Obstructive Lung Disorders (Asthma, COPD, Sleep Apnea, Cystic Fibrosis, Bronchial Disorders)

allergic/atopic asthma

chronic inflammatory disease causing narrowed airways reversible by bronchodilators
S/sx: wheezing, dyspnea, cough, chest tightness
→no cure, can be managed by bronchodilators and avoiding triggers to prevent exacerbations

allergic/atopic asthma

What is the second leading chronic condition in children, behind obesity?

allergic/atopic asthma

Etiology
1. Genetic
2. Enviromental (exposure to dust mites, molds, pollen, etc)
3. Tobacco smoke early on
4. Viruses/bacterial (RSV commonly associated with risk)
5. Obesity (strong link)
6. Occupational Exposures (bakers, farmers, detergent)

allergic/atopic asthma

Pathophysiology
Associated with IgE antibody hyper-reactivity
1. IgE binds to mast cells
2. mast cells release histamine, prostaglandins and leukotrines (inflammatory markers) = bronchial smooth muscle constriction
3. “bronchial spasms” → chronic inflammation leads to airway remodeling

allergic/atopic asthma

Confirm Diagnosis
1. Spirometry: decreased FEV/FVC1 ratio (obstructive pattern) that markedly improves with albuterol inhaler
OR
Methacholine/histamine challenge (rarely done, makes symptoms and PFT temporarily worse)

NO CXR, CT imaging, Labs

allergic/atopic asthma

Treatment
based on step-up (step-down) therapy
*always check for adherence to medication before stepping up with medication

rule of 2’s

Asthma considered uncontrolled if…
- uses rescue inhaler >2x a week
- >2x nighttime awakenings requiring albuterol/month
- >2x rescue medication refills in the past year
Way to determine need to step up to next level treatment

Albuterol

Beta2 Agonist (_____ (SABA), formoterol (LABA)); bronchodilators, rapid response in asthma treatment
MOA-relaxes airway smooth muscles, stabilize mast cell and prevent release of histamines
SE:Tachycardia, jitteryness

NIH/UptoDate Step 1 treatment (for everyone)

Fluticasone

Inhaled Corticosteroid (ICs);
MOA: Work via Anti-inflammatory effects,
Helps to prevent irreversible airway changes
SE: Hoarseness, oral thrush**Gargle/rinse mouth with water after use

NIH/UptoDate Step 2 treatment (add to Beta 2 agonist)

Singulair (Montelukast)

Adjunct Asthma Medication
leukotriene receptor antagonist (LTRA)

NIH/UptoDate Step 5 treatment (add to increased strength ICs)

oral corticosteroids (OCS)

Can be used daily for very severe asthma, often used short term for asthma flares

NIH/UptoDate Step 6 treatment (add on)

pulmonology consult

What is always recommended when managing step-up therapy for an asthma patient in steps 4-6 (NIH/UptoDate guidelines)?
Step 4: increase strength of inhaled steroid
Step 5: increase strength of steroid and add adjunctive therapy
Step 6. Add Oral steroids (chronic maintenance)

GINA

Step 1 and 2: low-dose inhaled corticosteroid-LABA prn (Budesonide-Formoterol, Symbicort)
Steps 3,4,5: increase low-dose maintenance ICS-LABA

Which asthma treatment guideline?

NIH/UptoDate

Step 1: Albuterol PRN for symptoms
Step 2: Albuterol PRN + inhaled corticosteroid (ICS)
Step 3: Albuterol PRN + inhaled corticosteroid + LABA
—pulmonology consult
Step 4: increase strength of inhaled steroid
Step 5: increase strength of steroid and add adjunctive therapy
Step 6. Add Oral steroids (chronic maintenance)

Which asthma treatment guideline?

LABA

NEVER use _____ as monotherapy for asthma [Black Box Warning]!
[Formoterol (Foradil), Salmeterol (Serevent), Aformoterol (Brovana), Indacaterol (Arcapta), Olodaterol (Striverdi), terbutaline]
↑risk of hospitalization and asthma-related death
→always use in combination with inhaled corticosteroids to eliminate risk

NIH/UptoDate Step 3 treatment

peak flow meter

tool used at home to get quick estimate of lung function (when asthma symptoms are well controlled)

atopic triad

1. Seasonal Allergies (allergic rhinitis)
2. Asthma
3. Eczema (atopic dermatitis)

Components of the ________

asthma exacerbation

acute worsening of asthma symptoms not responding to typical maintenance therapy (can be life threatening)
→precipitated by specific trigger (dust, pollen, infections)
→previous history of severe episodes are predictive

mild

_____ asthma exacerbation
-diffuse wheezing, slight shortness of breath
Tx: nebulized Albuterol or DuoNeb treatment in office

moderate

_____ asthma exacerbation
-increased respiratory effort/risk factors for severe
Tx: albuterol/DuoNeb + Oral/IM steroids (dexamethasone, prednisone, prednisolone)

severe

_____ asthma exacerbation
(marked respiratory distress)
Tx: albuterol/DuoNeb + IM steroids + call 911 for transport to ER

moderate

What type of asthma exacerbation is most common?
Tx: albuterol/DuoNeb + Oral/IM steroids (Dexamethasone, prednisone, prednisolone)

Dexamethasone

What steroid is given in conjunction with albuterol/DuoNeb to treat most adult asthma exacerbations (moderate/severe)?
→Has a long half life and stays in system w/ one time dose

Prednisone

Which steroid should be continued 5-7 days to prevent future flares in conjunction with albuterol/DuoNeb for adult asthma exacerbations (moderate/severe)?
→Do not need to taper if under 10 days

*Prednisolone can be used as an Rx for kids because it is liquid

untreated asthma

Complications of _________
1. recurrent flares (frequent hospitalization - $$$)
2. Chronic inflammation (bronchiectasis/COPD like symptoms)
3. Increased risk of pulmonary infections
4. Pregnancy complications
5. Disputed/poor sleep
6. Short life expectancy (if uncontrolled)

intrinsic asthma

non-allergic asthma usually an adult onset without atopic history NO seasonal allergies or eczema
→may be associated with elevated eosinophils

NOT associated with elevated serum IgE levels

intrinsic asthma

Which variant of asthma typically has an adult onset with NO history of seasonal allergies or eczema?

eosinophilic asthma

more severe, difficult to treat variant of asthma with adult onset
→associated with obesity, nasal polyps and chronic sinusitis

Pathophysiology
high levels of eosinophils (WBC type) in the airways and lungs
→eosinophils release inflammatory markers histamine and leukotriene causing airway constriction

eosinophilic asthma

Which variant of asthma is difficult to treat because it does not respond well to inhaled/oral corticosteroids?
Treatment
immunoglobulins: Benralizumab (Fasenra), Mepolizumab (Nucala), Reslizumab (Cinqair)

Aspirin Induced Asthma (AERD)

adult onset variant of asthma triggered by aspirin/NSAIDS

Pathophysiology
NSAIDs inhibit COX-1 enzyme → reduced prostaglandin production increases leukotriene production → bronchoconstriction and nasal congestion

Samter’s triad

nasal polyps/chronic sinusitis, asthma and aspirin sensitivity

Clinical presentation of Aspirin Induced Asthma (AERD)

Aspirin Induced Asthma (AERD)

Diagnosis
suspect in patients with respiratory symptoms after taking NSAIDs (30min-3 hours after)

Treatment
AVOID NSAIDs
Use leukotriene receptor antagonists (Singulair/Montelukast) if symptoms are not controlled with NSAID avoidance and typical asthma treatments

COPD

progressive lung disease associated with long term smoking (usually 20+ pack years - 90% of patients)
-Includes both Chronic Bronchitis & Emphysema
-majority of patients have combination phenotype

Etiology
-chronic exposure to air pollution, chronic chemical exposure (smoking), fumes from cooking
-1-3% have genetic mutation alpha-1 antitrypsin

COPD

Pathophysiology
-narrowing of airways, excessive mucus production, loss of cilia and destruction of alveoli

Clinical presentation
-progressive dyspnea
-chronic (productive) cough
-DOE (dyspnea on exertion)
-fatigue
-frequent respiratory infections

COPD

Diagnosis
chronic cough for 3+ months in a year for 2 consecutive years

Ddx
-Congestive heart failure (primary)
-Asthma (reversible)
-Lung Cancer (not mutually exclusive to either diagnosis)
-Interstitial lung disease
-Bronchiectasis Tuberculosis
-GERD
-Medication side effects (ACE inhibitors)

COPD

Spirometry: obstructive pattern: decreased FEV1/FVC ratio (<0.7) NOT reversible with bronchodilators

Diffusing Capacity of Lungs for Carbon Monoxide (DLCO):
-normal in bronchitis and asthma
-LOW in emphysema (destruction of alveoli reduces gas exchange)

COPD

Which obstructive lung disease is treated with LABA + LAMA combination inhaler (recommended for most patients: Group B)?

COPD

Additional Treatment
1. supplemental oxygen (when O2 <88%)
2. Roflumilast (Daliresp): improves lung function/reduces exacerbations
3. Azithromycin: prophylactic in severe cases
4. Vaccinations, Regular Exercise. Smoking Cessation
5. Pulmonary Rehab referral

COPD

What condition is treated based on severity (objective and subjective findings):
Objective:
1. Spirometry findings (GOLD grade-primarily FEV1 percentage)
2. Number and severity of exacerbations (“severe” if hospitalized)

Subjective:
1. MRC dyspnea Scale
2. CAT assessment

COPD

What obstructive lung disease are the GOLD Guidelines used to grade severity of airflow obstruction based on post-bronchodilator FEV1?

LABA/LAMA combos

Tiotropium and Olodaterol
Glycopyrrolate and Indacaterol
Glycopyrrolate and Formoterol
Aclidinium and Formoterol
Umeclidinium and Vilanterol

Treatment of COPD (Groups B/E)

emphysema

COPD phenotype: Etiology
Progressive destruction of alveolar membrane leading to decreased surface area of alveoli and impaired gas exchange
-difficulty getting air out “pink puffers”

emphysema

COPD phenotype: Pathophysiology
1. Alveolar cellular breakdown (big and floppy)
→ loss of surface area, hypoxia and hypercapnia (↑CO2)
2. Terminal bronchioles narrow
→ difficult exhaling, hyperinflation and air trapping
3. Capillaries stiffen and narrow
→ decreased blood flow, impaired gas diffusion

emphysema

COPD phenotype: Clinical Presentation
marked dyspnea on exertion
-pursed lip breathing (increase bronchial pressure, helps expel more CO2)
-prominent accessory breathing muscles
-thin and frail (from increased work breathing)
”pink puffers”

Physical exam
hyperinflation of lungs, hyperresonnance to percussion, barrel chested, difficulty getting air out of lungs

emphysema

COPD phenotype: CXR findings
Lung Hyperinflation (lungs appear darker than expected)
Lung Hyper-expansion (long lungs, more than 6 anterior ribs or more than 10 posterior ribs)
Flattened diaphragms
Barrel Chest (lateral View)
Small heart
Increased retrosternal airspace (lateral view)

chronic bronchitis

COPD phenotype: CXR findings
-Increased bronchovascular markings
-hyperexpansion of lungs “long lungs”
-Cardiomegaly

chronic bronchitis

COPD phenotype: Clinical Presentation
productive cough (hallmark)
obesity
low oxygen saturation
”blue bloaters”

Physical Exam
wheezing, ronchi, difficulty getting air into lungs

chronic bronchitis

COPD phenotype: Etiology
chronic inflammation of the bronchi (irreversible)

“blue bloaters”

chronic bronchitis

COPD phenotype: Pathophysiology
smoking leads to inflammation of airways →
chronic inflammation leads to structural/functional changes:
1. Narrowed airways (wheezing and dyspnea)
2. Goblet cell hyperplasia (increase mucus production, chronic productive cough)
3. Loss of cilia (decreased mucus/debris clearance, ↑↑risk infection)

infection

What triggers the majority of COPD exacerbations (flares)?
→also air pollution, idiopathic causes

COPD exacerbations

acute worsening of respiratory symptoms relative to patient baseline

Clinical Presentation
increased cough, sputum production, worsening dyspnea, increased inhaler use

COPD exacerbations

Physical Exam
PE: wheezing, tachypnea, tachycardia, fever
Workup: viral NAAT for influenza, COVID, RSV
CXR to exclude pneumonia/other pathology

Guidelines
determine if patient is stable for outpatient treatment (mild, no respiratory distress)
inpatient treatment with respiratory distress, emergent vitals, significant barriers to care/follow up

COPD exacerbations

Treatment
albuterol (nebulized) + oral steroids (prednisone x 5 days) +
antibiotics (Levofloxacin, when viral/flu testing is negative);
-antivirals (Paxlovid/Tamiflu for positive viral testing)
continue LABA/LAMA daily maintenance

Alpha-1 Antitrypsin Deficiency (AATD)

What genetic mutation causes 1-3% of emphysematous changes in younger, non-smoking patients?
→liver damage common

Alpha-1 Antitrypsin Deficiency (AATD)

Which variant of COPD should be suspected?
→young patient, non-smoker, has COPD/emphysema symptoms
→elevated liver enzymes without an obvious cause
→adult onset asthmatics that DO NOT improve on spirometry with bronchodilators

Alpha-1 Antitrypsin Deficiency (AATD)

Pathophysiology
AATD protein normally protects the body from autoimmune destruction of the lungs by neutrophil elastase enzyme
→mutation causes deficient AATD protein, increased neutrophil elastase enzyme damages healthy lung tissue

Alpha-1 Antitrypsin Deficiency (AATD)

CXR findings
diffuse emphysematous changes
”panlobular emphysematous changes” (hallmark)
may see emphysematous bullae

cystic fibrosis

Pathophysiology
autosomal recessive genetic disease, mutation affecting CFTR membrane protein involved in chloride ions

-protein dysfunction= ↓↓secretion of chloride from cell
outer membrane dehydration and thick, viscous secretions in the lungs, pancreas, liver, intestine, productive tract → chronic infections and loss of lung function

CFTR protein

Which protein is affected by an autosomal recessive mutation in cystic fibrosis disrupting the chloride ion gradient (↓extracellular chloride, ↑ intracellular chloride) and thick mucus on outer layer of cells?

cystic fibrosis

Which autosomal recessive condition has a hallmark symptom of thick extracellular mucus and decreased clearing in the respiratory system → chronic infections/inflammation/loss of lung function?

cystic fibrosis

Etiology
childhood infections: Staph aureus/H. influenza
teenage/Adult Infections: Pseudomonas or Staph aureus

Management
Recommend routine sputum cultures (every 3 months) and antibiotics for pulmonary exacerbations

pseudomonas

Which cystic fibrosis exacerbation is treated with respiratory fluroquinolones (Levaquin) and chronic azithromycin and inhaled tobramycin (after sputum culture)?

obstructive pattern

What pattern does cystic fibrosis show on pulmonary function test?
→FEV1 correlated to survival

cystic fibrosis

CXR
-lungs hyperinflated
-increased bronchial markings (bronchiectasis) “tram tracks”
-flattened diaphragms
-kyphosis of spine common late in disease

cystic fibrosis

Extrapulmonary manifestation: Pancreatic Effects
→mucus blocks pancreatic secretions → pancreatic enzyme deficiency/pancreatitis

1.Decreased fat absorption – steatorrhea (fatty, oily stool)
-Vitamin ADEK malabsorption, decrease Bone Mineral Density (vit D)
2. Decreased protein metabolism – malnutrition
• Failure to thrive
3. Insulin insufficiency – cystic fibrosis related diabetes

cystic fibrosis

Extrapulmonary manifestation: GI Effects
-Meconium ileus (newborn)
-small bowel obstruction after infancy (mimic appendicitis)
-progressive biliary disease/cirrhosis, cholelithiasis (gallstones)

meconium ileus

newborn is unable to pass first stool, 10-20% of newborns with cystic fibrosis
symptoms: abdominal distention, crying, vomiting

cystic fibrosis

Extrapulmonary manifestation: GU Effects
95% of AMAB patients are infertile (absence of Vas Deferens)
AFAB infertility (common)
Delayed puberty

cystic fibrosis

Other Extrapulmonary manifestations
Anemia
DVT
Electrolyte imbalances
Kidney stones
Aquagenic wrinkling - wrinkling palms after water
Spontaneous pneumothorax
Spontaneous hemoptysis

cystic fibrosis

Diagnosis
Patient must have:
-Clinical symptoms consistent with cystic fibrosis OR
-A positive newborn screen OR
-A sibling with cystic fibrosis

AND
-↑ Sweat Chloride Test >60 (routine newborn screening)
- Presence of two disease-causing mutations in the CFTR gene (one from each parent)
-Abnormal nasal potential difference (NPD)

chloride sweat testing

testing done to confirm newborn screening for cystic fibrosis after patient is 2 weeks old
→sweat cells have higher levels of chloride in cell (>60mmol/L)

Elexacaftor-tezacaftor-ivacaftor (ETI) (Trikafta)

approved for people >2yo with cystic fibrosis
MOA: CFTR modulator can almost completely prevent symptoms by targeting the abnormal protein to make it functional and open chloride ion channel
*Not all genetic mutations will respond to ETI therapy

→Take with fatty foods twice daily, avoid grapefruit, dosing age/weight dependence
Side effects: monitor elevated liver functions (AST/ALT)

Percussion vest (daily therapy) to help with mucus clearing

Ivacaftor

approved for kids 1 month to 2 years old with cystic fibrosis
→switch to ETI at age 2

Percussion vest (daily therapy) to help with mucus clearing

cystic fibrosis

-Manage hydration (helps keep mucus thin)
-Manage inflammation (steroids for flares)
-Azithromycin (maintenance for pseudomonas on culture)
-Treat infections with antibiotics
-Prevent Infections
-Increase sputum clearance – percussion vest, massage
-Nutrition (tight glucose control with diabetes)
-Treat complications

Obstructive Sleep Apnea (OSA)

Repeated episodes of upper airway obstruction during sleep (most common)
- Poor sleep impacts EVERYTHING
- obesity and alcohol use (most common)

S/S: Snoring (common, but not always present)
-morning headaches (bifrontal/squeezing), daytime sleepiness, mood changes, lack of concentration, nighttime awakenings w/ choking/gasping

Obstructive Sleep Apnea (OSA)

Risk Factors
Obesity, neck circumference, alcohol use
-Craniofacial Bone Structure
-Tongue size
-Tonsil size (esp. kids)
-Male sex
-Older age
-Smoking? – possible weak link
-Diabetes, CAD and previous stroke - weak associations

Obstructive Sleep Apnea (OSA)

Pathophysiology
-weight of surrounding adipose tissue in the neck and tongue causes pressure/partial airway collapse → apneic episodes

Physical exam
-narrow or crowded oropharynx (Mallampati Score, Friedman tongue position)
-obesity (BMI>30)
-large neck circumference (>17in males; >16in female)

Obstructive Sleep Apnea (OSA)

GOLD STANDARD for DIAGNOSIS:
overnight sleep study or polysomnography (PSG) in sleep lab
→especially airline pilots, police, bus drivers, security workers

Alternative
Home testing → for high likelihood symptoms, if negative send for further testing in lab

Obstructive Sleep Apnea (OSA)

Diagnosis
1. 5-14 apneic/hypopnea episodes per hour AND one sleep related condition (daytime sleepiness, fatigue, snoring, apneas
hypertension, mood disorder, CHF, stoke, DM2, A. Fib, CAD)
or
2. 15+ apneic/hypopnea episodes per hour

Obstructive Sleep Apnea (OSA)

Treatment
Mild cases: weight loss may be curative
Moderate/Severe: Weight loss + PAP therapy
→CPAP therapy: lifelong, “continuous positive airway pressure” prevents airway collapse

*surgery can be an option if refractory to PAP therapy
→Tonsillectomy (kids), uvuloplasty, maxillomandibular advancement, nasal polyp removal
-bariatric surgery (weight loss)
-hypoglossal nerve implant surgery

Obstructive Sleep Apnea (OSA)

Patient Education
Weight Loss may help with symptoms
Avoid alcohol
Avoid sleeping on back
Physical activity
Exercise
Smoking cessation
PAP treatment adherence

Pediatric Sleep Apnea

Risk Factors: Obesity and tonsillar hypertrophy
~affects an estimated 1-5% of kids

S/S: Associated with decreased growth and weight (reverses with treatment)

Dx: polysomnography in sleep center (home testing NOT recommended)
Tx: tonsillectomy, weight loss, CPAP
Pt ED: avoid second hand smoke, weight loss

Central Sleep Apnea (CSA)

Associated with heart failure, stroke, chronic opioid use
-Apneic episodes from nervous system disruption, chemoreceptors failure to respond to CO² levels
(no airway obstruction)
- May be associated with Cheyne-Stokes breathing

Cheyne-Stokes breathing

breathing pattern characterized by repeated hyperventilation followed by apneic episodes (central sleep apnea)
→associated with heart failure and strokes, poor prognosis

Central Sleep Apnea (CSA)

Pathophysiology
-central chemoreceptors fail to respond adequately to increasing CO² levels that control respirations and causes apnea/hypoventilation
→hypoventilation can cause respiratory acidosis

S/S: Snoring (common, but not always present)
- Daytime sleepiness, mood changes, lack of concentration, awakenings w/ choking/gasping, morning headaches

Central Sleep Apnea (CSA)

Tx: Acetazolamide (Diamox)
- Goal: Improve symptoms/overall health outcomes
- Mild OSA = Weight loss (may be curative)
- Mod/Severe = Weight loss + PAP therapy

Pt ED:
- reduce opioids, treat underlying heart failure, phrenic nerve stimulation

Acetazolamide (Diamox)

What medication can be used to treat central sleep apnea?
- Causes central acidosis which leads to respiratory compensation and increase in ventilation

obesity hypoventilation syndrome

Epidemiology/Etiology
associated with obstructive sleep apnea, affects 10-20% of patients with obesity (middle age/males)
-higher prevalence with BMI >40

impaired ventilation and respitaroy muscle function as a result of severe obesity

obesity hypoventilation syndrome

Pathophysiology
—chronic hypoventilation (↑ CO²) due to impaired breathing mechanism → hypoxemia and hypercapnia, especially during sleep

Clinical Presentation
-daytime hypoventilation (dyspnea, lethargy, morning headaches)
-OSA symptoms (snoring, apneas)
-cyanosis, peripheral edema, right sided heart failure (advanced cases)

obesity hypoventilation syndrome

What syndrome of chronic hypoventilation puts patients at risk for pulmonary hypertension and cor pulmonale (right sided heart failure)?
Tx: weight loss, CPAP/BiPAP, supplemental oxygen, manage heart failure/pulmonary hypertension

obesity

What is the biggest risk factor for sleep apnea?

polysomnography (PSG)

What is the gold standard for diagnosing obstructive sleep apnea?

Bronchitis

inflammation of the bronchi causing prolonged cough >2 weeks
-one of the most common complaints in acute care
-often follow viral URI infection (RARELY bacterial, no antibiotics)

Bronchitis

Which bronchial disease is one of the most common complaints in acute care causing prolonged cough >2 weeks?

Bronchitis

Etiology
-most commonly caused by viruses (post-viral irritation/inflammation)
→also by irritants such as wildfire smoke, second hand smoke or air pollutants *RARELY a bacterial infection (antibiotics typically not indicated)

Pathophysiology
URI → inflammation → increased mucus production + inflamed bronchial walls trigger cough reflex, narrow airways leading to wheezing

Bronchitis

Clinical Presentation
prolonged cough (hallmark symptom; ~1-4 weeks, usually 18 days)
-cough can be dry or productive, worse at night
-also wheezing, mild dyspnea, MSK chest pain from cough
-NO systemic symptoms (fever, chills, malaise, myalgias; more likely pneumonia)

Diagnosis
Clinical Diagnosis: Recent URI, Prolonged cough
-normal vitals, well appearing patient

Bronchitis

Treatment
self-limiting disease
-usually NO antibiotics indicated (exceptions based on comorbidities)
Treatment is symptomatic
-cough medicine PRN: Dextromethorphan (OTC suppressant), Guaifenesin (OTC expectorant), Benzonatate (Rx: Tessalon Perles)
-Albuterol inhaler (wheezing)

steroids

What medication is NOT recommended for bronchitis?

Bronchiolitis

Which bronchial disease affects infants and young kids (<3 yo) most commonly by RSV viral infection and is the leading cause of hospitalization in infants/young kids?

Bronchiolitis

inflammation of the small airway (bronchioles) in infants and young kids <3yo
Etiology
most commonly RSV, leading cause of hospitalization in infants/young kids
Causes some form of respiratory distress