Radiographic fibrosis score predicts survival in systemic sclerosis‐associated interstitial lung disease

Background and objective

Interstitial lung disease (ILD ) is a common pulmonary manifestation of systemic sclerosis (SSc ). It is unknown whether radiographic fibrosis score predicts mortality in SSc ‐associated ILD (SSc‐ILD ). We retrospectively analysed patients with SSc‐ILD to evaluate whether radiographic fibrosis score was a useful predictor of mortality.

Methods

We identified SSc‐ILD patients evaluated at Kurashiki Central Hospital (Japan) from 2006 to 2016, and radiographic fibrosis scores based on the extent of reticulation and honeycombing on high‐resolution computed tomography (HRCT ) scanning were calculated by manually tracing around each fibrotic area. Independent predictors of overall survival were determined using the Cox proportional hazards model.

Results

The study included 48 patients, of whom 19 had usual interstitial pneumonia on HRCT . The median follow‐up period was 56.6 months, and over the follow‐up period 15 patients died. The 5‐year survival was 72.4%. In the multivariate analysis, radiographic fibrosis score, age, being male and forced vital capacity were independently associated with an increased risk of death, while HRCT pattern was not.

Conclusion

A high radiographic fibrosis score was a poor prognostic factor in SSc‐ILD . More widespread fibrosis was associated with an increased risk of death, independent of HRCT pattern.

     

Radiological fibrosis score is strongly associated with worse survival in rheumatoid arthritis-related interstitial lung disease

Objectives: High-resolution computed tomography (HRCT) parenchymal patterns have been used to predict prognosis in patients with interstitial lung disease (ILD). In idiopathic pulmonary fibrosis, the fibrosis score (i.e. the combined extent of reticulation and honeycombing) has been associated with worse survival. This study aimed to identify HRCT patterns and patient characteristics that can predict poor prognosis in rheumatoid arthritis-related ILD (RA-ILD).

Methods: We retrospectively analysed 65 patients with newly diagnosed RA-ILD from 2007 to 2016 at Kurashiki Central hospital. Using univariate and bivariate Cox regression analysis, associations with mortality, were identified.

Results: During a median follow-up of 56.5 months, 16/65 (24.6%) patients died. Univariate analysis identified six significant poor prognostic factors: lower baseline % predicted forced vital capacity, total interstitial disease score, reticulation score, traction bronchiectasis score, fibrosis score, and definite UIP pattern. Fibrosis score remained to be an independently significant poor prognostic factor of survival on bivariate analysis. Patients with a fibrosis score >20% had higher mortality (HR, 9.019; 95% CI, 2.87–28.35; p?Conclusion: This study showed that fibrosis score is strongly associated with worse survival in RA-ILD, and patients with fibrosis score >20% had a 9.019-fold increased risk of mortality.     

Outcomes of patients with interstitial lung disease referred for lung transplant assessment

Background: Patients with interstitial lung disease (ILD) very frequently die before the opportunity to receive lung transplantation (LTx). This retrospective study describes the clinical course of 86 patients with ILD referred for LTx assessment between January 1999 and December 2002. Aims: (i) To describe the outcomes, (ii) to identify reasons of delay to transplantation, (iii) to describe the causes of death/complications and (iv) to assess the pathological diagnosis and concordance with explanted lung pathology. Methods: Data were collected from the case notes of all patients with ILD referred to the Alfred Hospital over a 4‐year period. Results: Twenty women and 66 men, mean age of 55 ± 8 years, were referred for LTx assessment. Forty‐five patients were deemed not suitable for LTx and 41 were listed. Twenty‐two patients underwent transplantation, 16 died on the waiting list and 7 are still on the waiting list. Complications were frequent (e.g. pulmonary embolism, malignancy and infection) and carried high mortality. Patients dying on the waiting list appeared generally to be in accelerated decline, dying shortly after listing, with no evidence in their lung function test assessment predicting them as a poor prognosis group. Conclusions: Serious complications and death on the waiting list of patients with idiopathic pulmonary fibrosis are high, not apparently because of delayed referral but usually in patients undergoing very rapid decline.     

KL-6 is a long-term disease-activity biomarker for interstitial lung disease associated with polymyositis/dermatomyositis,but is not a short-term disease-activity biomarker

Abstract

Objectives: We aimed to evaluate the usefulness of serum KL-6 for interstitial lung disease (ILD) with polymyositis/dermatomyositis (PM/DM).

Methods: All consecutive and previously untreated adult patients with PM/DM who were admitted to our hospital from 2010 to 2015 were included. The associations between serum KL-6 levels and clinical information were retrospectively analyzed.

Results: Baseline serum KL-6 levels were significantly higher in patients with ILD than in those without (n?=?41 and 15, respectively; p?<?.001). In the 14 patients whose ILD improved within 4 weeks post-treatment, their serum KL-6 levels did not significantly decrease at 2 weeks, 4 weeks, or 3 months post-treatment (p?=?1.00, 1.00, and .83, respectively). Conversely, their serum KL-6 levels significantly decreased at 6, 9, and 12 months post-treatment (p?=?.01 in all comparisons). In the 12 patients whose ILD remained unchanged or deteriorated in 4 weeks post-treatment, only the difference between their serum KL-6 levels at 3 and 12 months was significant (p?=?.003).

Conclusions: The present study validated the serum KL-6 as a diagnostic marker for ILD in PM/DM. However, serum KL-6 is not a short-term disease-activity biomarker for ILD with PM/DM, but it is a long-term disease-activity biomarker.     

Fractional analysis of bronchoalveolar lavage in systemic sclerosis-associated interstitial lung disease

BackgroundThe utility of bronchoalveolar lavage (BAL) in the evaluation of systemic sclerosis-associated interstitial lung disease (SSc-ILD) remains controversial. Fractional analysis of BAL (FBAL) is a technique that can analyze small airways and alveolar compartments separately and has proven informative in other ILDs. The aim of this study was to explore FBAL characteristics across the spectrum of SSc-ILD severity.MethodsWe retrospectively reviewed patients with SSc-ILD who underwent bronchoscopy with FBAL using three 50 mL aliquots of saline solution. These aliquots were analyzed separately for differential cell composition (FBAL-1, -2, and -3). We compared the FBAL cell composition to the progression of ILD and end-stages of ILD using Cox proportional hazards models.ResultsSixty-eight patients with SSc-ILD were enrolled in this study. The percentage of neutrophils and eosinophils was lower in FBAL-3 compared to FBAL-1. In contrast, the percentage of macrophages and lymphocytes was higher in FBAL-3. Neutrophils in FBAL-2, -3, and the estimated total FBAL cell fraction (FBAL-total) were negatively correlated with the forced vital capacity % predicted (r=−0.420, −0.362, −0.409, respectively). Although FBAL-total was not linked to the progression and end-stage of ILD, a high percentage of neutrophils in FBAL-3 was significantly associated with the development of end-stage ILD (HR 1.093, 95% CI: 1.003–1.190).ConclusionsA higher percentage of neutrophils in FBAL-3 is correlated with development of end-stage ILD in SSc-ILD as well as mortality.     

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.     

High‐dose prednisolone and bolus cyclophosphamide in interstitial lung disease associated with systemic sclerosis: a prospective open study

Aim: Currently, therapy for interstitial lung disease in patients with systemic sclerosis is unsatisfactory. A prospective open label study was conducted in a North Indian tertiary Institute to assess the efficacy of intermittent pulse cyclophosphamide (CYC) and high‐dose prednisolone in systemic sclerosis (SSc)‐related interstitial lung disease (ILD). Methods: Consecutive patients with SSc and ILD, diagnosed on spirometry, carbon monoxide diffusing capacity (DLCO) and high‐resolution computed tomography (HRCT) scan were treated. Pulmonary function tests were carried out at baseline and after 6 months. Patients received oral prednisolone 1 mg/kg body weight initially, with tapering to a dose of 7.5 mg/day was reached. Monthly CYC pulses were given for 6 months followed by 3‐monthly maintenance pulses. CYC was discontinued in patients with declining pulmonary function, adverse effects or static disease after 6 months. Results: Average disease duration of 36 patients was 59.78 ± 63.22 months. Seven patients improved (forced vital capacity [FVC] increase 10% or DLCO increase 15%), five deteriorated (FVC decline 10% or DLCO decline 15%) and 24 had stable disease. Thus, 31 out of 36 patients either improved or had static lung disease. Mean FVC (% of predicted) improved by 4.16% over 6 months (P = 0.069). Mean DLCO (% of predicted) improved by 5.66% (P = 0.27). Average % of predicted DLCO at baseline was 39%. Conclusion: High‐dose prednisolone with pulse CYC can either improve or stabilize lung functions in patients with severe systemic sclerosis lung disease irrespective of presence of ground glass appearance on HRCT.     

Unclassifiable interstitial lung disease: A review

Accurate classification of interstitial lung disease (ILD) requires a multidisciplinary approach that incorporates input from an experienced respirologist, chest radiologist and lung pathologist. Despite a thorough multidisciplinary evaluation, up to 15% of ILD patients have unclassifiable ILD and cannot be given a specific diagnosis. The objectives of this review are to discuss the definition and features of unclassifiable ILD, identify the barriers to ILD classification and outline an approach to management of unclassifiable ILD. Several recent studies have described the characteristics of these patients; however, there are inconsistencies in the definition and terminology of unclassifiable ILD due to limited research in this population. Additional studies are required to determine the appropriate evaluation and management of patients with unclassifiable ILD.     

Bronchoalveolar lavage cellular profiles in patients with systemic sclerosis–associated interstitial lung disease are not predictive of disease progression

Objective

To evaluate the prognostic value of bronchoalveolar lavage (BAL) cellular profiles in patients with systemic sclerosis–associated interstitial lung disease (SSc‐ILD).

Methods

BAL cellularity was examined in relation to mortality (n = 141), serial pulmonary function findings (n = 134), and “progression‐free survival” (n = 134), by proportional hazards analysis. Baseline severity was quantified according to the extent of disease on high‐resolution computed tomography, the diffusing capacity for carbon monoxide, and the presence or absence of pulmonary hypertension. Mortality was subclassified into overall mortality (during 10 years of followup), early mortality (occurring within 2 years of presentation), and late mortality (occurring 2–10 years after presentation).

Results

Overall mortality was associated with neutrophilia on BAL (hazard ratio 2.23 [95% confidence interval 1.20–4.14], P = 0.01), but this effect was lost when disease severity was taken into account. Early mortality was associated with neutrophilia on BAL (hazard ratio 8.40 [95% confidence interval 1.91–36.95], P = 0.005), independent of disease severity. Late mortality was not associated with neutrophilia on BAL. The presence of neutrophilia on BAL was not associated with time to decline in pulmonary function or progression‐free survival. Neither eosinophilia nor lymphocytosis on BAL was associated with mortality, rapidity of functional deterioration, or progression‐free survival. These findings were unaltered when treatment status was taken into account.

Conclusion

BAL findings provide only limited prognostic information in SSc‐ILD. Neutrophilia on BAL is linked to early mortality, but BAL findings are not linked to long‐term survival or the rapidity of progression of lung disease. The usefulness of BAL to define alveolitis in SSc is questionable.

     

Diagnostic utility of surgical lung biopsies in elderly patients with indeterminate interstitial lung disease

Background and objective

Idiopathic pulmonary fibrosis (IPF) is increasingly diagnosed by clinical and computed tomography (CT) criteria; however, surgical lung biopsy (SLB) may still be required in patients who lack definite CT features of usual interstitial pneumonia (UIP). We reviewed a cohort of elderly patients who underwent SLB, to evaluate the benefit of SLB in diagnosing idiopathic interstitial pneumonia (IIP).

Methods

We searched the pathology records of Mayo Clinic for ambulatory patients at least 75 years old, who underwent SLB between 2000 and 2012 for indeterminate IIP. Histologic slides were reviewed and clinical data were extracted from the record.

Results

A total of 55 patients (35 male) were enrolled. Median (interquartile range) age was 77 (76–80) years. Forced vital capacity was 70 (61–76)% and diffusing capacity of the lungs for carbon monoxide was 48 (42–54)% of predicted. In total, 37 (67%) patients had IPF, including 61% of those with HRCT findings inconsistent with UIP. Thirty‐day mortality was 10% and 90‐day mortality was 15%.

Conclusion

The high mortality rate of SLB complicates the risk–benefit analysis in elderly patients with IIP. The expected value of the SLB is probably highest when the HRCT features are inconsistent with UIP, due to the frequent (39%) retrieval of patterns other than UIP.