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Bronchiectasis - causes and diagnosis
Bronchiectasis is defined as abnormal irreversibly dilated and thick-walled bronchi resulting from destruction of the bronchial wall. Its pathogenesis involves defects in mucociliary clearance, cellular immunity, or associated conditions. High-resolution CT is helpful for diagnosis by showing features like tram lines or honeycombing. Additional tests may be needed to identify underlying causes. Microbiology of infected airways guides antimicrobial therapy for managing the vicious cycle of infection and inflammation that can progress the disease.
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Bronchiectasis - causes and diagnosis
- 1. Bronchiectasis Causes andDiagnosis S a n t i S i l a i r a t a n a , M D Pulmonar y Medicine Uni t , Depar tment of Medicine, Facul ty of Medicine Vaj i ra Hospi tal Navamindradhiraj Unive r s i ty
- 2. Bronchiectasis: Outline Disease definition Airway defense mechanisms Causes Pathology & Diagnosis Pathophysiology
- 3. Bronchiectasis /bräŋ′kē ek′təsis/ First original pathological description by René-Théophile-Hyacinthe Laennec in 1819 Abnormal irreversibly dilated and often thick-walled bronchi ! resulting from a variety of pathologic process that cause destruction of the bronchial wall and its surrounding supporting tissues
- 4. Airway Defense Mechanisms Mucociliary clearance Innate immunity Neutrophils Macrophages and dentritic cells NK cells Adaptive Immunity Cellular components Protein components Immunoglobulins T and B lymphocytes Toll-like receptors Antimicrobial proteins: Lysozymes, lactoferrins, peroxidase, defensin, cathecidins Inflammatory cytokines: interferons, cytokines, chemokines, complements Waterer G W. Clin Chest Med 33 (2012) 211-217.
- 5. Etiology of Bronchiectasis Chronic/persistent ! Endobronchial TB Bronchial obstruction ABPA Repeated/episodic GERD Aspirations Posterior nasal drip Acute/severe Measles Mucociliary defects 1o ciliary dyskinesia Influenza pneumonia inhalation injury Radiation injury Cystic fibrosis Cellular/immune defects Common variable immune deficiency X-link agammaglobulinemia Hyper IgE syndrome Alpha1-antitrypsin deficiency HIV infection Associated conditions Rheumatoid arthritis Sjögren syndrome Relapsing polychondritis SLE Airway defenses Injury events 1st hit Bronchiectasis 2nd hit
- 6. Reported Etiologies ofBronchiectasis Others 6% 2% 2% 3% 5% 7% 8% 24% 45% Idiopathic Rheumatoid arthritis GERD or aspiration Young syndrome Primary ciliary dyskinesia Allergic bronchopulmonary aspergillosis Immunodeficiency Postinfectious Quast T M, Self A R, Browning R F et al. Dis Mon 2008; 54: 527-539. Pasteur M C, Helliwell S M, Hughton S J et al. Am J Respir Crit Care Med 2006; 100: 2183-2189.
- 7. Pathogenesis of Bronchiectasis:The Vicious Cycle Release of inflammatory cytokines peroxidases, proteinases elastase, etc. Destruction of mucociliary and cartilagenous supporing structures Infection with acute inflammation and recruitment of inflmmatory cells Colonization and biofilm formation intermittent dispersals Impairment mucociliary clearance sputum retention Loss of ventilatory function
- 8. Pseudomonas aeruginosa inBronchiectasis Flagellum Mobility Release of the proinflammatory chemokines on attachment Pili Adherence to lipid membrane Release of toll-like receptors Recruitment of phagocytic cells Lipopolysaccharide Quarum sensing Alginate Adherence to the epithelial cells Pyocyanin Disruption of the epithelial cell wall Impairment of ciliary function Systemic inflammation Production of lactone cell-cell signaling Barker A F, Moulton B C. Clin Chest Med 33 (2012) 211-217.
- 9. Role of Biofilms Adapted from Beckford-Ball J. http://woundsinternational.wordpress.com
- 10. Histologic Changes inBronchiectasis Normal bronchus Bronchiectasis Cartilage destruction and fibrosis Mucosal and mucous gland hyperplasia Inflammatory cells infiltration Increased mucus and exudates
- 11. Diagnosis of Bronchiectasis:General Consideration Underlying or associated condition(s) Microbiology of the bronchiectatic airway Definitive diagnosis Severity of impairment
- 12. Clinical Manifestations ofBronchiectasis Clinical Features of bronchiectasis Clinical features of the associated/causative condition(s) History Chronic productive cough* Sputum production* Reported bouts of respiratory tract infection Physical examination Wheezing, rhonchi, crackles Clubbing Cyanosis CTDs Arthritis Sicca syndrome ABPA Prominent wheezing Bronchial obstruction localized wheezing PCD, CF, Young Syndrome Recurrent sinus disease Infertility
- 13. Pathological Classification ofBronchiectasis
- 14. Chest Radiograph Bronchialwall thickening and widening with parallel configuration “Tram track” sign
- 15. Chest Radiograph (2) Conglomerating cysts of varying size and wall thickness “Honeycomb” sign
- 16. High Resolution CT Cylindrical Saccular/Varicoid Cystic
- 17. Spirometry and ArterialBlood Gas Analysis Supportive evidence of airway disease (Obstructive defect) Severity assessment (Severe impairment = poor prognosis) Bronchodilator therapy (Positive bronchodilator response) Oxygen therapy (Hypoxemia)
- 18. Diagnosis of Bronchiectasis:General Consideration Microbiology of the bronchiectatic airway Definitive diagnosis Severity of impairment Underlying or associated condition(s)
- 19. Additional Tests forDiagnosis of Bronchiectasis Test/Procedure Suggestive clinical features Etiology Quantitative immunoglobulins (IgG, IgA, IgM) Concomitant sinus disease, recurrent infection Common variable immune deficiency Aspergillous-specific IgG, IgE level, aspergillus skin testing Asthma, central bronchiectasis, prominent mucus plugging Allergic bronchopulmonary aspergillosis IgE level Eczema, staphylococcal infections, retained primary teeth Hypergammaglobulinemia E (Job sydrome) Alpha-1 antitrypsin level Emphysema Alpha-1 antitrypsin deficiency Sweat chloride, nasal potential Concominant sinus disease, younger difference or CF mutation screen age, upper lobe disease Cystic fibrosis Bronchoscopy Unilateral focal disease Bronchial obstruction Metersky M L. Clin Chest Med 33 (2012) 211-217.
- 20. Additional Tests forDiagnosis of Bronchiectasis (2) Test/Procedure Suggestive clinical features Etiology Bronchoscopy with mycobacterial cultures “Tree-in-bud” on HRCT, nodules, cavity, scoliosis, pectus Nontuberculous mycobacteria and tuberculosis Ciliary biopsy, ciliary functional testing, nasal nitric oxide Childhood onset, sinus or ear infections, situs inversus, infertility Primary ciliary dyskinesia Swallow evaluation of esophageal pH measurement M avium disease Gastroesophageal reflux disease or aspiration IgG subclass levels, response to immunization, tests for qualitative Childhood onset, recurrent infections, Congenital immunodeficiency immune defects dysmorphic features Serology for autoimmune disease Arthritis, sicca syndrome Rheumatoid arthritis, Sjögren syndrome Serology for HIV infection Opportunistic infections, recurrent infections HIV disease Metersky M L. Clin Chest Med 33 (2012) 211-217.
- 21. Diagnostic Workup inBronchiectasis Chronic/persistent ! Endobronchial TB Bronchial obstruction ABPA Repeated/episodic GERD Aspirations Posterior nasal drip Mucociliary defects 1o ciliary dyskinesia Cystic fibrosis Acute/severe Measles ! ! Influenza pneumonia inhalation injury Radiation injury Cellular/immune defects Common variable immune deficiency X-link agammaglobulinemia Hyper IgE syndrome Alpha1-antitrypsin deficiency HIV infection Associated conditions Rheumatoid arthritis Sjögren syndrome Relapsing polychondritis SLE Ciliary biopsy/function test Sweat chloride CF mutation screening Quantitative immunoglobulins IgG or IgE levels AAT level Serology for HIV Serology for CTDs: ANA, Anti-Sm Anti-Ro, Anti-La etc. Esophageal pH Swallow evaluation Bronchoscopy Aspergillus IgG/IgE Aspergillus allergy test Metersky M L. Clin Chest Med 33 (2012) 211-217.
- 22. Diagnosis of Bronchiectasis:General Consideration Definitive diagnosis Severity of impairment Underlying or associated condition(s) Microbiology of the affected airways
- 23. Microbiology in Bronchiectasis Percentage (%) 50 40 30 20 10 0 H influenzae S pneumoniae Ps aeruginosa S aureus M catarrhalis 2 0 0 Aspergillus spp. Mycobacteria 2 or more 20 0 31 13 35 6 40 5 2 7 31 11 30 21 2 1 0 4 11 18 40 Li, 2005 Nicotra, 1995 Pasteur, 2000 Barker A F and Ahmed S Y, Fishman’s Pulmonary Diseases and Disorders, 4th Edition. 2008.
- 24. Bronchiectasis: Summary Abnormalirreversibly dilated and often thick-walled bronchi Pathogenesis related to one or more defects of mucociliary clearance, cellular and immunity defense mechanism or presence of associated conditions “The vicious cycle” and P aeruginosa contributes progression and severity of disease Imaging greatly helps in diagnosis: Tram line, honeycombing, cystic, signet ring sign Additional test may be required in specific clinical settings Microbiology of the diseased airway may aid proper antimicrobial therapy
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