Evidence Report 

Contract No. 290-02-0009 

Prepared by Minnesota Evidence-based Practice Center, Minneapolis, Minnesota

Use of Spirometry for Case Finding, Diagnosis, and 

Management of Chronic Obstructive Pulmonary Disease 

(COPD) 

Appendixes 
Appendix A 

Technical Expert Panel Members 
Technical Expert Panel Members and Areas of Expertise 

TEP Member Area of Expertise 

John Connett, PhD 

University of Minnesota School of Public Health 

Minneapolis, Minnesota 

Biostatistics

Anne Fuhlbrigge, MD 

Brigham and Women’s Hospital 

Harvard Medical School 

Boston, Massachusetts 

Epidemiology, COPD 

Anne Marie Joseph, MD 

VA Medical Center 

Minneapolis, Minnesota 

General medicine, smoking cessation 

Michael Light, MD 

University of Miami School of Medicine 

Miami, Florida 

Pediatrics, airways disease 

Katherine Sherif, MD 

Center for Women’s Health 

Drexel University College of Medicine 

Philadelphia, Pennsylvania 

General medicine, disease prevention 

Stuart W. Stoloff, MD 

Stuart W. Stoloff, MD, Ltd. 

Carson City, Nevada 

Primary care, airways disease 

Barbara Yawn 

Olmsted Medical Center 

Rochester, Minnesota 

Pulmonary care, airways disease 

153 
Appendix B 

Exact Search Strings 
Search Strings for Use of Spirometry for Case Finding, Diagnosis, and 

Management of Chronic Obstructive Pulmonary Disease (COPD)

Question 1 (prevalence)

The literature search was done on MEDLINE (via OVID) using the following combination of 

MeSH headings, keywords, and publication types: 

((copd.mp. OR 

Pulmonary Disease, Chronic Obstructive/ OR 

chronic obstructive pulmonary disease.mp. OR 

emphysema.mp. OR 

emphysema/ OR 

bronchitis.mp. OR 

bronchitis/ OR 

chronic bronchitis.mp. OR 

bronchitis, chronic/ OR 

airflow limitation.mp. OR 

airway obstruction/) 

AND 

(diagnosis.mp. OR 

diagnosis/ OR 

epidemiology.mp. OR 

epidemiology/ OR 

community.mp. OR 

residence characteristics/ OR 

catchment.mp. OR 

"catchment area (health)"/ OR 

prevalence.mp. OR 

prevalence/ OR 

incidence.mp. OR 

incidence/ OR

risk assessment.mp. OR 

risk assessment/ OR 

(high adj1 risk).ti,ab.) 

AND 

(spirometry.mp. or spirometry/ OR 

bronchospirometry.mp. OR 

bronchospirometry/ OR 

respiratory function tests.mp. OR 

respiratory function tests/) 

157 
AND 

(cohort studies/ OR 

case reports.pt. OR 

case-control studies/)) 

OR 

((exp pulmonary disease, chronic obstructive/ OR 

copd.mp.) 

AND 

(exp spirometry/ OR 

spiromet:.mp.) 

AND 

(exp pulmonary disease, chronic obstructive/ep OR

prevalen:.mp. OR 

prevalence/)) 

Question 2 (smoking cessation)

The literature search was done on MEDLINE (via OVID) using the following combination of 

MeSH headings, keywords, and publication types: 

((copd.mp. OR 

Pulmonary Disease, Chronic Obstructive/ OR 

chronic obstructive pulmonary disease.mp. OR 

emphysema.mp. OR 

emphysema/ OR 

bronchitis.mp. OR 

bronchitis/ OR 

chronic bronchitis.mp. OR 

bronchitis, chronic/ OR 

airflow limitation.mp. OR 

airway obstruction/) 

AND 

(spirometry.mp. OR 

spirometry/ OR 

bronchospirometry.mp. OR 

158 
bronchospirometry/ OR 

respiratory function tests.mp. OR 

respiratory function tests/) 

AND 

(smoking/ OR 

smoking cessation/ OR 

smoking cessation therapy.mp. OR 

smoking psychology.mp.) 

AND 

(randomized controlled trial.pt. OR 

controlled clinical trial.pt. OR 

case-control studies/)) 

OR 

((exp spirometry/ OR 

spiromet:.mp.) 

AND 

(smoking cessation/ OR 

(smoking adj cessation).mp. OR 

exp smoking/dh, dt, th)) 

Question 3 (Sin review update)

The literature search was done on MEDLINE (via OVID) using the following combination of 

MeSH headings, keywords, and publication types (search results were limited to controlled 

clinical trials, meta analyses or randomized controlled trials, and limited to references published 

from the years 2002 to 2004): 

Combination of short-acting β-2 agonists and ipratropium bromide

(obstructive.mp. OR 

chronic obstructive.mp. OR 

bronchitis.mp. OR 

bronchitis/ OR 

emphysema.mp. OR 

mediastinal emphysema / OR 

subcutaneous emphysema / OR 

emphysema / OR 

159 
pulmonary emphysema / OR 

airway obstruction.mp. OR 

airway obstruction/ OR 

copd.mp. OR 

Pulmonary Disease, Chronic Obstructive/ or 

lung diseases, obstructive/) 

AND 

(Ipratropium/ AND 

adrenergic β-agonists/) 

Long-acting β-2 Agonists

(obstructive.mp. OR 

chronic obstructive.mp. OR 

bronchitis.mp. OR 

bronchitis/ OR 

emphysema.mp. OR 

mediastinal emphysema / OR 

subcutaneous emphysema / OR 

emphysema / OR 

pulmonary emphysema / OR 

airway obstruction.mp. OR 

airway obstruction/ OR 

copd.mp. OR 

Pulmonary Disease, Chronic Obstructive/ or 

lung diseases, obstructive/) 

AND 

(adrenergic β-agonists/ OR 

receptors, adrenergic, β -2/ OR 

(adrenergic adj1 beta).ti,ab. OR 

salmeterol.mp. OR 

formoterol.mp.) 

Long-acting Anticholinergics

(obstructive.mp. OR 

chronic obstructive.mp. OR 

bronchitis.mp. OR 

bronchitis/ OR 

emphysema.mp. OR 

160 
mediastinal emphysema / OR 

subcutaneous emphysema / OR 

emphysema / OR 

pulmonary emphysema / OR 

airway obstruction.mp. OR 

airway obstruction/ OR 

copd.mp. OR 

Pulmonary Disease, Chronic Obstructive/ or 

lung diseases, obstructive/) 

AND 

(cholinergic antagonists/ OR 

tiotropium.mp. OR 

scopolamine derivatives/) 

Inhaled Corticosteroids

(obstructive.mp. OR 

chronic obstructive.mp. OR 

bronchitis.mp. OR 

bronchitis/ OR 

emphysema.mp. OR 

mediastinal emphysema / OR 

subcutaneous emphysema / OR 

emphysema / OR 

pulmonary emphysema / OR 

airway obstruction.mp. OR 

airway obstruction/ OR 

copd.mp. OR 

Pulmonary Disease, Chronic Obstructive/ or 

lung diseases, obstructive/) 

AND 

(glucocorticosteroids.mp. OR 

corticosteroids/ OR 

beclomethasone.mp. OR 

budesonide.mp. OR 

fluticasone.mp. OR 

triamcinolone.mp.) 

161 
Combination of Inhaled Corticosteroids and Long-Acting β-2 Agonists

(obstructive.mp. OR 

chronic obstructive.mp. OR 

bronchitis.mp. OR 

bronchitis/ OR 

emphysema.mp. OR 

mediastinal emphysema / OR 

subcutaneous emphysema / OR 

emphysema / OR 

pulmonary emphysema / OR 

airway obstruction.mp. OR 

airway obstruction/ OR 

copd.mp. OR 

Pulmonary Disease, Chronic Obstructive/ or 

lung diseases, obstructive/) 

AND 

(glucocorticosteroids.mp. OR 

corticosteroids/ OR 

beclomethasone.mp. OR 

budesonide.mp. OR 

fluticasone.mp. OR 

triamcinolone.mp.) 

AND 

(salmeterol.mp. OR 

formoterol.mp.) 

Non-invasive Mechanical Ventilation

(obstructive.mp. OR 

chronic obstructive.mp. OR 

bronchitis.mp. OR 

bronchitis/ OR 

emphysema.mp. OR 

mediastinal emphysema / OR 

subcutaneous emphysema / OR 

emphysema / OR 

pulmonary emphysema / OR 

airway obstruction.mp. OR 

airway obstruction/ OR 

copd.mp. OR 

162 
Pulmonary Disease, Chronic Obstructive/ or 

lung diseases, obstructive/) 

AND 

(nippv.mp. OR 

nimv.mp. OR 

bi-level.mp. OR 

respiration, artificial/ OR

positive-pressure respiration/) 

Pulmonary Rehabilitation

(obstructive.mp. OR 

chronic obstructive.mp. OR 

bronchitis.mp. OR 

bronchitis/ OR 

emphysema.mp. OR 

mediastinal emphysema / OR 

subcutaneous emphysema / OR 

emphysema / OR 

pulmonary emphysema / OR 

airway obstruction.mp. OR 

airway obstruction/ OR 

copd.mp. OR 

Pulmonary Disease, Chronic Obstructive/ or 

lung diseases, obstructive/) 

AND 

(exercise tolerance/ OR 

dyspnea/rh [Rehabilitation] OR 

exercise therapy/) 

Oxygen Therapy

(obstructive.mp. OR 

chronic obstructive.mp. OR 

bronchitis.mp. OR 

bronchitis/ OR 

emphysema.mp. OR 

mediastinal emphysema / OR 

subcutaneous emphysema / OR 

emphysema / OR 

163 
pulmonary emphysema / OR 

airway obstruction.mp. OR 

airway obstruction/ OR 

copd.mp. OR 

Pulmonary Disease, Chronic Obstructive/ or 

lung diseases, obstructive/) 

AND 

oxygen inhalation therapy/ 

Disease Management

(obstructive.mp. OR 

chronic obstructive.mp. OR 

bronchitis.mp. OR 

bronchitis/ OR 

emphysema.mp. OR 

mediastinal emphysema / OR 

subcutaneous emphysema / OR 

emphysema / OR 

pulmonary emphysema / OR 

airway obstruction.mp. OR 

airway obstruction/ OR 

copd.mp. OR 

Pulmonary Disease, Chronic Obstructive/ or 

lung diseases, obstructive/) 

AND 

(self care/ OR

patient education/ OR 

primary health care/) 

Question 4 (prognosis)

The literature search was done on MEDLINE (via OVID) using the following combination of 

MeSH headings, keywords, and publication types: 

((copd.mp. OR 

Pulmonary Disease, Chronic Obstructive/ OR 

chronic obstructive pulmonary disease.mp. OR 

emphysema.mp. OR 

164 
emphysema/ OR 

bronchitis.mp. OR 

bronchitis/ OR 

chronic bronchitis.mp. OR 

bronchitis, chronic/ OR 

airflow limitation.mp. OR 

airway obstruction/) 

AND 

(spirometry.mp. OR 

spirometry/ OR 

bronchospirometry.mp. OR 

bronchospirometry/ OR 

respiratory function tests.mp. OR 

respiratory function tests/) 

AND 

(prognosis/ OR 

prognosis.mp.) 

AND 

(cohort studies/ OR 

case reports.pt. OR 

case-control studies/)) 

OR 

((exp pulmonary disease, chronic obstructive/ OR 

copd.mp.) 

AND 

(exp spirometry/ OR 

spiromet:.mp.) 

AND 

(exp prognosis/ OR 

prognos:.mp.)) 

165 
Appendix C 

Abstraction Forms 
UNIQUE IDENTIFIER # 

Interventions for COPD / Spirometry 

Article Abstraction Form: 

Author (first):___________________________________ 

Journal:____________________________________________ Year Publication: _________ 

Country:_____________________________ (where study performed) 

 

Reviewer:_________________________ 

VERIFICATION/SELECTION OF STUDY ELIGIBILITY

Randomized Yes No Unclear 

Placebo or Control (usual care, O2) Yes No Unclear 

Subjects with COPD (any GOLD Stage) Yes No Unclear 

 (i.e irreversible airway obstruction, NOT asthma and NOT α-1 antitrypsin deficiency, or 

 were the outcomes in the group with COPD reported separately?

Age of subjects > 19 years of age Yes No Unclear 

Minimum of 50 subjects per arm Yes No Unclear 

Study duration > 3 months Yes No Unclear 

 (exception pulmonary rehabilitation) 

 

Were subjects stable for at least 1 month Yes No Unclear 

 prior to initiation of therapy 

Clinical outcomes of interest Yes No Unclear 

 (death, respiratory death, hospitalizations – any reason or COPD exacerbations, physician 

 visits – any reason or due to COPD, FEV1, FEV1/FVC ratio, SGRQ, CRQ QoL measures) 

 

* Using Spirometry for measurement of PFT Yes No Unclear

Stop if any of the above is “NO” 

METHODS 

Study Design and Conduct

Subject blinded Yes No Unclear 

Provider blinded Yes No Unclear 

Intention-to-treat analysis Yes No Unclear 

Crossover trial Yes No Unclear

169 
UNIQUE IDENTIFIER # 

RANDOMIZATION ALLOCATION CONCEALMENT METHOD (circle one) 

Clearly adequate: Centralized randomization by telephone, randomization scheme controlled by 

pharmacy, numbered or coded identical containers administered sequentially, on site computer 

system which can only be accessed after entering the characteristics of an enrolled participant, 

sequentially numbered sealed opaque envelopes. 

Clearly Inadequate: Alternation (odd-even, etc..), date of birth, date of week 

Unclear: Sealed envelopes but not sequentially numbered or opaque, other, list of random

numbers read by someone entering patient into trial (open list) or study noted to be random or 

“randomization” or “random allocation” but no details provided.

PARTICIPANTS 

Multi-center or single site (circle one) Total number of subjects eligible______________ 

Total # subjects enrolled ______________ Subjects completed trial:______________ 

Setting: Community Primary Clinic Specialty Clinic Nursing Home

(circle all that apply) Other ___________________________ 

Intervention

(or write in subgoups)

Placebo/control 

(write in) 

I II III

# Subjects: 

Mean age 

Men: 

n / N and % 

Women: 

n / N and % 

Age < 65* 

n / N and % 

Age > 65 

n / N and % 

Race: white 

n / N and % 

Race: black

n / N and % 

Race: Asian

n / N and % 

170 
UNIQUE IDENTIFIER # 

Race: Hispanic 

n / N and % 

Race: Other 

n/N and % 

Asthma

n/N and % 

Bronchitis 

n/N and % 

Emphysema

n/N and % 

SMOKING HISTORY

Intervention

(write in)

Placebo/control 

(write in) 

I II III

Current smoker 

Ex-smoker 

Never smoked 

Notes: 

INTERVENTION 

Drug name Dosing regimen (describe) 

I 

II 

Intervention

III 

Placebo /

Control 

Notes: 

Study duration (months): Mean _________ Median _________ 

Range:______________ months 

171 
UNIQUE IDENTIFIER # 

SUBJECTS RANDOMIZED / DROPOUTS / FOLLOWED 

Total 

Randomized 

Lost to 

attrition 

Due to side 

effects 

# available for 

follow-up 

I 

II 

III 

IV 

Intervention

V 

Placebo/Control 

Notes: 

QUALITY OF LIFE 

(provide SDs, SEs, p-values and confidence intervals when appropriate) 

Intervention

(write in in subgoups)

Placebo/control 

(write in) 

I II III

SGRQ*, 

baseline

SGRQ*, end 

SGRQ*, mean 

change 

CRQ **, 

baseline 

CRQ**, end 

CRQ**, mean 

change 

*St George’s Respiratory Questionnaire 

** Chronic Respiratory Questionnaire

172 
UNIQUE IDENTIFIER # 

CLINICAL OUTCOMES 

(provide SDs, SEs, p-values and confidence intervals when appropriate) 

Intervention

(write in in subgoups)

Placebo/control 

(write in) 

I II III

Deaths, all 

causes 

Death, 

respiratory

Total 

hospitalizations 

– any reason 

At least one 

hospitalization 

– any reason, 

Total 

hospitalizations 

– COPD 

exacerbations 

At least one 

hospitalization 

– COPD 

exacerbations 

Total physician 

visits – any 

reason 

At least one 

physician visit 

– any reason 

Total physician 

visits – due to 

COPD 

At least one 

physician visit 

– due to COPD 

Other

(describe) 

173 
UNIQUE IDENTIFIER # 

FORCED AIR EXPIRATORY VOLUME (FEV1) 

Intervention

(write in subgoups)

Placebo/control 

(write in) 

I II III

FEV1, mean at 

baseline (+ 

SD/SE if provided) 

FEV1, mean at 

follow-up (+ 

SD/SE if provided) 

FEV1, mean 

change (if 

provided) 

FEV1, value 

< 80% > 79%

predicted 

Stage 1:Mild 

FEV1 50%-

79% Stage 

2:Moderate 

FEV1 30-49% 

predicted: 

Stage 3 Severe 

FEV1 < 30% 

Stage 4 Very 

Severe 

Forced vital 

capacity ratio 

(FEV1/FVC), 

< 70%

Other 

174 
UNIQUE IDENTIFIER # 

CLINICAL SYMPTOMS 

Intervention

(write in subgoups)

Placebo/control 

(write in) 

I II III

Dyspnea 

n/N and % 

Baseline: 

Followup: 

Baseline: 

Followup:

Baseline: 

Followup:

Baseline: 

Follow-up:

Cough Baseline: 

Follow-p: 

Baseline: 

Followup:

Baseline: 

Followup: 

Baseline: 

Followup:

Sputum Baseline: 

Followup: 

Baseline: 

Followup:

Baseline: 

Followup: 

Baseline: 

Followup:

Wheeze Baseline: 

Followup: 

Baseline: 

Followup:

Baseline: 

Followup: 

Baseline: 

Followup:

Combined 

Clinical

Symptoms

Baseline: 

Followup: 

Baseline: 

Followup:

Baseline: 

Followup: 

Baseline: 

Followup:

Other Baseline: 

Followup: 

Baseline: 

Followup:

Baseline: 

Followup: 

Baseline: 

Followup:

* If you need more of this form __________________________________________ 

 [photocopy and attach additional sheets for more than 4 subgroups] 

175 
Interventions for Smoking Cessation with the Addition of 

Spirometry 

Article Abstraction Form: 

Author (first):________________________________________________ 

Journal:________________________________________ Year Publication: _________ 

Country:_____________________________ (where study performed) 

 

Reviewer:_________________________ 

VERIFICATION/SELECTION OF STUDY ELIGIBILITY

Randomized Yes No Unclear 

Placebo or Control Yes No Unclear 

Spirometry used Yes No Unclear 

Minimum of 50 subjects per arm Yes No Unclear 

Study duration > 3 months Yes No Unclear 

 

Stop if any of the above is “NO” 

METHODS 

Study Design and Conduct

Subject blinded Yes No Unclear 

Provider blinded Yes No Unclear 

Intention-to-treat analysis Yes No Unclear 

Crossover trial Yes No Unclear

RANDOMIZATION ALLOCATION CONCEALMENT METHOD (circle one) 

Clearly adequate: Centralized randomization by telephone, randomization scheme controlled by 

pharmacy, numbered or coded identical containers administered sequentially, on-site computer 

system which can only be accessed after entering the characteristics of an enrolled participant, 

sequentially numbered sealed opaque envelopes. 

Clearly Inadequate: Alternation (odd-even, etc..), date of birth, date of week 

Unclear: Sealed envelopes but not sequentially numbered or opaque, other, list of random

numbers read by someone entering patient into trial (open list) or study noted to be random or 

“randomization” or “random allocation” but no details provided.

177 
PARTICIPANTS 

Multicenter or single site (circle one) 

Total number of subjects eligible______________ 

Total # subjects enrolled ______________ Subjects completed trial:______________ 

Setting: Community Primary Clinic Specialty Clinic Nursing Home

(circle all that apply) Other ___________________________ 

Intervention

(write in) 

Placebo/control 

(write in) 

# Subjects: # Subjects:

Mean age Mean age

Men: 

n / N and % 

Men:

n / N and % 

Women: 

n / N and % 

Women:

n / N and % 

Age < 65* 

n / N and % 

Age > 65 

n / N and % 

Age > 65 

n / N and % 

Age > 65 

n / N and % 

Race: white 

n / N and % 

Race: white

n / N and % 

Race: black

n / N and % 

Race: black

n / N and % 

Race: Asian

n / N and % 

Race: Asian

n / N and % 

Race: Other 

n / N and % 

Race: Other

n / N and % 

Living status: alone 

n / N and % 

Living status: alone 

n / N and % 

Living status: with 

smoker 

Living status: with 

smoker 

Living status: with 

non smoker

Living status: with 

non smoker

COPD: 

n / N and % 

COPD:

n / N and % 

Emphysema:

n / N and % 

Emphysema:

n / N and % 

Other Other

Other Other

178 
SMOKING HISTORY 

(provide SDs, SEs, ranges, p-values and confidence intervals when appropriate) 

Intervention

(write in) 

Placebo/control 

(write in) 

Mean # cigarettes 

Smoked/day 

Mean # cigarettes 

Smoked/day 

Pack years Pack years

Mean age when 

starting smoking 

Mean age when 

starting smoking 

Nicotine content 

> 1 mg/cig 

Nicotine content

> 1 mg/cig 

Nicotine content 

< 1 mg/cig 

Nicotine content

< 1 mg/cig 

Any prior attempt to 

quit 

Any prior attempt to 

quit 

Prior attempts: none Prior attempts: none 

Prior attempts: 1-2 Prior attempts: 1-2 

Prior attempts: > 3 Prior attempts: > 3 

Previous nicotine 

patch use 

Previous nicotine

patch use 

Previous nicotine 

gum use 

Previous nicotine

gum use 

Mean Fagerström

score 

Mean Fagerström

score 

Other Other

Other Other

Other Other

Notes: 

179 
BASELINE LUNG FUNCTION 

(provide SDs, SEs, ranges, p-values and confidence intervals when appropriate) 

Intervention

(write in) 

Placebo / control 

(write in)

FEV1, mean FEV1, mean 

FEV1, value, 

% predicted 

FEV1, value, %

predicted 

Forced vital 

capacity ratio 

(FEV1/FVC), 

Forced vital

capacity ratio 

(FEV1/FVC), 

CO, ppb CO, ppb

INTERVENTION 

Intervention name: description Intervention frequency 

(describe) 

Intervention 

Placebo / 

Control 

Notes: 

Mean study duration _________ months 

Median study duration ________ months 

Range:______________ months 

180 
SUBJECTS RANDOMIZED / DROPOUTS / FOLLOWED 

Total 

Randomized 

Lost to 

attrition 

Due to side 

effects 

# available for 

follow-up 

Intervention 

Placebo/Control 

Notes: 

CESSATION 

(provide SDs, SEs, p-values and confidence intervals when appropriate) 

Intervention

(write in) 

Placebo/control 

(write in)

Quit rate, last 

followup 

Quit rate, last 

followup 

Made > 1 attempt 

to quit or “ever 

quit” 

Made > 1 attempt 

to quit or “ever 

quit” 

CO-validated 

cessation 

CO-validated

cessation 

Other (describe) Other (describe) 

Other (describe) Other (describe) 

Other (describe) Other (describe) 

181 
FORCED AIR EXPIRATORY VOLUME (FEV1) 

Intervention

(write in) 

Placebo / control 

(write in)

FEV1, mean at 

baseline (+ SD/SE if 

provided) 

FEV1, mean at 

baseline (+ SD/SE if 

provided) 

FEV1, mean at 

followup (+ SD/SE if

provided) 

FEV1, mean at 

followup (+ SD/SE if

provided) 

FEV1, mean 

change (if provided) 

FEV1, mean

change (if provided) 

FEV1, value 

< 80% predicted 

FEV1, value 

< 80% predicted 

Forced vital 

capacity ratio 

(FEV1/FVC), 

< 70%

Forced vital

capacity ratio 

(FEV1/FVC), 

< 70%

CO, ppb CO, ppb

QUALITY OF LIFE 

(provide SDs, SEs, p-values and confidence intervals when appropriate) 

Intervention

(write in) 

Placebo / control 

(write in)

SGRQ*, mean 

change 

SGRQ*, mean

change 

CRQ**, mean 

change 

CRQ**, mean

change 

*St George’s Respiratory Questionnaire 

** Chronic Respiratory Questionnaire 

182 
For SUBGROUPS - photocopy Outcomes pages and attach

Subgroup __________________________________________ 

Intervention

(write in) 

Placebo/control 

(write in) 

# Subjects: # Subjects:

Mean age Mean age

Men: 

n / N and % 

Men:

n / N and % 

Women: 

n / N and % 

Women:

n / N and % 

Age < 65* 

n / N and % 

Age > 65 

n / N and % 

Age > 65 

n / N and % 

Age > 65 

n / N and % 

Race: white 

n / N and % 

Race: white

n / N and % 

Race: black

n / N and % 

Race: black

n / N and % 

Race: Asian

n / N and % 

Race: Asian

n / N and % 

Race: Other 

n / N and % 

Race: Other

n / N and % 

SMOKING HISTORY 

Intervention

(write in) 

Placebo/control 

(write in) 

Mean # cigarettes 

Smoked/day 

Mean # cigarettes 

Smoked/day 

Pack years Pack years

Nicotine content 

> 1 mg/cig 

Nicotine content

> 1 mg/cig 

Nicotine content 

< 1 mg/cig 

Nicotine content

< 1 mg/cig 

183 
Any prior attempt to 

quit 

Any prior attempt to 

quit 

Prior attempts: none Prior attempts: none 

Prior attempts: 1-2 Prior attempts: 1-2 

Prior attempts: > 3 Prior attempts: > 3 

Other Other

Other Other

Notes: 

Subgroup 1________________________________________ 

[photocopy and attach additional sheets for more than 2 subgroups]

Total 

Randomized 

Total 

Dropouts 

Due to side 

effects 

# available for 

follow-up 

Intervention 

Placebo/Control 

Notes: 

184 
Prevalence COPD / Spirometry 

Article Abstraction Form: 

Author (first):___________________________________ 

Journal:________________________________________ Year Publication: _________ 

Country:_____________________________ (where study performed) 

 

Reviewer:_________________________ 

VERIFICATION/SELECTION OF STUDY ELIGIBILITY

Subjects with COPD Yes No Unclear 

 (i.e., irreversible airway obstruction, NOT asthma and NOT α-1 antitrypsin deficiency, or 

 were the outcomes in the group with COPD reported separately?

FEV1/FVC measured with spirometry Yes No Unclear 

TYPE OF STUDY 

Source of data: Epidemiologic survey Cohort study Case/Control 

(circle) 

Other (describe)______________________________________ 

Prospective_____ Retrospective______ Unclear_____ 

Subjects selected at random? Yes No Unclear 

Control Group (i.e subjects with no COPD)

 Yes No Unclear

Multivariate analyses used? Yes No Unclear 

185 
SUBJECTS 

Total number of subjects ______________ 

COPD subjects ______________ Control subjects __________________ 

Setting: Community Primary Clinic Specialty Clinic Nursing Home

(circle all that apply) 

Other (describe)______________________________________ 

DEMOGRAPHICS 

COPD subjects 

(write in) 

No COPD / Control 

(write in) 

# Subjects: # Subjects:

Mean age Mean age

Age, years 

(write in) 

Age, years

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Men: 

n / N and % 

Men:

n / N and % 

Women: 

n / N and % 

Women:

n / N and % 

Age < 65* 

n / N and % 

Age > 65 

n / N and % 

Age > 65 

n / N and % 

Age > 65 

n / N and % 

Race: white 

n / N and % 

Race: white

n / N and % 

Race: black

n / N and % 

Race: black

n / N and % 

Race: Asian

n / N and % 

Race: Asian

n / N and % 

Race: Other 

n / N and % 

Race: Other

n / N and % 

186 
SMOKING HISTORY 

COPD subjects 

(write in) 

No COPD / Control 

(write in) 

Current smoker Current smoker

Ex-smoker Ex-smoker

Never smoked Never smoked

Duration, pack years Duration, pack years

Other 

(write in) 

Other

(write in) 

Notes: 

FEV1/FVC 

COPD subjects 

(write in) 

No COPD / Control 

(write in) 

Mean FEV1, L Mean FEV1, L 

Mean FEV1, % of 

predicted 

Mean FEV1, % of 

predicted 

FEV1 < 50% 

predicted 

FEV1 < 50% 

predicted 

FEV1 50-70% 

predicted 

FEV1 50-70% 

predicted 

FEV1 70%-80% 

predicted 

FEV1 70%-80%

predicted 

FEV1/FVC <0.70 

and FEV1<50% 

predicted (severe) 

FEV1/FVC <0.70

and FEV1<50% 

predicted (severe) 

FEV1/FVC <0.70 

and FEV1>50-

<80% predicted 

(moderate) 

FEV1/FVC <0.70

and FEV1>50-

<80% predicted 

(moderate) 

FEV1/FVC <0.70 

and FEV1> 80% 

predicted (mold) 

FEV1/FVC <0.70

and FEV1> 80% 

predicted (mold) 

GOLD, stage 0 

Cough, FEV1/FVC 

>0.70 

GOLD, stage 0 

Cough, FEV1/FVC 

>0.70 

187 
COPD subjects 

(write in) 

No COPD / 

Control 

(write in) 

GOLD, stage 1 

FEV1/FVC <0.70, 

FEV1 > 80% pred 

GOLD, stage 1 

FEV1/FVC <0.70, 

FEV1 > 80% pred 

GOLD, stage 2 

FEV1/FVC <0.70, 

FEV1>30% and < 

80% pred 

GOLD, stage 2 

FEV1/FVC <0.70, 

FEV1>30% and < 

80% pred 

GOLD, stage 3 

FEV1/FVC <0.70, 

FEV1< 30% pred 

GOLD, stage 3 

FEV1/FVC <0.70, 

FEV1< 30% pred 

Other 

(write in) 

Other

(write in) 

Notes: 

188 
COPD SUBGROUPS (Based on severity—mild, moderate, severe—or GOLD stage) 

Subgroup 1 __________________________________________ 

[photocopy and attach additional sheets for more than 3 subgroups] 

COPD subjects 

(write in) 

No COPD / Control 

(write in) 

# Subjects: # Subjects:

Mean age Mean age

Age, years 

(write in) 

Age, years

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Men: 

n / N and % 

Men:

n / N and % 

Women: 

n / N and % 

Women:

n / N and % 

Age < 65* 

n / N and % 

Age > 65 

n / N and % 

Age > 65 

n / N and % 

Age > 65 

n / N and % 

Race: white 

n / N and % 

Race: white

n / N and % 

Race: black

n / N and % 

Race: black

n / N and % 

Race: Asian

n / N and % 

Race: Asian

n / N and % 

Race: Other 

n / N and % 

Race: Other

n / N and % 

189 
SMOKING HISTORY 

COPD subjects 

(write in) 

No COPD / Control 

(write in) 

Current smoker Current smoker

Ex-smoker Ex-smoker

Never smoked Never smoked

Duration, pack years Duration, pack years

Other 

(write in) 

Other

(write in) 

Notes: 

FEV1/FVC 

COPD subjects 

(write in) 

No COPD / Control 

(write in) 

Mean FEV1, L Mean FEV1, L 

Mean FEV1, % of 

predicted 

Mean FEV1, % of 

predicted 

FEV1 < 50% 

predicted 

FEV1 < 50% 

predicted 

FEV1 50-70% 

predicted 

FEV1 50-70% 

predicted 

FEV1 70%-80% 

predicted 

FEV1 70%-80%

predicted 

FEV1/FVC <0.70 

and FEV1<50% 

predicted (severe) 

FEV1/FVC <0.70

and FEV1<50% 

predicted (severe) 

FEV1/FVC <0.70 

and FEV1>50-

<80% predicted 

(moderate) 

FEV1/FVC <0.70

and FEV1>50-

<80% predicted 

(moderate) 

FEV1/FVC <0.70 

and FEV1> 80% 

predicted (mold) 

FEV1/FVC <0.70

and FEV1> 80% 

predicted (mold) 

GOLD, stage 0 

Cough, FEV1/FVC 

>0.70 

GOLD, stage 0 

Cough, FEV1/FVC 

>0.70 

190 
COPD subjects 

(write in) 

No COPD / 

Control 

(write in) 

GOLD, stage 1 

FEV1/FVC <0.70, 

FEV1 > 80% pred 

GOLD, stage 1 

FEV1/FVC <0.70, 

FEV1 > 80% pred 

GOLD, stage 2 

FEV1/FVC <0.70, 

FEV1>30% and < 

80% pred 

GOLD, stage 2 

FEV1/FVC <0.70, 

FEV1>30% and < 

80% pred 

GOLD, stage 3 

FEV1/FVC <0.70, 

FEV1< 30% pred 

GOLD, stage 3 

FEV1/FVC <0.70, 

FEV1< 30% pred 

Other 

(write in) 

Other

(write in) 

Notes: 

191 
Subgroup 2 __________________________________________ 

COPD 

(write in)________________________ 

COPD 

(write in)________________________ 

# Subjects: # Subjects:

Mean age Mean age

Age, years 

(write in) 

Age, years

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Men: 

n / N and % 

Men:

n / N and % 

Women: 

n / N and % 

Women:

n / N and % 

Age < 65* 

n / N and % 

Age > 65 

n / N and % 

Age > 65 

n / N and % 

Age > 65 

n / N and % 

Race: white 

n / N and % 

Race: white

n / N and % 

Race: black

n / N and % 

Race: black

n / N and % 

Race: Asian

n / N and % 

Race: Asian

n / N and % 

Race: Other 

n / N and % 

Race: Other

n / N and % 

192 
SMOKING HISTORY 

COPD subjects 

(write in) 

No COPD / Control 

(write in) 

Current smoker Current smoker

Ex-smoker Ex-smoker

Never smoked Never smoked

Duration, pack years Duration, pack years

Other 

(write in) 

Other

(write in) 

Notes: 

FEV1/FVC 

COPD subjects 

(write in) 

No COPD / Control 

(write in) 

Mean FEV1, L Mean FEV1, L 

Mean FEV1, % of 

predicted 

Mean FEV1, % of 

predicted 

FEV1 < 50% 

predicted 

FEV1 < 50% 

predicted 

FEV1 50-70% 

predicted 

FEV1 50-70% 

predicted 

FEV1 70%-80% 

predicted 

FEV1 70%-80%

predicted 

FEV1/FVC <0.70 

and FEV1<50% 

predicted (severe) 

FEV1/FVC <0.70

and FEV1<50% 

predicted (severe) 

FEV1/FVC <0.70 

and FEV1>50-

<80% predicted 

(moderate) 

FEV1/FVC <0.70

and FEV1>50-

<80% predicted 

(moderate) 

FEV1/FVC <0.70 

and FEV1> 80% 

predicted (mold) 

FEV1/FVC <0.70

and FEV1> 80% 

predicted (mold) 

GOLD, stage 0* 

Cough, FEV1/FVC 

>0.70 

GOLD, stage 0 

Cough, FEV1/FVC 

>0.70 

193 
COPD subjects 

(write in) 

No COPD / 

Control 

(write in) 

GOLD, stage 1 

FEV1/FVC <0.70, 

FEV1 > 80% pred 

GOLD, stage 1 

FEV1/FVC <0.70, 

FEV1 > 80% pred 

GOLD, stage 2 

FEV1/FVC <0.70, 

FEV1>30% and < 

80% pred 

GOLD, stage 2 

FEV1/FVC <0.70, 

FEV1>30% and < 

80% pred 

GOLD, stage 3 

FEV1/FVC <0.70, 

FEV1< 30% pred 

GOLD, stage 3 

FEV1/FVC <0.70, 

FEV1< 30% pred 

GOLD, stage 4 

Other 

(write in) 

Other

(write in) 

Notes: 

* GOLD, Stage 0 = at risk

GOLD, Stage 1 = mild COPD 

GOLD, Stage 2 = moderate COPD 

GOLD, Stage 3 = severe COPD 

GOLD, Stage 4 = very severe COPD 

194 
PREVALENCE (MILD COPD) 

Write in definition______________________________________________________ 

Time of followup___________________________ 

COPD subjects 

(write in) 

No COPD / Control 

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Men: 

n / N and % 

Men:

n / N and % 

Women: 

n / N and % 

Women:

n / N and % 

Race: white 

n / N and % 

Race: white

n / N and % 

Race: black

n / N and % 

Race: black

n / N and % 

Race: Asian

n / N and % 

Race: Asian

n / N and % 

Race: Other 

n / N and % 

Race: Other

n / N and % 

Current smoker Current smoker

Ex-smoker Ex-smoker

Never smoked Never smoked

195 
PREVALENCE (MODERATE COPD) 

Write in definition______________________________________________________ 

Time of follow-up___________________________ 

COPD subjects 

(write in) 

No COPD / Control 

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Men: 

n / N and % 

Men:

n / N and % 

Women: 

n / N and % 

Women:

n / N and % 

Race: white 

n / N and % 

Race: white

n / N and % 

Race: black

n / N and % 

Race: black

n / N and % 

Race: Asian

n / N and % 

Race: Asian

n / N and % 

Race: Other 

n / N and % 

Race: Other

n / N and % 

Current smoker Current smoker

Ex-smoker Ex-smoker

Never smoked Never smoked

Other 

196 
PREVALENCE (SEVERE COPD) 

Write in definition______________________________________________________ 

Time of followup___________________________ 

COPD subjects 

(write in) 

No COPD / Control 

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Age, years 

(write in) 

Age, years

(write in) 

Men: 

n / N and % 

Men:

n / N and % 

Women: 

n / N and % 

Women:

n / N and % 

Race: white 

n / N and % 

Race: white

n / N and % 

Race: black

n / N and % 

Race: black

n / N and % 

Race: Asian

n / N and % 

Race: Asian

n / N and % 

Race: Other 

n / N and % 

Race: Other

n / N and % 

Current smoker Current smoker

Ex-smoker Ex-smoker

Never smoked Never smoked

197 
POSTIVE PREDICTIVE VALUE 

COPD subjects 

(write in) 

No COPD / 

Control 

(write in) 

QUALITY OF LIFE 

(provide SDs, SEs, p-values and confidence intervals when appropriate) 

COPD subjects 

(write in) 

No COPD / Control 

(write in) 

SGRQ*, baseline SGRQ*, baseline 

SGRQ*, end SGRQ*, end

SGRQ*, mean 

change 

SGRQ*, mean

change 

CRQ **, baseline CRQ**, baseline 

CRQ**, end CRQ**, end 

CRQ**, mean 

change 

CRQ**, mean

change 

SF-36-Physical 

functioning 

SF-36-

SF-36-

*St George’s Respiratory Questionnaire 

** Chronic Respiratory Questionnaire 

For SUBGROUPS - photocopy Outcomes pages and attach

198 
Appendix D 

Evidence Tables 

and Figures 
Evidence Figure 1

227
Evidence Figure 2.

228
Evidence Figure 3.

234
Evidence Figure 4.

235
Evidence Figure 5.

236
Evidence Figure 6. 

237
Evidence Figure 7.

238
Evidence Figure 8.

239
Evidence Figure 9. 

240
Evidence Figure 10. 

241
Evidence Figure 11. 

242
Evidence Figure 12. 

243
Evidence Figure 13. 

244
Evidence Figure 14. 

245
Evidence Figure 15. 

253
Evidence Figure 16. 

254
Evidence Figure 17. 

255
Evidence Figure 18. 

256
Appendix D 

Evidence Tables 

and Figures 

Evidence Figure 1

227
Evidence Figure 2.

228
Evidence Figure 3.

234
Evidence Figure 4.

235
Evidence Figure 5.

236
Evidence Figure 6. 

237
Evidence Figure 7.

238
Evidence Figure 8.

239
Evidence Figure 9. 

240
Evidence Figure 10. 

241
Evidence Figure 11. 

242
Evidence Figure 12. 

243
Evidence Figure 13. 

244
Evidence Figure 14. 

245
Evidence Figure 15. 

253
Evidence Figure 16. 

254
Evidence Figure 17. 

255
Evidence Figure 18. 

256
201

Evidence Table 1. Prevalence of COPD based upon American Thoracic Society (ATS) or Global Initiative for Chronic Obstructiv

spirometric categories for gender 

Variable / Country; 

Study 

% Normal Spirometry 

and No Respiratory 

Symptoms (n / N) 

% GOLD 0 or "At 

Risk" / Normal 

Spirometry + 

Symptoms of Cough, 

Sputum (n / N) 

% GOLD 1 or Mild - 

FEV1/FVC <70 and 

FEV1 >80% 

Predicted) (n / N) 

% ATS 1 or GOLD 2 

or "Moderate" / 

FEV1/FVC <70 and 

FEV1 >50 to 80-85% 

Predicted) (n / N) 

% ATS 2 or 3 o

GOLD > 3 or 

"Severe" / FEV1/F

<70 and FEV1 <5

predicted) (n / N

National Health and Nutrition Examination Survey-NHANES III150Male Not reported Not reported 9.1 7.4 Not reported Female Not reported Not reported 4.9 5.8 Not reported National Health and Nutrition Examination Survey-NHANES I156Male 61.9 (1,552 / 2,508) 16.1 (see notes) 9.8 (246 / 2,508) 10 (251 / 2,508) 2.2 (55 / 2,508) 

Female 71.9 (2,182 / 3034) 16.1 (see notes) 6.2 (188 / 3,034) 4.6 (140 / 3,034) 1.2 (36 / 3,034) 

European Community Respiratory Health Survey157

Male 82.6 (6,145 / 7,441) 12.6 (940 / 7,441) 4.8 (356 / 7,441) see note see note Female 86.6 (6,422 / 7,414) 10.9 (811 / 7,414) 2.4 (181 / 7,414) see note see note Copenhagen City Heart Study149Male 74.7 (4,490 / 6,012) 7.1 (429 / 6,012) 6.7 (404 / 6,012) 11 (663 / 6,012) <1 (26 / 6,012) Female 83.9 (5,951 / 7,096) 4.7 (337 / 7,096) 3.6 (259 / 7,096) 7.6 (542 / 7,096) <1 (7 / 7,096) Mini-Finland Health Survey151Male 54 (1,740 / 3,255)* Not reported 36 (1,163 / 3,255) 10 (314 / 3,255) 1 (38 / 3,255) Female 61 (2,275 / 3,753)* Not reported 34 (1,286 / 3,753) 5 (184 / 3,753) 0.2 (8 / 3,753) Prevalence of COPD in Elderly Finns152Male 82.6 (252 / 305)* Not reported 3.6 (11 / 305) (FEV1

% predicted >80) 

11.8 (36 / 305) (FEV1

% predicted 40-79) 

2 (6 / 305) (FEV1

% predicted <40) 

Female 95.6 (435 / 455)* Not reported <1 (3 / 455) (FEV1 % 

predicted >80) 

2.9 (13 / 455) (FEV1

% predicted 40-79) 

<1 (4 / 455) (FEV1 

predicted <40) 
Evidence Table 1. Prevalence of COPD based upon American Thoracic Society (ATS) or Global Initiative for Chronic Obstructiv

spirometric categories for gender (continued) 

202

Variable / Country;

Study

% Normal Spirometry

and No Respiratory

Symptoms (n / N) 

% GOLD 0 or "At 

Risk" / Normal 

Spirometry + 

Symptoms of Cough, 

Sputum (n / N) 

% GOLD 1 or Mild -

FEV1/FVC <70 and

FEV1 >80%

Predicted) (n / N) 

% ATS 1 or GOLD 2 

or "Moderate" / 

FEV1/FVC <70 and

FEV1 >50 to 80-85%

Predicted) (n / N) 

% ATS 2 or 3 o

GOLD > 3 or 

"Severe" / FEV1/F

<70 and FEV1 <5

predicted) (n / N

Prevalence of COPD in Norwegians154Male: age 18-44 96.4* Not reported 1.3 2.3 0 Male: age 45-73 88.3* Not reported 2.4 8.6 0.6 Female: age 18-44 97.9* Not reported 1.2 0.7 0.1 Female: age 45-73 90.8* Not reported 0.9 8.1 0.2 * Subjects may or may not be symptomatic and include "at risk" 
Evidence Table 2. Prevalence of COPD based upon American Thoracic Society (ATS) or Global Initiative for Chronic Obstructiv

spirometric categories for ethnicity

Variable / Country;

Study

% Normal

Spirometry and No

Respiratory

Symptoms (n / N) 

% GOLD 0 or "At 

Risk" / Normal 

Spirometry + 

Symptoms of Cough, 

Sputum (n / N) 

% GOLD 1 or Mild -

FEV1/FVC <70 and

FEV1 >80%

Predicted) (n / N) 

% ATS 1 or GOLD 2 or 

"Moderate" / FEV1/FVC 

<70 and FEV1 >50 to

80-85% Predicted)

(n / N) 

% ATS 2 or 3 or

GOLD >3 or 

"Severe" / 

FEV1/FVC <70 an

FEV1 <50%

Predicted) (n / N

National Health and Nutrition Examination Survey-NHANES III150White Not reported Not reported 7.1 6.7 NR Black Not reported Not reported 5 5.6 NR Other Not reported Not reported 8 5.3 NR National Health and Nutrition Examination Survey-NHANES I156White 67.6 (3310 / 4896) 16.4 (803 / 4896) 

(see notes) 

7.5 (367 / 4,896) 6.9 (338 / 4,896) 1.6 (78 / 4,896) 

Non-white 65.3 (422 / 646) 14 (90 / 646) 

(see notes) 

10.5 (68 / 646) 8.4 (54 / 646) 1.8 (12 / 646) 

203
Evidence Table 3. Prevalence of COPD based upon American Thoracic Society (ATS) or Global Initiative for Chronic Obstructiv

spirometric categories for age, gender, and ethnicity

Variable / Country;

Study

% Normal

Spirometry and No

Respiratory

Symptoms (n / N) 

% GOLD 0 or "At Risk" / 

Normal Spirometry + 

Symptoms of Cough, 

Sputum (n / N) 

% GOLD 1 or Mild -

FEV1/FVC <70 and

FEV1 >80%

Predicted) (n / N) 

% ATS 1 or GOLD 2 or 

"Moderate" / FEV1/FVC 

<70 and FEV1 >50 to 80-

85% Predicted) (n / N) 

% A

or 

National Health and Nutrition Examination Survey-NHANES III150Black female, age 17-24 Not reported Not reported Not reported 1.1 Black female, age 25-44 Not reported Not reported Not reported 1.3 Black female, age 45-64 Not reported Not reported Not reported 6.5 Black female, age 65-74 Not reported Not reported Not reported 8.5 Black female, age 75-84 Not reported Not reported Not reported 6.7 Black female, age >85 Not reported Not reported Not reported 6.2 Black male, age 17-24 Not reported Not reported Not reported 2.7 Black male, age 25-44 Not reported Not reported Not reported 1.9 Black male, age 45-64 Not reported Not reported Not reported 10.8 Black male, age 65-74 Not reported Not reported Not reported 18.9 Black male, age 75-84 Not reported Not reported Not reported 30.1 Black male, age >85 Not reported Not reported Not reported 6.7 White female, age 17-24 Not reported Not reported Not reported 1 White female, age 25-44 Not reported Not reported Not reported 2.2 White female, age 45-64 Not reported Not reported Not reported 7.4 White female, age 65-74 Not reported Not reported Not reported 12.4 White female, age 75-84 Not reported Not reported Not reported 13.5 White female, age >85 Not reported Not reported Not reported 6.9 White male, age 17-24 Not reported Not reported Not reported 1.1 White male, age 25-44 Not reported Not reported Not reported 2.5 White male, age 45-64 Not reported Not reported Not reported 9.4 White male, age 65-74 Not reported Not reported Not reported 17.3 White male, age 75-84 Not reported Not reported Not reported 19.8 White male, age >85 Not reported Not reported Not reported 17.5 

204
Evidence Table 4. Prevalence of spirometric categories: American Thoracic Society (ATS) or Global Initiative for Chronic Obstr

(GOLD) category criteria for smoking status

Variable / 

Country; Study

% Normal

Spirometry and No

Respiratory

Symptoms (n / N) 

% GOLD 0 or "At 

Risk" / Normal 

Spirometry + 

Symptoms of Cough, 

Sputum (n / N) 

% GOLD 1 or Mild -

FEV1/FVC <70 and

FEV1 >80%

Predicted) (n / N) 

% ATS 1 or GOLD 2 

or "Moderate" / 

FEV1/FVC <70 and

FEV1 >50 to 80-85%

Predicted) (n / N) 

% ATS 2 or 3 or GO

>3 or "Severe" 

FEV1/FVC <70 an

FEV1 <50% Predict

(n / N) 

National Health and Nutrition Examination Survey-NHANES I150Current smoker 56.9 (1,321 / 2,323) 21.3 (494 / 2,323) 

(see notes) 

9.2 (213 / 2,323) 10.6 (247 / 2,323) 2.1 (48 / 2,323) 

Previous smoker 66.1 (734 / 1,110) 15.8 (175 / 1,110) 

(see notes) 

8.6 (96 / 1,110) 7.3 (81 / 1,110) 2.2 (24 / 1,110)

Never smoker 79.3 (1,672 / 2,109) 10.6 (223 / 2,109) 

(see notes) 

6.2 (130 / 2,109) 3 (64 / 2,109) <1 (20 / 2,109)

European Community Respiratory Health Survey157

Current smoker 75.8 (4,135 / 5,455) 19.1 (1,044 / 5,455) 5.1 (276 / 5,455) see note see note Previous smoker 89 (2,727 / 3,065) 7.6 (233 / 3,065) 3.4 (105 / 3,065) see note see note Never smoker 92 (5,705 / 6,203) 7.6 (469 / 6,203) <1 (29 / 6,203) see note see note Copenhagen City Heart Study149Current smoker 75.6 (6,265 / 8,255) 7.2 (597 / 8,255) 5.5 (457 / 8,255) 11.1 (916 / 8,255) <1 (20 / 8,255)

Previous smoker 83.4 (1,879 / 2,253) 4.4 (100/ 2,253) 4.7 (107 / 2,253) 6.9 (156 / 2,253) <1 (11 / 2,253)Never smoker 88.3 (2,297 / 2,600) 2.7 (69 / 2,600) 3.8 (99 / 2,600) 5.1 (133 / 2,600) <1 (2 / 2,600) 

205
Evidence Table 5. Losses to followup 

Study Group Length of

Followup

(months) 

N 

(# randomized) 

Loss to

Followup (n) 

Loss to

Followup (%) 

Segnan et al., 199179 All participants 12 923 120 13% 

Risser et al., 199080 Control 12 45 3 7%

Intervention 12 45 9 20%

Sippel et al., 199981 Control 9 102 19 18.6%

Intervention 9 103 13 12.6%

Richmond et al., 198582 Control 36 100 23 23%

Intervention 36 100 15 15%

Rose et al., 197884 Control 36 731 220 30%

Intervention 36 714 258 36%

Humerfelt et al., 199883 Control 12 1,310 109 8%

Intervention 12 1,300 219 17%

Li et al., 1984*85 All participants 11 579 129 22% 

Total 6,052 1,137 19%

* In study by Li et al, the results of three participants were not included in the final results as it was uncertain which 

treatment had been received.

206 
207

Evidence Table 6. Characteristics of studies of long-acting 

β2 agonists for COPD using spirometry 

Study 

(Reference) 

Study 

Duration 

Intervention(s), 

Dose Per Day; 

Control(s) 

Baseline FEV1

(L); % Predicted 

of Normal 

Description of Subjects/Inclusio

Calverly et al, 200388 1 year 1) Formoterol 4.5 ug b.i.d. (n=171) 

2) Budesonide 200 

ug, b.i.d. (n=257 

3) Formoterol 4.5ug 

+ Budesonide 160 ug, b.i.d. (n=254) 

4) Placebo (n-256) 

1) 1.00, 36% 2) 0.99, 36% 3) .98, 36% 4) 0.98, 36% 

Worldwide 15 countries, 75% men and 25% women); m

pack years = 39; Medication at enrollment: oral/inhaled β agonists = 50%, long acting β agonists = 29%, xanth

1) both genders at least 40 years old, with diagnosis o

4 with symptoms for more than 2 years) 

2) current or ex-smokers with smoking history of ≥10 p

3) FEV1/FVC ratio ≤70% 

4) FEV1 50% of the predicted normal 

5) ≥1 COPD exacerbation requiring a course of oral co

antibiotics 2-12 months before first clinic visit. 

Brusasco et al., 200389

6 months 1) Tiotropium 18 ug 

q.d. (n=402) 

2) Salmeterol 50 ug, 

b.i.d. (n=405) 

3) placebo (n=400) 

1) 1.12 (0.39), 

39% 

2) 1.07 (0.38), 

38% 

3) 1.09 (0.40), 

39% 

European, Canadian (18 countries) men and women (2

years = 44. 

1) relatively stable airway obstruction with FEV1 ≤65% 

≤70% of FVC 

2) over 40 years of age 3) with smoking history of >10 pack years. 

Calverley et al., 

200387 1 year 1) Salmeterol 50 ug, b.i.d. (n=372) 

2) Fluticasone 

50ug, b.i.d.(n=374) 

3) Salmeterol 50 ug 

+ Fluticasone 500 ug, b.i.d. (n=358) 

4) placebo (n=361) 

1) 1.25 (0.45), 

44% 

2) 1.26 (0.45), 

45% 

3) 1.31 (0.53), 

45% 

4) 1.27 (0.47), 

44% 

European et al. (25 countries) men and women (28%); 

smokers = 51%, pack years = 43. 

1) baseline FEV1 before bronchodilation that was 25-7

increase of less than 10% of predicted FEV1 30 min

salbutamol, and a prebronchodilator FEV1/FVC ratio 

2) at least 10 pack-years of smoking 3) of chronic bronchitis, at least one episode of acute 

per year in the previous 3 years 

4) at least one exacerbation in the year immediately b

treatment with oral corticosteroids, antibiotics, or bo

Celli et al., 

200390

3 months 1) Sibenadet 500 ug, 

t.i.d. (n=543) 

2) Salmeterol 50 ug, 

b.i.d. (n=554) 

3) placebo (n=271) 

1) 1.32 (0.48), 

42% 

2) 1.30 (0.46), 

42% 

3) 1.35 (0.50), 

44% 

Worldwide 15 countries (75% men and 25% women); C

Oriental (2%), Others (1%); mean age 64 (range 35-80Medication at enrollment: oral/inhaled steroids = 54%, 

55%, long acting β-agonists = 25%, xanthines 22%. 

1) both genders ranging in age from 40 to 80 years, w

symptoms for more than 2 years) 

2) current or ex-smokers with smoking history of ≥15 p

3) FEV1/FVC ratio ≤65% 

4) FEV1 20-70% of the predicted normal 5) FEV1 reversibility to 400 ug salbutamol of ≤15% or 

(Breathlessness, cough, and sputum scale) (1) 5.28
E

vidence Table 6. Characteristics of stu

dies of long-actin

g

β2 agonists for COPD using s

pirometry (continued) 

208

Study

(Reference) 

Study

Duration 

Intervention(s), 

Dose Per Day;

Control(s)

Baseline FEV1

(L); % Predicted 

of Normal 

Description of Subjects/Inclusio

Hanania et al., 

200391

6 months 1) Salmeterol 50 ug, 

b.i.d. (n=177) 

2) Fluticasone 250

ug, b.i.d. (n=183) 

3) Salmeterol 50 ug 

+ Fluticasone 250 ug b.i.d. (n=178) 

4) placebo (n=185) 

1) 1.25 (0.43), 

42% 

2) 1.31 (0.44), 

42% 

3) 1.25 (0.40), 

41% 

4) 1.29 (0.43), 

42% 

American men and 

women (37%), White (93%), Black 

mean age 64 (range 40-87); Current smokers = 47%, Concurrent theophylline use = 11%; Emphysema 67%

1) ≥40 years of age 2) current or former smokers 

with ≥20 pack-year histo

3) diagnosis of COPD by ATS 4) baseline F

E

V1/FVC ratio of ≤70% and baseline F

E

normal, but >0.70 L (or if ≤0.70 L, then >40% of pre

5) symptoms of chronic bronchitis and moderate dysp

Szafranski et al., 

200392

1 year 1) Formoterol 4.5 ug 

b.i.d.(n=201) 

2) Budesonide 200

ug, b.i.d. (n=198) 

3) Formoterol 4.5 

ug + Budesonide 160 ug, b.i.d. (n=208) 

4) placebo (n=205) 

1) 1.00; 36% 2) 1.01; 37% 3) 0.96; 36% 4) 0.98; 36% 

Multinational (11 countries) men and 

women (21%); m

Current smokers = 34%, pack years = 45; Previous us13%, short acting β agonists = 34%, long acting β ago

combined inhaled β agonists/anticholinergic 11%. 

1) adults 

with moderate-to-severe COPD (in line with G

diagnosis, management and prevention of C

OPD) 

2) outpatients aged ≥40 yrs 3) COPD symptoms for ≥2 years 4) ≥10 pack-years smoking history5) FE

V1/FVC ≤70% 

6) FE

V1 ≤50% predicted normal (stages IIB and III acc

classification) 

7) total symptom score (including shortness of breath, 

night-time a

wakenings; each symptom scored 0-4) 

days of the run-in period 

8) documented use of short-acting inhaled bronchodila

9) ≥1 severe C

OPD exacerbation 

within 2-12 month

Aalbers et al., 

200293

3 months 1) Formoterol 4.5 ug, 

b.i.d. (n=171) 

2) Formoterol 9 ug, 

b.i.d. (n=166) 

3) Formoterol 18 ug, 

b.i.d. (n=177) 

4) placebo (n=173) 

1) 1.44, 53% 2) 1.49, 54% 3) 1.51, 55% 4) 1.47, 54% 

European (9 countries) men and 

women (32%); mean 

Current smoker = 47%. 

1) male and female aged 50-80 years, 

with clinical dia

2) current or former smokers 

with smoking history of a

3) prebronchodilator F

E

V1 > 0.7 L and 40-70% of pred

4) FE

V1/FVC ratio <89% pred normal for females and 

5) total symptom score (night-ti

me sleep disturbance, 

chest tightness; each symptom scored 0-4) had to b

run-in period / total symptom score 5.63 (sleep distu2.56; cough 2.27; chest tightness 1.91). 
E

vidence Table 6. Characteristics of stu

dies of long-actin

g

β2 agonists for COPD using s

pirometry (continued) 

209

Study

(Reference) 

Study

Duration 

Intervention(s), 

Dose Per Day;

Control(s)

Baseline FEV1

(L); % Predicted 

of Normal 

Description of Subjects/Inclusio

Chapman et al., 

200294

6 months 1) Salmeterol 50 ug, 

b.i.d. (n=201) 

2) placebo (n=207) 

1) 1.19, 44% 2) 1.28, 46% 

European and Canadian (6 countries) men and 

women 

43%; Previous use corticosteroids = 61%, theophylline 

1) men and 

women 

with COPD aged 40 years or olde

written, informed consent 

2) taking anticholinergic agents (alone or as a combin

weeks 

3) history of smoking equivalent to at least 10 pack-ye4) sputum production on most days during at least thre

two consecutive years 

5) baseline (visits 1, 2, or 3) F

E

V1 85% or less of pred

6) baseline F

E

V1/FVC 70% or less of predicted

7) FE

V1 reversibility 5% to 15% of predicted, either by 

after inhalation of salbutamol at baseline or documereversibility after inhalation of a β2 agonist 

within pr

8) symptoms (daytime symptom scores 0-5; night-time 

least seven out of previous 14 day and night period

Donohue et al., 

200295

6 months 1) Salmeterol 50 ug, 

b.i.d. (n=213) 

2) 

Tiotropium 18 ug 

q.d. (n=209) 

3) placebo (n=201) 

1) 1.07 (0.37) 2) 1.11 (0.39) 3) 1.06 (0.36) 

European, American, and South African (12 countries) 

mean age 65; pack years = 47; Previous use β agonis

anticholinergics = 53%, steroids = 72%. 

1) relatively stable air

way obstruction 

with F

E

V1 ≤60% 

FEV1 ≤70% of FVC 

2) at least 40 years of age 3) 

with smoking history of >10 pack-years. 

Mahler et al., 

200296

6 months 1) Salmeterol 50 ug, 

b.i.d. (n=160) 

2) Fluticasone 500

ug, b.i.d. (n=168) 

3) Salmeterol 50 ug 

+ Fluticasone 500 ug b.i.d. (n=165) 

4) placebo (n=181) 

1) 1.24, 40% 2) 1.23, 41% 3) 1.27, 41% 4) 1.32, 41% 

American men and 

women (34%), White (93%), Black 

mean age 63 (range 40-90); Current smokers = 48%, Inhaled steroids use = 25%; Emphysema 76%. 

1) 40 years of age or older 2) current or former smokers 

with 20 pack-year or mor

3) diagnosis of COPD 4) baseline F

E

V1/FVC of 70% or less and baseline F

E

predicted but more than 0.70 L 

5) daily cough productive of sputum for 3 months of th

years and dyspnea. 
E

vidence Table 6. Characteristics of stu

dies of long-actin

g

β2 agonists for COPD using s

pirometry (continued) 

210

Study

(Reference) 

Study

Duration 

Intervention(s), 

Dose Per Day;

Control(s)

Baseline FEV1

(L); % Predicted 

of Normal 

Description of Subjects/Inclusio

Rossi et al., 

200297

1 year 1) Formoterol 12 

ug, b.i.d.(n=211) 

2) Formoterol 24 ug, 

b.i.d. (n=214) 

3) Oral slo

w-release 

theophylline 200/300 mg, b.i.d. (n=209) 

4) placebo (n=220) 

1) 1.36, 47% 2) 1.39, 47% 3) 1.33, 46% 4) 1.40, 49% 

European (13 countries) men and 

women (17%); mean 

1) male or female outpatients aged ≥40 years, with dia

either current or ex-smokers of >10 pack-years acc

2) FE

V1 <70% of the predicted value and ≥0.75 L, 

with 

of <88% of that predicted in men and <89% of that 

3) daytime and/or night-time symptoms (ability to perfo

breathlessness over the previous 24 hours, 

waking 

symptoms, breathlessness on rising, cough, and spsymptom scored 0-3) 

were to be present on at leas

period. 

Wadbo et al., 

200298

3 months 1) Formoterol 18 ug 

b.i.d. (n=61) 

2) Ipratropium 

bromide 80 ug,t.i.d. (n=62) 

3) placebo (n=60)

1) 33% 2) 34% 3) 33% 

S

wedish men and 

women (47%); mean age 64 (range 

28%. 

1) male and female outpatients, aged 40-75 years, cu

history of >10 pack-years and 

with a diagnosis of C

Respiratory Society

2) history of reduced exercise capacity due to dyspnea 3) FE

V1 <60% of predicted normal value and a quotien

4) the reversibility had to be <12% of predicted norma

inhalation of 120 ug ipratropium bromide via pressu27 ug formoterol via Turbuhaler given on t

wo separ

5) oxygen tension in arterial blood (Pa, O2) at rest the 

be >7.3 kPa. 

Dahl et al., 

200199

3 months 1) Formoterol 12 ug 

b.i.d. (n=194) 

2) Formoterol 24 ug 

b.i.d. (n=192) 

3) Ipratropium 

bromide 40 ug,t.i.d. (n=194) 

4) placebo (n=200) 

1) 1.33 (0.45), 

46% 

2) 1.31 (0.43), 

45% 

3) 1.29 (0.46), 

45% 

4) 1.29 (0.41), 

44% 

European and North American (11 countries) men and 

Current smokers = 47%, (mean) pack years = 43. 

1) male or female outpatients aged ≥40 years, with dia

to ATS guidelines, 

who 

were either current or ex-sm

gave 

written informed consent

2) FE

V1 <70% of predicted and >0.75 L, 

with the ratio 

of that predicted in men and <89% of that predicted 

3) daytime and/or nighttime symptoms (ability to perfo

breathlessness over the previous 24 hours, 

waking 

symptoms, breathlessness on rising, cough, and spsymptom scored 0-3) 

were to be present on at leas

period. 
E

vidence Table 6. Characteristics of stu

dies of long-actin

g

β2 agonists for COPD using s

pirometry (continued) 

211

Study

(Reference) 

Study

Duration 

Intervention(s), 

Dose Per Day;

Control(s)

Baseline FEV1

(L); % Predicted 

of Normal 

Description of Subjects/Inclusio

Rennard et al., 

2001100

3 months 1) Salmeterol 42 ug, 

b.i.d. (n=132) 

2) Ipratropium 36 ug, 

t.i.d. (n=138) 

3) placebo (n=135) 

1) 1.22 2) 1.28 3) 1.30 

American men and 

women (37%), White (94

%), Black 

age 63. 

1) at least 35 years of age 2) FE

V1 ≤65% of predicted and >0.70 L, 

with an F

E

V1

screening (or F

E

V1 ≥40% of predicted and <0.70 L) 

3) responsiveness to both inhaled albuterol and ipratro4) score at least 1 on the Modified Medical Research C

scale (0-4). 

van Noord et al., 

2000101

3 months 1) Salmeterol 50 ug, 

b.i.d. (n=47) 

2) Salmeterol 50 ug

(b.i.d.) + Ipratropium bromide 40 ug(q.i.d.) (n=47) 

3) placebo (n=50)

1) 1.20 (0.40), 

42% 

2) 1.20 (0.40 3) 1.20 (0.40, 

41% 

Dutch men and women (13%); mean age 64; Current s

β agonists = 100%, methylxanthines = 13%, anticholin= 85%, mucolytics = 32%. 

1) current or exsmokers 

with a smoking history equiva

COPD according to ATS criteria 

2) aged 40-75 years 3) no change in medication for COPD in the preceding 

changes in smoking habits during the last 6 months 

4) FE

V1 75% of predicted value after inhalation of 200 

dose inhaler (

MDI). 

Mahler et al., 

1999102

3 months 1) Salmeterol 42 ug, 

b.i.d. (n=135) 

2) Ipratropium 36 ug, 

q.i.d. (n=133) 

3) placebo (n=143) 

1) 42% 2) 37% 3) 41% 

American men and 

women (26%), White (91

%), Black 

Asian/Other (1%); mean age 63; Smoking (63 pack-yeemphysema 47%, both 29%. 

1) ≥35 years of age 2) ≥10 pack-year history of smoking 3) a diagnosis of COPD as defined by ATS 4) a baseline F

E

V1 ≤65% of the predicted normal valu

≥40% of predicted normal value) 

5) an F

E

V1/FVC ratio of ≤70%; 6) a baseline severity o

or higher on the modified Medical Research Counc

Jones and Bosh, 

199746

4 months 1) Salmeterol 50 ug, 

b.i.d. (n=94) 

2) Salmeterol 100

ug, b.i.d. (n=94)

3) placebo (n=95)

1) 1.40 (0.50), 

47% 

2) 1.40 (0.50), 

45% 

3) 1.30 (0.50), 

45% 

World

wide (17 countries) men and 

women (14%); mea

inhaled/oral steroids = 86%, methylxanthines 45%. 

1) ranging in age from 40 to 70 years 2) a baseline F

E

V1 of less than 70% predicted normal 

after 

withholding bronchodilator therapy for at least 

3) FE

V1/FVC ratio less than 60%

4) less than 15% reversibility of FEV1 follo

wing salbuta

inhaler or salbutamol 800 ug by breath-actuated de

5) daytime symptom scores of 2 or more, for at least 4 

in period using symptom scoring scheme (0-5). 
Evidence Table 6. Characteristics of studies of long-acting β2 agonists for COPD using spirometry (continued) 

212

Study

(Reference) 

Study

Duration 

Intervention(s), 

Dose Per Day;

Control(s)

Baseline FEV1

(L); % Predicted 

of Normal 

Description of Subjects/Inclusio

Boyd et al., 

1997103

4 months 1) Salmeterol 50 ug, 

b.i.d. (n=229) 

2) Salmeterol 100

ug, b.i.d. (n=218) 

3) placebo (n=227) 

1) 1.31 (0.51) 2) 1.23 (0.47) 3) 1.31 (0.53) 

European (18 countries) men and women (21%); mean 

Current smokers = 43%; Previous use inhaled/oral cormethylxanthines = 41%, anticholinergics = 19%, β ago

1) current or previous smokers aged 40-75 years, who 

most days during at least three consecutive months 

2) at or between Visits 1, 2, and 3, a measurement of 

normal and a FEV1/FVC ratio of ≤60% 

3) at Visits 1, 2, and 3 (or documented in the previous 

FEV1 of 5-15%, 15 minutes after inhalation of 400 oa metered-dose inhaler or DiskhalerTM inhaler, or 5 3 minutes at 8 L min-1 from a nebulizer 

4) daytime symptom score (scored 0-5; modified Medi

dyspnea scale) of ≥2 on at least 4 of the 7 days prio

Pooled summary Range 

 3 months 

– 1 year 

Total No. = 13,013 Range 

0.96 – 1.51; 33% - 55% 
213

Evidence Table 7. Characteristics of studies of tiotropium for COPD using spirometry 

Study Study

Duration 

Intervention(s), Dose 

Per Day; Control(s) 

Baseline FEV1 (L); % 

Predicted of Normal 

Description of Subjects / Inclusio

Brusasco et 

al., 200389

6 months 1) Tiotropium 18 ug 

q.d. (n=402) 

2) Salmeterol 50 ug 

b.i.d. (n=405) 

3) placebo (n=400) 

1) 1.12 (0.39), 39% 2) 1.07 (0.38) 3) 1.09 (0.40), 39% 

European, Canadian (18 countries) men and wom

64; pack years = 44. 

1) relatively stable airway obstruction with FEV1 ≤ 

normal and ≤ 70% of FVC 

2) over 40 years of age 3) with smoking history of >10 pack years. 

Casaburi et 

al., 2002104 1 year 1) Tiotropium 18 ug q.d. (n=550) 

2) placebo (n=371) 

1) 1.04 (0.41), 39% 2) 1.00 (0.44), 38% 

American and English men and women (35%); m

= 61; Previous use β agonists = 99%, theophyllin

anticholinergics = 56%, steroids = 49%. 

1) outpatients of either sex who were ≥40-years-

diagnosis of COPD by ATS 

2) at least 10 pack-year smoking history 3) clinically stable airway obstruction 4) FEV1 of ≤65% of predicted normal value and ≤

COPD symptom scores (wheezing, shortness of 

chest tightness). 

Donohue et 

al., 200295

6 months 1) Tiotropium 18 ug 

q.d. (n=209) 

2) Salmeterol 50 ug 

b.i.d. (n=213) 

3) placebo (n=201) 

1) 1.11 (0.39) 2) 1.07 (0.37) 3) 1.06 (0.36) 

European, American, and South African (12 coun

(25%); mean age 65; pack years = 47; Previous u

theophylline = 21%, anticholinergics = 53%, stero

1) relatively stable airway obstruction with FEV1 ≤ 

normal and FEV1 ≤ 70% of FVC 

2) at least 40 years of age 3) with smoking history of >10 pack-years. 

Vincken et al., 

2002105 1 year 1) Tiotropium 18 ug q.d. (n=356) 

2) Ipratropium bromide 

40 ug q.i.d. (n=179) 

1) 1.25 (0.43), 42% 2) 1.18 (0.37), 39% 

Dutch/Belgian men and women (15%); mean age 

years = 34; Previous use inhaled/oral β agonists 

16%, anticholinergics = 61%, inhaled/oral steroid

1) clinical diagnosis of COPD 2) FEV1 of ≤ 65% of the predicted normal value a

3) ≥ 40 years of age 4) smoking history of ≥10 pack-years. 

respiratory symptom (cough, sputum, dyspnea, o

van Noord et 

al., 2000106

3.3 months 1) Tiotropium 18 ug

q.d. (n=191) 

2) Ipratropium 40 ug 

q.i.d. (n=97) 

1) 1.24 (0.41), 42% 2) 1.19 (0.35), 40% 

Dutch men and women (16%); mean age 64; pac

use inhaled β agonists = 69%, theophylline = 14%

55%, inhaled/oral steroids = 86%. 

1) clinical diagnosis of COPD according to the AT2) stable airways obstruction with FEV1 of < 65% 

FEV1 to FVC of < 70% 

3) age at least 40 years 4) current or previous smokers (≥ 10 pack-years) 

Pooled summary 

Range 3.3 months - 1 year 

Total No. = 3,574 Range 

1.04 - 1.25; 38% - 42% 
E

vidence Table 8. Characteristics of stu

dies of ipratro

pium for COPD usin

g spiro

metr

y

214

Study

Stud

y

Duration 

Intervention(s), 

Dose Per Day;

Control(s)

Baseline FEV1 (L); 

% Pre

dicted of 

Normal 

Description of Subjects / Inclusion C

Vincken et al., 

2002105 1 year 1) Ipratropium bromide 40 ug 

q.i.d. (n=179) 

2) Tiotropium 18

ug q.d. (n=356) 

1) 1.18 (0.37), 39%2) 1.25 (0.43), 42%

Dutch/Belgian men and 

women (15

%); mean age 64 (rang

34; Previous use inhaled/oral β agonists = 81%, theophyl

anticholinergics = 61%, inhaled/oral steroids = 90%. 

1) clinical diagnosis of COPD 2) FE

V1 of ≤65% of the predicted normal value and ≤70

% 

3) ≥40 years of age 

4) smoking history of ≥10 pack-years. respiratory symptom (cough, sputum, dyspnea, or 

wheeze

Wadbo et al., 

200298

3 months 1) Ipratropium 

bromide 80 ug t.i.d. (n=62) 

2) Formoterol 18 

ug b.i.d. (n=61) 

3) placebo 

(n=60) 

1) 34% 2) 33% 3) 33% 

S

wedish men and 

women (47%); mean age 64 (range 47-

28%. 

1) male and female outpatients, aged 40-75 years, curren

history of >10 pack-years and 

with a diagnosis of COPD 

Respiratory Society

2) history of reduced exercise capacity due to dyspnea on 3) FE

V1 <60% of predicted normal value and a quotient F

4) the reversibility had to be <12% of predicted normal val

inhalation of 120 ug ipratropium bromide via pressurizeor 27 ug formoterol via Turbuhaler given on two separaapart 

5) oxygen tension in arterial blood (Pa, O2) at rest the sec

to be > 7.3 kPa. 

Dahl et al., 200199 3 months 1) Ipratropium 

bromide 40 ug t.i.d. (n=194) 

2) Formoterol 12 

ug b.i.d. (n=194) 

3) Formoterol 24 

ug b.i.d. (n=192) 

4) placebo 

(n=200) 

1) 1.29 (0.46), 45%2) 1.33 (0.45), 46%3) 1.31 (0.43), 45%4) 1.29 (0.41), 44%

European and North American (11 countries) men and 

wo

64; Current smokers = 47%, (mean) pack years = 43. 

1) male or female outpatients aged ≥40 years, with diagno

to ATS guidelines, 

who 

were either current or ex-smoke

and gave 

written informed consent 

2) FE

V1 <70% of predicted and >0.75 L, 

with the ratio F

E

V

88% of that predicted in men and <89% of that predicte

3) daytime and/or nighttime symptoms (ability to perform u

breathlessness over the previous 24 hours, 

waking at n

symptoms, breathlessness on rising, cough, and sputum symptom scored 0-3) 

were to be present on at least 4 o

period. 
E

vidence Table 8. Characteristics of stu

dies of ipratropium for COPD using s

pirometry (continued) 

215

Study

Stud

y

Duration 

Intervention(s), 

Dose Per Day;

Control(s)

Baseline FEV1 (L); 

% Pre

dicted of 

Normal 

Description of Subjects / Inclusion C

Rennard et al., 

2001100

3 months 1) Ipratropium 36 

ug t.i.d. (n=138) 

2) Salmeterol 42 

ug b.i.d. (n=132) 

3) placebo 

(n=135) 

1) 1.28 2) 1.22 3) 1.30 

American men and 

women (37%), White (94

%), Black (5%

age 63. 

1) at least 35 years of age 2) FE

V1 ≤ 65% of predicted and >0.70 L, 

with an F

E

V1/FV

screening (or F

E

V1 ≥ 40% of predicted and < 0.70 L) 

3) responsiveness to both inhaled albuterol and ipratropiu4) score at least 1 on the Modified Medical Research Cou

scale (0-4). 

van Noord et al., 

2000106

3.3 months 1) Ipratropium 

40 ug q.i.d. (n=97) 

2) 

Tiotropium 18 

ug q.d. (n=191) 

1) 1.19 (0.35); 40%2) 1.24 (0.41); 42%

Dutch men and women (16%); mean age 64; pack years = 

inhaled β agonists = 69%, theophylline = 14%, anticholineinhaled/oral steroids = 86%. 

1) clinical diagnosis of COPD according to the ATS criteria 2) stable airways obstruction with F

E

V1 of <65% predicted 

FVC of <70% 

3) age at least 40 years 4) current or previous smokers (≥10 pack-years). 

van Noord et al., 

2000101

3 months 1) Ipratropium 

bromide 40 ug (q.i.d.) + Salmeterol 50 ug (b.i.d.) (n=47) 

2) Salmeterol 50 

ug b.i.d. (n=47) 

3) placebo 

(n=50) 

1) 1.20 (0.40); 41%2) 1.20 (0.40); 42%3) 1.20 (0.40, 41%

Dutch men and women (13%); mean age 64; Current smo

use β agonists = 100%, methylxanthines = 13%, anticholincorticosteroids = 85%, mucolytics = 32%. 

1) current or exsmokers 

with a smoking history equivalen

COPD according to ATS criteria 

2) ages 40-75 years 3) no change in medication for COPD in the preceding 6 

w

changes in smoking habits during the last 6 months 

4) FE

V1 ≤75% of predicted value after inhalation of 200 ug 

dose inhaler (

MDI). 

Mahler et al., 

1999102

3 months 1) Ipratropium 36 

ug q.i.d. (n=133) 

2) Salmeterol 42 

ug b.i.d. (n=135) 

3) placebo 

(n=143) 

1) 37% 2) 42% 3) 41% 

American men and 

women (26%); White (91

%), Black (7%

Asian/Other (1%); mean age 63; Smoking (63 pack-years24%, emphysema 47%, both 29%. 

1) ≥35 years of age 

2) ≥10 pack-year history of smoking 

3) a diagnosis of COPD as defined by ATS 4) a baseline F

E

V1 ≤ 65% of the predicted normal value a

L, ≥40% of predicted normal value) 

5) an F

E

V1/FVC ratio of ≤70% 

6) a baseline severity of breathlessness of grade 1 or high

Medical Research Council dyspnea scale
E

vidence Table 8. Characteristics of stu

dies of ipratropium for COPD using s

pirometry (continued) 

216

Study

Stud

y

Duration 

Intervention(s), 

Dose Per Day;

Control(s)

Baseline FEV1 (L); 

% Pre

dicted of 

Normal 

Description of Subjects / Inclusion C

COMBIVENT 

Inhalation Study Group, 1997109

3 months 

(85 days) 

1) Ipratropium 

bromide 0.5 mg q.i.d. (n=214) 

2) Albuterol 

sulfate 3.0 m

g

q.i.d. (n=216) 

3) Combination 

(IB 0.5 mg +Albuterol 3.0mg), q.i.d. (n=222) 

1) 0.91 2) 0.91, 34% 3) 0.92, 35% 

American men and 

women (35%); White (93

%), Black (6%

age 65 (41-86). 

1) diagnosis of COPD 

who 

were at least 40 years old 

2) smoking history of at least 10 pack-years 3) stable airway obstruction 

with F

E

V1 ≤65% predicted no

4) taking at least two prescribed therapeutic agents for con

symptoms for at least 3 months before participation in t

LUNG HEALT

H

STUDY 

Anthonisen et al., 

199419

5 years 1) Ipratropium 

bromide t.i.d. plus smoking intervention (n=1961) 

2) smoking 

intervention and placebo (n=1962) 

3) Usual Care 

(no intervention) (n=1964) 

American men and 

women smokers, aged 35 to 60 years 

thought to be at high risk for C

OPD (spirometric signs of e

FEV1/FVC <70% 

with an F

E

V1 bet

ween 55 to 90%. 

1) Smoking defined as ≥10 cigarettes on at least 1 day du

preceding 1st screening visit 

COMBIVENT 

Inhalation Aerosol StudyGroup, 1994108

3 months  (85 days) 

1) Ipratropium 21 

ug t.i.d. 

(n=179) 

2) Albuterol 100 

ug t.i.d. 

(n=173) 

3) Combination 

(IB 21 ug +Albuterol 120 ug), t.i.d. (n=182) 

1) 1.00, 37% 2) 0.99, 37% 3) 1.00, 37% 

American men and 

women (35%); White (94

%), Black (5%

age 63 (40-88); Previous use inhaled β agonists = 93%, o

theophylline = 81%, anticholinergics = 43%, inhaled/oral s

1) diagnosis of COPD 

who 

were at least 40 years of age 

2) relatively stable, moderately severe airway obstruction 

predicted normal and FEV1 ≤70% of F

VC 

3) smoking history of more than 10 pack-years 4) regularly using at least t

wo prescribed therapeutic agen

COPD symptoms during the 3-month period immediateconsideration for entry into this trial. 

Pooled summary Range 

3 months 

(85 days) - 1 year 

Total No. = 9,819 Range 

0.91 - 1.33 

33% - 46% 
Evidence Table 9. Characteristics of studies of inhaled corticosteroids for COPD using spirometry

217

Study Study

Duration 

Intervention(s), 

Dose Per Day;

Control(s)

Baseline FEV1 (L); 

% Predicted of 

Normal 

Description of Subjects / Inclusio

Calverly et al, 

200388

See Long-Acting β2 Agonists for details 

Calverley et al,

200387

See Long-Acting β2 Agonists for details 

Hanania et al, 

200391

See Long-Acting β2 Agonists for details 

Szafranski et al, 

200392

See Long-Acting β2 Agonists for details 

Mahler et al, 

200296

See Long-Acting β2 Agonists for details

van der Valk et

al, 200286

6 months 1) Fluticasone 500 ug 

b.i.d. (n=123) 

2) placebo (n=121) 

1) Post 1.78 (0.53)2) Post 1.69 (0.53), 

56% 

Dutch men and women (16%), mean age 64 years. C

pack years = 38; Mean number of exacerbations prevuse corticosteroids = 83%, β agonists = 56%. 

1) clinical diagnosis of stable COPD by ATS criteria 2) no history of asthma 3) no exacerbation in the month before enrollment 4) current or former smoker 5) age between 40 and 75 years6) baseline prebronchodilator FEV1 value of 25 to 80% 

7) prebronchodilator ratio FEV1 inspirator vital capacit

less 

8) reversibility of FEV1 postinhalation of 80 ug if ipratr

metered dose inhalator with Aerochamber 12% of p

9) thin layer chromatography greater than the thin lay

predicted minus 1.64 SD 

10) no maintenance treatment of oral steroids or antibio11) no medical condition with low survival or serious ps

cardiac insufficiency, alcoholism) 

12) absence of any other active lung disease (e.g., sar13) use of medication such as nasal corticosteroids, th

acetylcysteine, and all other bronchodilators was a

Burge et al., 

2000111

3 years 1) Fluticasone 500 ug 

b.i.d. (n=376) 

2) placebo (n=375) 

1) 1.25 (0.44), 50%2) 1.23 (0.47), 50%

English men and women (25%); mean age 64 years; 

pack years = 44; Previous use inhaled corticosteroids 

1) current or former smokers aged 40-75 years with n2) baseline FEV1 after bronchodilator was at least 0.8 

predicted normal, and the ratio of FEV1 to forced vi

70% 

3) previous use of inhaled and oral corticosteroids wa
Evidence Table 9. Characteristics of studies of inhaled corticosteroids for COPD using spirometry (continued) 

218

Study Study

Duration 

Intervention(s), 

Dose Per Day;

Control(s)

Baseline FEV1 (L); 

% Predicted of 

Normal 

Description of Subjects / Inclusio

LHS Research 

Group, 2000114

4.5 years 1) Triamcinolone 600 

ug b.i.d. (n=559) 

2) placebo (n=557) 

1) 2.16 (0.62), 65%2) 2.10 (0.64), 63%

North American men and women (37%), White (95%)56; Current smokers = 90%; Chronic bronchitis 11%, 8%. 1) previously Lung Health Study participants 2) 40 to 69 years of age with airflow obstruction3) a ratio of FEV1 to FVC of less than 0.70 and a valu

the predicted value 

4) current smokers or quit within the previous two yeaDaily cough and phlegm ≥3 months/year 35%, Daily cyear 58%, Dyspnea while walking up a slight hill or hufrom a cold 31%. 

Pauwels et al., 

1999115 3 years 1) Budesonide 400 ug b.i.d. (n=634) 

2) placebo (n=643) 

1) 2.53 (0.64), 77%2) 2.54 (0.64), 77%

European (9 countries) men and women (27%); mean = 39; Previous use β agonists = 38%. 1) 30 to 65 years of age if currently smoking at least 5 

smoked cigarettes for at least 10 years or a smokinyears

2) FEV1 after the use of bronchodilator - between 50% 

normal value, and ratio of prebronchodilator FEV1 t

than 70% 

3) increase in FEV1 after inhalation of 1 mg of terbuta

inhaler - less than 10% of the predicted normal valu

4) change in FEV1 between the end of the first 3-mon

phase and the end of the second - less than 15%. 

Vestbo et al., 

1999112 3 years 1) Budesonide (800 ug, 400 ug b.i.d.) 

for 6 mo and (400 ug, b.i.d.) for 30 mo (n=145) 

2) placebo (n=145) 

1) Post 2.36 (0.79), 

86% 

2) Post 2.39 (0.86), 

87% 

Denmark men and women (40%); mean age 59 years1) CCHS participants 2) age 30-70 years 3) FEV1/FVC ratio 0.7 or less 

4) FEV1 reversibility after inhalation of 1.0 mg terbutal

than 15% of prebronchdilator FEV1

5) FEV1 reversibility after 10 days of treatment with or

daily of less than 15% of prebronchdilator FEV1

6) informed consent. Chronic mucus hypersecretion 35%, wheeze with dys

Weir et al., 

1999117 2 years 1) Beclomethasone dipropionate (750 

ug for less than 50 kg) and (1000 ug for greater than 50 kg), b.i.d., (n=49) 

2) placebo (n=49)

1) 1.07, 40% 2) 1.13, 41% 

English men and women (26%); mean age 67 years; pack years = 55 1) clinical diagnosis with COPD 2) adult onset airflow obstruction with FEV1 < 70% pre

<65%. 
Evidence Table 9. Characteristics of studies of inhaled corticosteroids for COPD using spirometry (continued) 

219

Study Study

Duration 

Intervention(s), 

Dose Per Day;

Control(s)

Baseline FEV1 (L); 

% Predicted of 

Normal 

Description of Subjects / Inclusio

Bourbeau et al., 

1998116

6 months 1) Budesonide 800

ug b.i.d, (n=39)

2) placebo (n=40)

1) 0.91 (0.33), 36%2) 0.95 (0.30), 37%

Canadian men and women (22%); mean age 66 yearspack years = 51 1) age 40 years old or older 2) smokers or ex-smokers 3) no history of allergic asthma during childhood or as 4) absence of exacerbation in respiratory symptoms d

study

5) pre-bronchodilator FEV1 less than 65% of predicted 

0.65 

6) post-bronchodilator FEV1 less than 80% 

7) regular treatment with at least one bronchodilator 8) no inhaled corticosteroids in the previous month or 

previous two months 

9) absence of any other active lung disease 

10) absence of diabetes, active peptic ulcer disease, u

pressure, or congestive heart failure

11) absence of disease other than COPD that might int

(dyspnea, fatigue, emotion, and mastery). 

Paggiaro et al., 

1998113

6 months 1) Fluticasone 

propionate 500 mg b.i.d. (n=142) 

2) placebo (n=139) 

1) 1.60 (0.58), 59%2) 1.52 (0.62), 55%

European (13 countries), New Zealand, and South Afr(23%); mean age 63 years (range 49-75); Current smβ agonists = 38%, methylxanthines = 34%, anticholine1) ages between 50 and 75 years with COPD by Euro

Consensus Statement 

2) if current or ex-smokers, with a history of smoking e

pack-years and chronic bronchitis 

3) history of at least one exacerbation each year for th

required a visit to their doctor or hospital, a high exinvestigator, of experiencing an exacerbation durinperiod, a regular productive cough, a predicted FEV

FEV1 to forced vital capacity of 70% or less, and re

than 15% after inhalation of 400 ug or 800 ug salbuinhaler or Diskhaler, respectively

4) a reversibility in FEV1 of more than 15% but a volum

mL 

Pooled 

summary

Range  6 months 

- 4.5 years

Total No. = 4,136 Range 

0.91 - 2.53; 36% - 

77% or 86% (post) 
Evidence Table 10. Characteristics of studies of sibanet (D2-receptor/β agonist) for COPD using spirometry

220

Study Study

Duration 

Intervention(s), 

Dose Per Day;

Control(s)

Baseline FEV1 (L); 

% Predicted of 

Normal 

Description of Subjects / Inclusi

Celli et al., 

200390

3 months 1) Sibenadet 500 ug 

t.i.d. (n=543) 

2) Salmeterol 50 ug 

b.i.d. (n=554) 

3) placebo (n=271) 

1) 1.32 (0.48), 42%2) 1.30 (0.46), 42%3) 1.35 (0.50), 44%

Worldwide 15 countries, 75% men and 25% women; COriental (2%), Others (1%); mean age 64 (range 35-8Medication at enrollment: oral/inhaled steroids = 54%55%, long acting β agonists = 25%, xanthines 22%. 1) both genders ranging in age from 40 to 80 years, w

symptoms for more than 2 years) 

2) current or ex-smokers with smoking history of ≥15 3) FEV1/FVC ratio ≤65% 

4) FEV1 20-70% of the predicted normal 5) FEV1 reversibility to 400 ug salbutamol of ≤15% or 

Mean daily BCSS (Breathlessness, cough, and sputu

Hiller et al., 

2003118

13 months 1) Sibenadet 500 ug 

t.i.d. (n=290) 

2) placebo (n=145) 

1) 1.25 (0.53), 41%2) 1.25 (0.49), 41%

American men and women (43%), mean age 64 (rang41%, pack years = 60; Medication at enrollment: corti

= 26%; Combined β agonist/anticholinergic 22%. 1) male and female patients with stable, uncomplicate

at least 2 years)

2) ages 40-80 years with a smoking history of at least 3) FEV1/FVC ratio of ≤70% 

4) FEV1 20-70% of the predicted normal range.

Laursen et al, 

2003119

3 months 1) Sibenadet 500 ug 

t.i.d.(n=524) 

2) placebo (n=526) 

1) 1.20 (0.36), 39%2) 1.1 (0.46), 40% 

European (3 countries) men and women (27%), mean Current smoker = 46%, pack years = 51. 1) male and female patients, ages 40-80 years, with s

≥2 years) 

2) smoking history of at least 15 pack-years 3) pre- and post-bronchodilator FEV1/FVC ≤ 65% 

4) pre- and post-bronchodilator FEV1 20-70% of the pMean daily BCSS (Breathlessness, cough and sputum 

Laursen et al, 

2003119

6.5 months 1) Sibenadet 500 ug 

t.i.d. (n=591) 

2) placebo (n=578) 

1) 1.40 (0.49), 41%2) 1.20 (0.46), 40%

European (3 countries) men and women (26%), mean Current smoker = 53%, pack years = 39. 1) male and female patients, ages 40-80 years, with s

≥2 years) 

2) smoking history of at least 15 pack-years 3) pre- and post-bronchodilator FEV1/FVC ≤ 65% 

4) pre- and post-bronchodilator FEV1 20-70% of the pMean daily BCSS (Breathlessness, cough and sputum 

Pooled 

summary

Range: 

3 months - 

13 months 

Total No. = 4,022 Range 

1.20 - 1.40; 39% 

- 42% 
221

Evidence Table 11. Characteristics of studies of pulmonary rehabilitation (program) for COPD using spirometry 

Study Study

Duration 

Intervention(s), 

Dose Per Day; 

Control(s) 

Baseline FEV1 (L); 

% Predicted of 

Normal 

Description of Subjects / Inclusio

Ries et al., 

2003121 2 years Experimental maintenance 

intervention (n=87); control (standard care) (n=85) 

1.07 (0.43); 45% American men and women (46%); mean age 67 year

More details document wasn't supplied (referred to o

Brooks et al., 

2002122 1 year Enhanced followup (n=50); 

control (conventional followup) (n=59) 

0.71 (0.04); 32% Canadian men and women (41%); mean age 68 yea

1) severe stable COPD (FEV1 <40% predicted, FEV1

2) completion of inpatient or outpatient rehabilitation 3) nonsmoker for a minimum of 6 months 4) aged 49-85 years 

Finnerty et al., 

2001123

6 months Rehabilitation 

(6-week outpatientbased program) (n=50); control (n=50) 

0.99 (0.36); 41% English men and women (32%); mean age 70 years; 

1) long-standing airways disease, classified as COP

respiratory team at the hospital) 

2) had their therapy optimized, the role of oral or inha

nebulized bronchodilator therapy 

3) assessed as to their ability to comply with requirem

specifically time and travel commitments involved 

Griffiths et al., 

2000124 1 year Rehabilitation (6-week 

multidisciplinary program) (n=99); control (n=101) 

0.91 (0.38); 40% English men and women (40%); mean age 68 years; 

1) clinical diagnosis with chronic obstructive bronchit

chronic poorly reversible asthma or bronchiectasis 

2) FEV1, measured at a time of clinical stability, less 

with less than 20% reversibility in response to inha

3) no change in symptoms or medication for 2 month4) additional, non-obstructive but disabling pulmonar

the spirometric criteria 

Ringbaek et al., 

2000125

8 weeks Rehabilitation (8 

week program) (n=24); control (n=21) 

50% Denmark men and women (84%); mean age 63 year

51%; Previous use oral/inhaled steroid 89%. 1) stable COPD with FEV1/FVC ratio <70%, FEV1 >0

2) age <75 years 3) oxygen saturation without oxygen supply >90% 
Evidence Table 11. Characteristics of studies of pulmonary rehabilitation (

program) for COPD using spirometry (continued) 

222

Study

Stud

y

Duration 

Intervention(s), 

Dose Per Day;

Control(s)

Baseline FEV1 (L); 

% Pre

dicted of 

Normal 

Description of Subjects / Inclusio

Engstrom et al.,

1999126 1 year Rehabilitation (physiotherapy

program) (n=26); control (n=24) 

31% 

S

wedish men and 

women (48%); mean age 66 years

20%, pack-years = 38. 1) diagnosis of COPD (chronic obstructive disease; d

10 pack years of smoking; debut of symptoms aftedyspnea mainly elicited by exercise or infections; significant allergy)

2) age 45-75 years 3) F

E

V1 of <50% pred. after bonchdilation

4) PaO2 of >8 kPa 5) stable clinical condition 

Wedzicha et al., 

1998127

(Moderate) 

8 weeks Rehabilitation 

(exercise training and education for 8 weeks) (n=33); control (education) (n=33) 

0.95 (0.32); 37% English men and 

women (49

%); mean age 67 years 

1) history of COPD 2) F

E

V1 <70% predicted, with <15% reversibility to in

3) exercise capacity that 

was limited by dyspnea

4) clinical stability for at least 3 

weeks prior to recruit

exacerbation over this period 

5) medical treatment 

was optimized prior to entry an

the rehabilitation programs 

Wedzicha et al., 

1998127

(Severe) 

8 weeks Rehabilitation 

(exercise training and education for 8 weeks) (n=30); control (education) (n=30) 

0.87 (0.41); 38% English men and 

women (49

%); mean age 67 years 

1) history of COPD 2) F

E

V1 <70% predicted, with <15% reversibility to in

3) exercise capacity that 

was limited by dyspnea

4) clinical stability for at least 3 

weeks prior to recruit

exacerbation over this period 

5) medical treatment 

was optimized prior to entry an

the rehabilitation programs 

Pooled summary Range 

8 

weeks - 2 

years 

Total No. = 693 Range 

0.71 - 1.07; 31% - 

50% 
223

Evidence Table 12. Characteristics of studies of disease management, education, and followup studies for COPD with/without 

Study 

(Reference) 

Study 

Duration 

Intervention(s), 

Dose Per Day; 

Control(s) 

Baseline FEV1

(L); % Predicted 

of Normal 

Description of Subjects / Inclusion 

Bourbean et al., 

2003159 1 year Self-management (n=96) 

Placebo (n=95) 

Post 1.00 (0.33) Canadian men and women (45%); mean age 69 years

Previous use β agonists = 96%, methylxanthines = 29steroids = 85%. 

1) stable COPD (respiratory symptoms and medicatio

weeks before enrollment) 

2) at least 50 years of age 3) current or previous smoker (at least 10 pack-years4) FEV1 after the use of bronchodilator between 25% 

normal value and FEV1/FVC ratio less than 70% 

5) no previous diagnosis of asthma, left congestive he

disease, dementia, or uncontrolled psychiatric illne

6) no participation in respiratory rehabilitation program 7) no long-term care facility stays Dyspnea 48% 

Monninkhof et al., 

2003160 1 year Self-management education + 

fitness program (n=127) 

Control (n=121) 

Post 1.71 (0.56); 

56% 

Dutch men and women (32%); mean age 65 years; CPrevious use long acting β agonists = 37%, inhaled co1) clinical diagnosis of stable COPD by STS criteria 2) no history of asthma 3) no exacerbation in the month prior to enrollment 4) current or former smoker 5) ages 40-75 years 6) baseline prebronchodilator FEV1 25-80% predicted 

7) prebronchodilator ratio FEV1/inspiratory vital capac

8) reversibility of FEV1 postinhalation of 80 ug of iprat

metered dose inhalator with aerochamber ≤12% p

9) TLC greater than TLC predicted - (1.64xSD) 

10) no maintenance treatment of oral steroids or antibi11) no medical condition with low survival or serious ps12) absence of any other active lung disease (e.g. sarc

Hermiz et al., 

200239

3 months Education/enhanced 

followup (home visits by nurse) (n=84) 

Control (standard 

care) (n=93) 

No spirometry Australian men and women (53%); mean age 67 year

1) ages 30-80 years who attended or admitted hospit

departments) with COPD (identified from their recoparticipate in the study) 

2) provided with written consent about the study 
Evidence Table 12. Characteristics of studies of disease management, education, and followup studies for COPD with/without 

224

Study 

(Reference) 

Study 

Duration 

Intervention(s), 

Dose Per Day; 

Control(s) 

Baseline FEV1

(L); % Predicted 

of Normal 

Description of Subjects / Inclusion 

Weinberger et al., 

2002161 1 year Pharmaceutical care program group 

(n=185) 

Peak flows meter 

monitoring control group (n=130) 

Usual care control 

(n=138) 

No spirometry American men and women (66%); mean age 62 years

smokers 38%; Previous use sympathomimetics = 60%inhaled/systemic corticosteroids = 58%. 

1) filled a prescription for methylxanthines, inhaled co

oral sympathomimetics, et al. during the preceding 

2) reported having COPD as active problems 3) 18 years or older 4) received 70% or more of their medications from a s5) reported no significant impairment in vision, hearin

precluded participation 

6) did not reside in an institution (e.g., nursing home) 7) provided written informed consent 

Gallefoss and 

Bakke, 2000162 1 year Education (n=31) Control (n=31) 59% Norway men and women (50%); mean age 58 years; 

1) COPD between 18 and 70 years of age, not suffer

disease 

2) FEV1 ≥40% and ≤80% of predicted 

3) 32% patients were reversible to ipratropium bromid

Watson et al., 

1997163

6 months Self-management 

(use of Action Plan & booklet) (n=29) 

Control (usual care) 

(n=27) 

37% New Zealand men and women (46%); mean age 68 y

29%. 

1) COPD as major functionally limiting disease (defin

criteria) 

2) smoking history of greater than 10 pack-years 3) FEV1 less than 65% of predicted 

4) ratio of FEV1/FVC less than 70% 

5) current use of bronchodilator therapy 

Weinberger et al., 

1996164

6 months Primary care 

intervention (n=295) 

Control (n=288) 

No spirometry American men and women (2%); mean age 63 years; 

65%, Black (non-Hispanic) 27%, Other 8%. 1) patients hospitalized in the General Medicine Serv2) diagnosis of COPD that documented in medical re

index admission (because they are prevalent amonpatients with this disease are commonly readmittedreadmissions to treat this disease might be reducephysicians provided intervention to outpatients 
Evidence Table 12. Characteristics of studies of disease management, education, and followup studies for COPD with/without 

225

Study 

(Reference) 

Study 

Duration 

Intervention(s), 

Dose Per Day; 

Control(s) 

Baseline FEV1

(L); % Predicted 

of Normal 

Description of Subjects / Inclusion 

Littlejohns et al., 

1991165 1 year Education/enhanced followup (n=73) 

Control (n=79) 

45% English men and women (35%); mean age 63 years; 

1) ages 30-75 years 2) no other major disease 3) prebronchodilator FEV1 less than 60% predicted 4) stable state as judged by the patient and physician 

perceived need for change in medication for at learecruitment 

5) informed written consent (Most days) cough 48%, produce sputum 38%, short 

Cockcroft et al., 

1987166

8 months Enhanced followup 

(group visited by respiratory health worker) (n=42) 

Control (n=33) 

0.78 (0.31) English men and women (32%); mean age 70 years (

= 27%. 1) patients suffered from chronic respiratory disability 2) patients who had been admitted to hospital at leas

3 years and new patients who had been seen with

Pooled summary Range 

 3 months 

- 1 year 

Total No. = 1,997 Range 

 0.78 - post 1.71;  37% - 59% 
Evidence Table 13. Characteristics of studies of non invasive mechanical ventilation for COPD using spirometry

226

Study Study

Duration 

Intervention(s), 

Dose Per Day;

Control(s)

Baseline FEV1 (L); 

% Predicted of 

Normal 

Description of Subjects / Inclus

Jolliet et al., 

2003167 2 years Noninvasive pressure support ventilation 

(He/O2) (n=59) 

Control (Air/O2) 

(n=64) 

0.73 (0.36) Switzerland / Belgian men and women (42%); mea

At least two of these criteria1) worsening dyspnea during the last 10 days 2) respiratory rate of >25 breaths/minute 3) arterial pH <7.35 4) PaCO2 of >50 torr 5) PaO2 of <50 torr Dyspnea (Borg scale) points 4.7 

Ambrosino et al., 

2002168

6 months Noninvasive positive 

pressure ventilation (n=63) 

Control (n=34)

30% Italian men and women (29%); mean age 68 years

Patients known to be affected with COPD, accordi

high probability of the disease based on their clexamination, chest radiography, and, when avafunction test 

Pooled summary Range 

6 months - 

2 years 

Total No. = 220 Range 

 0.73; 30% 
229

Evidence Table 14. Outcomes of studies of long-acting 

β2 agonists for COPD using spirometry 

Study Intervention Exacerbations: Total

Subjects with >1 

Episode n/N (%) 

Exacerbations - Other/ 

Hospitalizations Due to 

COPD/ or Other 

Mortality: n/N (%) St Geo

Q

Use of oral steroid bursts in 

management of COPD; n/N % 

Change p

1) Salmeterol 50 ug 

(n=405) 

142/405 (35) 56/405 (13.8) 6/405 (1.5) 2.8 (0.7) 

Brusasco et al., 

200389

2) placebo (n=400) 156/400 (39) 58/400 (400) 5/400 (1.3) 1.5 (0.7) 1) Salmeterol 50 ug 

b.i.d. (n=372) 

8/372 (2.2) 

Mean rate per patient/year 1.04 Not reported 

Treatment 

combin

-1.1 (-2.2 

Calverley et al., 

200387

 placebo (n=361) 19/361 (5.3) 1.3 Not reported -2.2 (-3.3 

"Deterioration of COPD"; n/N % 

1) Salmeterol 50 ug 

b.i.d. (n=554) 

95/554 (17.1) 74/553 (13.4) 1/554 (<1) Change p

 -5.3 (0.8) 

Celli et al., 

200390

2) placebo (n=271) 59/271 (21.9) 51/268 (19) 2/271 (<1) -3.2 (1.1) 1) Salmeterol 50 ug 

b.i.d. (n=177) 

Not reported Not reported 0/177 Chronic R

Questiodifferen

2.0 (ns vs

Hanania et al., 

200391

2) placebo (n=185) Not reported Not reported 0/185 

Mean exacerbation rates/year Change p

1) Formoterol 4.5 ug 

b.i.d.(n=201) 

Not reported 1.84 6/201 (3) -3.6 

Szafranski et al, 

200392

2) placebo (n=205) Not reported 1.87 9/205 (4.4) -0.03 1) Formoterol 4.5 ug 

b.i.d. (n=171) 

Not reported "Deterioration of COPD"; n/N % 

7/171 (4.1) 

Not reported Not report

2) Formoterol 9 ug 

b.i.d. (n=169) 

Not reported 12/169 (7.1) Not reported Not report

3) Formoterol 18 ug 

b.i.d. (n=178) 

Not reported 18/178 (10.1) Not reported Not report

Aalbers et al., 

200293

4) placebo (n=173) Not reported 16/173 (9.2) Not reported Not report1) Salmeterol 50 ug 

b.i.d. (n=201) 

52/201 (26) Not reported Not reported Change p

-2.4 (12.7) 

Chapman et al., 

200294

2) placebo (n=207) 68/207 (33) Not reported Not reported -0.9 (12.2) 1) Salmeterol 50 ug 

b.i.d. (n=213) 

82/213 (38.5) Not reported 3/213 (1.4) Change p

-3.54 (p=0

Donohue et al, 

200295

2) placebo (n=201) 92/201 (45.8) Not reported 4/201 (2) -2.43 
E

vidence Table 14. Outco

mes of stu

dies of lon

g-acting 

β2 agonists for COPD using s

pirometry (continued) 

230

Study Intervention Exacerbations: Total

Su

bjects with >1

Episode n/N (

%) 

Exacerbations - Other/ 

Hospitalizations Due to 

COPD/ or Other 

Mortality: n/N (%) St Geo

Q

1) Salmeterol 50 ug 

b.i.d. (n=160) 

Not reported Discontinuations due to 

exacerbations; n/N % 

9/160 (5.6) 

0/160 Chronic R

Questiodifferen

3.8 (ns vs

Mahler et al., 

200296

2) placebo (n=181) Not reported 16/181 (8.8) 3/181 (1.7) 1) Formoterol 12 ug 

b.i.d.(n=211) 

34/211 (16.1) COPD hospitalizations (severe 

exacerbations)

10/211 (4.7) 

3/211 (1.4) Change p

-5.3 (p=0.

2) Formoterol 24 ug 

b.i.d.(n=214) 

31/214 (14.5) 5/214 (2.3) 1/214 (<1) -6.1 (p=0.

Rossi et al., 

200297

3) placebo (n=220) 39/220 17.7) 20/220 (9.1) 0/220 -1.9 1) Formoterol 18 ug 

b.i.d. (n=61) 

"Adverse Events 

related to COPD" 

23/61 (37.7) 

"Deterioration of COPD leading 

to 

withdra

wal"; n/N % 

3/61 (4.9) 

Not reported Change p

0.0% (95%

Wadbo et al., 

200298

2) placebo (n=60) 23/60 (38.3) 6/60 (10.0) Not reported 1.5% (95

%

COPD hospitalizations; n/N % 

1) Formoterol 12 ug 

b.i.d. (n=194) 

"COPD Adverse 

Events" - includesexacerbations

25/194 (12.9) 

2/194 (1) 0/194 

Treatment 

-5.06 (p<0

2) Formoterol 24 ug 

b.i.d. (n=192) 

37/192 (19.3) 2/192 (1) 0/192 -3.3 (-5.8 

(p=0.00

Dahl et al., 

200199

3) placebo (n=200) 37/200 (18.5) 4/200 (2) 0/2001) Salmeterol 42 ug, 

b.i.d. (n=132) 

38/132 (28.8) First exacerb

ation during 

week 1; n/N % 

6/132 (4.6) 

0/132 Chronic R

Questiogroup 

10.3 (p=0.

Rennard et al., 

2001100

2) placebo (n=135) 41/135 (30.4) 20/135 (14.8) 1/135 6.81) Salmeterol 50 ug, 

b.i.d. (n=47) 

11/47 (23) Discontinuations due to 

exacerbations; n/N % 

3/47 (6.4) 

van Noord et al., Not reported Not report

2000101

2) placebo (n=50) 18/50 (36) 4/50 (8.0) Not reported Not report1) Salmeterol 42 ug 

b.i.d. (n=135) 

28/135 (20.7) First exacerb

ation during 

week 1; n/N 

%

7/135 (5.2) 

0/135 Chronic R

Questio

7.1 (1.4) (

Mahler et al., 

1999102

2) placebo (n=143) 47/143 (32.9) 21/143 (14.7) 0/143 2.1 (1.3) 
Evidence Table 14. Outcomes of studies of long-acting β2 agonists for COPD using spirometry (continued) 

231

Study Intervention Exacerbations: Total

Subjects with >1

Episode n/N (%) 

Exacerbations - Other/ 

Hospitalizations Due to 

COPD/ or Other 

Mortality: n/N (%) St Geo

Q

1) Salmeterol 50 ug 

b.i.d. (n=94) 

Not reported Not reported Not reported Change p

-6.8 (13.2) 

2) Salmeterol 100 ug 

b.i.d. (n=94) 

Not reported Not reported Not reported R -2.3 (11.6) 

Jones and Bosh

199746

3) placebo (n=95) Not reported Not reported Not reported -1.4 (11.7) 1) Salmeterol 50 ug 

b.i.d. (n=229) 

Boyd et al., 47/229 (21) Not reported 1/229 (<1) Not report

1997103

2) Salmeterol 100 ug 

(n=218) 

54/218 (25) Not reported 0/218 Not report

3) placebo (n=227) 59/227 (26) Not reported 1/227 (<1) Not report
232

Evidence Table 15. Summary of outcomes for interventions for COPD using spirometry - long-acting β2 agonists 

Studies N Duration Long-Acting

β2 Agonists 

Events, % 

Placebo 

Events, % 

ARR % 

[95%CI] 

Relative Risk [95%CI] 

Exacerbations: SalmeterolBrusasco, 200389 805 6 months 35.1 39 -4 [-11 to 3] 0.90 [0.75 to 1.08] 

Calverley, 200387 733 1 year 2.2 5.3 -3 [-6 to 0] 0.41 [0.18 to 0.92] Celli, 200390 825 3 months 17.1 21.8 -5 [-10 to 1] 0.79 [0.59 to 1.05] Chapman, 200294 408 6 months 25.9 32.9 -7 [-16 to 2] 0.79 [0.58 to 1.07] Rennard, 2001100 267 3 months 28.8 30.4 -2 [-13 to 9] 0.95 [0.65 to 1.37] 

Mahler, 200296 341 6 months 5.6 8.8 -3 [-9 to 2] 0.64 [0.29 to 1.40] 

van Noord, 2000101 97 3 months 23.4 36 -13 [-31 to 5] 0.65 [0.34 to 1.23] 

Mahler, 1999102 278 3 months 20.7 32.9 -12 [-22 to -2] 0.63 [0.42 to 0.95] 

Boyd, 1997103 674 4 months 22.6 26 -3 [-10 to 4] 0.87 [0.66 to 1.15] 

Overall 4428 3 months - 1 year 19.7 24.5 -5 [-7 to -2] 0.81 [0.73 to 0.90] 

Exacerbations: FormeterolCalverley, 200388 511 1 year 28.6 30.9 -2 [-10 to 6] 0.93 [0.71 to 1.21] 

Aalbers, 200293 691 3 months 7.1 9.2 -2 [-7 to 3] 0.77 [0.44 to 1.35] 

Rossi, 200297 645 1 year 27.5 34.1 -7 [-14 to 1] 0.81 [0.64 to 1.03] Wadbo, 200298 121 3 months 37.7 38.3 -1 [-18 to 17] 0.49 [0.13 to 1.88] 

Dahl, 200199 586 3 months 16.1 18.5 -2 [-9 to 4] 0.87 [0.60 to 1.26] 

Szafranski, 200392 406 1 year 18.9 25.9 -7 [-15 to 1] 0.73 [0.51 to 1.06] 

Overall 2960 3 months - 1 year 19.0 25.4 -4 [-7 to -1] 0.79 [0.67 to 0.94] OVERALL 7388 3 months - 1 year 19.4 24.8 -4 [-6 to -2] 0.82 [0.76 to 0.90] 

Studies N Duration Long-Acting

β2 Agonists 

Events, % 

Tiotropium 

Events, % 

ARR Relative Risk (95%CI 

Exacerbations: Salmeterol vs. TiotropiumBrusasco, 200389 807 6 months 35.1 32.1 3 [-4 to 9] 1.09 (0.90 to 1.33) Mortality: Salmeterol

Brusasco, 200389 805 6 months 1.5 1.3 0 [-1 to 2] 1.19 [0.36 to 3.85] 

Celli, 200390 825 3 months 0.18 0.73 -1 [-2 to 1] 0.24 [0.02 to 2.69] 

Hanania, 200391 362 6 months 0 0 0 [-1 to 1] Not estimable 

Mahler, 200296 341 6 months 0 1.7 -2 [-4 to 1] 0.16 [0.01 to 3.10] 

Rennard, 2001100 267 3 months 0 0.74 -1 [-3 to 1] 0.34 [0.01 to 8.29] 

Mahler, 1999102 278 3 months 0 0 0 [-1 to 1] Not estimable Boyd, 1997103 674 4 months 0.22 0.44 0 [-1 to 1] 0.51 [0.03 to 8.08] 

Overall 3552 3 months - 6 months 0.39 0.77 0 [-1 to 1] 0.57 [0.27 to 1.22] 
Evidence Table 15. Summary of outcomes for interventions for COPD using spirometry - long-acting β2 agonists (continued)

233

Studies N Duration Long-Acting

β2 Agonists

Events, %

Tiotropium 

Events, %

ARR Relative Risk (95%CI 

Mortality: FormoterolCalverley 200388 511 1 year 5.1 2 3. [0 to 6] 2.61 [0.94 to 7.21] 

Szafranski, 200392 406 1 year 3 4.4 -1 [-5 to 2] 0.68 [0.25 to 1.88] 

Rossi, 200297 645 1 year 0.94 0 1 [0 to 2] 4.67 [0.25 to 86.33] 

Dahl, 200199 586 3 months 0 0 0 [-1 to 1] Not estimable 

Overall 2148 3 months - 1 year 1.8 0.6 1 [0 to 2] 1.52 [0.79 to 2.94] OVERALL 5700 3 months - 1 year 0.96 1.1 0 [0 to 1] 1.00 [0.62 to 1.62] 

Mortality: Salmeterol vs. TiotropiumBrusasco, 200389 807 6 months 1.5 0.0025 1.5 5.96 (0.72 to 49.25) 

Studies N Duration Long-Acting

β2 Agonists:

Mean Change

Placebo:

Change

Weighted Mean

Difference (95%CI) 

St George's Respiratory Questionnaire - Mean units of change: SalmeterolBrusasco, 200389 805 6 months -2.8 -1.5 Not applicable -1.30 [-3.24 to 0.64] 

Celli, 200390 825 3 months -5.3 -3.2 Not applicable -2.10 [-4.61 to 0.41] Chapman, 200294 408 6 months -2.4 -0.9 Not applicable -1.50 [-4.32 to 1.32] Jones, 199746 283 4 months -6.8 -1.4 Not applicable -5.40 [-8.96 to -1.84] Overall 2321 3 months - 6 months -2.06 [-3.32 to -0.80] 

St George's Respiratory Questionnaire - Mean units of change: Formoterol

Calverley 200388 511 1 year Not reported Not reported Not applicable -4.1 

Dahl, 200199 12ug 388 3 months Not reported Not reported Not applicable -5.1 [-7.6 to -2.6] 

Dahl, 200199 24ug 392 3 months Not reported Not reported Not applicable -3.4 [-5.9 to -0.9] Wadbo, 200298 121 3 months 0 1.5 Not applicable -1.5 [-4.61 to 1.61] 

Overall 1412 3 monthsOVERALL 3733 3 months - 6 months -1.98 [-3.15 to -0.81] 
Evidence Table 16. Outcomes of studies of sibanet for COPD using s

pirometry

246

Study Interv

ention Exacerbations: Total

Su

bjects With >1 Episode 

n/N (%) 

Exacerbations - Other/ 

Hospitalizations Due to 

COPD / or Other 

Mortality: n/N (%) St Geo

Q

Deterioration of COPD; 

n/N % 

Treatme

pbo; 

1) Sibenadet 500 ug 

t.i.d. (n=543) 

116/543 (21.4) 89/543 (16.4) 3/543 (<1) -4.2 (0.8 

Celli et al., 200390

2) placebo (n=271) 59/271 (21.9) 51/268 (19) 2/271 (<1) -3.2 (1.1 

Deterioration of COPD; 

n/N % 

1) Sibenadet 500 ug 

t.i.d. (n=290) 

125/290 (43.1) 73/290 (25.2); 12 

discontinued the study 

3/290 (1.0) "No not

bet

w

group

Hiller et al., 

2003118

2) placebo (n=145) 66/145 (45.5) 39/145 (26.9); 3

discontinued the study 

2/145 (1.4) 

Deterioration of COPD; 

n/N % 

1) Sibenadet 

(n=535) 

77/524 (14.7)  (IT

T population)

56/535 (10.5) 4/535 (<1) "No stat

differbet

w

group

Laursen et al., 

2003119

2) placebo (n=537) 94/526 (17.9) 

 (IT

T population)

64/537 (11.9) 3/537 (<1) 

Deterioration of COPD; 

n/N % 

Change 

1) Sibenadet 

(n=609) 

139/591 (23.5))  (IT

T population)

128/609 (21) 12/609 (2.0) -3.25 (p 

Laursen et al., 

2003119

2) placebo (n=594) 149/578 (25.8) 

 (IT

T population)

115/594 (19.4) 9/594 (1.5) -2.33 
Evidence Table 17. Summary of outcomes for interventions for COPD using spirometry – sibanet 

247

Studies N Duration Sibanet

Events, %

Placebo

Events, %

ARR %

[95% CI] 

Relative Risk

[95% CI] 

ExacerbationsCelli, 200390 814 3 months 21.4 21.8 0 [-6 to 6] 0.98 [0.74 to 1.30] 

Hiller, 2003118 435 1 year 43.1 45.5 -2 [-12 to 7] 0.95 [0.76 to 1.18] Laursen, 2003119

 Study 1 

1061 3 months 14.7 17.9 -3 [-8 to 1] 0.82 [0.62 to 1.08] 

Laursen, 2003119 Study 2 

1169 6.5 months 23.5 25.8 -2 [-7 to 3] 0.91 [0.75 to 1.12] 

OVERALL 3479 3 months - 1 year 23.5 24.2 -2 [-5 to 1] 0.91 [0.81 to 1.03] Mortality

Celli, 200390 814 3 months 0.55 0.74 0 [-1 to 1] 0.75 [0.13 to 4.45] 

Hiller, 2003118 435 1 year 1 1.4 0 [-3 to 2] 0.75 [0.13 to 4.44] Laursen, 2003119

 Study 1 

1072 3 months 0.75 0.56 0 [-1 to 1] 1.34 [0.30 to 5.95] 

Laursen, 2003119 Study 2 

1203 6.5 months 2 1.5 0 [-1 to 2] 1.30 [0.55 to 3.06] 

OVERALL 3524 3 months - 1 year 1.1 1 0 [-1 to 1] 1.14 [0.60 to 2.15] 

Studies N Duration Long-Acting

β2 Agonists:

Mean Change

Placebo:

Change

Weighted Mean

Difference (95%CI) 

St George's Respiratory Questionnaire - Mean units of change

Celli, 200390 814 3 months -4.2 -3.2 Not applicable -1.00 [-3.51 to 1.51] 

Laursen, 2003119

 Study 2 

1203 6.5 months -3.3 -2.3 Not applicable -1 

* For 130 subjects assessed on day 1 only** For 152 subjects assessed on day 1 only 
248

Evidence Table 18. Outcomes of studies of pulmonary rehabilitation (program) for COPD using spirometry 

Study Intervention Exacerbations -Other/

Hospitalizations Due to 

COPD / or Other 

Mortality: n/N (%) St. George’s Res

Chronic Respiratory 

Score at 12 month

Experimental maintenance 

intervention (n=87); 

Not reported 10/87 (11.5) 96.0 (21.3) / n=74 

Ries et al., 2003121

Control (standard care) 

(n=85) 

Not reported 10/85 (11.8) 95.9 (21.1) / n=64 

Brooks et al., Enhanced followup (n=50) 35 episodes Not reported No significant chang

2002122 Control (conventional 

followup) (n=59) 

33 episodes Not reported 

Treatment difference 

for each group 

Rehabilitation (6-week 

outpatient-based program) (n=50); 

Not reported Not reported -8.1 (95% CI -14.9 to 

n=24, p<0.02 vs. c

Finnerty et al., 

2001123

Control (n=50) Not reported Not reported 57.1 (3.0 SE), n=25 

Number of patients admitted to 

hospital 

Treatment difference 

score for each gro

Rehabilitation (6-week 

multidisciplinary program) (n=99) 

40 (p=0.98 vs. control) 6/99 (6.1) -4.8 (95 %CI -8.4 to 

n=93 

Griffiths et al., 

2000124

Control (n=101) 41 12/101 (11.9) 69 (13.3), n=89 

Discontinuations due to 

exacerbation of COPD; n/N % 

Treatment difference 

Rehabilitation (8 week 

program) (n=24) 

3/24 (12.5) Not reported 0.1 (95% CI -9.8 to 1

Ringbaek et al., 

2000125

Control (n=21) 0/21 Not reported 

Deterioration of COPD; n/N % Change per group 

Rehabilitation 

(physiotherapy program) (n=26) 

4/26 (15.4) non-compliers to 

treatment 

0/26 0.3 (2.2) ITT pop. / -0

(n=20) 

Engstrom et al., 

1999126

Control (n=24) 3/24 (12.5) 0/24 2.1 (2.9)

Treatment difference 

group 

Rehabilitation (exercise 

training and education for 8 weeks) (n=33) 

Not reported 0/33 -5.4 (95% CI -10.7 to 

Wedzicha et al., 

1998127

(Moderate) 

Control (education) (n=33) Not reported 1/33 4 (95% CI 1 to 7) 
Evidence Table 18. Outcomes of studies of pulmonary rehabilitation (program) for COPD using spirometry (continued) 

249

Study Intervention Exacerbations -Other/

Hospitalizations Due to 

COPD / or Other 

Mortality: n/N (%) St. George’s Res

Rehabilitation (exercise 

training and education for 8 weeks) (n=30) 

Wedzicha et al., Not reported 0/30 0.93 (95% CI -3.9 to 

1998127

(Severe) 

Control (education) (n=30) Not reported 1/30 2 (95% CI -1 to 5) 
250

Evidence Table 19. Outcomes of studies of disease management, education, and followup studies for COPD with/without spiro

Study Intervention Exacerbations: Total

Subjects With >1 

Episode n/N (%) 

Exacerbations – Other / 

Hospitalizations due to 

COPD / or Other 

Mortality: n/N (%) S

Qu

Acute exacerbations

(episode) of COPD 

COPD hospitalizations; n/N % Trea

12-m

Self-management 

(n=96) 

299 31/96 (32.3) 5/96 (5.2) -2.0 

Bourbean et al., 

2003159

Usual care (placebo) 

(n=95) 

362 48/95 (50.5) 9/95 (9.5) 

Trea

Self-management 

(n=127) 

Not reported Not reported 3/127 (2.4) -0.6 

Monninkhof et al., 

2003160

Control (n=121) Not reported Not reported 3/121 (2.5) 

Trea

Enhanced followup 

(n=84) 

Not reported Not reported 9/84 (10.7) 1.32 

Hermiz et al., 

200239

Control (n=93) Not reported Not reported 10/93 (10.8) 

Breathing-related hospital or 

ED visit (%) 

Pharmaceutical care 

program group (n=185) 

Not reported 22.9 Not reported Not 

Peak flows meter 

monitoring control group (n=130) 

Not reported 23.9 Not reported Not 

Weinberger et al., 

2002161

Usual care control 

(n=138) 

Not reported 23.2 Not reported Not 

COPD hospitalizations; n/N % Mea

Education (n=31) Not reported 0/31 Not reported 40.0 Control (n=31) Not reported 2/31 (6.5) Not reported 43.1 

Gallefoss and 

Bakke, 2000162

p-va

Visits to GP or PN; n/N (%) Mea

Self-management (use 

of Action Plan & booklet) (n=29) 

Not reported 3/29 (10.3) 0/29 39 (1

th

Watson et al., 

1997163

Control (usual care) 

(n=27) 

Not reported 2/27 (7.4) 0/27 39 (1

Number of readmissions per 

month; mean (SD) 

According to total 

study group 

Primary care 

intervention (n=295) 

Not reported 0.19 (0.3) 59/695 (8.5) Not 

Control (n=288) Not reported 0.14 (0.2) 47/701 (6.7) Not 

Weinberger et al., 

1996164

p=0.005
Evidence Table 19. Outcomes of studies of disease management, education, and followup studies for COPD with/without spiro

251

Study Intervention Exacerbations: Total

Subjects With >1

Episode n/N (%) 

Exacerbations – Other / 

Hospitalizations due to

COPD / or Other 

Mortality: n/N (%) S

Qu

Number (%) of admissions to 

hospital 

Sick

ch

Education/enhanced

followup (n=73)

Not reported 12 (18) 3/73 (4.1) 0.63 

Control (n=79) Not reported 14 (21) 9/79 (11.4) -0.4 

Littlejohns et al., 

1991165

p=0.80 p=0.Respiratory illness

hospitalizations; n/N % 

Enhanced followup 

(group visited byrespiratory health worker) (n=42)

Not reported 22/42 (52.4) 5/42 (11.9) Not 

Cockcroft et al, 

1987166

Control (n=33) Not reported 11/33 (33.3) 7/33 (21.2) Not 
Evidence Table 20. Prevalence of symptoms in LH-1 subjects at 3 years by baseline spirometry according to treatment assignm

Dyspnea (%) Cough and Sputum (%) Respiratory Ho

Baseline Spirometry

Ipratropium Placebo Usual Care Ipratropium Placebo Usual Care Ipratropium 

Stage 0 and Normal 31.1 26.6 34 11 12.5 22 0.32 

Stage 1 25.8 27.6 32.5 16.9 11.8 26 0.29 

Stage 2 34.5 36.1 38 15.3 18.5 27.8 0.71 

Totals 31 31.2 35.5 14.9 15 26 0.48 

There are only 3 patients in Stage 3 and not represented here *Per 100 patient years 

252