Given the heterogeneity of interstitial lung diseases (ILD), a correct diagnosis often eludes clinicians.1 Guidelines have attempted to clarify and streamline the diagnostic process, but it is still common for more than half of patients who present with symptoms to be misdiagnosed.2,3 On average, it takes up to 2 years to diagnose idiopathic pulmonary fibrosis (IPF), one of the most common forms of ILD.4
An accurate diagnosis, which can improve quality of life by directing appropriate therapy, takes time because multidisciplinary assessments — clinical, radiologic, and pathologic — are essential.3 Despite advances in imaging, including the advent of high-resolution computed tomography (HRCT), no single test can pinpoint an ILD diagnosis.1 Even after a patient has undergone a combination of detailed medical and family history analysis, physical examination, serologic testing, imaging, and pulmonary function tests, the diagnosis may still not be obvious.1 If diagnosis remains elusive, lung biopsy may be considered to establish a specific diagnosis that will aid in assessing prognosis and guiding treatment. 1 Lung biopsy can be performed via bronchoscopy or surgical lung biopsy. 1
Barriers to Diagnosis
Pulmonologist Gregory P. Cosgrove, MD, FCCP, assistant director and endowed chair of interstitial lung disease at National Jewish Health in Denver, Colorado, and colleagues sought to determine why diagnosis for ILD takes so long by surveying patient members of the Pulmonary Fibrosis Foundation.3
In a survey of 600 patients (median age: 69 years for men and 62.5 years for women), the most common diagnosis was IPF (46.5%), followed by ILD (32.5%) and nonspecific interstitial pneumonia (15.5%).
- Nonspecific symptoms that lead patients to believe their condition is not urgent;
- Clinicians are more likely to consider common respiratory or cardiovascular diseases;
- Multiple tests may be necessary, causing patients to experience scheduling difficulties;
- Some patients may be subjected to costly invasive procedures as a result of previous inconclusive tests.3
Though 75% of respondents had visited at least 3 physicians to get a diagnosis, more than half of the patients (55%) surveyed said that they had been misdiagnosed at least once, with 38% receiving at least 2 misdiagnoses prior to receiving their current diagnosis of ILD. 3 Furthermore, 43% of patients had to wait >1 year from the onset of their first symptoms, and 19% waited ≥3 years for a correct diagnosis.
Fibrosis Predicts Worse Outcomes
When clinicians are determining the progression of ILD, they should consider whether the patient has fibrosis.6 An analysis of 2 major IPF studies revealed that untreated IPF has similar characteristics as ILD with fibrosis.6 The findings were based on decline in forced vital capacity and mortality in patients enrolled in the INBUILD (ClinicalTrials.gov Identifier: NCT02999178) and INPULSIS (ClinicalTrials.gov Identifier: NCT01335464 and NCT01335477) trials.
“Identifying the underlying antigen is critical to those patients for management and ignoring it is a serious mistake. Fibrosis markedly worsens the prognosis,” said lead author Kevin K. Brown, MD, pulmonologist and chair of the department of medicine at National Jewish Health.
Smokers Can Develop ILD
Smokers are an overlooked patient group that may be misdiagnosed with other pulmonary-related diseases.7 Although clinicians may first consider other diseases such as respiratory bronchiolitis-interstitial lung disease, desquamative interstitial pneumonia, pulmonary Langerhans cell histiocytosis, and acute eosinophilic pneumonia, they should not disregard ILD in patients with a smoking history.7 Because many patients with a history of smoking are now screened with chest CT scans, more incidental cases of ILD are being discovered.7
“[Our] paper demonstrates that lung disease in smokers is not restricted to problems like [chronic obstructive pulmonary disease] or lung cancer,” explains lead author Anupam Kumar, MD, from the division of pulmonary and critical care medicine at Spectrum Health-Michigan State University College of Human Medicine in Grand Rapids. “Therefore, pulmonologists may have a lower threshold of obtaining CT scans in smokers if they suspect they may have ILD. Early diagnosis gives clinicians yet another tool to educate and reinforce tobacco abstinence.”
COVID-19 Complicates ILD Evaluations
As rising rates of coronavirus disease 2019 (COVID-19) could potentially divert resources in pulmonary medicine, the time necessary for diagnostic workup for suspected ILD may be prolonged.8 In areas with a high volume of COVID-19 cases, surgical lung biopsies might be postponed because they pose a high risk of spreading aerosols among patients and healthcare professionals.7 In areas where elective surgeries have been postponed, patients may wait longer to have a diagnosis of ILD confirmed.8
If, however, bronchoscopy or surgical lung biopsy would guide urgent treatment, clinicians should consider performing these procedures rather than delaying life-sustaining therapy. In cases in which the diagnosis is <90% certain, clinicians need to consider the risk of community COVID-19 spread and treat empirically. Risk thresholds in some cases will be lowered, particularly with high-risk procedures such as biopsies, which could signify worse outcomes even in patients aged <75 years.9
A recently convened panel of the Fleischner Society, the international medical society for thoracic radiology, concurred that even imaging should be reconsidered in high-risk pandemic areas if a patient’s symptoms of COVID-19 are mild and the results would not guide diagnostic or therapeutic decisions.9 However, the panel did agree that imaging is essential for patients who have mild virus-like symptoms and a positive COVID-19 test.9
The COVID-19 pandemic has prolonged the time to ILD diagnosis by weeks, if not months. “It’s clearly slowed the rate at which people can be fully evaluated as patients are concerned about coming to healthcare institutions and the institutions have to alter their underlying process to account for the presence of an infectious pandemic,” states Dr Brown. “Some patients might have ILD at the time of diagnosis and for those patients, it is possible that COVID-19 could be responsible for their underlying disease and difficult to separate out. Radiographic abnormalities, a hallmark of severe SARS CoV-2 infection, sometimes can confuse things.”
“During the peak of the situation, we significantly increased our telehealth capabilities,” Dr Brown reported. “Our capacity to complete evaluations with radiology, pulmonary testing, and gas-exchange testing changed as we were not able to fully evaluate patients because of the virus.”
Summary and Clinical Applicability
Diagnosing ILD is challenging — now more than ever during the COVID-19 pandemic — yet it is critical for clinicians to ensure their patients receive the most appropriate treatment. Guidelines and registries may help to identify certain characteristics of the heterogeneous disease to enable clinicians to arrive at the correct diagnosis.
Gregory P. Cosgrove, MD, FCCP, declared affiliations with Boehringer Ingelheim; Genentech, Inc; and Veracyte, Inc. Kevin K. Brown, MD, declared affiliations with Biogen Inc; Aeolus; Astra Zeneca; aTyr Pharma, Inc; Boehringer Ingelheim; Galapagos NV; Galecto, Inc; Genentech/Roche; Genoa Pharmaceuticals, Inc; Gilead Sciences; Global Blood Therapeutics; MedImmune, LLC; Patara; ProMetic Life Sciences, Inc; Veracyte, Inc; and Third Pole, Inc. Anupam Kumar, MD, declared an affiliation with Boehringer Ingelheim.
- Ryu JH, Daniels CE, Hartman TE, Yi ES. Diagnosis of interstitial lung diseases. Mayo Clin Proc. 2007;82(8):976-986.
- 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.
- 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;18:9.
- Southern BD. Patients with interstitial lung disease and pulmonary sarcoidosis are at high risk for severe illness related to COVID-19. Published online June 18, 2020. Cleve Clin J Med. doi:10.3949/ccjm.87a.ccc026
- Fischer A, Swigris J. What rheumatologists need to know about diagnosing and managing interstitial lung disease (ILD). The Rheumatologist. https://www.the-rheumatologist.org/article/what-rheumatologists-need-to-know-about-diagnosing-and-managing-interstitial-lung-disease-ild/. Updated December 1, 2012. Accessed August 5, 2020.
- Brown KK, Martinez FJ, Walsh SLF, et al. The natural history of progressive fibrosing interstitial lung diseases. Eur Respir J. 2020;55(6):2000085.
- Kumar A, Cherian SV, Vassallo R, Yi ES, Ryu JH. Current concepts in pathogenesis, diagnosis, and management of smoking-related interstitial lung diseases. Chest. 2018;154(2):394-408.
- Wong AW, Fidler L, Marcoux V, et al. Practical considerations for the diagnosis and treatment of fibrotic interstitial lung disease during the COVID-19 pandemic. Chest. 2020;S0012-3692(20)30756-X.
- Rubin GD, Ryerson CJ, Haramati LB, et al. The role of chest imaging in patient management during the COVID-19 pandemic: a multinational consensus statement from the Fleischner Society. Radiology. 2020;296(1):172-180.
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Reviewed August 2020