Pulmonary Function Testing in Cystic Fibrosis Ramachandra R. Sista, MD Division of Pulmonary & Critical Care Medicine Stanford University Cystic Fibrosis – Multisystem disorder CFTR [Ion Channel] ‘Mutations’ • Defective epithelial salt and fluid transport • 1 in 2-3K live births in US Cystic Fibrosis - Airways Respiratory Tract/Sinus disease • Chronic airway Inflammation • Colonization by bacteria • Rhinosinusitis • Nasal polyps • Bronchitis/bronchiectasis • Hemoptysis • Productive cough • Copious sputum production/secretions • Lung hyperinflation • PFT evidence for obstructive ventilatory limitation CF – Airways Cystic Fibrosis – Lung Function Respiratory Pump Thorax Diaphragm Abdomen Abdomen Airways [Trachobronchial tree] Gas Exchange [Functional units] Pulmonary Function Testing [PFT] • Spirometry (Flow Volume Loop) ± BDR • Lung volumes • Diffusion capacity (DLCO) Spirometry Simple, reproducible and office-based • How much of air can you move? - in & out - [vital capacity] • How fast can you move? - in & out - [flow / time] • Based on these two - FVC and FEV1 Spirometry • Monitoring of spirometry – simple and quick • Early recognition and quick intervention for pulmonary decline / acute exacerbation • Minimize loss of lung function Impact of Respiratory Pathogens • Staph (MRSA, MSSA) • Pseudomonas (mucoid, non-mucoid, MDR) • Haemophilus influenza • Stenotrophamonas maltophilia • Burkholderia cepacia • Achromobacter xylocans • Non-tuberculous mycobacteria [NTM – eg. MAC] • Aspergillus species [ABPA] Impact of Respiratory Pathogens Impact of Airway therapies Pulmonary therapies • Antibiotics (PO, IV, IH) • Macrolide therapy (anti-inflammatory/neutrophil) • Bronchodilators • Treatment of ABPA • DNAase (Dornase, Pulmozyme) • Hypertonic saline • N-acetylcysteine • Chest physiotherapy • Exercise Hypertonic saline Anti Inflammatory Agents CFRD, Nutrition and Lung function • Very important part of successful CF management • Aggressive management of CFRD • Neutrophil dysfunction • Associated with accelerated loss of lung function • Increased mortality risk Nutrition and BMI FEV1 Percent Predicted vs. BMI in Adults 20 to 40 Years 90 FEV1 Percent Predicted 80 Males 70 60 50 40 30 15 16 17 18 19 20 21 22 BMI 23 24 25 26 27 28 29 30 FEV1 percent is positively correlated with BMI percentile for patients 20 to 40 years of age (correlation = 0.92, p < 0.0001) CFRD – Glucose Control – FEV1 Semin Respir Crit Care Med 2007 Cystic Fibrosis - Cornerstones • Airway clearance • Dornase alfa (2.5 mg nebulized daily) • Nebulized antibiotics • Oral azithromycin • Inhaled hypertonic saline [7% 2-4 times per day] • Aggressive antibiotic therapy for exacerbations • Nutritional support (high-caloric, high-salt diet) • Replacement of fat-soluble vitamins [A, D, E, K] • Exercise Cystic Fibrosis - Cornerstones • Airway clearance • Dornase alfa (2.5 mg nebulized daily) • Nebulized antibiotics • Oral azithromycin • Inhaled hypertonic saline [7% 2-4 times per day] • Aggressive antibiotic therapy for exacerbations • Nutritional support (high-caloric, high-salt diet) • Replacement of fat-soluble vitamins [A, D, E, K] • Exercise Acknowledgement David Weill, MD Gundeep Dhillon, MD Paul Mohabir, MD Kathy Gesley Nicole Eden Lara Freet Lesley Seeger CF Clinical Research Team Pediatric Pulmonologists