Idiopathic Pulmonary FibrosisSynonyms: fibrosing alveolitis, cryptogenic fibrosing alveolitis

Introduction [1] Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterised initially by the presence ofinflammatory cells within the alveoli. This is followed by thickening and fibrosis of the alveolar walls. The aetiologyand pathogenesis are as yet unknown. In order to improve identification, the following definition has been suppliedby the American Thoracic Society and European Respiratory Society guidelines: [2]

"... specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause, occurring primarily inolder adults, and limited to the lungs. It is characterized by progressive worsening of dyspnea and lung functionand is associated with a poor prognosis."

The condition is part of a spectrum of conditions known as interstitial lung disease.

Theories about the underlying pathological process are changing. It used to be thought that the initial trigger factorfor fibrosis was a generalised inflammatory condition of interstitial lung tissue with subsequent scarring. Lack ofresponse to steroids and immune modulators suggested this was unlikely. It is now considered that changesoccur at endothelial cell level, due to a response to some irritant, such as cigarette smoke, gastro-oesophagealreflux, environmental pollution. In IPF, the repair mechanism which subsequently comes into play is impaired,leading to excessive production of myofibroblasts and accumulation of extracellular matrix.

EpidemiologyEstmated incidences of IPF are between 6.8-16.3 per 100,000 person-years. [2] The incidence was noted to beincreasing, in a UK study between 1991 and 2003, by more than 10%. [2] Interestingly, this increase in incidencedoes not appear to relate to increasing age or improvement in diagnosis rates.

It is most common in people aged in their 50s and affects men to a slightly greater degree than women (M:F ratio1.7:1).

The disease may show familial clusters (20pack years.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.Chronic viral infections have been investigated as potential risk factors, with a focus on hepatitis C andEpstein-Barr viruses.Gastro-oesophageal reflux disease with micro-aspiration.

Presentation [1] Symptoms

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.

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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.

SignsThese may include:

Exertional dyspnoea progressing to breathlessness at rest.Tachypnoea.Cough.Clubbing (50%).Cyanosis.Fine bilateral basal crepitations particularly at the end of expiration.Signs of cor pulmonale and right heart failure in the later stages.

Diagnosis [2] Guidelines suggested the presence of the following confirms the diagnosis of IPF:

Exclusion of other known causes of pulmonary fibrosis.In cases where biopsy not taken - HRCT reveals pattern of usual interstitial pneumonia (subpleuralbasal predominance, reticular pattern, honeycombing, and absence of inconsistent features e.g.micronodules or cysts).Where biopsy is available, a combination of partial high-resolution CT (HRCT) criteria and suggestivehistopathological features are present (eg, usual interstitial pattern histopathologically confirmed bypresence of marked fibrosis/honeycombing, patchy lung involvement, fibroblast foci, and no featuressuggesting an alternative diagnosis - eg, granulomata or hyaline membranes).

Differential diagnosis [1] [4]Due to the nonspecific nature of the presenting symptoms and signs, there are many other diagnoses whichmust 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.

Investigations [1] Laboratory tests

FBC may show mild anaemia 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.Arterial blood gases.

Radio-imagingCXR will show abnormalities in 95% of patients. The most common finding is bilateral basal andperipheral infiltrates. The fibrosis may also produce a honeycombing effect.HRCT scanning.

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Lung function testsThese may show:

A restrictive defect (forced expiratory volume in one second (FEV1) is usually less than 80% ofpredicted value, forced vital capacity (FVC) is usually less than 3 litres, FEV1/FVC ratio is normal,because both are reduced).Reduced gas transfer.Reduced lung volumes.

Bronchiolar lavageThis is not vital for the diagnosis of IPF but is sometimes used to exclude other diseases. [2]

HistologyLung biopsy is useful in some cases (see 'Diagnosis', above) but not mandatory.

Associated diseasesIPF may be found in association with several autoimmune disorders such as:

Thyroid diseaseSystemic sclerosisRheumatoid arthritisAutoimmune liver diseaseSystemic lupus erythematosis

Management [2] There is no consensus regarding management.

SupportiveManagement should be under a multidisciplinary team. [2] Supportive therapy with oxygen is recommended for those with significant resting hypoxaemiaPhysiotherapy 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.Proton-pump inhibitor therapy should be considered in all and has been associated with stabilisation inlung function. [2] In end-stage disease, opiates may help excessive cough.

Medical [2] It has been acknowledged for some time that the effectiveness of current medical therapies has beendisappointing and recent research highlighting the likely aetiology of IPF explains why. The search is therefore onfor more targeted treatment but standard drug regimes should be offered until these avenues of research cometo 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 tohave any treatment for their IPF in the early stages, particularly if they have significant comorbidities.The most common current therapeutic regimens include combined acetylcysteine and azathioprineand prednisoneThe current evidence does not recommend monotherapy with any of the following: corticosteroids,bosentan, colchicine, etanercept, acetylcysteine, interferon- and ciclosporin A.Pirfenidone - a growth factor inhibitor - has shown promising results in trials and has been approvedfor use in the UK and may be appropriate for some patients.Anticoagulants may also need to be considered.

Surgical

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Lung transplant may be required for patients who fail to respond to medical therapy.

Other treatments which may need to be consideredAcute exacerbations - corticosteroids are recommended.Pulmonary hypertension - treatment is not recommended in the majority but clinicians need to revieweach case individually.

Complications These may include: [2]

Pulmonary hypertensionLung cancerPulmonary embolismRight ventricular failureCoronary artery disease

Prognosis The prognosis is poor, with a five-year survival rate of only 50-56%. [2] Some patients may die from an acuteexacerbation of the condition itself, whilst the remainder succumb to a condition associated with increasedcardiovascular risk or lung cancer. The estimated mortality rates are 64.3 deaths per million in men and 58.4deaths per million in women. [1]

One study found that IPF patients who developed pulmonary hypertension or emphysema had a significantlypoorer prognosis than those who did not. [5]

A more favourable prognosis is also associated with female sex, younger age and shorter duration of symptoms.The development of pulmonary hypertension indicates a poor prognosis. [6]

It is hoped that the advent of emerging therapies will improve the prognosis.

Further reading & referencesIdiopathic pulmonary fibrosis: the diagnosis and management of suspected idiopathic pulmonary fibrosis, NICE clinicalguideline (Jun 2013)Interstitial lung disease guideline; British Thoracic Society (September 2008)Dixon S, Benamore R; The idiopathic interstitial pneumonias: understanding key radiological features. Clin Radiol. 2010Oct;65(10):823-31. Epub 2010 May 7.

1. Godfrey A et al , Idiopathic Pulmonary Fibrosis, Medscape, Jul 20122. Idiopathic Pulmonary Fibrosis: Evidence-based Guidelines for Diagnosis and Management, European Respiratory Society

and others (2011)3. 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 3.4. Michaelson JE, Aguayo SM, Roman J; Idiopathic pulmonary fibrosis: a practical approach for diagnosis and management.

Chest. 2000 Sep;118(3):788-94.5. 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 18.6. Noth I, Martinez FJ; Recent advances in idiopathic pulmonary fibrosis. Chest. 2007 Aug;132(2):637-50.

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medicalconditions. EMIS has used all reasonable care in compiling the information but make no warranty as to itsaccuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions.For details see our conditions.

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Original Author:Dr Laurence Knott

Current Version:Dr Gurvinder Rull

Peer Reviewer:Prof Cathy Jackson

Document ID:1709 (v23)

Last Checked:11/10/2012

Next Review:10/10/2017

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