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Challenging Case of a Patient with Asthma and Persistent Airway Obstruction
This content is developed and funded by AstraZeneca.
Z4-79967 | December 2025
Disclaimer
These are hypothetical patient cases and outcomes may not be reflective of clinical studies or real-life circumstances. Please always consult guidelines and local prescribing information in your country of practice, as information may vary.
This case describes hypothetical patient scenarios. Outcomes presented may not reflect clinical study results or real-world practice. Please consult relevant clinical guidelines and local prescribing information for your country of practice as information may vary. This material is intended for healthcare professionals only. The views expressed are those of the authors and do not necessarily reflect the views of EMJ or AstraZeneca.
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Patient Background
A new patient presents to your office, a 62-year-old White male with a history of COPD (diagnosed ~8 years ago by GP), who is a former smoker (15 pack years, quit 12 years ago). Although he typically does not experience breathlessness with his ADL, he has noticed a decline in his ability to keep up with and engage in physical activities with his grandchildren. Previously, he was able to swim laps in the pool three times a week, but he has experienced a noticeable decrease in his endurance over the past couple of years.
Patient with COPD
He reports intermittent or episodic symptoms of:
ADL: activities of daily life; COPD: chronic obstructive pulmonary disease; GP: general practitioner.
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Past Medical History
Over the past year
Baseline Characteristics and Comorbidities
bEOS: blood eosinophils.
Click to explore patient background
Patient Characteristics
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The patient has experienced two exacerbations, one which required hospitalisation.
He does not typically experience breathlessness with his daily activities, but has noticed a decline in his ability to keep up and engage in physical activities with his grandchildren.
Previously, he was able to swim laps in the pool three times a week, but he has experienced a notable decrease in his endurance over the past couple of years.
Can do activities at home including gardening.
No tightness in chest.
The patient has been on ICS/LABA/LAMA therapy for ~13 months, but his symptoms are not improving. Given the patient’s history, symptomology, and lack of improvement on triple therapy, what are your next steps?
bEOS: blood eosinophils; COPD: chronic obstructive pulmonary disease; FeNo: fractional exhaled nitric oxide; GP: general practitioner; ICS: inhaled corticosteroids; LABA: long-acting beta-agonists; LAMA: long-acting muscarinic antagonists; OCS: oral corticosteroids.
A
Assume patient has great inhaler technique and adherence
B
GP initial diagnosis of COPD is accurate, and patient should add maintenance OCS to treatment regimen
C
Perform a bronchodilator reversibility test to assess the degree of airflow limitation improvement after bronchodilator use
D
Conduct a full diagnostic workup including lung function tests, imaging and assessments of biomarkers such as bEOS and FeNO
E
Obtain a sputum culture
F
Continue current therapy
Outcome: A bronchodilator reversibility test, full diagnostic workup including lung function tests and biomarker assessment, and a sputum culture should all be carried out.
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Choose all that apply:
The correct answers are C,D and E
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Persistent airway obstruction (PAO) is a clinical phenotype of asthma1
Asthma is a heterogeneous condition characterised by airway obstruction and includes several different clinical phenotypes.1 Asthma with persistent airway obstruction is considered a clinical phenotype, and is characterised by persistent airway limitation with or without reversibility.1 Persistent airway obstruction associated with asthma has some reversible obstruction with appropriate treatment.2,3
GINA: Global Initiative for Asthma. 1. Global Initiative for Asthma (GINA). Global strategy for asthma Management and prevention. 2025. Available at https://ginasthma.org/2025-gina-strategy-report/ Last accessed: 31 October 2025. 2. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. 2025. Available at: https://goldcopd.org/2025-gold-report/. Last accessed 31 October 2025. 3. Chipps BE et al. Ann Allergy Asthma Immunol. 2020;124(1):79-86. 4. Kole TM et al. Lancet Respir Med. 2023;11(1):55-64. 5. Del Olmo Sansone RA et al. Am J Respir Crit Care Med. 2023;207:A1149.
Persistent airway obstruction is reported to be experienced by: 4,5
23 - 33%
of all patients with asthma
45%
of all patients with GINA Step 4
12%
of all patients with GINA Step 5
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PAO: persistent airway obstruction. *ATLANTIS study is a post-hoc analysis (N=773) of the prevalence, clinical characteristics and implications of PAO across asthma severities. PAO was defined as post-bronchodilator FEV1/FVC of less than the lower limit of normal at recruitment. 1. Kole TM et al. Lancet Respir Med. 2023;11(1):55-64.
Features associated with higher prevalence of PAO in asthma
In the ATLANTIS study*, the below features were independently associated with higher prevalence of PAO in asthma:1
Older Age1
Male1
GINA Step 4-51
Higher blood eosinophil count1
Current smokers1
Former smoking, blood monocytes, and blood neutrophils were not significantly associated with PAO.2
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COPD: chronic obstructive pulmonary disease: ICS: inhaled corticosteroids; PAO: persistent airway obstruction. *Cross-sectional multicohort study of adults aged ≥50 years from nine CADSET cohorts' spirometry data (N=69789). Clinical characteristics and comorbidities of airway obstruction were compared with asthma only (without airway obstruction) and COPD only. 1. Global Initiative for Asthma (GINA). Global strategy for asthma Management and prevention. 2025. Available at https://ginasthma.org/2025-gina-strategy-report/ Last accessed: 31 October 2025.. 2. Bertels X et al. BMJ Open Respir Res. 2023;10(1):e001760.
Differentiating patients with asthma and PAO from those with COPD can be challenging1
Asthma with PAO may present as:1 Intermittent or episodic symptoms, which may have started before or after age 40 years Previous smoker Current/childhood asthma diagnosis, and symptoms improving spontaneously or with bronchodilators or ICS
Compared with COPD, patients with asthma with PAO may have the following profile:2* Younger in age Less often current smokers Less pack-years
Distinguishing asthma with persistent airway obstruction from COPD can be challenging due to overlapping clinical features.1
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BD: bronchodilator; FEV1: Forced Expiratory Volume in 1 second; FVC: forced vital capacity; *common and more likely when FEV1 is low; †compatible with asthma and COPD. 1. Global Initiative for Asthma (GINA). Global strategy for asthma Management and prevention. 2025. Available at https://ginasthma.org/2025-gina-strategy-report/ Last accessed: 31 October 2025. 2. Bertels X et al. BMJ Open Respir Res. 2023;10(1):e001760.
Lung function testing is essential in identifying patients with airway obstruction
Persistent expiratory airflow limitation
Variable expiratory airflow
Diagnosis of asthma with PAO requires syndromic categorisation with a thorough diagnostic history1
In these patients to confirm presence of persistent expiratory airflow limitation and variable expiratory airflow limitation:1
Reduced post-BD FEV1/FVC <0.7 required for diagnosis Post-BD FEV1 ≥80% predicted compatible with mild airflow limitation
Post-BD increase in FEV1 ≥12% and 200 mL from baseline (reversible airflow limitation)* or post-BD increase in FEV1 >12% and 400 mL from baseline (marked reversibility)†
It seems the GP accurately diagnosed the patient with COPD; therefore, patient should continue current therapy
Patient seems to have chronic airflow obstruction but given his reversibility and biomarkers, his diagnosis is more likely to be asthma
Obtain a chest CT to gather more information as the diagnosis is not clear
Patient’s symptoms may be due to an allergy. Refer to allergist
Outcome: The patient seems to have persistent airflow obstruction, but given the reversibility and biomarkers, his diagnosis is likely to be asthma. Obtain a chest CT to further investigate.
Infection has been ruled out in this patient and diagnostic workup presents as below. Spirometry shows patient has reduced post-BD FEV1/FVC and reversibility of 21.4%. Which of the following is true?
ACQ-5 score, Asthma Control Questionnaire-5 score; BD, bronchodilator; bEOS, blood eosinophils; COPD: chronic obstructive pulmonary disease; FeNO, Fractional Exhaled Nitric Oxide; FEV1, Forced Expiratory Volume in 1 second; FVC, Forced Vital Capacity; IgE, Immunoglobulin E; L, liters; ppb, parts per billion; PN, Predicted Normal; QoL, Quality of Life; uL, microlitre; U/L, units per litre.
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The correct answers are B and C
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1. Hanania NA et al. Ann Allergy Asthma Immunol. 2022;130(2023):206-14. 2. Kole TM et al. Lancet Respir Med. 2023;11(1):55-64. 3. Contoli M et al. J Allergy Clin Immunol. 2010;125:830-7. 4. Rutting S et al. Front Physiol. 2022;13:898208. 5. Siddiqui S et al. J Allergy Clin Immunol. 2023;152(4):841-57. 6. Varicchi G et al. Allergy. 2022;77(12):3538-52. 7. Hough KP et al. Front Med (Lausanne). 2020;7:191. 8. Huang S et al. Eur Respir J. 2015; 45:338-46.
Airway remodelling is thought to be the main contributor to airway obstruction1-3
Remodeling in asthma involves pathophysiologic structural changes, such as increased vascularity, mucus gland hyperplasia, hypertrophy and/or increased volume fraction of extracellular matrix and thickening of airway smooth muscle and reticular lamina.4
It is thought that eosinophils may play a significant role in the global pathogenesis of airway remodeling.4,5 Activated eosinophils secrete Type 2 cytokines (e.g., IL-5, IL-4, IL-13) and release TGF-β which are strongly implicated in airway remodelling, particularly in epithelial-mesenchymal transition, subepithelial and peribronchial fibrosis.6,7
Patients with asthma and airway obstruction typically experience worse asthma outcomes than those without airway obstruction including:3,8 Increased risk of exacerbation Worse symptoms Increased small airway dysfunction Greater decline in FEV1 Increased mortality
AL: airway limitation; bEOS: blood eosinophils; FeNO: fractional exhaled nitric oxide; FEV1: forced expiratory volume in one second; FVC: forced vital capacity; PAO: persistent airway obstruction; ppb: parts per billion. *(1.6 [95% Cl: 0.5-2.7; p=0.004]) † (3.5 [95% Cl: 1.0-6.0, p=0.006]). Study included adult patients from the Copenhagen General Population Study with measurements of bEOS (N=15,605) and FeNO (N=2583) from a follow-up examination and assessment on FEV1 decline in the preceding 10 years; †asthma with persistent obstruction was defined as individuals with pre and postbronchodilator FEV1/FVC <0.70 and FEV1 reversibility <12% and <200 mL and with self-reported diagnosis of asthma. 1. Colak T et al. Thorax. 2024;79(4):349-58.
Accelerated lung function decline in patients with asthma with PAO and elevated blood eosinophils
Compared to patients with asthma with full reversibility* patients with asthma with PAO had greater decline in FEV1 in individuals with bEOS ≥300 cells/μL and greater decline in FEV1 (mL/year) per 100 cells/μL increase in bEOS. Similar findings were seen with FeNO ≥20 ppb.1,†
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Elevated blood eosinophils and FeNO are thought to be important predictors of lung function decline in patients with asthma, particularly in patients with PAO.1
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1. Halpin DMG. Clin Chest Med. 2020;41(3):395-403. 2. Postma DS, Rabe KF. N Engl J Med. 2015;373(13):1241-9. 3. Global Initiative for Asthma (GINA). Global strategy for asthma Management and prevention. 2025. Available at https://ginasthma.org/2025-gina-strategy-report/ Last accessed: 31 October 2025.
Distinguishing asthma with PAO from COPD can be challenging due to overlapping clinical features1,2
Distinguishing asthma with airway obstruction from COPD is challenging, yet differential diagnosis is essential for correct prognosis and response to treatment.3 According to the GINA 2025 report, in patients with features of asthma with airway obstruction, initial pharmacologic intervention should address asthma.3
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COPD: chronic obstructive pulmonary disease. 1. Diagnosis of Diseases of Chronic Airflow Limitation. Asthma COPD and Asthma – COPD Overlap Syndrome (ACOS). 2014. Available at: https://ginasthma.org/wp-content/uploads/2019/11/GINA_GOLD_ACOS_2014-wms.pdf. Last accessed: 31 October 2025.
This patient has features of asthma with persistent airway obstruction. Which of the following statements are true?
Outcome: The diagnostic criteria for COPD and asthma with airway obstruction often overlap. For patients with asthma with airway obstruction, GINA guidelines recommend to treat as asthma.1
For patients with asthma with airway obstruction, it is recommended you treat as asthma
For patients with features of asthma with airway obstruction, you must treat as COPD
There are no differences in treatment recommendations for asthma with airway obstruction and COPD
Symptoms of asthma with airway obstruction and COPD may be similar and the diagnostic criteria often overlap
The correct answers are A and D
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ICS: inhaled corticosteroids; LABA: long-acting beta-agonists; LAMA: long-acting muscarinic antagonists; OCS: oral corticosteroids; SABA: short-acting beta agonists.
Recommend patient to remain on current therapy of ICS/LABA/LAMA for another 6 months
Remove LAMA and only give ICS/LABA
Remove LABA and only give ICS/LAMA
Recommend adding maintenance OCS
Add as-needed SABA
Consider starting biologic therapy
Based off the patient’s symptoms, and current treatment, how would you optimise this patient’s treatment therapy?
The answer is F
Considering that this patient has asthma with persistent airway obstruction and continues to have symptoms, exacerbations in the last 12 months while on his current therapy, and elevated blood eosinophil levels, starting a biologic therapy may help optimise his treatment.
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The patient was diagnosed with asthma and persistent airway obstruction
Diagnosed with asthma and persistent airway obstruction
Soon after diagnosis, biologic therapy was initiated
6 months later, the patient feels much better, and is able to engage with his grandchildren and participate in daily activities
These are hypothetical patient cases and outcomes may not be reflective of clinical studies or real-life circumstances.
Please always consult guidelines and local prescribing information in your country of practice, as information may vary.
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Summary and key learnings
> Persistent airflow obstruction is a clinical phenotype of asthma1
> Eosinophils are central to the pathogenesis of airway remodeling,2 a key mechanism in the development of PAO3
> Diagnosing PAO requires syndromic categorisation and a comprehensive diagnostic history to differentiate from COPD,1 which shares overlapping clinical features.4,5
> Patients with asthma and airway obstruction typically experience worse asthma outcomes than those without airway obstruction, including increased risk of exacerbation, worse symptoms, increased small airway dysfunction, greater decline in FEV1 and increased mortality.6
> According to the GINA 2025 report, in patients with features of asthma with airway obstruction, initial pharmacologic intervention should address asthma.1
COPD: chronic obstructive pulmonary disease; FEV1: forced expiratory volume in one second; GINA: Global Initiative for Asthma; PAO: persistent airway obstruction. *ATLANTIS study post-hoc analysis (N=773) of the prevalence, clinical characteristics and implications of PAO across asthma severities. PAO was defined as post-bronchodilator FEV1/FVC of less than the lower limit of normal at recruitment. 1. Global Initiative for Asthma (GINA). Global strategy for asthma Management and prevention. 2025. Available at https://ginasthma.org/2025-gina-strategy-report/ Last accessed: 31 October 2025. 2. Varicchi G et al. Allergy. 2022;77(12):3538-52. 3. Rutting S et al. Front Physiol. 2022;13:898208. 4. Halpin DMG. Clin Chest Med. 2020;41(3):395-403. 5. Postma DS, Rabe KF. N Engl J Med. 2015;373(13):1241-9. 6. Huang S et al. Eur Respir J. 2015;45:338-46.
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Thank you
