Interstitial Lung Disease Subtypes Research Articles

Effect of breathing exercises on patients with interstitial lung disease: A systematic review and meta-analysis.

This study was designed to synthesize the efficacy and safety of breathing exercises in interstitial lung disease (ILD) patients by reviewing the literature and comparing the impact of different control group types, ILD subtypes, breathing exercise action modes or methods, and intervention durations on clinical efficacy. Systematic searches were conducted across 9 electronic databases, including PubMed, to retrieve English and Chinese studies reporting on ILD patients from inception to February 12, 2024. Study selection and data extraction were independently conducted by two researchers. The quality of the included studies was assessed using the Cochrane risk of bias tool. The data were analysed using RevMan 5.4 and STATA 17.0 software. The search identified 25 studies. Compared to the control group, the breathing exercise group exhibited significantly improved lung function (FVC%pred: MD = 3.46, 95%CI = 1.04 to 5.88; DLCO%pred: MD = 3.20, 95% CI = 2.91 to 3.48), dyspnoea (MRC or mMRC scale: MD = -0.50, 95%CI = -0.77 to -0.22), exercise capacity (6MWD: MD = 32.65, 95% CI = 14.77 to 50.53), and HRQoL (SGRQ: MD = -6.53, 95% CI = -8.72 to -4.34) in ILD patients. According to the subgroup analysis, significant improvements consistent with the overall results were observed in the control group with usual treatment. Compared with the control group, breathing exercises had varying degrees of improvement in the mixed diagnostic group, known-cause group, and fibrotic group of ILD patients; breathing exercises alone significantly improved DLCO%pred, MRC (or mMRC), and SGRQ; and the improvement in breathing exercises as part of pulmonary rehabilitation (PR) was more notable. Different durations of breathing exercise could promote the efficacy of different aspects of treatment for ILD patients. Compared with usual treatment, breathing exercises can improve lung function, exercise capacity, and HRQoL in ILD patients, particularly without high requirements for intervention duration. The efficacy of breathing exercises varies for different ILD subtypes, and incorporating breathing exercises as part of PR can be more beneficial for ILD patients. No studies have shown significant risks for ILD patients engaging in breathing exercises.

Acute Exacerbation of Interstitial Lung Disease: Definitions, Epidemiology, Prognosis and Management.

Abstract Acute exacerbation of interstitial ling disease (AE-ILD) denotes a rapid deterioration of respiratory function often leading to ICU admission due to severe hypoxemia. Definitions encompass the diverse spectrum of interstitial lung diseases and specific criteria for AE-ILD, originally established for idiopathic pulmonary fibrosis (IPF) and later expanded to other interstitial lung diseases. The incidence varies among the various interstitial lung disease subtypes, with around 10% of interstitial lung disease patients experiencing acute exacerbations within the initial two years of diagnosis. Clinical risk factors encompass advanced interstitial lung disease, compromised pulmonary function, and coexisting conditions. Prognostic markers include baseline pulmonary parameters, blood markers, and a newly developed Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) staging system. However, due to the scarcity of randomized studies, optimal treatment strategies remain uncertain. Current guidelines propose supportive care and oxygen therapy, with cautious use of corticosteroids in AE-IPF. Antibiotics are employed to manage infections, with procalcitonin-guided therapy showing potential. Management involves exposure elimination, targeted antibiotics, and antacid and antifibrotic use. For severe cases, mechanical ventilation, extracorporeal membrane oxygenation (ECMO), and even transplantation are considered. To conclude, AE-ILD poses formidable challenges and high mortality rates. Given the lack of standardized approaches, the pursuit of randomized trials is vital to enhance the understanding and management of AE-ILD, optimizing patient outcomes within the ICU setting. Keywords: acute exacerbation, interstitial lung disease, idiopathic pulmonary fibrosis, intensive care unit, definition.

High Interleukin-13 level is associated with disease stability in interstitial Lung disease

Cytokines can help predict prognosis in interstitial lung disease (ILD) and to differentiate between ILD subtypes. The objectives of our study were to evaluate association of baseline cytokine levels with time to ILD progression and to compare baseline cytokine levels between ILD subtypes. We quantified 27 cytokines using a multiplex assay in peripheral blood samples from 77 patients. Cox proportional hazards regression analysis was performed to evaluate cytokine impact on the time to progression in the total cohort and within each ILD type. We evaluated for significant differences in cytokine levels between ILD types using ANOVA, Wilcoxon signed-rank test and Tukey method. Higher IL-13 level was associated with longer time to progression (hazard ratio 0.52 [0.33-0.81], p-value 0.004). FGF-β, GM-CSF, and IL-17 levels differed significantly between fibrotic and inflammatory ILD subgroups. IL-13 may be a useful biomarker predicting ILD stability.

Machine learning classifier is associated with mortality in interstitial lung disease: a retrospective validation study leveraging registry data

BackgroundMortality prediction in interstitial lung disease (ILD) poses a significant challenge to clinicians due to heterogeneity across disease subtypes. Currently, forced vital capacity (FVC) and Gender, Age, and Physiology (GAP) score are the two most utilized metrics in prognostication. Recently, a machine learning classifier system, Fibresolve, designed to identify a variety of computed tomography (CT) patterns associated with idiopathic pulmonary fibrosis (IPF), was demonstrated to have a significant association with mortality across multiple subtypes of ILD. The purpose of this follow-up study was to retrospectively validate these findings in a large, external cohort of patients with ILD.MethodsIn this multi-center validation study, Fibresolve was applied to chest CT scans of patients with confirmed ILD that had available follow-up data. Fibresolve scores categorized by tertile were analyzed using Cox regression analysis adjusted for tobacco use and modified GAP (mGAP) score.ResultsOf 643 patients included, 446 (69.3%) died over a median follow-up time of 144 [1-821] weeks. The median [range] mGAP score was 5 [3–7]. In multivariable analysis, Fibresolve score categorized by tertile was significantly associated with mortality (Tertile 2 HR 1.47, 95% CI 0.82–2.37, p = 0.11; Tertile 3 HR 3.12, 95% CI 1.98–4.90, p < 0.001). Subgroup analyses revealed significant associations amongst those with non-IPF ILDs (Tertile 2 HR 1.95, 95% CI 1.28–2.97, Tertile 3 HR 4.66, 95% CI 2.94–7.38) and severe disease, defined by a FVC ≤ 75% (Tertile 2 HR 2.29, 95% CI 1.43–3.67, Tertile 3 HR 4.80, 95% CI 2.93–7.86).ConclusionsFibresolve is independently associated with mortality in ILD, particularly amongst patients with non-IPF ILDs and in those with severe disease.

Pursuing Clinical Predictors and Biomarkers for Progression in ILD: Analysis of the Pulmonary Fibrosis Foundation (PFF) Registry

IntroductionPulmonary fibrosis is a characteristic of various interstitial lung diseases (ILDs) with differing etiologies. Clinical trials in progressive pulmonary fibrosis (PPF) enroll patients based on previously described clinical criteria for past progression, which include a clinical practice guideline for PPF classification and inclusion criteria from the INBUILD trial. In this study, we compared the ability of past FVC (forced vital capacity) progression and baseline biomarker levels to predict future progression in a cohort of patients from the PFF Patient Registry.MethodsBiomarkers previously associated with pathobiology and/or progression in pulmonary fibrosis were selected to reflect cellular senescence (telomere length), pulmonary epithelium (SP-D, RAGE), myeloid activation (CXCL13, YKL40, CCL18, OPN) and fibroblast activation (POSTN, COMP, PROC3).ResultsPFF or INBUILD-like clinical criteria was used to separate patients into past progressor and non-past progressor groups, and neither clinical criterion appeared to enrich for patients with greater future lung function decline. All baseline biomarkers measured were differentially expressed in patient groups compared to healthy controls. Baseline levels of SP-D and POSTN showed the highest correlations with FVC slope over one year, though correlations were low.ConclusionsOur findings provide further evidence that prior decline in lung function may not predict future disease progression for ILD patients, and elevate the need for molecular definitions of a progressive phenotype. Across ILD subtypes, certain shared pathobiologies may be present based on the molecular profile of certain biomarker groups observed. In particular, SP-D may be a common marker of pulmonary injury and future lung function decline across ILDs.

Clinical characteristics and outcome of lung cancer in patients with fibrosing interstitial lung disease

BackgroundLung cancer (LC) is an important comorbidity of interstitial lung disease (ILD) and has a poor prognosis. The clinical characteristics and outcome of each ILD subtype in LC patients have not been sufficiently investigated. Therefore, this study aimed to evaluate the difference between idiopathic pulmonary fibrosis (IPF) and non-IPF ILD as well as prognostic factors in patients with ILD-LC.MethodsThe medical records of 163 patients diagnosed with ILD-LC at Asan Medical Center from January 2018 to May 2023 were retrospectively reviewed. Baseline characteristics and clinical outcomes were compared between the IPF-LC and non-IPF ILD-LC groups, and prognostic factors were analyzed using the Cox proportional-hazard model.ResultsThe median follow-up period was 11 months after the cancer diagnosis. No statistically significant differences were observed in clinical characteristics and mortality rates (median survival: 26 vs. 20 months, p = 0.530) between the groups. The independent prognostic factors in patients with ILD-LC were higher level of Krebs von den Lungen-6 (≥ 1000 U/mL, hazard ratio [HR] 1.970, 95% confidence interval [CI] 1.026-3.783, p = 0.025) and advanced clinical stage of LC (compared with stage I, HR 3.876 for stage II, p = 0.025, HR 5.092 for stage III, p = 0.002, and HR 5.626 for stage IV, p = 0.002). In terms of treatment, surgery was the significant factor for survival (HR 0.235; 95% CI 0.106-0.520; p < 0.001).ConclusionsNo survival difference was observed between IPF-LC and non-IPF ILD-LC patients. A higher level of Krebs von den Lungen-6 may act as a prognostic marker in ILD-LC patients.

Clinical Characteristics and Outcomes of Interstitial Lung Disease in Primary Sjögren's Syndrome: A Retrospective Cohort Study.

To describe the characteristics of primary Sjögren's syndrome (pSS) patients with interstitial lung disease (ILD) and to assess treatment response. All patients of pSS from 2010 to 2019 were retrospectively identified. Lung function tests, high resolution computed tomography (HRCT) findings, and treatment outcomes were analysed. Out of 550 patients with pSS, ILD was detected in 33 patients (frequency of 6 %). The mean(±SD) age at the diagnosis of pSS was 50 (± 9.3) years. 28/33(84.8%) were females. ILD onset preceded pSS diagnosis in 2 (6%) patients, simultaneously diagnosed in 21 (63.6%) patients and developed after pSS onset in 10 (30.3%) patients. 5 patients (15.15 %) were asymptomatic for ILD. Non-specific interstitial pneumonia (NSIP) accounted for the most frequent ILD subtype, in 15 patients (45.5%). Mycophenolate mofetil (MMF) was the most frequently used steroid sparing agent, in 25 patients (75.7%). 7 patients were lost to follow up. Response was seen in 22 patients, whereas 3 patients were non responders. There was one mortality due to lower respiratory tract infection-related sepsis. Presence of sicca symptoms [91.5% vs 8.7% (p<0.001)], NSIP pattern of ILD [90% vs 10% (p = 0.002)], and absence of Raynaud's phenomenon [91.7% vs 8.3% (p<0.001)] were significantly associated with responder status when compared to non-responders. ILD in primary Sjögren's syndrome is not an uncommon entity, and immunosuppression with steroids along with steroid-sparing agents led to good clinical outcomes of ILD in a majority of the patients in our cohort.

Health care costs and utilization of progressive fibrosing lung disease by underlying interstitial lung disease type.

Fibrosing interstitial lung disease (ILD) encompasses more than 200 diverse pulmonary disorders, of which up to 40% become progressive. The 4 underlying ILD types most likely to result in progression are unclassified ILD/idiopathic interstitial pneumonia (IIP), autoimmune ILDs, exposure-related ILD/hypersensitivity pneumonitis, and sarcoidosis. To compare health care resource utilization (HCRU) and costs among patients with fibrosing ILD that has progressed ("progressive" fibrosing cohort) vs patients whose fibrosis did not meet criteria set for progression ("not yet progressed" cohort). This was a noninterventional study of commercial enrollees and Medicare Advantage with Part D beneficiaries, which used administrative claims data for the period from October 1, 2015, through May 31, 2021. Adult patients (aged ≥18 years) with fibrosing ILD and 12 months of continuous health plan enrollment were included. Patients with idiopathic pulmonary fibrosis, baseline ILD diagnoses, or missing demographic data were excluded. Patients were first classified according to the underlying type of fibrosing ILD. For statistical analyses of outcomes, 2 cohorts were compared within each subtype: progressive fibrosing ILD vs not yet progressed ILD. The final study population included propensity score-matched (PSM) patients (1:1) based on pre-ILD baseline demographic and clinical characteristics. HCRU categories included inpatient hospitalization counts and the number of inpatient days and total costs (in 2021 US dollars), analyzed descriptively and weighted by the per-patient-per-month cost. Lin's regression was used to predict 12-month total cost estimates for comparison by cohort. The distribution by underlying conditions was as follows: autoimmune ILD (n = 4,156), HP (n = 8,181), sarcoidosis (n = 775), and unclassified ILD/IIP (n = 18,635). After PSM, pre-ILD baseline variables were generally well balanced between the progressive and not yet progressed fibrosing ILD cohorts. For all underlying subtypes of ILD, patients in the progressive cohort had significantly more utilization and higher costs compared with patients in the not yet progressed cohort. Progressive cohorts had significantly higher adjusted rates of inpatient days among patients with at least 1 inpatient stay compared with the not yet progressed cohorts (all P < 0.01). In addition, the progressive cohorts had significantly higher adjusted 12-month total costs, with the differences ranging from $24,493 to $55,072 (all comparisons P < 0.001). Irrespective of underlying ILD type, patients with progressive fibrosing ILD had significantly increased HCRU and cost relative to those whose fibrosing ILD had not yet progressed.

Multidisciplinary-derived clinical score for accurate prediction of long-term mortality in fibrotic lung disease patients

BackgroundIdiopathic pulmonary fibrosis (IPF) stands out as one of the most aggressive forms of interstitial lung diseases (ILDs), currently without a definitive cure. Multidisciplinary discussion (MDD) is now considered a cornerstone in diagnosing and differentiating ILD subtypes. The Gender-Age-Physiology (GAP) score, developed to assess IPF prognosis based on sex, age, forced vital capacity, and diffusion capacity for carbon monoxide (DLCO), is limited in not considering dyspnea and functional impairment during the walking test. We proposed a MDD-based clinical score for mortality prediction among those patients.MethodsFrom December 2018 to December 2019, we enrolled ILD patients with IPF and non-IPF and followed-up them till December 2020. Based on DLCO, modified Medical Research Council (mMRC) Dyspnea Scale, and six-minute walking test (6MWT) distance, a functional score was developed for mortality prediction.ResultsWe enrolled 104 ILD patients, 12 (11.5%) died by the one-year follow-up. In receiver operating characteristic (ROC) curve analysis, DLCO (% predicted) was the most accurate variable predicting one-year mortality with an area under curve (AUC) of 0.88 (95% confidence interval [CI] = 0.80–0.94), followed by mMRC Dyspnea Score (AUC = 0.82 [95% CI = 0.73–0.89]), 6MWT distance (AUC = 0.80 [95% CI = 0.71–0.88]), and GAP score (AUC = 0.77 [95% CI = 0.67–0.84]). Only the GAP score (hazard ratio [HR] = 1.55, 95% CI = 1.03–2.34, p = 0.0.37) and functional score (HR = 3.45, 95% CI = 1.11–10.73, p = 0.032) were significantly associated with one-year mortality in multivariable analysis.ConclusionThe clinical score composite of DLCO, mMRC Dyspnea Scale, and 6MWT distance could provide an accurate prediction for long-term mortality in ILD patients, laying out a helpful tool for managing and following these patients.

Hospitalization Rates in Interstitial Lung Disease: An Analysis of the Pulmonary Fibrosis Foundation Registry.

Rationale: Little is known about hospitalization in other types of interstitial lung disease (ILD) besides idiopathic pulmonary fibrosis (IPF). Objectives: To determine the frequency of hospitalizations in various types of ILD and elucidate the association of hospitalization with outcomes. Methods: An analysis of the Pulmonary Fibrosis Foundation Patient Registry data was performed. Inpatient hospitalization rates and survival posthospitalization were compared for various types of ILD. Measurements and Main Results: Hospitalization rates were similar across ILD types: 40.6% of participants with IPF, 42.8% of participants with connective tissue disease-related ILD (CTD-ILD), 44.9% of participants with non-IPF idiopathic interstitial pneumonia (IIP), 46.5% of participants with chronic hypersensitivity pneumonitis (CHP), and 53.3% of participants with "other" ILD. All-cause hospitalization was not associated with decreased transplant-free survival (adjusted hazard ratio [AHR], 1.20; 95% confidence interval [CI] = 0.98, 1.46; P = 0.0759) after adjusting for comorbidities and severity of illness; however, respiratory-related hospitalization was (AHR, 1.53; 95% CI = 1.23, 1.90; P = 0.0001). Participants with CTD-ILD (HR, 0.43; 95% CI = 0.25, 0.75; P = 0.0031) and non-IPF IIP (HR, 0.3; 95% CI = 0.15, 0.58; P = 0.005) had a lower risk of death posthospitalization compared with those with IPF, whereas those with chronic hypersensitivity pneumonitis (HR, 0.67; 95% CI = 0.37, 1.20; P = 0.1747) or other ILD (HR, 0.54; 95% CI = 0.19, 1.54; P = 0.25) had a risk comparable with that for IPF. Conclusions: Rates of hospitalization are similar across ILD subtypes. The risk of death or transplant after posthospitalization is lower in patients with CTD-ILD and non-IPF IIP, compared with patients with IPF. In a mixed population of participants with ILD, all-cause hospitalizations were not associated with decreased transplant-free survival; however respiratory-related hospitalizations were.

Prognostic value of serum oncomarkers for patients hospitalized with acute exacerbation of interstitial lung disease.

Different types of inflammatory processes and fibrosis have been implicated in the pathogenesis of interstitial lung disease (ILD), a heterogeneous, diffuse, parenchymal lung disease. Acute exacerbation (AE) of ILD is characterized by significant respiratory deterioration and is associated with high mortality rates. Several serum oncomarkers have been used to determine the prognosis of ILD; however, the prognostic value of serum oncomarker levels in patients with AE-ILD remains unclear. To evaluate the prognostic value of serum oncomarker levels in patients with AE-ILD and its main subtypes. Retrospective study. The serum levels of 8 oncomarkers in 281 patients hospitalized with AE-ILD at our institution between 2017 and 2022 were retrospectively reviewed. The baseline characteristics and serum oncomarker levels were compared between the survival and non-survival groups of AE-ILD and its main subtypes. Multivariate logistic regression analysis was performed to identify independent prognosis-related markers, and the best prognostic predictor was analyzed using receiver operating characteristic curve (ROC) analysis. Idiopathic pulmonary fibrosis (IPF; n = 65), idiopathic nonspecific interstitial pneumonia (iNSIP; n = 26), and connective tissue disease-associated interstitial lung disease (CTD-ILD; n = 161) were the three main subtypes of ILD. The in-hospital mortality rate among patients with AE-ILD was 21%. The serum oncomarker levels of most patients with AE-ILD and its main subtypes in the non-survival group were higher than those in the survival group. Multivariate analysis revealed that ferritin and cytokeratin 19 fragments (CYFRA21-1) were independent prognostic risk factors for patients hospitalized with AE-ILD or AE-CTD-ILD. CYFRA21-1 was identified as an independent prognostic risk factor for patients hospitalized with AE-IPF or AE-iNSIP. CYFRA21-1 may be a viable biomarker for predicting the prognosis of patients with AE-ILD, regardless of the underlying subtype of ILD. Ferritin has a prognostic value in patients with AE-ILD or AE-CTD-ILD.

Prevalence and clinical characteristics of patients with rheumatoid arthritis with interstitial lung disease using unstructured healthcare data and machine learning

ObjectivesReal-world data regarding rheumatoid arthritis (RA) and its association with interstitial lung disease (ILD) is still scarce. This study aimed to estimate the prevalence of RA and ILD in patients...

Assessment of Precision Irradiation in Early Non-Small Cell Lung Cancer and Interstitial Lung Disease (ASPIRE-ILD): Primary Analysis of a Phase II Trial

The use of stereotactic ablative radiotherapy (SABR) in patients with fibrotic interstitial lung disease (ILD) has been associated with an increased risk of toxicity, but patients with ILD and lung cancer may have no other options for curative-intent treatment. The goal of the ASPIRE-ILD trial was to assess the benefits and toxicities of SABR in patients with fibrotic ILD. We enrolled patients with fibrotic ILD and a diagnosis of T1-2N0 NSCLC who were not candidates for surgery. All patients were centrally reviewed prior to enrollment to confirm the presence and subtype of ILD. After stratification by the ILD-GAP score (a measure of ILD severity and prognosis), patients were treated with SABR to a dose of 50 Gy in 5 fractions EOD (BED = 100 Gy10), with a built-in de-escalation protocol in case of unacceptable toxicity. The primary endpoint was overall survival (OS), powered to distinguish 1-year OS >70% vs. an unacceptable rate of ≤50%. Secondary endpoints included toxicity (CTC-AE version 4.0), progression-free survival (PFS), local control (LC), patient-reported outcomes (FACT-L quality of life and cough severity), and changes in pulmonary function tests (PFTs). The study pre-specified that SABR would be considered worthwhile if median OS was >1 year, with a grade 3-4 toxicity risk <35% and a grade 5 toxicity risk <15%. Target accrual was 39 treated patients. Thirty-nine patients were enrolled and treated with SABR between March 2019 and January 2022, all to a dose of 50 Gy in 5 fractions, at 5 institutions in Canada and 1 in Scotland. Median age was 78 years (interquartile range: 67-83), 59% were male, and 92% had a history of smoking (median 43 pack-years). At baseline, 70% reported dyspnea, median FEV1 was 80% predicted and median DLCO was 49% predicted. ILD-GAP scores were as follows: ≤2 (i.e., best ILD status): n = 14; 3-5: n = 23; ≥6 (i.e., worst ILD status): n = 2. Median follow-up was 19 months. OS at 1-year was 78.9% (p<0.001 by binomial test vs. the unacceptable rate). Median OS was 25 months, median PFS was 19 months, and 2-year LC was 92%. AE rates (possibly, probably or definitely related) were as follows (highest grade per patient): grade 1-2: n = 12 (31%); grade 3: n = 4 (10%); grade 4; n = 0; grade 5 n = 3 (7.7%, all due to respiratory deterioration). AE rates did not differ by ILD-GAP category or ILD subtype. FACT-L scores trended downward over time (p = 0.07), and cough severity scale scores worsened over time (p = 0.02). Comparing last-available PFTs with baseline, DLCO declined (median: -4%; p = 0.046), FVC trended downward (median: -2.5%; p = 0.11), and FEV1 remained stable (median change: 0%). The use of SABR in patients with ILD met the pre-specified acceptability thresholds for both toxicity and efficacy, supporting the use of SABR for curative-intent treatment after a careful discussion of risks and benefits. Further studies exploring pharmacologic options to reduce toxicity may be beneficial in this population. ().

Predicting New-onset Exertional and Resting Hypoxemia in Fibrotic Interstitial Lung Disease.

Rationale: Hypoxemia in fibrotic interstitial lung disease (ILD) indicates disease progression and is of prognostic significance. The onset of hypoxemia signifies disease progression and predicts mortality in fibrotic ILD. Accurately predicting new-onset exertional and resting hypoxemia prompts appropriate patient discussion and timely consideration of home oxygen. Objectives: We derived and externally validated a risk prediction tool for both new-onset exertional and new-onset resting hypoxemia. Methods: This study used ILD registries from Canada for the derivation cohort and from Australia and the United States for the validation cohort. New-onset exertional and resting hypoxemia were defined as nadir oxyhemoglobin saturation < 88% during 6-minute-walk tests, resting oxyhemoglobin saturation < 88%, or the initiation of ambulatory or continuous oxygen. Candidate predictors included patient demographics, ILD subtypes, and pulmonary function. Time-varying Cox regression was used to identify the top-performing prediction model according to Akaike information criterion and clinical usability. Model performance was assessed using Harrell's C-index and goodness-of-fit (GoF) likelihood ratio test. A categorized risk prediction tool was developed. Results: The best-performing prediction model for both new-onset exertional and new-onset resting hypoxemia included age, body mass index, a diagnosis of idiopathic pulmonary fibrosis, and percent predicted forced vital capacity and diffusing capacity of carbon monoxide. The risk prediction tool exhibited good performance for exertional hypoxemia (C-index, 0.70; GoF, P = 0.85) and resting hypoxemia (C-index, 0.77; GoF, P = 0.27) in the derivation cohort, with similar performance in the validation cohort except calibration for resting hypoxemia (GoF, P = 0.001). Conclusions: This clinically applicable risk prediction tool predicted new-onset exertional and resting hypoxemia at 6 months in the derivation cohort and a diverse validation cohort. Suboptimal GoF in the validation cohort likely reflected overestimation of hypoxemia risk and indicated that the model is not flawed because of underestimation of hypoxemia.

Clinical behaviour and mortality in idiopathic vs secondary nonspecific interstitial pneumonia.

Nonspecific interstitial pneumonia (NSIP) is a subtype of interstitial lung disease which can either be idiopathic or secondary to other conditions. Idiopathic NSIP is a relatively rare entity and diagnosis should be considered carefully as it is mainly a diagnosis of exclusion. The aim of this retrospective study was to evaluate a cohort of NSIP patients with a view to identifying any clinical and mortality differences between idiopathic and secondary varieties. We screened 700 patients from our interstitial lung disease database and identified 44 cases of NSIP retrospectively. Statistical analysis was conducted to evaluate if there was a difference in demographics such as gender and ethnicity, physiological parameters including forced vital capacity, diffusing capacity, average oxygen saturations, and immunology profile between two groups. Furthermore, a difference in mortality was evaluated between idiopathic and secondary NSIP. The data analysis showed that 63.6% (28 of 44) of patients had idiopathic NSIP versus 36.4% (16 of 44) of patients had secondary NSIP. Majority of the secondary NSIP patients had an underlying connective tissue disease. In the idiopathic variety, there was a male preponderance (64.2%, P = .02) which was statistically different compared to relatively equal gender divide in secondary NSIP which was statistically insignificant (male vs. female: 43.8% vs. 56.3%, respectively, P = .42). The mean age of the idiopathic group was 74 years compared to 64 years in the secondary group which was statistically different (P = .01). In both groups (idiopathic and secondary NSIP), more than two-thirds (68%) were of White British ethnicity. Immunology profile was similar across both groups with no statistical difference in IgM, IgG, or IgA levels. At the time of analysis, there were 17.9% deaths (5 of 28) in the idiopathic NSIP group versus 6.3% (1 of 16) in the secondary NSIP group but this was not statistically significant (P = .14). Similarly, there was no statistically significant difference in the forced vital capacity (P = .59), diffusing capacity (P = .88), and resting oxygen saturations (P = .28) between idiopathic and secondary NSIP varieties. Our analysis showed that there was a statistically significant difference in gender (male preponderance in idiopathic NSIP only) and mean age difference among both varieties. There were no statistically significant differences in the clinical features and outcomes including mortality, physiological, and immunological parameters between idiopathic and secondary NSIP. Idiopathic NSIP was more common than secondary NSIP and secondary NSIP is mostly due to underlying connective tissue disease.

Tobacco smoking is associated with combined pulmonary fibrosis and emphysema and worse outcomes in interstitial lung disease.

Tobacco smoking is an established cause of pulmonary disease whose contribution to interstitial lung disease (ILD) is incompletely characterized. We hypothesized that compared with nonsmokers, subjects who smoked tobacco would differ in their clinical phenotype and have greater mortality. We performed a retrospective cohort study of tobacco smoking in ILD. We evaluated demographic and clinical characteristics, time to clinically meaningful lung function decline (LFD), and mortality in patients stratified by tobacco smoking status (ever vs. never) within a tertiary center ILD registry (2006-2021) and replicated mortality outcomes across four nontertiary medical centers. Data were analyzed by two-sided t tests, Poisson generalized linear models, and Cox proportional hazard models adjusted for age, sex, forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLCO), ILD subtype, antifibrotic therapy, and hospital center. Of 1,163 study participants, 651 were tobacco smokers. Smokers were more likely to be older, male, have idiopathic pulmonary fibrosis (IPF), coronary artery disease, CT honeycombing and emphysema, higher FVC, and lower DLCO than nonsmokers (P < 0.01). Time to LFD in smokers was shorter (19.7 ± 20 mo vs. 24.8 ± 29 mo; P = 0.038) and survival time was decreased [10.75 (10.08-11.50) yr vs. 20 (18.67-21.25) yr; adjusted mortality HR = 1.50, 95%CI 1.17-1.92; P < 0.0001] compared with nonsmokers. Smokers had 12% greater odds of death for every additional 10 pack yr of smoking (P < 0.0001). Mortality outcomes remained consistent in the nontertiary cohort (HR = 1.51, 95%CI = 1.03-2.23; P = 0.036). Tobacco smokers with ILD have a distinct clinical phenotype strongly associated with the syndrome of combined PF and emphysema, shorter time to LFD, and decreased survival. Smoking prevention may improve ILD outcomes.NEW & NOTEWORTHY Smoking in ILD is associated with combined pulmonary fibrosis and emphysema and worse clinical outcomes.

Interstitial lung disease diagnosis and prognosis using an AI system integrating longitudinal data

For accurate diagnosis of interstitial lung disease (ILD), a consensus of radiologic, pathological, and clinical findings is vital. Management of ILD also requires thorough follow-up with computed tomography (CT) studies and lung function tests to assess disease progression, severity, and response to treatment. However, accurate classification of ILD subtypes can be challenging, especially for those not accustomed to reading chest CTs regularly. Dynamic models to predict patient survival rates based on longitudinal data are challenging to create due to disease complexity, variation, and irregular visit intervals. Here, we utilize RadImageNet pretrained models to diagnose five types of ILD with multimodal data and a transformer model to determine a patient’s 3-year survival rate. When clinical history and associated CT scans are available, the proposed deep learning system can help clinicians diagnose and classify ILD patients and, importantly, dynamically predict disease progression and prognosis.

The alternative approach: genomic classifiers for prognostication in interstitial lung disease

Interstitial lung disease (ILD) reflects a large group of entities characterised by pulmonary parenchymal inflammation and fibrosis, with many patients suffering from functional limitation, progressive symptoms and accelerated mortality [1]. Idiopathic pulmonary fibrosis (IPF), which is characterised by a usual interstitial pneumonia (UIP) pattern on imaging and histology, is the most common and deadly form of ILD [2, 3]. Prognosis and treatment approaches differ between ILD subtypes, making an accurate diagnosis crucial; however, this can be challenging due to overlapping clinical and morphological presentations of some ILDs. The potential of genomic classifiers for ILD prognostication has not been exhausted yet <http://bit.ly/3ZMMdjx>

Treatable traits in interstitial lung diseases: a call to action

Despite growing interest in the management of interstitial lung diseases (ILDs) and many clinical trials, treatment options for ILDs remain scarce. This reality stems from variability in disease pathogenesis across ILD subtypes, unpredictable natural history, and heterogeneous treatment responses. 1 Kokosi MA Margaritopoulos GA Wells AU Personalised medicine in interstitial lung diseases: number 6 in the Series “personalised medicine in respiratory diseases” edited by Renaud Louis and Nicolas Roche. Eur Respir Rev. 2018; 27170117 Crossref PubMed Scopus (10) Google Scholar Some data suggest that diverse forms of ILD might share pathogenetic and biological pathways and could therefore be amenable to similar treatment strategies. 1 Kokosi MA Margaritopoulos GA Wells AU Personalised medicine in interstitial lung diseases: number 6 in the Series “personalised medicine in respiratory diseases” edited by Renaud Louis and Nicolas Roche. Eur Respir Rev. 2018; 27170117 Crossref PubMed Scopus (10) Google Scholar , 2 Hoffmann-Vold AM Weigt SS Saggar R et al. Endotype-phenotyping may predict a treatment response in progressive fibrosing interstitial lung disease. EBioMedicine. 2019; 50: 379-386 Summary Full Text Full Text PDF PubMed Scopus (29) Google Scholar This evidence points to the existence of treatable traits—specific disease characteristics that are clinically relevant and modifiable through pharmacological or non-pharmacological interventions—that cut across traditional diagnostic categories. 3 McDonald VM Fingleton J Agusti A et al. Treatable traits: a new paradigm for 21st century management of chronic airway diseases: Treatable Traits Down Under International Workshop report. Eur Respir J. 2019; 531802058 Crossref Scopus (110) Google Scholar

Influence of thoracic radiology training on classification of interstitial lung diseases

IntroductionInterpretation of high-resolution CT images plays an important role in the diagnosis and management of interstitial lung diseases. However, interreader variation may exist due to varying levels of training and expertise. This study aims to evaluate interreader variation and the role of thoracic radiology training in classifying interstitial lung disease (ILD). MethodsThis is a retrospective study where seven physicians (radiologists, thoracic radiologists, and a pulmonologist) classified the subtypes of ILD of 128 patients from a tertiary referral center, all selected from the Interstitial Lung Disease Registry which consists of patients from November 2014 to January 2021. Each patient was diagnosed with a subtype of interstitial lung disease by a consensus diagnosis from pathology, radiology, and pulmonology. Each reader was provided with only clinical history, only CT images, or both. Reader sensitivity and specificity and interreader agreements using Cohen's κ were calculated. ResultsInterreader agreement based only on clinical history, only on radiologic information, or combination of both was most consistent amongst readers with thoracic radiology training, ranging from fair (Cohen's κ: 0.2–0.46), moderate to almost perfect (Cohen's κ: 0.55–0.92), and moderate to almost perfect (Cohen's κ: 0.53–0.91) respectively. Radiologists with any thoracic training showed both increased sensitivity and specificity for NSIP as compared to other radiologists and the pulmonologist when using only clinical history, only CT information, or combination of both (p < 0.05). ConclusionsReaders with thoracic radiology training showed the least interreader variation and were more sensitive and specific at classifying certain subtypes of ILD. Summary sentenceThoracic radiology training may improve sensitivity and specificity in classifying ILD based on HRCT images and clinical history.