Bronchiectasis

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

Morphological types
Cylindrical or tubular bronchiectasis
Varicose saccular or cystic bronchiectasis

Bronchiectasis

Causes and pathogenesis Microbiology /common pathogens Therapeutic Goals

Ct/cxr

Ct/cxr

CAUSES
Disease
COPD Chronic cough* Rheumatoid arthritis Inflammatory bowel disease HIV/AIDS (mean CD4 60-65) Sarcoidosis Asthma (steroid requiring) Allergic bronchopulmonary mycosis Alpha-one anti-trypsin deficiency Chronic variable immunodeficiency Sjogrens
*- patients with productive cough - patients with respiratory symptoms

Bronchiectasis
29% 4-18% 3-30% 76-86% 11-30% 7% 4-19%** 98% 43-61% 58% 38%
[Palombini 1999, Smyrnios 1995] [Saraux 1997, Despaux 1997] [Spira 1998, Mahadeva 2000, Garg 1993] [Jeena 1998, Verghese1994, Monteverde 1999] [Brauner 1989] [Nuhoglu 1999] [Mitchell 2000]

[kauczor 2000, king 1996]

[Garcia 2001]

[Koyama 2001]

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

Childhood Infections

M. Tb.

Infection Inflammation Bronchiectasis

Altered development

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

Airway Damage
Failure to Resolve Inflammation
Inappropriate inflammation
e.g. ABPM, CF (?)

Impaired clearance of stimuli

Bacteria, mucus, toxins

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

Childhood Infections

M. Tb.

Infection

Inflammation*
Bronchiectasis

Impaired Clearance

Altered development

Impaired Clearance
Altered ciliary Function
PCD, smoking, CFTR, Youngs

Mucus rheology
CFTR, Mucoid Ps. A

Dilated or obstructed airways

Impaired cough, foreign bodies, aspiration

Impaired Immunity
Ineffective inflammation

Acquired
Chemo-immunomodulation

Congenital/innate

HIV/AIDS
Childhood Infections

Chemo-Immunosuppression
anti-TNF, MTX, anti-neoplastics

M. Tb.

Innate Deficiency
CGD, CVID, Igopathy (IFN)

Infection Inflammation Bronchiectasis Impaired Clearance

foreign body, CF

Altered development

HIV/AIDS
Childhood Infections

Chemo-Immunosuppression Innate Deficiency

M. Tb.

Infection

Auto-Immune
ABPM

RA, Sjogrens, IBD

Inflammation Bronchiectasis

Impaired Clearance

Altered development

HIV/AIDS
Childhood Infections

Chemo-Immunosuppression Innate Deficiency

M. Tb.

Infection

Auto-Immune
ABPM

Inflammation Bronchiectasis

Impaired Clearance

Altered development

HIV/AIDS
Childhood Infections

Chemo-Immunosuppression Innate Deficiency

M. Tb.

Infection

Auto-Immune
ABPM

Inflammation Bronchiectasis

Impaired Clearance

Altered development

Bronchiectasis
Epidemiology and Etiology
Who?

Patients

- with altered immune system - with persistent respiratory symptoms

Why?

Persistent inflammation in the respiratory system

Bronchiectasis Therapy
Decrease inflammation

antibiotics clearance
Flutter, IPPV, Vest, Bronchodilators, hypertonic saline

(anti-inflammatory chemotherapy)
Steroids, macrolides, interferon-gamma, ibuprofen

(surgical resection)

When to suspect bronchiectasis?

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

Clinical Characteristics
Focal Sputum production Mild <15 cc/d Moderate 15-150 cc/d Severe >150 cc/d Hemoptysis Dyspnea Chest pain Systemic
Malnutriton/wasting Chronic Inflammation
gammaglobulinemia CRP Sed rate anemia

Bronchiectasis Therapy
Antibiotics

Episodic or suppressive antibiotics?

Yes. Selective pressure vs. suppression of damage

Bronchiectasis Therapy
Antibiotics

Pro
Decrease inflammation Slow progression Eradication?

Con Select resistance Cost Side effects adherence difficult (e.g.

Huong et al.)

Bronchiectasis Therapy
Antibiotics when to use?

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

No: Minimal disease without organism Patient Intolerant Unaffordable

Bronchiectasis Therapy
Decrease inflammation

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

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 endexpiratory pressure maintain the patency of the airway during exhalation

 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

Surgery
Localised bronchiectasis Proximal obstructive lesion Massive hemoptysis Recurrent infections

Cystic Fibrosis
Epidemiology

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

CF Genetics
Autosomal recessive, non-lethal >900 identified aberrations Genotypephenotype correlation poor Survival benefit (?) Heterozygote-phenotypes postulated
(pancreatitis, ABPA, MOTT bronchiectasis)

CFTR
cystic fibrosis transmembrane regulator
chloride channel epithelial cells variable genotype - phenotype linkage various defects identified
ion transport regulation processing production

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

Major Clinical Manifestations

Sinusitis, polyps Lung
Chronic infections Obstructive disease

GI
Insufficiency CFRDM Liver disease

Reproductive
Decreased fertility

22/yo male ja Fev1: deltaF508/deltaF508

CF: respiratory pathology

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

CF: pathologic changes

Chronic bronchiectasis Obstructive lung disease Respiratory failure* Transplantation/death

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

Diagnosis of CF
Clinical setting
Chronic sinopulmonary disease GI +/ Nutritional disease Salt loss syndromes

CFTR abnormality
Abnormal sweat test
> 60

Nasal potential Mutational analysis

>2

Vicious loops
Infection

Bronchial Obstruction

Inflammation

Bronchiectasis

Summary
diagnosis
History
Prior infections, exposures Time course Other manifestations?

management
Treat bronchiectasis
Clearance Antibiotics Immune-modulation

Chest Imaging
Define region, pattern

Balance burden of disease vs burden of therapy

(Sputum, Symptoms, PFTs, Weight, X-rays)

Sputum culture Determine causal disease

sweat testing immune testing serologic testing

Other
Underlying disease therapy Transplantation Management of complications
Collapse, plugs, hemoptysis

Vicious loop

Antibiotics
tobramycin

Infection

Bronchial Obstruction

Inflammation

Clearance
Albuterol, DNase, Therapy vest

Anti-inflammatory
Inhaled steroids

Bronchiectasis

THE END