Simon Walsh

Quadriceps wasting and physical inactivity in patients with COPD

Quadriceps weakness is an important complication of advanced chronic obstructive pulmonary disease (COPD) but few data exist concerning muscle bulk in early disease. We hypothesised that quadriceps bulk, measured by ultrasound rectus femoris cross-sectional area (USRFCSA), would be reduced in mild, as well as advanced, COPD compared with controls, and would correlate with physical activity. 161 patients with stable COPD and 40 healthy subjects had a measurement of USRFCSA and wore a multisensor armband to record physical activity. USRFCSA was reduced in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I patients compared with healthy subjects (p=0.0002). Stage II–IV patients had reduced USRFCSA (p<0.0001) compared with controls but were not significantly different from those with stage I disease. Physical activity level was reduced in stage I (p=0.002) and stage II–IV disease compared with controls. Using regression analysis, physical activity level was independently associated with USRFCSA in stage I (p=0.01) but not stage II–IV disease, where residual volume to total lung capacity ratio was the only independent predictor of physical activity level. Quadriceps wasting exists in patients with mild, as well as advanced, COPD, and is independently associated with physical inactivity in GOLD stage I disease. The identification of these patients may guide early lifestyle and therapeutic interventions.

Multicentre evaluation of multidisciplinary team meeting agreement on diagnosis in diffuse parenchymal lung disease: a case-cohort study

BACKGROUND Diffuse parenchymal lung disease represents a diverse and challenging group of pulmonary disorders. A consistent diagnostic approach to diffuse parenchymal lung disease is crucial if clinical trial data are to be applied to individual patients. We aimed to evaluate inter-multidisciplinary team agreement for the diagnosis of diffuse parenchymal lung disease. METHODS We did a multicentre evaluation of clinical data of patients who presented to the interstitial lung disease unit of the Royal Brompton and Harefield NHS Foundation Trust (London, UK; host institution) and required multidisciplinary team meeting (MDTM) characterisation between March 1, 2010, and Aug 31, 2010. Only patients whose baseline clinical, radiological, and, if biopsy was taken, pathological data were undertaken at the host institution were included. Seven MDTMs, consisting of at least one clinician, radiologist, and pathologist, from seven countries (Denmark, France, Italy, Japan, Netherlands, Portugal, and the UK) evaluated cases of diffuse parenchymal lung disease in a two-stage process between Jan 1, and Oct 15, 2015. First, the clinician, radiologist, and pathologist (if lung biopsy was completed) independently evaluated each case, selected up to five differential diagnoses from a choice of diffuse lung diseases, and chose likelihoods (censored at 5% and summing to 100% in each case) for each of their differential diagnoses, without inter-disciplinary consultation. Second, these specialists convened at an MDTM and reviewed all data, selected up to five differential diagnoses, and chose diagnosis likelihoods. We compared inter-observer and inter-MDTM agreements on patient first-choice diagnoses using Cohens kappa coefficient (κ). We then estimated inter-observer and inter-MDTM agreement on the probability of diagnosis using weighted kappa coefficient (κw). We compared inter-observer and inter-MDTM confidence of patient first-choice diagnosis. Finally, we evaluated the prognostic significance of a first-choice diagnosis of idiopathic pulmonary fibrosis (IPF) versus not IPF for MDTMs, clinicians, and radiologists, using univariate Cox regression analysis. FINDINGS 70 patients were included in the final study cohort. Clinicians, radiologists, pathologists, and the MDTMs assigned their patient diagnoses between Jan 1, and Oct 15, 2015. IPF made up 88 (18%) of all 490 MDTM first-choice diagnoses. Inter-MDTM agreement for first-choice diagnoses overall was moderate (κ=0·50). Inter-MDTM agreement on diagnostic likelihoods was good for IPF (κw=0·71 [IQR 0·64-0·77]) and connective tissue disease-related interstitial lung disease (κw=0·73 [0·68-0·78]); moderate for non-specific interstitial pneumonia (NSIP; κw=0·42 [0·37-0·49]); and fair for hypersensitivity pneumonitis (κw=0·29 [0·24-0·40]). High-confidence diagnoses (>65% likelihood) of IPF were given in 68 (77%) of 88 cases by MDTMs, 62 (65%) of 96 cases by clinicians, and in 57 (66%) of 86 cases by radiologists. Greater prognostic separation was shown for an MDTM diagnosis of IPF than compared with individual clinicians diagnosis of this disease in five of seven MDTMs, and radiologists diagnosis of IPF in four of seven MDTMs. INTERPRETATION Agreement between MDTMs for diagnosis in diffuse lung disease is acceptable and good for a diagnosis of IPF, as validated by the non-significant greater prognostic separation of an IPF diagnosis made by MDTMs than the separation of a diagnosis made by individual clinicians or radiologists. Furthermore, MDTMs made the diagnosis of IPF with higher confidence and more frequently than did clinicians or radiologists. This difference is of particular importance, because accurate and consistent diagnoses of IPF are needed if clinical outcomes are to be optimised. Inter-multidisciplinary team agreement for a diagnosis of hypersensitivity pneumonitis is low, highlighting an urgent need for standardised diagnostic guidelines for this disease. FUNDING National Institute of Health Research, Imperial College London.

Interobserver agreement for the ATS/ERS/JRS/ALAT criteria for a UIP pattern on CT

Objectives To establish the level of observer variation for the current ATS/ERS/JRS/ALAT criteria for a diagnosis of usual interstitial pneumonia (UIP) on CT among a large group of thoracic radiologists of varying levels of experience. Materials and methods 112 observers (96 of whom were thoracic radiologists) categorised CTs of 150 consecutive patients with fibrotic lung disease using the ATS/ERS/JRS/ALAT CT criteria for a UIP pattern (3 categories—UIP, possibly UIP and inconsistent with UIP). The presence of honeycombing, traction bronchiectasis and emphysema was also scored using a 3-point scale (definitely present, possibly present, absent). Observer agreement for the UIP categorisation and for the 3 CT patterns in the entire observer group and in subgroups stratified by observer experience, were evaluated. Results Interobserver agreement across the diagnosis category scores among the 112 observers was moderate, ranging from 0.48 (IQR 0.18) for general radiologists to 0.52 (IQR 0.20) for thoracic radiologists of 10–20 years’ experience. A binary score for UIP versus possible or inconsistent with UIP was examined. Observer agreement for this binary score was only moderate. No significant differences in agreement levels were identified when the CTs were stratified according to multidisciplinary team (MDT) diagnosis or patient age or when observers were categorised according to experience. Observer agreement for each of honeycombing, traction bronchiectasis and emphysema were 0.59±0.12, 0.42±0.15 and 0.43±0.18, respectively. Conclusions Interobserver agreement for the current ATS/ERS/JRS/ALAT CT criteria for UIP is only moderate among thoracic radiologists, irrespective of their experience, and did not vary with patient age or the MDT diagnosis.

Connective tissue disease related fibrotic lung disease: high resolution computed tomographic and pulmonary function indices as prognostic determinants

Purpose To determine high resolution computed tomography (HRCT) patterns and pulmonary function indices which are associated with increased mortality in patients with connective tissue disease related fibrotic lung disease (CTD-FLD). Methods HRCTs from 168 patients with CTD-FLD were scored by 2 observers for a variety of HRCT patterns and traction bronchiectasis. A radiological diagnosis of usual interstitial pneumonia (UIP), fibrotic non-specific interstitial pneumonia (NSIP) or indeterminate was also assigned. Using Cox regression analysis, associations with mortality were identified. Honeycombing and traction bronchiectasis scores were converted to binary absence/presence scores and also tested. A subgroup analysis of patients with biopsy material (n=51) was performed by classifying patients according to radiological and histopathological diagnoses, as concordant UIP, discordant UIP and fibrotic NSIP. The prognostic separation of this classification was also evaluated. Results Severity of traction bronchiectasis (HR 1.10, p=0.001, 95% CIs 1.04 to 1.17), increasing extent of honeycombing (HR 1.08, p=0.021, 95% CI 1.03 to 1.13) and reduction in DLco (HR 0.97, p=0.013, 95% CI 0.95 to 0.99) were independently associated with increased mortality. Interobserver agreement and prognostic strength were higher for binary traction bronchiectasis scores (weighted κ (κw)=0.69, HR 4.00, p=0.001, 95%CI 1.19 to 13.38), than binary honeycombing scores (κw=0.50, HR 2.87, p=0.022, 95% CI 1.53 to 5.43). The radiological-histopathological classification was strongly associated with increased mortality (HR 2.74, p<0.001, 95% CI 1.57 to 4.77) and patients with discordant UIP had a better prognosis than concordant UIP but worse prognosis than fibrotic NSIP. Conclusions Severity of traction bronchiectasis, extent of honeycombing and DLco are strongly associated with mortality in CTD-FLD. Interobserver agreement for traction bronchiectasis is higher than for honeycombing. In CTD-FLD, radiological diagnosis has survival implications in biopsy proven UIP.

Chronic hypersensitivity pneumonitis: high resolution computed tomography patterns and pulmonary function indices as prognostic determinants

AbstractObjectivesTo investigate high resolution computed tomography (HRCT) and pulmonary function indices (PFTs) for determining prognosis in patients with chronic fibrotic hypersensitivity pneumonitis (CHP).MethodsCase records, PFTs (FEV1, FVC and DLco) and HRCTs of ninety-two patients with chronic hypersensitivity pneumonitis were evaluated. HRCT studies were scored by two observers for total disease extent, ground-glass opacification, fine and coarse reticulation, microcystic and macrocystic honeycombing, centrilobular emphysema and consolidation. Traction bronchiectasis within each pattern was graded. Using Cox proportional hazards regression models the prognostic strength of individual HRCT patterns and pulmonary function test variables were determined.ResultsThere were forty two deaths during the study period. Increasing severity of traction bronchiectasis was the strongest predictor of mortality (HR 1.10, P < 0.001, 95%CI 1.04-1.16). Increasing global interstitial disease extent (HR 1.02, P = 0.02, 95%CI 1.00-1.03), microcystic honeycombing (HR 1.09, P = 0.019, 95%CI 1.01-1.17) and macrocystic honeycombing (HR 1.06, P < 0.01, 95%CI 1.01-1.10) were also independent predictors of mortality. In contrast, no individual PFT variable was predictive of mortality once HRCT patterns were accounted for.ConclusionHRCT patterns, in particular, severity of traction bronchiectasis and extent of honeycombing are superior to pulmonary function tests for predicting mortality in patients with CHP.Key Points• HRCT is increasingly used to assess chronic fibrotic hypersensitivity pneumonitis. • HRCT patterns are superior to pulmonary function tests for predicting mortality. • Extensive traction bronchiectasis strongly predicts poor survival in chronic hypersensitivity pneumonitis.

An integrated clinicoradiological staging system for pulmonary sarcoidosis: a case-cohort study

BACKGROUND Mortality in pulmonary sarcoidosis is highly variable and a reliable prognostic algorithm for disease staging and for guiding management decisions is needed. The objective of this study is to derive and test a staging system for determining prognosis in pulmonary sarcoidosis. METHODS We identified the prognostic value of high-resolution computed tomography (HRCT) patterns and pulmonary function tests, including the composite physiological index (CPI) in patients with pulmonary sarcoidosis. We integrated prognostic physiological and HRCT variables to form a clinical staging algorithm predictive of mortality in a test cohort. The staging system was externally validated in a separate cohort by the same methods of discrimination used in the primary analysis and tested for clinical applicability by four test observers. FINDINGS The test cohort included 251 patients with pulmonary sarcoidosis in the study referred to the Sarcoidosis clinic at the Royal Brompton Hospital, UK, between Jan 1, 2000, and June 30, 2010. The CPI was the strongest predictor of mortality (HR 1·04, 95% CI 1·02-1·06, p<0·0001) in the test cohort. An optimal CPI threshold of 40 units was identified (HR 4·24, 2·84-6·33, p<0·0001). The CPI40, main pulmonary artery diameter to ascending aorta diameter ratio (MPAD/AAD), and an extent of fibrosis threshold of 20% were combined to form a staging algorithm. When assessed in the validation cohort (n=252), this staging system was strikingly more predictive of mortality than any individual variable alone (HR 5·89, 2·68-10·08, p<0·0001). The staging system was successfully applied to the test and validation cohorts combined, by two radiologists and two physicians. INTERPRETATION A clear prognostic separation of patients with pulmonary sarcoidosis is provided by a simple staging system integrating the CPI and two HRCT variables.

Smoking‐related emphysema is associated with idiopathic pulmonary fibrosis and rheumatoid lung

A combined pulmonary fibrosis/emphysema syndrome has been proposed, but the basis for this syndrome is currently uncertain. The aim was to evaluate the prevalence of emphysema in idiopathic pulmonary fibrosis (IPF) and rheumatoid lung (rheumatoid arthritis‐interstitial lung disease (RA‐ILD)), and to compare the morphological features of lung fibrosis between smokers and non‐smokers.

Mortality prediction in idiopathic pulmonary fibrosis: evaluation of computer-based CT analysis with conventional severity measures

Computer-based computed tomography (CT) analysis can provide objective quantitation of disease in idiopathic pulmonary fibrosis (IPF). A computer algorithm, CALIPER, was compared with conventional CT and pulmonary function measures of disease severity for mortality prediction. CT and pulmonary function variables (forced expiratory volume in 1 s, forced vital capacity, diffusion capacity of the lung for carbon monoxide, transfer coefficient of the lung for carbon monoxide and composite physiologic index (CPI)) of 283 consecutive patients with a multidisciplinary diagnosis of IPF were evaluated against mortality. Visual and CALIPER CT features included total extent of interstitial lung disease, honeycombing, reticular pattern, ground glass opacities and emphysema. In addition, CALIPER scored pulmonary vessel volume (PVV) while traction bronchiectasis and consolidation were only scored visually. A combination of mortality predictors was compared with the Gender, Age, Physiology model. On univariate analyses, all visual and CALIPER-derived interstitial features and functional indices were predictive of mortality to a 0.01 level of significance. On multivariate analysis, visual CT parameters were discarded. Independent predictors of mortality were CPI (hazard ratio (95% CI) 1.05 (1.02–1.07), p<0.001) and two CALIPER parameters: PVV (1.23 (1.08–1.40), p=0.001) and honeycombing (1.18 (1.06–1.32), p=0.002). A three-group staging system derived from this model was powerfully predictive of mortality (2.23 (1.85–2.69), p<0.0001). CALIPER-derived parameters, in particular PVV, are more accurate prognostically than traditional visual CT scores. Quantitative tools such as CALIPER have the potential to improve staging systems in IPF. CALIPER-derived parameters such as pulmonary vessel volume are more accurate prognostically than visual CT scores http://ow.ly/2b5G304exlA

Automated Quantitative Computed Tomography Versus Visual Computed Tomography Scoring in Idiopathic Pulmonary Fibrosis: Validation Against Pulmonary Function.

Purpose: The aim of the study was to determine whether a novel computed tomography (CT) postprocessing software technique (CALIPER) is superior to visual CT scoring as judged by functional correlations in idiopathic pulmonary fibrosis (IPF). Materials and Methods: A total of 283 consecutive patients with IPF had CT parenchymal patterns evaluated quantitatively with CALIPER and by visual scoring. These 2 techniques were evaluated against: forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLco), carbon monoxide transfer coefficient (Kco), and a composite physiological index (CPI), with regard to extent of interstitial lung disease (ILD), extent of emphysema, and pulmonary vascular abnormalities. Results: CALIPER-derived estimates of ILD extent demonstrated stronger univariate correlations than visual scores for most pulmonary function tests (PFTs): (FEV1: CALIPER R2=0.29, visual R2=0.18; FVC: CALIPER R2=0.41, visual R2=0.27; DLco: CALIPER R2=0.31, visual R2=0.35; CPI: CALIPER R2=0.48, visual R2=0.44). Correlations between CT measures of emphysema extent and PFTs were weak and did not differ significantly between CALIPER and visual scoring. Intriguingly, the pulmonary vessel volume provided similar correlations to total ILD extent scored by CALIPER for FVC, DLco, and CPI (FVC: R2=0.45; DLco: R2=0.34; CPI: R2=0.53). Conclusions: CALIPER was superior to visual scoring as validated by functional correlations with PFTs. The pulmonary vessel volume, a novel CALIPER CT parameter with no visual scoring equivalent, has the potential to be a CT feature in the assessment of patients with IPF and requires further exploration.

Diffuse interstitial lung disease: overlaps and uncertainties

Histopathological analysis of lung biopsy material allows the diagnosis of idiopathic interstitial pneumonias; however, the strength of this diagnosis is sometimes subverted by interobserver variation and sampling. The American Thoracic Society and European Respiratory Society recommendations of 2002 provide a framework for the diagnosis of interstitial lung disease (ILD) and proposed an integrated clinical, radiological and histopathological approach. These recommendations represent a break with tradition by replacing the ‘gold standard’ of histopathology with the combined ‘silver standards’ of clinical, imaging and histopathological information. One of the pitfalls of a rigid classification system for the diagnosis of interstitial lung disease is its failure to accommodate the phenomenon of overlapping disease patterns. This article reviews the various ways that interstitial lung disease may be classified and discusses their applicability. In addition the issue of overlap disease patterns is considered in the context of histopathological interobserver variation and sampling error and how a pigeonhole approach to disease classification may overlook these hybrid entities.