A brief overview of Chronic Obstructive Pulmonary Disease.pptx

A brief introduction of COPD, from the aspect of a 5th year medical school student

1. COPD A brief overview

2. Overview A type of  obstructive lung disease  characterized by long-term breathing problems and poor airflow. [1] [8]  The main symptoms include  shortness of breath  and  cough  with  sputum  production. [1]  COPD is a  progressive disease , meaning it typically worsens over time. [9]  Eventually,  everyday activities  such as walking or getting dressed become difficult. Chronic bronchitis  and  emphysema  are older terms used for different types of COPD. [10] [11] [12]   The term "chronic bronchitis" is still used to define a productive cough that is present for at least three months each year for two years. [1]  Those with such a cough are at a greater risk of developing COPD. [13]   The term "emphysema" is also used for the  abnormal presence of air or other gas within tissues .

3. T obacco smoking , is the major cause of th e disease, a smaller number of cases can be also caused by  factors  such as  air pollution  and  genetics . [2]   In the  developing world , one of the common sources of air pollution is poorly vented heating and  cooking fires . [3]  Long-term exposure to these irritants causes an  inflammatory response  in the  lungs , resulting in narrowing of the  small airways  and breakdown of lung tissue. [5]   The diagnosis is based on poor airflow as measured by  lung function tests . [4]   In contrast to  asthma , the airflow reduction does not improve much with the use of a  bronchodilator . [3] [15]

4. Definition Reduction of FEV1, forced vital capacity(FVC), and the FEV1:FVC ratio<80%(or <70% in some guidelines) are the hallmark of airway obstruction. Total lung capacity(TLC) is increased due to lung hyperinflation, secondary to expiratory flow limitation(Total Lung Capacity: the maximum volume of air the lungs can accommodate or sum of all volume compartments or volume of air in lungs after maximum inspiration) GOLD grade Severity FEV 1  % predicted Mild (GOLD 1) ≥ 80 Moderate (GOLD 2) 50–79 Severe (GOLD 3) 30–49 Very severe (GOLD 4) <30

5. Centrilobular emphysema and chronic bronchitis(both complications of smoking) can overlap in clinical and pathologic findings, but significant bronchoconstriction is not a feature of emphysema. Sulfur dioxide is a gas that contributes to obstructive lung diseases, particularly chronic bronchitis and asthma.

6. Chronic bronchitis Defined as a productive cough that lasts for three months or more per year for at least two years. Chronic bronchitis is a disease of smokers and individuals living in areas of poor air quality, which explains the chronic cough with mucoid sputum production. Chronic bronchitis can be complicated by pulmonary hypertension and cor pulmonale. There are few characteristic microscopic features of chronic bronchitis, so it is mainly defined clinically A diagnosis of chronic bronchitis can be made based on the patient’s symptoms and biopsy results. Along with the hypertrophy of mucus-secreting glands and goblet cells, one typically sees an inflammatory infiltrate with a lymphocytic predominance, squamous cell metaplasia, and fibrosis

7. Chronic bronchitis is a respiratory disease marked by overproduction of mucus and mucins. The excess mucus is produced by goblet cells and enlarged submucosal glands in response to long-term irritation. Mucins thicken mucus, and their concentration has been found to be high in cases of chronic bronchitis, and also to correlate with the severity of the disease. In COPD, those with the chronic bronchitic phenotype with associated chronic excess mucus, experience a worse quality of life than those without. Excess mucus can narrow the airways, thereby limiting airflow and accelerating the decline in lung function, and result in COPD. Excess mucus shows itself as a chronic productive cough and its severity and volume of sputum can fluctuate in periods of acute exacerbations. The increased secretions are initially cleared by coughing. The cough is often worse soon after awakening, and the sputum produced may have a yellow or green color and may be streaked with specks of blood. In the early stages, a cough can maintain mucus clearance. However, with continued excessive secretion, mucus clearance is impaired and when the airways become obstructed a cough becomes ineffective. Effective muco-ciliary clearance depends on airway hydration, ciliary beating, and the rates of mucin secretion. Each of these factors is impaired in chronic bronchitis. Chronic bronchitis can lead to a higher number of and a faster decline in lung function.

8. Chronic bronchitis does not lead to diffuse pulmonary fibrosis. The increase in mucous glands with chronic bronchitis leads to copious/rich sputum production In some cases episodes of bronchoconstriction set off by viral infections may suggest a superimposed element of nonatopic asthma Estimates of the number of people with COPD who have chronic bronchitis are 7 to 40%. Estimates of the number of people who smoke and have chronic bronchitis who also have COPD is 60%. Additional info

9. Emphysema Defined as the "abnormal permanent enlargement of the airspaces distal to the terminal bronchioles accompanied by destruction of the alveolar wall and without obvious fibrosis". Emphysema is best evaluated on CT, although indirect signs can be noticed on conventional radiography in a proportion of cases.

10. Emphysema Emphysema is one of a heterogeneous group of pathological processes forming  chronic obstructive pulmonary disease  and is itself a relatively vague term encompassing a number of entities and morphological patterns including: morphologic subtypes centrilobular emphysema  (most common) panlobular emphysema paraseptal emphysema paracicatricial emphysema localized emphysema idiopathic giant bullous emphysema  (or  vanishing lung syndrome ) congenital lobar emphysema pulmonary interstitial emphysema Classification

11. The three morphologic subtypes of emphysema are named according to their relationship to the  secondary pulmonary lobule . Centrilobular emphysema  is the most frequently encountered type and affects the proximal respiratory bronchioles, particularly of the upper zones. It has a strong dose-dependent association with smoking  3 . Rarely, severe centrilobular emphysema can be seen in the bases in patients with  Salla disease   4 . Panlobular emphysema  (also known as panacinar emphysema) ,  in contrast, affects the entire secondary pulmonary lobule and is more pronounced in the lower zones, matching areas of maximal blood flow. It is seen particularly in  alpha-1-antitrypsin deficiency  (exacerbated by smoking)  2-4 , intravenous injection of methylphenidate ( Ritalin lung )  3  or  Swyer -James syndrome   4 . Paraseptal emphysema  affects the peripheral parts of the  secondary pulmonary lobule , and is usually located adjacent to the pleural surfaces (including  pleural fissures )  3 . It is also associated with smoking and can lead to the formation of subpleural bullae and spontaneous  pneumothorax   3 . Emphysema Classification

12. Distal Acinar/ Paraseptal Distal acinar ( paraseptal ) emphysema is localized, beneath pleura typically in an upper lung lobe, and may occur in an area of fibrosis or scar formation. the lesions are usually less than 2 cm in diameter they are prone to rupture spontaneously or with minor trauma, leading to pneumothorax can be a cause for spontaneous pneumothorax in young adults Emphysema

13. results from damage to the central part of the lung acinus, with dilation that primarily affects the respiratory bronchioles relative spares the distal alveolar ducts and alveolar sacs. Smoking is a major cause of this disease The subtle but long-term inflammation that can accompany smoking leads to increased neutrophil and macrophage elaboration of elastase that is not sufficiently inhibited by the antiprotease action of α1-antitrypsin. This results in a loss of lung tissue over decades. Centrilobular Emphysema

14. α1-Antitrypsin deficiency(relatively uncommon) can lead to a panlobular pattern of emphysema α1-antitrypsin is the major circulating antielastase can involve most of the lung lobule and can be seen in all lobes worse in the lower lobes In panacinar emphysema, the lung lobule is involved from the respiratory bronchiole to the terminal alveoli Panlobular Emphysema

15. α1- Antitrypsin deficiency --overview an inherited disease, typically with the PiZZ genotype; liver disease may also occur. PiMM : 100% (normal) PiMS : 80% of normal serum level of A1AT PiSS : 60% of normal serum level of A1AT PiMZ : 60% of normal serum level of A1AT PiSZ : 40% of normal serum level of A1AT PiZZ : 10-15% (severe alpha-1 antitrypsin deficiency) The most common cause of severe deficiency, PiZ , is a single base-pair substitution leading to a glutamate to lysine mutation

16. α1- Antitrypsin deficiency ---symptoms Individuals with A1AD may develop  chronic obstructive pulmonary disease  ( emphysema ) during their thirties or forties even without a history of  smoking , though smoking greatly increases the risk. [7]  Symptoms may include  shortness of breath  (on exertion and later at rest),  wheezing , and  sputum  production. Symptoms may resemble recurrent respiratory infections or  asthma . [8] More severe forms of A1AD can include impaired liver function, leading to  cirrhosis  and liver failure (15%). In newborns, alpha-1 antitrypsin deficiency can result in early onset  jaundice  followed by prolonged jaundice. It is a leading reason for  liver transplantation  in newborns. Apart from COPD and chronic liver disease, α 1 -antitrypsin deficiency has been associated with necrotizing  panniculitis  (a skin condition) and with  granulomatosis with polyangiitis  in which inflammation of the blood vessels may affect a number of organs but predominantly the lungs and the kidneys

17. α1- Antitrypsin deficiency ---causes & pathophysiology A1AT is produced in the  liver , and one of its functions is to protect the  lungs  from  neutrophil elastase , an enzyme that can disrupt connective tissue. [7]  Normal blood levels of alpha-1 antitrypsin may vary with analytical method but are typically around 1.0-2.7 g/l. [12]  In individuals with PiSS , PiMZ and PiSZ   genotypes , blood levels of A1AT are reduced to between 40 and 60% of normal levels; this is usually sufficient to protect the lungs from the effects of  elastase  in people who do not smoke. However, in individuals with the PiZZ genotype, A1AT levels are less than 15% of normal, and they are likely to develop  panlobular emphysema  at a young age. Between 10 and 15% of these people will develop  liver fibrosis  or  liver cirrhosis , because the A1AT is not secreted properly and therefore accumulates in the liver. [13]  A  liver biopsy  in such cases will reveal  PAS -positive,  diastase -resistant granules. Unlike glycogen and other mucins which are diastase sensitive (i.e., diastase treatment disables PAS staining), A1AT deficient hepatocytes will stain with PAS even after diastase treatment - a state thus referred to as "diastase resistant". Cigarette smoke is especially harmful to individuals with A1AD. [7]  In addition to increasing the  inflammatory  reaction in the  airways , cigarette smoke directly inactivates alpha-1 antitrypsin by  oxidizing  essential  methionine  residues to  sulfoxide  forms, decreasing the  enzyme  activity by a factor of 2,000.

18. Symptoms The symptoms/signs of pulmonary heart disease ( cor pulmonale) can be non-specific and depend on the stage of the disorder, and can include blood backing up into the  systemic venous system , including the  hepatic vein . [7] [8]  As pulmonary heart disease progresses, most individuals will develop symptoms like: [1] Shortness of breath Wheezing Cyanosis Ascites Jaundice Enlargement of the liver Raised  jugular venous pressure  (JVP) Third heart sound Intercostal recession Presence of abnormal  heart sounds Diagnosis Chest  x-ray  – right ventricular hypertrophy, right atrial dilatation, prominent pulmonary artery ECG  – right ventricular hypertrophy, dysrhythmia, P pulmonale (characteristic peaked  P wave ) Thrombophilia  screen- to detect chronic venous thromboembolism (proteins C and S,  antithrombin III ,  homocysteine  levels) Ddx Atrial myxoma Congestive heart failure Constrictive pericarditis Infiltrative  cardiomyopathies Right heart failure  (right ventricular infarction) Ventricular septal defect Pulmonary heart disease / C or pulmonale

19. Pulmonary heart disease / C or pulmonale Pathophysiology T he  enlargement  and  failure  of the  right ventricle  of the  heart  as a response to increased vascular resistance (such as from  pulmonic stenosis ) or high blood pressure in the lungs. According to Voelkel , et al., pressure overload is the initial step for changes in RV, other factors include: [14] Ischemia Inflammation Oxidative  damage Epigenetics Abnormal cardiac energetics C auses Acute respiratory distress syndrome  (ARDS) [10] COPD [2] Primary  pulmonary hypertension [2] Blood clots  in lungs [2] Kyphoscoliosis [2] Interstitial lung disease [2] Cystic fibrosis [2] Sarcoidosis [11] Obstructive sleep apnea  (untreated) [2] Sickle cell anemia [12] Bronchopulmonary dysplasia  (in infants) [13]

20. Acute exacerbation of chronic obstructive pulmonary disease A sudden worsening of  chronic obstructive pulmonary disease  (COPD) symptoms including  shortness of breath , quantity and color of  phlegm  that typically lasts for several days. An abrupt worsening in COPD symptoms may cause rupture of the airways in the  lungs , which in turn may cause a  spontaneous pneumothorax . [4] In infection, there is often weakness, fever and chills. If due to a bacterial infection, the sputum may be slightly streaked with blood and coloured yellow or green. [5] Diagnosis CXR, Sputum culture, Symptoms and others Prevention Smoking cessation  and avoiding inhaled irritants [5]   influenza  and  pneumococcal vaccinations [5] Regular exercise, appropriate rest, and healthy nutrition [5] Maintaining good fluid intake and humidity(to reduce the formation of thick sputum and chest congestion)

21. Causes Other causes include Allergens , Toxins, including a variety of different chemicals [5] Air pollution Failing to follow a  drug therapy  program, e.g. improper use of an  inhaler Respiratory infection , being responsible for approximately half of COPD exacerbations. Approximately half of these are due to viral infections and another half appears to be caused by bacterial infections. [6]   Common bacterial pathogens of acute exacerbations include  H. influenzae ,  S. pneumoniae  and  M oraxella catarrhalis . [7]   Less common bacterial pathogens include  Chlamydia pneumoniae  and  MRSA . [7]   Pathogens seen more frequently in patients with impaired lung function (FEV<35% of predicted) include  H. parainfluenzae  (after repeated use of antibiotics),  Mycoplasma pneumoniae  and G(-),  opportunistic pathogens  like  P. aeruginosa  and  Klebsiella pneumoniae . [7] In one-third of all COPD exacerbation cases, the cause cannot be identified.

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