COPDCOPD

Dr. Tanvir us Salam, FCCPAssociate Professor of Medicine

Post Graduate Medical Institute/LGH Lahore

CChronichronic O Obstructivebstructive P Pulmonaryulmonary D Diseasesiseases

• Asthma• Chronic Bronchitis• Emphysema• Bronchiectasis• Cystic fibrosis

DefinitionDefinition

• Asthma– Chronic inflammatory disorder of the airways– Airway obstruction– Recurrent and reversible

• Atopy– Production of abnormal amounts of IgE antibodies

in response to contact with aeroallergens

• Airway Hyperresponsiveness– This is an abnormality of the airways that allows

them to narrow too easily and too much

COPD COPD

• Chronic Bronchitis is defined by the presence of a productive cough for more than three months' duration in two successive years

• Emphysema is a pathological definition, with enlargement of air spaces and destruction of lung parenchyma, loss of lung elasticity distal to terminal airways

AsthmaAsthma

• Chronic inflammatory disease of airway• Most common chronic disease of childhood• 5-10% of population are affected• More common in developed countries• 2:1 male/female ratio in childhood• Is asthma increasing?• Causing restricted activity and hospitalization• Death rate on the rise

COPDCOPD

• 14 million people in the united states have COPD• 14 percent of white male smokers, as compared with

approximately 3 percent of white male nonsmokers• COPD is now the sixth leading cause of death and it

is the only common cause of death that is increasing in incidence

• The world health organization predicts that by 2020 COPD will rise from its current ranking as the 12th most prevalent disease worldwide to the 5th and from the 6th most common cause of death to the 3rd

Relationship of Wheeze, Asthma, Relationship of Wheeze, Asthma, AHRAHR

Atopy

wheeze

AHR

Currentasthma

AirwayHyperresponsiveness

Plasmaleakage

Mucus hypersecretion

Inflammatorycell recruitmentand activation

Neural activation

Virus-infected epithelium

RV-Induced Airway InflammationRV-Induced Airway Inflammation

Types Types

• Persistent asthma• Obstructed asthma• Episodic asthma• Asthma in remission• Potential asthma• Trivial wheeze• Extrinsic/Atopic asthma• Occupational asthma• Intrinsic asthma

Risk FactorsRisk Factors

• Inducers– Allergens– House dust mites– Respiratory infections– Passive smoking– Genetics

• Trigger– Allergens– Exercise– Infections– Air pollution– Weather– Smells and irritants– Emotional factors– Food

Causes of Asthma ExacerbationsCauses of Asthma Exacerbations

Pathological FeaturesPathological Features

• Macroscopic features– Over inflated lungs– Wide spread plugging of the airways with thick

secretions– Normal lung parenchyma

Pathologic FeaturesPathologic Features

• Microscopic features– Infiltration of epithelium with inflammatory cells– Shedding of the epithelium– Thickened basement membrane– Increased cells in lamina propria– Smooth muscle and mucous glands are

hypertrophied

Cellular Mechanisms Involved in Cellular Mechanisms Involved in Airway InflammationAirway Inflammation

INFLAMATION

ANTIGEN

IgEMast cell

Bronchospasm

Neutrophils

B cell Macrophage

Macrophage

Eosinophil

T cell

PathophysiologyPathophysiology

• Reduction in airway diameter– Contraction of smooth muscles– Vascular congestion and edema of bronchial walls– Tenacious secretions

• Increased airway resistance– Decreased forced expiratory volumes

• Hyperinflation• Mismatched V/P

Molecular Genetics in COPDMolecular Genetics in COPD

• In patients with (alpha)1-antitrypsin deficiency

– Early emphysema develops that is exacerbated by smoking, indicating a clear genetic predisposition to COPD

– However, less than 1 percent of patients with COPD have (alpha)1-antitrypsin deficiency

Molecular Genetics in COPDMolecular Genetics in COPD

• A polymorphic variant of microsomal epoxide hydrolase, an enzyme involved in the metabolism of epoxides that may be generated in tobacco smoke, has been associated with a quintupling of the risk of COPD.

Risk FactorsRisk Factors

• In industrialized countries, cigarette smoking accounts for most cases of COPD

• In developing countries other environmental pollutants, such as particulates associated with cooking in confined spaces, are important causes

• Air pollution (particularly with sulfur dioxide and particulates), exposure to certain occupational chemicals (such as cadmium), and passive smoking may all be risk factors

InflammationInflammation

• Now apparent that there is a chronic inflammatory process in COPD– But it differs markedly from that seen in asthma,

with different inflammatory cells, mediators, inflammatory effects, and responses to treatment

– In contrast to the situation with asthma, eosinophils are not prominent except during exacerbations or in patients with concomitant asthma

– Most inflammation in COPD occurs in the peripheral airways (bronchioles) and lung parenchyma.

– The bronchioles are obstructed by fibrosis and infiltration with macrophages and T lymphocytes.

– Destruction of lung parenchyma and an increased number of macrophages and T lymphocytes, which are predominantly CD8+ (cytotoxic) T cells.

Acute ExacerbationsAcute Exacerbations

• It is now evident that many exacerbations in COPD, as in asthma, are due to upper respiratory tract viral infections (such as rhinovirus infection) and to environmental factors, such as air pollution and temperature.

• There is an increase in neutrophils and in the concentrations of interleukin-6 and interleukin-8 in sputum during an exacerbation, and patients who have frequent exacerbations have higher levels of interleukin-6, even when COPD is stable.

Acute ExacerbationsAcute Exacerbations

• Bronchial biopsies show no increase in sputum eosinophils during exacerbations in patients with severe COPD.

• An increase in markers of oxidative stress and exhaled nitric oxide, presumably reflecting increased airway inflammation, is observed during exacerbations.

Medical History in AsthmaMedical History in Asthma

• Development of disease– Age of onset and

diagnosis– History of early life injury– Progress of disease– Present management– Co-morbid condition

• Family history– History of asthma,

allergy, sinusitis, rhinitis, or nasal polyps in close relatives

• Social history– Characteristics of home– Smoking– School characteristics– Work place– Level of education

Medical History in COPDMedical History in COPD

Aggravating factors • All smokers!• Viral respiratory

infection• Environmental

allergens, indoor and out door

• Exercise• Occupational chemicals• Irritants

Aggravating factors• Emotional expressions• Drugs• Food, food additives and

preservatives• Change in weather,

exposure to cold air• Endocrine factors

Medical History bothMedical History both

• Symptoms– Cough– Wheezing– Shortness of breath– Chest tightness– Fever– Sputum production

Physical ExaminationPhysical Examination

• Tachypnoea• Tachycardia• Pulsus Paradoxus• Cyanosis• Accessory muscle use• Prolonged expiration• Wheeze• Anxious look• Position and diaphoresis

InvestigationsInvestigations

• Chest x-ray• Sinuses x-ray• ECG• DLC (eosinophilia)• Sputum examination• Pulmonary function test

– Spirometry– ABG– Pulse oximetery

Classification of Asthma SeverityClassification of Asthma SeveritySymptoms Nighttime

symptomsLungFunction

Mild Intermittent Symptoms < 2/ wk Exacerbations brief

< 2/ month FEV 1 > 80%PEF variability <20%

Mild persistent Symptoms> 2/ wk But > 1/ day May affect activity

> 2/ month FEV 1 > 80%PEF variability 20-30

ModeratePersistent

Daily symptoms Affect activity Daily use of agonist

> 1/ wk FEV 1 >60%, <80%PEF variability >30%

Severe Persistent Continual symptoms Limited activity Frequent exacerbations

Frequent FEV 1 < 60%PEF variability >30%

Treatment of AsthmaTreatment of Asthma

• Beta2-agonist– Inhaled

• Short acting

• Long acting

– Oral

• Anticholinergics• Methylxanthines• Mast cell stabilizer

– Cromlyn sodium – Nedocromil

• Corticosteroids– Inhaled– Systemic

• Leukotrine modifiers

Therapeutic Measures in COPDTherapeutic Measures in COPD

• Antismoking Measures • Bronchodilators • Antibiotics • Oxygen • Corticosteroids• Noninvasive Ventilation • Pulmonary Rehabilitation • Lung-Volume-Reduction Surgery

Short Acting Inhaled Β2 AgonistShort Acting Inhaled Β2 Agonist

• Indications– Relief of acute symptoms– Preventive prior to exercise

• Mechanism– Smooth muscle relaxation

• Adverse effects– Tachycardia, Skeletal muscle tremor, Hypokalemia,

headache, increased lactic acid

• Therapeutic issues– Drug of choice for acute spasm– Mild intermittent asthma

Long Acting Β2 Agonist Long Acting Β2 Agonist

• Indications– Long term prevention of symptoms, nocturnal– Not to be used to treat acute attack

• Mechanisms– Smooth muscle relaxation– Inhibit mast cell mediator release– Onset ( 15-30 min.), Duration (>12 hours)

• Adverse effects– QT prolongation– Other same as short acting

• Therapeutic issues– Added to standard treatment with inhaled Corticosteroids

Systemic Β2 AgonistSystemic Β2 Agonist

• Inhaled beta agonist are preferred because they have fewer side effect

AnticholinergicsAnticholinergics

• Indication– Relief of acute symptoms

• Mechanisms– Competitive inhibition of muscarinic cholinergic receptors– Reduces intrinsic vagal tone to the airways– Decrease mucus gland secretions

• Adverse effects– Dry mouth and respiratory secretions

• Therapeutic issues– Reverses only cholinergically mediated bronchospasm– Additive effect to β agonist – Treatment of choice for spasm induced by beta-blocker

MethylxanthinesMethylxanthines

• Indications– Long tern control and prevention of symptoms, especially

nocturnal symptoms

• Mechanisms– Smooth muscle relaxation from phosphodiestrase inhibition– Increase diaphragm contractility and mucocilliary clearance

• Adverse effects– Dose related toxiicities include tachycardia, nausea, vomiting

SVT, headache, seizures– Usual doses include insomnia, gastric upset, increase in

hyperactivity in children, difficulty in urination in elderly

Therapeutic Measures in COPDTherapeutic Measures in COPD

• Antismoking Measures • Bronchodilators • Antibiotics • Oxygen • Corticosteroids• Noninvasive Ventilation • Pulmonary Rehabilitation • Lung-Volume-Reduction Surgery

Antismoking MeasuresAntismoking Measures

• Smoking cessation is the only measure that will slow the progression of COPD

• Nicotine-replacement therapy (by gum, transdermal patch, or inhaler) provides help to patients in quitting smoking

• The use of the recently introduced drug bupropion, a noradrenergic antidepressant, has proved to be the most effective strategy to date– A recent controlled trial showed that after a 9-week course of

bupropion, abstinence rates were 30 percent at 12 months, as compared with only 15 percent with placebo

– The abstinence rate was slightly improved with the addition of a nicotine patch.

Bronchodilators Bronchodilators are the are the mainstay of mainstay of current drug current drug therapy for therapy for COPD.COPD.

BronchodilatorsBronchodilators

• Bronchodilators cause only a small (<10 percent) increase in FEV1 in patients with COPD

• These drugs may improve symptoms by reducing hyperinflation and thus dyspnea

• They may improve exercise tolerance, despite the fact that there is little improvement in spirometric measurements

BronchodilatorsBronchodilators

• Several studies have demonstrated the usefulness of the long-acting inhaled (beta)2-agonists salmeterol and formoterol in COPD.

• An additional benefit of long-acting (beta)2-agonists in COPD may be a reduction in infective exacerbations, since these drugs reduce the adhesion of bacteria such as Haemophilus influenzae to airway epithelial cells.

BronchodilatorsBronchodilators

• COPD appears to be more effectively treated by anticholinergic drugs than by (beta)2-agonists, in sharp contrast to asthma, for which (beta)2-agonists are more effective.

• A new anticholinergic drug, tiotropium bromide, which is not yet available for prescription, has a prolonged duration of action and is suitable for once-daily inhalation in COPD.

Antibiotics Antibiotics

• Acute exacerbations of COPD are commonly assumed to be due to bacterial infection, since they may be associated with increased volume and purulence of the sputum.

• Exacerbations may be due to viral infections of the upper respiratory tract or may be noninfective, so that antibiotic treatment is not always warranted.

AntibioticsAntibiotics

• A meta-analysis of controlled trials of antibiotics in COPD showed a statistically significant but small benefit of antibiotics in terms of clinical outcome and lung function.

• There is no evidence that prophylactic antibiotics prevent acute exacerbations

Oxygen Oxygen

• Long-term oxygen therapy:– reduced mortality – improvement in quality of life in patients with

severe COPD and chronic hypoxemia (partial pressure of arterial oxygen, <55 mm Hg).

– Oxygen does not increase survival in patients with less severe hypoxemia

– The selection of patients is important in prescribing this expensive therapy.

In patients with COPD who have In patients with COPD who have nocturnal hypoxemia, nocturnal nocturnal hypoxemia, nocturnal treatment with oxygen does not treatment with oxygen does not appear to increase survival or appear to increase survival or delay the prescription of delay the prescription of continuous oxygen therapycontinuous oxygen therapy

CorticosteroidsCorticosteroids

• Inhaled corticosteroids are now the mainstay of therapy for chronic asthma

• However, the inflammation in COPD is not suppressed by inhaled or oral corticosteroids, even at high doses.

• This lack of effect may be due to the fact that corticosteroids prolong the survival of neutrophils and do not suppress neutrophilic inflammation in COPD.

• Approximately 10 percent of patients with stable COPD have some symptomatic and objective improvement with oral corticosteroids. It is likely that these patients have concomitant asthma, since both diseases are very common. Indeed, airway hyperresponsiveness, a characteristic of asthma, may predict an accelerated decline in FEV1 in patients with COPD.

• long-term treatment with high doses of inhaled corticosteroids reduced the progression of COPD, even when treatment was started before the disease became symptomatic.

• Inhaled corticosteroids may slightly reduce the severity of acute exacerbations, but it is unlikely that their use can be justified in view of the risk of systemic side effects in these susceptible patients and the expense of using high-dose inhaled corticosteroids for several years.

• By contrast, two recent studies have demonstrated a beneficial effect of systemic corticosteroids in treating acute exacerbations of COPD, with improved clinical outcome and reduced length of hospitalization.

• The reasons for this discrepancy between the responses to corticosteroids in acute and chronic COPD may be related to differences in the inflammatory response (such as increased numbers of eosinophils) or airway edema in exacerbations.

Noninvasive VentilationNoninvasive Ventilation

Noninvasive positive-pressure ventilation Noninvasive positive-pressure ventilation with a simple nasal maskwith a simple nasal mask

• Which eliminates the necessity for endotracheal intubation,

• Reduces the need for mechanical ventilation in acute exacerbations of COPD in the hospital,

• used at home may improve oxygenation and reduce hospital admissions in patients with severe COPD and hypercapnia

• The combination of noninvasive positive-pressure ventilation and long-term oxygen therapy may be more effective,

Pulmonary Rehabilitation Pulmonary Rehabilitation

• Pulmonary rehabilitation consisting of a structured program of education, exercise, and physiotherapy has been shown in controlled trials to improve exercise capacity and quality of life among patients with severe COPD and to reduce the amount of health care needed

Lung-Volume-Reduction Surgery Lung-Volume-Reduction Surgery

• The reduction in hyperinflation improves the mechanical efficiency of the inspiratory muscles

• Careful selection of patients after a period of pulmonary rehabilitation is essential.

• Patients with localized upper-lobe emphysema appear to do best; relatively low lung resistance during inspiration appears to be a good predictor of improved FEV1 after surgery.

Functional improvementsFunctional improvements

• increased FEV1,

• reduced total lung capacity and functional residual capacity,

• improved function of respiratory muscles, • improved exercise capacity, and• improved quality of life.

ThankyouThankyou