CHULA JOURNAL OF INTERNAL MEDICINE VOLUME 21 NO.3 JUL.-SEP ISSN

❹ ISSN 0857-5630 2 CHULA JOURNAL OF INTERNAL MEDICINE VOLUME 21 NO.3 JUL.-SEP. 2008 ❹ ❶ ❶ 6 ❹ ❹ ❹ 10 ❹ ❹ ❹ ❹ ⓿ ⓿ ❹ ❹ ❹

❹ ❶ 6 10 ❹ ❹ ❹ ❹ ❶ ❹ ❹ ❹ ❹ ❹ ❹ 2 ⓿ ❶ ⓿ ⓿ ❶ ❹ 1 ❹ ❹ ❹ ❹ ❹ ❹ ⓿ ❹ ❹ ❽ ❹❾ ❹ ❹ ❹ ❶ ❹ ⓿ ❹ ❹ ❹ ❹ ❹ ❹ ⓿ ❹ ❹ ❶ ❹ ❶

⓿ ❹ ❹ ❹ ⓿ ❶ ❹ ⓿ ❹ ❶ ❶ ⓿ ⓿ ❶ ❹ ❶ ❹ ❹ ❹ ❹ ❶ ❹ ❶ 3 ⓿ ❶ ❶ ⓿ ❶ 3 ❶ ❹ ⓿ ❹ ❶ ❹ ❶ ❶ ⓿ ❶ ⓿ 4 ❶ ⓿ ⓿ ⓿ ⓿ ❹ ❹ ❹ ⓿ ❹ ❶ ❹ ❹ ❹ ❹ ❹ ❶ ❹ ⓿ ❹ ❶ ❹ ❹ ❹ ❹ ⓿ ❹ ❹ ⓿ ❹ ⓿ ❶ &

❹ 2 ⓿ ❶ ❶ ⓿ ❶ ❶ 6 ❹ & ⓿ ❶ ❶ ❹ ❶ ❶ ❶ 6 ❹ ⓿ ❶ ❹ ❶ ⓿

❹ 2 ❶ ❹ ❶ ❶ 6 ❹ ❹ ❹ 10 ❹ ❹ ❹ ❹ ⓿ ⓿ ❹ ❹ ❹ ❹ ❶

⓿ ❹ ❶ ⓿ ❹ ⓿ ❶ ⓿ ❹ ❹ ❹ ❹ ⓿ ❹ ❶ ⓿ ⓿ ❹ ⓿ ❹ ❹ ❹ ❹ ⓿ ❹ ❶ ❶ ⓿ ❶ ⓿ ❹ ⓿ ⓿ ⓿ ⓿ ❶ ⓿ ⓿ ❶ ❶ β ⓿

❶ ⓿ ⓿ ❶ ❶ 6 ❹ ⓿ ⓿ ⓿ ⓿ ❶ ❶ ❶ ❶ & ❶ ❶ 6 ❶ ❶ ❶ ⓿ ⓿ ⓿ ❶ ⓿ ❶ ⓿ ❶ ❶ ❼ ❶ ❶ 6 & & ⓿ ⓿ ⓿ ⓿ & ⓿ ❶

❶ ⓿ ❶ ❶ ⓿ ⓿ ⓿ ⓿ ⓿ ❶ ⓿ ❶ ❶ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ❹ 2 ❶ ❶ ⓿

2 2 ❽ ❾ ❶ ❶ ❶ ❶ 6 ❹ ❶ ⓿ ❶ ⓿ ⓿ ❶ ⓿ ⓿ ❶ ⓿ ❹ ⓿ ❶ ⓿ ❹ ❹ ❹ ❶ ❹ ❶ ❹ ❹ ❹ ❹ ❹ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ❹ ⓿ ⓿ ⓿ ❹ ⓿ ⓿ ❹ ⓿ ❹ ❹ ❹ ❹ ❶ ⓿ ❶ ⓿

2 2 ❽ ❾ ❹ ❹ ❹ ❹ ❶ 6 ❹ ⓿ ❹ ❹ ❹ ❹ ❹ ❹ ⓿ ⓿ ❶ ⓿ ❹ ⓿ ⓿ ⓿ ⓿ ⓿ ❹ ⓿ ⓿ ⓿ ❹ ⓿ ⓿ ❹ ⓿ ❹ ❹ ❹ ❹ ❶ ⓿ ❶ ⓿

2 2 ❽ ❾ & & ❶ ❹ ❹ ❹ ❹ ❹ ❹ ❹ ❹ ⓿ ❹ ❹ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ❹ ⓿ ⓿ ❹ ⓿ ❹ ❹ ❹ ❹ ❶ ⓿ ❶ ⓿

2 2 ❽ ❶ 6 ❾ ❹ ❹ 2 ❹ ❶ 6 ❹ ❹ ❶ 6 ❹ ❶ 6 ❹ ❹ ❹ ❹ ❶ 6 ❶ 6 ❹ ❹ ❹ ❶ 6 ❹ ❶ 6 ❶ 6 ❹ ⓿ ⓿ ⓿ ⓿ ⓿ ❹ ⓿ ⓿ ⓿ ❹ ⓿ ⓿ ❹ ⓿ ❹ ❹ ❹ ❹ ❶ ⓿ ❶ ⓿

2 2 ❽ ❾ ⓿ ❹ ❹ ❹ ❹ ❹ ❹ ❹ ❹ ❹ ❹ ❹ 1 ❹ ❹ ❹ ❹ ❹ ❹ & ❹ ❹ & ❹ & ⓿ ⓿ ⓿ ⓿ ⓿ ❹ ⓿ ⓿ ⓿ ❹ ⓿ ⓿ ❹ ⓿ ❹ ❹ ❹ ❹ ❶ ⓿ ❶ ⓿

2 2 ❽ ❾ ❹ ❹ ❹ ❹ ❹ ❹ ❹ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ❹ ⓿ ⓿ ⓿ ❹ ⓿ ⓿ ❹ ⓿ ❹ ❹ ❹ ❹ ❶ ⓿ ❶ ⓿

2 2 ❽ ❾ ❹ & ❹ ⓿ ❹ ❹ ❹ ❹ 1 ❹ & ❹ ❹ ❹ ⓿ ❹ ❹ ❹ ❹ ❹ ❹ ❹ & ❹ ⓿ ⓿ ⓿ ⓿ ⓿ ❹ ⓿ ⓿ ⓿ ❹ ⓿ ⓿ ❹ ⓿ ❹ ❹ ❹ ❹ ❶ ⓿ ❶ ⓿

2 2 ❽ ❾ & ⓿ ❹ ❹ ❹ ❹ 1 ❹ ❹ ❹ ❹ 1 ❹ ❹ ⓿ ❹ ⓿ ⓿ ⓿ ⓿ ⓿ ❹ ⓿ ⓿ ⓿ ❹ ⓿ ⓿ ❹ ⓿ ❹ ❹ ❹ ❹ ❶ ⓿ ❶ ⓿

❹ ❹ ⓿ ❹ ⓿ ❹ ⓿ ❹ ❹ ⓿ ❹ ⓿ ❹ ❹ ⓿ ❹ ❹ ⓿ ⓿ ❹ ❹ ⓿ ❹ ⓿ ❹ ⓿ ❹ ⓿ ❹ ⓿ ❹ ❹ ⓿ ❹ ❹ ⓿ ⓿ ⓿ ⓿ ❹ ⓿ ⓿ ⓿ ❹ ⓿ ⓿ ❹ ⓿ ❹ ❹ ❹ ❹ ❶ ⓿ ❶ ⓿

❹ ❹ ❹ ⓿ ❹ ❶ ❹ ❶ ❶ ⓿ ❹ ❶ ❹ ⓿ ❶ ❶ ⓿ ❹ ⓿ ❹ ❹ ❹ ❹ ❹ ⓿ ❹ ❶ ❹ ❹ ⓿ ❹ ❹ ❹ ❶ ❶ ❹ ❶ ⓿ 2 ❶ ❶ ⓿ ❹ ⓿ ⓿ ❹ ⓿

❶ 2 ❹ ❹ ❶ ❶ ❶ ❹ ❹

* ❹ ❹ ❶ ❹ ❹ ❹ ❹ ❹ ❹ ❹ ❶ ⓿ ❶ ❹ ❶ 6 ❶ ❶ ❶ 6 ❶ ⓿ ❶ ❶ ❶ ⓿ ⓿ ⓿ 2 ⓿ ❶ ⓿ ❶ ❶ 6 ❹ ❶ ⓿ ⓿ ❶ ❶ ❹ ❶ ⓿ ❶ ❹ ❶ ⓿ ❶ ❶ ⓿ ⓿ β ❶ ⓿ ❹ ❶ ❶ ❶ ⓿ ⓿ ❶ ❶ ❶

2 ⓿ ⓿ ❶ ❶ ⓿ ❶ ⓿ ⓿ ⓿ ⓿ ⓿ ❶ ❶ ⓿ ⓿ ❶ ⓿ 2 ⓿ ❶ 6 ❶ ❶ ❶ ❶ 7 ❶ 6 ⓿ ⓿ ⓿ ❶ 6 ❶ 2 ❶ 6 ❶ ❶ ⓿ ❶ ❶ ❶ ❶ ❶ 6 ❶ ❶ ⓿ ❶ ❶ 6 ⓿ ❶ 2 ❶ ⓿ ❶ ❶ 6 ⓿ ⓿ ❶ 6 ❶ ⓿ 2 2 6 ❶ ❶ ❶ ⓿ ⓿ ⓿ ❶ ❶ ❶ ❶ ⓿ ❶ 6 ⓿ ⓿ ❶ ⓿ ❶ ❶ ⓿ ❹ ❹ ❶ ❶ ⓿ ❹ ⓿ ❶ ⓿ ❶ ❶ ❶ ❶ ⓿ ❶ 6 ❶ ❶ ❶ ⓿ ❶ ❶ ❹ ❶ 6

❹ ❶ ⓿ ❹ ❹ ❶ ❶ ❶ & ⓿ ❶ ⓿ ❹ ⓿ & ❶ ⓿ ❶ ⓿ ⓿ ❶ ❶ ❶ ❶ ❶ ❶ ⓿ ⓿ ❹ ⓿ ⓿ ⓿ ❶ 6 ❹ ⓿ ⓿ ❶ ❶ ⓿ ⓿ ❹ ⓿ ❹ ❹ ⓿ Clinical history Co-morbid conditions History of frequent exacerbations Severity of COPD Physical findings Hemodynamic evaluation Use accessory respiratory muscles, tachypnea Persistent symptoms after initial therapy Diagnostic procedures Oxygen saturation Arterial blood gases Chest radiography Blood tests Serum drug concentrations Sputum gram stain and culture Electrocardiography Level I + + Mild/moderate Stable Not present No Yes No No No If applicable No No L + + M + + Y Y Y Y I Y Y ⓿

2 ❶ ❶ ❶ 6 ❶ ⓿ ⓿ ❶ ⓿ ❶ ❶ ❶ ❶ ⓿ ❹ ❶ ❶ ⓿ ⓿ ⓿ ❶ ⓿ ❶ 6 ❶ ❶ ⓿ ❶ ⓿ ❶ ❶ ❶ 6 ⓿ ❶ ❶ ❶ 6 ⓿ ⓿ ⓿ ❶ ❶ 6 ❶ ❶ ❶ ❶ ❶ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ❶ ❶ ⓿ ❶ 6 ❶ ❶ ❶ ❶ 6 ❶ 6 ⓿ ❶ ⓿ 2 ❶ ⓿ ❶

❹ ❶ ⓿ ⓿ ❶ ❶ ⓿ & ⓿ ⓿ ❶ ❶ 6 & ⓿ ❶ ⓿ ⓿ ⓿ ⓿ ⓿ ❶ ⓿ ⓿ ❶ ❶ 6 ❶ ⓿ ❶ ❶ 6 ❶ ⓿ Patient education Check inhalation technique Consider use of spacer devices ⓿ ⓿ ⓿ ⓿ ⓿ ❶ ⓿ ❶ ❶ ⓿ ⓿ ⓿ ⓿ ❶ 6 ❶ ❶ ⓿ ❶ ❶ Bronchodilators Short-acting β 2 -agonist and/or ipratropium MDI with spacer or hand-held nebulizer as nee Consider adding long-acting bronchodilator if patient is not using it Corticosteroids (the actual dose may vary) Prednisone 30 40 mg per os q day for 10 days Consider using an inhaled corticosteroid Antibiotics May be initiated in patients with altered sputum characteristics Choice should be based on local bacteria resistance patterns Amoxicillin/ampicillin, cephalosporins Doxycycline Macrolides If the patient has failed prior antibiotic therapy consider: Amoxicillin/clavulanate Respiratory fluoroquinolones ❶ 6

2 Bronchodilators Short acting β 2- agonist (albuterol, salbutamol) and/or Ipratropium MDI with spacer or hand-held nebuliser as needed Supplemental oxygen (if saturation <90% ) Corticosteroids If patient tolerates, prednisone 30 40 mg per os q day for 10 days If patient can not tolerate oral intake, equivalent dose i.v. for up to 14 days Consider use inhaled corticosteroids by MDI or hand-held nebuliser Antibiotics (based on local bacteria resistance patterns) May be initiated in patients that have a change in their sputum characteristics (purulence and/or Choice should be based on local bacteria resistance patterns Amoxicillin/clavulanate Respiratory fluoroquinolones (gatifloxacin, levofloxacin, moxifloxacin) If Pseudomonas spp. and/or other Enterobacterecae spp. are suspected, consider combination th ❶ 6 Supplemental oxygen Ventilatory support Bronchodilators Short-acting β 2- agonist (albuterol, salbutamol) and ipratropium MDI with spacer, two puffs eve If the patient is on the ventilator, consider MDI administration, consider long-acting β-agonist Corticosteroids If patient tolerates oral medications, prednisone 30 40 mg per os q day for 10 days If patient can not tolerate, give the equivalent dose i.v. for up 14 days Consider use inhaled corticosteroids by MDI or hand-held nebuliser Antibiotics (based on local bacteria resistance patterns) Choice should be based on local bacteria resistance patterns Amoxicillin/clavulanate Respiratory fluoroquinolones (gatifloxacin, levofloxacin, moxifloxacin) If Pseudomonas spp. and or other Enterobacterecae spp. are suspected consider combination the ❶ 6

❹ ⓿ ❶ ❶ 6 ⓿ ❶ ❶ 6 ❶ ❶ ❶ ❶ 6 ⓿ ⓿ ❶ 6 ❶ ❶ ❶ ❶ ❶ ⓿ ❶ ⓿ ❶ ❶ ⓿ ❶ ❶ ❶ ❶ ⓿ ❶ ⓿ ⓿ ⓿ ❶ ⓿ ❶ ⓿ ❶ ⓿ ❶ ⓿ ❶ ❶ ❹ ❶ ❶ ⓿ ❶ ❶ ⓿ & ❶ ⓿ ❶ ⓿ ⓿ ❶ 6 ❶ ⓿ ❶ ⓿ ⓿ ❶ 6 ❶ ❶ ❶ ❶ ⓿ ❶ ❶ ❶ ⓿ ❶ ⓿ ❶ ❶ ❶ ⓿ ⓿ ❶ ⓿ ❶ ⓿ ⓿ ⓿ ⓿ ⓿ ❶ ❶ ❹ ❶ ❶ ❶ ❶ ⓿ ⓿ ❶ ❶ ⓿ β ❶ ⓿ ⓿ ❶ ❶ ⓿ ❶ β ❶ ⓿ ⓿ ❶ ❶ ❹ ⓿ ❶ β ⓿ ❶ β ❶ 6 ⓿ ⓿ ❶ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ❶ ⓿ & ❶ ⓿ ⓿ ⓿ ⓿ ⓿ ❶ ❶ ⓿ ❶ ⓿ ⓿ ❶ ❶ ❶ ❶ ⓿ ⓿ ❶ ⓿ ❶ ⓿ ❶ ⓿ ⓿ ❶ 6

2 ❶ β ⓿ ❶ ❶ β ⓿ & ❶ ⓿ ❶ ❶ ❶ β ❶ ❶ β ⓿ ⓿ ❶ ❶ ❶ ❶ ⓿ ⓿ ❶ ❶ ⓿ ⓿ ❹ ⓿ ⓿ ⓿ ❶ ❶ ❶ ❶ ⓿ ⓿ ❶ ❶ ⓿ ❶ ⓿ ❶ ❹

❹ ❶ ⓿ ⓿ ❶ ❶ 6 ❶ ⓿ ⓿ ❶ ⓿ ⓿ ⓿ ❶ ⓿ ❶ ⓿ ⓿ ❶ ❶ ⓿ ❶ ⓿ ❶ ⓿ ⓿ ❹ ❶ 6 ⓿ ❶ ❶

2 ❶ ❶ ❶ ❶ ❶

❹ ❶ ❶ ⓿ ❶ ⓿ ⓿ ❶ ⓿ ❹ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ❶ ⓿ ❶ ⓿ ❶ ❶ ❶ ⓿ ❶ ⓿ ⓿ ❶ ⓿ ⓿ ⓿ ❶ ❶ ⓿ ❶ ❶ ⓿ ❶ ❶ ❶ ⓿ ⓿ ⓿ ❶ ❶

2 Study 1 Setting n (n males) Corticosteroids Aaron Outpatient 147 (84) Oral prednisone 40 mg x 2003 Albert 1980 Bullard 1996 Davies 1999 Emerman 1989 Maltais 2002 Niewoehner 1999 Rostom 1994 Thompson 1996 Wood- Baker 1997 Inpatient 45 ( 45) IV methylpred.0.5 mg/kg ED-Inpatient 76% 113 (97) IV hydrocortisone x 96 h Inpatient 50 (34) Oral prednisone 30 mg x ED-Inpatient 63% 96 (50) IV 100 mg methylpred n Inpatient 128 (105) Oral prednisone 40 mg x Inpatient 268 (265) IV methylpred nisolone 7 over 57 days or IN methy Inpatient 30 (NK) IV methylpred nisolone 7 Outpatient 27 (26) Oral prednisone 60 mg ta Inpatient 47 (30) Oral prednisone high dos 0.6-0.3 mg/kg x 14 day ❶ ⓿ 2 ❶ ⓿

❹ ❶ ⓿ ⓿ ⓿ ⓿ ⓿ ❶ ❶ ❶ ❶ ❶ 6 ❶ ⓿ ❶ ❶ ⓿ ⓿ ❶ ❶ ⓿ ❶ ⓿ ❶ ❶ ⓿ ❶ ❶ ⓿ ❶ ⓿ ⓿ ❶ ⓿ ⓿ ⓿ ⓿ ❶ ❶ ❶ ❹ ❶ 6 & ⓿ ❶ ❶ ⓿ ❶ & ❶ ⓿ ❶ ❶ ⓿ ❶ &

2 ⓿ ❶ ❶ ⓿ ❶ & ❶ ❶ ❶ ❶ ❶ ⓿ ❶ ❶ ❶ ⓿ ❶ ❶ ❶ ❶ ⓿ ⓿ ❶ ⓿ ⓿ ❶ ⓿ ❶ ❶ ⓿ ❶ ❶ ❶ ⓿ ❶ ⓿ ⓿ ❶ ❶ ❶ ⓿ ⓿ ⓿ ⓿ ❶ ❶ ❶ ❶ ❶ ❶ ❶ ❶ ⓿ ⓿ ⓿ ❶ ❶ 6 ❶ ❶ ❶ ❶ ❶ ❶ ⓿ ❶ ❶ ❶ 6 ❶ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ❹ ⓿ ❶ ⓿ & ⓿ & ⓿ ❶ 6 ❶ ❶ ❶ 6 ❶ ❶ ❶ ⓿ ❶ 6 ❶ ⓿ ❶ ⓿ ⓿ ⓿

❹ ❶ ❶ ❶ ❶ ❶ ⓿ ⓿ ❶ ❶ ⓿ ⓿ ❶ ❶ 6 ⓿ ❶ ❶ ❶ ⓿ ❶ ❶ ⓿ ❶ ❶ ⓿ ⓿ ❶ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ❶ ❶ ⓿ ⓿ ❶ ❶ ❶ ⓿ ⓿ ⓿ ❶ 6 ❶ ❶ 6 ⓿ ❶ ❶ 6 ❶ ❶ 6 ❶ ❶ 6 ❶ ❶ ❶ ❶ 7 ⓿ ❶ ⓿ ⓿ ⓿ ⓿ ❶ ⓿ ❶ ⓿ ❶ ❶ 6 ❶ ⓿ ⓿ ❶

2 ❶ 6 ❶ ⓿ ⓿ ❶ ❶ 6 ❶ ⓿ ⓿ ❶

❹ ❶ 6 ❶ ⓿ ⓿ ❶ ❶ ❶ 6 ❶ ⓿ ⓿ ❶

2 ❶ 6 ❶ ⓿ ⓿ ❶ ❶ 6 ❶ ⓿ ⓿ ❶

❹ ❶ ❶ ⓿ 2 ❶ ❶ ❶ ❶ ⓿ ❶ ⓿ ❶ ❹ ❹ ❶ 6 ❶ ⓿ ⓿ ❶ ⓿ ❶ 6 ❶ ❶ ⓿ ⓿ ❶ ⓿ ❶ ⓿ ⓿ ⓿ ❶ ⓿ ❶ ❶ ⓿ ❶ ❶ ❶ & & ❶ ⓿ ⓿ ❶ ❶ ❶ ⓿ ⓿ ❶ ⓿ ⓿ ❶ ❶ 6 ⓿ ⓿ ❶ ❶ ❶ ❶ ❶ ⓿ ❶ ⓿ ❶ ⓿ ❶ ❶ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ❶ ⓿ ❶ ❶ ⓿ ❶ ⓿ ❶ ❶ ⓿ ⓿ β ❶ ⓿ ❹ ❶ ❶ ❶ ⓿ ⓿ ❶ ❶ ❶ ❶ ❶ ❶ ❶ ⓿ ❶ ❶ ❶ ❶ β ❶ ⓿ ⓿ ❶ ⓿ ❶ ⓿ ⓿ ⓿ ❶ ❶ ❶ ❹ ⓿ ❶ ⓿ ⓿ ❶ ⓿ ❶ ❶ ❶ ❶ ❶ ❹

2 ❶ ❶ ❶ ❶ ⓿ ❶ ⓿ ⓿ ⓿ ❶ ❶ ❶ 6 ❶ ❶ ⓿ ⓿ ⓿ ❶ ❶ ❶ ❶ ⓿ ⓿ ❶ ⓿ ❶ ❶ ❶ & & & & & & &

❹ & & & & & & & & & &

2 & & & & & & & & & & &

❹ & & & &

2 & & & & & & &

❶ ❶ 6 ❹ * ❹ ❹ 10 ❹ ❶ ❹ ❹ ❹ ❹ ❹ ❹ ⓿ ❶ 6 ⓿ ❶ ❶ 6 ⓿ 2 ⓿ ⓿ ❶ 6 ⓿ ❶ ⓿ ⓿ ❶ 6 ❶ ⓿ ⓿ ❶ ⓿ ❶ ❶ ❹ ❶ ⓿ ❹ ⓿ ❶ 6 ❶ ⓿ ⓿ ⓿ ❶ ❶ ❶ ⓿ ⓿ ❶ ⓿ ❶ ⓿ ❶ 6 ❶ 6 ⓿ ❶ ❶ 6 ⓿ ⓿ ❶ ❶ ❶ 6 ❶ 6 ❶ ❶ 6 ❶ ❶ 6 ❶ 6 ⓿ ❶ ❶

2 2 ⓿ ❶ 6 ⓿ ⓿ 2 ± ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ❶ ⓿ ⓿ ⓿ ❶ ⓿ 2 ⓿ ❶ ⓿ ⓿ ⓿ 2 ⓿ ❶ ⓿ ⓿ ⓿ ⓿ 2 ⓿ ⓿ ⓿ ⓿ ❶ ⓿ ❶ ⓿ ⓿ ⓿ ❶ ⓿ ❶ ⓿ ⓿ ⓿ ❶ ⓿ ⓿ ⓿ ⓿ ❶ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ❶ ⓿ ❶ ❶ ⓿ ❶ & ❶ & ❶ ❶ ⓿ ⓿ ⓿ ❶ ⓿ ⓿ ⓿ ⓿ ❶ ⓿ ⓿ ⓿ ⓿ ❶ ⓿ ❶ ⓿ ⓿ ⓿ ❶ ❶ ⓿ ⓿ ⓿ ❶ ❶ ❹ ❶ ❶ ❶ 6 ⓿ ❶ ⓿ ❶ ❶ 7 ❶ ⓿ 7 ⓿ ⓿ ❶ ❶ 6 ⓿ ⓿ ❶ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ❹ ⓿ ⓿ ❶ ❶ ❶ 6 & ⓿ 2 ❶ ⓿ ❶ 6 ❶ ⓿ 2 ❶ ⓿ ⓿ ⓿ ⓿ ⓿ ❶ ❶ ❶ 6 ❶ ⓿ ❶ ⓿ ❹

❶ ❹ Gender Variable Number (%) Male Female 32(64) 18(36) Age (year ± SD) 65.6 + 11.2 Mean follow up time (month ± SD) 28.4 + 16.5 GFR/year (mean ± SD) -8.6 + 16.2 Initial GFR [mean ± SD ( ml/min)] 39.7 + 12.5 Body Weight (kg ± SD) 67.4 + 13.5 Blood Pressure Systolic (mmhg ± SD) Diastolic (mmhg ± SD) MAP (mmhg ± SD) Pulse pressure (mmhg ± SD) Co-morbidity DM HT Dyslipidemia CAD CVA Gout Medication ASA CCB Beta-blocker Erythropoietin Statins ACEI 135.3 + 16.8 77.8 + 7.1 96.9 + 8.4 57.5 + 16.1 30(60) 50(100) 41(84) 9(18) 4(8) 13(26) 25(50) 37(74) 35(70) 4(8) 36(72) 33(66) Lab Mean Hct [mean ± SD (%)] 35.7 + 5.7 ❶ ❶ 6 ❹ ❶ 6 ❹ ❹ ❶ ❶ ❹ ⓿ ⓿ ⓿ ❶ 6 ⓿ 2 &

2 GFR/year Group 1 Grou N 23 10 Age ± SD (year) 68.2 ± 10.9 63.6 ± Initial GFR mean ± SD (ml/min) 34.6 ± 11.8 38.6 ± Body Male [mean ± SD (Kg)] 68.0 ± 11.2 70.8 ± weight Female [mean ± SD (Kg)] 55.0 ± 6.6 70.1 ± SBP [mean ± SD (mmhg)] 134.1 ± 12.8 135.0 ± DBP [mean ± SD (mmhg)] 78.7 ± 6.2 80.0 ± MAP [mean ± SD (mmhg)] 97.1 ± 6.8 98.3 ± Pulse pressure [mean ± SD (mmhg)] 55.4 ± 12.5 55.0 ± 24-hr urine protein [mean ± SD (g)] 1.2 ± 2.1 1.3 ± HCO 3 [mean ± SD (mmol/dl)] 24.1 ± 3.4 23.0 ± Ca x PO 4 (mean ± SD) 33.0 ± 7.1 30.1 ± Albumin level [mean ± SD (gm/dl)] 4.0 ± 0.5 4.0 ± Uric acid level [mean ± SD (mg/dl)] 7.3 ± 1.2 8.1 ± Hct level [mean ± SD (%)] 36.3 ± 6.0 34.4 ± LDL level [mean ± SD (mg/dl)] 99.1 ± 29.5 103.8 ± HDL level [mean ± SD (mg/dl)] 50.5 ± 17.6 47.0 ± Triglyceride level [mean ± SD (mg/dl)] 168.9 ± 160.2 171.9 ± 737 14 82 ⓿ ⓿ ⓿ ⓿ ⓿ 2 2 ⓿ 2 2 ⓿ 2

❶ ❹ ⓿ ⓿ ❶ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ❶ ⓿ Yes DM -11.5 ± 17.5 ACEI -10.6 ± 17.7 Statins -11.2 ± 17.5 Betablocker -9.9 ± 15.1 Calcium channel blocker -10.5 ± 15.1 Erythropoietin -15.8 ± 11.3 Aspirin Low dose (<325 mg) -6.7 ±13.6 High dose (>325 mg) -12.9 ± 22.0 GFR ⓿ ⓿ ⓿ ⓿ ⓿

2 & & ⓿ & ⓿ ❶ 6 ⓿ ❶ 6 ⓿ ⓿ ❶ 6 ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ❹ ⓿ ⓿ ⓿ ⓿ 2 ⓿ ❶ 6 ⓿ ⓿ ❹ ⓿ ❹ ❶ ❶ ⓿ & ❶ 6 ⓿ ⓿ ❹ ⓿ ⓿ ❶ ⓿ ⓿ ⓿ ❶ ⓿ ❶ ⓿

❶ ❹ ⓿ β ⓿ ⓿ ❶ 6 ⓿ ⓿ ⓿ ❶ ⓿ ⓿ ❶ ⓿ 7 ❶ ❶ ⓿ ❹ ⓿ ❶ 6 2 ❶ 6 2 ⓿ ⓿ ❶ 6 ❶ ⓿ ⓿ ⓿ ⓿ ❶ ⓿ ⓿ ❶ 6 ⓿ ⓿ ❶ ❶ ⓿ ⓿ ⓿ ❶ ❹ ❶ ⓿ ❹ ⓿ ⓿ ⓿ ❶ 6 & ❶ ❶ ⓿ ❶ 6 ⓿ ❹ ⓿ ❶ ❶ 6 ❶ ⓿ ❹ ❶ 6 ❶ 6 ⓿ ❶ ⓿ ❹ ⓿ ⓿ ❶ 6 ⓿ ⓿ ⓿ ❶ 6 ⓿ ❶ ⓿ ❹ ⓿ ❶ 6 ⓿ ❶ ⓿

2 ❹ ⓿ ❶ ❶ ⓿ & ⓿ ⓿ ❶ 6 ⓿ ❶ ❶ ⓿ ⓿ ❹ ❶ ⓿ ❹ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ❶ ⓿ ⓿ ⓿ ❶ ⓿ ❶ ⓿ ⓿ ❶ & ⓿ ❶ ⓿ ⓿ ❶ ❶ 6 ❶ 6 ❹ ⓿ ❶ ❶ 6 ❶ ⓿ & ❹ ❶ ❶ ⓿ ❶ 6 ❶ ⓿ & ⓿ ⓿ ❹ ⓿ ⓿ ❶ 6 ❶ ⓿ ❶ ⓿ ⓿ & ❶ 6 ⓿ ❶ ⓿ 2 ⓿ 2 ❶ ❶ 6 ⓿ ⓿ ❶ ⓿ ❶ ❹ ❶ ⓿ ❶ 6 ⓿ ❶ 6 ❶ ⓿ ❶ 6 ⓿

❶ ❹ ❹ ⓿ ❶ 6 ⓿ ⓿ ⓿ 2 2 ❶ ❶ 6 ❶ ⓿ ⓿ ❶ ❶ ⓿ ❶ ❶ ⓿ ⓿ & ❶ ❶ ⓿ & ❹ ❶ ❶ ❶ ❹ ⓿ ⓿ ⓿ ❶ ❶ ⓿ ⓿ ❶ ⓿ ⓿ ⓿ ❶ ⓿ ❹ ⓿ ⓿

2 ⓿ ❶ ⓿ ⓿ ⓿ ⓿ ⓿ ❶ ⓿ ⓿ ❶ ❶ ⓿ ⓿ ⓿ ❶ ⓿ ⓿ ⓿ ❶ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ❶ ❶ ❶ ⓿ & ⓿ ❶ ❶ ⓿ ❶ ❶ ⓿ ⓿ ⓿ ❶ ⓿ ❶ ⓿ ❶ ⓿ ⓿ ❶ ⓿ ⓿ ❶ ⓿ ⓿ ⓿ ❶ ⓿ ❶ 6 ❶ ⓿ ❶ ⓿ ⓿ ❶ ⓿ ⓿ ❶ ❶ ❶ ❶ ❶ & & & & & & & & & & & & & & & & &

❶ ❹ & & & & & & & & & & & & & & & & & & & & & & & & & &

2 & & & & & & & & & & & & & & & & & & & & & & & & &

❶ ❹ & & & & & & & & & & & & & & & & & &

& & & & & & & & & & & &

❹ ❹ ❹ ❹ ❹ ❹ ❹ ⓿ ❶ ⓿ ❶ ⓿ ❶ 6 ❶ ⓿ ❶ 6 2 ⓿ 2 ❶ ⓿ ❶ 6 ⓿ ❹ ❶ ⓿ ❶ ❶ ⓿ ❶ 6 & ❹ ❶ ❶ 6 & ❶ ❶ ❹ ❶ ⓿ ❶ ❶ 6 ❶ ❶ ❶ 6 ⓿ ⓿ ⓿ ⓿ & ❶ ❶ ❶ ⓿ & ❶ ⓿ ❶ ❶ ⓿ ❶ ⓿ ❶ ❶ ⓿ ⓿ ❶ 6 ⓿ ⓿ ⓿ ❶ ⓿ ❶ ❶ ⓿ ❶ ❶ ⓿ ❶ 6 ❶ ❶ ❶ 2 ❶ ❶ ⓿ ❶ ❶

2 ❹ ❹ ❹ ❹ ❹ ❹ ❹ ❶ ❶ 6 ❹ ❶ ❶ ❹ ⓿ ❶ ❶ ⓿ ❹ ❶ ⓿ ❶ ⓿ ❹ ❶ ⓿ ⓿ ⓿ ❶ ⓿ ❶ ❹ ❶ ⓿ ❶ ❶ ❶ ❶ ❶ ❶ ❶ ❶ ⓿ ❶ ❶ ⓿ ⓿ ⓿ ❶ 6 ❶ 6 & ⓿ ⓿ ⓿ ❶ ❶ ⓿ ❹ ❶ 6 ❶ ❶ ⓿ ❶ ❶ ⓿ ⓿ ❶ ⓿ ❶ ❶ ⓿ ⓿ ⓿ ❶ ⓿ ❶ ⓿ ⓿ ❶ ❶ ❶ ⓿ ❶ ❹ ❶ ❶ ⓿ ⓿ ⓿ ❶ ❶ ❶ ❶ 6 ⓿ ❶ ⓿ ⓿ ⓿ ❶ ⓿ ❶ ❶ ⓿ ⓿ ❶ ⓿ ❶ ❶ ⓿ ❶ ❶ ❶ ❶ ⓿ ⓿ ⓿ ⓿ ❶ ⓿ ⓿ ❶ ⓿ ❶ ⓿ ⓿ ❶ ❶ ⓿ ⓿ ❶ ❶ ❶ ❶ ❶ ❶ ⓿ ❶ 6 ❶ ❶ ❶ ⓿ ❶ 6 ⓿ ❶ ❶ & &

❹ ❶ ❹ ❹ ❹ ❹ ⓿ ❶ ❶ ❹ ❹ ❹ ❶ 6 ⓿ 2 ❶ 6 ❶ ⓿ & ⓿ ❶ ❶ ⓿ ❶ ❶ ⓿ ⓿ ❶ ⓿ ⓿ ❶ ❶ ⓿ ❶ ⓿ ⓿ ❶ ⓿ ⓿ ❶ ❶ ❶ ⓿ ⓿ ⓿ ⓿ ⓿ ❶ ❶ ⓿ ❶ ⓿ ⓿ ❶ ❶ ❶ ⓿ ⓿ ❶ ⓿ ❶ ⓿ ⓿ ⓿ ❹ ❶ ⓿ ⓿ ⓿ ❶ ⓿ ❶ ⓿ ❹ ⓿ ❶ ❶ ⓿ ❶ ❶ ⓿ & ❶ ⓿ ❶ ⓿ ❹ ⓿ ⓿ 2 ⓿ ⓿ ⓿ ❶ ❶ ❶ ⓿ ⓿ ❶ ❶ ⓿ ⓿ ❶ 2 2 ❶ ⓿

2 & & & µ µ µ ❶ ⓿ ❶ 6

❹ ⓿ ❶ 6 ❹ ❹ ⓿ ❶ 6 ❶ ❶ ⓿ ⓿ ⓿ ❹ ❹ ⓿ ❶ ❶ ❶ ❶ ⓿ ❶ 2 ⓿ 2 ❶ ❶ ⓿ ❶ ❶ 6 ❶ 6 ⓿ ❶ ❶ ❶ ❶ ❶ ⓿ ❶ 6 ⓿ ❶ ❶ ❶ ⓿ ❹ ❶ ⓿ ❶ ⓿ ⓿ ❶ ⓿ ❶ ⓿ ❶ 6 ❶ ⓿ ❶ ⓿ ❹ ❶ ⓿ ❶

2 & & ❶ ❶ ⓿ ⓿ ❶ 6 ❶

❹ ❶ 6 ❶ & ⓿ ❶ ⓿ ⓿ ❶ 6 ❶ ⓿ ❶ ⓿ 2 ❶ ⓿ 2 ⓿ ⓿ 6 6 6 ❶ ❶ 6 ❶ ⓿ ⓿ ❶ ❶ ❶ ❶ ⓿ ❶ 6 ❶ ⓿ ⓿ ❶ ⓿ ⓿ ❶ ⓿ ⓿ ❶ ❶ & &

❹ ❹ ❹ ❶ ⓿ 2 ⓿ ⓿ ⓿ ❶ 6 ❶ ⓿ ⓿ ❶ 6 ❶

❹ ❹ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ❶ ⓿ ⓿ & ⓿ ❹ ⓿ ⓿ ⓿ ❹ ⓿ ⓿ ⓿ ⓿ ⓿ & ⓿ ⓿ ❶ & ⓿ & ❶ ❶ & ❶ ❶ ⓿ & ⓿ ⓿ ⓿ & ⓿ ⓿ ⓿ & ❶ ⓿ ⓿ ⓿ & ❶ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ❹ ❶ ⓿ ⓿ ⓿ ⓿ ⓿ ❶ ❶ & & & & & & ❶ ⓿ ⓿ ⓿ & ⓿ &

2 ❶ ❶ 6 ❶ ⓿ ⓿ ⓿ ❶ 6 ⓿ & ❶ ⓿ ❶ ❶ ⓿ & ⓿ ⓿ ❶ ⓿ ❶ & ⓿ ⓿ ❶ 6 ⓿ ❶ ❶ 6 ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ & ⓿ ⓿ & ❶ ❶ 6 & & ⓿ ⓿ ⓿ ⓿ ⓿ ❶ & ❶ ❹ ❶ ❶ ❶ ⓿ ❶ ❶ ⓿ ⓿ ⓿ ❶ ❶ ❶ ⓿ ❶ ⓿ & ⓿ ⓿ ❶ & ⓿ ⓿ ❶ ⓿ ❶ ❶ ❶ &

⓿ ❹ ❹ ❶ ❹ ❹ ❹ ❹ ❹ ❹ ❹ ❶ 6 ⓿ 2 ⓿ ❶ ⓿ ❶

2 ❶ 6 ⓿ 2 & ❶ ⓿ ❶ ❶ ❶ ❹ ❹ ⓿ ❶ ⓿ ❶ ⓿ ❶

❹ ❶ ❶ ❶ ⓿ ⓿ & ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ❶

2 ⓿ ❶ ⓿ ⓿ ❶ ❶ ⓿ ⓿ ⓿ ❶ ❶ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿ ⓿