Idiopathic Interstitial Lung Disease Research Articles

CD4+CXCR4+ T cells as a novel prognostic biomarker in patients with idiopathic inflammatory myopathy-associated interstitial lung disease.

There is an unmet need for the development of new biomarkers for idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD). Peripheral CD4+CXCR4+ T cells, stromal cell-derived factor-1 and Krebs von den Lungen-6 were measured in patients with IIM-ILD (n = 85) and controls. The relation to pulmonary functions, high-resolution CT scores, specific clinical phenotypes and survival was analysed. Cytokine-expression profiling of these CD4+CXCR4+ T cells and their co-culture with pulmonary fibroblasts were conducted. The peripheral percentages of CD4+CXCR4+ T cells were significantly elevated in IIM-ILD patients, and correlated with high-resolution CT score (r = 0.7136, P < 0.0001) and pulmonary function impairments, such as percentage of forced volume vital capacity (r = -0.4734, P = 0.0005). They were associated with anti-melanoma differentiation-associated gene 5 autoantibodies and the amyopathic DM phenotype. In IIM-ILD, peripheral percentages of CD4+CXCR4+ T cells ⩾30% revealed a 6-month mortality as high as 47%. These CD4+CXCR4+ T cells express high levels of IL-21 and IL-6. In vitro blockade of IL-21 signalling by neutralization of IL-21 or Janus kinase inhibitor could abolished the fibroblast proliferation. Overall, peripheral CD4+CXCR4+ T cells appear to be a potentially valuable novel biomarker associated with the severity and prognosis of IIM-ILD. They promote pulmonary fibroblast proliferation via IL-21, which may herald future targeted treatments for this severe disease.

Systematic review and meta-analysis of prognostic factors for idiopathic inflammatory myopathy-associated interstitial lung disease

ObjectiveTo clarify prognostic factors for idiopathic inflammatory myopathy (IIM)-associated interstitial lung disease (ILD).DesignSystematic review and meta-analysis using the Grades of Recommendation, Assessment, Development and Evaluation system.Data sourcesMedline, EMBASE and Science...

Specialist palliative care, psychology, interstitial lung disease (ILD) multidisciplinary team meeting: a novel model to address palliative care needs

IntroductionPatients with progressive idiopathic fibrotic interstitial lung disease (ILD), such as those with idiopathic pulmonary fibrosis (IPF), can have an aggressive disease course, with a median survival of only 3–5...

Diagnosis and Treatment of Interstitial Lung Diseases

Interstitial lung diseases compromise a group of diffuse predominantly chronic inflammatory and fibrosing disorders of the lung parenchyma. This article reviews practice-relevant publications on the diagnosis and treatment of idiopathic pulmonary fibrosis - the most common form of idiopathic interstitial lung diseases. The new patient questionnaire of the German Society of Pneumology facilitates collection of a complex case history of diverse interstitial lung diseases in individual patients. The Fleischner Society White Paper emphasize the importance of high-resolution computer tomography in the diagnosis of IPF. Histological diagnosis of the fibrotic changes is necessary in two situations: in case of CT findings indeterminate or suggestive for a diagnosis other than IPF and in case of inconsistence of medical history, laboratory findings and diagnostic imaging. The new international guidelines emphasize the importance of the interdisciplinary discussion prior to invasive diagnostic procedures, especially in the case of nonspecific interstitial lung changes. Bronchoscopy with lung cryobiopsy has gained importance in recent years. The recommendation to standardize this diagnostic method is speicified in a recently published expert opinion. The German Guideline for Idiopathic Pulmonary Fibrosis, published in 2017 suggests current therapeutic standards in this disease. The treatment with one of two registered antifibrotic drugs (pirfenidone, nintedanib) is to be started as soon as possible after the diagnosis and should be a long-term therapy. In case of intolerance or a significant progress of the disease despite the treatment, the therapy switching to an alternative drug may be considered. The combination of both therapies is not recommended. In current studies, new drugs are being tested (e. g. the serum protein pentraxin 2, antibodies against the growth factor CTGF). On the other hand, the efficacy of the registered antifibrotic medicaments, nintedanib and pirfenidone, in interstitial lung diseases other than idiopathic pulmonary fibrosis is being evaluated.

Pirfenidone-induced photosensitivity confirmed by pathological phototest.

Idiopathic pulmonary fibrosis (IPF) is an idiopathic interstitial progressive fibrotic lung disease and the most lethal of all interstitial lung diseases. Pirfenidone is a novel antifibrotic and anti-inflammatory agent which reduces decline in lung function and prolonges progression-free survival. It has a favourable benefit-risk profile and is generally well tolerated. However gastrointestinal events, photosensitivity reactions and rash are the most common adverse events. We report a 71-year-old man with 1 week history of erythematous partially pruritic lesions on both sides of the neck and the back of the hands limited to sun exposed areas. He had been diagnosed with IPF and was being treated with pirfenidone (Esbriet) for 8 months. We suspected a photosensitivity reaction caused by pirfenidone. A phototest and a punch biopsy were performed. The phototest had a pathological result. The minimal erythema dose was decreased, presenting with erythema and edema starting from 7 mJ/cm2 of UVB and an aberrant response to UVA starting from 2 J/cm2. Histopathological examination revealed spongiotic acute dermatitis with focal presence of necrotic keratinocytes. The patient was diagnosed with pirfenidone-induced photosensitivity and treated with high potency topical steroid leading to the resolution of the lesions, without the need for discontinuation of the drug. To our Knowledge, this is the first pirfenidone-induced photosensitivity reported case confirmed by pathological phototest. Patient education and photoprotection advice are essential for prevention.

Characteristics of lung cancer among patients with idiopathic pulmonary fibrosis and interstitial lung disease \u2013 analysis of institutional and population data

BackgroundLung Cancer is occasionally observed in patients with Idiopathic Pulmonary Fibrosis (IPF). We sought to describe the epidemiologic and clinical characteristics of lung cancer for patients with IPF and other interstitial lung disease (ILD) using institutional and statewide data registries.MethodsWe conducted a retrospective analysis of IPF and non-IPF ILD patients from the ILD center registry, to compare with lung cancer registries at the University of Pittsburgh as well as with population data of lung cancer obtained from Pennsylvania Department of Health between 2000 and 2015.ResultsAmong 1108 IPF patients, 31 patients were identified with IPF and lung cancer. The age-adjusted standard incidence ratio of lung cancer was 3.34 (with IPF) and 2.3 (with non-IPF ILD) (between-group Hazard ratio = 1.4, p = 0.3). Lung cancer worsened the mortality of IPF (p < 0.001). Lung cancer with IPF had higher mortality compared to lung cancer in non-IPF ILD (Hazard ratio = 6.2, p = 0.001). Lung cancer among IPF was characterized by a predilection for lower lobes (63% vs. 26% in non-IPF lung cancer, p < 0.001) and by squamous cell histology (41% vs. 29%, p = 0.07). Increased incidence of lung cancer was observed among single lung transplant (SLT) recipients for IPF (13 out of 97, 13.4%), with increased mortality compared to SLT for IPF without lung cancer (p = 0.028) during observational period.ConclusionsLung cancer is approximately 3.34 times more frequently diagnosed in IPF patients compared to general population, and associated with worse prognosis compared with IPF without lung cancer, with squamous cell carcinoma and lower lobe predilection. The causality between non-smoking IPF patients and lung cancer is to be determined.

Clinical and Histopathologic Features of Interstitial Lung Disease in Erdheim⁻Chester Disease.

Limited information is available regarding interstitial lung disease (ILD) in Erdheim–Chester disease (ECD), a rare multisystemic non-Langerhans cell histiocytosis. Sixty-two biopsy-confirmed ECD patients were divided into those with no ILD (19.5%), minimal ILD (32%), mild ILD (29%), and moderate/severe ILD (19.5%), based on computed tomography (CT) findings. Dyspnea affected at least half of the patients with mild or moderate/severe ILD. Diffusion capacity was significantly reduced in ECD patients with minimal ILD. Disease severity was inversely correlated with pulmonary function measurements; no correlation with BRAF V600E mutation status was seen. Reticulations and ground-glass opacities were the predominant findings on CT images. Automated CT scores were significantly higher in patients with moderate/severe ILD, compared to those in other groups. Immunostaining of lung biopsies was consistent with ECD. Histopathology findings included subpleural and septal fibrosis, with areas of interspersed normal lung, diffuse interstitial fibrosis, histiocytes with foamy cytoplasm embedded in fibrosis, lymphoid aggregates, and focal type II alveolar cell hyperplasia. In conclusion, ILD of varying severity may affect a high proportion of ECD patients. Histopathology features of ILD in ECD can mimic interstitial fibrosis patterns observed in idiopathic ILD.

Symptom prevalence of patients with fibrotic interstitial lung disease: a systematic literature review

BackgroundThose affected by advanced fibrotic interstitial lung diseases have limited treatment options and in the terminal stages, the focus of care is on symptom management. However, quantitatively, little is known about symptom prevalence. We aimed to determine the prevalence of symptoms in Progressive Idiopathic Fibrotic Interstitial Lung Disease (PIF-ILD).MethodsSearches on eight electronic databases including MEDLINE for clinical studies between 1966 and 2015 where the target population was adults with PIF-ILD and for whom the prevalence of symptoms had been calculated.ResultsA total of 4086 titles were screened for eligibility criteria; 23 studies were included for analysis. The highest prevalence was that for breathlessness (54–98%) and cough (59–100%) followed by heartburn (25–65%) and depression (10–49%). The heterogeneity of studies limited their comparability, but many of the symptoms present in patients with other end-stage disease were also seen in PIF-ILD.ConclusionsThis is the first quantitative review of symptoms in people with Progressive Idiopathic Fibrotic Interstitial Lung Diseases. Symptoms are common, often multiple and have a comparable prevalence to those experienced in other advanced diseases. Quantification of these data provides valuable information to inform the allocation of resources.

Management of Interstitial Lung Disease in Patients With Myositis Specific Autoantibodies.

To review advances in the management of idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-associated ILD) in the past 5years, with highlights in myositis-specific antibody (MSA) groups. With the recent advent of widespread MSA testing, the study of specific homogeneous autoantibody-based subgroups of IIM-associated ILD is now possible. The prevalence, severity, prognosis, and response to treatment are under study for these individual MSAs. Early evidence suggests that PL-7- and PL-12-positive patients are more likely to have ILD and worse severity, compared to Jo-1 patients. Many medications have been efficacious for the treatment of IIM-associated ILD, including calcineurin inhibitors, rituximab, and cyclophosphamide. We suggest vigilant screening and monitoring of ILD in IIM patients with focus on the potential side effects associated with therapy and thus advocate appropriate vaccination, PCP prophylaxis, and bone health protection. Many different agents are used to manage patients with ILD with no comparative effectiveness studies to guide the clinician. The possibility of using MSAs to help guide treatment decisions is an appealing, although unproven, focus of research. Unfortunately, the rarity of non-Jo-1 myositis-specific antibodies has precluded robust study of response to treatment and overall management. Ongoing clinical trials and working groups are coordinating efforts to provide evidence-based management.

Nouveau concept d’IPAF (pneumopathie interstitielle avec manifestations auto-immunes)

Interstitial lung disease (ILD) often complicates connective tissue disease. Sometimes, patients with interstitial lung disease have auto-immune features, but fail to meet diagnostic criteria for a specific connective tissue disease. The management of this group of patients is difficult, as the border between idiopathic ILD and connective tissue disease is unclear. Multidisciplinary discussion involving a rheumatologist experienced in systemic diseases is useful when a connective tissue disease is suspected. Several classifications have been proposed to standardize this group of patients, but none has been validated. Recently, an international task force of the American Thoracic Society and the European Respiratory Society proposed a new terminology and consensus criteria defining interstitial pneumonia with auto-immune features (IPAF) in order to standardize and better characterize this group of patients. In this monograph, we will study the new concept of IPAF, after having detailed the previous concepts. We will then describe the recent cohorts resulting from this new classification and future perspectives that remain to be explored further.

Advances in autoantibodies of idiopathic inflammatory myopathy and interstitial lung disease

Advances in autoantibodies of idiopathic inflammatory myopathy and interstitial lung disease

Role of gastroesophageal reflux disease in idiopathic interstitial lung disease

Role of gastroesophageal reflux disease in idiopathic interstitial lung disease

Hepatitis C Virus-Associated Extrahepatic Manifestations in Lung and Heart and Antiviral Therapy-Related Cardiopulmonary Toxicity.

Besides liver cirrhosis and hepatocellular carcinoma, chronic hepatitis C virus (HCV) infection is associated with many extrahepatic manifestations (EHMs). HCV exhibits lymphotropism that is responsible for various EHM. An important characteristic of HCV is escape from the immune system, which enables it to produce chronic infections and autoimmune disorders along with accumulation of circulating immune complexes. These EHMs have large spectrum, because they affect many organs such as heart, lungs, kidney, brain, thyroid, and skin. HCV-related cardiac and pulmonary manifestations include myocarditis, cardiomyopathies, cardiovascular diseases (i.e., Stroke, ischemic heart disease), chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, asthma, and interstitial lung diseases. This review discusses etiology and pathogenesis of HCV-associated cardiac and pulmonary manifestations and how different genes, immune system, indirectly linked factors (mixed cryoglobulinemia), liver cirrhosis, and antiviral treatment are involved in HCV-related heart and lung diseases, however, their exact mechanism is not clear.

Year in review 2016: Interstitial lung disease, pulmonary vascular disease, pulmonary function, paediatric lung disease, cystic fibrosis and sleep.

Year in review 2016: Interstitial lung disease, pulmonary vascular disease, pulmonary function, paediatric lung disease, cystic fibrosis and sleep.

Sirtuin 7 is decreased in pulmonary fibrosis and regulates the fibrotic phenotype of lung fibroblasts.

Pulmonary fibrosis is a severe condition with no cure and limited therapeutic options. A better understanding of its pathophysiology is needed. Recent studies have suggested that pulmonary fibrosis may be driven by accelerated aging-related mechanisms. Sirtuins (SIRTs), particularly SIRT1, SIRT3, and SIRT6, are well-known mediators of aging; however, limited data exist on the contribution of sirtuins to lung fibrosis. We assessed the mRNA and protein levels of all seven known sirtuins in primary lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated interstitial lung disease (SSc-ILD) in comparison with lung fibroblasts from healthy controls. These unbiased tests revealed a tendency for all sirtuins to be expressed at lower levels in fibroblasts from patients compared with controls, but the greatest decrease was observed with SIRT7. Similarly, SIRT7 was decreased in lung tissues of bleomycin-challenged mice. Inhibition of SIRT7 with siRNA in cultured lung fibroblasts resulted in an increase in collagen and α-smooth muscle actin (α-SMA). Reciprocally, overexpression of SIRT7 resulted in lower basal and TGF-β-induced levels of COL1A1, COL1A2, COL3A1, and α-SMA mRNAs, as well as collagen and α-SMA proteins. Induced changes in SIRT7 had no effect on endogenous TGF-β mRNA levels or latent TGF-β activation, but overexpression of SIRT7 reduced the levels of Smad3 mRNA and protein. In conclusion, the decline in SIRT7 in lung fibroblasts has a profibrotic effect, which is mediated by changes in Smad3 levels.

Prevalence and characterization of non-sicca onset primary Sjögren syndrome with interstitial lung involvement.

Primary Sjögren syndrome (pSS)-related interstitial lung disease (ILD) involved about 10-20% of patients. In 20% of cases, ILD can be diagnosed before pSS; anyway, few studies have investigated the frequency of ILD as the first clinically relevant manifestation of pSS, generally referred to retrospective studies. Aim of our prospective study was to describe prevalence, clinical, serological, and instrumental features of non-sicca onset pSS patients with interstitial lung involvement. During a period of 48months, all consecutive patients diagnosed as pSS were enrolled. For all patients, the reason for the first visit was recorded. When present, ILD was categorized as definite, possible, or inconsistent with usual interstitial pneumonia (UIP) pattern, according to the current criteria. ILD was the main presenting symptom in 13/77 new diagnoses of pSS patients; in particular, 6/13 patients were initially diagnosed as idiopathic ILD, and only later developed clinical manifestations suggestive for pSS; ILD-pSS patients were older than others and showed a higher EULAR primary Sjögren's syndrome disease activity index. A radiologic definite or possible UIP pattern was detected in 12/13 pSS. For the first time, we prospectively observed a prevalence of 16.8% of non-sicca onset pSS patients with ILD. Interestingly, UIP pattern was the most frequently detected, while typical autoantibodies were often absent. These features stressed the importance of differential diagnosis in the first stage of the disease, considering the possible poorer prognosis in this subgroup of patients. Multidisciplinary approach is crucial for a correct and early diagnosis, at both onset and follow-up.

A New Variant of Combined Pulmonary Fibrosis and Emphysema from Long- Term High-Dose of Glucocorticoid Therapy: A Case Report

Recent studies have described the combination of both pulmonary emphysema and idiopathic interstitial lung disease (ILDs) by means of high-resolution computed axial tomography (HRCT). Definition of this syndrome was first named by Cottin et al. as combined pulmonary fibrosis and emphysema (CPFE). Functional and radiological findings have showed that these patients are suffering from severe breathlessness, but whose pulmonary functional tests revealed no signs of obstruction, normal static lung volumes, and depressed DLco, most with a history of smoking. The radiological and endoscopic studies especially show that these patients have both areas of upper-lobe predominant emphysema and lesions compatible with fibrosis in both lung bases. No prior research has reported any cases of such condition in person with no prior history of smoking as well as long-term high-dose of glucocorticoid therapy. In this case report, we discuss the presentation, diagnosis, and management of a 53-year-old non-smoker with increasing shortness of breath with a long-term high-dose of glucocorticoid therapy discovered to have an abnormal variant or presentation of CPFE. The cause of disease was attributed to a certain history of smoking in most studies, other potential risk factors have yet to be properly analyzed. This clinical report features a special case about the problem and solution surrounding this issue.

A New Variant of Combined Pulmonary Fibrosis and Emphysema from Long-Term High-Dose of Glucocorticoid Therapy: A Case Report

Recent studies have described the combination of both pulmonary emphysema and idiopathic interstitial lung disease (ILDs) by means of high-resolution computed axial tomography (HRCT). Definition of this syndrome was first named by Cottin as combined pulmonary fibrosis and emphysema (CPFE). Functional and radiological findings have showed that these patients are suffering from severe breathlessness, but whose pulmonary functional tests revealed no signs of obstruction, normal static lung volumes, and depressed DLco, most with a history of smoking [1] [2]. The radiological and endoscopic studies especially show that these patients have both areas of upper-lobe predominant emphysema and lesions compatible with fibrosis in both lung bases [3]. No prior research has reported any cases of such condition in person with no prior history of smoking as well as long-term high-dose of glucocorticoid therapy. In this case report, we discuss the presentation, diagnosis, and management of a 53-year-old non-smoker with increasing shortness of breath with a long-term high-dose of glucocorticoid therapy discovered to have an abnormal variant or presentation of CPFE. The cause of disease was attributed to a certain history of smoking in most studies; other potential risk factors have yet to be properly analyzed. This clinical report features a special case about the problem and solution surrounding this issue.

Phosphodiesterase-5 inhibitors: Raynaud's and beyond

Phosphodiesterases (PDE) are a group of ubiquitously present enzymes involved in regulation of various cellular pathways. PDE5 acts to metabolize cyclic guanosine monophosphate (GMP). The various PDE5 inhibitors available are sildenafil, tadalafil, vardenafil, and mirodenafil. We shall discuss the roles of various PDE5 inhibitors in rheumatic diseases. PDE5 inhibitors prevent degradation of cyclic GMP; hence, they have vasodilatory properties which render them useful in the management of secondary Raynaud's phenomenon. They have also demonstrated efficacy in the healing of digital ulcers in systemic sclerosis and potentially prevent the formation of new digital ulcers. Their vasodilatory property has also been utilized in the management of pulmonary arterial hypertension, wherein their ability to favorably affect hemodynamics of a pressure-overloaded right heart is beneficial. Recent evidences have suggested a potential antifibrotic role of these agents, and studies in idiopathic pulmonary fibrosis and systemic sclerosis-associated interstitial lung disease hold promise for future exploration of these agents for these indications.

Idiopathic Lymphoid Interstitial Pneumonia: A Case Report

Idiopathic Lymphoid Interstitial Pneumonia (LIP) is considered to be a rare interstitial lung disease. The initial American Thoracic Society/European Respiratory Society (ATS/ERS) International multidisciplinary consensus paper on Idiopathic Interstitial Pneumonia of 2002, LIP was classified as one of the seven major idiopathic interstitial lung diseases. Since the first description of LIP in 1969, so far only 14 biopsy proven cases of idiopathic LIP have been described in the literature. The clinical course is reported to be highly variable in this rare form of interstitial pneumonia.