Opinion Leaders to Improve Care After COPD or Asthma Emergency Department (ED) Visits.
Phase: NA
Conditions: Chronic Obstructive Pulmonary Disease
Sponsor: University of Alberta

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The Lung Attack Alert Study 
(TLAL Study) 
 
 
 
 
 
 
 
Mohit Bhutani MD, FRCPC 
 
Brian H. Rowe MD, MSc, CCFP(EM) 
 
 
 
 
 
 
Original: December 2, 2009 
Edmonton, AB 
 
Revision 1: April 11, 2010 
Edmonton, AB 
(Web randomization, medication revision) 
 
Revision 2: October 18, 2010 
Edmonton, AB 
(CAT form added) 
 
 
 

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Introduction 
 
Chronic Obstructive Pulmonary Disease (COPD) is the 4th leading cause of 
mortality in Canada1, and accounts for significant morbidity in patients affected 
by the disease. COPD is now seen as a disease that is both preventable and 
treatable. In order to better facilitate treatment for these patients, a number of 
national and international consensus guidelines have been developed to help 
physicians in the diagnosis and chronic management of these patients. 
 
The Canadian Thoracic Society published guidelines on the management of 
COPD in 20072 (updated in 2008) to help physicians optimize the care of patients 
with COPD. The guidelines were based on current evidence within the medical 
literature. Despite the availability of guidelines for COPD (as well as other 
specialties), implementation of guidelines into daily clinical practice, remains a 
challenge.  
 
Patients who experience an Acute Exacerbation of COPD (AECOPD) have an 
increased risk of mortality3. They represent an important subset of patients with 
COPD who need their management urgently optimized, to guideline standards, in 
order to improve their survival. These patients most often present to their local 
emergency departments (ED) for the acute episode. For patients who are 
admitted to hospital, an opportunity exists to re-evaluate their chronic 
management and therefore optimize their care. However, for patients who are 
not admitted to hospital, follow up care is often left to their primary care physician 
(PCP), if they have one. Information regarding how frequently this occurs, and 
what the outcomes of these follow up visits with their PCP is unknown. Although 
the national rate of patient follow up of patients by their PCP within the first 
month following an AECOPD is unknown, locally it is only 30%4. This low rate of 
follow up represents a lost opportunity for reassessment of both the acute and 
chronic management of these patients, as well, represents a delay in optimizing 
their care to help improve their long term survival. One of the factors contributing 
to this low rate of follow-up, is poor or delayed communication between the ED 
and PCP. 
 
It is our belief that improving the communication between the ED and the PCP 
regarding patients, who are discharged from the ED after being treated for their 
AECOPD, will improve the rates of patient follow up. Furthermore, if the 
communication highlights care gaps in the chronic management of COPD, this 
may result in an adjustment in management such that the patients’ treatment will 
be more in keeping with current guideline recommendations. 

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Methods 
This study will be a 1 year randomized controlled trial to assess the impact of the 
“Lung Attack Alert” on rates of follow up by PCP of their patients following 
presentation to the ED for an AECOPD. The tool being assessed is labeled as 
the “Lung Attack Alert”(see Appendix 1). This is a novel information sheet that is 
intended for the PCP. The Lung Attack Alert summarizes the following points:  
 
a) that the PCP’s COPD patient has had a presentation to the ED for an 
AECOPD but did not require a prolonged hospital admission; 
 
b) a description of the discharge management from the ED will be 
provided; 
 
c) a recommendation to the PCP to follow up with the patient within 1-2 
weeks after discharge from the ED; 
 
d) Care gaps identified in the patients chronic management of COPD 
based on the Canadian Thoracic Society 2007(updated 2008) guidelines 
will be highlighted for the PCP to address at the next outpatient follow up 
 
Each Lung Attack Alert will be individualized to the patients care gap(s) 
identified during screening. 
 
This study will enroll consecutive patients who present to the ED at the University 
of Alberta Hospital and the North East Community Center (both located in urban 
Edmonton), who present with an AECOPD, but who do not require admission to 
hospital.  
 
ED physicians or the study coordinator will screen patients who present to the 
ED with an AECOPD, who have recovered from the acute event and are 
considered safe for discharge. All patients will receive usual care within the ED 
prior to screening and entry into the study. This may consist of the use of any or 
all of the following: oxygen, acute bronchodilators (+/- use of nebulizers or MDI), 
administration of oral/IV corticosteroids, intravenous fluids, non-invasive 
ventilation (NIV), oral or intravenous antibiotics as required. 
 
Patients will be screened by either the ED physicians who will notify our study 
coordinator regarding the eligibility of a patient or directly by the study 
coordinator. Eligible patients (Appendix 2) will be provided with a patient 
information sheet (Appendix 3) outlining the rationale for the study. If the patient 
is agreeable to participate, a consent form will be signed and witnessed by either 
the ED physician or study coordinator (Appendix 4). To be enrolled into the 
study patients must satisfy all inclusion and exclusion criteria.  
 
 
 

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Inclusion: 
 
 
 
 
Appropriately signed and dated informed consent has been 
obtained  
 
 
 
ED patients presenting with an acute exacerbation of COPD 
requiring treatment in the ED; 
 
Previous physician-diagnosis of COPD (e.g., emphysema, 
chronic bronchitis or COPD) either previously or within the 
ED; 
 
 
 
Age >40 years of age; 
 
 
 
Current or former smokers of more than 10 pack years 
(number of packs of cigarettes {or pipe and/or cigars) 
smoked per day X the number of years of smoking); 
 
 
 
FEV1/FVC ratio < 0.7 for age, sex and height (either known 
or determined within the ED); 
  
 
 
Patients can read and comprehend English language. 
 
Exclusion: 
 
Patients presenting for prescription renewal; 
 
Patients who require hospitalization; 
 
Patients who do not have a primary care physician or 
patients for whom a family physician cannot be found; 
 
Patients who have already been enrolled in the study; 
 
Patients with a ED physician-diagnosis of primary asthma, 
pneumonia, HIV/AIDS, immuno-compromise, or life 
expectance of < 90 days. 
 
Patients who, in the opinion of the investigator, should be 
excluded. 
 
 
Using concealment of allocation, patients will be randomized using computerized 
random numbers tables to control and intervention groups. Randomization will be 
in a 1:1 distribution between the control and intervention group.  
 
Upon enrollment into the study, basic information regarding the patient and their 
disease status will be collected. An ED chart review will be completed to 
document ED care. We will complete the COPD Assessment Test (CAT), a 

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new questionnaire for people with COPD. It is designed to measure the 
impact of COPD on a person's life and is freely available on the internet 
(www.catestonline.org). See Appendix 6 for the complete set of information 
to be collected.   
 
All patients enrolled in the study will be discharged home with a standardized 
protocol for the outpatient management of the AECOPD (Appendix 5). This will 
include a standardized length and dose of both oral corticosteroids (oral 
prednisone 50 mg once daily X 10 days) and antibiotics (oral Doxycycline 100 
mg twice daily X 5 days or Levofloxacin 750 mg once daily X 5 days). The 
dosage and length of therapy is based on current standards and 
recommendations outlined in the CTS 2007 (updated 2008) consensus 
guidelines. The standardized medications will be provided for the patient at no 
cost to the patient themselves by the Central Research Pharmacy at the 
University of Alberta Hospital). 
 
After normal working hours(see below), when research staff are not available, 
patients who are eligible and who have consented to enter the study but have 
been discharged from the ED, will be contacted by the study coordinator the next 
morning by phone. Randomization will take place at that time and the appropriate 
process will take place thereafter. Those patients who are discharged from the 
ED will receive the outpatient treatment package (by the consenting ED 
physician) used in the study (Appendix 5) for the medical management of their 
AECOPD. The outpatient medication package will be readily available in the ED, 
in a reserved area for the study. This is to ensure that there is no delay in their 
treatment, as well, that their acute management does not impact the effect of the 
Lung Attack Alert. 
 
As per the above randomization process, patients will be randomized into either 
the control group or the intervention group using a web-based randomization 
process (Epidemiology Coordinating and Research {EPICORE} Centre, 
Edmonton, AB; http://www.epicore.ualberta.ca). 
 
The control group will be discharged from the ED, with the standardized 
outpatient protocol (Appendix 5) and will be advised to follow up with their PCP. 
They will be provided with general information regarding COPD in the form of the 
“Breathworks” program pamphlets established by the Canadian Lung 
Association. These are readily available in print and online, and they are 
information guides for patients with COPD. The patients will then be contacted by 
a research staff member unaware of the allocation of treatment at day 30 and 90 
post discharge from the ED to discuss the primary and secondary outcomes 
(Appendix 7). 
 
The intervention group will also be advised to follow up with their PCP, along 
with the standardized outpatient protocol for their acute exacerbation (Appendix 

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5). They will be provided with general information regarding COPD in the form of 
the “Breathworks” program. The intervention group will have the Lung Attack 
Alert form completed by the research study staff. The form will highlight the 
information already discussed earlier. This will then be faxed to their primary care 
physician by the study coordinator. The patients will then be contacted by a 
research staff member unaware of the allocation of treatment at day 30 and 90 
post discharge from the ED to discuss the primary and secondary outcomes 
(Appendix 7). 
 
Outcomes 
 
The Primary Endpoint of this study is the rate of follow up of the patient by their 
primary care provider for review of the acute and chronic management of their 
COPD and addressing any issues on the Lung Attack Alert, within the first 90 
days after discharge from the ED. The study coordinator will contact all patients 
enrolled on day 30 after admission to the ED to determine if a follow up visit has 
occurred and if any of the recommendations noted on the Lung Attack Alert have 
been implemented.  
 
A number of Secondary Endpoints will be collected. These include 1) relapse of 
the AECOPD requiring acute intervention (ED or clinic) within the 90-day study 
period; 2) admission to the hospital within the 90-day study period; 3) review and 
adjustment of the management of COPD at day 90 post discharge from the ED 
4) Proportion of patients who completed their acute management within the 90-
day study period and 5) length of stay within the ED. 
 
The study coordinator will contact the PCP of patients in the intervention group to 
survey the usefulness of the Lung Attack Alert once the study is complete. This 
survey will assess the clinical utility of the alert and the ease of use of the 
information provided in the alert to aid in clinical management.  
 
Statistics 
 
Sample Size Considerations:  
Calculations for the estimated sample size were completed using a formula for 
calculation of dichotomous response variables with two independent samples.  
We assumed α = 0.05 (accepted standard value), power (1- β) = 0.80, and that 
30% of patients in the control group would see their PCP within 30-days. This 
estimate of 30-day follow-up is taken directly from recent administrative data from 
Alberta. The sample size was therefore calculated to detect a 30% absolute 
difference in 30-day follow-up (30% of the standard-care vs. 60% of enhanced 
care groups).  In addition, we used 1-tailed estimates due to the assumption that 
the intervention will not decrease the follow-up of patients with COPD. The total 
sample size was estimated at 98 (49/group) patients; however, if we assume 
~10% attrition (see previous COPD study), the total sample size is estimated at 
110 patients. 

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Recruitment plan: 
We have full-time research staff nurses at the UAH (coverage 16 hours/day; 
08:00-24:00 M-F; 10:00-18:00 S&S) and at the NECHC (8 hours/ day; 10:00-
18:00). We will increase our coverage if the numbers indicate the need to do so. 
We anticipate 5/month at the UAH and 4/month at the NECHC.  Approximately 
one year of enrolment (February 2010-March 2011) should provide the numbers 
required for this study. 
 
Principal analysis of the primary outcome measure: 
The final analysis will be performed on an "intention to treat" basis. Using this 
approach, patients will be included in the analysis according to the group to 
which they were randomized. Baseline characteristics in the two treatment arms 
will be compared using univariate descriptive statistics. The principal analysis of 
30-day relapse will be done using an unadjusted 2 comparing the proportion of 
events in each treatment group. A logistic regression procedure will be employed 
to adjust raw relapse proportions using significant co-variates (such as patient 
use of inhaled steroids, current smoking status, etc) which may influence 
outcomes 
 
We chose the proportion of PCP visits within 30 days as a primary outcome 
measure rather than survival time to relapse. We believe that it is more relevant 
to both patients and physicians to know if the enhanced intervention will stimulate 
a PCP visit rather than examining relapse (which may be affected by age, 
severity, type of treatment received, smoking status, etc). Therefore, unadjusted 
2 followed by logistic regression procedures were chosen over log-rank tests 
followed by Cox proportional hazards modelling. Both alternative analytic 
approaches mentioned will still be performed and reported. 
 
Principal analysis of the secondary outcome measure: 
All secondary outcome measures will be assessed at 30 days and 90 days and 
will be analysed using an "intention to treat" analysis. Patients will be contacted 
to see if they have had an urgent visit (to ED or their PCP).  If they describe a 
relapse (an unscheduled visit for worsening COPD), then we will obtain further 
information from their medical records and/or treating physician. Those patients 
who relapse within the first 30 days of the trial will have measurements of 
oxygenation, airflow obstruction, dyspnea, and quality-of-life done on the day of 
relapse (either from the family physician or the EDs where they attend). These 
values will be counted as the last day values for purposes of the analysis (i.e., 
endpoint analysis, with the last observation carried forward). 
 
Continuous outcome measures including absolute and percent changes in FEV1, 
oxygen saturation, Transitional Dyspnea Index scores, and changes from Day 1 
to Day 30 in the scores of the four components of the Chronic Respiratory 
Questionnaire will be analysed using either parametric procedures (independent t 
tests) initially, or with non-parametric methods (Wilcoxon Rank Sum) if the data is 
not normally distributed. At 90 days, the proportion of patients who achieve 

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compliance with recommendations (for LAAC, LABA/ICS combinations, and 
rehabilitation referral), relapse and are hospitalized will be compared using 
unadjusted χ2 tests followed by logistic regression procedures. Survival analyses 
(log-rank tests followed by Cox proportional hazards modelling) will be used to 
compare time to relapse. 

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Relapse Assessment and Adjudication: 
Each patient who relapses will have assessment to verify the location, treatment 
received and the severity. In most cases, this will occur at the primary ED setting; 
however, in some cases, patients may relapse back to their Family Physician's 
office.  In each case, study staff will either collect ED data (with hospital relapse 
through direct patient chart review) or primary care data (through contact with the 
Family Physician's office).  A relapse chart review will be completed and 
adjudication will be made independently by two study physicians (MB, BHR).  
Patient will be placed into one of the following relapse categories: relapse without 
treatment-discharged; relapse with acute/ED treatment and no chronic 
management change-discharged; relapse with acute/ED treatment and chronic 
management change-discharged; relapse with acute/ED treatment and chronic 
management change-admitted; died. 
 
Ethics, informed consent and regulatory considerations 
The full program will be reviewed and the patient consent form approved by the 
University of Alberta Research Ethics Board. 
 
It is the responsibility of the ED physician/designee to provide each subject with 
verbal and written study related information, using the IRB/IEC approved 
informed consent document. 
 
Each subject must voluntarily provide written informed consent (including 
consent for the use and disclosure of research-related health information). The 
consent must be obtained prior to performing any study-related procedures that 
are not part of normal patient care, including screening. A copy of the signed 
informed consent must be given to the study subject and also placed on the 
chart. 
 
Safety 
 
Serious Adverse Event (SAE) Reporting Requirements:   
 
Adverse event information is not expected to be available from the source data 
used, and therefore will not be routinely collected in this study. However, should 
the Investigator/Sponsor become aware of a serious adverse event attributable 
to a GSK marketed product during the conduct of the study, it must be reported 
to GlaxoSmithKline within 24 hours of first identification. 
 
For detailed reporting procedure and SAE definition, please see Appendix 9 
 

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Budget (See Appendix 8 for full details) 
 
The Total Budget for this project will be $151,797.10 
 
The Budget is based on the following: 
 
 
Study Cost: $116,767.00($1061.52/patient) 
 
Institutional Costs: The University of Alberta Institutional Costs is 30% in 
addition to the expected costs of the Study. For our study this totals:  
$35,030.10 
 
The total of $151,797.10 is required to complete this study.  We believe that our 
budget projections are based on realistic amounts that will be required to conduct 
a 2-site study that will involve emergency departments within Edmonton.  It is 
estimated the study will require 12 months to enroll 110 patients and complete 
follow-up.  We anticipate it will take the coordinator one month to organize the 
study supplies and sites in advance of enrollment.  Another two to three months 
will be needed to complete data entry and analysis for the 110 patients and to 
prepare a manuscript for publication. 
 
Pilot Work: 
An “Emergency COPD Research Program” has been developed in Edmonton 
over the past 2 years. Dr. Bhutani has extensive experience with the 
management of clinical COPD through the Lung Health Centre and the 
Edmonton General Hospital. Dr. Rowe has extensive experience in clinical trials 
and Airway Disease research. In addition, his research team is already in place 
to assist with the recruitment and follow-up of these patients. 
 
Anticipated Results: 
The results of this study will be used widely by clinicians to inform decisions 
regarding the care of patients seen in the emergency department with COPD 
exacerbations. If our study shows that addition of LAL referral to corticosteroids, 
antibiotics and bronchodilators does improve follow-up and evidence-based care. 
its use should be encouraged in this patient population. This would be important 
information, since it is widely recognized that efforts to improve follow-up, 
medication review, and prevention/rehabilitation programs are important. 
Conversely, if our study shows LAL referral does not improve follow-up and other 
outcomes, then renewed efforts will be required to seek interventions that are 
effective. Thus, the results of this trial, whether positive or negative, should help 
to standardize and improve care for COPD outpatients who present with an 
exacerbation of their disease. 
 
 

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Time Lines 
 
HREB Review: February 16, 2010  (Pro00011325) 
 
Study Set Up: March 2010 
 
First Patient In: April 12, 2010 
 
Last Patient Out: July 2011 
 
Data Entry/Analysis: August 2011 
 
Abstract/Manuscript: October 2011 
 
References: 
                                              
1Deaths by selected groups causes, sex and geography-
Canada.<www.statcan/ca/english/freepub/84F0209XIE/2003000/t001_en.pdf> 
 
2 DE O’Donnell, S Aaron, J Bourbeau et al. Canadian Thoracic Society recommendations for management 
of chronic obstructive pulmonary disease-2007 update. Can Respir J 2007;14(Suppl B): 5B-32B 
 
3 Seemungal TA, Donaldson GC, Paul EA, Bestall JC, Jeffries DJ, Wedzicha JA. Effects of exacerbation 
on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 
1998;157:1418-22 
4 Rosychuk RJ, Rowe BH, Voaklander DC, Klassen TP, Senthilselvan,A, Marrie TJ. Visits to Alberta 
Emergency Departments for Chronic Obstructive Pulmonary Disease (COPD): April 1, 1999 to March 31, 
2005. CANA website