Chronic Obstructive Pulmonary Disease

THE Guideline
Global Initiative for Chronic Obstructive Lung Disease (GOLD), World Health Organization (WHO), National Heart, Lung and Blood Institute (NHLBI)

Definition of COPD
COPD is a preventable and treatable chronic lung disease characterized by airflow limitation that is not fully reversible
The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases, primarily caused by cigarette smoking
Although COPD affect the lungs, it also produces significant systemic consequences
Adapted from the Global Initiative for Chronic Obstructive Lung Disease 2007
ATS/ERS Guidelines 2004

Epidemiology of COPD
4th leading cause of death in world
4th leading cause of death in U.S.A.
3rd most common reason for hospitalization.
Rare under 40, сommon in elderly
greater in men than in women.
Prevalence of 9.34/1,000 in men and 7.33/1,000 in women (Global Burden of Disease Study, 2007).

COPD includes:
chronic bronchitis
chronic bronchiolitis (small air way disease)
Emphysema

Risk Factors for COPD
Host factors
Alpha-1-antitrypsin deficiency
airway hyperrespon- siveness
Disordered lung development
Environmental factors
Tobacco smoke
Occupational dusts/chemicals
Air pollution
Childhood infections

Risk factors
cigarette smoking remains
the most important.
Susceptibility to cigarette smoke varies but both the dose and duration of smoking appear to be important and it is unusual to develop COPD with less than 10 pack years.
(1 pack year = 20 cigarettes / day /year).

Alpha-1-antitrypsin deficiency
α1-Antitrypsin is a proteinase inhibitor which is produced in the liver, secreted into the blood and diffuses into the lungs.
Mechanism of action: an inhibition of proteolytic enzymes such as neutrophil elastase, which are capable of destroying alveolar wall connective tissue.

Pathophysiology
COPD has both
Pulmonary components
Systemic components

Pulmonary components:
Mucus secretion An enlargement of mucous secreting glands and an increasing number of goblet cells in the large airways → increase mucous that causes chronic bronchitis
Loss of elastic tissue surrounding the smaller airways combined by inflammation and fibrosis in the airway wall → airflow limitation.

Pulmonary components:
Premature airway closure leads to gas trapping and hyperinflation →
↓ pulmonary and chest wall compliance. (during exercise the time available for expiration shortens resulting in progressive hyperinflation)

Pulmonary components:
Flattening of the diaphragmatic muscles and increase horizontal alignment of the intercostals muscles → mechanical disadvantage of respiratory muscles → increase work of breathing first on exercise but then at rest.

Pulmonary components:
In the alveolar capillary units the unopposed action of proteases and oxidants → destruction of the alveoli → bullae formation in some individuals which → impaired gas exchange and respiratory failure.

Systemic components:
1. Skeletal muscle weakness.
2. Increase circulating inflammatory markers.
3. Impaired salt and water excretion leading to peripheral edema.
4. Altered fat metabolism contributing to weight loss.
5. Increase prevalence of osteoporosis.

Pathophysiology (conclusion)
inflammation, bronchial wall
edema, mucous secretion,
hyperinflation and air trapping
Increase in proteinases &
free radicals lead to
parenchymal destruction
Changes in pulmonary
vasculature lead to
ventilation-perfusion
mismatching,
pulmonary hypertension
cor pulmonale

COPD: Pathology

Assess for COPD:
Cough
intermittent or daily
present throughout day, seldom only nocturnal
Sputum
Any pattern of chronic sputum production
Dyspnea
Progressive and Persistent
"increased effort to breathe" "heaviness" "air hunger" or "gasping"
Worse on exercise
Worse during respiratory infections

Diagnosis of COPD
Considered in patients with cough, sputum production, or dyspnoea +/- risk factors.
Confirmed by spirometry.
FEV1/FVC <70% + postbronchodilator FEV1 <80% of predicted value.
A low peak expiratory flow has poor specificity for the diagnosis of COPD.

Classification of COPD
Stage 0 At Risk
Stage I Mild
Stage II Moderate
Stage III Severe
Stage IV Very Severe

Stage 0 At Risk
Normal spirometry
+/- Chronic symptoms (cough, sputum, production)

Stage I Mild COPD
FEV1/FVC <70%
FEV1 >80% predicted
With or without chronic symptoms (cough, sputum production)

Stage II Moderate COPD
FEV1/FVC <70%
50%
With or without chronic symptoms (cough, sputum production)

Stage III Severe COPD
FEV1/FVC <70%
30%
With or without chronic symptoms (cough, sputum production)

Stage IV Very Severe COPD
FEV1/FVC <70%
FEV1 <30% predicted or FEV1 <50% predicted plus
chronic respiratory failure

Diagnosis of COPD

Healthy Respiratory Mucosa
This electron micrograph shows the respiratory mucosa in a healthy state
The cells are fully ciliated
The cilia beat in a co-ordinated fashion to move mucus out of the airways (mucociliary transport)
Scanning electron micrograph showing a sheet of mucus being moved along by the cilia

Damaged Respiratory Mucosa
Damage to the cilia and epithelium occur as a result of disease processes in COPD. This can also occur as a result of bacterial damage
This slide shows the result of bacterial infection stripping away the cilia from the mucosa
The damage to the cilia means they are less effective in removing mucus from the airways

smokers lung – Emphysema

Emphysema
Dilation of alveolar wall
↓ alveolar capillary network, loss of guy rope effect
↓ lung tissue elasticity
Caused by smoking » irritation » inflammation » neutrophils and macrophages » release neutrophil elastase (type of proteases)
Emphysema
Normal Lung

Emphysema
is defined pathologically as dilatation and destruction of the lung tissue distal to the terminal bronchiole.

classification
Centri-acinar emphysema.
Pan-acinar emphysema.
Irregular emphysema.

Centri-acinar emphysema
Distension and damage of lung tissue is concentrated around the respiratory bronchioles, whilst the more distal alveolar ducts and alveoli tend to be well preserved
is associated with substantial airflow limitation

Pan-acinar emphysema
Distension and destruction appear to involve the whole of the acinus, and in the extreme form the lung becomes a mass of bullae.
Occurs in α1-antitrypsin deficiency

Irregular emphysema
scarring and damage affect the lung parenchyma patchily without particular regard for acinar structure

Spirometry
Normal flow-volume loop
Flow-volume loop in severe COPD

Pulmonary Function Tests

Assess:
Measure Airflow Limitation
Patients with COPD typically show a decrease in both FEV1 and FVC
Postbronchodilator FEV1 < 80% predicted + FEV1/FVC < 70% confirms the presence of airflow limitation that is not fully reversible
FEV1/FVC < 70% is an early sign of airflow limitation in patients whose FEV1 remains normal (>80% predicted).

GOALS of COPD MANAGEMENT
Relieve symptoms
Prevent disease progression
Improve exercise tolerance Improve health status
Prevent and treat complications
Prevent and treat exacerbations
Reduce mortality

General Points
Only smoking cessation and O2 therapy have been shown to prolong survival
Other therapies aimed at relieving symptoms, improving quality of life, reducing exacerbations and need for hospitalizations

Exacerbation management
Chronic stable management
Adjuvant therapy

Beta2-Agonists
Short acting B2-Agonists:
Salbutamol ( albuterol )(4-6hrs)
fenoterol (4-6hrs)
levalbuterol (6-8hrs)
terbutaline(4-6hrs)
Long acting B2-Agonists (LABA ) - Therapy for Stage 2 , 3 and stages 4 of COPD.
salmeterol (12+ hrs)
formoterol (12+hrs)

Beta2-Agonists
Excellent bronchodilator and quick effect. Therapy for all stages, mostly rescue and as needed dosing every 4 to 6 hours for shortness of breath.
Relax airway smooth muscles by stimulation of B2- adrenergic receptors which increases cyclic AMP and produce antagonist effect to bronchoconstriction.
Excess doses cause tremors, anxiety, tachycardia, arrhythmias, hypokalemia

Anticholinergics
Short acting Anticholinergics
ipratropium bromide (6-8 hrs) now nebulised and inhaler
oxitropium bromide (7-9hrs) in solution and inhaler
Research brought quaternary compound of atropine
Long acting
Tiotropium inhaled (24+hrs) aerolised powder. ipratropium bromide/salbutamol (Combivent) fenoterol/ipratropium bromide (Berodual)

Anticholinergics (Tiotropium)
Block muscarinic receptors and prevent smooth muscle contraction while ↓ release of secretion from submucosal glands.
Ipratropium bromide, devoid of systemic effects, the nebulization dosage is 0.5mg every 4 hours

Drug therapy for COPD begins with long acting anticholinergics and beta-2 agonist bronchodilators. These provide symptom relief but do not stop progression of the disease

Inhaled Steroids
Front line therapy for COPD stages 3 and 4
Budenoside Nebulizer
Inhaled fluticasone
Inhaled triamcinolone
Inhaled beclomethasone
Inhaled budenoside
LABA and budenoside mixed in inhaler

Treatment of Stable COPD
Other Medications
Chronic oral Prednisone
Use in chronic COPD is controversial. No effect on survival. May improve symptoms and reduce hospitalizations in some patients already at maximum treatment
Mucolytics & Expectorants
Relives symptoms from copious, viscous secretions
Oral Theophylline (If inhalers not sufficient ) Side effects are common

Methylxanthines
Multiple modes of action : bronchodilatation, ↑ dia-phragmatic contractility, stimulation of respiratory drive, inotropism, ↑ mucociliary clearance, and synergy with ß2-Agonists and Anticholinergics
5mg/kg IV over 10 to 15 min then 0.5mg/kg/hr if normal liver function
1mg/kg IV elevate a 2μg/ml in blood level (await blood level results before IV dose when patient on oral aminophylline)
Lower dosing : Alcoholism, old age, chronic liver disease, CHF, fever, erythromycin. ciprofloxacin or H2-blocker

Mucokinetic Medications
Nebulized water and saline and oral expectorants guaifenesin and saturated iodide are of no benefit
Acetylcysteine cause reflex bronchoconstriction
Clinical improvement with oral iodinated glycerol but can cause thyroid dysfunction
Simple oral hydration is the easiest and safest agent

Treatment of Stable COPD:
Home Oxygen Therapy
> 15 hours/day reduces mortality Criteria for O2 therapy
Pa O2 < 55 mm Hg (O2 saturation < 88%) at rest or during exercise or sleep or
Pa O2 < 60 mm Hg and hematocrit >52%

Exacerbations in COPD
Etiology
Primary
– viral and bacterial infections
– air pollution
– discontinuation of medications
– unknown reasons
Secondary
– pneumonia, pulmonary embolism, heart failure
pneumothorax,

COPD Exacerbations
Primary symptom— increased dyspnea —may be accompanied by wheezing and tightening of chest, increased cough and volume of sputum, a change in the color of sputum
Possible malaise, insomnia, sleepiness, fatigue, fever, depression, confusion
Most commonly caused by infection of the airways and air pollution
Diagnosed through a targeted history and physical, spirometry, arterial blood gases or pulse oximetry

Antibiotics
– Have proven beneficial in treating acute infective exacerbations of COPD
– Should be used in patient with 2 or more symptoms :
worsening dyspnea
increased sputum volume
increased sputum purulence

Antibiotics in Acute
Exacerbations of COPD
Traditional regimen: three to 14 days of tetracycline, amoxicillin or fluorquinolone
Choice of agent should reflect local patterns of antibiotic sensitivity among S. pneumoniae, H. influenzae and M. catarrhalis
Exacerbations have been linked to new strains of these organisms
Treatment may include amoxicilin, macrolide, quinilone or tetracycline

Inpatient Treatment of Acute Exacerbations
Oxygen to keep O2 sat >90%
Nebulizer treatments with bronchodilators
Steroids (40 to 60 mg daily for 7 to 14 days, IV or PO)
Antibiotics Fluids

Oxygen therapy
Generally only considered in severe (stage III) COPD patients with PaO2 <55 mmHg
• Goal: to increase PaO2 to 60 mmHg or an SaO2 of >90%
• Administration: long-term continuous therapy, during exercise, or to relieve dyspnoea
• Benefits: long-term administration (>15 h/day) increases survival, improves haemodynamics, exercise capacity, lung mechanics and mental state
• Limitations: cost of supplemental home delivery is high

Phosphodiesterase-4 Inhibition
(Roflumilast)
Inhibition raises intracellular levels of cAMP resulting in downregulation of signaling pathways in inflammatory cells
Major isoenzyme in inflammatory cells
implicated in inflammatory airway disease

COPD
Airway
obstruction
Exacerbation
Mucus
hypersecretion
Continued
smoking
Lung
inflammation
Alveolar
destruction
Impaired
mucus clearance
Submucosal gland
hypertrophy
Exacerbation
Exacerbation
Hypoxemia
DEATH
“The Downward Spiral”

SMOKERS
“Hope and expect for the best.
Prepare for the worst.”
Back AL, Arnold RM, Quill TE. Hope for the best, and prepare for the worst. Ann Intern Med 2003;138:439-43.

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