As front-line health care providers, family physicians play an essential role in the early detection of idiopathic pulmonary fibrosis (IPF) and the timely referral to a pulmonologist. The disease is rare and includes signs and symptoms that make it difficult to distinguish among other interstitial lung diseases (ILDs). By identifying suspected cases of IPF at primary care visits, family physicians have an opportunity to refer patients earlier and enable diagnosis and treatment sooner. This makes education about IPF a key factor in early detection, which can potentially lead to better health outcomes. Diagnostic criteria and treatment options presented in this brochure are based on specialist guidelines that have not been reviewed or endorsed by the AAFP. However given the limited guidance for IPF, the information is presented for consideration in management of this disease.
Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial lung disease (ILD) of unknown cause.1 ILDs may be a result of a number of insults to the lungs (e.g., medication, connective tissue disease, occupational or environmental exposures).2
Idiopathic pulmonary fibrosis is characterized by a progressive breathlessness and cough, as well as a decline in lung function.1
The most common symptoms of IPF are dyspnea and cough.2 Dyspnea is usually exertional and associated with walking up inclines or steps.2 The cough is typically described as “dry” and “hacking,” and may start with a tickle in the throat.3 The severity of these symptoms varies.
Other possible symptoms of IPF are fatigue and problems with sleeping.3 Symptoms that have not been associated with IPF include chest pain, fever, rash, weight loss, and myalgia or arthralgia,4 although these may be seen in various other forms of ILD.
Knowledge of a patient’s medical history and exposures is vital to diagnosing IPF and essential to excluding other ILDs. Questions should focus on the following:
The physical examination should focus on two key signs:
Idiopathic pulmonary fibrosis is unlikely in the presence of signs of connective tissue disease, such as joint deformity, synovitis, muscle weakness, and rash.4 Instead, these signs should prompt a workup for rheumatologic disease.4
The cause of IPF is unknown, but some patients have a higher risk, including those who:
No one clinical factor indicates IPF. Rather, a patient’s entire clinical context should be considered when making a diagnosis of IPF.
While IPF is rare, a lack of large-scale studies makes it difficult to estimate the incidence of the disease. We do know that the incidence of IPF increases with age, occurring most often after 55 years, and slightly more often in men.7 Among all individuals 55 to 64 years old, the incidence is 19.3 cases per 100,000 person-years.7
Misdiagnosis and delays in diagnosis of IPF are common. In one study, IPF was most often misdiagnosed as asthma (13.5%), pneumonia (13.0%), or bronchitis (12.3%).8 Delays in diagnosis have been reported to be from one year to as long as three years, with longer delays associated with an increased risk of death.4,7
Idiopathic pulmonary fibrosis is difficult to diagnose for several reasons, including:2
The diagnosis of IPF is challenging and one of exclusion. No one clinical factor indicates IPF. Rather, a patient’s entire clinical context should be considered when making a diagnosis of IPF. Currently, standards for diagnosis include: a multidisciplinary discussion (MDD) among pulmonologists, radiologists, and pathologists discussing all features of the patient’s presentation, radiographic findings, and pathologic findings (if available). The discussion should address the following:9
MDD enhances the accuracy of diagnosis, with family physicians playing a vital role through early detection and timely referral. Excluding other causes of disease relies on recognizing the signs and symptoms of the disease, as well as:9
Documenting risk factors
Referrals should include a complete documentation of findings.10,11 Diagnosing IPF requires not only knowledge of the signs and symptoms of IPF, but also the ability to distinguish it from other diseases with similar clinical presentations.
Most objective testing is not part of the recommended diagnostic criteria. Nevertheless, the results of some tests can help exclude other diagnoses and/or add to the clinical context of IPF.
Although laboratory testing is not useful in diagnosing IPF, guidelines recommend serologic testing for most patients to exclude underlying connective tissue disease.9 Such testing may include rheumatoid factor, anti-cyclic citrullinated peptide, and anti-nuclear antibodies.9 An extractable nuclear antigen panel is often times helpful to identify other connective tissue diseases, such as Sjögren’s syndrome, systemic lupus erythematosus, and scleroderma, all of which are also associated with ILDs.12
The sensitivity of chest radiographs for the detection of subtle interstitial changes is low.4 An indication of IPF is symmetric peripheral, basilar reticular opacity with loss of volume in the lower lobe.4 However, some patients with IPF may have normal findings on chest radiographs.4
Pulmonary function tests are integral to monitoring progression of IPF and staging of disease severity.4 The results may also be helpful in establishing an initial diagnosis of IPF. The forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide are usually decreased, but these values may be normal early in the disease course.4
The radiographic standard for the diagnosis of IPF is an HRCT of the chest.9 An HRCT is a special, non-contrast chest computed tomography (CT) that obtains thin slice (< 2 millimeters), volumetric images of the lungs enhanced with special software algorithms. A pattern of UIP on HRCT is characterized by a subpleural, basilar predominance, and honeycombing with or without peripheral traction bronchiectasis or bronchiolectasis with a relative paucity of ground-glass opacities.4,9
The UIP pattern on HRCT is highly accurate for a UIP pattern on histologic examination of a surgical lung biopsy specimen.9 Thus, surgical lung biopsy is needed only when the findings on HRCT are not “classic” for UIP.9
It is essential for HRCT images to be interpreted by a radiologist experienced with ILDs. The decision to pursue surgical lung biopsy is best left to the providers in the MDD, as many factors go into this decision.
Idiopathic pulmonary fibrosis should be considered for all patients with unexplained chronic exertional dyspnea, and those who present with a cough, bibasilar inspiratory crackles, and finger clubbing.9 The disease most often occurs in individuals older than 50, men, and smokers.4,9 The index of suspicion for connective tissue disease should be high for women younger than 60 years.9
An HRCT should be ordered for any patient who has abnormal findings on chest radiographs and clinical findings that are consistent with an ILD.4
A complete report of the family physician’s ﬁndings is an important aspect of a referral to conﬁrm IPF. A thorough referral report should include the following:11
Pulmonary function tests are integral to monitoring progression of IPF and staging of disease severity. The results may also be helpful in establishing an initial diagnosis of IPF.
The pathogenesis of IPF is unknown.4 It was believed that IPF was caused by generalized inﬂammation that progressed to widespread parenchymal fibrosis.13,14 This was questioned when IPF failed to respond to anti-inﬂammatory drugs and immune modulators.13 Studies now suggest that exposure to external stimuli (e.g., smoke, environmental agents) can lead to damage of alveolar epithelial cells, subsequent activation of mesenchymal cells, and excess accumulation of extracellular matrix.13,14 A genetic basis for IPF is still being explored.
Patients with IPF are at an increased risk for several comorbidities, including coronary artery disease, lung cancer, obstructive sleep apnea, emphysema, pulmonary hypertension, pulmonary infection, gastroesophageal reﬂux disease, hiatal hernia, and diabetes mellitus.2,4,15
The course of IPF is unpredictable, and many people experience acute exacerbations of the disease. In one study, 72% of 1,735 patients with IPF sought urgent, outpatient care because of a suspected exacerbation of the disease, and 39% of the patients had at least one all-cause hospitalization.16 These disease-related interruptions diminish patients’ quality of life.
The goals of treatment are to slow progression of the disease, reduce symptoms, and improve the quality of life. IPF is currently treated with a combination of antifibrotic drugs and pulmonary rehabilitation.2,4,17 The need for oxygen therapy should be assessed, and lung transplantation is an option for moderate to severe disease in select patients.2,4 Clinical trials and registries may be available for patient involvement in your area.
Until 2014, no approved drugs were available for the treatment of IPF. Now, two first-in-class antifibrotic drugs are approved by the Food and Drug Administration (FDA). Studies have shown both drugs slow disease progression in patients with IPF, as measured by the decline in FVC.18-20
Overall, adverse events were tolerable.19,20 The most common were gastrointestinal- or skin-related adverse events.19,20
A systematic review of nine studies demonstrated that pulmonary rehabilitation is beneficial for people with interstitial lung disease, including IPF.21 According to the findings, pulmonary rehabilitation was safe and was associated with short-term improvements in functional exercise capacity, dyspnea, and quality of life.21
A more recent systematic review and meta-analysis (five randomized controlled trials) focused on only IPF and showed that pulmonary rehabilitation was associated with increased exercise tolerance and improved quality of life.22
Patients derive the most benefit from pulmonary rehabilitation early in the course of the disease.23 As such, pulmonary rehabilitation should begin immediately after diagnosis.
Patients with IPF should be assessed for the need for oxygen therapy. This is best accomplished by a six-minute walk study. If the patient’s oxygen saturation drops below 88%, then an oxygen titration component should be performed.2 This can help determine the least amount of oxygen necessary to maintain saturations above 88% with exertion.2
Management of Comorbidities
Most specialty centers advocate for aggressive management of comorbidities.
Lung transplantation is a potential option for patients with moderate to severe IPF, and it is the only treatment associated with prolonged survival.2,4,24 While the number of single-lung transplantations has remained steady, the number of double-lung transplantations has increased since the mid-1990s.25 There is no evidence showing the benefit of single- versus double-lung transplantation.17
Idiopathic pulmonary fibrosis has a substantial impact on health-related quality of life, primarily attributed to a high-symptom burden and functional limitations. People with IPF have reported that the most troublesome symptoms are dyspnea, severe coughing, and persistent fatigue.26 Limited mobility is also an issue.26 One study reported that individuals with IPF were sedentary for more than nine hours per day.27 People with IPF become frustrated as they lose the ability to engage in activities they once enjoyed.26
Difficulty interacting with friends and family, and the financial strain are also primary challenges.26 Depression is common and is also a substantial factor of health-related quality of life.28-30 In one study, nearly 26% of patients with IPF experienced symptoms of depression.30
Diagnosing IPF is challenging, but guidelines are available to help primary care physicians identify patients with IPF and make earlier referrals. Early referral means earlier treatment, which can help improve patient outcomes.
In addition to their vital role in early detection and referral, family physicians play an important role in the ongoing care of their patients with IPF. Family physicians can contribute to the care of patients with IPF in the following ways:
Patients value a trusted source of information and may ask their family physician for information and advice. Family physicians should provide their patients with guidance for self-management of their disease and recommend credible resources for patient education.
Resources for Patient Education on IPF
1. Torrisi SE, Pavone M, Vancheri A, Vancheri C. When to start and when to stop antiﬁbrotictherapies. Eur Respir. Rev. 2017;26(145).
2. Raghu G, Collard HR, Egan JJ, et al. An oﬃ cial 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.
3. National Jewish Health. PeerView Institute for Medical Education. Idiopathic pulmonary ﬁbrosis: a guide for providers. Accessed July 26, 2018.
4. Oldham JM, Noth I. Idiopathic pulmonary ﬁbrosis: early detection and referral. Respir Med. 2014;108(6):819-829.
5. Schwaiblmair M, Behr W, Haeckel T, Markl B, Foerg W, Berghaus T. Drug induced interstitial lung disease. Open Respir Med J. 2012;6:63-74.
6. Antin-Ozerkis D. Interstitial lung disease: a clinical overview and general approach. Thoracic key. Chapter 54. Section 11. Accessed July 26, 2018.
7. Raghu G, Chen SY, Hou Q, Yeh WS, Collard HR. Incidence and prevalence of idiopathic pulmonary ﬁbrosis in US adults 18-64 years old. Eur Respir J. 2016;48(1):179-186.
8. Cosgrove GP, Bianchi P, Danese S, Lederer DJ. Barriers to timely diagnosis of interstitial lung disease in the real world: the INTENSITY survey. BMC Pulm Med. 2018;18(1):9.
9. Raghu G, Remy-Jardin M, Myers JL, et al. Diagnosis of idiopathic pulmonary fibrosis. An official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2018;198(5):e44-e68.
10. Lamas DJ, Kawut SM, Bagiella E, Philip N, Arcasory SM, Lederer DJ. Delayed access and survival in idiopathic pulmonary fibrosis: a cohort study. Am J Respir Crit Care Med. 2011;184(7):842-847.
11. Purokivi M, Hodgson U, Myllarniemi M, Salomaa ER, Kaarteenaho R. Are physicians in primary health care able to recognize pulmonary ﬁbrosis? Eur Clin Respir J. 2017;4(1):1290339.
12. Hiepe F, Dorner T, Burmester G. Antinuclear antibody- and extractable nuclear antigen-related diseases. Int Arch Allergy Immunol. 2000;123(1):5-9.
13. Harari S, Caminati A. IPF: new insight on pathogenesis and treatment. Allergy. 2010;65(5):537-553.
14. Sgalla G, Iovene B, Calvello M, Ori M, Varone F, Richeldi L. Idiopathic pulmonary ﬁbrosis: pathogenesis and management. Respir Res. 2018;19(1):32.
15. Suzuki A, Kondoh Y. The clinical impact of major comorbidities on idiopathic pulmonary ﬁbrosis. Respir Investig. 2017;55(2):94-103.
16. Yu YF, Wu N, Chuang CC, et al. Patterns and economic burden of hospitalizations and exacerbations among patients diagnosed with idiopathic pulmonary ﬁbrosis. J Manag Care Spec Pharm. 2016;22(4):414-423.
17. 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-e19.
18. Fleetwood K, McCool R, Glanville J, et al. Systematic review and network meta-analysis of idiopathic pulmonary ﬁbrosis treatments. J Manag Care Spec Pharm. 2017;23(3-b Suppl):S5-S16.
19. King TE, Bradford WZ, Castro-Bernardini S, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary ﬁbrosis. N Engl J Med. 2014;370(22):2083-2092.
20. Richeldi L, duBois RM, Raghu G, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22):2071-2082.
21. Dowman L, Hill CJ, Holland AE. Pulmonary rehabilitation for interstitial lung disease. Cochrane Database Syst Rev. 2014;10:CD006322.
22. Gomes-Neto M, Silva CM, Ezequiel D, Conceicao CS, Saquetto M, Machado AS. Impact of pulmonary rehabilitation on exercise tolerance and quality of life in patients with idiopathic pulmonary ﬁbrosis: a systematic review and meta-analysis. J Cardiopulm Rehabil Prev. 2018;Jan 18 [Epub ahead of print].
23. Holland AE, Hill CJ, Glaspole I, Goh N, McDonald CF. Predictors of beneﬁt following pulmonary rehabilitation for interstitial lung disease. Respir Med. 2012;106(3):429-435.
24. Thabut G, Mal H, Castier Y, et al. Survival beneﬁt of lung transplantation for patients with idiopathic pulmonary ﬁbrosis. J Thorac Cardiovasc Surg. 2003;126(2):469-475.
25. Christie JD, Edwards LB, Kucheryavaya AY, et al. The registry of the International Society for Heart and Lung Transplantation: 29th adult lung and heart-lung transplant report—2012. J Heart Lung Transplant. 2012;31(10):1073-1086.
26. Center for Drug Evaluation and Research. The voice of the patient. Idiopathic pulmonary ﬁbrosis. U.S. Food and Drug Administration. Washington, DC: 2015. https://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFee/UCM440829.pdf. Accessed April 18, 2018.
27. Atkins C, Baxer M, Jones A, Wilson A. Measuring sedentary behaviors in patients with idiopathic pulmonary ﬁbrosis using wrist-worn accelerometers. Clin Respir J. 2018;12(2):746-753.
28. Glaspole IN, Chapman SA, Cooper WA, et al. Health-related quality of life in idiopathic pulmonary ﬁbrosis: data from the Australian IPF registry. Respirology. 2017;22(5):950-956.
29. Matsuda T, Taniguchi H, Ando M, et al. Depression is signiﬁcantly associated with health status in patients with idiopathic pulmonary ﬁbrosis. Intern Med. 2017;56(13):1637-1644.
30. Lee YJ, Choi SM, Lee YJ, et al. Clinical impact of depression and anxiety in patients with idiopathic pulmonary ﬁbrosis. PLoS One. 2017;12(9):e0184300.