Interstitial lung disease: raising the index of suspicion in primary care.
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ABSTRACT:
SUBMITTER: Zibrak JD
PROVIDER: S-EPMC4373409 | biostudies-other | 2014
REPOSITORIES: biostudies-other
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Project description:Primary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune disease characterized by typical autoantibody production and lymphocytic-mediated exocrine gland damage. Interstitial lung disease (ILD) is a common complication of pSS and can be associated with a poor prognosis. However, the pathogenesis of ILD in pSS is still unclear. In this study, we used RNA sequencing to investigate the gene-expression profile of the minor salivary glands (MSGs) from 36 patients with ILD-pSS and 128 patients with non-ILD-pSS. In the remarkably enriched chemokine-mediated signaling pathway, CXCR2 was found to be significantly elevated in both MSG and plasma from pSS patients with versus without ILD (p < 0.001). Furthermore, the CXCR2 expression level in MSG and plasma was significantly associated with the diffusing capacity of the lungs for carbon monoxide, erythrocyte sedimentation rate, and EULAR Sjögren’s Syndrome Disease Activity Index in ILD-pSS. Therefore, with its potential role in ILD progression in patients with pSS and its strong association with clinical manifestations of the disease, CXCR2 may serve as a useful index for disease activity in ILD associated with pSS.
2021-06-02 | GSE171896 | GEO
Project description:The widespread use of high-resolution computed tomography in clinical and research settings has increased the detection of interstitial lung abnormalities (ILA) in asymptomatic and undiagnosed individuals. We reported that in smokers, ILA were present in about 1 of every 12 high-resolution computed tomographic scans; however, the long-term significance of these subclinical changes remains unclear. Studies in families affected with pulmonary fibrosis, smokers with chronic obstructive pulmonary disease, and patients with inflammatory lung disease have shown that asymptomatic and undiagnosed individuals with ILA have reductions in lung volume, functional limitations, increased pulmonary symptoms, histopathologic changes, and molecular profiles similar to those observed in patients with clinically significant interstitial lung disease (ILD). These findings suggest that, in select at-risk populations, ILA may represent early stages of pulmonary fibrosis or subclinical ILD. The growing interest surrounding this topic is motivated by our poor understanding of the inciting events and natural history of ILD, coupled with a lack of effective therapies. In this perspective, we outline past and current research focused on validating radiologic, physiological, and molecular methods to detect subclinical ILD. We discuss the limitations of the available cross-sectional studies and the need for future longitudinal studies to determine the prognostic and therapeutic implications of subclinical ILD in populations at risk of developing clinically significant ILD.
| S-EPMC3373068 | biostudies-literature
Project description:Objectives The aim of this study was to investigate serum biomarkers linked to primary Sjögren's syndrome (pSS)-associated interstitial lung disease (ILD). Methods 69 pSS patients were consecutively enrolled and evaluated via quantitative ILD scoring based on high-resolution computed tomography (HRCT). Biomarkers of interest were assessed by multiplex enzyme-linked immunosorbent assays (ELISAs). Results Among consecutively enrolled patients with pSS, the presence of pSS–ILD was 50% based on the presence of radiographically defined interstitial lung abnormalities (ILA) meeting specified criteria for mild/moderate (ILA 2) or severe (ILA 3) disease. Age, immunoglobulin M (IgM), C-reactive protein (CRP), and serum levels of eotaxin/CCL11, Krebs von den Lungen-6 (KL-6), TNFα, and TGFα were significantly higher in the combined pSS–ILD group (ILA 2 + ILA 3) than in the pSS–no-ILD and pSS–indeterminate ILD groups (ILA 0 and ILA 1, respectively) in unadjusted analyses (p < 0.05 for all variables). A binary logistic regression model revealed that disease duration and KL-6 levels were associated with the presence of pSS–ILD (p < 0.05). Complementary least absolute shrinkage and selection operator (LASSO) modeling showed that age, KL-6, and TNF-α effectively differentiated pSS–ILD (ILA 2 + ILA3) from pSS without ILD (ILA 0 + ILA 1), with an area under the curve (AUC) of 0.883 (p value < 0.0001). Conclusions Patient age, disease duration, and serum levels of both KL-6 and TNFα were the most discriminating factors associated with the presence of ILD in our pSS patients. Higher levels of CRP, IgM, eotaxin, TGFα, and TNFα should also prompt the search for occult as well as clinically evident lung involvement based on statistically significant univariate associations with pSS–ILD. Clinical trial registration None. Supplementary Information The online version contains supplementary material available at 10.1186/s40001-022-00828-3.
| S-EPMC9549683 | biostudies-literature
Project description:AbstractAim of the study was to determine the characteristics and prognosis, and to identify the risk factors for mortality in patients with primary Sjögren syndrome (pSS) with interstitial lung disease (pSS-ILD).A total of 1422 patients with SS were screened and 178 patients with pSS-ILD were recruited. The medical records and outcomes were retrospectively reviewed. Overall survival and case control study were performed to explore the predictors of death.Among 178 pSS-ILD patients, 87.1% were women. Mean age was 61.59 ± 11.69-year-old. Median disease duration was 72.0 (24.0, 156.0) months. Nonspecific interstitial pneumonia was the predominant high-resolution computed tomography pattern (44.9%). Impairment in diffusion capacity was the most common abnormality of pulmonary function test (75.8%) and the most severe consequence. Type 1 respiratory failure and hypoxia were observed in 15.0% and 30.0% patients, respectively. Mean survival time after confirmation of pSS-ILD diagnosis was 9.0 (6.8, 13.0) years. The 10-year survival rate for all patients with pSS-ILD was 81.7%. Forty-four (24.7%) of 178 patients died during the follow-up period. The most predominant cause of death was respiratory failure (n = 27). Twenty-seven patients died of ILD and formed study group. The 78 patients who survived formed control group. Age and smoking were risk factors for mortality in patients with pSS-ILD. In addition, severity of ILD, as reflected by high-resolution computed tomography, pulmonary function test, and arterial blood gas, was an independent risk factor. However, inflammation status (erythrocyte sedimentation rate, C-reactive protein) and anti-Sjögren syndrome-related antigen A and anti-Sjögren syndrome-related antigen B were not.ILD is a severe complication of pSS. Age, smoking, and severity of lung involvement are more critical for prognosis rather than inflammation status and autoantibodies.
| S-EPMC8415932 | biostudies-literature
Project description:Interstitial lung disease (ILD) is frequently a complication of rheumatoid arthritis (RA) as an extra-articular manifestation which has a poor prognosis. Acute-onset diffuse ILD (AoDILD) occasionally occurs in RA and includes acute exacerbation of ILD, drug-induced ILD, and Pneumocystis pneumonia. AoDILD also confers a poor prognosis in RA. Previously-established biomarkers for ILD include Krebs von den lungen-6 and surfactant protein-D originally defined in patients with idiopathic pulmonary fibrosis; the sensitivity of these markers for RA-associated ILD (RA-ILD) is low. Although many studies on ILD markers have been performed in idiopathic pulmonary fibrosis, only a few validation studies in RA-ILD or AoDILD have been reported. Biomarkers for RA-ILD and AoDILD are thus still required. Recently, genomic, cytokine, antibody, and metabolomic profiles of RA-ILD or AoDILD have been investigated with the aim of improving biomarkers. In this review, we summarize current preliminary data on these potential biomarkers for RA-ILD or AoDILD. The development of biomarkers on RA-ILD has only just begun. When validated, such candidate biomarkers will provide valuable information on pathogenesis, prognosis, and drug responses in RA-ILD in future.
| S-EPMC8216360 | biostudies-literature
Project description:Systemic sclerosis is a heterogeneous disease of unknown etiology with limited effective therapies. It is characterized by autoimmunity, vasculopathy, and fibrosis and is clinically manifested by multiorgan involvement. Interstitial lung disease is a common complication of systemic sclerosis and is associated with significant morbidity and mortality. The diagnosis of interstitial lung disease hinges on careful clinical evaluation and pulmonary function tests and high-resolution computed tomography. Effective therapeutic options are still limited. Several experimental therapies are currently in early-phase clinical trials and show promise.
| S-EPMC4385198 | biostudies-literature
Project description:Interstitial lung disease (ILD) is comprised of a heterogeneous group of disorders with highly variable natural histories and response to therapies. Pharmacogenetics focuses on the variability in drug response because of the presence of genetic factors that influence drug metabolism or disease activity. In this article, we review relevant drug-specific and disease-specific polymorphisms that may influence therapeutic response, and then highlight a recently identified drug-gene interaction in patients with idiopathic pulmonary fibrosis (IPF).The emergence of high-throughput genomic technology has allowed for identification of gene polymorphisms associated with susceptibility to specific disease states, including IPF and several connective tissue diseases known to cause ILD. IPF risk loci span a diverse group of genes, while most associated with connective tissue disease are critical to immune signaling. A recent pharmacogenetic analysis of patients enrolled in an IPF clinical trial identified a variant within TOLLIP to be associated with differential response to N-acetylcysteine therapy.Though few pharmacogenetic investigations have been conducted in patients with ILD to date, ample opportunities for pharmacogenetic exploration exist in this patient population. Such exploration will advance our understanding of specific ILDs and help usher in an era of personalized medicine.
| S-EPMC5004343 | biostudies-literature
Project description:The term 'interstitial lung disease' (ILD) refers to a group of disorders involving both the airspaces and tissue compartments of the lung, and these disorders are more accurately termed diffuse lung diseases. Although rare, they are associated with significant morbidity and mortality, with the prognosis depending upon the specific diagnosis. The major categories of ILD in children that present in the neonatal period include developmental disorders, growth disorders, surfactant dysfunction disorders, and specific conditions of unknown etiology unique to infancy. Whereas lung histopathology has been the gold standard for the diagnosis of ILD, as many of the disorders have a genetic basis, non-invasive diagnosis is feasible, and characteristic clinical and imaging features may allow for specific diagnosis in some circumstances. The underlying mechanisms, clinical, imaging, and lung pathology features and outcomes of ILD presenting in newborns are reviewed with an emphasis on genetic mechanisms and diagnosis.
| S-EPMC5537026 | biostudies-literature
Project description:There has been tremendous progress in the approach to childhood interstitial lung diseases (chILD), with particular recognition that interstitial lung disease (ILD) in infants is often distinct from the forms that occur in older children and adults. Diagnosis is challenging because of the rarity of ILD and the fact that the presenting symptoms of ILD often overlap those of common respiratory disorders. This review summarizes the newly published recommendations for diagnosis and management, and highlights the recent scientific advances in several specific forms of chILD.Clinical practice guidelines emphasize the role for chest computed tomography, genetic testing, and lung biopsy in the diagnostic evaluation of children with suspected ILD. Recent studies have better defined the characteristics and molecular understanding of several different forms of ILD, including neuroendocrine cell hyperplasia of infancy and ILD, due to mutations in genes affecting surfactant production and metabolism. Despite significant progress, definitive therapies are often lacking.chILD encompasses a collection of rare, diffuse lung diseases. Timely recognition of children with suspected ILD and initiation of appropriate diagnostic evaluations will facilitate medical management. Systematic approaches to clinical care and further studies are needed to improve the outcomes of children with these rare disorders.
| S-EPMC4130649 | biostudies-literature
Project description:Interstitial lung diseases (ILD) encompass a group of conditions involving fibrosis and/or inflammation of the pulmonary parenchyma. Telomeres are repetitive DNA sequences at chromosome ends which protect against genome instability. At each cell division, telomeres shorten, but the telomerase complex partially counteracts progressive loss of telomeres by catalysing the synthesis of telomeric repeats. Once critical telomere shortening is reached, cell cycle arrest or apoptosis are triggered. Telomeres progressively shorten with age. A number of rare genetic mutations have been identified in genes encoding for components of the telomerase complex, including telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC), in familial and, less frequently, in sporadic fibrotic ILDs. Defects in telomerase result in extremely short telomeres. More rapidly progressive disease is observed in fibrotic ILD patients with telomere gene mutations, regardless of underlying diagnosis. Associations with common single nucleotide polymorphisms in telomere related genes have also been demonstrated for various ILDs. Shorter peripheral blood telomere lengths compared to age-matched healthy individuals are found in a proportion of patients with fibrotic ILDs, and in idiopathic pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (HP) have been linked to worse survival, independently of disease severity. Greater susceptibility to immunosuppressant-induced side effects in patients with short telomeres has been described in patients with IPF and with fibrotic HP. Here, we discuss recent evidence for the involvement of telomere length and genetic variations in the development, progression, and treatment of fibrotic ILDs.
| S-EPMC8037770 | biostudies-literature