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°¡ µÐȵȴÙ.
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¤»óȽÃÄѼ± 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.