Idiopathic pulmonary fibrosis (IPF) is a progressive, interstitial lung disease with a poor prognosis. The median survival rate is 3 to 5 years after diagnosis and without treatment.1 The most common symptoms of IPF include chronic cough and exertional dyspnea.1 There is currently no cure for the disease and most treatment is based on symptom management.
A number of pharmacological agents have been proposed and tested for IPF management over the years. Two fairly recent treatments, pirfenidone and nintedanib, are available and have been shown to slow the decline in forced vital capacity (FVC).
Pirfenidone is an oral antifibrotic drug that has been shown in vitro to regulate proinflammatory and profibrotic cytokine cascades.2 In animal models, it has been shown to reduce the proliferation of fibroblasts and the synthesis of collagen.2 Pooled analysis of several clinical trials also indicated that pirfenidone may reduce mortality.3 Treatment guidelines presented by the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society (ATS/ERS/JRS/ALAT) from 2015 suggest shared decision-making with the patient on the use of pirfenidone as most effective, given the high cost of the treatment, unclear effects on quality of life, and possible adverse effects, such as photosensitivity, fatigue, stomach discomfort, and anorexia.2
Nintedanib is a tyrosine kinase inhibitor that targets several growth factor receptors, such as fibroblast growth factor, vascular endothelial growth factor, and platelet-derived growth factor.2 Pooled data from 3 clinical trials suggested reductions in mortality, although significance was not reached.4 Analysis of the pooled data did show a reduction in the frequency of acute exacerbations, however,4 diarrhea and nausea are the 2 most commonly reported adverse events.4
As high as 90% of IPF patients have been observed with abnormal gastroesophageal reflux (GER).2 Since GER can result in pneumonitis from aspiration and microaspiration and may play a role in the pathogenesis and progression of IPF,5 the ATS/ERS/JRS/ALAT guidelines recommend the use of antacid treatments, such as proton pump inhibitors and histamine-2 blocker receptor antagonists, in patients with IPF.2
Some previous treatment evaluations resulted in strong recommendations against their use by the 2015 ATS/ERS/JRS/ALAT guidelines. These treatments include the anticoagulant warfarin; the selective endothelin receptor antagonist ambrisentan; the tyrosine kinase receptor imatinib; and the combination therapy of prednisone, azathioprine, and N-acetylcysteine (NAC).2 Conditional recommendations were made against the use of the phosphodiesterase-5 inhibitor sildenafil, as well as NAC monotherapy, and the dual endothelin receptor antagonists macitentan and bosentan.2 These decisions were made based on inconclusive or negative results from studies.
Some patients may experience episodes of acute respiratory deterioration, called acute exacerbations, that usually coincide with new radiologic abnormalities.5 These acute exacerbations may affect between 4% and 20% of patients annually; they have a poor prognosis, with a median survival of about 3 months after the exacerbation.5 No pharmacological therapies have been proven effective through clinical trials for the treatment of acute exacerbations, although the ATS/ERS/JRS/ALAT made recommendations for the use of corticosteroids in their 2011 guidelines.6 Some limited evidence may support the use of opioids during hospital stays for exacerbations.3
Pharmacological management of symptoms for palliative care may also be helpful, however evidence for their benefit has not been established. A review article found that systemic administration of morphine may have a beneficial effect on dyspnea or exercise capacity.7 Chronic cough, which may affect up to 80% of patients, is usually refractory to anti-tussive treatments.8 Oral corticosteroids and opioids are often used to treat cough but their benefits are not clear.8 A small study in IPF patients showed that thalidomide may help to lessen cough symptoms but was associated with a high rate of adverse events.9
A number of nonpharmacological treatments may be helpful in supportive care to improve the patient’s quality of life. IPF patients with resting hypoxia (SpO2<88%) may benefit from supplemental oxygen and it was recommended in the 2011 ATS/ERS/JRS/ALAT guidelines.6 Supplemental oxygen may improve exercise capacity and quality of life in these patients. Its effects on exertional dyspnea are inconsistent, however.1
Patients with IPF also commonly experience functional deconditioning due to their reduced lung function. Pulmonary rehabilitation, including various forms of exercise interventions as well as breathing exercises, has been shown to improve dyspnea, health-related quality of life, and exercise capacity.3 These improvements may be lost after 6 months, however, especially if patients do not keep up with their rehabilitation program.8
IPF has become the most common indication for lung transplantation and may increase patient survival.5 Lung transplant is recommended by the ATS/ERS/JRS/ALAT according to their 2011 guidelines, although only in select patients.6 The guidelines do not make a recommendation of single- versus double-lung transplantation, however, it did recommend that patients be screened for lung transplantation at an early stage since the disease is progressive and can be unpredictable in its course.6
- Quinn C, Wisse A, Manns ST. Clinical course and management of idiopathic pulmonary fibrosis. Multidiscip Respir Med. 2019;14(1):35.
- Raghu G, Rochwerg B, Zhang Y, et al. An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis. an update of the 2011 clinical practice guideline. Am J Respir Crit Care Med. 2015;192(2):e3-19.
- Rozenberg D, Sitzer N, Porter S, et al. Idiopathic pulmonary fibrosis: a review of disease, pharmacological, and nonpharmacological strategies with a focus on symptoms, function, and health-related quality of life. J Pain Symptom Manage. 2020;59(6):1362-1378.
- Richeldi L, Cottin V, du Bois RM, et al. Nintedanib in patients with idiopathic pulmonary fibrosis: combined evidence from the tomorrow and inpulsis® trials. Respir Med. 2016;113:74-79.
- Spagnolo P, Tzouvelekis A, Bonella F. The management of patients with idiopathic pulmonary fibrosis. Front Med (Lausanne). 2018;5. doi:10.3389/fmed.2018.00148
- Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183(6):788-824.
- Kohberg C, Andersen CU, Bendstrup E. Opioids: an unexplored option for treatment of dyspnea in IPF. Eur Clin Respir J. 2016;3(1):30629.
- Sgalla G, Iovene B, Calvello M, Ori M, Varone F, Richeldi L. Idiopathic pulmonary fibrosis: pathogenesis and management. Respir Res. 2018;19(1):32.
- Horton MR, Santopietro V, Mathew L, et al. Thalidomide for the treatment of cough in idiopathic pulmonary fibrosis: a randomized trial: a randomized trial. Ann Intern Med. 2012;157(6):398-406.
Reviewed by Harshi Dhingra, MD, on 7/2/2021.