Maryl Kreider

Echocardiographic and Hemodynamic Predictors of Mortality in Idiopathic Pulmonary Fibrosis

BACKGROUND Idiopathic pulmonary fibrosis (IPF) can lead to the development of pulmonary hypertension, which is associated with an increased risk of death. In pulmonary arterial hypertension, survival is directly related to the capacity of the right ventricle to adapt to elevated pulmonary vascular load. The relative importance of right ventricular function in IPF is not well understood. Our objective was to evaluate right ventricular echocardiographic and hemodynamic predictors of mortality in a cohort of patients with IPF referred for lung transplant evaluation. METHODS We performed a retrospective cohort study of 135 patients who met 2011 American Thoracic Society/European Respiratory Society criteria for IPF and who were evaluated for lung transplantation at the Hospital of the University of Pennsylvania. RESULTS Right ventricle:left ventricle diameter ratio (hazard ratio [HR], 4.5; 95% CI, 1.7-11.9), moderate to severe right atrial and right ventricular dilation (HR, 2.9; 95% CI, 1.4-5.9; and HR, 2.7; 95% CI, 1.4-5.4, respectively) and right ventricular dysfunction (HR, 5.5; 95% CI, 2.6-11.5) were associated with an increased risk of death. Higher pulmonary vascular resistance was also associated with increased mortality (HR per 1 Wood unit, 1.3; 95% CI, 1.1-1.5). These risk factors were independent of age, sex, race, height, weight, FVC, and lung transplantation status. Other hemodynamic indices, such as mean pulmonary artery pressure and cardiac index, were not associated with outcome. CONCLUSIONS Right-sided heart size and right ventricular dysfunction measured by echocardiography and higher pulmonary vascular resistance by invasive hemodynamic assessment predict mortality in patients with IPF evaluated for lung transplantation.

Selection of Candidates for Lung Transplantation

The selection of candidates for lung transplantation requires an appreciation of the natural history of lung disease to determine when the disease has entered an advanced and imminently life-threatening stage. It also requires an understanding of the impact of preexisting medical comorbidities on transplant outcomes. Finally, selection is influenced by the particular metric by which outcomes are judged to be successful (e.g., maximizing short-term net survival benefit versus maximizing post-transplant longevity). This article will discuss general and disease-specific criteria used to select patients for lung transplantation and determine the appropriate timing of listing. It will highlight current guidelines put forth by the International Society of Heart and Lung Transplantation and will explore the published data upon which these guidelines are based.

Computational analysis of thoracic multidetector row HRCT for segmentation and quantification of small airway air trapping and emphysema in obstructive pulmonary disease.

RATIONALE AND OBJECTIVES Obstructive pulmonary disease phenotypes are related to variable combinations of emphysema and small-airway disease, the latter manifested as air trapping (AT) on imaging. The investigators propose a method to extract AT information quantitatively from thoracic multi-detector row high-resolution computed tomography (HRCT), validated by pulmonary function testing (PFT) correlation. MATERIALS AND METHODS Seventeen patients with obstructive pulmonary disease who underwent HRCT and PFT within a 3-day interval were retrospectively identified. Thin-section volumetric HRCT in inspiration and expiration was registered and analyzed using custom-made software. Nonaerated regions of lung were segmented through exclusion of voxels > -50 Hounsfield units (HU); emphysematous areas were segmented as voxels < -950 HU on inspiratory images. Small-airway AT volume (ATV) was segmented as regions of lung voxels whose attenuation values increased by less than a specified change threshold (set from 5 to 300 HU in 25-HU increments) between inspiration and expiration. Inspiratory and expiratory total segmented lung volumes, emphysema volume (EV), and ATV for each threshold were subsequently calculated and correlated with PFT parameters. RESULTS A strong positive correlation was obtained between total segmented lung volume in inspiration and total lung capacity (r = 0.83). A strong negative correlation (r = -0.80) was obtained between EV and the ratio between forced expiratory volume in 1 second and forced vital capacity. Stronger negative correlation with forced expiratory volume in 1 second/forced vital capacity (r = -0.85) was demonstrated when ATV (threshold, 50 HU) was added to EV, indicating improved quantification of total AT to predict obstructive disease severity. A moderately strong positive correlation between ATV and residual volume was observed, with a maximum r value of 0.72 (threshold, 25 HU), greater than that between EV and residual volume (r = 0.58). The benefit of ATV quantification was greater in a subgroup of patients with negligible emphysema compared to patients with moderate to severe emphysema. CONCLUSIONS Small-airway AT segmentation in conjunction with emphysema segmentation through computer-assisted methodologies may provide better correlations with key PFT parameters, suggesting that the quantification of emphysema-related and small airway-related components of AT from thoracic HRCT has great potential to elucidate phenotypic differences in patients with chronic obstructive pulmonary disease.

Pulmonary Involvement in Sjögren Syndrome

Sjögren syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic inflammation of exocrine glands and a variety of extraglandular sites. Lung involvement as defined by symptoms and either pulmonary function testing or radiographic abnormalities occurs in approximately 10 to 20% of patients. Subclinical lung disease is even more frequent and often includes evidence of small airways disease and airway inflammation. In general, patients will have evidence of both airway and interstitial lung disease by radiographs and pathology. Bronchiolitis and bronchiectasis are the most common airway manifestations while the interstitial pathologies associated with SS include nonspecific interstitial pneumonitis, usual interstitial pneumonitis, and lymphocytic interstitial pneumonitis. Patients with SS are also at an increased risk of lymphoma. A protean of other lung abnormalities including amyloidosis, granulomatous lung disease, pseudolymphoma, pulmonary hypertension, and pleural disease have been described.

Exposure to Ambient Particulate Matter Is Associated With Accelerated Functional Decline in Idiopathic Pulmonary Fibrosis

Background Idiopathic pulmonary fibrosis (IPF), a progressive disease with an unknown pathogenesis, may be due in part to an abnormal response to injurious stimuli by alveolar epithelial cells. Air pollution and particulate inhalation of matter evoke a wide variety of pulmonary and systemic inflammatory diseases. We therefore hypothesized that increased average ambient particulate matter (PM) concentrations would be associated with an accelerated rate of decline in FVC in IPF. Methods We identified a cohort of subjects seen at a single university referral center from 2007 to 2013. Average concentrations of particulate matter < 10 and < 2.5 &mgr;g/m3 (PM10 and PM2.5, respectively) were assigned to each patient based on geocoded residential addresses. A linear multivariable mixed‐effects model determined the association between the rate of decline in FVC and average PM concentration, controlling for baseline FVC at first measurement and other covariates. Results One hundred thirty‐five subjects were included in the final analysis after exclusion of subjects missing repeated spirometry measurements and those for whom exposure data were not available. There was a significant association between PM10 levels and the rate of decline in FVC during the study period, with each &mgr;g/m3 increase in PM10 corresponding with an additional 46 cc/y decline in FVC (P = .008). Conclusions Ambient air pollution, as measured by average PM10 concentration, is associated with an increase in the rate of decline of FVC in IPF, suggesting a potential mechanistic role for air pollution in the progression of disease.

Interstitial Lung Disease in the Elderly

Background Despite the relationship between idiopathic pulmonary fibrosis (IPF) and advancing age, little is known about the epidemiology of interstitial lung disease (ILD) in the elderly. We describe the diagnoses, clinical characteristics, and outcomes of patients who were elderly at the time of ILD diagnosis. Methods Among subjects from a prospective cohort study of ILD, elderly was defined as age ≥ 70 years. Diagnoses were derived from a multidisciplinary review. Differences between elderly and nonelderly groups were determined using the χ2 test and analysis of variance. Results Of the 327 subjects enrolled, 80 (24%) were elderly. The majority of elderly subjects were white men. The most common diagnoses were unclassifiable ILD (45%), IPF (34%), connective tissue disease (CTD)‐ILD (11%), and hypersensitivity pneumonitis (8%). Most elderly subjects (74%) with unclassifiable ILD had an imaging pattern inconsistent with usual interstitial pneumonia (UIP). There were no significant differences in pulmonary function or 3‐year mortality between nonelderly and elderly subjects combined or in a subgroup analysis of those with IPF. Conclusions Although IPF was the single most common diagnosis, the majority of elderly subjects had non‐IPF ILD. Our findings highlight the need for every patient with new‐onset ILD, regardless of age, to be surveyed for exposures and findings of CTD. Unclassifiable ILD was common among the elderly, but for most, the radiographic pattern was inconsistent with UIP. Although the effect of ILD may be more pronounced in the elderly due to reduced global functionality, ILD was not more severe or aggressive in this group.

A Comparative Study of HRCT Image Metrics and PFT Values for Characterization of ILD and COPD

RATIONALE AND OBJECTIVES The aim of this study was to compare the performance of various image-based metrics computed from thoracic high-resolution computed tomography (HRCT) with data from pulmonary function testing (PFT) in characterizing interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS Fourteen patients with ILD and 11 with COPD had undergone both PFT and HRCT within 3 days. For each patient, 93 image-based metrics were computed, and their relationships with the 21 clinically used PFT parameters were analyzed using a minimal-redundancy-maximal-relevance statistical framework. The first 20 features were selected among the total of 114 mixed image metrics and PFT values in the characterization of ILD and COPD. RESULTS Among the best-performing 20 features, 14 were image metrics, derived from attenuation histograms and texture descriptions. The highest relevance value computed from PFT parameters was 0.47, and the highest from image metrics was 0.52, given the theoretical bound as [0, 0.69]. The ILD or COPD classifier using the first four features achieved a 1.92% error rate. CONCLUSIONS Some image metrics are not only as good discriminators as PFT for the characterization of ILD and COPD but are also not redundant when PFT values are provided. Image metrics of attenuation histogram statistics and texture descriptions may be valuable for further investigation in computer-assisted diagnosis.

Factors associated with the use of corticosteroids in the initial management of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) has not been shown to respond to corticosteroid therapy; however, many patients receive these drugs at the time of diagnosis. The factors that are associated with the decision to prescribe corticosteroids have not been examined.

Effect of treatment guidelines on the initial management of idiopathic pulmonary fibrosis

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disease with no known aetiology and no proven treatment. Despite the absence of efficacy data, many physicians treat IPF with corticosteroids either as monotherapy or in combination with a cytotoxic agent. Specialty society guidelines published in 1999 and 2000 recognize that treatment may not be appropriate for all patients with IPF, but recommend that if treatment is to be initiated, a combination of corticosteroids with a cytotoxic agent is preferred over corticosteroids alone. It is not known how the use of corticosteroids and cytotoxic agents in the treatment of IPF has changed over time and whether published guidelines have altered prescribing practices. WHAT THIS STUDY ADDS The results of this study demonstrate a modest but statistically significant reduction in the overall use of corticosteroids since the publication of treatment guidelines. At the same time, there was a more pronounced increase in the combined use of corticosteroids and cytotoxic agents consistent with recommendations. Even with the increase in the use of combination therapy, corticosteroid monotherapy remained the most commonly prescribed regimen among treated patients. Given the lack of established benefit and the risks associated with corticosteroid therapy, the reasons for the continued use of corticosteroid monotherapy in the majority of treated patients warrant further investigation. AIMS To assess the impact of specialty society guidelines on the use of corticosteroids and cytotoxic agents in the initial management of patients with idiopathic pulmonary fibrosis. METHODS A retrospective cohort study of 941 patients with an incident diagnosis of IPF was conducted using a large medical records database. The primary outcome was a new prescription for corticosteroids with or without a cytotoxic agent within 30 days of diagnosis. The primary exposure was whether diagnosis occurred before or after the publication of treatment guidelines. Logistic regression was used to control for changes in population demographics and disease characteristics across time. RESULTS In total, 187 patients (19.9%) received a new corticosteroid prescription within 30 days of diagnosis. Fewer patients received corticosteroids after the publication of guidelines (22.2% vs. 17.7%; adjusted OR for steroid use after the publication of guidelines 0.65, 95% confidence interval 0.46, 0.92, P = 0.014). Among the 187 patients treated with corticosteroids, 22 (11.8%) also received a cytotoxic agent. The use of cytotoxic agents among users of corticosteroids increased significantly after the publication of guidelines (5.1% vs. 19.3%) with a fully adjusted OR = 4.71 (95% CI 1.56, 14.21, P = 0.006). CONCLUSIONS Since the publication of treatment guidelines, there has been a small reduction in the overall use of corticosteroids. Consistent with these guidelines, the use of cytotoxic agents among those prescribed corticosteroids has increased significantly; however, the use of these agents remains uncommon.

Computational analysis of HRCT images for characterization and differentiation of ILD and COPD

Several image metrics have been proposed for pulmonary assessment via thoracic high-resolution computed tomography (HRCT) for various pathologies. This paper describes a systematic analysis of several such metrics for differentiating between interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD). HRCT inspiratory and expiratory images for 14 patients with ILD and 11 patients with COPD were acquired retrospectively. Data from pulmonary function testings (PFT) were also acquired retrospectively for each patient. Using a discriminative subset of image metrics, our study shows that computational analysis of thoracic HRCT images permits differentiation between ILD and COPD groups.