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Medinsight: Asthma and COPD Management and Emerging Therapies (2025 Update) PDF Free Download

Medinsight: Asthma and COPD Management and Emerging Therapies (2025 Update) PDF free Download. Think more deeply and widely.

Asthma and COPD
Management and Emerging
Therapies (2025 Update)
Past to Present
The Inhaler Journey in COPD & Asthma
Single Inhaler Triple Therapy (SITT)
with Extrafine Beclomethasone, Formoterol,
and Glycopyrronium in Asthma and COPD
Enlightening Medical Excellence
VOL 2 l ISSUE 2
Dear Doctor,
Welcome to this special respiratory-focused edition of Medinsight, proudly
presented by the Department of Medical Affairs at Eskayef Pharmaceuticals
Ltd.
This issue is dedicated to enhancing clinical knowledge in the management
of Asthma and COPD, two of the most pressing chronic respiratory
conditions of our time. We bring to you expert-driven insights into:
• Asthma and COPD: 2025 Update – A comprehensive overview of the
latest treatment guidelines, emerging therapies, and the role of
personalized medicine in optimizing patient outcomes.
• The Inhaler Journey – A reflection on how far inhaler technology has
come, improving drug delivery, patient compliance, and therapeutic
success through smarter, more efficient devices.
• Single Inhaler Triple Therapy (SITT) – An evidence-based exploration
of combining Extra-fine Beclomethasone (ICS), Formoterol (LABA),
and Glycopyrronium (LAMA) into one inhaler, significantly improving
lung function and quality of life in COPD and severe asthma.
We are also excited to introduce Trioson, our next-generation single inhaler
triple therapy—bringing together these three key agents in one convenient,
patient-friendly device. Designed to simplify treatment and elevate
real-world outcomes, Trioson represents our commitment to innovative,
patient-centered respiratory care.
We trust this edition will support your ongoing efforts to provide
cutting-edge, compassionate care in respiratory medicine. As always,
Eskayef remains committed to empowering your clinical decisions with
science, innovation, and purpose.
Together, let’s advance the future of respiratory health.
Warm regards,
Dr. Mohammad Murad Hossain
Assistant General Manager, Medical Affairs
Eskayef Pharmaceuticals Ltd.
E-mail: murad@skf.transcombd.com
Editorial
Dr. Mohammad Mujahidul Islam
Mr. Binay Das
Dr. Mohammad Mizanur Rahman
Dr. Mohammad Murad Hossain
Mr. H.M. Alamgir
Dr. Md. Naimul Islam Khan
Dr. Mostofa Monowarul
Dr. Khandaker Morshedul Alam Azad
Dr. Sabrin Khan Mou
02
MedInsight
What Are the Phenotypes of Asthma?
BASED ON AIRWAY INFLAMMATION
• Eosinophilic
• Neutrophilic
• Pauci-granulocytic
BASED ON CLINICAL FEATURES
• Mild, moderate, or severe asthma
• Exacerbation-prone
• Treatment-resistant
• Early-onset or late-onset asthma
• Asthma in the elderly
BASED ON PULMONARY FUNCTION
• With a component of fixed airway obstruction
• With marked/rapid fluctuations of airway caliber
• With marked hyperinflation
BASED ON TRIGGERS
• Allergic or non-allergic asthma
• Aspirin or non-steroidal anti-inflammatory drugs
• Occupational allergens or irritants
• Hormones: premenstrual and menopausal asthma
• Exercise- or cold air—induced asthma
• Asthma in the high-level athlete • Asthma in the smoker
BASED ON ASSOCIATED COMORBID CONDITIONS
• Rhinitis/rhinosinusitis, nasal polyps, and aspirin intolerance
• Psychological disturbances (e.g., depression, anxiety disorders)
• With dysfunctional breathing (hyperventilation syndrome,
vocal cord dysfunction)
• With associated chronic obstructive pulmonary disease
• Asthma in the obesle
In normal lungs, air moves freely through wide, clear airways. Asthmatic lungs' airways become narrowed,
inflamed, and filled with thick mucus, making breathing hard and triggering symptoms like wheezing, coughing, and
shortness of breath.
Management and Emerging
Therapies (2025 Update)
Asthma & COPD
Asthma is a chronic airway disease characterized by inflammation that
causes symptoms like wheezing, breathlessness, chest tightness, and
coughing. While mild attacks may resolve without treatment, proper
management can help reduce the frequency and severity of attacks. In
severe cases, emergency assistance is crucial.
Asthma affects approximately 262 million people globally, with
prevalence rates varying between 1% and 18%. In Bangladesh,
the prevalence has remained stable at around 7% for over a
decade. Additionally, asthma ranks fifth among the leading causes of
disease-related deaths in the country.
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The Global Initiative for Asthma (GINA) classifies asthma severity by observing clinical symptoms before
treatment. This helps guide appropriate stepwise management.
This staging reflects how often symptoms appear, how badly they affect sleep and activity, and how much lung
function is compromised. Such pre-treatment assessment ensures tailored, effective asthma care from the start.
The GINA 2025 guideline for personalized asthma management in adults and adolescents aged 12 and older. It outlines a
stepwise treatment approach under Track 1, the preferred regimen, which uses ICS-formoterol as both controller and
reliever to reduce exacerbation risk and simplify therapy. The steps progress from as-needed low-dose ICS-formoterol
(Steps 1–2), to MART (Maintenance and Reliever Therapy) with increasing doses (Steps 3–4), and finally to Step 5, which
includes add-on therapies like LAMA or biologics based on patient phenotype.
Severity Daytime Symptoms Night Symptoms PEF/FEV1 PEF Variability
STEP 1: Intermittent <1/week, asymptomatic between attacks ≤2/month ≥80% <20%
STEP 2: Mild Persistent >1/week but <1/day, may affect activity >2/month ≥80% 20–30%
STEP 3: Moderate Persistent Daily, affects activity >1/week 60–80% >30%
STEP 4: Severe Persistent Continuous, limits physical activity Frequent ≤60% >30%
ASTHMA TREATMENT STEPS IN ADULTS AND ADOLESCENTS
*AIR: Anti-inflammatory reliever; Ig: immunoglobulin; ICS: inhaled corticosteroids; HDM: house dust mits; IL: interleukin; LABA: long-acting beta2-agonist; LAMA: long-
acting muscarinic antagonist; MART: maintenance-and reliever therapy with ICS-formoterol; OCS: oral corticosteroid; SLIT: sublingual immunotherapy; TSLP: thymic
stromal lymphopoietin. †If prescribing LTRA, advise patient/caregiver about risk of neuropsychiatric adverse effects.
TRACK 1: PREFERRED
CONTROLLER and RELIEVER
GINA 2025
Adults & adolescents
12+ years
TRACK 2: Alternative
CONTROLLER and RELIEVER
STEPS 1 - 2
STEP 1
Using ICS-formoterol as the reliever
reduces the risk of exacerbations
compared with using a SABA reliever,
and is a simpler regimen.
Before considering a regimen
with SABA reliever, check if the
patients Is likely to adhere to daily
controller treatment
AIR-only: low-dose ICS-formoterol as needed
Reliever only, if SABA,
take ICS with each dose
STEP 2
STEP 3
STEP 4
Low dose
maintenance ICS
Low dose
maintenance
ICS-LABA
Medium dose
maintenance
ICS-LABA
Add-on LAMA.
Refer for assessment of
phenotype. Consider trial
of high dose maintenance
ICS-LABA. Consider
anti-IgE, anti-IL5/5R,
anti-IL4Rα, anti-TSLP.
STEP 3
STEP 4
MART with
low-dose maintenance
ICS-formoterol
RELIEVER: As-needed low-dose ICS-formoterol
RELIEVER: As-needed ICS-SABA, or as-needed SABA.
MART with
medium-dose
maintenance
ICS-formoterol
STEP 5
Add-on LAMA.
Refer for assessment of
phenotype. Consider trial
of high dose maintenance
ICS-formoterol; Consider
anti-IgE, anti-IL5/5R,
anti-IL4Rα, anti-TSLP.
See GINA
severe
Asthma guide
Montelukast 10 mg tablet
Quality Montelukast
for Quality life
05
MedInsight
GINA 2025 outlines a stepwise treatment plan starting with low-dose ICS used with SABA in Step 1, progressing to daily
low-dose ICS or LTRA in Step 2, and advancing to low-dose ICS-LABA or medium-dose ICS in Step 3. Step 4 includes
medium-dose ICS-LABA or low-dose ICS-formoterol MART, while Step 5 involves referral for phenotype assessment and
consideration of higher-dose or add-on therapies. The guideline also highlights the importance of monitoring inhaler
technique, adherence, comorbidities, and incorporating non-pharmacological strategies.
ASTHMA TREATMENT STEPS FOR CHILDREN 6–11 YEARS
The GINA 2025 guideline for managing asthma in children aged 5 years and younger using a personalized, stepwise approach.
Treatment steps range from intermittent ICS use during viral illnesses (Step 1) to daily low-dose ICS (Step 2), doubling the ICS dose
(Step 3), and specialist referral if control remains poor (Step 4).
ASTHMA TREATMENT STEPS FOR CHILDREN 5 YEARS AND YOUNGER
STEP 1
STEP 2
STEP 3
STEP 4
Double ‘low dose’ ICS
Continue
controller & refer
for specialist
assessment
Consider specialist
referral
PREFERRED
CONTROLLER
CHOICE
Other controller options
(limited indications, or
less evidence for efficacy
or safety)
(Insufficient
evidence for daily
controller)
Consider intermittent
short course ICS at
onset of viral illness
Infrequent acute
(e.g viral-induced)
wheezing episodes
and no or minimal
interval asthma
symptoms
Asthma symptoms not well-controlled,
or one or more severe exacerbations in the past year
Asthma not well
controlled on
low dose ICS
Before stepping up, check for alternative diagnosis
and inhaler skills, review adherence and exposures
Asthma not well
controlled on
double ICS
Daily low dose inhaled corticosteroid (ICS)
Daily leukotriene receptor antagonist (LTRA),
or intermittent short course of ICS at onset of
respiratory illness
CONSIDER
THIS STEP FOR
CHILDREN WITH:
As-needed short acting beta-against
RELIEVER
GINA 2025
Children 5 years and younger
GINA 2025
Children 6-11 years
PREFERRED
CONTROLLER
STEP 1
STEP 2
STEP 3
STEP 4
STEP 5
to prevent exacerbations
and control symptoms
Low dose ICS
taken whenever
SABA taken*
Daily low dose inhaled corticosteroid (ICS)
Low-dose ICS-LABA,
OR medium-dose
ICS, OR very low
dose ICS-formoterol
maintenance and
reliever (MART)*
Medium-dose
ICS-LABA, OR
low-dose ICS-
formoterol MART*
OR
refer for expert
advice
Refer for
phenotypic
assessment
+ higher dose
ICS-LABA or
add-on therapy,
e.g. LAMA,
anti-IgE, anti-
IL4Rα, anti-IL5
Daily leukotriene receptor antagonist (LTRA), or
low dose ICS taken whenever SABA taken*
Low dose
ICS + LTRA
Add tiotropium
or add LTRA
Only as last resort,
consider add-on
low dose OCS, but
consider side-effects.
Other controller options
(limited indications, or
less evidence for efficacy
or safety)
As-needed SABA (or ICS-formoterol reliever* in MART in Steps 3 and 4)
RELIEVER
introduces,
Better than
Salbutamol
Salbutamol 90 mcg & Budesonide 80 mcg Inhaler
The GINA & US NAEPP guidelines recommend addition of ICS with Salbutamol for acute asthma
• As-needed low-dose ICS-formoterol reduces the risk of severe exacerbations and emergency department visits or
hospitalizations by 65%, compared with SABA-only treatment. This anti-inflammatory reliever regimen (AIR only)
significantly reduces severe exacerbations regardless of the patient’s baseline symptom frequency, lung function,
exacerbation history or inflammatory profile (high or low blood eosinophils or FeNO).
• Starting treatment with SABA alone trains patients to regard it as their main asthma treatment, and increases the risk of
poor adherence when daily ICS is subsequently prescribed.
• Early initiation of low-dose ICS in patients with asthma leads to a greater improvement in lung function than if symptoms
have been present for more than 2–4 years. One study showed that after this time, higher ICS doses were required, and
lower lung function was achieved.
• Patients not taking ICS who experience a severe exacerbation have a greater long-term decline in lung function than
those who are taking ICS.
• For patients with occupational asthma, early removal from exposure to the sensitizing agent and early ICS-containing
treatment increase the probability of resolution of symptoms, and improvement of lung function and airway
hyperresponsiveness.
GINA recommends ICS-containing medication from diagnosis for several reasons:
GINA 2025: What is New?
Please Scan
the QR Code
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MedInsight
p Type 2 Inflammation Biomarkers
• Blood eosinophils and FeNO now
emphasized in diagnosis &
management.
• Circadian variability matters —
interpret with caution.
• New resource: Appendix A
consolidates biomarker info.
p Risk Factors for Severe
Exacerbation
• ORACLE2 study supports
considering multiple risk factors, not
just biomarkers.
• Real-world studies needed to
validate findings.
• External factors like pollution and
weather can affect risk.
p Climate Change & Extreme Weather
• New section added.
• Heat and cold increase exacerbation
risk and healthcare demand.
p Asthma in Children ≤5 Years
• Asthma diagnosis can now be made
in this age group.
• Use a pragmatic 3-point criteria:
1. Recurrent wheeze
2. No better explanation
3. Response to treatment
• Updated treatment & oxygen targets
• Strong evidence for ICS-formoterol
dose adjustment in Track 1.
• Limited support for ICS dose
doubling in Track 2.
p Emergency Care Guidance
• Clearer SABA dosing.
• Nebulized magnesium is no longer
recommended.
p Severe Asthma Workup
• Decision tree simplified.
• Confirm diagnosis after specialist
assessment.
• Reassess biomarkers if context
changes.
• Biologics evaluated up to 5 years.
p Diagnosis in Adults & Adolescents
• Clearer diagnostic flowchart.
• Biomarkers included.
• Term changed from “variable
expiratory airflow limitation” to
“variable expiratory airflow.”
p Personalized Asthma Management
• “Assess–Adjust–Review” cycle
redesigned.
• Use biomarkers after addressing
adherence & technique issues.
• Highlights individualized care vs.
population guidelines.
p Treatment Updates
• Track 1 (Preferred): ICS-formoterol
as both controller & reliever.
• Track 2: Step 4 now suggests
medium-dose ICS-LABA, not
high-dose.
• Fenoterol no longer recommended
due to heart risks.
• Fluticasone furoate doses
reclassified (100 mcg =
low-medium, 200 mcg =
medium-high).
p Asthma Action Plans Revised
• Now split by Track 1 vs. Track 2
strategy.
Nornal Lung COPD
Loss of elasticity
hyperinflammation, and
increased airspacess
Emphysema Bronchitis
Mucus overproduction
and hypersecretion
Pollutants,
toxic gases
and smoking
What happens in COPD?
In a healthy lung, the airways remain open and elastic, allowing smooth airflow to the alveoli, where oxygen
exchange occurs efficiently. The alveolar walls are intact, and minimal mucus production supports optimal lung
function.
In Chronic Obstructive Pulmonary Disease (COPD), persistent exposure to irritants (e.g., smoking) leads to
chronic inflammation. This results in thickened bronchial walls, excessive mucus secretion, and narrowing of
airways. The alveoli become damaged and lose their elasticity, impairing gas exchange. These structural
changes cause airflow limitation that is progressive and only partially reversible, forming the core
pathophysiology of COPD.
Chronic Obstructive Pulmonary
Disease (COPD) is a progressive lung
condition characterized by persistent
airflow limitation, mainly due to long-term
exposure to harmful substances like
tobacco smoke. Key symptoms include
shortness of breath, chronic cough, and
sputum production. COPD encompasses
emphysema, chronic bronchitis, and small airway
disease and is diagnosed through spirometry. Globally,
COPD is a significant health issue, ranking as the third
leading cause of death and affecting about 10.3% of the population, particularly in low - and
middle-income countries, where men are more affected. In high-income nations, aging and long-term
smoking contribute to its prevalence. Recent studies show that in Bangladesh, COPD prevalence is 12.5%
(GOLD criteria) and 11.9% (LLN criteria), with higher rates in males (22%), rural populations (17%), and
older individuals (27.5% among those aged 60-69).
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MedInsight
Childhood
120%
100%
80%
60%
Lung Function
(%predicted peak)
4 0%
2 0%
0%
0 0 20 30 40 50 60 70 80 90
Puberty Adulthood Aging
Supranormal
Normal
Pseudonornal
Below Normal
Accelerated
Decline
Catch-Up
Growth Failure
Premature
Death
Age (Year)
Trajectories of lung function: development & aging
Proposed Taxonomy (Etiotypes) for COPD
Classification Description
Genetically determined COPD
(COPD-G)
COPD due to abnormal lung development
(COPD-D)
Environmental COPD
COPD due to infections (COPD-l)
COPD & asthma (COPD-A)
Cigarette smoking COPD (COPD-C)
Biomass and pollution exposure
COPD (COPD-P)
Alpha-1 antitrypsin deficiency (AATD)
Other genetic variants with smaller effects acting in
combination
Early life events, including premature birth and low birthweight,
among others
Exposure to household pollution, ambient air pollution, wildfire smoke,
occupational hazard
Childhood infections, tuberculosis-associated COPO,
HIV-associated COPD
Particularly childhood asthma
• Exposure to tobacco smoke, including in utero or
via passive smoking
• Vaping or e-cigarette use
• Cannabis
This table shows how COPD
can develop through different
lung function patterns: normal
growth with accelerated decline
(e.g., smoking), impaired lung
growth from early life factors,
or a mix of both. It highlights
that not all COPD results from
adult exposures—early-life
insults (like infections or
maternal smoking) can also
lower peak FEV1.
Lung function normally peaks by age 20–25, then gradually declines with age. However, early-life factors like
poor lung development or childhood illness can lead to lower peak function or faster decline, increasing the risk
of COPD. Some people develop COPD from low lung growth, others from accelerated decline, or both. Aging
and structural mismatches in the lungs (like dysanapsis) also contribute. Understanding these trajectories
opens opportunities for early intervention and prevention of COPD.
The GOLD 2025 report introduces a proposed taxonomy of COPD based on etiotypes, which reflects the
diverse causes and mechanisms behind the disease. This new classification aims to move beyond the
traditional smoking-related model and better capture the heterogeneity of COPD.
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MedInsight
Combined Initial COPD Assessment
GOLD ABE Assessment Tool
Spirometrically
confirmed diagnosis
Assessment of airflow
obstruction
Assessment of
symptoms/risk of
exacerbations
Post-bronchodilator
FEV1/FVC < 0.7
GOLD 1 ≥80
GOLD 2 50-79
GOLD 3 30-49
GOLD 4 <30
≥ 2 moderate
exacer bations or
≥ 1 leading to
hospitalization
0 or 1 moderate
exacerbation
(not leading to
hospitalization)
mMRC 0-1
CAT < 10
mMRC ≥ 2
CAT ≥ 10
FEV1
(% predicted)
E
B
SYMPTOMS
A
GRADE
EXACERBATION
HISTORY
(PER YEAR)
The GOLD ABE Assessment Tool (2025 update) is a structured approach to guide the initial pharmacological
treatment of COPD based on three key components. This classification helps tailor initial treatment, such as
choosing between bronchodilators, dual therapy, or adding inhaled corticosteroids based on eosinophil count
and exacerbation history. The GOLD ABE tool groups patients into categories A, B, or E based on symptom
burden (mMRC or CAT score) and exacerbation history.
In the GOLD 2025 report, the section on
pre- and post-bronchodilator spirometry
has been expanded to improve diagnostic
accuracy for COPD. The core diagnostic
criterion remains a post-bronchodilator
FEV1/FVC ratio < 0.7, but the report now
emphasizes that relying solely on this fixed
ratio can lead to overdiagnosis in older
adults and underdiagnosis in younger
individuals, especially in mild cases. To
address this, the use of Lower Limit of
Normal (LLN) values and z-scores is
encouraged for more precise interpretation.
Additionally, if pre-bronchodilator
spirometry does not show obstruction,
post-bronchodilator testing may not be
necessary unless there is strong clinical
suspicion of COPD
*mMRC (Modified Medical Research Council) Dyspnea Scale
CAT (COPD Assessment Test)
Measure
Pre-Bronchodilator
FEV1/FVC
Measure
Post-Bronchodilator
FEV1/FVC
FEV1/FVC
≥ 0.7
FEV1/FVC
≥ 0.7
Not COPD
FEV1/FVC
< 0.7
FEV1/FVC
< 0.7
Flow response: needs
follow-up with repeat
assessment
COPD
confirmed
Measure Post-Bronchodilator
FEV1/FVC if volume responder
suspected e.g., low FEV1 or high
symptoms
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MedInsight
Single inhaler therapy may be more convenient and effective than multiple inhalers; single inhalers improve adherence to treatment. Consider
de-escalation of ICS if pneumonia or other considerable side-effects. In case of blood eos ≥ 300 cells/µL de-escalation is more likely to be
associated with the development of exacerbations. Exacerbations refers to the number of exacerbations per year.
DYSPNEA EXACERBATIONS
LABA or LAMA LABA or LAMA
If blood
eos < 300
If blood
eos ≥ 300
LABA + LAMA* • LABA + LAMA*
If blood
eos < 100 If blood
eos ≥ 100 If blood
eos ≥ 300
Roflumilast
FEV1 < 50% &
chronic bronchitis
Azithromycin
preferentially in
former smokers
• Consider switching inhaler device or
molecules
• Implement or escalate non-pharmacological
treatment(s)
• Consider adding ensifentrine
• Investigate (and treat) other causes
of dyspnea
Dupilumab
chronic
bronchitis
LABA + LAMA + ICS*
After starting treatment, adjustments are based on whether the patient has persistent dyspnea or
exacerbations. If dyspnea continues, escalate to dual bronchodilation (LABA + LAMA). If exacerbations persist,
consider adding ICS based on blood eosinophil count. For patients already on triple therapy, options include
macrolides, roflumilast, or biologics. Treatment is personalized and guided by symptoms, exacerbation history,
and biomarkers.
Follow-up Pharmacological Treatment
Initial Pharmacological Treatment
The GOLD 2025 initial pharmacological treatment for COPD is guided by the ABE Assessment Tool, which
classifies patients based on symptom burden and exacerbation risk. Here's a summary of the recommended
treatments for each group:
LABA+LAMA*
LABA+LAMA*
A bronchodilotor
GROUP E
GROUP A GROUP B
consider LAVA+LAMA+ICS* if blood eos ≥ 300
mMRC 0-1, CAT<10 mMRC ≥ 2, CAT ≥10
≥ 2 moderate
exacerbations or
≥1 leading to
hospitalization
o or 1 moderate
exacerbations
(not leading to
hospital admission}
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MedInsight
Patient currently on
LABA+ICS
• No current exacerbations
• Previous positive treatment
response
• No relevant
exacerbation history
Low
symptom
load
Continue
treatment
High
symptom
load
Consider
escalating to
LABA+LAMA+ICS
Consider
changing to
LABA+LAMA
• Current exacerbations
Blood
eosinophils
< 100 / µL
Blood
eosinophils
≥ 100 / µL
*Patient previously had exacerbations and responded to LABA+ICS treatment
Factors to consider when adding ICS to long-acting bronchodilators:
(note the scenario is different when considering ICS withdrawal)
History of hospitalization(s) for exacerbations of COPD*
≥ 2 moderate exacerbations of COPD per year*
Blood eosinophils ≥ 300 cells/µL
History of, or concomitant asthma
STRONGLY
FAVORS USE
1 moderate exacerbation of COPD per year*
Blood eosinophils 100 to < 300 cells/µL
FAVORS USE
Repeated pneumonia events
Blood eosinophils < 100 cells/µL
History of mycobacterial infection
AGAINST USE
For patients currently on LABA + ICS, the GOLD 2025 guidelines recommend reassessing treatment based on
symptoms and exacerbation history. If the patient continues to experience dyspnea, switching to LABA + LAMA
may provide better symptom control. If exacerbations persist, especially with a blood eosinophil count ≥100
cells/µL, stepping up to triple therapy (LABA + LAMA + ICS) is advised. However, if the patient is stable and
responding well, continuing LABA + ICS is acceptable, with regular monitoring. The decision should always
consider the original reason for initiating ICS and the patient’s current clinical status.
When considering adding an inhaled corticosteroid (ICS) to long-acting bronchodilators (LABA and/or LAMA)
in COPD management, the GOLD 2025 guidelines recommend evaluating several key factors.
Management of Patients Currently on LABA+ICS
Factors to Consider when Initiating ICS Treatment
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Non-pharmacological therapy is a cornerstone of COPD management and complements pharmacological
treatment to improve patient outcomes. Key interventions include smoking cessation, which is the most effective
way to slow disease progression, and pulmonary rehabilitation, which enhances exercise capacity, reduces
symptoms, and improves quality of life. Long-term oxygen therapy (LTOT) is recommended for patients with
severe resting hypoxemia, while noninvasive positive pressure ventilation (NPPV) may benefit those with
chronic hypercapnic respiratory failure. For advanced cases, lung volume reduction surgery (LVRS) and lung
transplantation are considered in carefully selected patients. Additional strategies such as vaccinations,
nutritional support, psychosocial care, and patient education play vital roles in comprehensive COPD care.
Summary of Non-Pharmacological Therapies in COPD
Smoking Cessation • Proven to reduce long-term mortality.
• Lung Health Study: 10-week intervention led to lower mortality over 14.5 years in mildly
symptomatic patients vs. usual care.
Pulmonary
Rehabilitation (PR)
• Reduces mortality when initiated during hospitalization or within 4 weeks post-discharge.
• Supported by: RCTs and a real-world cohort of 190,000 patients, where PR within 90 days showed
significant survival benefit.
Long-Term Oxygen
Therapy (LTOT)
• Beneficial in COPD patients with PaO2 ≤ 55 mmHg, or <60 mmHg with cor pulmonale or
polycythemia.
• NOTT & MRC Trials: Survival improved with ≥15–19 hours of daily oxygen use.
• No benefit in moderate desaturation.
Non-Invasive Ventilation
(NPPV)
• Recent trials using higher inspiratory pressure (IPAP) in stable, hypercapnic COPD patients showed
mortality benefit.
• Meta-analyses support use in selected patients, despite earlier inconsistent RCT results.
Lung Transplantation • Observational data suggest survival benefit in carefully selected COPD patients.
• ~40% of transplanted patients gain an estimated 2-year increase in life expectancy.
Lung Volume Reduction
Surgery (LVRS)
• Improves survival in patients with severe upper-lobe emphysema and low exercise capacity post-PR.
• Higher mortality in patients with non-upper-lobe emphysema and high exercise capacity when
compared to medical therapy.
Triple therapy in COPD—combining a LABA (long-acting beta-agonist), LAMA (long-acting muscarinic
antagonist), and ICS (inhaled corticosteroid)—is recommended for patients with persistent symptoms or
frequent exacerbations despite dual therapy. The GOLD 2025 guidelines emphasize its use particularly in those
with blood eosinophil counts ≥100 cells/µL, with the greatest benefit seen at ≥300 cells/µL. Triple therapy has
been shown to reduce exacerbations, improve lung function, and enhance quality of life, and may even lower
mortality in high-risk patients. However, ICS use should be carefully considered due to the risk of pneumonia,
especially in patients with low eosinophil levels. Regular reassessment is essential to ensure ongoing benefit
and minimize side effects.
1. Removed:
• Entire COVID-19 & COPD chapter.
2. New Additions:
• 3 new figures (Pre-/Post-Bronchodilator Spirometry,
LABA+ICS Management, PH-COPD Treatment).
• New sections: Dysbiosis, Climate Change & COPD,
Cardiovascular Risk (R COPD), Pulmonary Hypertension.
3. Key Updates:
• Vaccination guidelines (aligned with CDC).
• Spirometry expanded (LIN/z-scores, new reference values).
• New drugs added: Ensifentrine
(bronchodilator/anti-inflammatory) & Dupilumab
(anti-inflammatory).
• ICS withdrawal guidance revised.
• CT imaging now covers emphysema, nodules, and
comorbidities.
4. Reorganization:
• Remote follow-up moved to Self-management section.
• COPD checklist shifted to Appendix.
Focus:
• New treatments, expanded diagnostics, and environmental
impacts on COPD.
GOLD 2025: What is New?
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MedInsight
Interventional Therapies in Stable COPD
Syndromic Approach to Initial Treatment in Points with Asthma and/or COPD
Lung Volume
Reduction Surgery
Lung volume reduction surgery improves survival in severe emphysema patients with upper-lobe
emphysema and low post-rehabilitation exercise capacity
Bullectomy In selected patients, bullectomy is associated with decreased dyspnea, improved lung function,
and exercise tolerance
Lung Transplantation • In appropriately selected patients with very severe COPD, lung transplantation has been shown
to improve quality of life and functional capacity
• In patients with very severe COPD (progressive disease, BODE score of 7 to 10, and not
candidates for lung volume reduction), lung transplantation may be considered for referral with
at least one of the following:
(1) History of hospitalization for exacerbation associated with acute hypercapnia
(PCO2>50PCO2>50 mmHg);
(2) Pulmonary hypertension and/or cor pulmonale, despite oxygen therapy; or
(3) FEV1 < 20% and either DLco < 20% or homogenous distribution of emphysema
Bronchoscopic Interventions
Bronchoscopic
Interventions Under
Study
In select patients with advanced emphysema, bronchoscopic interventions reduce end-expiratory
lung volume and improve exercise tolerance, health status, and lung function at 6-12 months
following treatment.
• Endobronchial valves • Lung coils • Vapor ablation
Phase III trials are currently being conducted to determine the efficacy of treatments for patients
with refractory exacerbations and chronic bronchitis using cryospray, rheoplasty, and targeted lung
denervation technology.
The GINA 2025 and GOLD 2025 guidelines emphasize evidence-based, personalized management for asthma and COPD, respectively.
GINA 2025 highlights the preferred use of ICS-formoterol as both maintenance and reliever therapy (MART) to reduce exacerbations and
simplify treatment, while also addressing non-pharmacological strategies like smoking cessation and allergen avoidance. For COPD,
GOLD 2025 prioritizes bronchodilation with LAMA/LABA and incorporates ICS in high-risk patients, alongside pulmonary rehabilitation
and vaccination. Both guidelines recognize asthma-COPD overlap (ACO) and stress the importance of biomarker-guided therapy (e.g.,
eosinophils for ICS or biologics), with implementation challenges remaining in low-resource settings.
CLINICAL PHENOTYPE - ADULTS WITH CHRONIC RESPIRATORY SYMPTOMS (dyspnea, cough, chest tightness, wheeze)
INITIAL PHARMACOLOGICAL TREATMENT (as well as treating comorbidities and risk factors)
REVIEW PATIENT AFTER 2-3 MONTHS. REFER FOR EXPERT ADVICE IF DIAGNOSTIC UNCERTAINTY OR INADEQUATE RESPONSE
HIGHLY LIKELY TO BE ASTHMA FEATURES OF BOTH ASTHMA + COPD
TREAT AS ASTHMA
LIKELY TO BE COPD
If several of the following features
TREAT AS COPD
if several of the following features
TREAT AS ASTHMA
HISTORY
• ICS-CONTAINING TREATMENT IS ESSENTIAL
• ICS-CONTAINING TREATMENT IS ESSENTIAL
• TREAT AS COPD (see GOLD report)
• DO NOT GIVE LABA and/or LAMA without ICS • DO NOT GIVE LABA and/or LAMA without ICS
• Maintenance OCS only as last resort • Maintenance OCS only as last resort
• Avoid high dose ICS, avoid maintenance OCS
• Reliever containing ICS is not recommended
- GINA Track 1 with ICS-formoterol as reliever is
the preferred regimen.
• Add-on LABA and/or LAMA usually also needed.
• Additional COPD treatments as per GOLD
- Initially maintenance LABA-LAMA
- Add ICS as per GOLD for patients with
hospitalizations, ≥2 exacerbations/year
requiring OCS, or blood eosinophils ≥300µl
to reduce risk of severe exacerbations and
death.
to reduce risk of severe exacerbations and
death.
LUNG FUNCTION
• Symptoms vary over time and in intensity
- Triggers may include laughter, exercise,
allergens, seasonal
- Onset before age 40 years
- Symptoms improve spontaneously or
with bronchodilators (minutes) or ICS
(days to weeks)
• Current asthma diagnosis, or asthma diagnosis
in childhood
• Symptoms intermittent or episodic
- May have started before or after age 40
• May have a history of smoking and/or other
toxic exposures, or history of low birth weight
or respiratory illness such as tuberculosis
• Any of asthma features at left (e.g., common
triggers; symptoms improve spontaneously or
with bronchodilators or ICS; current asthma
diagnosis or asthma diagnosis in childhood)
• Persistent expiratory airflow limitation
• With or without bronchodilator reversibility
• Variable expiratory airflow limitation
• Persistent airflow limitation may be present
HISTORY
• Dyspnea persistent (most days)
- Onset after age 40 years
- Limitation of physical activity
- May have been preceded by cough/sputum
- Bronchodilator provides only limited relief
• History of smoking and/or other toxic exposure,
or history of low birth weight or respiratory illness
such as tuberculosis
• No past or current diagnosis of asthma
• Persistent expiratory airflow limitation
• With or without bronchodilator reversibility
HISTORY
LUNG FUNCTION
LUNG FUNCTION
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MedInsight
Available Medications used in Asthma and/or COPD
Generic Drug Name Inhaler Type Nebulizer Oral/Injectable Delivery Duraon of Acon
BETA-Agonists
Short-acng (SABA)
Fenoterol MDI √ tablet, soluon variable
Levalbuterol MDI √ variable
Salbutamol (albuterol) MDI & DPI √ syrup, tablet variable
Terbutaline DPI tablet variable
Long-acng (LABA)
Arformoterol √ 12 hours
Formoterol DPI √ 12 hours
Indacaterol DPI 24 hours
Olodaterol SMI 24 hours
Salmeterol MDI & DPI 12 hours
Ancholinergics
Short-acng (SAMA)
Ipratropium bromide MDI √ 6-8 hours
Oxitropium bromide MDI √ 7-9 hours
Long-acng (LAMA)
Acidinium bromide DPI 12 hours
Glycopyrronium bromide DPI soluon variable
Tiotropium DPI, SMI, MDI 24 hours
Umeclidinium DPI 24 hours
Glycopyrronium √ 12 hours
Revefenacin √ 24 hours
Combinaon Short-Acng Beta-Agonist Plus Ancholinergic in One Device (SABA+SAMA)
Fenoterol/Ipratropium SMI √ 6-8 hours
Salbutamol/Ipratropium SMI, MDI √ variable
Combinaon Long-Acng Beta-Agonist Plus Ancholinergic in One Device (LABA+LAMA)
Formoterol/acidinium DPI 12 hours
Formoterol/glycopyrronium MDI 12 hours
Indacaterol/glycopyrronium DPI 12-24 hours
Vilanterol/umeclidinium DPI 24 hours
Olodaterol/otropium SMI 24 hours
Methylxanthines
Aminophylline √ soluon, injectable variable
Theophylline (SR) √ tablet, capsule, elixir, soluon, variable
injectable
Combinaon of Long-Acng Beta-Agonist Plus Corcosteroid in One Device (LABA+ICS)
Formoterol/beclometasone MDI, DPI 12 hours
Formoterol/budesonide MDI, DPI 12 hours
Formoterol/mometasone MDI 12 hours
Salmeterol/flu:icasone propionate MDI, DPI 12 hours
Vilanterol/flu:icasone furoate DPI 24 hours
Triple Combinaon in One Device (LABA+LAMA+ICS)
Flucasone/umeclidinium/vilanterol DPI 24 hours
Beclometasone/formoterol/glycopyrronium
MDI, DPI 12 hours
Budesonide/formoterol/glycopyrrolate MDI 12 hours
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MedInsight
ICS + LABA + LAMA Inhaler
For many years, the treatment of asthma and chronic obstructive
pulmonary disease (COPD) has centered on combinations of
bronchodilators and inhaled corticosteroids. Patients found quick
relief from short-acting β2-agonists and short-acting muscarinic
antagonists, but these therapies offered little in the way of
sustained control. As the diseases progressed to moderate or
severe stages, inhaled corticosteroids were paired with
long-acting β2-agonists (LABA) to provide a more consistent
therapeutic effect. Even so, a significant proportion of
patients—nearly 30 to 50% in the case of asthma—remained
inadequately controlled. Similarly, many individuals living with
COPD continued to endure frequent exacerbations and persistent
symptoms despite regular ICS and LABA therapy.
It was in response to these gaps in treatment that triple therapy
emerged, a formulation combining ICS, LABA, and long-acting
muscarinic antagonists (LAMA). This marked a significant leap
forward, not just in pharmacology but in the overall approach to
disease management. By integrating these three agents, single
inhaler triple therapy offered a more comprehensive
strategy—reducing inflammation, sustaining bronchodilation, and
blocking the effects of acetylcholine-induced bronchoconstriction.
A major breakthrough came in September 2017 when both the
U.S. Food and Drug Administration and the European Medicines
Agency approved the first single-inhaler triple therapy for COPD.
This innovation brought together the three medications into one
convenient device, simplifying usage for patients and improving
adherence. Then in November 2020, Australia’s Therapeutic
Goods Administration approved an extra-fine formulation of triple
therapy. This inhaler contained beclometasone dipropionate,
formoterol fumarate, and glycopyrronium bromide, marking a new
standard in precision therapy.
Following closely, the European
Commission granted its approval to the same extra-fine formulation
in April 2021. The unique feature of this formulation was its ability to
improve drug deposition in the lungs, particularly in the small
airways, an area often under-addressed in conventional inhaler
therapies. As research began to uncover the pivotal role of small
airways in both asthma and COPD, the relevance of such targeted
formulations became even clearer.
In a prospective study involving 773 asthma patients, an astonishing
91% were found to have dysfunction in the small airways. In
another observational study of 202 COPD patients with elevated CAT
scores, 93% showed similar involvement.
These findings brought to light an often-overlooked dimension of
obstructive airway disease and highlighted the pressing need for
treatments that could effectively reach these peripheral regions of
the lung.
The combination of extra-fine beclometasone with formoterol and
glycopyrronium further strengthened the therapeutic impact.
Formoterol, known for its rapid onset of action, begins working
within just 1-3 minutes, offering fast relief while maintaining
bronchodilation for up to 12 hours. Glycopyrronium complements
this with its long-acting muscarinic receptor blockade. What makes
it particularly effective is its 4-fold selectivity for M3 receptors over
M2, targeting bronchial smooth muscle while minimizing unwanted
cardiac effects.
Taken together, this single inhaler triple therapy represents a new era
in the management of asthma and COPD. It is not just the
combination of drugs that makes the difference, but how they are
delivered—finely tuned to penetrate the small airways, tailored to
reduce inflammation and bronchoconstriction simultaneously, and
engineered for maximum safety and convenience. In a landscape
where many patients still struggle with inadequate control, these
innovations offer renewed hope and a more targeted path forward.
Single Inhaler Triple Therapy (SITT) with
Extrafine Beclomethasone, Formoterol,
and Glycopyrronium in Asthma and COPD
Extra-fine beclometasone, a key component of the newer single
inhaler triple therapies, quickly stood out for its clinical
advantages. Its small particle size 1.1µm
allowed for superior lung
deposition and distribution, reaching deep into both central and
peripheral airways. Compared to more traditional corticosteroids
like budesonide, fluticasone, and mometasone, beclometasone
offered enhanced anti-inflammatory effects with significantly
lower systemic absorption, reducing the risk of steroid-related
side effects and offering a safer long-term treatment option.
To reach the airways,
particles should be
smaller than 5 µm; ICS
with particles on the
larger side of this range
have more deposition
in the upper airway
than ICS of extrafine
particle size 1 (< 2 µm),
which distribute more
uniformly across the
lower airway."
1 µm
2 µm
3 µm
4 µm
5 µm
16
MedInsight
Proven Clinical Evidence
TRIMARAN & TRIGGER
Study Summary
Study Design:
Both trials were randomized, double-blind,
parallel-group, active-controlled studies lasting 52
weeks. The TRIMARAN trial was conducted at 171
sites across 16 countries, while the TRIGGER trial had
221 sites in 17 countries.
Patient Group:
• Age: 18–75 years
• Uncontrolled asthma (ACQ-7 ≥1.5)
• History of at least one asthma exacerbation in the
past year
• Required medium-dose ICS/LABA (TRIMARAN) or
high-dose ICS/LABA (TRIGGER)
• Pre-bronchodilator FEV1 <80% of predicted normal
• Diagnosed with asthma before age 40
Treatment Groups:
• TRIMARAN (Medium-Dose ICS/LABA):
BDP/FF/G (100 µg BDP, 6 µg FF, 10 µg G) vs.
BDP/FF (100 µg BDP, 6 µg FF)
• TRIGGER (High-Dose ICS/LABA):
BDP/FF/G (200 µg BDP, 6 µg FF, 10 µg G) vs.
BDP/FF (200 µg BDP, 6 µg FF) vs. BDP/FF +
Tiotropium (200 µg BDP, 6 µg FF + 2.5 µg
Tiotropium)
Results:
LUNG FUNCTION IMPROVEMENT
A. Predose FEV1
♦ TRIMARAN: BDP/FF/G improved FEV1 by +57 mL
(p=0.0080)
♦ TRIGGER: BDP/FF/G improved FEV1 by +73 mL
(p=0.0025)
B. Peak FEV1
• TRIMARAN: +84 mL Peak FEV1 (p=0.0002),
TRIGGER: +105 mL Peak FEV1 (p<0.0001),
C. Morning PEF
• TRIMARAN: +8.5 L/min PEF (p=0.0006)
• TRIGGER: +7.8 L/min PEF (p=0.0014)
ASTHMA EXACERBATIONS
• TRIMARAN: 15% reduction in moderate/severe
exacerbations with BDP/FF/G (p=0.033)
• TRIGGER: 12% reduction, moderate/severe
exacerbations with BDP/FF/G (p=0.11)
• Pooled Analysis: 23% reduction in severe
exacerbations with BDP/FF/G (p=0.0076)
Conclusion:
In uncontrolled asthma, single-inhaler triple therapy
(BDP/FF/G) has demonstrated significant
improvements in lung function and a reduced risk of
exacerbations. It is well-tolerated, with no
unexpected safety concerns.
73mL
(Change from baseline:
229 mL vs 127 mL [p=.0025])
57mL
(Change from baseline:
185 mL vs 127 mL [p=.0080])
TRIMARAN TRIGGER
15
%Recduction in rate of moderate and
severe exacerbations over 52 weeks
(annualised rate:1.83 vs. 2.16 [ARR 0.33
RR 0.85, p=0.033])
BDP/FF/G pooled (n=1146)
BDP/FF pooled (n=1145)
Severe exacerbations Moderate exacerbations Moderate and severe
exacerbations
Rate ratio* 0·77
(0·64 to 0·93); p=0·0076
0·24
(0·21 to 0·28)
0·31
(0·27 to 0·35)
1·52
(1·39 to 1·65)
1·72
(1·58 to 1·87)
1·79
(1·65 to 1·94)
2·07
(1·92 to 2·24)
0
2·5
2·0
1·5
1·0
0·5
Annualised rate of exacerbations
Rate ratio 0·88
(0·78 to 1·00); p=0·043
Rate ratio 0·86
(0·77 to 0·96); p=0·0083
Ref.: https://doi.org/10.1016/S0140-6736(19)32215-9
j.c.virchow@med.uni-rostock.de
17
MedInsight
Proven Clinical Evidence
Results
LUNG FUNCTION
• Pre-dose FEV1 improved by +81 mL (p<0・001)
• 2-hour post-dose FEV1 improved by +117 mL
(p<0.001)
EXACERBATION
• 23% reduction in moderate-to-severe exacerbations
(p=0.005)
• 33% reduction in frequent exacerbators; longer time
to first exacerbation (HR 0.80, p=0.020)
SYMPTOMS & QOL
• SGRQ (St. George’s Respiratory Questionnaire):
Significant QoL (Quality of Life) improvement at
Weeks 4, 12, 52
Conclusion:
Single-inhaler BDP/FF/GB significantly improved lung function and reduced exacerbation risk, especially in
frequent exacerbators; QoL improved, safety profile comparable to dual therapy.
Study Design
Randomized, double-blind, parallel-group, 52-week trial at 159 sites in 14 countries; 2-week BDP/FF run-in, then
comparison of BDP/FF/GB vs BDP/FF.
Patient Group
• 1,368 COPD patients (≥40 years)
• Post-BD FEV1 <50%, ≥1 moderate/severe exacerbation in past year
• CAT score ≥10, BDI score ≤10
TRILOGY Study Summary
0·45
0·33
0·12
0·56
0·43
0·14
0
0·1
0·2
Annualised exacerbation rate
0·3
0·4
0·5
0·6
Moderate/severe
exacerbations
Moderate
exacerbations
Severe
exacerbations
BDP/FF/GB (N=687)
BDP/FF (N=680)
BDP/FF/GB
BDP/FF
–7·0
–6·0
–5·0
–4·0
–3·0
–2·0
–1·0
0
SGRQ total score adjusted mean change from baseline
*
*
†
524012 26 40
Time since randomisation (weeks)
Treatment Groups:
• Triple Therapy: BDP/FF/G 100/6/10 µg via pMDI, 2
puffs BID (Total daily: 400/24/40 µg)
• Dual Therapy (Comparator): BDP/FF 100/6 µg via
pMDI, 2 puffs BID
Ref.: dsingh@meu.org.uk
19
MedInsight
Controls Moderate to Severe
Asthma Effectively
ICS + LABA + LAMA Inhaler
Study Design:
A Phase II, double-blind, double-dummy, randomized,
multicenter, three-way crossover trial (June
2018–March 2019) comparing extrafine BDP/FF/G DPI
(88/5/9 µg) with BDP/FF/G pMDI (87/5/9 µg) and
BDP/FF pMDI (100/6 µg) in COPD patients. Each
treatment lasted 4 weeks, separated by 2-week
washouts.
Patient Group:
Patients aged 40–85 years with a ≥12-month
diagnosis of COPD, FEV1 30–80% predicted
post-bronchodilator, and stable symptoms. All
patients received 2 inhalations BID of each treatment
during respective periods.
Treatment Groups (Short):
• Triple Therapy (BDP/FF/G): 100/6/10 µg per puff, 2
puffs BID (pMDI)
• Dual Therapy (BDP/FF): 100/6 µg per puff, 2 puffs
BID (pMDI)
Result:
Lung Function (Co-primary Endpoints): BDP/FF/G DPI
and pMDI showed non-inferior efficacy in FEV1
• AUC0-12h and 24-h trough FEV1 on Day 28.
AUC0-12h: −20 mL (95% CI: −35 to −6)
Trough FEV1: +3 mL (95% CI: −15 to 20)
Exacerbation Rate:
• 23% reduction in moderate-to-severe exacerbations
with BDP/FF/G pMDI vs. BDP/FF pMDI.
• Time to first exacerbation significantly prolonged
with triple therapy.
Symptom Control:
• Significant SGRQ improvement in both triple therapy
groups, especially in the symptoms domain.
Safety:
• All formulations were well tolerated with comparable
safety profiles; no new safety signals.
Proven Clinical Evidence
TRI-D Study Summary
Conclusion:
In moderate-to-severe COPD patients, BDP/FF/G
DPI was non-inferior to the pMDI version for
improving lung function and reducing
exacerbations. With comparable safety and efficacy,
the DPI formulation offers a viable alternative,
supporting patient preference and personalized
inhaler choice in clinical practice.
Conclusion:
In high-risk COPD patients, single-inhaler extrafine triple therapy (BDP/FF/G) significantly reduced
moderate-to-severe exacerbations versus dual bronchodilator (IND/GLY), without increasing pneumonia risk.
The greatest benefit was seen in patients with chronic bronchitis and elevated eosinophils, supporting its use in
these subgroups.
Subgroups:
♦
Chronic bronchitis: 25% reduction (p=0.010)
♦
Eosinophils ≥2%: 19% reduction (p=0.029)
• Lung Function & QoL: No significant difference in
FEV1 or SGRQ scores
• Pneumonia Risk: Similar (BDP/FF/G: 3.7%,
IND/GLY: 3.5%)
• Adherence: Very high in both groups (≈98.5%)
TRIBUTE Study Summary
Recduction in rate of moderate and
severe exacerbations over 52 weeks
(Annualized rate; 0.50 vs 0.59 [RR=0.848,p=043])
15%
23%
Ref.: doi: 10.1016/S0140-6736(18)30206-X. Epub 2018 Feb 9. & https://pubmed.ncbi.nlm.nih.gov/29429593/
Ref.: International Journal of Chronic Obstructive Pulmonary Disease, PMCID: PMC7814657 DOI: 10.2147/COPD.S291030
21
MedInsight
Management
Patient 2 (Asthama and COPD or possible asthma with non-T2
inflammation) Management approach in primary care
Inclusion of an ICS is currently the consensusbased
recommended treatment for patients with COPD with a
childhood history of asthma
• Aim for low-dose ICS Fixed airflow obstruction (associated
with future risk of exacerbations)
• Step up to long-acting bronchodilator therapy
• Use of an ICS/LABA combination
• Addition of a LAMA if ongoing frequentexacerbations (more
than two per year) Evaluate for bronchiectasis
• Chest CT scan If chronic mucus hypersecretion
• Physiotherapy review for chest clearance Include antibiotic
therapy targeted against Haemophilus influenzae during
exacerbations Impaired exercise capacity and breathlessness
• Assess for deconditioning. Refer forpulmonary rehabilitation
Further management options in specialist centres
• Further down-titration of ICS is recommended if FeNO
confirms the ongoing absence of eosinophilic airway
inflammation
• Consider the use of mucolytics if difficult to clear secretions
• Consider a macrolide antibiotic for persistent exacerbations
CASE-2
Susan is 54 years old with a longstanding history of asthma
since childhood that has been poorly controlled. She
experiences regular cough and purulent sputum. She is often
breathless on exertion, suchas walking up one flight of stairs.
Her exacerbations are increasing in frequency, with three in the
past 12 months, all requiring treatment with antibiotics. She
has no history of atopy.
She has a 10 pack year smoking history, but has recently
quit. Susan has severe airflow obstruction (FEV1 48%
predicted) but no significant BDR (100 mL and 5% response
to salbutamol). Her blood eosinophils level is 0.1 × 109/L
and FeNO is 13 ppb. Sputum microbiology reveals infection
with Haemophilus influenzae. Her chest CT scan is clear, with
no emphysema or bronchiectasis.
What are the alternative disease labels for Patient 2?
Asthma with non-T2 inflammation.
CASE-3
John, 73 years old, has declining exercise tolerance in the last
12 months, which is now limited to 100 m on the flat. He is an
active smoker of 40 pack years. He has no previous history of
asthma or atopy. John has frequent exacerbations, with four
in the past year, all requiring oral prednisone. He has
moderate airflow obstruction (FEV1 62% predicted) and
significant BDR (400 mL and 20% response to salbutamol).
John’s blood eosinophils level is at 0.3 × 109/L and FeNO at 55
ppb. He has no lower respiratory tract infection. A chest CT
scan reveals widespread centrilobular emphysema.
What are the alternative disease labels for Patient 3?
COPD with eosinophilic inflammation or COPD with
bronchodilator reversibility.
Management
Patient 3 (Asthama and COPD or possible COPD with
eosinophilic inflammation or bronchodilator reversibility)
Management approach in primary care
Airflow obstruction
• Treat with long-acting bronchodilators
• Given severe airflow obstruction, begin treatment with
LABA/LAMA combination (no role for stepped introduction)
Eosinophilic airway inflammation
• Add ICS Impaired exercise capacity and breathlessness
• Assess for deconditioning
• Refer for pulmonary rehabilitation Recommend smoking
cessation to
• Improve response to ICS
• Reduce mucus hypersecretion
• Decrease exacerbation frequency
• Slow decline in lung function Further management options
inspecialist centres
• Titrate ICS dose based on response to FeNO and blood
eosinophils
• If the patient has persistent exacerbations andrefractory
eosinophilic airway inflammation,add monoclonal antibodies
directed against anti-IL-5 – targeting this patient’s asthma
traits and inflammatory phenotype*
• Evaluate for extrathoracic causes of frequent exacerbations,
including chronic rhinosinusitis, vocal cord dysfunction,
anxiety or depression, dysfunctional breathing.
Case studies
23
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