Causes of Acute Exacerbation of Cystic Fibrosis
Acute exacerbations of cystic fibrosis are primarily caused by respiratory infections, with Pseudomonas aeruginosa being the most common bacterial pathogen, followed by viral infections such as rhinovirus, and environmental factors that trigger increased inflammation in the airways. 1, 2
Bacterial Infections
Pseudomonas aeruginosa
- Most common and significant bacterial pathogen in CF patients 1
- Presence of P. aeruginosa in the airways, especially mucoid strains, causes:
- Immediate and rapid reduction of lung function
- Increased sputum volumes
- Higher neutrophil numbers and inflammatory response
- Progressive lung damage and respiratory failure if left untreated 1
- Chronic P. aeruginosa infection leads to:
- More frequent exacerbations
- Faster decline in pulmonary function
- Increased morbidity and mortality 1
Other Bacterial Pathogens
- Staphylococcus aureus (including MRSA)
- Klebsiella species
- Haemophilus influenzae
- Achromobacter xylosoxidans
- Stenotrophomonas maltophilia 3
Viral Infections
Viral infections are increasingly recognized as significant triggers of CF exacerbations:
Present in up to 80% of exacerbations in children with CF 2
Most common viral pathogens:
Viral-bacterial co-infections:
- Significant relationship between influenza A, enterovirus, human metapneumovirus and bacterial infections 2
- Viruses can facilitate bacterial colonization and worsen exacerbations 4
- Non-mucoid P. aeruginosa with rhinovirus co-infection increases IL-1β production and compromises epithelial barrier function 5
Pathophysiological Mechanisms
Inflammation and Immune Response
- Increased inflammation with higher neutrophil numbers and released serine proteinases 1
- Altered cytokine production during infections:
- Increased IL-1β during viral-bacterial co-infections
- Protease-mediated degradation of IL-6 during non-mucoid P. aeruginosa and rhinovirus co-infection 5
- Compromised epithelial barrier function during co-infections 5
Upper Respiratory Tract Involvement
- Paranasal sinuses serve as a reservoir for bacteria and a site for bacterial adaptation 3
- Infections can spread from sinuses to the lower respiratory tract 3
Clinical Presentation and Diagnosis
Signs and symptoms of an acute exacerbation include:
- Increased cough and sputum production
- Changes in sputum characteristics (color, consistency)
- Decreased pulmonary function (FEV1)
- Increased respiratory rate
- Fever
- Decreased appetite and weight loss 1
Diagnosis typically involves:
- Clinical assessment
- Pulmonary function testing
- Sputum culture for bacterial pathogens
- Nasal swabs with multiplex PCR for viral detection 2
Prevention and Management
- Regular monitoring with monthly or at least quarterly microbiological cultures 6
- Early treatment of P. aeruginosa colonization with combination therapy:
- Inhaled antibiotics (colistin or tobramycin)
- Oral ciprofloxacin 6
- For acute exacerbations:
Important Considerations
- The relationship between bacterial density reduction and improvement in lung function suggests that antibiotic therapy directly impacts clinical outcomes 1
- CF patients with CFRD (CF-related diabetes) have a greater frequency and severity of pulmonary exacerbations 1
- Proper nebulizer hygiene and technique are essential when using inhaled antibiotics 6
- Monthly monitoring for P. aeruginosa in patients without previous colonization is recommended 6
Understanding these causes and mechanisms is crucial for early intervention and effective management of acute exacerbations in CF patients, ultimately improving long-term outcomes and quality of life.