PDE4 Inhibitors in the Spotlight, a New Breathing Trial Opens, and Our AI Flags Three Inhaled Drug Candidates

Where things stand now

IPF still has no cure. Scar tissue that has already formed in the lungs cannot be reversed by any available medicine. The two longest-standing approved drugs, pirfenidone and nintedanib, slow the disease. A newer approved option, Nerandomilast (also called Jascayd), targets a protein called PDE4B and was approved by the FDA in October 2025. It slows disease progression but does not undo damage. Inhaled Treprostinil (Tyvaso) completed a positive Phase III trial and an FDA filing is expected in 2026. Admilparant is still in its own Phase III trial. Everything else in the pipeline is investigational, meaning it is still being tested and is not available as a standard treatment.

The best option right now

For patients right now, the honestly framed picture is this: the approved anti-fibrotic drugs (including the newly approved Nerandomilast) can slow how fast the disease gets worse, but none of them restore lost lung function or remove scar tissue. Which drug fits a specific person depends on their other health conditions and how they tolerate side effects. A new paper this week looked at how body weight and BMI affect patients taking nintedanib in trials, which is a useful reminder that individual factors matter a lot. Patients should make decisions with their own specialist. No drug in the current data guarantees results.

How close are we to regeneration

Actual lung regeneration, meaning regrowing healthy tissue to replace scar, is a research goal, not an available treatment. The most forward-looking experimental ideas in the current data include uPAR-CAR-T therapy, which uses engineered immune cells to clear out old, damaged cells that drive scarring (still preclinical, meaning tested only in the lab, not yet in people). A combination approach pairing senolytics (drugs that clear out those same damaged cells) with a molecule called RSPO3 to help grow new lung cells is still at the concept and preclinical stage. These are promising directions, but there is a long road of testing before anything like this would be available to patients.

Study of the week

The study of the week, by Kurasawa, Tanaka, Miyao, and colleagues, published in Respiratory Investigation in 2026, looked at fluid collected from deep in patients' lungs during a procedure called bronchoalveolar lavage, which is basically a gentle rinse of the airways that doctors can analyze. The researchers measured dozens of small signaling proteins called cytokines in that fluid, then used a computer to group patients into clusters based on their cytokine patterns. The finding is that different cytokine patterns seem to predict different outcomes, meaning some patient groups do better and some do worse. This matters because it hints that IPF and related lung diseases may not be one single thing but a collection of subtypes. If doctors could one day identify which subtype a patient has, they might be able to choose treatments more precisely. This is early research and does not change treatment today.

What changed since last week

No trials that were already running changed status this week. One brand new trial opened (NCT07820254), recruiting patients to study inspiratory flow rate capability, which is a measure of how forcefully a person with pulmonary fibrosis can breathe in through an inhaler device. This is important because if patients cannot inhale strongly enough, inhaled medicines may not reach deep into the lungs where they are needed. Twelve new papers appeared across topics including PDE4 inhibitors as a drug class, side effect comparisons between pirfenidone and nintedanib, pulmonary hypertension (high blood pressure in the lung's blood vessels) as a complication of fibrosis, and the harm caused by delayed diagnosis.

What our own software did this week

The following is output from PF-Atlas's own software, a genetic-algorithm solver combined with an AI literature scan. This is our own platform's computer-generated output, not outside clinical findings, and these are hypotheses for researchers to consider, not treatments or proven therapies. This week the software ran four scans and flagged three new candidate ideas: an inhaled form of Triiodothyronine (T3) targeting a receptor called TRb1, which is a thyroid hormone angle on fibrosis; a molecule called Radioprotectin-1 (RP-1), which is a selective activator of a receptor called LPA2 and could work in the opposite direction to the LPA1 blockers already in trials; and an inhaled form of Neuregulin-1b (NRG1b), a protein that may support lung cell repair. The software also added two entries involving Human Urine-Derived Stem Cells to its research pool. None of these are available treatments. They are computer-generated starting points that researchers may choose to investigate further.

Sources this week

• Inspiratory Flow Rate Capability in Pulmonary Fibrosis Patients · new trial NCT07820254 on ClinicalTrials.gov ↗

• TBDs: To test or not test. · American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists 2026 PMID 42768725 on PubMed ↗
• The emerging role of PDE4 inhibitors for the treatment of pulmonary fibrosis. · Expert review of clinical pharmacology 2026 PMID 42768757 on PubMed ↗
• Epidemiological and Clinical Characteristics of Interstitial Lung Diseases in Kuwait: A Nine-Year Single-Center Observational Prospective Study. · Medical principles and practice : international journal of the Kuwait University, Health Science Centre 2026 PMID 42766484 on PubMed ↗
• Review of the Impact of Weight Loss and Body Mass Index in Clinical Trials of Nintedanib in Interstitial Lung Disease. · Advances in therapy 2026 PMID 42766097 on PubMed ↗
• Characteristics, prognosis, and risk factors for relapse in patients with cryptogenic organizing pneumonia: A prospective cohort study in China. · Chinese medical journal 2026 PMID 42604996 on PubMed ↗
• Gastrointestinal and skin safety evaluation of pirfenidone versus nintedanib: an analysis of real-world pharmacovigilance and randomized controlled trials. · Naunyn-Schmiedeberg's archives of pharmacology 2026 PMID 42760377 on PubMed ↗
• Non-invasive risk stratification of pulmonary hypertension in idiopathic pulmonary fibrosis: a screening approach from a prospective observational study. · Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace 2026 PMID 42765303 on PubMed ↗
• The Efficacy of Antifibrotics in Combined Pulmonary Fibrosis and Emphysema: A Nationwide Multicentre Retrospective Cohort Study. · Archivos de bronconeumologia 2026 PMID 42760209 on PubMed ↗
• Impact of time to diagnosis in patients with progressive fibrotic ILD: a systematic review. · BMJ open respiratory research 2026 PMID 42760140 on PubMed ↗
• Pirfenidone exerts anti-inflammatory effects by inhibiting CXCL6 to alleviate idiopathic pulmonary fibrosis. · International immunopharmacology 2026 PMID 42759355 on PubMed ↗
• Bronchoalveolar lavage fluid cytokine-based clustering identifies prognostically relevant cytokine phenotypes across interstitial lung diseases. · Respiratory investigation 2026 PMID 42759121 on PubMed ↗
• Prevalence and predictors of pulmonary hypertension in patients with progressive pulmonary fibrosis: A retrospective study. · Respiratory investigation 2026 PMID 42759120 on PubMed ↗
• Residential indoor air monitoring to assess long-term exposure to air pollution in susceptible populations for epidemiology: overview and early findings. · Environmental health : a global access science source 2026 PMID 42754883 on PubMed ↗
• Methodological Clarification is Needed Regarding Joinpoint Analyses and ICD-10 Coding of Idiopathic Pulmonary Fibrosis Mortality in Spain. · Archivos de bronconeumologia 2026 PMID 42754499 on PubMed ↗
• Cadherin-11 Regulation of Type II Alveolar Epithelial Cells During Pulmonary Fibrosis. · American journal of physiology. Cell physiology 2026 PMID 42750185 on PubMed ↗
• Pathological Th2 cell activation via STAT6 pathway for pulmonary fibrosis. · American journal of respiratory cell and molecular biology 2026 PMID 42750119 on PubMed ↗
• Dupilumab Alleviates Pulmonary Fibrosis by Interrupting Profibrotic Macrophage-Fibroblast Crosstalk and IL4R/JAK/STAT Signaling. · Lung 2026 PMID 42747578 on PubMed ↗
• Mannose-modified tobacco mosaic virus-mediated macrophage regulation inhibits pulmonary fibrosis progression. · Journal of materials chemistry. B 2026 PMID 42544440 on PubMed ↗
• Corrigendum to "Evaluation of radiological lung pattern and disease progression in patients with asbestosis compared to patients with idiopathic pulmonary fibrosis" [Respir. Med. 262, (2026)]. · Respiratory medicine 2026 PMID 42744670 on PubMed ↗
• Randomised controlled trial of partitioned aerobic exercise training using one-leg cycling in patients with idiopathic pulmonary fibrosis. · Thorax 2026 PMID 42744588 on PubMed ↗