Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

acute exacerbation

1st line – admission to the hospital + supportive care + high-dose corticosteroid

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ACUTE
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acute exacerbation
1st line – 

admission to the hospital + supportive care + high-dose corticosteroid

Acute exacerbations are defined as acute, clinically significant, respiratory deteriorations associated with new widespread alveolar abnormality and no identifiable cause (see Diagnostic criteria).[15] A subset of patients has a disease course characterised by intermittent acute exacerbations followed by an abrupt and often permanent decline in pulmonary function.[15] Short-term mortality rates, including inpatient mortality, are high in these patients.[63][64]

There is no standard of care for acute exacerbation of idiopathic pulmonary fibrosis (IPF).[65] Patients receive supportive care with (or without) unproven therapies.[15]

Supportive care focuses on symptom palliation and the correction of hypoxaemia with supplemental oxygen. ATS/ERS/JRS/ALAT guidelines weakly recommend against using mechanical ventilation to treat respiratory failure in most patients with IPF because the in-hospital mortality reaches 90%.[5]

High-dose corticosteroids are used in the treatment of acute exacerbations, despite a lack of supporting evidence.[3][4][5]

Primary options

prednisolone: 0.5 mg/kg orally once daily for 4 weeks, then 0.25 mg/kg orally once daily for 8 weeks, followed by 0.125 mg/kg orally once daily thereafter, taper according to response

Consider – cytotoxic therapy

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ACUTE
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acute exacerbation
Consider – 

cytotoxic therapy

Additional treatment recommended for SOME patients in selected patient group

Despite a lack of supporting evidence, high-dose corticosteroids, with or without cytotoxic agents, are often used in the treatment of acute exacerbations. Short-term mortality rates, including inpatient mortality, are high.[63][64]

​One phase 3 placebo-controlled trial concluded that adding intravenous cyclophosphamide to glucocorticoids increased mortality at 3 months.[66]

The ATS/ERS/JRS/ALAT guidelines make no recommendation regarding the use of cytotoxic agents.[3][4][5]

Primary options

cyclophosphamide: consult specialist for guidance on dose

ONGOING

all patients not currently experiencing acute exacerbation

1st line – antifibrotic therapy

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ONGOING
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all patients not currently experiencing acute exacerbation
1st line – 

antifibrotic therapy

Initial therapy is typically with pirfenidone or nintedanib based on conditional recommendations in the ATS/ERS/JRS/ALAT guidelines.[4][5]​​[Evidence A][Evidence B]

Randomised placebo-controlled trials have reported significant reductions in decline of forced vital capacity with antifibrotic agents.[74][75]​​ 

Network meta-analyses conclude that pirfenidone and nintedanib probably reduce mortality in patients with idiopathic pulmonary fibrosis.[68][78]​​​​[79]

Pirfenidone and nintedanib have not been compared directly in clinical trials and have not been studied in combination; combination therapy is not recommended.[69] The decision to prescribe is based on availability, patient preference, and adverse effects.[70][71]

Primary options

pirfenidone: 267 mg orally three times daily initially on days 1-7, followed by 534 mg three times daily on days 8-14, then 801 mg three times daily thereafter

OR

nintedanib: 150 mg orally twice daily

Plus – cessation of smoking and drugs associated with pulmonary toxicity

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ONGOING
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all patients not currently experiencing acute exacerbation
Plus – 

cessation of smoking and drugs associated with pulmonary toxicity

Treatment recommended for ALL patients in selected patient group

Patients who continue to smoke cigarettes should be advised to quit (see Smoking cessation).

Avoid or withdraw inhalational agents or toxic medications (e.g., bleomycin, amiodarone, acetylsalicylic acid, methotrexate, busulfan, mitomycin) that may cause additional irreversible lung injury.[91] 

Plus – pulmonary rehabilitation

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ONGOING
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all patients not currently experiencing acute exacerbation
Plus – 

pulmonary rehabilitation

Treatment recommended for ALL patients in selected patient group

Pulmonary rehabilitation programmes typically include assessment, participation in a regular exercise‐training programme (aerobic and resistance), education, and behavioural change.[92][93]​​​​​​ They are safe, improve exercise capacity, and may improve both dyspnoea and health-related quality of life in patients with idiopathic pulmonary fibrosis.[5][93][95]​​ These changes are probably clinically meaningful for patients and appear to persist over 6-12 months.[93][95]

Consider – oxygen

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ONGOING
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all patients not currently experiencing acute exacerbation
Consider – 

oxygen

Additional treatment recommended for SOME patients in selected patient group

Monitor all patients for the development of hypoxaemia.

Severe hypoxaemia (PaO₂ ≤55 mmHg or oxygen saturation ≤89%) at rest or with exertion should be managed by supplemental oxygen, which is strongly recommended by the ATS/ERS/JRS/ALAT guidelines and by the 2020 ATS guideline on home oxygen therapy for adults with chronic lung disease.[3][96][Evidence C]​ Oxygen therapy may improve exercise tolerance and reduce the risk of developing pulmonary hypertension and cor pulmonale.[97]

Consider – proton-pump inhibitor

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ONGOING
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all patients not currently experiencing acute exacerbation
Consider – 

proton-pump inhibitor

Additional treatment recommended for SOME patients in selected patient group

Symptomatic reflux should be treated as usual (see Gastro-oesophageal reflux disease). ATS/ERS/JRS/ALAT guidelines conditionally recommend against the medical or surgical treatment of asymptomatic gastro-oesophageal reflux for the purpose of improving respiratory outcomes.[5][98]​​[Evidence C]

Primary options

lansoprazole: 15 mg orally once or twice daily

OR

omeprazole: 20 mg orally once or twice daily

OR

pantoprazole: 20 mg orally once or twice daily

Consider – palliative care

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ONGOING
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all patients not currently experiencing acute exacerbation
Consider – 

palliative care

Additional treatment recommended for SOME patients in selected patient group

Consider whenever physical, psychological, social, or existential needs are identified. Unmet needs can arise at any point along the disease trajectory; therefore, palliative care should be integrated early and within routine care.[99]

Barriers to palliative care, such as fear of talking about the future, diagnostic uncertainty, and confusion about the roles of palliative care should be tackled to avoid unnecessary delays in referral.[100]

Generalists should address palliative care needs in the first instance and provide access to specialist palliative care as needed. Suggested triggers for referral include starting oxygen therapy or ventilatory support, persistent uncontrolled symptoms, functional decline, and when considering opioids.[99]

Follow a holistic and multi-disciplinary person-centred approach to control core symptoms (i.e., shortness of breath, cough, and fatigue) and improve quality of life for people with serious health-related suffering. The needs of informal carer should also be considered.

Palliative care options are available for uncontrolled symptoms of cough and dyspnoea.[5] Oral or parenteral opioids may have a role in the palliation of dyspnoea.[101] [ Cochrane Clinical Answers logo ] [Evidence C]​​ ​Low-dose, controlled-release morphine may help to reduce awake cough frequency and can improve quality of life when significant IPF-related cough is present.[102] Consult your local palliative care guidelines for more information.

Limited evidence also suggests that comprehensive, home-based, palliative care interventions may improve quality of life and decrease anxiety and depression in patients with interstitial lung disease.[103]

Discuss advance care planning in accordance with patient preferences and revisit decisions periodically.[99] Initiating such discussions is challenging. Ensuring patient comfort is central to compassionate end-of-life care for the terminally ill.

2nd line – lung transplantation

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all patients not currently experiencing acute exacerbation
2nd line – 

lung transplantation

Should be considered for patients with progressive physiological deterioration despite optimal medical management, contraindications to pharmacological treatment, severe functional impairment, oxygen dependency, and/or a deteriorating course.

A consensus statement by the International Society for Heart and Lung Transplantation recommends lung transplantation as an option for adults with chronic, end-stage lung disease if they are at high (>50%) risk of death from lung disease within 2 years if lung transplantation is not performed and if they have a high (>80%) likelihood of 5-year post-transplant survival if graft function is adequate.[105] Referral is made at time of diagnosis to avoid missing potentially eligible patients (i.e., those who meet the minimal clinical criteria), especially if familial pulmonary fibrosis is present. Patients treated with antifibrotic therapy are eligible for referral.[105] 

The timing of listing for transplant (which necessitates thorough evaluation and careful risk-to-benefit assessment) should consider the rate of progression despite standard management, expected prognosis, age, comorbidities, and transplant risks.[105] Relevant contraindications include significant extrapulmonary disorders (e.g., liver, renal, or cardiac dysfunction) or unstable or inadequate psychosocial profile/stability that may negatively influence survival.

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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