Decline In Forced Vital Capacity Research Articles

E038 Predictors for pulmonary function decline in interstitial lung disease

Abstract Background/Aims Interstitial lung disease (ILD) is commonly associated with a decline in forced vital capacity (FVC). The most substantial loss of lung function typically occurs early in the course of the disease. The natural history of ILD varies among individuals. Several studies have employed FVC decline as the primary endpoint and NICE has recently approved antifibrotics based on this as an endpoint. An FVC reduction exceeding 10% has consistently been shown to correlate with poorer survival, leading to evidence-based guidelines recommending, an absolute decrease in FVC of 10% can be used as a surrogate marker of mortality. Aim: To obtain insights into the decline in lung function in patients with ILD, by comparing FVC measurements at baseline and 52 weeks. We hypothesised that the rate of absolute decline is increased with higher age, active smoking, sex, duration of ILD and comorbidities. Methods This was a retrospective study conducted at Southend University Hospital, involving a single-centre cohort of ILD patients identified from the ILD multidisciplinary team from 2016-June 2023. Data collection included parameters such as age at ILD onset, gender, occupation, smoking history, serial pulmonary function tests, imaging, comorbidities, survival outcomes, causes of death, and treatment regimens. Results Data from 197 patients were included in this study. Mean age of the cohort at diagnosis was 74. Men 112 (57%) and females 85 (43%). Among the study population 128 had a history of ex or current smoking. Mean duration of ILD was 40 months, ranging from 2 to 168 months. Of the participants 115 were deceased & 83 remained alive. We included most common conditions in the analysis: idiopathic pulmonary fibrosis (IPF) = 65, RA = 22, idiopathic pulmonary fibrosis with autoimmune features (IPAF) =15, hypersensitivity pneumonitis (HP) = 20, unclassified=25, SSc-ILD = 13, Sjogren’s = 2, myositis = 1, vasculitis = 3 and sarcoidosis = 7. For analysis, we included RA, SSc, Sjogren’s, vasculitis, ankylosing spondylitis, myositis, and sarcoidosis in the CTD -ILD group. 23 were excluded from analysis (COOP, OP, CPFE, PPFE and drug induced pneumonitis). We categorised disease progression as severe, if FVC decline exceeded 10%. This was achieved as follows; 3/36 in CTD -ILD, 2/10 in IPAF, 6/16 in HP, 5/19 unclassified in ILD and 14/47 in IPF (χ²=7.5, p = 0.109). Moderate disease progression was defined as an FVC decline between 5- 10%. It was achieved in 6/36 in CTD -ILD, 3/16 in HP, 1/19 in unclassified and 5/47 in IPF (χ²=3.8, p = 0.439).In univariate analysis, none of the predictors achieved significance for severe or moderate progression among subgroups. In multivariate analysis, only the disease subgroup achieved significance in predicting significant lung function decline progression. Conclusion The rate of decline in lung function during follow-up differed across the subgroups based on clinical factors and demographics. This data supports the unpredictable nature of ILD. Disclosure G.M. Koduri: Corporate appointments; NONE. Consultancies; NONE. Shareholder/stock ownership; NONE. Royalties; NONE. Honoraria; NONE. Member of speakers’ bureau; NONE. Grants/research support; NONE. Other; NONE.

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.

Clinical characterization and outcomes of impulse oscillometry-defined bronchodilator response: an ECOPD cohort-based study

BackgroundThe clinical significance of the impulse oscillometry-defined small airway bronchodilator response (IOS-BDR) is not well-known. Accordingly, this study investigated the clinical characteristics of IOS-BDR and explored the association between lung function decline, acute respiratory exacerbations, and IOS-BDR.MethodsParticipants were recruited from an Early Chronic Obstructive Pulmonary Disease (ECOPD) cohort subset and were followed up for two years with visits at baseline, 12 months, and 24 months. Chronic obstructive pulmonary disease (COPD) was defined as a post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio < 0.70. IOS-BDR was defined as meeting any one of the following criteria: an absolute change in respiratory system resistance at 5 Hz ≤ − 0.137 kPa/L/s, an absolute change in respiratory system reactance at 5 Hz ≥ 0.055 kPa/L/s, or an absolute change in reactance area ≤ − 0.390 kPa/L. The association between IOS-BDR and a decline in lung function was explored with linear mixed-effects model. The association between IOS-BDR and the risk of acute respiratory exacerbations at the two-year follow-up was analyzed with the logistic regression model.ResultsThis study involved 466 participants (92 participants with IOS-BDR and 374 participants without IOS-BDR). Participants with IOS-BDR had higher COPD assessment test and modified Medical Research Council dyspnea scale scores, more severe emphysema, air trapping, and rapid decline in FVC than those without IOS-BDR over 2-year follow-up. IOS-BDR was not associated with the risk of acute respiratory exacerbations at the 2-year follow-up.ConclusionsThe participants with IOS-BDR had more respiratory symptoms, radiographic structural changes, and had an increase in decline in lung function than those without IOS-BDR.Trial registrationChinese Clinical Trial Registry, ChiCTR1900024643. Registered on 19 July, 2019.

Overview of Rheumatoid Arthritis-Associated Interstitial Lung Disease and Its Treatment.

Interstitial lung disease (ILD) is a common pulmonary complication of rheumatoid arthritis (RA), causing significant morbidity and mortality. Optimal treatment for RA-ILD is not yet well defined. Reliable prognostic indicators are largely byproducts of prior ILD progression, including low or decreasing forced vital capacity and extensive or worsening fibrosis on imaging. In the absence of validated tools to predict treatment response, decisions about whether to initiate or augment treatment are instead based on clinical judgment. In general, treatment should be initiated in patients who are symptomatic, progressing, or at high risk of poor outcomes. Retrospective data suggest that mycophenolate mofetil, azathioprine, and rituximab are likely effective therapies for RA-ILD. Abatacept is also emerging as a potential first-line treatment option for patients with RA-ILD. Further, recent data demonstrate that immunosuppression may be beneficial even in patients with a usual interstitial pneumonia (UIP) pattern on imaging, suggesting that immunosuppression should be considered irrespective of imaging pattern. Recent randomized controlled trials have shown that antifibrotic medications, such as nintedanib and likely pirfenidone, slow forced vital capacity decline in RA-ILD. Consideration can be given to antifibrotic initiation in patients progressing despite immunosuppression, particularly in patients with a UIP pattern. Future research directions include developing tools to predict which patients will remain stable from patients who will progress, discriminating patients who will respond to treatment from nonresponders, and developing algorithms for starting immunosuppression, antifibrotics, or both as first-line therapies.

Impact of surgical lung biopsy on lung function and survival in patients with idiopathic pulmonary fibrosis in a multi-centre registry cohort.

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. 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. 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). 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.

Spirometric Assessment of Pulmonary Function Tests in Asthma Patients.

Asthma is a chronic airway inflammatory disorder that imposes substantial morbidity and mortality. Spirometry is a significant tool for the objective measurement ofobstruction amongasthmatics. The present study was conducted to assess the pulmonary function test parameters among asthmatics and compare the observed and predicted values. This cross-sectional research was performed on 120 asthmatic patients who attended a tertiary care healthcare center and underwent spirometry evaluation. The spirometry indices such as forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC ratio, peak expiratory flow rate (PEFR), and maximal voluntary ventilation (MVV) were recorded. Further, a gender-wise comparisonof spirometry indices was also done. There was a substantial decrease in FVC (2.05 ± 0.12 vs. 2.75 ± 0.24 L/sec; p = 0.02), FEV1 (1.78 ± 0.16 vs. 2.38 ± 0.32 L/sec; p = 0.01), FEV1/FVCratio (74 ± 4.38 vs. 83 ± 5.76 %; p = 0.01), PEFR (4.76 ± 0.42 vs. 5.82 ± 0.65 L/sec; p = 0.03), and MVV (78.65 ± 28.45 vs. 115.87 ± 32.15 L/min; p = 0.001) for observed andpredicted values.Female asthmatic patients displayed a substantial decline in FVC (p = 0.001), FEV1 (p = 0.006), FEV1/FVC (p = 0.001), and MVV (p = 0.01) when compared to males. This study suggests that asthmatic individuals had impaired lung function upon initial assessment.Female asthmatic patients studied are at increased risk of asthma severity when compared to males.

A Comparison of the Effectiveness of Nintedanib and Pirfenidone in Treating Idiopathic Pulmonary Fibrosis: A Systematic Review.

Idiopathic pulmonary fibrosis (IPF), which shares a radiographic pattern with the usual interstitial pneumonia (UIP), is a specific form of chronic and progressive interstitial lung disorder resulting in persistent fibrosis and impaired lung function. Most of the patients suffer from dyspnea which adversely affects health-related quality of life (HRQOL). The underlying etiology of the disease is not yet understood, but research done on the subject reveals that aberrant repair mechanisms and dysregulated immune responses may be the cause.It can affect any age group but predominantly affects patients who are above 50 years of age. It has been observed that in addition to age, the reasons are also related to smoking, pollution, and inhalation of harmful elements. As the cause of IPF is still unknown and there is no cure yet, presently, it is treated to delay lung function loss with antifibrotic medications, nintedanib, and pirfenidone. However, both nintedanib and perfenidone have side effects which affect different patients in different ways and with different levels of severity, thereby making the treatment even more challenging for medical practitioners. The present systematic review aims at studying the efficacy of pirfenidone and nintedanib in relieving symptoms and in extending survival in patients. A detailed search was done in relevant articles listed in PubMed, ScienceDirect, and the New England Journal of Medicine between 2018 and 2023. It was observed that the most accepted way of measuring the progression of IPF is the evaluation of pulmonary function by assessing the forced vital capacity (FVC). Several studies have shown that the decline in FVC over a period of 6-12 months is directly associated with a higher mortality rate. The outcomes were similar in both male and female irrespective of age, gender, and ethnicity. However, some patients being treated with pirfenidone and nintedanib experienced various side-effects which were mainly gastrointestinal like diarrhea, dyspepsia, and vomiting. In the case of pirfenidone, some patients also experienced photosensitivity and skin rashes. In cases where the side-effects are extremely severe and are more threatening than the disease itself, the treatment has to be discontinued. The survival rate in patients with IPF is marked by a median of 3-5 yearsthat is even lower than many cancers; hence, the treatment should be started as soon as the disease is detected. However, further research is needed to establish the etiology of IPF and to establish treatments that can stop its progression.

Forced Expiratory Volume in One Second Quotient (FEV1Q) as a Prognostic Factor in Amyotrophic Lateral Sclerosis Patients: Comparing Its Predictive Value to Other Lung Function Measurements.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting the first and second motor neurons. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) have conventionally served as indicators of respiratory muscle strength. Recently, FEV1Q (FEV1 divided by the sex-specific first percentile values of absolute FEV1 in adults with lung disease) has been suggested as a predictor of mortality. While FVC has been utilized as a prognostic factor, FEV1Q has not yet been examined. This retrospective unicenter study evaluated FEV1Q as a predictor of mortality in ALS patients, comparing its predictive efficacy with other measurements, including FEV1, FVC, sniff nasal inspiratory pressure, and maximal inspiratory pressure. The study utilized univariate analysis for each variable employing the Cox proportional hazards model to determine the statistical significance and predictive power of each measurement. Forty-five patients were included, female predominant (60%) and an average age at diagnosis of 69.2 ± 11 years. Almost all (95%) met the criteria for non-invasive ventilation (NIV) and initiated (93%) during the study period, a mean of 137 days after diagnosis. The mortality rate observed was 57%, occurring at a median of 398 days post-diagnosis. On average, patients underwent 1.7 pulmonary function tests, revealing a decline in various parameters, including FEV1, FEV1Q, and FVC. However, only FEV1Q was a statistically significant predictor of mortality (p < 0.0083) in a Cox regression analysis. A negative coefficient for FEV1Q indicated that higher values were associated with a reduced mortality risk, with an average FEV1Q of 2.68 observed at the time of death. FEV1Q emerged as the only statistically significant predictor of mortality among the evaluated respiratory measurements in ALS patients. This study is the first to focus on applying FEV1Q in the clinical evaluation of ALS, marking an initial step in understanding its potential role in patient follow-up. However, further studies are needed before these findings can be incorporated into clinical practice.

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

A phase II trial reported clinical benefit over 28 weeks in patients with idiopathic pulmonary fibrosis who received zinpentraxin alfa. To investigate the efficacy and safety of zinpentraxin alfa in patients with idiopathic pulmonary fibrosis in a phase III trial. This 52-week phase III, double-blind, placebo-controlled, pivotal trial was conducted at 275 sites in 29 countries. Patients with idiopathic pulmonary fibrosis were randomized 1:1 to intravenous placebo or zinpentraxin alfa 10 mg/kg every four weeks. The primary endpoint was absolute change from baseline to Week 52 in forced vital capacity. Secondary endpoints included absolute change from baseline to Week 52 in percent predicted forced vital capacity and six-minute walking distance. Safety was monitored via adverse events. Post-hoc analysis of the phase II and phase III data explored changes in forced vital capacity and their impact on the efficacy 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 following a pre-specified futility analysis that demonstrated no treatment benefit of zinpentraxin alfa over placebo. In the final analysis, absolute change from baseline to Week 52 in forced vital capacity 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 ≥1 adverse event. Post-hoc analysis revealed that extreme forced vital capacity decline in two placebo-treated patients resulted in the clinical benefit of zinpentraxin alfa reported by phase II. Zinpentraxin alfa treatment did not benefit patients with idiopathic pulmonary fibrosis over placebo. Learnings from this program may help improve decision-making around trials in idiopathic pulmonary fibrosis. Clinical trial registration available at www. gov, ID: NCT04552899.

Lung imaging patterns in connective tissue disease–associated interstitial lung disease impact prognosis and immunosuppression response

Abstract Objectives Interstitial lung disease (ILD) in CTDs has highly variable morphology. We aimed to identify imaging features and their impact on ILD progression, mortality, and immunosuppression response. Methods Patients with CTD-ILD had high-resolution chest CT (HRCT) reviewed by expert radiologists blinded to clinical data for overall imaging pattern [usual interstitial pneumonia (UIP); non-specific interstitial pneumonia (NSIP); organizing pneumonia (OP); fibrotic hypersensitivity pneumonitis (fHP); and other]. Transplant-free survival and change in percent-predicted forced vital capacity (FVC) were compared using Cox and linear mixed-effects models adjusted for age, sex, smoking, and baseline FVC. FVC decline after immunosuppression was compared with pre-treatment. Results Among 645 CTD-ILD patients, the most frequent CTDs were SSc (n = 215), RA (n = 127), and inflammatory myopathies (n = 100). NSIP was the most common pattern (54%), followed by UIP (20%), fHP (9%), and OP (5%). Compared with the case for patients with UIP, FVC decline was slower in patients with NSIP (by 1.1%/year, 95% CI 0.2, 1.9) or OP (by 3.5%/year, 95% CI 2.0, 4.9), and mortality was lower in patients with NSIP [hazard ratio (HR) 0.65, 95% CI 0.45, 0.93] or OP (HR 0.18, 95% CI 0.05, 0.57), but higher in fHP (HR 1.58, 95% CI 1.01, 2.40). The extent of fibrosis also predicted FVC decline and mortality. After immunosuppression, FVC decline was slower compared with pre-treatment in NSIP (by 2.1%/year, 95% CI 1.4, 2.8), with no change for UIP or fHP. Conclusion Multiple radiologic patterns are possible in CTD-ILD, including a fHP pattern. NSIP and OP were associated with better outcomes and response to immunosuppression, while fHP had worse survival compared with UIP.

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.

Deep Learning Classification of Usual Interstitial Pneumonia Predicts Outcomes.

Computed tomography (CT) enables noninvasive diagnosis of usual interstitial pneumonia (UIP), but enhanced image analyses are needed to overcome the limitations of visual assessment. Apply multiple instance learning (MIL) to develop an explainable deep learning algorithm for prediction of UIP from CT and validate its performance in independent cohorts. We trained a MIL algorithm using a pooled dataset (n=2,143) and tested it in three independent populations: data from a prior publication (n=127), a single-institution clinical cohort (n=239), and a national registry of patients with pulmonary fibrosis (n=979). We tested UIP classification performance using receiver operating characteristic (ROC) analysis with histologic UIP as ground truth. Cox proportional hazards and linear mixed effects models were used to examine associations between MIL predictions and survival or longitudinal forced vital capacity (FVC). In two cohorts with biopsy data, MIL improved accuracy for histologic UIP (area under the curve [AUC] 0.77 [n=127] and 0.79 [n=239]) compared to visual assessment (AUC 0.65 and 0.71). In cohorts with survival data, MIL UIP classifications were significant for mortality ([n=239, mortality to April 2021] unadjusted hazard ratio 3.1 95% confidence interval [CI] [1.96, 4.91] p<0.001, and [n=979, mortality to July 2022] 3.64 95% CI [2.66, 4.97] p<0.001). Individuals classified as UIP positive by the algorithm had a significantly greater annual decline in FVC than those classified as UIP negative (-88 ml/year versus -45 ml/year, n=979 p<0.01), adjusting for extent of lung fibrosis. Computerized assessment using MIL identifies clinically significant features of UIP on CT. Such a method could improve confidence in radiologic assessment of patients with interstitial lung disease, potentially enabling earlier and more precise diagnosis.

ISABELA Studies: Plasma Exposure and Target Engagement Do Not Explain the Lack of Efficacy of Ziritaxestat in Patients with Idiopathic Pulmonary Fibrosis.

Autotaxin (ATX) contributes to the production of lysophosphatidic acid (LPA), which is associated with fibrosis development in idiopathic pulmonary fibrosis (IPF). The ATX inhibitor ziritaxestat failed to reduce decline in forced vital capacity (FVC) in patients with IPF in ISABELA 1 and 2 (NCT03711162 and NCT03733444), two identically designed phase III studies. In the current analysis, we evaluated pharmacokinetic and pharmacodynamic data from the pooled ISABELA studies to determine whether the lack of efficacy could be attributed to insufficient exposure and/or target engagement. Nonlinear mixed effect modeling was performed to predict ziritaxestat exposure in individual patients and describe its effect on LPA C18:2 levels. We assessed whether there was a correlation between ziritaxestat and ATX concentration and evaluated the relationship between LPA C18:2 reduction and change from baseline in FVC. Ziritaxestat exposure in patients with IPF was numerically lower in those who received ziritaxestat on top of pirfenidone than in those who received ziritaxestat on top of nintedanib or ziritaxestat alone. In most patients, LPA C18:2 reduction was comparable to that reported in healthy volunteers. ATX concentrations increased over time and correlated weakly with ziritaxestat exposure and LPA C18:2 reduction. No correlation between reduction in LPA C18:2 and change from baseline in FVC was apparent. Based on these evaluations, exposure and target engagement are not thought to have contributed to the lack of efficacy observed. We hypothesize that the lack of efficacy of ziritaxestat in the ISABELA program, despite adequate LPA reduction, could be due to the involvement of an alternative pro-fibrotic pathway.

Characteristics and disease course of untreated patients with interstitial lung disease associated with systemic sclerosis in a real-life two-centre cohort

BackgroundInterstitial lung disease (ILD) is the leading cause of death in systemic sclerosis (SSc). According to expert statements, not all SSc-ILD patients require pharmacological therapy.ObjectivesTo describe disease characteristics and disease...

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.

Systemic-Sclerosis-Related Interstitial Lung Disease: A Review of the Literature and Recommended Approach for Clinical Pharmacists.

To describe the efficacy, safety, and clinical utility of pharmacologic agents in the treatment of systemic sclerosis-related interstitial lung disease (SSc-ILD). A review of the literature was performed using the terms lung diseases, (interstitial/therapy) AND (scleroderma, systemic/therapy) OR (scleroderma, systemic) AND (lung diseases, interstitial/therapy) in PubMed, Ovid MEDLINE, CINAHL, and Web of Science. ClinicalTrials.gov was also searched to identify ongoing studies. The initial search was performed in October 2022, with follow-up searches performed in October 2023. Articles reviewed were limited to those written in the English language, human studies, and adult populations. A variety of therapeutic agents, including mycophenolate, azathioprine, cyclophosphamide (CYC), rituximab (RTX), nintedanib, and tocilizumab (TCZ) have slowed the rate of decline in forced vital capacity (FVC) and disease progression. Only nintedanib and TCZ have a labeled indication for SSc-ILD. Two agents, belimumab and pirfenidone, have shown encouraging results in smaller phase II and phase III studies, but have yet to be approved by the Food and Drug Administration. Patients with pulmonary manifestations of SSc-ILD have worse outcomes and lower survival rates compared with those without. It is imperative that disease management be individualized to achieve optimal patient-centered care. Pharmacists are uniquely suited to support this individualized management. Numerous pharmacologic agents have been studied and repurposed in the treatment of SSc-ILD, with nintedanib and TCZ gaining approval to slow the rate of decline in pulmonary function in SSc-ILD. Other agents, including belimumab and pirfenidone, are on the horizon as potential treatment options; but further studies are needed to compare their efficacy and safety with the current standard of care.

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.

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,...

Employment of the Envisia Genomic Classifier in Conjunction With Cryobiopsy in Patients With Undiagnosed Interstitial Lung Disease

BackgroundThe Envisia Genomic Classifier (EGC) is a clinically validated molecular diagnostic test identifying usual interstitial pneumonia (UIP), increasing the diagnostic confidence for idiopathic pulmonary fibrosis (IPF) in patients with interstitial lung disease (ILD). Research QuestionWhat is the association of EGC and lung cryobiopsy on clinical management decisions in patients with fibrotic ILD? Study Design and MethodsRetrospective analysis of patients at multi-medical centers. We assessed the change in management strategy following EGC and cryobiopsy. We evaluated the association between genomic UIP classification and disease progression using ATS definition of progressive pulmonary fibrosis (method 1); or combined endpoint of death from any cause, lung transplant, or ⩾10% relative decline in forced vital capacity (FVC) (method 2). RESULTSIn patients that were EGC positive for UIP (gcUIP+), 78.6% were diagnosed with IPF. Cryobiopsy and EGC test results changed management strategy for 59.5% of patients in the cohort that was gcUIP+, 21.4% of patients that had indeterminate cryobiopsy interpretations were gcUIP+, leading to change in treatment strategy of an additional 16.7%. There was a decrease in follow up without treatment from 64.3 % to 11.9 % (P<0.001). Utilization of immunosuppressive drugs decreased from 23.8% to 9.5% (P=0.06) and there was an increase in treatment with antifibrotics drugs from 11.9% to 71.4% (P<0.001). A Kaplan-Meier curve of disease progression did not reach statistical significance on multivariable analysis (HR 1.4, 95% CI 0.4–4.2; p=0.55; method 1) and (HR 1.3, 95% CI 0.8-2.1; p=0.29; method 2). Analysis of gcUIP+, patients who were not prescribed antifibrotics showed disease progression compared to patients with gcUIP- (HR=1.8, 95%CI=0.99-3.4, p=0.053) ConclusionsThis study suggests that combined EGC and cryobiopsy is associated with change in therapeutic strategy in patients with undiagnosed ILD. The EGC might serve as a predictor for disease progression in patients not treated with antifibrotics.