-term prophylactic therapy with antibiotics for chronic bronchitis

-

s n oi

Who benefits from Antibiotics? t

si a br

ti ec

hc a x E

n et

or

-

uc A

Outpatient (Oral)

B – si it hc n or

Inpatient (IV or PO)

Treatment Options B ic n

-

Consider if severe symptoms, hypoxia, FEV 4 exacerbations in p ast year Patients with comorbidities (asthma, CAD, diabetes, heart disease) Need for home O 2 Steroid-dependent Marked airway obstruction (FEV1 < 50% predicted) Amoxicillin/clavulanate Cephalosporin (Cefpodoxime, cefuroxime axetil) Macrolide (azithro, claritro; NOT erythro) Respiratory fluoroquinolone (levo, moxi, gemi) Respiratory fluoroquinolone (IV/PO) Cefuroxime (IV/PO) Ceftriaxone (IV) Piperacillin-tazobactam (IV) Corticosteroids (INH, PO, IV) Beta-agonists Anticholinergics (INH) – ipratropium, tiotropium)

Isolate for 5 days from start of treatment Early treatment within first few weeks will lessen co ughing paroxysms and prevent spread Reduction in treatment response after first few weeks Macrolides (azithromycin in children < 1 month) TMP/SMX

Compiled by Abbie Pettigrew, class of 2016

74 – Pulmonology

Tuberculosis Pharmacology Cultures/Drug Susceptibility

Drug Resistance

-

Gold standard for confirming TB Culture all specimens, even if smear negative Results 4-14 days when liquid medium systems used If culture-positive, do susceptibility testing (INH, RIF, EMB on initial isolate) Any one TB drug Mono-resistant

Poly-resistant Multidrug resistant (MDR TB) Extensively drug resistant (XDR TB)

Increased Risk for Drug Resistance

Direct Observed Therapy (DOT) Initiating Treatment

-

At least any 2 TB drugs (but not both INH and RIF)

-

At least INH and RIF

-

INF, RIF, AND resistant to any fluoroquinolone AND at least 1 of the 3 injectable (e.g., amikacin, kanamycin, or capreomycin)

-

History of treatment with TB drugs Contacts of person with drug-resistant TB Foreign-born from high prevalent drug resistant areas Smears or cultures positive despite 2 months of treatment Inadequate treatment regimens for >2 weeks Patients not on DOT in the past or who had irregular treatment

Health care worker watches patient swallow each dose Preferred for all patients  – reduces total number of doses and encounters Can reduce acquired drug resistance, treatment failure, and relapse Nearly all regimens can be intermittent if given as DOT

Before Initiating Treatment for LTBI

-

Rule out TB disease (i.e. wait for culture results) Determine prior history of treatment for LTBI or TB disease Assess risks and benefits of treatment Determine current and previous drug therapy

First-Line Drugs

Treatment Options

-

Antituberculosis Drugs

SecondLine Drugs

-

Isoniazid (INH) Rifampin (RIF) – Rifabutin (RBT), Rifapentine (RPT) Pyrazinamide (PZA) Ethambutol (EMB)

-

Streptomycin (SM) Cycloserine p-Aminosalicylic acid Ethionamide Amikacin or kanamycin

-

Capreomycin Levofloxacin Moxifloxacin Bedaquine

Compiled by Abbie Pettigrew, class of 2016

75 – Pulmonology

Drug

Regimen -

INH -

-

Treatment Options

Latent TB

9 mo (preferred) daily OR Intermittent via DOT Option for 6 months

12 weekly doses via DOT

Indications/Comment Indications/Comment -

-

-

Also may be used during pregnancy and breastfeeding (with pyridoxine supplementation) 6 mo QD or BIW (less effective) may be used if unable to complete 9 mo Otherwise healthy > 12 years HIV+ otherwise healthy and NOT on ART

Exclusions -

-

INH + RPT -

Daily x4 months

-

Daily x2 months

RIF

RIF + PZA

Basic Principles

Active Disease Most Common Treatment

-

6 mo regiment excludes: HIV+ wit previous pulmonary TB disease, children, and/or immunosuppressed Pregnancy: give with pyridoxine < 12 years HIV+ receiving ART Pregnant or women expecting to become pregnant Presumed INH or RIF resistance

Intolerance to INH Exposure to INH-resistant TB If RIF cannot be used, RBT may be subbed (e.g. HIV+ receiving protease inhibitors) -

No longer recommended d/t association with severe liver injury

-

Provided safest, most effective therapy in the shortest time Multiple drugs to which organisms are susceptible Never add single drug to failing regimen Ensure adherence to therapy 2 months Initial Phase - Standard 4 drug regimens (INH, RIF, PZA, EMB) One regimen excludes PZA Usually INH + RIF x 4 months Extend to 7 months if: o Cavitary pulmonary disease AND + sputum cultures at completion of initial phase (2 mo) Continuation o Initial phase excluded PZA Phase o Qweek INH and RPT is started in continuation phase and sputum specimen collected at end of initial phase is culture + o HIV-infected with + 2 month sputum culture For patients receiving medications having unacceptable reactions New Role of Rifabutin (RBT) with RIF (e.g. HIV/AIDS) Rifamycin Used in Qweek cont. phase for HIV-neg. adults with drug-susceptible Rifapentine (RPT) Drugs non-cavitary TB and neg. AFB smears at completion of initial phase Compiled by Abbie Pettigrew, class of 2016

76 – Pulmonology

Caused by

Adverse Reactions Hepatitis

Signs and Symptoms

Comments

Abdominal pain, abnormal LFT, fatigue, lack of appetite, nausea, vomiting, yellowish skin/eyes, dark urine, flu-like illness, fever 3+ days

-

Peripheral neuropathy

Tingling sensation in hands and feet

-

GI intolerance

Upset stomach, vomiting, lack of appetite

Arthralgia, arthritis

Joint aches

Increased uric acid

Gout (rare)

Eye damage

Blurred or changed vision Changed color vision Easy bruising, slow blood clotting Upset stomach Rash, sunburn-like reaction NUMERUS due to enzyme induction (usually lessens effect of interacting drug) Orange sweat, urine, tears Permanently stained soft contact lenses

INH, PZA, RIF

-

INH

Common Adverse Reactions

PZA

EMB

RIF, RBT, RPT

RIF

Thrombocytopenia GI intolerance Phototoxicity DRUG INTERACTIONS Discoloration of body fluids

Patient

Baseline Examinations Recommended

All patients Patients at risk for hepatitis B or C Patients taking EMB HIV-infected patients

Patient All patients

Monitoring During Treatment

Patients taking EMB Extrapulmonary TB HIV-infected, pregnancy or early post-partum, chronic liver disease, regular EtOH use, abnormal baseline results, high risk or signs of toxicity

Mild INH-induced LFT ↑ in up to 20%, usually return to normal ↑ risk: HIV, hx liver disease, regular EtOH consumption, pregnancy or postpartum, other hepatotoxins ↑ risk: alcoholism, diabetes, malnutrition  give these people pyridoxine

Recommended Test AST, ALT, bilirubin, alkaline phosphatase, serum creatinine, platelet count Serologic tests Test visual acuity (Snellen chart) and color vision (Ishihara) Obtain CD4+ lymphocyte count

Recommendations Repeat monthly clinical evaluations (possible ADRs, adherence) Sputum AFB Q2 weeks Monthly sputum AFB/culture (until 2 consecutive cultures negative Additional susceptibility tests if culture positive after 3 months Question monthly regarding visual disturbances Repeat Qmonth Snellen and Ishihara if dose >15-20 mg/kg or >2 mo Evaluation depends on sites involved and ease specimens can be obtained Repeat lab monitoring for hepatotoxicity Compiled by Abbie Pettigrew, class of 2016

77 – Pulmonology

Pregnant or breastfeeding Infants/children

Special Populations

HIV Extrapulmonary disease

-

Liver Kidney

Organ dysfunction Failure/relapse XDR/MDR

Treatment Failure

Close Contacts

A positive culture after 4 months of treatment in whom medication ingestion was insured

Evaluate for latent infection and active disease

Pyridoxine supplement Avoid streptomycin Avoid EMB Three times weekly regimens Use DOT Multiple rifamycin drug interactions with ART Use DOT NOT Qweek continuation phase INH + RPT BIW INH-RIF or INH-RBT shouldn’t be used with CD4+ < 100 Risk of reactivation syndrome Generally similar to pulmonary disease Might need to avoid hepatotoxic agents Increase interval, NOT dose

-

Add at least THREE new drugs

-

Consult an expert Symptoms don’t improve in 2 months of therapy Symptoms worsen after improving initially Culture results + after 2 months of treatment Culture results become + after being -

Early Indications

-

TST or IGRA +

No prior history Documented history of completed LTBIB treatment Low risk High risk (children