Positron emission tomography in interstitial lung disease

BACKGROUND AND OBJECTIVES: A high rate of glycolysis may reflect the inflammatory activity of interstitial lung disease (ILD). This prospective study investigated whether PET can distinguish IPF, a primarily fibrotic process, from other entities of ILD that have a marked inflammatory component. METHODS: Twenty-one patients referred for surgical lung biopsy because of diffuse ILD underwent PET at the time of the lung biopsy. PET transmission scans were obtained after injecting (18)FDG intravenously. Regions of interest (ROI) were drawn on the lung images, and the standardized uptake value (SUV) was calculated for these ROI. RESULTS: Of the 21 patients studied, 14 had IPF, four had non-specific interstitial pneumonia, and the remaining three patients each had respiratory bronchiolitis-ILD, sarcoidosis and Langerhan's cell histiocytosis. There was no statistically significant difference in the SUV between IPF patients and non-IPF patients (P = 0.26), although patients with IPF tended to have higher SUV. Radiographic changes tended to be more prominent in the lung bases in patients with IPF compared with non-IPF patients; however, the median ratio of SUV measured in the upper fields to the whole lungs in IPF patients was not significantly different compared with the median ratio in non-IPF patients (P = 0.31). CONCLUSION: PET does not allow differentiation of IPF from a non-IPF diffuse interstitial pulmonary process.     

Predictive factors for the long-term use of pirfenidone in patients with fibrosing interstitial lung disease

BackgroundPirfenidone is an anti-fibrotic agent approved for idiopathic pulmonary fibrosis (IPF), and long-term treatment data and the effect of continuation after disease progression have been reported. The efficacy and safety of pirfenidone in fibrosing interstitial lung disease (ILD) patients without IPF have been recently reported in clinical trials; therefore, the benefits of long-term treatment are also expected. This study aims to analyze the long-term treatment data of pirfenidone and clarify the predictive factors for long-term use of pirfenidone in non-IPF patients.MethodsWe retrospectively reviewed the records of consecutive fibrosing ILD patients who started using pirfenidone between 2008 and 2014.ResultsOf the 266 fibrosing ILD patients, 167 patients had IPF, and 99 had non-IPF. Despite the non-significant differences in body size and pulmonary function between IPF and non-IPF patients, the non-IPF patients had better overall survival than the IPF patients (median 4.06 years vs. 2.09 years, p < 0.0001). In addition, the non-IPF patients had a significantly longer time to treatment discontinuation than the IPF patients (median 2.20 years vs. 1.20 years, p = 0.002). Multivariate logistic regression analysis for ≥2 years of use of pirfenidone showed that the percent predicted forced vital capacity (%FVC) and age were predictive factors common to both IPF and non-IPF patients.ConclusionsOur results indicate that non-IPF patients can continue using pirfenidone for longer durations than IPF patients. Initiation of pirfenidone for fibrosing ILD patients with higher %FVC and younger age would lead to long-term use of pirfenidone.     

Cluster phenotypes in a non-idiopathic pulmonary fibrosis fibrotic interstitial lung diseases cohort in Singapore

BackgroundNon-idiopathic pulmonary fibrosis fibrosing interstitial lung diseases (F-ILDs) may demonstrate a progressive disease trajectory similar to idiopathic pulmonary fibrosis (IPF). We aimed to identify novel F-ILD phenotypes in a multi-ethnic South-East Asian population.MethodsF-ILD subjects (n=201) were analysed using unsupervised hierarchical cluster analysis and their outcomes compared against IPF (n=86).ResultsFour clusters were identified. Cluster 1 (n=53, 26.4%) comprised older Chinese males with high body mass index (BMI) and comorbidity burden, higher baseline forced vital capacity (FVC) percentage predicted and lower diffusing capacity of the lung for carbon monoxide (DLCO) percentage predicted. They had similar mortality to IPF. Cluster 2 (n=67, 33.3%) had younger female non-smokers with low comorbidity burden, groundglass changes on high-resolution chest computed tomography (HRCT) and a positive anti-nuclear antibody (ANA) titre ≥1:160. They had lower baseline FVC and higher DLCO, low mortality and slower lung function decline. Cluster 3 (n=42, 20.9%) consisted male smokers with low comorbidity burden, emphysema on HRCT and high baseline lung function. They had low mortality and slow lung function decline. Cluster 4 (n=39, 19.4%) was the highest risk and comprised of mainly Indians with high BMI. They had the highest proportion of ischemic heart disease (IHD) and previous pulmonary tuberculosis. Subjects had the lowest baseline lung function, highest mortality, and fastest lung function decline. Survival differences across clusters remained significant following adjustment for treatment.ConclusionsWe identified four distinct F-ILD clinical phenotypes with varying disease trajectories. This demonstrates heterogeneity in F-ILD and the need for complementary approaches for classification and prognostication beyond ATS/ERS guideline diagnosis.     

Immunomodulatory treatment in unclassifiable interstitial lung disease: A retrospective study of treatment response

Background and Objective

The optimal management of unclassifiable Interstitial lung disease (ILD) remains a challenge. The aim of this study was to describe pulmonary function trajectories for patients treated with immunomodulatory therapy and for untreated patients.

Methods

Clinical information and treatment data were obtained retrospectively at two ILD centres. Pulmonary function data were analysed using (1) mixed effects linear regression models with and without clinical covariates and (2) propensity score matching using gender, age, physiology (GAP) stage, smoking and presence of ground glass opacities.

Results

Sixty-five percent of the 249 patients included received corticosteroids and/or other immunomodulators. Treated patients had lower forced vital capacity (FVC) (72% vs. 83% predicted) and diffusing capacity for carbon monoxide (DLco) (44% vs. 60% predicted). In mixed effects linear regression, the adjusted change in FVC was −0.22%, [−0.34; −0.11], and −0.15% [−0.28;-0.012] for DLco. The difference in pulmonary function decline between treated and untreated patients was insignificant, −0.082% per month, [−0.28; 0.11], p = 0.10 for FVC and −0.14% per month, [−0.36; 0.079], p = 0.15, for DLco. In propensity score matched analysis, the difference in change in FVC was 0.039% per month, p = 0.12, and for DLco, 0.0085% per month, p = 0.7.

Conclusion

The pulmonary function trajectories for treated and untreated patients were parallel, despite treated patients having more severe disease at baseline. The persisting differences between the groups suggest no overall effect, although improvement or stabilization may be seen in some patients. Prospective studies are needed to define subsets of patients with unclassifiable interstitial lung disease and their optimal management.     

Protective and therapeutic experience of perioperative safety in extremely elderly patients with biliary diseases

To explore the protective and therapeutic measures of improving perioperative safety in extremely elderly patients with biliary diseases, so as to improve the therapeutic efficacy of surgery.A retrospective case–control study of 412 elderly patients with biliary diseases was carried out from July 2013 to July 2019. Seventy eight cases were divided into the high age (HA) group (≥80 years) and 334 into the middle–low age (MLA) group (60–79 years).In the HA compared with MLA group,

• 1.Preoperative coexisting diseases: the occurrence of coexisting coronary heart disease (CHD), hypertension, chronic bronchitis with emphysema, hypoproteinemia, and anemia were significantly increased;
• 2.Laboratory examinations: function of liver, kidneys, heart, lungs, and blood coagulation significantly declined;
• 3.Surgical procedures: open cholecystectomy with transcystic common bile duct (CBD) exploration significantly higher, while laparoscopic cholecystectomy significantly lower;
• 4.Operative effects: intraoperative blood loss, operation time, postoperative hospital stay, and length of hospitalization significantly increased or prolonged;
• 5.Postoperative complications: postoperative respiratory failure, pulmonary infection, anemia and electrolyte disorder significantly increased;
• 6.Therapeutic outcomes: no significant difference in the therapeutic effects.

Although the surgical risk was significantly increased, there was no significant difference in the therapeutic efficacy in the HA compared with MLA group, suggesting that surgical treatment in extremely elderly patients with biliary diseases is safe and feasible. The key is to actively treat preoperative coexisting diseases, strictly adhere to surgical indications, reasonably select surgical procedures, precisely perform the operation, closely monitor and control intraoperative emergencies, timely prevent and treat postoperative complications, so as to improve the perioperative safety of extremely elderly patients with biliary diseases.     

Decline in forced vital capacity as a surrogate for mortality in patients with pulmonary fibrosis

Background and Objective

Surrogate endpoints enable determination of meaningful treatment effects more efficiently than applying the endpoint of ultimate interest. We used data from trials of nintedanib in subjects with pulmonary fibrosis to assess decline in forced vital capacity (FVC) as a surrogate for mortality.

Methods

Data from the nintedanib and placebo groups of trials in subjects with idiopathic pulmonary fibrosis, other forms of progressive pulmonary fibrosis, and pulmonary fibrosis due to systemic sclerosis (NCT00514683, NCT01335464, NCT01335477, NCT01979952, NCT02999178, NCT02597933) were pooled. Using joint models for longitudinal and time-to-event data, we assessed the association between decline in FVC % predicted and time to death over 52 weeks. The rate of change in FVC % predicted and the current value of FVC % predicted were modelled longitudinally and estimates applied as predictors in time-to-event models.

Results

Among 2583 subjects with pulmonary fibrosis, both a greater rate of decline in FVC % predicted and a lower current value of FVC % predicted were associated with an increased risk of death over 52 weeks (HR 1.79 [95% CI: 1.57, 2.03] and HR 1.24 [1.17, 1.32] per 5-percentage point decrease, respectively). Associations between the rate of change in FVC % predicted and the risk of death were consistent between patients with IPF and other ILDs.

Conclusion

Data from clinical trials in subjects with pulmonary fibrosis of diverse aetiology demonstrate a strong association between decline in FVC % predicted and mortality over 52 weeks, supporting FVC decline as a surrogate for mortality in these patients.     

Current perspective of progressive-fibrosing interstitial lung disease

Interstitial lung disease (ILD) is a parenchymal lung disease and restrictive disorder that presents as diffuse infiltrative shadows. The initial diagnosis of ILD is important because management strategies depend on the disease pathogenesis.Connective-tissue disease (CTD)-associated ILD including rheumatoid arthritis (RA), systemic sclerosis (SSc) requires a thorough evaluation of chronic respiratory symptoms such as non-productive cough and exertional dyspnea, as well as physical findings. Moreover, myeloperoxidase-positive anti-neutrophilic cytoplasmic antibody (MPO-ANCA)-associated vasculitis with ILD also shows disease progression. In CTD-associated ILD, the first-line treatment is anti-inflammatory drugs such as prednisolone or immunosuppressants. In hypersensitivity pneumonitis (HP), detailed environmental history-taking is crucial. Therefore, systematic standardized questionnaires are needed. However, the causative antigens are often not identified in daily clinical practice. When an antigen is identified or suspected, the first action is avoidance. If antigen avoidance does not contribute to clinical improvement, anti-inflammatory drugs such as prednisolone might be introduced. Regarding sarcoidosis, while most patients do not require treatment for lung involvement, some need anti-inflammatory drugs or immunosuppressants. Additionally, steroid treatment should be considered for the critical status of extrapulmonary sarcoidosis including cardiac, neurogenic and ocular sarcoidosis. Once starting treatment for ILD, multi-dimensional approaches are applied, including symptom tracking, chest imaging, pulmonary function test (PFT), and 6-min walking test. Recently, the concept of progressive-fibrosing interstitial lung disease (PF-ILD) has been proposed as a new disease entity. The definition of PF-ILD includes symptom progression, PFT decline, and extension of chest high-resolution computed tomography (HRCT) findings. This mini-review describes the background, definition, clinical characteristics, management, and challenges of PF-ILD.     

Lung transplant candidates with idiopathic pulmonary fibrosis and long-term pirfenidone therapy: Treatment feasibility influences waitlist survival

Background

Idiopathic pulmonary fibrosis (IPF) is a chronically progressive lung disease with exceptionally poor prognosis. While lung transplantation (LTx) is considered the last-resort therapeutic option, dismal waitlist mortality still hampers the salvage of patients with IPF. Pirfenidone, originally designed for IPF treatment, has increasingly been utilized. This study aimed to evaluate whether Pirfenidone could influence outcomes of patients with IPF on the Japanese LTx waitlist.

Isolated diffusing capacity reduction in systemic sclerosis

Objective. To determine the long-term outcome of patients with systemic sclerosis (SSc) and an isolated reduction in the diffusing capacity for carbon monoxide (DLco) at the time of initial evaluation. Methods. Patients with an isolated reduction in DLco (i.e., normal forced vital capacity [FVC] and normal ratio of the forced expiratory volume in one second [FEV₁] to the FVC) on initial evaluation were identified from among 815 patients with SSc who were carefully followed up throughout their illness. We requested that patients have repeat pulmonary function testing (PFT), and the outcomes of these tests, as well as cardiopulmonary and survival outcomes, were determined. Results. An isolated reduction in DLco, with a normal FVC was detected in 152 (19%) of the 815 patients. A subset of those with an isolated reduction in DLco (11%) developed isolated pulmonary hypertension and had severely reduced survival rates. Pulmonary hypertension was strongly associated with an initial DLco of < 55% of predicted normal and a FVC (% predicted)/DLco (% predicted) ratio of > 1.4. Among all patients in whom this ratio was > 1.4, 22% developed isolated pulmonary hypertension, compared with only 2% of those whose ratio was <1.4 (P < 0.01). Of the 152 patients with isolated DLco reduction, 73 (48%) underwent PFTs a mean of 5.4 years (range 2.0–13.2) after the initial PFT. Only 6 (8%) of these 73 patients ever had serious pulmonary disease: 5 had isolated pulmonary hypertension, and 1 had severe pulmonary fibrosis. Half of the patients with a low initial DLco demonstrated a significant improvement (>20%) at followup testing that could not be explained by the demographic, clinical, or laboratory findings at the first visit. Conclusion. Isolated reduction in DLco is a frequent abnormality in SSc. Overall, it is associated with a good prognosis for survival and for pulmonary morbidity. A small subset of patients (11%) who have a very low DLco (<55% of predicted) have developed isolated pulmonary hypertension, all of whom had limited scleroderma.     

Observation of the analgesic effect of superficial or deep anterior serratus plane block on patients undergoing thoracoscopic lobectomy

The effectiveness of anterior serratus plane block in postoperative analgesia of thoracic surgery is beginning to emerge. Currently, there are 2 methods of anterior serratus plane block: deep serratus plane block (DSPB) and superficial serratus plane block (SSPB). In clinical practice, there is no an unified view regarding the advantages and disadvantages between 2 methods. This study aimed to observe and compare the analgesic effects of 2 methods on patients undergoing thoracoscopic lobectomy, in order to provide some suggestions for anesthesiologists when they choose anterior serratus plane block to perform postoperative analgesia for patients.Patients were randomly divided into 3 groups (21 patients/group):

• 1.general anesthesia group (P group);
• 2.combined general anesthesia and SSPB group (S group), and
• 3.combined general anesthesia and DSPB group (D group).

The patients in groups S and D received 0.4 ml/kg of 0.375% ropivacaine for ultrasound-guided block after surgery. Postoperatively, flurbiprofen was used for rescue analgesia.Visual analog scale (VAS) pain scores were recorded at 6 hours, 12 hours, and 24 hours after surgery, and rescue analgesia, post-operative nausea, and vomiting were reported within 24 hours after surgery. At 6 hours, 12 hours, and 24 hours, the VAS scores and the rescue analgesia rates in groups S and D were significantly lower than those in group P (all P < .001). With prolonging time, the VAS in group D was significantly increased by 0.11 per hour as compared with that of group P (P < .0001); VAS in group D was significantly increased by 0.12 per hour as compared with that of group S (P < .0001).Ultrasound-guided anterior serratus plane block can provide adequate analgesia for patients undergoing thoracoscopy lobectomy. SSPB can significantly improve VAS scores as compared to DSPB at 24 hours.     

The effect of emphysema on lung function and survival in patients with idiopathic pulmonary fibrosis

Background and objective: In this study the prevalence, lung function and prognosis of IPF combined with emphysema were evaluated. Methods: Consecutive patients with usual interstitial pneumonia (UIP) on high‐resolution computed tomography (HRCT), with or without emphysema, were assessed retrospectively. The area of fibrosis in the base of the lungs was assessed by HRCT as minimal (<2 cm from the subpleura), moderate (≥2 cm from the subpleura, <1/3 of the area of the base of the lungs) or severe (≥1/3 of the area of the base of the lungs). Results: Among 660 patients with UIP on HRCT, 221 showed upper‐lobe emphysema. Pulmonary function results for patients with UIP and UIP/emphysema, respectively, were: FVC, 71.8% and 87.1%; FEV1%, 86.7% and 87.9%; and DL_CO, 74.3% and 65.2% of predicted. The relationship between FVC, the extent of fibrosis and survival was investigated in 362 patients with records of pulmonary function tests and no lung cancer at the time of entry into the study. Although the extent of fibrosis was similar between the groups, 71.3% of UIP patients met the lung volume criteria for IPF (FVC <80% of predicted), whereas only 26.5% of UIP/emphysema patients met the lung volume criteria for IPF. Median survival was 7.5 years in the UIP group and 8.5 years in the UIP/emphysema group. Conclusions: Emphysema was a common finding in patients with UIP. Patients with UIP and emphysema had greater lung volumes and better survival compared with those with UIP alone.     

Long-term exposure to low concentrations of air pollution and decline in lung function in people with idiopathic pulmonary fibrosis: Evidence from Australia

Background and Objective

Little is known about the association between ambient air pollution and idiopathic pulmonary fibrosis (IPF) in areas with lower levels of exposure. We aimed to investigate the impact of air pollution on lung function and rapid progression of IPF in Australia.

Methods

Participants were recruited from the Australian IPF Registry (n = 570). The impact of air pollution on changes in lung function was assessed using linear mixed models and Cox regression was used to investigate the association with rapid progression.

Results

Median (25th–75th percentiles) annual fine particulate matter (<2.5 μm, PM_2.5) and nitrogen dioxide (NO₂) were 6.8 (5.7, 7.9) μg/m³ and 6.7 (4.9, 8.2) ppb, respectively. Compared to living more than 100 m from a major road, living within 100 m was associated with a 1.3% predicted/year (95% confidence interval [CI] −2.4 to −0.3) faster annual decline in diffusing capacity of the lungs for carbon monoxide (DLco). Each interquartile range (IQR) of 2.2 μg/m³ increase in PM_2.5 was associated with a 0.9% predicted/year (95% CI −1.6 to −0.3) faster annual decline in DLco, while there was no association observed with NO₂. There was also no association between air pollution and rapid progression of IPF.

Conclusion

Living near a major road and increased PM_2.5 were both associated with an increased rate of annual decline in DLco. This study adds to the evidence supporting the negative effects of air pollution on lung function decline in people with IPF living at low-level concentrations of exposure.     

Two‐year experience with mycophenolate mofetil in patients with scleroderma lung disease: a case series

To assess the effect of mycophenolate mofetil (MMF) on pulmonary functions in patients with systemic sclerosis‐associated lung disease (SSc‐ILD) who experienced an inadequate response to first line cyclophosphamide (CYC) therapy. Twelve consecutive SSc‐ILD patients who received MMF due to inadequate response to CYC as a first line agent, were retrospectively reviewed. Over the course of 2 years, pulmonary function tests (PFT) and high‐resolution computed tomography (HRCT) scans were performed. Following initial baseline tests, PFTs were continued at a frequency of every 6 months and HRCT scans were performed every 12 months. After MMF treatment, values of forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) improved in three (25%) and two (16.6%) patients, respectively. It is also noted that the evaluation of serial HCRT scans showed no change in 54.5% of patients. Our case series suggested that PFT and imaging scores seemed to be stabilized by MMF in SSc‐ILD patients who were inadequate responders to CYC.     

Treatment of idiopathic pulmonary fibrosis in Australia and New Zealand: A position statement from the Thoracic Society of Australia and New Zealand and the Lung Foundation Australia

Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease (ILD) of unknown aetiology with a median survival of only 2–5 years. It is characterized by progressive dyspnoea and worsening lung function, ultimately resulting in death. Until recently, there were no effective therapies for IPF; however, with the publication of two landmark clinical trials in 2014, the anti‐fibrotic therapies, nintedanib and pirfenidone, have gained widespread approval. This position paper aims to highlight the current evidence for the treatment of IPF, with particular application to the Australian and New Zealand population. We also consider areas in which evidence is currently lacking, especially with regard to the broader IPF severity spectrum and treatment of co‐morbid conditions. The utility of non‐pharmacological therapies including pulmonary rehabilitation, oxygen as well as symptom management thought to be important in the holistic care of IPF patients are also discussed.     

Multiple breath washout: A new and promising lung function test for patients with idiopathic pulmonary fibrosis

Background and objective

Idiopathic pulmonary fibrosis (IPF) is a devastating progressive lung disease affecting the parenchyma. Nitrogen multiple‐breath washout (N₂‐MBW) is a lung function test that measures ventilation inhomogeneity, a biomarker of small airway disease. We assessed clinical properties of N₂‐MBW in IPF.

Methods

In this prospective cohort pilot study, 25 IPF patients and 25 healthy controls were assessed at baseline and 10 patients at median 6.2 months later. Outcomes included the lung clearance index (LCI) from N₂‐MBW, forced vital capacity (FVC) from spirometry, diffusion capacity of the lungs for carbon monoxide (DL_CO), bronchiectasis score from computed tomography scans, the Gender–Age–Physiology (GAP score for IPF) stage and death or lung transplantation (LTx). Study end points were feasibility, repeatability, discriminative capacity and correlation with disease severity and structural lung damage.

Results

All patients were able to perform N₂‐MBW. LCI was repeatable and reproducible. Median (interquartile range (IQR)) LCI in IPF was 11.6 (10.1–13.8) in IPF versus 7.3 (6.9–8.4) in controls (P < 0.0001). LCI correlated with DL_CO corrected for haemoglobin (corrDL_CO; r = −0.49, P = 0.016), bronchiectasis score (r = 0.45, P = 0.024) and the GAP stage (r = 0.59, P = 0.002), but not with FVC. FVC was not related to bronchiectasis. During follow‐up, six patients died and one received LTx. LCI correlated with the latter compound outcome: hazard ratio (95% CI) was 2.43 (1.26; 4.69) per one LCI SD from the patient population.

Conclusion

N₂‐MBW is a feasible, reliable and valid lung function test in IPF. LCI correlates with diffusion impairment, structural airway damage and clinical disease severity. LCI is a promising surveillance tool in IPF that may predict mortality.

     

Human epididymis protein 4 is a new biomarker to predict the prognosis of progressive fibrosing interstitial lung disease

BackgroundThe clinical course and prognosis of progressive fibrosing interstitial lung diseases (PF-ILDs) vary between individuals. Notably, predictive serum biomarkers for disease management are needed. Serum human epididymis protein 4 (HE4) is reportedly elevated in patients with idiopathic pulmonary ?brosis (IPF); however, its clinical utility remains unknown. We evaluated the potential of serum HE4 as a biomarker for patients with PF-ILD.MethodsSerum HE4 was measured in a retrospective study consisting of 34 patients with PF-ILD and 40 healthy volunteers. The relationship between serum HE4 levels and clinical parameters or prognosis was investigated. To validate the significance of results obtained, a prospective observational study was performed in 37 patients presenting PF-ILD and 40 control patients without PF-ILD.ResultsSerum HE4 levels were higher in patients with PF-ILD than in healthy volunteers (P < 0.01). Moreover, serum HE4 levels correlated with the extent of honeycombing on chest high-resolution computed tomography (r = 0.41, P = 0.015). In multivariate analysis using the Cox proportional hazard model, higher HE4 levels (>238 pmol/L) were associated with an elevated mortality risk; hazard ratio (HR) 7.27, 95% CI 1.56–34.0, P = 0.01 in the derivation cohort; HR 44.3, 95% CI 4.19–468, P < 0.01 in validation cohort.ConclusionsSerum HE4 levels may serve as a new diagnostic and prognostic biomarker for patients with PF-ILD.     

Novedades diagnósticas y terapéuticas en fibrosis pulmonar progresiva

In addition to idiopathic pulmonary fibrosis (IPF), other diffuse interstitial lung diseases (ILD) are also associated with pulmonary fibrosis and occur in a variable proportion of patients, depending on the entity. The name given to this fibrotic component, that may progress despite treatment, is progressive pulmonary fibrosis (PPF). In this context, PPF is not an entity per se but a common clinical condition or behavior that may occur in association with different types of fibrosing diffuse ILDs, compromising patient prognosis. PPF is identified from worsening clinical, physiological, and/or radiological criteria during patient follow-up. Randomized clinical trials in patients with IPF or progressive non-IPF ILD have shown that treatment with antifibrotic drugs, either nintedanib or pirfenidone, slows progression. We are seeing the start of a new era in the clinical management of this subgroup of patients, offering the perfect opportunity for exploring still uncharted territories.     

Clinicopathologic characteristic and prognosis in idiopathic membranous nephropathy patients with focal segmental sclerosis lesion: A retrospective observational study

To explore the clinicopathological characteristics and prognosis of idiopathic membranous nephropathy (IMN) with focal segmental sclerosis lesions (FSL).A total of 70 IMN patients with FSL (FSL+group) were enrolled in this study, and 140 patients were randomly selected by age and sex matching as disease controls (FSL-group). The clinical and renal histopathological data on renal biopsy and clinical data of patients regularly followed were collected. Serum anti-phospholipase A2 receptor (PLA2R) autoantibody, thrombospondin type-1 domain-containing 7A (7A) autoantibody, glomerular PLA2R and 7A expression, and IgG4 deposition were detected. First, the clinical and pathological significance of IMN combined with the FSL group was analyzed. Whether FSL is a risk factor for renal outcomes was further analyzed.

• 1.Compared with the FSL- group, patients in the FSL+ group had a significantly higher incidence of hypertension and a longer duration of hypertension as well as higher levels of systolic blood pressure, serum creatinine, serum triglycerides, serum cholesterol, 24-hour urinary protein excretion, and lower eGFR and urine osmotic pressure. Patients in the FSL+ group had an increased frequency of Churg stage III and more severe glomerulosclerosis and interstitial fibrosis. The remission rate was significantly lower in the FSL+ group than in the FSL- group (50.0% vs 75.9%, P = .027).
• 2.Multivariate Cox regression analysis showed that FSL (HR = 3.01, 95%CI = 1.07–8.52, P = .038) was an independent risk factor for progression of renal function deterioration, and FSL (HR = 3.25, 95%CI = 1.43–7.38, P = .005) and high levels of serum anti-PLA2R antibody (HR = 1.89, 95%CI = 1.27–2.82, P = .002) were independent risk factors for nonremission of IMN.

IMN patients who developed FSL had more severe clinical and pathological characteristics than those without FSL. FSL was an independent risk factor for poorer prognosis. When the appearance of FSL in IMN patients with a high level of serum anti-PLA2R antibody, the treatment needs to be more aggressive to promote remission and to delay the progression of renal function.     

[Translated article] Diagnostic and Therapeutic Developments in Progressive Pulmonary Fibrosis

In addition to idiopathic pulmonary fibrosis (IPF), other diffuse interstitial lung diseases (ILD) are also associated with pulmonary fibrosis and occur in a variable proportion of patients, depending on the entity. The name given to this fibrotic component, that may progress despite treatment, is progressive pulmonary fibrosis (PPF). In this context, PPF is not an entity per se but a common clinical condition or behavior that may occur in association with different types of fibrosing diffuse ILDs, compromising patient prognosis. PPF is identified from worsening clinical, physiological, and/or radiological criteria during patient follow-up. Randomized clinical trials in patients with IPF or progressive non-IPF ILD have shown that treatment with antifibrotic drugs, either nintedanib or pirfenidone, slows progression. We are seeing the start of a new era in the clinical management of this subgroup of patients, offering the perfect opportunity for exploring still uncharted territories.     

Gremlin-1 for the Differential Diagnosis of Idiopathic Pulmonary Fibrosis Versus Other Interstitial Lung Diseases: A Clinical and Pathophysiological Analysis

Purpose

The differential diagnosis of interstitial lung diseases (ILDs), particularly idiopathic pulmonary fibrosis (IPF) versus other non-IPF ILDs, is important for selecting the appropriate treatment. This retrospective study aimed to explore the utility of gremlin-1 for the differential diagnosis.

Methods

Serum gremlin-1 concentrations were measured using an ELISA in 50 patients with IPF, 42 patients with non-IPF ILD, and 30 healthy controls. The baseline clinical data, including pulmonary functions, prognosis, and three serum biomarkers (Krebs von den Lungen-6 [KL6], surfactant protein-D [SP-D], and lactate dehydrogenase [LDH]), were obtained through a medical record review for analyzing their associations with serum gremlin-1 concentrations. To evaluate the origin of gremlin-1, we performed immunostaining on lung sections.

Results

Serum gremlin-1 concentrations were significantly higher in patients with IPF (mean concentration, 14.4 ng/mL), followed by those with non-IPF ILD (8.8 ng/mL) and healthy controls (1.6 ng/mL). The area under the curve for IPF versus non-IPF ILDs was 0.759 (95% confidence interval, 0.661–0.857), which was superior to that of KL6/SP-D/LDH. The sensitivity and specificity for gremlin-1 (cutoff, 10.4 ng/mL) was 72 and 69%, respectively. By contrast, serum gremlin-1 concentrations were not associated with the pulmonary functions nor the prognosis in all patients with ILDs. In immunostaining, the gremlin-1 was broadly upregulated in IPF lungs, particularly at myofibroblasts, bronchiolar/alveolar epithelium, and CD163-positive M2-like macrophages.

Conclusions

Gremlin-1 may be a useful biomarker to improve the diagnostic accuracy for IPF compared to non-IPF ILDs, suggesting a role of this molecule in the pathogenesis of IPF.