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Background Management of patients with interstitial lung disease (ILD) requires subspecialized, comprehensive, multidisciplinary care. The Pulmonary Fibrosis Foundation established the Care Center Network (CCN) in 2013 with identified criteria to become a designated CCN site. Despite these criteria, the essential components of an ILD clinic remain unknown. Research Questions How are ILD clinics within the CCN structured? What are the essential components of an ILD clinic according to ILD physician experts, patients, and caregivers? Study Design and Methods This study had three components. First, all 68 CCN sites were surveyed to determine the characteristics of their current ILD clinics. Second, an online, three-round modified Delphi survey was conducted between October and December 2019 with 48 ILD experts participating in total. Items for round 1 were generated using expert interviews. During rounds 1 and 2, experts rated the importance of each item on a 5-point Likert scale. The a priori threshold for consensus was more than 75% of experts rating an item as important or very important. In round 3, experts graded items that met consensus and ranked items deemed essential for an ILD clinic. Third, ILD patient and caregiver focus groups were conducted and analyzed for content to determine their perspectives of an ideal ILD clinic. Results Forty items across four categories (members, infrastructure, resources, and multidisciplinary conference) achieved consensus as essential to an ILD clinic. Patient and caregiver focus groups identified three major themes: comprehensive, patient-centered medical care; expanded access to care; and comprehensive support for living and coping with ILD. Interpretation The essential components of an ILD clinic are well-aligned between physician experts and patients. Future research can use these findings to evaluate the impact of these components on patient outcomes and to inform best practices for ILD clinics throughout the world.

Hypersensitivity pneumonitis (HP) is an immunologically mediated form of lung disease resulting from inhalational exposure to any of a large variety of antigens. A subgroup of patients with HP develops pulmonary fibrosis (fibrotic HP; FHP), a significant cause of morbidity and mortality. This study will evaluate the safety and efficacy of the antifibrotic pirfenidone in treating FHP. This single-centre, randomised, double-blind, placebo-controlled trial is enrolling adults with FHP (ClinicalTrials.gov: NCT02958917). Study participants must have fibrotic abnormalities involving ≥5% of the lung parenchyma on high-resolution computed tomography scan, forced vital capacity (FVC) ≥40% and diffusing capacity of the lung for carbon monoxide ≥30% of predicted values. Study participants will be randomised in a 2:1 ratio to receive pirfenidone 2403 mg·day−1 or placebo. The primary efficacy end-point is the mean change in FVC % predicted from baseline to week 52. A number of secondary end-points have been chosen to evaluate the safety and efficacy in different domains., The design of a phase II study of 52 weeks of pirfenidone or placebo on top of standard of care in patients with fibrotic HP (ClinicalTrials.gov NCT02958917) https://bit.ly/32CfeSF

The American Thoracic Society Core Curriculum updates clinicians annually in adult and pediatric pulmonary disease, medical critical care, and sleep medicine in a 3- to 4-year recurring cycle of topics. The topics of the 2020 Pulmonary Core Curriculum include pulmonary vascular disease (submassive pulmonary embolism, chronic thromboembolic pulmonary hypertension, and pulmonary hypertension) and pulmonary infections (community-acquired pneumonia, pulmonary nontuberculous mycobacteria, opportunistic infections in immunocompromised hosts, and coronavirus disease [COVID-19]).

Background: Whether graduating pulmonary and critical care medicine (PCCM) fellows feel adequately trained in interstitial lung disease (ILD) remains unknown. In addition, there are no published data describing the current approach to educating trainees about ILD. Objective: To characterize the present state of ILD training during fellowship and to determine graduating PCCM fellows’ perceived abilities to diagnose and manage ILD. Methods: We surveyed PCCM fellowship program directors nationwide and compared their perceptions of graduating fellows’ abilities to diagnose, provide initial management to, and offer longitudinal care to patients with ILD using a series of unpaired t tests. We also inquired about existing practices for educating fellows about ILD. We then surveyed graduating PCCM fellows from 19 different preselected programs to assess comfort level with ILD in comparison with other core clinical domains. Results: Program director respondents (n = 74, 40% response rate) rated graduating fellows’ abilities to establish specific ILD diagnoses and to provide initial management similarly (4.3 ± 0.8 on five-point Likert scale), whereas the ability to provide longitudinal expert care was rated significantly lower (3.8 ± 0.9, P = 0.001). Most respondents (n = 52, 70.3%) reported having dedicated outpatient ILD specialists with whom fellows could rotate, but only half required this rotation. In addition, very few (n = 17, 23.0%) reported that a majority of patients with suspected or newly diagnosed ILD were scheduled in fellow clinics, many of whom received subsequent longitudinal care from dedicated ILD specialists. Among 71 third-year fellow respondents, confidence in managing ILD was rated poorly (3.2 ± 1.0 on a five-point Likert scale) in contrast to more common diseases like chronic obstructive pulmonary disease (4.4 ± 0.7, P

Rheumatoid arthritis is an autoimmune disease that classically presents as a symmetrical inflammatory polyarthritis. Extra-articular manifestations are prevalent, with the lungs being the most common site [1], and interstitial lung disease (ILD) being the most severe form of pulmonary involvement. In some studies, the median survival of patients with rheumatoid arthritis and a usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography (HRCT) is around 3 years (similar to that in idiopathic pulmonary fibrosis (IPF) [2, 3]); however, in other studies, median survival is >7 years [4, 5]. When present, ILD accounts for 10–20% of all deaths in rheumatoid arthritis [6]., Age of ILD onset is similar in patients with RA-UIP and RA-NSIP but duration of RA before ILD onset differs https://bit.ly/3lgjfDJ

Massive hemoptysis is a high-risk, low-frequency clinical scenario, and teaching the management of this emergency should extend beyond reliance on clinical exposure. Massive hemoptysis requires emergent intervention to avoid asphyxiation and death. Practitioners need both cognitive and procedural skills to intervene in a high-stress situation. Cognitive aids have demonstrated benefits in other emergency settings, but no such tool exists for massive hemoptysis. Using expert recommendations, we developed the ABCDE Approach for Massive Hemoptysis, a cognitively accessible, prioritized toolbox of interventions designed to assist learners in organizing an approach to these high-risk and time-sensitive patient cases. Herein we present the elements and use of the ABCDE approach. Providing a cognitive approach to massive hemoptysis is an important first step in improving education for this potentially fatal clinical scenario.

BackgroundMatrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) play important roles in the turnover of extracellular matrix and in the pathogenesis of idiopathic pulmonary fibrosis (IPF). This study aimed to determine the utility of circulating MMPs and TIMPs in distinguishing patients with IPF from controls and to explore associations between MMPs/TIMPs and measures of disease severity in patients with IPF.MethodsThe IPF cohort (n = 300) came from the IPF-PRO Registry, an observational multicenter registry of patients with IPF that was diagnosed or confirmed at the enrolling center in the past 6 months. Controls (n = 100) without known lung disease came from a population-based registry. Generalized linear models were used to compare circulating concentrations of MMPs 1, 2, 3, 7, 8, 9, 12, and 13 and TIMPs 1, 2, and 4 between patients with IPF and controls, and to investigate associations between circulating levels of these proteins and measures of IPF severity. Multivariable models were fit to identify the MMP/TIMPs that best distinguished patients with IPF from controls.ResultsAll the MMP/TIMPs analyzed were present at significantly higher levels in patients with IPF compared with controls except for TIMP2. Multivariable analyses selected MMP8, MMP9 and TIMP1 as top candidates for distinguishing patients with IPF from controls. Higher concentrations of MMP7, MMP12, MMP13 and TIMP4 were significantly associated with lower diffusion capacity of the lung for carbon monoxide (DLCO) % predicted and higher composite physiologic index (worse disease). MMP9 was associated with the composite physiologic index. No MMP/TIMPs were associated with forced vital capacity % predicted.ConclusionsCirculating MMPs and TIMPs were broadly elevated among patients with IPF. Select MMP/TIMPs strongly associated with measures of disease severity. Our results identify potential MMP/TIMP targets for further development as disease-related biomarkers.

Rationale: Progression of idiopathic pulmonary fibrosis (IPF) is accompanied by worsening of symptoms, exercise capacity, and health-related quality of life. However, the utility of patient-reported outcomes as predictors of mortality remains uncertain. Objectives: To assess whether patient-reported outcomes are independently associated with mortality beyond clinical risk factors in patients with IPF. Methods: Data from the observational IPF Prospective Outcomes Registry were used to examine associations between patient-reported outcomes at enrollment and the composite outcome of death or lung transplant in the following year. Associations were examined using univariable models and models adjusted for age and clinical variables that have been associated with death or lung transplant in patients with IPF in this cohort (oxygen use, forced vital capacity % predicted, and diffusing capacity of the lungs for carbon monoxide % predicted at enrollment). Results: Among 662 patients, 45 died and 12 underwent lung transplant over 1 year. In the model adjusted for age and clinical variables that were associated with death or lung transplant, worse scores on the St. George’s Respiratory Questionnaire (SGRQ) total score (hazard ratio [HR], 1.22 [95% confidence interval (CI), 1.01–1.48] per 10-point increase), SGRQ activity score (HR, 1.25 [95% CI, 1.02–1.54] per 10-point increase) and SGRQ symptoms score (HR, 1.17 [95% CI, 1.01–1.36] per 10-point increase) were associated with death or lung transplant over 1 year. Conclusions: Patient-reported outcomes that assess symptoms and physical activity are independently associated with mortality in patients with IPF.

Purpose Interstitial lung disease is a common extra-articular manifestation of rheumatoid arthritis (RA-ILD) and is associated with significant morbidity and mortality. However, limited data exist regarding predictors of mortality. We sought to examine the prognostic value of the high-resolution computed tomography (HRCT) patterns in patients with RA-ILD. Materials and methods RA-ILD patients with HRCT patterns of usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP) were identified among a longitudinal cohort of individuals evaluated at National Jewish Health. A total of 158 subjects were included in the study. For each subject, the earliest available HRCT was reviewed independently by two expert thoracic radiologists blinded to clinical data. HRCT patterns were classified as demonstrating definite UIP, possible UIP, or NSIP. Kaplan-Meier curves were generated and survival was compared among the three patterns using a log rank test for trend. Results One hundred subjects (63%) had HRCT findings classified as definite UIP, 23 (15%) as possible UIP and 35 (22%) as NSIP. No difference in survival was seen between subjects with definite UIP versus those with possible UIP. The combined group of subjects with either definite- or possible UIP had significantly worse survival than those with NSIP (log-rank p = 0.03). Conclusions In patients with RA-ILD, patients with either definite UIP or possible UIP have equally poor survival when compared to those with an NSIP pattern.

BACKGROUND The usual interstitial pneumonia (UIP) pattern of lung injury may occur in the setting of connective tissue disease (CTD), but it is most commonly found in the absence of a known cause, in the clinical context of idiopathic pulmonary fibrosis (IPF). Our objective was to observe and compare longitudinal changes in pulmonary function and survival between patients with biopsy-proven UIP found in the clinical context of either CTD or IPF. METHODS We used longitudinal data analytic models to compare groups (IPF [n = 321] and CTD-UIP [n = 56]) on % predicted FVC (FVC %) or % predicted diffusing capacity of the lung for carbon monoxide (Dlco%), and we used both unadjusted and multivariable techniques to compare survival between these groups. RESULTS There were no significant differences between groups in longitudinal changes in FVC % or Dlco% up to diagnosis, or from diagnosis to 10 years beyond (over which time, the mean decrease in FVC % per year [95% CI] was 4.1 [3.4, 4.9] for IPF and 3.5 [1.8, 5.1] for CTD-UIP, P = .49 for difference; and the mean decrease in Dlco% per year was 4.7 [4.0, 5.3] for IPF and 4.3 [3.0, 5.6] for CTD-UIP, P = .60 for difference). Despite the lack of differences in pulmonary function, subjects with IPF had worse survival in unadjusted (log-rank P = .003) and certain multivariable analyses. CONCLUSIONS Despite no significant differences in changes in pulmonary function over time, patients with CTD-UIP (at least those with certain classifiable CTDs) live longer than patients with IPF—an observation that we suspect is due to an increased rate of mortal acute exacerbations in patients with IPF.

Radiologists have a critical role in the evaluation and diagnosis of suspected idiopathic pulmonary fibrosis (IPF). Accurate pattern identification on imaging is key in the multidisciplinary diagnostic process and frequently obviates the need for a surgical lung biopsy. In this review, we describe the clinical and imaging features of IPF in the context of recently revised international guidelines; contrast findings in other diseases that may inform differential diagnosis of fibrotic lung disease; and highlight common complications associated with pulmonary fibrosis.

Summary Background Fibrosis or inflammation of the bronchioles is a well-known manifestation of connective tissue disease (CTD). However, the natural history of CTD-related bronchiolitis is largely unknown. Methods We analyzed consecutive patients evaluated at National Jewish Health (Denver, CO) from 1998 to 2008 with CTD and surgical lung biopsy-confirmed bronchiolitis. Linear mixed effects models were used to estimate the longitudinal postbronchodilator FEV 1 %predicted (%pred) course and differences between subjects with or without constrictive bronchiolitis (CB). Results Of 28 subjects with a mean age of 53 ± 9 years, fourteen (50%) had CB. The most common CTD diagnosis was rheumatoid arthritis ( n = 14; 50%). There were no significant differences in demographics, smoking status, underlying CTD diagnoses, 6-min walk distance, dyspnea score or drug therapy between subjects with CB and those with cellular bronchiolitis. Three subjects with CB (11%) and four with cellular bronchiolitis (14%) died. Compared with subjects with CB, those with cellular bronchiolitis had higher mean FEV 1 %pred at all times. There were no significant differences in FEV 1 %pred slope within- or between-groups (CB vs. cellular bronchiolitis) preceding surgical lung biopsy or afterward. Conclusion Subjects with CTD-related CB had lower FEV 1 %pred values than those with CTD-related cellular bronchiolitis at all time points, but FEV 1 %pred remained stable over time in both groups regardless of therapy received.

Introduction: Pulmonary hypertension (PH) is a potentially severe complication of interstitial lung disease (ILD) that results from multiple mechanisms, including hypoxic pulmonary vasoconstriction. Because hyperoxia may have vasodilatory effects, we tested whether acute hyperoxia improved hemodynamics and pulmonary vascular stiffness in an ILD-PH cohort. Methods: Patients with ILD and suspected PH underwent right heart catheterization (RHC). Patients with low peripheral oxygen saturation (SpO 2 ) were administered supplemental O 2 to achieve an SpO 2 ≥ 90% and then haemodynamic data were collected. Hemodynamics were repeated after 100% FiO 2 for 5 minutes. Results: The cohort comprised 23 patients with ILD and RHC-proven PH (mean pulmonary artery pressure (mPAP) 33±7.34 mmHg, pulmonary artery occlusion pressure 12±2.5 mmHg, pulmonary vascular resistance (PVR) 4.9±2.8 Wood9s Units (WU), and capacitance 2.07±0.89 mL/mmHg. 11 patients required supplemental oxygen to achieve an SpO 2 >90% The baseline mean SpO 2 was 94.4%; 3 patients were hypoxic (PaO 2 2 improved SpO 2 (+4.1%), reduced mPAP (-2.7±4.3 mmHg, p=0.002), PVR (-0.78±1.24 WU, p=0.0007), and pulmonary vascular stiffness (increased capacitance) (+0.39±0.48 mmHg/mL, p Discussion: Hyperoxia acutely improves hemodynamics and vascular stiffness even in the absence of hypoxaemia, suggesting oxygen supplementation may be beneficial in normoxic ILD PH. Because proximal pulmonary arterial remodeling contributes significantly to overall vascular stiffness, these acute changes in stiffness with hyperoxia suggest previously undescribed improvements in proximal arterial mechanics.

Granulomatous-lymphocytic interstitial lung disease (GLILD) has emerged as a major cause of morbidity in patients with common variable immunodeficiency (CVID). While GLILD is among the most serious noninfectious pulmonary complications of CVID, risk factors for this condition have not been reported.To identify clinical, physiologic, and serologic risk factors for GLILD in adults with CVID.Of 345 consecutive adult patients with CVID, we identified 34 in the National Jewish Health research database who had a radiographic-pathologic diagnosis of GLILD evaluated between 2002 and 2014. Each case was age and sex matched to 52 CVID control subjects. We used logistic regression to determine independent predictors of GLILD. A mixed effects model was used to estimate the longitudinal change in percent predicted FVC.The mean time from CVID diagnosis to GLILD detection was 7.8 years. Compared with matched control subjects, cases were more likely to have a history of autoimmune cytopenia, hypersplenism, polyarthritis, lower marginal zone and switched memory B cells, and restrictive lung function. Multivariate analysis revealed that hypersplenism (odds ratio [OR], 24; 95% confidence interval [CI], 4.5-179.1), polyarthritis (OR, 19; 95% CI, 2.3-206.8), and percent predicted FVC (OR, 0.93; 95% CI, 0.87-0.98) were independently associated with the development of GLILD. The rate of change of percent predicted FVC (slope, P = 0.48) did not vary significantly in patients with GLILD over a mean follow-up of 7 years after diagnosis.Hypersplenism and polyarthritis are strong risk factors for GLILD in patients with CVID. Percent predicted FVC remained stable over time in patients with GLILD.

Summary Objective We sought to characterize a novel cohort of patients with lung disease, anti-cyclic citrullinated peptide (CCP) antibody positivity, without rheumatoid arthritis (RA) or other connective tissue disease (CTD). Methods The study sample included 74 subjects with respiratory symptoms, evaluated January 2008–January 2010 and found to have a positive anti-CCP antibody but no evidence for RA or other CTD. Each underwent serologic testing, pulmonary physiology testing, and thoracic high-resolution computed tomography (HRCT) scan as part of routine clinical evaluation. Results The majority of subjects were women, and most were former cigarette smokers. Four distinct radiographic phenotypes were identified: isolated airways disease (54%), isolated interstitial lung disease (ILD) (14%), mixed airways disease and ILD (26%), and combined pulmonary fibrosis with emphysema (7%). This cohort had a predominance of airways disease, either in isolation or along with a usual interstitial pneumonia-pattern of ILD. Among subjects with high-titer anti-CCP positivity ( n =33), three developed the articular manifestations of RA during a median follow-up of 449 days. Conclusion We have described a unique cohort of patients with anti-CCP antibody positivity and lung disease in the absence of existing RA or other CTD. The lung phenotypic characteristics of this cohort resemble those of established RA and a few of these patients have developed articular RA within a short period of follow-up. The implications of a positive anti-CCP antibody among patients with lung disease but not RA are not yet known, but we believe requires further investigation.

A recently published report from the United Kingdom suggested an association between sarcoidosis and pulmonary embolism (PE). We sought to examine whether this association was present among US decedents with sarcoidosis.We used data from the National Center for Health Statistics to investigate the association between sarcoidosis and PE among US decedents from 1988 to 2007.From 1988 to 2007, there were 46,450,489 deaths in the United States and 23,679 decedents with sarcoidosis mentioned on their death certificates. Among these, 602 (2.54%) had PE mentioned on their death certificates, compared with only 1.13% of the background population (P.0001 for comparison). The association between sarcoidosis and PE was significant regardless of gender (OR, 2.07; 95% CI, 1.80-2.39; P.0001 for men and OR, 1.76; 95% CI, 1.59-1.96; P ≤ .0001 for women) or race (OR, 1.57; 95% CI, 1.41-1.76; P.0001 for blacks and OR, 1.87; 95% CI, 1.63-2.14; P.0001 for whites). Among decedents with sarcoidosis, there was no difference in risk of PE between men and women (2.30% vs 2.54%, χ(2) = 1.32, P = .25) or between blacks and whites (2.60% vs 2.23%, χ(2) = 3.09, P = .08). The association between sarcoidosis and PE held regardless of age.Using death certificate data from 1988 to 2007, we detected an association between sarcoidosis and PE regardless of gender, race, or age. Further investigation is needed to decipher the mechanisms of this apparent association.

Recent epidemiological studies have suggested an increased risk of venous thromboembolism (VTE) in lung fibrosis. Large-scale epidemiological data regarding the risk of VTE in pulmonary fibrosis-associated mortality have not been published. Using data from the National Center for Health Statistics from 1988-2007, we determined the risk of VTE in decedents with pulmonary fibrosis in the USA. We analysed 46,450,489 records, of which 218,991 met our criteria for idiopathic pulmonary fibrosis. Among these, 3,815 (1.74%) records also contained a diagnostic code for VTE. The risk of VTE in pulmonary fibrosis decedents was 34% higher than in the background population, and 44% and 54% greater than among decedents with chronic obstructive pulmonary disease and lung cancer, respectively. Those with VTE and pulmonary fibrosis died at a younger age than those with pulmonary fibrosis alone (females: 74.3 versus 77.4 yrs (p

Rationale: It has been nearly 20 years since sarcoidosis mortality was examined at the population level in the United States.Objectives: To examine mortality rates and underlying causes of death among United States decedents with sarcoidosis from 1988–2007.Methods: We used data from the National Center for Health Statistics to (1) calculate age-adjusted sarcoidosis-associated mortality rates; (2) examine how those rates differ by age, sex, and race and ethnicity; and (3) determine underlying causes of death among sarcoidosis decedents.Measurements and Main Results: From 1988–2007, there were 46,450,489 deaths in the United States and 23,679 decedents with sarcoidosis mentioned on their death certificates. Over this time, the age-adjusted, sarcoidosis-related mortality rate increased 50.5% in women and 30.1% in men. The greatest absolute increase in death rates was among non-Hispanic black females. Regardless of sex or race, mortality rates climbed most in decedents 55 years or older. The most common cause...

Background and objective: A comprehensive diagnostic evaluation is recommended for all patients with fibrotic lung disease and acute respiratory decompensation. However, the effect on clinical outcomes of this evaluation remains unknown. Methods: We evaluated 27 consecutive patients with fibrotic lung disease who were hospitalized for an acute respiratory decline between June 2006 and April 2009. An interstitial lung disease expert assisted with the acute care of each patient. A retrospective review of the patient charts was performed to obtain demographic and clinical data, and to assess outcomes. Results: Using a strict definition of acute exacerbation (AE) of fibrotic lung disease derived from the IPF Network Pulmonary Perspective statement, 10 of the 27 patients were classified as definite AE and nine as suspected AE. In eight patients, infectious agents were identified as potential explanations for the respiratory decline. No patients with congestive heart failure or pulmonary embolism were identified. Overall survival to discharge was 37.0%. One-year survival was 14.8%. There were no differences in outcomes for patients with AE compared with those for whom potential infectious aetiologies were identified (log rank, P = 0.932). Patients with IPF showed a decreased rate of survival compared with patients with non-IPF fibrotic disease (1-year survival 0% vs 28.6%, log rank, P = 0.045). Conclusions: In patients with fibrotic lung disease and an acute respiratory decline, a detailed diagnostic evaluation revealed a potential infectious aetiology in up to one-third of cases. However, there was no association between this finding and outcomes in these patients. One-year survival was dismal in patients who suffered an acute respiratory decompensation.

Background It is now recognized that a significant portion of patients with idiopathic pulmonary fibrosis (IPF) can have sudden and rapid deteriorations in disease course that cannot be explained by infection, heart failure, or thromboembolic disease. These events are often fatal and have been termed acute exacerbations (AEs) of underlying disease. While best described in patients with IPF, they have also been reported in patients with other forms of interstitial lung disease. We sought to determine if this same phenomenon occurs in patients with hypersensitivity pneumonitis (HP). Methods We retrospectively reviewed our clinical experience at National Jewish Medical and Research Center for patients with surgical lung biopsy-proven fibrotic HP who had an acute decline in respiratory status and met criteria similar to those proposed for the diagnosis of an AE of IPF. Results Over a 2-year period, we identified four patients with an AE of fibrotic HP. All patients had a clinical course similar to that most frequently described in AEs of IPF: respiratory failure requiring assisted ventilation, lack of clinical response to high-dose corticosteroid therapy, and a poor prognosis (all cases resulted in death or emergent lung transplantation). Lung biopsy at the time of the AE, explant, or autopsy revealed organizing diffuse alveolar damage superimposed on fibrotic lung disease. Conclusions Fibrotic HP, like other forms of fibrotic lung disease, can be associated with AEs of disease. Further investigation into similarities and pathways common in AEs of various fibrotic lung diseases may yield additional insight into this recently recognized syndrome.

Interstitial lung disease (ILD) is a common pulmonary manifestation of rheumatoid arthritis. There is lack of clarity around predictors of mortality and disease behaviour over time in these patients.We identified rheumatoid arthritis-related interstitial lung disease (RA-ILD) patients evaluated at National Jewish Health (Denver, CO, USA) from 1995 to 2013 whose baseline high-resolution computed tomography (HRCT) scans showed either a nonspecific interstitial pneumonia (NSIP) or a “definite” or “possible” usual interstitial pneumonia (UIP) pattern. We used univariate, multivariate and longitudinal analytical methods to identify clinical predictors of mortality and to model disease behaviour over time.The cohort included 137 subjects; 108 had UIP on HRCT (RA-UIP) and 29 had NSIP on HRCT (RA-NSIP). Those with RA-UIP had a shorter survival time than those with RA-NSIP (log rank p=0.02). In a model controlling for age, sex, smoking and HRCT pattern, a lower baseline % predicted forced vital capacity (FVC % pred) (HR 1.46; pData from this study suggest that in RA-ILD, disease progression and survival differ between subgroups defined by HRCT pattern; however, when controlling for potentially influential variables, pulmonary physiology, but not HRCT pattern, independently predicts mortality.

Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrosing interstitial lung disease of unknown etiology characterized by progressive lung scarring and a median survival of 3-5 years from the time of diagnosis. The most recent consensus guidelines adopt a diagnostic process that characterizes patients as having a final diagnosis of IPF, probable IPF, or possible IPF determined from a combination of the clinical context and specific chest imaging and histologic disease patterns. Based on currently available data, the enrollment criteria for treatment trials could be expanded to include not only patients with IPF but also those with probable and possible IPF without adversely affecting trial design or outcomes.

Background The cornerstone of hypersensitivity pneumonitis (HP) management is having patients avoid the inciting antigen (IA). Often, despite an exhaustive search, an IA cannot be found. The objective of this study was to examine whether identifying the IA impacts survival in patients with chronic HP. Methods We used the Kaplan-Meier method to display, and the log-rank test to compare, survival curves of patients with well-characterized chronic HP stratified on identification of an IA exposure. A Cox proportional hazards (PH) model was used to identify independent predictors in time-to-death analysis. Results Of 142 patients, 67 (47%) had an identified IA, and 75 (53%) had an unidentified IA. Compared with survivors, patients who died (n = 80, 56%) were older, more likely to have smoked, had lower total lung capacity % predicted and FVC % predicted, had higher severity of dyspnea, were more likely to have pulmonary fibrosis, and were less likely to have an identifiable IA. In a Cox PH model, the inability to identify an IA (hazard ratio [HR], 1.76; 95% CI, 1.01–3.07), older age (HR, 1.04; 95% CI, 1.01–1.07), the presences of pulmonary fibrosis (HR, 2.43; 95% CI, 1.36–4.35), a lower FVC% (HR, 1.36; 95% CI, 1.10–1.68), and a history of smoking (HR, 2.01; 95% C1, 1.15–3.50) were independent predictors of shorter survival. After adjusting for mean age, presence of fibrosis, mean FVC%, mean diffusing capacity of the lung for carbon monoxide (%), and history of smoking, survival was longer for patients with an identified IA exposure than those with an unidentified IA exposure (median, 8.75 years vs 4.88 years; P = .047). Conclusions Among patients with chronic HP, when adjusting for a number of potentially influential predictors, including the presence of fibrosis, the inability to identify an IA was independently associated with shortened survival.

Objective.Small series suggest mycophenolate mofetil (MMF) is well tolerated and may be an effective therapy for connective tissue disease-associated interstitial lung disease (CTD-ILD). We examined the tolerability and longitudinal changes in pulmonary physiology in a large and diverse cohort of patients with CTD-ILD treated with MMF.Methods.We identified consecutive patients evaluated at our center between January 2008 and January 2011 and prescribed MMF for CTD-ILD. We assessed safety and tolerability of MMF and used longitudinal data analyses to examine changes in pulmonary physiology over time, before and after initiation of MMF.Results.We identified 125 subjects treated with MMF for a median 897 days. MMF was discontinued in 13 subjects. MMF was associated with significant improvements in estimated percentage of predicted forced vital capacity (FVC%) from MMF initiation to 52, 104, and 156 weeks (4.9% ± 1.9%, p = 0.01; 6.1% ± 1.8%, p = 0.0008; and 7.3% ± 2.6%, p = 0.004, respectively); and in estimated percentage predicted diffusing capacity (DLCO%) from MMF initiation to 52 and 104 weeks (6.3% ± 2.8%, p = 0.02; 7.1% ± 2.8%, p = 0.01). In the subgroup without usual interstitial pneumonia (UIP)-pattern injury, MMF significantly improved FVC% and DLCO%, and in the subgroup with UIP-pattern injury, MMF was associated with stability in FVC% and DLCO%.Conclusion.In a large diverse cohort of CTD-ILD, MMF was well tolerated and had a low rate of discontinuation. Treatment with MMF was associated with either stable or improved pulmonary physiology over a median 2.5 years of followup. MMF appears to be a promising therapy for the spectrum of CTD-ILD.

This chapter details the clinical presentation, pathophysiology, diagnosis, and management of pulmonary alveolar proteinosis and lymphangioleiomyomatosis (LAM). It also highlights other, rarer, interstitial lung diseases (ILDs) including aspiration-related ILD, lipoid pneumonia, amyloidosis, Erdheim–Chester disease, Hermansky–Pudlak syndrome, neurofibromatosis, pulmonary alveolar microlithiasis, bronchioloalveolar cell carcinoma, and lymphangitic carcinomatosis.

It is now recognized that a significant portion of patients with idiopathic pulmonary fibrosis (IPF) can have sudden and rapid deteriorations in disease course that cannot be explained by infection, heart failure, or thromboembolic disease. These events are often fatal and have been termed acute exacerbations (AEs) of underlying disease. While best described in patients with IPF, they have also been reported in patients with other forms of interstitial lung disease. We sought to determine if this same phenomenon occurs in patients with hypersensitivity pneumonitis (HP).We retrospectively reviewed our clinical experience at National Jewish Medical and Research Center for patients with surgical lung biopsy-proven fibrotic HP who had an acute decline in respiratory status and met criteria similar to those proposed for the diagnosis of an AE of IPF.Over a 2-year period, we identified four patients with an AE of fibrotic HP. All patients had a clinical course similar to that most frequently described in AEs of IPF: respiratory failure requiring assisted ventilation, lack of clinical response to high-dose corticosteroid therapy, and a poor prognosis (all cases resulted in death or emergent lung transplantation). Lung biopsy at the time of the AE, explant, or autopsy revealed organizing diffuse alveolar damage superimposed on fibrotic lung disease.Fibrotic HP, like other forms of fibrotic lung disease, can be associated with AEs of disease. Further investigation into similarities and pathways common in AEs of various fibrotic lung diseases may yield additional insight into this recently recognized syndrome.

idiopathic pulmonary fibrosis (IPF) is a chronic, fibrosing interstitial lung disease of unknown etiology. An estimated 200,000 Americans are presently living with IPF, and the prevalence appears to be increasing. Mean survival from the time of diagnosis is only 2–3 years, and unfortunately there