PULMONARY

Editor: Jacob Lee, MD
Faculty Editor: Blake Funke, MD

Basics of Blood Gases

Author: Hannah Kieffer

Measuring Oxygenation - see also 'Hypoxia and Hypoxemia' for additional details

  • Systemic O2 Delivery = 13.4 x (Cardiac Output) x (Hb) x (O2 Saturation)

  • SpO2 vs PaO2: Before obtaining a blood gas, consider first whether you need laboratory testing to confirm oxygenation

SpO2 (pulse oximetry): reports oxygen saturation based on percentage of hemoglobin bound to oxygen; often considered a better reflection of oxygen content in the blood - Pros of SpO2: Non-invasive, easier to trend, inexpensive - Cons of SpO2: Less accurate in certain disease states as well as patients with darker skin and nail polish

PaO2 (partial pressure of oxygen in arterial blood): reports concentration of O2 in plasma - Pros of PaO2: provides more precise oxygenation status - Cons of PaO2: invasive (requires ABG), expensive (~$100-200)

When to get an ABG vs rely on SpO2: - Unreliable pulse oximetry wave form (e.g. non-pulsatile flow from ECMO, bad pleth) - Poor perfusion in severe shock - Severe anemia (SpO2 can be falsely reassuring) - Methemoglobinemia – artificially lowers SpO2 without affecting PaO2 and O2 delivery - When calculating PaO2/FiO2 ratio for determining hypoxemia severity (determine whether to prone patients)

A-a gradient: The difference between the oxygen levels in the alveoli vs arteries; helps determine the etiology of hypoxemia - Equation = PAO2 (alveolar O2) – PaO2 (arterial O2) - A-a gradient is assessing whether the oxygen being inhaled is getting into the blood - To calculate PAO2, MD Calc formula available - Acceptable level increases with age; to estimate normal A-a gradient= (Age +10)/4

Differential: see 'Hypoxia and Hypoxemia' for more details - High: Dysfunction to the alveolar/capillary unit, defect in diffusion, V/Q mismatch, or right-left shunt - Normal or Low: Hypoventilation or low FiO2

Measuring Ventilation

Ventilation is typically assessed by measuring the PCO2 (partial pressure of carbon dioxide) - PCO2 can be measured arterially (PaCO2; gold standard) or venously (PvO2; approximation of ventilation)

Blood Gases: ABG vs VBG

Blood Gas Reliable Values Pros Cons Comments
ABG pH, PaO2, PaCO2, HCO3 Gold standard for determining oxygenation, ventilation, and acid-base status Invasive and expensive. VBG usually adequate for clinical decision making. Usually obtained by RT, more cumbersome to obtain unless patient has an arterial line
VBG pH, PvCO2, HCO3 Non-invasive, cheaper, pH reliably correlates to ABG Cannot assess oxygenation, PCO2 and HCO3 are less accurate than ABG especially in certain conditions (shock, hypercapnia) Can be drawn off a peripheral IV or central line. A peripheral VBG PvO2 cannot be substituted for a Mixed Venous O2 from a central line

Culturally, we use VBGs most often for: - Assessing ventilation (pCO2):** - Concern for COPD exacerbation, to assess CO2 retention - Respiratory support adjustments: Assessment of patient's response to BiPAP or mechanical ventilation / determine whether setting changes are indicated - Generalized mental status changes, e.g. lethargy, confusion - Hypoventilation -> increased pCO2 and decreased pH -> encephalopathy

  • Assessing Acid/Base status (DKA, renal failure, sepsis, etc)
  • Important to note, as stated above, VBG PCO2 and HCO3 are less accurate in shock and hypercapnia, so interpret with caution

Assessing Respiratory Acid/Base Status:

Respiratory Status pH PaCO2 (Primary Change) HCO3 (Compensation) Etiology/DDx
Normal 7.36-7.44 36-44 22-26
Respiratory Acidosis =< 7.35 >= 45 mmHG Acute: 1 mEq increase per 10 mmHG increase in PCO2; Chronic: 3-4 mEq increase per 10 mmHg increase in PCO2 Impaired gas exchange, decreased respiratory drive, chest/diaphragm dysfunction, iatrogenic (vent issues)
Respiratory Alkalosis >= 7.45 =< 35 mmHg Acute: 2 mEq decrease per 10 mmHg PCO2; Chronic: 4-5 mEq decrease per 10 mmHg decrease in PCO2 Increased respiratory drive (pain, fever, anxiety), hypoxia-induced (high altitude, PE, anemia), sepsis, iatrogenic (vent issues)

In a compensated respiratory disturbance (i.e. normal pH): you do not need to intervene and try to normalize the PCO2)

Further management largely depends on underlying cause - In general, avoid correcting respiratory acidosis with sodium bicarbonate, even if not fully compensated; there is a lack of evidence demonstrating clinical benefit and potential risks associated - See Nephrology section for further discussion on metabolic acid/base disorders

Hypoxia and Hypoxemia

Author: Jacob Lee

Background and Definitions

Hypoxia: A condition where the oxygen supply is inadequate either to the body as a whole (general hypoxia) or to a specific region (tissue hypoxia)

Hypoxemia: low oxygen in arterial blood, as measured by PaO2 or SpO2

Can be both hypoxic without hypoxemia (i.e. anemia, cardiogenic shock) and hypoxemic without hypoxia (i.e. mild V/Q mismatch states) but severe hypoxemia will almost always cause hypoxia

Measuring Oxygenation

Two major ways to measure oxygenation, which are inter-related:

SpO2 (oxygen saturation by pulse oximetry or "pulse ox") - the percentage of hemoglobin that's saturated with oxygen; ≥95% considered normal

PaO2 - partial pressure of oxygen in arterial blood; 75-100 considered normal

SpO2 and PaO2 can be interconverted using the oxygen-hemoglobin dissociation curve (sigmoidal curve) - PaO2 ~100 → SpO2 ~98-100%; PaO2 ~ 60 → SpO2 ~90%; Below PaO2 of 60, small decreases in PaO2 cause large drops in SpO2 (hemoglobin loses affinity for oxygen) - The curve can shift to the right (hemoglobin has lower affinity for oxygen) due to elevated levels of CO2, low pH, and increased temperature/fever

A-a gradient: the difference in the partial pressure of oxygen as measured in the alveoli (A) and arterial blood (a); normal is (Age+10)/4; See 'Basics of Blood Gases' for more details

Mechanisms of Hypoxia

  • Hypoxemic Hypoxia – low PaO2 leads to poor tissue oxygenation (examples below)
  • Anemic Hypoxia – normal PaO2 but reduced hemoglobin leads to reduced oxygen carrying capacity and thus decreased tissue oxygenation (i.e. anemia, CO poisoning, methemoglobinemia)
  • Circulatory Hypoxia – states of inadequate perfusion (shock) leading to poor tissue oxygenation (i.e. shock, heart failure, ischemia)
  • Histotoxic Hypoxia – inability of tissues to use oxygen (i.e. cyanide poisoning, mitochondrial dysfunction, sepsis)
  • Demand Hypoxia – oxygen requirements exceed oxygen delivery (i.e. hypermetabolic states such as thyrotoxicosis, sepsis, prolonged seizures, prolonged exercise)
Mechanism Pathophysiology Improvement with Supplemental O2 A-a Gradient Examples
Low FiO2 Low fraction of inspired oxygen causes low PAO2 and thus low PaO2 Yes Normal High-Altitude
Hypoventilation Low oxygen delivery from low RR or TV to the alveoli reduces PAO2 and thus low PaO2 Yes, if ventilation (RR or TV) increase Normal Neuromuscular disease, obesity hypoventilation syndrome, opioid overdose
V/Q Mismatch 1. V/Q >1 (more ventilation relative to perfusion) PAO2 is normal but inadequate perfusion limits gas exchange
2. V/Q <1 (less ventilation relative to perfusion) blood oxygenation is impaired due to poor gas exchange		 Yes Elevated 1. Pulmonary Embolism
2. Pneumonia, ARDS, Pulmonary Edema
Right-to-left Shunt 1. Anatomic: Blood bypasses the alveolar-capillary interface and does not participate in gas exchange
2. Physiologic: Gas exchange is impaired		 1. Anatomic - no
2. Physiologic - yes		 Elevated 1. Heart defects, AV malformations
2. Diffuse parenchymal disease
Diffusion Limitation Adequate PAO2 but oxygen cannot effectively cross into the bloodstream Yes Elevated ILD

Important to note that causes of hypoxia/hypoxemia are often multifactorial and may not fit neatly into only one of the above categories

Differential diagnosis for hypoxia based on anatomical location

Anatomical Location Differential Diagnosis
Airways COPD (chronic bronchitis), CF/bronchiectasis, bronchitis, severe asthma
Alveoli Blood (DAH), Pus (Pneumonia), Water (pulmonary edema) Protein/Cells/Other:(ARDS, pneumonitis), atelectasis, emphysema
Interstitium/Parenchyma Interstitial lung disease
Vascular/Cardiac Pulmonary Emboli, intra/extrapulmonary shunts
Pleural Space and Chest Wall Pleural effusions, PTX, neuromuscular weakness, tense ascites
More likely to cause dyspnea, need to be severe to cause hypoxia

Evaluation

  1. For new or increasing oxygen requirements, evaluate patient at bedside with a focused physical exam, taking particular note of signs of respiratory distress
  2. Ensure pleth has good waveform – consider switching pulse ox probe to different anatomic location (earlobe, forehead) if poor circulation (vasculopathy, scleroderma)
  3. Labs: Blood gas (VBG vs ABG), Lactic acid, CBC; consider infectious workup with blood/sputum cultures, RPP, CMP, BNP, troponin, lipase.
  4. D-Dimer rarely helpful in our patient population
  5. Imaging:
Study Indications Comments
CXR First study for hypoxia / hypoxemia
CT Indicated if CXR nondiagnostic or evaluating for pathology not well identified with CXR - Without contrast – best to evaluate lung parenchyma
- High Resolution – best for ILD
- With contrast – highlights the pleura and mediastinum
- CTA/CTPE – CTA bronchial artery protocol for massive hemoptysis, CTPE for PE
US Evaluation for shunting TTE with bubble study great for evaluation of anatomic shunt; POCUS helpful for evaluation of lung slide/Kerley B lines as well as diaphragm paralysis
  1. Outpatient PFTs if suspected obstructive or restrictive disease

Management

  • Should be directed at underlying cause
  • For acute decompensation - bronchodilators, IV diuretics, IV antibiotics, anticoagulation, or steroids can be given depending on clinical picture

  • See 'COPD Exacerbation, Heart Failure, Pneumonia, Pulmonary Embolism, Chest Tubes' for more specific management strategies

  • Supplemental Oxygen Therapy

  • Goal SpO2 is 92-96% for most pts; 88-92%; for patients with chronic hypoxia from COPD (i.e., on home O2)
  • See 'Modes of O2 Delivery' for nuances in choosing the correct oxygen delivery system in patient

Pulmonary Function Tests (PFTs)

Author: Jacob Lee

Full PFTs include: Spirometry + Body Plethysmography + DLCO

  • General indications to order PFTs: unexplained respiratory signs/symptoms, preoperative risk assessment, diagnosis of COPD, ILD
Test Important Measurements Indications/Uses
Spirometry FVC, FEV1, PEF (with and/or without a bronchodilator) Diagnosis of obstructive lung disease/asthma, disease monitoring
Body Plethysmography TLC, RV Diagnosis of restrictive lung disease, evaluation of air trapping, disease monitoring
Diffusion Capacity DLCO Differentiation between intrapulmonary and extrapulmonary restriction, unexplained hypoxemia, disease monitoring
  • Relative Contraindications: acute MI, decompensated heart failure, PTX, PE, recent surgery, cerebral aneurysm, respiratory infections, hemoptysis

Tips for ordering

  • Initial diagnostic workup: Full PFTs with bronchodilator challenge
  • Chronic Lung disease: Depends on disease being monitored
  • Asthma: Typically patients will have a PEF meter they can use at home and do not need formal reassessment routinely; can check FEV1 with spirometry
  • COPD: Spirometry to track FEV1/FVC over time ± DLCO
  • Cystic Fibrosis: for flares, will typically only track FEV1 while inpatient, will get repeat full set of PFTs once flare has resolved to establish new baseline
  • ILD: Full PFTs

Interpretation

  • First, assess validity. The PFT report will state whether the results were consistent and reproducible
  • When looking at specific values, you should look at percent predicted, then if low should look at the actual value and if it falls below the confidence interval to confirm

Obstructive Pattern: - FEV1/FVC =< 0.7 (GOLD) or < LLN (ATS/ERS) indicates obstructive disease - A low FVC with an increased TLC is also suggestive of obstructive lung disease, but is not diagnostic per ATS/ERS/GOLD guidelines - Increased RV and TLC compared to FVC is suggestive of air trapping

Restricted Pattern: - TLC < 80% (GOLD) or < LLN (GOLD/ATS/ERS) is diagnostic of restrictive disease - Reduced FVC is suggestive, but not diagnostic of restrictive disease - FEV1 is commonly low too but FEV1/FVC ratio is normal in isolated restrictive disease

Mixed Obstructive and Restrictive Deficits: - Both low FEV1/FVC and TLC

Impaired Gas Exchange: - DLCO can help differentiate between pathologies of both obstructive and restrictive lung diseases and may even suggest pathology in the absence of obstructive or restrictive patterns

Normal DLCO: - Normal DLCO + obstruction: asthma, early COPD/CF - Normal DLCO + restriction: pleural disease, chest wall disorders (obesity, scoliosis), neuromuscular disorders (ALS, MG)

Low DLCO: <LLN (ATS/ERS) or <80% (GOLD) is low - Low DLCO + obstruction: emphysema/late COPD, CF, bronchiectasis - Low DLCO + restriction: ILD, pneumonitis, lung resection - Low DLCO + normal spirometry: anemia, pulmonary hypertension, pulmonary embolism, early ILD, pulmonary edema, mixed obstruction/restriction pattern (pseudonormalization of PFTs)

High DLCO: >120-140% or > 95th percentile/ULN (ATS/ERS) - L→R shunt, alveolar hemorrhage, polycythemia, asthma

Bronchodilator response: indicates reversible airflow obstruction (common in asthma) - Positive: Increase in FEV1 and/or FVC by ≥ 12% AND ≥ 200 mL from baseline after bronchodilator administration

Can try to induce bronchospasm/bronchoconstriction with a methacholine challenge to confirm diagnosis of asthma but test is imperfect

Acute Asthma Exacerbation

Author: Rafael J. Fernandez III, Stacy McIntyre

Presentation

  • Sub-acute to acute progressive worsening of dyspnea, chest tightness, wheezing, and cough
  • Important historical cues: Prior hx of asthma, adherence to controller medications, triggers (exercise, allergens, cold)
  • Risk stratifying: Hx of intubations/ exacerbations, recent steroid course for exacerbation
  • Physical exam: wheezing, poor air movement, tachypnea, ↑ work of breathing, hypoxemia
  • Peak flows can help and are often cited in literature but do not change management acutely, can be useful as baseline for assessing response to therapy.
  • PEF <200 L/min or PEF <50% predicted indicates severe obstruction, PEF <70% predicted indicates moderate exacerbation)

Evaluation

Generally aimed at ruling out causes for exacerbation and other diagnoses; these are not required but should be considered in pts being admitted for inpt management: - EKG, trop, BNP, D-dimer to assess for cardiac cause (ACS, CHF, PE) - CXR to rule out underlying process (PNA, PTX, atelectasis) - ABG/VBG not routinely needed unless ill-appearing, tachypneic, or lethargic/altered - Dangerous signs and possible ICU if: - Tachypnea >30 and/or significantly increased work-of-breathing - Hypercapnia or even normocapnia (these pts are usually hyperventilating; a normal CO2 in a severe asthma exacerbation could indicate impending respiratory failure) - Altered mental status - Requiring continuous nebulizers

Management

Good asthma care requires frequent re-evaluation. Generally, reassess q1h after treatment initiation. If deteriorating, step up the ladder of management

  • ABC: if not protecting airway, intubate and admit to ICU
  • Peak expiratory flow (Order in EPIC "Peak Flow Measurement"). If pt cannot do it, consider A/VBG if ill-appearing, tachypneic, lethargic/AMS, or thinking about engaging ICU
  • SpO2 goal 93-95%. Avoid hyperoxia
  • Further work-up: Not required, but aimed at ruling out causes of exacerbation and other dx
  • CBC w/ diff (looking at eosinophils)
  • CXR to rule out underlying process (PNA, PTX, atelectasis)
Mild/Moderate Severe ICU
Assessment Physical Exam: Wheezing, Phrase Dyspnea, Tachypnea, Tachycardia (100-120), No Accessory Muscle Use
Objective Data: O2 Saturation 90-95% on RA
, PEF > 50% Predicted		 Physical Exam: Wheezing, Single Word Dyspnea, + Accessory Muscle Use, Tripoding, Tachypnea >30, Tachycardia >120
Objective Data: O2 Saturation <90% on RA, PEF < 50% Predicted		 Physical Exam: Drowsy, AMS. silent chest, Increased work of breathing
Objective Data: CO2 on Blood Gas Low at first (Hyperventilation) Normal or High → Impending Respiratory Failure, Requiring Continuous Nebulizers to maintain O2 saturations
Management SABA Nebulizer ± Ipratropium, Supplemental O2 to 93-95%, Begin Oral Prednisone 60mg SABA/Ipratropium Nebulizer, Supplemental O2 to 93-95%, Begin Oral Prednisone 60mg, Consider IV Magnesium 4g 20 minutes, Consider High Dose ICS Continuous DuoNebs, IV Methylprednisolone 125 q6hr (as likely can't protect airway), IV Magnesium 4g 20 minutes, Consider High Dose Inhaled Corticosteroid, NPO, IV Fluids to make up insensible losses (consider comorbidities though)

Adapted from GINA 2022 Guidelines, Box 4-4 (https://www.ginasthma.org)

Further Management

  • Corticosteroids: dosing based on severity of illness
  • Oral equivalent to IV (Lancet 1986;1:181-184)
  • Transition to PO and lower dose after improving air movement, work of breathing and gas exchange
  • Will need minimum of 5-7 days of oral corticosteroids.

  • Good data for no need to taper in general population, sometimes considered in someone with multiple severe exacerbations.

  • Step down SABA-Nebulizer treatments based on wheezing

  • Inspiratory/Expiratory wheezing q2 -> q3; Mostly Expiratory wheezing q3 -> q4; Minimal Wheezing q4 -> q6 or PRN. (Pediatrics 2000; 106 (5): 1006–12)
  • No need for empiric antibiotics unless there is concern for bacterial infection, then treat as Pneumonia (see Pneumonia chapters)

Prior to discharge:

  • Ensure that pt is on appropriate controller medications.
  • See outpt management section but consider starting an ICS/LABA as part of SMART (JAMA 2018; 319(14):1485–1496)
  • Evaluate for causes of acute exacerbation to prevent future events (noncompliance, resp viruses, allergies, exposures, etc.). Evaluate for asthma inflammatory phenotype after recovery (IgE, peripheral eos, ABPA)
  • Can consider writing a simple asthma action plan (https://ginasthma.org/wp-content/uploads/2021/05/GINA-Pt-Guide-2021-copy.pdf)
  • Consider follow up with PCP vs. pulmonologist for evaluation of outpt regimen

COPD Exacerbation

Author: Brian Haimerl

Etiology: infection (~70%; viral more often than bacterial), allergens, pollution, seasonal variations (colder temperatures), PE

Presentation: acute increase/worsening (< 14d) in 1 or more "cardinal symptom" (cough, sputum production/purulence, dyspnea)

  • Often associated with tachypnea, tachycardia, and diffuse wheezing
  • Confounders/contributors: Pts with COPD can have other causes of respiratory distress including ACS, decompensated heart failure, PE, PNA, PTX, sepsis, acidosis

Evaluation

Initial Assessment: ABCs

  • Airway: Ensure pt is protecting airway - CO2 narcosis can impair consciousness
  • Breathing: focus on respiratory status
  • Evaluate for wheezes, rales, rhonchi, stridor, air movement, and work of breathing
  • Severe respiratory insufficiency: accessory muscle use, fragmented speech, inability to lie supine, diaphoresis, agitation, asynchrony between chest and abdominal wall with respiration, failure to improve with initial emergency treatment
  • Impending respiratory arrest: Inability to maintain respiratory effort, cyanosis, hemodynamic instability, and depressed mental status
  • Circulation
  • Assess for signs of hemodynamic instability (hypotension, severe tachycardia or tachypnea, cold vs warm extremities, capillary refill, mental status)

Subsequent Workup: - Labs: ABG/VBG, CBC, CMP, troponin, BNP, sputum cx, RPP, blood cultures - Imaging: CXR, POCUS (assess for lung slide, B-lines), - Consider: - Lactate, procalcitonin, urine Legionella, fungal workup in select pts - Extremity Doppler US (Assess for DVT) - CTA PE: Not recommended for every pt admitted for COPD exacerbation; use clinical judgement and scoring tools (Well's Criteria) to make clinical decision; studies show up to 25% of patients admitted for AECOPD have concurrent PE

Management

Supplemental O2: target saturation 88-92% for everyone - BiPAP typically appropriate for severe COPD exacerbation unless contraindication (vomiting, obtundation, facial trauma) - BiPAP is ordered as IPAP and EPAP, 12/5 is often a good start - If obtunded, in severe respiratory distress, hemodynamic instability →intubation

Bronchodilators/Inhalers - Order "Respiratory Care Therapy Management Protocol" at VUMC - RT evaluates the pt and based on physical exam will give a duoneb. Continues to assess the pt and treats based on severity of the exacerbation - If ordering bronchodilators individually: - Albuterol 2.5 mg diluted to 3 mL via nebulizer or 4 to 8 inhalations from MDI every 4 hours while awake (RT) or more frequently if needed - Ipratropium 500 mcg via nebulizer, or 4-8 inhalations from MDI q4 hrs while awake - Preferred is Duoneb (albuterol and ipratropium) q4-6 hours at VUMC - There is no respiratory order protocol at the VA, order individually as above - Home Inhalers: Usually continue home long-acting bronchodilators (LABA/LAMA) w/ or w/o ICS during exacerbations unless receiving frequent scheduled nebs (per GOLD 2023)

Steroids: Indicated for moderate to severe exacerbations (almost anyone being admitted) - IV vs. PO: studies have shown no significant differences in treatment failure, mortality, hospital readmissions, or LOS between IV or PO - Generally, PO prednisone 40mg x5d is appropriate - In severe exacerbations, may receive IV methylprednisolone 125mg in ER (this will count as day 1 when converting to PO prednisone) - Consider steroid taper if pt has not substantially recovered, has frequent exacerbations,

Antibiotics: Recommended by GOLD guidelines if all 3 cardinal symptoms or 2 if one is purulent sputum - Azithromycin (500mg x 1 then 250mg daily x 4 or 500mg daily x 3) or doxycycline 100 mg BID if concern for QT prolongation. Can consider respiratory fluroquinolone in certain high-risk pts - Pseudomonal coverage if: chronic colonization or infection past 12mo, FEV1 <30% predicted, bronchiectasis, BSA use w/in past 3mo, chronic systemic glucocorticoid use - Refer to Pneumonia in Infection Disease chapter if treating concomitant pneumonia

Other Inpatient Therapies - Magnesium: Often used In the ED (2g IV mag sulfate), though not great data. Has bronchodilator activity and reduced hospitalizations when used in stable COPD pts - Reasonable to give as low risk (consider renal insufficiency or myasthenia patients) - Pulmonary Hygiene: consider guaifenesin / other airway clearance therapy

Discharge Planning: - Controller medications/inhalers (see COPD in Outpt chapter) - Make sure any new inhalers are covered by insurance prior to discharge - Provide inhaler education and consider use of a spacer - Vaccinations (influenza, COVID, pneumococcal, RSV) - Early follow-up w/ COPD provider (w/in 1mo) -- Increased 90d mortality for those who do not attend early f/u - Fellows will often arrange early outpatient follow up if on a pulmonary service

Cystic Fibrosis (CF) Exacerbation

Author: Hannah Kieffer

Background

  • Presentation: Acute worsening of pulmonary symptoms such as new/worsening cough, congestion, sputum production or change in sputum quality, dyspnea. May have constitutional symptoms including fever, fatigue, poor appetite
  • Pathogenesis: viral infections, bacterial overgrowth (most common include Pseudomonas, S. aureus, Burkholderia), NTM, treatment non-adherence

Evaluation

  • History: Always ask about hemoptysis – see "Hemoptysis" section if present
  • Labs: Sputum culture (specify CF culture), RPP
  • Imaging: CXR PA and lateral
  • See "Cystic Fibrosis" Admission order set in Epic to reference work up suggestions

Severity Grading

  • No exact protocol. Determined by the degree of change from baseline versus the severity of the symptoms

Management

  • All pts need a Cystic Fibrosis Pulmonary consult (unless on Rogers Pulmonary if attending specializes in CF). FYI there is no fellow so don't worry when you have to page an attending
  • Often these pts are direct admissions from CF clinic and the attending will help guide management
  • Notably, some mild cases do not require admission; can be managed outpatient with increased airway clearance frequency and oral antibiotics

Inpatient Management: for moderate to severe exacerbations

  • All CF pts are placed on contact precautions no matter the indication for their hospitalization

Antibiotic selection - Be aware that the antibiotic doses are NOT the typical doses used for other indications. Use Epic Order Set: Adult Cystic Fibrosis (or per CF team, pharmacy) - Check CF notes, recent hospitalizations, culture data (e.g. MRSA, MSSA, Pseudomonas) to determine previously colonized bacteria to target - If they were recently admitted and improved on a certain antibiotic regimen, it is usually a good empiric choice. CF team will ultimately guide regimen - Most patients will receive dual IV anti-pseudomonal coverage (per previous CF Foundation recommendations) - General coverage for Pseudomonas: penicillin class (cephalosporin, carbapenem, extended penicillin) AND aminoglycoside or ciprofloxacin. Second line Colistin. - General coverage for MRSA: vancomycin (Bactrim or linezolid for allergies) - Treatment duration is based on improvement in symptoms and FEV1 recovery, usually 14-21 days - In most cases, hold home suppressive antibiotics (inhaled tobramycin, azithromycin) during a flare. Check with CF attending as there are some exceptions

Airway/sputum clearance - Schedule Albuterol nebs prior to airway clearance regimen or inhaled treatment - Continue home regimen. May include: Pulmozyme, hypertonic saline, positive end expiratory pressure valve (PEP e.g. Flutter, Acapella), chest percussive devices (vest, wand) - See 'Airway Clearance Therapy' for additional details - Consider increasing frequency of airway clearance regimen from home baseline

CF modulators (e.g. Trikafta -ivacaftor/tezacaftor/elaxacaftor): - Continue if on at home - Needs a non-formulary order to use own supply - Time with fat rich meal for absorption

Nutrition/GI - Continue any home pancreatic enzymes, order at bedside for pt administration - Always continue ADEK vitamins - Daily to 3 times a week weight checks - Nutrition consult - Should be on a bowel regimen

Other - Glucocorticoids - Consider if patient presents with features of acute asthma episode - Note: their use has not been demonstrated to improve outcomes - Tamiflu if test positive for Influenza

DIOS - Distal Intestinal Obstruction Syndrome

  • Acute obstruction (complete or incomplete) in ileocecum by inspissated intestinal contents. Presents with progressive cramping, abdominal pain (RLQ)/distension, constipation, poor appetite, and possibly vomiting that often looks like mechanical obstruction
  • Pathogenesis: multifactorial including insufficient pancreatic enzyme activity, dehydration, and intestinal dysmotility
  • CT can help rule out acute intraabdominal pathology (intussusception, SBO, appendicitis, volvulus) and typically shows proximal small bowel dilation and stool burden in distal ileum
  • Treatment: If tolerating PO, treat with Miralax and/or Golytely. If not tolerating PO or with bilious vomiting, might need hyperosmolar contrast enema (gastrografin). RARELY requires surgery, try medical management first
  • Prevention is key! Pts with CF should be on a bowel regimen in the outpatient setting.

Hemoptysis

Authors: Angela Liu, Henry Brems

Background

  • Distinguish between massive (>600cc/24hr or >100cc/hr) and non-massive hemoptysis. Can be difficult to quantify expectorated blood volume and volume that is retained in lungs
  • Massive is potentially life-threatening due to impaired ventilation
  • UGIB (hematemesis) and nasopharyngeal bleeds can easily mimic hemoptysis

Presentation based on source of bleed:

Structure Etiologies
Airways Bronchitis (common cause of non-massive), bronchiectasis (especially in CF pts), neoplasm
Alveolar/Parenchymal Infectious (bacterial PNA, abscess, TB, fungal, aspergilloma), rheumatologic (Goodpasture's, GPA, Behcet's)
Vascular PE, AVM, CHF, mitral stenosis, bronchovascular fistula
Other Coagulopathy, traumatic, foreign-body, iatrogenic, cocaine-induced

Evaluation

  • Determine coagulation status: medications, PT/PTT, platelets
  • Labs: CBC, BMP, coags, UA (for hematuria), ABG (evaluate oxygenation), type and screen
  • Consider ANA, ANCA, anti-GBM, anti-cardiopipin, IFNG release assay, sputum culture (bacteria, fungal, AFB), sputum cytology (if not undergoing bronchoscopy), and RPP depending on clinical context
  • Imaging: CXR first (to evaluate etiology and to localize the source to a side). Chest CT depending on prior workup, severity of bleed, and stability of pt
  • Bronchoscopy is sometimes indicated to localize bleeding source.

Management

  • Urgent evaluation if any hemodynamic compromise, hypoxia, hypercarbia, or respiratory distress
  • Ensure a secure airway: massive hemoptysis may require intubation and MICU transfer
  • Reverse underlying coagulopathy if present. Consider trending HCT
  • If unilateral bleed, place bleeding lung down. Ex: if the source is left lung, place pt on left side to prevent filling 'good' lung with blood (include this info in sign-out if known)
  • Urgent Pulmonary consult if clinical instability: Bronchoscopy is diagnostic and therapeutic.
  • Obtain CT Bronchial Artery Protocol if concern for bronchial artery source (especially in CF pts) so embolization can be planned
  • Order this at VUMC with a CTA Chest (NOT a CTA PE as that will be timed incorrectly) and include "bronchial artery protocol" in comments for the study
  • Consider IR consult for angiography as diagnostic and therapeutic option
  • Consult early if there is massive hemoptysis. If bronchoscopy is attempted but fails to stop the bleed, they can get to angiography fastest if IR has already been made aware
  • Recurrent hemoptysis is still typically controlled with repeat embolization.

Interstitial Lung Disease (ILD)

Authors: Madelaine Behrens, Jacob Lee

Background

  • Heterogenous group of parenchymal lung diseases characterized by inflammation and subsequent fibrosis of the lung parenchyma, particularly the interstitium
  • Pathophysiology: Repetitive cycles of inflammation leads to scarring with associated loss of lung volume, compliance and impaired gas exchange

Etiologies

  • ILD can be broadly divided into primary (idiopathic) causes and secondary causes
Idiopathic Interstitial Pneumonias (IIPs) Secondary Causes
Chronic Fibrosing: Idiopathic pulmonary fibrosis (IPF), Nonspecific interstitial pneumonia (NSIP) Connective tissue disease: systemic sclerosis (most common cause of ILD), Sjogren's, RA (ILD is the most common pulmonary manifestation), dermatomyositis, polymyositis, SLE (least common to cause ILD), MCTD
Smoking-Related: Respiratory Bronchiolitis-Associated ILD (RB-ILD), Desquamatitive interstitial pneumonia (DIP) Hypersensitivity pneumonitis (organic): farm exposures, chickens, pesticide, stored grains, mold (e.g. water damage in home, hot tub)
Acute/Subacute: Acute interstitial pneumonia (AIP), Cryptogenic organizing pneumonia (COP, formerly BOOP) Iatrogenic*: amiodarone, bleomycin, MTX, busulfan, immunotherapies, TKI, TNF-a inhibitors, nitrofurantoin, hydralazine, radiation
Rare IIPs: Lymphoid interstitial pneumonia (LIP), Pleuroparenchymal fibroelastosis (PPFE), Acute fibrinous and organizing pneumonia-pattern (AFOP) Pneumoconioses (inorganic): coal mines, silica, asbestos, beryllium, organic solvents, heavy metals
Unclassifiable ILD Sarcoidosis
Vasculitis: granulomatis with polyangiitis, eosinophilic granulomatosis with polyangiitis
Other: pulmonary alveolar proteinosis, lymphangioleiomyomatosis, amyloidosis, pulmonary Langerhans cell histiocytosis

*Over 150 medications are linked to ILD (www.pneumotox.com is the best reference for drugs associated with specific ILD patterns)

Evaluation

Symptoms: progressive, dry cough, dyspnea, and fatigue are classic for IIPs - Other symptoms are usually related to the underlying secondary cause

History: - PMHx: AI disease (should ask about Raynaud's in particular), vasculitis, arthritis, lung disease - Occupational/environmental exposures: pets (birds), allergens, mold/stagnant water, asbestos, silica, coal, beryllium, heavy metals - Medications/Therapeutics: amiodarone, nitrofurantoin, chemotherapy, immunotherapy, radiation - Smoking and smoke exposure

Physical Exam: - Respiratory: fine, 'velcro-like' crackles that do not clear with cough suggest fibrosis; wheezing, rhonchi are atypical - Cardio: TR suggests pulmonary HTN - MSK: clubbing, joint swelling/tenderness/deformities - Skin: Raynaud's, sclerosis, rash

Diagnostics:

Imaging: - CXR: first study but not usually sensitive nor specific enough to diagnose, reticular infiltrates may be seen - CT non-contrast is best to evaluate the lung parenchyma. In particular, HRCT protocol (inspiratory and expiratory films in the supine and prone position) is the gold standard for diagnostic imaging - Supine vs prone imaging helps rule out atelectasis - Inspiratory vs expiratory cuts help to identify air trapping (seen as mosaicism worse with expiration)

IIPs Pattern and Radiographic Features

IIPs Pattern Radiographic features Clinical features
Usual interstitial pneumonia (UIP) Septal thickening, Basilar and subpleural (peripheral) predominant fibrosis/ reticulation, honeycombing, and traction bronchiectasis/ bronchiectasis with minimal GGOs. Predominantly seen in IPF, but is also seen in many progressive fibrosing diseases, as well as radiation and chemo/immunotherapy induced ILDs. Generally this radiographic pattern progresses more quickly irrespective of the underlying cause.
Non-Specific Interstitial Pneumonia (NSIP) Bilateral, Peri-bronchovascular predominant GGOs with subpleural sparing and most pronounced at the bases; increased reticular patterns, and mosaic attenuation due to air trapping. Minimal or absent honeycombing May be idiopathic, or secondary to medications or connective tissue diseases. Steroid responsive. Can coexist with UIP
Acute interstitial pneumonia (AIP) Diffuse GGOs with consolidation and lobular sparing; radiologically indistinguishable from ARDS Rapid onset (7-10 days) fever, cough, SOB. High morbidity/mortality, usually presenting as ARDS.
Cryptogenic organizing pneumonia (COP) Patchy GGOs with consolidation most predominant in the periphery and at the bases; Subpleural and peribronchial multifocal migratory consolidations. Can present clinically with cough, DOE, malaise, fevers. Steroid-responsive (must rule out inciting process first by obtaining infectious workup, reviewing meds, radiation history, etc.)
Pattern Radiographic features Clinical features
Desquamative interstitial pneumonia (DIP) Many have normal CXRs. Ground glass opacities without the peripheral reticular opacities characteristic of UIP Young current or former smokers with subacute dyspnea, wheezing and cough. In biopsy, intraluminal macrophages containing dusty light brown pigment. Good prognosis - reversible with smoking cessation.
Respiratory bronchiolitis-associated ILD (RB-ILD) Bronchial thickening, centrilobular nodules, patchy GGOs; predominantly upper-lobe distribution Young current or former smokers with subacute dyspnea, wheezing and cough. In biopsy, intraluminal macrophages containing dusty light brown pigment. Good prognosis - reversible with smoking cessation.

Secondary ILDs with Characteristic Imaging Findings

Pattern Radiographic features Clinical features
Hypersensitivity Pneumonitis Centrilobular nodules, mosaic air trapping in an upper lobe-predominant distribution Acute: flu-like symptoms, dyspnea without wheezing that subsides within hours to days after removal of inciting antigen. Chronic: insidious onset fatigue, cough, dyspnea, with bilateral rales
Sarcoidosis Bilateral hilar and mediastinal lymph node enlargement; parenchymal involvement can present as reticulonodular opacities, nodules. Fibrosis will appear in late stages Highly variable disease manifestations. Typically sudden onset with spontaneous remission in the majority of patients

Labs without Pulmonology consult: - ESR, CRP, ANA w/ reflex ENA, RF, CCP, C3, C4 - CBC with diff: evaluate eosinophilia or cytopenias concerning for autoimmune disease - CMP, CK, aldolase: to assess for other organ involvement, hypercalcemia (can be seen in sarcoid or other granulomatous disease) - RPP, sputum culture

Labs in conjunction with Pulmonology: - Myositis panel: anti-synthetase syndrome commonly presents without muscle signs/symptoms, anti-Scl-70 and anti-RNP - Hypersensitivity pneumonitis panel: (needs to be sent to a highly specialized lab for crucial immunoprecipitation technique) - Histo antigen, blasto antigen, aspergillus galactomannan, 1-3-β-D-glucan, sputum GMS; consider NTM and HIV

PFTs: usually restrictive lung disease +/- low DLCO - Spirometry: expect to see ↓ FEV1 and FVC with FEV1/FVC >0.7 - Body Plethysmography: ↓ TLC, RV, and/or FRC - Sarcoidosis can present as obstructive, restrictive, or mixed pattern - DLCO: Usually low and monitored for disease progression

Bronchoscopy and biopsy: - BAL is not diagnostic ILD: may help rule out infection and understand the underlying inflammatory response - Consider when there is diagnostic uncertainty or concern for superimposed infection - Surgical lung biopsy is gold standard but often patients too sick to tolerate - Transbronchial lung biopsy (TBLB) is usually nondiagnostic in ILD outside of sarcoidosis or HP. Cryobiopsy can be considered an alternative to surgical lung biopsy for histopathology.

Other tests to consider: - 6-minute walk test: prognostic value - TTE to evaluate for pHTN - SLP evaluation for indolent aspiration

Management

Acute exacerbation (AE-ILD) - Diagnostic criteria: known diagnosis of ILD, clinical decline within 1 month duration, CT evidence of new/worsening bilateral GGO and/or consolidation superimposed on a background pattern consistent with the ILD, NOT due to another cause - Chest CT is imaging standard - Important to distinguish between infection and ILD flare – where bronchoscopy can be particularly helpful - Rule out worsening respiratory status due to identifiable cause (heart failure, infection, PE), support with supplemental O2 - Discontinue any potentially contributory medications - Empiric antibiotics are generally a good idea while ruling out infection; for patients on IS, empiric coverage of PJP should be considered - If infection ruled out, pulse-dose steroids followed by a prolonged taper is recommended although response is subtype dependent and often limited. This should be done under pulmonary guidance - Don't make changes to IS without pulm/rheum input - Often patients require ICU care due to oxygen requirements, important to discuss GOC and Code Status each hospitalization - ECMO, intubation with mechanical ventilation can be a bridge to transplant

Chronic Therapy

Antifibrotics

  • Main utility is in IPF; can be used for fibrosis due to any etiology

Nintedanib (Ofev): Tyrosine Kinase Inhibitor - INBUILD & INPULSIS trials: decreases rate of decline in FVC, no reduction on mortality - Adverse effects: abdominal pain, nausea, vomiting, diarrhea, anorexia, weight loss, elevated AST and ALT

Pirfenidone: TGF-B inhibitor - RELIEF & ASCEND trials: May slow rate of decline of DLCO and 6MWT distance, no mortality reduction - Adverse effects: GI discomfort and photosensitivity

Immunosuppression

  • MUST rule out infection prior to use
  • Generally use mycophenolate and azathioprine; can also use cyclophosphamide, rituximab, and calcineurin inhibitors
  • Steroid/immunosuppression responsive (generally): COP, NSIP (cellular subtype), CTILD, inflammatory HP, sarcoidosis, vasculitis-associated ILDs
  • Not usually steroid responsive: IPF, fibrotic HP
  • For AE-ILD, steroids may still be given as a last resort

Other Considerations

  • Smoking cessation and exposure elimination are paramount
  • Drug removal: consider discontinuing amiodarone, checkpoint inhibitor, etc
  • Hypersensitivity pneumonitis: antigen exposure elimination
  • Eosinophilic pneumonia: steroids; biologics can be used (send to Allergy clinic)
  • Consider lung transplant eval for progressive or rapidly decompensating fibrotic lung disease
  • Pulmonary rehabilitation is crucial (trend towards mortality benefit)

Lung Masses

Author: Sybil Watkins, Chandler Montgomery

Background

Definitions

  • Lesion < 3 cm = pulmonary nodule
  • Lesion > 3 cm = lung mass
  • Pulmonary nodules are common and often benign, but presence of lung mass (>3cm) should prompt workup as chance of malignancy is high (>50%)
  • Refer to "Pulmonary Nodule" chapter

Differential Diagnosis

Malignant - Primary non-small cell lung cancer (NSCLC): adenocarcinoma (~40%), squamous cell (SCC, ~20%), large cell carcinoma (~5%) - Metastatic: commonly melanoma, sarcoma, colon, breast, renal, testicular - Often multiple nodules/masses (e.g. cannonball) - Neuroendocrine: small cell lung cancer (SCLC, ~15%), carcinoid, large cell neuroendocrine

Infectious - Granulomatous: TB, non-TB mycobacterium, endemic fungal (histo, blasto, coccidio) - May have component of calcification - Abscess: Staph aureus, Klebsiella, anaerobes, polymicrobial (aspiration) - Septic emboli, hydatid cyst, aspergilloma

Other - Hamartoma, AVM, pulmonary infarct, inflammatory nodule (GPA, RA), sarcoidosis

Evaluation

History

  • Smoking, cough, hemoptysis, dyspnea, chest pain, weight loss, fevers, night sweats, hoarseness (recurrent laryngeal nerve involvement), bone pain, FND, Horner's syndrome
  • Lung cancer should always be considered in a pt with recurrent pneumonia (post-obstructive) or smoking history with new cough or hemoptysis

Exam

  • Cachexia, LAD, bone pain, hepatomegaly, FND, SVC syndrome, digital clubbing

Imaging

CXR - Poor sensitivity for lung nodules, may show large mass or malignant effusion

CT chest (with contrast if possible—better evaluation of mediastinum/LNs) - Review prior chest imaging to assess age and growth pattern of lesion(s) - Benign features: small (sub-centimeter), calcified, fat attenuation, stable over 2 years, multiple nodules - Concerning features: large, growth, spiculation, upper lobe location, thick-walled cavitation, mediastinal invasion - Location: adenocarcinoma often more peripheral, SCC often more central, SCLC associated with massive LAD, mediastinal invasion, and large hilar masses

Look for Paraneoplastic Syndromes

  • SCLC: SIADH, Lambert-Eaton, Cushing's syndrome
  • SCC: hypercalcemia (PTHrP)
  • Dermatomyositis, polymyositis, hypertrophic pulmonary osteoarthropathy (periostitis of long bones)
  • Marantic endocarditis
  • Hypercoagulability leading to venous thromboembolism

Staging/Diagnosis

Imaging - CT chest (with contrast if possible) and CTAP w/contrast vs. PET/CT to assess for metastasis - Consider MRI brain if clinical stage III or IV disease

Biopsy: careful planning is key - For metastatic disease, obtain tissue from least invasive site - FNA or excision of palpable lymph node (cytology dept, US-guided procedure, EGS) - Pleural effusion: thoracentesis w/ cytology might provide initial info (sensitivity ~60%) - If uncertain how to best obtain tissue, consult IR, interventional pulm, and/or oncology to discuss approach - Surgical Bx: Wedge resection/lobectomy often preferred if solitary nodule amenable to both diagnostic and therapeutic resection in good surgical candidate - Bronchoscopy with EBUS (endobronchial US) often used to obtain biopsy of mediastinal tissue or central/peri-bronchial lesion - Navigational bronchoscopy: allows for more precise maneuvering of scope/instrument into the periphery of the lungs under direct visualization while ensuring stability during sampling of target lesions; increased diagnostic yield - Trans-thoracic needle aspiration (TTNA): peripheral lesions not amenable to bronchoscopy

Management

NSCLC: Planning is complex, usually discussed at multidisciplinary tumor board - Stage I/II: surgical resection ± adjuvant chemotherapy - Stage III: more complex requiring multidisciplinary approach, typically combined chemoradiotherapy specifically with immunotherapy agents - Stage IV: chemo ± targeted therapy depending on PD-L1 expression, presence of driver mutations for EGFR, ALK, ROS-1, BRAF, MET, RET, others

SCLC - Usually widely metastatic at time of diagnosis (~70%), treated with systemic chemo/radiation specifically with immunotherapy agents

Lung Nodule

Author: David Krasinski

Background

  • Definition: focal, distinct radiographic density completely surrounded by lung tissue <3cm (mass >3cm – see "Lung Mass" chapter)
  • Prevalence: 30% of all chest CTs. Most commonly are incidentalomas. >95% are benign.
  • Larger and irregularly shaped nodules are more likely to be malignant.

Etiologies

CT Pattern Pathology Etiologies
Random: hematogenous spread Infections Miliary TB, septic emboli
Malignancy Sarcomas, carcinomas
Other Langerhans cell histiocytosis
Centrilobular: most diseases that track airways Infectious Granulomas from fungi, mycobacteria, prior bacterial infx (nocardia/S. aureus)
Inflammatory Aspiration, hypersensitivity pneumonitis, bronchogenic cyst
Malignancy Bronchogenic carcinomas (central: SCC, small-cell), peripheral (adenoCa, large cell)
Peri lymphatic: lymph system spread Inflammatory Sarcoidosis, pneumoconiosis
Malignant Lymphangitic carcinomatosis, lymphoma, metastatic sarcomas/carcinomas
Benign Hamartomas, fibromas, hemangiomas, leiomyomas, amyloidoma

(Please refer to physical handbook for radiographic image associated with the above table)

Management of Solitary Lung Nodule

History

  • Hx of exposures (tobacco, asbestos, mining, biomass fuel), geographical epidemiology (histo/coccidio/TB), B-symptoms, personal and FxHx of malignancy

Assess Patient Risk for Malignancy

High risk: - Greater than 60yo, current smoker or heavy smoking history, history of cancer, FxHx lung cancer, irregular or spiculated, upper lobe, ≥2.3cm, double diameter or volume in past year - There are online risk calculators (Brock, Mayo, Herder) helpful for providers who are not experts in lung nodule risk stratification

Benign imaging features: - Central calcification, popcorn-like (hamartomas), laminated, stippled

Consider Pulmonary referral if: - High risk features, known malignancy or recent history of malignancy, organ transplant or other immunocompromising condition, age <35yo

Fleischner Guidelines for Nodules <8mm

Risk for Malignancy Solid <6mm Solid 6-8mm Solid ≥8mm Subsolid (GGO ± solid component)
Low No follow-up CT at 6-12mo and consider at 18-24mo Refer to Pulm. CT in 3mo. Consider PET + tissue sampling* If >6mm, refer to Pulm. If malignant, may be slow growing. Requires follow up to 5 years. Initially every 6mo
High Optional CT in 12mo CT at 6-12mo and at 18-24mo Refer to Pulm. CT in 3mo. Consider PET + tissue sampling* If >6mm, refer to Pulm. If malignant, may be slow growing. Requires follow up to 5 years. Initially every 6mo

*Tissue sampling usually occurs via transthoracic needle biopsy (via IR), VATS (via thoracic surgery), or transbronchial biopsy (via interventional pulm).

ACCP 2013 Chest Guidelines for Workup of Nodules 8-30mm

Low to Moderate Surgical Risk: - Assess clinical probability of cancer: - Very low (<5%): CT surveillance - Low/mod (5-65%): PET to assess nodule - Negative or mild uptake: CT surveillance OR nonsurgical biopsy - Mod or intense uptake: nonsurgical biopsy or surgical resection - High (>65%): Standard stage eval (±PET) - No met: Surgical resection or SBRT or RFA - +Met (N2, 3): chemotherapy or chemoradiation (after biopsy)

High Surgical Risk: - Nonsurgical biopsy OR CT surveillance - Malignant: Standard stage eval (±PET) - No met: Surgical resection or SBRT or RFA - +Met (N2, 3): chemotherapy or chemoradiation (after biopsy) - Nondiagnostic: CT surveillance - Specific Benign: Specific treatment

Pleural Effusions

Author: David Krasinski

Background

  • There is a normal influx of fluid into the pleural space due to leaky capillary membranes and the pleural space's negative pressure. This fluid is constantly reabsorbed by lymphatics. An imbalance in the system will result in accumulation.

Examples of Dysfunction in Homeostasis

  • Increased influx: ↑ filtration from the capillaries from high intravascular hydrostatic pressure (e.g. heart failure, renal failure) or low intravascular oncotic pressure
  • Other liquid entry into the pleural space through anatomic deficits: CSF, chyle, urine, blood, ascites (the diaphragm is naturally porous)
  • Decreased efflux: obstruction of the parietal pleural stoma (from protein or cellular debris in exudative pleural effusions)
  • Increased systemic venous pressure: lymphatic system drains into the systemic venous circulation so high venous pressure prevents lymphatics from draining appropriately

Presentation

  • May be asymptomatic
  • Chest pain: usually pleuritic via parietal pleural innervation
  • Dyspnea and tachypnea without hypoxia (unless concurrent airspace disease): Dyspnea is thought to be mediated by branches of the phrenic n. that are under pressure from effusion
  • Exam: ↓ breath sounds, ↓ chest wall excursion, ↓ tactile fremitus, dullness to percussion

Evaluation

CXR: Ideally supine AP, lateral upright and decubitus lateral - Fluid accumulates first in subpulmonic space and then in posterior costophrenic recess - 50cc: Visible in posterior costophrenic angle on lateral film - 200cc: Visible on AP costophrenic angle on AP film - 500cc: Obliteration of hemidiaphragm - If effusion moves with gravity, suggests free flowing

POCUS: assess size, location, loculations

CT with contrast: not always indicated; helpful to evaluate septations

Thoracentesis: see "Procedures section"

Interpretation of Pleural Studies

Obtain: - Pleural LDH, protein, cell count/diff, gram stain w/ culture, pH - Consider pleural cytology, hematocrit, triglyceride, glucose, and amylase - Need serum LDH and protein

Light's Criteria

1 of the following to be considered an exudative effusion: - Pleural to serum protein ratio > 0.5 - Pleural to serum LDH ratio > 0.6 - Pleural LDH > 2/3 upper limit of normal range of serum LDH

Transudative: CHF exacerbation, hepatic hydrothorax, atelectasis (caused by increased intrapleural negative pressure), hypoalbuminemia, renal failure

Exudative: infections (bacterial, TB, fungal), malignant, rheumatologic, PE

Hemothorax: pleural hematocrit >50% of blood hematocrit

Chylothorax: pleural TG >100mg/dl

Concern for esophageal rupture: elevated salivary amylase

Other Tips

  • Protein: >5 think TB or malignancy, <0.5 think urine, CSF, peritoneal dialysate
  • Glucose: <60 think about malignancy, TB, or rheumatologic, less likely hemothorax or parapneumonic
  • Cell count/diff: polys represent an acute process, monocytes represent a chronic process, lymphocytes think about TB or malignancy, eosinophils think about air/blood, TB, malignancy, asbestos, drugs
  • Two separate processes may co-occur, and a transudate may mask an exudative effusion; if concerned for this and you have clinical stability, trial diuresis prior to thoracentesis

Management

Parapneumonic effusion: most common exudative process - Uncomplicated: systemic antibiotic for pneumonia - Complicated (positive culture or gram stain, OR loculated OR pH<7.20 OR glucose less than 60): needs chest tube + MIST2 protocol (intrapleural alteplase 10 mg BID in 30 mL of saline AND intrapleural DNase 5 mg BID in 30 mL of water for a total of 3 days)

Hepatic hydrothorax: - Avoid chest tubes. Cirrhosis medical management ± TIPS. - Spontaneous bacterial empyema might occur. Perform thoracentesis if suspected.

Tuberculosis effusions: - Treat as active TB. Often resolves with treatment.

Malignant pleural effusion: - If cytology isolates malignant cells in pleural space, this often automatically classifies that malignancy as an advanced/metastatic stage. Tends to recur. - If recurrent, either do 1) serial thoracentesis, 2) PleurX catheter (tunneled chest tube) or 3) chemical pleurodesis (obliteration of pleural space with talc or tetracycline)

Pulmonary Hypertension

Author: Jessica Reed

Classification

WHO Group Pathophysiology Etiologies
Group 1. Pulmonary arterial hypertension Proliferation and hyperplasia of vascular wall leading to increased pulmonary vascular resistance Idiopathic, heritable (BMPR2 mutation), drug-induced/toxin-induced (methamphetamine, Fen-Phen), connective tissue disease (scleroderma), HIV, portal HTN, congenital heart disease (ASD, VSD, PDA), schistosomiasis (#1 cause of PAH worldwide), Pulmonary veno-occlusive disease (PVOD), Pulmonary capillary hemangiomatosis
Group 2. Left heart disease Elevated end diastolic filling pressure. Increased PCWP. HFrEF, HFpEF, aortic/mitral valve disease, stiff LA
Group 3. Lung diseases or chronic hypoxemia Hypoxic pulmonary vasoconstriction leads to vascular bed remodeling COPD, ILD, OSA, chronic high-altitude exposure, developmental lung disorders, chronic alveolar hypoventilation
Group 4. Chronic thromboembolic pulmonary hypertension (CTEPH) Chronic pulmonary embolism. Incomplete fibrinolysis and organization of thrombus Thrombotic and non-thrombotic emboli (parasites, foreign bodies, tumor)
Group 5. Multifactorial Varied Hematologic disorders (sickle cell disease), chronic hemolytic anemia, sarcoidosis, pulmonary Langerhans cell histiocytosis, fibrosing mediastinitis, ESRD

Presentation

Symptoms: - Exertional dyspnea, presyncope, fatigue, exertional chest pain, edema, syncope (concern for severe PH)

Physical Exam Findings: - JVD, RV Heave, Widely split S2, tricuspid regurg murmur, Hepatomegaly, ascites, rales (pulmonary edema), LE edema

Presentation can be variable and depends on group, underlying etiology and functional class at time of presentation. Main chief complaint for admission: volume overload secondary to RV failure and/or hypoxia

Evaluation

Labs: - CBC with diff (assess for anemia, polycythemia), BNP, CMP, blood gas to assess for chronic hypercarbia - If suspected but undiagnosed: TSH, HIV, rheumatologic serologies (ANA w/reflex ENA, RF/CCP, ANCA, Scl-70, Ro/La)

Imaging: - CXR: Possible Cardiac enlargement, PA dilation, hilar fullness - TTE with bubble: RVSP >35-40 is concerning for PH. TTE can show evidence of RV dilation and dysfunction (TAPSE <1.6cm), RA dilation, septal flattening, pericardial effusion, bubble study for shunt, LV dysfunction - CT angiogram: evaluates for acute and chronic thrombi using contrast media; consider V/Q scan in setting of AKI and advanced CKD (discuss risk and benefits) - V/Q scan: better performance in evaluating small chronic embolism in contrast to CTA - High-res CT: for better evaluation of lung parenchyma in patients with ILD

Additional Testing: - EKG: right atrial enlargement (peaked P waves), RBBB, RV hypertrophy - 6-min walk test: important for prognostication, baseline exertional capacity, and to evaluate treatment response - PFT: rule out obstructive and restrictive disease; isolated DLCO reduction can be seen with PAH - Sleep study: evaluation for chronic hypoxemia from OSA; if low suspicion for OSA/CSA, can start with overnight oximetry - RHC (see below)

Diagnosis and Diagnostic Algorithm

  1. Clinical Suspicion of PH (see presentation)
  2. Initial Non-Invasive Testing (TTE, CXR, Labs, PFTs, EKG)
  3. Further Imaging (CT Chest/V/Q scan)
  4. Referral to PH Center*
  5. Confirmatory Testing (RHC is diagnostic)

  6. Additional Tests

  7. May be suspected from clinical presentation and echo

  8. A right heart catheterization is the gold standard for PH diagnosis and will differentiate between precapillary and postcapillary PH
  9. Nitric oxide challenge during RHC assesses for drug response
  10. Fluid challenge with 500ml LR during RHC assesses left heart compliance
  11. Referral to PH Center is particularly recommended for suspected PAH (Group 1), CTEPH (Group 4), or severe PH with RV dysfunction

RHC: required for diagnosis and to determine therapeutic options; measures mPAP, PWP, PVR, CO, CI - Acute vasoreactivity testing (AVT) - Nitric oxide challenge during RHC assesses for drug response and possible therapeutic options - Positive: mPAP decreases by ≥10 mmHg and mPAP reaches ≤40 mmHg, no decrease in cardiac output - Fluid challenge with 500ml LR during RHC assesses left heart compliance - Negative Fluid Challenge: PCWP remains ≤15 mmHg

Definitions Characteristics Causes
Pre-capillary PH mPAP > 20 mmHg, PWP ≤15 mmHg, PVR ≥2 WU Groups 1, 3, 4, 5
Post-capillary PH mPAP > 20 mmHg, PWP > 15 mmHg, PVR < 2 WU Group 2
Combined pre- and post-capillary PH mPAP > 20 mmHg, PWP > 15 mmHg, PVR ≥2 WU Group 2, 5

General Management

  • Immunizations: Strong recommendations for yearly influenza, COVID-19, and pneumococcal vaccinations
  • Pregnancy Counseling: recommend patients avoid pregnancy due to high maternal and fetal risks (RH failure, increased mortality)
  • Treatment Goals: Focus on preventing right heart failure, maximizing PH therapies, symptom relief, quality of life, and functional class improvement (NYHA class)
  • Oxygenation Goal: Maintain oxygen saturation >90%
  • Volume/Hemodynamic Management: try to avoid giving fluids, especially if significant RV dysfunction as this is more likely to throw off Frank-Starling curve than overdiuresis
  • Classic teaching of pre-load dependence is more accurate for acute RV dysfunction than chronic and diuresis is often warranted during episodes of RHF
  • Specialist Consultation: Consult pulmonary hypertension specialists when considering starting, holding, or changing PH medications; Do not change therapy at VUMC without PH consult
  • Regular Follow-Up: Q3-6M visits, assessment of NYHA functional Class for treatment escalation, serial echocardiograms, 6minute walk and RHC if clinically indicated

Disease Specific Therapeutics and Interventions

Therapy MOA/Rationale Patient Population/Considerations
Oral CCBs (Nifedipine, diltiazem, amlodipine) Induce vasodilation by inhibiting calcium influx in pulmonary artery smooth muscle, promoting muscle relaxation Used ONLY in pts w/ Group 1 PH who had a positive vasoreactivity challenge on RHC as above
Anticoagulation (DOAC, VKA) Prevent new thrombus formation and promoting the resolution of any existing acute thrombi For pts with confirmed CTEPH (Group 4). Should be worked up for hypercoagulability including antiphospholipid syndrome.

PAH-specific medications (in order of escalation)

Therapy MOA/Rationale Patient Population/Considerations
Endothelin receptor antagonists (e.g., bosentan, ambrisentan, macitentan) Block endothelin-1 receptors, reducing vasoconstriction and proliferation See notes 1, 2, 3 below.
Phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil) Inhibit PDE-5, increasing cGMP levels and promoting vasodilation See notes 1, 2, 3 below.
Prostacyclin analogs (e.g., epoprostenol, treprostinil) Mimic prostacyclin, leading to vasodilation and inhibition of platelet aggregation See notes 1, 2, 3 below.
Prostacyclin receptor agonists (e.g., selexipag) Activate prostacyclin receptors, causing vasodilation See notes 1, 2, 3 below.
Soluble guanylate cyclase stimulators (e.g., riociguat) Stimulate sGC, increasing cGMP independent of nitric oxide leading to vasodilation See notes 1, 2, 3 below.
Sotatercept An activin receptor type IIA-Fc fusion protein, works by binding to free activins, restoring balance between the activin proliferative and BMP antiproliferative pathways in the pulmonary arteries Used as add on therapy in Group 1 PH to enhance exercise capacity, improve functional class, and reduce clinical worsening
  1. All therapies given under the direction of PH specialist.
  2. Important Notes on Prostacyclin Based Therapies:
  3. Side effects include jaw pain, flushing, arthralgias, and diarrhea.
  4. IV formulations are administered through a continuous pump.
  5. Never stop IV prostacyclin therapy inpatient since even brief pauses can cause rebound vasoconstriction and death.
  6. Epoprostenol: IV (Veletri) or inhaled (Flolan); half-life 4 minutes.
  7. Treprostinil: IV/subcutaneous/inhaled/PO; half-life 4 hours
  8. Selexipag (Uptravi): PO, half-life hours
  9. Treatment escalation is based on a pt's risk stratification

Procedural Considerations

  • Atrial septostomy: creation of a R→L shunt to offload the RV
  • VA ECMO can be used as bridge to medical therapy or for lung transplant
  • Lung transplantation can be considered for pts who are candidates and failing maximal medical therapy

Poor Prognostic Factors

  • NYHA Functional Class III and IV: Indicates severe symptoms and significant limitations in physical activity
  • 6-minute walk test less than 300 meters: correlates with worse functional capacity and right ventricular dysfunction
  • AKI and/or hyponatremia: AKI and hyponatremia are markers of severe right heart failure and systemic congestion, indicating poor renal perfusion and neurohormonal activation, both of which are associated with increased mortality
  • Low SBP (SBP < 90): reflects poor cardiac output and advanced right ventricular failure
  • Poor hemodynamics on RHC (right atrial pressure > 20 mmHg; cardiac index less than 2)
  • TTE findings: tricuspid annular plane systolic excursion (TAPSE, marker of global RV function) < 1.8, pericardial effusion, and severe RV dysfunction

Airway Clearance Therapy

Author: Jacob Lee

Definition: A variety of noninvasive techniques designed to mobilize and remove secretions to improve gas exchange and work of breathing (American Association for Respiratory Care)

  • By expelling mucous and secretions, airway clearance therapy (ACT) aims to decrease airway inflammation, prevent obstruction and subsequent atelectasis and infection and thereby improve gas exchange and respiratory symptoms
  • All ACTs aim to make cough more productive

Uses

In general, ACT is used for pathologies that cause retained secretions, mucous plugging due to overproduction or impaired mucociliary clearance

Indications

  • Cystic fibrosis
  • Non-CF bronchiectasis
  • COPD with chronic sputum production or recurrent infections
  • Recurrent aspiration/aspiration pneumonia
  • Neuromuscular diseases involving the respiratory muscles
  • Prolonged ventilator-dependence/ventilator weaning

Contraindications

  • Hemodynamically unstable
  • Hemoptysis
  • PTX
  • Recent lung surgery or trauma

Components

Therapy Description Order Set Comments
Chest Physiotherapy (CPT) Patient assumes sequence of positions aimed at "draining" each of the lobes of the lung by gravity. Usually combined with percussion or vibration techniques CPPD Panel (RT Bronchial Hygiene Protocol) – usually TID Done with RT. Better tolerated than vest physiotherapy, can be combined with a percussive/vibratory device such as a wand
High Frequency Chest Wall Compression (HFCWC) – 'Vest Physiotherapy' An inflatable vest with a compressor rapidly inflates and deflates vest to "break up" thickened mucus from airway wall. Can target specific areas depending on the vest Vest Physiotherapy Usually done with RT. Vest can be uncomfortable and difficult to tolerate particularly for elderly/frail patients- in which case can use a 'wand'
Positive Expiratory Pressure (PEP) Patient exhales against fixed or fluttering resistor that allows air to get behind mucus, helps move mucus from airway walls, and holds airways open longer for improved ventilation PEP Therapy or Oscillatory PEP Therapy Also commonly called Flutter valve, Acapella, AerobikA. Can find these in any RT station and bring it to the patient
Cough Assist Via mask or trach/vent connection – applies positive pressure to fill the lungs, then quickly switches to negative pressure to produce a high expiratory flow rate to simulate a cough that is intended to produce expectorant Cough Assist Treatment Panel Most effective in patients with neuromuscular weakness affecting diaphragmatic strength – muscular dystrophy, myasthenia gravis, spinal cord lesions, SMA

Adjuncts

Not technically considered ACT but can improve cough productivity

Mucolytics: Dornase Alfa, N-acetylcysteine (NAC), Hypertonic Saline (3-7%) - Hypertonic saline can cause bronchospasm and can be poorly tolerated, consider combining with DuoNebs either before or after

Expectorants: Guaifenesin

Considerations

  • CF patients typically have a routine that involves CPT, vest physiotherapy, and PEP valve in addition to their inhaler therapies, ask them their home routine, then ask the CF team if it should be more aggressive (increased frequency)

Chest Tubes

Author: Jacob Lee

Background

Nomenclature Size Insertion Technique Specific Indications
Small Bore - Straight or Pigtail (coiled at the end to prevent dislodgement) ≤14F Seldinger PTX, uncomplicated pleural effusions, initial empyema drainage (BTS guidelines)
Medium-Bore 15-23F Seldinger or Surgical Larger pleural effusions or complex/exudative effusions
Large-Bore (Surgical) 24-40F Surgical Thoracostomy Post-operative drainage, hemothorax, thick exudative effusions

Other Indications and Considerations

  • Malignant effusions and hepatic hydrothorax are generally palliative measures only
  • Large-bore/surgical chest tube should be placed for acute hemothorax, not pigtail
  • Smaller size results in less tissue disruption but more likely to clog or kink

Contraindications

Absolute: need for emergent thoracotomy

Relative: Coagulopathy (INR Goal < 2-3 depending on proceduralist comfortability), large pulmonary bullae, pleural/pulmonary adhesions, skin infection at insertion site

Placement

  • Consult pulmonology – they will decide whether interventional pulmonology/radiology needs to place the tube

Location: related to pathology - Pneumothorax - anterior near the apex of the lung in the 2nd intercostal space, midaxillary line - Effusion (water, pus, blood, chyle) – depends on where the fluid is located but in general placed posterior near the base of the lung (fifth or sixth intercostal space, midaxillary line)

Potential complications: organ damage/perforation (lung, heart, diaphragm, intraabdominal), trauma of the intercostal neurovascular bundle, subcutaneous emphysema, pneumothorax, infection, re-expansion pulmonary edema

Understanding the Atrium

After the chest tube is placed, it is connected to the Atrium which can be connected to the wall for suction.

Please refer to the physical handbook for the diagram which is described below.

(A) Dry suction control - determines the level of suction out of the chest tube and is set by the provider (typically -20 cm H2O). It is important to note that while the atrium is linked to the wall suction via suction port (H) the level of chest tube suction is determined by (A), regardless of what the wall suction setting is

(B) Water seal chamber - if the atrium is disconnected from the wall suction, it is on "water seal" (i.e., to gravity). This allows for the one-way flow of pleural space contents out of the chest. This space also shows 'tidaling' in certain instances explained below

(C) Air leak monitor - if air bubbles are present in the water seal chamber, then that indicates the presence of air in the pleural space

(D) Collection chamber - drains the pleural fluid contents via the chest tube

(E) Suction verification window - will be orange if suction is on and atrium is functioning appropriately

Normal Findings and Troubleshooting

Tidaling: a normal finding referring to the rise (during inspiration) and fall (during expiration) of fluid in the water seal chamber - Indicates communication between pleural space and the drainage system and that the system is functioning correctly - Lack of tidaling can be seen in several instances: lung has fully re-expanded, chest tube is blocked (clogged/kinked), suction is turned on, or tube is dislodged/mispositioned

Output in the absence of pathology can be up to roughly 150 cc/day which is the amount of fluid the pleural space produces daily

In general, CXR is first study to order in evaluating a patient with a chest tube who undergoes a change in clinical status

Air leaks: If bubbles are present in the water seal chamber, this indicates air in the pleural space. Intermittent bubbling is common in a PTX while air is still escaping from the pleural space. Continuous bubbling suggests an ongoing air leak. Two main categories of air leaks: - Patient-related/originating from pleural space: Persistent air in the pleural space; seen in alveolar-pleural fistula, PTX (expected initially; should decrease over time as lung re-expands), mechanical ventilation - System-Related/chest tube or drainage system: Air not originating from pleural space but the system; seen in chest tube dislodgement, faulty dressing seal at insertion site, cracked or damaged drain system

To identify the etiology of a new air leak, try clamping the chest tube: - Clamp near patient and bubbling stops → leak in pleural space - Clamp near patient and bubbling continues → leak in the drainage system or tubing

Clogging: Would see debris in the collection chamber and lack of tidaling in the water seal chamber - In pts with viscous fluid output (ex- empyema), important to flush the chest tube with normal saline flushes at least twice daily to prevent clogging - For clog- try flushing 10cc of sterile saline toward the pt or "stripping" the chest tube by pressing the chest tube with your fingers and pulling towards the drainage system - Always consult pulmonary for chest tube management unless another team (eg, thoracics) is actively managing

Removal

Generally, chest tubes are removed when the underlying condition requiring their insertion has plateaued, improved, or resolved - Effusions: less than 150 cc in 24 hours - PTX: step wise approach. Usually once air leak resolves, will transition from wall suction to water seal with a CXR prior to transitioning and prior to removal. Generally guided by the team that placed the tube

Chest tube should be removed while pt hums (to prevent inhalation during removal that could introduce air into pleural space). Pigtail catheters must be "unlocked" prior to removal to release the pigtail

Home Oxygen Therapies

Author: Mackenzie Samson

Summary of Medicare Part B Guidelines for Home Oxygen

Conditions for which oxygen therapy may be covered

  • Severe lung disease including COPD and ILD, CF, bronchiectasis, widespread neoplasms
  • Hypoxia related symptoms or findings expected to improve with O2: pulmonary hypertension, cor pulmonale, erythrocytosis, impaired cognition, nocturnal restlessness, morning headache

Qualifying Tests and Requirements

  • Testing must be performed with a pt in chronic stable condition or within two days of discharge from an inpt hospital stay (after treatment of acute exacerbating conditions)
  • Criteria: Resting SpO2 ≤88% (or PaO2 <55) or SpO2 <88% with ambulation
  • Must be documented in chart

Special Considerations

  • Medicare requires an additional walk on 4L/min showing desaturation if the pt needs a flow rate of 5L/min or higher
  • Because of the risk of desaturation with exertion and the intrinsic error in the pulse ox (around 3%), pts with resting SpO2 ≤92% should have amb sats checked
  • Pts with Raynaud's or poor circulation may have inaccurate finger pulse oximeter readings. Consider using a head saturation monitor

VA Specific Guidance

Will need to document ambulatory saturations in notes as above. Call the Oxygen Clinic (number listed in all team rooms) and talk with your case manager

Summary of Medicare Part C Guidelines for Home Respiratory Assist Devices (CPAP/BiPAP)

Restrictive thoracic disorders

Covered if the following criteria are met: - Documentation of a neuromuscular disease/severe thoracic cage abnormality AND one of the following: - PaCO2 ≥45 mmHg on ABG, performed while awake and on home O2 requirement - Sleep oximetry demonstrates oxygen saturation ≤88% for ≥5 minutes of nocturnal recording time performed while on home O2 requirement - For a neuromuscular disease (only), either: Maximal inspiratory pressure < 60cm H2O or forced vital capacity < 50% predicted and COPD may not contribute significantly

Severe COPD

Covered if the following criteria are met: - PaCO2 ≥52 mmHg on ABG, performed while awake and on pt's prescribed home O2 - Sleep oximetry demonstrates oxygen saturation ≤88% for ≥5 minutes of nocturnal recording time, performed while breathing oxygen at 2LPM or pt's prescribed FiO2 (whichever is higher). Also requires that OSA had been considered and ruled out (formal sleep testing not required)

Hypoventilation Syndrome

Covered if criteria 1, 2, AND either 3 or 4 are met: 1. PaCO2 ≥45 mmHg on ABG, performed while awake and on home O2 requirement, AND 2. Spirometry shows an FEV1/FVC ≥70% AND 3. ABG PaCO2, performed during sleep or immediately upon awakening that demonstrates worsening PaCO2 of ≥7 mmHg compared to the original result in criterion 1 OR 4. A facility-based PSG or HST demonstrates oxygen saturation ≤88% for ≥5 minutes of nocturnal recording time that is not caused by obstructive upper airway events

OSA

  • An initial screening for OSA in the hospital is nocturnal pulse oximetry. The distinct "saw-tooth" pattern representing intermittent hypoxia is suggestive of OSA, and a formal NPSG or home sleep test is recommended to evaluate for OSA. This is done on an outpt basis only once acute issues have fully resolved
  • Home CPAP/BiPAP covered IF:
  • The diagnosis of central sleep apnea or complex sleep apnea and
  • Significant improvement of the sleep-associated hypoventilation occurs with the use of the device

Inhaler Therapy

Author: Jacob Lee

Current Inhaler Device Delivery Options

Device Mechanism Pros Cons Examples
Metered dose inhaler (MDI) Pressurized canister releases a measured dose of aerosolized medication Delivers precise & consistent doses when used correctly. Can be used with spacer Requires hand-breath coordination (timing 3-5 seconds slow inhalation with 5-10 seconds breath hold with release of medicine) Albuterol, Fluticasone (Flovent), Ipratropium (Atrovent), Budesonide/Formoterol (Symbicort)
Soft mist inhaler (SMI) Uses a mechanical spring to generate slow-moving mist that is inhaled without a propellant Releases a mist that lasts longer and is slower than MDIs. Better lung deposition than MDI. Easier to use for patients with poor coordination Typically more expensive and less options. Must be primed if not used frequently. Tiotropium (Spiriva Respimat), Ipratropium/Albuterol (Combivent)
Dry powder inhaler (DPI) Delivers a fine powder of medication when inhaling without a propellant Environmentally friendly (no HFA – propellants). Breath actuated (no need for coordination) Relies on patients inspiratory effort which needs to be strong to get adequate lung deposition. Inconsistent dose delivery Fluticasone (Arnuity Ellipta, Flovent Diskus), Salmeterol/Fluticasone (Advair Diskus), Umeclidium/Vilanterol (Anoro Ellipta), Budesonide (Pulmicort), Trelegy
Nebulizer Converts a liquid medication into a fine mist, allowing it to be inhaled using a mask or mouthpiece Does not require deep inhalation effort or coordination. Ideal for emergencies. Continuous medication delivery Short-acting. Expensive. Not always portable. Longer administration time Albuterol (Ventolin), Ipratropium (Atrovent), Albuterol/Ipratropium (DuoNeb), Budesonide (Pulmicort), Hypertonic Saline, Dornase Alfa, Tobramycin

Videos Demonstrating Appropriate Techniques

https://www.nationaljewish.org/conditions/medications/inhaled-medication-asthma-inhaler-copd-inhaler/instructional-videos

Classes of Inhaled Medications

Bronchodilators

Beta Agonists: beta-2 agonism of bronchial smooth muscle for bronchodilation; also decreases mast cell mediator release - Short-acting beta agonists (SABA): albuterol, levalbuterol (theoretically has less side effects but data does not support this); available as both MDI and nebs - Long-acting beta agonist (LABA): same as SABA but longer acting. Ex: formoterol (shortest acting LABA), salmeterol, olodaterol - LABA monotherapy for asthma should be avoided due to increased risk for mortality

Anticholinergics: block M3 receptors in airway smooth muscle leading to both bronchodilation and decreased bronchial secretions - Short-acting muscarinic antagonists (SAMA): ipratropium (Atrovent) - Long-acting muscarinic antagonists (LAMA): tiotropium (Spiriva), revefenacin (Yupelri) - Indicated for COPD, not generally indicated for asthma unless part of a combination inhaler for exacerbation or triple therapy for maintenance for refractory disease

COPD and asthma exacerbation: bronchodilation and secretion inhibition in acute setting - Ipratropium (Atrovent) intermittent nebulizer or Ipratropium-albuterol (Duo-Neb) intermittent or continuous nebulizer

Corticosteroids

Suppress airway inflammation - NOT bronchodilators - Budesonide inhaler (Pulmicort) or neb, fluticasone furoate (Arnuity Ellipta)

Combination Therapies

Combine beta-2 agonists, antimuscarinics, and/or corticosteroids. Generally better to combine multiple medications in a single inhaler rather than each individually (improved outcomes likely related to compliance) - SABA/SAMA: albuterol/ipratropium available as nebulizer (DuoNeb) or MDI (Combivent) - SABA/ICS: albuterol/budesonide (AirSupra) - LABA/ICS: only way to get LABA due to aforementioned increased mortality in LABA monotherapy; vilanterol-fluticasone (Breo Ellipta), salmeterol-fluticasone (Advair Diskus/HFA) - LAMA/LABA: umeclidinium/vilanterol (Anoro) - LABA/LAMA/ICS: triple therapy for refractory COPD/asthma. Formoterol/glycopyrrolate/budesonide (Breztri – now available inpatient as an MDI), vilanterol/umeclidinium/fluticasone (Trelegy – only outpatient as a DPI)

Airway Clearance Agents

Expectorants: Hypertonic saline, NS, 3% and 7% - Can be used to thin secretions and produce deep cough in pts who need to expectorate as part of treatment. For CF, chronic tracheostomy, NM weakness. No evidence for benefit in COPD

Mucolytics: - Enzymatic Agents (Dornase alpha/Pulmozyme/DNAse): enzyme that breaks down polymerized DNA in high concentrations in CF airways; indicated specifically for CF pts - Disulfide disruptors (NAC/Mucomyst): Sever disulfide bonds of glycoproteins in mucus, lowering its viscosity and making it more amenable to suction, expectoration

Antibiotics

  • Generally used in pts with CF, non-CF bronchiectasis for suppressive therapy, may be indicated for VAP as salvage therapy
  • Tobramycin: only nebulized antibiotic available at VUMC
  • Pentamidine: nebulized antibiotic for PJP prophylaxis, given monthly

VUMC Inpatient Options

  • SABA: Albuterol (Proventil/Ventolin/Proair) - MDI, neb, continuous aerosol available
  • SABA/SAMA: Ipratropium-albuterol (Duo-Neb) - neb and continuous neb available
  • LABA – only available in combination w/ ICS. LABA/ICS: vilanterol-fluticasone (Breo Ellipta), salmeterol-fluticasone (Advair Diskus/HFA)
  • LAMA: Tiotropium (Spiriva Respimat)
  • ICS: Budesonide inhaler (Pulmicort) or neb, fluticasone furoate (Arnuity Ellipta)
  • Triple therapies: Breztri; if insurance won't cover, Combine ICS/LABA with LAMA as replacement