The CARE-COAD #2 Study

(The second Chronic Obstructive Airways Disease study)

Notes

1. Preliminary discussions with the COAD #1 investigators and other CARE members has led us to develop a protocol for COAD #2.
2. For ease in abbreviation, we shall use the term COAD to denote all of the following terms: Chronic Obstructive Airways Disease/Chronic Airflow Limitation/Chronic Obstructive Lung Disease/Chronic Obstructive Pulmonary Disease. It includes patients with underlying asthma and/or partial/complete reversibility with bronchodilators. We have found 41 patient characteristics that have been used to diagnose COAD. In our pilot study, we looked at a few of these (history of smoking, laryngeal height/descent and wheezing) to see how they related to simultaneous spirometry. In this study, we are continuing in our attempt to whittle the 41 items down to just the accurate and precise ones by looking at a few others.
3. Our definition of COAD is an FEV1 < 5^th percentile, and/or FEV1/FVC < 5^th percentile (but we will also analyse the results using other definitions such as FEV1/FVC < 70%, and % predicted FEV1).
4. The terms "spirometry" and "spirometrist" will be used to denote any measure of lung function, carried out by anyone with at least rudimentary training in the use of a simple (hand-held) or fancy (pulmonary function lab) device for measuring lung function. It is vital that the spirometrist is blind to the clinical examination (and that the clinician be blind to the results of spirometry). The hand-held spirometers should be checked by a local Pulmonary function Lab before the study.
5. Each participating investigator should take responsibility for finding out and adhering to their local policy for the ethics approval of this study. Where we work, formal ethics approval is not necessary, but this varies by site. In the rare (we hope!) case in which ethics approval is required only for examining normal patients, participants are encouraged to enter "known" and "suspected" patients while awaiting approval for the "normal group". (To save yourselves some time, you, might want to see about getting blanket approval for future studies).
6. This study will begin February 1, 1999 and will be completed by March 8, 1999. 

Study Questions

1. Among consecutive patients known^* by their examiners to have COAD, what is the accuracy (singly or in combination and validated against "blind" spirometry) of the following items?
   • smoking history (pack-years smoking history)
   • age
   • sex
   • forced expiratory time
   • wheeze

^* known: known to have an FEV1 < 5^th percentile and/or an FEV1/FVC <5^th percentile or < 0.7; or patient states they've been told they have COAD; or patient is taking inhaled bronchodilators and/or inhaled steroids AND PFTs are not completely normal between exacerbations.

2. Among consecutive patients not known but suspected^† by their examiners (or by their referring clinicians) to have COAD, what is the accuracy of these items?

^† suspected: satisfies none of the criteria for "known" COAD, but either is referred to you by a clinician for suspected COAD or you, at the conclusion of the history, think that it is clinically sensible to suspect COAD.

3. Among patients who are neither known nor suspected by their examiners to have COAD, what is the accuracy of these items?

Definition of Disease

1. We have asked our respirology colleagues to refer any "official" definitions to us.
2. Our literature search revealed a 1996 review of articles published in Chest and Thorax from July 1991 to July 1993 whose titles or summaries referred to "asthma", "chronic obstructive lung disease", or "chronic airflow obstruction". They found 11 different criteria, the most common of which was an FEV1/FVC < 0.7 (Quadrelli SA et al. Respiration 1996;63:131-6). However, The American Thoracic Society suggests that this is not an appropriate reference standard to use and suggests using an FEV1/FVC < 5^th percentile or an FEV1 < 5^th percentile (Am Rev Respir Dis 1991;144:1202-18). The British Thoracic Society suggests using % predicted FEV1. We will try various definitions based on FE1/FVC and FEV1 (again, regardless of whether the target disorder is asthma and/or is partially-reversible with bronchodilators).

Sampling of Investigators

1. Investigators will join the study as "teams" of 2 or more (either 2 clinicians or 1 clinician and 1 spirometrist) to enable the independent, blind comparison of the clinical findings with spirometry. However, solo clinicians can enrol in the study if they can arrange independent, blind spirometry for the day(s) of the study.
2. The clinical collaborators will be multinational.
3. The clinical collaborators will include clinicians working in 2 different practice settings:
   • First contact clinician seeing self-referred patients (primary care). Examples include Commonwealth GPs, Family Practitioners, U.S.-style General Internists, some Accident and Emergency clinicians, and others who provide first-contact primary care.
   • Second contact with patients referred by other clinicians. Examples include General Physicians, Geriatricians, and some Accident and Emergency Room clinicians who see patients referred to them by primary care clinicians.
4. Investigators will enrol AT LEAST 12 patients per participating clinician/team (4 patients with known COAD; 4 patients suspected of COAD; 4 neither known nor suspected).
5. Investigators will use email and internet for recruitment, data submission, presentation and discussion of study results, and generation of manuscripts.

Sampling of Study Patients

1. Patients will be admitted consecutively (i.e. consecutive eligible patients that the investigator sees in a time period specified by the investigator). For example, patients can be recruited on different clinic days but would still be considered consecutive, elgible patients.
2. Patients will be of 3 sorts:
   • "Known": patients known to have an FEV1 < 5^th percentile and/or an FEV1/FVC < 5^th percentile (or < 0.7); or patient states they've been told they have COAD (chronic bronchitis/emphysema); or patient is taking inhaled bronchodilators and/or inhaled steroids AND PFTs are not completely normal between exacerbations.
   • "Suspected": patients who satisfy none of the criteria for "known" COAD, but either are referred to participating clinicians for suspected COAD, or participating clinicians, after taking a history, think that it is clinically sensible to suspect COAD.
   • "Normal": patients neither known nor suspected of COAD.
Patients "known" or "suspected" of having COAD may have asthma as part of their presentation, and its status will be noted during the clinical examination.
3. "Known" and "suspected" patients can be enrolled during exacerbations of COAD (as long as there is independent, blind spirometry within 30 minutes of the exam, and is no bronchodilator treatment in between the exam and spirometry).
4. Exclusions:
   • patients who don't want to participate
   • patients with a terminal illness whose goals of therapy are comfort and dignity
   • patients < 50 years of age (no upper age limit)
   • patients whose respiratory distress is too severe to withhold bronchodilators until after spirometry
   • patients who are medically unstable from other causes (acute MI, on their way to ICU etc)
   • patients admitted for overdose
   • patients who are unable (due to cognition, level of consciousness, or language) to co-operate in either the exam or spirometry

Clinical Examination

1. Information will be collected on the following items:
   • age
   • sex
   • height (in cm and rounded up to nearest cm)
   • pack/years smoking history (calculated by multiplying the number of packs the patient smokes each day by the number of years the patient has smoked)
2. Forced Expiratory Time^*(time taken to exhale from the total lung capacity to the residual volume)
   • With the patient sitting upright, the patient is asked to take a deep breath in and to blow it out through his/her mouth as hard and as fast as possible
   • While the patient is exhaling, the clinician places the bell of the stethoscope over the trachea in the suprasternal notch and the duration of audible exhalation will be timed with a watch with a second hand to the nearest second
   • The clinician should provide encouragement to the patient until exhalation is complete:
     • "Take a deep breath in - as full as you can"
     • "Once you've taken this deep breath, blow out through your mouth as hard and as fast as you can"
     • "Keep blowing until your lungs are completely empty"
     • "Keep blowing, keep blowing, ..." (in a positive, encouraging tone of voice)
   • Practice runs can be done until the patient has learned the protocol
   • Two runs of the FET will be done and the fastest result will be recorded

^* Lal S et al. BMJ 1964;1:814-17

3. Wheezes
   • Listen on deep respiration over 4 spots on the patient - bilateral upper and lower back
   • Any expiratory wheeze (continuous adventitious lung sound^† ) heard in any of these spots is considered positive for wheezing
   • Auscultation can be performed on bare skin or through the patient's clothing but this should be noted on the data collection form

^† Sapira JD. The art and science of physical diagnosis. Urban & Schwarzenberg: Munich, 1990.

4. The duration of the clinical exam (which only includes the information obtained on history and the 2 physical exam manoeuvres) will be recorded.

Spirometers and Spirometry

1. The spirometer should provide FEV1 and FVC (PEFR is optional but insufficient by itself)
2. Any hand-held spirometers should be checked by a local Pulmonary Function Lab before the study
3. Spirometry will be carried out by standard protocol:
   • blind to the clinical exam results
   • done at least twice, with the higher result submitted
   • done with standardised encouragement:
     • "Take a deep breath in - as full as you can"
     • "As soon as you have filled your lungs, put the end of the tube in your mouth and blow the air out as hard and as fast as you can"
     • "Keep blowing until your lungs are completely empty"
     • "Keep blowing, keep blowing, etc..." (in a positive encouraging tone of voice)
4. Will be carried out within 30 minutes of the clinical exam, with no bronchodilators administered in between. The time taken to complete spirometry will be recorded.
5. Please note whether it was a poor spirometric effort by the patient. This assessment may be made using your clinical expertise or by your spirometer.

Data Recording and Submission

Data submission will be by an internet data collection system. Patient identity will be anonymous. Each investigator should have their own method of assigning patient ID numbers which should also be entered on the data collection sheets. To qualify for the study, each patient should have both a clinical exam data collection sheet and a spirometry data collection sheet.

Analyses

Reporting the Results and Rules for Credit, Co-Authorship and Acknowledgement

1. First analyses and draft reports will be sent only to participating investigators
2. After the investigators are satisfied with the analyses and reports, PowerPoint slides will be sent (electronically) to each investigator (for local presentation), and the study will be summarised on the Internet (in a fashion that will not jeopardise its publication in a journal)
3. Abstracts will be proposed and submitted to national and international meetings by mutual agreement with authorship that includes the phrase "on behalf of the CARE-COAD Study #2 Group"
4. Manuscripts will be submitted by mutual agreement with authorship that includes the phrase "on behalf of the CARE-COAD Study #2 Group"
5. Publications will include a list of all participants in descending order, who submitted usable data on 12 or more patients and all methodologists involved with the study