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Interstitial Lung Disease and Vasculitis176
https://t.me/med1917
Transplant
•
• Patients should be considered for transplant if they are:
• Under the age of 65.
• Have failed trial of treatment.
• With one of:
• TLCO < 40%.
• Progressive FVC decline >
• Resting hypoxia.
• Pulmonary hypertension.
8. PROGNOSIS
Median survival is 3–5 years.
•
Patients who receive single lung transplant:
•
10%
within 6 months.
• 1 year actuarial survival of 80%.
• 3 year survival of 55%.
Factors associated with poor prognosis:
•
• 10% decline of FVC over 6 months:
– 2.4-fold increased risk of death.
• Pulmonary hypertension:
– Increased symptoms.
– Increased 1-year mortality.
– More likely to have complications from lung transplant.
• Oxygen desaturation below 88% on a 6-minute walk test:
– 4-year survival of 35% compared to a survival of 69% in those who
did not desaturate below 88%.
• Male sex.
• Older age.
• Multiple hospital admissions.
• Low T.
11.3 OTHER IDIOPATHIC INTERSTITIAL
PNEUMONIAS
1. NONSPECIFIC INTERSTITIAL PNEUMONIA (NSIP)
NSIP is an idiopathic interstitial pneumonia that is not pathologically com-
•
patible with usual, desquamative or acute interstitial pneumonia (see below).
Patients with NSIP have a greater response to steroids and a better prognosis
•
than those with IPF.
NSIP presents in a younger population, typically those in the fifth and sixth
•
Respiratory Medicine
decades.
Often associated with connective tissue disease.
•
Presentation:
•
11.3 Other Idiopathic Interstitial Pneumonias
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• Similar manner to IPF:
– Cough
– Dyspnoea of gradual onset.
• Examination findings:
– Inspiratory crackles
– Sometimes finger clubbing.
HRCT findings differ from IPF and show diffuse ground glass change
•
(See Figure 11.4).
Histology is variable, and can be characterised as either:
•
• Cellular: interstitial inflammation with no fibrosis, associated with
good prognosis.
• Fibrotic: interstitial fibrosis more homogenous than in UIP and with no
characteristic fibroblastic foci.
Treatment is predominately with steroids, and sometimes other
•
immunosuppressants.
177
Figure 11.4 High-resolution chest CT of patient with NSIP showing diffuse ground
glass changes.
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2. CRYPTOGENIC ORGANISING PNEUMONIA (COP)
In COP alveolar buds fill with granulation tissue, which is made up of a mix
•
of myofibroblasts and connective tissue.
Patients present with a short history (<3 months) of cough and dyspnoea, often
•
accompanied by systemic features such as weight loss, malaise and fever.
HRCT shows either areas of consolidation with ground glass change or a
•
solitary nodule.
COP is treated with a tapered course of prednisolone over several months.
•
• Patients usually respond promptly to steroids.
• May relapse as the dose is reduced.
• 6 to 12 months of treatment is normally required.
3. RESPIRATORY BRONCHIOLITIS–ASSOCIATED INTERSTITIAL
LUNG DISEASE (RB-ILD)
Proliferation of bronchiolar pigmented macrophages in the terminal bronchi-
•
oles causing interstitial lung disease.
RB-ILD occurs in smokers (>30-year pack history).
•
More common in males.
•
Presents in the fourth to fifth decades.
•
Patients present with mild dyspnoea and cough.
•
HRCT demonstrates ground glass changes with thick-walled airways and
•
centrilobular nodules.
Smoking cessation is essential to treatment.
•
Steroids may provide some benefit.
•
4. LYMPHOID INTERSTITIAL PNEUMONIA (LIP)
Interstitial pneumonia caused by lymphoid infiltrates.
•
Patients present with gradual onset of dyspnoea over several years.
•
• May also have a history of fever or weight loss.
LIP is associated with:
•
• Connective tissue disease (e.g. Sjögren’s syndrome).
• Autoimmune disease (e.g. myasthenia gravis, pernicious anaemia).
• Immunodeficiency (e.g. common variable immunodeficiency, HIV).
HRCT shows ground glass change and can demonstrate nodules or lung cysts.
•
Steroids are the mainstay of treatment.
•
One-third of patients progress to chronic fibrosis.
•
5. DESQUAMATIVE INTERSTITIAL PNEUMONIA (DIP)
Caused by abnormal proliferation of pigmented macrophages as in RB-ILD,
•
however in DIP they are found throughout the alveolar air spaces.
Respiratory Medicine
11.4 Hypersensitivity Pneumonitis (HSP)
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Highly associated with smoking.
•
Treatment is the same as RB-ILD.
•
Prognosis is good.
•
6. ACUTE INTERSTITIAL PNEUMONIA
Diffuse alveolar damage and fibrosis associated with rapid onset of dyspnoea
•
followed by respiratory failure.
CXR shows bilateral diffuse airway shadowing, which can spare heart bor-
•
ders and hilum.
HRCT shows ground glass change progressing to reticulation and cystic
•
change.
Lung biopsy demonstrates diffuse alveolar damage comprising of hyaline
•
membranes, necrosis of alveolar lining cells, fibroblastic tissue, scarring and
honeycombing – but is rarely done as patients are usually too ill.
Treatment is supportive, and level 2/3 care may be offered in patients with
•
single organ failure, although prognosis is extremely poor with 70% mortality at 3 months.
High-dose steroids (e.g. IV methylprednisolone) and antibiotics are often
•
used.
It is important to look carefully for evidence of underlying connective tissue
•
disease or opportunistic infection (e.g. PJP), which might require specific
treatments.
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11.4 HYPERSENSITIVITY PNEUMONITIS (HSP)
1. DEFINITION
Previously called extrinsic allergic alveolitis.
•
Immunological reaction within the lung in response to inhaled antigens (see
•
Table 11.1) that can have variable clinical presentation.
2. EPIDEMIOLOGY
Variable depending on antigen and time of year.
•
• Farmer’s lung 12–2300 per 100,000.
• Bird fancier’s lung 20–20,000 per 100,000.
3. AETIOLOGY
• Due to exposure to organic and inorganic airborne antigens.
• Certain occupations carry a higher risk – agriculture and cattle workers,
bird and poultry handlers, veterinary work and animal handling, grain
and flour processing, construction.
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Table 11.1 Causes of EAA.
Form of EAA Precipitant/Antigen
Farmers’ lung Mouldy hay (Saccharopolyspora
rectivirgula)
Bird fancier’s lung Avian proteins
Cheese worker’s lung Cheese mould (Penicillium casei)
Malt worker’s lung Mouldy malt (Aspergillus clavatus)
Mushroom worker’s lung Mushroom compost (actinomycetes)
Hot tub lung Mycobacterium avium
Chemical worker’s lung Many antigens during manufacture of
plastics, rubber etc.
4. PATHOPHYSIOLOGY
Types III and IV hypersensitivity reactions identified (see MICRO-Print,
•
below).
Possibly TH1 pathway is dominant upon interaction with inhaled antigen.
•
IgG precipitins may be detected.
•
MICRO-print
Hypersensitivity Reactions
Undesirable reactions produced by the host immune system to anti-
gens. Type III and IV are implicated in EAA.
Type I – Allergy: Fast, IgE mediated response. Occurs in minutes.
•
E.g. asthma, anaphylaxis.
Type II – Cytotoxic: IgM/IgG binds to a target (host) cell, trigger-
•
ing destruction of that cell. E.g. autoimmune haemolytic anaemia,
Goodpasture’s syndrome.
Type III – Immune complex: IgG binds to a soluble antigen, form-
•
ing immune complexes which are deposited on tissues and initiate
inflammation e.g. post streptococcal glomerulonephritis.
Type IV – Delayed-type hypersensitivity: T helper cells (Th1 cells)
•
are activated by antigen presenting cells. Later exposure to that
antigen activates macrophages and an inflammatory response. E.g.
contact dermatitis, Mantoux test.
Respiratory Medicine
11.4 Hypersensitivity Pneumonitis (HSP)
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5. CLINICAL FEATURES
Acute form:
•
• Symptom onset within 4 hours of exposure.
• Can resolve within hours to weeks if antigen exposure is ceased.
Disease can be insidious, leading to progressive symptoms.
•
Symptoms:
•
• Cough
• Breathlessness
• Fever
• Malaise
• Weight loss.
Signs:
•
• Crackles audible on auscultation.
• Clubbing can be present in progressive disease.
• Respiratory failure in late disease.
6. INVESTIGATIONS
Serum precipitins
•
• Precipitins against relevant antigen can be raised, e.g. avian, but com-
mercially available assay may not be available for many antigens.
CXR
•
• Can be normal especially in acute EAA if timing is incorrect in relation
to antigen exposure.
• In chronic disease, nodular-reticular change visible in mid and upper
zones.
HRCT
•
• Combination of centrilobular lung nodules, ground glass changes, air
trapping and fibrosis in late stages (mainly mid-zone).
Pulmonary function tests
•
• Reduced Tlco in chronic disease.
• Spirometry is either restrictive or mixed obstructive – restrictive pattern.
Inhalation challenge testing
•
• Exposure to offending environment with antigen with clinical assess-
ment including real-time lung function and radiology assessment.
• Provided by specialist centres.
BAL
•
• Lymphocytosis evident.
• CD4+/CD8+ ratio < 1.
• BAL neutrophilia and eosinophilia also can be present.
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Biopsy
•
• Surgical lung biopsy required in diagnostic doubt.
• Small non-caseating ill-defined granulomas seen along bronchioles.
• Bronchocentric distribution of mononuclear cell infiltration.
• Peribronchiolar fibrosis with Schaumann bodies.
Diagnosis is usually made in a multidisciplinary setting based on integration
•
of clinical, serological, radiological and pathological features.
7. MANAGEMENT
Removal from antigen.
•
Change in work practice if relevant.
•
Respiratory protective masks may help.
•
Corticosteroid therapy (may not reverse process in progressive HSP with
•
end stage fibrosis) with prednisolone at 0.5 mg/kg with tapering over 4–6
months.
8. PROGNOSIS
Cessation of antigen exposure +/− corticosteroid therapy in most patients will
•
lead to good resolution of EAA changes.
In severe disease resolution may take years.
•
Disease may sometimes progress despite elimination of culprit antigen, but
•
should prompt reconsideration of diagnosis.
11.5 ILD ASSOCIATED WITH
NON-PULMONARY CONDITIONS
1. DRUGS
Interstitial lung disease can occur as a result of drug side effects:
•
• Amiodarone
• Bleomycin
• Methotrexate
• Nitrofurantoin.
2. SYSTEMIC RHEUMATIC CONDITIONS
Rheumatoid arthritis
•
SLE
•
Systemic sclerosis
•
Ankylosing spondylitis
•
Dermatomyositis
•
Polymyositis.
Respiratory Medicine
•
11.6 Vasculitis and the Lung
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3. VASCULITIS: SEE SECTION11.6
MICRO-case
You are working as a respiratory physician when a 70-year-old gentleman comes to see you after a GP referral. He has suffered with shortness
of breath which he first noticed around 6 months ago. Over the last 6
months, it has worsened progressively, limiting his exercise tolerance
significantly. He has also lost around a stone in weight over the same time
period. He does not have a cough or wheeze. On examination, you note
fine bibasal inspiratory crackles on auscultation.
Chest X-ray showed basal reticular shadowing. An HRCT demonstrated honeycombing. Spirometry reveals an FEV
both values are reduced. Tlco is also reduced. All blood tests are normal.
His medication history is reviewed: he takes amlodipine for blood
pressure and simvastatin for high cholesterol but no other medications.
He formerly worked as a maths teacher and has never been exposed to
asbestos or other dusts.
Having excluded all other causes for pulmonary fibrosis, you diagnose
probable IPF, which is later confirmed at a multidisciplinary meeting. Due
to the characteristic HRCT changes, biopsy is not indicated. Treatment
with nintedanib is recommended.
Key Points
Pulmonary fibrosis may have an insidious onset.
•
Progressive shortness of breath is the most common presenting
•
feature.
Honeycombing on HRCT is characteristic of UIP.
•
Biopsy may be required in cases where the diagnosis is not evident
•
from HRCT alone.
Good history taking is essential to establish the cause of fibrosis, e.g.
•
occupational (see Chapter16 for more information), drug induced,
systemic and familial disease.
/FVC ratio of 0.9 but
1
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11.6 VASCULITIS AND THE LUNG
e systemic vasculitides are a heterogeneous group of disorders characterised
•
by an inflammatory destructive process affecting blood vessels.
e lung is frequently involved with various clinical presentations.
•
ese vasculitides may be primary or associated with other systemic disease
•
such as connective-tissue disease.
e primary vasculitides affecting the lung are often associated with ANCA
•
(antinuclear cytoplasmic antibody) positivity.
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Indirect immunofluorescent staining patterns differentiate two main types:
•
• Cytoplasmic ANCA (c-ANCA) are primarily, but not exclusively,
directed against proteinase 3 (PR-3).
• Perinuclear ANCA (p-ANCA) are most commonly directed against
myeloperoxidase (MPO).
e ANCA blood test is very important in diagnosis, classification and moni-
•
toring response to treatment.
11.7 EOSINOPHILIC GRANULOMATOSIS WITH
POLYANGIITIS (EGPA)
1. DEFINITION AND EPIDEMIOLOGY
An eosinophil-rich and granulomatous necrotising vasculitis affecting small
•
to medium-sized vessels in the upper and lower respiratory tract.
Previously termed Churg-Strauss syndrome.
•
Carries an association with asthma and should therefore be considered in the
•
presence of a blood eosinophilia.
It is the rarest of all the anti-neutrophil cytoplasmic auto-antibody (ANCA)
•
vasculitides with an epidemiology of 1–3 cases per million, with a slight male
predominance.
2. AETIOLOGY AND PATHOPHYSIOLOGY
Aetiology and pathogenesis is unknown.
•
An association with inhaled glucocorticoid therapy, leukotriene modifying
•
agents and omalizumab has been noted but may reflect unmasking of EGPA
with reduction of oral corticosteroid therapy.
ere are 3 pathological phases to the disease that classically occur sequentially
•
(See Figure 11.5).
Respiratory Medicine
Figure 11.5 Pathophysiology of EPGA.
11.8 Granulomatosis with Polyangiitis (GPA)
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3. CLASSIFICATION
e presence of 4 or more of the following criteria as defined by the Ameri-
•
can College of Rheumatology:
• Asthma.
• Peak peripheral eosinophilia > 10% of total WCC.
• Peripheral neuropathy attributable to a systemic vasculitis.
• Transient pulmonary infiltrates on chest X-ray (CXR).
• Paranasal sinus abnormality.
• Extravascular eosinophils seen on blood vessel biopsy.
11.8 GRANULOMATOSIS WITH POLYANGIITIS
(GPA)
1. DEFINITION AND EPIDEMIOLOGY
An ANCA-positive systemic vasculitis that involves small and medium-sized
•
vessels with demonstration of presence of granulomas.
Previously termed Wegener’s granulomatosis.
•
Prevalence of 160 cases per million.
•
• Mean age of onset: 40 - 60 years.
• Caucasian population.
• Incidence increases relative to distance from the equator.
• No gender predominance.
GPA can affect many organ systems, but the classical triad of involvement is:
•
• Upper respiratory tract
• Lower respiratory tract
• Pauci-immune glomerulonephritis.
185
2. AETIOLOGY AND PATHOPHYSIOLOGY
Aetiology of the disease is poorly understood, but an auto-immune non-
•
infectious aetiology has been suggested.
Necrotising vasculitis and granuloma formation are the classical histopatho-
•
logical findings in this disease.
• ere are few or no immune deposits in affected tissue.
• T cells are involved in granuloma formation and maintenance.
• B cells are also implicated.
3. CLASSIFICATION AND DIAGNOSIS
ere is no widely accepted formal classification of this disease.
•
e American College of Rheumatologists used the following criteria for
•
patients being enrolled into research studies:
Respiratory Medicine
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