Breathe Easier Earlier: Screening and Treating Asthma and COPD

Authors:
Michelle Balli, PharmD, BCACP
Michelle Hernandez, PharmD

Reviewers:
Johnathan Hughes, PharmD, BCACP, BCPS
Caitlyn Tyus, PharmD

Citation: Aaron SD, Vandemheen KL, Whitmore GA, et al. Early Diagnosis and Treatment of COPD and Asthma – A Randomized, Controlled Trial. N Engl J Med. 2024 Jun 13;390(22):2061-2073. 

The Problem

Asthma and chronic obstructive pulmonary disease (COPD) are underdiagnosed due to the underuse of spirometry, underreporting of symptoms, and economic barriers. Undiagnosed patients may have decreased quality of life and place more burden on the health system for acute symptom management.^1-2 Is there an effective way to capture undiagnosed symptomatic patients and route them for appropriate management of respiratory symptoms?

What’s Known

Symptoms of asthma and COPD often overlap and include shortness of breath, cough, wheezing, and chest tightness.^3-4 Spirometry and symptom assessment are used for diagnosis. Chronic airway inflammation characterizes asthma, and diagnostic spirometry testing shows reversibility with forced expiratory volume in one second (FEV₁) or forced vital capacity (FVC) increasing after bronchodilator administration.³  Conversely, COPD is characterized by airflow obstruction and is diagnosed with a post-bronchodilator FEV₁/FVC < 0.7.⁴

The US Preventive Services Task Force recommends against routinely screening for COPD in adults without respiratory symptoms due to the lack of data demonstrating positive effects from screening on morbidity or mortality.⁵ However, active case finding may be used to identify patients with respiratory symptoms who have not yet been diagnosed with a respiratory disease. Through case finding, information on symptoms and risk factors can be obtained and assessed to consider referral for diagnostic testing.⁶

What’s New

The Undiagnosed COPD and Asthma Population (UCAP) trial was a combined case-finding and randomized, controlled treatment study conducted in Canada from 2017-2024.⁷ Adults 18 years of age or older were contacted to assess for respiratory symptoms in the previous 6 months. Those with symptoms completed the Asthma Screening Questionnaire. Participants who were 60 years or older and participants who were younger than 60 years with an Asthma Screening Questionnaire lower than 6 also completed the COPD Diagnostic Questionnaire. Invitations for spirometry were extended to participants with a score of 6 or higher on the Asthma Screening Questionnaire or a score of 20 or higher on the COPD Diagnostic Questionnaire. Spirometry reports were categorized as consistent with asthma or COPD.

Participants were then randomly assigned 1:1 to receive treatment provided by a pulmonologist and an asthma-COPD educator (intervention group) or by their primary care practitioner (usual-care group). The ideal design would have compared an intervention group with undiagnosed and untreated patients; however, this design would have been unethical as participants were symptomatic. Participants in the usual care group had a copy of their spirometry sent to their physician, who was responsible for providing usual care. Participants in the intervention group were scheduled with a pulmonologist and asthma-COPD educator on the day of randomization and at month 4. The intervention group received guideline-recommended medication treatment as well as education on the disease state, exercise, weight management, proper inhaler technique, and allergen/smoke avoidance. Participants in both groups received smoking cessation counseling and referral to a smoking cessation program. Monthly calls were conducted during the 12-month trial period to determine if outcome events occurred. At 6 and 12 months from randomization, participants in both groups underwent repeat spirometry and assessment of secondary outcomes. Smoking cessation was assessed at 12 months.

The primary outcome was an annualized rate of participant-initiated healthcare use for respiratory-related symptoms over the 1-year prospective follow-up period. Nurse practitioner, primary care physician, specialist, or emergency department visits and hospitalizations for respiratory-related illness were counted as outcome events. Secondary outcomes included changes from baseline to 1 year in quality of life (SGRQ and SF-36), respiratory symptom burden (CAT), prebronchodilator FEV₁ and percentage of the predicted normal FEV₁, and participant-reported smoking cessation. 

Over one million automated calls were conducted to assess for respiratory symptoms. Trial personnel attempted contact with 49, 594 participants with respiratory symptoms. Through active case finding, 508 eligible participants were randomized (253 assigned to the intervention group and 255 to the usual-care group). Baseline characteristics in the two groups were similar (see Table 1). Approximately half of participants had an asthma diagnosis and many had a previous or current smoking history. Most participants did not report baseline respiratory medication use.

Table 1. Baseline Characteristics

Characteristic	Intervention N = 253	Usual Care N = 255
Age (years)	63.4 + 13.4	62.8 + 13.6
Male sex	64%	58%
Body Mass Index	29.6 + 7.7	30.0 + 6.5
Diagnosis
Asthma	49%	50%
COPD	51%	50%
Prebronchodilator spirometry
FEV1 – liter	2.25 + 0.76	2.29 + 0.81
FEV1% of predicted normal value	76.1 + 17.5	78.5 + 18.6
Ratio of FEV1 to FVC	0.62 + 0.10	0.63 + 0.10
Postbronchodilator Spirometry
FEV1 – liter	2.46 + 0.80	2.48 + 0.86
FEV1 – % of predicted normal value	83.0 + 17.5	85.2 + 19.0
Ratio of FEV1 to FVC	0.65 + 0.11	0.66 + 0.10
Change in FEV1 from prebronchodilator value	9.7 + 7.9	9.1 + 7.9
Smoking Status
Lifetime Smoker (%)	25	27
Former Smoker (%)	49	46
Current Smoker (%)	25	27
Smoking history
Median pack-year (IQR)	20 (0-40)	18 (0-40)
Symptom or quality-of-life questionnaire score
CAT	17.6 + 7.3	17.6 + 7.2
SGRQ	39.2 + 18.7	38.4 + 17.3
SF-36	61.6 + 17.3	64.0 + 17.3
Respiratory medication use
No medication	81%	88%
SABA as needed	18%	11%
LAMA, LABA, or ICS	1.2%	1.2%

The number of participants who had a primary outcome was lower in the intervention group compared to the usual-care group (0.53 vs. 1.12 events per person-year; incidence rate ratio, 0.48; 95% CI 0.36-0.63; P<0.001). The rate of emergency department and specialist visits between the two groups did not differ, but there was a difference in the rate of primary care visits between the two groups (incidence rate ratio 0.39; 95% CI 0.29 to 0.53). SGRQ and CAT scores demonstrated meaningful changes in both groups (see Table 2). The prebronchodilator FEV₁  increased from baseline to 12 months by 119 mL in the intervention group compared to 22 mL in the usual care group, with an intervention effect of 94 mL (95% CI, 50 to 138). Additionally, nine smokers in the intervention group (14%) vs 5 smokers (7%) in the usual care group reported quitting at 12 months.  

Table 2. Outcomes 

Outcome	Incidence Rate Ratio (95% CI)	P-value
Primary Outcome	0.48 (0.36 – 0.63)	<0.001
– Asthma subgroup	0.49 (0.33 – 0.73)
– COPD subgroup	0.46 (0.31- 0.67)
Outcome	Mean Difference
SGRQ total score change over 12 mo – points	-3.5 (-6.0 to -0.9)
CAT total score change over 12 mo – points	-1.3 (-2.4 to -0.1)
Prebronchodilator FEV1 change over 12 mo – percentage points	3.2 (1.5 to 4.9)
SF-36 total score change over 12 mo – points	1.9 (-0.4 to 4.2)

New treatment for asthma or COPD was initiated in 92% of participants in the intervention group versus 60% in the usual care group. Participants in the usual care group were more likely to have no respiratory treatments or only a SABA during the trial period (See Table 3). Common adverse events reported were related to dizziness, syncope, or muscle cramping. 

Table 3. Most Frequent Treatments Received during the 12-Month Trial Period 

Treatment	Intervention N = 253	Usual Care N = 255
LABA + ICS	39.9%	20.8%
ICS	22.1%	12.5%
LAMA + LABA	13.4%	2.4%
LAMA	12.6%	10.6%
LAMA + LABA + ICS	11.5%	3.5%
No respiratory treatments during the entire trial period	7.5%	36.1%
SABA only	5.9%	13.7%

Our Critical Appraisal

This trial provides new evidence on the benefits of active case finding for undiagnosed asthma or COPD; however, there was a very low return on investment given the sheer number of calls made to identify potential participants. The case-finding approach used was inefficient, requiring over 38,000 interviews to enroll slightly more than 500 patients with mild-moderate respiratory symptoms. There was a significant difference in the primary outcome in those who obtained treatment from the pulmonologist and asthma-COPD educator. The design of the primary outcome favored the intervention group as these participants had an initial visit on randomization that didn’t count towards the primary outcome. Despite both treatment groups showing clinically significant improvements in respiratory symptoms and quality of life, most of these participants with mild-moderate disease likely could have been managed appropriately in a primary care setting with sufficient clinical staff support. 

Differences in prescribing patterns were noted between the two groups. More patients in the usual care group were prescribed a SABA only, whereas higher percentages of patients in the intervention group were prescribed an ICS, LAMA + LABA, or LAMA + LABA + ICS. Antibiotic prescription rates with action plans were not reported. Further, the authors did not report differentiation of medication use among patients diagnosed with asthma versus COPD or the appropriateness of the selected medications.  Medication adherence was not measured or reported, which is notable as poor adherence to respiratory medications is common and leads to increased healthcare costs.⁸

Additional limitations in the trial include insufficient power to detect a significant difference in the secondary outcomes in the asthma or COPD groups. Additionally, this trial was conducted in Canada, whose healthcare system and financing are different than the United States. The intervention group received treatment from a pulmonologist and asthma-COPD educator, which could be challenging to implement in most areas.  However, ambulatory care and community pharmacists are well-equipped to serve as asthma-COPD educators and can prescribe appropriate treatments under collaborative practice agreements.

The Bottom Line

Early diagnosis of asthma and COPD in previously undiagnosed patients contributed to clinically significant improvements in symptoms and quality of life but requires sufficient manpower to proactively engage in case-finding. The design of this study inherently favored the intervention group with regard to the primary outcome.

The Key Points

• Asthma and COPD are underdiagnosed, but active case-finding may be useful to improve referral for diagnostic testing in patients with respiratory symptoms.
• Patients with mild to moderate respiratory disease may be managed appropriately in primary care settings.
• Pharmacists can play an important role by identifying patients (earlier!) with respiratory symptoms, referring them for appropriate diagnostic testing, and implementing guideline-directed treatments. 

FINAL NOTE:  This program will be available for recertification credit through the American Pharmacists Association (APhA) Board Prep and Recertification Program.  To learn more, visit the APhA Geriatric Board Prep and Recertification website and sign up for the Evidence-Based Practice Series.

References