MILAN — The European Respiratory Society (ERS) Congress 2023 dedicated an entire session to the multifaceted challenges and ongoing debates surrounding progressive pulmonary fibrosis (PPF). Renowned medical professionals and experts congregated in Milan to explore the current landscape and future prospects of diagnosing PPF, with a particular focus on expediting the diagnostic process.

Anna Podolanczuk, MD, assistant professor of medicine at Weill Cornell Medical College in New York City, dissected the diagnostic intricacies of PPF, addressing not only the existing challenges but also the opportunities to streamline diagnosis.

As the session’s co-chair, Michael Kreuter, MD, director of the Lung Center at University Hospital, Mainz, Germany, emphasized the importance of patients’ voices in understanding and addressing diseases. Joining him as a co-chair was Marlies S. Wijsenbeek, a pulmonary physician and the head of the Interstitial Lung Disease Centre at Erasmus University Medical Centre in Rotterdam, the Netherlands.

The session commenced with a powerful testament from Elisabeth Robertson, a PPF patient representative from the UK. Diagnosed with PPF in 2011, her journey to diagnosis was far from straightforward, and she spoke in a video about the frustrations she encountered due to the lack of accessible information. Robertson called for a clearer diagnostic pathway.

Timely Diagnosis: Key to Better Outcomes

Despite advancements in PPF diagnosis, considerable challenges persist in the diagnostic odyssey of this recently defined phenotype. Podolanczuk underscored the significance of early diagnosis, citing Robertson’s personal experience as a poignant example. An early diagnosis not only alleviates patients’ uncertainties and anxieties about their future but also enables the utilization of available treatments, such as antifibrotic therapies, which can slow the decline in forced vital capacity (FVC) in patients with progressive fibrotic interstitial lung diseases.

Data gleaned from the INBUILD trial was presented, revealing that patients in the placebo group experienced a nearly 200 mL decline in lung function over 52 weeks. Podolanczuk stressed that initiating antifibrotic therapies sooner could lead to better outcomes, as baseline conditions are likely to worsen over time.

“General practitioners can have a role in diagnosing and managing PPF. They are the frontline. We need to increase awareness, because they are generally not aware of this disease, and they usually think about COPD, asthma, or cardiovascular diseases whenever a patient presents with such symptoms,” Podolanczuk told Medscape Medical News.

Defining the Challenge

The foundation of any diagnosis lies in a clear definition and established diagnostic criteria. During the session, it became apparent that different criteria could be employed for PPF diagnosis, leading to the identification of distinct patient populations.

In 2022, the Official ATS/ERS/JRS/ALAT Clinical Practice Guideline provided the first comprehensive definition of the PPF phenotype. According to this guideline, PPF is defined by the presence of at least two of three criteria: worsening symptoms, radiological progression, or physiologic progression defined as a ≥5% absolute decline in FVC or ≥10% absolute decline in diffusion lung CO (DLCO) within the past year in a patient with interstitial lung disease (ILD) and lung scarring other than idiopathic pulmonary fibrosis (IPF), with no alternative explanation.

“Definitions from the guidelines were based on the available trials at that moment. Registry data suggest that using different criteria will probably lead to the identification of different, but always progressive, populations,” Wijsenbeek commented to Medscape Medical News. “I think we should not worry too much about the details of the criteria and it is good that we have a multimodality assessment: we ask the patient, we look at the pictures and we measure the lung function. Combining those data, you can have a robust indication of progression.”

The Current Landscape

Currently, PPF diagnosis hinges on a combination of CT scans, patient narratives, and, in some cases, histological examination. Wijsenbeek stressed the need to transition to novel diagnostic modalities, including tools that can be readily employed by GPs in their practices.

“GPs have to care about a lot of different diseases, and it makes it more complicated to be aware of conditions like PPF: symptoms are in fact extremely unspecific” Kreuter told Medscape Medical News. “My suggestion to GPs is to pay attention to the so-called inspiratory crackles because they represent a very early and specific sign of lung fibrosis. This sound does not resemble any other sound that you can hear with your stethoscope: it is like the sound you make walking on fresh snow,” he added, recommending a referral to the pulmonologist in case of identification of inspiratory crackles.

Additionally, several biomarkers can contribute to early PPF diagnosis, including the identification of the usual interstitial pneumonia (UIP) pattern through biopsy or imaging. “We know that this pattern predicts poor outcomes regardless of ILD type,” Podolanczuk explained, underlining the possibility of using a molecular classifier to identify a UIP pattern on transbronchial lung biopsy. “This is an already existing technology used to identify a gene expression pattern that is strongly predictive of a UIP pattern,” she said.

Furthermore, blood biomarkers, such as high peripheral blood monocyte count and telomere length, hold promise for early PPF detection and prognosis assessment.

The Road Ahead

The diagnostic landscape for PPF is evolving rapidly, with various emerging biomarkers and tools showing promise. Proteomics, alongside home spirometry as a digital biomarker for frequent FVC monitoring, have demonstrated potential for identifying patients who may benefit from early treatment. A 2022 study defined a 12-proteomic biomarkers signature of progressive fibrosing ILD that can identify patients who may benefit from early treatment and is predictive of outcomes regardless of the underlying CT pattern.

The integration of artificial intelligence into the interpretation of CT and x-ray images represents another avenue of advancement in PPF diagnosis. Podolanczuk highlighted the role of AI and quantitative CTs in enhancing diagnostic accuracy. She also mentioned innovative imaging methods, such as hyperpolarized gas MRI and endobronchial optical coherence tomography (EB-OCT), which offer new insights into disease progression and treatment response.

Beyond imaging and AI, various research tools are entering the diagnostic arena, including real-time breath analysis for distinguishing between different respiratory conditions. These tools collectively promise to shorten the time from symptom presentation to PPF diagnosis, a vital step in improving patient outcomes. In the words of Podolanczuk, “How early is too early to identify these patients? Let me say that there’s no such thing as ‘too early’ in the diagnosis of PPF!”

Podolanczuk disclosed grant funding from NHLBI, ALA, Three Lakes Foundation; consulting fees from Regeneron, Roche, Imvaria, Boehringer Ingelheim, Veracyte, United Therapeutics, Eisai; and honoraria from NACE and EBSCO/DynaMed. Robertson disclosed having no conflict.

European Respiratory Society (ERS) International Congress 2023. September 9-13, 2023, Milan, Italy.

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