Scientific Letter
Combined Pulmonary Fibrosis and Emphysema Versus Idiopathic Pulmonary Fibrosis Versus Emphysema: A Clinical Perspective
Comparación con perspectiva clínica de la combinación de fibrosis pulmonar y enfisema, la fibrosis pulmonar idiopática y el enfisema
Maria Aurora Mendes
, Miguel Guimarães, Sofia Neves, Sérgio Campainha
Corresponding author
Pulmonology Department, Centro Hospitalar Vila Nova de Gaia/Espinho, Portugal
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In view of that, this study aims to identify functional features that can help to distinguish CPFE from idiopathic pulmonary fibrosis (IPF) and/or emphysema.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We performed a retrospective analysis of patients with CPFE and IPF followed in an Interstitial Lung Diseases (ILDs) Outpatient Clinic between 2011 and 2016. A convenience sample of patients with emphysema attending a Chronic Obstructive Pulmonary Disease (COPD) Outpatient Clinic was obtained.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The diagnosis of CPFE and IPF was established by multidisciplinary discussion. The diagnostic criteria for IPF were applied according to the 2011 ATS/ERS/JRS/ALAT guidelines for diagnosis and management of IPF. CPFE was only considered in patients with emphysema involving at least 10% of the whole lung. The diagnosis of emphysema was established by visual assessment of HRCT.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Demographics, pulmonary function test results and evidence of pulmonary hypertension (PH) at diagnosis were reviewed from medical records. Only data regarding pulmonary function tests and echocardiograms performed up to 6 months within the baseline HRCT was included. PH was defined as a systolic arterial pulmonary pressure<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>40<span class="elsevierStyleHsp" style=""></span>mmHg plus central venous pressure on echocardiogram.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Kruskal–Wallis test was used to compare pulmonary function test results at diagnosis between groups. Statistical significance was set at <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05.</p><p id="par0030" class="elsevierStylePara elsevierViewall">We identified 14 patients with CPFE, 49 with IPF (35 UIP pattern; 16 possible/inconsistent UIP, who underwent lung biopsy) and 57 with emphysema. Overall, 85% were men with a median age at diagnosis of 68.5 years (IQR 61.0–75.0) and 21% were never smokers. All CPFE patients were male and all but two were current or ex-smokers. The median age at diagnosis was 66.5 years (IQR 60.8–77.0) and 30.8% of CPFE patients had PH at diagnosis. No significant differences between patients with CPFE and patients with IPF or emphysema were found regarding gender, age at diagnosis, smoking history or prevalence of PH at diagnosis.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The pulmonary function test results at diagnosis are presented in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Compared to patients with emphysema, those with CPFE had lower RV% pred (<span class="elsevierStyleItalic">p</span> 0.005), TLC% pred (<span class="elsevierStyleItalic">p</span> 0.012) and RV/TLC ratio (<span class="elsevierStyleItalic">p</span> 0.001), and higher FEV1% (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001) and FEV1/FVC ratio (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001; all pairwise comparisons). FVC% pred (<span class="elsevierStyleItalic">p</span> 0.104) and DLCO% pred (<span class="elsevierStyleItalic">p</span> 0.118) did not differ between the three groups of patients. No significant differences in analysed pulmonary function test parameters were found comparing patients with CPFE and IPF.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">In our study, CPFE was mainly diagnosed in elderly male smokers, as previously described.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">1,3,5–9,12–14</span></a> Almost a third of CPFE patients had PH at diagnosis, and this prevalence did not significantly differ in comparison with IPF or emphysema patients. However, there is previous evidence that PH is more frequent in CPFE than IPF or emphysema patients.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">1,5–9,12</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">To the best of our knowledge, RV/TLC ratio has not been described in CPFE, or even compared between CPFE, IPF and emphysema patients. We found that CPFE patients had significantly lower RV/TLC ratio than emphysema patients (39.8 vs. 56.8). Accordingly, a normal (lower than 40) or slightly increased RV/TLC ratio could help to discriminate patients with emphysema and superimposed fibrosis from patients only with emphysema.</p><p id="par0050" class="elsevierStylePara elsevierViewall">CPFE patients had significantly lower static lung volumes and higher FEV1% pred and FEV1/FVC ratio compared to emphysema patients, which is in accordance with previous studies.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">3,5</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">A trend towards higher lung volumes was seen comparing CPFE and IPF patients, but did not reach statistical significance. Our IPF patients had median lung volumes at diagnosis within the normal or near-normal range, which could underestimate the difference between these two groups of patients. Kohashi et al. also did not find significant differences in FEV1% pred, FVC% pred and FEV1/FVC ratio between IPF alone and IPF-emphysema.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a> However, other studies have consistently shown higher lung volumes and lower FEV1/FVC ratio in CPFE versus IPF.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">5,13,14</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Although CPFE patients presented the lowest median DLCO% pred, this functional parameter did not significantly differ between the three groups of patients. This result is not accordant with previous studies. More than 20 years ago, Wells et al. showed that patients with IPF and emphysema had lower DLCO% pred by approximately 15% as compared to patients with IPF alone,<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a> and subsequent studies have also suggested that DLCO% pred is significantly lower in CPFE versus IPF.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">3,5</span></a> It is possible that the extent of fibrosis and emphysema (i.e. stage of disease at diagnosis) and PH could have influenced our results as suggested by other studies.<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">9,12,14</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The main strengths of our research are: (i) direct comparison of static lung volumes and DLCO% pred between CPFE, IPF and emphysema patients, (ii) use of “real-life” data, and (iii) pre-specified threshold of at least 10% of emphysema to define CPFE.</p><p id="par0070" class="elsevierStylePara elsevierViewall">This study has also some limitations: (i) its retrospective nature, (ii) the relative small number of CPFE patients analysed, (iii) the lack of a quantitative evaluation of the extent of fibrosis or emphysema and (iv) selection bias of emphysema patients from a COPD Outpatient Clinic; all emphysema patients had evidence of airflow obstruction, which is not always observed in clinical practice.</p><p id="par0075" class="elsevierStylePara elsevierViewall">In daily clinical practice, to accurately diagnose CPFE may be difficult as it shares many clinical and radiological characteristics with other smoking-related lung diseases. This study showed that a lower RV/TLC ratio could be a potential surrogate to distinguish between CPFE and emphysema when diagnostic work-up raises doubts.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">% pred: predicted percentage. RV: residual volume. TLC: total lung capacity. FEV1: forced expiratory volume in the first second. FVC: forced vital capacity.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total<br><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>120 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">CPFE<br><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>14 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IPF<br><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>49 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Emphysema<br><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>57 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Overall<br><span class="elsevierStyleItalic">p</span>-value \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">RV% pred<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">108.6 (79.5–180.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">105.2 (81.5–118.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">84.6 (74.1–92.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">182.2 (143.2–223.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.000 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TLC% pred<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">96.5 (77.8–118.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">95.8 (80.2–103.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">77.7 (69.2–91.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">119.6 (111.4–137.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.000 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">RV/TLC ratio<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">46.2 (39.8–57.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">39.8 (33.5–47.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">43.3 (38.7–45.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">56.8 (49.7–64.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.000 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FEV1% pred<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">70.0 (46.2–90.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">92.5 (77.0–106.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">84.5 (76.9–104.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">46.3 (38.9–55.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.000 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FVC% pred<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">83.0 (74.0–98.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">95.5 (83.0–110.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">81.3 (69.9–92.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">84.0 (75.3–98.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.104 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FEV1/FVC ratio<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">69.9 (43.4–82.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">77.2 (71.0–85.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">82.5 (79.8–87.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">43.2 (35.6–50.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.000 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DLCO% pred<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">45.8 (36.5–61.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">37.8 (33.9–64.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">53.1 (38.9–64.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">44.0 (35.7–58.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.118 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2022438.png" ] ] ] "notaPie" => array:3 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">27 patients without RV% pred, TLC% pred and RV/TLC ratio results up to 6 months within the baseline HRCT.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">4 patients without FEV1% pred, FVC% pred and FEV1/FVC ratio results up to 6 months within the baseline HRCT.</p>" ] 2 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "c" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">23 patients without DLCO% pred results up to 6 months within the baseline HRCT.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Comparison of pulmonary function test results at diagnosis between the three groups of patients.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0080" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Combined pulmonary fibrosis and emphysema: a distinct underrecognised entity" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 32 | 16 | 48 |
| 2024 September | 45 | 20 | 65 |
| 2024 August | 49 | 37 | 86 |
| 2024 July | 55 | 24 | 79 |
| 2024 June | 48 | 30 | 78 |
| 2024 May | 66 | 32 | 98 |
| 2024 April | 25 | 31 | 56 |
| 2024 March | 31 | 16 | 47 |
| 2024 February | 24 | 19 | 43 |
| 2023 March | 8 | 1 | 9 |
| 2023 February | 39 | 15 | 54 |
| 2023 January | 22 | 24 | 46 |
| 2022 December | 40 | 29 | 69 |
| 2022 November | 46 | 16 | 62 |
| 2022 October | 54 | 30 | 84 |
| 2022 September | 49 | 33 | 82 |
| 2022 August | 40 | 32 | 72 |
| 2022 July | 34 | 47 | 81 |
| 2022 June | 26 | 27 | 53 |
| 2022 May | 32 | 32 | 64 |
| 2022 April | 29 | 37 | 66 |
| 2022 March | 33 | 34 | 67 |
| 2022 February | 37 | 38 | 75 |
| 2022 January | 42 | 32 | 74 |
| 2021 December | 20 | 36 | 56 |
| 2021 November | 30 | 33 | 63 |
| 2021 October | 31 | 40 | 71 |
| 2021 September | 30 | 39 | 69 |
| 2021 August | 36 | 29 | 65 |
| 2021 July | 25 | 22 | 47 |
| 2021 June | 33 | 37 | 70 |
| 2021 May | 32 | 49 | 81 |
| 2020 March | 16 | 4 | 20 |
| 2020 February | 18 | 12 | 30 |
| 2020 January | 26 | 20 | 46 |
| 2019 December | 20 | 16 | 36 |
| 2019 November | 24 | 16 | 40 |
| 2019 October | 1 | 0 | 1 |
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