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