Case 3 – Turning Blue

August 29, 2011

Case centres on a COPD sufferer. He is a smoker, working on cutting down his cigarette consumption. Despite treatment he experiences progressive disablement due to COPD and repeated infections.

  1. pathophysiology of COPD – emphysema (cause and consequence), polycythemia and inflammations
  2. “nictotine fix” – composition of cigarette smoke, what it does, why is it addictive? smoking as a social/occupational risk
  3. tests – how and why
  4. treatments – pharmacology (mechanisms)
  5. infections as complication of COPD

Airway tone and pressures

August 29, 2011

[K&C] Airway tone shows a circadian rhythm which is greatest at 0400 and lowest mid afternoon, hence asthma symptoms often worse early morning. Airways expand as lung volume is increased, and at full inspiration, TLC, they are 30-40% larger in calibre than at full expiration, RV. In COPD the small airways are narrowed and this can be partially compensated by breathing at a larger lung volume. The airways become smaller, and greater in number, towards the periphery. The total cross sectional area of airways increases and the resistance to airflow decreases, until the terminal airways where airflow occurs solely by diffusion. Air pressure increases towards the trachea as resistance increases.

Adrenoceptors on bronchial muscles respond to circulating catecholamines; there is no direct sympathetic innervation.

Between the alveolus and the mouth there is a point where airway pressure equals intrapleural pressure, and airways collapse temporarily, and tend to vibrate. The elastic recoil pressure of the lungs decreases with decreasing volume, so the collapse point moves towards the smaller airways. Where there is pathological loss of recoil pressure, e.g. COPD, the collapse point starts even further upstream and causes expiratory flow limitation. FEV1 is a useful clinical index of this phenomenon. To compensate, these patients often ‘purse their lips’ in order to increase airway pressure so that their peripheral airways do not collapse. On inspiration, the intraplueral pressure is always less than the intraluminal pressure within the intrathoracic airways, so there is no limitation to airflow with increasing effort. Inspiratory flow is limited only by the power of the inspiratory muscles.

In subjects with healthy lungs, maximal flow rates are rarely achieved even during vigorous exercise. In patients with severe COPD, limitation of expiratory flow occurs even during tidal breathing at rest. To increase ventilation these patients have to breathe at higher lung volumes and allow more time for expiration which both reduce the tendency for airway collapse. To compensate they increase flow rates during inspiration, where there is relatively less flow limitation.



Treatments for COPD

August 29, 2011

Buproprion and NRT treatments for Smoking cessation

Bronchodilator and Glucocorticoid – see Asthma treatments

Oxygen Therapy

Extremely important in COPD exacerbations. Care must be taken to raise the arterial oxygen saturation, if possible to >90%, without increasing the arterial oxygen saturation. Low dose oxygen may be necessary (e.g. 24% by venturi mask, or 1-2L/min by nasal cannulae) if there is a tendency to retain carbon dioxide (type 2 respiratory failure (type 1 is hypoxaemic with PaO2 < 60mmHg (8 kPa) with a normal or low PaCO2; type 2 is hypercapnic with PaCO2 > 50mmHg (6.5 kPa) and frequently patient is also hypoxic. Respiratory failure can also be acute or chronic). Long-term domiciliary oxygen treatment, usually delivered via nasal cannulae, improves symptoms and survival in COPD with respiratory failure (with an arterial oxygen tension less than 7.3 kPa). It should not be used unless respiratory failure persists for 3-4 weeks despite optimal drug therapy and without a clinical exacerbation. It should not be used by smokers because of the fire risk. To improve survival, oxygen must be used for at least 15h per day.

Venturi masks can accurately provide concentrations 24-60% O2. Greater concentrations of oxygen (>60%) may damage the alveolar membrane when inhaled for more than 48 hours. Progression to the adult respiratory distress syndrome with high protein alveolar oedema and pulmonary radiographic infiltrates is associated with high mortality.

In healthy people, breathing is triggered by rising levels of carbon dioxide in the blood. However, in people with severe COPD, breathing may become controlled by an alternative system in which breathing is triggered by falling levels of oxygen in the blood. In this case, inhaling oxygen will tend to shut down breathing, with dangerous consequences. Careful testing, including blood tests, will therefore be necessary before starting oxygen therapy, but in many cases oxygen can be provided safely (in cases of hypoxia with chronic hypercarbia, tissue perfusion is important and may require mechanical ventilation). http://www.abpi.org.uk/publications/publication_details/targetCOPD/q4.asp

ABC of Oxygen, Acute oxygen therapy, NT Bateman, RM Leach, www.bmj.com/cgi/content/full/317/7161/798

Full face mask, and nose mask, from

Venturi valves and venturi mask kit from www.mayohealthcare.com.au

Coloured valves indicate oxygen concentrations, from blue (24% O2) to green (60% O2)


(cefuroxime, erythormycin) – also link to semester 1 antibacterials

Agents affecting the cell wall: beta-lactam antibacterials

Cephalosporins (e.g. cefuroxime is a second generation cephalosporin)

Like penicillins, cephalosporins have a beta-lactam ring. To this ring is fused a dihydrothiazine ring, which makes them more resistant to hydrolysis by beta-lactamases. They inhibit bacterial cell wall synthesis in a manner similar to that of the penicillins.

Succeeding generations of cephalosporins tend to have increased activity against Gram-negative bacilli, usually at the expense of Gram-positive activity, and increased ability to cross the blood-bran barrier. Cefuroxime has activity against staphylococci and most streptococci, and some gram-negative bacteria such as haemophilus influenzae and Neisseria gohorrhoea; but not enterococci. They cross the blood-brain barrier well. It has high resistance to beta-lactamases. It is acid-labile and must be given by parenteral route, or as a prodrug for oral use – cefuroxime axetil, which has good absorption and is hydrolised at first pass through the liver to cefuroxime. It is excreted by kidney and has short half-life.

Unwanted Effects

  • Nausea, vomiting, abdominal discomfort.
  • Rashes, including erythema multiforme and toxic epidermal necrolysis
  • can produce hypersensitivity reactions similar to those observed in penicillins. ~10% of those allergic to penicillins shop cross-allergy to cephalosporins. A history of serious reaction to penicillins precludes the administration of cephalosporins.
  • Diarrhoea or antibiotic-associated colitis can be caused by disturbance of normal bowel flora. This is more common with oral cephalosporins.

Agents affecting bacterial protein synthesis

Macrolides, e.g. erythromycin

Macrolides interfere with bacterial protein synthesis by binding reversibly to the 50S subunit of the bacterial ribosome. This causes dissociation of the peptidyl transfer RNA (tRNA) from its translocation site. The action is primarily bacteriostatic (stops bacteria from reproducing, while not necessarily harming them otherwise).

Erythromycin has a similar spectrum of activity to broad-spectrum penicillins, and is often used for treatment in people who are penicillin-allergic. It is effective against Gram-positive bacteria and gut anaerobes, but has poor activity against Haemophilus influenzae. It is also used for infections by Legionella, Mycoplasma, Chlamydia, mycobacteria and Campylobacter species and for Bordetella pertussis. Although erythromycin is primarily bacteriostatic, it is bactericidal at high concentrations for some Gram-positive species, such as group A streptococci and pneumococci.

Bacteria become resistant to macrolides by activation of an efflux mechanism. To a lesser extent, there is also a gene mutation that encodes for a methyltranferase that modifies the target site on the ribosome.

Erythromycin is adequately absorbed from the gut. It is destroyed at acid pH and is, therefore, given as an enteric-coated tablet or as an ester prodrug (erythromycin ehtyl succinate), which is acid-stable. Erythromycin can also be administered intravenously. It is metabolised in the liver and has a short half-life.

Unwanted effects

  • Epigastric discomfort, nausea, vomiting and diarrhoea are common with the oral preparation.
  • Rashes
  • Cholestatic jaundice with erythromycin, usually if treatment is continued for mote than 2 weeks.
  • Prolongation of the Q-T interval on the ECG, with a predisposition to ventricular arrhythmias.
  • Inhibition of p450 drug-metabolising enzymes and can elevate levels of drugs requiring these enzymes for metabolism, e.g. carbamazepine and ciclosporin.

Assessing COPD

August 29, 2011

(see also Pulse Oximetry)
Blood Pressure
COPD can cause high blood pressure in the lungs.  This can lead to “cor pulmonale,” a form of heart disease secondary to lung disease [www.americanheart.org]. Among all individuals, including those with COPD, there is a protective mechanism in the lung that causes constriction of blood vessels in areas of the lung that have a low concentration of oxygen. Instead, blood is diverted to other well-ventilated parts of the lung where exchange can take place. Unfortunately, although this mechanism improves the efficiency of oxygen and carbon dioxide exchange, the constriction of the blood vessels also causes the blood pressure in the lungs to rise, a condition called pulmonary hypertension. The increased pressure may lead to right-heart failure (vena cava –> right –> tricuspid –> lungs –> left –> bicuspid –> aorta). This often can be detected first in a patient by the presence of ankle swelling. Oxygen inhaled by patients with COPD can relax the blood vessels and decrease blood pressure in the lungs.
Spirometry measures air flow and volume. Normally, the lung empties 70 percent to 75 percent of its total air volume within one second. It is now known that the forced expiratory volume in six seconds FEV6 is an excellent surrogate for FVC. Thus, doing a six-second expiratory manoeuvre is more pleasant for the patient and more convenient for the tester. Normal values for lung function in spirometry are based on patient age, gender and height. Because of arm and leg span differences, black non-smokers tend to have normal values of about 15 percent less than white non-smokers.
Lung function
Lung function measures elastic recoil, large and small airway resistance, interdependence between airways and alveoli, and muscular effort and coordination. In patients with ventilatory abnormalities, such as emphysema, airflow is limited by loss of elastic recoil, and in those with conditions like bronchospasm, mucosal oedema, mucus retention and inflammation, the airway narrows.
Since airflow disorders lower the FEV1 before the FVC, the ratio between the two is the starting point in interpretation. If the patient’s FEV1/FVC ratio is low, for instance less than 70 percent, then the patient has an obstructive defect. Patients with complete or nearly complete airway obstructions that resolve with inhaled bronchodilator use have asthma. Those with irreversible airflow obstructions have COPD. However, considerable overlaps between asthma and COPD are common. Marked hyperinflation, which leads to air trapping, lowers vital capacity.
Spirometric abnormalities are also predictors of heart attack, lung cancer and stroke. A low vital capacity in heart disease may be due to pulmonary congestion, pleural effusion, cardiomegaly or muscular weakness. With any degree of airflow obstruction, the risk of lung cancer is three to five times higher, depending on the patient’s age and smoking history.
http://www.nlhep.org/spirom1.html – National Lung Health Education Program and
http://www.nlhep.org/resources/SpirometryMadeSimple.htm – Spirometry Made Simple, TL. Petty

Polycythemia – defined as an increase in haemoglobin, PCV (packed cell volume) and red cell count. PCV is a more reliable indicator of polycythaemia than is Hb, which may be disproportionately low in iron deficiency. Polycythamia can be divided into absolute erythrocytosis where there is a true increase in red cell volume, or relative erythrocytosis where the red cell volume is normal but there is a decrease in the plasma volume. Absolute erythrocytosis is due to primary polycythemia (PV = Polycythemia vera) or secondary polycythemia. Secondary polycythemia can be due to an appropriate increase in erythropoeietin in response to anoxia eg through high altitude, heavy smoking, lung disease, cardiovascular disease (left-to-right shunt) or mutant high oxygen affinity haemoglobin, e.g. congenital polycythemia; or due to an inappropriate increase in erythropoietin, either congenital or due to renal or liver disease, tumours, or certain drugs. Heavy smoking can produce as much as 10% carboxyhaemoglobin and this can produce polycythemia because of a reduction in the oxygen-carryingcapacity of the blood. Complications of polycythemia include thrombosis, haemorrhage and cardiac failure. Treatment is by treating the precipitating factor. Venesection (giving blood) may be symptomatically helpful in the hypoxic patient, particularly if the PCV is above 0.55L/L.


Pulse Oximetry

August 29, 2011

Pulse oximetry is a simple non-invasive method of monitoring the percentage of haemoglobin (Hb) which is saturated with oxygen. The pulse oximeter consists of a probe attached to the patient’s finger or ear lobe which is linked to a computerised unit. The unit displays the percentage of Hb saturated with oxygen together with an audible signal for each pulse beat, a calculated heart rate and in some models, a graphical display of the blood flow past the probe. Audible alarms which can be programmed by the user are provided. An oximeter detects hypoxia before the patient becomes clinically cyanosed.

Nail varnish may cause falsely low readings. However the units are not affected by jaundice, dark skin or anaemia. Pulse oximetry cannot distinguish between different forms of haemoglobin. Carbo-xyhaemoglobin (haemoglobin combined with carbon monoxide) is registered as 90% oxygenated haemoglobin and 10% desaturated haemoglobin – therefore the oximeter will overestimate the saturation. The presence of methaemoglobin will prevent the oximeter working accurately and the readings will tend towards 85%, regardless of the true saturation.

Oxygen saturation does not reflect the patient’s ability to ventilate. Utilization of SpO2 in a patient with obstructive pulmonary disease may be very misleading. As the degree of lung disease increases, the patient’s drive to breathe may shift from an increased carbon dioxide stimulus to a hypoxic stimulus. Therefore, enhancing the patient’s Sp02 may limit his or her ability to ventilate. The baseline Sp02 for a patient with known severe restrictive disease needs to be considered. [http://www.aacn.org/WD/Practice/Docs/ch_14_PO.pdf]

Pulse oximeters may be used in a variety of situations but are of particular value for monitoring oxygenation and pulse rates throughout anaesthesia. They are also widely used during the recovery phase. The oxygen saturation should always be above 95%. In patients with long standing respiratory disease or those with cyanotic congenital heart disease readings may be lower and reflect the severity of the underlying disease.

In intensive care oximeters are used extensively during mechanical ventilation and frequently detect problems with oxygenation before they are noticed clinically. They are used as a guide for weaning from ventilation and also to help assess whether a patient’s oxygen therapy is adequate. In some hospitals oximeters are used on the wards and in casualty departments. When patients are sedated for procedures such as endoscopy, oximetry has been shown to increase safety by alerting the staff to unexpected hypoxia.

Oximeters give no information about the level of CO2 and therefore have limitations in the assessment of patients developing respiratory failure due to CO2 retention. On rare occasions oximeters may develop faults and like all monitoring the reading should always be interpreted in association with the patient’s clinical condition. Never ignore a reading which suggests the patient is becoming hypoxic. There is no doubt that pulse oximetry is the greatest advance in patient monitoring for many years and it is hoped that their use will eventually become routine during anaesthesia and surgery world wide. Since pulse oximeters cost at least £1200 their purchase will depend mainly on economic considerations.


How does an oximeter work? A source of light originates from the probe at two wavelengths (650nm and 805nm). The light is partly absorbed by haemoglobin, by amounts which differ depending on whether it is saturated or desaturated with oxygen. By calculating the absorption at the two wavelengths the processor can compute the proportion of haemoglobin which is oxygenated. The oximeter is dependant on a pulsatile flow and produces a graph of the quality of flow. Where flow is sluggish (eg hypovolaemia or vasoconstriction) the pulse oximeter may be unable to function. The computer within the oximeter is capable of distinguishing pulsatile flow from other more static signals (such as tissue or venous signals) to display only the arterial flow.


Smoking, health risk, and addiction

August 29, 2011

[K&C, and Marks et al Health Psychology]

General household surveys in UK show decline in prevalence of smoking in early 90s, but more recent increase in prevalence. At present, 28% of men and women >=16 years old smoke, most common (40%) 16-34 age group, and it is in this age group that the increase has occurred. Uptake of smoking occurs largely in adolescence, associated with parental and peer smoking. At age 15, more boys than girls smoke. A greater proportion of manual workers than professional workers smoke. Rates are higher than this, and increasing, in developing world. Brief psychological therapies for smoking cessation based on cognitive behavioural therapy are showing considerable promise.

Cigarette smoke contains polycyclic aromatic hydrocarbons and nitrosamines, which are potent carcinogens and mutagens in animals. It causes release of enzymes from neutrophil granulocytes and macrophages that are capable of destroying elastin and leading to lung damage. Pulmonary epithelial permeability increases even in symptomless cigarette smokers, and correlates with the concentration of carboxyhaemoglobin in the blood. This altered permeability possibly allows easier access to carcinogens.


<2% of smokers can limit themselves to occasional or intermittent smoking.

Effects of smoking on the lung:

  • Large Airways: Increase in submucosal gland volume, increase in number of goblet cells; chronic inflammation, metaplasia and dysplasia of the surface epithelium.
  • Small Airways: Increase in the number and distribution of goblet cells; airway inflammation and fibrosis. Epithelial metaplasia / dysplasia, carcinoma
  • Parenchyma: proximal acinar scarring, increase in alveolar macrophage numbers, emphysema (centri-acinar, pan-acinar)

Sputum production and airflow limitation increase with daily cigarette consumption, and effort tolerance decreases, partly owing to high levels of carboxyhaemoglobin in bronchitis patients. Smoking and asbestos exposure are synergistic in producing bronchial carcinoma, increasing the risk in asbestos workers by up to 5-8 times that of non-smokers.

Quitting smoking

Cigarette smokers who change to other forms of tobacco can reduce the risk, even if they continue to inhale, and are better off changing to cigars or pipes.

Nicotine replacement therapy (NRT) and buproprion as aids to smoking cessation for those smoking >10/day. NRT is the preferred choice and there is no evidence that combined therapy offers any advantage. Therapy should be changed after 3 months if abstinence is not achieved

[Waller et al, Medical Pharmacology and Therapeutics]

Established cardiovascular disease is a caution for, but not a contraindication to, nicotine replacement therapy. Behavioural therapy enhances the success rate achieved by NRT. Use of NRT doubles the chance of achieving abstinence.

Buproprion is an atypical antidepressant. Most antidepressants are ineffective for smoking cessation, but the use of buproprion is associated with smoking cessation rates equal to or slightly greater than NRT. Treatment should be started 1 week prior to quit date. Additional benefit that smokers who use buproprion as an aid to quitting are less likely to gain weight.

Buproprion is a weak inhibitor of neuronal reuptake of noradrenaline and dopamine, and probably works by enhancing mesolimbic dopaminergic activity. It is given as a modified-release formulation and has a long half-life. Elimination is by hepatic metabolism, which also generates active metabolites. Unwanted effects include anxiety, headache, insomnia and dry mouth. There is an increased risk of epileptic seizures, and buproprion should be avoided if there is a past history of seizures. Recent evidence indicates that, in contrast to other antidepressants that have been studied, nortriptyline is as effective as buproprion for smoking cessation.



August 29, 2011

COPD refers to emphysema, chronic bronchitis, or a combination of the two. These cause severe difficulties in ventilation and in oxygenation of the blood, and are among the major causes of disability and death in the US.

Airway obstruction is not caused by increased smooth muscle contraction in these diseases as it is in asthma. In emphysema the cause of obstruction is destruction and collapse of the smaller airways. Emphysema is characterised by the destruction of the alveolar walls leading to an increase in compliance (compliance = the magnitude of change in lung volume produced by a given change in the transpulmonary pressure). Chronic bronchitis is characterised by excessive mucus production in the bronchi and chronic inflammatory changes in the small airways. Obstruction is caused by accumulation of the mucus in the airways and thickening of the inflamed airways. The same agents that cause emphysema, such as smoking, also cause chronic bronchitis, which is why the two diseases frequently coexist.

[Kumar and Clark]

The global initiative in obstructive lung disease (GOLD) predicts that COPD will become the third most common cause of death and fifth most common cause of disability world-wide by 2020.

The term COPD brings together a variety of syndromes associated with destruction of the lung and airflow obstruction. Chronic asthma, chronic bronchitis, emphysema, pink puffers and blue bloaters. “COPD is a disease state characterised by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases.” (GOLD)

  • Loss of elasticity and alveolar attachments of airways due to emphysema → reduces elastic recoil and airways collapse during expiration.
  • Inflammation and scarring cause the small airways to narrow
  • Mucus secretion blocks airways
  • Combined these lead to hyperinflation of the lung and breathlessness

COPD is caused by long term exposure to toxic particles and gases. In developed countries, cigarette smoking accounts for 90% of cases. Airflow limitation increases with age, and increases more rapidly in smokers. The rate of increase in someone who has quit smoking is the same as that in someone who never smoked, although it may start from a lower level due to the damage of previous smoking. In developing countries, COPD is caused by cigarette smoking and smoke from cooking fuels. Only 10-20% of heavy smokers develop COPD, indicating individual susceptibility. Risk of death for person smoking 30/day is 20x that of a non-smoker. Autopsy studies have shown that substantial numbers of centri-acinar emphysematous spaces are found in the lungs of 50% of British smokers over the age of 60 years and are unrelated to the diagnosis of significant respiratory disease before death. Climate and air pollution have some affect. Urbanisation, social class and occupation may also have an effect on aetiology but difficult to separate from smoking.

In UK, COPD accounts for 7% of all days off work due to sickness. But the number of patients discharged from hospital with this diagnosis has been falling steadily and the death rate has fallen in the last 25 years from 200 to 70 per 100,000 in the UK.


The most consistent pathological finding is hypertrophy and increase in number of the mucus secreting goblet cells of the bronchial tree, evenly distributed throughout the lung but mainly seen in the larger bronchi. In more advanced cases the bronchi themselves are obviously inflamed and pus is seen in the lumen. Microscopically there is infiltration of the bronchi and bronchioles with acute and chronic inflammatory cells and lymphoid follicles in severe disease. In contrast to asthma, the lymphocytic infiltrate is predominantly CD8+. The epithelial layer may become ulcerated and, when the ulcers heal, squamous epithelium may replace the columnar cells. The inflammation is followed by scarring and a remodelling process that thickens the walls and leads to widespread narrowing in the small airways.

The small airways are particularly affected early in the disease, initially without the development of any significant breathlessness. This initial inflammation of the small airways is reversible and accounts for the improvement in airway function if smoking is stopped early. In later stages the inflammation continues even if smoking is stopped.

Further progression of the disease leads to progressive squamous cell metaplasia, and fibrosis of the bronchial walls. The physiological consequence of these changes is the development of airflow limitation. If the airway narrowing is combined with emphysema (causing loss of the elastic recoil of the lung with collapse of small airways during aspiration) the resulting airflow limitation is even more severe.

Emphysema is defined pathologically as dilation and destruction of the lung tissue distal to the terminal bronchiole:

  • Centri-acinar emphysema – damage concentrated around the respiratory bronchioles; extremely common form of emphysema, and when of modest extent it is not normally disabling, but severe Centri-acinar emphysema is associated with substantial airflow limitation.
  • Pan-acinar emphysema – less common, damage appears to involve the whole of the acinus, and in the extreme form the lung becomes a mass of bullae. Severe airflow limitation and Va/Q mismatch occur. This type of emphysema occurs in alpha1-antitrypsin deficiency.
  • Irregular emphysema produces damage and scarring affecting the lung parenchyma patchily without particular regard for acinar structure.

Emphysema leads to expiratory airflow limitation and air trapping. The loss of lung elastic recoil results in an increase in TLC while the loss of alveoli results in decreased gas transfer.

Va/Q mismatch occurs partly because of damage and mucus plugging, and partly because of the rapid expiratory closure of the smaller airways owing to loss of elastic recoil. This leads to a decrease in PaO2 and an increase in the work of respiration.

PaCO2 excretion is not impaired to the same extent and many patients will show low normal PaCO2 values – the “pink puffers” who seek to maintain normal blood gases by increasing their respiratory effort. Other patients fail to maintain their respiratory effort and thus their carbon dioxide levels increase. In the short term, the rise in CO2 leads to stimulation of respiration but in the long term these patients often become insensitive to CO2 and come to depend on hypoxaemia to drive their ventilation. These patients appear less breathless, and because they run low O2 values they start to retain fluid and stimulate the production of erythrocytes (polycythemia). So they become bloated, plethoric and cyanosed. Attempts to abolish hypoxaemia by administering oxygen can make the situation much worse by decreasing respiratory drive in these patients who rely on hypoxia to drive their ventilation.

Loss of 50ml/yr FEV1 in COPD compared to 20mL/yr in healthy people.


Cigarette Smoking

Bronchoalveolar washes have shown that smokers have neutrophil granulocytes present within the lumen of the bronchial tree that are absent in non-smokers. Also, small airways of smokers are infiltrated by granulocytes capable of releasing elastases and proteases, which possibly help to produce emphysema. It is suggested that imbalance between protease and antiprotease activity may produce the damage. Alpha1-antitrypsin is a major serum antiprotease which can be inactivated by cigarette smoke.

The hypertrophy of mucous glands in the larger airways is thought to be a direct response to persistent irritation resulting from the inhalation of cigarette smoke. The smoke has adverse effect on surfactant, favouring overdistension of the lungs.

alpha1-Antitrypsin deficiency

alpha1-antitrypsin inhibitor is produced in liver, secreted into blood and diffuses into the lungs where it acts as antiprotesase that inhibits neutrophil elastase, a proteolytic enzyme capable of destroying alveolar wall connective tissue. There are >75 alleles of the alpha1-antitryptin inhibitor gene, of which 3 main phenotypes. ~1in5000 in UK are homozygous deficient, and those who develop chest disease are usually, but not always, smokers. Hereditary alpha1-antitryptin deficiency accounts for ~2% of emphysema cases.

Clinical Features

Characteristic symptoms are cough with production of sputum, wheeze and breathlessness following many years of smokers cough and frequent chest infections. Can be worsened by, e.g., cold, foggy weather, pollution. With advanced disease, breathlessness becomes severe even after mild exercise such as dressing.

Only sign in mild disease is wheeze throughout the chest. In severe disease patient is tachypnoeic with prolonged expiration, using accessory muscles to breathe, and may show intercostal indrawing on inspiration and pursing of lips on expiration



More than 40 per cent of smokers aged 61-62 and 50 per cent of those aged 76-77 have COPD

Stopping smoking is the only measure that has been conclusively shown to slow further progression of the disease. After stopping smoking, the rate of decline of lung function slows, approaching that in non-smokers. Preventing a exacerbations of COPD is also important, as it has been found that frequent exacerbations are associated with a more rapid decline in lung function. Respiratory infections are a common cause of such exacerbations, so vaccination against influenza and pneumonia may help protect against accelerated decline in lung function. Combinations of inhaled steroids and bronchodilators used in more advanced COPD reduce the frequency and severity of exacerbations and also the risk of death.

In mild COPD (for example, where breathlessness occurs only on exercising), an inhaled short-acting bronchodilator may be sufficient to control the symptoms. If a single bronchodilator is not sufficient, a combination of two types of shortacting bronchodilators may be tried, or a longacting inhaled bronchodilator can be used instead. In more severe cases, guidelines recommend trying a combination of an inhaled long-acting bronchodilator and an inhaled corticosteroid for an initial period of four weeks. If this combination is still not sufficient to provide relief, theophylline, taken by mouth, may be added. However, this can cause unpleasant side-effects and must be closely monitored

Many other therapies can be used to improve the quality of life of people with COPD. Anxiety or depression can be treated by behavioural therapy and medication. Dietary advice can help prevent weight loss and muscle-wasting. Treatment with a mucolytic medicine may ease sputum production. Pulmonary rehabilitation increases exercise tolerance, promoting independence and emotional well-being. Disease flare-ups due to infections such as pneumonia and flu can be prevented by vaccination.


<h2>Infections as complication of COPD</h2>


Patients with COPD often cope badly with respiratory infections, which can be precipitating cause of acute exacerbations. But its not clear if infections affect the progressive airflow limitation. Prompt use of antibiotics and flu jabs are appropriate.