Department of Medicine Manipal College of Medical Sciences C O P D ALOK SINHA Department of Medicine Manipal College of Medical Sciences Pokhara, Nepal

Chronic obstruction of lung airflow . DEFINATION Chronic obstruction of lung airflow which is permanent & progressive over time

COPD is comprised primarily of . COPD is comprised primarily of Chronic bronchitis Emphysema

. Asthma also is a pulmonary disease in which there is obstruction to the flow of air out of the lungs obstruction in asthma usually is reversible Between "attacks" of asthma the flow of air through the airways usually is good (With execptions)

Emphysema and Ch.Bronchitis are two ends of spectrum of COPD with various shades in between Emphysema and Ch.Bronchitis .

Defining feature of COPD is irreversible airflow limitation during forced expiration FEV1(<80%) & FEV1/FVC (<70%) are reduced EMPHYSEMA a result of a loss of elastic recoil due to lung tissue destruction Pathology starts beyond terminal bronchioles CHR. BRONCHITIS increase in resistance of the conducting airways due to accumulation of inflammatory mucous exudates in the lumens of small airways Thickening of their walls Pathology confined up to terminal bronchioles

Ch. Bronchitis Emphysema

Chronic Bronchitis Inflammation & swelling of the airways lining narrowing and obstruction of airways due to Hyperplasia of mucus-producing glands Over production of mucous - further obstruction of the airways - increases likelihood of bacterial lung infections

Reid index - chronic bronchitis Ratio of the thickness of mucous gland layer to thickness of wall between epithelium & cartilage. Normal Reid index is less than 0.4 is increased in chronic bronchitis.

Pulmonary capillary bed relatively undamaged . Pulmonary capillary bed relatively undamaged Centrilobular Emphysema present to a variable degree

Centrilobular emphysema Normal Pulmonary vessels in between alveoli are undamaged

Body responds by decreasing ventilation and increasing cardiac output. Compared to Emphysema Air way narrowing is more Pulmonary circulation is less affected Body responds by decreasing ventilation and increasing cardiac output. due to rapid circulation in a poorly ventilated lung – increase in physiological shunt leading to Hypoxemia Polycythemia V/Q mismatch

Eventually, hypercapnia and respiratory acidosis develop Leading to pulmonary artery vasoconstriction and pulmonary hypertension with cor pulmonale Patients have signs of right heart failure and are known as “Blue bloaters"

Emphysema Permanent enlargement of the air spaces distal to the terminal bronchioles, with destruction of their walls reduces the elasticity of the lung collapse of the bronchioles obstructing airflow out of the alveoli Inspiration Expiration

Air trapping in the alveoli Inability of the lung to shrink during exhalation Amount of air inhaled is reduced Less air for the exchange of gasses in lungs Trapped air compress adjacent less damaged lung tissue compromising their function .

Panacinar emphysema Destruction of the alveoli – blood vessels obstrcted/destroyed reduced diffusing capacity of the lung for carbon monoxide (DLCO)

Now identify them

Normal lung

Emphysematous lung

Destruction of the alveolar walls decreases the number of capillaries gas exchange decreases (decreased DLCO) due to relatively limited blood flow through a fairly well oxygenated lung – increase in physiological dead space with normal blood gases and pressures in the lung, (in contrast to the blue bloaters.) The body compensates with lowered cardiac output hyperventilation . V/Q mismatch

Normally expiration is passive process- effortless extra effort required to exhale due to collapse of airways Lungs are already inflated due to air trapping so more effort required to inhale further Work of breathing is increased Reduced gaseous exchange increase the Breathing rate

Because of low cardiac output, rest of body suffers from tissue hypoxia and pulmonary cachexia. Eventually, develop muscle wasting and weight loss and are identified as “Pink puffers"

Causes for cachexia in emphysema Increased work of breathing Low cardiac out put Increase in TNF alpha and other mediators of inflammation

Pulmonary capillary bed relatively damaged EMPHYSEMA Pulmonary capillary bed relatively damaged V/Q mismatch - relatively limited blood flow through a fairly well oxygenated lung with normal blood gases & pressures in the Lung - Dead Space Body compensates with lowered cardiac output and Hyperventilation CHR. BRONCHITIS Pulmonary capillary bed relatively undamaged V/Q mismatch – rapid circulation in a poorly ventilated lung, leading to hypoxemia and Polycythemia Shunt Body responds by increasing cardiac output & decreasing ventilation .

Chronic Asthma Obstruction to the flow of air is due to inflammation of the airways -thickening of the airway walls lead to scarring and fixed airway obstruction spasm of smooth muscles - bronchospasm reversible subsides spontaneously or with the use of bronchodilators

Etiology

Smoking responsible for 90% of COPD not all cigarette smokers develop COPD-15% will (don’t tell this to smokers) Smokers with COPD have higher death rates than non smokers with COPD Have more frequent respiratory symptoms coughing, shortness of breath passive smoking – equally harmful

MECHANISM Irritation of cigarette smoke attracts cells to the lungs that promote inflammation. They release elastase -breaks down the elastic fibers in lung tissue Increases mucus production Decreases ciliary motility

2. Air pollution Role of outdoor air pollution – unclear most common cause of COPD in non industrialized world is indoor air pollution due to indoor stoves used for cooking – biomass fuel 3. Occupational pollutants: Cadmium & Silica - increase the risk of COPD

Alpha-1 antitrypsin deficiency Genetic disorder Accounts for less than 1% of the COPD Enzyme elastase is found normally in lungs.It can break down the elastin and damage the airways and alveoli Alpha-1 antitrypsin produced by liver block the damaging effects of elastase on elastin. .

Alpha-1 antitrypsin deficiency causes 1. Early on set of emphysema- homozygos 2. Accelerated emphysema in smokers- hetrozygos 3. Chronic liver disease leading to cirrhosis due to their defective release leading to intra hepatic accumulation .

Clinical features of COPD

Progressive exercise intolerance Alteration in mental status Patients with COPD present with a combination of signs and symptoms of chronic bronchitis emphysema Symptoms Worsening dyspnea Progressive exercise intolerance Alteration in mental status In addition, some important clinical and historical differences exist between the types of COPD . Common symptoms

Chronic bronchitis Emphysema Productive cough, with progression over time to intermittent dyspnoea Cough and sputum on most days -at least 3 consecutive months for at least 2 successive years Morning headache – CO2 retention Hemoptysis – usually small Frequent & recurrent pulmonary infections Progressive cardiac/respiratory failure over time, with oedema and weight gain Emphysema A long history of progressive dyspnea with late onset of nonproductive cough Occasional mucopurulent relapses Eventual cachexia and respiratory failure .

0 No breathlessness except with strenuous exercise 19.29 MODIFIED MRC DYSPNOEA SCALE Grade Degree of breathlessness 0 No breathlessness except with strenuous exercise 1 Breathlessness when hurrying on the level or walking up a slight hill .

2 Walks slower than contemporaries on level ground because of breathlessness or has to stop for breath when walking at own pace 3 Stops for breath after walking about 100 m or after a few minutes on level ground 4 Too breathless to leave the house, or breathless when dressing or undressing

Exclude Infection malignancy & other causes Haemoptysis may complicate exacerbations of COPD but should not be attributed to COPD without thorough investigation Exclude Infection malignancy & other causes

Physical Examination

Barrel shaped chest sternum more arched spine unduly concave AP diam > Trans diamt (5 : 7) horizontal ribs

Emphysema

Normal Compare it with Previous one

Movement of chest wall diminished & reduced expansion < 2 cm (from neutral to maximum inspiration) COPD Normal TLC IRV TLC IC VT ERV FRC RV

Laboured breathing – pursed lip breathing Increased hollow in supraclavicular & suprasternal space Indrawing of intercostal spaces Accessory muscles of inspiration / expiration active

Apical impulse/Apex beat – not visible/palpable Tracheal span reduced - < 2 c.m. Tracheal tug – may be present Indicates the severity of disease Apical impulse/Apex beat – not visible/palpable

Hyper resonant note, liver & cardiac dullness diminished or obliterated Breath sounds –diminished, vesicular with prolonged expiration Ronchi or wheeze during expiration Crepitations may be present more during inspiration

pump handle action of the upper 8 ribs Inspiration: result of active contraction Diaphragm External intercoastals pump handle action of the upper 8 ribs increases the AP diameter of the chest bucket handle action of the lower 4 ribs increases the transverse diameter of the chest resulting in costal elevation & lateral expansion

dimension by upper ribs; Pump- Handle Motion Increase in A-P dimension by upper ribs; Pump- Handle Motion                              mywebpages.comcast.net/wnor/respap.gif

Increase in transverse dimension by lower ribs; Bucket-handle motion                              mywebpages.comcast.net/wnor/respap.gif

Hutchison's Clinical Methods (22E) page 55 Movement of the chest Body: Look at the chest movements. Are they symmetrical? If they seem to be diminished on one side, that is likely to be the side on which there is an abnormality. Intercostal recession - a drawing-in of the intercostal spaces with inspiration - may indicate severe upper airways obstruction, as in laryngeal disease, or tumours of the trachea. In COPD the lower ribs often move inwards on inspiration instead of the normal outwards movement

Hoover's sign refers to the inspiratory retraction of the lower intercostal spaces results from alteration in dynamics of diaphragmatic contraction due to hyperinflation resulting in traction on the rib margins by the flattened diaphragm Seen in up to 70% of patients with severe obstruction can be an excellent marker for severe airway obstruction

Features of CO2 narcosis headache Flapping tremors full & bounding pulse Warm & moist extrimites Detoriation of consciousness Papilloedema

Chronic bronchitis Emphysema Patients may be obese. Frequent cough and expectoration are typical. Use of accessory muscles of respiration not so prominent Coarse rhonchi and wheezing may be heard on auscultation. Patients may have signs of right heart failure - edema & cyanosis. Emphysema    Patients may be very thin with a barrel chest. Typically have little or no cough or expectoration. Breathing may be assisted by pursed lips & use of accessory respiratory musls. chest hyper resonant wheezing may be heard; heart sounds very distant Overall appearance is more like classic COPD exacerbation. Rt H.F. usually not seen till late .

Finger clubbing is not consistent with COPD and should alert the physician to potentially more serious pathology. persistent crepts raise the possibility of bronchiectasis

. INVESTIGATIONS

PFT Obstructive pattern Reduced FEV1 to <80% predicted (FEV1 is the measurement of choice to assess progression of COPD) FEV1/FVC < 0.7 Minimal bronchodilator reversibility (<15%, usually <10%) Raised total lung volume, FRC, and residual volume because of emphysema, air trapping, and loss of elastic recoil

PEFR diary – less than 20% variation Decreased TLCO and kCO because presence of emphysema decreases surface area available for gas diffusion PEFR diary – less than 20% variation No change in FEV1: FVC with exercise (absence of exercise induced bronchospasm) TLCO=CO transfer factor for whole lung KCO=gas transfer coefficient

Flow Volume Curves 25% 50% 75% In early C.O.P.D. FEV1 may be normal but FEF25%-75% is reduced

Pulmonary function tests (Summary)   Decreased forced expiratory volume in 1 second (FEV1) with concomitant reduction in FEV1/forced vital capacity (FVC) ratio Poor/absent reversibility with bronchodilators FVC normal or reduced Normal or increased total lung capacity (TLC) Increased residual volume (RV) Normal or reduced diffusing capacity .

Arterial blood gas   Arterial blood gas (ABG) analysis provides the best clues as to acuteness and severity pH usually is near normal due to renal compensation in chronic disease Generally, consider any pH below 7.3 a sign of acute respiratory compromise ? .

These patients tend to retain sodium. Serum chemistry   These patients tend to retain sodium. Diuretics, beta-adrenergic agonists, and theophylline act to lower potassium levels serum potassium should be monitored carefully. Beta-adrenergic agonists also increase renal excretion of serum calcium and magnesium, which may be important in the presence of hypokalemia .

CBC - Polycythemia Hematocrit > 50

Chronic bronchitis is associated with Chest radiography  Chronic bronchitis is associated with increased bronchovascular markings Cardiomegaly Features of pulmonary hypertension .

Emphysema is associated with a small heart hyperinflation flat hemidiaphragms possible bullous changes

SUBPLEURAL BULLAE Bleb BULLAE

. .

BLEBS

Chest radiography Chronic bronchitis associated with increased broncho vascular markings cardiomegaly. Emphysema associated with small heart hyperinflation flat hemidiaphram possible bullous changes.

CT scan Is useful -detection, characterisation and quantification -more sensitive than the chest X-ray at detecting bullae.

Pulse oximetry does not offer as much information as ABG analysis. When combined with clinical observation, this test can be a powerful tool for instant feedback on the patient's status. .

ASSESSMENT OF SEVERITY OF COPD GOLD CRITERIA Global Initiative for Chronic Obstructive Lung Disease

cough, sputum production Normal spirometry Stage Symptoms Characteristics 0: at risk cough, sputum production Normal spirometry I : mild COPD ,, (With or without) FEV1/FVC < 70% FEV1 ≥ 80% predicted IIA: moderate COPD FEV1 = 50 – 80% IIB: Potential for severe exacerb. FEV1 = 30 – 50% severe COPD FEV1 < 30% predicted Or < 50% with signs of resp.failure or CCF

Management

EMERGENCY TREATMENT .

Acute exacerbation

Treat bronchospasm and inflammation Treat hypoxia Treat bronchospasm and inflammation Treat any underlying cause if present Infection Pneumothorax Assess the need for intensive care

Initial treatment 1. Sit the patient up in bed 2. Oxygen: Adequate oxygen should be given to relieve hypoxia With administration of oxygen, PO2 and PCO2 rise but not in proportion to the very minor changes in respiratory drive

Supply the patient with enough oxygen to maintain a near normal saturation (above 90%) do not be concerned about oxygen supplementation leading to clinical deterioration If the patient's condition is that tenuous, intubation most likely is needed anyway .

3. Bronchodilators

short-acting beta-agonist short-acting anticholinergics Bronchodilator   short-acting beta-agonist short-acting anticholinergics given initially by nebulizer therapy .

stimulation of receptors relaxes airway smooth muscles It help in COPD by- stimulation of receptors relaxes airway smooth muscles increases mucociliary clearance decreases mucous production Delivered by- Nebulizer M D I with space halers – if nebulizer not available Parentral in refractory cases .

Nebulization with short acting bronchodilators Salbutamol 5mg or Terbutaline 10mg administered with O2 repeat up to every 15-30 minutes if required continuous nebulization of salbutamol 10mg/h if inadequate response to initial treatment Monitor Serum K+ regularly to prevent hypokalemia as a side effect

Anticholinergics act via inhibition of cyclic guanosine monophosphate (GMP)–mediated bronchoconstriction. decrease mucus production improve mucociliary clearance Ipratropium bromide -agent of choice Add ipratropium bromide 0.5mg 6 hourly if initial response to –Beta-2 agonists is poor

In severe airflow obstruction combination of . In severe airflow obstruction combination of Ipratropium Salbutamol/albuterol provide better broncho dilatation than used alone

Obtain iv access 4. Start Steroids: Hydrocortisone - 200mg intravenously Repeat 6 – 8 hourly Or Methylprednisolone: 1-2 mg/kg IV q6h; not to exceed 125 mg Follow up with oral corticosteroid - Prednisolone (40 to 60 mg / day) in tapering doses (steroids should still be used in pregnant women as the risk of foetal anoxia from the asthma is high)

5. Antibiotics Antibiotics in chest infection Prefferably a purulent sputum/ or fever abnormal CXR raised WBC should provide coverage against Pneumococcus H influenzae Legionella species Gram-negative enterics Prefferably a fluroquinolone or Co Amoxyclav 650 m.g.X 3 or Doxycyclline 100 m.g. X 2

Monitoring progress Pre- and post-nebulizer peak flows Repeated arterial blood gases 1-2 hourly or according to response especially if SaO2 <93%

If response not brisk or patient's condition is deteriorating Continue oxygen and nebulized beta2-agonist every 15 minutes 7. magnesium sulphate iv single dose 1.2-2g infused over 20 minutes 8. iv Aminophylline infusion Loading dose: 250mg (4-5mg/kg) iv in 20 min Maintenance infusion: 0.5- 0.7mg/kg/h (250mg in 1 litre N saline at 2- 4 ml/kg/h)

Consider iv salbutamol infusion Loading dose: 100- 300µg over 10 minutes Maintenance infusion: 5 -20µg/min (5mg in 500ml saline at 1- 3ml/min) Side Effects: tremor tachycardia hypokalaemia hyperglycaemia Summon anaesthetic help

Indications for admission to intensive care unit Hypoxia (PaO2 <8kPa (60mmHg) despite FiO2 of 60% Rising PaCO2 or PaCO2 >6kPa (45mmHg) Exhaustion, drowsiness, or coma Respiratory arrest Failure to improve despite adequate therapy

Heliox (ie, mixture of helium and oxygen) inhalation may be tried NON INVASIVE POSITIVE PRESSURE VENTILATION continuous positive airway pressure (CPAP) biphasic positive airway pressure (BiPAP) prevents airways collapse & air trapping reduces the need for endotracheal intubation Heliox (ie, mixture of helium and oxygen) inhalation may be tried .

definitive airway management via Intubation & mechanical ventilation . When every thing fails definitive airway management via Intubation & mechanical ventilation

high risk of complications overall mortality of ~13%. life saving high risk of complications overall mortality of ~13%. hypotension in ~38% Barotrauma seen in ~14% pneumothorax pneumo-mediastinum subcutaneous emphysema

On-going therapy continue nebulized beta2-agonist, reducing to 4-hourly and withdraw after 24- 48 hours Peak flow rate should be measured before and after each nebulizer Maintain O2 sats >92%

Continue nebulized ipratropium bromide 6-hourly until the condition is improving Continue steroids, hydrocortisone 100mg q6h iv switching to 30- 60mg o d oral prednisolone when able to swallow, and continue for 10-14 days Monitor serum K+ daily and supplement as necessary

Discharge PEF should be 75% of best without significant morning dipping should be established on inhalers with no requirement for nebulizers for 24- 48 hours prior to discharge.

Ambulatory patients

Smoking cessation

Aids for stopping smoking Nicotine patch Medicines Nicotine gum

Inhaled Corticosteroids (ICS) Pulmonary rehabilitation Physiotherapy Oxygen therapy Bronchodilators Inhaled Corticosteroids (ICS) Pulmonary rehabilitation Physiotherapy Annual influenza & pneumococcal vaccine Surgical intervention

Oxygen therapy LTOT via an oxygen concentrator for patients in respiratory failure, with PaO2 < 55 mm / Hg (7.3 kPa) with any PCO2 PaO2 of 7.3 – 8 kPa (55 – 60 mm) with any of: secondary polycythaemia peripheral oedema pulmonary hypertension present FEV1 < 1.5 liters use for a minimum of 15 hours per day (including Sleep)

LONG-TERM DOMICILIARY OXYGEN THERAPY (LTOT) improves survival, reduces secondary polycythaemia prevents progression of primary pulmonary hypertension. Use at least 15 hours/day at 2-4 litres/min to achieve a PaO2 > 8 kPa (60 mmHg) without unacceptable rise in PaCO2 MUST STOP SMOKING

a. N O T PaO2 < 55 mm SaO2 < 88%- while awake Decrease in PaO2 > 10 mm & SaO2 > 5% while asleep c. Supplementation during exercise when after exercise the gas saturation comes down

Bronchodilators Ipratropium bromide by M.D.I. – 2 puffs (36-72 mcg) X 6h Nebul. Long acting beta2 agonist Salmeterol Bambuterol less expensive than above rapid onset more side effects Theophylline -have other effects on diaphragm, resp centre etc

Inhaled corticosteroids (ICS) reduce the frequency & severity of exacerbations recommended in patients with severe disease 1.FEV1 < 50% 2.two or more exacerbations requiring antibiotics or oral steroids per year. previuos response to steroids during acute exacerbation concomitent asthma Has no role in modifying the disease as opposed to bronchial asthma (no need to give early in disease) The combination of ICS with long-acting β2-agonists produces further improvement in breathlessness and reduces the frequency and severity of exacerbations. (Role of oral CS)

Incentive Spirometry

QUIZ How much capitation fee will be charged at MCOMS if she takes admission ? COMPLICATIONS

COPD Cor pulmonale Due to Treatment (P.T.) pneumothorax Cachexia Acute exacerbations Respiratory failure Secondary polycythemia

Cor pulmonale caused by pulmonary hypertension This leads to enlargement and subsequent failure of the right side of the heart

pneumothorax consider in all patients with COPD with acute exacerbation Due to rupture of subpleural bullae Blebs

Acute exacerbations due to Acute infections – preventive role of pneumococcal and influenza vaccine Recent increase in size of bullae

Secondary polycythemia due to hypoxia Increases blood viscosity Pulmonary hypertension thrombosis Hematocrit > 60 then phlebotomy is done

Acute or chronic respiratory failure Acute Due to infections Associated with resp. acidosis Chronic Type I Type II in severe COPD when FEV1< 1 liter Associated with features of CO2 narcosis

Cachexia Increased work of respiration Reduced appetite and absorbtion Release of inflammatory mediators (TNF alfa)

Bronchial Asthma Vs COPD

airflow obstruction due to inflammation & increased airway hyper-responsive ness & bronchospasm which is variable over short periods of time reversible with treatment Mostly by allergens in atopic persons Mostly affects the young people Chronic obstruction of lung airflow which is permanent & progressive over time Due to the chemical irritation of the airways caused by smoke(ing) Disease of middle aged & elderly cause Age group

Chest normal in between the attacks Airway obstruction due to Smooth muscle spasm oedema Chest normal in between the attacks Emphysematous changes do not occur Does not progress to cor pulmonale or type II respiratory failure Pathogenesis Due to Loss of elastic recoil: Emphysema Remodeling of the air way: Ch Bronchitis Features of air way obstruction always seen Seen after some years Many cases develop these complication Clinical features Complications

Pulmonary Function Test Obstructive picture + FEV1 ≥ 15% (and 200 ml) increase following administration of a bronchodilator/trial of corticosteroids > 20% diurnal variation on ≥ 3 days in a week for 2 weeks on PEF diary FEV1 ≥ 15% decrease after 6 mins of exercise Normal in between attacks. Hyper inflated lungs at the time of acute attack Obstructive pattern + Minimal bronchodilator reversibility (<15%, usually <10%) < 20% diurnal variation on ≥ 3 days in a week for 2 weeks on PEF diary No change in FEV1: FVC with exercise (absence of exercise induced bronchospasm) Shows Emphysematous changes with bullae Features of pulmonary hypertension X ray chest