How do infections trigger asthma attacks?

How Infections Trigger Asthma Attacks

Respiratory viral infections, particularly rhinovirus, are the predominant triggers for acute worsening of asthma symptoms, responsible for approximately 80-85% of exacerbations in children and 50% in adults. 1

Mechanisms of Infection-Triggered Asthma Exacerbations

Viral Infections

• Viral infections cause neutrophilic inflammation of both upper and lower airways, leading to increased airway inflammation and hyperresponsiveness 1, 2
• Rhinovirus, respiratory syncytial virus (RSV), and influenza are the most common viral triggers for asthma exacerbations 3
• Viruses trigger inflammatory cascades that lead to increased mucus production, bronchial hyperresponsiveness, and airflow obstruction 2
• Experimental models show rhinovirus increases eosinophilic inflammation and airway hyperresponsiveness, particularly in allergic individuals 1

Bacterial Infections

• Atypical bacteria, particularly Chlamydia pneumoniae and Mycoplasma pneumoniae, play significant roles in both inducing and exacerbating asthma 4
• Streptococcus pneumoniae, Hemophilus influenzae, and Moraxella catarrhalis have been linked to asthma exacerbations, especially when sinusitis is present 5
• Bacterial infections can contribute to both the initial development and subsequent exacerbation of asthma 4

Pathophysiological Changes During Infection

Airway Inflammation

• Infections cause accumulation of inflammatory cells in the airway mucosa and submucosa, including neutrophils, lymphocytes, and eosinophils 3
• Viral infections enhance production of inflammatory mediators from airway epithelial cells, mast cells, and other inflammatory cells 3
• Key inflammatory mediators released include IL-1, IL-6, IL-8, GM-CSF, RANTES, histamine, and intercellular adhesion molecule-1 3

Airway Function Changes

• Infections lead to bronchoconstriction through direct effects on airway smooth muscle 6
• Airway hyperresponsiveness increases during infections, causing exaggerated bronchoconstrictor responses to various stimuli 7
• Airway edema, mucus hypersecretion, and formation of mucus plugs further limit airflow 6
• Viral infections affect the barrier function of airway epithelial cells and vascular endothelial cells 3

Immune System Involvement

Altered Immune Responses

• Patients with asthma may have impaired interferon responses in airway epithelial cells, leading to augmented viral replication 3
• Mycoplasma infections can activate innate immunity and increase Th2-dominant immune responses 8
• Cysteinyl leukotrienes and transforming growth factor beta are involved in increased airway hyperresponsiveness during Mycoplasma infections 8

The Hygiene Hypothesis

• The hygiene hypothesis suggests that certain infections early in life may actually protect against asthma development 6
• This theory proposes that early childhood infections help direct the immune system away from allergic (Th2) responses 6
• However, certain infections like RSV and specific bacteria clearly exacerbate rather than protect against asthma 6

Clinical Implications

Risk Factors

• Patients with asthma experience more severe and prolonged symptoms from viral infections compared to non-asthmatic individuals 2
• Multiple triggers, including infections, correlate with more severe disease 9
• Early-life infections with microbes like Chlamydia pneumoniae may alter the lung microbiome, affecting asthma risk and treatment outcomes 4

Management Considerations

• Biological therapies like omalizumab can reduce the frequency of infection-triggered exacerbations 2
• Macrolide antibiotics may improve asthma control through both anti-inflammatory effects and by eradicating certain bacteria like Mycoplasma 8
• Patients should have written action plans for managing infection-triggered exacerbations 2

Pitfalls in Understanding Infection-Triggered Asthma

• Bacterial causes of exacerbations have received less attention than viral triggers but may be equally important 5
• Distinguishing between viral and bacterial infections can be challenging as both can cause neutrophilic inflammation 2
• Not all infections worsen asthma; the hygiene hypothesis suggests some may be protective, creating complexity in understanding the relationship 6