Medical Archive

Pathogenesis

Neutrophil elastase (MMP9): cause alveolar damage, reduced ciliary motion, increased mucus secretion by goblet cells.
CD8+ T-cell: alveolar destruction

Inflammation and extracellular matrix proteolysis

?????? ?? Elastase vs ?1 antitrypsin? ?? ??
??? ????? 3??; ??, Airway ??, ?1-antitrypsin deficiency

Pathology

Large airways

Chronic bronchitis

• Diagnostic criteria
  • Productive cough > 3 months in a year for > 2 consecutive years.
• ?? ??? ?? ????, ??? ??. ?? ?? ?, normal recoil .
• Cyanosis (‘blue bloaters’) – Mucus plugs trap carbon dioxide; ?Paco2, and ?PaO2
• Pathology
  • Leads to increased thickness of mucus glands relative to overall bronchial wall thickness (Reid index increases to> 50%; normally <40%).
    

Small airways

Small bronchiole? ??? ??

Lung parenchyma

Emphysema

• Due to imbalance of proteases and antiproteases
  • Inflammation in the lung normally leads to release of proteases(elastease) by neutrophils and macrophages.
  • Excessive inflammation or lack of A1AT(which neutralizes proteases) leads to destruction of the alveolar air sacs.
• Pathologic types
  • Centriacinar – associated with smoking, frequently in upper lobes.
  • Panacinar – associated with ?1-antitrypsin deficiency.
• Smoking is the most common cause of emphysema.
• ?Compliance(???), ?recoil, ?DLCO
• CXR: Barrel chest
• Hypoxemia (due to destruction of capillaries in the alveolar sac) and cor pulmonale are late complications.

Pathophysiology

Airflow obstruction

“Airway limitation that is not fully reversible” (cf. ??? reversible??)

Hyperinflation

???? ?? (?? ?? ??) ? ???? ?? (?? ?????)

Gas exchange

Risk factors

Cigarette smoking

Airway responsiveness and COPD

Respiratory infections

Occupational exposures

Ambient air pollution

Passive, or second-hand, smoking exposure

Genetic considerations

?1-deficiency 

• Rare cause of emphysema.
• Pathophysiology
  • Liver cirrhosis may also be present (mutant A1AT accumulates in the endoplasmic reticulum of hepatocytes). Biopsy reveals pink, PAS-positive globules in hepatocytes
  • PiM is the normal allele, PiZ is the most common clinically relevant mutation. PiMZ heterozygotes are usually asymptomatic. However, significant risk for emphysema with smoking exists
• Clinical presentation
  • Early onset (age <50) panacinar emphysema, basilar lung area predominantly.
    • Cf) tobacco-related centriacinar emphysema predominantly affects the upper lung lobes, possibly d/t higher V/Q ratio in those regions.
  • Tobacco exposure dramatically accelerates the development of emphysema
    • By inducing inflammation
    • Permanently inactivating the already low quantities of AAT through oxidation of a crucial methionine residue.
  • Some patients develop liver disease d/t intrahepatocyte accumulation of polymerized AAT molecules
    • P10 S3 C337 Cirrhosis and Its Complications
• Diagnosis
  • ?Serum A1AT level & genetic testing.
• Treatment
  • IV supplementation with pooled human AAT.

Other genetic risk factors

Natural history

Clinical presentation

History

Cough, sputum, exertional dyspnea

# Complication
Cor pulmonale, 2° polycythemia vera (? phlebotomy), Respiratory failure

# Subcutaneous emphysema
COPD? ?? 2?? ???? ?? ??.

Physical findings

??? barrel chest
Clubbing? ???? COPD?? ??? ??

# Pulmonary cachexia

BMI ?20kg/m2 or weight loss >5%.
Occurs 20%-40% of patients with COPD.
Correlates with disease severity.

Laboratory findings

PaO2, PaCO2? ???? ???. Hypoxia? V/Q mismatch ??? ??? O2 ??????.

PFT? ??, ????? gold standard
??? ??? ?? ? FEV1/FVC<70%? ? ??. Severity? FEV1? ??(??? ??

XR: hyperinflation, bullae ? ??
CT: emphysema ?? ??. ??? ??? ??? ??

Asthma COPD overlap syndrome (ACOS)

? ??? ??? ?? ??. ??? ??? GOLD guideline ?? (???? ???)

Treatment

Stable phase COPD

???? ??? ???

??, O2
Lung volume reduction surgery (LVRS)
Influenza vaccination
? ??? ?? ??? ?? ??.

Pharmacotherapy

Smoking cessation

??? ?? ??. But FEV1 ????? ?? ???

Bronchodilators

• SABA (Salbutamol, ???), SAMA (ipratropium)
• LABA (Salmeterol, ?????), LAMA (tiotropium)
• ICS
  • FEV1??? ??? exacerbation ?? ??.
  • Ix: 2?/yr ?? ?? ?? ?, Reversibility? ??? ?
• OCS

Theophylline

PDE4 inhibitor

Block the degradation of cAMP ? ?airway inflammation and smooth muscle relaxation
e.g., roflumilast

Antibiotics

If >2 cardinal symptoms: ?dyspnea, douch, sputum production (change from baseline)

Oxygen

2° polycythemia ??, cor pulmonale ??
1L/min ? FiO2 0.04 ??(PaO2 20%?). ?? ??? FiO2 <0.28 ??.
?? ??? hypercapnia? ???? ? ??.

• Long-term home oxygen therapy (LTOT)
  • Goal SaO2: 90-90%
  • Indication
    • SaO2 <88% or PaO2 ?55%
    • SaO2 <90% or PaO2 ?60%
      + pulmonary hypertension / cor pulmonale / evidence of RHF / Hct >55%
  • Survival benefits are significant when it is used for ?15 hours a day.

?1AT augmentation therapy

Available for individuals with severe ?1AT deficiency.

Nonpharmacologic therapy

Pulmonary rehabillitation

??: exercise tolerance?, ??? ???? ???
Influenza vaccine, (Pneumococcal vaccine)
A group ???? ?????? ??

LVRS

????: diffuse emphysema, pul HTN, Stage IV

Lung transplant

65? ??, medical Tx??? ?, ?? ??? ???? ??? ?

Exacerbations of COPD

• Pathophysiology
  • Worsening of underlying inflammation, 
• Etiology
  • Infection(70-80%)
    • Viral(40-50%): rhinovirus, influenza, parainfluenza, coronavirus, adenovirus
    • Bacterial: H.influenza, M.catarrhalis, S.pneumonia
  • Arrhythmia
  • Air pollution, pulmonary embolism
• Clinical presentation
  • Characterized by a change in >1 of the following. Add antibiotics if >2 cardinal symptoms
    • Cough severity or frequency
    • Volume or character of sputum production
    • Level of dyspnea
  • Jugular venous distension (JVD), especially during expiration, d/t increased intrathoracic pressure.

Prevention

• ICS, LABA, Vaccination

Treatment of acute exacerbations

• Oxygen (SaO2 90%, PaO2 60% ??)
• Inhaled bronchodilators
• Systemic glucocorticoids
• Antibiotics if ?2 cardinal symptoms
  • Macrolides, respiratory fluoroquinolones, or penicillin/beta-lactamase inhibitors.
  • Typically, 3-7 days.
• Oseltamivir if evidence of influenza
• NPPV
  • If ventilatory failure (PaCO2>45 or pH<7.35)
  • ?? ?? ??? ?? (e.g. ??????)
• Tracheal intubation
  • If NPPV failed or contraindicated
• Mechanical ventilation
  • Mental ?(????? ?? NIPPV ?? ??)

CO2 narcosis (CO2 retention)

• Pathophysiology
  • O2 ??? ?? vasodilation, steal? ?? ??? V/Q mismatch is major cause.
    (Reversal of hypoxic pulmonary vasoconstriction)
  • Haldane effect: Hb? O2? ???? CO2 uptake? ??? ?.
  • ?Respiratory drive
  • Resultant ?CO2
    • ? acidosis ? ?level of consciousness
    • ? cerebral vasodilation ? may induce seizure
• Management
  • Goal SaO2 of 90-93% or PaO2 60-70mmHg.
  • Significant acidosis, severely reduced level of consciousness require mechanical ventilation.