Fibrosing alveolitis therapy

1. Fibrosing alveolitis therapy
Prepared By:
Marwa Mamoon Abbass
Medical Hawler University
/Pharmacy College
5th Stage
2011-2012

2. Fibrosing alveolitis
Synonyms: Idiopathic Pulmonary Fibrosis ,cryptogenic fibrosing alveolitis.
 is a chronic lung disease characterized initially by the presence of
inflammatory cells within the alveoli. This is followed by thickening and
fibrosis of the alveolar walls. The etiology and pathogenesis are as yet
unknown.
A form called the Hamman-Rich syndrome has a particularly poor
prognosis. This is an acute interstitial pneumonia which presents with
cough, fever and breathlessness. Histology shows bilateral diffuse alveolar
damage. The condition usually progresses rapidly to acute respiratory
distress and is often fatal (100% of patients between 5-26 days from
admission).(2)

3.  The condition is part of a spectrum of conditions
known as interstitial lung disease. The term
cryptogenic fibrosing alveolitis should be reserved
for those patients in whom lung histology has
shown to demonstrate the pathological changes
termed 'usual interstitial pneumonitis' (UIP). This is
characterized by patchy interstitial changes, a
honeycomb appearance to the lung tissue and
eosinophilic infiltration.(3)

4.  Pathogenesis(1)
• Theories about the underlying pathological process are changing. It
used to be thought that the initial trigger factor for fibrosis was a
generalized inflammatory condition of interstitial lung tissue with
subsequent scarring. Lack of response to steroids and immune
modulators suggested this was unlikely. It is now considered that
changes occur at endothelial cell level due to a response to some
irritant, such as cigarette smoke, gastro-oesophageal reflux,
environmental pollution.
• the repair mechanism which subsequently comes into play is impaired,
leading to excessive production of myofibroblasts and accumulation of
extracellular matrix.
20% of patients have a positive family history, suggesting a genetic
cause. Proposed mechanisms are mutations affecting surfactant C
production and dysfunction of epithelial regeneration.

5.  Risk factors
•The condition is common in certain
occupations - for example, in people
who work with silica, asbestos, heavy
metals or mouldy foliage.
•Environmental factors include pigeon
breeding and contaminated ventilation
systems.
•It can be an adverse effect
of amiodarone.

6.  Signs (1)
These may include:
•Exertional dyspnoea progressing to
breathlessness at rest.
•Tachypnoea.
•Cough.
•Clubbing (50%).
•Cyanosis.
•Fine bilateral basal crepitations
particularly at the end of expiration
('Velcro rales').
•Signs of cor pulmonale and right heart
failure in the later stages.

7.  Symptoms (1)
•The most common symptoms are progressively increasing
shortness of breath and dry cough.
•5% of patients diagnosed opportunistically have no initial
symptoms.
•50% of patients are systemically unwell and may have a flu
like illness, fatigue or weight loss.
•Spontaneous remissions do not occur (in contrast to
sarcoidosis).
•Extrapulmonary features may include arthralgia, muscle
pains and skin rashes.
•Obstructive sleep apnoea may be a common presenting
feature.

8.  Differential diagnosis (1,8)
Due to the nonspecific nature of the presenting symptoms and
signs, there are many other diagnoses which must be considered,
ranging from very common disorders such as heart failure
through to much rarer diseases.
- Diagnoses to be considered include:
•Heart failure.
•Chronic obstructive pulmonary disease (COPD).
•Sarcoidosis.
•Pulmonary embolism.
•Lymphangitis carcinomatosis.
•Extrinsic allergic alveolitis.
•Pneumonia.
•Asbestosis.

9. heart disease cancer
cerebrovascular diseases chronic lower respiratory diseases
accidents diabetes
alzheimer's kidney diseases
septicemia other causes
1.30% 20.20% * death may occur
1.50% 30.30% When there is
1.90%
fibrosing alveolitis
2.90% in combination with
4.10% other diseases (16) .
5.20% 7% 23%
Top ten causes of dea

10.  Investigations (1)
 Laboratory tests
•FBC may show mild anemia or may be normal.
•ESR and CRP may be raised in 50% of patients.
•Antinuclear factor and rheumatoid factor may be raised in up to a third of
all patients.
 Radio-imaging
•CXR will show abnormalities in 95% of patients. The most common finding
is bilateral basal and peripheral infiltrates. The fibrosis may also produce a
honeycombing effect.
•High-resolution CT (HRCT) scanning. The specificity of this has been
questioned in recent years but it is still a useful screening tool to decide
whether or not to proceed to lung histology tests. Typically, a ground glass
appearance is indicative of fibrosing alveolitis, whereas a reticular pattern
is more predominant in other types of interstitial lung disease.(3,9)

11.  Lung function tests
These may show:
• A restrictive defect (forced expiratory volume in one
second (FEV1) is usually less than 80% of predicted
value, forced vital capacity (FVC) is usually less than 3
liters, FEV1/FVC ratio is normal, because both are
reduced).
• Reduced gas transfer.
• Reduced lung volumes.
Bronchiolar lavage
This is not vital for the diagnosis of fibrosing alveolitis
but is sometimes used to exclude other diseases. (10)

12.  Histology
Lung biopsy is the definitive method of arriving at the diagnosis
but, as the lesions need to be separated both in time and
space, a large biopsy, e.g. open lung biopsy or several smaller
biopsies, may be required.
 Associated diseases
Fibrosing alveolitis may be found in association with several
autoimmune disorders such as:
•Thyroid disease.
•Systemic sclerosis.
•Rheumatoid arthritis.
•Autoimmune liver disease.
•Systemic lupus erythematosis.

13.  Management (1,10)
There is no consensus regarding management.(11)
 Nondrug management:
•Supportive therapy with oxygen and physiotherapy may be
helpful.
•Regular exercise and weight control should be encouraged.
•Vaccinate against influenza and pneumococcus.
•Encourage the patient to stop smoking if he or she continues
to do so.

14.  Drug management
It has been acknowledged for some time that the effectiveness of current
medical therapies has been disappointing and recent research highlighting
the likely etiology of fibrosing alveolitis explains why. The search is therefore
on for more targeted treatment but standard drug regimes should be offered
until these avenues of research come to fruition. Medication should be
initiated under specialist supervision.
•The risks and benefits of all options should be discussed with patients and
some may prefer not to have any treatment for their Fibrosing alveolitis in the
early stages, particularly if they have significant comorbidities.
•Current British Thoracic Society (BTS) guidelines do not recommend
steroids as monotherapy. Systematic reviews suggest that the optimal first-
line treatment is a combination of prednisolone and azathioprine (the latter
substituted by colchicine if it cannot be tolerated).

15. •Pirfenidone - a growth factor inhibitor - has shown promising
results in trials and has been approved for use in the UK; the
intended launch date is mid-2012.(12)
•The use of N-acetylcysteine - an antioxidant - is currently
being investigated as a therapy, either in combination with
prednisolone and azathioprine or as monotherapy.
•Bosentan, imatinib and interferon-γ, all once thought to be
promising treatments, have proved disappointing in Phase III
studies.(6)
•Opiates are useful to control cough in end-stage disease.
•Proton pump inhibitors should be trialed due to the high
associated incidence of gastro-oesophageal disease.

16. References
1.Godfrey A et al; Pulmonary Fibrosis, Idiopathic, Medscape, Aug 2010
2.Avnon LS, Pikovsky O, Sion-Vardy N, et al; Acute interstitial pneumonia-Hamman-Rich syndrome: clinical characteristics and
Anesth Analg. 2009 Jan;108(1):232-7.
3.Katzenstein AL, Myers JL; Idiopathic pulmonary fibrosis: clinical relevance of pathologic classification. Am J Respir Crit Care Med.
1998 Apr;157(4 Pt 1):1301-15.; Am J Respir Crit Care Med. 1998 Apr;157(4 Pt 1):1301-15.
4.Gribbin J, Hubbard RB, Le Jeune I, et al; The incidence and mortality of idiopathic pulmonary fibrosis and sarcoidosis in the UK.
Thorax. 2006 Jul 14;.; Thorax. 2006 Jul 14.
5.Gustafson T, Dahlman-Hoglund A, Nilsson K, et al; Occupational exposure and severe pulmonary fibrosis. Respir Med. 2007
Oct;101(10):2207-12. Epub 2007 Jul 12.
6.Guenther A; The European IPF Network: towards better care for a dreadful disease Eur Respir J. 2011 Apr;37(4):747-748
7.Olson AL, Swigris JJ, Lezotte DC, et al; Mortality from pulmonary fibrosis increased in the United States from 1992 to 2003. Am J
Respir Crit Care Med. 2007 Aug 1;176(3):277-84. Epub 2007 May 3.
8.Michaelson JE, Aguayo SM, Roman J; Idiopathic pulmonary fibrosis: a practical approach for diagnosis and management. Chest.
2000 Sep;118(3):788-94.; Chest. 2000 Sep;118(3):788-94.
9.Gulati M; Diagnostic assessment of patients with interstitial lung disease. Prim Care Respir J. 2011 Apr 20. pii: pcrj-2010-07-0078.
doi.
10.Interstitial lung disease guideline, British Thoracic Society (September 2008)
11.Collard HR, Loyd JE, King TE Jr, et al; Current diagnosis and management of idiopathic pulmonary fibrosis: a survey of
academic physicians. Respir Med. 2007 Sep;101(9):2011-6. Epub 2007 May 16.
12.Pirfenidone, New Drugs Online, 2011.
13.Le Jeune I, Gribbin J, West J, et al; The incidence of cancer in patients with idiopathic pulmonary fibrosis and sarcoidosis in the
UK. Respir Med. 2007 Dec;101(12):2534-40. Epub 2007 Sep 17.
14.Mejia M, Carrillo G, Rojas-Serrano J, et al; Idiopathic pulmonary fibrosis and emphysema: decreased survival associated with
Chest. 2009 Jul;136(1):10-5. Epub 2009 Feb 18.
15.Noth I, Martinez FJ; Recent advances in idiopathic pulmonary fibrosis. Chest. 2007 Aug;132(2):637-50.
16.http://www.rightdiagnosis.com/death/overview.htm