What cells are primarily responsible for asthma?

Cells Responsible for Asthma

The primary cells responsible for asthma are mast cells, eosinophils, T lymphocytes (particularly Th2 cells), neutrophils, macrophages, and epithelial cells, with eosinophils and T lymphocytes playing the most crucial roles in the inflammatory process that drives asthma pathophysiology. 1

Key Inflammatory Cells in Asthma

Primary Cells

• Eosinophils: Central to allergic/T2-high asthma, releasing inflammatory mediators that cause airway damage and hyperresponsiveness 1, 2
• T lymphocytes: Particularly CD4+ Th2 cells that orchestrate the allergic response through cytokine production (IL-4, IL-5, IL-13) 3, 4
• Mast cells: Release histamine and other mediators during allergen exposure, causing immediate bronchoconstriction 1, 5

Secondary Cells

• Neutrophils: Predominant in specific asthma phenotypes including severe asthma, sudden-onset fatal exacerbations, occupational asthma, and in smokers 1
• Macrophages: Contribute to chronic inflammation and remodeling 1, 5
• Epithelial cells: Both targets of inflammation and active participants in the inflammatory response 1, 5

Asthma Phenotypes and Cell Predominance

Eosinophilic/T2-High Asthma

This is the classic allergic asthma pattern characterized by:

• Predominance of eosinophils and Th2 lymphocytes 2
• Production of Th2 cytokines (IL-4, IL-5) 3
• Good response to corticosteroid therapy 1
• Often associated with atopy and allergic triggers 1

Neutrophilic/T2-Low Asthma

This phenotype is characterized by:

• Predominance of neutrophils rather than eosinophils 1
• Often seen in severe, refractory asthma 1
• Associated with sudden-onset fatal exacerbations 1
• More common in smokers and those with occupational asthma 1
• Less responsive to conventional corticosteroid therapy 1

Non-Asthmatic Eosinophilic Bronchitis (NAEB)

This related condition shares features with asthma but has important differences:

• Similar eosinophilic inflammation to asthma 1
• Lacks airway hyperresponsiveness characteristic of asthma 1
• Different pattern of mast cell localization compared to asthma 1
• Responds to anti-inflammatory treatments 1

Pathophysiological Mechanisms

Inflammatory Cascade

1. Allergen exposure activates mast cells and Th2 lymphocytes 2
2. Th2 cells release cytokines (IL-4, IL-5, IL-13) 3
3. IL-5 recruits and activates eosinophils 2
4. Activated inflammatory cells release mediators causing:
   • Bronchoconstriction
   • Mucus hypersecretion
   • Airway edema
   • Airway hyperresponsiveness 1

Airway Remodeling

Chronic inflammation leads to structural changes:

• Subbasement membrane fibrosis 1
• Smooth muscle hypertrophy 1
• Mucus gland hyperplasia 1
• Angiogenesis 1
• These changes may lead to fixed airflow obstruction over time 1

Clinical Implications

Diagnostic Considerations

• Sputum cell counts can help identify the predominant inflammatory cell type 1
• Blood eosinophil counts and fractional exhaled nitric oxide (FeNO) can indicate eosinophilic inflammation 1
• Different cell patterns may require different treatment approaches 6

Treatment Implications

• Eosinophilic asthma typically responds well to corticosteroids 1
• Neutrophilic asthma may be less responsive to conventional steroid therapy 1
• Phenotype switching can occur due to environmental factors, aging, infections, or treatment effects, requiring reassessment of inflammatory patterns and treatment adjustments 6

Pitfalls and Caveats

• Asthma phenotypes can change over time (phenotype switching), requiring periodic reassessment of inflammatory patterns 6
• Corticosteroids may prolong neutrophil survival by decreasing apoptosis, potentially worsening neutrophilic inflammation 1
• The presence of neutrophils doesn't exclude eosinophilic inflammation; mixed patterns can occur 1
• Focusing solely on one cell type may lead to suboptimal treatment in patients with mixed inflammatory patterns 6
• Environmental exposures, infections, and aging can all modify the inflammatory cell pattern in asthma 6

Understanding the cellular basis of asthma is crucial for appropriate phenotyping and targeted therapy selection, ultimately improving control of symptoms and reducing the risk of exacerbations and long-term complications.