View
13
Download
0
Category
Preview:
Citation preview
Bronchiectasis
Ulla Møller Weinreich
Forskningsansvarlig overlæge, ph.d, klinisk lektor
Lungemedicinsk afdeling
Aalborg Universitetshospital
Disclosure
• UMW has received salary for educational activity from Novartis, Astra Zeneca, Pfizer, Chiesi, Boehringer Ingelheim, Teva and Fisher&Paykel
• UMW has conducting pharma-initiated studies with Novartis, Astra Zeneca, Boehringer Ingelheim, Teva and Sanofi
• UMW has received funding for studies from Fisher&Paykel
Have you spoken to a bronchiectasis patient this week?
Probably
Under-diagnosed
Under-estimated
Under-treated
CF/non-CF bronkiektasier
René Hyacinte Laennec
• 1819 described the patological dilatation of the airways
Bronchiectasis, patoanatomical definition
Abnorm and irreversible dilatation of the airways; abnorm condition, disponerer to disease
Other CT findings
Bronchiectasis subtypes
Bronchiectasis, clinical definition
Chronic productive cough, repetitive infections and possibly bronchial obstructivity
Cough during airway infections
and so on…
Bronchiectasis, prevalens
• Increases with age, majority women
• Europe: 0,7‰ – 1%
• North Amerika: 4-5 ‰ (insurance data)
• 1/350.000 Japan-> 1,5% in Australian aboriginals
Bronchiectasis, causes/ predispositions
• Post-infectious:
pneumonia/viral infections
M tuberkulosis infections
NTM (M. avium, M abscessus)
• Primary immunodeficiencies (IgA-, IgG4 (and 2) deficiencies, mannosebinding lectin deficiencies, CVID)
• ABPA (Allergic bronchopulmonary aspergillosis), often prevh astma. Often proximal ectasis, often migrating pulmonary lesions
Obstructive pulmonary diseases
COPD Asthma ACOS
Bronchiectasis
BACOS
BCOS BAOS
Bronchiectasis, causes/ predispositions
• Up to 40% of asthmatics have co-existing ectasis
• 7-60% of COPD-patients have co-existing ectasis.
• OBS
Productive cough
Frequent exacerbators
Discrepancy between smoking history and lung function
Discrepancy between lung function and physical abilities
Bronchiectasis, causes/ predispositions
• Αlfa-1-antitrypsindeficiency: Up to 27% of patients, associated with non-PiZ phenotypes
• IBD: ~ 0.2%. Chronic bronchitis ->bronchiectasis. Bronchorrhea
• Autoimmune diseases: RA (2-10%), Mb. Sjögren, SLE, Scleroderma, anchylosating spondylitis and vasculitis. Often asymptomatic.
• CF: Obs symptomatic carriers amongst adults.
• Ciliary dyskinesia. Uknown prevalens. Ofte symptomatic from childhood. Young’s syndrom: Ectasis, rhinosinuitis and infertility. Obs situs inversus.
• Malignant hematologic diseases, small materials
Bronchiectasis, causes/ predispositions
• GORD – correlation still not quite understood – pepsin?
• HIV – ectasis may be associated to infections
• Yellow nail: yellow nails, lymph edema and chronic respiratory symptoms.
• Tracheobronkomalaci (Mb Mounier-Kuhn). Proximal ectasis, mild symptoms
Combined diseases
COPD Asthma ACOS
Bronchiectasis
BACOS
BCOS BAOS
RA BROS
RCOS
BRCOS
Hvorfor skal voksen-læger interessere sig for CF
• Patienter med mildere mutationer diagnosticeres nogle gange senere I livet
• CRMS: CTFR-related metabolic syndrome: vægttab, pancreatitis, pulmonale infektioner, sinuitis
Levy et al J Pediatr. 2015 Jun; 166(6): 1337–1341.
Asymptomatic bronchiectasis
• Prevalens unknown (1 study, 9%)
• Unknown whether all bronchiectasis start as asymptomatic bronchiectasis
• Asymptomatic bronchiectasis may become symptomatic in connection to immune modulation.
Idiopatic bronchiectasis
• In 26-30% of all patients no underlying cause can be identified
Bronchiectasis in children
• CF – undiagnosed
• Ciliary Dyskinesia
• Gamma-globulin deficiencies ( IgA)
• Other immunodeficiencies
• Asthma
• Idiapathic
• Even when diagnosed, often undertreated, left with poor lung function in adulthood
Den wicket cirkel-theory
Airway inflammation
Airway structural damage
Bacterial colonisation
Hypersecretion
Ciliary dysfunistion
Airway remodelling
Elastase
Cathepepsins
Matrix metalloproteinases
Proteinasis
ROS
Interleukin 8
Leukotrien B4
TNFα
Interleukin 1β
Den onde cirkel-teori?
Airway inflammation
Airway structural damage
Bacterial colonisation
Hyper secretion
Ciliary dysfunction
Airway remodelling
Elastase
Cathepepsiner
Matrix metalloproteinaser
Proteinase
ROS
Interleukin 8
Leukotrien B4
TNFα
Interleukin 1β
Neutrophils
• Bronchiectasis is a neutrophil driven condition
• Primary cell type in bronchial lavage
• Increased migration to the airways both in stable phase and during exacerbations
• Recruitment
Recruitment • Transendothelial migration
• ICAM-1 og VCAM-1 results in adherence of neutrophils
• Increased presence of pro-inflammatory markers
• Chemotaxia-> neutrophils migrating to inflamed areas.
• High levels of chemo-attractive agencies in sputum from bronchiectasis patients
• Despite this – reduced fagocytosis
ICAM-1 VCAM-1
CD11 CD18
Reduced fagocytosis
• Elastasis and peptids from the neutrophils -> reduces Fcγ and complement factor 1
• Elastasis -> reduced fragmentation of immuno globulins -> reduced complement-reaction
• immunodeficiencies: Reduced immuno globulins and mannose binding lectins-> reduced complement reaction
Neutrophils are not deficient outside the airways • The inflammatory environment
in the airways is inhibitory for the neutrophils
• Α-defensin produced by the neutrophils has a self-inhibitory effect of fagocytosis
• Neutrophil elastasis is essential for the patological proces
Elastasis
Destruction of epithelial cells
-> reduced ciliary mobility
Increases mucus
production
Reduction of neutrophil fagocytosis
Pro-inflamma-
tory
Reduction of elastin and collagen in basal cell
membranes
colonisation
• Haemophilus influenzae: Survives within the macrophage and endothelial cells. may produce biofilm.
• Pseudomonas aeruginosa: colonisation facilitated by hypoxia. The bacteria changes caracter as colonisating bacteria (down regulation of virulence and mucoid production -> biofilm)
• Staphylococcus aureus: Reduced virulence, makes biofilm, survives intra cellulary and is resistant to treatment.
When to suspect bronchiectasis
• continuous cough and sputum
• Frequent and/or prolonged lower airway infections
• Sinuitis/rhiniis symptoms
• Dispositions
• Fatigue
Diagnostics
• HR-CT
• Immuno globulins, incl IgG sub classes, mannosebinding lectins (streptococcus immune status, antitrypsin)
• In case of nasale symptoms examination for nasal polyposis/chronic rhinitis
• Spirometry
• Thorough investigation for comorbidity.
• Verify a possible asthma diagnosis
2mm snit alm. CT i lungevindue 1mm snit HRCT i lungevindue
HR-CT vs CT thorax
• Thin slices
• Max 1 mm, max 1 sek scan time (rotation time)
• Full scan in expiration phase
• Downside: radiation
Treatment
• PEP-flute
• Physical exersice
• Steroid?
• Mucolytica?
Behandling
• PEP-flute
• exercise
• Steroid?
• Mucolytica?
• Rhinitis-treatment
Spirometry
Normal
Obstructive
• Inflammation of small airways
Restrictive component:
• Middle lobe syndrome
• Fibrotic sequelae after infection
Exacerbation
• Increased cough
• Increased sputum
• Increased colouring of sputum
• Worsening of general symptoms (fatigue, malaise)
• Possibly hemopthysis
• Poss pleuritis
• Poss temperature
• Poss increased CRP
Antibiotics treatment
• Microbiological targeted treatment:
Fortnight of antibiotic treatment for exacerbations (Amoxacillin w/ Clavulanic acid)
Targeted treatment after sputum culture. Obs Ps. ae; No real evidence of duration of treatment, ie two antibiotics in two weeks
After 3 or more exacerbations/year: Azithromycin, 250 mg x 3/week (other regimes exist Side effects: elevated liver enzymes, prolonges QT, tinnitus, reduced hearing
Pseudomonas-litteratur
Go look for them – When you know what to look for they’re right under your nose
medscape/bronchieectasis
Recommended