Adult Asthma: A Clinical Guide

Definition

Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation. It is defined by the history of variable respiratory symptoms such as wheeze, shortness of breath, chest tightness, and cough, and by variable expiratory airflow limitation (1, 2). This definition, emphasized by both the Malaysian Clinical Practice Guidelines (CPG) and the Global Initiative for Asthma (GINA), reframes asthma not just as a condition of bronchospasm, but as a chronic inflammatory disease requiring anti-inflammatory treatment. The term "heterogeneous" is critical; it acknowledges that asthma is not one single entity but an umbrella term for different underlying disease mechanisms (endotypes) that result in similar clinical presentations (phenotypes). "Variable expiratory airflow limitation" is the physiological hallmark, meaning the obstruction to airflow changes over time, either spontaneously or with treatment. This variability is what distinguishes asthma from conditions with fixed airflow obstruction, like COPD.

Epidemiology

In Malaysia, asthma represents a significant public health issue. The National Health and Morbidity Survey (NHMS) 2023 reported a known asthma prevalence of 6.2% among adults, with an additional 2.7% having probable undiagnosed asthma (3). This highlights a substantial population needing accurate diagnosis and management, with a considerable diagnostic gap. Suboptimal control is a major and persistent concern; multiple local studies have consistently shown that a large proportion of Malaysian patients have partly controlled or uncontrolled asthma. This is often linked to the underutilization of, and poor adherence to, inhaled corticosteroid (ICS) therapy, the cornerstone of management (4). This "real-world" evidence-practice gap may be driven by factors such as lack of patient education, concerns about steroid side effects, incorrect inhaler technique, and the cost of medication.

Globally, asthma affected an estimated 262 million people and caused 455,000 deaths in 2019 (5). While prevalence is high in developed nations, over 80% of asthma-related mortality occurs in low- and middle-income countries. This stark disparity underscores critical global inequities in healthcare, highlighting the impact of socioeconomic factors on access to essential, life-saving medications like ICS (5).

Pathophysiology

The clinical signs of asthma are driven by a triad of chronic airway inflammation, airway hyperresponsiveness, and, in the long term, airway remodeling. Understanding this cascade is fundamental to modern management.

The core of asthma's pathophysiology is chronic inflammation, which is now understood to be heterogeneous. The main distinction is between T2-high and T2-low asthma.

• T2-High (Eosinophilic) Asthma: This is the most common and best-understood endotype, accounting for over 50% of cases, and is often allergic ("atopic") and starts in childhood. It is driven by an overactive Type 2 immune response, orchestrated by T-helper 2 (Th2) cells. Upon exposure to an allergen, Th2 cells release key cytokines: Interleukin-4 (IL-4), which drives B-cells to produce allergen-specific IgE; Interleukin-5 (IL-5), the master regulator of eosinophils, promoting their production, activation, and survival; and Interleukin-13 (IL-13), a crucial driver of airway hyperresponsiveness, mucus production, and fibrosis (6). This IgE-eosinophil dominant pathway is the primary target of inhaled corticosteroids and the newer biologic agents (e.g., anti-IgE, anti-IL5).

• T2-Low (Non-Eosinophilic) Asthma: This group is more diverse and includes neutrophilic or paucigranulocytic (few inflammatory cells) asthma. It is more common in adult-onset asthma, obesity-related asthma, and in smokers. The inflammation is thought to be driven by different immune pathways, such as Th1 and Th17 cells, which recruit neutrophils instead of eosinophils. Because these pathways are not effectively suppressed by corticosteroids, these patients are often less responsive to standard ICS therapy, posing a significant management challenge (6).

This underlying inflammation leads to Airway Hyperresponsiveness (AHR), an exaggerated bronchoconstrictor response to various triggers like exercise, cold air, or allergens that would not affect a healthy individual (7). This is the direct cause of the variable symptoms patients experience. Over time, uncontrolled inflammation and repeated cycles of injury and repair lead to Airway Remodeling. This refers to permanent structural changes in the airway wall, including thickening of the basement membrane (subepithelial fibrosis), an increase in the size and number of airway smooth muscle cells (hypertrophy and hyperplasia), proliferation of blood vessels (angiogenesis), and an increase in mucus-producing goblet cells. This process can lead to a progressive, irreversible loss of lung function and fixed airflow limitation, making the disease clinically similar to COPD (8). This provides a powerful rationale for consistent use of anti-inflammatory controller therapy not just for symptom control, but to preserve long-term lung health.

Clinical Presentation

The classic presentation involves a pattern of variable and recurring respiratory symptoms. The key to diagnosis is recognizing this variability.

• Diagnostic Clues: The diagnosis is strongly suggested by the presence of more than one cardinal symptom (wheeze, shortness of breath, cough, chest tightness) that varies in intensity and is often worse at night or upon waking, sometimes causing sleep disturbance. A careful history will reveal that symptoms are typically triggered by factors like viral infections (a common cold "going to the chest"), exercise (especially in cold air), exposure to allergens (e.g., cats, dust), or irritants (e.g., smoke, strong perfumes) (1).

• Common Symptoms (>50%):

  • Wheezing: A high-pitched, musical whistling sound on expiration, caused by turbulent airflow through narrowed airways.

  • Shortness of Breath (Dyspnea): A distressing sensation of being unable to get enough air.

  • Cough: Often non-productive, persistent, and characteristically worse at night. In "cough-variant asthma," a chronic dry cough may be the sole presenting symptom, making diagnosis more challenging.

  • Chest Tightness: Often described by patients as a "band-like" sensation or a feeling of pressure on the chest.

• ⚠️ Red Flag Signs & Symptoms: These indicate a severe, life-threatening exacerbation requiring immediate and aggressive intervention. Every houseman must recognize these signs of impending respiratory failure.

  • Inability to speak in complete sentences: The patient can only speak in single words, indicating severe breathlessness.

  • Drowsiness, confusion, or agitation: These are ominous signs of significant hypoxia and/or hypercapnia (rising CO2) affecting the central nervous system.

  • A "silent chest": In a patient who is clearly in severe respiratory distress, the disappearance of wheeze is a pre-terminal sign. It indicates that airflow has become so minimal that it is insufficient to generate sound, heralding respiratory arrest (9).

  • Cyanosis: A bluish discoloration of the lips and tongue indicating severe systemic hypoxemia.

  • Bradycardia or hypotension: These are late and grave signs of cardiovascular collapse.

  • Use of accessory muscles and paradoxical thoraco-abdominal movement: Visible use of neck muscles (sternocleidomastoids) and inward movement of the abdomen during inspiration indicate diaphragmatic fatigue and extreme work of breathing.

Complications

• Acute: Severe exacerbation leading to status asthmaticus (a prolonged, severe attack unresponsive to standard bronchodilators), respiratory failure requiring mechanical ventilation, and pneumothorax or pneumomediastinum from high airway pressures.

• Chronic: Airway remodeling with fixed airflow limitation leading to a COPD-like picture, recurrent pneumonia due to mucus plugging and impaired clearance, bronchiectasis, and significant psychological morbidity including anxiety and depression related to the chronic nature of the disease.

Prognosis

With appropriate management and adherence to therapy, the prognosis for most patients with asthma is excellent. The primary goal is to achieve good control, allowing patients to lead normal, active lives with minimal disruption. However, several factors worsen prognosis. Poor adherence to treatment, particularly to ICS, is the most common cause of poor outcomes. Continued smoking drastically accelerates lung function decline and reduces the effectiveness of corticosteroids. Frequent exacerbations act as episodes of acute injury that contribute to progressive, irreversible airway remodeling (1).

Differential Diagnosis

• Chronic Obstructive Pulmonary Disease (COPD): This is a key differential, especially in adults over 40 with a significant smoking history. COPD typically presents with persistent, progressive dyspnea and chronic productive cough. While both can have wheeze, the airflow limitation in COPD shows little or no reversibility on spirometry (post-bronchodilator FEV1/FVC ratio <0.7). However, Asthma-COPD Overlap (ACO), where a patient has features of both diseases, is increasingly recognized (2).

• Congestive Heart Failure ("Cardiac Asthma"): Consider this in older patients with cardiovascular risk factors, particularly if they have orthopnea, paroxysmal nocturnal dyspnea, pitting edema, and bilateral basal crackles on examination. A chest X-ray showing cardiomegaly and pulmonary edema, along with elevated cardiac biomarkers (BNP), can help differentiate (9).

• Vocal Cord Dysfunction (VCD): This can mimic acute asthma with wheezing (more accurately, an inspiratory stridor) and dyspnea. The key difference is that the obstruction in VCD is laryngeal, often heard loudest over the neck. Spirometry may show a flattened inspiratory loop. Symptoms often have a sudden onset, can be triggered by stress or irritants, and resolve quickly once the trigger is removed. Direct laryngoscopy during an episode confirms the diagnosis (9).

• Gastroesophageal Reflux Disease (GERD): Chronic cough, especially at night or after meals, can be a primary symptom of GERD due to microaspiration of gastric contents. Consider this if the patient also reports heartburn or regurgitation, although these "classic" reflux symptoms may be absent ("silent reflux"). A therapeutic trial of a proton pump inhibitor may be both diagnostic and therapeutic.

Investigations

The justification for each test is integrated into its description, linking the rationale to the clinical action.

Immediate & Bedside Tests (in an acute setting)

• Pulse Oximetry (SpO2): This is a mandatory, non-invasive "fifth vital sign" to rapidly assess for hypoxemia (the action), which is a direct consequence of severe airflow obstruction and ventilation-perfusion (V/Q) mismatch (the rationale). The target is to maintain SpO2 ≥94% (2).

• Peak Expiratory Flow (PEF): A bedside PEF measurement provides a quick, objective, and quantifiable measure of airflow obstruction severity (the action), which is essential for triaging the patient's attack severity (mild, moderate, severe) and serially monitoring their response to initial bronchodilator treatment (the rationale).

Diagnostic Workup

• First-Line Investigation (Spirometry): The Malaysian CPG identifies spirometry as the preferred and essential tool for diagnosis (2). It is performed to objectively confirm the presence of airflow limitation (FEV1/FVC < lower limit of normal) and its characteristic variability (the rationale). These are the core physiological pillars of the asthma definition, and demonstrating them confirms the clinical diagnosis (the action). Significant reversibility, the hallmark of asthma, is shown by an increase in FEV1 of >12% AND >200 mL from baseline after administering a short-acting beta2-agonist (SABA) (1, 2).

• Gold Standard: While spirometry is the primary diagnostic tool, a bronchial challenge test (e.g., with methacholine) can be considered the gold standard for confirming airway hyperresponsiveness when spirometry is normal but clinical suspicion remains high. It directly measures AHR. A positive test (a fall in FEV1 of ≥20% at a standardized concentration) confirms the underlying pathophysiology of asthma (7). It has a high negative predictive value, making it very useful to rule out asthma in cases of diagnostic uncertainty.

Monitoring & Staging

• Chest X-ray: A CXR is not for routine diagnosis of stable asthma. However, it is crucial in a severe or atypical acute exacerbation to exclude important alternative diagnoses or complications (the action), such as a pneumothorax, lobar collapse from a mucus plug, pneumonia, or signs of heart failure, all of which can mimic or complicate a severe attack (the rationale) (9).

• Full Blood Count (FBC): An FBC is a simple and useful test to identify an elevated peripheral blood eosinophil count (the rationale). This finding supports a T2-high inflammatory phenotype, which not only predicts a good clinical response to ICS but is also a key biomarker used to determine a patient's suitability for specific biologic therapies like anti-IL5 agents (the action) (1).

• Allergy Testing: For patients with a history suggesting atopy (e.g., personal or family history of eczema or allergic rhinitis), skin prick tests or blood tests for specific IgE can identify relevant allergic triggers like house dust mites or cat dander (the rationale). This is essential for providing targeted, effective advice on environmental trigger avoidance, which is a key component of a comprehensive non-pharmacological management plan (the action) (9).

Management

Management Principles

The management of asthma, as outlined by GINA and the Malaysian CPG, is built on a continuous cycle of assessment, treatment adjustment, and review. It has dual goals: achieving good symptom control in the present and minimizing future risk of adverse outcomes like exacerbations and lung function decline (1, 2). A core, non-negotiable principle of modern asthma care is that SABA monotherapy is no longer recommended for adults. Because asthma is a chronic inflammatory disease, all adults should receive ICS-containing treatment to address the underlying pathology and reduce the risk of severe, life-threatening exacerbations (1, 2).

Acute Stabilisation (The First Hour of a Severe Exacerbation)

• Airway/Breathing: Administer high-flow oxygen via a face mask with the goal of maintaining SpO2 ≥94% (the action). This is critical to correct hypoxemia caused by severe V/Q mismatch and prevent end-organ hypoxia (the rationale).

• Circulation: Secure intravenous (IV) access promptly. While large-volume fluid resuscitation is not typically required, reliable IV access is vital for administering IV medications like corticosteroids or magnesium sulphate if needed (the rationale).

• Disability/Exposure: Continuously assess conscious level. Drowsiness or confusion are red flags for impending respiratory failure and the need for escalation to critical care.

• Key Medications:

  • Inhaled SABA: Administer high-dose Salbutamol (e.g., 5mg via nebulizer or 4-10 puffs via a metered-dose inhaler [MDI] with a spacer), repeated every 20 minutes for the first hour (the action). This provides rapid relaxation of airway smooth muscle to relieve life-threatening bronchoconstriction (the rationale). An MDI with a spacer is as effective as a nebulizer in most situations and may be preferred to reduce aerosol generation (2).

  • Inhaled Anticholinergic: Add Ipratropium Bromide (0.5mg) to the nebulized salbutamol for all moderate-to-severe attacks (the action). It provides synergistic bronchodilation by blocking cholinergic-mediated bronchoconstriction, offering additional benefit over SABA alone (the rationale) (2).

  • Systemic Corticosteroids: Administer oral Prednisolone (e.g., 40-50mg) or IV Hydrocortisone (e.g., 100mg) early to all patients with a moderate or severe exacerbation (the action). This is crucial to suppress the intense underlying airway inflammation driving the attack, which accelerates recovery, reduces the rate of relapse, and prevents progression to a more severe state (the rationale) (2).

Definitive Therapy

Long-term management follows a stepwise approach, aiming to find the lowest dose of treatment that maintains control. The GINA guidelines provide two tracks (1).

• Track 1 (Preferred): Low-Dose ICS-Formoterol as Maintenance and Reliever Therapy (MART). This is the preferred evidence-based strategy because it ensures a patient receives an anti-inflammatory ICS dose whenever they feel symptoms and use their reliever. This single inhaler approach simplifies treatment and directly links symptom relief with anti-inflammatory action. Formoterol's rapid onset of action makes it suitable as a reliever, while its long-acting properties contribute to maintenance control.

  • Step 1-2 (Mild Asthma): As-needed low-dose ICS-formoterol.

  • Step 3 (Moderate Asthma): Daily low-dose ICS-formoterol maintenance PLUS as-needed for relief (MART).

  • Step 4 (Severe Asthma): Daily medium-dose ICS-formoterol maintenance PLUS as-needed for relief (MART).

  • Step 5 (Very Severe Asthma): Add-on Long-Acting Muscarinic Antagonist (LAMA). Refer for phenotype assessment (blood eosinophils, FeNO, IgE) and consideration of biologic therapy (e.g., anti-IgE, anti-IL5).

• Track 2 (Alternative): SABA as Reliever. This track is an alternative when MART is not feasible or preferred. The guiding principle is that the SABA reliever must always be prescribed alongside a regular, separate ICS-containing controller inhaler to ensure the underlying inflammation is treated.

  • Step 1-2: Daily low-dose ICS with as-needed SABA.

  • Step 3: Daily low-dose ICS/LABA combination inhaler with as-needed SABA.

  • Step 4: Daily medium/high-dose ICS/LABA combination with as-needed SABA.

  • Step 5: Add-on LAMA and refer for specialist care and consideration of biologics.

Supportive & Symptomatic Care

• Patient Education: This is a paramount and ongoing process. Educate patients on the chronic inflammatory nature of their disease, the crucial difference between "reliever" (SABA) and "controller" (ICS) inhalers, and meticulously check and correct their inhaler technique at every visit.

• Written Asthma Action Plan (WAAP): All patients should have a personalized, easy-to-understand WAAP. This empowers self-management by providing clear instructions on how to monitor their symptoms or PEF, how to adjust their medication (e.g., when to increase controller dose), and when to seek urgent medical help.

• Trigger Avoidance: Provide specific, practical advice based on allergy testing and a detailed environmental history. This may include using allergen-proof bedding, HEPA air filters, or discussing workplace modifications for occupational asthma.

• Smoking Cessation: Strongly and repeatedly advise all patients who smoke or vape to quit, and offer referral to smoking cessation services. This is one of the most impactful interventions for improving asthma outcomes (2).

Key Nursing & Monitoring Instructions

• In an acute setting, monitor vital signs frequently, especially respiratory rate, heart rate, and SpO2. Be alert for tachycardia and tremor, which are side effects of high-dose SABA.

• Strictly chart all reliever medication use, as increasing need indicates worsening control.

• Continuously observe for signs of clinical deterioration, particularly increasing fatigue, drowsiness, or inability to speak, which are more reliable than wheeze severity.

• Inform medical staff immediately if SpO2 drops below 94%, the patient develops a silent chest, becomes confused, or if there is a rise in the PaCO2 on an arterial blood gas.

Long-Term Plan & Patient Education

• Schedule regular follow-up appointments (e.g., every 3-6 months for stable patients) to assess symptom control, adherence, and inhaler technique.

• Perform spirometry periodically (e.g., at diagnosis, 3-6 months after starting treatment to establish personal best, and then at least annually) to monitor for long-term decline in lung function, a sign of airway remodeling.

• Educate patients on recognizing the signs of worsening symptoms and how to correctly use their WAAP. Emphasize that the ultimate goal of treatment is not just to be symptom-free, but to enable them to live a full, physically active life with minimal limitations.

When to Escalate

A house officer must recognize the limits of their capability and call for senior help in a timely and appropriate manner.

Call Your Senior (MO/Specialist) if:

• The patient presents with any life-threatening features (silent chest, confusion, cyanosis, exhaustion).

• The patient is not responding adequately to initial treatment after the first hour (e.g., PEF remains <50% of predicted, SpO2 not improving despite oxygen).

• The patient appears physically exhausted, as this indicates impending respiratory muscle failure.

• An arterial blood gas (ABG) shows a normal or rising PaCO2 (a PaCO2 > 45 mmHg is a very ominous sign indicating respiratory muscle fatigue and failure to maintain ventilation) or a severe, uncompensated acidosis (e.g., pH < 7.25).

Referral Criteria:

• Refer to a respiratory specialist for any patient requiring Step 4 or 5 management to optimize therapy and assess for advanced treatments.

• Refer for consideration of biologic therapy if asthma remains uncontrolled despite optimal high-dose ICS/LABA/LAMA therapy and good adherence.

• Refer to a specialist if the diagnosis is uncertain, if there are features of complications like bronchiectasis, or if occupational asthma is suspected, which may require specialized investigation and management.

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References

(1) Global Initiative for Asthma. (2024). Global Strategy for Asthma Management and Prevention, 2024. https://ginasthma.org/2024-report/

(2) Ministry of Health Malaysia. (2017). Clinical Practice Guidelines on the Management of Asthma in Adults. Putrajaya: MOH. https://www.moh.gov.my/moh/resources/Penerbitan/CPG/Respiratory/CPG%20Management%20of%20Asthma%20in%20Adults.pdf

(3) Institute for Public Health (IPH), National Institutes of Health (NIH), Ministry of Health Malaysia. (2023). National Health and Morbidity Survey (NHMS) 2023: Fact Sheet. https://iku.nih.gov.my/images/nhms2023/fact-sheet-nhms-2023.pdf

(4) Chan, G. Y., et al. (2020). Asthma control and asthma treatment adherence in primary care: results from the prospective, multicentre, non-interventional, observational cohort ASCOPE study in Malaysia. Medical Journal of Malaysia, 75(4), 369-377.

(5) World Health Organization. (2024). Asthma. https://www.who.int/news-room/fact-sheets/detail/asthma

(6) Wenzel, S. E. (2021). Type 2 inflammation in asthma: new insights into the role of the epithelium and treating the right patient. The Journal of Allergy and Clinical Immunology: In Practice, 9(4), 1409-1419.

(7) Fahy, J. V. (2015). Type 2 inflammation in asthma--present in most, absent in many. Nature Reviews Immunology, 15(1), 57–65.

(8) Hough, K. P., et al. (2020). Airway remodeling in asthma. Frontiers in Medicine, 7, 191.

(9) Boulet, L. P., & O'Byrne, P. M. (2015). Asthma and exercise-induced bronchoconstriction in athletes. New England Journal of Medicine, 372(7), 641-648.