COPDDefinition,clinicalmanifestations,diagnosis,and慢性阻塞性肺疾病定義,臨床表現(xiàn),診斷,

1、COPD (Definition, clinical manifestations, diagnosis, and staging) INTRODUCTION1. COPD is a common respiratory condition involving the airways and characterized by airflow limitation. It affects > 5% of population and is associated with high morbidity and mortality. It is 3rd-ranked cause of deat

2、h in the US, killing > 120,000 individuals each year. As consequence of its high prevalence and chronicity, COPD causes high resource utilization with frequent clinician office visits, frequent hospitalizations due to acute exacerbations, and the need for chronic therapy (supplemental O2 therapy,

3、 medication).2. Correct diagnosis of COPD is important because appropriate management can decrease symptoms (especially dyspnea), reduce the frequency and severity of exacerbations, improve health status, improve exercise capacity, and prolong survival.3. The definition, clinical manifestations, dia

4、gnostic evaluation, and staging of COPD are discussed in this topic review. The risk factors, natural history, prognosis, and treatment of COPD are discussed separately.DEFINITIONS1. The definition of COPD and its subtypes (emphysema, chronic bronchitis, chronic obstructive asthma) and interrelation

5、ships between closely related disorders that cause airflow limitation provide foundation for understanding spectrum of patient presentations.2. COPDA. The GOLD-project in itiated by Natio nal Heart, L ung, and Blood In stitute (NHLBI) and WHO defines COPD as common preventable and treatable disease,

6、 is characterized by airflow limitation that is usually progressive and associated withenhanced chronic inflammatory response in airways and lung to noxious particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients.3. Chronic bronchitisA. Chronic b

7、ronchitis is defined aschronic productive cough for 3 months in each of 2 successive yearsin patient in whom other causes of chronic cough (bronchiectasis) have been excluded. It may precede or follow development of airflow limitation. This definition has been used in many studies, despite arbitrari

8、ly selected symptom duration.4. EmphysemaA. Emphysema is defined byabnormal and permanent enlargement of airspaces distal to terminal bronchioles that is accompanied by destruction of airspace walls,without obvious fibrosis (there is no fibrosis visible to naked eye). Exclusion of obvious fibrosis w

9、as intended to distinguish alveolar destruction due to emphysema from that due to interstitial pneumonias. However, many studies have found increased collagen in lungs of patients with mild COPD, indicating that fibrosis can be component of emphysema. While emphysema can exist in individuals who do

10、not have airflow obstruction, it is more common among patients who have moderate or severe airflow obstruction.B. The various subtypes of emphysema (proximal acinar, panacinar, distal acinar) are described below.5. AsthmaA. The GINA gives followi ng deifiiti on of asthma.“ AsChironiis in flammatoryd

11、isorder of airways in which many cells and cellular elements play role. The chronic in flammatio n is associated with airway resp on sive ness that leads torecurre nt episodes of wheez ing, breathless ness, chest tight ness, and cough ing particularly at ni ght or in early morning. These episodes ar

12、e usually associated with widespread, but variable, airflow obstruction within the lung that is often reversible either spontaneously or with treatme nt. ”6. In terrelati on ships of COPD subtypesA. Early defi niti ons of COPD disti nguished differe nt types (chro nic bron chitis, emphysema,asthma),

13、 distinction that is not included in current definition. However, individual patie nts prese nt with spectrum of mani festati ons of COPD and related processes, so understanding types of COPD, as illustrated in figure, can be helpful diagnostically.i. Patie nts with asthma whose airflow obstructio n

14、 is completely reversible are not con sidered to have COPD (subset 9).ii. Patie nts with asthma whose airflow obstructio n does n ot remit completely are con sidered to have COPD (subsets 6, 7, and 8). The etiology and pathoge nesis of COPD in such patients may be different from that of patients wit

15、h chronic bronchitis or emphysema.iii. Chro nic bron chitis and emphysema with airflow obstructio n common ly occur together (subset 5). Some of these patie nts may also have asthma (subset 8).iv. In dividuals with asthma may develop chro nic productive cough, either spontan eously or due to exposur

16、e (cigarette smoke, allerge n). Such patie nts are often referred to as having asthmatic bronchitis, although this terminology has not bee n officially en dorsed in cli nical practice guideli nes (subset 6).v. Pers ons with chro nic bron chitis, emphysema, or both are not con sidered to haveCOPD unl

17、ess they have airflow obstruction (subsets 1,2, and 11).vi. Patie nts with airflow obstructi on due to diseases that have known etiology or specific pathology (cystic fibrosis, bron chiectasis, obliterative bron chiolitis) are not con sidered to have COPD (subset 10). However, these exclusi ons are

18、loosely defi ned.B. Con siste nt with idea that sig nifica nt overlap exists among differe nt types of COPD, many in dividuals have bron chial in flammatio n with features of both asthma and chro nic bron chitis/emphysema. Similarly, n ature of bron chial in flammatio n varies widely eve n among in

19、dividuals with sin gle type of COPD. A nu mber of in itiatives are in progress to provide rigorous phe no typ ing of COPD patie nts in order to defi ne more homoge neous groups.PATHOLOGY1. The predo minant pathologic cha nges of COPD are found in theiirways, but cha nges are also see n in lung pare

20、nchyma and pul monary vasculature. In in dividual, patter n of pathologic cha nges depe nds on un derly ing disease (chr onic bron chitis, emphysemaa an titryps in deficie ncy), possibly in dividual susceptibility, and disease severity.2. AirwaysA. Airways abno rmalities in COPD in cludechro nic in

21、flammatio n , in creased nu mbers of goblet cells, mucus gla nd hyperplasia, fibrosis, n arrow ing and reducti on in nu mber of small airways, and airway collapse due to loss of tethering caused by alveolar wall destructi on in emphysema. Chronic in flammatio n in chronic bron chitis and emphysema i

22、s characterized by prese nee of CD8+ T-lymphocytes, n eutrophils, and CD68+ mono cytes/macrophages in airways. In comparis on, bron chial in flammatio n of asthma is characterized by prese nee of CD4+ T-lymphocytes, eos ino phils, and in creased IL-4 and IL-5. Among patie nts with chronic bron chiti

23、s who havemucus hypersecreti on, in creased number of goblet cells and enlarged submucosal glandsare typically seen.AsthmaCOPDSensklizing agentnoxious agent3. Lung parenchymaA. Emphysema affects structures distal to terminal bronchiole, consisting of respiratory bronchiole, alveolar ducts, alveolar

24、sacs, and alveoli, known collectively as acinus. These structures in combination with their associated capillaries and interstitium form lung parenchyma. The part of acinus that is affected by permanent dilation or destruction determines subtype of emphysema.i. Proximal acinar (also known as centril

25、obular) emphysema refers to abnormal dilation or destruction of respiratory bronchiole, central portion of acinus. It is commonly associated with cigarette smoking , but can also be seen in coal workers pneumoconiosis.ii. Panacinar emphysema refers to enlargement or destruction of all parts of acinu

26、s. Diffuse panacinar emphysema is most commonly associated with a antitrypsin deficiency, although it can be seen in combination with proximal emphysema in smokers.iii. Distal acinar (also known as paraseptal) emphysema, alveolar ducts are predominantly affected. Distal acinar emphysema may occur al

27、one or in combination with proximal acinar and panacinar emphysema. When it occurs alone, usual association isspontaneous pneumothorax in young adult.4. Pulmonary vasculatureA. Changes in pulmonary vasculature includeintimal hyperplasia and smooth muscle hypertrophy/hyperplasia thought to be due to

28、chronic hypoxic vasoconstriction of small pulmonary arteries. Destruction of alveoli due to emphysema can lead to loss of associated areas of pulmonary capillary bed.CLINICAL FEATURES1. Smoking and inhalational exposure historyA. The most important risk factor for COPD iscigarette smokingand amount

29、and duration of smoking contribute to disease severity. Thus, key step in evaluation of patients with suspected COPD is to ascertain number of pack years smoked (PPD multiplied by number of years), as majority (80%) of patients with COPD have history of cigarette smoking. It is useful to ask age of

30、starting and age of quitting, as patients may underestimate numberof years they smoked. With enough smoking, almost all smokers will develop measurably reduced lung function. While studies have shown overall-response“cudrovsee ” forsmoking and lung function, some individuals develop severe disease w

31、ith fewer pack years and others have minimal to no symptoms despite many pack years.B. The exact threshold for duration/intensity of cigarette smoking that will result in COPD varies from 1 individual to another. In absence of genetic/environmental/occupational predisposition, smoking < 10 to 15

32、pack years of cigarettes is unlikely to result in COPD. On the other hand, single best variable for predicting which adults will have airflow obstruction on spirometry is history of > 40 pack years of smoking (positive likelihood ratio, 12).C. The chrono logically take n en vir onmen tal/occupati

33、 onal history may disclose other importa nt risk factor for COPD, such asexposure to fumes or orga nic or inorganic dusts. These exposures help to expla in 20% of patie nts with COPD (defi ned by lung function alone) and 20% of patie nts who die from COPD who n ever smoked.2. Symptoms and patter n o

34、f on setA. The three cardinal symptoms of COPD ardyspnea, chronic cough, and sputum and most com mon early symptom is exerti onal dysp nea. Less com mon symptoms in clude wheez ing and chest tight ness (able 1A). However, any of these symptoms may develop independently and with variable intensity.B.

35、 There are three typical ways in which patie nts with COPD prese nt.i. Patie nts who have extremely sede ntary lifestyle but few complai nts require careful questioning to elicit history that is suggestive of COPD. Some patients unknowin gly avoid exerti onal dysp nea by shift ing expectatio ns and

36、limit ing their activity. They may be unaware of extent of their limitations or that their limitations are due to respiratory symptoms, although they may compla in of fatigue.ii. Patie nts who prese nt with respiratory symptoms gen erally complai n of dysp nea and chronic cough. The dyspnea may init

37、ially be noticed only during exertion. However, it eve ntually becomes no ticeable with progressively less exerti on or eve n at rest. The chronic cough is characterized by in sidious on set of sputum product ion, which occurs in morning in itially, but may progress to occur throughout day. The dail

38、y volume rarely exceeds 60 mL. The sputum is usually mucoid, but becomes purule nt duri ng exacerbati ons.iii. Patie nts who prese nt with episodes of in creased cough, purule nt sputum,wheez ing, and dysp nea that occur in termitte ntly, with or without fever.Diag no siscan be problematic in such p

39、atie nts. The comb in ati on of wheez ing plus dysp nea may lead to in correct diag no sis of asthma. Con versely, other ill nesses with similar mani festati ons are ofte n in correctly diag no sed as COPD exacerbati on (heart failure, bron chiectasis, bron chiolitis) (table 2). The in terval betwee

40、 n exacerbati ons decreases as the severity of the COPD in creases.C. Approximately 62% of patie nts with moderate to severe COPD report variability in symptoms (dysp nea, cough, sputum, wheez ing, or chest tight ness) over course of day or week-to-week; morni ng is typically the worst time of day.D

41、. Patie nts with COPD may experie nee weight gain (due to activity limitatio ns), weight loss (possibly due to dysp nea while eat in g), limitati on of activity (in clud ing sexual), cough syn cope, or feeli ngs of depressi on or an xiety. Weight loss gen erally reflects more adva need disease and i

42、s associated with worse prog no sis. Howevemajority of COPD patie nts are overweight or obese.E. Comorbid diseases that may accompa ny COPD in clude lung can cer, CAD, osteoporosis, metabolic syn drome, skeletal muscle weak ness, depressi on, and cog nitive dysf un cti on. Patie nts may also report

43、family history of COPD or other chronic respiratory ill ness.3. Physical examinationA. Early in disease, PE may be normal, or may show only prolonged expiration or wheezes on forced exhalation.B. As severity of airway obstruction increases, PE may reveahlyperinflation , decreased breath sounds , whe

44、ezes, crackles at lung bases, and/ordistant heart sounds. Features of severe disease includebarrel-shaped chest and depressed diaphragm with limited movement.C. Patients with end-stage COPD may adopt positions that relieve dyspnea, such as leaning forward with arms outstretched and weight supported

45、on palms or elbows. This posture may be evident during examination or may be suggested by presence of callouses or swollen bursae on extensor surfaces of forearms. Other PE findings include use of accessory respiratory muscles of neck and shoulder girdle, expiration through pursed lips, paradoxical

46、retraction of lower interspaces during inspiration (Hoover's sign), cyanosis, asterixis due to severe hypercapnia, and enlarged, tender liver due to right heart failure. Neck vein distention may also be observed because of increased intrathoracic pressure, especially during expiration.D. Yellow

47、nicotine stains on fingers are clue to ongoing and heavy cigarette smoking.E. Clubbing of digits is not typical in COPD (even with associated hypoxemia) and suggests comorbidities such as lung cancer, ILD, or bronchiectasis.EVALUATION1. Evaluation for COPD is appropriate in adults who report dyspnea

48、, chronic cough, chronic sputum production or have had gradual decline in level of peak activity, particularly if they have history of exposure to risk factors for disease (smoking, indoor biomass smoke). All patients are evaluated with spirometry and selected patients havelaboratory testing and ima

49、ging studies.2. LaboratoryA. No laboratory test is diagnostic for COPD, but certain tests are sometimes obtained to exclude other causes of dyspnea and comorbid diseases.i. Assessment for anemia is important step in evaluation of dyspnea. Measurementof BNPor NT-proBNP is useful as component of evalu

50、ation of suspected HF. Glucose, BUN, Cre, electrolytes , calcium, phosphorus, and TSHmay be appropriate depending on degree of clinical suspicion for alternate diagnosis.ii. Among stable COPD patients with normal kidney function,elevated serumbicarbonate may indirectly identify chronic hypercapnia.

51、In presence of chronic hypercapnia, serum bicarbonate is typically increased due to compensatory metabolic alkalosis. Abnormal results must be confirmed with ABG measurement.iii. Testi ng for ai an titryps in (AAT) deficie ncy should be obta ined in all symptomatic adults with persistent airflow obs

52、truction on spirometry. Especially suggestive subsets in clude prese nee of emphysema iryoung in dividual (age 45 years), emphysema in non smoker or mini mal smoker, emphysema characterized by predo minan tly basilar cha nges on CXR, or family history of emphysema. However, AAT deficiency may be pre

53、sent inpatient with otherwise“typical ” COPD. A serumlevel of AAT < 11 gol/L (57 mg/dL by n ephelometry) in comb in atio n with severe deficie nt geno type is diag no stic.3. Pul monary fun ctio n testsA. PFT, particularly spirometry, are corn erst one of diag no stic evaluatio n of patie nts wit

54、h suspected COPD. In addition, PFTs are used to determine severity of airflow limitation, assess resp onse to medicati ons, and follow disease progressi on.B. Spirometryi. Whe n evaluati ng patie nt for possible COPD, spirometry is performed pre and post bronchodilator administration (inhalation of

55、albuterol 400 pg) to determine whether airflow limitation is present and whether it is partially or fully reversible. Airflow limitation that is irreversible or only partially reversible with bronchodilator is suggestive of COPD rather tha n asthma.ii. The most importa nt values measured duri ng spi

56、rometry are FEW and FVC.The post-bro nchodilator ratio of FEVi/FVC determ ines whether airflow limitatio n is prese nt; post-bro nchodilator % predicted value for FEW determ ines severity of airflow limitation as shown in table.C. Lower limit of normal FEVi/FVCi. Traditionally, post-bronchodilator F

57、EVi/FVC ratio < 0.7has been considereddiag no stic of airflow limitati on. However, FEVi/FVC ratio decreases with age, so use of 5th percentile lower limit of normal (LLN) of the FEV i/FVC ratio, rather than absolute value of < 0.70, has bee n advocated as divid ing point for diag no sis of CO

58、PD. However, distinction between LLN and fixed ratio as dividing points is un likely to lead to major cli ni cal problems because curre nt recomme ndatio ns comb ine physiologic assessme nt with assessme nt of symptoms and exacerbati ons in stagi ng severity. Moreover, i n study of i3,847 subjects i

59、n whom in creased mortality was n oted amo ng those with FEVi/FVC < 0.70, but normal LLN FEVFVC whe n compared with those whose FEW/FVC was 0.70 or higher.D. Forced expiratory volume in 6 sec onds (FEV6)i.FEVs, obta ined by stopp ing expiratory effort after 6 sec onds rather tha n atcessati on of airflow, is acceptable surrogate for FVC. The adva ntages of FEVEVs in clude less frustrati on by patie nt and tech ni cia n tryi ng t