What is the treatment approach for patients with airways hypersensitivity?

Treatment Approach for Airways Hypersensitivity

The treatment of airways hypersensitivity should focus on identifying the specific type of hypersensitivity, with inhaled corticosteroids as first-line therapy for most forms, supplemented by bronchodilators, antigen avoidance strategies, and in some cases, desensitization protocols. 1

Types of Airways Hypersensitivity

• Airways hypersensitivity can manifest as airway hyperresponsiveness (AHR) in asthma, characterized by increased sensitivity to inhaled stimuli and variable airflow limitation 1
• Aspirin-exacerbated respiratory disease (AERD) represents a specific form of airways hypersensitivity to COX-1 inhibitors 1
• Hypersensitivity pneumonitis (HP) is an immunologically mediated lung disease caused by inhaled antigens, affecting both airways and lung parenchyma 2, 3

Diagnostic Approach

• Airway hyperresponsiveness can be measured by direct challenge tests (methacholine, histamine) or indirect challenge tests (hypertonic saline, adenosine monophosphate, mannitol) 1
• For AERD, diagnostic uncertainty may require an aspirin challenge to confirm the diagnosis 1
• Measurement of pulmonary function, including FEV1, is essential for diagnosis and monitoring response to treatment 1

Treatment Strategies

Pharmacologic Management

• Inhaled corticosteroids (ICS) are the cornerstone of treatment for airways hypersensitivity in asthma, reducing both airway hypersensitivity and the maximal degree of airway narrowing 4
• Long-acting beta-agonists (LABAs) in combination with ICS provide additional bronchodilation and control of symptoms 5
• Leukotriene modifiers may be particularly beneficial in AERD and should be considered as pretreatment for patients preparing for aspirin desensitization 1

Specific Approaches for Different Types

For Asthma-Related Airways Hypersensitivity:

• Start with medium-dose ICS with or without LABA, titrating based on symptom control 1, 5
• Monitor airway function with spirometry or peak flow measurements 1
• Consider adding leukotriene modifiers if symptoms persist despite ICS/LABA therapy 1

For AERD:

• Avoid aspirin and other COX-1 inhibitors (see Table XVIII in evidence) 1
• Consider aspirin desensitization for patients with poorly controlled upper and lower respiratory disease despite appropriate medications 1
• Aspirin desensitization protocols typically start with small doses (20-40 mg) and gradually increase to therapeutic doses (325-650 mg) 1
• After successful desensitization, daily aspirin therapy (650 mg twice daily initially) is required to maintain tolerance 1

For Hypersensitivity Pneumonitis:

• Antigen identification and avoidance is the primary treatment strategy 2, 3
• For non-fibrotic HP with severe symptoms, prednisone at 1-2 mg/kg/day tapered over 4-8 weeks is recommended 2
• For fibrotic HP, immunosuppressive therapy may be needed when complete antigen avoidance cannot be achieved 2, 3

Monitoring and Follow-up

• Regular assessment of lung function (FEV1, FVC, DLCO) is essential to monitor response to treatment 1, 2
• In asthma, monitor for improvement in airway hyperresponsiveness, which may require repeated challenge testing 1, 6
• For AERD patients on aspirin therapy, monitor for gastritis and gastrointestinal bleeding; consider enteric-coated aspirin and gastrointestinal prophylaxis 1

Common Pitfalls and Caveats

• Failure to identify and avoid triggering antigens can lead to persistent symptoms and disease progression 2, 3
• Gaps in aspirin doses >48 hours in AERD patients may lead to loss of tolerance and require repeat desensitization 1
• Systemic corticosteroids can cause significant adverse effects including immunosuppression, hypercorticism, adrenal suppression, and reduced bone mineral density 5
• Relying solely on bronchodilators without addressing underlying inflammation may lead to inadequate control of airways hypersensitivity 1, 7

Special Considerations

• Patients with severe asthma may have steroid resistance or require "higher than expected" doses, suggesting altered steroid responsiveness 1
• Alternative anti-inflammatory and immunomodulating drugs (methotrexate, gold, cyclosporine) may be considered in refractory cases, but have limited efficacy and significant side effects 1
• For patients with allergic bronchopulmonary aspergillosis (ABPA), treatment should consist of a combination of corticosteroids and itraconazole 1