COPD/Cystic fibrosis

Question 1

COPD

Answer 1

Chronic lung disease characterized by progressive airflow limitation resulting from airway disease and/or parenchymal destruction

Subtypes:
Differing presentations and response to therapy
Patients may have any combination of both:
Chronic bronchitis
Emphysema

Epidemiology:
Prevalence: 16 million people in the United States
Age:
Prevalence peaks around 50–60 years of age
Age of onset is lower for heavy smokers
Sex:
More prevalent in men
Rates in women are rising

Question 2

COPD

etiology
Acquired and genetic

Answer 2

Cigarette smoking (90% of cases)
2nd-hand smoke
Air pollution
Occupational exposure to toxins
Alpha-1 antitrypsin (AAT) deficiency

Question 3

COPD

RF

Answer 3

Premature birth
Low body weight
Lower socioeconomic status
Poor nutrition
Childhood respiratory disorders
Pre-existing airway reactivity

Question 4

Chronic Bronchitis

Pathogenesis

Answer 4

Inhaled agents cause chronic inflammation in the airways, which lead to progressive airway obstruction through:

• Damage to endothelial cells → ↓ mucociliary clearance
• Mucous gland hyperplasia → mucous hypersecretion and plugging
• Airway edema and smooth muscle hyperplasia → luminal narrowing
  Peribronchial fibrosis → bronchial distortion

Question 5

Emphysema

Patho

Answer 5

In normal lungs, there is a balance between:
Proteases → break down elastin and connective tissue as part of normal tissue repair
Antiproteases → balance protease activity

In emphysema:
Inflammatory response → activated neutrophils release proteases
Protease activity exceeds antiprotease activity → tissue destruction (alveoli)
Enlarged alveoli
↓ Elastic recoil
↑ Compliance
Consequences:
Airway closure during expiration → obstruction
Air trapping → lung hyperinflation

Question 6

emphysema

Morphologic patterns

Answer 6

Centriacinar emphysema (associated with cigarette smoking):
Destruction of the respiratory bronchioles and a central portion of the acini
More severe in the apical lung fields

Panacinar emphysema (associated with AAT deficiency):
Destruction of all parts of the acinus (gas-exchange units of the lungs)
More severe in the basal lung fields

Acini– resp bronchioles, alveolar ducts, alveolar sacs, and alveoli

Question 7

COPD?

PE findings

Answer 7

Extremities:
Digital clubbing
Cyanosis
Central – lips and tongue; relates to poor blood oxygenation in the lungs
Peripheral – extremities or fingers; oxygen-depleted peripheral blood
Findings suggestive of cor pulmonale:
Jugular venous distension (JVD)
Peripheral edema

Question 8

COPD

Nail clubbing

Answer 8

Bulbous enlargement of the distal fingertip and increased longitudinal and transverse nail plate curvature

Schamroth sign
Loss of the diamond shaped window normally visible when the dorsal surfaces of the terminal phalanges of corresponding fingers from opposite hands are placed together

Lovibond’s angle
Angle located at the junction between the nail plate and proximal nail fold, and which is normally less than 160 degrees

Question 9

COPD

Clinical Phenotypes
“Blue Bloaters”

Answer 9

Signs and symptoms are associated more frequently with either chronic bronchitis or emphysema

Chronic bronchitis - “blue bloater”:
Patients are generally overweight
Frequent, productive cough
Peripheral edema
Cyanosis

Question 10

Question 11

COPD

Clinical Phenotypes
“Pink Puffer”

Answer 11

Emphysema (“pink puffer”):
Patients are generally thin
Barrel chest
Infrequent cough
Pursed lip breathing
Accessory muscle use
Tripod positioning
Hyperresonant chest

Question 12

Question 13

COPD

Dx

Answer 13

Pulmonary Function Test
Spirometry
↓ Forced expiratory volume in 1 second (FEV1): maximum volume of air forcefully expired 1 second after maximal inspiration
↓ Forced vital capacity (FVC): maximum volume of air forcefully expired after maximal inspiration
Greater loss of FEV1than FVC → ↓
FEV1/FVC ratio:FEV1/FVC: < 70%
FEV1/FVC: < 50% indicates severe disease
↑ Total lung capacity
↑ Residual volume due to air trapping (useless volume)
Post-bronchodilator test
Used to assess the reversibility of the obstructive condition

Question 14

COPD

Assessing Disease Pattern & Severity

Answer 14

Categorizes patients based on assessment of symptoms and risk of future exacerbations and hospitalizations
Patient is classified as being in groups (A, B or E)
Symptoms are assessed using the modified Medical Research Council (mMRC) dyspnea scale

Question 15

Question 16

Assessing Disease Pattern & Severity

CAT

Answer 16

COPD Assessment Test (CAT)
https://www.mdcalc.com/copd-assessment-test-cat
Quantifies impact of COPD symptoms on patient’s overall health
Components: cough, phlegm, chest tightness, breathlessness, activities, confidence, sleep, and energy with each scored 0-5
CAT ≥10 corresponds to either GOLD Group B or E
CAT < 10corresponds toGOLD Group A or E

Question 17

Answer 17

2023 GOLD Guide for COPD

Question 18

Question 19

COPD

Labs for Dx

Answer 19

Laboratory studies:
Arterial blood gas (ABG):
* Hypoxemia
* Progressive
* Often worse during acute exacerbation
* Hypercapnia
* pH is usually near normal due to renal compensation (↑ serum HCO3)

Alpha-1 antitrypsin (AAT) testing
Recommended if symptoms are not of the typical presentation
Younger
Nonsmoker
Basal lung involvement

Question 20

COPD

CXR

Answer 20

Chest X-ray:
Barrel-shaped chest
Wide intercostal spaces
Hyperinflation
Flattened, low diaphragm
Narrow cardiac shadow
Attenuated peripheral vascular markings (due to parenchymal destruction)

Chest CT:
Helps to access the extent and distribution of emphysema
Identify coexisting or complicating disorders (pneumonia, lung cancer, …)

Question 21

COPD

Bleb and Bulla

Answer 21

Bleb
Small collection of air between the lung and the outer surface of the lung (visceral pleura)
Usually found in the upper lobe of the lung
Can rupture causing a pneumothorax
Bulla
Formed from blebs that become larger or come together (>1 cm)

Hyperinflated lungs with diffuse reticular changes.Large (25 cm) right lung bulla.No infiltrate noted. No pneumothorax.

Question 22

COPD

General management

Answer 22

General management
Smoking cessation(critical for slowing lung function decline)
Vaccinations:
Pneumococcal pneumonia
Influenza
Covid-19
Pulmonary rehabilitation:
Guided exercise and behavioral interventions
Goal is to improve functional capacity
O2therapy – prolongation of life:
If O2saturation is < 88% in a stable patient
If concurrent pulmonary hypertension and right-sided heart failure

Question 23

COPD

Tx

Answer 23

Pharmacotherapy
Initial selection is based on the severity of symptoms and risk of exacerbations

Bronchodilators:
Short acting (used as needed for rescue)
Beta-2 adrenergic agonists
Muscarinic antagonists
Long acting
Beta-2 adrenergic agonists
Muscarinic antagonists
Inhaled corticosteroids
Theophylline(oral bronchodilator)
Mucolytics

Question 24

COPD

Short-acting bronchodilators

Answer 24

Recommended for all patients with COPD
Group A patients – minimally symptomatic, low risk of exacerbation
Short-acting beta agonists (SABA)
albuterol (ProAir, Proventil, Ventolin) and levalbuterol (Xopenex)

Short-acting (anticholinergic) muscarinic antagonists (SAMA)
ipratropium (Atrovent)
Advantage:
Rapid onset of action to improve symptoms and lung function
Disadvantage:
Relatively short duration of action, about four to six hours
Used alone or in combination for relief of intermittent symptoms of COPD
Combination therapy is often preferred
ipratropium-albuterol (Combivent)
Achieve greater bronchodilator response than either one alone

Question 25

COPD

Long-acting bronchodilators

Answer 25

Shown to be superior to short-acting bronchodilators
Long-acting beta agonist (LABA)
salmeterol (Serevent),formoterol (Perforomist),arformoterol (Brovana)
Long-acting muscarinic antagonist (LAMA)
tiotropium (Spiriva), aclidinium (Tudorza), umeclidinium (Incruse)

Group B patients – more symptomatic, low risk of exacerbation
Regular use of a long-acting bronchodilators (beta agonist + antimuscarinic agent)
LABA – resting tachycardia, tremor
LAMA – dry mouth, constipation, urinary retention

Question 26

COPD

Management of Group C & D

Answer 26

Group E – more or less symptomatic, high risk of exacerbation
Regular use of a long-acting bronchodilators (beta agonist + antimuscarinic agent)
Patients with a blood eosinophil count ≥300 cells/microL or features of asthma-COPD overlap, an inhaled glucocorticoid (ICS) should be added
budesonide or fluticasone
ICS should NOT be used as sole therapy for COPD
Adverse effects: dysphonia, skin bruising, oral candidiasis, lung infection, osteopenia/osteoporosis, HPA axis suppression

Question 27

COPD

Management of Acute Exacerbations

Answer 27

Outpatient or inpatient therapy depending upon severity
Short-acting bronchodilators:
Scheduled every 4–6 hours
Continuous nebulization may be needed for severe bronchospasm
Long-acting bronchodilators
Systemic corticosteroids

Indications for antibiotics (Augmentin as first-line option):
Purulent sputum
Increased dyspnea
Moderate or severe exacerbation requiring hospitalization

Controlled O2therapy for acute respiratory failure:
Nasal cannula
Noninvasive ventilation:
Hypercapnia and hypoxemia
Significant effort to breathe
Invasive ventilation:
Severe respiratory failure
May be difficult to wean patients with severe COPD

Question 28

Answer 28

Question 29

CF

general

Answer 29

Inherited (autosomal recessive) disease of the exocrine glands affecting primarily the gastrointestinal and respiratory systems
Caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene
>1,500 causative mutations have been identified
Type of mutation is crucial in determining the severity of the disease
Most common mutation:
delta F508 mutation (deletion)on chromosome 7 → loss of phenylalanine in position 508
Most common life-threatening genetic disease in the white population
3-4% of the white population carries the autosomal recessive trait
Incidence in the United States: 1 in 3,400 live births

Question 30

CF

Normal Functioning of CFTR

Answer 30

CFTR (cystic fibrosis transmembrane conductance regulator) gene
Codes for the CFTR protein → Cyclic adenosine monophosphate (cAMP)–regulated chloride channel, regulating chloride, sodium, and bicarbonate transport across epithelial membranes and into various secretions
Water is attracted to the secretions leading to thinning

Pathophysiology
Mutated CFTR → absent or dysfunctional chloride channel → dysfunctional transport of chloride → abnormal secondary transport of sodium and water
Disease manifests only in homozygotes

Question 31

Question 32

Answer 32

CFTR proteinwith the ∆F508 mutation getsmisfoldedand can’t migrate from the endoplasmic reticulum to thecell membrane, meaning there is a lack ofCFTR proteinon the epithelial surface

Less chloride ions out → less water drawn into secretions = thickened secretions

Question 33

CF

Patho

Answer 33

Absent or dysfunctionalchloridechannel → dysfunctional transport ofchloride→ abnormal secondary transport ofsodiumand water

Inthe sweat glands:
Inability to reabsorbchloridefrom the lumen → reduced reabsorption ofsodiumand water → sweat with elevated levels ofsodiumchloride

In the rest ofexocrine glands:
Inability to secretechlorideinto the lumen → accumulation of intracellularchloride→ increasedsodiumand water reabsorption → formation of hyperviscous mucus → accumulation of secretions → blockage of small passages → chronicinflammation→ multiple organ damage

Question 34

CF

Clin Man

Respiratory system

Answer 34

Ineffectivemucociliary clearance
Obstruction of thealveoli/bronchioleswith an increased risk of infection
Chronic/recurrent sinus infections
Nasal polyps
Recurrent pulmonary infections
Early in the course….Staphylococcus aureus is the most common pathogen
Later in the course….Pseudomonas aeruginosais the most common pathogen (multidrug-resistant strains)

Persistent or recurrent cough, increased sputum production, gagging, intercostal retractions, barrel-chest deformity

Question 35

CF

Clin Man

GI system

Answer 35

Gastrointestinal system
Small intestine
Thick secretions impair absorption, increasing the risk of obstruction
Large intestine
Incompletely digested macronutrients lead to thick stool, predisposing patient to impaction and obstruction
Meconium ileus:
Surgical emergency
Failure to pass meconium within 48 hours of life in newborn (10-20% pf patients)
Abdominal distention, vomiting, poor appetite, inadequate weight gain

At risk for rectal prolapse due to straining

Question 36

Question 37

CF

Clin man

Pancreas

Answer 37

Thick secretions block pancreatic duct and impair fat absorption (deficiency of fat-soluble vitamins)
Decreased bicarbonate damages digestive lining and impairs absorption
Pancreatic enzymes cannot be released and slowly destroy pancreas, leading to fibrosis and impaired endocrine function (diabetes)
Abdominal pain; abdominal cramping; bloating; frequent bulky, oily stools (steatorrhea); weight loss

Question 38

COPD

Clin Man

Hepatobiliary

Answer 38

Hepatobiliary
Bile is dehydrated, leading to gallstones (asymptomatic)
Chronic cholestasis leads to inflammation and fibrosis, which results in cirrhosis and portal hypertension
Right upper quadrant pain after large, fatty meals; nausea; vomiting; jaundice

Question 39

CF

Clin man

reproductive system

Answer 39

Reproductive system
Males
Infertility and delayed secondary sexual development due to:
Obstructive azoospermia due to bilateral aplasia/atresia of the vas deferens
Undescended testicle; 15x more likely than in the general population

Females
Reduced fertility due to:
Viscous cervical mucus
Amenorrhea
Excessive sweating (hot weather or fever) leads to hyponatremic/hypochloremic dehydration

Question 40

CF

CF PANCREAS

Answer 40

C: Chronic cough
F:Failure to thrive

P: Pancreatic insufficiency (exocrine)
A:Alkalosisandhypotonicdehydration
N: Nasal polyps, neonataldehydration
C:Clubbingof fingers – chronic pulmonary disease
R:Rectal prolapse
E: Electrolyte elevation (sweat)
A:Atresia, absence ofvas deferens
S: Sputum withStaphylococcus aureusorPseudomonas; Stones in the gallbladder

Question 41

CF

Newborn Screening

Answer 41

Measurement of immunoreactive trypsinogen (IRT)
A pancreatic enzyme released when there is pancreatic damage
If elevated → mutation analysis of CFTR
If results indicate CF → sweat chloride test
Infant - at least 2 weeks of age with a weight over 2 kg
10% are not diagnosed until adolescence or early adulthood

Question 42

Question 43

COPD

Sweat chloride test

Answer 43

Gold-standard of diagnosis
Pilocarpine iontophoresis used to determine sweat chloride concentration
> 60 mmol/L in 2 tests = diagnosis of CF
Infants who have a positive newborn screening result and evidence of possible CFTR dysfunction but do not meet the diagnostic criteria for CF are classified as having CFTR-related metabolic syndrome (CRMS)

<= 29 rules out CF
30-59 is intermediate

Question 44

Cystic fibrosis

Fecal elastase and Airway culture

Answer 44

Fecal elastase
Pancreatic insufficiency can be detected when screening the stool for pancreatic elastase-1, which is absent in 80% of people with CF

Airway culture
Persistent detection of the following bacteria in respiratory secretion and sputum
80% growS. aureus or Pseudomonas aeruginosa

Haemophilus influenzae, Burkholderia cepacia, Stenotrophomonas maltophilia
All (exceptS. aureus) would be unusual in people without CF

Question 45

CF

Tx multidisciplinary

Answer 45

Multidisciplinary approach
Therapies:
Antibiotics, inhaled drugs to thin airway secretions, and physical maneuvers to clear airway secretions (airway clearance techniques (ACTs))

Inhaled bronchodilators and sometimes corticosteroids

Pancreatic enzyme replacement and vitamin supplementation

High-calorie diet (sometimes requiring supplemental enteral tube feedings)

Question 46

CF

Prevention of infection

Answer 46

Prevention of infection:
All routine childhood vaccines, annual influenza vaccine, high-risk protocol for pneumococcal vaccine, covid-19 vaccine
Palivizumab to prevent respiratory syncytial virus infection

Question 47

CF

Prognosis

Answer 47

Largely determined by the degree of pulmonary involvement (deterioration is inevitable)
CF patients have a median life expectancy of 45 years
50% of patients die before the age of 18 from respiratory failure and cor pulmonale
Steady improvement over the past 5 years due to early diagnosis and aggressive treatment

The prognosis depends on several factors:
Age
Gene variant
Colonization by multi-drug resistant pathogens
Lung function
Complications
Access to medical care