Copd

Dr. Prasad B. Chinchole
Pharm D
Assi. Professor
SCOP, Almala
@ Dr. Prasad B. Chinchole

• Chronic obstructive pulmonary disease (COPD) is characterized by
airflow limitation that is not fully reversible.
• Otherwise known as chronic obstructive airway disease(COAD) or
chronic obstructive lung disease.
• The most common conditions comprising COPD are chronic
bronchitis and emphysema.

COPD: Chronic, slowly progressive disorder characterized
by airway obstruction, which does not change markedly over
several months.
Definition

Chronic bronchitis: Chronic/recurrent cough with sputum production
on most of days for at least 3 months of the year during at least 2
consecutive years, in the absence of other diseases recognized to
cause sputum production.
Emphysema: An abnormal permanent enlargement of air spaces distal
to the terminal bronchioles, accompanied by destruction of their walls
and without obvious fibrosis.

• Major cause of morbidity & mortality in all industrialized countries
& largest single cause of lost working days in UK.
• About 30000 deaths/year in UK and is accountable for more than
12% of all hospital admissions.
• CB – common in areas of high atmospheric pollution and in people
with dusty occupations like foundry workers and coal miners.
Epidemiology

• Tobacco smoking is the most important risk factor
• Incidence in non-smokers – less than 5%.
• Tobacco exposure – 15% of smokers susceptible to induce COPD.
• Other noxious contributory particles are -exposure to chemical fumes , dust
and gases .
• The age when cigarette smoking started, total pack years of smoking &
current status of smoking---predict COPD mortality
• Total pack year = (number of cigarettes per day / 20) X number of years of
smoking
• 1-20 pack-year → 10% risk for mild COPD, 4% for severe risk 61 pack-year
→ 24% & 7% respectively.
• Additional risk factor-natural ageing process of lungs
• Genetic factor-alpha-1 antitrypsin deficiency
ETIOLOGY

• Cigarette smoking & air pollution.
• Normally cilia & mucus in bronchi protect against inhaled irritants
which are trapped & expectorated.
• Persistent irritation-cigarette smoking- cause exaggeration in
response of these protective mech. Inhibit mucociliary clearance.
• Hypersecretion of mucus results from hypertrophy & proliferation
of mucus producing glands.
Chronic Bronchitis

• Irritation from smoke lead to brochiolitis, alveolitis.
• Macrophages & neutrophils infiltrate the epithelium & trigger
epithelium destruction.
• Plugging of bronchioles & alveoli with mucus & particulate
matter.
• Additional Risk → ageing process of lungs.

 Different etiologies to CB, but often co-exit with it.
 Results from gradual progressive loss of elastic tissue with in the lungs
due to an imbalance between proteolytic enzymes & protective factors.
 Macrophages & neutrophils release lysosomal enzymes such as elastase
that are capable of destroying connective tissue in the lungs.
Emphysema

In normal condition, protective factor α1 -antitrypsin (α1-
protease inhibitor) → inhibits proteolytic enzymes & so
prevent damage.
Deficiency of α1-antitrypsins → predispose to emphysema.

Pathophysiology

2 pathological processes underlying in development:
1. Hypersensitivity disorder, characterized by expectoration with ↑
susceptibility to respiratory infections.
2. An obstructive disorder that results from smooth muscle constriction
& may/may not be associated with emphysema.
Chronic bronchitis

• Hypersecretion of thick & viscous mucus results from proliferation
of mucus secreting glands & goblets cells in the bronchial
epithelium.
• Excess mucus production → destruction of alveoli & loss of their
gas exchange function.
• Pus & infected mucus accumulated, leading to recurrent/ chronic
viral & bacterial infection.
• Common agents: Streptococcus pneumonia, Moraxella catarrhalis,
Haemophilus influenza, Staphylococcus aureus, Pseudomonas
aeruginosa species.

• Thickening of bronchioles & alveolar walls → lead to blockade &
obstruction of airways.
• Alveolar distension & destruction results distortion of blood
vessels that are closely associated with the alveoli → ↑BP.
• ↓ Gas diffusion across alveolar epithelium → low partial pressure
of oxygen in blood vessels (hypoxia) due to imbalance between
ventilation & perfusion. Leads to polycythaemia, which make more
viscous.

• Sustained pulmonary HTN → thickening of walls of pulmonary arterioles,
which associated with pulmonary remodeling & ↑Rt ventricular pressure
with in heart → Rt ventricular hypertrophy, dilatation & progressive Rt
ventricular failure (cor pulmonale).
• Pulmonary edema → due to physiological changes subsequent to the
hypoxemia & hypercapnia, such as activation of RAA system, salt & water
retention & ↓renal blood flow.
• Bronchiectasis → pathological changes in lungs where bronchi become
permanently dilated.
• In severe infection, bronchioles & alveoli become permanently damaged &
do not return to normal size & shape.

• Progressive, destructive, enlargement of the respiratory bronchioles,
alveolar duct, alveolar sac.
• Loss of available gas exchange surface → leads to an ↑ in dead space &
impaired gas exchange.
• Loss of elastic recoil in small airways which (vital for maintaining force
of expiration), leads to tendency for them to collapse, particularly during
expiration.
• ↑ thoracic gas volume & hyperinflation of lungs results.
Emphysema

1. Centrilobular (centriacinar) emphysema:- destruction of respiratory
bronchioles, alveolar ducts & alveoli.
common in upper lobes of lungs of cigarette smokers & coal miners.
2. Panlobular (Panacinar) emphysema:- associated with α1 anti-trypsin
deficiency, all lung segments are involved. Alveoli enlarge and pulmonary
vascular bed is destroyed.
3. Paraseptal emphysema:- lung periphery adjacent to fibrotic regions is the
site of alveolar distention & alveolar wall destruction.
Types

• Macrophages & neutrophils release proteolytic enzyme elastase,
which is normally inhibited by α1 anti-trypsin.
• In smokers elastase release is more. Elastase break-down elastin
which is an integral protein of alveoli.
• Matrix repair may be inhibited, in smokers.

• Loss of ventricular capacity due to loss of elastic recoil mean that
unlike bronchitis, ventilation / perforation ratio is normally
maintained.
• Experience dyspnoea, than a bronchitis, but better able to preserve
gas exchange, as the respiratory centers are more.
• Don’t lead to cor pulmonale / polycythaemia as in bronchitis.

• Objective measurement of airways obstruction with spirometric
tests & after exclusion of other possible diagnosis such as asthma.
• History of chronic progressive symptoms (cough &/ wheeze, &/
breathlessness).
• Objective evidence of airway obstruction, ideally by spirometric
testing, that does not return to normal with treatment.
Diagnosis

3 factors confirming diagnosis:
- a self reported H/O COPD
- smoking in excess of 40 packs years
- age > 45 yrs, age < 45yrs virtually rules out a COPD diagnosis.
Passes through mild to moderate to severe.

Clinical Presentation

oExcess mucus pdn & degree of bronchospasm resulting wheezing &
dyspnoea.
oHypoxia & hypercapnia (↑CO2 level in tissue)
oProductive cough, over wt & physical exertion difficult due to
dyspnoea.
Chronic Bronchitis

o ‘Blue bloater’→
Tendency of patient to retain CO2 caused by a ↓ responsiveness of the
respiratory centre to prolonged hypoxemia that leads to cyanosis & also the
tendency for peripheral edema to occur.
o Patients lose ability to↑ the rate & depth of ventilation in response to
persistent hypoxemia.
oSevere → chest diameter ↑ed, classical barrel chest.
oAs obstruction worsens → hypoxemia ↑, leading to pulmonary HTN.

oRt ventricular strain leads to Rt ventricular failure,
which is characterized by jugular venous distension,
hepatomegaly, & peripheral edema → consequences
of ↑ in systemic venous blood pressure.
oRecurrent LRTI.
o↑ in volume of thick & viscous sputum: yellow/green
in colour, contain bacterial pathogens, squamous
epithelial cells, alveolar macrophages & saliva; no
pyrexia.

• ↑ing dyspnoea at rest, minimal cough, sputum is scanty & mucoid.
• Tachypnoea due to respiratory centers are responsive to mild hypoxemia &
will have a flushed appearance.
• Patient with emphysema will be thin & have puffed lips in an effort to
compensate for lack of elastic recoil & exhale a larger volume of air.
• Pulmonary HTN is mild, cor pulmonale is rare.
• ‘Pink puffer’: hyperventilate to compensate for hypoxia by breathing in short
puffs, appear pink with little CO2 retention & little evidence of edema.
Emphysema

• 2 specific problems common in COPD:
Sleep apnea syndrome: frequent/prolonged pause of breathing during
sleep. Leads to deterioration in arterial blood gases & ↓ in saturation of
hemoglobin with oxygen – pulmonary HTN & cardiac arrhythmia and
premature cardiac failure.
Acute respiratory failure: if PO2 suddenly drops & then is ↑ PCo2 that ↓
pH to 7.3 or less. It causes acute exacerbation of CB with an ↑ed volume &
viscosity of sputum. Impairs ventilation & cause more severe hypoxemia &
hypercapnia.
Restlessness, confusion, tachycardia, cyanosis, sweating, hypotension &
eventual unconsciousness.

• PFT – used for determination of severity of disease & response of
therapy.
• Assessment of airflow limitation through spirometry is the standard for
diagnosing and monitoring COPD.
• The forced expiratory volume after 1 second (FEV1) is generally
reduced except in very mild disease.
• The forced vital capacity (FVC) may also be decreased.
• The hallmark of COPD is a reduced FEV1:FVC ratio to less than 70%.
• A postbronchodilator FEV1 that is less than 80% of predicted confirms
the presence of airflow limitation that is not fully reversible.
Investigations

Severity Classification for Chronic
Obstructive Pulmonary Disease
Severity Stage Classification Predicted FEV1
0 At risk ≥80%
1 Mild ≥80%
2 Moderate ≥50% and <80%
3 Severe ≥30% and <50%
4 Very Severe <30% (or <50% with
respiratory failure)

• An improvement in FEV1 of less than 12% after inhalation of a rapid
acting bronchodilator is considered to be evidence of irreversible airflow
obstruction.
• A low peak expiratory flow is consistent with COPD but not used as a
diagnostic tool.

Significant changes in arterial blood gases are not usually present until
the FEV1 is less than 1 L.
• Patients with severe COPD can have a low arterial oxygen tension
(PaO2 45 to 60 mm Hg) and an elevated arterial carbon dioxide tension
(PaCO2 50 to 60 mm Hg).
• Hypoxemia results from hypoventilation (V) of lung tissue relative to
perfusion (Q) of the area.
• The low V:Q ratio progresses over several years, resulting in a
consistent decline in the PaO2.
ARTERIAL BLOOD GASES

• During COPD exacerbation respiratory distress occurs due to the sharp rise
in PaCO2 resulting in an uncompensated respiratory acidosis.
• The diagnosis of acute respiratory failure in COPD is made on the basis of
an acute drop in PaO2 of 10 to 15 mm Hg or any acute increase in PaCO2
that decreases the serum pH to 7.3 or less.

• Additional acute clinical manifestations include restlessness,
confusion, tachycardia, diaphoresis, cyanosis, hypotension, irregular
breathing and unconsciousness.
• The most common cause of acute respiratory failure in COPD is
acute exacerbation of bronchitis with an increase in sputum volume
and viscosity.
• This serves to worsen obstruction and further impair alveolar
ventilation, resulting in worsening hypoxemia and hypercapnia.

 Hb level increases.
 Chest radiographs
o In emphysema: flattened diaphragm with a loss of peripheral vascular
markings & the appearance of bullae.
oIn bronchitis: increased bronchovascular marking & cardiomegaly with
prominent pulmonary arteries.

• To relieve symptoms
• To prevent disease progression
• To improve exercise tolerance
• To improve overall health status
• To prevent and treat exacerbations
• To prevent and treat complications
• To reduce morbidity and mortality
Goals of treatment

Treatment

• Smoking cessation is the most effective strategy to reduce the risk of
developing COPD and the only intervention proven to affect the
longterm decline in FEV1 and slow the progression of COPD.
• Pulmonary rehabilitation programs include exercise training along
with smoking cessation, optimal medical treatment, psychosocial
support, and health education.
• Annual vaccination with the inactivated intramuscular influenza
vaccine is recommended.
• One dose of the polyvalent pneumococcal vaccine is indicated for
patients at any age with COPD.
Non pharmacological

 Education
 Stop smoking
 Avoid irritants & dusty environments
 Weight loss
 Physiotherapy
 Occupation therapy & social support
 Prophylactic influenza vaccination
General Measures

• Bronchodilators are used to control symptoms and inhaled therapy is
generally preferred
• Additional therapies should be added in a stepwise manner depending
on response and disease severity.
• Clinical benefits of bronchodilators include increased exercise capacity,
decreased air trapping, and relief of symptoms such as dyspnoea.
• However, significant improvements in pulmonary function
measurements such as FEV1 may not be observed
Pharmacotherapy

 β2 agonist cause bronchodilation by stimulating the enzyme
adenyl cyclase to increase the formation of adenosine 3',5'
monophosphate.
Improve mucociliary clearance.
Agents with greater β2 selectivity & longer duration of action
are preferred – albuterol, terbutaline, salmeterol.
Dose can be increased in acute exacerbation, limiting factor is
excessive increase in heart rate.
Sympathomimetics

• Albuterol, levalbuterol, bitolterol, pirbuterol, and terbutaline are
the preferred short-acting agents because they have greater β2
selectivity and longer durations of action than other short-acting agents
(isoproterenol, metaproterenol, and isoetharine).
• Formoterol and salmeterol are long-acting inhaled β2-agonists that
are dosed every 12 hours on a scheduled basis and provide
bronchodilation throughout the dosing interval.
• They are not indicated for acute relief of symptoms.

When given by inhalation, anticholinergic agents produce bronchodilation
by competitively inhibiting cholinergic receptors in bronchial smooth
muscle.
• 1st line, greater improvement in PFT, effective for years of regular
continuous use.
Anticholinergics

• Ipratropium bromide has a slower onset of action than short-acting β2-
agonists but a longer duration of action.
• Tiotropium bromide is a long-acting agent that protects against
cholinergic bronchoconstriction for more than 24 hours.
• Ipratropium is preferred due to fewer side effects.
• Available as MDI and as solution for inhalation, peak effects in 1.5-2
hrs, duration of action is 4-6 hrs.

 Combination is more effective than single drug alone. Especially as
the disease progresses and symptoms worsen over time.
 Before using, the dose of anticholinergics should first be titrated.
 Anticholinergics should be used 2 hours prior to using
sympathomimetics.
• A combination product containing albuterol and ipratropium
(Combivent) is available as an MDI for chronic maintenance
therapy of COPD.
Combination of Anticholinergics & Sympathomimetics

• Inhibition of phosphodiesterase,
• Inhibition of calcium ion influx into smooth muscle,
• prostaglandin antagonism,
• stimulation of endogenous catecholamines,
• Adenosine receptor antagonism,
• Inhibition of release of mediators from mast cells and
leukocytes.
Methylxanthines

• Chronic theophylline use in COPD has been shown to produce
improvements in lung function, including vital capacity and FEV1.
• Theophylline 3rd line therapy in COPD
• Inhaled bronchodilator therapy is preferred over theophylline for
COPD.
• Objective measurement like FEV1monitor.
• Subjective parameters like perceived exercise tolerance.

• Anti inflammatory mechanisms exert their beneficial effects in COPD
include reduction in capillary permeability to ↓ mucus, inhibition of
release of proteolytic enzyme from leukocytes & inhibition of
prostaglandins.
• Corticosteroids are initiated during an acute exacerbation when the patient
is deteriorating/ not improving by other agents.
Corticosteroids

• Patients taking chronic oral steroids who present in acute distress should
be immediately started on parenteral therapy.
• Therapy is initiated with methylpredinisolone 0.5-1.0mg/kg IV every
6hrs.
• If symptoms are stabilized switched to prednisolone 40-60mg/day.
Steroid should be stopped in 7-14 days.
• If prolonged therapy is needed, a low morning daily dose- 7.5mg/day/
alternate day therapy should be employed.
• Inhaled corticosteroids may be some benefit in COPD

oLong-term oxygen therapy instituted in conditions:
- a resting PaO2 of <55mmHg;
- evidence of Rt heart failure, polycythemia /
impaired neuropsychiatric function with a PaO2 of <60mmHg.
oAlso be used during exercise in patients who show serious hypoxemia
during episodes of increased activity, and during the night in individuals
who have nocturnal hypoxemia.
oPractical method of admin with nasal cannula, which provide 24-28%
of oxygen. The goal is to raise the PaO2 above 60mm Hg.
Long-Term Oxygen

• They are reasonable in patients who exhibit signs suggestive of bronchial infections,
such as ↑ sputum, ↑ viscosity of sputum, and/or change in sputum colour.
• Oral amoxicillin & ampicillin are choice if not allergic to penicillin.
• Others- tetracyclins, cephalosporin, cotrimoxazole & Azithromycin.
• Therapy generally for 7-10 days.
• Patients should receive one dose of pneumococcal and influenza vaccine.
Antibiotics

• Oxygen therapy should be considered for any patient with hypoxemia
during an exacerbation.
• Caution must be used because many COPD patients rely on mild
hypoxemia to trigger their drive to breathe.
• Overly aggressive oxygen administration to patients with chronic
hypercapnia may result in respiratory depression and respiratory failure.
• Oxygen therapy should be used to achieve a PaO2 of greater than 60
mm Hg or oxygen saturation of greater than 90%.
• Arterial blood gases should be obtained after oxygen initiation to
monitor carbon dioxide retention resulting from hypoventilation.
TREATMENT OF CHRONIC OBSTRUCTIVE
PULMONARY DISEASE EXACERBATION.

Bronchodilators
• The dose and frequency of bronchodilators are increased during acute
exacerbations to provide symptomatic relief.
• Short-acting β2-agonists are preferred because of their rapid onset of
action.
• Anticholinergic agents may be added if symptoms persist despite
increased doses of β2-agonists.
• Nebulization may be considered for patients with severe dyspnea who are
unable to hold their breath after actuation of an MDI
• Clinical evidence supporting theophylline use during exacerbations is
lacking,

Corticosteroids
• Results from clinical trials suggest that patients with acute COPD
exacerbations should receive a short course of IV or oral corticosteroids.
• Although the optimal dose and duration of treatment are unknown, it
appears that a regimen of prednisone 40 mg orally daily (or equivalent)
for 10 to 14 days can be effective for most patients.
• If treatment is continued for longer than 2 weeks, a tapering oral
schedule should be employed to avoid hypothalamic-pituitary-adrenal
axis suppression.

Antimicrobial Therapy
• Although most exacerbations of COPD are thought to be caused by viral or
bacterial infections, as many as 30% of exacerbations are caused by
unknown factors.
• Antibiotics are of most benefit and should be initiated if at least two of the
following three symptoms are present:
(1) increased dyspnoea;
(2) increased sputum volume;
(3) increased sputum purulence.

• Selection of empiric antimicrobial therapy should be based on the most
likely organisms.
• The most common organisms for acute exacerbation of COPD are
Haemophilus influenzae, Moraxella catarrhalis, Streptococcus
pneumoniae and H. parainfluenzae.
• In uncomplicated exacerbations, recommended therapy includes a
macrolide (azithromycin, clarithromycin), second- or third-generation
cephalosporin, or doxycycline.

• In complicated exacerbations where drug-resistant pneumococci, β-lactamase-
producing H. influenzae and M. catarrhalis, and some enteric gram negative
organisms may be present,
• Recommended therapy includes amoxicillin/ clavulanate or a
fluoroquinolone with enhanced pneumococcal activity (levofloxacin,
gemifloxacin, moxifloxacin).
• In complicated exacerbations with risk of Pseudomonas aeruginosa,
recommended therapy includes a fluoroquinolone with enhanced pneumococcal
and P. aeruginosa activity (levofloxacin).
• If IV therapy is required, a β-lactamase resistant penicillin with
antipseudomonal activity or a third- or fourth-generation cephalosporin with
antipseudomonal activity should be used.

oThe pharmacologic plan for the given patient require consideration of
risk/benefit ratio carefully, comprehensive plan to assess subjectively &
objectively the efficacy & toxicity of the chosen therapy.
oObjective outcome measurements: FEV1:FVC and peak flow;
improvement in the distance covered in a 6-or-12 mts walk; objectively
observed reduction in dyspnoea, medication use, and nocturnal symptoms.
oSubjective parameters- perceived improvement in exercise tolerance.
Evaluation of Therapeutic Outcomes

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