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COPD

- Chronic bronchitis, Emphysema & Airways obstruction

1. Á¤ÀÇ

¨ç emphysema : terminal bronchioleÀÌÇϺÎÀ§ airspaceÀÇ permanent & destructive

enlargement

¨è chronic bronchitis : 2³â°£ 3°³¿ù ÀÌ»óÀÇ productive cough

(´Ù¸¥ ¿øÀÎÀÌ ¹èÁ¦µÈ »óÅ¿¡¼­)

* chronic bronchitis´Â airway limitationÀÌ ¾øÀ»¼ö ÀÖÁö¸¸ COPD´Â Ç×»ó ÀÓ»óÀûÀ¸·Î ÀǹÌÀÖ´Â

airflow limitationÀ» ÀÏÀ¸Å²´Ù.

2. ¿ªÇÐ

M>F, Caucasians > African

low socioeconomic status, low birthweight¿¡¼­¡è

60-70´ë peak

3. º´ÀÎ

oxidant activity¡è, antioxidant activity¡é : oxidative stress => inflammatory process

i) cigarette smoking : oxygen free radical¡è(superoxide, hydrogen peroxide, hypochlorous

acid)

ferritin¿¡¼­ Fe2++ release

cigarette tar¿¡ NO ÇÔÀ¯ -> NO synthaseÀ¯¹ß

oxidant¿¡ ÀÇÇØ cytotoxic peroxynitrate·Î ´ë»ç

¥á1-AT inactivation

neutrophil transit time´ÜÃà, adhesion¡è, deformability¡é

ii) airway submucosa : CD8 lymphocyte & eosinophil, macrophage, mast cell¡è

smoker¿¡¼­ epithelium¿¡ neutrophilÀÌ Áõ°¡ÇØ ÀÖÁö¸¸ airway obstruction°ú´Â °ü°è°¡

¾ø´Ù.

iii) macrophage & mast cell : TGF-¥â»ý¼º(fibrogenesis¿Í °ü·ÃµÈ peptide)

TGF-¥â¿Í FEV1Àº negative correlationÀ» º¸ÀÓ.

4. À§ÇèÀÎÀÚ

COPD = FEV1¡é, FEV1 °¨¼Ò¼Óµµ¡è

1) Smoking : chronic bronchitis & emphysemaÁ¤µµ¿Í °¡Àå ÈçÈ÷ »ó°üÀÖ´Ù.

i) respiratory epithelial ciliary movement¼Õ»ó

ii) alveolar macrophage fx ¹æÇØ

iii) mucus-secreting glandÀÇ hypertrophy & hyperplasia

iv) emphysematous damage(°³¿¡¼­ massive exposure½Ã)

v) antiprotease¾ïÁ¦

vi) PMNL·Î ÇÏ¿©±Ý proteolytic enzymeÀ» ºÐºñÅä·Ï ÇÔ.

vii) submucosal irritant receptor¸¦ ÀÚ±ØÇÏ¿© vagally mediated smooth-muscle

constriction

Èí¿¬Áߴܽà ½ÉÇÑ Æó¼â°¡ ¿ÏÀüÈ÷ ȸº¹µÇÁø ¾ÊÀ¸³ª lung fuction°¨¼Ò¼Óµµ°¡ µÐÈ­µÈ´Ù.

2) Air pollution : SO2, NO2

3) Occupation : inorganic or organic dust or noxious gas exposure

4) infection

5. Genetic considerations

Èí¿¬ÀÚ Áß ´ÜÁö 15-20%¸¸ COPD°¡ ¹ßÇöµÈ´Ù. ÀÌ´Â ¾Æ¸¶µµ tabacco smoker¿¡ ´ëÇÑ genetic

susceptibility°¡ ÀÖÁö ¾ÊÀ»±î »ý°¢ÇÏ°Ô ÇÑ´Ù. ½ÖµÕÀÌ ¿¬±¸¿¡¼­ smoking½Ã FEV1ÀÌ ¹ÐÁ¢È÷

¼­·Î ¿¬°üÀÌ ÀÖ¾ú´Ù.

1) ¥á1-AT deficiency - autosomal dominant interitence

¨ç mc deficienty allele = PiZZ phenotype(Á¤»óÀÇ 16%, 2.5-7 umol)

single a.a substitution 342Glu -> Lys

oxidation & spontaneous polymerization¿¡ vulnerable, antiprotease deficiency

PiZZ : mc disease-related ¥á1-AT abnormality

µ¿¾çÀΰú ¾ÆÇÁ¸®Ä«Àο¡°Ô µå¹°´Ù.

¨è PiSS phenotype(Á¤»óÀÇ 52%, 15-33 umol)

¨é Pinull : no detectable antiprotease level

ÀÓ»óÀûÀ¸·Î ÀǹÌÀÖ´Â ¥á1-AT deficiency´Â PiZZ, Pinullnull or PinullZ¿Í °ü·Ã(11 umol/LÀÌÇÏ).

6. º´¸®

squamous metaplasia, ciliated cell atrophy, mucus gland hypertrophy,

remodeled epithelium -> cytokine»ý»ê -> inflammatory processÁõÆø

1) small airway - the major site of airflow limitation, lumen narrowing

CD8+ T lymphocyte & B lymphocyte(+)

subepithelial lamina reticularis thickening(asthmaÀÇ Æ¯Â¡)Àº ¾ø´Ù.

2) central airway : subepithelial inflammation

eosinophil & CD8+ T lymphocyte¡è

neutrophilÀº epithelium¿¡ Á¸ÀçÇÑ´Ù(subepithelial layer¿£ ¾ø´Ù).

3) Emphysema

¨ç centriacinar emphysema : ÁÖ·Î respiratory bronchiole¿¡ ±¹ÇÑ.

centrally destroyed : V/Q ratio¡è

peripheral destroyed : V/Q ration¡é, (A-a)DO2¡è

¨è panacinar emphysema

alveolar-capillary gas exchange surface°¨¼Ò

elastic recoil loss

7. º´Å»ý¸®

1) Airflow limitation Fig 258-1

2) Hyperinflation

RV, FRC, TLC¡è, dynamic hyperinflation, diaphragmatic flattening.

VC¡é

3) Impaired gas exchange

mismatchingÀÌ ½ÉÇϸé ABGAÀÌ»óÀ¸·Î ³ªÅ¸³².

alveolar capillary°¡ intactÇϸé V/Q ratio¡é, mild to moderate hypoxemia.

emphysema°¡ µÇ¸é alveolar wall destruction

-> alveolar capillary perfusion¡é, V/Q match´Â Àß À¯Áö.

shunt hypoxemia´Â unusual.

4) pulmonary circulation

chronic hypoxia with heavy cigarette smoking

-> pul. vascular constriction»Ó¸¸ ¾Æ´Ï¶ó 2ndary erythrocytosis°¡ À¯¹ßµÇ¾î

pul. vascular resistance±îÁö »ý±ä´Ù.

5) renal & hormonal dysfunction

chronic hypoxemia & hypercapnia

-> norepinephrine, renin, aldosterone¡è, ADH¡é

-> renal a.µµ pul a.¿Í À¯»çÇÑ ¼Õ»óÀ» º¸ÀÓ.

-> salt & water excretionÀå¾Ö, RV dysfunction

: phlethoric & cyanotic manifestation

6) cachexia

weight loss : advanced COPDȯÀÚ¿¡¼­.

ÃÖ±Ù hypoxemia°¡ TNF-¥á levelÀ» Áõ°¡½ÃŲ´Ù°í ¾Ë·ÁÁ³´Âµ¥ ÀÌ TNF-¥á level°ú

weight loss»çÀÌ¿£ Á÷Á¢ÀûÀÎ »ó°ü°ü°è°¡ ÀÖ´Ù.

7) peripheral m. dysfunction

protein, muscle loss°¡ ÀϾ.

8) osteoporosis

1/3 : 1SD¡é, 1/3 : 2SD¡é

vertebral fracture°¡ ÈçÇÏ´Ù.

chronic glucocorticoid therapy¸¦ ¹Þ´Â ȯÀÚ¿¡¼­ ´õ ½ÉÇÏ´Ù.

8. ÀÚ¿¬°æ°ú

FEV1´Â 25¼¼¶§ peak¸¦ ÀÌ·ç°í ±× ÀÌÈÄ·Î °¨¼ÒÇÑ´Ù.

°¨¼Ò¼Óµµ: Á¤»ó 35 ml/year COPD: 50-100 ml/year

acute exacerbationÀÌ °¨¼Ò¼Óµµ¸¦ º¯È­½ÃŰÁø ¾Ê´Â´Ù.

FEV1<40%ÀÏ ¶§ exertional dyspnea

FEV1<25%ÀÏ ¶§ resting dyspnea, CO2 retention, cor pulmonale°¡ ÈçÈ÷ ÀϾ.

1) exacerbation

hyperventilation & work of breathing¡è

diaphragmatic fx & neuromuscular drive°¡ PaCO2Áõ°¡¸¦ º¸»óÇÒ¼ö ÀÖÀ»¶© ±¦ÂúÁö¸¸

respiratory pump capacity¸¦ ³Ñ¾î¼­¸é hypercapnia & resp. acidemia°¡ ¹ß»ýÇÑ´Ù.

cardiac outputÀÌ ÃæºÐÈ÷ º¸»óµÇÁö ¾ÊÀ¸¸é V/Q mismatch & hypercapnia·Î ÀÎÇÑ

hypoxemia°¡ ¹ß»ýÇÑ´Ù.

´ëºÎºÐ COPD exacerbationÀº acute tracheobronchitis·Î ÀÎÇϸç infection ¶§¹®ÀÌ´Ù.

* most infection = primary bacterial infection

DDx> LV failure, cardiac arrhythmia, pneumothorax, pneumonia, pul. thromboembolism

upper airway obstruction, aspiration, rhinitis or sinusitis, asthma or GE reflux

9. ÀÓ»ó¹ßÇö

1) Hx & P/E

2) Radiographic findings

smokers - upper lobe¿¡ more prominent

¥á1-AT deficiency - basal zone

local radiolucencies > 1cm => bullaeÁ¸ÀçÀǹÌ. emphysema¿¡ ´ëÇØ highly specific.

CT : greater sensitivity & specificity for emphysema

±×·¯³ª bronchiectasis Áø´Ü ¹× bullous diseaseÁø´ÜÀ» Á¦¿ÜÇϰí´Â °ÅÀÇ ÇÊ¿äÄ¡ ¾Ê´Ù.

3) PFT

normal FEV1À̸é COPD¸¦ ¹èÁ¦ÇÒ¼ö ÀÖ´Ù.

spirogram : volume change¡é, 3-5ÃÊÈÄ¿¡ plateauµµ´Þ½ÇÆÐ.

continued airflow 10ÃÊ ÀÌ»ó Áö¼Ó(forced expiration½Ã)

serial spirometry°¡ FEV1 °¨¼Ò¼Óµµ¸¦ Æò°¡Çϴµ¥ Áß¿äÇÏ´Ù.

inhaled bronchodilator(°¡Àå ÈçÈ÷ short-acting ¥â2-agonist)Åõ¿©ÀüÈÄ reversibilityÆò°¡

°Ë»ç´Â ȯÀÚ°¡ ¾ÈÁ¤»óÅ¿¡¼­ ½ÃÇàÇØ¾ß ÇÑ´Ù.

°Ë»çÀü: short-acting bronchodilator - 6½Ã°£ ÁßÁö

long-acting bronchodilator - 12½Ã°£ ÁßÁö

theophylline - 24½Ã°£ ÁßÁö

* significant responseÀÇ Á¤ÀÇ : 12%(or 200mL) in FEV1 or FVC

bronchodilator´Â PFT½Ã acute response¿©ºÎ¿¡ °ü°è¾øÀÌ ¸ðµÎ Åõ¿©ÇÑ´Ù.

* ATS COPD staging(FEV1¿¡ ÀÇÇÑ)

mild(stage I) FEV1¡Ã50%

moderate(stage II) 35-49%

severe(stage III) <35%

lung volume: hyperinflationÆò°¡¿¡ À¯¿ë.

DLCO : emphysema¿Í negative correlation but not specific.

*¥á1-AT level check

: routineÀ¸·Î ½ÃÇàÇÏÁø ¾ÊÀ¸³ª ´ÙÀ½°ú °°Àº °æ¿ì¿£ ½ÃÇàÇÑ´Ù.

i) chronic airflow obstruction or chronic bronchitis in nonsmoker

ii) COPD pt with bronchiectasis, cirrhosis without apparent risk

iii) premature emphysema

iv) basilar emphysema

v) 50¼¼¡é with unremitting asthma

vi) ¥á1-AT family Hx(+)

10. Ä¡·á

1) smoking cessation

FEV1È£Àü»Ó¸¸ ¾Æ´Ï¶ó malignancy, cardiovascular ds°¨¼Ò·Î ÀÎÇØ »ýÁ¸·üÀÌ Çâ»óµÈ´Ù.

FEV1°¨¼Ò¼Óµµ°¡ nonsmoker ¼öÁØÀÌ µÈ´Ù.

2) Bronchodilator

airflowÈ£Àü, end-expiratory lung volume & air-trappingÀ» °³¼±½ÃÅ´À¸·Î½á dyspnea,

exercise tolerance°¡ È£ÀüµÈ´Ù.

*3 major classes of bronchodilators

¨ç short or long acting ¥â2-agonist

i) short-acting ¥â2-agonist = albuterol, pirbuterol, terbutaline, metaproterenol.

(albuterol=Volmax 4mg= Ventolin 1B= 100mg/20mL. Terbutaline=Bricanyl turbuhaler)

bronchoselective & minimal effects on HR & BP

5-15ºÐ¿¡ significant bronchodilation. 4-6½Ã°£µ¿¾È effective.

ii) long-acting ¥â2-agonist(oral sustained-release albuterol & inhaled salmeterol)

15-30ºÐ¿¡ ÃÖ´ëÈ¿°ú ³ªÅ¸³ª¼­ 12½Ã°£ Áö¼Ó

¨è anticholinergic agent(ipratropium bromide = Atrovent)

30-60ºÐ¿¡ ÃÖ´ëÈ¿°ú ³ªÅ¸³ª¼­ 4-6½Ã°£ Áö¼Ó

¨é Theophylline : orally 12-24½Ã°£

Tab 258-1

IpratropiumÀ» ±ÔÄ¢ÀûÀ¸·Î »ç¿ëÇÔÀ¸·Î½á baseline FEV1ÀÌ È£ÀüµÈ´Ù(short-acting

¥â2-agonist¿Í ºñ±³ÇÒ¶§).

µÎ°¡Áö ÇÔ²² »ç¿ë½Ã ´Üµ¶º¸´Ù greater clinical efficacy(S/E Áõ°¡¡¿)

Salmeterol : ½Ã°£ÀÌ Áö³ª¸é¼­ baseline FEV1È£Àü

theophylline : weak bronchodilator with narrow therapeutic window

±×·¯³ª ¸¹Àº ÀÓ»óÀû ÀÕÁ¡ÀÌ ÀÖ´Ù.

i) ventilatory drive¡è

ii) diaphragmatic contractility¡è

iii) C.O¡è

therapeutic range : 10-20 ug/mL

ÀÌ À̻󿡼± greater toxicity(+), old pt, heart & kidney diseaseÀÖÀ» ¶§ À§ÇèÀÌ Áõ°¡ÇÑ´Ù.

3) Glucocorticoid

asthmatic feature°¡ ¸¹À»¼ö·Ï ¹ÝÀÀ¡è

10%¿¡¼­¸¸ ÁÖ°üÀû È£ÀüÀ» º¸À̰í 20%±îÁö¸¸ FEV, FVC Áõ°¡¸¦ º¸ÀδÙ.

inhaled glucocorticoid : FEV1°¨¼Ò¼Óµµ¸¦ º¯È­½ÃŰÁö ¾Ê°í COPD exacerbationºóµµ¸¦

°¨¼Ò½ÃŰÁö ¾ÊÀ¸³ª severity¸¦ °¨¼Ò½ÃŲ´Ù.

sx & exercise tolerance¸¦ È£Àü½ÃŲ´Ù.

4) ¥á1-AT deficiency management

Èí¿¬ÀÌ ÀÌ º´ÀÇ pathogenesis¿¡ Áß½ÉÀû ¿ªÇÒÀ» ÇϹǷΠ±Ý¿¬ÀÌ Ä¡·áÀÇ ±âº»ÀÌ´Ù.

¿ÜºÎ¿¡¼­ ¥á1-ATÀ» Åõ¿©(60mg/kg ÁÖ 5ȸ)´Â ºñ¿ëÀÌ ºñ½Î°í, Åõ¿©¹æ¹ýÀÌ ºÒÆíÇϹǷÎ

18¼¼ ÀÌ»óÀÇ ¥á1-AT levelÀÌ 11 umol/LÀÌÇÏÀΠȯÀÚ¿¡¼­¸¸ »ç¿ëÇÑ´Ù.

augmentation tx·Î FEV1 °¨¼Ò¼Óµµ°¡ °¨¼ÒÇÑ´Ù.

5) oxygen : long-term O2 therapy

2ndary polycythemia¸¦ reverse

body weightÈ£Àü

cor pulmonale°³¼±

neuropsychiatric fx°³¼±, exercise tolerance°³¼±, living activity°³¼±

Optimum medical tx 30-90ÀÏÈÄ medical stabilityµ¿¾È resting ABGA¸¦ ÃøÁ¤ÇÏ¿© long-term

tx¿©ºÎ¸¦ °áÁ¤ÇÑ´Ù.

* ÀûÀÀÁõ

¨ç PaO2 ¡Â 55mmHg or SaO2 ¡Â88%

¨è PaO2 56-59 mmHg with SaO2 ¡Ã89%

with cor pulmonale or pul hypertension evidence(+)

¨é PaO2 ¡Ã 60 mmHg with SaO2 ¡Ã 90%

with exercise or sleep½Ã hypoxemia

¼ö¸é½Ã & normal working½Ã SaO2 ¡Ã90%À¯ÁöÇÑ´Ù.

ÃÖ¼Ò ÇÏ·ç 15½Ã°£ »ç¿ëÇϸé survival benefitÀÌ ÀÖ´Ù.

nasal cannula, 2-5 L/min

* Á¾·ù : compressed gas(tank), compressed liquid, CO2 concentrator

6) Prophylaxis

¸Å³â influenza vaccination

pneumococcal vaccination with 23-valent polysaccharide(Æò»ý 1¹ø)

Amantadine : inflenzaÀ¯Çà½Ã unvaccinated pt

7) Rehabilitation

8) Transplantation

FEV1 < 25% with pul hypertension or cor pulmonale

PaCO2=55mmHg & progressive deterioration

asthma, other reversible air flow limitationÀº Á¦¿Ü.

rehabilitation & long-term O2 therapy°¡ ÀûÀýÇØ¾ß ÇÑ´Ù.

9) Lung volume reduction surgery(LVRS)

stage III emphysema¿¡¼­ dyspnea, exercise fx°³¼±¸ñÀûÀ¸·Î ½ÃÇà.

tissue resection -> elastic recoilÈ£Àü, hyperinflation°¨¼Ò, diaphragmatic fx°³¼±.

airflow & exercise capacity 25-50%È£Àü

hospital mortality 5-18%, hospital stay 9-18ÀÏ with frequent significant air leak

* CIx : lung transplantation°ú µ¿ÀÏ

(active smoking, marked obesity or cachexia, pul. rehabilitationÀ» ¼º°øÀûÀ¸·Î

½ÃÇà¹ÞÀ»¼ö ¾ø´Â ȯÀÚ)

10) Exacerbation tx

¨ç home tx : anticholinergic + short-acting ¥â2 agonist

sputum¡è or breathlessness => antibioticsÃß°¡

mc : S. pneumonia, H. influenza, Moraxella catarrhalis

oral glucocorticoid : 20-40 mg ¡¿ 7-10 days

short-term(<3ÁÖ)ÀÏ ¶§ tapering Çʿ䡿

¨è hospital management

¥â2 agonist + anticholinergics q 4-6 hr

high dose ¥â2-agonist : hypokalemiaÀ¯¹ß

theophylline : 10-20 ug/mL

oral glucocorticoid : FEV1Áߵ È£Àü

ÃÖ±Ù COPD exacerbation½Ã enterobacteriaceae¹ß°ß

-> 2¼¼´ë ȤÀº 3¼¼´ë cephalosporin or fluoroquinolone, 2¼¼´ë macrolide,

extended-spectrum penicilliņ̵

pH<7.25 + PaO2 < 50 mmHg => ÁÖÀDZí°Ô °üÂû

hypercapnia risk°¡ ³ôÀ» ¶§ O2´Â ventri mask·Î Åõ¿©Åä·Ï ÇÑ´Ù(FiO2 0.24-0.28)

* mechanical ventilation

: respiratory distress, impaired consciousness, RR>35ȸ/min, abd. paradox,

severe hypoxemia, pH<7.25

=> noninvasive(mask) or invasive(intubation)

Intubation½Ã SaO2¡Ã 90%, PaO2 60-65%

FiO2 0.24-0.4, pH>7.25À¯Áö

PaCO2¸¦ Á¤»óÈ­½ÃÄѼ± ¾ÈµÈ´Ù.

intrinsic PEEPÀÌ »ý±âÁö ¾Êµµ·Ï Á¶½ÉÇÑ´Ù.

: expiratory timeÀ» ÃæºÐÈ÷ ÁÖ°í °¡´ÉÇÑ complete emptyingµÇ°Ô TV & RR´Â ÃÖ¼ÒÈ­ÇÑ´Ù.