Visual analogue scales for interstitial lung disease:a prospective validation study

Rationale: Visual analogue scales (VAS) are simple symptom assessment tools which have not been validated in interstitial lung disease (ILD). Simple measures of ILD disease burden would be valuable for non-specialist clinicians monitoring disease away from ILD specialist centres.Objective: To validate VAS to assess change in dyspnoea, cough and fatigue in ILD, and to define the minimal clinically important difference (MCID) for change in these.METHODS:64 patients with ILD completed VAS for dyspnoea, cough and fatigue. Baseline King's Brief ILD questionnaire (K-BILD) scores, lung function and 6-minute walk test results were collected. Tests were repeated 3-6 months later, in addition to a 7-point Likert scale. The MCID was estimated using median change in VAS in patients who reported "small but just worthwhile change" in symptoms at follow-up. Methods were repeated in a validation cohort of 31 ILD patients to confirm findings.Results: VAS scores were significantly higher for patients who reported a "small but just worthwhile change" in symptoms versus "no change" or "not worthwhile change" (p < 0.01). The MCID for VAS Dyspnoea was estimated as 22.0mm and 14.5mm for VAS Fatigue. These results were reproducible in the validation cohort. Results were not significant for VAS Cough. Change in VAS Dyspnoea correlated with change in K-BILD (r=-0.51, p < 0.01), forced vital capacity (r=-0.32, p = 0.01) and 6-minute walking distance (r=-0.37, p = 0.01).Conclusion: The VAS is valid for assessing change in dyspnoea and fatigue in ILD. The MCID is estimated as 22.0mm for dyspnoea and 14.5mm for fatigue. This could be used to monitor disease in settings away from ILD specialist revie

The prognostic value of cardiopulmonary exercise testing in interstitial lung disease:a systematic review

The heterogeneity of interstitial lung disease (ILD) results in prognostic uncertainty concerning end of life discussions and optimal timing for transplantation. Effective prognostic markers and prediction models are needed. Cardio-Pulmonary Exercise Testing (CPET) provides a comprehensive assessment of the physiological changes in the respiratory, cardiovascular, and musculoskeletal systems in a controlled laboratory environment. It has shown promise as a prognostic factor for other chronic respiratory conditions. We sought to evaluate the prognostic value of CPET in predicting outcomes in longitudinal studies of ILD . Medline, Embase and Cochrane systematic review databases were used to identify studies reporting prognostic value of CPET in predicting outcomes in longitudinal studies of ILD. Study quality was assessed using the Quality in Prognosis Study risk of bias tool.Thirteen studies were included that reported the prognostic value of CPET in ILD. All studies reported at least one CPET parameter predicting clinical outcomes in ILD; with survival being the principle outcome assessed. Maximum oxygen consumption, reduced ventilatory efficiency and exercise induced hypoxaemia were all reported to have prognostic value in ILD. Issues with study design (primarily due to inherent problems of retrospective studies, patient selection and presentation of numerous CPET parameters), insufficient adjustment for important confounders and inadequate statistical analyses limits the strength of conclusions that can be drawn at this stage.There is insufficient evidence to confirm the value of CPET in facilitating ‘real-world’ clinical decisions in ILD. Additional prospective studies are required to validate the putative prognostic associations reported in previous studies in carefully phenotyped patient populations. <br/

The not so innocent bystander:an unusual cause of progressive breathlessness

This case report discusses a 76-year-old man who presented with symptomatic diffuse alveolar-septal and tracheobronchial amyloidosis with a low-grade monoclonal gammopathy. This patient had a combination of both symptomatic diffuse alveolar-septal interstitial disease and tracheobronchial amyloidosis, features that contradict the widely accepted presentations seen in this disease. First, tracheobronchial amyloidosis has been documented as localised disease without systemic involvement. Second, diffuse alveolar-septal interstitial disease is rarely identified with clinical symptoms unless there is significant cardiac involvement. This case highlights a number learning points in the diagnosis and management of systemic amyloid light chain amyloidosis;(1) There is a need for a high index of suspicion for diagnosis due to the potential subtlety of a plasma cell clone underlying AL amyloidosis, requiring serum-free light chain assays to increase sensitivity; (2) Haematological response and recovery of organ dysfunction are not a linear relationship due to the slower reversal of amyloid deposition; therefore, ongoing monitoring is required to identify those in need of repeated therapy. However, haematological response is a marker of overall survival and (3) Multisystem assessment and multidisciplinary collaboration are critical in optimising the care of patients with systemic AL amyloidosis.</p

Idiopathic Pulmonary Fibrosis (IPF):An Overview

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterised by chronic, progressive scarring of the lungs and the pathological hallmark of usual interstitial pneumonia. Current paradigms suggest alveolar epithelial cell damage is a key initiating factor. Globally, incidence of the disease is rising, with associated high morbidity, mortality, and economic healthcare burden. Diagnosis relies on a multidisciplinary team approach with exclusion of other causes of interstitial lung disease. Over recent years, two novel antifibrotic therapies, pirfenidone and nintedanib, have been developed, providing treatment options for many patients with IPF, with several other agents in early clinical trials. Current efforts are directed at identifying key biomarkers that may direct more customized patient-centred healthcare to improve outcomes for these patients in the future

The Role of Vascular Endothelial Growth Factor in Systemic Sclerosis

The pathological hallmarks of Systemic sclerosis (SSc) constitute an inter-related triad of autoimmunity, vasculopathy and tissue remodeling. Many signaling mediators have been implicated in SSc pathology; most focusing on individual components of this pathogenic triad and current treatment paradigms tend to approach management of such as distinct entities. The present review shall examine the role of vascular endothelial growth factor (VEGF) in SSc pathogenesis. We shall outline potential mechanisms whereby differential vascular endothelial growth factor-A (VEGF-A) isoform expression (through conventional and alternative VEGF-A splicing,) may influence the relevant burden of vasculopathy and fibrosis offering novel insight into clinical heterogeneity and disease progression in SSc. Emerging therapeutic approaches targeting VEGF signaling pathways might play an important role in the management of SSc, and differential VEGF-A splice isoform expression may provide a tool for personalized medicine approaches to disease management.</p

High frequency ultrasound assessment of systemic sclerosis skin involvement:intra-observer repeatability and relationship with clinician assessment and dermal collagen content

OBJECTIVE: The modified Rodnan skin score (mRSS) remains the preferred method for skin assessment in systemic sclerosis (SSc). There are concerns regarding high inter-observer variability of mRSS and negative clinical trials utilising mRSS as the primary endpoint. High frequency ultrasound (HFUS) allows objective assessment of cutaneous fibrosis in SSc. We investigated the relationship between HFUS with both mRSS and dermal collagen.METHODS: Skin thickness (ST), echogenicity and novel Shear wave elastography (SWE) were assessed in 53 SSc patients and 15 healthy controls (HC) at the finger, hand, forearm and abdomen. The relationship between HFUS parameters with mRSS (n=53) and dermal collagen (10 SSc patients and 10 HC) was investigated. Intra-observer repeatability of HFUS was calculated using intra-class correlation coefficients (ICCs).RESULTS: HFUS assessment of ST (hand/forearm) and SWE (finger/hand) correlated with local mRSS at some sites. Subclinical abnormalities in ST, echogenicity and SWE were present in clinically uninvolved SSc skin. Additionally, changes in echogenicity and SWE were sometimes apparent despite objectively normal ST on HFUS. ST, SWE and local mRSS correlated strongly with collagen quantification (rho 0.697, 0.709, 0.649 respectively). Intra-observer repeatability was high for all HFUS parameters (ICCs for ST 0.946-0.978, echogenicity 0.648- 0.865 and SWE 0.953-0.973).CONCLUSION: Our data demonstrates excellent reproducibility and reassuring convergent validity with dermal collagen content. Detection of subclinical abnormalities is an additional benefit of HFUS. The observed correlations with collagen quantification support further investigation of HFUS as an alternative to mRSS in clinical trial settings.</p