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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The clinical entity of combined pulmonary fibrosis and emphysema &#40;CPFE&#41; is characterized by the admixture of fibrosis and emphysema on high resolution computed tomography &#40;HRCT&#41;&#46; It can be observed in the context of idiopathic interstitial pneumonias such as idiopathic pulmonary fibrosis &#40;IPF&#41; and non-specific interstitial pneumonia &#40;NSIP&#41; and in interstitial lung diseases associated with connective tissue disorders &#40;CTD-ILDs&#41; such as rheumatoid arthritis &#40;RA&#41; and systemic sclerosis &#40;SSc&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">1&#8211;3</span></a> It is still unclear whether this entity represents a distinct syndrome&#44; a specific subtype of fibrosis&#44; or a coincidental co-existence of two processes&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">In contrast to isolated pulmonary fibrosis and emphysema&#44; no specific pathogenic pathways which could lead to different treatment approach for CPFE have yet been identified&#46; However&#44; common pathogenetic pathways&#44; such as increase in oxidative stress&#44; accelerated lung aging associated with genetic abnormalities &#40;for example&#44; mutations in the telomerase genes&#41;&#44; and increased neutrophil elastases are involved in both disorders&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a> Historically&#44; the presence of radiologic emphysema was associated with smoking&#46; Interestingly&#44; in smokers with IPF&#44; NSIP&#44; rheumatoid and pulmonary scleroderma&#44; the development of emphysema was associated with a lower pack-year smoking history than in smokers without fibrosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">1&#8211;3</span></a> This could be viewed as indirect evidence of an interaction between fibrosis and smoking in the development of emphysema in this subgroup of patients&#46; More intriguingly&#44; in a large cohort of 333 patients with pulmonary scleroderma&#44; 15&#47;41 patients with CPFE were non-smokers&#44; raising the possibility of an autoimmune origin of emphysema in this subgroup&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a> Obviously&#44; in the absence of a control cohort&#44; these results should be interpreted with caution&#44; and need to be confirmed at the cellular and biological level&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">CPFE poses significant difficulties in the diagnosis of the radiologic pattern of pulmonary fibrosis&#46; It is generally accepted that in ILDs&#44; diagnosis means prognosis&#46; In clinical practice&#44; the main concern is to distinguish IPF&#44; the most common and severe form of ILD&#44; from other fibrotic lung disease such as NSIP&#44; some subtypes of chronic hypersensitivity pneumonitis&#44; and unclassifiable ILD&#44; which generally have a better prognosis&#46; In CPFE&#44; it is often difficult to distinguish between honeycombing cysts&#44; the main characteristic of usual interstitial pneumonia &#40;UIP&#41; which is the radiologic counterpart of IPF&#44; and pseudocysts due to admixture of emphysema and fibrosis&#46; This difficulty was underlined in a recent study in the diagnosis of UIP among thoracic radiologists with special interest in ILDs&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> Quantification of the extent of both processes is also problematic&#46; Some experts have suggested using density masking&#44; but the main constraint in this case is that areas of low density could correspond to either emphysema&#44; or honeycombing&#44; or traction bronchiectasis&#46; The likely contamination of CPFE cohorts with entities like NSIP&#44; and the difficulty in including patients with the same extent of emphysema and fibrosis has led to conflicting results regarding the prognostic significance of CPFE&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">6&#8211;8</span></a> Mejia et al&#46; reported an interesting finding&#44; namely&#44; that worse prognosis in CPFE was due to the high prevalence of pulmonary hypertension &#40;PH&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">6</span></a> Although this could facilitate early diagnosis of PH&#44; it is clinically irrelevant because no effective treatment is available for PH associated with IPF or CPFE&#46; In scleroderma lung&#44; which exhibits different clinical behavior from IPF&#44; the presence of trivial emphysema did not influence the prevalence of PH on echocardiography at presentation compared to patients with isolated fibrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a> After adjustment for the extent of fibrosis on HRCT&#44; emphysema was associated with an additional average reduction of 24&#46;1&#37; from baseline DLco levels and a 34&#46;8&#37; increase in the FVC&#47;DLco ratio&#44; but there was no overall significant effect on forced vital capacity &#40;FVC&#41; levels&#46; These effects did not differ between smokers and nonsmokers&#44; and on multivariate analysis pulmonary function tests were not influenced by either smoking status or total pack-years after adjusting for the extent of pulmonary fibrosis or the presence of emphysema&#46; The FVC&#47;DLco ratio is used in SSc as a marker of PH&#44; and a value greater than 1&#46;6 calls for an echocardiogram&#46; However&#44; this study showed that in the presence of emphysema&#44; the ratio is not a reliable marker for echocardiographic features of PH&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The coexistence of emphysema and fibrosis has a significant attenuating effect on serial FVC decline&#44; with major implications for routine IPF monitoring and the use of serial FVC as a primary endpoint in IPF treatment trials&#46; In a well-defined pharmaceutical IPF cohort&#44; patients with IPF and concurrent emphysema had a significantly slower rate of decline of FVC than patients with IPF only when the extent of emphysema on HRCT was greater than 15&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">9</span></a> It should also be stressed that the coexistence of emphysema with IPF leads to spurious preservation of FVC&#44; which has implications in the approval of antifibrotic drugs in countries where an upper limit for FVC is used to assess eligibility for treatment&#46; There is still insufficient evidence to support the use of the composite physiolocic index &#40;cpi&#41;&#44; which takes into account the presence of emphysema&#44; as an end-point in these patients&#46; Baseline cpi correlates with the extent of IPF disease on CT and is superior to individual lung function variables in predicting survival in patients with concomitant radiologic emphysema&#44; whereas in IPF patients without emphysema&#44; baseline cpi has the same predictive value as baseline DLco&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">10</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In the context of CTD-ILDs&#44; the impact of concurrent emphysema on serial changes in FVC&#44; which is also used as the primary end-point in clinical trials in SSc-ILD&#44;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">11</span></a> has not yet been studied&#46; Recently though&#44; it was observed that the presence of limited emphysema had no effect on baseline FVC after adjustment for the extent of ILD&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In conclusion&#44; the coexistence of emphysema with fibrosis remains controversial&#46; This entity is not characterized by the activation of any particular pathways that can lead to the development of disease-specific treatment&#46; In the case of IPF&#44; the presence of emphysema causes difficulties in monitoring the behavior of the disease and the response to treatment due to the attenuating effect on serial FVC decline&#46; Moreover&#44; the preservation of FVC precludes the use of antifibrotic drugs in countries where an upper limit of FVC is used&#46; These important observations must be taken into account by expert groups involved in establishing the most appropriate management strategy for this subgroup of patients&#46;</p></span>"
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Editorial
Controversies in Fibrosis and Emphysema
Controversias en la fibrosis y el enfisema
Katerina M. Antonioua,
Corresponding author
kantoniou@med.uoc.gr

Corresponding author.
, Eleni Bibakia, George A. Margaritopoulosb
a Department of Thoracic Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece
b Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK
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        "titulo" => "Controversias en la fibrosis y el enfisema"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The clinical entity of combined pulmonary fibrosis and emphysema &#40;CPFE&#41; is characterized by the admixture of fibrosis and emphysema on high resolution computed tomography &#40;HRCT&#41;&#46; It can be observed in the context of idiopathic interstitial pneumonias such as idiopathic pulmonary fibrosis &#40;IPF&#41; and non-specific interstitial pneumonia &#40;NSIP&#41; and in interstitial lung diseases associated with connective tissue disorders &#40;CTD-ILDs&#41; such as rheumatoid arthritis &#40;RA&#41; and systemic sclerosis &#40;SSc&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">1&#8211;3</span></a> It is still unclear whether this entity represents a distinct syndrome&#44; a specific subtype of fibrosis&#44; or a coincidental co-existence of two processes&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">In contrast to isolated pulmonary fibrosis and emphysema&#44; no specific pathogenic pathways which could lead to different treatment approach for CPFE have yet been identified&#46; However&#44; common pathogenetic pathways&#44; such as increase in oxidative stress&#44; accelerated lung aging associated with genetic abnormalities &#40;for example&#44; mutations in the telomerase genes&#41;&#44; and increased neutrophil elastases are involved in both disorders&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a> Historically&#44; the presence of radiologic emphysema was associated with smoking&#46; Interestingly&#44; in smokers with IPF&#44; NSIP&#44; rheumatoid and pulmonary scleroderma&#44; the development of emphysema was associated with a lower pack-year smoking history than in smokers without fibrosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">1&#8211;3</span></a> This could be viewed as indirect evidence of an interaction between fibrosis and smoking in the development of emphysema in this subgroup of patients&#46; More intriguingly&#44; in a large cohort of 333 patients with pulmonary scleroderma&#44; 15&#47;41 patients with CPFE were non-smokers&#44; raising the possibility of an autoimmune origin of emphysema in this subgroup&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a> Obviously&#44; in the absence of a control cohort&#44; these results should be interpreted with caution&#44; and need to be confirmed at the cellular and biological level&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">CPFE poses significant difficulties in the diagnosis of the radiologic pattern of pulmonary fibrosis&#46; It is generally accepted that in ILDs&#44; diagnosis means prognosis&#46; In clinical practice&#44; the main concern is to distinguish IPF&#44; the most common and severe form of ILD&#44; from other fibrotic lung disease such as NSIP&#44; some subtypes of chronic hypersensitivity pneumonitis&#44; and unclassifiable ILD&#44; which generally have a better prognosis&#46; In CPFE&#44; it is often difficult to distinguish between honeycombing cysts&#44; the main characteristic of usual interstitial pneumonia &#40;UIP&#41; which is the radiologic counterpart of IPF&#44; and pseudocysts due to admixture of emphysema and fibrosis&#46; This difficulty was underlined in a recent study in the diagnosis of UIP among thoracic radiologists with special interest in ILDs&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> Quantification of the extent of both processes is also problematic&#46; Some experts have suggested using density masking&#44; but the main constraint in this case is that areas of low density could correspond to either emphysema&#44; or honeycombing&#44; or traction bronchiectasis&#46; The likely contamination of CPFE cohorts with entities like NSIP&#44; and the difficulty in including patients with the same extent of emphysema and fibrosis has led to conflicting results regarding the prognostic significance of CPFE&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">6&#8211;8</span></a> Mejia et al&#46; reported an interesting finding&#44; namely&#44; that worse prognosis in CPFE was due to the high prevalence of pulmonary hypertension &#40;PH&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">6</span></a> Although this could facilitate early diagnosis of PH&#44; it is clinically irrelevant because no effective treatment is available for PH associated with IPF or CPFE&#46; In scleroderma lung&#44; which exhibits different clinical behavior from IPF&#44; the presence of trivial emphysema did not influence the prevalence of PH on echocardiography at presentation compared to patients with isolated fibrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a> After adjustment for the extent of fibrosis on HRCT&#44; emphysema was associated with an additional average reduction of 24&#46;1&#37; from baseline DLco levels and a 34&#46;8&#37; increase in the FVC&#47;DLco ratio&#44; but there was no overall significant effect on forced vital capacity &#40;FVC&#41; levels&#46; These effects did not differ between smokers and nonsmokers&#44; and on multivariate analysis pulmonary function tests were not influenced by either smoking status or total pack-years after adjusting for the extent of pulmonary fibrosis or the presence of emphysema&#46; The FVC&#47;DLco ratio is used in SSc as a marker of PH&#44; and a value greater than 1&#46;6 calls for an echocardiogram&#46; However&#44; this study showed that in the presence of emphysema&#44; the ratio is not a reliable marker for echocardiographic features of PH&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The coexistence of emphysema and fibrosis has a significant attenuating effect on serial FVC decline&#44; with major implications for routine IPF monitoring and the use of serial FVC as a primary endpoint in IPF treatment trials&#46; In a well-defined pharmaceutical IPF cohort&#44; patients with IPF and concurrent emphysema had a significantly slower rate of decline of FVC than patients with IPF only when the extent of emphysema on HRCT was greater than 15&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">9</span></a> It should also be stressed that the coexistence of emphysema with IPF leads to spurious preservation of FVC&#44; which has implications in the approval of antifibrotic drugs in countries where an upper limit for FVC is used to assess eligibility for treatment&#46; There is still insufficient evidence to support the use of the composite physiolocic index &#40;cpi&#41;&#44; which takes into account the presence of emphysema&#44; as an end-point in these patients&#46; Baseline cpi correlates with the extent of IPF disease on CT and is superior to individual lung function variables in predicting survival in patients with concomitant radiologic emphysema&#44; whereas in IPF patients without emphysema&#44; baseline cpi has the same predictive value as baseline DLco&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">10</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In the context of CTD-ILDs&#44; the impact of concurrent emphysema on serial changes in FVC&#44; which is also used as the primary end-point in clinical trials in SSc-ILD&#44;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">11</span></a> has not yet been studied&#46; Recently though&#44; it was observed that the presence of limited emphysema had no effect on baseline FVC after adjustment for the extent of ILD&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In conclusion&#44; the coexistence of emphysema with fibrosis remains controversial&#46; This entity is not characterized by the activation of any particular pathways that can lead to the development of disease-specific treatment&#46; In the case of IPF&#44; the presence of emphysema causes difficulties in monitoring the behavior of the disease and the response to treatment due to the attenuating effect on serial FVC decline&#46; Moreover&#44; the preservation of FVC precludes the use of antifibrotic drugs in countries where an upper limit of FVC is used&#46; These important observations must be taken into account by expert groups involved in establishing the most appropriate management strategy for this subgroup of patients&#46;</p></span>"
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Article information
ISSN: 15792129
Original language: English
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2024 August 45 32 77
2024 July 28 23 51
2024 June 40 23 63
2024 May 53 29 82
2024 April 27 27 54
2024 March 39 16 55
2024 February 27 18 45
2023 March 11 3 14
2023 February 29 20 49
2023 January 26 34 60
2022 December 40 25 65
2022 November 39 31 70
2022 October 35 34 69
2022 September 28 20 48
2022 August 29 42 71
2022 July 37 44 81
2022 June 22 29 51
2022 May 27 32 59
2022 April 27 31 58
2022 March 33 37 70
2022 February 33 30 63
2022 January 27 39 66
2021 December 22 38 60
2021 November 31 35 66
2021 October 37 47 84
2021 September 25 40 65
2021 August 21 32 53
2021 July 25 25 50
2021 June 30 26 56
2021 May 30 34 64
2021 April 81 75 156
2021 March 36 16 52
2021 February 27 15 42
2021 January 31 9 40
2020 December 25 15 40
2020 November 24 18 42
2020 October 43 15 58
2020 September 14 11 25
2020 August 21 9 30
2020 July 26 23 49
2020 June 18 5 23
2020 May 16 13 29
2020 April 31 17 48
2020 March 16 8 24
2020 February 17 18 35
2020 January 26 17 43
2019 December 13 9 22
2019 November 22 15 37
2019 October 14 7 21
2019 September 16 8 24
2019 August 24 13 37
2019 July 22 11 33
2019 June 13 3 16
2019 May 159 16 175
2019 April 14 15 29
2019 March 19 16 35
2019 February 25 13 38
2019 January 18 10 28
2018 December 17 12 29
2018 November 28 14 42
2018 October 36 16 52
2018 September 38 13 51
2018 May 3 1 4
2018 April 14 3 17
2018 March 7 5 12
2018 February 11 3 14
2018 January 15 5 20
2017 December 18 5 23
2017 November 12 5 17
2017 October 13 9 22
2017 September 19 12 31
2017 August 16 9 25
2017 May 2 4 6
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