Prognosis of idiopathic pulmonary fibrosis without anti-fibrotic therapy: a systematic review

In addition to facilitating healthcare delivery planning, reliable information about prognosis is essential for treatment decisions in patients with idiopathic pulmonary fibrosis (IPF). This review aimed to evaluate the prognosis of patients with IPF without anti-fibrotic therapy. We included all cohort studies and the placebo arms of randomised controlled trials (RCTs) in IPF and follow-up of ≥12 months. Two reviewers independently evaluated studies for inclusion, assessed risk of bias and extracted data. A total of 154 cohort studies and 16 RCTs were included. The pooled proportions of mortality were 0.12 (95% CI 0.09–0.14) at 1–2 years, 0.38 (95% CI 0.34–0.42) between 2–5 years, and 0.69 (95% CI 0.59–0.78) at ≥5 years. The pooled mean overall survival was 4 years (95% CI 3.7–4.6) for studies with a follow-up duration of 10 years. At <2 years, forced vital capacity and diffusing capacity of the lung for carbon monoxide declined by a mean of 6.76% predicted (95% CI −8.92 −4.61) and 3% predicted (95% CI −5.14 −1.52), respectively. Although heterogeneity was high, subgroup analyses revealed lower pooled proportions of mortality at 1 year in the RCT participants (0.07 (95% CI 0.05–0.09)) versus cohort study participants (0.14 (95% CI 0.12–0.17)). This review provides comprehensive information on the prognosis of IPF, which can inform treatment discussions with patients and comparisons for future studies with new therapies.

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Serum biomarker CA 15-3 as predictor of response to antifibrotic treatment and survival in idiopathic pulmonary fibrosis

Biomarkers in Medicine ◽

10.2217/bmm-2020-0165 ◽

2020 ◽

Vol 14 (11) ◽

pp. 997-1007

Author(s):

Sofia A Moll ◽

Ivo A Wiertz ◽

Adriane DM Vorselaars ◽

Pieter Zanen ◽

Henk JT Ruven ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Pulmonary Function ◽

Vital Capacity ◽

Mixed Model ◽

Pulmonary Function Tests ◽

Hazard Ratio ◽

Poor Survival ◽

Function Test

Aim: Cancer antigen 15-3 (CA 15-3) is a baseline biomarker in idiopathic pulmonary fibrosis (IPF), but its value during follow-up is unknown. Materials and methods: Associations between serum CA 15-3 and pulmonary function tests during 1-year follow-up were evaluated by a mixed model in 132 IPF treated with pirfenidone or nintedanib. Results: Increased baseline (median: 56 kU/l) and follow-up CA 15-3 levels were inversely associated with forced vital capacity and diffusing capacity of the lung for carbon monoxide (estimates respectively: -5.21 and -4.69; p < 0.001). Baseline and 6-month CA 15-3 above 58.5 (hazard ratio: 1.67; p = 0.031) and 50.5 kU/l (hazard ratio: 2.99; p < 0.001), respectively, showed impaired survival compared with lower levels. Conclusion: CA 15-3 is associated with pulmonary function test during follow-up in IPF on antifibrotic treatment. Higher (follow-up) values are related with poor survival. Therefore, CA 15-3 is a promising follow-up biomarker in IPF.

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An updated approach to determine minimal clinically important differences in idiopathic pulmonary fibrosis

ERJ Open Research ◽

10.1183/23120541.00142-2021 ◽

2021 ◽

pp. 00142-2021

Author(s):

Mohleen Kang ◽

Srihari Veeraraghavan ◽

Greg S. Martin ◽

Jordan A. Kempker

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Short Form ◽

Area Under The Curve ◽

Receiver Operating Curve ◽

Physical Component Score ◽

Sf 36 ◽

Patient Related Outcome ◽

Randomised Controlled

IntroductionCurrent medications for idiopathic pulmonary fibrosis (IPF) have not been shown to have impact on patient related outcome measures (PROMs) highlighting the need for accurate Minimal Clinically Important Differences (MCID) values. Recently published consensus standards for MCID studies support using anchor-based over distribution-based methods. The aim of this study was to estimate MCID values for worsening in IPF using only an anchor-based approach.MethodsWe conducted secondary analyses of three randomised controlled trials with different inclusion criteria and follow-up intervals. The Health Transition question in the Short Form Health Survey 36 (SF-36) questionnaire was used as the anchor. We used receiver operating curve to assess responsiveness between the anchor and ten variables (four physiologic measures and six PROMs). We used an anchor-based method to determine the MCID values of variables that met the responsiveness criteria (area under the curve≥0.70).ResultsSix minute walk distance (6 MWD), the St. George's Respiratory Questionnaire (SGRQ), physical component score of SF-36 (SF-36 PCS), and University of California, San Diego, Shortness of Breath Questionnaire (UCSD SOBQ) met the responsiveness criteria. The MCID value for 6 MWD was −75 meters. The MCID value for SF-36 PCS was −7 points. MCID value for SGRQ was 11points. MCID value for the UCSD SOBQ was 11 points.ConclusionsThe MCID estimates of 6 MWD, SGRQ, SF-36, UCSD SOBQ using only anchor-based methods were considerably higher compared to previously proposed values. A single MCID value may not be applicable across all classes of disease severity or durations of follow-up time.

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Adherence to guidelines in idiopathic pulmonary fibrosis: a follow-up national survey

ERJ Open Research ◽

10.1183/23120541.00032-2015 ◽

2015 ◽

Vol 1 (2) ◽

pp. 00032-2015 ◽

Cited By ~ 6

Author(s):

Vincent Cottin ◽

Emmanuel Bergot ◽

Arnaud Bourdin ◽

Jacques Cadranel ◽

Philippe Camus ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Vital Capacity ◽

Substantial Improvement ◽

Diffusing Capacity ◽

Adherence To Guidelines ◽

Therapeutic Practice ◽

Practical Guidelines ◽

E Mail

A new survey coordinated by the French expert centres for rare pulmonary diseases investigated French pulmonologists' diagnostic and therapeutic practice for idiopathic pulmonary fibrosis (IPF) and explored changes since a previous survey in 2011–2012.From May 16 to August 30, 2014, 524 pulmonologists were contacted. Those following at least one patient with IPF were invited to complete a questionnaire administered by telephone or e-mail.166 (31.7%) pulmonologists, 161 (97%) of whom had participated to the first survey, completed the questionnaire. Of those, 46% and 52%, respectively, discussed the cases with radiologists and pathologists. Out of 144 pulmonologists practicing outside of expert centres, 80% indicated referring patients to those centres. The 2013 French practical guidelines for IPF were known by 92% of pulmonologists involved in IPF, 96% of whom considered them appropriate for practice. The multidisciplinary discussion form for IPF diagnosis was known by 74% and considered appropriate by 94%. Diagnosis and management resulted from multidisciplinary discussion in 50% of the cases. About 58% of patients were diagnosed with “mild to moderate IPF” as defined by forced vital capacity ≥50% of the predicted value and diffusing capacity for carbon monoxide ≥35% of predicted. At the time of the survey, 31% of physicians were using pirfenidone to treat patients with “mild-to-moderately severe IPF” and 30% generally prescribed no treatment.Substantial improvement has occurred since the 2011–2012 survey with regard to knowledge of guidelines and proper management of IPF. Early diagnosis still needs to be improved through the network of expert centres.

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Importance of serial changes in biomarkers in idiopathic pulmonary fibrosis

ERJ Open Research ◽

10.1183/23120541.00019-2016 ◽

2017 ◽

Vol 3 (3) ◽

pp. 00019-2016 ◽

Cited By ~ 13

Author(s):

Akihiko Sokai ◽

Kiminobu Tanizawa ◽

Tomohiro Handa ◽

Kumiko Kanatani ◽

Takeshi Kubo ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Vital Capacity ◽

Surfactant Protein ◽

Surfactant Protein D ◽

Prognostic Information ◽

The Mean ◽

Serial Measurements ◽

Overall Mortality

The clinical significance of serial changes in serum biomarkers in patients with idiopathic pulmonary fibrosis (IPF) remains to be established. This retrospective study was conducted to clarify the associations of serial changes in serum Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) with changes in physiological indices and overall mortality in IPF.The study subjects were 75 patients with IPF. The 6 month change in serum KL-6 was significantly correlated with changes in the percentage of the predicted forced vital capacity (FVC % pred) and the percentage of the predicted diffusing capacity of the lung for carbon monoxide (% DLCO), while the 6 month change in serum SP-D was correlated only with % DLCO. During the mean follow-up period of 647 days, 22 (29.3%) patients died. An increase in serum KL-6 over a 6 month period was a significant predictor of mortality even after adjustment for %FVC, % DLCO and serum KL-6 at the baseline (hazard ratio 1.10 per 100 U·mL−1, 95% CI 1.01–1.18, p=0.03), whereas the 6 month increase in serum SP-D was not significant.Serial measurements of serum KL-6 may provide additional prognostic information compared to that provided by physiological parameters in patients with IPF.

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Epithelial Alarmins in Serum and Exhaled Breath in Patients with Idiopathic Pulmonary Fibrosis: A Prospective One-Year Follow-Up Cohort Study

Journal of Clinical Medicine ◽

10.3390/jcm8101590 ◽

2019 ◽

Vol 8 (10) ◽

pp. 1590 ◽

Cited By ~ 2

Author(s):

Majewski ◽

Szewczyk ◽

Białas ◽

Miłkowska-Dymanowska ◽

Górski ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Exhaled Breath Condensate ◽

Exhaled Breath ◽

Antifibrotic Therapy ◽

Lung Compartment ◽

Before And After ◽

One Year ◽

Study Participants

Background: Recently, epithelial alarmins have been shown to play important roles in non-allergen driven respiratory diseases like idiopathic pulmonary fibrosis (IPF). Little is known about the expression of the epithelial alarmins in IPF. Methods: This study aimed to prospectively examine interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP) levels in the serum and exhaled breath condensate (EBC) in patients with IPF before and after one-year of antifibrotic treatment. A total of 82 volunteers, including 52 patients diagnosed with IPF that qualified for antifibrotic therapy as well as 30 controls, were examined. All study participants underwent baseline peripheral blood and EBC sampling. In 35 out of 52 IPF subjects, a follow-up sampling was performed after 12 months of antifibrotic treatment. Concentrations of alarmins in the serum and EBC were evaluated by means of ELISA. Results: Baseline TSLP concentrations were significantly elevated in patients with IPF compared to controls both in the serum (p < 0.05) and EBC (p < 0.0001). Baseline IL-25 and IL-33 serum and EBC levels did not differ significantly between IPF subjects and controls. Prospective analysis of changes in the epithelial alarmin levels showed significantly decreased IL-25 and TSLP EBC concentrations after 12 months of antifibrotic treatment (p < 0.05), which was observed in the subgroup of IPF patients treated with pirfenidone, but not in those treated with nintedanib. In stable patients with IPF over a study period (absolute forced vital capacity (FVC) % of predicted decline/year ≤ 5%, n = 25), a significant decrease in the EBC levels of both IL-25 and TSLP after 12 months of antifibrotic treatment was noted (p < 0.05), whereas, in progressor IPF patients (absolute FVC % of predicted decline/year > 5%, n = 10), a significant decrease was noted in the IL-25 EBC levels only (p < 0.05). Conclusions: Elevated TSLP levels in patients with IPF and their significant decrease in the lung compartment during antifibrotic therapy in stable patients with IPF, but not in progressors, support its significant contribution to pro-fibrotic type 2 immune responses in IPF. Noted changes in the epithelial alarmins concentration in the lung compartment during pirfenidone therapy may suggest its possible interaction with epithelial alarmins pathways in IPF.

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Does Technetium-99m Diethylenetriaminepentaacetate Clearance Predict the Clinical Course of Idiopathic Pulmonary Fibrosis?

Canadian Respiratory Journal ◽

10.1155/2004/185705 ◽

2004 ◽

Vol 11 (7) ◽

pp. 477-479 ◽

Cited By ~ 6

Author(s):

Marco Mura ◽

Gelorma Belmonte ◽

Stefano Fanti ◽

Angela Maria Pacilli ◽

Luca Fasano ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Vital Capacity ◽

Clinical Course ◽

Pulmonary Function Tests ◽

Functional Tests ◽

High Resolution Computed Tomography ◽

Technetium 99M ◽

Potential Indicator

Clearance of inhaled technetium-99m diethylenetriaminepentaacetate (99mTc-DTPA) is a potential indicator of disease activity and progression in idiopathic pulmonary fibrosis (IPF). The objective of the present study was to evaluate the prognostic value of99mTc-DTPA scans in IPF. A total of 22 patients (18 males), aged 33 to 80 years with IPF were followed for six to 20 months (mean 13 months). At diagnosis, high resolution computed tomography (HRCT) scans showed a honeycomb pattern with bibasilar reticular opacities in all cases. At T0 (diagnosis) and T1 (follow-up), each patient had pulmonary function tests (forced vital capacity, diffusing capacity of the lung for carbon monoxide and partial arterial O2pressure), extension of fibrosis evaluated by HRCT visual score and99mTc-DTPA lung clearance. Results at T0 and T1 were compared, taking into account the whole population and patients with relatively fast and slow99mTc-DTPA wash-out.99mTc-DTPA clearance did not show any significant correlation with functional tests or HRCT score. These findings indicate that clearance of inhaled99mTc-DTPA is not of value in following the progress of IPF.

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Gender Differences in Idiopathic Pulmonary Fibrosis: Are Men and Women Equal?

Frontiers in Medicine ◽

10.3389/fmed.2021.713698 ◽

2021 ◽

Vol 8 ◽

Author(s):

Lucile Sesé ◽

Hilario Nunes ◽

Vincent Cottin ◽

Dominique Israel-Biet ◽

Bruno Crestani ◽

...

Keyword(s):

Gender Differences ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Vital Capacity ◽

Advanced Disease ◽

Male Predominance ◽

Chi Squared ◽

Gender Characteristics ◽

Exposure History

Background: Idiopathic pulmonary fibrosis (IPF) is characterized by a male predominance. The aim of the study was to explore gender differences in a well-designed French multicentre prospective IPF cohort (COhorte FIbrose, COFI) with a 5-year follow-up.Methods: Between 2007 and 2010, 236 patients with incident IPF were included in COFI. Gender characteristics were compared using a t-test, Chi-squared test and ANOVA, as appropriate. Survival analyses were performed.Results: Fifty-one (22%) females and 185 (78%) males with an average age at diagnosis of 70.1 ± 9.20 and 67.4 ± 10.9 years, respectively, were included in the cohort. Women were significantly less exposed to tobacco smoke [never n = 32 (62.7%) vs. n = 39 (21.1%), p < 0.001] and to occupational exposure [n = 7 (13.7%) vs. n = 63 (34.1%), p = 0.012]. Baseline forced vital capacity, % of predicted (FVC%) was significantly better in women compare to men (83.0% ± 25.0 v. 75.4% ± 18.7 p = 0.046). At presentation honeycombing and emphysema on CT scan were less common in women [n = 40 (78.4%) vs. n = 167 (90.3%) p = 0.041] and [n = 6 (11.8%) vs. n = 48 (25.9%) p = 0.029], respectively. During follow-up fewer women were transplanted compared to men [n = 1 (1.96%) vs. n = 20 (10.8%) p = 0.039]. Medians of survival were comparable by gender [31 months (CI 95%: 28–40) vs. 40 months (CI 95%: 33–72) p = 0.2]. After adjusting for age and FVC at inclusion, being a woman was not associated to a better survival.Conclusions: Women appear to have less advanced disease at diagnosis, maybe due to less exposure history compare to men. Disease progression and overall survival remains comparable regardless gender, but women have less access to lung transplantation.

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