Bronchiectasis/asthma and vasculitis

What is bronchiectasis?

Abnormal irreversible dilatation of the bronchi caused by destruction of the muscle and elastic tissue

What disease is bronchiectasis classified as?

an obstructive lung disease

Bronchiectasis is a disease which involves a vicious circle of?

transmural infection and inflammation with mediator release

What does the prognosis of bronchiectasis depend on?

underlying cause and extent of lung involved

What are the causes of upper lobe bronchiectasis?

Cystic fibrosis

Tuberculosis

What are the causes of central lobe bronchiectasis?

Cystic fibrosis

ABPA

Congenital Tracheo-bronchomegaly

What are the causes of lower lobe bronchiectasis?

Childhood infection

Aspirations

Immunodeficiency

Bronchiectasis is due to what in terms of infection?

- sequel of bronchopneumonia and bronchiolitis in childhood which has imperfectly resolved

- Pneumonia complicating measles or whooping cough

- Allergic Bronchopulmonary Aspergillosis (ABPA)

- Chronic tuberculous cavities

- Primary Mycobacterium avium complex infection

What is the incidence of pneumonia complicated measles or whooping cough reduced by?

Incidence reduced due to effective childhood immunisation

strategies

What are some congenital conditions that lead to bronchiectasis?

Primary ciliary dyskinesia

Alpha-1-antitrypsin deficiency

Cystic Fibrosis

Young's syndrome

Marfan syndrome (very rarely)

Kartageners Syndrome

How does primary ciliary dyskinesia cause bronchiectasis?

Poorly functioning cilia contribute to retention of secretions and recurrent infections

What does young's syndrome cause?

Chronic sinopulmonary infections

Male infertility

What is kartageners syndrome characterised by?

by a triad of dextrocardia, bronchiectasis and severe sinusitis

What is the inheritance of Kartageners syndrome?

Autosomal recessively inherited condition

What does Kartageners syndrome affect?

Affects the mobility of the cilia

What are some immunodeficiencies that lead to bronchiectasis?

Persons with humoral immunodeficiency syndromes involving deficiencies of IgG, IgM and IgA (i.e. Hypogammaglobulinaemia)

Immunodeficiency due to malignancy e.g. myeloma, lymphoma

Immunoglobulin replacement reduces the frequency of infections and prevents ongoing airway destruction

What are some reasons why bronchial obstruction could lead to bronchiectasis?

• Inhaled / aspirated foreign bodies

• Tumour

• Mucus plugs in asthma

• Compressive lymphadenopathy

• Chronic aspiration

What are some rheumatic conditions that could lead to bronchiectasis?

Sjogrens Syndrome

Systemic Lupus Erythematosus

Rheumatoid arthritis

Also associated with inflammatory bowel disease

especially ulcerative colitis

The induction of bronchiectasis requires two factors which are?

An infectious insult

Impairment of drainage, airway obstruction

What is the pathogenesis behind bronchiectasis?

Involved bronchi are dilated, inflamed and easily collapsible, resulting in airflow obstruction and impaired clearance of secretions

What is the vicious cycle of bronchiectasis?

Destruction, release, viscous lung secretion, microbial colonisation, inflammation and early death

What are the symptoms of bronchiectasis?

Productive cough with purulent sputum

Sputum may be mucoid, mucopurulent, thick or viscous

Blood streaked sputum or copious haemoptysis may result

from erosive airway damage due to acute infection

Dyspnoea and wheezing in 75%

Pleuritic pain in 50%

Recurrent LRTI

What are the clinical findings of bronchiectasis?

Crackles, coarse crepitations and rhonchi on auscultation

Clubbing a common finding in the past, rare now 3%

Major confounding disease is COPD

What are the complications of bronchiectasis?

• Massive haemoptysis

• Respiratory failure

• Pneumonia

• Pleural effusion

• Brain abscess

• Amyloidosis

What are some respiratory pathogens in bronchiectasis?

staphylococcus aureus, haemophlyus influenza, pseudomonas aeruginosa

What is pleural effusion?

Accumulation of fluid in the pleural space

What is empyema?

accumulation of infected fluid in the pleural space

What is present normally in the parietal space ?

Normally a small amount of thin, pale yellow fluid is

present in the pleural space to allow movement of the

visceral pleural against the parietal pleura

What are pleural effusions classified as?

TRANSUDATE EXUDATE

Describe transudates

low specific gravity, low protein and few cells

What are causes of transudate?

include heart failure, fluid overload, nephrotic syndrome, Peritoneal dialysis

(anything to do with pressures)

Describe exudate

high specific gravity, high protein and lots of cells

What are causes of exudate?

infection, malignancy, pulmonary emboli (increased permeability)

When will pleural fluid accumulate?

when the rate of pleural fluid formation is greater that the rate of pleural fluid removal by the lymphatics

When do transudative effusions occur?

when alterations in the systemic factors that influence pleural fluid movement result in a pleural effusion

What are some examples od transudative effusion?

elevated visceral pleural capillary pressure with left heart failure, elevated parietal pleural capillary pressure with right heart failure, decreased serum oncotic pressure with nephrotic syndrome, hepatic cirrhosis

When do exudative effusions occur?

when the pleural surfaces are altered. Inflammation of the pleura, leading to increased protein in the pleural space is the most common cause of exudative effusion

How can we diagnose pleural effusion?

• CXR

+/- CT Thorax

Blood tests

• Thoracocentesis

What is asthma?

an inflammatory disorder characterised by hyper-responsiveness of the airway to various stimuli resulting in wide spread narrowing of the airways

Is asthma reversible?

The changes are reversible, either spontaneously or with therapy

What does the inflammatory process of asthma include?

T lymphocytes, mast cells in eosinophils and is associated with exudation of plasma, oedema and smooth muscle hypertrophy, deposition of matrix, mucus plugging and epithelial damage

What is the definition of asthma?

Episodic, reversible bronchospasm (airflow obstruction) resulting from exaggerated bronchoconstriction in response to various stimuli

What are the symptoms of asthma?

Recurrent episodes of wheezing, breathlessness, chest

tightness and coughing

Is asthma chronic or acute?

Chronic

What asthma triggered by?

a wide variety of

inciting agents

What is the prevalence of asthma?

Asthma is common

300 million people worldwide

10-15% of children, 7-10% of adults

Asthma is most common in which population?

Young children commonest; boys>girls

Asthma is least common in which population?

Adolescents least common, higher frequency in adults

Which type of asthma has good prognosis?

Childhood asthma has a good prognosis

What is the pathophysiology behind asthma?

Inflammation of the airways

Smooth muscle surrounding airway becomes oedematous and tightens airway

Reduces amount of air that can pass through leading to wheeze

Airway epithelium becomes oedematous, erythematous and inflamed

What are the inflammatory mediators in asthma?

Type 2 T helper lymphocytes, IL-4, IL-5, IL-13

Eosinophils, IgE, Mast cells, histamine, leucotrienes

What are the symptoms of asthma upon history taking ?

Episodic SOB Wheeze Chest tightness Cough

+/- sputum production Generally worse in morning History: elicit triggers

What are the causative factors for asthma?

Allergic and Intrinsic (Non-allergic)

What is allergic factor of asthma due to?

Atopic related disease (Allergic) as evidenced by increased IgE

levels and immediate hypersensitivity on skin testing

predominates in childhood asthma

What is non-allergic asthma associated with?

Non-allergic or intrinsic asthma is associated with an older age

and may be difficult to manage. Often associated with COPD

What are the genetic factors of asthma?

no single gene but several, in combination

with environmental factors, influence development

What are the environmental factors of asthma?

early childhood exposure to allergens and maternal smoking - house dust mite allergens, cockroach

allergy in U.S.A,

What are some viral infections that cause asthma?

rhino virus - RSV

What are occupational sensitisers for asthma?

250 materials in workplace cause

occupational asthma, isocyanates, wood dust, bleaches, allergens from animals

How does cold air and exercise lead to asthma?

exercise-induced wheeze is drive by release of histamine, prostaglandins (PGs) and leukotrienes (LTs) from mast cells

How does atmospheric pollution and irritant dusts cause asthma?

many patients with asthma experience worsening of symptoms on exposure to tobacco smoke, car exhaust fumes, solvents, sulphur dioxide, ozone etc.

Why is diet important with asthma?

increased intake of fresh fruit & vegetables shown to be protective

How do emotions lead to asthma?

emotional factors influence asthma both acutely and chronically

What drugs can lead to asthma?

NSAIDs, aspirin, ibuprofen are implemented in triggering asthma - 5% of patients (particularly prevalent in patients with nasal polyps and asthma)

Beta blockers - direct parasympathetic innervation that tends to produce bronchoconstriction

What are some microscopic features of asthma?

Airway infiltration by neutrophils and eosinophils

Mast cell degranulation

Basement membrane thickening

Loss of epithelial integrity

Occlusion of bronchial lumen by mucus

Hyperplasia and hypertrophy of bronchial smooth muscle and goblet cells

What are some vascular lung diseases?

Pulmonary embolism

Pulmonary infarction

Haemorrhage

Vasculitis

What are pulmonary embolisms?

a complication arising from deep vein thrombosis that results in a blood clot blocking the pulmonary artery or its branches

What are the sources pulmonary embolism?

Venous and right side of heart

>95% arise from thrombi in deep veins of lower legs (popliteal vein or above)

Thromboemboli do not usually arise from superficial or smaller leg veins

What is the mortality rate of pulmonary thromboembolism?

50,000 deaths / year in USA

What are risk factors of pulmonary embolism?

Immobilisation

Severe trauma

CCF

Pregnancy

OCP

Malignancy

Hypercoagulable states

Connective tissue disease

What are some hyper-coagulable states?

Factor V leiden mutation

Protein C, Protein S deficiency

Antithrombin III deficiency

Lupus anticoagulant

Homocysteinuria

What is Virchow's triad?

Blood flow stasis

Hypercoagulable state

Endothelial damage

What do symptoms of pulmonary embolism depend on?

Depends on size of the embolism, which in turn dictates the size of the occluded pulmonary artery

What are the consequences of PE?

Increase in pulmonary artery pressure from blockage of flow and vasospasm caused by neurogenic mechanisms and release of mediators

Ischaemia of downstream pulmonary parenchyma

Occlusion of a major vessel causes a sudden increase in pulmonary artery pressure, diminished cardiac output, acute cor pulmonale and possibly sudden death

Occlusion of a smaller vessel is less catastrophic and may even be clinically silent

What are clinical manifestations of PE?

Silent (60-80%)

Sudden death (5%)

Obstruction of small to medium pulmonary branches

(10-15%)

Recurrent PEs (3%)

When is PE silent?

Small and embolic mass is removed by fibrinolytic activity

Bronchial circulation sustains viability of affected lung

parenchyma

When does PE result sudden death?

Acute cor pulmonale, cardiovascular collapse when >60% of

the vasculature is obstructed

What does obstruction of small to medium pulmonary branches cause? what do patients complain of?

pulmonary infarction; patients complain of

dyspnoea, haemoptysis, pleuritic chest pain

What may recurrent PEs lead to?

to pulmonary hypertension, chronic right sided heart stain (chronic cor pulmonale, pulmonary vascular sclerosis

What is the classic presentation of PE?

Sudden onset pleuritic chest pain

SOB

Hypoxia

Syncope, seizures

Decreased level of consciousness

New onset atrial fibrillation

Haemoptysis

Infarction of the lung is usually where?

Usually peripheral

What does infarction look like of the lung?

Wedge shaped with the base at the pleural surface

Haemorrhage and appear as raised red-blue areas in early stage

What is adjacent pleural covered in when there is infarction of the lung? what can it cause?

in a fibrinous exudate; can cause pleuritic chest pain and effusion

What are some non thrombotic emboli?

Air embolism

Fat embolism

Amniotic fluid embolism

Foreign body embolism

Bone marrow embolism

What does diffuse alveolar haemorrhage present as?

Present as a triad

Haemoptysis

Anaemia

Diffuse pulmonary infiltrates

What is the prototype of diffuse alveolar haemorrhage?

Goodpasture syndrome

What are secondary causes of diffuse alveolar haemorrhage?

Necrotizing bacterial pneumonia

Bleeding diathesis

Passive venous congestion

What is goodpasture syndrome?

Rapidly progressive glomerulonephritis plus haemorrhagic interstitial pneumonitis

What are renal and pulmonary lesions in goodpasture syndrome due to?

caused by antibodies to antigens common to glomerular and pulmonary basement membranes

Goodpasture syndrome is an example of what type of hypersensitivity?

type II cytotoxic antibody mediated hypersensitivity

Antibodies can be detected in the serum of how many patients with goodpasture syndrome?

>90% of patients (Anti glomerular basement membrane antibodies; also called anti-GBM disease)

What do lungs show in goodpasture syndrome?

lungs shows focal necrosis of alveolar walls associated with intra-alveolar haemorrhages, fibrous thickening of septae

What is seen in an acute setting of goodpasture syndrome?

Haemosiderin laden macrophages

What is the management of goodpasture syndrome?

Plasmapheresis and immunosuppressive therapy

Describe how the management for goodpasture syndrome works

Plasma exchange removes offending antibodies and immunosuppressive drugs inhibit antibody production

What are some diseases where vasculitis affects the lung

Pulmonary angiitis and granulomatosis (GPA; aka Wegener granulomatosis)

Churg-Strauss syndrome

Collagen vascular disorders

What is granulomatosis with polyangiitis (GPA) also known as?

WEGENER'S GRANULOMATOSIS; ANCA ASSOCIATED VASCULITI

What is the hallmarks of GPA?

Pauci-immune vasculitis of small to medium sized vessels

Necrotising granulomatous inflammation

What does ANCA stand for?

Anti-neutrophil cytoplasmic antibodies

What is cytoplasmic ANCA (c-ANCA) directed against?

PR3 is most specific for GPA