The CARE-COAD #3 Study (The third Chronic Obstructive Airways Disease study)
a multinational e-mail/web-based study
Copyright ©2003, CARE-COAD #3 THROAT
* Completed August 2003 *

1. For ease in abbreviation we shall use the term COAD to denote all of the following terms: chronic obstructive airways disease/chronic obstructive lung disease/chronic airflow limitation/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 this study we are attempting to look at some of the features that were found to be accurate in our previous studies.
2. 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).
3. 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 simple (handheld) 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 clinicians be blind to the results of spirometry). The handheld spirometers should be checked by a local pulmonary function lab before the study.
4. Each participating investigator should take responsibility for finding out and adhering to their local policy for the ethics approval of this study. Formal ethics approval 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.
5. This study will begin February 22, 2003 and will be completed by June 30, 2003.

1. Among consecutive patients known^* by their examiners to have COAD, what is the reliability and 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 on auscultation
• Maximum laryngeal height



^* known: known to have an FEV₁ < 5^th percentile and/or an FEV₁/FVC < 5^th percentile or < 0.7; or patient states that 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 and reliability of the above 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 and reliability of the above items?

We have asked our respirology colleagues to refer any 'official' definitions and have conducted a literature review on this topic. 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' or '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. As was done with COAD1 and COAD2, we will try various definitions based on FEV₁/FVC and FEV₁ (again regardless of whether the target disorder is asthma and/or is partially reversible with bronchodilators).

1. Investigators will join the study as teams of 2 or 3 (either 1 clinician and 1 spirometrist or 2 clinicians and 1 spirometrist) to enable the independent, blind comparison of the clinical findings with spirometry. However, solo clinicians can enroll 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 clinicians seeing self-referred patients (primary care). Examples include Commonwealth GPs, family practitioners, US-style general internists, some Emergency physicians, nurse practitioners and others who provide first-contact primary care.
• Second contact clinicians seeing patients referred by other clinicians. Examples include general internists, geriatricians, respirologists.
4. Investigators will enroll at least 12 patients per participating team (4 patients with known COAD, 4 patients suspected of COAD, 4 patients neither known nor suspected of COAD).
5. Investigators will use email and the Internet for recruitment, data submission, presentation and discussion of study results and generation of manuscripts.

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, eligible 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 that 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.
• Suspected: Patients who satisfy none of the criteria for 'known' COAD but either is 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 there 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 the ICU etc.)
   • Patients admitted for overdose
   • Patients who are unable (due to cognition, level of consciousness, or language) to cooperate in either the exam or spirometry
   • Patients enrolled in COAD1 or COAD2

1. Information will be collected on the following items:
   • Age
   • Sex
   • Height (in cm and rounded up to the 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 as 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 the 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 faster result will be recorded. Record if the FET is > 9 seconds

   ^*Lal S et al. BMJ 1964;1:814-7.

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 with the diaphragm of the stethoscope in any of these sports 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. Maximum laryngeal height (Please view video clip for details (please be patient as it is a large video - 4.2MB).
   • At end-inspiration with the patient sitting up, looking straight ahead and with hands relaxed in his/her lap, palpate the top of the thyroid cartilage which is readily identified by the notch on it superior edge.
   • The clinician's index finger is hooked over the thyroid cartilage and the rest of the fingers are used to measure the distance from the top of the thyroid cartilage to the sternal notch in fingerbreadths.
   • Convert these fingerbreadths to centimetres and record this distance. Record if the maximum laryngeal height is < 4 cm
5. If possible, the clinical exam will be repeated within 30 minutes of the first examination (and if no bronchodilators given in the interval) by a second clinician who will be blind to the results of the first examination and to the spirometry.

1. The spirometer should provide FEV₁ and FVC (PEFR is optional but insufficient by itself).
2. Any handheld 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 results of the clinical exam
   • Done at least twice with the higher result recorded
   • Done with the 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...' (in a positive, encouraging tone of voice)
4. Will be carried out within 30 minutes of the clinical examination, 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.

This process will be streamlined and simple, with ticks for as many items as possible. The forms can be downloaded as an Adobe PDF file by clicking here.  Please keep a copy of your completed data forms in case the journal to which we submit the publication would like random checks done on them.

Data submission will be by an Internet data collection system. Patient identify will be anonymous. Each investigator should have their own method of assigning patient ID numbers that 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.

Simple analyses will follow the approaches outlined in the JAMA 'Primer' (JAMA 1992;267:2638-44). We will also do multivariate analyses looking for combinations of symptoms and signs. Early returns will serve as 'training' sets and later returns as 'test' sets for more complex combinations of findings.

1. First analyses and draft reports will be sent only to participating investigators.
2. After the investigators are satisfied with the analyses and reports, the manuscript will be submitted to an appropriate 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#3 Study Group'.
4. Manuscripts will be submitted by mutual agreement with authorship that includes the phrase 'on behalf of the CARE-COAD#3 Study Group'.
5. Publications will include a list of all participants in descending order, who submitted useable data on 12 or more patients and all methodologists involved with the study.

* Any comments or concerns about this protocol, please email carestudy@rogers.com.