The Burden of Progressive Fibrosing Interstitial Lung Disease: A DELPHI Approach

Introduction: The term progressive fibrosing interstitial lung disease (ILD) describes patients with fibrotic ILDs who, irrespective of the aetiology of the disease, show a progressive course of their disease despite current available (and non-licensed) treatment. Besides in idiopathic pulmonary fibrosis, little is known about management and the burden of patients with fibrotic ILD, particularly those with a progressive behaviour. Methods: Using the Delphi method, 40 European experts in ILD management delivered information on management of (progressive) fibrosing ILD and on the impact of the disease on patients’ quality of life (QoL) and healthcare resource utilisation (HCRU). Annual costs were calculated for progressive and non-/slow-progressive fibrosing ILD for diagnosis, follow-up management, exacerbation management, and end-of-life care based on the survey data. Results: Physicians reported that progression in fibrosing ILD worsens QoL in both patients and their caregivers. Progression of fibrosing ILD was associated with a greater use of HCRU for follow-up visits and maintenance treatment compared with the non-/slow progression. The number of patients who suffered at least one acute exacerbation was reported to be more than three times higher in progressive fibrosing ILD patients than in patients with non-/slow-progressive fibrosing ILD. On average, annual estimated costs of progressive fibrosing ILD per patient were 1.8 times higher than those of the non-/slow-progressive form of the disease.

The Burden of Progressive Fibrosing Interstitial Lung Disease: A DELPHI Approach

Introduction: The term progressive fibrosing interstitial lung disease (ILD) describes patients with fibrotic ILDs who, irrespective of the aetiology of the disease, show a progressive course of their disease despite current available (and non-licensed) treatment. Besides in idiopathic pulmonary fibrosis, little is known about management and the burden of patients with fibrotic ILD, particularly those with a progressive behaviour. Methods: Using the Delphi method, 40 European experts in ILD management delivered information on management of (progressive) fibrosing ILD and on the impact of the disease on patients' quality of life (QoL) and healthcare resource utilisation (HCRU). Annual costs were calculated for progressive and non-/slow-progressive fibrosing ILD for diagnosis, follow-up management, exacerbation management, and end-of-life care based on the survey data. Results: Physicians reported that progression in fibrosing ILD worsens QoL in both patients and their caregivers. Progression of fibrosing ILD was associated with a greater use of HCRU for follow-up visits and maintenance treatment compared with the non-/slow progression. The number of patients who suffered at least one acute exacerbation was reported to be more than three times higher in progressive fibrosing ILD patients than in patients with non-/slow-progressive fibrosing ILD. On average, annual estimated costs of progressive fibrosing ILD per patient were 1.8 times higher than those of the non-/slow-progressive form of the disease. Conclusions: Progression in fibrosing ILD causes a significant impact on QoL and HCRU and costs. These survey data underline the need for safe and effective therapies to slow the disease progression.</div

Idiopathic pulmonary fibrosis: Best practice in monitoring and managing a relentless fibrotic disease

Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease that is, by definition, progressive. Progression of IPF is reflected by a decline in lung function, worsening of dyspnea and exercise capacity, and deterioration in health-related quality of life. In the short term, the course of disease for an individual patient is impossible to predict. A period of relative stability in forced vital capacity (FVC) does not mean that FVC will remain stable in the near future. Frequent monitoring using multiple assessments, not limited to pulmonary function tests, is important to evaluate disease progression in individual patients and ensure that patients are offered appropriate care. Optimal management of IPF requires a multidimensional approach, including both pharmacological therapy to slow decline in lung function and supportive care to preserve patients' quality of life

Static and dynamic mechanics of the murine lung after intratracheal bleomycin

<p>Abstract</p> <p>Background</p> <p>Despite its widespread use in pulmonary fibrosis research, the bleomycin mouse model has not been thoroughly validated from a pulmonary functional standpoint using new technologies. Purpose of this study was to systematically assess the functional alterations induced in murine lungs by fibrogenic agent bleomycin and to compare the forced oscillation technique with quasi-static pressure-volume curves in mice following bleomycin exposure.</p> <p>Methods</p> <p>Single intratracheal injections of saline (50 μL) or bleomycin (2 mg/Kg in 50 μL saline) were administered to C57BL/6 (<it>n </it>= 40) and Balb/c (<it>n </it>= 32) mice. Injury/fibrosis score, tissue volume density (TVD), collagen content, airway resistance (<it>R_N</it>), tissue damping (<it>G</it>) and elastance coefficient (<it>H</it>), hysteresivity (<it>η</it>), and area of pressure-volume curve (PV-A) were determined after 7 and 21 days (inflammation and fibrosis stage, respectively). Statistical hypothesis testing was performed using one-way ANOVA with LSD <it>post hoc </it>tests.</p> <p>Results</p> <p>Both C57BL/6 and Balb/c mice developed weight loss and lung inflammation after bleomycin. However, only C57BL/6 mice displayed cachexia and fibrosis, evidenced by increased fibrosis score, TVD, and collagen. At day 7, PV-A increased significantly and <it>G </it>and <it>H </it>non-significantly in bleomycin-exposed C57BL/6 mice compared to saline controls and further increase in all parameters was documented at day 21. <it>G </it>and <it>H</it>, but not PV-A, correlated well with the presence of fibrosis based on histology, TVD and collagen. In Balb/c mice, no change in collagen content, histology score, TVD, <it>H </it>and <it>G </it>was noted following bleomycin exposure, yet PV-A increased significantly compared to saline controls.</p> <p>Conclusions</p> <p>Lung dysfunction in the bleomycin model is more pronounced during the fibrosis stage rather than the inflammation stage. Forced oscillation mechanics are accurate indicators of experimental bleomycin-induced lung fibrosis. Quasi-static PV-curves may be more sensitive than forced oscillations at detecting inflammation and fibrosis.</p

Diagnostic value of triggering receptor expressed on myeloid cells-1 and C-reactive protein for patients with lung infiltrates: an observational study

<p>Abstract</p> <p>Background</p> <p>Differential diagnosis of patients with lung infiltrates remains a challenge. Triggering receptor expressed on myeloid cells (TREM)-1 is a neutrophil and monocyte receptor up-regulated during infection. The aim of this study was to evaluate the diagnostic accuracy of TREM-1 and of C-reactive protein (CRP) from patients with lung infiltrates to discern community acquired lung infections.</p> <p>Methods</p> <p>68 patients admitted to a medical ward with acute respiratory illness were enrolled in the study. Neutrophil and monocyte TREM-1 expression were measured by flow cytometry, sTREM-1 by an enzyme immunoassay and C-reactive protein by nephelometry. Clinical pulmonary infection score was recorded.</p> <p>Results</p> <p>34 patients were diagnosed with bacterial community acquired pneumonia (group A) and 34 with non-bacterial pulmonary disease (group B). Median serum TREM-1 concentration was 102.09 pg/ml in group A and lower than 15.10 pg/ml (p < 0.0001) in group B. Mean±SE neutrophil TREM-1 expression was 4.67 ± 0.53 MFI in group A and 2.64 ± 0.25 MFI (p = 0.001) in group B. Monocyte TREM-1 expression was 4.2 ± 0.42 MFI in group A and 2.64 ± 0.35 MFI (p = 0.007) in group B and mean±SE CRP was 18.03 ± 2 mg/ml in group A and 7.1 ± 1.54 mg/ml (p < 0.001) in group B. A cut-off of 19.53 pg/ml of sTREM-1 with sensitivity 82.6% and specificity 63% to discriminate between infectious and non-infectious pulmonary infiltrates was found. sTREM-1 at admission greater than 180 pg/ml was accompanied with unfavourable outcome.</p> <p>Conclusion</p> <p>TREM-1 myeloid expression and sTREM-1 are reliable markers of bacterial infection among patients with pulmonary infiltrates; sTREM-1 is a predictor of final outcome.</p

EFFECTS OF AIR POLLUTION AND PASSIVE SMOKING ON RESPIRATORY FUNCTION IN CHILDREN 10-12 YEARS OLD

IN ORDER TO ASSESS POSSIBLE ADVERSE EFFECTS OF AIR POLLUTION AND PASSIVE SMOKING ON RESPIRATORY FUNCTION IN CHILDREN, A CROSS SECTIONAL EPIDEMIOLOGICAL SURVEYWAS CARRIED OUT IN A POPULATION OF 887 CHILDREN 10-12 YEARS OLD OF ATHENS CITYOF EXTREMELY HIGH LEVELS OF AIR POLLUTION AND 1032 CHILDREN OF SAME AGE, LIVING IN 4 OTHER CITIES IN GREECE WITH VERY LOW LEVELS OF OUTDOOR POLLUTION. ALL CHILDREN WERE INTERVIEWED TO A SINGLE QUESTIONNAIRE REGARDING SMOKING HABITS OF THEIR FAMILY RESPIRATORY DISEASES AND TIME LIVING IN THE CITY AND THEN UNDERWENTAN EXPIRATORY FLOW-VOLUME TEST. A TWO WAYS ANALYSIS OF VARIANCE AND COVARIANCEOF RESULTS WERE PERFORMED. WE FOUND THAT FEV, FVC ABD FVC% PREDICTED WERE SIGNIFICANTLY LOWER IN CHILDREN LIVING IN THE HIGH POLLUTED AREA (P<0.0001). PASSIVE SMOKING IN ALL TWO LEVELS CONSIDERED WAS NOT FOUND TO INFLUENCE VENTILATORY FUNCTION. WE CONCLUDE THAT THE HIGHLY POLLUTED AIR OF ATHENS ADVERSELY AFFECTS RESPIRATORY FUNCTION OF CHILDREN.ΜΕ ΣΚΟΠΟ ΤΗ ΔΙΕΡΕΥΝΗΣΗ ΠΙΘΑΝΩΝ ΑΡΝΗΤΙΚΩΝ ΕΠΙΠΤΩΣΕΩΝ ΕΞΑΙΤΙΑΣ ΤΗΣ ΑΤΜΟΣΦΑΙΡΙΚΗΣ ΡΥΠΑΝΣΗΣ ΚΑΙ ΤΟΥ ΠΑΘΗΤΙΚΟΥ ΚΑΠΝΙΣΜΑΤΟΣ ΣΤΗΝ ΑΝΑΠΝΕΥΣΤΙΚΗ ΛΕΙΤΟΥΡΓΙΑ ΠΑΙΔΙΩΝ ΕΠΙΧΕΙΡΗΘΗΚΕ ΕΠΙΔΗΜΙΟΛΟΓΙΚΗ ΕΡΕΥΝΑ ΣΕ ΠΛΗΘΥΣΜΟ 887 ΠΑΙΔΙΩΝ 10-12 ΕΤΩΝ ΤΗΣ ΑΘΗΝΑΣ ΠΟΛΗΣ ΜΕ ΠΟΛΥ ΥΨΗΛΟ ΕΠΙΠΕΔΟ ΑΤΜΟΣΦΑΙΡΙΚΗΣ ΡΥΠΑΝΣΗΣ ΚΑΙ ΣΕ ΠΛΗΘΥΣΜΟ 1032 ΠΑΙΔΙΩΝ ΠΟΥ ΖΟΥΣΑΝ ΣΕ 4 ΕΠΑΡΧΙΑΚΕΣ ΠΟΛΕΙΣ ΤΗΣ ΕΛΛΑΔΑΣ ΠΟΛΕΙΣ ΜΕ ΠΟΛΥ ΧΑΜΗΛΑ ΕΠΙΠΕΔΑ ΑΤΜΟΣΦΑΡΙΚΗΣ ΡΥΠΑΝΣΗΣ. ΟΛΑ ΤΑ ΠΑΙΔΙΑ ΚΛΗΘΗΚΑΝ ΝΑ ΑΠΑΝΤΗΣΟΥΝ ΣΕ ΕΝΑ ΑΠΛΟ ΕΡΩΤΗΜΑΤΟΛΟΓΙΟ ΠΟΥ ΑΦΟΡΟΥΣΕ ΤΙΣ ΚΑΠΝΙΣΤΙΚΕΣ ΣΥΝΗΘΕΙΕΣ ΤΩΝ ΓΟΝΕΩΝ ΤΟΥΣ, ΑΝΑΠΝΕΥΣΤΙΚΕΣ ΠΑΘΗΣΕΙΣ ΚΑΙ ΧΡΟΝΟ ΖΩΗΣ ΣΤΗ ΣΥΓΚΕΚΡΙΜΕΝΗ ΠΟΛΗ ΚΑΙ ΣΤΗ ΣΥΝΕΧΕΙΑ ΕΚΤΕΛΟΥΝΤΑΝ ΜΙΑ ΑΝΑΠΝΕΥΣΤΙΚΗ ΔΟΚΙΜΑΣΙΑ ΡΟΗΣ-ΟΓΚΟΥ. Η ΣΤΑΤΙΣΤΙΚΗ ΜΕΘΟΔΟΛΟΓΙΑ ΠΟΥ ΕΠΙΛΕΧΘΗΚΕ ΓΙΑ ΤΗΝ ΑΝΑΛΥΣΗ ΤΩΝ ΑΠΟΤΕΛΕΣΜΑΤΩΝ ΕΙΝΑΙ ΕΚΕΙΝΗ ΤΗΣ ΑΝΑΛΥΣΗΣ ΔΙΑΚΥΜΑΝΣΗΣ- ΣΥΝΔΙΑΚΥΜΑΝΣΗΣ. ΑΠΟ ΤΑ ΑΠΟΤΕΛΕΣΜΑΤΑ ΜΑΣ ΠΡΟΚΥΠΤΕΙ ΟΤΙ FEV, FVC ΚΑΙ FVC% ΤΟΥ ΠΡΟΒΛΕΠΟΜΕΝΟΥ ΠΑΡΟΥΣΙΑΖΟΥΝ ΤΙΜΕΣ ΣΤΑΤΙΣΤΙΚΑ ΣΗΜΑΝΤΙΚΑ ΧΑΜΗΛΩΤΕΡΕΣ ΣΤΑ ΠΑΙΔΙΑ ΠΟΥ ΖΟΥΝ ΣΤΗΝ ΠΕΡΙΟΧΗ ΥΨΗΛΗΣ ΡΥΠΑΝΣΗΣ (Ρ<0.0001). ΤΟ ΠΑΘΗΤΙΚΟ ΚΑΠΝΙΣΜΑ ΚΑΙ ΣΤΑ ΔΥΟ ΕΠΙΠΕΔΑ ΠΟΥ ΔΙΕΡΕΥΝΗΘΗΚΕ ΔΕΝ ΒΡΕΘΗΚΕ ΝΑ ΕΠΗΡΕΑΖΕΙ ΤΗΝ ΑΝΑΠΝΕΥΣΤΙΚΗ ΛΕΙΤΟΥΡΓΙΑ ΤΩΝ ΠΑΙΔΙΩΝ. ΣΥΜΠΕΡΑΙΝΕΤΑΙ ΟΤΙ ΤΑ ΥΨΗΛΑ ΕΠΙΠΕΔΑ ΑΤΜΟΣΦΑΙΡΙΚΗΣ ΡΥΠΑΝΣΗΣ ΤΗΣ ΠΟΛΗΣ ΤΩΝ ΑΘΗΝΩΝ ΕΧΟΥΝ ΕΠΗΡΕΑΣΕΙ ΑΡΝΗΤΙΚΑ ΤΗΝ ΑΝΑΠΝΕΥΣΤΙΚΗ ΛΕΙΤΟΥΡΓΙΑ ΤΩΝ ΠΑΙΔΙΩΝ

Diagnosis of Idiopathic Pulmonary Fibrosis “Pragmatic Challenges in Clinical Practice”

The past few years have signaled a major breakthrough on the management of idiopathic pulmonary fibrosis (IPF). Finally, we have drugs in our arsenal able to slow down the inexorable disease natural course. On the other hand, the latter evidence has increased the responsibility for a timely and accurate diagnosis. Establishment of IPF diagnosis directly affects the choice of appropriate treatment. The current diagnostic guidelines represent a major step forward providing an evidence-based road map; yet, clinicians are encountering major diagnostic dilemmas that inevitably affect therapeutic decisions. This review article aims to summarize the current state of knowledge on the diagnostic procedure of IPF based on the current guidelines and discuss pragmatic difficulties and challenges encountered by clinicians with regards to their applicability in the everyday clinical practice

Serum uric acid as a predictor of mortality and future exacerbations of COPD

Serum uric acid is increased in respiratory disease, especially in the presence of hypoxia and systemic inflammation. We evaluated serum uric acid as a biomarker for prediction of mortality and future acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Serum uric acid was measured in 314 eligible consecutive patients on admission for AECOPD. Patients were evaluated monthly for 1 year. Uric acid levels were higher in patients with more severe airflow limitation and in those experiencing frequent exacerbations. High uric acid levels (&gt;= 6.9 mg.dL(-1)) were an independent predictor of 30-day mortality in multivariate Cox regression analysis (HR 1.317, 95% CI 1.011-1.736; p=0.044), but not of 1-year mortality. Patients with high serum uric acid required more prolonged hospitalisation, and more often needed noninvasive ventilation and admission to the intensive care unit within 30 days. In addition, high uric acid levels were associated with increased risk and hospitalisation for AECOPD in 1 year in multivariate Poisson regression analysis (incidence rate ratio 1.184 (95% CI 1.125-1.246) and 1.190 (95% CI 1.105-1.282), respectively; both p&lt;0.001). Serum uric acid is associated with increased 30-day mortality and risk for AECOPD and hospitalisations in 1-year follow-up. This low-cost biomarker may be useful in the identification of high-risk chronic obstructive pulmonary disease patients that could benefit from intensive management