CHRONIC CHRONIC OBSTRUCTIVEOBSTRUCTIVE

PULMONARY DISEASE PULMONARY DISEASE

Chronic Obstructive Chronic Obstructive Pulmonary Disease Pulmonary Disease

(COPD)(COPD) Chronic Obstructive Airway disease Chronic Obstructive Airway disease

(COAD)(COAD)

DEFINITIONDEFINITION

COPD is a disease state characterized by COPD is a disease state characterized by increase in resistance to airflow due to partial or increase in resistance to airflow due to partial or complete obstruction of airway at any level from complete obstruction of airway at any level from the trachea to respiratory bronchiole. Changes the trachea to respiratory bronchiole. Changes are usually irreversible esp. in chronic bronchitis are usually irreversible esp. in chronic bronchitis and emphysema.and emphysema.

- Predominant symptom; Dyspnoea- Predominant symptom; Dyspnoea

- Predominant cause; Smoking- Predominant cause; Smoking

Pulmonary function testsPulmonary function tests show : show :

1-Increased pulmonary resistance1-Increased pulmonary resistance

2- Limitation of maximal expiratory 2- Limitation of maximal expiratory

flow rates (reduced FEV1).flow rates (reduced FEV1).

1.1. EMPHYSEMAEMPHYSEMA

2.2. CHRONIC BRONCHITISCHRONIC BRONCHITIS

3.3. ASTHMA ASTHMA

4.4. BRONCHIECTASISBRONCHIECTASIS

Emphysema.Emphysema.

--Abnormal permanent enlargement of the Abnormal permanent enlargement of the

distal air spaces due to destruction of the distal air spaces due to destruction of the

alveolar walls and loss of respiratory tissue.alveolar walls and loss of respiratory tissue.

-“Obstruction” is caused by lack of elastic -“Obstruction” is caused by lack of elastic

recoil. recoil.

Etiology:Etiology:

1-1- Most common cause is Most common cause is smokingsmoking: produces : produces

combination of emphysema and chronic inflammation combination of emphysema and chronic inflammation

2- 2- GeneticGenetic deficiency of alpha1 antitrypsin (Pi locus on deficiency of alpha1 antitrypsin (Pi locus on

chromosome 14) ; alpha-1-antitrypsin deficiency chromosome 14) ; alpha-1-antitrypsin deficiency

produces almost pure emphysemaproduces almost pure emphysema

Pathogenesis:Pathogenesis:

1- 1- Protease-antiprotease imbalanceProtease-antiprotease imbalance ::

. Alpha1 antitrypsin present in serum, tissue . Alpha1 antitrypsin present in serum, tissue fluids, macrophagesfluids, macrophages

. Inhibitor of proteases (esp. elastase secreted . Inhibitor of proteases (esp. elastase secreted by neutrophils by neutrophils

during inflammation)during inflammation)

.Stimulus--TNF,IL8--Increased neutrophils--Release of .Stimulus--TNF,IL8--Increased neutrophils--Release of

proteases(elastase,proteinase-3,cathepsin-G)--Elastic lung tissue proteases(elastase,proteinase-3,cathepsin-G)--Elastic lung tissue

destructiondestruction

Pathogenesis

2- Oxidant-antioxidant imbalance:

Smoking--Free O2 radicals--Deplete Antioxidant in lung (superoxide dismutase, glutathione)—Damage of lung tissue

Types of EmphysemaTypes of Emphysema

1-Centroacinar (Centrilobar) 1-Centroacinar (Centrilobar) EmphysemaEmphysema

-- -- Affects central (proximal) parts of the acini Affects central (proximal) parts of the acini

(respiratory bronchioles) but spares the distal (respiratory bronchioles) but spares the distal

alveoli.alveoli.

- More severe in upper lobes, especially apical - More severe in upper lobes, especially apical

segments segments

..

Causes:-Smoking-Coal dust

2-Panacinar (Panlobar) 2-Panacinar (Panlobar) EmphysemaEmphysema

-- -- Uniform enlargement of the acini in a lobule.Uniform enlargement of the acini in a lobule.

- May not necessarily involve entire lung- May not necessarily involve entire lung

- Predominantly lower lobes.- Predominantly lower lobes.

- - Alpha -1- antitrypsin deficiencyAlpha -1- antitrypsin deficiency is prototype. is prototype.

3-Paraseptal (Distal 3-Paraseptal (Distal Acinar) EmphysemaAcinar) Emphysema

-- -- Proximal acinus normal, distal part involvedProximal acinus normal, distal part involved

- Most prominent adjacent to pleura and along - Most prominent adjacent to pleura and along

the lobular connective tissue septa.the lobular connective tissue septa.

- Probably underlies - Probably underlies spontaneous spontaneous

pneumothoraxpneumothorax in young adults.in young adults.

4-Bullous Emphysema4-Bullous Emphysema

-- -- Any form of emphysema which produces Any form of emphysema which produces

large subpleural blebs or bullae (> 1cm).large subpleural blebs or bullae (> 1cm).

- Localized accentuation of any one of the - Localized accentuation of any one of the

type.type.

5-Interstitial Emphysema5-Interstitial Emphysema

Air penetration into the connective tissue Air penetration into the connective tissue

stroma of the :stroma of the :

- lung- lung

- mediastinum or- mediastinum or

- subcutaneous tissue. - subcutaneous tissue.

6-Compensatory 6-Compensatory “Emphysema”“Emphysema”

- - Dilatation of alveoli in response to loss of Dilatation of alveoli in response to loss of

lung substance elsewherelung substance elsewhere..

- - Actually hyperinflation since no Actually hyperinflation since no

destruction of septal walls.destruction of septal walls.

7-Senile “Emphysema”7-Senile “Emphysema”

- - Change in geometry of lung with larger Change in geometry of lung with larger

alveolar ducts and smaller alveoli.alveolar ducts and smaller alveoli.

- No loss of lung tissue; hence not really - No loss of lung tissue; hence not really

an emphysema.an emphysema.

Chronic BronchitisChronic Bronchitis

- - Clinical definitionClinical definition: persistent cough with : persistent cough with

sputum production for at least three months in at sputum production for at least three months in at

least two consecutive years.least two consecutive years.

- Can occur with or without evidence of airway - Can occur with or without evidence of airway

obstruction obstruction

- - SmokingSmoking is the most important cause. is the most important cause.

::

Basic Mechanism: Basic Mechanism: Hypersecretion of mucusHypersecretion of mucus HistologyHistology

-Increased numbers of goblet cells in small airways as -Increased numbers of goblet cells in small airways as

well as large airways.well as large airways.

-Increased size of submucosal glands in large airways -Increased size of submucosal glands in large airways

(Reid index: ratio of thickness of mucosal glands to (Reid index: ratio of thickness of mucosal glands to

thickness of wall between epithelium and cartilage)thickness of wall between epithelium and cartilage)

-Peribronchiolar chronic inflammation.-Peribronchiolar chronic inflammation.

BronchiectasisBronchiectasis

- - Permanent abnormal dilation of bronchi and Permanent abnormal dilation of bronchi and

bronchioles, bronchioles,

- Usually associated with chronic necrotizing - Usually associated with chronic necrotizing

inflammation inflammation

- Patients have fever, cough, foul–smelling sputum.- Patients have fever, cough, foul–smelling sputum.

- More common in left lung, lower lobes.- More common in left lung, lower lobes.

Causes:Causes:

Obstruction (tumor, mucus) Obstruction (tumor, mucus)

CongenitalCongenital

Intralobar sequestration Intralobar sequestration

Cystic fibrosisCystic fibrosis

Immotile cilia syndrome Immotile cilia syndrome

Necrotizing pneumoniaNecrotizing pneumonia

Kartaganer’s SyndromeKartaganer’s Syndrome

AsthmaAsthma

- - Increased responsiveness of Increased responsiveness of

tracheobronchial tree to various stimuli, tracheobronchial tree to various stimuli,

leading to paroxysmal airway constrictionleading to paroxysmal airway constriction

- Unremitting attacks (status asthmaticus) - Unremitting attacks (status asthmaticus)

can be fatal.can be fatal.

Etiology :Etiology :

1- Extrinsic Factors (atopic, allergic); most 1- Extrinsic Factors (atopic, allergic); most

commoncommon

2- Intrinsic Factors (idiosyncratic); now 2- Intrinsic Factors (idiosyncratic); now

recognize mixed.recognize mixed.

Basic MechanismBasic Mechanism

- Bronchial plugging by thick mucous plugs - Bronchial plugging by thick mucous plugs

containing eosinophils, whorls of shed epithelium containing eosinophils, whorls of shed epithelium

(Curschmann’s spirals), and Charcot – Leyden (Curschmann’s spirals), and Charcot – Leyden

crystals (Eosinophil membrane protein); crystals (Eosinophil membrane protein);

- Distal air- spaces become over distended.- Distal air- spaces become over distended.

Histology:Histology:

-Thick basement membrane-Thick basement membrane

-Edema and infiltration of the bronchial walls by -Edema and infiltration of the bronchial walls by

inflammatory cells with prominence of inflammatory cells with prominence of

eosinophils, eosinophils,

- Hypertrophy of bronchial wall muscle.- Hypertrophy of bronchial wall muscle.

Therapeutic agentsTherapeutic agents are aimed at increasing are aimed at increasing

cAMP levels either by :cAMP levels either by :

- increasing production (ß-agonists, e.g - increasing production (ß-agonists, e.g

epinephrine) orepinephrine) or

- decreasing degradation (Methyl xanthines, e.g - decreasing degradation (Methyl xanthines, e.g

theophylline). theophylline).

- Cromolyn sodium prevents mast cell - Cromolyn sodium prevents mast cell

degranulation. degranulation.

Allergic Allergic Bronchopulmonary Bronchopulmonary

Aspergillosis Aspergillosis

Occur in chronic asthmatics; hypersensitivity to non – Occur in chronic asthmatics; hypersensitivity to non –

invasive Aspergillus.invasive Aspergillus.

Bronchocentric granulomatous inflammation, mucus Bronchocentric granulomatous inflammation, mucus

impaction of bronchi, eosinophilic pneumoniaimpaction of bronchi, eosinophilic pneumonia..

Distinctive promixal bronchiectasis (?Pathgnomonic)Distinctive promixal bronchiectasis (?Pathgnomonic)

Burden of AsthmaBurden of Asthma

Prevalence increasing in developed countries Prevalence increasing in developed countries more than developing or underdeveloped more than developing or underdeveloped countries affecting 10 -15% of population.countries affecting 10 -15% of population.

The number of children with asthma has The number of children with asthma has increased six-fold in the last 25 yearsincreased six-fold in the last 25 years

Between 100 and 150 million people around Between 100 and 150 million people around the globe the globe

5.1 million people in the UK have asthma5.1 million people in the UK have asthma In South Asia (including Pakistan) rough In South Asia (including Pakistan) rough

estimates indicate a prevalence of between estimates indicate a prevalence of between 10% and 15% 10% and 15%

Burden of AsthmaBurden of Asthma

World-wide, the economic costs World-wide, the economic costs associated with asthma are estimated associated with asthma are estimated to exceed those of TB and HIV/AIDS to exceed those of TB and HIV/AIDS combined. combined.

In the United States, for example, In the United States, for example, annual asthma care costs (direct and annual asthma care costs (direct and indirect) exceed US$6 billion. indirect) exceed US$6 billion.

At present Britain spends about US$1.8 At present Britain spends about US$1.8 billion on health care for asthma and billion on health care for asthma and because of days lost through illness because of days lost through illness

Burden of AsthmaBurden of Asthma

0 20 40 60 80 Deaths per Million

1999

20112010Target

0

5

10

15

20

25

1980 1985 1990 1995 2000

Age-adjusted death rate per million

Under 5 years

5-14 years

15-34 years

35-64 years

65 years and over

CLASSIFICATION OF CLASSIFICATION OF ASTHMAASTHMA

EXTRINSICEXTRINSICImplying a definite external causeImplying a definite external causeAtopic individualsAtopic individualsPositive skin prick testPositive skin prick testMore common More common Early onset in childhoodEarly onset in childhood INTRINSIC OR CRYPTOGENICINTRINSIC OR CRYPTOGENICLate onset (middle age)Late onset (middle age)

Etiology and Etiology and PathogenesisPathogenesis

AllergyAllergy Airway hyperresponsivenessAirway hyperresponsiveness Genetic factorsGenetic factors Asthma triggersAsthma triggers

The Underlying MechanismThe Underlying Mechanism

INFLAMMATIONINFLAMMATION

Risk Factors (for development of asthma)

AirwayHyperresponsiveness Airflow

Limitation

Symptoms- (shortness of breath,

cough, wheeze)

Risk Factors(for exacerbations)

Pathological changesPathological changes

Genetic FactorsGenetic Factors

Candidate genes on chromosome Candidate genes on chromosome 5q31-335q31-33

(IL4 GENE CLUSTER)(IL4 GENE CLUSTER)

Responsible for production of Responsible for production of cytokines ,IL3,IL4 ,IL9 ,IL13, GM-cytokines ,IL3,IL4 ,IL9 ,IL13, GM-CSFCSF

Gene A

Gene B

Gene D

Gene E

Gene CAtopysusceptible

Asthmasusceptible

Asthma triggersAsthma triggers Indoor allergens Outdoor allergens Occupational

sensitizers Tobacco smoke Air Pollution Respiratory

Infections Parasitic infections

Socioeconomic factors Family size Diet and drugs Obesity Exercise Exercise Acid refluxAcid reflux

Burden of COPD

The global burden of COPD will increase enormously over the foreseeable future as the toll from tobacco use in developing countries becomes apparent.

In UK and USA COPD occurs in 18% male smokers14% female smokers6-7% those who have never smoked

Direct and Indirect Costs of COPD, (US $ Billions)

Direct Medical Cost: $18.0

Total Indirect Cost: $ 14.1

Mortality related IDC 7.3 Morbidity related IDC 6.8

Total Cost $32.1

Risk Factors for COPD

Host Factors Genes (e.g. alpha1-antitrypsin

deficiency) Hyperresponsiveness Lung growthExposure Tobacco smoke Occupational dusts and chemicals Infections Socioeconomic status

Pathogenesis of COPD

NOXIOUS AGENT(tobacco smoke, pollutants, occupational agent)

Genetic factors

Respiratory infection

Other

COPD

Noxious particles

and gases

Lung inflammation

Host factors

COPD pathology

ProteinasesOxidative stress

Anti-proteinasesAnti-oxidants

Repair mechanisms

ASTHMAASTHMASensitizing agent

COPDCOPDNoxious agent

Asthmatic airway inflammationCD4+ T-lymphocytes

Eosinophils

COPD airway inflammationCD8+ T-lymphocytes

MacrophagesNeutrophils

Airflow limitationCompletelyreversible

Completelyirreversible

Symptoms and SignsSymptoms and Signs Acute attack of Acute attack of

asthmaasthmaIntermittent dyspnoeaIntermittent dyspnoeaCough, Cough,

sputum ,wheezesputum ,wheezeTachypnoeaTachypnoeaHyperinflated chestHyperinflated chestHyperresonant Hyperresonant

percussion notepercussion noteDiminished air entryDiminished air entryWidespread Widespread

polyphonic wheezepolyphonic wheeze

Acute exacerbation of Acute exacerbation of COPDCOPD

Dyspnoea , cough ,sputum, Dyspnoea , cough ,sputum, wheezewheeze

TachyponeaTachyponeaUse of accessory musclesUse of accessory musclesreduced cricosternal distance reduced cricosternal distance

<3cm<3cmReduced expansionReduced expansionHyperinflationHyperinflationHyperresonant percussion Hyperresonant percussion

notenoteQuiet breath soundsQuiet breath soundsWheeze , cyanosisWheeze , cyanosisCor pulmonaleCor pulmonale

Signs of severe attack of Signs of severe attack of asthmaasthma

Inability to complete sentenceInability to complete sentence Pulse>110Pulse>110 Respiratory rate >25Respiratory rate >25 PEFRPEFR

<50%of predicted<50%of predicted

Signs of Life threatening Signs of Life threatening attackattack

Silent chest Silent chest CyanosisCyanosis BradycardiaBradycardia ExhaustionExhaustion ConfusionConfusion Feeble respiratory effortFeeble respiratory effort PEFR <33% of predictedPEFR <33% of predicted Low pH <7.35, PaO2< 8KPa , Low pH <7.35, PaO2< 8KPa ,

PaCO2>5KPaPaCO2>5KPa

Investigations for acute Investigations for acute attack of asthmaattack of asthma

Full Blood CountFull Blood Count Urine Complete and ElectrolytesUrine Complete and Electrolytes PEFR (pt may be too ill to perform it PEFR (pt may be too ill to perform it

well)well) Arterial Blood GasesArterial Blood Gases Pulse oximetryPulse oximetry ECG ECG CXRCXR

Investigations for Acute Investigations for Acute Exacerbation of COPDExacerbation of COPD

Full Blood CountFull Blood Count Urine Complete and ElectrolytesUrine Complete and Electrolytes PEFR (pt may be too ill to perform it well)PEFR (pt may be too ill to perform it well) Arterial Blood GasesArterial Blood Gases Pulse oximetryPulse oximetry ECG ECG CXRCXR Blood cultures (if Pyrexial)Blood cultures (if Pyrexial) Sputum for cultureSputum for culture

Differential DiagnosisDifferential Diagnosis

AsthmaAsthma COPDCOPD Pneumothorax Pneumothorax Pulmonary edemaPulmonary edema Upper respiratory tract obstructionUpper respiratory tract obstruction Pulmonary embolusPulmonary embolus AnaphylaxisAnaphylaxis

Management PlanManagement Plan

Immediate management to stabilize Immediate management to stabilize the patientthe patient

Long term management of diseaseLong term management of disease

Prevention of further attacksPrevention of further attacks

Immediate management of Immediate management of acute asthmatic attackacute asthmatic attack

B2 AgonistsB2 Agonists

Salbutamol 5mg or Terbutaline 10mg Salbutamol 5mg or Terbutaline 10mg nebulized with O2nebulized with O2

(se;tacchycardia,tremor,hypokalemia,ar(se;tacchycardia,tremor,hypokalemia,arrythmia)rythmia)

CorticosteroidsCorticosteroids

Hydrocortisone 200 mg iv or Hydrocortisone 200 mg iv or Prednisolone 30 mg oral (both if very Prednisolone 30 mg oral (both if very ill)ill)

Immediate management of Immediate management of acute asthmatic attackacute asthmatic attack

Additional management in Life Additional management in Life threatening attackthreatening attack

Nebulize with Anti cholinergics Nebulize with Anti cholinergics (Ipratropium 0.5 mg add to B2agonist)(Ipratropium 0.5 mg add to B2agonist)

Aminophylline Aminophylline

250 mg (5mg/kg) I/V over 20 mins250 mg (5mg/kg) I/V over 20 mins I/V B2 agonistsI/V B2 agonists

Salbutamol or Terbutaline 0.25mg over 10 Salbutamol or Terbutaline 0.25mg over 10 minsmins

Effects of Corticosteroids in Effects of Corticosteroids in Acute Asthma Acute Asthma

Systemic Systemic CorticosteroidsCorticosteroids

Anti-inflammatoryAnti-inflammatory Late improvement in Late improvement in

outcomes (> 6 hrs)outcomes (> 6 hrs) Corticosteroids Corticosteroids

induce induce transcriptional transcriptional effects synthesis of effects synthesis of new proteinsnew proteins

Inhaled CorticosteroidsInhaled Corticosteroids TopicalTopical Early improvement in Early improvement in

outcomes (< 3 h)outcomes (< 3 h) Corticosteroids up-Corticosteroids up-

regulating regulating postsynaptic postsynaptic adrenergic receptors adrenergic receptors airway mucosa, airway mucosa, vasoconstriction vasoconstriction decrease airway decrease airway mucosal blood flow, mucosal blood flow, mucosal mucosal decongestiondecongestion

Complications Complications

Respiratory failureRespiratory failureType I continuous O2 Type I continuous O2 Type II controlled O2Type II controlled O2 Intubation and ventilation Intubation and ventilation Cor pulmonaleCor pulmonale Pneumothorax (ruptured bulla …Pneumothorax (ruptured bulla …

bullous lung disease, Indication of bullous lung disease, Indication of surgery)surgery)

Chest infection (pneumonia)Chest infection (pneumonia) PolycythemiaPolycythemia

ComplicationsComplications

Respiratory failureRespiratory failure Treatment options;Treatment options; Noninvasive Positive Pressure VentilationNoninvasive Positive Pressure Ventilation

IntubationIntubation

Sedatives and Neuromuscular BlockersSedatives and Neuromuscular Blockers

PREVENTIONPREVENTION

Elimination of risk factorsElimination of risk factors Patient education and informationPatient education and information Advice on not missing the doseAdvice on not missing the dose Proper management planProper management plan Addition of mast cell stabilizers like Addition of mast cell stabilizers like

sodium cromoglycate and nedocromil sodium cromoglycate and nedocromil and leukotriene antagonists e.g; and leukotriene antagonists e.g; montelukast and zafirlukast to montelukast and zafirlukast to traditional therapytraditional therapy