Background The treatment of chronic hypersensitivity pneumonitis (cHP) often includes systemic oral corticosteroids, but the optimal pharmacologic management remains unclear. The morbidity associated ...with prednisone has motivated the search for alternative therapies. We aimed to determine the effect of treatment with mycophenolate mofetil (MMF) or azathioprine (AZA) on lung function in patients with cHP. Methods Patients with cHP treated with either MMF or AZA were retrospectively identified from four interstitial lung disease centers. Change in lung function before and after treatment initiation was analyzed using linear mixed-effects modeling (LMM), adjusting for age, sex, smoking history, and prednisone use. Results Seventy patients were included: 51 were treated with MMF and 19 with AZA. Median follow-up after treatment initiation was 11 months. Prior to treatment initiation, FVC and diffusion capacity of the lung for carbon monoxide (D lco ) % predicted were declining at a mean rate of 0.12% ( P < .001) and 0.10% ( P < .001) per month, respectively. Treatment with either MMF or AZA was not associated with improved FVC (0.5% at 1 year; P = .46) but was associated with a statistically significant improvement in D lco of 4.2% ( P < .001) after 1 year of treatment. Results were similar in the subgroup of patients treated with MMF for 1 year; the FVC increased nonsignificantly by 1.3% ( P = .103) and D lco increased by 3.9% ( P < .001). Conclusions Treatment with MMF or AZA is associated with improvements in D lco in patients with cHP. Prospective randomized trials are needed to validate their effectiveness for cHP.
Background It is unknown if the radiographic fibrosis score predicts mortality in persistent hypersensitivity pneumonitis (HP) and if survival is similar to that observed in idiopathic pulmonary ...fibrosis (IPF) when adjusting for the extent of radiographic fibrosis. Methods We reviewed records from 177 patients with HP and 224 patients with IPF whose diagnoses were established by multidisciplinary consensus. Two thoracic radiologists scored high-resolution CT (HRCT) scan lung images. Independent predictors of transplant-free survival were determined using a Cox proportional hazards analysis. Kaplan-Meier survival curves were constructed, stratified by disease as well as fibrosis score. Results HRCT scan fibrosis score and radiographic reticulation independently predicted time to death or lung transplantation. Clinical predictors included a history of cigarette smoking, auscultatory crackles on lung examination, baseline FVC, and FEV1 /FVC ratio. The majority of HP deaths occurred in patients with both radiographic reticulation and auscultatory crackles on examination, compared with patients with only one of these manifestations ( P < .0001). Patients with IPF had worse survival than those with HP at any given degree of radiographic fibrosis (hazard ratio 2.31; P < .01). Conclusions Survival in patients with HP was superior to that of those with IPF with similar degrees of radiographic fibrosis. The combination of auscultatory crackles and radiographic reticulation identified patients with HP who had a particularly poor outcome.
BACKGROUND Mortality risk prediction tools have been developed in idiopathic pulmonary fibrosis, however, it is unknown whether these models accurately estimate mortality in systemic ...sclerosis-associated interstitial lung disease (SSc-ILD). Methods: Four baseline risk prediction models—the Composite Physiologic Index, the Interstitial Lung Disease-Gender, Age, Physiology Index, the du Bois index, and the modified du Bois index—were calculated for patients recruited from a specialized SSc-ILD clinic. Each baseline model was assessed using logistic regression analysis with 1-year mortality as the outcome variable. Discrimination was quantified using the area under the receiver operating characteristic curve. Calibration was assessed using the goodness-of-fit test. The incremental prognostic ability of additional predictor variables was determined by adding prespecified variables to each baseline model. Results: The 156 patients with SSc-ILD completed 1,294 pulmonary function tests, 725 6-min walk tests, and 637 echocardiograms. Median survival was 15.0 years from the time of SSc-ILD diagnosis. All baseline models were significant predictors of 1-year mortality in SSc-ILD. The modified du Bois index had an area under the receiver operating characteristic curve of 0.84, compared with 0.77 to 0.81 in the other models. Calibration was acceptable for the modified du Bois index, but was poor for the other models. All baseline models include FVC and 6-min walk distance was identified as an additional independent predictor of 1-year mortality. Conclusions The modified du Bois index has good discrimination and calibration for the prediction of 1-year mortality in SSc-ILD. FVC and 6-min walk distance are important independent predictors of 1-year mortality in SSc-ILD. CHEST 2015; 148(5):1268-1275
Background Combined pulmonary fibrosis and emphysema (CPFE) is increasingly recognized, but its prevalence and prognosis remain unclear. We sought to determine the prevalence, clinical features, and ...prognosis of CPFE in idiopathic pulmonary fibrosis (IPF), using a standardized and reproducible definition. Methods Patients with IPF were identified from two ongoing cohorts. Two radiologists scored emphysema and fibrosis severity on high-resolution CT (HRCT) scans. CPFE was defined as ≥ 10% emphysema on HRCT scan. Clinical characteristics and outcomes of patients with CPFE and IPF and those with non-CPFE IPF were compared with unadjusted analysis and then analysis after adjustment for HRCT fibrosis score. Mortality was compared using competing risks regression to handle lung transplantation. Sensitivity analyses were performed using Cox proportional hazards, including time to death (transplantation censored) and time to death or transplant. Results CPFE criteria were met in 29 of 365 patients with IPF (8%), with high agreement between radiologists (κ = 0.74). Patients with CPFE had less fibrosis on HRCT scans and higher FVC, but greater oxygen requirements ( P ≤ .01 for all comparisons). Findings were maintained with adjustment for fibrosis severity. Inhaled therapies for COPD were used by 53% of patients with CPFE. There was no significant difference in mortality comparing patients with CPFE and IPF to those with non-CPFE IPF (hazard ratio, 1.14; 95% CI, 0.61-2.13; P = .69). Conclusions CPFE was identified in 8% of patients with IPF and is a distinct, clinical phenotype with potential therapies that remain underutilized. Patients with CPFE and IPF and those with non-CPFE IPF have similar mortality.
Abstract Background Context Frailty is defined as a state of decreased reserve and susceptibility to stressors. The relationship between frailty and postoperative outcomes after degenerative spine ...surgery has not been studied. Purpose This study aimed to (1) determine prevalence of frailty in the degenerative spine population; (2) describe patient characteristics associated with frailty; and (3) determine the association between frailty and postoperative complications, mortality, length of stay, and discharge disposition. Study Design This is a retrospective analysis on a prospectively collected cohort from the National Surgical Quality Improvement Program (NSQIP). Patient Sample A total of 53,080 patients who underwent degenerative spine surgery between 2006 and 2012 were included in the study. Outcome Measures A modified frailty index (mFI) with 11 variables derived from the NSQIP dataset was used to determine prevalence of frailty and its correlation with a composite outcome of perioperative complications as well as hospital length of stay, mortality, and discharge disposition. Methods After calculating the mFI for each patient, the prevalence and predictors of frailty were determined for our cohort. The association of frailty with postoperative outcomes was determined after adjusting for known and suspected confounders using multivariate logistic regression. Results Frailty was present in 2,041 patients within the total population (4%) and in 8% of patients older than 65 years. Frailty severity increased with increasing age, male sex, African American race, higher body mass index, recent weight loss, paraplegia or quadriplegia, American Society of Anesthesiologists (ASA) score, and preadmission residence in a care facility. Frailty severity was an independent predictor of major complication (OR 1.15 for every 0.10 increase in mFI, 95%CI 1.09–1.21, p<.0005) and specifically predicted reoperation for postsurgical infection (OR 1.3, 95%CI 1.16–1.46, p<.0005). Prolonged length of stay and discharge to a new facility were also independently predicted by frailty severity (p<.0005). Frailty severity predicted 30-day mortality on unadjusted (OR 2.05, 95%CI 1.70–2.48, p<.0005) and adjusted analyses (OR 1.48, 95%CI 1.18–1.86, p<.0005). Conclusions Frailty is an important predictor of postoperative outcomes following degenerative spine surgery. Preoperative recognition of frailty may be useful for perioperative optimization, risk stratification, and patient counseling.
Background Risk prediction is challenging in chronic interstitial lung disease (ILD) because of heterogeneity in disease-specific and patient-specific variables. Our objective was to determine ...whether mortality is accurately predicted in patients with chronic ILD using the GAP model, a clinical prediction model based on sex, age, and lung physiology, that was previously validated in patients with idiopathic pulmonary fibrosis. Methods Patients with idiopathic pulmonary fibrosis (n = 307), chronic hypersensitivity pneumonitis (n = 206), connective tissue disease-associated ILD (n = 281), idiopathic nonspecific interstitial pneumonia (n = 45), or unclassifiable ILD (n = 173) were selected from an ongoing database (N = 1,012). Performance of the previously validated GAP model was compared with novel prediction models in each ILD subtype and the combined cohort. Patients with follow-up pulmonary function data were used for longitudinal model validation. Results The GAP model had good performance in all ILD subtypes (c-index, 74.6 in the combined cohort), which was maintained at all stages of disease severity and during follow-up evaluation. The GAP model had similar performance compared with alternative prediction models. A modified ILD-GAP Index was developed for application across all ILD subtypes to provide disease-specific survival estimates using a single risk prediction model. This was done by adding a disease subtype variable that accounted for better adjusted survival in connective tissue disease-associated ILD, chronic hypersensitivity pneumonitis, and idiopathic nonspecific interstitial pneumonia. Conclusion The GAP model accurately predicts risk of death in chronic ILD. The ILD-GAP model accurately predicts mortality in major chronic ILD subtypes and at all stages of disease.
BACKGROUND Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in patients with systemic sclerosis (SSc); however, prognostication of SSc-associated ILD (SSc-ILD) remains ...challenging. We conducted a systematic review to identify variables that predict mortality and ILD progression in SSc-ILD. METHODS Three databases were searched to identify all studies relating to predictors of mortality or ILD progression in SSc-ILD. Studies were eligible if they were published in English and included ≥ 10 adults with SSc-ILD. Two authors independently reviewed and extracted data from acceptable studies. RESULTS The initial search identified 3,145 unique citations. Twenty-seven studies, including six abstracts, met the inclusion criteria. A total of 1,616 patients with SSc-ILD were included. Patient-specific, ILD-specific, and SSc-specific variables predicted mortality and progression; however, most predictors were identified in only one study. Most studies did not fully account for potential confounders, and none of the studies included a validation cohort. Older age, lower FVC, and lower diffusing capacity of carbon monoxide predicted mortality in more than one study. Male sex, extent of disease on high-resolution CT (HRCT) scan, presence of honeycombing, elevated KL-6 values, and increased alveolar epithelial permeability were identified as predictors of both mortality and ILD progression on unadjusted analysis. The extent of disease on HRCT scan was the only variable that independently predicted both mortality and ILD progression. CONCLUSIONS Mortality and ILD progression were predicted by several patient-specific, ILD-specific, and SSc-specific factors. Additional prospective studies are required to validate these preliminary findings and to identify combinations of variables that accurately predict the prognosis of SSc-ILD.
Abstract Context Little is known about the treatment and correlates of dyspnea in idiopathic pulmonary fibrosis (IPF). Objectives The objective of this systematic review was to summarize the ...literature regarding the treatment and correlates of dyspnea in IPF. Methods MEDLINE, EMBASE, and all Evidence-Based Medicine Reviews were searched for publications that evaluated treatment or correlates of dyspnea in IPF. Reference lists and recent review articles also were searched. Results The heterogeneity of included studies did not permit meta-analysis. Dyspnea improved in studies of sildenafil, pulmonary rehabilitation, and prednisone with colchicine. Additional studies of these three treatments, however, found discordant results. One study suggested that assisted ventilation delivered by facemask improved exertional dyspnea. Oxygen and opioids improve dyspnea in other chronic lung diseases, but data in IPF are limited. Correlates of dyspnea included functional and physiological measures and comorbid diseases. Conclusion Sildenafil and pulmonary rehabilitation should be considered as potential therapies for dyspnea in selected patients with IPF. Supplemental oxygen and opioids may be additional potential therapies; however, the evidence supporting their use is weak. Additional research should focus on the management of functional status and comorbidities as potential treatments for dyspnea.
Background Little is understood about the characteristics of dyspnea in patients with interstitial lung disease (ILD), and its severity is likely influenced by multiple factors. Depression and ...functional status are known to influence dyspnea in patients with COPD. The aim of this study was to determine the relationship of dyspnea with clinical parameters, including depression and functional status, in patients with ILD. Methods Dyspnea was measured with the Baseline Dyspnea Index and the University of California San Diego Shortness of Breath Questionnaire. Clinical parameters were recorded. Regression analysis was performed to determine independent correlates of dyspnea. Results Fifty-two subjects were enrolled. The two dyspnea scales were strongly correlated ( r = −0.79; P < .00005). The mean levels of dyspnea were 6.5 and 41.0, representing a moderate degree of dyspnea. Clinically meaningful depressive symptoms were found in 23% of subjects. Independent correlates of dyspnea severity for each dyspnea scale were depression score ( P = .002 and P < .0005), 4-m walk time ( P = .001 and P = .06), FVC ( P = .07 and P = .004), and diffusing capacity of the lung for carbon monoxide ( P = .007). BMI had borderline significant association with the Baseline Dyspnea Index ( P = .10). Conclusions In patients with ILD, dyspnea is associated with depression score, functional status, and pulmonary function. These results suggest that attention to depression and functional status is important in these patients and that treatment directed at these comorbidities may improve dyspnea and quality of life. Trial registry ClinicalTrials.gov ; No.: NCT00611182 ; URL: www.clinicaltrials.gov
Connective tissue diseases (CTDs) can affect the lungs through diseases of the chest wall, pleura, vasculature, airways, and parenchyma. Interstitial lung disease (ILD) is a common complication of ...CTD associated with increased morbidity and mortality. This article describes the evaluation of respiratory impairment in patients with CTD and summarizes the evidence that guides diagnosis and management of CTD-ILD. Patients with CTD with suspected ILD should undergo clinical, physiologic, and radiologic studies to evaluate for the presence of ILD, and these results should be integrated in a multidisciplinary setting to guide diagnosis and management. Screening for ILD may also be appropriate in asymptomatic patients with high-risk features.
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