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Original Research: Diffuse Lung Disease |

Clinical Features and Outcomes in Combined Pulmonary Fibrosis and Emphysema in Idiopathic Pulmonary FibrosisCombined Pulmonary Fibrosis and Emphysema FREE TO VIEW

Christopher J. Ryerson, MD; Thomas Hartman, MD; Brett M. Elicker, MD; Brett Ley, MD; Joyce S. Lee, MD; Marta Abbritti, MD; Kirk D. Jones, MD; Talmadge E. King, Jr, MD; Jay Ryu, MD, FCCP; Harold R. Collard, MD, FCCP
Author and Funding Information

From the Department of Medicine (Dr Ryerson), University of British Columbia, Vancouver, BC, Canada; Department of Radiology (Dr Hartman), Department of Medicine (Dr Ryu), Mayo Clinic, Rochester, MN; Department of Radiology (Dr Elicker), Department of Medicine (Drs Ley, Lee, King, and Collard), and Department of Pathology (Dr Jones), University of California San Francisco, San Francisco, CA; and the Pulmonary Institute and Respiratory Intensive Care Unit (Dr Abbritti), S. Maria della Misericordia Hospital, Perugia, Italy.

Correspondence to: Christopher J. Ryerson, MD, St. Paul’s Hospital Ward 8B, 1081 Burrard St, Vancouver, BC, V6Z 1Y6, Canada; e-mail: chris.ryerson@hli.ubc.ca


Funding/Support: The authors have reported to CHEST that no funding was received for this study.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;144(1):234-240. doi:10.1378/chest.12-2403
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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.

Figures in this Article

The syndrome of combined pulmonary fibrosis and emphysema (CPFE) has been proposed as an important phenotype of pulmonary fibrosis, defined by the presence of emphysema and parenchymal fibrosis in the same patient.1 Previous studies have compared clinical features and outcomes in CPFE to control subjects without emphysema, and have shown that patients with CPFE have distinct clinical features,27 and possibly different outcomes.26 Patients with CPFE are commonly men with a heavy-smoking history, severe dyspnea on exertion, and relatively preserved lung volumes associated with disproportionate impairment of gas exchange.17 These patients appear to develop severe pulmonary arterial hypertension and more frequent lung cancer14; however, the reported impact of CPFE on survival is inconsistent in the existing literature.26,8

Most previous studies of CPFE have significant limitations, including imprecise definitions of CPFE, heterogeneous patient populations (ie, a variety of causes of pulmonary fibrosis with different natural histories), and lack of controlling for confounders. To address these limitations, we evaluated two large cohorts of patients with well-characterized idiopathic pulmonary fibrosis (IPF), the most common of the idiopathic, interstitial pneumonias. Our main objectives were to (1) determine the prevalence of CPFE in IPF using a standardized and reproducible definition of CPFE, (2) describe the clinical features of CPFE in IPF, and (3) determine the prognostic importance of CPFE in IPF.

Study Patients

Patients were identified through the University of California San Francisco (UCSF) and Mayo Clinic Rochester (Mayo) interstitial lung disease (ILD) databases between January 2000 and July 2010. Patients were included if they had a diagnosis of IPF based on multidisciplinary review according to established criteria9,10 and had a high-resolution CT (HRCT) scan within 1 year of their initial clinic consultation. Patients without a HRCT scan available for re-review were excluded (n = 71). A total of 365 patients with a diagnosis of IPF had a HRCT scan available and were included in the final study population (UCSF, n = 192; Mayo, n = 173). The clinical features of these cohorts have previously been described.11 The institutional review boards approved the protocol at each institution (UCSF Committee on Human Research, approval number 10-01592; Mayo Clinic Institutional Review Board approval number 06-002543).

Measurements

Baseline information was recorded and questionnaires completed at the time of initial consultation. Dyspnea severity was measured using the self-administered dyspnea component of the Clinical, Radiographic, and Physiologic scoring system.12 Resting oxygen saturation, the need for long-term oxygen therapy, and pulmonary artery pressures were recorded. Pulmonary function tests were performed according to standard techniques.1315 Systolic pulmonary artery pressures were evaluated by echocardiogram for the 72 UCSF patients who had an echocardiogram within 1 year of their clinic visit. The use of inhaler therapies was determined based on chart review. Date of death or transplant was recorded. Vital status and date of death were verified using the US Social Security Death Index.

Radiologic Measurements

HRCT scans were independently reviewed by two experienced thoracic radiologists who were blinded to other patient data. Fibrosis score was determined by estimating the percent of reticular change and honeycombing in upper, mid, and lower areas of each lung, and averaging these scores to produce a total fibrosis score.16 A total of 40 HRCT scans were unable to be deidentified and were, thus, evaluated by only one radiologist. For all other HRCT scans, the fibrosis scores from the two radiologists were averaged to produce the most generalizable estimate. Emphysema score was calculated in a similar manner. Emphysema was defined as a hyperlucent area of lung that lacked a distinct wall. A priori, we chose to dichotomize the total emphysema score at a threshold of ≥ 10% to indicate patients with CPFE. This threshold was chosen because a 10% threshold corresponds to GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage II or worse in patients with isolated COPD,17 suggesting that this amount of emphysema is expected to have symptomatic and physiologic consequences.18 In addition, a threshold of 10% has previously been used to define CPFE with excellent interrater reliability (κ = 0.89).3

Statistical Analysis

Interrater agreement between radiologists was reported using a κ statistic and percent agreement for dichotomized emphysema score and an intraclass correlation coefficient for total fibrosis score. The bivariate associations of CPFE were tested using the χ2 test, Fisher exact test, Student t test, or Wilcoxon rank-sum test as appropriate. These comparisons were followed by logistic regression with adjustment for total HRCT scan fibrosis score (as a measure of severity of underlying IPF). The following predefined, independent variables were evaluated: age, sex, BMI, smoking history, dyspnea score, use of long-term oxygen therapy, pulmonary arterial pressure, pulmonary function tests, and HRCT scan fibrosis score.

Fine-Gray competing-risks regression analysis was used to evaluate the relationship of CPFE with risk of death, treating transplantation as a competing risk.19 Logistic regression was used to evaluate the relationship of emphysema with disease progression, defined as any of the following within 12 months of the initial ILD Clinic visit: 10% relative decline in FVC % predicted, 15% relative decline in diffusing capacity of the lung for carbon monoxide (Dlco) % predicted, lung transplantation, or death due to any cause. The ability of emphysema to predict these outcomes was also tested with adjustment for baseline fibrosis score. All data analysis was performed using Stata, version 11.2 (StataCorp LP).

Prevalence of CPFE in IPF

Criteria for CPFE were met in 29 of 365 patients, representing 8.0% of the overall cohort (95% CI, 5.1%-10.6%) (Fig 1). There was no difference in the frequency of CPFE between cohorts (8.9% in UCSF and 6.9% in Mayo, P = .50). Forty-nine patients (13.4%) had ≥ 5% emphysema and 106 patients (29.0%) had at least some emphysema detectable on HRCT scan. In 17 patients, the extent of emphysema was greater than that of fibrosis; 15 of these patients met our definition of CPFE. When present, emphysema was predominantly in the upper and mid lung zones, with fibrosis predominantly in the lower and mid zones (Fig 2). Overall agreement between the two radiologists on the presence of CPFE was 96%, with a κ of 0.74, and did not change significantly for different threshold definitions. The intraclass correlation coefficient for total fibrosis score was 0.79. One radiologist scored slightly higher for emphysema score (mean difference, 0.82%; 95% CI, 0.45%-1.20%), but slightly lower for fibrosis score (mean difference, 2.66%; 95% CI, 1.85%-3.46%).

Figure Jump LinkFigure 1. Distribution of emphysema score. Scores were averaged for the two radiologists. CPFE = combined pulmonary fibrosis and emphysema.Grahic Jump Location
Figure Jump LinkFigure 2. Mean extent of fibrosis and emphysema in upper, mid, and lower lung zone. Scores were averaged for the corresponding areas in the right and left lungs. See Figure 1 legend for expansion of abbreviation.Grahic Jump Location
Clinical Features of CPFE in IPF

Baseline clinical features of patients with and without CPFE are compared in Table 1. On unadjusted analysis, patients with CPFE had more extensive smoking history, greater oxygen requirements, higher pulmonary artery pressure, less restrictive physiology, and lower diffusing capacity. These differences were maintained with adjustment for fibrosis score (Table 2). Comparison of patients with CPFE to smokers in the IPF-without-emphysema group showed similar differences (ie, the observed between-group differences were not entirely explained by the presence of never smokers in the patients with IPF but without emphysema [data not shown]). Patients with CPFE had a lower total fibrosis score, and this difference was consistent in upper, mid, and lower lung zones (Fig 2). Patients with CPFE were more likely to be identified by themselves or their physician as having COPD and were treated more often with short-acting bronchodilators and long-acting anticholinergics (Table 3). However, only 53% of patients with CPFE reported use of inhaled therapy for COPD. Patients with mild emphysema (defined as > 0% and < 10% emphysema by HRCT scan) had clinical and physiologic findings similar to patients with no emphysema (e-Table 1).

Table Graphic Jump Location
Table 1 —Baseline Patient Characteristics

Data are presented as mean (SD) unless otherwise indicated. CPFE = combined pulmonary fibrosis and emphysema; Dlco = diffusing capacity of the lung for carbon monoxide; HRCT = high-resolution CT; RV = residual volume; SPAP = systolic pulmonary artery pressure; TLC = total lung capacity.

a 

P values are reported for the difference between groups, using a χ2 test, Fisher exact test, t test, or Wilcoxon rank-sum test as appropriate.

b 

Data are available only for the University of California San Francisco cohort.

Table Graphic Jump Location
Table 2 —Fibrosis-Adjusted Comparison of CPFE and Non-CPFE Baseline Characteristics

See Table 1 legend for expansion of abbreviations.

a 

Data are available only for the University of California San Francisco cohort.

b 

Reported as OR.

c 

Reported as hazard ratio, based on competing risk model of time to death.

Table Graphic Jump Location
Table 3 —Diagnosis and Management of Emphysema at Presentationa

Data given as No. (%) unless otherwise indicated. See Table 1 legend for expansion of abbreviation.

a 

Diagnosis and management data are available only for the University of California San Francisco cohort.

b 

Treatment data were obtained at the time of the initial consultation.

Outcomes of CPFE in IPF

Median transplant-free survival was 2.8 years in patients with CPFE (95% CI, 1.3-5.0 years), and 2.8 years in IPF patients without emphysema (95% CI, 2.5-3.6 years) (Fig 3). Using a competing risk analysis, CPFE had similar risk of death compared with IPF on unadjusted analysis (hazard ratio [HR], 1.08; 95% CI, 0.67-1.73; P = .75) and with adjustment for baseline fibrosis score (HR, 1.14; 95% CI, 0.61-2.13; P = .69) (Table 2). CPFE had a higher risk of death on adjusted analysis when considering transplantation an outcome equivalent to death (ie, transplant-free survival; HR, 1.60; 95% CI, 1.00-2.54; P = .048), but not when censoring for transplantation (HR, 1.50; 95% CI, 0.91-2.47; P = .12).

Figure Jump LinkFigure 3. Kaplan-Meier survival curves stratified by CPFE vs non-CPFE. Survival curves and P value represent time to death or transplant. See Figure 1 legend for expansion of abbreviation.Grahic Jump Location

Follow-up pulmonary function test data were available at 12 months for 52% of the combined cohort (n = 190). Patients with follow-up data available were more likely to be on oxygen at baseline (33% vs 22%; P = .02), but had no other differences in baseline characteristics. Disease progression occurred in 135 patients (71%) during the initial 12 months of follow-up, defined by decline in FVC (n = 21), decline in Dlco (n = 24), decline in both FVC and Dlco (n = 12), death (n = 68), or transplant (n = 10). There was no association between the diagnosis of CPFE and disease progression on unadjusted or adjusted analyses (Table 2).

This is the first IPF-specific multicenter study of CPFE, and unlike previous studies, we used both a standardized definition of CPFE and rigorous statistical methods to determine differences in clinical features and outcomes. We restricted our analysis to patients with IPF to reduce potential bias that would be introduced by inclusion of other ILDs that have distinct natural histories and variable association with smoking. In addition, we chose a prespecified cutoff of ≥ 10% emphysema to define CPFE based on its ease of use, excellent interrater reliability, and its potential clinical relevance in identifying GOLD stage II equivalent disease.

Previous studies of CPFE have included other ILD subtypes and used different thresholds of emphysema, and different definitions of CPFE have been suggested in recent review articles.20,21 We believe our more restrictive criteria for CPFE are an improvement upon previous definitions based on the reasons outlined here; however, we acknowledge it may not be appropriate for all research questions. For example, examination of the physiologic implications of overlapping restrictive and obstructive lung disease may not require limitation to only IPF. Conversely, studies comparing biologic mechanisms of CPFE to isolated lung fibrosis may require a more homogeneous ILD (eg, only IPF), but may not need a specific threshold of emphysema. Our study also does not address whether CPFE is a phenotype of IPF, or a more general condition occurring in lung fibrosis of any cause (ie, not just IPF). Moreover, CPFE could alternatively be regarded as a phenotype of emphysema (a universal feature in the patients with CPFE described in the literature is the presence of emphysema, not a particular subtype of lung fibrosis). Additional research is required to validate our definition of CPFE and to determine the clinical significance of ≥ 10% emphysema on HRCT scan.

Patients with IPF and CPFE have less physiologic restriction and worse gas exchange compared with patients with IPF but without emphysema. The higher FVC found in patients with CPFE is only partially explained by less severe fibrosis in these patients, as illustrated by the difference in FVC that remains after adjustment for fibrosis score. It seems most likely that emphysema is mitigating the impact of the fibrosis on ventilatory physiology. Fibrosis and emphysema have similar and cumulative effects on gas exchange, reflected by disproportionate oxygen requirement, low Dlco, and pulmonary hypertension in CPFE.

The patients with CPFE had milder radiographic fibrosis at presentation than those with IPF without emphysema. We believe this is due to additional symptoms of emphysema that bring patients to medical attention earlier. A second possibility is that extent of fibrosis is underestimated on HRCT scans when scored in the presence of significant emphysema. We believe this is less likely in our cohort given the strong agreement for both fibrosis and emphysema scores between two experienced thoracic radiologists, as well as the consistently lower fibrosis score in upper, mid, and lower lungs of patients with CPFE. If emphysema severity was itself impacting estimation of fibrosis severity, we would expect minimal difference in fibrosis scores between the two groups in the lower lobes where emphysema is typically absent. A third possibility is that our CPFE population may include some patients with non-IPF ILD who had less severe fibrosis. The coexistence of emphysema with other fibrotic ILD (eg, nonspecific interstitial pneumonia) may mimic radiographic honeycombing, thus satisfying a major diagnostic criterion for IPF.22 We believe inclusion of non-IPF ILD in our CPFE cohort is unlikely based on the clinical characteristics of the patients with CPFE (elderly, predominantly male smokers), and the available follow-up data that did not reveal an alternative ILD on subsequent review.

Only half of the patients with CPFE were on inhaled therapy for COPD. It is unknown if therapies for COPD are effective in patients with CPFE, as these patients have been excluded from major clinical trials in COPD. Treatment trials of such therapies in CPFE may not be feasible, so treatment strategies in CPFE will likely need to be extrapolated from the existing evidence in COPD. By using a 10% threshold to define CPFE, which likely corresponds to GOLD stage 2 disease or worse,17 we identified a population of patients who might benefit from short-acting and long-acting bronchodilators, with addition of inhaled corticosteroids in some patients.18 Given that IPF lacks definitive therapy, there is significant appeal in managing comorbidities that may improve outcomes.

We observed no clear difference in survival despite significantly less fibrosis in patients with CPFE. We believe that the similar mortality in CPFE and IPF without emphysema is a reflection of the approximately balanced mortality risk factors in CPFE (worse oxygenation and pulmonary hypertension) and IPF without emphysema (more fibrosis). It is possible, however, that differences in the rates of other unmeasured comorbidities could confound this result. Previous studies conflict on whether patients with CPFE have different outcomes compared with patients with IPF without emphysema.26,8 This discord may be explained by differing definitions of CPFE in these studies and inadequate adjustment for ILD subtype and severity on statistical analysis. For example, if patients with both nonspecific interstitial pneumonia and IPF were included, IPF would likely have been disproportionately represented in the CPFE population on the basis of a stronger association with smoking, and thus outcomes could have appeared worse in the CPFE population due to the worse survival seen in IPF compared with other ILDs.

Previous studies of CPFE have used the composite physiologic index (CPI) as a means to estimate fibrosis severity,23 based on the development of the CPI as a method to predict fibrosis on HRCT scans.24 Instead, we used two blinded and independent thoracic radiologists to directly estimate fibrotic burden for all of the patients and used this variable in our adjusted analyses rather than the CPI. We used a competing risk analysis, since survival in IPF is complicated by lung transplantation, which is a nonrandom event that should neither be censored nor considered equivalent to death. Our relatively small number of patients with CPFE could limit our ability to detect a true difference in mortality; however, the 95% CI of this HR (0.67-1.73) suggests that any difference in mortality, if present, is relatively modest.

In summary, CPFE is a distinct clinical phenotype of IPF, likely resulting from the overlap of two diseases that share common risk factors. We believe future study of CPFE will benefit from a more refined definition, and we propose the criteria used in this study for future research of CPFE in patients with IPF. We anticipate that these criteria may change as we learn more about this condition. Prospective, population-based studies are required to determine whether our findings are generalizable to a broader IPF population. A remaining question is whether CPFE represents a biologically distinct condition (ie, a different disease) or is just IPF and emphysema in the same patient. Future research in CPFE will require evaluation of underlying biologic pathways to address this question and explain why some smokers develop emphysema, some IPF, and some CPFE.

Author contributions: Drs Ryerson and Collard had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Ryerson: contributed to conception of the study design, performed the data analysis, produced the initial draft of the manuscript, approved the final manuscript, and served as principal author.

Dr Hartman: contributed to data interpretation and preparation and approval of the final manuscript.

Dr Elicker: contributed to data interpretation and preparation and approval of the final manuscript.

Dr Ley: contributed to data interpretation and preparation and approval of the final manuscript.

Dr Lee: contributed to data interpretation and preparation and approval of the final manuscript.

Dr Abbritti: contributed to data interpretation and preparation and approval of the final manuscript.

Dr Jones: contributed to data interpretation and preparation and approval of the final manuscript.

Dr King: contributed to data interpretation and preparation and approval of the final manuscript.

Dr Ryu: contributed to data interpretation and preparation and approval of the final manuscript.

Dr Collard: contributed to conception of the study design, performed the data analysis, produced the initial draft of the manuscript, and approved the final manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Collard has served as a consultant for industry and receives grant support from governmental, university, and industry sources. The remaining authors have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Other contributions: The authors would like to acknowledge the providers and staff of the UCSF and Mayo Clinic Rochester Interstitial Lung Disease Programs, the members of the Interstitial Lung Disease Consortium for their continued referral of patients to our centers, and the patients with IPF who, through their generosity and efforts, allow us to conduct clinical research studies such as this in an effort to improve the lives of patients with IPF.

Additional information: The e-Table can be found in the “Supplemental Materials” area of the online article.

CPFE

combined pulmonary fibrosis and emphysema

CPI

composite physiologic index

Dlco

diffusing capacity of the lung for carbon monoxide

GOLD

Global Initiative for Chronic Obstructive Lung Disease

HR

hazard ratio

HRCT

high-resolution CT

ILD

interstitial lung disease

IPF

idiopathic pulmonary fibrosis

Mayo

Mayo Clinic Rochester

UCSF

University of California San Francisco

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Kurashima K, Takayanagi N, Tsuchiya N, et al. The effect of emphysema on lung function and survival in patients with idiopathic pulmonary fibrosis. Respirology. 2010;15(5):843-848. [CrossRef] [PubMed]
 
Mejía M, Carrillo G, Rojas-Serrano J, et al. Idiopathic pulmonary fibrosis and emphysema: decreased survival associated with severe pulmonary arterial hypertension. Chest. 2009;136(1):10-15. [CrossRef] [PubMed]
 
Todd NW, Jeudy J, Lavania S, et al. Centrilobular emphysema combined with pulmonary fibrosis results in improved survival. Fibrogenesis Tissue Repair. 2011;4(1):6. [CrossRef] [PubMed]
 
Jankowich MD, Rounds S. Combined pulmonary fibrosis and emphysema alters physiology but has similar mortality to pulmonary fibrosis without emphysema. Lung. 2010;188(5):365-373. [CrossRef] [PubMed]
 
Akagi T, Matsumoto T, Harada T, et al. Coexistent emphysema delays the decrease of vital capacity in idiopathic pulmonary fibrosis. Respir Med. 2009;103(8):1209-1215. [CrossRef] [PubMed]
 
Tasaka S, Mizoguchi K, Funatsu Y, et al. Cytokine profile of bronchoalveolar lavage fluid in patients with combined pulmonary fibrosis and emphysema. Respirology. 2012;17(5):814-820. [CrossRef] [PubMed]
 
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Figures

Figure Jump LinkFigure 1. Distribution of emphysema score. Scores were averaged for the two radiologists. CPFE = combined pulmonary fibrosis and emphysema.Grahic Jump Location
Figure Jump LinkFigure 2. Mean extent of fibrosis and emphysema in upper, mid, and lower lung zone. Scores were averaged for the corresponding areas in the right and left lungs. See Figure 1 legend for expansion of abbreviation.Grahic Jump Location
Figure Jump LinkFigure 3. Kaplan-Meier survival curves stratified by CPFE vs non-CPFE. Survival curves and P value represent time to death or transplant. See Figure 1 legend for expansion of abbreviation.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Baseline Patient Characteristics

Data are presented as mean (SD) unless otherwise indicated. CPFE = combined pulmonary fibrosis and emphysema; Dlco = diffusing capacity of the lung for carbon monoxide; HRCT = high-resolution CT; RV = residual volume; SPAP = systolic pulmonary artery pressure; TLC = total lung capacity.

a 

P values are reported for the difference between groups, using a χ2 test, Fisher exact test, t test, or Wilcoxon rank-sum test as appropriate.

b 

Data are available only for the University of California San Francisco cohort.

Table Graphic Jump Location
Table 2 —Fibrosis-Adjusted Comparison of CPFE and Non-CPFE Baseline Characteristics

See Table 1 legend for expansion of abbreviations.

a 

Data are available only for the University of California San Francisco cohort.

b 

Reported as OR.

c 

Reported as hazard ratio, based on competing risk model of time to death.

Table Graphic Jump Location
Table 3 —Diagnosis and Management of Emphysema at Presentationa

Data given as No. (%) unless otherwise indicated. See Table 1 legend for expansion of abbreviation.

a 

Diagnosis and management data are available only for the University of California San Francisco cohort.

b 

Treatment data were obtained at the time of the initial consultation.

References

Cottin V, Nunes H, Brillet PY, et al; Groupe d’Etude et de Recherche sur les Maladies Orphelines Pulmonaires (GERM O P). Combined pulmonary fibrosis and emphysema: a distinct underrecognised entity. Eur Respir J. 2005;26(4):586-593. [CrossRef] [PubMed]
 
Kurashima K, Takayanagi N, Tsuchiya N, et al. The effect of emphysema on lung function and survival in patients with idiopathic pulmonary fibrosis. Respirology. 2010;15(5):843-848. [CrossRef] [PubMed]
 
Mejía M, Carrillo G, Rojas-Serrano J, et al. Idiopathic pulmonary fibrosis and emphysema: decreased survival associated with severe pulmonary arterial hypertension. Chest. 2009;136(1):10-15. [CrossRef] [PubMed]
 
Todd NW, Jeudy J, Lavania S, et al. Centrilobular emphysema combined with pulmonary fibrosis results in improved survival. Fibrogenesis Tissue Repair. 2011;4(1):6. [CrossRef] [PubMed]
 
Jankowich MD, Rounds S. Combined pulmonary fibrosis and emphysema alters physiology but has similar mortality to pulmonary fibrosis without emphysema. Lung. 2010;188(5):365-373. [CrossRef] [PubMed]
 
Akagi T, Matsumoto T, Harada T, et al. Coexistent emphysema delays the decrease of vital capacity in idiopathic pulmonary fibrosis. Respir Med. 2009;103(8):1209-1215. [CrossRef] [PubMed]
 
Tasaka S, Mizoguchi K, Funatsu Y, et al. Cytokine profile of bronchoalveolar lavage fluid in patients with combined pulmonary fibrosis and emphysema. Respirology. 2012;17(5):814-820. [CrossRef] [PubMed]
 
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