Fibrosis is a pathological process of irreversible thickening and scarring of the lung parenchyma, leading to decreased lung capacity. This condition is a progressive deterioration of respiratory function that often decreases patient quality of life and leads to early mortality. The reported incidence of Idiopathic Pulmonary Fibrosis (IPF), one of the most common types of ILD, varies from 2.8 to 9.3 cases per 100,000 population in Europe and the US annually.19
ILD poses significant financial pressure on individual patients and the healthcare system. In North America, the estimated annual per capita cost of patients with IPF was approximately $20,000, 2.5–3.5 times higher than the average national healthcare expenditure.20
The updated guideline on IPF and Progressive Pulmonary Fibrosis (PPF) published recently in the American Journal of Respiratory and Critical Care Medicine was one of the most important topics in the field of ILD discussed at the congress. Prior guidelines addressing the diagnosis and management of IPF were published in 2011, 2015, and 2018. A. Bush (UK), G. Raghu (USA), and M. Molina-Molina (Spain) reviewed the new guideline updates in a panel discussion.21
IPF is a chronic, fibrosing interstitial pneumonia of unknown cause associated with radiological and histologic features of usual interstitial pneumonia. It is characterized by the irreversible loss of lung function due to fibrosis, which manifests as symptoms of increasing cough and dyspnea, impaired quality of life, and decreased lung function. The disease usually carries a poor prognosis with a median survival of 2–3 years if left untreated.
Our understanding of the pathophysiology of IPF and potential therapies for IPF has significantly improved in recent years. However, there is still no treatment to prevent or stop the disease progression. IPF remains an area of high unmet clinical needs that include methods of early diagnosis, improved drug safety and efficacy, improvement in patient quality of life, and treatments for patients with severe disease.
The new guideline includes two changes in disease diagnostic strategy. First, transbronchial lung cryobiopsy (TBLC) is now considered an acceptable alternative to surgical lung biopsy in patients with ILD of an undetermined type. Medical centers with experience in performing and interpreting TBLC have demonstrated the usefulness of this procedure, thus emphasizing the importance of the chosen facility and the clinician’s experience in performing the TBLC and interpreting the samples. However, TBLC may not be appropriate for all patients. The second change to the diagnostic algorithm is that patients with a high-resolution computed tomography (HRCT) pattern of probable usual interstitial pneumonia (UIP) are now managed similarly to patients with confirmed UIP.
Clinicians must agree on a unified definition of PPF. The new guideline defines it as having at least two of the following criteria occurring within the past year with no alternative explanation:
The developers of the new guideline extrapolated the absolute decline numbers for DLCO from IPF data, correcting the ones indicated in the previous guideline of 2019 (10% and 15%, correspondingly). This correction became possible based on the number of clinical trials showing a reasonable threshold for minimally significant clinical changes.
An additional protocol update recommends against using antacid medications to treat patients with IPF to improve respiratory outcomes, as there is no evidence to support such an approach. The new guidance suggests using them only for managing symptomatic gastroesophageal reflux disease and also recommends against performing anti-reflux surgery in patients with IPF to improve respiratory outcomes.
The current therapeutic armamentarium for IPF is limited to two medications, nintedanib and pirfenidone, both oral agents that slow the progression of the disease but do not improve the quality of life and the fatal prognosis. Additionally, many patients stop using these drugs due to their significant side effects, mainly on the gastrointestinal system. The committee recommends further research regarding the efficacy and safety of pirfenidone in non-IPF ILD manifesting PPF.
Pirfenidone is a promising therapy for non-IPF PPF. However, recommendations to use the drug should be taken with caution as the estimated effects were derived from a single clinical trial with only 127 patients. The guideline recommends nintedanib for treating PPF in patients who have failed standard management for fibrotic ILD, but the effects of therapy may differ depending on the type of underlying ILD; further research is necessary to investigate the efficacy and safety.
The use of corticosteroids in IPF cases has been widely discussed. Corticosteroids have been the mainstay of IPF therapy for decades. Still, their efficacy is not well-proven which, in combination with a high incidence of toxicities, calls into question their use's real benefit. However, if a patient does not reach the IPF pattern, the clinical condition may require a disease-modifying agent such as corticosteroids in an immune-modulating regimen. A case of hypersensitivity pneumonitis may also justify the use of corticosteroids.
Another point is whether physicians should use corticosteroids to treat acute exacerbation. In such situations, they can be used, but the dosage and duration of the course are left to the physician’s discretion due to a lack of clinical evidence. The route of administration (oral or intravenous) is also up to the physician, depending on the patient’s condition. Ultimately, using inhaled corticosteroids to treat acute IPF exacerbation is not clinically reasonable.
With the current lack of effective treatment for severe IPF, several abstracts focused on the search for potential therapeutic targets. A. Prasse (Germany) presented research results investigating the potential role of non-junctional claudin-1 (CLDN1) in treating IPF.22 The rationale for this research was the previously shown therapeutic effect of monoclonal antibodies targeting CLDN1 in liver fibrosis with high efficacy and safety. This study suggested that high CLDN1 expression in the bronchial epithelium may denote a subcluster of proliferating cells. Their inhibition by monoclonal antibodies may provide an opportunity for restricting pulmonary remodeling in IPF patients.
A. Jahn (Spain) presented another potential therapeutic agent, mesenchymal stem cell (MSC) derived biospheres (BS).23 The team based its hypothesis on the data that MSCs have regenerative potential and might boost this reparative effect if applied in high numbers. The study’s results demonstrated an increased regenerative potential in an in vitro lung epithelial cell model. The authors hypothesized that BS of lung MSC might be an innovative tool for treating interstitial lung diseases.
Such an approach is not unique to IPF but has also been considered for other indications. Several abstracts presented at the congress highlighted the potential role of BS in the treatment of IPF, ARDS, COPD, and acute lung injury. Biospheres or extracellular vesicles have promising potential as diagnostic and treatment agents in various therapeutic areas, including dermatology, cardiovascular, and pulmonary diseases. Still, the need for more standardization in isolation and analysis methods represents the main challenge for clinical trials.
