Development of a multivariable prediction model for progression of systemic sclerosis-associated interstitial lung disease.

OBJECTIVE: To develop a multivariable model for predicting the progression of systemic sclerosis-associated interstitial lung disease (SSc-ILD) over 52 weeks. METHODS: We used logistic regression models to analyse associations between candidate predictors assessed at baseline and progression of SSc-ILD (absolute decline in forced vital capacity (FVC) % predicted >5% or death) over 52 weeks in the placebo group of the SENSCIS trial. Analyses were performed in the overall placebo group and in a subgroup with early and/or inflammatory SSc and/or severe skin fibrosis (<18 months since first non-Raynaud symptom, elevated inflammatory markers, and/or modified Rodnan skin score (mRSS) >18) at baseline. Model performance was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: In the overall placebo group (n=288), the performance of the final multivariable model for predicting SSc-ILD progression was moderate (apparent AUC: 0.63). A stronger model, with an apparent AUC of 0.75, was developed in the subgroup with early and/or inflammatory SSc and/or severe skin fibrosis at baseline (n=155). This model included diffusing capacity of the lung for carbon monoxide (DLco) % predicted, time since first non-Raynaud symptom, mRSS, anti-topoisomerase I antibody status and mycophenolate use. CONCLUSION: Prediction of the progression of SSc-ILD may require different approaches in distinct subgroups of patients. Among patients with SSc-ILD and early and/or inflammatory SSc and/or severe skin fibrosis, a nomogram based on a multivariable model may be of value for identifying patients at risk of short-term progression.

Effect of abatacept versus conventional synthetic disease modifying anti-rheumatic drugs on rheumatoid arthritis-associated interstitial lung disease.

BACKGROUND/AIMS: To compare the effects of abatacept and conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) on the progression and development of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: This multi-center retrospective study included RA patients receiving abatacept or csDMARDs who underwent at least two pulmonary function tests and/or chest high-resolution computed tomography (HRCT). We compared the following outcomes between the groups: progression of RA-ILD, development of new ILD in RA patients without ILD at baseline, 28-joint Disease Activity Score with the erythrocyte sedimentation rate (DAS28-ESR), and safety. Longitudinal changes were compared between the groups by using a generalized estimating equation. RESULTS: The study included 123 patients who were treated with abatacept (n = 59) or csDMARDs (n = 64). Nineteen (32.2%) and 38 (59.4%) patients treated with abatacept and csDMARDs, respectively, presented with RA-ILD at baseline. Newly developed ILD occurred in one patient receiving triple csDMARDs for 32 months. Among patients with RA-ILD at baseline, ILD progressed in 21.1% of cases treated with abatacept and 34.2% of cases treated with csDMARDs during a median 21-month follow-up. Longitudinal changes in forced vital capacity and diffusing capacity for carbon monoxide were comparable between the two groups. However, the abatacept group showed a more significant decrease in DAS28-ESR and glucocorticoid doses than csDMARDs group during the follow-up. The safety of both regimens was comparable. CONCLUSION: Abatacept and csDMARDs showed comparable effects on the development and stabilization of RA-ILD. Nevertheless, compared to csDMARDs, abatacept demonstrated a significant improvement in disease activity and led to reduced glucocorticoid use.

Outcome of immune checkpoint inhibitor treatment in non-small cell lung cancer patients with interstitial lung abnormalities: clinical utility of subcategorizing interstitial lung abnormalities.

Interstitial lung abnormalities (ILAs) are immune checkpoint inhibitor (ICI)-related pneumonitis (ICI-P) risk factors. However, the relationship between imaging patterns and immunotherapy outcomes, and treatment strategies remain unclear in patients with non-small cell lung cancer (NSCLC) and ILAs. We retrospectively evaluated patients with ILAs-complicated NSCLC who received ICI therapy. ILAs were subcategorized as non-subpleural, subpleural non-fibrotic, and subpleural fibrotic (SF) based on the 2020 position paper by the Fleischner Society. We investigated ICI-P incidence, ICI-P risk factors, lung cancer prognosis, and ILAs radiological progression. Of the 481 ICI-treated patients, 79 (16.4%) had ILAs (45 non-SF and 34 SF). The ICI-P cumulative incidence (hazard ratio, 4.57; 95% confidence interval [CI], 1.90-10.98; p = 0.001) and any grade and grade ≥ 3 ICI-P incidences were higher in patients with SF-ILAs than in those with non-SF-ILAs (all grades: 7/45 [15.6%)] vs. 18/34 [52.9%]; p < 0.001; grade ≥ 3: 1/45 [2.2%] vs. 10/34 [29.4%]; p = 0.001). According to multivariate analysis, SF-ILAs independently predicted ICI-P (odds ratio, 5.35; 95% CI 1.62-17.61; p = 0.006). Patients with SF-ILAs had shorter progression-free and overall survival and higher ICI-P-related respiratory failure death rates than those with non-SF-ILAs. Approximately 2.5 times more patients with SF-ILAs showed progression by the 2-year follow-up than those with non-SF-ILAs. SF-ILAs is an independent strong predictor of ICI-P development in patients with NSCLC, may increase ICI-P severity, worsen prognosis, and accelerate ILAs progression. ILAs subcategorization is an important treatment strategy for patients with lung cancer treated with ICIs.

Hallazgos imagenológicos torácicos en seguimiento de pacientes con síndrome PostCovid-19 / Thoracic imagenological findings in follow-up of patients with Post-Covid-19 syndrome

Objetivo: Describir los hallazgos imagenológicos en radiografías de tórax y ecografías pulmonares de pacientes con síndrome post-COVID-19. Métodos: estudio descriptivo, prospectivo y transversal que incluyó pacientes con síndrome post-COVID-19, sometidos a radiografías de tórax y ecografías pulmonares en el Servicio de Neumonología Clínica del Hospital Dr. José Ignacio Baldo, entre enero y octubre de 2022, con la finalidad de establecer su evolución imagenológica pulmonar. Se utilizó estadística descriptiva, chi-cuadrado de Pearson y prueba kappa de concordancia, considerando significativo un valor de p < 0,05. Resultados: La muestra consistió en 58 pacientes con una edad media de 55 ± 13 años, predominando el sexo femenino (58,6%). El 60,3% mostró alteraciones en la radiografía de tórax; un 74,3% con patrón intersticial bilateral y un 25,7% con patrón intersticial unilateral. La ecografía reveló patrón intersticial en el 43,1% de los casos y se observaron dos microconsolidaciones subpleurales. Conclusiones: Las radiografías de tórax y las ecografías pulmonares son herramientas imagenológicas eficaces, accesibles y económicas para detectar alteraciones en pacientes con síndrome post-COVID-19. (AU)

Objective: To describe imaging findings in chest radiographs and lung ultrasounds of patients with post-COVID-19 syndrome. Methods: A descriptive, prospective, and cross-sectional study was carried out that included patients with post-COVID-19 syndrome, who underwent chest radiographs and lung ultrasounds at the Clinical Pneumonology Service of Dr. José Ignacio Baldo Hospital, between January and October 2022. Descriptive statistics, Pearson's chi-square, and kappa concordance test were used, considering a p-value < 0.05 significant. Results: The sample consisted of 58 patients with an average age of 55 ± 13 years, with a predominance of females (58.6%). 60.3% showed alterations in the chest radiograph; 74.3% with a bilateral interstitial pattern and 25.7% with a unilateral interstitial pattern. The ultrasound revealed an interstitial pattern in 43.1% of the cases and two subpleural microconsolidations were observed. Conclusions: Chest radiographs and lung ultrasounds are effective, accessible, and economical imaging tools to detect alterations in patients with post-COVID-19 syndrome. (AU)

Evidence from recent clinical trials in fibrotic interstitial lung diseases.

PURPOSE OF REVIEW: Idiopathic pulmonary fibrosis (IPF) is the prototype of fibrosing interstitial lung diseases. It is mirrored by progressive pulmonary fibrosis (PPF), an umbrella term which characterizes disease behavior of various fibrotic interstitial lung diseases with irreversible progression, accounting for loss of lung function, exercise intolerance and respiratory failure leading to early mortality. Pirfenidone and nintedanib halve the decline in lung function but do not halt disease progression. RECENT FINDINGS: Since the publication in 2014 of pivotal pirfenidone and nintedanib studies, a number of clinical trials were conducted, many of them did not reach their primary endpoints. In IPF, promising phase 2 trials were followed by large phase 3 trials that did not confirm a favorable efficacy to tolerability favorable profile, including those with ziritaxestat, an autotaxin-1 inhibitor, zinpentraxin-alpha (human recombinant pentraxin-2), and the monoclonal antibody pamrevlumab targeting connective tissue growth factor. Nevertheless, newer compounds that hold promise are currently being evaluated in phase 3 or phase 2b randomized controlled trials, including: nerandomilast, a preferential phosphodiesterase 4B inhibitor; admilparant, a lysophosphatidic acid receptor antagonist; inhaled treprostinil, a prostacyclin agonist; and bexotegrast, a dual-selective inhibitor of αvß6 and αvß1 integrins. Nerandomilast, admilparant, inhaled treprostinil, and inhaled AP01 (pirfenidone), are currently studied in patients with PPF. SUMMARY: Despite recent frustrating negative results, there is a growing portfolio of candidate drugs developed in both IPF and PPF.

Value of bronchoalveolar lavage fluid metagenomic next-generation sequencing in acute exacerbation of fibrosing interstitial lung disease: an individualized treatment protocol based on microbiological evidence.

BACKGROUND: Acute exacerbation of fibrosing interstitial lung diseases (AE-ILD) is a serious life-threatening event per year. Methylprednisolone and/or immunosuppressive agents (ISA) are a mainstay in any regimen, under the premise that pulmonary infection has been promptly identified and controlled. We investigated the value of bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) on the treatment adjustment of AE-ILD. METHODS: We conducted a cross-sectional observational study. All data were collected prospectively and retrospectively analyzed. We included fifty-six patients with AE-ILD and nineteen stable ILD who underwent BALF mNGS at the beginning of admission. RESULTS: Patients with a variety of ILD classification were included. Connective-tissue disease related ILD (CTD-ILD) occupy the most common underlying non-idiopathic pulmonary fibrosis (non-IPF). The infection-triggered AE accounted for 39.29%, with the majority of cases being mixed infections. The microorganisms load in the AE-ILD group was significantly higher. After adjusted by mNGS, the therapy coverage number of pathogens was significantly higher compared to the initial treatment (p < 0.001). After treatment, the GGO score and the consolidation score were significantly lower during follow up in survivors (1.57 ± 0.53 vs. 2.38 ± 0.83 with p < 0.001, 1.11 ± 0.24 vs. 1.49 ± 0.47 with p < 0.001, respectively). Some detected microorganisms, such as Tropheryma whipplei, Mycobacterium, Aspergillus, and mixed infections were difficult to be fully covered by empirical medication. BALF mNGS was also very helpful for excluding infections and early administration of methylprednisolone and/or ISA. CONCLUSIONS: mNGS has been shown to be a useful tool to determine pathogens in patients with AE-ILD, the results should be fully analyzed. The comprehensive treatment protocol based on mNGS has been shown crucial in AE-ILD patients.

Key learnings from the INBUILD trial in patients with progressive pulmonary fibrosis.

In a patient with interstitial lung disease (ILD) of known or unknown etiology other than idiopathic pulmonary fibrosis (IPF), progressive pulmonary fibrosis (PPF) is defined by worsening lung fibrosis on high-resolution computed tomography (HRCT), decline in lung function, and/or deterioration in symptoms. The INBUILD trial involved 663 patients with PPF who were randomized to receive nintedanib or placebo. The median exposure to trial medication was approximately 19 months. The INBUILD trial provided valuable learnings about the course of PPF and the efficacy and safety of nintedanib. The relative effect of nintedanib on reducing the rate of forced vital capacity decline was consistent across subgroups based on ILD diagnosis, HRCT pattern, and disease severity at baseline, and between patients who were and were not taking glucocorticoids or disease-modifying anti-rheumatic drugs and/or glucocorticoids at baseline. The adverse events most frequently associated with nintedanib were gastrointestinal, particularly diarrhea, but nintedanib was discontinued in only a minority of cases. The results of the INBUILD trial highlight the importance of prompt detection and treatment of PPF and the utility of nintedanib as a treatment option.

What did we find out from the INBUILD trial about progressive lung fibrosis?Lung fibrosis is a rare disease in which the lung tissue becomes scarred and hardened. This makes it more difficult for the lungs to inflate and for the lungs to exchange oxygen with the blood. In some patients, lung fibrosis gets worse over time. This is known as progressive lung fibrosis. In the INBUILD trial, researchers looked at the effects of a drug called nintedanib in patients with progressive lung fibrosis. In this trial, 663 patients were randomly allocated to receive either nintedanib or a placebo and then followed for approximately 19 months. The patients and the researchers did not know which patients were taking the active drug (nintedanib) and which patients were taking placebo. The results showed that the criteria used to find patients with progressive lung fibrosis to take part in the trial successfully identified patients whose disease would continue to worsen. These criteria were based on a decline in the volume (size) of the lungs, worsening symptoms such as shortness of breath, and worsening of changes seen on a scan of the chest. The trial results also showed that nintedanib slowed down loss of lung function and had a similar benefit in patients with different severities of disease at the start of the trial. The most common side-effects of nintedanib were gastrointestinal problems, particularly diarrhea, but most patients given nintedanib were able to cope with these side-effects without needing to stop treatment. Large trials like the INBUILD trial are important for helping us understand how diseases progress and in which patients particular drugs should be used.

Anti-Helicobacter pylori Infection Treatment and Pulmonary Hypersensitivity: Case Series and Review of the Literature.

BACKGROUND: Helicobacter pylori (H. pylori) infection is currently widespread throughout the world. Bismuth-containing quadruple therapy is widely used, but it has rarely been associated with interstitial lung disease. CASE PRESENTATION: We described six cases with similar clinical symptoms and typical pulmonary interstitial imaging changes during anti-H. pylori therapy, usually on Days 7-12 following treatment. Anti-H. pylori infection treatment was discontinued when it was suspected to be the cause of the clinical symptoms, and all of the patients accepted observation therapy. All of them had a favorable outcome, the clinical symptoms returned to normal almost 1 week later, and the chest computed tomography (CT) scan images showed remarkable absorption 4 weeks later. CONCLUSIONS: Drug interactions could be the cause, and the most likely drug was furazolidone. All of the patients recovered quickly after drug discontinuation, and low-dose steroid may help shorten the recovery time.

Abatacept versus tumor necrosis factor inhibitors on mortality and medical utilizations in the treatment of rheumatoid arthritis associated interstitial lung disease: a large-scale real-world retrospective cohort study.

Rheumatoid arthritis is a chronic inflammatory disease, and interstitial lung disease is one of the important extra-articular manifestations. There is limited evidence comparing abatacept (ABA) and tumor necrosis factor inhibitors (TNFi) regarding the risk of mortality among patients with rheumatoid arthritis associated interstitial lung disease (RA-ILD). The aim of this study is to investigate the risk of mortality in patients with RA-ILD treated with ABA compared to TNFi. This retrospective cohort study utilized TriNetX electronic health record database. We enrolled patients who were diagnosed with RA-ILD and had received a new prescription for either ABA or TNFi. Patients were categorized into two cohorts based on their initial prescription. The primary outcome was all-cause mortality, and secondary outcomes were healthcare utilizations, including hospitalization, critical care services, and mechanical ventilation. Subgroup analyses were performed on age, presence of anti-citrullinated peptide antibodies (ACPA), and cardiovascular risk. Among 34,388 RA-ILD patients, 895 were selected for each group (ABA and TNFi) following propensity score matching. The ABA group exhibited a higher all-cause mortality risk. (HR 1.296, 95% CI 1.006-1.671). Subgroup analysis showed a heightened risk of receiving mechanical ventilation in ABA-treated patients aged 18-64 years old (HR 1.853, 95% CI 1.002-3.426), and those with cardiovascular risk factors (HR 2.015, 95% CI 1.118-3.630). Another subgroup analysis indicated a higher risk of mortality among ABA-treated patients with positive-ACPA. (HR 4.138 95% CI 1.343-12.75). This real-world data research demonstrated a higher risk of all-cause mortality in RA-ILD patients treated with ABA compared to TNFi, particularly those aged 18-64 years, lacking cardiovascular risk factors, and positive-ACPA. ABA was associated with an increased risk of mechanical ventilation in patients aged 18-64 years and those with cardiovascular risk factors.

Tocilizumab Treatment in a Patient of Refractory Anti-EJ Positive ASyS: A Case Report.

Anti-synthetase syndrome (ASyS) is an autoimmune disease characterized by the presence of autoantibodies to aminoacyl-tRNA synthetases accompanied with various organ involvements, including the lung, joints, and skin. The ASyS-related interstitial lung disease (ILD) can be seen in the vast majority of patients. The extent of lung involvement has a significant impact on patient prognosis; the occurrence of rapid-progressive ILD could prominently increase mortality. The mainstay of treatment is prednisone in combination with conventional synthetic disease-modifying anti-rheumatic drugs or some biologic disease-modifying anti-rheumatic drugs (DMARDs). Tocilizumab (TCZ), a recombinant humanized anti-interleukin (IL)-6 receptor monoclonal antibody, has also been used to treat some systemic autoimmune rheumatic diseases associated with ILD. Although the most recent American College of Rheumatology (ACR) Guideline for the Treatment of Interstitial Lung Disease conditionally recommends against the use of TCZ as a treatment option for people with idiopathic inflammatory myopathy (IIM)-ILD progression despite initial ILD treatment, the treatment effect of TCZ in ASyS patients remains obscure, particularly for refractory cases with anti-non-Jo1 antibodies. This report describes a case of Chinese ASyS patients with anti-EJ-positive antibodies who presented with typical proximal muscle weakness, elevated creatine kinase, and ILD with non-specific interstitial pneumonia (NSIP) pattern, along with typical skin involvement such as mechanic's hand. The patients were resistant to various treatments, including rituximab (RTX), but benefited from TCZ. In this case, TCZ shows good therapeutic efficacy in a fatal acute exacerbation of ILD with a hyperinflammatory status, resulting in a relative remission of the disease flare and full preservation of lung function with a positive long-term treatment outcome.

Clinical best practices in interdisciplinary management of human epidermal growth factor receptor 2 antibody-drug conjugates-induced interstitial lung disease/pneumonitis: An expert consensus in China.

Antibody-drug conjugates (ADCs) have demonstrated effectiveness in treating various cancers, particularly exhibiting specificity in targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Recent advancements in phase 3 clinical trials have broadened current understanding of ADCs, especially trastuzumab deruxtecan, in treating other HER2-expressing malignancies. This expansion of knowledge has led to the US Food and Drug Administration's approval of trastuzumab deruxtecan for HER2-positive and HER2-low breast cancer, HER2-positive gastric cancer, and HER2-mutant nonsmall cell lung cancer. Concurrent with the increasing use of ADCs in oncology, there is growing concern among health care professionals regarding the rise in the incidence of interstitial lung disease or pneumonitis (ILD/p), which is associated with anti-HER2 ADC therapy. Studies on anti-HER2 ADCs have reported varying ILD/p mortality rates. Consequently, it is crucial to establish guidelines for the diagnosis and management of ILD/p in patients receiving anti-HER2 ADC therapy. To this end, a panel of Chinese experts was convened to formulate a strategic approach for the identification and management of ILD/p in patients treated with anti-HER2 ADC therapy. This report presents the expert panel's opinions and recommendations, which are intended to guide the management of ILD/p induced by anti-HER2 ADC therapy in clinical practice.

A case report of interstitial pneumonia induced by vedolizumab in a patient with ulcerative colitis.

RATIONALE: The interstitial pneumonia (IP) linked to vedolizumab (VDZ) in patients with ulcerative colitis (UC) is rare. Prompt diagnosis and treatment can improve patient outcomes. PATIENT CONCERNS: A 39-year-old man with UC who received VDZ as sole therapy developed symptoms such as chest tightness, cough, and suffocation. DIAGNOSES: IP was confirmed through pulmonary function tests, chest computed tomography, and bronchoscopic biopsy. INTERVENTIONS: The patient was given methylprednisolone and VDZ cessation. OUTCOMES: The patient's symptoms improved and remained symptom-free after nearly 2 years. LESSONS: VDZ-induced IP should be considered when evaluating pulmonary infections in UC patients treated with VDZ.

Tocilizumab plus Nintedanib for progressive interstitial lung disease in systemic sclerosis: a one-year observational study.

Randomized controlled trials have recently shown that both the IL-6 inhibitor Tocilizumab and the antifibrotic Nintedanib are efficacious for Systemic Sclerosis (SSc)-associated progressive interstitial lung disease (ILD). Since real-world clinical data on Tocilizumab/Nintedanib combination are lacking, we report on their long-term safety and efficacy. Consecutive patients who received off-label Tocilizumab for SSc plus Nintedanib for progressive ILD were retrospectively studied. Adverse events, and changes in Forced Vital Capacity (FVC), Diffucing Capacity for Carbon Monoxide (DLCO) and high resolution chest tomography (HRCT) between baseline and 6 and 12 months were assessed. Tocilizumab/Nintedanib combination was well tolerated by all 20 patients [aged 52 ± 13 years (mean ± SD), 14 women, 15 diffuse SSc, disease duration of 5.7 ± 4.9 years]; 7 of 20 patients received concomitant mycophenolate mofetil safely. No serious adverse events or laboratory abnormalities were noted. Five patients developed persistent diarrhea and 2 of them reduced dosage of Nintedanib. Baseline FVC (74%±12%) and DLCO (45%±10%) remained overall stable both at 6 months (73.5%±13% and 46%±11%, respectively) and 12 months (73%±14% and 45%±11%, respectively), regardless of disease duration. The extent of fibrotic reticular pattern in available pairs of HRCTs (n = 12) remained also stable at 12 months, whereas proportion (%) of ground glass opacities decreased from 29%±16 to 21%±14% (p = 0.048); improvement in HRCTs by almost 75% was noted in 2 of these12 patients. Tocilizumab/Nintedanib combination for one year was safe and stabilized lung function in real-world SSc patients with progressive ILD. Additional studies of this combination treatment in SSc-ILD are warranted.

Selexipag for patients with pulmonary hypertension associated with lung disease: A preliminary study.

BACKGROUND: Pulmonary arterial hypertension (PAH)-specific therapies are generally ineffective in patients with pulmonary hypertension associated with lung disease (PH-LD). The aim of this preliminary study was to evaluate the potential efficacy of selexipag, titrated according to individual tolerance, in patients with PH-LD. METHODS: Consecutive patients diagnosed with PH-LD between October 2016 and March 2019, who received selexipag treatment, were retrospectively evaluated. Specific parameters, including changes in hemodynamic parameters, 6-min walk distance (6MWD), and partial pressure of atrial oxygen/fraction of inspiratory oxygen (PaO2/FiO2) were evaluated. Patients whose 6MWD improved ≥20 m were defined as responders. RESULTS: Eight patients with PH-LD were included, comprising four with chronic obstructive pulmonary disease (COPD), two with interstitial lung disease (ILD) related to rheumatoid arthritis, one with ILD related to systemic sclerosis, and one with pulmonary Langerhans cell histiocytosis. No statistically significant improvements in hemodynamic parameters and 6MWD were noted following selexipag treatment. However, four patients showed improvements in 6MWD ≥20 m at follow-up and were considered responders. They had a higher body mass index (BMI) and lower PaO2/FiO2 at baseline than non-responders (p = 0.02 and p = 0.04, respectively). No Grade 3 or 4 adverse events were observed. CONCLUSIONS: Selexipag was effective in half of the PH-LD cases, emphasizing higher BMI and lower PaO2/FiO2 as possible indicators for favorable response. Since selexipag starting at a low dose with subsequent titration may reduce the risk of early adverse events, it can be considered a treatment option for PH-LD. Further large-scale studies are warranted to confirm these findings.

Rheumatoid arthritis extra-articular lung disease: new insights on pathogenesis and experimental drugs.

INTRODUCTION: Pulmonary involvement is one of the most common extra-articular manifestations of rheumatoid arthritis (RA), a systemic inflammatory disease characterized by joint swelling and tenderness. All lung compartments can be interested in the course of RA, including parenchyma, airways, and, more rarely, pleura and vasculature. AREAS COVERED: The aim of this paper is to review the main RA lung manifestations, focusing on pathogenesis, clinical and therapeutic issues of RA-related interstitial lung disease (ILD). Despite an increasing number of studies in the last years, pathogenesis of RA-ILD remains largely debated and the treatment of RA patients with lung involvement is still challenging in these patients. EXPERT OPINION: Management of RA-ILD is largely based on expert-opinion. Due to the broad clinical manifestations, including both joints and pulmonary involvement, multidisciplinary discussion, including rheumatologist and pulmonologist, is essential, not only for diagnosis, but also to evaluate the best therapeutic approach and follow-up. In fact, the coexistence of different lung manifestations may influence the treatment response and safety. The identification of biomarkers and risk-factors for an early identification of RA patients at risk of developing ILD remains a need that still needs to be fulfilled, and that will require further investigation in the next years.

Antifibrotic therapy in progressive pulmonary fibrosis: a review of recent advances.

INTRODUCTION: Progressive pulmonary fibrosis (PPF) is a manifestation of a heterogenous group of underlying interstitial lung disease (ILD) diagnoses, defined as non-idiopathic pulmonary fibrosis (IPF) progressive fibrotic ILD meeting at least two of the following criteria in the previous 12 months: worsening respiratory symptoms, absolute decline in forced vital capacity (FVC) more than or equal to 5% and/or absolute decline in diffusing capacity for carbon monoxide (DLCO) more than or equal to 10% and/or radiological progression. AREAS COVERED: The authors subjectively reviewed a synthesis of literature from PubMed to identify recent advances in the diagnosis and characterisation of PPF, treatment recommendations, and management challenges. This review provides a comprehensive summary of recent advances and highlights future directions for the diagnosis, management, and treatment of PPF. EXPERT OPINION: Recent advances in defining the criteria for PPF diagnosis and licensing of treatment are likely to support further characterisation of the PPF patient population and improve our understanding of prevalence. The diagnosis of PPF remains challenging with the need for a specialised ILD multidisciplinary team (MDT) approach. The evidence base supports the use of immunomodulatory therapy to treat inflammatory ILDs and antifibrotic therapy where PPF develops. Treatment needs to be tailored to the specific underlying disease and determined on a case-by-case basis.

Radioproteomics stratifies molecular response to antifibrotic treatment in pulmonary fibrosis.

Antifibrotic therapy with nintedanib is the clinical mainstay in the treatment of progressive fibrosing interstitial lung disease (ILD). High-dimensional medical image analysis, known as radiomics, provides quantitative insights into organ-scale pathophysiology, generating digital disease fingerprints. Here, we performed an integrative analysis of radiomic and proteomic profiles (radioproteomics) to assess whether changes in radiomic signatures can stratify the degree of antifibrotic response to nintedanib in (experimental) fibrosing ILD. Unsupervised clustering of delta radiomic profiles revealed 2 distinct imaging phenotypes in mice treated with nintedanib, contrary to conventional densitometry readouts, which showed a more uniform response. Integrative analysis of delta radiomics and proteomics demonstrated that these phenotypes reflected different treatment response states, as further evidenced on transcriptional and cellular levels. Importantly, radioproteomics signatures paralleled disease- and drug-related biological pathway activity with high specificity, including extracellular matrix (ECM) remodeling, cell cycle activity, wound healing, and metabolic activity. Evaluation of the preclinical molecular response-defining features, particularly those linked to ECM remodeling, in a cohort of nintedanib-treated fibrosing patients with ILD, accurately stratified patients based on their extent of lung function decline. In conclusion, delta radiomics has great potential to serve as a noninvasive and readily accessible surrogate of molecular response phenotypes in fibrosing ILD. This could pave the way for personalized treatment strategies and improved patient outcomes.