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A subset of interstitial lung diseases (ILDs) with autoimmune traits—including connective tissue disease-associated ILD (CTD-ILD) and interstitial pneumonia with autoimmune features (IPAF)—develops progressive fibrosing (PF)-ILD. The aim of our study was to evaluate the clinical characteristics and predictors of longitudinal lung function (LF) chan...
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Context 1
... influencing rapid progression qualifying as PF-ILD included malignancy as a comorbidity, ANA, anti-SS-A antibodies, and post-exercise pulse increase at the 6MWT ( Table 5). Malignancy was diagnosed in seven patients (two males and five females) including CML (1), lung (2), ovarian (1), breast (1), esophageal (1), and laryngeal cancer (1). ...Citations
... Previous studies have also suggested that high dietary sodium intake is an environmental risk factor for the occurrence and development of autoimmune diseases by promoting a shift in T-helper (Th)-1 and Th17 proinflammatory phenotypes 19,20 . Autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis, are widely known as important risk factors for the occurrence and development of ILD 21,22 . Approximately 20% of ILD may be attributed to autoimmune diseases 21,22 . ...
... Autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis, are widely known as important risk factors for the occurrence and development of ILD 21,22 . Approximately 20% of ILD may be attributed to autoimmune diseases 21,22 . Furthermore, increases in Th17 cells and IL-17 itself secondary to high sodium levels were found to promote pulmonary inflammation and fibrosis processes by promoting cytokine production and fibroblast proliferation 23 . ...
This study investigated the relationships between dietary sodium intake and the incidence and prevalence of interstitial lung disease (ILD) and pulmonary sarcoidosis using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. This study assessed the strength of the abovementioned relationships via LASSO analysis and a generalized additive model with Poisson regression and determined the nonlinear and lagged effects via a distributed lag nonlinear model (DLNM). In the past three decades, global dietary sodium intake has decreased gradually. Two LASSO and generalized additive analyses both suggested that dietary sodium intake is obviously correlated with the incidence and prevalence of ILD and pulmonary sarcoidosis. The overall exposure‒response curve revealed a dose‒effect relationship between dietary sodium intake and the incidence and prevalence of ILD and pulmonary sarcoidosis. The maximum lag-specific RR of extremely high dietary sodium intake was 1.75 (95% CI: 1.61–1.91, lag 0 year) for incidence and 3.19 (95% CI: 2.24–4.53, lag 0 year) for prevalence relative to the reference. Our study suggests that dietary sodium intake is positively associated with the incidence and prevalence of ILD and pulmonary sarcoidosis. These findings may have important policy implications for dietary sodium intake-reduction strategies to decrease the burden of respiratory diseases and promote public health.
... 1,5 Nagy et al. documented a ILD prevalence of 50.8% for SSc, 20.6% for RA, 9.5% for SLE, 9.5% for others (MCTD and UCTD), 6.4% for IIM, and 3.2% for vasculitis. 26 CTD has been identified as a sub-group of pathologies that can lead to a progressive fibrosant pattern unrelated to idiopathic pulmonary fibrosis; consequently, it has been the subject of numerous epidemiological, historical, prospective, and real-world studies. 45 AR and SSc have been identified as the primary causes of the progressive pattern, 26,[50][51][52] whereas Sjogren syndrome, MCTD, UCTD, IIM, and SLE account for a smaller proportion of cases. ...
... 26 CTD has been identified as a sub-group of pathologies that can lead to a progressive fibrosant pattern unrelated to idiopathic pulmonary fibrosis; consequently, it has been the subject of numerous epidemiological, historical, prospective, and real-world studies. 45 AR and SSc have been identified as the primary causes of the progressive pattern, 26,[50][51][52] whereas Sjogren syndrome, MCTD, UCTD, IIM, and SLE account for a smaller proportion of cases. 12,13 Even in the largest clinical trials or observational studies, insufficient data are available for these pathologies, 53 limiting the ability to analyze the epidemiology, risks, and treatment of PPF in diseases other than RA and SSc. ...
Introduction
Connective tissue disease-related interstitial lung disease (CTD-ILD) accounts for 30% of all cases of ILD. Some patients progress and develop progressive pulmonary fibrosis, which has a prognosis comparable to interstitial pulmonary fibrosis. In this study, relevant evidence about epidemiology, risk factors, biomarkers, and treatment are reviewed.
Materials and methods
A systematic review of the literature was carried out. Original observational and descriptive articles were included. Articles not providing information about the CTD diagnosis were excluded. PUBMED, EMBASE, SCOPUS, and LILACS were all searched. The total number of articles obtained was 528; data were extracted from 61 original articles.
Results
On average, ILD in these patients progressed by 33.7% over time. Patients with progressive pulmonary fibrosis had a similar 3.7-year median survival as those with idiopathic pulmonary fibrosis. Mortality was markedly increased (hazards ratio 3.29; 95% CI 2.76–3.82). A progressive course was seen in 34% of scleroderma (SSc) related ILD cases. Six interferon-induced proteins and a proteomic profile of 12 biomarkers were used to predict progression and response to treatment. The INBUILD and SENSCIS studies that assessed the effectiveness of nintedanib effectiveness revealed a reduced decrease in forced vital capacity. Progression in rheumatoid arthritis (RA) related ILD ranges from 38% to 50%. Control of RA disease activity and use of antifibrotics benefit the lungs.
Conclusion
A significant proportion of patients with CTD-ILD have progressive lung disease, with the corresponding adverse mortality effects. The majority of the data regarding CTD-ILD are from cohorts of patients with RA-ILD and SSc-ILD, in which antifibrotics and concurrent immunosuppressive treatments have been effective. There is not enough information available on other autoimmune disorders to draw any firm conclusions regarding progression rates or treatment effects.
... Analyses of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1 ), FEV 1 /FVC and total lung capacity (TLC) were performed by electronic spirometer according to the current guidelines at the Department of Pulmonology as previously described [30]. Lung diffusion capacity was measured using the single-breath CO method (D LCO ), and the transfer coefficient of the lung for CO (K LCO ) was also calculated (PDD: 301/s, Piston, Budapest, Hungary). ...
Diagnosing interstitial lung disease (ILD) can be a challenging process. New biomarkers may support diagnostic decisions. Elevated serum progranulin (PGRN) levels have been reported in liver fibrosis and dermatomyositis-associated acute interstitial pneumonia. Our aim was to assess the role of PGRN in the differential diagnosis of idiopathic pulmonary fibrosis (IPF) and other ILDs. Serum levels of PGRN were measured by enzyme-linked immunosorbent assay in stable IPF (n = 40), non-IPF ILD (n = 48) and healthy controls (n = 17). Patient characteristics, lung function, CO diffusion (DLCO), arterial blood gases, 6-min walk test, laboratory parameters and high-resolution (HR)CT pattern were assessed. In stable IPF, PGRN levels did not differ from healthy controls; however, serum PGRN levels were significantly higher in non-IPF ILD patients compared to healthy subjects and IPF (53.47 ± 15.38 vs. 40.99 ± 5.33 vs. 44.66 ± 7.77 ng/mL respectively; p < 0.01). The HRCT pattern of usual interstitial pneumonia (UIP) was associated with normal PGRN level, while for non-UIP patterns, significantly elevated PGRN level was measured. Elevated serum PGRN levels may be associated with non-IPF ILD, especially non-UIP patterns and might be helpful in cases of unclear radiological patterns in the differentiation between IPF and other ILDs.
... In presence of respiratory failure, long term oxygen treatment is required for clinical control and symptomatic relief; and all patients eventually require pulmonary rehabilitation (4). Currently the justification for antifibrotic treatment is lacking due to insufficient data and studies are underway for their role in disease control (5). ...
Interstitial Pneumonia with Autoimmune Features (IPAF) is a newly defined connective tissue disease (CTD) related pulmonary involvement in 2015 by the European Respiratory Society and American Thoracic Society. It is used to define the subgroup of patients with no known CTD history. In this case report, we present a patient with IPAF diagnosis, who had rapid clinical deterioration after a COVID-19 infection, which was attributed to a newly diagnosed pulmonary hypertension. A 69-year-old male patient with chronic obstructive pulmonary disease (COPD) diagnosis was on the routine follow-up for a duration of five years. He had been diagnosed with type 2 diabetes mellitus and gout, with under constant follow-up for a known cardiovascular arterial disease history. During a routine pulmonary evaluation, the patient had stated a worsening exercise capacity and an increase in coughing. The requested high-resolution computed tomography showed emphysema at the upper lobes and a reticular pattern at the lower lobes, with honeycombing, traction bronchiectasis, and ground-glass findings. After a rheumatology consultation, which excluded the presence of an underlying rheumatological disease, the patient was diagnosed with IPAF. Under immunosuppressive treatment, the patient complained of increased dyspnea at a routine follow-up after a COVID infection in 2021, and antifibrotic treatment was initiated due to the progression of pulmonary fibrosis. During routine follow-up, further limitation in exercise capacity was evident, for which extra-pulmonary involvement was investigated. Pulmonary hypertension (PH) diagnosis was confirmed with vasoreactivity positivity; however, due to both progression in IPAF and concurrent PH, the patient was lost during the follow-up. As seen in this case, despite being stable for years, the addition of another comorbidity may rapidly worsen a patient’s otherwise stable clinical condition. While antifibrotic regimens may be used on a case-by-case basis, their effect on disease progression may not be sufficient to control an already present comorbidity, such as pulmonary hypertension.
... We present data from a retrospective cohort of similar demographics to other reported IIP populations (19,20). Also alike many working groups, there was a considerable number of patients diagnosed with undifferentiated or pulmonary-dominant CTD before the concept of IPAF was introduced. ...
Objectives
To assess performance of interstitial pneumonia (IP) with autoimmune features (IPAF) criteria in clinical practice and describe the utility of additional workup in identifying patients with underlying connective tissue diseases (CTD).
Methods
We set a retrospective study of our patients with autoimmune IP, who were allocated to CTD-IP, IPAF or undifferentiated autoimmune IP (uAIP) subgroups according to the updated classification criteria. Presence of the process-related variables comprising IPAF defining domains was scrutinized in all patients, and, when available, the results of nailfold videocapillaroscopy (NVC) were recorded.
Results
Thirty nine out of 118 patients, accounting for 71% of former undifferentiated cases, fulfilled IPAF criteria. Arthritis and Raynaud’s phenomenon were prevalent in this subgroup. While systemic sclerosis-specific autoantibodies were restricted to CTD-IP patients, anti-tRNA synthetase antibodies were also present in IPAF. In contrast, rheumatoid factor, anti-Ro antibodies and ANA nucleolar patterns could be found in all subgroups. Usual interstitial pneumonia (UIP) / possible UIP were the most frequently observed radiographic patterns Therefore, the presence of thoracic multicompartimental findings as also performance of open lung biopsies were useful in characterizing as IPAF those UIP cases lacking a clinical domain. Interestingly, we could observe NVC abnormalities in 54% of IPAF and 36% of uAIP tested patients, even though many of them did not report Raynaud’s phenomenon.
Conclusion
Besides application of IPAF criteria, distribution of IPAF defining variables along with NVC exams help identify more homogeneous phenotypic subgroups of autoimmune IP of potential relevance beyond clinical diagnosis.
... Another clinical challenge is in establishing a subset of clinical traits associated with the development of progressive interstitial fibrosis and the loss of lung function. Another retrospective study [5] on individuals with IPAF and CTD-ILD revealed that yearly decline in the forced vital capacity (FVC) is significantly more pronounced in IPAF than in CTD-ILD. Progression is influenced by the presence of anti-Sjögren's syndrome-related antigen A (anti-SSA) antibodies and postexercise pulse increase in the 6-minute walking test (6MWT) [5]. ...
... Another retrospective study [5] on individuals with IPAF and CTD-ILD revealed that yearly decline in the forced vital capacity (FVC) is significantly more pronounced in IPAF than in CTD-ILD. Progression is influenced by the presence of anti-Sjögren's syndrome-related antigen A (anti-SSA) antibodies and postexercise pulse increase in the 6-minute walking test (6MWT) [5]. ...
Background
“Interstitial lung disease” (ILD) is a broad term encompassing diseases of different backgrounds. “Interstitial pneumonia with autoimmune features” (IPAF) is a recent term that implies the presence of autoimmunity.
Objective
This study aims to determine the characteristics of Polish patients with IPAF, compare them with patients with other interstitial pneumonias, and search for the prognostic and diagnostic biomarkers of IPAF in serum and bronchoalveolar lavage fluid (BALF).
Methods
This multicenter prospective study plans to recruit 240 participants divided into 1 study group and 2 control groups. Biological fluid samples will be collected according to Polish Respiratory Society management guidelines and stored at –80°C for further tests. Prospective 5-year observations of 60 newly diagnosed individuals are planned. The study will be divided into subsections. First, we plan to characterize Polish patients with IPAF (study group) against their peers with other ILDs (2 control groups). Control group 1 will comprise patients with idiopathic ILDs, including mainly idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia. Control group 2 will comprise patients with connective tissue disease–associated interstitial lung diseases, such as rheumatoid arthritis, systemic sclerosis, polymyositis, dermatomyositis, Sjögren’s syndrome, mixed connective tissue disease, and systemic lupus erythematosus. Radiological and functional parameters will be analyzed. Patients will be compared in terms of high-resolution computed tomography results, the 6-minute walking test performance, and pulmonary function test parameters. The diagnosis of IPAF will be reassessed on a regular basis through multidisciplinary discussion in order to determine its clinical stability. In the laboratory arm, inflammation and fibrosis pathways will be assessed. Cytokine levels (interleukin 8, transforming growth factor beta 1, chemokine C-C motif ligand [CXCL]18, CXCL1, surfactant protein [SP]-A, SP-D, Krebs von den Lungen-6 protein, and chitinase 1) will be measured in serum and BALF. A comparative analysis of serum and BALF cytokine levels will be performed in order to establish potential differences between systemic and local inflammatory pathways. In the quality of life (QoL) arm of the study, dyspnea and cough and their impact on various aspects of the QoL will be assessed. Depression and anxiety will be measured with the Hospital Anxiety and Depression Modified Scale and the 9-item Patient Health Questionnaire, and potential correlations with symptom prevalence will be assessed.
Results
This study will start recruiting patients to phase 1 in October 2023. The final results will be available in 2028. We plan to publish preliminary results after 2-3 years from the start of phase 1.
Conclusions
This study will be a step toward a better understanding of IPAF etiopathogenesis and outcomes.
International Registered Report Identifier (IRRID)
PRR1-10.2196/44802
... The SSc-ILD Safety and Efficacy of Nintedanib in Systemic Sclerosis (SENSCIS) clinical trial confirmed that the annual rate of FVC decline in placebo-treated patients was on average −93.3 mL/year, and 46% of participants without specific treatment lost over 5% of FVC during a 1-year follow-up [7]. Furthermore, recent studies additionally suggested that SSc-ILD patients might lose lung function even in the physiological range and should be followed more closely to prevent functional deterioration [8]. ...
... At each follow-up visit, routine PFTs, ABGs, and the 6MWT were documented. Methods of the measurements (PFTs, ABGs, 6MWT, and HRCT) were described in detail in our previous study [8]. The median follow-up was 34 months and the functional decline of PPF was established throughout the follow-up according to the criteria of ≥ 5% FVC decline and/or ≥10% DLCO decline within 1 year. ...
... Treatment of SSc-ILD is challenging. Our data confirmed better functional outcome in ISU and/or biological-therapy-treated SSc-ILD, emphasizing early and specific SSc treatment [8,30]. An SENSCIS subanalysis evaluated the effectiveness of nintedanib as an antifibrotic agent among SSc-ILD patients with or without baseline mycophenolate mofetil (MMF) treatment [7]. ...
Interstitial lung disease (ILD) is the leading cause of mortality in systemic sclerosis (SSc). Progressive pulmonary fibrosis (PPF) is defined as progression in 2 domains including clinical, radiological or lung-function parameters. Our aim was to assess predictors of functional decline in SSc-ILD patients and compare disease behavior to that in idiopathic pulmonary fibrosis (IPF) patients. Patients with normal forced vital capacity (FVC > 80% predicted; SSc-ILD: n = 31; IPF: n = 53) were followed for at least 1 year. Predictors of functional decline including clinical symptoms, comorbidities, lung-function values, high-resolution CT pattern, and treatment data were analyzed. SSc-ILD patents were significantly younger (59.8 ± 13.1) and more often women (93 %) than IPF patients. The median yearly FVC decline was similar in both groups (SSc-ILD = −67.5 and IPF = −65.3 mL/year). A total of 11 SSc-ILD patients met the PPF criteria for functional deterioration, presenting an FVC decline of −153.9 mL/year. Cough and pulmonary hypertension were significant prognostic factors for SSc-ILD functional progression. SSc-ILD patients with normal initial spirometry presenting with cough and PH are at higher risk for showing progressive functional decline.
... The follow-up (and also treatment time) of at least 31 months (in the longest case 53 months) until June 2021 included radiological controls, therapy management, LF, DLCO and KLCO tests. In this analysis, PF-ILD was defined as a FVC relative annual decline ≥5% in addition to either a deterioration of clinical symptoms or a progression of fibrosis on HRCT, as mentioned previously [10,31]. ...
(1) Background: Systemic sclerosis (SSc) is frequently associated with interstitial lung diseases (ILDs). The progressive form of SSc-ILD often limits patient survival. The aim of our study is to evaluate the clinical characteristics and predictors of lung function changes in SSc-ILD patients treated in a real-world setting. (2) Methods: All SSc-ILD cases previously confirmed by rheumatologists and a multidisciplinary ILD team between January 2017 and June 2019 were included (n = 54). The detailed medical history, clinical parameters and HRCT were analyzed. The longitudinal follow-up for pulmonary symptoms, functional parameters and treatment were performed for at least 2 years in no treatment, immunosuppression and biological treatment subgroups. (3) Results: In SSc-ILD patients (age 58.7 ± 13.3 years, 87.0% women), the main symptoms included dyspnea, cough, crackles and the Raynaud’s phenomenon. The functional decline was most prominent in untreated patients, and a normal body mass index (BMI < 25 kg/m2) was associated with a significant risk of deterioration. The majority of patients improved or were stable during follow-up. The progressive fibrosing-ILD criteria were met by 15 patients, the highest proportion being in the untreated subgroup. (4) Conclusions: SSc-ILD patients who are overweight are at a lower risk of the functional decline and progressive phenotype especially affecting untreated patients. The close monitoring of lung involvement and a regular BMI measurement are advised and early treatment interventions are encouraged.
Background
Anti-fibrotics can reduce restrictive impairment in idiopathic pulmonary fibrosis (IPF). However, its effectiveness in non-IPF progressive fibrosing interstitial lung disease (non-IPF PF-ILD) remains uncertain.
Objective
We assess the efficacy and safety of anti-fibrotics pirfenidone and nintedanib versus placebo among non-IPF PF-ILD adult patients.
Methods
Meta-analysis was performed using PubMed, SCOPUS, and Cochrane databases to identify randomized controlled trials (RCTs). At respective centers, non-IPF PF-ILD was defined as clinical and radiological findings inconsistent with IPF and greater than 5 % forced vital capacity (FVC) decline, worsening radiological fibrosis or respiratory symptoms.
Results
Among seven RCTs involving 1,816 non-IPF PF-ILD patients, anti-fibrotics significantly reduced decline in FVC from baseline in milliliters (MD -66.80milliliters; P < 0.01) and percent predicted (MD -1.80 %; P < 0.01) compared to placebo. However, severity of FVC decline was less than 10 % (P = 0.33) in both groups. No significant difference in the decline of 6MWD from baseline in meters (P = 0.19) while on anti-fibrotics, although those on pirfenidone had less decline in 6MWD (MD -25.12 m; P < 0.01) versus placebo. The rates of all-cause mortality (P = 0.34), all-cause hospitalization (P = 0.44), and hospitalization for respiratory etiology (P = 0.06) were comparable in both groups. Adverse events of nausea/vomiting (54.2 % vs. 20.3 %; P < 0.01), diarrhea (65.2 % vs. 27.6 %; P = 0.02), anorexia/weight loss (23.0 % vs. 7.7 %; P < 0.01), neurological disorders (20.8 % vs. 12.6 %; P < 0.01), and events requiring therapy discontinuation were higher (18.4 % vs. 9.9 %; P < 0.01) in the anti-fibrotic group. Other adverse events of skin (P = 0.18) and respiratory disorders (P = 0.20) were equal.
Conclusion
The advent of anti-fibrotics offers alternative treatment to reduce lung function decline.
