expert roundtables

Idiopathic Pulmonary Fibrosis: Challenges and Opportunities in Diagnosis and Treatment

by Charles D. Burger, MD; Steven D. Nathan, MD; and Justin Oldham, MD, MS

Overview

Clinicians face multiple obstacles and challenges to the early diagnosis and treatment of idiopathic pulmonary fibrosis (IPF), including its similarity in presentation to more prevalent diseases such as chronic obstructive pulmonary disease, congestive heart failure, and asthma. Our featured experts identify barriers and opportunities to overcome them.

Q:

What obstacles stand in the way of the early diagnosis and treatment of IPF, and how can these challenges be overcome?

Charles D. Burger, MD

Professor of Medicine, Mayo Clinic College of Medicine
Consultant, Pulmonary, Allergy, Sleep, and Critical Care Medicine
Medical Director, Pulmonary Hypertension Clinic
Medical Director, Lymphangioleiomyomatosis Clinic
Mayo Clinic
Jacksonville, FL

“The nonspecific presentation of IPF makes obtaining an early diagnosis challenging, as exertional dyspnea may be attributed to any number of cardiopulmonary conditions.”

Charles D. Burger, MD

Interstitial lung diseases, including IPF, are all defined by the presence of interstitial parenchymal changes on chest imaging. The presenting symptoms may be nonspecific since they are shared with other more common maladies. In addition, significant lung damage may have already occurred before shortness of breath with exertion is noticed. The nonspecific presentation of IPF makes obtaining an early diagnosis challenging, as exertional dyspnea may be attributed to any number of cardiopulmonary conditions.

Various strategies and medications are available to manage the progression of IPF and the side effects of treatment. Importantly, multidisciplinary teams are key to diagnosing and managing IPF most effectively, but this model of care is not always accessible. Pharmacologic agents, while effective, can be costly and require prior authorization by payers. Many of these medications may also be accompanied by side effects that may result in dose reductions or medication discontinuation.

Steven D. Nathan, MD

Medical Director
Advanced Lung Disease and Transplant Program
Inova Fairfax Hospital
Falls Church, VA

“Antifibrotics do not reverse IPF, but they do decrease the rate of progression. This makes early diagnosis even more important, as the earlier in the disease process that lung function can be preserved, the better for the patient over the long-term.”

Steven D. Nathan, MD

Patients with interstitial lung diseases such as IPF suffer from undue delays in diagnosis, as their primary symptoms (ie, shortness of breath with or without cough) are also associated with more prevalent conditions (eg, chronic obstructive pulmonary disease, congestive heart failure, asthma). These conditions, like IPF, may affect older male smokers at high rates. In addition to presenting with these nonspecific symptoms, patients may also have normal pulmonary function test results, often causing IPF to be overlooked as a potential cause of the patient’s symptoms. Although useful, pulmonary function tests are rather blunt instruments in that only significant declines in forced vital capacity are likely to be detected and acted upon. Patients with IPF also have a higher propensity for certain comorbidities, including obstructive sleep apnea, coronary artery disease, pulmonary emboli, and pulmonary hypertension.

Awareness of subtle reticulations on high-resolution computed tomography (HRCT) is important, as radiologists often report “chronic scarring at the bases,” which may be interpreted by the primary care provider as minor scarring that requires no further exploration when, in fact, these changes may be an early indication of IPF. Both radiologists and primary care providers benefit from continuing education with regard to these subtle findings. Together with a comprehensive clinical evaluation, the HRCT is sufficient to make the diagnosis of IPF in many cases; however, in some cases, a lung biopsy may be needed to attain a confident diagnosis of IPF. Antifibrotics have supplanted the immunosuppressive therapies, which are now known to be more harmful than helpful to patients with IPF. Antifibrotics do not reverse IPF, but they do decrease the rate of progression. This makes early diagnosis even more important, as the earlier in the disease process that lung function can be preserved, the better for the patient over the long-term.

Justin Oldham, MD, MS

Assistant Professor of Medicine
Director, Interstitial Lung Disease Program
University of California, Davis
Sacramento, CA

“Continuing education in primary care, along with targeted screening for IPF of select patients, present an opportunity to mitigate those referral and diagnostic delays and to prevent these patients from being treated inappropriately with immunosuppressive therapy.”

Justin M. Oldham, MD, MS

Owing to the nonspecific signs and symptoms of IPF, these patients have notoriously long referral and diagnostic delays that prevent prompt and appropriate workup. Attention to subtle changes on the CT scan, as well as to subtle changes in pulmonary function testing in the primary care setting, is the lowest-hanging fruit to start addressing the unmet need of early detection. Continuing education in primary care, along with targeted screening for IPF of select patients, present an opportunity to mitigate those referral and diagnostic delays and to prevent these patients from being treated inappropriately with immunosuppressive therapy. The PANTHER-IPF trial revealed that combination therapy with prednisone, azathioprine, and N-acetylcysteine was most likely harming patients with IPF, since these patients had higher hospitalization and mortality rates with this regimen compared with placebo.

It is recommended that primary care providers begin with at least a pulmonary function test, and, preferably, with an HRCT, especially when evaluating older patients with a history of smoking, as well as those with cough and/or dyspnea and Velcro crackles on clinical examination. Usual interstitial pneumonia is the pattern seen on HRCT; no biopsy is needed in cases of a definite usual interstitial pneumonia pattern, but biopsy can be helpful in cases of an indeterminate pattern on HRCT. Biopsies should be limited to those who are healthy enough for the procedure and for whom therapy would change based on the results. The INBUILD study provides justification for antifibrotic therapy in those patients who demonstrate progression of a variety of fibrotic lung conditions. The addition of an immunosuppressant may also be warranted if significant inflammation is suspected based on the HRCT or confirmed on lung biopsy.

References

Albera C, Costabel U, Fagan EA, et al. Efficacy of pirfenidone in patients with idiopathic pulmonary fibrosis with more preserved lung function. Eur Respir J. 2016;48(3):843-851. doi:10.1183/13993003.01966-2015

Flaherty KR, Wells AU, Cottin V, et al; INBUILD Trial Investigators. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med. 2019;381(18):1718-1727. doi:10.1056/NEJMoa1908681

Hewson T, McKeever TM, Gibson JE, Navaratnam V, Hubbard RB, Hutchinson JP. Timing of onset of symptoms in people with idiopathic pulmonary fibrosis. Thorax. 2017 Oct 11;thoraxjnl-2017-210177. doi:10.1136/thoraxjnl-2017-210177

Idiopathic Pulmonary Fibrosis Clinical Research Network; Raghu G, Anstrom KJ, King Jr TE, Lasky JA, Martinez FJ. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N Engl J Med. 2012;366(21):1968-1977. doi:10.1056/NEJMoa1113354

Kolb M, Richeldi L, Behr J, et al. Nintedanib in patients with idiopathic pulmonary fibrosis and preserved lung volume. Thorax. 2017;72(4):340-346. doi:10.1136/thoraxjnl-2016-208710

Lederer DJ, Martinez FJ. Idiopathic pulmonary fibrosis. N Engl J Med. 2018;378(19):1811‐1823. doi:10.1056/NEJMra1705751

Wells AU, Flaherty KR, Brown KK, et al; INBUILD Trial Investigators. Nintedanib in patients with progressive fibrosing interstitial lung diseases-subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: a randomised, double-blind, placebo-controlled, parallel-group trial. Lancet Respir Med. 2020;8(5):453-460. doi:10.1016/S2213-2600(20)30036-9

More in Interstitial Lung Disease

Thumb

Interstitial Lung Disease

Clarified Hemodynamic Definitions of WHO Group 3 Pulmonary Hypertension

Clinical Topic Updates by Steven D. Nathan, MD

The updated hemodynamic criteria for pulmonary hypertension (PH) could lead to the earlier detection and treatment of patients with World Health Or...READ MORE

Thumb

Interstitial Lung Disease

Research on Pulmonary Hypertension–Specific Therapeutics for Patients With Chronic Lung Disease

Clinical Topic Updates by Steven D. Nathan, MD

Research continues to unfold on possible new treatments for pulmonary hypertension (PH) in patients with chronic lung disease (CLD), including thos...READ MORE

Thumb

Interstitial Lung Disease

Pulmonary Rehabilitation in Interstitial Lung Disease

Patient Care Perspectives by Charles D. Burger, MD

Pulmonary rehabilitation is a viable treatment for many patients with interstitial lung disease (ILD), with benefits that may include increased exe...READ MORE

More In Pulmonology

Interstitial Lung Disease

Present And Future Therapies For Interstitial Lung Disease And Associated Pulmonary Hypertension

Expert Roundtables by Charles D. Burger, MD; Steven D. Nathan, MD; and Justin Oldham, MD, MS

Interstitial Lung Disease

Improving Exercise Tolerance In Patients With Idiopathic Interstitial Pneumonias

Patient Care Perspectives by Justin Oldham, MD, MS

Interstitial Lung Disease

Respiratory Decline In Patients With Combined Pulmonary Fibrosis And Emphysema

Patient Care Perspectives by Charles D. Burger, MD