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Bronchiectasis

• Dr.Balamugesh

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• Chronic dilation of the bronchi marked by fetid
  breath and paroxysmal coughing, with the
  expectoration of mucopurulent matter.

Dorlands Illustrated Medical Dictionary 28th
Ed., W.B. Saunders Company
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Morphological types

• Cylindrical or tubular bronchiectasis
• Varicose
• saccular or cystic bronchiectasis

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Bronchiectasis

• Causes and pathogenesis
• Microbiology /common pathogens
• Therapeutic Goals

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Ct/cxr
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Ct/cxr
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CAUSES
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Bronchiectasis

• Worldwide, infection is the primary cause
• M. Tuberculosis
• Childhood illnesses
• Rubeola, B. Pertussis

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Infection
Inflammation
Bronchiectasis
Altered development
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Inflammation

• Characteristics across etiologies
• Persistent
• Neutrophil dominant
• Pro-inflammatory cytokines (IL-8, IL-1, TNF-a)
• Low anti-inflammatory cytokines (IL-10)

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Airway Damage Failure to Resolve Inflammation

• Inappropriate inflammation
• e.g. ABPM, CF (?)
• Impaired clearance of stimuli
• Bacteria, mucus, toxins

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Airway Damage Failure to Resolve Inflammation

• Altered Airway Milieu
• Proteolytic damage
• -e.g. cleaved receptors
• -impaired macrophage function
• Oxidant stress
• -low antioxidants associated with worse disease
• -dysregulation of signaling and cellular
  function

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Childhood Infections
M. Tb.
Infection
Impaired Clearance
Inflammation
Bronchiectasis
Altered development
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Impaired Clearance

• Altered ciliary Function
• PCD, smoking, CFTR, Youngs
• Mucus rheology
• CFTR, Mucoid Ps. A
• Dilated or obstructed airways
• Impaired cough, foreign bodies, aspiration

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Impaired ImmunityIneffective inflammation

• Acquired
• Chemo-immunomodulation
• Congenital/innate

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HIV/AIDS
Chemo-Immunosuppression anti-TNF, MTX,
anti-neoplastics
Childhood Infections
M. Tb.
Innate Deficiency CGD, CVID, Igopathy (IFN)
Infection
Impaired Clearance foreign body, CF
Inflammation
Bronchiectasis
Altered development
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Chemo-Immunosuppression
HIV/AIDS
Childhood Infections
M. Tb.
Innate Deficiency
Infection
Impaired Clearance
Inflammation
Auto-Immune RA, Sjogrens, IBD ABPM
Bronchiectasis
Altered development
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Chemo-Immunosuppression
HIV/AIDS
Childhood Infections
M. Tb.
Innate Deficiency
Infection
Impaired Clearance
Inflammation
Auto-Immune ABPM
Bronchiectasis
Altered development
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Chemo-Immunosuppression
HIV/AIDS
Childhood Infections
M. Tb.
Innate Deficiency
Infection
Impaired Clearance
Inflammation
Auto-Immune ABPM
Bronchiectasis
Altered development
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BronchiectasisEpidemiology and Etiology

• Who?
• Patients - with altered immune system
• - with persistent respiratory symptoms
• Why?
• Persistent inflammation in the respiratory system

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Bronchiectasis TherapyDecrease inflammation

• antibiotics
• clearance
• Flutter, IPPV, Vest, Bronchodilators, hypertonic
  saline
• (anti-inflammatory chemotherapy)
• Steroids, macrolides, interferon-gamma, ibuprofen
• (surgical resection)

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When to suspect bronchiectasis?

• Chronic cough, sputum
• Coarse rales
• Persistent respiratory symptoms
• Recurrent pneumonia
• Progressive obstructive lung disease
• Funny bugs

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Clinical Characteristics

• Focal
• Sputum production
• Mild lt15 cc/d
• Moderate 15-150 cc/d
• Severe gt150 cc/d
• Hemoptysis
• Dyspnea
• Chest pain

• Systemic
• Malnutriton/wasting
• Chronic Inflammation
• gammaglobulinemia
• CRP
• Sed rate
• anemia

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Bronchiectasis TherapyAntibiotics

• Episodic or suppressive antibiotics?
• Yes.
• Selective pressure vs. suppression of damage

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Bronchiectasis TherapyAntibiotics

• Pro
• Decrease inflammation
• Slow progression
• Eradication?

Con Select resistance Cost Side effects adherence
difficult (e.g. Huong et al.)
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Bronchiectasis TherapyAntibiotics when to use?

• Yes
• Evidence of exacerbation
• Progressive decline
• Frequent exacerbator
• Active inflammation (?)

No Minimal disease without organism Patient
Intolerant Unaffordable
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Bronchiectasis TherapyDecrease inflammation

• Clearance
• Immunomodulatory chemotherapy
• proposed therapies
• Steroids
• Macrolides, tetracyclines
• interferon-gamma
• ibuprofen

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Bronchopulmonary Hygiene

• removal of respiratory secretions is beneficial
• chest percussion and postural drainage
• chest clapping or cupping
• inflatable vests or mechanical vibrators
• Oral devices that apply positive end-expiratory
  pressure maintain the patency of the airway
  during exhalation

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• Maintaining adequate systemic hydration, enhanced
  by nebulization with saline,
• Acetylcysteine delivered by nebulizer thins
  secretions
• aerosolized recombinant human DNase (rhDNase) in
  patients with cystic fibrosis

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Surgery

• Localised bronchiectasis
• Proximal obstructive lesion
• Massive hemoptysis
• Recurrent infections

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Cystic FibrosisEpidemiology

• 1/2500 caucasian births (3-5 carrier rate)
• Autosomal recessive defect of CFTR
• Gene identified 1989 on Cr. 7
• 30,000 affected in USA
• 12,000 adults
• survival 31 years

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CF Genetics

• Autosomal recessive, non-lethal
• gt900 identified aberrations
• Genotypephenotype correlation poor
• Survival benefit (?)
• Heterozygote-phenotypes postulated (pancreatitis,
  ABPA, MOTT bronchiectasis)

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CFTRcystic fibrosis transmembrane regulator

• chloride channel
• epithelial cells
• variable genotype - phenotype linkage
• various defects identified
• ion transport
• regulation
• processing
• production

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Results of Decreased CFTR Function

• Primary
• Increased water resorption increased mucus
  viscosity
• Altered cellular signaling intra/trans(?)
• (?) altered cholera toxin effects
• Secondary
• Obstruction
• Inflammation
• Dysfunction

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Major Clinical Manifestations

• Sinusitis, polyps
• Lung
• Chronic infections
• Obstructive disease
• GI
• Insufficiency
• CFRDM
• Liver disease
• Reproductive
• Decreased fertility

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22/yo male ja Fev1 deltaF508/deltaF508
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CF respiratory pathology

• Inflammation starts as early as 4 weeks of age
• Culture negative
• BAL increased IL-8, LTB4, neutrophils,
  macrophages

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CF pathologic changes

• Chronic bronchiectasis
• Obstructive lung disease
• Respiratory failure
• Transplantation/death

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The CF Diagnosis earlyor typical presentation

• Newborn screening
• Serum trypsinogen with confirmatory sweat
  chloride testing
• Meconium Ileus
• Failure to thrive/malabsorption
• Recurrent sino-pulmonary disease

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Diagnosis of CF

• Clinical setting
• Chronic sino-pulmonary disease
• GI / Nutritional disease
• Salt loss syndromes

• CFTR abnormality
• Abnormal sweat test
• gt 60
• Nasal potential
• Mutational analysis
• gt 2

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Vicious loops
Infection
Bronchial Obstruction
Inflammation
Bronchiectasis
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Summary
management
diagnosis

• History
• Prior infections, exposures
• Time course
• Other manifestations?
• Chest Imaging
• Define region, pattern
• Sputum culture
• Determine causal disease
• sweat testing
• immune testing
• serologic testing

• Treat bronchiectasis
• Clearance
• Antibiotics
• Immune-modulation
• Balance burden of disease vs burden of therapy
• (Sputum, Symptoms, PFTs, Weight, X-rays)
• Other
• Underlying disease therapy
• Transplantation
• Management of complications
• Collapse, plugs, hemoptysis

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Vicious loop
Antibiotics tobramycin
Infection
Bronchial Obstruction
Inflammation
Clearance Albuterol, DNase, Therapy vest
Anti-inflammatory Inhaled steroids
Bronchiectasis