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Background and Purpose: Toll‐like receptors 4 (TLR4) and TLR7/TLR8 play an important role in mediating the inflammatory effects of bacterial and viral pathogens. Interleukin‐1 receptor‐associated kinase 4 (IRAK4) is an important regulator of signalling by toll‐like receptor (TLR) and hence is a potential therapeutic target in diseases characterized by increased lung inflammatory signalling. Experimental Approach: We used an established murine model of acute lung inflammation, and studied human lung tissue ex vivo, to investigate the effects of inhibiting IRAK4 on lung inflammatory pathways. Key Results: We show that TLR4 stimulation produces an inflammatory response characterized by neutrophil influx and tumour necrosis factor‐α (TNF‐α) production in murine lungs and that these responses are markedly reduced in IRAK4 kinase‐dead mice. In addition, we characterize a novel selective IRAK4 inhibitor, BI1543673, and show that this compound can reduce lipopolysaccharide (LPS)‐induced airway inflammation in wild‐type mice. Additionally, BI1543673 reduced inflammatory responses to both TLR4 and TLR7/8 stimulation in human lung tissue studied ex vivo. Conclusion and Implications: These data demonstrate a key role for IRAK4 signalling in lung inflammation and suggest that IRAK4 inhibition has potential utility to treat lung diseases characterized by inflammatory responses driven through TLR4 and TLR7/8. [ABSTRACT FROM AUTHOR]

To evaluate experience in a tertiary rheumatology service with melanoma differentiation‐association‐protein‐5 (MDA5) disease and testing, patients with positive autoantibody results were reviewed for the presence of clinical disease. Anti‐MDA5 positivity was detected in 2% of myositis‐specific antibody tests. Of these, 29% did not have features consistent with anti‐MDA5 disease. However, when present, MDA5 disease is severe with a high mortality. [ABSTRACT FROM AUTHOR]

Background: Patients with early‐stage lung cancer and interstitial lung disease have a poorer prognosis than those without interstitial lung disease. This study aimed to compare the long‐term outcomes of lobar and sublobar resections in these patients. Methods: We retrospectively analyzed 138 consecutive patients with clinical stage I non‐small cell lung cancer and interstitial lung disease who underwent surgical treatment at two institutions between January 2010 and December 2020. Propensity score matching analysis was performed to adjust for baseline characteristics. Results: Thirty‐six patients underwent sublobar resection and 102 underwent lobar resection. The median follow‐up was 45.7 months. In all patients, 5‐year overall survival (OS) rates were 33.2% and 73.2%, and 5‐year recurrence‐free survival (RFS) rates were 24.2% and 60.1% in the sublobar and lobar resection groups, respectively (p < 0.01, <0.01). Death due to lung cancer and locoregional recurrence were significantly more frequent in the sublobar resection group than in the lobar resection group (p = 0.034, <0.01, respectively). On propensity score matching analysis, the 5‐year OS rates of the 19 matched pairs were 46.3% and 73.2%, and the RFS rates were 31.6% and 67.6% in the sublobar and lobar resection groups, respectively (p = 0.036, <0.01). The Cox proportional hazards model demonstrated a significant association between lobar resection and improved survival (p = 0.047). Conclusion: The patients in the lobar resection group had better survival rates than those in the sublobar resection group. In terms of long‐term prognosis, deliberately limited surgery may not be necessary for patients who tolerate lobectomy. [ABSTRACT FROM AUTHOR]

Background and Objective: The global incidence of interstitial lung disease (ILD) has risen over the past few decades. However, few studies have evaluated the status and incidence trends of ILD in Brazil, Russia, India, China and South Africa (BRICS). This study assesses the trends of ILD incidence across the BRICS with an emphasis on ILD changes from 1990 to 2019. Methods: Incidence rates were estimated by the data obtained from the Global Burden of Disease Study 2019 (GBD 2019). Age‐period‐cohort modelling was used to estimate the effects on ILD from 1990 to 2019, and the net drift and local drift were calculated. Results: In 2019, a total of 11.4 million cases of ILD were reported in the BRICS countries. From 1990 to 2019, the incidence rate of ILD in BRICS showed an upward trend. India consistently reported the highest incidence rate, while China showed the fastest growth rate (107.6%). Russia reported a similar incidence rates for men and women, with a lower age of peak incidence compared to the other four countries. We found the time effect was unfavourable for BRICS in the first decade, especially for Brazil; in China and Brazil, the risk of people born after 1960 has rapidly decreased. Conclusion: ILD shows a rising incidence in BRICS. with the trends varying based on age and other environmental factors. BRICS should strengthen specific public health approaches and policies for different stages and populations. [ABSTRACT FROM AUTHOR]

Background: Mycophenolate mofetil (MMF) has been used to treat interstitial lung disease (ILD), but mycophenolate (MPA) pharmacokinetics was not reported for this use. This ancillary study of the EVER‐ILD protocol aimed at describing the pharmacokinetic variability of MPA using population modelling in ILD. Methods: Concentrations of MPA were measured during an 8‐h course for 27 ILD patients treated with 1000 mg MMF b.i.d. Absorption, distribution and elimination of MPA were described using population compartment models with first‐order transfer and elimination rate constants, while accounting for both absorption peaks using gamma absorption models. Results: The pharmacokinetics of MPA was best described using a two‐compartment model and two gamma absorption models, model performances of this model were still similar to those of a one gamma absorption model. This pharmacokinetics seemed to be notably influenced by body weight, renal function and inflammatory status. The distribubtion value area under the concentration curve between two administrations of MMF was AUC12 = 52.5 mg.h/L in median (interquartile range: 42.2–58.0 mg.h/L). Conclusion: This is the first study reporting MPA pharmacokinetics in ILD. This pharmacokinetics appears to be similar to other indications and should be further investigated in future studies. [ABSTRACT FROM AUTHOR]

VEXAS (Vacuoles, E1 enzyme, X‐linked, Autoinflammatory, Somatic) syndrome is a rare and recently identified disease resulting from a somatic mutation in the X‐linked UBA1 gene in cells of myeloid lineage. It can present in a myriad of ways with the potential to affect various organ systems, including the lungs. VEXAS is usually steroid responsive, but no strong data exists for the use of a steroid‐sparing agent. There is limited emerging evidence for haematopoietic stem cell transplantation in a select number of cases. Regardless, prognosis for this condition is poor and a treatment algorithm remains a priority. Herein, we present a case of VEXAS that came to attention with discovery of a relatively asymptomatic interstitial lung disease and led to recurrent febrile episodes with evolving multi‐organ involvement. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Acute digital ischemia is a rare manifestation of anti‐synthetase syndrome in the absence of Raynaud's phenomenon. A high index of suspicion may result in early diagnosis and better clinical outcomes. A 61‐year‐old male patient was admitted to the hospital for worsening arthralgias with morning stiffness lasting hours, as well as left sided headaches, and jaw pain while eating. He had significant weight loss and subjective fever at home. Multiple fingers and toes were noted to be ischemic. His laboratory workup was pertinent for significantly elevated inflammatory markers, and mild Creatinine kinase elevation. Chest imaging and later lung biopsy were notable for organizing pneumonia. Conventional angiogram showed evidence of significant digital disease without collaterals. Subsequent autoimmune screening tests with extended myositis‐specific and myositis‐associated panels revealed a strongly positive anti‐PL‐12 antibody and moderately positive anti‐ SSA‐52KD IgG ab. After ruling out infectious etiologies and malignancy, anti‐synthetase syndrome (ASyS) diagnosis was considered in the presence of ischemic digits, organizing pneumonia, polyarthralgia, constitutional symptoms, increased inflammatory markers and positive antibodies. The patient was treated with high dose prednisone and mycophenolate mofetil along with amlodipine and sildenafil for digital vasodilation. Acute digital ischemia may be the first manifestation of ASyS with ILD. A high index of suspicion is warranted for early diagnosis and better outcomes. [ABSTRACT FROM AUTHOR]

The study aimed to investigate the expression profiles of transcription factors, cytokines, and co‐stimulatory molecules in helper T (Th)‐cell subsets within bronchoalveolar lavage (BAL) samples of patients with interstitial lung diseases (ILDs). Twenty ILDs patients were included in the study, comprising those with idiopathic pulmonary fibrosis (IPF) (n:8), autoimmune‐related ILDs (auto‐ILD) (n:4), and orphan diseases (O‐ILD) (n:8), alongside five control subjects. Flow cytometry was employed to evaluate the Th to cytotoxic T cell (CTL) ratio in BAL fluid, while cytopathological examination assessed macrophages, lymphocytes, and neutrophils. Quantitative real‐time polymerase chain reaction was utilized to investigate the expressions in Th1, Th2, Th17, and regulatory T (Treg) cells. Results revealed elevated Th cell to CTL ratios across all patient groups compared to controls. Furthermore, upregulation of Th1, Th2, Th17, and T‐cell factors was observed in all patient groups compared to controls. Interestingly, upregulation of CD28 and downregulation of CTLA‐4 and PD‐1 gene expression were consistent across all ILDs groups, highlighting potential immune dysregulation. This study provides a comprehensive exploration of molecular immunological mechanisms in ILDs patients, underscoring the dominance of Th2 and Th17 responses and revealing novel findings regarding the dysregulation of CD28, CTLA‐4, and PD‐1 expressions in ILDs for the first time. [ABSTRACT FROM AUTHOR]

Background: Previous studies involving risk–benefit analysis of trastuzumab deruxtecan (DS‐8201) have indicated the benefit of this treatment, although it may increase the risk of interstitial lung disease (ILD) and/or pneumonitis in certain patients. This study aimed to assess the safety of DS‐8201. Methods: A search was done for relevant articles in four electronic databases: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov. All reports published up until November 2, 2022, were included, and study types were restricted to clinical trials; the last search was then updated to January 10, 2023. We also assessed the quality of the literature with the Cochrane Handbook for Systematic Reviews of Interventions and the Methodological Index for Non‐Randomized Studies tool, and then performed a meta‐analysis with R version 4.2.1. Results: A total of 1428 patients reported in 13 articles were included in this study. The analysis revealed that the most common all‐grade treatment‐emergent adverse events (TEAEs) were nausea and fatigue. The most common TEAE of grade 3 or above (grade ≥3) was neutropenia. The incidences of ILD and/or pneumonitis for all‐grade and grade ≥3 TEAEs were 12.5% and 2.2%, respectively. Conclusions: This comprehensive summary of the incidence of TEAEs associated with DS‐8201 in clinical trials provides an important guide for clinicians. The most common TEAEs were gastrointestinal reactions and fatigue; meanwhile, the most common grade ≥3 TEAE was hematological toxicity. ILD and/or pneumonitis were specific adverse drug reactions associated with DS‐8201, of which physicians should be particularly aware for their higher morbidity and rates of grade ≥3 TEAEs. This study aimed to assess the safety of trastuzumab deruxtecan (DS‐8201) with a focus on interstitial lung disease and/or pneumonitis via the method of systematic review and single‐arm meta‐analysis. This comprehensive summary of the incidence of treatment‐emergent adverse events associated with DS‐8201 in clinical trials provides an important guide for clinicians. [ABSTRACT FROM AUTHOR]

Background and Objective: Evidence for the benefit of steroid therapy in acute exacerbations (AEs) of idiopathic pulmonary fibrosis (IPF) is limited; however, they remain a cornerstone of management in other fibrotic interstitial lung diseases. This retrospective observational study assesses the effect of steroid treatment on in‐hospital mortality in patients with acute exacerbation of fibrotic interstitial lung disease (AE‐FILD) including IPF and non‐IPF ILDs. Methods: AE‐FILD cases over a 10‐year period were filtered using a code‐based algorithm followed by individual case evaluation. Binary logistic regression analysis was used to assess the relationship between corticosteroid treatment (defined as ≥0.5 mg/kg/day of prednisolone‐equivalent for ≥3 days within the first 72 h of admission) and in‐hospital mortality or need for lung transplantation. Secondary outcomes included readmission, overall survival, requirement for domiciliary oxygen and rehabilitation. Results: Across two centres a total of 107 AE‐FILD subjects were included, of which 46 patients (43%) received acute steroid treatment. The steroid cohort was of younger age with fewer comorbidities but had higher oxygen requirements. Pre‐admission FVC and DLCO, distribution of diagnoses and smoking history were similar. The mean steroid treatment dose was 4.59 mg/kg/day. Steroid use appeared to be associated with increased risk of inpatient mortality or transplantation (OR 4.11; 95% CI 1.00–16.83; p = 0.049). In the steroid group, there appeared to be a reduced risk of all‐cause mortality in non‐IPF patients (HR 0.21; 95% CI 0.04–0.96; p = 0.04) compared to their IPF counterparts. Median survival was reduced in the steroid group (221 vs. 520.5 days) with increased risk of all‐cause mortality (HR 3.25; 95% CI 1.56–6.77; p < 0.01). Conclusion: In this two‐centre retrospective study of 107 patients, AE‐FILD demonstrates a high risk of mortality, at a level similar to that seen for AE‐IPF, despite steroid treatment. Clinicians should consider other precipitating factors for exacerbations and use steroids judiciously. Further prospective trials are needed to determine the role of corticosteroids in AE‐FILD. This is a multicentre retrospective observational study comparing the outcomes of acute exacerbation of fibrotic ILD between steroid and non‐steroid treatment. Those who were administered steroids were younger, had fewer comorbidities but greater oxygen requirement and lower physiologic reserve. When adjusted for these variables, there appeared no survival benefit and potential increased risk of death in those who were given steroids. See relatededitorial [ABSTRACT FROM AUTHOR]

SUMMARY OF KEY POINTS: In this review, we have discussed several important developments in 2023 in Interstitial Lung Disease (ILD). The association of pollution with genetic predispositions increased the risk of Idiopathic Pulmonary Fibrosis (IPF). An interesting comorbidity of malnutrition was not adequately recognized in ILD. Novel genes have been identified in IPF involving predominantly short telomere length and surfactant protein production leading to alveolar epithelial cell dysfunction. Genetics also predicted progression in IPF. Crosstalk between vascular endothelial cells and fibroblasts in IPF mediated by bone morphogenic protein signalling may be important for remodelling of the lung. A novel modality for monitoring of disease included the 4‐min gait speed. New treatment modalities include inhaled pirfenidone, efzofitimod, for sarcoidosis, and earlier use of immunosuppression in connective tissue disease‐ILD. [ABSTRACT FROM AUTHOR]

Hypersensitivity pneumonitis (HP) is an immune‐mediated interstitial lung disease (ILD) relating to specific occupational, environmental or medication exposures. Disease behaviour is influenced by the nature of exposure and the host response, with varying degrees of lung inflammation and fibrosis seen within individuals. The differentiation of HP from other ILDs is important due to distinct causes, pathophysiology, prognosis and management implications. This Thoracic Society of Australia and New Zealand (TSANZ) position statement aims to provide an up‐to‐date summary of the evidence for clinicians relating to the diagnosis and management of HP in adults, in the Australian and New Zealand context. This document highlights recent relevant findings and gaps in the literature for which further research is required. [ABSTRACT FROM AUTHOR]

Background and Objective: There are few studies that have used inspiratory muscle training (IMT) as an intervention for patients with isolated idiopathic pulmonary fibrosis (IPF). This study aimed to investigate and interpret the effects of home‐based telerehabilitation‐assisted IMT in patients with IPF. Methods: Twenty‐eight participants with IPF took part in the study. Lung function tests, functional exercise capacity by 6‐min walk distance (6MWD), dyspnoea perception by modified medical research council dyspnoea scale (mMRC), and inspiratory muscle strength by maximal inspiratory pressure (MIP) were assessed. IMT was performed twice a day, 7 days/week, for 8 weeks. The intervention group (n = 14) performed IMT at 50% of their baseline MIP while the control group (n = 14) performed IMT without applied resistance. Loading intensity was progressed by keeping the load at 4–6 on a modified Borg scale for the highest tolerable perceived respiratory effort for each patient. Results: Dyspnoea based on mMRC score (p < 0.001, η2 effect size = 0.48) significantly decreased within the intervention group compared with the control group. There were significant increases in the intervention group compared to the control group based on 6MWD (p < 0.001, η2 effect size = 0.43), MIP (p = 0.006, η2 effect size = 0.25) and MIP % predicted (p = 0.008, η2 effect size = 0.25). Conclusion: The findings of this study suggest that an 8‐week home‐based telerehabilitation‐assisted IMT intervention produced improvements in inspiratory muscle strength, leading to improvements in functional exercise capacity and dyspnoea. An 8‐week home‐based telerehabilitation‐assisted inspiratory muscle training is an effective intervention that improves respiratory muscle strength and functional exercise capacity and decreases dyspnoea in patients with idiopathic pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Background and Purpose: The PDE4 family is considered a prime target for therapeutic intervention in several fibro‐inflammatory diseases. We have investigated the molecular mechanisms of nerandomilast (BI 1015550), a preferential PDE4B inhibitor. Experimental Approach: In addition to clinically relevant parameters of idiopathic pulmonary fibrosis (IPF; lung function measurement/high‐resolution computed tomography scan/AI‐Ashcroft score), whole‐lung homogenates from a therapeutic male Wistar rat model of pulmonary fibrosis were analysed by next‐generation sequencing (NGS). Data were matched with public domain data derived from human IPF samples to investigate how well the rat model reflected human IPF. We scored the top counter‐regulated genes following treatment with nerandomilast in human single cells and validated disease markers discovered in the rat model using a human disease‐relevant in vitro assay of IPF. Key Results: Nerandomilast improved the decline of lung function parameters in bleomycin‐treated animals. In the NGS study, most transcripts deregulated by bleomycin treatment were normalised by nerandomilast treatment. Most notably, a significant number of deregulated transcripts that were identified in human IPF disease were also found in the animal model and reversed by nerandomilast. Mapping to single‐cell data revealed the strongest effects on mesenchymal, epithelial and endothelial cell populations. In a primary human epithelial cell culture system, several disease‐related (bio)markers were inhibited by nerandomilast in a concentration‐dependent manner. Conclusions and Implications: This study further supports the available knowledge about the anti‐inflammatory/antifibrotic mechanisms of nerandomilast and provides novel insights into the mode of action and signalling pathways influenced by nerandomilast treatment of lung fibrosis. [ABSTRACT FROM AUTHOR]

In the two decades that have elapsed since the initial proposal of neuroendocrine cell hyperplasia of infancy (NEHI), several hundred cases have been reported and researched. However, a comprehensive analysis of research progress remains absent from the literature. The present article endeavors to evaluate the current progress of NEHI research and offer a reference for the clinical management of this condition. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The development of connective tissue disease‐associated lung diseases (CTD‐LD) occurs in association with specific human leukocyte antigens (HLA). For CTD‐LD patients who require lung transplant, it is unknown whether utilization of donor organs expressing these same HLA impacts posttransplant outcomes. Methods: Using the Scientific Registry of Transplant Recipients, we assessed whether CTD‐LD lung transplant recipients in the United States have worse bronchiolitis obliterans (BOS)‐free survival based on the degree of donor HLA matching. This included overall degree of donor‐recipient HLA matching, donor‐recipient matching at DR loci, and recipient matching with specific donor HLA antigens associated with the development of pulmonary disease in their condition. Results: Among 1413 patients with CTD‐ILD, highly HLA‐matched donor‐recipients did not have worse adjusted survival (hazard ratio [HR] = 0.93, 95% confidence interval [CI] = 0.58–1.51, p = 0.77). Recipients who were fully matched at HLA DR did not have worse survival (HR = 0.82, 95% CI = 0.56–1.19, p = 0.29). Finally, among individual CTD‐LD, including rheumatoid arthritis, systemic sclerosis, the idiopathic inflammatory myopathies, and systemic lupus erythematous, transplant with a donor expressing HLA antigens associated with lung manifestations in these conditions was not associated with worse BOS‐free survival. Conclusions: Among transplant recipients with CTD‐LD, HLA donor‐recipient matching, including at the DR loci, does not result in worse BOS‐free survival. Based on these findings, there is no reason to treat these as unacceptable antigens when considering donor offers for CTD‐LD candidates. [ABSTRACT FROM AUTHOR]

Background and Objective: Chronic interstitial lung disease (ILD) occurs rarely with systemic lupus erythematosus (SLE) as compared with other connective tissue diseases. This multicentric retrospective study of patients with SLE‐ILD from the OrphaLung and French SLE networks during 2005–2020 aimed to describe the characteristics of patients with SLE‐ILD and analyse factors associated with prognosis. Methods: We analysed data for 89 patients with SLE‐ILD (82 women, 92.1%) (median age at SLE diagnosis: 35 years [interquartile range 27–47]). All patients met the 2019 EULAR/ACR criteria for the diagnosis of SLE. Results: Forty two (47.2%) patients were positive for anti‐ribonuclear protein antibodies and 45 (50.6%) for anti SSA/Ro antibodies. A total of 58 (65.2%) patients had another connective tissue disease: Sjögren's syndrome (n = 33, 37.1%), systemic sclerosis (n = 14, 15.7%), inflammatory myopathy (n = 6, 6.7%), or rheumatoid arthritis (n = 6, 6.7%). ILD was diagnosed along with SLE in 25 (28.1%) patients and at a median of 6 (0–14) years after the SLE diagnosis. The most frequent CT pattern was suggestive of non‐specific interstitial pneumonia (n = 41, 46.0%) with or without superimposed organizing pneumonia. After a median follow‐up of 86.5 [39.5–161.2] months, 18 (20.2%) patients had died and 6 (6.7%) underwent lung transplantation. The median 5‐year and 10‐year transplantation‐free survival were 96% (92–100) and 87% (78–97). In total, 44 (49.4%) patients showed ILD progression. Cutaneous manifestations and Raynaud's phenomenon were associated with better survival. Only forced vital capacity was significantly associated with survival and ILD progression. Conclusion: ILD is a rare manifestation of SLE with good overall prognosis but with possible risk of ILD progression. Patients with SLE‐ILD frequently have another connective tissue disease. [ABSTRACT FROM AUTHOR]

Diagnosis and treatment of pulmonary hypertension (PH) in patients with lung diseases (PH‐LD) remain unestablished and pose significant challenges. In this report, we present a case of a 77‐year‐old patient with an indeterminate for usual interstitial pneumonia pattern along with chronic obstructive pulmonary disease, who developed groups 1 and 3 PH. Following diagnosis, upfront triple oral combination therapy (UTOCT) with macitentan, sildenafil, and selexipag was initiated. Stability in disease progression was achieved over 4 years with the addition of pirfenidone to address interstitial lung disease progression. To the best of our knowledge, this represents the first reported case of PH‐LD, where disease control was maintained with the addition of pirfenidone to UTOCT. This case suggests that some patients with PH‐LD, presenting with groups 1 and 3 PH, may benefit from combined UTOCT and antifibrotic agents, potentially improving symptoms and extending their prognosis. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, aberrant immune activation, and extensive tissue fibrosis of the skin and internal organs. Because of the complicated nature of its pathogenesis, the underlying mechanisms of SSc remain incompletely understood. Angiogenic factor with a G‐patch domain and a Forkhead‐associated domain 1 (AGGF1) is a critical factor in angiogenesis expressed on vascular endothelial cells, associated with inflammatory and fibrotic responses. To elucidate the possible implication of AGGF1 in SSc pathogenesis, we investigated the association between serum AGGF1 levels and clinical manifestations in SSc patients. We conducted a cross‐sectional analysis of AGGF1 levels in sera from 60 SSc patients and 19 healthy controls with enzyme‐linked immunosorbent assay. Serum AGGF1 levels in SSc patients were significantly higher than those in healthy individuals. In particular, diffuse cutaneous SSc patients with shorter disease duration had higher levels compared to those with longer disease duration and limited cutaneous SSc patients. Patients with higher serum AGGF1 levels had a higher incidence of digital ulcers, higher modified Rodnan Skin Scores (mRSS), elevated serum Krebs von den Lungen‐6 (KL‐6) levels, C‐reactive protein levels, and right ventricular systolic pressures (RVSP) on the echocardiogram, whereas they had reduced percentage of vital capacity (%VC) and percentage of diffusing capacity of the lungs for carbon monoxide (%DLCO) in pulmonary functional tests. In line, serum AGGF1 levels were significantly correlated with mRSS, serum KL‐6 and surfactant protein D levels, RVSP, and %DLCO. These results uncovered notable correlations between serum AGGF1 levels and key cutaneous and vascular involvements in SSc, suggesting potential roles of AGGF1 in SSc pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Although transbronchial lung cryobiopsy (TBLC) is widely used in diagnostic algorithms for various interstitial lung diseases (ILDs), its real‐world utility in the therapeutic decision‐making strategy for ILD patients remains unclear, in particular, when judging the time to start antifibrotic agents. Methods: We analyzed medical records of 40 consecutive patients with idiopathic or fibrotic hypersensitivity pneumonitis who underwent TBLC. A TBLC‐based usual interstitial pneumonia (UIP) score was used to assess three morphologic descriptors: patchy fibrosis, fibroblastic foci, and honeycombing. Results: In our 40 patients with ILD, the most frequent radiological feature was indeterminate for UIP (45.0%). Final diagnosis included idiopathic pulmonary fibrosis (22.5%), fibrotic nonspecific interstitial pneumonia (5.0%), fibrotic hypersensitivity pneumonitis (35.0%), and unclassifiable ILD (37.5%). Linear mixed‐effects analysis showed that declines in the slopes of %FVC and %DLCO in patients with TBLC‐based UIP "Score ≥ 2" were significantly steeper than those of patients with "Score ≤ 1." During follow‐up of patients with Score ≥ 2 (n = 24), more than half of them (n = 17) received an antifibrotic agent, with most patients (n = 13) receiving early administration of the antifibrotic agent within 6 months after the TBLC procedure. Conclusions: TBLC‐based UIP Score ≥ 2 indicated the increased possibility of a progressive fibrosis course that may prove helpful in predicting progressive pulmonary fibrosis/progressive fibrosing ILD even if disease is temporarily stabilized due to anti‐inflammatory agents. Patients may benefit from early introduction of antifibrotic agents by treating clinicians. [ABSTRACT FROM AUTHOR]

Background and Objective: Establishing an accurate and timely diagnosis of idiopathic pulmonary fibrosis (IPF) is essential for appropriate management and prognostication. In some cases, surgical lung biopsy (SLB) is performed but carries non‐negligible risk. The objective of this retrospective study was to determine if SLB is associated with accelerated lung function decline in patients with IPF using the Canadian Registry for Pulmonary Fibrosis. Methods: Linear mixed models and Cox proportional hazards regression models were used to compare decline in forced vital capacity (FVC)%, diffusion capacity of the lung (DLCO%) and risk of death or lung transplantation between SLB and non‐SLB patients. Adjustments were made for baseline age, sex, smoking history, antifibrotic use, and lung function. A similar analysis compared lung function changes 12 months pre‐ and post‐SLB. Results: A total of 81 SLB patients and 468 non‐SLB patients were included. In the SLB group, the post‐biopsy annual FVC% decline was 2.0% (±0.8) in unadjusted, and 2.1% (±0.8) in adjusted models. There was no difference in FVC% decline, DLCO% decline, or time to death or lung transplantation between the two groups, in adjusted or unadjusted models (all p‐values >0.07). In the pre‐post SLB group, no differences were identified in FVC% decline in unadjusted or adjusted models (p = 0.07 for both). Conclusion: No association between SLB and lung function decline or risk of death or lung transplantation was identified in this multi‐centre study of patients with IPF. [ABSTRACT FROM AUTHOR]

Aim: To evaluate whether seasonal changes influence fluctuations in serum Krebs von den Lungen‐6 (KL‐6) levels in systemic sclerosis‐related interstitial lung disease (SSc‐ILD). Methods: Summer was defined as the period between July and September, and winter as between December and February. The study was conducted between 2015 and 2016, with a focus on these two seasons. A diagnosis of ILD and ILD progression overtime were evaluated using chest computed tomography. Among patients with SSc‐ILD, those with data on serum KL‐6 and lactate dehydrogenase (LDH) levels in the 2015 winter, 2015 summer, and 2016 winter seasons were included. Patients with comorbidities that could affect serum KL‐6 levels were excluded. Results: Of 60 patients with SSc‐ILD, 52 (86.7%) had stable ILD, 5 (8.3%) had worsened ILD, and 3 (5.0%) had improved ILD. Serum KL‐6 levels were significantly higher during the winter than those during the summer (2015 winter vs. 2015 summer: 649 U/mL vs. 585 U/mL, p <.0001; 2016 winter vs. 2015 summer: 690 U/mL vs. 585 U/mL, p <.0001). No significant differences were observed between the winters of 2015 and 2016 (649 U/mL vs. 690 U/mL, p =.78). However, serum LDH levels did not exhibit seasonal fluctuations (2015 winter vs. 2015 summer: 203 U/L vs. 199 U/L, p =.3; 2016 winter vs. 2015 summer: 201 U/L vs. 199 U/L, p =.6; 2015 winter vs. 2016 winter: 203 U/L vs. 201 U/L, p =.24). Conclusion: Seasonal fluctuations in serum KL‐6 levels were observed in patients with SSc‐ILD. [ABSTRACT FROM AUTHOR]

Interstitial lung disease (ILD) has been identified as a prevalent complication and significant contributor to mortality in individuals with pemphigus. In this study, a murine model of pemphigus was developed through the subcutaneous administration of serum IgG obtained from pemphigus patients, allowing for an investigation into the association between pemphigus and ILD. Pulmonary interstitial lesions were identified in the lungs of a pemphigus mouse model through histopathology, RT‐qPCR and Sircol assay analyses. The severity of these lesions was found to be positively associated with the concentration of IgG in the injected serum. Additionally, DIF staining revealed the deposition of serum IgG in the lung tissue of pemphigus mice, indicating that the subcutaneous administration of human IgG directly impacted the lung tissue of the mice, resulting in damage. This study confirms the presence of pulmonary interstitial lesions in the pemphigus mouse model and establishes a link between pemphigus and ILD. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis‐associated interstitial lung disease (RA‐ILD) is a serious and common extra‐articular disease manifestation. Patients with RA‐ILD experience reduced bacterial diversity and gut bacteriome alterations. However, the gut mycobiome and virome in these patients have been largely neglected. In this study, we performed whole‐metagenome shotgun sequencing on fecal samples from 30 patients with RA‐ILD, and 30 with RA‐non‐ILD, and 40 matched healthy controls. The gut bacteriome and mycobiome were explored using a reference‐based approach, while the gut virome was profiled based on a nonredundant viral operational taxonomic unit (vOTU) catalog. The results revealed significant alterations in the gut microbiomes of both RA‐ILD and RA‐non‐ILD groups compared with healthy controls. These alterations encompassed changes in the relative abundances of 351 bacterial species, 65 fungal species, and 4,367 vOTUs. Bacteria such as Bifidobacterium longum, Dorea formicigenerans, and Collinsella aerofaciens were enriched in both patient groups. Ruminococcus gnavus (RA‐ILD), Gemmiger formicilis, and Ruminococcus bromii (RA‐non‐ILD) were uniquely enriched. Conversely, Faecalibacterium prausnitzii, Bacteroides spp., and Roseburia inulinivorans showed depletion in both patient groups. Mycobiome analysis revealed depletion of certain fungi, including Saccharomyces cerevisiae and Candida albicans, in patients with RA compared with healthy subjects. Notably, gut virome alterations were characterized by an increase in Siphoviridae and a decrease in Myoviridae, Microviridae, and Autographiviridae in both patient groups. Hence, multikingdom gut microbial signatures showed promise as diagnostic indicators for both RA‐ILD and RA‐non‐ILD. Overall, this study provides comprehensive insights into the fecal virome, bacteriome, and mycobiome landscapes of RA‐ILD and RA‐non‐ILD gut microbiota, thereby offering potential biomarkers for further mechanistic and clinical research. [ABSTRACT FROM AUTHOR]

Background and Objective: Interstitial lung disease (ILD) is characterized by dyspnoea on exertion and exercise‐induced hypoxaemia. High‐flow nasal cannula (HFNC) therapy reduces the respiratory workload through higher gas flow and oxygen supplementation, which may affect exercise tolerance. This study aimed to examine the effects of oxygen and gas flow rates through HFNC therapy on exercise tolerance in ILD patients. Methods: We conducted three‐treatment crossover study. All ILD patients performed the exercises on room air (ROOM AIR setting: flow, 0 L/min; fraction of inspired oxygen [FiO2], 0.21), HFNC (FLOW setting: flow 40 L/min, FiO2 0.21), and HFNC with oxygen supplementation (FLOW + OXYGEN setting: flow 40 L/min, FiO2 0.6). The primary endpoint was the endurance time, measured using constant‐load cycle ergometry exercise testing at a peak work rate of 80%. Results: Twenty‐five participants (10 men, 71.2 ± 6.7 years) were enrolled. The increase in exercise duration between the ROOM AIR and FLOW was 46.3 s (95% CI, −6.1 to 98.7; p = 0.083), and the FLOW and FLOW + OXYGEN was 91.5 s (39.1–143.9; p < 0.001). The percutaneous oxygen saturation (SpO2) at rest was significantly higher with the FLOW + OXYGEN setting than with the ROOM AIR and FLOW settings, and the difference persisted during exercise. At equivalent time points during exercise, the SpO2 with the FLOW setting was significantly higher than that with the ROOM AIR setting. Conclusion: Oxygen supplementation in HFNC therapy improved exercise tolerance and SpO2. We found that gas flow alone did not improve exercise tolerance, but improved SpO2 during exercise. [ABSTRACT FROM AUTHOR]

Background and Objective: Bronchoscopic transbronchial lung cryobiopsy (TBLC) is a guideline‐endorsed alternative to surgical lung biopsy for tissue diagnosis in unclassifiable interstitial lung disease (ILD). The reported incidence of post‐procedural bleeding has varied widely. We aimed to characterize the incidence, severity and risk factors for clinically significant bleeding following TBLC using an expert‐consensus airway bleeding scale, in addition to other complications and diagnostic yield. Methods: A retrospective cohort study of consecutive adult outpatients with unclassifiable ILD who underwent TBLC following multidisciplinary discussion at a single centre in the UK between July 2016 and December 2021. TBLC was performed under general anaesthesia with fluoroscopic guidance and a prophylactic endobronchial balloon. Results: One hundred twenty‐six patients underwent TBLC (68.3% male; mean age 62.7 years; FVC 86.2%; DLCO 54.5%). Significant bleeding requiring balloon blocker reinflation for >20 min, admission to ICU, packed red blood cell transfusion, bronchial artery embolization, resuscitation or procedural abandonment, occurred in 10 cases (7.9%). Significant bleeding was associated with traction bronchiectasis on HRCT (OR 7.1, CI 1.1–59.1, p = 0.042), a TBLC histological pattern of UIP (OR 4.0, CI 1.1–14, p = 0.046) and the presence of medium‐large vessels on histology (OR 37.3, CI 6.5–212, p < 0.001). BMI ≥30 (p = 0.017) and traction bronchiectasis on HRCT (p = 0.025) were significant multivariate predictors of longer total bleeding time (p = 0.017). Pneumothorax occurred in nine cases (7.1%) and the 30‐day mortality was 0%. Diagnostic yield was 80.6%. Conclusion: TBLC has an acceptable safety profile in experienced hands. Radiological traction bronchiectasis and obesity increase the risk of significant bleeding following TBLC. Transbronchial lung cryobiopsy can be performed safely in experienced hands. Radiological traction bronchiectasis and obesity increase the risk of significant bleeding. [ABSTRACT FROM AUTHOR]

Objective: To investigate the prognostic factors of patients with anti‐melanoma differentiation‐associated gene 5 (MDA5) positive clinically amyopathic dermatomyositis (CADM) and interstitial lung disease (ILD). Methods: A retrospective analysis was conducted on clinical data of 125 patients with anti‐MDA5 + CADM‐ILD collected from 10 branches in eastern China between December 2014 and December 2022. Prognostic factors were analyzed using χ2 test, Log‐rank test, COX and logistic regression analysis. Results: In this cohort, 125 anti‐MDA5 + CADM‐ILD patients exhibited a rapidly progressive interstitial lung disease (RPILD) incidence of 37.6%, and an overall mortality rate of 24.8%. One patient was lost to follow‐up. After diagnosis of RPILD, a mortality rate of 53.2% occurred in patients died within 3 months, and that of 5.6% appeared in those who survived for more than 3 months. Multiple factor analysis revealed that C‐reactive protein (CRP) ≥ 10 mg/L (p = 0.01) and recombinant human tripartite motif containing 21 (Ro52) (+) (p = 0.003) were associated with a higher risk of RPILD in anti‐MDA5 + CADM‐ILD patients; CRP ≥ 10 mg/L (p = 0.018) and the presence of RPILD (p = 0.003) were identified as the factors influencing survival time in these patients, while arthritis was the protective factor (p = 0.016). Conclusion: Patients with anti‐MDA5 + CADM‐ILD will have a higher mortality rate, and the initial 3 months after diagnosis of RPILD is considered the risk window for the dismal prognosis. Patients with CRP ≥ 10 mg/L, Ro52 (+) and RPILD may be related to a shorter survival time, while patients complicated with arthritis may present with relatively mild conditions. [ABSTRACT FROM AUTHOR]

Introduction: Clinically amyopathic dermatomyositis (CADM) with anti‐melanoma differentiation‐associated gene 5 (MDA5) antibody (Ab) with rapidly progressive interstitial lung disease (RP‐ILD) is often refractory for intensive immunosuppression. In this study, we verified the effectiveness and safety of plasma exchange (PEx) for this lethal disease. Methods: We retrospectively examined the clinical course and adverse effect (AE) of 12 patients with anti‐MDA5 Ab–positive CADM between January 2017 and December 2021 in our hospital. Results: Five out of six patients treated with simple PEx using fresh frozen plasma or 5% albumin survived with or without home oxygen therapy. Multiple PEx (15–20 times) were required to achieve satisfactory improvement as well as remission of CADM. The AEs caused by PEx were resolved using conventional methods. Conclusion: PEx might be a promising option for controlling the disease activity of anti‐MDA5 Ab–positive CADM with severe RP‐ILD and may contribute to better survival. [ABSTRACT FROM AUTHOR]

Filgotinib, a janus kinase 1 (JAK1) inhibitor, is used in the treatment of rheumatoid arthritis (RA). RA‐associated interstitial lung disease (RA‐ILD) is a severe RA complication with no established effective treatment. We report the case of a patient with RA‐ILD successfully treated with filgotinib. A 46‐year‐old woman with RA and RA‐ILD, presenting with a non‐specific interstitial pneumonia pattern, was refractory to abatacept and prednisolone but responded to filgotinib. Both arthritis and RA‐ILD improved significantly, and the patient remained in remission for over 12 months. Basic research indicates that JAK1 plays a role in the cytokine signal transduction in ILD; however, there are no clinical reports on the efficacy of filgotinib in RA‐ILD. This case suggests filgotinib as a potential treatment for patients with RA‐ILD, particularly in the early stages of this disease. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID‐19) often leads to a spectrum of pulmonary complications, including interstitial lung disease (ILD) with the potential for fibrotic sequelae. Assessing the presence of ongoing active inflammation versus established residual fibrosis as a result of lung parenchymal injury and repair in these patients is a clinical challenge. Better understanding of the disease process is crucial for guiding appropriate therapeutic strategies. We aim to investigate the use of positron emission tomography / computer tomography (PET/CT) scans and their role in diagnosing interstitial pneumonitis (IP) post COVID infections. [ABSTRACT FROM AUTHOR]

This article discusses the impact of hiatus hernia (HH) in patients with hypersensitivity pneumonitis (HP). The study found that about one-third of HP patients had HH, which is higher than the general population. However, the causal relationship between HH and lung fibrosis has not been established. The study also found that the presence and size of HH were not associated with body mass index (BMI) or the extent of fibrosis on CT scans. Additionally, there was no relationship between HH and baseline lung function. In patients with a usual interstitial pneumonia (UIP) pattern on CT, there was a trend towards poorer survival and lung function decline in those with HH. Consolidation, a CT marker of aspiration, was more prevalent in HP patients with larger HH. Further research is needed to understand the potential role of HH in the development of HP. [Extracted from the article]

Background and Objective: The identification of progression in patients with fibrosing non‐idiopathic pulmonary fibrosis (IPF) interstitial lung diseases (ILDs) represents an ongoing clinical challenge. Lung function decline alone may have significant limitations in the detection of clinically significant progression. We hypothesized that longitudinal changes of 6‐min walk distance (6MWD) from baseline, simultaneously considered with measures of lung function, may independently predict survival and identifying clinically significant progression of disease. Methods: Forced vital capacity (FVC), diffusing lung capacity (DLCO) and 6MWD were considered both at baseline and at 1 year in a discovery cohort (n = 105) and in a validation cohort (n = 138) from different centres. The primary endpoint was lung transplant (LTx)‐free survival. Results: Average follow‐up was 3 years in both cohorts. Combined incidence of deaths and LTx was 29% and 21%, respectively. No collinearity and no strong correlations were observed among FVC, DLCO and 6MWD longitudinal changes. While age, gender and BMI were not significant, 6MWD decline ≥24 m predicted LTx‐free‐survival significantly and independently from FVC and DLCO declines, with high sensitivity and specificity, in both the discovery and the validation cohorts. Although FVC and DLCO declines remained significant predictors of LTx‐free survival, 6MWD decline was more accurate than the proposed ATS/ERS/JRS/ALAT functional criteria. Results were confirmed after stratifying patients by baseline FVC. Conclusion: Longitudinal declines of 6MWD are associated with poor survival in fibrosing ILDs across a wide range of baseline severity, with high accuracy. 6MWD longitudinal decline is largely independent from lung function decline and may be integrated into the routine assessment of progression. We show that a 6MWD decline from baseline predicts lung transplant‐free survival in fibrosing ILDs. It is a robust and independent predictor of survival in fibrosing ILDs, with accuracy even superior to that of ATS/ERS/JRS/ALAT functional criteria. The implementation of 6MWD in the assessment of disease progression may be considered. See relatededitorial [ABSTRACT FROM AUTHOR]

Objectives: This study investigates the role of TNF‐induced protein 3 (TNFAIP3) and CCAAT/enhancer‐binding protein β (C/EBPβ) in alveolar macrophages (AMs) of patients with systemic sclerosis‐associated interstitial lung disease (SSc‐ILD) and their influence on pulmonary fibrosis. Methods: Transfection of HEK293T cells and AMs with plasmids carrying TNFAIP3 and C/EBPβ was performed, followed by co‐culturing AMs with pulmonary fibroblasts. Immunoblotting analysis was then utilized to assess the expression of TNFAIP3, C/EBPβ, and collagen type 1 (Col1). Quantitative PCR analysis was conducted to quantify the mRNA levels of C/EBPβ, IL‐10, and TGF‐β1. STRING database analysis, and immunoprecipitation assays were employed to investigate the interactions between TNFAIP3 and C/EBPβ. Results: TNFAIP3 expression was significantly reduced in SSc‐ILD AMs, correlating with increased Col1 production in fibroblasts. Overexpression of TNFAIP3 inhibited this pro‐fibrotic activity. Conversely, C/EBPβ expression was elevated in SSc‐ILD AMs, and its reduction through TNFAIP3 restoration decreased pro‐fibrotic cytokines IL‐10 and TGFβ1 levels. Protein–protein interaction studies confirmed the regulatory relationship between TNFAIP3 and C/EBPβ. Conclusions: This study highlights the important role of TNFAIP3 in regulating pulmonary fibrosis in SSc‐ILD by modulating C/EBPβ expression in AMs. These findings suggest that targeting TNFAIP3 could be a potential therapeutic strategy for managing SSc‐ILD patients. [ABSTRACT FROM AUTHOR]

Purpose: Pulmonary fibrosis (PF) is a severe, progressive disease, which may be caused by exposure to certain medications. Methods: We queried the U.S. FDA Adverse Event Reporting System (FAERS) from 2000 to 2022, using the search terms "pulmonary fibrosis" and "idiopathic pulmonary fibrosis" and excluded reports with patients under the age of 18 years, and patients with unknown sex or age. Reports were sorted by generic drug names, counted, and plotted over time using a best‐fit trendline based on an exponential function. Results: From 2000 to 2022, there were 24 095 935 adverse drug events reported in FAERS, of which 17 520 (0.07%) were reported as PF. After excluding reports containing patients with unknown age (5255, 30%), sex (122, 0.7%), and age below 18 years old (155, 0.9%), our study included 11 988 reports. The mean age of the study sample was 66.5 ± 13.1 years, and 6248 patients (52.1%) were male. Plotting the 11 988 reports by year revealed an exponential best fit line (R2 = 0.88) with a positive slope over time. The top five drug classes associated with PF were disease modifying antirheumatic drugs (DMARDs, 39.4%), antineoplastic agents (26.4%), cardiovascular agents (12.6%), corticosteroids (4.6%), and immunosuppressive agents (4.0%). Conclusion: A 23‐year analysis of the FAERS database revealed exponentially increasing adverse event reports of PF. Significant annual increases in reporting of PF suspected with DMARDs and antineoplastic agents were identified. Our study highlights important trends, which should be used to guide PF research related to drugs of potential importance. [ABSTRACT FROM AUTHOR]

Background and Objective: Variants in surfactant genes SFTPC or ABCA3 are responsible for interstitial lung disease (ILD) in children and adults, with few studies in adults. Methods: We conducted a multicentre retrospective study of all consecutive adult patients diagnosed with ILD associated with variants in SFTPC or ABCA3 in the French rare pulmonary diseases network, OrphaLung. Variants and chest computed tomography (CT) features were centrally reviewed. Results: We included 36 patients (median age: 34 years, 20 males), 22 in the SFTPC group and 14 in the ABCA3 group. Clinical characteristics were similar between groups. Baseline median FVC was 59% ([52–72]) and DLco was 44% ([35–50]). An unclassifiable pattern of fibrosing ILD was the most frequent on chest CT, found in 85% of patients, however with a distinct phenotype with ground‐glass opacities and/or cysts. Nonspecific interstitial pneumonia and usual interstitial pneumonia were the most common histological patterns in the ABCA3 group and in the SFTPC group, respectively. Annually, FVC and DLCO declined by 1.87% and 2.43% in the SFTPC group, respectively, and by 0.72% and 0.95% in the ABCA3 group, respectively (FVC, p = 0.014 and DLCO, p = 0.004 for comparison between groups). Median time to death or lung transplantation was 10 years in the SFTPC group and was not reached at the end of follow‐up in the ABCA3 group. Conclusion: SFTPC and ABCA3‐associated ILD present with a distinct phenotype and prognosis. A radiologic pattern of fibrosing ILD with ground‐glass opacities and/or cysts is frequently found in these rare conditions. [ABSTRACT FROM AUTHOR]

Background and Objective: Real‐life data on suspected familial fibrosis, defined as the occurrence of the disease in a patient younger than 50 and/or having at least one relative affected by pulmonary fibrosis remain scarce. Methods: The Belgian and Luxembourg IPF registry (PROOF‐Next) is a multicentric prospective longitudinal and observational study set in Belgium and Luxembourg. We compared characteristics and clinical course of patients with suspected familial pulmonary fibrosis (FPF) and sporadic IPF. Results: We included 618 patients in the analysis, of whom 76 (12%) fulfilled criteria for FPF. They were significantly younger than sIPF (median age (range) 65 (43–87), vs. 72 (51–98), p = 0.0001). Male gender proportion and smoking status did not differ between groups, but the number of pack‐year among current and former smokers was lower in FPF (20 vs. 25, p = 0.02). Besides, 87% of FPF and 76% of sIPF were treated with antifibrotic (p = 0.047). Baseline pulmonary function tests were similar in both groups, as well as median time before progression and transplant‐free survival. Finally, genetic testing, performed in a minority, led to the identification of 10 telomerase‐related gene variants. Conclusion: Although younger and exposed to less tobacco, patients with FPF show an equally aggressive progression as observed in sporadic IPF patients. These results warrant early referral of FPF patients to expert centres for optimal management. Familial clustering affects about 10% of idiopathic pulmonary fibrosis. This prospective multicentric study provides a reliable estimate of familial fibrosis among IPF patients and demonstrates similar dismal prognosis despite a younger age and a lighter exposure to smoking. Our results warrant early referral of familial fibrosis patients to expert centres. See relatededitorial [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) adds a substantial disease burden, including higher mortality, when associated with interstitial lung disease (ILD), a severe, chronic, progressive condition. Yet little is known of the lived experiences, perspectives, priorities, and viewpoints of patients and carers living with PH‐ILD. The Voice of the Patient meeting at the center of this qualitative research study aims to provide these difficult‐to‐obtain insights from a European perspective for the first time. The multistakeholder approach brought together four PH‐ILD patients, three primary caregivers, two patient associations, clinical experts, sponsor representatives, and a facilitator. Of the six major themes identified in the thematic analysis, symptoms, and physical limitations were the most impactful. Shortness of breath was the most bothersome symptom affecting patients daily. Further symptoms included fatigue, cough, dizziness, syncope, edema, and palpitations. Physical limitations focused on reduced mobility, impacting patients' ability to perform daily tasks, hobbies, sports, and to enjoy travel. Existing antifibrotic and pulmonary arterial hypertension‐targeted treatments were perceived as beneficial. However, despite advances in treatment, severe disease burdens and high unmet medical needs persist from the perspectives of patients. Most meaningful to patients' daily wellbeing was supplemental oxygen, enabling greater mobility. Patients and carers reported difficulties and barriers in navigating the healthcare system and obtaining adequate information to reduce their considerable uncertainties, documenting the substantial challenges that rare and complex conditions such as PH‐ILD pose for routine clinical practice beyond PH expert centers and indicating an urgent need for high‐quality patient‐ and clinician‐directed information to support patient‐centered care. [ABSTRACT FROM AUTHOR]

A 65-year-old man presented with intermittent fever and progressive shortness of breath. He responded poorly to antibiotics and corticosteroids (methylprednisolone 40 mg/d). Chest computed tomography scans showed diffuse consolidations and ground glass density patchy opacities in both lungs and these lesions progressed rapidly. The diagnosis of acute fibrinous and organizing pneumonia (AFOP) was confirmed through transbronchial cryobiopsy. This patient had prostate cancer with bone metastasis for 4 months and took the anti-prostate cancer medications including apalutamide and leuprorelin acetate. Considering his medication history, the patient was diagnosed with AFOP induced by anti-prostate cancer medications through panel discussion of multidisciplinary teams. Intravenous methylprednisolone of 500 mg/day was administered for 3 days and then slowly tapered. The patient's shortness of breath gradually subsided. In addition, the lesions in the lungs improved significantly on follow up imaging. AFOP induced by anti-prostate cancer medications is rare. To our knowledge, this is the first reported case and high-dose glucocorticoid treatment may be required in some of these cases. [ABSTRACT FROM AUTHOR]

Background and Objective: The acute‐phase protein C‐reactive protein (CRP) is known to be associated with poor outcomes in cancer and cardiovascular disease, but there is limited evidence of its prognostic implications in interstitial lung diseases (ILDs). We therefore set out to test whether baseline serum CRP levels are associated with mortality in four different ILDs. Methods: In this retrospective study, clinically measured CRP levels, as well as baseline demographics and lung function measures, were collected for ILD patients first presenting to the Royal Brompton Hospital between January 2010 and December 2019. Cox regression analysis was used to determine the relationship with 5‐year mortality. Results: Patients included in the study were: idiopathic pulmonary fibrosis (IPF) n = 422, fibrotic hypersensitivity pneumonitis (fHP) n = 233, rheumatoid arthritis associated ILD (RA‐ILD) n = 111 and Systemic Sclerosis associated ILD (SSc‐ILD) n = 86. Patients with a recent history of infection were excluded. Higher CRP levels were associated with shorter 5‐year survival in all four disease groups on both univariable analyses, and after adjusting for age, gender, smoking history, immunosuppressive therapy and baseline disease severity (IPF: HR (95% CI): 1.3 (1.1–1.5), p = 0.003, fHP: 1.5 (1.2–1.9), p = 0.001, RA‐ILD: 1.4 (1.1–1.84), p = 0.01 and SSc‐ILD: 2.7 (1.6–4.5), p < 0.001). Conclusion: Higher CRP levels are independently associated with reduced 5‐year survival in IPF, fHP, RA‐ILD and SSc‐ILD. [ABSTRACT FROM AUTHOR]

This article discusses a case of a 10-year-old girl who was diagnosed with juvenile dermatomyositis (JDM), a rare autoimmune disorder. The patient presented with symptoms such as joint pain, edema, and skin rash. The diagnosis was confirmed through physical examination, laboratory tests, and imaging. The patient's condition worsened and she developed complications including interstitial lung disease (ILD) and macrophage activation syndrome (MAS). Despite treatment with various medications and therapies, the patient's condition deteriorated and she ultimately died due to multiple organ failure. The article highlights the challenges in diagnosing and treating JDM, particularly in cases with complications. The authors suggest that more intensive therapy and the use of immune regulators may be necessary for better outcomes in these cases. [Extracted from the article]

Refractory pneumothorax associated with interstitial lung disease (ILD) remains a challenging condition due to the patient's tolerability and lung compliance that restrict the feasibility of aggressive interventions. Additionally, many cases recur after improvement with treatment, and reports of successful management for this complicated condition are limited. Herein, we report the case of a 60‐year‐old man with ILD, utilizing home oxygen therapy, who experienced a successful recovery from a surgical intervention under local anaesthesia for pneumothorax. This case highlights the potential for operative intervention under local anaesthesia as a viable option for patients who do not respond to internal approaches. [ABSTRACT FROM AUTHOR]

See relatedarticle [ABSTRACT FROM AUTHOR]

This article discusses the importance of increased clinical and radiological awareness of incidentally discovered interstitial lung abnormalities (ILAs) on CT chest scans. ILAs are radiological abnormalities that are only discovered incidentally and have been associated with a possible evolution to clinical interstitial lung diseases (ILDs). However, ILAs are not a clinical entity themselves and can be challenging to diagnose. The article emphasizes the need for improved reporting and recognition of ILAs by radiologists and clinicians to prevent diagnostic delays and improve patient outcomes. It suggests strategies such as using structured model reports and encouraging the use of artificial intelligence tools to aid in ILA identification. [Extracted from the article]

Interstitial lung diseases (ILDs) are chronic conditions that significantly impact patients' quality of life, exercise capacity, and lifespan. Managing ILDs poses challenges across low-income, middle-income, and high-income countries due to various factors such as weather, air pollution, cultural beliefs, and income levels. High-income countries are perceived to have better resources for ILD care, but they still face challenges such as delays in access to healthcare and a lack of trained personnel. Middle-income and low-income countries struggle with limited healthcare infrastructure, high costs of diagnostic tests, delays in diagnosis, and inadequate rehabilitation and palliative care facilities. Disparities in health insurance coverage and access to medications also exist. Collaborative efforts, education, and research are needed to address these challenges and improve ILD management globally. [Extracted from the article]

Idiopathic pulmonary fibrosis (IPF) is a progressive disease leading to significant morbidity and mortality. In 2017 the Thoracic Society of Australia and New Zealand (TSANZ) and Lung Foundation Australia (LFA) published a position statement on the treatment of IPF. Since that time, subsidized anti‐fibrotic therapy in the form of pirfenidone and nintedanib is now available in both Australia and New Zealand. More recently, evidence has been published in support of nintedanib for non‐IPF progressive pulmonary fibrosis (PPF). Additionally, there have been numerous publications relating to the non‐pharmacologic management of IPF and PPF. This 2023 update to the position statement for treatment of IPF summarizes developments since 2017 and reaffirms the importance of a multi‐faceted approach to the management of IPF and progressive pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Background and Objective: The lung immune prognostic index (LIPI), a simple index calculated from the blood lactate dehydrogenase level and derived neutrophil‐to‐lymphocyte ratio, is thought to be associated with host immune status. However, the utility of LIPI in patients with idiopathic interstitial pneumonias (IIPs) is unknown. Methods: In this multicentre, retrospective, observational study, an association between LIPI and the survival of patients with IIPs was evaluated. Results: Exploratory and validation cohorts consisting of 460 and 414 patients with IIPs, respectively, were included (159 and 159 patients had idiopathic pulmonary fibrosis [IPF], and 301 and 255 had non‐IPF, respectively). In the exploratory cohort, patients with IPF and a low LIPI had significantly better survival than those with a high LIPI (median of 5.6 years vs. 3.9 years, p = 0.016). The predictive ability of LIPI for the survival of patients with IPF was validated in the validation cohort (median of 8.5 years vs. 4.4 years, p = 0.003). In a multivariate Cox proportional hazard analysis, LIPI was selected as an independent predictive factor for the survival of IPF patients. There was no significant association between LIPI and survival of non‐IPF patients in the exploratory and validation cohorts. Conclusion: The LIPI was a predictive factor for the survival of patients with IPF and could aid the management of IPF. [ABSTRACT FROM AUTHOR]

Background: The main subtypes of idiopathic inflammatory myopathies (IIMs)--polymyositis (PM) and dermatomyositis (DM)--are often presented as interstitial lung disease (ILD) in clinical practice; therefore, many researchers have combined the three studies into PM/DM with ILD. Methods: Using bibliometrics, the research status, progress, and hotspots of PM/DM with ILD between 2000 and 2022 were studied. Literature data on PM/DM with ILD were retrieved from the Web of Science (WoS) database for the research period. Visualization software, including VOSviewer, Pajek, CiteSpace, and Scimago Graphica were used for bibliometric analysis. Results: A total of 1555 relevant articles were obtained, and the overall research in this field showed an increasing trend. Regarding contributing countries and venues, Japan published the most articles while Rheumatology was the most prolific journal. Regarding authors, the most published article was by Wang Guochun from Changchun University of Technology in China. Keyword analysis and cocited literature cluster analysis showed that diagnosis, classification, autoantibodies, antibodies, prognosis, complications, and treatment of PM/DM with ILD have been hot topics in this field recently. Moreover, our study shows that anti-mda5 antibody, mortality, gene 5 antibody, IIMs, double-blind, and prognostic factors, among others, may be new hot topics. Conclusion: This study found that research on PM/DM with ILD has increased over time, and scholars are paying more attention to this field. The development of new drugs for the management, treatment, and prevention of PM/DM with ILD is the primary task of researchers and a direction for future research in this field. [ABSTRACT FROM AUTHOR]