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Bronchiectasis - DSR

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Bronchiectasis Ulla Møller Weinreich Forskningsansvarlig overlæge, ph.d, klinisk lektor Lungemedicinsk afdeling Aalborg Universitetshospital
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Page 1: Bronchiectasis - DSR

Bronchiectasis

Ulla Møller Weinreich

Forskningsansvarlig overlæge, ph.d, klinisk lektor

Lungemedicinsk afdeling

Aalborg Universitetshospital

Page 2: Bronchiectasis - DSR

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

Page 3: Bronchiectasis - DSR

Have you spoken to a bronchiectasis patient this week?

Probably

Under-diagnosed

Under-estimated

Under-treated

Page 4: Bronchiectasis - DSR

CF/non-CF bronkiektasier

Page 5: Bronchiectasis - DSR

René Hyacinte Laennec

• 1819 described the patological dilatation of the airways

Page 6: Bronchiectasis - DSR

Bronchiectasis, patoanatomical definition

Abnorm and irreversible dilatation of the airways; abnorm condition, disponerer to disease

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Other CT findings

Page 8: Bronchiectasis - DSR

Bronchiectasis subtypes

Page 9: Bronchiectasis - DSR

Bronchiectasis, clinical definition

Chronic productive cough, repetitive infections and possibly bronchial obstructivity

Cough during airway infections

and so on…

Page 10: Bronchiectasis - DSR

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

Page 11: Bronchiectasis - DSR

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

Page 12: Bronchiectasis - DSR

Obstructive pulmonary diseases

COPD Asthma ACOS

Bronchiectasis

BACOS

BCOS BAOS

Page 13: Bronchiectasis - DSR

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

Page 14: Bronchiectasis - DSR

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

Page 15: Bronchiectasis - DSR

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

Page 16: Bronchiectasis - DSR

Combined diseases

COPD Asthma ACOS

Bronchiectasis

BACOS

BCOS BAOS

RA BROS

RCOS

BRCOS

Page 17: Bronchiectasis - DSR
Page 18: Bronchiectasis - DSR

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.

Page 19: Bronchiectasis - DSR

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.

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Idiopatic bronchiectasis

• In 26-30% of all patients no underlying cause can be identified

Page 21: Bronchiectasis - DSR

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

Page 22: Bronchiectasis - DSR

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

Page 23: Bronchiectasis - DSR

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

Page 24: Bronchiectasis - DSR

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

Page 25: Bronchiectasis - DSR

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

Page 26: Bronchiectasis - DSR

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

Page 27: Bronchiectasis - DSR

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

Page 28: Bronchiectasis - DSR

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

Page 29: Bronchiectasis - DSR

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.

Page 30: Bronchiectasis - DSR

When to suspect bronchiectasis

• continuous cough and sputum

• Frequent and/or prolonged lower airway infections

• Sinuitis/rhiniis symptoms

• Dispositions

• Fatigue

Page 31: Bronchiectasis - DSR

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

Page 32: Bronchiectasis - DSR

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

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Treatment

• PEP-flute

• Physical exersice

• Steroid?

• Mucolytica?

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Behandling

• PEP-flute

• exercise

• Steroid?

• Mucolytica?

• Rhinitis-treatment

Page 35: Bronchiectasis - DSR

Spirometry

Normal

Obstructive

• Inflammation of small airways

Restrictive component:

• Middle lobe syndrome

• Fibrotic sequelae after infection

Page 36: Bronchiectasis - DSR

Exacerbation

• Increased cough

• Increased sputum

• Increased colouring of sputum

• Worsening of general symptoms (fatigue, malaise)

• Possibly hemopthysis

• Poss pleuritis

• Poss temperature

• Poss increased CRP

Page 37: Bronchiectasis - DSR

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

Page 38: Bronchiectasis - DSR

Pseudomonas-litteratur


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