Change In Forced Vital Capacity Research Articles

Pamrevlumab for Idiopathic Pulmonary Fibrosis

Current treatments for idiopathic pulmonary fibrosis slow the rate of lung function decline, but may be associated with adverse events that affect medication adherence. In phase 2 trials, pamrevlumab (a fully human monoclonal antibody that binds to and inhibits connective tissue growth factor activity) attenuated the progression of idiopathic pulmonary fibrosis without substantial adverse events. To assess the efficacy and safety of pamrevlumab for patients with idiopathic pulmonary fibrosis. Phase 3 randomized clinical trial including 356 patients aged 40 to 85 years with idiopathic pulmonary fibrosis who were not receiving antifibrotic treatment with nintedanib or pirfenidone at enrollment. Patients were recruited from 117 sites in 9 countries between July 18, 2019, and July 29, 2022; the last follow-up encounter occurred on August 28, 2023. Pamrevlumab (30 mg/kg administered intravenously every 3 weeks; n = 181) or placebo (n = 175) for 48 weeks. The primary outcome was absolute change in forced vital capacity (FVC) from baseline to week 48. There were 5 secondary outcomes (including time to disease progression, which was defined as a decline of ≥10% in predicted FVC or death). The exploratory outcomes included patient-reported symptoms. Adverse events were reported. Among 356 patients (mean age, 70.5 years; 258 [72.5%] were men; 221 [62.1%] were White), 277 (77.8%) completed the trial. There was no significant between-group difference for absolute change in FVC from baseline to week 48 (least-squares mean, -260 mL [95% CI, -350 to -170 mL] in the pamrevlumab group vs -330 mL [95% CI, -430 to -230 mL] in the placebo group; mean between-group difference, 70 mL [95% CI, -60 to 190 mL], P = .29). There were no significant between-group differences in any of the secondary outcomes or in the patient-reported outcomes. In the pamrevlumab group, there were 160 patients (88.4%) with treatment-related adverse events and 51 patients (28.2%) with serious adverse events vs 151 (86.3%) and 60 (34.3%), respectively, in the placebo group. During the study, 23 patients died in each group (12.7% in the pamrevlumab group vs 13.1% in the placebo group). Among patients with idiopathic pulmonary fibrosis treated with pamrevlumab or placebo, there was no statistically significant between-group difference for the primary outcome of absolute change in FVC from baseline to week 48. ClinicalTrials.gov Identifier: NCT03955146.

Longitudinal changes in serum immunoglobulin G testing in patients with fibrotic avian hypersensitivity pneumonitis

BackgroundEvaluation of the antigen responsible for fibrotic hypersensitivity pneumonitis (HP) is challenging. Serum immunoglobulin (Ig) G testing against HP-associated antigens is performed. Although single-serum IgG testing has been investigated, multiple-serum IgG testing has not yet been studied.MethodsThis study included patients who underwent histopathological examination and positive inhalation challenge test as well as those with moderate or high HP guideline confidence level. Serum IgG testing against pigeon serum was conducted twice using two methods: enzyme linked-immunosorbent assay (ELISA) and ImmunoCAP. The association between changes in serum IgG antibody titers and changes in forced vital capacity (FVC) and other parameters was investigated.ResultsIn this study, 28 patients (mean age, 64.5 years; mean FVC, 85.3%) with fibrotic avian HP were selected, of whom 20 and 8 underwent surgical lung biopsy and transbronchial lung cryobiopsy, respectively. Of the 28 patients, 19 had been keeping birds for more than 6 months. A correlation was observed between the annual changes in serum IgG antibody titers by ELISA and changes in relative FVC (r = − 0.6221, p < 0.001). Furthermore, there was a correlation between the annual changes in serum IgG antibody titers by ImmunoCAP and changes in relative FVC (r = − 0.4302, p = 0.022). Multiple regression analysis revealed that the change in serum IgG antibody titers by both ELISA and ImmunoCAP also influenced the relative FVC change (p = 0.012 and p = 0.015, respectively). Moreover, 13 patients were given additional treatments between the first and second blood test; however, the additional treatment group was not significantly different in relative FVC change compared to the group with no additional treatment (p = 0.982).ConclusionsIn patients with fibrotic avian HP, the annual changes in serum IgG testing were correlated with FVC changes, highlighting the importance of serum IgG testing over time.

Prognostic implication of 1-year decline in diffusing capacity in newly diagnosed idiopathic pulmonary fibrosis

The progression of idiopathic pulmonary fibrosis (IPF) is assessed through serial monitoring of forced vital capacity (FVC). Currently, data regarding the clinical significance of longitudinal changes in diffusing capacity for carbon monoxide (DLCO) is lacking. We investigated the prognostic implications of a 1-year decline in DLCO in 319 patients newly diagnosed with IPF at a tertiary hospital between January 2010 and December 2020. Changes in FVC and DLCO over the first year after the initial diagnosis were reviewed; a decline in FVC ≥ 5% and DLCO ≥ 10% predicted were considered significant changes. During the first year after diagnosis, a significant decline in FVC and DLCO was observed in 101 (31.7%) and 64 (20.1%) patients, respectively. Multivariable analysis showed that a 1-year decline in FVC ≥ 5% predicted (aHR 2.74, 95% CI 1.88–4.00) and 1-year decline in DLCO ≥ 10% predicted (aHR 2.31, 95% CI 1.47–3.62) were independently associated with a higher risk of subsequent mortality. The prognostic impact of a decline in DLCO remained significant regardless of changes in FVC, presence of emphysema, or radiographic indications of pulmonary hypertension. Therefore, serial monitoring of DLCO should be recommended because it may offer additional prognostic information compared with monitoring of FVC alone.

Respiratory function in adult patients with spinal muscular atrophy treated with nusinersen - a monocenter observational study.

Insufficiency of respiratory muscles is the most important reason for mortality in the natural history of SMA. Thus, improvement or stabilization of respiratory function by disease-modifying therapies (DMT) is a very important issue. We examined respiratory function using forced vital capacity (FVC) in 42 adult SMA patients (2 SMA type 1, 15 SMA type 2, 24 SMA type 3, 1 SMA type 4, median age 37 years, range 17-61 years) treated with nusinersen for a median of 22.1 months (range 2.1 to 46.7 months). Change in FVC was assessed using mixed effects linear regression models. Baseline FVC differed significantly between SMA type 1 (4.0, 8.0%), 2 (median 22.0%, IQR 18.0-44.0), 3 (median 81.0%, IQR 67.0-90.8) and, respectively, type 4 (84.0%) patients reflecting the heterogeneity of respiratory impairment based on the SMA type in adulthood (p < 0.0001). FVC remained stable during follow-up (mean -0.047, 95% CI -0.115 to 0.020, p = 0.17); however, subgroup analysis showed an increase in FVC of type 2 patients (mean 0.144, 95% CI 0.086 to 0.202, p < 0.0001) and a decrease in FVC of type 3/4 patients (-0.142, 95% CI -0.239 to -0.044, p = 0.005). The observed improvement in FVC in patients with SMA type 2 can be seen as a therapeutic response differing from the progressive decline typically seen in the spontaneous course. For SMA type 3/4 patients approaching normal spirometry at baseline, FVC may only be of limited use as an outcome parameter due to ceiling effects.

Compatible with fibrotic hypersensitivity pneumonitis on high-resolution computed tomography: from the ATS/JRS/ALAT 2020 hypersensitivity pneumonitis guidelines.

In compatible with fibrotic hypersensitivity pneumonitis (HP) of the computed tomography (CT) classification using the American Thoracic Society (ATS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) HP guidelines, the lung fibrosis pattern was classified as either a usual interstitial pneumonia (UIP) pattern or a diffuse ground-glass opacity (GGO) pattern with subtle fibrosis. We investigated whether patients with the same imaging classification had different disease progression. We also attempted to reclassify these patients using the CHEST HP guidelines. Patients with fibrotic HP who had compatible CT pattern in the ATS/JRS/ALAT classification were investigated retrospectively. With 62 patients in the UIP pattern group and 25 patients in the diffuse GGO pattern group, 87 patients with fibrotic HP had compatible pattern on CT. Annual forced vital capacity changes in the UIP pattern group and diffuse GGO pattern group were -2.7% and +3.3% (P=0.004), respectively. The 5-year survival rates in the UIP pattern group and diffuse GGO pattern group were 86% and 100% (P=0.02). In UIP pattern group in the ATS/JRS/ALAT classification, 27% patients were classified as typical fibrotic HP pattern in the CHEST guidelines. In the diffuse GGO pattern group, 52% patients were classified as typical pattern of fibrotic HP. In the CHEST guidelines, more patients in the GGO pattern were classified as typical pattern compared with those in the UIP pattern (P=0.02). The two patterns in compatible with fibrotic HP of CT classification using the ATS/JRS/ALAT HP guidelines had different disease progression. Typical patterns were more frequent in the CHEST guidelines than the ATS/JRS/ALAT guidelines.

Survival and Lung Function Changes in Hypersensitivity Pneumonitis According to Radiological Phenotypes Compared With Idiopathic Pulmonary Fibrosis.

The main objective of this study was to estimate survival and changes in lung function in patients with chronic hypersensitivity pneumonitis (HP), both fibrotic (f-HP) and nonfibrotic (nf-HP), and to compare them with those in patients with idiopathic pulmonary fibrosis (IPF). HP was diagnosed based on antigen exposure, HRCT (high-resolution CT scan), BAL (bronchoalveolar lavage), and histology. According to HRCT, HP was classified into fibrotic and non-fibrotic phenotypes. In most cases, IPF was diagnosed based on HRCT findings. We identified 84 patients: 46 with IPF, 18 with f-HP, and 20 with nf-HP. Five-year survival was 23.9% in IPF, 72% in f-HP, and 100% in nf-HP (p <0.0001). Honeycombing was associated with decreased survival in IPF (p <0.001) and in f-HP (p <0.0001). The mean loss of FVC (forced vital capacity) % pred. (percent predicted) was -18.3% in IPF (p =0.001), -4.8% in f-HP, and -6.0% in nf-HP. The mean change in DLCO (diffusion capacity for carbon monoxide) % pred. was -10.2% in IPF (p <0.002), -0.5% in f-HP, and +1.9% in nf-HP. The agreement between radiological phenotypes and histology in HP was 89.6%. We found shorter survival in IPF, followed by f-HP, and nf-HP. Over time, we did not find significant changes in FVC% pred. or DLCO% pred. in HP, while a significant decline in IPF was noted. In HP, we found strong agreement between radiological phenotypes and histology. Radiological signs suggestive of lung fibrosis in HP were reliable for the diagnosis of f-HP and seem to have intrinsic prognostic value.

Comparing the safety and efficacy of nintedanib starting dose in patients with connective tissue disease-associated interstitial lung diseases

Objective This study aimed to analyse whether initiating nintedanib treatment at a reduced dose could improve the treatment continuation rate while maintaining efficacy in patients with connective tissue disease (CTD)-associated interstitial lung disease. Method In total, 51 patients (age 61.6 ± 13.2 years; 38 women, 13 men) were retrospectively analysed. The primary endpoint was the cumulative discontinuation rate due to adverse events. Secondary endpoints included changes in drug dosage, efficacy evaluated based on annual changes in forced vital capacity (FVC), and safety assessed based on the frequency of adverse events. Results Eighteen patients who started treatment at the standard dose of 300 mg (standard dosage group) were compared with 33 patients who started treatment at a reduced dose (reduced dosage group). Systemic sclerosis was the most common CTD (n = 32), followed by idiopathic inflammatory myopathies and, rarely, rheumatoid arthritis. Both groups exhibited comparable cumulative discontinuation rates due to adverse events and similar frequencies of adverse events. No significant differences were observed in maintenance doses between the two groups; however, patients in the reduced dosage group had a lower cumulative dose for up to 52 weeks than those in the standard dosage group. No significant differences were observed in changes in FVC between the two groups. Conclusion There was no evidence for a difference between the two groups in terms of discontinuation rates, efficacy, and safety. To provide further evidence, future studies using more precise dose-escalation protocols are warranted.

Zinpentraxin Alfa for Idiopathic Pulmonary Fibrosis: The Randomized Phase III STARSCAPE Trial.

Rationale: A phase II trial reported clinical benefit over 28 weeks in patients with idiopathic pulmonary fibrosis (IPF) who received zinpentraxin alfa. Objectives: To investigate the efficacy and safety of zinpentraxin alfa in patients with IPF in a phase III trial. Methods: This 52-week phase III, double-blind, placebo-controlled, pivotal trial was conducted at 275 sites in 29 countries. Patients with IPF were randomized 1:1 to intravenous placebo or zinpentraxin alfa 10 mg/kg every 4 weeks. The primary endpoint was absolute change from baseline to Week 52 in FVC. Secondary endpoints included absolute change from baseline to Week 52 in percent predicted FVC and 6-minute walk distance. Safety was monitored via adverse events. Post hoc analysis of the phase II and phase III data explored changes in FVC and their impact on the efficacy results. Measurements and Main Results: Of 664 randomized patients, 333 were assigned to placebo and 331 to zinpentraxin alfa. Four of the 664 randomized patients were never administered study drug. The trial was terminated early after a prespecified futility analysis that demonstrated no treatment benefit of zinpentraxin alfa over placebo. In the final analysis, absolute change from baseline to Week 52 in FVC was similar between placebo and zinpentraxin alfa (-214.89 ml and -235.72 ml; P = 0.5420); there were no apparent treatment effects on secondary endpoints. Overall, 72.3% and 74.6% of patients receiving placebo and zinpentraxin alfa, respectively, experienced one or more adverse events. Post hoc analysis revealed that extreme FVC decline in two placebo-treated patients resulted in the clinical benefit of zinpentraxin alfa reported by phase II. Conclusions: Zinpentraxin alfa treatment did not benefit patients with IPF over placebo. Learnings from this program may help improve decision making around trials in IPF. Clinical trial registered with www.clinicaltrials.gov (NCT04552899).

Use of 6-minute walk distance to predict lung transplant-free survival in fibrosing non-IPF interstitial lung diseases.

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. 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. 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. 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.

Rituximab compared to intravenous cyclophosphamide in adults with connective tissue disease-associated interstitial lung disease: the RECITAL RCT

Background Interstitial lung disease frequently complicates systemic autoimmune disorders including scleroderma, idiopathic inflammatory myositis and mixed connective tissue disease, resulting in considerable morbidity and mortality. Based on the results of trials undertaken in scleroderma, cyclophosphamide is the standard of care for individuals with severe or progressive connective tissue disease-associated interstitial lung disease. Observational studies suggest that the anti-CD20 monoclonal antibody, rituximab is an effective rescue therapy in treatment of refractory connective tissue disease-associated interstitial lung disease, but it has not been studied as first-line therapy in clinical trials. Objectives To compare the safety and efficacy of rituximab against that of cyclophosphamide as treatment for individuals with severe, progressive interstitial lung disease associated with scleroderma, idiopathic inflammatory myositis or mixed connective tissue disease. Methods This was a Phase IIb, multicentre, randomised, double-blind, double-dummy study assessing the superiority of rituximab compared with cyclophosphamide, conducted in rheumatology or interstitial lung disease units at 11 UK centres. The study recruited individuals with extensive and/or progressive connective tissue disease-associated interstitial lung disease, excluding those with significant comorbidities, including airflow obstruction. Participants were randomised 1 : 1 to receive either rituximab 1 g given intravenously, twice at an interval of 2 weeks, or intravenous cyclophosphamide given monthly for 6 months at a dose of 600 mg/m2 body surface area. The primary end point for the study was the change in forced vital capacity at 24 weeks. Secondary end points included safety and tolerability, corticosteroid exposure, forced vital capacity change at 48 weeks and patient-reported quality of life. A cost-effectiveness analysis was undertaken to assess the impact of rituximab use in the United Kingdom National Health Service. Results One hundred and one subjects (70 females) with a mean age of 56.3 years were randomised; 51 to rituximab and 50 to cyclophosphamide. Ninety-seven were included in the modified intention-to-treat population for the primary and secondary efficacy analyses (49 in the rituximab group and 48 in the cyclophosphamide group). 38.6% had scleroderma, 44.6% idiopathic inflammatory myositis and 16.8% mixed connective tissue disease. Four subjects withdrew prior to the first dose of therapy (two in each arm). At 24 weeks, both rituximab and cyclophosphamide improved forced vital capacity from baseline [(mean ± standard deviation) 97 ± 234 and 99 ± 329 ml, respectively]. Using an adjusted mixed-effects model corrected for diagnosis and baseline forced vital capacity the difference in forced vital capacity at 24 weeks between rituximab and cyclophosphamide was −40 ml (95% CI −153 to 74 ml), p = 0.49. Other physiological and quality-of-life parameters improved in both arms following treatment but were not statistically significantly different between groups. Numerically fewer adverse events were reported by subjects receiving rituximab. Corticosteroid exposure over the 48 weeks of the trial was numerically less in the rituximab arm [13,291 (±14,657) mg of hydrocortisone equivalent per subject in the cyclophosphamide arm versus 11,469 (±10,041) mg per subject in the rituximab group; these differences did not reach statistical significance]. Limitations of the study include a disproportionate number of subjects being recruited from a single centre and insufficient subjects in each subgroup to determine whether there were treatment differences between individual connective tissue diseases. Based on the results of the trial, from a UK healthcare payer perspective, rituximab is more cost-effective than cyclophosphamide as a treatment for severe or progressive connective tissue disease-interstitial lung disease. Conclusions Rituximab improved forced vital capacity and patient-reported quality of life at 24 weeks but was not superior to cyclophosphamide. Rituximab should be considered as a therapeutic alternative to cyclophosphamide in individuals with connective tissue disease-associated interstitial lung disease requiring systemic therapy. Future work should explore the role of repeated dosing of rituximab and the use of rituximab earlier in the course of connective tissue disease-associated interstitial lung disease. Trial registration This trial is registered as ISRCTN16474148. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation Programme (NIHR award ref: 11/116/03) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 4. See the NIHR Funding and Awards website for further award information.

Estimating the effect of nintedanib on forced vital capacity in children and adolescents with fibrosing interstitial lung disease using a Bayesian dynamic borrowing approach.

The rarity of childhood interstitial lung disease (chILD) makes it challenging to conduct powered trials. In the InPedILD trial, among 39 children and adolescents with fibrosing ILD, there was a numerical benefit of nintedanib versus placebo on change in forced vital capacity (FVC) over 24 weeks (difference in mean change in FVC % predicted of 1.21 [95% confidence interval: -3.40, 5.81]). Nintedanib has shown a consistent effect on FVC across populations of adults with different diagnoses of fibrosing ILD. In a Bayesian dynamic borrowing analysis, prespecified before data unblinding, we incorporated data on the effect of nintedanib in adults and the data from the InPedILD trial to estimate the effect of nintedanib on FVC in children and adolescents with fibrosing ILD. The data from adults were represented as a meta-analytic predictive (MAP) prior distribution with mean 1.69 (95% credible interval: 0.49, 3.08). The adult data were weighted according to expert judgment on their relevance to the efficacy of nintedanib in chILD, obtained in a formal elicitation exercise. Combined data from the MAP prior and InPedILD trial analyzed within the Bayesian framework resulted in a median difference between nintedanib and placebo in change in FVC % predicted at Week 24 of 1.63 (95% credible interval: -0.69, 3.40). The posterior probability for superiority of nintedanib versus placebo was 95.5%, reaching the predefined success criterion of at least 90%. These findings, together with the safety data from the InPedILD trial, support the use of nintedanib in children and adolescents with fibrosing ILDs.

A comparative study of bronchodilator response: utilizing pre-bronchodilator versus predicted normal values

BackgroundA positive bronchodilator response has been defined as a 12% increase in the forced expiratory volume in one second (FEV1) or forced vital capacity (FVC) from their respective pre-bronchodilator values, combined with at least a 0.2 L absolute change. Recent recommendations suggested the use of the percent change in FEV1 and FVC relative to their predicted normal values without having applied them in patients with airflow obstruction. The aim of the current study was to compare the two approaches over a wide range of pre-bronchodilator FEV1 and FVC values.MethodsA retrospective review of consecutive patients undergoing spirometry and bronchodilator testing was completed. The change in FEV1 and FVC with a bronchodilator was expressed relative to the pre-bronchodilator and predicted normal FEV1 and FVC.ResultsIn 1,040 patients with a non-paradoxical change in FEV1, 19.0% had a ≥ 12% change in FEV1 using their pre-bronchodilator value compared to 5.7% using their predicted normal value. For FVC, the respective values were 12.7% vs. 5.8%. The difference was retained in patients with a ≥ 0.2 L change in FEV1 or FVC. In unobstructed patients, the upper threshold (two standard deviations above the mean) of the bronchodilator response was 14% for FEV1 and 10% for FVC using predicted normal values.ConclusionsExpressing the percent change in FEV1 and FVC relative to predicted normal values reduces the over-estimation of the bronchodilator response, especially in patients with a very low pre-bronchodilator FEV1, including in those with a ≥ 0.2 L change in FEV1. Irrespective of pre-bronchodilator values, a ≥ 14% change in FEV1 and ≥ 10% change in FVC relative to the predicted normal values could be considered a positive bronchodilator response.

Baseline absolute monocyte count predicts lung function decline among patients with systemic sclerosis-associated interstitial lung disease: A post hoc analysis from the focuSSced trial

ObjectiveInterstitial lung disease (ILD) is the leading cause of death in adults with systemic sclerosis (SSc). The identification of biomarkers to predict progression of SSc-ILD is an important unmet need. The purpose of this study was to determine whether an elevated baseline absolute monocyte count (AMC) is associated with a decline in forced vital capacity (FVC) at 48 weeks among participants with SSc-ILD enrolled in the phase 3 focuSSced trial. MethodsWe performed a post-hoc analysis of the focuSSced trial, a multicenter, double-blind, randomized, placebo-controlled trial of adults with diffuse cutaneous SSc for ≤ 60 months. Participants received subcutaneous tocilizumab 162 mg or placebo weekly for 48 weeks. We examined the relationship between baseline AMC and FVC at 48 weeks using a General Linear Model adjusted for potential confounders. ResultsThe 136 participants with SSc-ILD in focuSSced were included in this study. Among participants assigned to the placebo group, there was a statistically significant inverse association between baseline AMC and change in FVC from baseline at week 48 in both unadjusted (β coefficient -0.539, 95 % CI -1.032 to -0.047, p-value=0.032) and multivariable-adjusted (β coefficient -0.573, 95 % CI -1.086 to -0.060, p-value=0.029) models. Among participants with SSc-ILD assigned to the tocilizumab group, there was no statistically significant association between baseline AMC and change in FVC from baseline at week 48 in unadjusted or fully adjusted models. ConclusionAMC may be a biomarker of disease progression in SSc-ILD, especially in those with early SSc with elevated circulating inflammatory markers. These results should be validated in other SSc-ILD cohorts.

A prospective cohort study of periostin as a serum biomarker in patients with idiopathic pulmonary fibrosis treated with nintedanib

This study investigated the utility of periostin, a matricellular protein, as a prognostic biomarker in patients with idiopathic pulmonary fibrosis (IPF) who received nintedanib. Monomeric and total periostin levels were measured by enzyme-linked immunosorbent assay in 87 eligible patients who participated in a multicenter prospective study. Forty-three antifibrotic drug-naive patients with IPF described in previous studies were set as historical controls. Monomeric and total periostin levels were not significantly associated with the change in forced vital capacity (FVC) or diffusing capacity of the lungs for carbon monoxide (DLCO) during any follow-up period. Higher monomeric and total periostin levels were independent risk factors for overall survival in the Cox proportional hazard model. In the analysis of nintedanib effectiveness, higher binarized monomeric periostin levels were associated with more favorable suppressive effects on decreased vital capacity (VC) and DLCO in the treatment group compared with historical controls. Higher binarized levels of total periostin were associated with more favorable suppressive effects on decreased DLCO but not VC. In conclusion, higher periostin levels were independently associated with survival and better therapeutic effectiveness in patients with IPF treated with nintedanib. Periostin assessments may contribute to determining therapeutic strategies for patients with IPF.

Extracting forced vital capacity from the electronic health record through natural language processing in rheumatoid arthritis-associated interstitial lung disease.

To develop a natural language processing (NLP) tool to extract forced vital capacity (FVC) values from electronic health record (EHR) notes in patients with rheumatoid arthritis-interstitial lung disease (RA-ILD). We selected RA-ILD patients (n = 7485) in the Veterans Health Administration (VA) between 2000 and 2020 using validated ICD-9/10 codes. We identified numeric values in proximity to FVC string patterns from clinical notes in the EHR. Subsequently, we performed processing steps to account for variability in note structure, related pulmonary function test (PFT) output, and values copied across notes, then assigned dates from linked administrative procedure records. NLP-derived FVC values were compared to values recorded directly from PFT equipment available on a subset of patients. We identified 5911 FVC values (n = 1844 patients) from PFT equipment and 15 383 values (n = 4982 patients) by NLP. Among 2610 date-matched FVC values from NLP and PFT equipment, 95.8% of values were within 5% predicted. The mean (SD) difference was 0.09% (5.9), and values strongly correlated (r = 0.94, p < 0.001), with a precision of 0.87 (95% CI 0.86, 0.88). NLP captured more patients with longitudinal FVC values (n = 3069 vs. n = 1164). Mean (SD) change in FVC %-predicted per year was similar between sources (-1.5 [30.0] NLP vs. -0.9 [16.6] PFT equipment; standardized response mean = 0.05 for both). NLP of EHR notes increases the capture of accurate, longitudinal FVC values by three-fold over PFT equipment. Use of this NLP tool can facilitate pharmacoepidemiologic research in RA-ILD and other lung diseases by capturing this critical measure of disease severity.

Pulmonary function assessment after COVID-19 in vaccinated healthcare workers

COVID-19 typically presents with flu-like symptoms due to the viral infection itself. The most severe cases are characterised by lung damage, an important factor in fatal outcome due to alveolar damage. In some cases, patients develop a long COVID with persistent symptoms of chest pain and fatigue. Causes, including organ damage or inflammation, are being investigated. Clinical outcomes are variable and permanent lung damage is not fully understood, while vaccination is effective against severe infection but its effect on respiratory function in mild cases remains uncertain. This retrospective study aims to analyse changes in lung function in HCWs who had COVID-19 between 2020 and 2022, comparing their spirometric test results before and after the pandemic and taking into account their vaccination status. 321 HCWs were included in the study. The study examined spirometric parameters both before and after the pandemic, and all measured outcomes except the FEV1/FVC ratio showed a significant decrease during the study period. We then assessed the association between SARS-CoV-2 infection and changes in lung function parameters, analysing infections in 2020, 2021 and 2022 separately. We found a statistically significant difference in Forced vital capacity (FVC) between infected and non-infected subjects in 2020 and 2021, but not in 2022. To evaluate the protective effect of SARS-CoV-2 vaccination on respiratory function, a linear regression analysis was performed using changes in FVC, Forced expiratory volume in 1 s (FEV1), FVC/FEV1 ratio and Peak expiratory flow (PEF) as dependent variables. The analysis showed that the decline in FVC was significantly lower in subjects who had been vaccinated prior to infection. The study concludes that subclinical SARS-CoV-2 infections in 2020 and 2021 worsened respiratory parameters (FVC and FEV1), but vaccination protected against these effects. Even healthy individuals with previous infections showed respiratory changes, with vaccination providing protection, especially for FVC decline. This highlights the importance of vaccinating healthcare workers against COVID-19.

Efficacy and safety of combination therapy with pirfenidone and nintedanib in patients with idiopathic pulmonary fibrosis.

Background: Recent studies have suggested that combination therapy with pirfenidone and nintedanib is safe and tolerable in patients with idiopathic pulmonary fibrosis (IPF). However, data from real-world practice are limited. Thus, we aimed to investigate the safety and efficacy of this combination therapy in patients with IPF in a real-world setting. Methods: A multicenter retrospective cohort study was conducted to investigate the safety and efficacy of combination therapy with pirfenidone and nintedanib in 45 patients with IPF. Incidences of adverse events and rates of lung function decline were compared before and after the combination therapy. Propensity score matching was performed to compare the outcomes between the combination and monotherapy groups. Results: The mean age of the patients was 68.8years, and 82.2% of them were male. The median follow-up duration after combination therapy was 12.1months. The majority of the patients (97.8%) received nintedanib as an add-on to pirfenidone. The most common adverse events after the combination therapy were diarrhea and anorexia. Pirfenidone or nintedanib was stopped in 12 patients owing to gastrointestinal AEs, lung transplantation, or financial problems. In patients with serial lung function data, the rate of decline in the forced vital capacity was significantly reduced after the combination therapy. In the matched analysis, the combination group had a higher incidence of diarrhea than the monotherapy group without an increase in serious adverse events; however, the two groups had similar changes in forced vital capacity (FVC). Conclusion: The combination of pirfenidone and nintedanib in patients with IPF has the potential to reduce the rate of FVC decline. However, in the matched analysis, FVC decline was comparable between the patients on combination therapy and those on monotherapy. The incidence of certain adverse events, particularly diarrhea, was higher with combination therapy, but serious adverse events were similar between the groups.

Antifibrotic Agents in Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Systematic Review and Meta-Analysis.

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a common extra-articular clinical manifestation of rheumatoid arthritis (RA) that has negative impacts on morbidity and mortality. In addition, there has been no proven treatment for RA-ILD to date. Thus, we planned a meta-analysis of a literature search to confirm the clinical effects of antifibrotic agents in RA-ILD patients. We conducted the literature search in Ovid MEDLIVE® databases, Cochrane Library databases, EMBASE, and KoreaMed and identified references elucidating the role of nintedanib or pirfenidone in adult patients with RA-ILD. Among the identified studies, those with comparative interventions, complete results of clinical trials, and available full text were included in the analysis. The primary outcome was the effect of the antifibrotic agent on disease progression in RA-ILD patients assessed with a mean difference in the change of forced vital capacity (FVC) and the proportion of patients with an increase in percent predicted FVC of 10% or more over 52 weeks. Analysis for heterogeneity was assessed through I2 statistics. Meta-analysis with a fixed effect model was performed on changes in FVC. A total of 153 articles were identified through database searches, of which 28 were excluded because of duplication. After additional screening, 109 studies were selected with full text and two articles qualified for analysis according to the set inclusion and exclusion criteria. As a result, two randomized controlled studies were selected, comparing nintedanib and pirfenidone to placebo, respectively. The meta-analysis revealed that antifibrotic agents showed a significant reduction in FVC decline compared to placebo in patients with RA-ILD (mean difference, 88.30; 95% CI, 37.10-139.50). Additionally, there were significantly fewer patients experienced an increase in percent predicted FVC of 10% or more in the antifibrotic agent group compared to the placebo group (Odds ratio 0.42; 95% CI 0.19-0.95, p = 0.04). There was no significant heterogeneity between the two included studies (χ2 = 0.35, p = 0.0007, I2 = 0%). The meta-analysis suggests that nintedanib and pirfenidone may have clinical utility in reducing disease progression in patients with RA-ILD. Further research is needed to confirm the clinical benefits of antifibrotic agents in RA-ILD.

Modelling the longitudinal measurement of chronic obstructive pulmonary disease outpatient follow-up in the northwestern Ethiopia

Chronic obstructive pulmonary disease is a condition which can be prevented and treated and is characterized by difficulty of breathing that is not entirely curable. The overall objective of this study was to model the variation of longitudinal measurement over time for outpatients with chronic obstructive pulmonary diseases at the University of Gondar referral hospital. From February 1, 2019, to February 1, 2022, a retrospective study of outpatients with chronic obstructive pulmonary disease was conducted in a hospital. The data was extracted from all patients' data records from the patient’s chart. The information includes the fundamental demographic and clinical details of each outpatients with chronic obstructive pulmonary disease. Mixed linear model were used to investigate the determinant factor of chronic obstructive pulmonary disease. From a total of 266 outpatients, Averages of the ratio of forced expiratory volume to forced vital capacity among chronic obstructive pulmonary disease patients were 0.65, with a standard deviation of 0.043. Comorbidities (average = 2.18, 95% CI 0.43:3.9, P = 0.0133), HIV(average = 4.83, 95% CI 1.94:7.72, P = 0.0012), education (average = 2.98; 95% CI 0.75:4.8, P = 0.008), and weight (average = 0.178, 95% CI 0.045:0.311, P = 0.009) are risk factors for change in forced vital capacity. This study clearly shows that there is a high COPD prevalence in Ethiopia. The risk factors for chronic obstructive pulmonary diseases are the smoking status, comorbidities, HIV, education status of the patient, weight, and time of the visit.

Systemic corticosteroids in fibrotic lung disease: a systematic review and meta-analysis

ObjectivesWe aimed to assess the available evidence for corticosteroids in fibrotic interstitial lung disease (fILD) to inform the randomised embedded multifactorial adaptive platform ILD.DesignSystematic review and meta-analysis.Data sourcesWe searched Embase,...