13 bronchiectasis-dr khinchi

Bronchiectasis

Dr Yog Raj Khinchi

Chronic Bronchitis Definition

ADULTS: Productive cough daily for 3 months/year for 2 consecutive years.

CHILDREN: Productive cough of >2 months duration or recurrent episodes of productive cough >4 times/year.

Bronchitis is a state of

increased mucus production,

with or without adequate

mucociliary transport, that

requires cough for clearance of

airway secretions.

Airway Stimulus/Injury

Increasing Secretion Production

Effective Cough

Secretion Inspissation Airway

Obstruction Recurrent/Persistent

Infection

Increased Mucociliary Clearance

Chronic Bronchitis: Underlying Conditions

Chronic Airway Infection/Inflammation:

• Asthma• Cystic Fibrosis• Aspiration syndromes• Chronic foreign body• Tuberculosis

Primary Host Defense Abnormalities:

• Ciliary dyskinesias• Immunodeficiencies• Congenital• Acquired (HIV)

Inefficient Cough Syndromes:

• Airway compression• Trachobronchomalacia• Neuromuscular weakness• Tracheostomies• Bronchiolitis obliterans

Bronchiectasis Pathogenesis

Airway Injury + Secretion Stimuli

Secretion Stasis Infection

Airway Destruction + Airway Dilation

FIGURE 2

CF vs. Idiopathic Bronchiectasis

CYSTIC FIBROSIS

IDIOPATHIC BRONCHIECTATIS

Multi-organ Involvement Sinopulmonary Involvement

Diffuse Multifocal

Pseudomones Mouth Flora

Tenacious Secretions Mucoid/Coughable

50% Bronchodilator Response

50% Bronchodilator Response

Progressive Outcome Variable Outcome

Treatments for Idiopathic (Post-Infectious) Bronchiectasis

Reduce Secretion Production:

• Reduce Irritant Exposure• Reduce Aspiration Events • Reduce GER

Reduce Infection Exposure: • Dental Hygiene Antibiotics for: Upper Airway Lower Airway Exacerbations

Promote Secretion Clearance:

• Chest Physiotherapy

Reduce Airway Obstruction: • ?Bronchodilators• Inhaled Steroids

Prevent Infection: • Immunizations• ?Palivizumab, Flu shots• Pneumococcal vaccine (7 + 23 valent)

Bronchiectasis

• Irreversible, abnormal dilatation of one or more bronchi, with chronic airway inflammation. Associated chronic cough, sputum production, recurrent chest infections, airflow obstruction, and malaise

• Prevalence unknown (not common)• Pathological endpoint with many underlying causes

Pathogens associated with exacerbations and disease progression in bronchiectasis

Haemophilus influenzaeHaemophilus parainfluenzaePseudomonas aeruginosa

Streptococcus pneumoniaeMoraxella catarrhalisStaphylocccus aureusStenotrophomonas maltophiliaGram-negative enterobacter

• Non-tuberculosis mycobacteria– M. avium complex (MAC)– M. kansasii– M. chelonae– M. fortuitum– M. malmoense– M. xenopi

• Aspergillus-related disease

Causes / associations of bronchiectasis

• Idiopathic• Postinfectious• Humoral immunodeficiency• Allergic bronchopulmonary aspergillosis (ABPA)• Aspiration/GI reflux• Rheumatoid arthritis• Youngs Syndrome• Cystic Fibrosis• Ciliary dysfunction• Ulcerative colitis• Panbronchiolitis• Congenital• Yellow nail syndrome

Evidence for dysregulated immunity in bronchiectasis

• Increased susceptibility to infection - bacterial, non-tuberculous mycobacterial (NTM), and aspergillus-related lung disease

• Associated with autoimmune disease such as the inflammatory bowel disease, ulcerative colitis

• Neutrophils are markedly raised, as predicted from high local levels IL-8

• Associated with immune deficiency syndromes such as TAP deficiency syndrome






Bronchiectasis associated with increased susceptibility to specific pathogens

Haemophilus influenzaeHaemophilus parainfluenzaePseudomonas aeruginosa

Streptococcus pneumoniaeMoraxella catarrhalisStaphylocccus aureusStenotrophomonas maltophiliaGram-negative enterobacter

• Non-tuberculosis mycobacteria– M. avium complex (MAC)– M. kansasii– M. chelonae– M. fortuitum– M. malmoense– M. xenopi

• Aspergillus-related disease






Bronchiectasis associated with autoimmune disease

• Rheumatoid arthritis• Systemic lupus erythematosus• Relapsing polychondritis• Inflammatory bowel disease -

Ulcerative colitis and Crohn’s disease






Suppurative Lung Disease

• Bronchiectasis• Lung abcess• Empyema

Brochiectasis• Def:destructive lung disease :chronic permanent and

abnormal dilatation of bronchial wall with variable inflammatory process in the lung. Chronic bronchial sepsis

• Pathology: non-inflammatory:congenital

acquired: Bronchial wall dilatation. excess mucus. loss of connective tissue support inflammation with metaplasia of ciliated

epithelium to squamous or columnar + micro-abcess formation. Collapsibility of the wall leads to obstructive defect on spirometry.

Notes

• Bronchiectasis is of two types:1- Dry: there is dilatation,

destruction, but no purulent secretion.

2- Suppurative (refers to chronic bronchial sepsis): this is bronchiectasis that have suppuration ( pus formation).

Pathogenesis

• Vicious cycle: infectious insult & impaired drainage &/or defect in host defence

• Role of positive : genetic susceptibilty family history

Notes• Normally, in healthy individuals the immune system

and mechanical system (cilia function) are intact, resulting in good clearance of microorganisms leading to recovery.

• Therefore, with impaired cilia function and/or host defense a vicious cycle (ongoing inflammation) will occur leading to bronchiectasis.

• People with family history and genetic susceptibility (e.g a-1 antitrypsin deficiency), when having a microbial insult, they can not clear it probably because of defective immune and/or mechanical drainage system.

• The most important organisms are: H.influenza, encapsulated streptococcus pneumoniae, and pseudomonus.

Classification

Spectrum:• 1.follicular cylindrical:transmural inflammation, loss of bronchial

elastic tissue, mucosal edema; post infectious• 2.Saccular:ulceration ,craters; general dilatation specially terminal

(saccules). (varicose:distortion by scarring and obstructions)• 3. Atelactatic: localised, could be secondary to 1, or 2.importance to site and

distribution: lobar or segmental.

Notes• Another type of classification is:1- follicular cylindrical :it is called follicular

because of presence of lymphoid follicles in the bronchus. But it is generally called cylindrical because it is transmural and localized to one bronchus.

2- saccular: so called because there are succule like formation at the terminal part of the bronchus.

- varicose: this is when you have two types together cylindrical and saccular.

Causes of bronchiectasis

Congenital:elastic bronchial wall def.

other congenital abnormalities,lung sequestration

Mechanical bronchial obstruction:Intrinsic and extrinsic:Lymph node or scaring :post-TBForeign body: selective lobesChild vs adult

Notes• Causes:1- congenital:in fetus, the lung is not mature enough

because its blood supply is deprived, therefore making it liable to bronchiectasis.

2- bronchial obstruction: the process of obstruction will cause stagnation of secretion which will then start the process of microbial infection leading to abcess formation and then tissue destruction, hence bronchiectasis.

- Bronchial obstruction can be intrinsic (in wall or lumen) or extrinsic (external compression).

Cont’d Notes

- TB produces both intrinsic (by scarring) and extrensic (compression by lymph node).

• The common site of obstruction is the right posterior upper lobe.

• Obstruction of airways in children can be caused by inhaling a foreign body, and the inhalation of a foreign body also leads to lung abcess.

• Obstruction in adults can occur due to inhaling chemicals or impaired gastroesophageal reflex and aspiration.

*Cont’d Causes *Inflammatory pneumonitis -Aspiration:chemical ,gastric -Inhalation: fumes

*Granulomata and fibrosis: sarcoidosis ,TB,IPF

*Immunological over-response: ABPA (allergic bronchial pulmonary aspergellosis), post lung transplant

*Immune deficiency Primary: children: hypogammaglobinaemia:repeated

sinopulmonary infection Secondary: AIDS, CA

Cont’d Causes*Mucociliary clearance defects -Genetic -Primary ciliary dyskinesia :cilia abnormal 50% Kartegner’s:S.I, sinusitis Bronchiectasis. -Cystic Fibrosis: abnormal mucus content.*Acquired: -Young’s: sinusitis ,bronchiectasis ,obstructive azoospermia.

Abnormal mucus.- -Post-infective bronchial damage:measles, pertussis.

MAI.Viral.Mycoplasma- Toxins: SO2,smoking, lidocaine. Asthma.*Rheumatic and systemic inflammatory diseases:e.g IBD (inflammatory

bowel disease).

*Idiopathic (including diffuse panbronchiolitis), good % with no cause

Notes• In cystic fibrosis, the cilia is normal but the mucus

is abnormal because there is a block in the chlorine channel (not responsive to cyclic AMP) causing the mucus to become more sticky. This disease is characterized by increased Na and Cl in sweat, which is detected by sweating test.

• Kartegner syndrome: is a type of primary ciliary dyskinesia which is also associated with sinusitis, bronchiectasis, and transposition of the viscera.

• Young’s disease is characterized by high lipid content of mucus.

• Idiopathic: panbronchiolitis (responsive to macrolide) is found mainly in Japanese and East Asia.

Cont’s Notes

• ABPA causes hyper immune activity.

• Atypical mycobacterial infection and uncontrolled asthma can cause abnormal cilia.

*Mucociliary clearance defects

• *Genetic: Cystic fibrosis: AR, Gene mutation,chromosome 7,Transmembrane conductance regulator pr-CFTR

commonest:deletion at 508 impairment of chloride channel.non respondent cyclic-AMP.

Cl- and water not excreted but Na and its water absorbed ,mucus get thickened.Sweat content of Na , Cl altered.

Clinical manifestation of cystic fibrosis

Primary• Bronchiectasis *Nasal polyps• Bronchiolitis, bronchitis * Cirrhosis• Infertility * Meconium ileus• Pancreatic insufficiency• Pneumonia• Salt loss

Secondary

*Atelectasis * Allergic bronchopulmonary*Clubbing aspergillosis*Malabsorption * cholelithiasis*Heat prostration * Cor pulmonale*Hypochloraemic * Conductive hearing loss hypokalaemic alkalosis * Diabetes mellitus

Diagnosis of Bronchiectasis

• 1.History: usually :muco-purulent sputum, cough.

occasionally recurrent hemoptysis, recurrent feverLess specific : dyspnea, wheeze ,pleuritic pain

• 2.Examination: Early: normal nowadays:clubbing 3%,crackles70% rarely :Core pulmonale( right ventricular

hypertrophy due to pulmonary hypertension),CCF.

NotesThe most important sign is is abundant productive

cough increasing with lying down.• The second important manifestations are lung

abcess, infective emboli, clubbing and amyloidosis (AA type).

• How hemoptysis occurs?An insult causes injury, followed by healing and

neovascularization. These new formed blood vessels are weak and fragile, hence easily ruptured causing hemoptysis.

- Wheeze: musical sounds produced by air passing through narrowed airways (during inspiration & expiration).

- Crackles (crepitations): non-musical sounds mainly heard during inspiration caused by reopening of occluded small airways.

Investigation• Sputum: gram stain,selective media ( it is done not to

miss certain organisms),semi –quantitative• !!TB, fungal• CXR: early volume loss,vascular crowdening late:cylindrical tramline,cystic.• Disribution: central ABPA, LL: idiopathic UL: CF or variant

Investigation• Bronchogram: surgery• HRCT: standard• Sinus X-Ray• PFT: normal,obstructive,air trapping• Specific: Ig level:IgA (in immunocompromised

patients).• precipitin level is measured in skin, sputum and serum. If it

is high in 2 out of the 3 sites, we think of ABPA.• Brochoscopy

Notes• Bronchogram: do a bronchoscope then

inject a dye. It is done when you are planning for surgery.

• HRCT= high resolution CT scan.• Sinus X-ray is done to rule out sinusitis• PFT is early normal, later:obstruction/ air

trappin• Bronchoscopy is indicated in case of

hemoptysis and it is important to rule out obstructive lesions (e.g. foreign bodies) and TB. These three conditions are not responding to antibiotics.

Notes

• The previous slide shows CT taken during inspiration.

• Usually, a blood vessel has a bronchus beside it that has the same size.

• So, if you see a bronchus larger than the accompanied vessel then suspect bronchiectasis.

Notes

• The previous CT was taken for the same patient during full expiration, which is better than the full inspiratory CT.

Cont’d investigation

• UGI Endoscopy• Anti protease level• Sweat test• Genetic studies• Rh. Factor

Complication• Mostly: infective

exacerbation,haemoptysis• Rarely now: metastatic spread of

infection empyema amyloidosis clubbing joint pain

• Note: certain complications are rare because of early detection.

Management• Prevention:• Medical treatment:control infection ,bronchial hygiene

• Antibiotic:acute exacerbation: cover I.infl., strep.

Prophylactic:several protocols: commoner : 10days/Month or 10 days alternate with 10 free days.

• Bronchodilator• IV Ig if deficient• Oral Steroid:only ABPA vs inhaled steroids • Mucolyte :debatable.role of ACC ( N-acetylcystin

which is antioxidant), DNAs• Anti-fungal :itracanazole: ABPA• Future treatment:Antiprotease replacement • CF treatment (very complicated)

Notes• Management of bronchiectasis includes:- 1- Giving Igs for immunocompromised patients.- 2- Vaccination for H. influenza, pneumococcus and

influenza.- 3- Screening for TB (very important).- 4- Bronchodilators (almost always given).- 5- Steroids (only for ABPA because of the

hyperimmunity).- 6- mucolytics: make sputum more liquid and less

viscus (not important except DNAs in cystic fibrosis patients to improve their lung function).

Cont’d management

PhysiotherapyCorner stone:Postural drainage, hydration ,nebulized saline*Surgery: .Massive haemoptysis: > 600ml/day. .Localized troublesome resectable bronchiectasis .Palliative for important stump.

Notes

- physiotherapy: teach the patient how to drain his lung (lungs should be drained daily).

- Surgery: is indicated:1- when there is severe hemoptysis2- if one lobe causing problems to the patient, so

you resect it to prevent damage to other lobes3- if you have a diffuse lung disease and one

particular area which is more problematic, then you resect it.

- Mild hemoptysis: loss of 200-300ml/day.- Moderate hemoptysis: loss of 300-600ml/day.- Severe hemoptysis: loss of > 600ml/day.

Cont’d management Haemoptysis:*Mild: antibiotic*Severe: surgery or bronchial artery embolization Lung Transplant: always double.- Indication for transplantation: bilateral, advanced,

and bleeding bronchiectasis.- 2 lungs should be transplanted because if you

transplant one lung only, the diseased lung you left in the body can affect the new transplanted lung to become also infected.

Bronchiectasis

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

Morphological types

• Cylindrical or tubular bronchiectasis

• Varicose

• saccular or cystic bronchiectasis

Bronchiectasis

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

Ct/cxr

Ct/cxr

Worldwide, infection is the primary cause– M. Tuberculosis– Childhood illnesses

• Rubeola, B. Pertussis

Bronchiectasis

Bronchiectasis

Inflammation

Infection

Childhood Infections M. Tb.

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 inflammatione.g. ABPM, CF (?)

– Impaired clearance of stimuliBacteria, mucus, toxins

Airway Damage Failure to Resolve Inflammation

– Altered Airway MilieuProteolytic damage

-e.g. cleaved receptors-impaired macrophage function*

Oxidant stress-low antioxidants associated with worse disease-dysregulation of signaling and cellular function‡

Bronchiectasis

Inflammation*

Infection

Impaired Clearance


Altered development

Impaired Clearance

Altered ciliary FunctionPCD, smoking, CFTR, Young’s

Mucus rheologyCFTR, Mucoid Ps. A

Dilated or obstructed airways Impaired cough, foreign bodies, aspiration

Impaired ImmunityIneffective inflammation

Acquired

Chemo-immunomodulation

Congenital/innate

Bronchiectasis

Inflammation

Infection

HIV/AIDS Chemo-Immunosuppressionanti-TNF, MTX, anti-neoplastics

Innate DeficiencyCGD, CVID, Ig’opathy (IFN)


Impaired Clearance foreign body, CF

Altered development

Bronchiectasis

Inflammation

Infection

Childhood Infections

HIV/AIDS Chemo-Immunosuppression

Innate Deficiency

Impaired Clearance

Auto-Immune RA, Sjogren’s, IBDABPM

Altered development

M. Tb.

Bronchiectasis

Inflammation

Infection



Innate Deficiency

Impaired Clearance

Auto-Immune ABPM

Altered development

M. Tb.

Bronchiectasis

Inflammation

Infection



Innate Deficiency

Impaired Clearance

Auto-Immune ABPM

Altered development

M. Tb.

BronchiectasisEpidemiology and Etiology

Who?

Patients - with altered immune system - with persistent respiratory symptoms

Why?

Persistent inflammation in the respiratory system

Bronchiectasis TherapyDecrease inflammation

antibioticsclearance

– Flutter, IPPV, Vest, Bronchodilators, hypertonic saline

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

(surgical resection)

When to suspect bronchiectasis?

Chronic cough, sputumCoarse ralesPersistent respiratory

symptoms Recurrent pneumoniaProgressive 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 TherapyAntibiotics

Episodic or suppressive antibiotics?

Yes.

Selective pressure vs. suppression of damage


• Pro– Decrease

inflammation– Slow progression– Eradication?

ConSelect resistanceCostSide effectsadherence difficult (e.g. Huong et al.)


• Pro– Decrease

inflammation– Slow progression– Eradication?

ConSelect resistanceCostSide effectsadherence difficult (e.g. Huong et al.)

Bronchiectasis TherapyAntibiotics when to use?

• Yes:– Evidence of

exacerbation– Progressive decline– “Frequent

exacerbator”– Active

inflammation (?)

No:Minimal disease without organismPatient Intolerant“Unaffordable”

Bronchiectasis TherapyDecrease inflammation

ClearanceImmunomodulatory chemotherapyproposed 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 end-expiratory

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

Vicious loops

Bronchiectasis

InflammationBronchial

Obstruction

Infection

Summary

• 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, PFT’s, Weight, X-rays)

• Other…– Underlying disease therapy– Transplantation– Management of complications

• Collapse, plugs, hemoptysis

diagnosis management

Vicious loop

Bronchiectasis

InflammationBronchial

Obstruction

Infection

ClearanceAlbuterol, DNase,Therapy vest

Antibioticstobramycin

Anti-inflammatoryInhaled steroids

Bronchiectasis

Dilated airways with frequently thickened walls

Bronchiectasis: Clinical

Note: Bronchiectasis may happen 2/2 COPD or may be a separate process with very similar symptoms

Clinical:• Cough (90 %)• Daily sputum production (76%)• Dyspnea (72%)• Hemoptysis (56%)• Recurrent pleurisy

Pathophysiology

2 Prerequisites:

• Infectious insult

• Impairment of drainage, airway obstruction, and/or a defect in host defense.

Pathophys Continued• Infection: Bacterial, mycobacterial, esp. ABPA central airway

bronchiectasis

• Airway obstruction: intraluminal tumor, foreign body, lymph nodes, COPD

• Immunodeficiency: ciliary dyskinesia, HIV, hypogammaglobulinemia, cystic fibrosis

(obstruction and immunodef.)

http://www.meddean.luc.edu/lumen/meded/Radio/curriculum/Harrisons/Pulmonary/CF3d.jpg

Characteristic central bronchiectasis 2/2 ABPA

Note characteristic location in the upper lobes and superior segments of lower lobes

Exacerbation: Etiology +RxColonization/infection: • Hemophilus• Pseudomonas• MAI• Aspergillus

Very difficult to distinguish colonization from acute infection with these bugs.

Psuedomonas colonized more bronchiectasis on CT; increased number of hospitalizations vs H. flu colonization

Effect of sputum bacteriology on the quality of life of patients with bronchiectasis. Wilson CB; Jones PW; O'Leary CJ; Hansell DM; Cole PJ; Wilson R Eur

Respir J 1997 Aug;10(8):1754-60.

Treatment: fluoroquinolone

Prevention

• Antibiotics-Controversial:Consider Macrolide TIWCipro qd X 7-14 D/ month

• Bronchial Hygiene, physiotherapy, pulmonary rehab

• ?bronchodilators, and steroids• Surgery

CXR 08/21

CXR08/23

CXR08/28

CXR08/31

HRCT08/31

CXR09/01

CXR09/09

CXR09/15

Bronchiectasis

Introduction

• Chronic daily cough w/ viscid sputum• Bronchial wall thickening and luminal dilation

on CT• Prevalence varies

– Associated w/ ↑age, female• Management

– Infection control– ↑ bronchial hygiene– Surgical resection in selected p’t

Pathophysiology

• Permanent abnormal dilation and destruction of bronchial walls

• Two factors– Infection– Impairment of drainage, airway obstruction,

and/or defect in host defense• Biomarkers: inflammatory cells or 8-iso-

prostaglandin F(2α) in sputum

Etiology• Pulmonary infections

– viral, mycoplasma, TB, MAC• Airway obstruction• Defective host defenses• ABPA (allergic bronchopulmonary aspergillosis)• Rheumatic and other systemic dz

– RA, Sjogren’s syndrome– Ulcerative colitis

• Dyskinetic cilia• Cystic fibrosis ← rare in TW• Cigarette smoking?

Diagnostic Evaluation

• CBC w/ differential• Ig quantification• Sputum culture and smear

– bacteria, mycobacteria, fungi• CXR

– Linear atelectasis, tram track, ring shadow, irregular peripheral opacities

• HRCT: defining test • PFT

CXR of Bronchiectasis


Hansell DM - Radiol Clin North Am - 01-JAN-1998; 36(1): 107-28


Hansell DM - Radiol Clin North Am - 01-JAN-1998; 36(1): 107-28

HRCT• Sensitivitiy ~97%• Findings

– Airway dilation– Lack of tapering of bronchi– Bronchial wall thickening– Mucopurulent plugs or debris– Cyst– Pneumonia, LAP, emphysema

• Distributions– Upper lobe– Central distribution

HRCT

Radiol Clin N Am 43(2005) 513-542

HRCT

HRCT

Management

• Infection control• ↑ bronchial hygiene• Surgical resection in selected p’t

Infection Control

• Acute exacerbation– ↑viscous, dark sputum, lassitude, SOB, pleurisy– Fevers and chills generally absent– CXR rarely show new infiltrates– H. influenzae and P. aeruginosa– FQ is reasonable (eg. ciprofloxacin) for 7~10 days

Prevention

• Daily ciprofloxacin (500~1500mg) in 2~3 doses• Macrolide daily or three times weekly• Daily use of a high dose oral antibiotic, such as

amoxicillin 3 g/day• Aerosolization of an antibiotic• Intermittent intravenous antibiotics

Problematic Pathogen

• Pseudomonas aeruginosa– Almost impossible to irradicate– Wilson CB et al.

• Reduced QoL• More extensive bronchiectasis on CT • Increased number of hospitalizations

– Ciprofloxacin quickly develops resistance

Bronchial Hygiene• Oral hydration• Nebulization

– Normal saline– Acetylcyteine– Recombinant DNAase– Hypertonic saline, mannitol, dextran, lactose

• Physiotherapy– Chest percussion– Prone position

• Bronchodilator? Steroid? NSAID?

Surgical Intervention

• Removal of the most involved segments• Most common: middle and lower lobe

resecton• Hemoptysis:

– Bronchial a. embolization• Lung transplantation

Lung Transplantation• Overall 1-year survival : 68% (54-91%)• Overall 5-year survival : 62% (41-83%)• Subgroup

– SLTX : 1 yr survival 57% (20%-94%) n=4• Mean FEV1 : 50% predicted (34%-61%), • Mean FVC : 53% predicted (46-63%)

– 2 lungs : 1 yr survival 73% (51-96%) n = 10• Mean FEV1 : 73% predicted (58%-97%), • Mean FVC : 68% predicted (53%-94%)

Chapter 14 Bronchiectasis

Figure 14–1. Bronchiectasis. A, Varicose bronchiectasis. B, Cylindrical bronchiectasis. C, Saccular bronchiectasis. Also illustrated are excessive bronchial secretions (D) and atelectasis (E), which are

both common anatomic alterations of the lungs in this disease.

D

E

AB

C

Three Forms of Bronchiectasis

• Varicose bronchiectasis• Cylindrical bronchiectasis• Saccular bronchiectasis

Anatomic Alterations of the Lungs

• Chronic dilation and distortion of bronchial airways• Excessive production of often foul-smelling sputum• Smooth muscle constriction of bronchial airways• Hyperinflation of alveoli (air-trapping)• Atelectasis, consolidation, and parenchymal fibrosis• Hemorrhage secondary to bronchial arterial erosion

Etiology

• Acquired bronchiectasis– Recurrent pulmonary infection– Bronchial obstruction

• Congenital bronchiectasis– Kartagener’s syndrome– Hypogammaglobulinemia– Cystic fibrosis

Overview of the Cardiopulmonary Clinical Manifestations Associated

with BRONCHIECTASISThe following clinical manifestations result from the pathophysiologic mechanisms caused (or activated) by Atelectasis (see Figure 9-12), Consolidation (see Figure 9-8), Bronchospasm (see Figure 9-10), and Excessive Bronchial Secretions (see Figure 9-11)—the major anatomic alterations of the lungs associated with bronchiectasis (see Figure 14-1).

Figure 9-7. Atelectasis clinical scenario.

Figure 9-8. Alveolar consolidation clinical scenario.

Figure 9-9. Increased alveolar-capillary membrane thickness clinical scenario.

Figure 9-10. Bronchospasm clinical scenario (e.g., asthma).

Figure 9-11. Excessive bronchial secretions clinical scenario.

General Management of Bronchiectasis

General treatment includes:• Controlling pulmonary infections• Controlling airway secretions• Preventing complications


Respiratory care treatment protocols• Oxygen therapy protocol• Bronchopulmonary hygiene therapy protocol• Hyperinflation therapy protocol• Aerosolized medication protocol• Mechanical ventilation protocol


Other medications commonly prescribedby the physician• Xanthines• Expectorants• Antibiotics

BRONCHIECTASISRADIOLOGICAL FEATURES

BRONCHIECTASISTHE CHEST RADIOGRAPH

• Often normal if not severe• Too many white lines extending from the hila

= tram-tracks• Elongated (tubular) opacities (white)• Small circles containing air (black) or fluid and

air (air-fluid level)

• Often normal if not severe• Too many white lines extending from the hila

= tram-tracks• Elongated (tubular) opacities (white)• Small circles containing air (black) or fluid and

air (air-fluid level)

MILD BRONCHIECTASISNormal chest radiographpresents with hemoptysis

MODERATE BRONCHIECTASIS- Coarse white linesextending out from hila

TOO MANY WHITE LINES

SEVERE BRONCHIECTASIS

Circle filledwith air



RINGS (CYSTS) CONTAINING AIR-FLUID LEVELS

BRONCHIECTASISTHE CT SCAN

• Signet ring sign• Tram-tracks• String of beads• Circles filled with air or air and fluid• Tubular and branching opacities• Bronchi visible within 1 cm of the pleura• Scarring

• Signet ring sign• Tram-tracks• String of beads• Circles filled with air or air and fluid• Tubular and branching opacities• Bronchi visible within 1 cm of the pleura• Scarring

SIGNET-RING SIGN

Dilated bronchus(ring)

Normal pulmonaryartery (pearl)

Dilated bronchus

BRONCHIECTASIS

String of beads

BRONCHIECTASIS

Bronchi visiblewithin 1 cm of the pleura

Destroyedlung(Scarring)

BRONCHIECTASIS

CAUSES OF BRONCHIECTASIS

• Congenital• Acquired

• Congenital• Acquired

CONGENITAL CAUSES OF BRONCHIECTASIS

• Cystic fibrosis• Immotile cilia syndrome

• Cystic fibrosis• Immotile cilia syndrome

CYSTIC FIBROSIS

• Diffuse bronchiectasis• Most severe in the upper lobes

• Diffuse bronchiectasis• Most severe in the upper lobes

CYSTIC FIBROSIS

CYSTIC FIBROSIS

Worse in theupper lung zones

IMMOTILE CILIA SYNDROME

• Diffuse bronchiectasis• May have situs inversus (Kartagener’s

syndrome

• Diffuse bronchiectasis• May have situs inversus (Kartagener’s

syndrome

Bronchiectasis

Dextrocardia

KARTAGENER’S SYNDROME

Bronchiectasis




Dextrocardia

Dilatedbronchus

CAUSES OF ACQUIRED BRONCHIECTASIS

• Post-infectious• Post-obstructive

– aspirated foreign body– slow-growing tumour

• Post-infectious• Post-obstructive

– aspirated foreign body– slow-growing tumour

POST-INFECTIOUS BRONCHIECTASIS

• Affects the part of the lung which was involved with pneumonia

• Often diffuse as most commonly secondary to a viral pneumonia

• Affects the part of the lung which was involved with pneumonia

• Often diffuse as most commonly secondary to a viral pneumonia

POST-OBSTRUCTIVE BRONCHIECTASIS

• Focal or localized because only distal to the obstructing lesion

• Dilated bronchi distal to obstruction filled with mucus instead of air

• Focal or localized because only distal to the obstructing lesion

• Dilated bronchi distal to obstruction filled with mucus instead of air

FOCAL BRONCHIECTASIS

FOCAL BRONCHIECTASIS

Branchingtubular opacities

FOCALBRONCHIECTASIS

Focal bronchiectasisdue to slow-growingendobronchial tumour

Branchingtubular opacity

Dilated bronchifilled with mucus

Focal bronchiectasisdue to slow-growingendobronchial tumour

Dilated bronchifilled with mucusinstead of air due toproximal obstruction

PULMONARY EMBOLISM

RADIOLOGICAL FEATURES

Lung - Pathology

• Pulmonary Edema• 1. Hemodynamic disturbances(↑ capillary hydrostatic pressure), MCC-

LVF, Heart failure cells • 2. ↓ oncotic pressure (Hypoalbuminemia) Renal failure,

Malnutrition, Cirrhosis• 3. Microvascular injury - ↑ capillary permeability,

– Seen in ARDS following a) Infection -viral pneumoniab) Gases, Aspiration, Drugs--heroin, Paraquat (herbicide) c) Shock, Trauma, Sepsis, DIC

• ARDS: • Also known as ***Diffuse Alveolar Damage (DAD) pulmonary

edema (protein rich) hyaline membrane disease hypoxemia (refractory to oxygen Rx )

• Mortality in 50% of cases • Clinical Manifestations: respiratory insufficiency, Cyanosis, arterial

hypoxemia multi-organ failure• Acute interstitial pneumonia Cause is unknown (Unlike

ARDS) but Radiographic and Pathologic features, mortality similar to ARDS

• Bronchiectasis • Infection + permanent dilatation of bronchi• Causes:

• infections and causes of bronchial obstruction (FB, mucus plugs, tumors, sequestrations, cystic fibrosis)

• immotile cilia (Kartagener’s )syndrome (Bronchiectasis, dextrocardia -situs inversus, chronic sinusitis, and infertility)

• Clinically:

• Chronic cough, productive of purulent sputum• Dyspnea and orthopnea in severe cases• later obstructive respiratory insufficiency & Corpulmonale

Bronchiectasis Gross

• Distended peripheral bronchi (Due to weakening of wall)

Bronchiectasis Gross

PRIMARY ANTIBODY DEFICIENCY

(PAD)&

BRONCHIECTASIS

(UKPIN / BTS GUIDELINES)

BRONCHIECTASIS

A destructive lung disease characterised by:

Abnormal & permanent dilatation of medium sized bronchi

An associated, persistent and variable inflammatory process producing damage to bronchial elastic and muscular elements

PATHOLOGY

Neutrophil proteases(acute infection in a normal or compromised host)

Epithelial injury

+Structural protein damage

Damaged, dilated airway

Mucous retention / chronic, recurrent infection

Ongoing inflammation / tissue damage / repair

BRONCHIECTASIS - aetiology Infection - pertussis, influenza, measles, TB, necrotising peumonia Bronchial obstruction - mucoid impaction, ABPA Congenital anatomical lung abnormality Inherited disorders - ciliary dysfunction - cystic fibrosis - alpha-1 AT deficiency

• Undefined (29 - 49%)

BRONCHIECTASIS OF UNDEFINED AETIOLOGY

REF. NOS. ANALYTE % age ABN.

Hilton & Doyle 1978

53 IgG/A/M 0 -

Murphy et al 1984

23 IgG/A/M, Gsub 0 -

Barker et al 1987

30 IgG/A/M, Gsub 37 Panhypoγ (9/30) IgM (2/30)

De Gracia et al 1996

65 Gsub, Hib 48 IgG2 Hib (10/19)

Hill et al 1998

89 Gsub 6 IgG4

Stead et al 2002

56 IgG/A/M, Gsub Hib, Pneum

23 IgG4 Pneum (1/29)

BRONCHIECTASISPasteur et al. Am J Respir Crit Care Med (2000) 162, 1277-1284

ASSOCIATION n %Idiopathic 80 53

ABPA 11 7

PAD 11 7Neutrophil defect 1 <1

Rheumatoid disease 4 3

Ulcerative colitis 2 <1

Ciliary dysfunction 3 1.5

Young’s syndrome 5 3

Cystic fibrosis 4 3

Post-infectious 44 9

Aspiration/reflux 6 4

Other defineable 2 <1

BRONCHIECTASIS in PADCVID • 53% (Hausser et al 1983)• 44% (Watts et al 1986)• 18% (Hermazewski & Webster 1993) • 20% (UK PAD Audit 1993-96)• 27% (‘chronic lung disease’) (Cunningham Rundles 1999)• 58% (Garcia 2001)• 43% (Busse et al 2002)

XLA• 7% (Hermazewski & Webster 1993)• 12% (UK PAD Audit 1993-96)• 20% (Quartier et al 1999)

RESPIRATORY INFECTIONS

Figure 2 Types of infection in the 37 patients receiving immunoglobulin replacement treatment. The numbers of each type of infection are listed by each chart section.

DIAGNOSTIC DELAY Average: diagnosis - 6.3 years treatment - additional 3.9 Diagnostic delay > 2 years: risk of bronchiectasis sinusitis iron deficiency (UK PAD Audit 1993-96) 3

Strongest predictor of chronic pulmonary disease in treated patients is established lung disease at time of presentation n= XLAx10, CVIDx12 IMIg x 18, IVIg x 3, FFP x 1 (all + daily antibiotic) (Sweinberg et al 1991) 3

UK PAD AUDIT 1993-96

Development of bronchiectasis following diagnosis:

<1980 1981-87 >1988 77% 70% 42%

CHRONIC LUNG DISEASE in PAD

Damage sustained prior to active treatment

and/or

Continued inflammation despite treatment

AIMS

Define evidence-based guidelines relevant to:

investigation level appropriate to screen for significant antibody deficiency in all patients with bronchiectasis

diagnosis & management of bronchiectasis complicating primary antibody deficiency

GUIDELINES Simple Evidence-based Consistent with existing, recognised standards Realistic Explicit Clear & well documented Credible & widely supported Results orientated (outcomes)

Valid Reproducible Reliable• Involving & representative of key disciplines Clinically applicable Clinically flexible Scheduled for review

GUIDELINES

LITERATURE REVIEW

Meta-analyses Systematic reviews RCTs Longitudinal studies Case control/cohort studies Case reports/case series Expert opinions

DATABASES

Ovid Online Collection - Medline, preMedline - CINAHL, EMBASE - Journals@ovid EBM Reviews - Cochrane Systematic Reviews - Cochrane Controlled Trials - Effectiveness Reviews Abstracts - ACP Journal Club Allied & Complementary Medicine Specialty Contacts

mailto:Journals@ovid

GUIDELINES

EVIDENCE RECOMMENDATION 1 A

2 B

3 C

4 D

(Good Practice Points) SIGN, RCPCH, BTS

DIAGNOSIS PRIMARY ANTIBODY DEFICIENCY

Humoral abnormalities are common in bronchiectasis 3

Respiratory Physician + Immunologist 4 Diagnosis of significant antibody deficiency should entail use of

established and widely accepted criteria: 4

- Primary Immunodeficiency Diseases. Report of an IUIS Scientific Group Clinical & Experimental Immunology 1999 (118), Suppl 1:1-34 - Diagnostic Criteria for Primary Immunodeficiencies. Clinical Immunology 1999 (93), 190-197 - Practice parameters for the Diagnosis & Management of Immunodeficiency. Annals of Allergy, Asthma & Immunology 1996 (76), 282-294

PFTs

- Reversible/irreversible bronchial obstruction- Granulomatous disease etc.

Correlate poorly with Radiology (bronchiectasis) 3 - Pulmonary abnormalities in patients with primary hypogammaglobulinaemia Kainulainen et al. Jounal of Allergy & Clinical Immunology (1999) 104, 1031-1036 - Pulmonary manifestations of hypogammaglobulinaemia Dukes et al. Thorax (1978) 33, 603-607 - Radiologic findings of adult primary immunodeficiency disorders: contribution of CT Obregon et al. Chest (1994) 106, 490-495

• Static volumes/flow-volume loops

RADIOLOGY - CXR

Bronchiectasis

- vessel ‘crowding’- loss of vessel markings- tramline/ring shadows- cystic lesions/ air-fluid levels- evidence of TB

Poor: diagnostic sensitivity monitoring of progression

3

RADIOLOGY - HRCT

- bronchial dilatation - bronchial wall thickening- classification (pathology)

sensitivity (97%) > CXR 3

chromosomal radiosensitivity - plain CXR (x 3 days background) - HRCT: x 30-40 - conventional CT: x 200• ? routine baseline • ? (a)symptomatic monitoring

UNSUSPECTED DISEASE(Clinical v CXR v HRCT)

Bronchiectasis in Hypogammaglobulinaemia - A Computed Tomography assessment. Curtin et al. Clinical Radiology (1991) 44, 82-84

Radiologic Findings of Adult primary Immunodeficiency Disorders. Obregon et al. Chest (1994)106, 490-495

Chest High Resolution CT in Adults with Primary Humoral Immundeficiency. Feydy et al. British Journal of Radiology (1996) 69, 1108-1116

Clinical Utility of High-Resolution Pulmonary Computed Tomography in Children with Antibody Deficiency. Manson et al. Pediatric Radiology (1997) 27, 794-798

The Value of Computed Tomography in the Diagnosis & Management of Bronchiectasis. Pang et al. Clinical Radiology (1989) 40, 40-44

Review Article: Imaging in Bronchiectasis. Smith et al. British Journal of Radiology (1996) 69, 589-593

3

RADIOLOGYKainulainen et al 1999

CVID x 18, XLA x 4

CXR HRCTBronchiectasis 3 16

3 year follow-up Disease progression (5)

Serum IgG Case No T=0 T=36 1 9.9 10.0 2 4.6 6.1 8 3.7 5.1 10 3.7 4.9 21 3.1 5.7

RADIOLOGY - HRCT

RCP Specialty Specific Standards

‘Fit’ patients…….CT scanning should be undertaken in a minority of patients but usually not more than once ayear or if respiratory function tests or symptoms deteriorate

JCIA November 2001 4

MANAGEMENT – GENERAL ISSUES

Shared Care (Immunologist/Respiratory Physician) optimal 4 Bronchodilators (reversible airflow obstruction) Mucolytics - insufficient evidence to evaluate routine use (Cochrane Database of Systematic Reviews. 3, 2003) Physical therapy - insufficient evidence to support or refute usage

(Cochrane Database of Systematic Reviews. 3, 2003) Anti-inflammatory agents

REPLACEMENT THERAPY Risk/benefit assessment

4 IV/Sc routes optimal 2 pulmonary infections in XLA/CVID (v untreated) 2 Optimal dosing/frequency/serum IgG level not established Tailor route/dose/infusion frequency

3

--------------------------------------------------------------- Maintain IgG >5g/l

2 Paediatric target: mid reference range 4 IgG: >8g/l infection (v 5g/l, XLA, children) 3 9.4 g/l infection (v 6.5g/l, XLA/CVID, children/adults)

3 High v standard doses infections (no. & duration) 2 days hospitalised serum IgG Insidious disease progression despite ‘adequate’ replacement

3

REPLACEMENT THERAPYHigh dose v low dose: secondary outcome, pulmonary function

Eijkhout et al 2001 (randomised, double-blind, multicentre, crossover, n=43) High dose (mean trough IgG 9.4 g/l): PEFR 37.3 l/min Standard dose (mean trough IgG 6.5 g/l): PEFR 11.4 l/min NS

Roifman & Gelfand 1988 (ramdomised, crossover, n=12)

High dose FVC & FEV1 p<0.01

Roifman et al 1987 (randomised, crossover, n=12)

Mean FEV1 & FVC high dose phase v low dose phase p<0.01

Bernatowska et al 1987 (two-dose, crossover, non-randomised, n=13)

High dose Max. expiratory flow & FEV1 NA

ACUTE INFECTIONMICROBIOLOGY Culture & sensitivity routinely in acute setting 3 Value unclear in chronic situation - confirm original pathogen - ? emerging resistance - additional pathogens

ANTIBIOTICS Effectiveness established in exacerbations (bronchiectasis) 2

Higher doses for longer periods 4 Local treatment protocols 4

ANTIBIOTIC PROPHYLAXIS Chronic bronchitis - no place in routine treatment (Cochrane Database of Systematic Reviews. 3, 2003)

Cystic fibrosis benefits - principally staphylococci - infancy 3/6 years - ? older children/adults - ? > 3years treatment (The Cochrane Library, Oxford. 2, 2003) (Cochrane Database of Systematic Reviews. 3, 2003)

• Bronchiectasis - limited meta-analysis (6 RCTs) - marginal benefit / cautious support (Evans et al. Thorax 2001)

ANTIBIOTIC PROPHYLAXIS No robust data v placebo No substantial data v (or additional to) IVIg/SCIg (Silk et al. 1990) ? Single intervention in mild antibody deficiency - not in more severe phenotypes / tissue damage Papworth protocol: consider if: > 3 exacerbations / year 4 radiological / PFT deterioration ? Eradication/clean-up therapy prior to prophylaxis - no clear evidence of benefit in antibody deficiency + structural lung damage Development of local protocols for management of infections (esp. with Primary Care) and initiating prophylaxis 4

(Heelan et al., ESID 2002)

Percentage of sputum samples growing pathogensbefore and after prophylactic ciprofloxacin

0

10

20

30

40

50

60

70

Prior tociprofloxacin

Onciprofloxacin

all pathogens

H. Infl (allisolates)H Infl. (resistantto ciprofloxacin)

%

ANTIBIOTIC PROPHYLAXIS

SURGERY Diagnostic delay > 2 years: need for surgical procedures Adequate

treatment: lobectomy/pneumonectomy by 95% (UK PAD Audit 1993-96) 3

Important treatment option with favourable outcomes especially in focal bronchiectasis (Cohen et al 1994, Mansharamani & Koziel 2003) 3

QUESTIONS / ISSUES HRCT in routine screening & monitoring Radiological changes a primary therapeutic target - Does HRCT modify our current assumptions about criteria for adequate treatment of antibody deficiency disorders? Correct level of Ig treatment - arbitrary target serum level (evidence) or individualised (clinical + HRCT factors) - single intervention universally applicable in all patients (probably not) - higher doses: expense, complications, limited commodity Roles of: antibiotics anti-inflammatory agents bronchodilators aids to airway clearance Role of co-factors (e.g. -1AT) Selective IgA deficiency

PIN GUIDELINES Identify need for focused clinical research Encourage debate and discussion Reflect uncertainties in the field Proscriptive as necessary, flexible where possible

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